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Oxidation dye composition for keratin fibers comprising a nonionic amphiphilic polymer

The invention relates to an oxidation dye composition for keratin fibres, and in particular for human keratin fibres such as the hair, comprising, in a medium which is suitable for dyeing, at least one oxidation dye precursor and optionally one or more couplers, characterized in that it also comprises a nonionic amphiphilic polymer containing at least one fatty chain and at least one hydrophilic unit. The invention also relates to the processes and dyeing devices using the said oxidation dye composition.

1-29. (canceled) 30. A composition for the oxidation dyeing of keratin fibres comprising: at least one oxidation dye precursor, and at least one nonionic amphiphilic polymer comprising at least one fatty chain and at least one hydrophilic unit, said at least one nonionic amphiphilic polymer being chosen from: (1) celluloses modified with groups containing at least one fatty chain, and (2) hydroxypropyl guars modified with groups containing at least one fatty chain. 31. A composition according to claim 30, wherein said composition further contains a medium suitable for dyeing. 32. A composition according to claim 31, wherein said human keratin fibres are human hair. 33. A composition according to claim 32, wherein said celluloses are hydroxyethyl celluloses modified with groups containing at least one group chosen from alkyl, arylalkyl, and alkylaryl. 34. A composition according to claim 33, wherein said hydroxyethyl celluloses contain at least one C8-C22 alkyl group. 35. A composition according to claim 32, wherein said celluloses contain at least one polyalkylene glycol alkylphenyl ether group. 36. A composition according to claim 32, wherein said at least one oxidation dye precursor is chosen from ortho- and para-phenylenediamines, bis(phenyl)alkylenediamines, ortho- and para-aminophenols, heterocyclic bases, and acid addition salts thereof. 37. A composition according to claim 32, wherein said at least one oxidation dye precursor is present in concentrations ranging from 0.0005 to 12% by weight relative to the total weight of the composition. 38. A composition according to claim 30, wherein said composition further contains at least one coupler. 39. A composition according to claim 38, wherein said at least one coupler is chosen from meta-phenylenediamines, meta-aminophenols, meta-diphenols, heterocyclic couplers, and acid addition salts thereof. 40. A composition according to claim 39, wherein said at least one coupler is present in concentrations ranging from 0.0001 to 10% by weight relative to the total weight of the composition. 41. A composition according to claim 39, wherein said acid addition salts are chosen from hydrochlorides, hydrobromides, sulphates, tartrates, lactates, and acetates. 42. A composition according to claim 36, wherein said acid addition salts are chosen from hydrochlorides, hydrobromides, sulphates, tartrates, lactates, and acetates. 43. A composition according to claim 31, wherein said composition further comprises at least one direct dye. 44. A composition according to claim 31, wherein said composition further comprises at least one additional polymer chosen from cationic and amphoteric substantive polymers. 45. A composition according to claim 44, wherein said at least one additional polymer is a quaternary polyammonium polymer comprising repeating units corresponding to formula (IV) below: and wherein the molecular weight of said at least one additional polymer, determined by gel chromatography, ranges from 9500 to 9900. 46. A composition according to claim 44, wherein said at least one additional polymer is a quaternary polyammonium polymer comprising repeating units corresponding to formula (V) below: and wherein the molecular weight of said at least one additional polymer, determined by gel chromatography, is about 1200. 47. A composition according to claim 31, wherein said composition further comprises at least one reducing agent which is present in an amount ranging from 0.05 to 3% by weight relative to the total weight of the composition. 48. A composition according to claim 31, wherein said composition further comprises an oxidizing agent. 49. A composition according to claim 48, wherein said composition has a pH ranging from 4 to 11. 50. A composition according to claim 48, wherein said oxidizing agent is chosen from hydrogen peroxide, urea peroxide, alkali metal bromates and ferricyanides, and persalts. 51. A composition according to claim 50, wherein said oxidizing agent is an aqueous hydrogen peroxide solution having a titre ranging from 2.5 to 40 volumes. 52. A composition according to claim 51, wherein said at least one nonionic amphiphilic polymer is present in an amount ranging from 0.05 to 10% by weight relative to the total weight of the composition. 53. A composition according to claim 52, wherein said at least one nonionic amphiphilic polymer is present in an amount ranging from 0.2 to 5% by weight relative to the total weight of the composition. 54. A process for the oxidation dyeing of keratin fibres comprising the steps of: applying to said fibres a composition for the oxidation dyeing of keratin fibres comprising: at least one oxidation dye precursor, and at least one nonionic amphiphilic polymer comprising at least one fatty chain and at least one hydrophilic unit, said at least one nonionic amphiphilic polymer being chosen from: (1) celluloses modified with groups containing at least one fatty chain, and (2) hydroxypropyl guars modified with groups containing at least one fatty chain; and applying an oxidizing agent to said fibres in alkaline, neutral or acidic medium to develop color. 55. A process according to claim 54, wherein said keratin fibres are human hair. 56. A composition for the oxidation dyeing of keratin fibres comprising: a dye composition comprising: at least one oxidation dye precursor, and at least one nonionic amphiphilic polymer comprising at least one fatty chain and at least one hydrophilic unit, said at least one nonionic amphiphilic polymer being chosen from: (1) celluloses modified with groups containing at least one fatty chain, and (2) hydroxypropyl guars modified with groups containing at least one fatty chain; and an oxidizing composition comprising an oxidizing agent, wherein said oxidizing composition does not contain any of said nonionic amphiphilic polymer. 57. A composition for the oxidation dyeing of keratin fibres comprising: a dye composition comprising: at least one oxidation dye precursor, and at least one nonionic amphiphilic polymer comprising at least one fatty chain and at least one hydrophilic unit, said at least one nonionic amphiphilic polymer being chosen from: (1) celluloses modified with groups containing at least one fatty chain, and (2) hydroxypropyl guars modified with groups containing at least one fatty chain; and an oxidizing composition comprising an oxidizing agent, wherein said oxidizing composition further comprises at least one nonionic amphiphilic polymer comprising at least one fatty chain and at least one hydrophilic unit, said at least one nonionic amphiphilic polymer being chosen from: (1) celluloses modified with groups containing at least one fatty chain, and (2) hydroxypropyl guars modified with groups containing at least one fatty chain. 58. A process for the oxidation dyeing of keratin fibres comprising the steps of: applying to said fibres at least one composition comprising, in a medium which is suitable for dyeing: at least one oxidation dye precursor, and at least one nonionic amphiphilic polymer comprising at least one fatty chain and at least one hydrophilic unit, said at least one nonionic amphiphilic polymer being chosen from: (1) celluloses modified with groups containing at least one fatty chain, and (2) hydroxypropyl guars modified with groups containing at least one fatty chain; and applying an oxidizing composition comprising an oxidizing agent to said fibres in alkaline, neutral, or acidic medium to develop color, wherein said oxidizing composition does not contain any of said nonionic amphiphilic polymer. 59. A process according to claim 58, wherein said keratin fibres are human hair. 60. A multi-compartment kit for dyeing keratin fibres comprising a first compartment and a second compartment, wherein said first compartment contains a composition for the oxidation dyeing of keratin fibres comprising: at least one oxidation dye precursor, and at least one nonionic amphiphilic polymer comprising at least one fatty chain and at least one hydrophilic unit, said at least one nonionic amphiphilic polymer being chosen from: (1) celluloses modified with groups containing at least one fatty chain, and (2) hydroxypropyl guars modified with groups containing at least one fatty chain; and wherein said second compartment contains an oxidizing composition comprising an oxidizing agent in a medium which is suitable for dyeing. 61. A multi-compartment kit or device according to claim 60, wherein said keratin fibres are human hair. 62. A multi-compartment kit for dyeing keratin fibres comprising a first compartment and a second compartment, wherein said first compartment contains a composition for the oxidation dyeing of keratin fibres comprising: at least one oxidation dye precursor, and at least one nonionic amphiphilic polymer comprising at least one fatty chain and at least one hydrophilic unit, said at least one nonionic amphiphilic polymer being chosen from (1) celluloses modified with groups containing at least one fatty chain, and (2) hydroxypropyl guars modified with groups containing at least one fatty chain; and wherein said second compartment contains an oxidizing composition comprising an oxidizing agent used in a medium which is suitable for dyeing, wherein said oxidizing composition does not contain any of said nonionic amphiphilic polymer. 63. A ready-to-use composition for the oxidation dyeing of keratin fibres comprising: at least one oxidation dye precursor, at least one nonionic amphiphilic polymer comprising at least one fatty chain and at least one hydrophilic unit, said at least one nonionic amphiphilic polymer being chosen from: (1) celluloses modified with groups containing at least one fatty chain, and (2) hydroxypropyl guars modified with groups containing at least one fatty chain; and an oxidizing agent. 64. A process for the oxidation dyeing of keratin fibres comprising the steps of: applying to said fibres at least one composition comprising, in a medium which is suitable for dyeing: at least one oxidation dye precursor, and at least one nonionic amphiphilic polymer comprising at least one fatty chain and at least one hydrophilic unit, said at least one nonionic amphiphilic polymer being chosen from: (1) celluloses modified with groups containing at least one fatty chain, and (2) hydroxypropyl guars modified with groups containing at least one fatty chain; and applying an oxidizing composition comprising an oxidizing agent to said fibres in alkaline, neutral, or acidic medium to develop color, wherein said oxidizing composition further comprises at least one nonionic amphiphilic polymer comprising at least one fatty chain and at least one hydrophilic unit, said at least one nonionic amphiphilic polymer being chosen from: (1) celluloses modified with groups containing at least one fatty chain, and (2) hydroxypropyl guars modified with groups containing at least one fatty chain. 65. A process according to claim 64, wherein said keratin fibres are human hair. 66. A multi-compartment kit for dyeing keratin fibres comprising a first compartment and a second compartment, wherein said first compartment contains a composition for the oxidation dyeing of keratin fibres comprising: at least one oxidation dye precursor, and at least one nonionic amphiphilic polymer comprising at least one fatty chain and at least one hydrophilic unit, said at least one nonionic amphiphilic polymer being chosen from (1) celluloses modified with groups containing at least one fatty chain, and (2) hydroxypropyl guars modified with groups containing at least one fatty chain; and wherein said second compartment contains an oxidizing composition comprising an oxidizing agent used in a medium which is suitable for dyeing, wherein said oxidizing composition further comprises at least one nonionic amphiphilic polymer comprising at least one fatty chain and at least one hydrophilic unit, said at least one nonionic amphiphilic polymer being chosen from: (1) celluloses modified with groups containing at least one fatty chain, and (2) hydroxypropyl guars modified with groups containing at least one fatty chain.

Abdominal bench with constant gap torso cushion

A unique abdominal bench with a pivoting torso section has a number of pivots, rods, and levers that allow the fixed seat section, of the abdominal bench to remain a constant distance from the pivoting torso section during an abdominal exercise. The leg section of the abdominal bench pivots towards the abdomen, as does the torso section when the torso is raised. The leg section is pivotably connected to the torso section through a number of rods, pivots and levers such that the gap between the seat and torso section remains the same. A push rod is connected to the pivoting leg brace and is in turn connected to a torso bracket through several guide rods and a dog-leg lever. The push rod, guide rods and the dog-leg lever allow the torso section to remain a constant distance from the fixed seat section. Allowing the torso and seat section to remain a constant distance eliminates the pressure on the lower body of the exerciser and will not cause any movement of the lower body of the exerciser with respect to the torso section.

1. An abdominal bench with a fixed seat and a pivoting torso section, comprising: a) a frame supporting a leg and footrest brace, a torso section, and a fixed seat; b) a leg and footrest brace, pivotably connected to said frame, having a footrest end and a lower end, said lower end of said leg and footrest brace pivotably connected to a push rod; c) a push rod pivotably connected at one end to said leg and footrest brace and at the other end to a torso bracket; d) at least one guide rod pivotably connected at one end to said frame and at the other end to the lower end of a dog-leg lever; e) a dog-lever, connected at an upper end to said torso brace, in the center to said torso bracket and at the lower end to at least one guide rod; f) a short lever, pivotably connected at one end to a torso brace and pivotably connected at the other end to a torso bracket; g) a torso bracket connected to said leg and footrest brace by said push rod, guide rod, dog-leg lever and short lever; h) a torso cushion secured on top of said torso brace.

<SOH> BACKGROUND OF THE INVETION <EOH>This invention relates generally to the field of exercise equipment. More particularly, an abdominal bench is presented which has a unique system of pivots that increases the effectiveness of the abdominal exercise by maintaining the distance between the torso and seat cushions. In the field of exercise equipment, abdominal benches have been previously utilized to exercise the abdominal muscles. Essentially, an abdominal bench is a short bench having at least one cushion. The exerciser would lie on the abdominal bench and do sit-ups, also known as abdominal crunches. Several benches have been devised to increase the effectiveness of the exercise. The most common abdominal bench has one cushion to support both the torso and seat of the exerciser. More sophisticated benches have separate cushions for the torso and seat of the user. To utilize the bench, the exerciser would place his or her lower body on one seat cushion while his or her upper torso would rest on the torso cushion. The upper torso portion of the abdominal bench may pivot about a single pivot point. When the exerciser grasps the handles at the top end of the exercise bench and pulls himself upward, he accomplishes an abdominal crunch exercise. Repeating the exercise allows one to tone and strengthen the abdominal muscles. One of drawbacks with these standard abdominal benches is that the single pivot point for the torso section pushes the torso section towards the lower portion of the body at the same time as the exerciser is doing the abdominal exercise. This forward motion of the torso also moves the lower portion of the exerciser's body. This motion reduces the effectiveness of the abdominal exercise. It is an object of this invention to eliminate the pushing of the torso towards the seat in an abdominal exercise. Other abdominal benches have a footrest in addition to the seat and torso and handle portions of the bench. In accomplishing an abdominal exercise using this particular device, the exerciser would pull inwardly with his legs as well as pulling upwardly with his torso to accomplish the abdominal exercise. This exercise has been found to be effective. However, one drawback in the single pivot torso abdominal bench with footrests is that the torso section pushes on the lower body section thus decreasing the effectiveness of the exercise. It would be highly desirable to have an abdominal bench utilizing both handles and footrests and a pivoting torso section, where the torso section and fixed seat section remained a constant distance from each other. Maintaining the constant gap between the torso and fixed seat cushions eliminates the movement of the torso section of the exerciser's body towards the seat, and hence the lower portion of the exerciser's. body. It is an object of this invention to provide an abdominal bench where the pivoting torso section of the bench and the fixed seat section of the bench remain a constant distance apart. It is another object of this invention to provide a pivoting abdominal bench such that the movement of the upper torso section of the exerciser does not also force movement of the lower section of the exerciser. In order to keep a constant gap between the upper torso cushion and the fixed seat cushion, a distinct system of pivots has been devised. The pivot system eliminates the movement of the lower seat section of the exerciser as the upper torso section of the exerciser is moved forward. Keeping this same gap, there is little or no pressure exerted on the legs, and hence the footrest section of the exerciser, when, the upper torso is lifted. It is a still further object of this invention to provide an effective abdominal exercise such that the movement of the upper torso section does not force movement in the lower seat and leg section of the exerciser. Other and further objects of this invention will become apparent upon reading the below described specification.

<SOH> BRIEF DESCRIPTION OF THE PREFERRED EMBODIMENT <EOH>A pivoting abdominal bench has a fixed seat section and a pivoting upper torso section. The bench also has a pivoting leg and footrest section. The lower end of the leg and, footrest section is connected to a push rod. The push rod is connected to the lower end of the pivoting torso section. At least one guide rod is pivotably connected between the frame and a dog-leg lever. The dog-leg lever is pivotably connected to the lower part of the torso section. The arrangement of the rods, levers and pivots allows the exerciser to pivot the upper torso section upward while pivoting the leg and feet inwardly toward the abdomen. Due to the unique pivot system and the connection of the foot and leg rest to the torso section through the push rod, the torso section remains a constant distance from the seat section during the exercise. The constant gap between the pivoting torso section and the fixed seat section eliminates any pressure on the lower portion of the body that could result from the raising of the torso during the exercises.

Optical semiconductor device and fabrication method therefor

An optical semiconductor device such as, for example, a quantum dot SOA and a fabrication method therefor are disclosed wherein an active layer and a current constriction structure can be formed leftwardly and rightwardly symmetrically to minimize the polarization dependency. The fabrication method for an optical semiconductor device includes the steps of forming a semiconductor layer on a semiconductor substrate, forming a groove by removing the semiconductor layer at an opening of a mask, forming a first clad layer in the form of a projection having two symmetrical inclined faces in the groove by selective growth by using the mask as a selective growth mask, forming an active layer on the two inclined faces of the first clad layer, and removing the mask and burying the active layer with a second clad layer.

1. A fabrication method for an optical semiconductor device, comprising the steps of: forming a semiconductor layer on a semiconductor substrate; forming a groove by removing the semiconductor layer at an opening of a mask; forming a first clad layer in the form of a projection having two symmetrical inclined faces in the groove by selective growth by using the mask as a selective growth mask; forming an active layer on the two inclined faces of the first clad layer; and removing the mask and burying the active layer with a second clad layer. 2. The fabrication method for an optical semiconductor device as claimed in claim 1, wherein, at the semiconductor layer forming step, a plurality of current block layers having different conduction types are formed as the semiconductor layer. 3. The fabrication method for an optical semiconductor device as claimed in claim 1, wherein, at the groove forming step, a dielectric mask having a striped opening extending in the [110] direction is formed as the mask. 4. The fabrication method for an optical semiconductor device as claimed in claim 1, wherein, at the groove forming step, a mask having an opening of a width corresponding to a desired active layer width is formed as the mask. 5. The fabrication method for an optical semiconductor device as claimed in claim 1, wherein, at the active layer forming step, an active layer formed from one of quantum dots, quantum wires and quantum wells is formed as the active layer. 6. The fabrication method for an optical semiconductor device as claimed in claim 1, wherein: at the semiconductor layer forming step, the semiconductor layer is formed on a (001) semiconductor substrate; at the first clad layer forming step, the first clad layer having two (111) B surfaces on the (001) semiconductor substrate; and at the active layer forming step, the active layer is formed on the two (111) B surfaces of the first clad layer. 7. The fabrication method for an optical semiconductor device as claimed in claim 1, wherein: at the semiconductor layer forming step, a semi-insulating current block layer and an n-type current block layer are formed in order as the semiconductor layer on an n-type semiconductor substrate; at the groove forming step, a dielectric mask is formed as the mask, and the semi-insulating current block layer and the n-type current block layer at the opening are etched to form the groove; at the first clad layer forming step, an n-side clad layer is formed as the first clad layer in the groove; at the active layer forming step, an active layer is formed on the two inclined faces of the n-side clad layer; and at the active layer burying step, the dielectric mask is removed and the active layer is buried with a p-side clad layer as the second clad layer. 8. The fabrication method for an optical semiconductor device as claimed in claim 1, wherein, at the semiconductor layer forming step, an n-type current block layer and a p-type current block layer are formed in-order as the semiconductor layer on a p-type semiconductor substrate; at the groove forming step, a dielectric mask is formed as the mask, and the n-type current block layer and the p-type current block layer at the opening are etched to form the groove; at the first clad layer forming step, a p-side clad layer is formed as the first clad layer in the groove; at the active layer forming step, an active layer is formed on the two inclined faces of the p-side clad layer; and at the active layer burying step, the dielectric mask is removed and the active layer is buried with an n-side clad layer as the second clad layer. 9. The fabrication method for an optical semiconductor device as claimed in claim 1, further comprising, after all of the steps, the conditional step of forming electrodes at the top and the bottom. 10. An optical semiconductor device, comprising: a semiconductor substrate; a clad layer in the form of a projection formed on said semiconductor substrate and having two symmetrical inclined faces; an active layer formed on the two inclined faces of said clad layer; and a semiconductor layer formed in a contacting relationship with at least side faces of said clad layer and having an equal thickness at portions in the proximity of contacting portions thereof with said clad layer and any other portion thereof than the portions. 11. The optical semiconductor device as claimed in claim 10, wherein said active layer is formed from one of quantum dots, quantum wires and quantum wells is formed as the active layer. 12. The optical semiconductor device as claimed in claim 10, wherein said semiconductor layer includes a plurality of semiconductor layers having different conduction types in which a current constriction structure can be formed. 13. The optical semiconductor device as claimed in claim 10, wherein said clad layer is formed on a (001) semiconductor substrate and each of said inclined faces thereof is formed as a (111) B surface, and said active layer is formed on the two (111) B surfaces of said clad layer. 14. The optical semiconductor device as claimed in claim 10, wherein said clad layer and said active layer extend in a [110] direction. 15. The optical semiconductor device as claimed in claim 10, wherein said semiconductor substrate is an n-type semiconductor substrate while said clad layer is an n-side clad layer, and said semiconductor layer includes a semi-insulating current block layer and an n-type current block layer. 16. The optical semiconductor device as claimed in claim 10, wherein said semiconductor substrate is a p-type semiconductor substrate while said clad-layer is a p-side clad layer, and said semiconductor layer includes an n-type current block layer and a p-type current block layer.

<SOH> BACKGROUND OF THE INVENTION <EOH>(1) Field of the Invention This invention relates to an optical semiconductor device for use with optical communication and a fabrication method therefor, and more particularly to an optical semiconductor device suitable for use, for example, with a semiconductor optical amplifier wherein quantum dots are used for an active layer and a fabrication method for the optical semiconductor device. (2) Description of the Related Art In recent years, an optical semiconductor amplifier (hereinafter referred to as quantum dot SOA) having an active layer formed from quantum dots has a broad gain bandwidth and is expected promising as a device which can amplify CWDM (Coarse Wavelength Division Multiplexing) signals. In order to place a quantum dot SOA into practical use, it is demanded not only to expand the gain bandwidth but also to reduce the polarization dependency and finally achieve polarization independent. For example, if an active layer is formed on a face parallel to a substrate in a quantum dot SOA, then since the dots have a flattened shape, the gain with regard to TE polarized light is high and a high polarization dependency is exhibited. Therefore, as a structure for reducing the polarization dependency, an optical semiconductor device wherein quantum dots are formed, for example, on an inclined surface has been proposed (refer to, for example, Japanese Patent Laid-Open No. 2003-204121). Meanwhile, a semiconductor laser formed taking the polarization dependency into consideration is disclosed, for example, in Japanese Patent Laid-Open No. Hei 10-41587.

<SOH> SUMMARY OF THE INVENTION <EOH>In the following, an example of a fabrication method for an optical semiconductor device (optical semiconductor element) having an active layer formed from quantum dots on an inclined face is described with reference to FIGS. 3 (A) to 3 (F). First, a dielectric mask (for example, a SiO 2 mask) 51 having an opening is formed on an n-InP substrate 50 as shown in FIG. 3 (A). Then, a lower side cladding layer 52 made of n-InP is grown on the n-InP substrate 50 by a metal organic-chemical phase vapor deposition growth method using the dielectric mask 51 as a selective growth mask as seen in FIG. 3 (B). In this instance, the lower side cladding layer 52 has a ridge structure of a triangular cross section at the opening and has two symmetrical inclined faces. Thereafter, the dielectric mask 51 is removed as seen in FIG. 3 (C), and then an active layer 53 is grown on the overall area of the n-InP substrate 50 and the lower side cladding layer 52 as seen in FIG. 3 (D). Then, p-InP layers 54 and 55 serving as an upper side cladding layer are formed on the active layer 53 as seen in FIGS. 3 (D) and 3 (E). Finally, a mesa-shape forming mask (for example, a dielectric mask) having a striped opening of a width of approximately 1.5 μm is formed as shown in FIG. 3 (F), and etching (by wet etching or dry etching) is performed using the mesa-shape forming mask, thereby the shape of a mesa is formed. Thereafter, a p electrode 56 and an n electrode 57 are formed at the top and the bottom, respectively. An SOA fabricated in this manner and having the active layer 53 formed from quantum dots on inclined faces substantially perpendicular to each other has an extremely reduced polarization dependency because the gains with regard to TE polarized light and TM polarized light are leftwardly and rightwardly symmetrical to each other. However, such a quantum dot SOA as shown in FIG. 3 (F) exhibits high operating current because it is an optical semiconductor device of the ridge type. Further, where the conventional mesa-shape forming technique is applied to a quantum dot SOA having a mesa shape of a width of approximately 1 to 2 μm, it is difficult to perform positioning with a high degree of accuracy of a mesa-shape forming mask (for example, a striped dielectric mask) which is used upon exposure at an etching step. Therefore, it is very difficult to form an active layer, which is formed from quantum dots on the two inclined faces of the lower side cladding layer 52 included in the mesa shape, leftwardly and rightwardly symmetrically (leftwardly and rightwardly symmetrically with respect to a vertical line passing the apex of the lower side cladding layer formed so as to have a substantially triangular sectional shape). If the active layer formed from quantum dots is not formed leftwardly and rightwardly symmetrically, then it is difficult to achieve the polarization independent. It is to be noted that, in order to reduce the operating current, it is effective to provide a current constriction (blocking) structure around the active layer. Therefore, it is a possible idea to provide, after the mesa shape is formed in such a manner as described above, for example, a current constriction structure formed from a p-InP current block layer 58 , an n-InP current block layer 59 and a p-InP layer 55 A, which serves as an upper side cladding layer, stacked in order on the opposite sides of the mesa structure as seen in FIG. 4 . Also in this instance, it is difficult to perform positioning of a mesa-shape forming mask with a high degree of accuracy, and it is very difficult to form an active layer formed from quantum dots leftwardly and rightwardly symmetrically. Therefore, it is difficult to achieve the polarization independent. It is an object of the present invention to provide an optical semiconductor device and a fabrication method therefor wherein an active layer and a current constriction structure can be formed leftwardly and rightwardly symmetrically to achieve the polarization independent (non-dependency). In order to attain the object described above, according to an aspect of the present invention, there is provided a fabrication method for an optical semiconductor device, comprising the steps of forming a semiconductor layer on a semiconductor substrate, forming a groove by removing the semiconductor layer at an opening of a mask, forming a first cladding layer in the form of a projection having two symmetrical inclined faces in the groove by selective growth by using the mask as a selective growth mask, forming an active layer on the two inclined faces of the first cladding layer, and removing the mask and burying the active layer with a second cladding layer. According to another aspect of the present invention, there is provided an optical semiconductor device, comprising a semiconductor substrate, a cladding layer in the form of a projection formed on the semiconductor substrate and having two symmetrical inclined faces, an active layer formed on the two inclined faces of the cladding layer, and a semiconductor layer formed in a contacting relationship with at least side faces of the cladding layer and having an equal thickness at portions in the proximity of contacting portions thereof with the cladding layer and any other portion thereof than the portions. With the fabrication method for an optical semiconductor device and the optical semiconductor device, the active layer and a current constriction structure are formed leftwardly and rightwardly symmetrically, and consequently, there is an advantage that the polarization dependency is lowered and finally the polarization independent (non-dependency) can be achieved. If the present invention is applied, for example, to a quantum dot SOA, then such advantages can be achieved that the gain bandwidth can be expanded, that the operating current can be reduced, that the polarization dependency is reduced and that the polarization non-dependency can be implemented and besides that the yield can be enhanced. The above and other objects, features and advantages of the present invention will become apparent from the following description and the appended claims, taken in conjunction with the accompanying drawings.

Controlled-release compositions

A solid dosage formulation having a core with a pharmacological agent dispersed in a first controlled-release matrix from which release of the agent is relatively slow; and a coat formed over the core and having the agent dispersed in a second controlled-release matrix from which release of the agent is relatively fast. The first matrix can be a cross-linked high amylose starch and the second matrix can be a mixture of polyvinyl acetate and polyvinylpyrrolidone.

1. A solid dosage formulation comprising: a core comprising a pharmacological agent dispersed in a first controlled-release matrix comprising cross-linked high amylose starch, from which matrix release of the agent is relatively slow; and a coat formed over the core and comprising said agent dispersed in a second controlled-release matrix from which release of the agent is relatively fast. 2. The formulation of claim 1, wherein the coat and core comprise relative amounts of the agent such that release of the agent from the formulation is biphasic. 3. The formulation of claim 1, wherein the agent is soluble in water, and the first matrix is relatively hydrophilic relative to the second matrix. 4. The formulation of claim 1, wherein the agent is present in the formulation as an ionic salt. 5. The formulation of claim 4, wherein the agent contains an amino group. 6. The formulation of claim 5, wherein the agent is present in the formulation as a hydrochloride salt. 7. The formulation of claim 2, wherein the rate of release of the agent from the coat is at least twice the rate of release of the agent from the core, or wherein the rate of release of the agent from the coat is at least three times the rate of release of the agent from the core, and preferably, wherein the rate of release of the agent from the coat is up to fifteen times the rate of release of the agent from the core, or wherein the rate of release of the agent from the coat is up to twelve times the rate of release of the agent from the core, or wherein the rate of release of the agent from the coat is up to ten times the rate of release of the agent from the core, or wherein the rate of release of the agent from the coat is up to eight times the rate of release of the agent from the core, or wherein the rate of release of the agent from the coat is up to six times the rate of release of the agent from the core, or wherein the rate of release of the agent from the coat is about four times the rate of release of the agent from the core. 8. The formulation of any claim 1, wherein between 10% and 30% per hour of the agent present at 0 hours is released between 0 and 2 hours when tested in vitro using a USP Type I apparatus in 50 mM phosphate, pH 6.8, and stirring between 50 and 150 rpm. 9. The formulation of claim 1, wherein between 10% and 40% of the agent is released from the formulation between 0 and about 2 hours of measurement, between about 30% and 60% of the agent is released from the formulation between 2 and about 7 hours of the measurement, between about 50% and 80% of the agent is released from the formulation between 7 and about 12 hours of measurement, and between about 80% and 100% of the agent is released from the formulation after about 20 hours of measurement. 10. The formulation of claim 1 wherein the active agent is an analgesic 11. The formulation of claim 10, wherein the active agent is tramadol. 12. The formulation of claim 1, wherein each of the agent is soluble in water at least to the extent of 1 g/L, or more than 10 g/L, or more than 100 g/L, or more than 500 g/L, or more than 1000 g/L, or more than 2000 g/L. 13. The formulation of any claim 1, wherein the ratio of the core to the coat (w/w) is between about 1 and about 0.1, or between about 0.9 and about 0.2, or between about 0.8 and about 0.2, or between about 0.7 and about 0.2, or between about 0.5 and about 0.2, or between about 0.4 and about 0.2, or about 0.35. 14. The formulation of claim 1, wherein the ratio of the agent in core to the agent in the coat (w/w) is between about 0.1 and about 10, or between about 0.1 and about 8, or between about 0.2 and about 7, or between about 0.3 and about 6, or between about 0.4 and about 5, or between about 0.5 and about 4, or between about 0.6 and about 3, or between about 0.6 and about 2, or between about 0.6 and about 1.5, or between about 0.6 and about 1.3, or between about 0.7 and about 1, or between about 0.7 and about 0.9 or about 0.8. 15. The formulation of claim 1, wherein the core is between about 10% and about 90% by weight agent, or between about 20% and about 80% by weight agent, or between about 30% and about 70% by weight agent, or between about 40% and about 60% by weight agent, or about 50% by weight agent. 16. The formulation of claim 1, wherein the coat is between about 5% and about 90% by weight agent, or between about 5% and about 80% by weight agent, or between about 10% and about 70% by weight agent, or between about 10% and about 60% by weight agent, or between about 15% and about 50% by weight agent, or between about 15% and about 45% by weight agent, or between about 15% and about 40% by weight agent, or between about 20% and about 35% by weight agent, or between about 20% and about 30% by weight agent. 17. The formulation of claim 1 wherein the ratio of the matrix of the coat to the agent of the coat (w/w) is between about 0.1 and about 10, or between about 0.2 and about 9, or between about 0.2 and about 8, or between about 0.3 and about 7, or between about 0.4 and about 6, or between about 0.5 and about 5, or between about 0.6 and about 4, or between about 0.7 and about 4 or between about 1 and about 4, or between about 1 and about 3 and about 1.5 and about 2.5. 18. The formulation of claim 1, wherein the ratio of the matrix of the core to the agent of the core (w/w) is between about 0.1 and about 10, or between about 0.2 and about 9, or between about 0.3 and about 7, or between about 0.4 and about 6, or between about 0.5 and about 5, or between about 0.5 and about 4, or between about 0.5 and about 3, or between about 0.6 and about 3, or between about 0.7 and about 2 or between about 0.8 and about 1.5, or between about 0.9 and about 1.5, or between about 0.9 and about 1.3, or about 1, or is about 0.55. 19. The formulation of claim 1, wherein the agent is soluble in water at room temperature (about 21° C.) to the extent of at least 0.5 gm per mL. 20. The formulation of claim 1, wherein the agent contains an acid group, a base group or both an acid group and a base group, and the agent is present in the form of a salt thereof. 21. The formulation of claim 1, wherein the agent contains a base group. 22. The formulation of claim 1, wherein the agent contains an ionizable group and said group is at least 90% ionized in gastric juices (0.1M HCl). 23. The formulation of claim 1, wherein the agent is selected from the group consisting of isonicotinic acid hydrazide, sodium salicylate, pseudoephedrine hydrochloride, pseudoephedrine sulfate, acetaminophen or diclofenac sodium, verapamil, glipizide, nifedipine, felodipine, betahistine, albuterol, acrivastine, omeprazole, misoprostol, tramadol, oxybutynin, trimebutine, ciprofloxacin, and salts thereof. In addition, the pharmaceutical agent can be an antifungal agent, such as ketoconazole, or an analgesic agent such as acetylsalicylic acid, acetaminophen, paracetamol, ibuprofen, ketoprofen, indomethacin, diflunisal, naproxen, ketorolac, diclofenac, tolmetin, sulindac, phenacetin, piroxicam, mefamanic acid, dextromethorphan, other non-steroidal anti-inflammatory drugs including salicylates, pharmaceutically acceptable salts thereof or mixtures thereof. 24. The formulation of claim 1, wherein the core is prepared by compression. 25. The formulation of any claim 1, wherein the coat is prepared by compression. 26. The formulation of claim 25, wherein coat is compressed over a separately prepared said core. 27. The formulation of claim 1, wherein the coat comprises an admixture of polyvinyl acetate, polyvinylpyrrolidone. 28. The formulation of claim 27, wherein the ratio of polyvinyl acetate and polyvinylpyrrolidone in the coat (w/w) is between about 6:4 and 9:1, or 7:3 and 9:2, or about 8:2. 29. The formulation of claim 27, wherein the coat further comprises a binding agent. 30. The formulation of claim 29, wherein the binding agent is xanthan gum. 31. The formulation of claim 30, wherein the formulation is a tablet, and wherein said cross-linked high amylose starch comprises a chemically-modified, cross-linked high amylose starch prepared by a method comprising: (a) cross-linking high amylose starch, followed by (b) chemically modifying the cross-linked high amylose starch, followed by (c) gelatinization, and (d) drying to obtain a powder of said controlled release excipient; wherein said cross-linked high amylose starch is characterized in that upon solubilization in 90% DMSO at 80° C. for about three days and gel permeation chromatography, the height of the peak corresponding to amylose in said cross-linked high amylose starch is at least 90% of that of the peak corresponding to amylose in said high amylose starch prior to (a). 32. The formulation of claim 1, wherein the core further comprises a lubricant; and wherein the lubricant is optionally hydrogenated vegetable oil. 33. The formulation of claim 1, wherein the coat further comprises a lubricant, and wherein the lubricant is optionally hydrogenated vegetable oil. 34. The formulation of claim 1, wherein the formulation is a tablet formulated for oral administration. 35. A solid dosage formulation comprising: a core comprising a pharmacological agent dispersed in a first controlled-release matrix from which release of the agent is relatively slow; and a coat formed over the core and comprising said agent dispersed in a second controlled-release matrix, the second controlled-release matrix comprising a physical mixture of polyvinyl acetate and polyvinylpyrrolidone and from which release of the agent is relatively fast. 36. A solid dosage formulation comprising: a core comprising a pharmacological agent dispersed in a first controlled-release matrix comprising cross-linked high amylose starch, from which matrix release of the agent is relatively slow; and a coat formed over the core and comprising a pharmacological agent in a second controlled-release matrix, the second controlled-release matrix comprising a physical mixture of polyvinyl acetate and polyvinylpyrrolidone, and wherein: release of the agent from the matrix of the core is relatively slow with respect to release of the agent from the matrix of the coat. 37. A solid dosage formulation comprising: a core comprising a pharmacological agent in a first controlled-release matrix; and a coat as defined in claim 36, and wherein: release of the agent from the matrix of the core is relatively slow with respect to release of the agent from the matrix of the coat. 38. A solid dosage formulation comprising a pharmacological agent for release thereof over an extended period of time, the formulation comprising: a core comprising agent in a first controlled-release release matrix, the controlled-release matrix comprising cross-linked high amylose starch; and a coat formed over the core and comprising the agent in a second controlled-release matrix, the second controlled-release matrix comprising a physical mixture as defined in claim 36, and wherein: the agent is present in the core sufficient to obtain release into an aqueous environment, e.g. gastric juices, of no more than 50% of the agent from the formulation within one quarter of the period. 39. The formulation of claim 38, wherein the period is between about 12 and about 24 hours, and between about 30% and about 70% of the agent is in the core. 40. The formulation of claim 36, wherein each of the agent in the first matrix and the agent in the second matrix is soluble in water at least to the extent of 1 g/L, or more than 10 g/L, or more than 100 g/L, or more than 500 g/L, or more than 1000 g/L, or more than 2000 g/L. 41. The formulation of claim 36, wherein the agent is an analgesic. 42. A controlled released tablet comprising: a compressed core comprising cross-linked high amylose starch having tramadol, or a salt thereof, embedded therein; and a coat formed over the core by compression, and comprising a physical mixture of polyvinyl acetate, polyvinylpyrrolidone, a binder, tramadol; and wherein: the ratio of the core/coat (w/w) is between about 0.2 and 0.6; the ratio of the tramadol in the core to the tramadol in the coat is between about 0.7 and about 1; the ratio of polyvinyl acetate/polyvinylpyrrolidne (w/w) is between about 6:4 and 9:1; and the rate of release of tramadol from the coat matrix is at least twice the rate of release of tramadol from the core when measured by a USP Type I apparatus in 50 mM phosphate, pH 6.8, and between 50 and 150 rpm. 43. A method of manufacturing a controlled-release medication, the method comprising: (i) blending a pharmacological agent and a first matrix material comprising a cross-linked high amylose starch; (ii) forming the resultant blend of step (i) into a core; (iii) blending a pharmacological agent and a second matrix material comprising a relatively fast release material with respect to the first matrix material; (iv) forming the resultant blend of step (iii) as a coat onto the exterior of the core. 44. A method of manufacturing a controlled-release medication, the method comprising: (i) blending a pharmacological agent and a first matrix material; (ii) forming the resultant blend of step (i) into a core; (iii) blending a pharmacological agent and a second matrix material claim 36, said second matrix material being a relatively fast release material with respect to the first matrix material; (iv) forming the resultant blend of step (iii) as a coat onto the exterior of the core. 45. The method of claim 43, wherein step (ii) comprises compressing the resultant blend of step (i). 46. The method of claim 43, wherein step (iii) comprises compressing the resultant blend of step (iii) onto the exterior of the core. 47. The method of claim 43, wherein the agent in the core and the coat is tramadol, the total amount of tramadol in the medication is effective as a daily dosage. 48. An oral tramadol pharmaceutical composition suitable for once daily administration comprising an effective amount of tramadol or a pharmaceutically acceptable salt thereof providing after a single administration in vivo, a median time to tramadol peak plasma concentration (Tmax) between 2 and 8 hours and a mean peak tramadol plasma concentrations (Cmax) which are less than three times the mean plasma concentration obtained 24 hours after administration (C24h) of a single dose of such composition. 49. The composition of claim 48, wherein said mean peak tramadol plasma concentrations (Cmax) are less than two times the mean plasma concentration obtained 24 hours after administration (C24h) of a single dose of such composition. 50. An oral tramadol pharmaceutical composition suitable for successive administration, once daily, comprising an effective amount of tramadol or a pharmaceutically acceptable salt thereof providing in vivo a steady state in which, during a given 24 hour period, a tramadol maximum mean plasma concentration (Cmax) of between 2 and 3 times a tramadol minimum mean plasma concentration (Cmin) is obtained. 51. The composition of claim 50, wherein said mean Cmax is no greater than 350 ng/ml. 52. The composition of claim 51, wherein the mean plasma concentration of tramadol is less than 90 percent of Cmax for at least 18 hours of a said 24 hour period. 53. The composition of claim 48, comprising a formulation, as appropriate, comprising a core comprising a pharmacological agent dispersed in a first controlled-release marix comprising cross-linked high amylose starch, from which matrix release of the agent is relatively slow: and a coat formed over the core and comprising said agent dispersed in a second conrolled-release matrix from which release of the agent is relatively fast. 54. A solid dosage formulation comprising: a core comprising a pharmacological agent dispersed in a first controlled-release matrix comprising cross-linked high amylose starch; and a coat formed over the core and comprising said agent dispersed in a second controlled-release matrix, different from the first such that release of the agent from the formulation is biphasic. 55. A solid dosage formulation comprising: a core comprising a pharmacological agent dispersed in a first controlled-release matrix; and a coat formed over the core and comprising said agent dispersed in a second controlled-release matrix as defined in claim 36 such that release of the agent from the formulation is biphasic. 56. A solid dosage formulation comprising: a core comprising a pharmacological agent dispersed in a controlled-release matrix comprising a cross-linked high amylose starch; and a coat formed over the core and comprising a pharmacological agent in a second controlled-release matrix as defined in claim 36. 57. A solid dosage formulation comprising: a core comprising about 50 mg, or about 75 mg or about 100 mg or about 125 mg or about 150 mg or about 175 mg or about 200 mg or about 225 mg or about 250 mg or about 275 mg or about 300 mg or about 325 mg or about 350 mg or about 375 mg or about 400 mg tramadol dispersed in a controlled-release matrix comprising a cross-linked high amylose starch; and a coat formed over the core and comprising a pharmacological agent in a second controlled-release matrix as defined in claim 36. 58. A method of medical treatment which comprises administering to a patient a solid dosage formulation as defined in claim 1.

<SOH> BACKGROUND OF THE INVENTION <EOH>An important factor influencing the rate of absorption of an active agent administered as a tablet or other solid dosage formulation, and thus the efficacy and safety of the formulation, is the rate of dissolution of the dosage form in the body fluids of a human or animal The ability of components of the formulation to influence the rate of release of the active agent(s) thus constitutes the basis for the so-called controlled-release, extended-release, sustained-release or prolonged-action pharmaceutical preparations that are designed to produce slow, uniform release and absorption of the active agent over a period of hours, days, weeks, or months. Advantages of controlled-release formulations include a reduction in the required frequency of administration of the drug as compared to immediate-release dosage forms, often resulting in improved patient compliance; maintenance of a relatively stable concentration of the drug in the body leading to a sustained therapeutic effect over a set period of time; and decreased incidence and intensity of undesired side effects of the active agent resulting from a reduction of the high plasma concentrations that often occur after administration of immediate-release dosage forms Many materials have been proposed and developed as matrices for controlled release of active agents, i.e. drugs, pro-drugs, etc. These include polymeric materials such as polyvinyl chloride, polyethylene amides, ethyl cellulose, silicone and poly (hydroxymethyl methacrylate). See, for example, U.S. Pat. No. 3,087,860 to Endicott et al.; U.S. Pat. No. 2,987,445 to Levesque et al.; Salomon et al., Pharm. Acta Helv., 55, 174-182 (1980); Korsmeyer, Diffusion Controlled Systems: Hydrogels, Chap. 2, pp 15-37 in Polymers for Controlled Drug Delivery, Ed Tarcha, CRC Press, Boca Raton, Fla. USA (1991); and Buri et al., Pharm. Acta Helv. 55, 189-197(1980). High amylose starch has also been used for controlled-release purposes, and, in particular, recent advances have been made using cross-linked high amylose starch. For example, U.S. Pat. No. 5,456,921 (Mateescu et al.), which issued Oct. 10, 1995, U.S. Pat. No. 5,616,343 (Cartilier et al.), which issued Apr. 1, 1997, U.S. Pat. No. 6,284,273 (Lenaerts et al.), which issued Sep. 4, 2001, U.S. Pat. No. 6,419,957 (Lenaerts et al.), which issued Jul. 16, 2002, and U.S. Pat. No. 6,607,748 (Lenaerts et al.), which issued Aug. 19, 2003, describe solid controlled release oral pharmaceutical dosage units in the form of tablets comprising a dry powder of a pharmaceutical product and a dry powder of cross-linked high amylose starch in which the cross-linked high amylose starch includes a mixture of about 10-60% by weight of amylopectin and about 40-90% amylose. Further examples of controlled-release materials include Kollidon™ SR marketed by BASF (Germany), this material being a physical mixture of polyvinyl acetate (PVA) and polyvinylpyrrolidone (povidone), reportedly made up of about 80% PVA and 19% povidone, and approximately 0.8% sodium dodecylsulfate and about 0.2% silica as stabilizer. BASF Technical Information (July 2001) discloses that Kollidon™ SR can be used in the preparation of sustained release matrix dosage forms including tablets, pellets and granules, and that different technologies such as direct compression, roller compaction, wet granulation and extrusion may be employed in the manufacture of pharmaceutical formulations. A number of patent publications provide further information on PVA-povidone mixtures: U.S. Patent Publication No. 2001/0038852 (Kolter et al.) published Nov. 8, 2001; U.S. Patent Publication No. 2002/0012701 (Kolter et al.) published Jan. 31, 2002, and U.S. Patent Publication No. 2003/0021846 (Kolter et al.) published Jan. 30, 2003. Extended and controlled release formulations relating to tramadol have been suggested, examples being described in: U.S. Patent Publication No. 2003/0143270, (Deboeck et al.) published Jul. 31, 2003; U.S. Pat. No. 6,254,887 (Miller et al.) issued Jul. 3, 2001; U.S. Patent Publication No. 2001/0036477 (Miller et al.) published Nov. 1, 2001; U.S. Pat. No. 6,326,027 (Miller et al.) issued Dec. 4, 2001, WO 03/080031 (CILAG AG et al.) published Oct. 2, 2003. Articles have been published in which comparative data between “once-daily” tramadol formulations and immediate release tramadol formulations are presented: Adler et al., “A Comparison of Once-Daily Tramadol with Normal Release Tramadol in the Treatment of Pain in Osteoarthritis,” The Journal of Rheumatology (2002) 29(10): 2195-2199; and Bodalia et al., “A Comparison of the Pharmacokinetics, Clinical Efficacy, and Tolerability of Once-Daily Tramadol Tablets with Normal Release Tramadol Capsules,” Journal of Pain and Symptom Management (2003) 25(2): 142-149. Citation or identification of any reference in this specification is not intended to be construed as an admission that such reference is available as prior art to the present invention.

<SOH> SUMMARY OF THE INVENTION <EOH>The present invention relates to a solid dosage formulation that provides for controlled-release of a pharmacological agent. In one embodiment, the formulation includes a core having a pharmacological agent dispersed in a first controlled-release matrix comprising cross-linked high amylose starch, from which matrix release of the agent is relatively slow. There is a coat formed over the core and the coat includes the agent dispersed in a second controlled-release matrix from which release of the agent is relatively fast. In the context of this invention, “relatively fast” means at least twice as fast when the initial rate of release of an agent is measured under the same conditions separately for each matrix material. To make such a measurement, one makes a formulation having the agent of the core and the agent of the coat differentially labeled from each other. In the case of tramadol, for example, the tramadol of the core could be labeled with 15 N and the tramadol of the coat could be labeled with 13 C. There are many ways known to a skilled person for differentially labeling such a compound so that its diffusion from the formulation can be traced without significantly affecting its rate of diffusion. A skilled person could estimate such relative rates to a reasonable approximation, provided the rates are sufficiently different from each other, from the z behavior observed for release of the agent from a single formulation, e.g., from the rates at t=0, and t=12 hr of FIG. 2 . Typically, the measurement would be made under the conditions set forth in connection with FIG. 2 . In another broad embodiment, the invention is a solid dosage formulation having a core with a pharmacological agent in a first controlled-release matrix. There is a coat formed over the core having the pharmacological agent in a second controlled-release matrix. The second controlled-release matrix is a physical mixture of polyvinyl acetate and polyvinylpyrrolidone, and release of the agent from the matrix of the core is relatively slow with respect to release of the agent from the matrix of the coat. Relatively slow means no more than half as fast when the initial rate of release of an agent is measured under the same conditions separately for each matrix material, the measurement being determined as described above in connection with the determination of relatively fast. The agent in the core and coat may, in either embodiment, be the same or different. In a preferred embodiment, the formulation includes a single agent that is tramadol. In a preferred aspect of the invention, the coat and core comprise relative amounts of the agent such that release of the agent from the formulation is biphasic. Preferably, the agent is soluble in water, and the first matrix is relatively hydrophilic relative to the second matrix. Many agents are capable of forming ionic salts, and this is often the preferred form of the agent for incorporation into a formulation of the invention. Preferred agents contain at least one amino group, and these are conveniently incorporated in the form of, for example a hydrochloride salt. Preferably, the rate of release of the agent from the coat is at least twice the rate of release of the agent from the core. Other relative rates are possible: the rate of release of the agent from the coat can be at least three times the rate of release of the agent from the core; the rate of release of the agent from the coat can be up to fifteen times the rate of release of the agent from the core; the rate of release of the agent from the coat can be up to twelve times the rate of release of the agent from the core; the rate of release of the agent from the coat can be up to ten times the rate of release of the agent from the core; the rate of release of the agent from the coat can be up to eight times the rate of release of the agent from the core; the rate of release of the agent from the coat can be up to six times the rate of release of the agent from the core; or the rate of release of the agent from the coat can be about four times the rate of release of the agent from the core. In other embodiments, biphasic release behavior is observed, and the rate of release of the agent from the coat is between three and nine times the rate of release of the agent from the core, more preferably the rate of release of the agent from the coat is between four and eight times the rate of release of the agent from the core, more preferably the rate of release of the agent from the coat is between five and seven times the rate of release of the agent from the core. In certain embodiments, between 10% and 30% per hour of the agent is released between 0 and 2 hours when tested in vitro using a USP Type I apparatus in 50 mM phosphate, pH 6.8, and stirring between 50 and 150 rpm In certain embodiments, between 10% and 40% of the agent is released from the formulation between 0 and about 2 hours of measurement, between about 30% and 60% of the agent is released from the formulation between 2 and about 7 hours of the measurement, between about 50% and 80% of the agent is released from the formulation between 7 and about 12 hours of measurement, and between about 80% and 100% of the agent is released from the formulation after about 20 hours of measurement. A preferred active agent of both the core and the coat is an analgesic, specifically, the active can be tramadol. An agent of the formulation of the invention is preferred to be soluble in water at least to the extent of 1 g/L, or more than 10 g/L, or more than 100 g/L, or more than 500 g/L, or more than 1000 g/L, or more than 2000 g/L. In certain embodiments, the formulation of the invention is generated to have the ratio of the core to the coat (w/w) between about 1 and about 0.1, or between about 0.9 and about 0.2, or between about 0.8 and about 0.2, or between about 0.7 and about 0.2, or between about 0.5 and about 0.2, or between about 0.4 and about 0.2, or about 0.35. In this context, it is the total weight of the core and the total weight of the coat that would be considered when determining the weight ratio. In certain embodiments, the ratio of the agent in core to the agent in the coat (w/w) is between about 0.1 and about 10, or between about 0.1 and about 8, or between about 0.2 and about 7, or between about 0.3 and about 6, or between about 0.4 and about 5, or between about 0.5 and about 4, or between about 0.6 and about 3, or between about 0.6 and about 2, or between about 0.6 and about 1.5, or between about 0.6 and about 1.3, or between about 0.7 and about 1, or between about 0.7 and about 0.9 or about 0.8. In particular embodiments of the invention, a formulation is one in which the core is between about 10% and about 90% by weight agent, or between about 20% and about 80% by weight agent, or between about 30% and about 70% by weight agent, or between about 40% and about 60% by weight agent, or about 50% by weight agent. In particular embodiments, a formulation of the invention is one in which the coat is between about 5% and about 90% by weight agent, or between about 5% and about 80% by weight agent, or between about 10% and about 70% by weight agent, or between about 10% and about 60% by weight agent, or between about 15% and about 50% by weight agent, or between about 15% and about 45% by weight agent, or between about 15% and about 40% by weight agent, or between about 20% and about 35% by weight agent, or between about 20% and about 30% by weight agent. According to certain aspects of the invention, the formulation is such that the ratio of the matrix of the coat to the agent of the. coat (w/w) is between about 0.1 and about 10, or between about 0.2 and about 9, or between about 0.2 and about 8, or between about 0.3 and about 7, or between about 0.4 and about 6, or between about 0.5 and about 5, or between about 0.6 and about 4, or between about 0.7 and about 4 or between about 1 and about 4, or between about 1 and about 3 and about 1.5 and about 2.5. According to certain aspects, the formulation is such that the ratio of the matrix of the core to the agent of the core (w/w) is between about 0.1 and about 10, or between about 0.2 and about 9, or between about 0.3 and about 7, or between about 0.4 and about 6, or between about 0.5 and about 5, or between about 0.5 and about 4, or between about 0.5 and about 3, or between about 0.6 and about 3, or between about 0.7 and about 2 or between about 0.8 and about 1.5, or between about 0.9 and about 1.5, or between about 0.9 and about 1.3, or about 1, or is about 0.55. Preferably, the agent is a single agent soluble in water at room temperature (about 21° C.) to the extent of at least 0.5 gm per mL. In certain aspects, each agent of the formulation contains an acid group, a base group or both an add group and a base group, and each agent is present in the form of a salt of such group. Preferably, the agent contains an ionizable group and said group is at least 90% ionized in gastric juices (0.1M HCl). Agents of a formulation of the invention can be any one or more of the following: isonicotnic acid hydrazide, sodium salicylate, pseudoephedrine hydrochloride, pseudoephedrine sulfate, acetaminophen or diclofenac sodium, verapamil, glipizide, nifedipine, felodipine, betahistine, albuterol, acrivastine, omeprazole, misoprostol, tramadol, oxybutynin, trimebutine, ciprofloxacin, and salts thereof. In addition, the pharmaceutical agent can be an antifungal agent, such as ketoconazole, or an analgesic agent such as acetylsalicylic acid, acetaminophen, paracetamol, ibuprofen, ketoprofen, indomethacin, diflunisal, naproxen, ketorolac, diclofenac, tolmetin, sulindac, phenacetin, piroxicam, mefamanic acid, dextromethorphan, other non-steroidal anti-inflammatory drugs including salicylates, pharmaceutically acceptable salts thereof or mixtures thereof. Preferably, a formulation of the invention is prepared by compression. Typically, the core is formed, by compression, and then the coat is prepared by being compressed onto the pre-formed core. In a preferred aspect, the coat is made up of an admixture of polyvinyl acetate, polyvinylpyrrolidone. The ratio of polyvinyl acetate and polyvinylpyrrolidone in the coat (w/w) is usually between about 6:4 and 9:1, or 7:3 and 9:2, or it is about 8:2. The coat often includes a binding agent, a preferred binding agent being xanthan gum. The formulation can be a tablet, and a preferred cross-linked high amylose starch is a chemically-modified, cross-linked high amylose starch prepared by a method comprising: (a) cross-linking high amylose starch, followed by (b) chemically modifying the cross-linked high amylose starch, followed by (c) gelatinization, and (d) drying to obtain a powder of said controlled release excipient; wherein said cross-linked high amylose starch is characterized in that upon solubilization in 90% DMSO at 80° C. for about three days and gel permeation chromatography, the height of the peak corresponding to amylose in said cross-linked high amylose starch is at least 90% of that of the peak corresponding to amylose in said high amylose starch prior to (a). Another process for obtaining a cross-linked high amylose starch for formulations of this invention includes: (a) cross-linking high amylose starch thereby forming a reaction medium containing a reaction product consisting of a cross-linked high amylose starch slurry; (b) subjecting said cross-linked high amylose starch slurry from step (a) to chemical modification at a temperature of about 10 to about 90° C. for about 1 to about 72 hours; (c) neutralizing said reaction medium obtained in step (b) with an acid, washing the slurry formed and optionally dewatering or to form a starch cake or a dry powder; (d) diluting said slurry or re-slurrifying said starch cake or said dry powder from step (c) with water to form a slurry at a concentration of about 2% to about 40% w/w, adjusting pH to a desired value between about 3 and about 12, and gelatinizing said slurry at a temperature of about 80 to 180° C. for about 1 second to about 120 minutes; and (e) drying the thermally treated product obtained in step (d) to obtain said controlled release excipient consisting mainly of chemically modified and cross-linked high amylose starch in form of a powder. Another process for manufacturing, in an aqueous medium, a controlled release excipient consisting primarily of cross-linked high amylose starch is one including (a) subjecting high amylose starch to chemical modification at a temperature of about 10 to about 90° C. for about 1 to about 72 hours thereby forming a reaction medium containing a chemically modified high amylose slurry; (b) cross-linking said chemically modified high amylose starch in said slurry obtained in step (a); (c) neutralizing said slurry obtained in step (b) with an acid, washing the slurry formed and optionally dewatering to form a starch cake or drying to form dry powder; (d) diluting said slurry, or re-slurrifying said starch cake or said dry powder from step (c) with water to form a slurry at a concentration of about 2% to about 40% w/w, adjusting pH to a desired value between about 3 and about 12, and gelatinizing said slurry at a temperature of about 80 to 180° C. for about 1 second to about 120 minutes; and (e) drying the thermally treated product obtained in step (d) to obtain said controlled release excipient consisting mainly of chemically modified and cross-linked high amylose starch in form of a powder. Another process for obtaining a cross-linked high amylose starch for this invention includes: (a) cross-linking high amylose starch, followed by (b) chemically modifying the cross-linked high amylose starch, followed by (c) gelatinization, and (d) drying to obtain a powder of said controlled release excipient; wherein said cross-linked high amylose starch is characterized in that upon solubilization in 90% DMSO at 80° C. for about three days and gel permeation chromatography, the height of the peak corresponding to amylose in said cross-linked high amylose starch is at least 90% of that of the peak corresponding to amylose in said high amylose starch prior to (a). Another process for obtaining a cross-linked high amylose starch for this invention includes: (a) cross-linking high amylose starch, followed by (b) chemically modifying the cross-linked high amylose starch, followed by (c) gelatinization, and (d) drying to obtain a powder of said controlled release excipient; wherein said cross-linked high amylose starch is characterized in that less than about 20% of the amylose present in said high amylose starch prior to (a) is chemically cross-linked to amylopectin. Another process for obtaining a cross-linked high amylose starch for this invention includes: (a) cross-linking high amylose starch, followed by (b) chemically modifying the cross-linked high amylose starch, followed by (c) gelatinization, and (d) drying to obtain a powder of said controlled release excipient; wherein said cross-linked high amylose starch is characterized in that upon solubilization in 90% DMSO at 80° C. for about three days and gel permeation chromatography, less than about 20% of the amylose present prior to (a) is chemically cross-linked to and eluted with amylopectin. Another process for obtaining a cross-linked high amylose starch for this invention includes: (a) cross-linking high amylose starch, followed by (b) chemically modifying the cross-linked high amylose starch, followed by (c) gelatinization, and (d) drying to obtain a powder of said controlled release excipient; wherein said cross-linked high amylose starch is characterized in that upon solubilization in 90% DMSO at 80° C. for about three days and gel permeation chromatography, the height of the peak corresponding to amylose is higher than that of the peak corresponding to amylopectin-containing entities. Another process for obtaining a cross-linked high amylose starch for this invention includes: (a) cross-linking high amylose starch, followed by (b) chemically modifying the cross-linked high amylose starch, followed by (c) gelatinization, and (d) drying to obtain a powder of said controlled release excipient; wherein said cross-linked high amylose starch is characterized in that less than about 20% of the amylose present in said high amylose starch prior to (a) is chemically cross-linked to amylopectin. Another process for obtaining a cross-linked high amylose starch for this invention includes: (a) cross-linking high amylose starch, followed by (b) chemically modifying the cross-linked high amylose starch, followed by (c) gelatinization, and (d) drying to obtain a powder of said controlled release excipient; wherein said cross-linked high amylose starch is characterized in that upon solubilization in 90% DMSO at 80° C. for about three days and gel permeation chromatography, less than about 20% of the amylose present prior to (a) is chemically cross-linked to and eluted with amylopectin. Another process for obtaining a cross-linked high amylose starch for this invention includes: (a) cross-linking high amylose starch, followed by (b) chemically modifying the cross-linked high amylose starch, followed by (c) gelatinization, and (d) drying to obtain a powder of said controlled release excipient; wherein said cross-linked high amylose starch is characterized in that upon solubilization in 90% DMSO at 80° C. for about three days and gel permeation chromatography, the height of the peak corresponding to amylose is higher than that of the peak corresponding to amylopectin-containing entities. Of course, a product having the structure of a cross-linked high amylose starch obtained by one of these processes, even though the manufacturing process is not identical one of these is also within the scope of this invention The core of a formulation of this invention often includes a lubricant which is optionally hydrogenated vegetable oil. In a preferred aspect, a formulation of the invention is a tablet formulated for oral administration. In one particular embodiment, the invention is a solid dosage formulation that includes: a core having a pharmacological agent dispersed in a first controlled-release matrix from which release of the agent is relatively slow; and a coat formed over the core and comprising said agent dispersed in a second controlled-release matrix, the second controlled-release matrix comprising a physical mixture of polyvinyl acetate and polyvinylpyrrolidone and from which release of the agent is relatively fast. In another embodiment, the invention provides a solid dosage formulation that includes: a core comprising a pharmacological agent dispersed in a first controlled-release matrix comprising cross-linked high amylose starch, from which matrix release of the agent is relatively slow; and a coat formed over the core and comprising a pharmacological agent in a second controlled-release matrix, the second controlled-release matrix comprising a physical mixture of polyvinyl acetate and polyvinylpyrrolidone, and wherein: release of the agent from the matrix of the core is relatively slow with respect to release of the agent from the matrix of the coat Another aspect of the invention is a solid dosage formulation that includes: a core comprising a pharmacological agent in a first controlled-release matrix; and a coat formed over the core and comprising a pharmacological agent in a second controlled-release matrix, the second controlled-release matrix comprising a physical mixture of polyvinyl acetate and polyvinylpyrrolidone, and wherein: release of the agent from the matrix of the core is relatively slow with respect to release of the agent from the matrix of the coat. In another aspect, the invention includes a solid dosage formulation comprising a pharmacological agent for release thereof over an extended period of time, the formulation comprising: a core comprising agent in a first controlled-release release matrix, the controlled-release matrix comprising cross-linked high amylose starch; and a coat formed over the core and comprising the agent in a second controlled-release matrix, the second controlled-release matrix comprising a physical mixture of polyvinyl acetate and polyvinylpyrrolidone, and wherein: the agent is present in the core sufficient to obtain release into an aqueous environment, e.g. gastric juices, of no more than 50% of the agent from the formulation within one quarter of the period. In such a formulation, the period can be between about 12 and about 24 hours, and between about 30% and about 70% of the agent is in the core. The agent in the first matrix and the agent in the second matrix is preferably soluble in water at least to the extent of 1 g/L, or more than 10 g/L, or more than 100 g/L, or more than 500 g/L, or more than 1000 g/L, or more than 2000 g/L. The agent can be an analgesic. A particular embodiment of the invention includes a solid dosage formulation for use for a period of every four hours, or every six hours, every eight hours, every twelve hours, or every twenty-four hours, the formulation comprising: a compressed core comprising a pharmacological agent including an amino group, the agent being present as a pharmacologically acceptable salt and being dispersed in a first controlled-release matrix comprising cross-linked high amylose starch; and a coat formed by compression over the core and comprising the agent in a second controlled-release matrix, the second controlled-release matrix comprising a physical mixture of polyvinyl acetate and polyvinylpyrrolidone, and wherein release of the agent from the formulation over the period includes a first phase with the average rate of release over the first 5% of the period being between three and eight times the rate of release of the agent half way through the period. In a particular aspect of this particular embodiment, the ratio of the agent in core to the agent in the coat (w/w) is between 0.2 and about 7, the core is between 20% and 80% by weight agent, the coat is between 15% and 50% by weight agent, and the ratio of the matrix of the coat to the agent of the coat (w/w) is between 0.3 and 7. Further, the preferred agent is tramadol, and preferably the coat includes a binding agent. In another aspect, the invention is a controlled released tablet comprising: a compressed core comprising cross-linked high amylose starch having tramadol, or a salt thereof, embedded therein; and a coat formed over the core by compression, and comprising a physical mixture of polyvinyl acetate, polyvinylpyrrolidone, a binder, tramadol; and wherein: the ratio of the core/coat (w/w) is between about 0.2 and 0.6; the ratio of the tramadol in the core to the tramadol in the coat is between about 0.7 and about 1; the ratio of polyvinyl acetate/polyvinylpyrrolidne (w/w) is between about 6:4 and 9:1; and the rate of release of tramadol from the coat matrix is at least twice the rate of release of tramadol from the core when measured by a USP Type I apparatus in 50 mM phosphate, pH 6.8, and between 50 and 150 rpm. The invention includes a method of manufacturing a controlled-release medication, the method comprising: (i) blending a pharmacological agent and a first matrix material comprising a cross-linked high amylose starch; (ii) forming the resultant blend of step (i) into a core; (iii) blending a pharmacological agent and a second matrix material comprising a relatively fast release material with respect to the first matrix material; (iv) forming the resultant blend of step (iii) as a coat onto the exterior of the core. A method of manufacturing a controlled-release medication of invention can include: (i) blending a pharmacological agent and a first matrix material; (ii) forming the resultant blend of step (i) into a core; (iii) blending a pharmacological agent and a second matrix material, the second matrix material comprising a physical mixture of polyvinyl acetate and polyvinylpyrrolidone and being a relatively fast release material with respect to the first matrix material; (iv) forming the resultant blend of step (iii) as a coat onto the exterior of the core. Step (ii) preferably comprises compressing the resultant blend of step (i). Step (iii) can comprise compressing the resultant blend of step (iii) onto the exterior of the core. The agent in the core and the coat is preferably tramadol, the total amount of tramadol in the medication is effective as a daily dosage, and the medication comprises a formulation, as appropriate as defined within this specification. The invention includes an oral tramadol pharmaceutical composition suitable for once daily administration comprising an effective amount of tramadol or a pharmaceutically acceptable salt thereof providing after a single administration in vivo, a median time to tramadol peak plasma concentration (T max ) between 2 and 8 hours and a mean peak tramadol plasma concentrations (C max ) which are less than three times the mean plasma concentration obtained 24 hours after administration (C 24h ) of a single dose of such composition. Such a composition can be such that said mean peak tramadol plasma concentrations (C max ) are less than two times the mean plasma concentration obtained 24 hours after administration (C 24h ) of a single dose of such composition. In another embodiment, the invention is an oral tramadol pharmaceutical composition suitable for successive administration, once daily, comprising an effective amount of tramadol or a pharmaceutically acceptable salt thereof providing in vivo a steady state in which, during a given 24 hour period, a tramadol maximum mean plasma concentration (C max ) of between 2 and 3 times a tramadol minimum mean plasma concentration (C min ) is obtained. According to a particular aspect, the mean C max is no greater than 350 ng/ml. Tthe mean plasma concentration of tramadol is preferably less than 90 percent of C max for at least 18 hours of a said 24 hour period. The invention includes a solid dosage formulation comprising: a core comprising a pharmacological agent dispersed in a first controlled-release matrix comprising cross-linked high amylose starch; and a coat formed over the core and comprising said agent dispersed in a second controlled-release matrix, different from the first such that release of the agent from the formulation is biphasic. According to another aspect, the invention is a solid dosage formulation comprising: a core comprising a pharmacological agent dispersed in a first controlled-release matrix; and a coat formed over the core and comprising said agent dispersed in a second controlled-release matrix comprising a physical mixture of polyvinyl acetate and polyvinylpyrrolidone such that release of the agent from the formulation is biphasic. According to yet another aspect, the invention is a solid dosage formulation comprising: a core comprising a pharmacological agent dispersed in a controlled-release matrix comprising a cross-linked high amylose starch; and a coat formed over the core and comprising a pharmacological agent in a second controlled-release matrix comprising a physical mixture of polyvinyl acetate and polyvinylpyrrolidone. In another embodiment, the invention is a solid dosage formulation comprising: a core comprising about 50 mg, or about 75 mg or about 100 mg or about 125 mg or about 150 mg or about 175 mg or about 200 mg or about 225 mg or about 250 mg or about 275 mg or about 300 mg or about 325 mg or about 350 mg or about 375 mg or about 400 mg tramadol dispersed in a controlled-release matrix comprising a cross-linked high amylose starch; and a coat formed over the core and comprising a pharmacological agent in a second controlled-release matrix comprising a physical mixture of polyvinyl acetate and polyvinylpyrrolidone. The term “comprising” as used herein is used in its open-ended sense, unless the context would dictate otherwise. That is, a formulation comprising first and second matrices and an agent, for example, could thus also include other ingredients, such as a lubricant. Formulations of the above-described formulations provide advantageous characteristics in vivo, as set out further below. Another aspect of the invention is thus a once daily oral pharmaceutical composition for controlled release of tramadol or a salt thereof, in which the composition, upon initial administration of one dose, provides an onset of analgesic effect within 2 hours, which analgesic effect continues for at least 24 hours after administration. Another aspect of the invention is a once daily oral pharmaceutical composition for controlled release of tramadol or a salt thereof, wherein the composition, upon initial administration of one dose, provides a mean plasma concentration of at least 100 ng/mL within 2 hours of administration and continues to provide a mean plasma concentration of at least 100 ng/mL for at least 22 hours after administration. Another aspect of the invention is a once daily oral pharmaceutical composition for controlled release of tramadol or a salt thereof, wherein the composition, upon initial administration of one dose, provides a mean plasma concentration of at least 100 ng/mL within 2 hours of administration and continues to provide a mean plasma concentration of at least 100 ng/mL for at least 23 hours after administration. In another aspect, the invention is a once daily oral pharmaceutical composition for controlled release of tramadol or a salt thereof, wherein the composition, upon initial administration of one dose, provides a mean plasma concentration of at least 100 ng/mL within 2 hours of administration and continues to provide a mean plasma concentration of at least 100 ng/mL for at least 24 hours after administration. A once daily oral pharmaceutical composition of the invention, in a preferred aspect, includes about 200 mg of tramadol or a salt thereof. In yet another aspect, the invention is a once daily oral pharmaceutical composition for controlled release of tramadol or a salt thereof comprising 100 mg of tramadol or a salt thereof, wherein the composition, upon initial administration of one dose, provides a mean plasma concentration of at least 50 ng/mL within 2 hours of administration and continues to provide a mean plasma concentration of at least 50 ng/mL for at least 22 hours after administration. According to another aspect, the invention provides a once daily oral pharmaceutical composition for controlled release of tramadol or a salt thereof comprising 100 mg of tramadol or a salt thereof, wherein the composition, upon initial administration of one dose, provides a mean plasma concentration of at least 50 ng/mL within 2 hours of administration and continues to provide a mean plasma concentration of at least 50 ng/mL for at least 23 hours after administration. Another aspect of the invention is a once daily oral pharmaceutical composition for controlled release of tramadol or a salt thereof comprising 300 mg of tramadol or a salt thereof, wherein the composition, upon initial administration of one dose, provides a mean plasma concentration of at least 150 ng/mL within 2 hours of administration and continues to provide a mean plasma concentration of at least 150 ng/mL for at least 22 hours after administration. Another aspect of the invention is a once daily oral pharmaceutical composition for controlled release of tramadol or a salt thereof comprising 300 mg of tramadol or a salt thereof, wherein the composition, upon initial administration of one dose, provides a mean plasma concentration of at least 150 ng/mL within 2 hours of administration and continues to provide a mean plasma concentration of at least 150 ng/mL for at least 23 hours after administration. Another aspect of the invention is a once daily oral pharmaceutical composition for controlled release of tramadol or a salt thereof comprising 300 mg of tramadol or a salt thereof, wherein the composition, upon initial administration of one dose, provides a mean plasma concentration of at least 150 ng/mL within 2 hours of administration and continues to provide a mean plasma concentration of at least 150 ng/mL for at least 24 hours after administration. In another aspect of the A once daily oral pharmaceutical composition for controlled release of tramadol or a salt thereof comprising 200 mg of tramadol or a salt thereof, wherein upon initial administration of 400 mg, the composition provides a mean plasma concentration of at least 200 ng/mL for at least 22 hours after administration. Another aspect of the invention is a once daily oral pharmaceutical composition for controlled release of tramadol or a salt thereof comprising 200 mg of tramadol or a salt thereof, wherein upon initial administration of 400 mg, the composition provides a mean plasma concentration of at least 190 ng/mL for at least 23 hours after administration. Another aspect of the invention is a once daily oral pharmaceutical composition for controlled release of tramadol or a salt thereof comprising 200 mg of tramadol or a salt thereof, wherein upon initial administration of 400 mg, the composition provides a mean plasma concentration of at least 180 ng/mL for at least 24 hours after administration. The invention also provides a once daily oral pharmaceutical composition wherein the mean maximum plasma concentration (C max ) is less than 100 ng/mL. Further, a once daily oral pharmaceutical composition of the invention can provide a mean maximum plasma concentration (C max ) is less than 300 ng/mL, or a mean maximum plasma concentration (C max ) is less than 200 ng/mL. A once daily oral pharmaceutical composition of the invention can be such that the mean maximum plasma concentration (C max ) is less than 2.2 times the mean plasma concentration obtained 24 hours after administration (C 24h ). The once daily oral pharmaceutical composition can be such that the mean maximum plasma concentration (C max ) is less than 300 ng/mL. The mean maximum plasma concentration (C max ) can be less than two times the mean plasma concentration obtained 24 hours after administration (C 24h ). The mean maximum plasma concentration (C max ) can be less than 2.3 times the mean plasma concentration obtained 24 hours after administration (C 24h ). The once daily oral pharmaceutical composition of the invention can provide a median time to the mean maximum plasma concentration (t max ) of between 2 and 10 hours, or between 3 and 6 hours, or between 5 and 6 hours. The invention also provides a once daily oral pharmaceutical composition for controlled release of tramadol or a salt thereof comprising 200 mg of tramadol or a salt thereof, wherein the composition, upon initial administration of one dose, provides an O-desmethyltramadol mean plasma concentration of at least 24 ng/mL within 2 hours of administration and continues to provide an O-desmethyltramadol mean plasma concentration of at least 25 ng/mL for at least 24 hours after administration. According to another embodiment, the invention provides a once daily oral pharmaceutical composition for controlled release of tramadol or a salt thereof comprising 100 mg of tramadol or a salt thereof, wherein the composition, upon initial administration of one dose, provides an O-desmethyltramadol mean plasma concentration of at least 11 ng/mL within 2 hours of administration and continues to provide an O-desmethyltramadol mean plasma concentration of at least 12 ng/mL for at least 24 hours after administration. According to another embodiment, the invention provides a once daily oral pharmaceutical composition for controlled release of tramadol or a salt thereof comprising 300 mg of tramadol or a salt thereof, wherein the composition, upon initial administration of one dose, provides an O-desmethyltramadol mean plasma concentration of at least 32 ng/mL within 2 hours of administration and continues to provide an O-desmethyltramadol mean plasma concentration of at least 32 ng/mL for at least 24 hours after administration. In another embodiment, the invention is a once daily oral pharmaceutical composition for controlled release of tramadol or a salt thereof comprising 200 mg of tramadol or a salt thereof, wherein upon initial administration of 400 mg, the composition provides an O-desmethyltramadol mean plasma concentration of at least 50 ng/mL within 2 hours of administration and continues to provide an O-desmethyltramadol mean plasma concentration of at least 50 ng/mL for at least 24 hours after administration. One object of the present invention is to provide flexible dosing options for patients with different analgesic requirements with a once daily formulation. One embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose of 100 mg would provide the desired early onset of action but achieve mean tramadol plasma concentrations of at least 45 ng/mL between 2 and 24 hours. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose of 200 mg would provide the desired early onset of action but achieve mean tramadol plasma concentrations of at least 100 ng/mL between 2 and 24 hours. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose of 300 mg would provide the desired early onset of action but achieve mean tramadol plasma concentrations of at least 150 ng/mL between 2 and 24 hours. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose of 400 mg would provide the desired early onset of action but achieve mean tramadol plasma concentrations of at least 180 ng/mL between 2 and 24 hours. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose would provide a C′ max to dose ratio of from about 0.90 to about 1.0. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose would provide a tramadol plasma concentration which rises steadily until peak tramadol concentrations are attained at a T max of about 4 hours to about 6 hours. Preferably, the T max occurs at about 5 hours to about 5.5 hours. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose would provide a tramadol plasma concentration which, after T max , declines in a slow but steady manner, reflecting continuing absorption in addition to elimination processes. Preferably, the decline in the tramadol plasma concentration after T max occurs in a log-linear fashion with a mean apparent terminal elimination half-life of between about 5.5 hours and about 6.5 hours. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose would provide a tramadol plasma concentration which, after T max , declines in a slow but steady manner, reflecting continuing absorption in addition to elimination processes, and which absorption continues for at least 20 hours after T max A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose provides a tramadol plasma concentration which, after T max , declines in a log-linear fashion with an apparent terminal elimination rate constant (λ z ) of about 0.12 h −1 for the tramadol plasma concentration. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose would provide a mean residence time (MRT) of tramadol ranging from about 15 hours and about 18 hours. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose would provide a half value duration (HVD) of tramadol which ranges from about 22.5 hours to about 25.4 hours. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose would provide a C′ max to AUC 0-∞ ratio of from about 0.04 h −1 to about 0.06 h −1 . Preferably, the C′ max to AUC 0-∞ ratio is from about 0.04 h −1 to about 0.05 h −1 . The ratio C′ max /AUC 0-∞ is used for evaluating the rate of drug absorption. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose would provide a mean AUC 0-24 with respect to the tramadol plasma concentration which increases proportionally with dose over the range of dosage strengths of 100 mg to 300 mg of the controlled release composition. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose of 100 mg would provide a mean AUC 0-Tmax of from about 610 ng·h/mL to about 630 ng·h/mL. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose of 200 mg would provide a mean AUC 0-Tmax of from about 910 ng·h/mL to about 920 ng·h/mL. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose of 300 mg would provide a mean AUC 0-Tmax of from about 1570 ng·h/mL to about 1590 ng·h/mL. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose provides a mean ratio of AUC 0-24 /AUC 0-∞ of tramadol plasma concentration which ranges between about 70% and about 85%. Preferably, the mean ratio of AUC 0-24 /AUC 0-∞ of tramadol plasma concentration ranges between about 74% and about 80%. As a result, about 15% to about 30% of the administered dose is still circulating in the plasma 24 hours post-dose, depending on the dose administered. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose would provide a ratio of the C′ max to the dose released to the blood plasma in the first 24 hours (that is, AUC 0-24 /AUC 0-∞ multiplied by the dose) of from about 1.10 to about 1.35. Preferably the ratio is from about 1.15 to about 1.31. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose, would provide a ratio of the C′ max /T max to the dose administered of from about 0.10 to about 0.20. Preferably the ratio is from about 0.12 to about 0.19. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose would provide a slope in ng/ml-hr following the peak blood plasma concentration level, which does not exceed a factor of about 0.035 of the total dose administered in mg. Preferably, the factor is about 0.03. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose would provide a ratio of the C′ max calculated with respect to the blood plasma concentration of O-desmethyltramadol, to the dose of tramadol from about 0.19 to about 0.22. Preferably the ratio is from about 0.20 to 0.21. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose would provide an O-desmethyltramadol plasma concentration which rises steadily until peak tramadol concentrations are attained at a T max of about 8 hours to about 16 hours. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose would provide an O-desmethyltramadol plasma concentration which, after T max , declines in a slow but steady manner, reflecting continuing tramadol absorption and subsequent metabolite formation in addition to elimination processes. Preferably, the decline in the O-desmethyltramadol plasma concentration occurs in a log-linear fashion with a mean apparent terminal elimination half-life of between about 6.7 hours and about 8.1 hours. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose would provide, after T max , the formation of metabolite for at least 18 hours. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose would, after T max , provide a decline in the O-desmethyltramadol plasma concentration in a log-linear fashion with an apparent terminal elimination rate constant (λ z ) for O-desmethyltramadol concentration of about 0.1 h −1 . A further object of the invention is to provide a once daily formulation which upon initial ingestion of 100 mg, 200 mg and 300 mg strengths provides a half value duration (HVD) of O-desmethyltramadol plasma concentration which ranges from 25.6 to 28.1 hours. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose would provide a half value duration (HVD) of O-desmethyltramadol which ranges from about 25.6 hours to about 28.1 hours. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose would provide a C′ max to AUC 0-∞ ratio calculated with respect to the O-desmethyltramadol plasma concentration, of about 0.04 h −1 . The ratio C′ max /AUC 0-∞ is used for evaluating the rate of metabolite formation. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose would provide a mean AUC 0-24 calculated with respect to the O-desmethyltramadol plasma concentration, which increases proportionally with dose over the range of dosage strengths of 100 mg to 300 Mg of the controlled release composition. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose of 100 mg would provide a mean AUC 0-Tmax with respect to the O-desmethyltramadol plasma concentration of from about 175 ng·h/mL to about 180 ng·h/mL. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose of 200 mg would provide a mean AUC 0-Tmax with respect to the O-desmethyltramadol plasma concentration of from about 530 ng·h/mL to about 550 ng·h/mL. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose of 300 mg would provide a mean AUC 0-Tmax with respect to the O-desmethyltramadol plasma concentration of from about 580 ng·h/mL to about 590 ng·h/mL. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose provides a mean ratio of AUC 0-24 /AUC 0-∞ of O-desmethyltramadol plasma concentration which ranges between about 65% and about 80%. Preferably, the mean ratio of AUC 0-24 /AUC 0-∞ of O-desmethyltramadol plasma concentration ranges between about 68% and about 75%. As a result, about 25% to about 32% of the active metabolite is still circulating in the plasma 24 hours post-dose. A further embodiment of the present invention is to provide a once daily formulation which upon initial ingestion of a dose would provide a ratio of the C′ max calculated with respect to the O-desmethyltramadol plasma concentration, to the O-desmethyltramadol blood plasma concentration in the first 24 hours (AUC 0-24 /AUC 0-∞ multiplied by the dose of tramadol) of from about 0.0025 to about 0.0035. Preferably the ratio is from about 0.0027 to about 0.0031. The present invention may be understood more fully by reference to the following detailed description and illustrative examples which are intended to exemplify non-limiting embodiments of the invention.

Digital entertainment distribution system

Customers can browse, preview, select and purchase digital entertainment products, such as music or movies, at kiosks or point-of-sale locations connected to a central source of digital entertainment content. The products can be paid for or their price subsidized by credits which the customers have obtained from non-competing companies as part of those companies' own marketing efforts.

1. A system for distributing and selling digital entertainment content, said system comprising an in-person access network with terminals installed at pre-established locations, where potential customers can sample, select, purchase and obtain on the spot entertainment products in physical media or by download, and/or an internet access site with a similar functionality, and a system of redeemable credits for non-competing companies marketing consumer product goods and services, which credits, once distributed to these companies' customers with their products or otherwise, allow said customers to pay at least part of the price of said content at said access locations or sites, by applying said credits towards the price of said content. 2. A method of distributing and selling digital entertainment content, said method comprising the steps of providing a remotely and/or locally accessible source of entertainment content, providing a plurality of in-person content access locations connected to said source and having means for attracting customer attention and desire to interact, means for searching said source, means for previewing content, and means for selling and delivering selected content to customers in physical carriers, providing a web site having means for offering a similar presentation and functionality as said locations, dependent on customers' access point set-up, providing exclusive per-product category sponsors, who deal in non-competing products, means for purchasing credit issuing rights, and inducing said sponsors to execute such rights by regularly and or periodically distributing free credits to their customers, which credits, are applicable to the purchase price of said selected content, and providing entertainment content broadcasters' promotional efforts, content broadcast information and content related news. 3. The invention of claim 2, further comprising distributing said credits by additional means other than through said non-competing sponsors. 4. The invention of claim 2, wherein said credits are distributed upon sale of sponsors' products. 5. The invention of claim 2, wherein said credits are distributed by the sponsors other than in association with their product sales. 6. The invention of claim 2, further comprising advertising the availability of said content and the availability of credits which can be applied against purchase of selected content. 7. The invention of claim 6, further comprising inducing entertainment content customers to effectively utilize such credits in their purchases of entertainment products 8. The invention of claim 7, further comprising causing customers that use credits to pay for part or all of the price of said entertainment content to perceive that they can buy said content consistently at a reduced price or free in some proportion, depending on the channel's policies, the credits the customer has accumulated and the products he purchases. 9. The invention of claim 6, wherein said advertising is by direct mail, fax or email. 10. The invention of claim 6, wherein said advertising is through mass media, public signs, shows, events and other promotional activity. 11. The invention of claim 6, wherein said advertising is done by said sponsors. 12. The invention of claim 2, further comprising providing statistical information and exchanging operational information to said sponsors 13. The invention of claim 2, further comprising a mechanism to sell credits to customers through an agent network 14. The invention of claim 2, further comprising a mechanism to sell credits to customers through other means different than through an agent network 15. The invention of claim 2, further comprising purchasing content from content owners 16. The invention of claim 2, further comprising providing content owners a means to upload content and for making such content available to consumers through an embodiment of the invention. 17. The invention of claim 2, further comprising providing statistical information and exchanging operational information to said content owners. 18. The invention of claim 2, further comprising identifying other content related to said selected content. 19. The invention of claim 2, further comprising providing alternative electronic formats for said selected content. 20. The invention of claim 2, further comprising providing alternative carrier options for said selected content. 21. The invention of claim 2, further comprising providing immediate preview of selected content. 22. The invention of claim 2, wherein the searching means is adapted to permit search on multiple variables. 23. The invention of claim 2, wherein said variables are selected from the group consisting of title, author, performer, period, musical category, lyrics segment, ranks, air play information from radio, open TV, cable TV or other broadcast company, events, and shows.

<SOH> BACKGROUND <EOH>There are many systems currently in use through which one may listen to or purchase music and other digital content in CD-like media, or download such content. In systems having conventional brick and mortar distribution channels (stores that distribute physical merchandise), a prerequisite is that the customer must have previously decided to approach the entertainment offer. Mainstream access to this offer is mostly limited to specific stores, like music or video stores or specific departments of larger stores. The offer is not personalized and cannot be customized because it is prepackaged. With most such systems, the product search mechanism is restricted to a few variables and normally requires staff assistance. Inventory is typically limited to circumstantial stock, and sample availability is limited. To assure availability, it may be necessary to purchase products at selection time. The customer may be able to view only previews (not the full product) before buying, and the sample system may be slow or inconvenient. In these systems, there are limited carrier and format options. The product price is perceived to be high, as it has to include all of the content and the seller's costs and margins. Another problem with prior systems is that other content related to a selected item is generally not readily available and accessible with the main product. Product promotion is limited to the product owners' initiatives or the sellers' initiatives and customers face heterogeneous purchase experiences. In prior systems having World Wide Web distribution channels, it is also a prerequisite that the customer must have previously decided to approach the entertainment offer. In such other systems, access to desired content is not simple for the average consumer, sampling is dependent on internet connection speed and product carriers and formats available to customers are limited to customers' hardware and software setup. Payment options are also limited. Also, as in prior brick and mortar systems, web based distribution channels' product promotion is limited to the product owners' or the sellers' initiatives.

<SOH> SUMMARY OF THE INVENTION <EOH>This invention provides a new sales and distribution channel for entertainment products and services, which overcomes the identified shortcomings of prior content distribution and sales systems. A purpose of the invention is to provide consumers more dedicated access points and longer in-person access hours, wider content base and range, greater ease of use, a simple homogeneous and appealing interface, a variety of carriers and formats, personalized and fully customizable products, a structurally sustained lower pricing capability, and multiple payment alternatives. Another object of the invention is to achieve increased sales and a legal auditable distribution mechanism for entertainment content product and service providers. Other objects are to reduce inventory requirements, logistics and marketing costs. The invention provides several advantages over prior systems. For example, whereas previous systems require that a customer first decide to approach the entertainment offer, this invention does not require previous decision since it continually offers entertainment products through dedicated highly visible points of access, such as touchscreen terminals and kiosks, in locations target customers visit most frequently in ordinary activities not directly related to entertainment. To maximize such incidental contact, the invention makes entertainment content widely available through a vast network of heterogeneous third party locations (e.g., school and college recreational areas, bars, fast food restaurants, coffee stores, shopping mall walkways, etc.) throughout its area of coverage. In contrast to prepackaged systems, this invention allows customers to obtain standard or personalized and fully customized products to the extent permitted by the products themselves. By choosing a combination of image, sound and data products that the invention makes available, customers are able to build their own selection of items. For example, in the case of music products, a customer can select specific title selections, with or without related content such as video clips, karaoke, tabs, lyrics, artist bios, etc., in specific play order, and then choose a medium such as CD (or any other available physical carrier like a DVD) with personalized cover art and customer selected formats. Alternatively, he can decide simply to download the content onto a digital device like a personal digital player or recorder, a cell phone, or any other digital device supported by the invention, in a customer selected format. Mixed products can also be made available, i.e., music titles, plus video games, plus sports events images, all in one carrier. This invention limits the need for staff assistance, in that it allows multiple search variables based on the information on its on-line content database, and in that it has a simple human-oriented inviting touch screen and/or voice command interface supported by context sensitive or customer requested tutorials and an option to access online help, live, from specialists. Inasmuch as the invention includes a digital database and distribution arrangement composed of one or many related databases, it is not limited by physical stocks. Consequently, product samples of all products carried are readily available and may be instantaneously accessed. This invention provides greater format flexibility, allowing the selection of at least CDs and PDA-type devices, and at least the following formats: MP-3, WAV, MPEG, MOV, DV x , JPG, GIF, BMP, PDF, EXE. Another attractive feature of this invention is that it makes available to the customer a wide range of related product offerings, e.g., music titles, karaoke versions, tabs, lyrics etc. The invention, rather than forcing on-the-spot product purchase, maintains digital content in its database so that content selections may be placed in wish lists to be edited and/or purchased in future customer access opportunities. In contrast to internet solutions, this invention allows customers at all the inventive system's locations to obtain products purchased from the system quickly and in physical carriers that are produced on the spot under industry quality standards, besides providing the ability to make downloads. A particularly important feature of this invention is that it provides customers with a structural, consistent and sustainable mechanism to reduce product prices and make them flexible. In practice, not only can customers buy entertainment credits, using any of the payment methods available in an average store; they can also obtain Entertainment Credits regularly from system sponsors without paying a price. Consequently, when system customers use a portion of the credits they have earned to pay for entertainment content, they normally pay less for these products and in some circumstances they can even get the products virtually free. This increases the customers' fidelity toward the channel, discouraging illegal purchase or file sharing practices. It is also important to point out that this mechanism benefits content owners in that their royalties or prices are paid by the system on content sold as if customers had paid the full price and in that customers rehabilitated from illegal practices translate into more sales for them too. As the invention provides a distinct single brand channel based on a unique customer interface, computer application and infrastructure and consequently, functionality and policies are homogeneous throughout the system. As with prior systems, content owner initiatives and the channel's own initiatives may lead to content purchase; however, in addition, the system has the continued promotional support of a sponsor network, an agent network, and an associated media network.

Method for manufacturing a master, master, method for manufacturing optical elements and optical element

The invention relates to a method for manufacturing of a master for manufacturing of optical elements having optically effective structures by moulding structures, which are formed on the master, onto a surface of an optical substrate, comprising the steps of: providing a substrate; coating a surface of said substrate for forming a coating on said substrate; and patterning said coating for forming structures in said coating. The invention also relates to a master for manufacturing of optical elements, to a method for manufacturing of optical elements as well as to an optical element having at least one surface, wherein at least in portions of said surface optically effective structures are formed.

1. A method for manufacturing a master for the manufacture of optical elements with structures having an optical effect by moulding or hot embossing structures formed on the master onto a surface of an optical substrate, said method comprising the steps of: Providing a substrate; coating a surface of the substrate in order to form a coating on the substrate; and structuring the coating in order to form structures within the coating. 2. The method according to claim 1, wherein the step of structuring the coating comprises one of ion beam etching (IBE), reactive ion beam etching (RIBE) and chemical-assisted ion beam etching (CAIBE). 3. The method according to claim 1, wherein the step of coating the surface of the substrate further comprises the step of forming a mask layer and forming a pattern in the mask layer. 4. The method according to claim 3, wherein the step of forming the mask layer comprises the step of applying a photoresist layer on the coating. 5. The method according to claim 4, wherein the step of forming the pattern in the mask layer comprises the steps of: providing a mask layer that is in contact with the photoresist layer or disposed in its immediate vicinity, and exposing the photoresist layer via the mask layer in order to form structures within the photoresist layer. 6. The method according to claim 1, wherein the step of structuring the coating comprises the step of directly processing of the coating or of a mask layer. 7. The method according to claim 6, wherein the step of directly processing comprises the step of writing of structures into the coating or into the mask layer by means of ion or electron beams. 8. The method according to claim 7, wherein the mask layer comprises a photoresist layer. 9. The method according to claim 6, wherein the step of directly processing comprises a laser ablation for forming structures within the coating or in the mask layer. 10. The method according to claim 1, wherein the step of coating the surface of the substrate comprises the coating of the surface of the substrate with a material that lowers the wettability of the master with the material of the optical substrate. 11. The method according to claim 1, wherein the coefficient of thermal expansion of the material of the coating that is matched to the coefficient of thermal expansion of the material of the substrate. 12. The method according to claim 1, wherein the step of structuring the coating comprises the step of forming depressions within the coating, and wherein said depressions do not extend to the underside of the coating. 13. The method according to claim 1, wherein the step of structuring the coating comprises the step of forming structures in at least one section of the coating, and wherein the structures cause formation of diffractive optical structures after the moulding by means of hot-forming or hot-embossing. 14. The method according to claim 13, wherein the step of coating the surface of the substrate comprises forming of a coating (3) with a thickness d that is defined by d>λ/Δn, wherein λ corresponds to a wavelength of the light that is refracted by the diffractive optical structures, and wherein Δn corresponds to a difference between the refractive index of the material of the optical substrate and the refractive index of air. 15. The method according to claim 13, wherein the structures within the coating are formed in m processing steps, and wherein the structures are formed in a stepped fashion and comprise as many as 2m different height levels. 16. The method according to claim 13, wherein the structures within the coating are computer-generated holograms. 17. The method according to claim 1, wherein the step of structuring the coating comprises forming structures at least in a section, said structures causing formation of refractive optical structures on the surface of the optical substrate after the moulding by means of hot-forming or hot-embossing. 18. A master for manufacturing optical elements with structures having an optical effect by moulding or hot embossing structures formed on the master onto a surface of an optical substrate, wherein the master comprises a substrate with a coating formed thereon, and wherein structures are formed on the master to be moulded or hot-embossed onto the surface of the optical substrate, wherein the structures are formed within the coating. 19. The master according to claim 18, wherein said master is manufactured by the steps of: Providing a substrate; coating a surface of the substrate in order to form a coating on the substrate; and structuring the coating in order to form structures within the coating. 20. The master according to claim 18, wherein the substrate is at least sectionally formed in a stepped fashion or at least sectionally comprises depressions and/or elevations. 21. A method for manufacturing optical elements comprising structures having an optical effect, wherein said method comprises the steps of: providing a master that comprises a substrate and a coating applied on the substrate, wherein structures are formed within the coating, and moulding or hot embossing the structures onto a surface of an optical substrate in order to form structures having an optical effect on the surface. 22. The method according to claim 21, wherein the step of providing the master comprises the processing steps of: Providing a substrate; coating a surface of the substrate in order to form a coating on the substrate; and structuring the coating in order to form structures within the coating. 23. The method according to claim 21, wherein the step of moulding or hot embossing the structures comprises hot-forming or hot-embossing of the surface of the optical substrate. 24. The method according to claim 21, wherein the step of moulding or hot embossing the structures comprises embossing of a plastic or polymer layer and hardening of the plastic or polymer layer in order to form a layer, in which the structures having an optical effect are formed. 25. The method according to claim 24, wherein the plastic layer is provided as a synthetic resin layer. 26. The method according to claim 25, wherein the step of hardening the synthetic resin layer comprises UV irradiation of the synthetic resin layer. 27. The method according to claim 21, wherein the step of moulding or hot embossing the structures comprises the steps of: providing a cavity with at least one wall section that is formed by a master produced by the steps of: Providing a substrate; coating a surface of the substrate in order to form a coating on the substrate; and structuring the coating in order to form structures within the coating; and injection-moulding, pressing, blowing or pressing-and-blowing one of a molten glass, a molten glass ceramics precursor glass, a plastic and a polymer into the cavity in order to form the optical substrate, the surface of which comprises the structures having an optical effect. 28. An optical element with at least one surface, on which structures having an optical effect are at least sectionally formed, wherein the structures having an optical effect are produced by means of a method comprising the steps of: providing a master that comprises a substrate and a coating applied on the substrate, wherein structures are formed within the coating, and moulding or hot embossing the structures onto a surface of an optical substrate in order to form structures having an optical effect on the surface.

<SOH> BACKGROUND OF INVENTION <EOH>Optical elements of the aforementioned type are usually manufactured from transparent materials, for example, glass, glass ceramics or plastic. In order to reduce or compensate optical aberrations, the structures having an optical effect needed to be produced in a highly precise fashion. Manufacturing methods with mechanical processing steps are known for this purpose, for example, the grinding and polishing of lenses or the production of gratings, in particular of blazed gratings, by forming grooves on an optical substrate. In other pertinent manufacturing methods known from the state of the art, the structures having an optical effect are produced by moulding or hot embossing structures produced on a master or a tool on the surface of an optical substrate. In this case, the structures produced on the master correspond to a negative of the structures having an optical effect to be produced. Hot-forming or hot-embossing methods are employed for moulding or hot embossing the structures produced on the master on the surface of the optical substrate. In these methods, the optical substrate is heated to a temperature, at which its surface can be deformed, wherein the optical substrate and the master are pressed against one another with sufficient pressure for moulding or hot embossing the structures produced on the master on the surface of the optical substrate. In another known method, the material of the optical substrate is poured or injected into a mould, in which the master is suitably arranged. The latter-mentioned method is particularly suitable for the mass production of optical elements consisting of plastic materials. One common aspect of all aforementioned methods is that the master and the optical substrate need to be separated from one another (demoulded). This limits the attainable aspect ratio, i.e., the depth-to-width ratio, of the structures to be realized, namely to values of approximately 1:1. Since the moulding or hot embossing process always takes place near or above the melting temperature of the material of the optical substrate, it is unavoidable that the material of the optical substrate tends to adhere to the master during the demoulding process, i.e., when the master is lifted off the optical substrate. This lowers the accuracy of the moulding or hot embossing process and adversely affects the service life of the master and its precision. In this respect, it needs to be taken into account that the advantages of the aforementioned moulding techniques are only cost-effective if a large quantity of optical elements can be manufactured with constant precision by means of the same master without requiring costly subsequent processing steps. The reason for this can be seen, in particular, in the comparatively high costs for manufacturing precise masters and hot-forming or hot-embossing tools. It is known to provide the surface of the master with a protective coating in order to prevent the material of the master from directly adhering to the optical substrate. Such a protective coating needs to fulfill strict requirements. The protective coating, in particular, needs to be connected to the substrate of the master in a rigidly adhering fashion, wherein the wettability of the protective coating with the material of the optical substrate should also be low. This significantly restricts the selection of materials for the protective coating, as well as the coating techniques for coating the master substrate. In addition, a highly homogenous and true-to-contour coating needs to be applied on the structured surface of the master with the chosen coating technique such that the coated structures on the surface of the master can be moulded or hot embossed on the substrate precisely. This additionally restricts the selection of materials for the protective coating and of the coating technique to be used. The structures can be produced very precisely on the surface of a master substrate with techniques known from the manufacture of semiconductor components, particularly photolithography techniques. However, the protective coating leads to a certain distortion of the structures, particularly to the rounding of edges and to surface roughness. These effects need to be taken into account, in particular, when moulding very fine structures and/or structures with high aspect ratios. Consequently, it would be desirable to develop precise and durable masters or tools for use in hot-forming and hot-embossing methods. Since the masters are used, in particular, for the mass production of optical elements, significant economical advantages can also be attained in the mass production of optical elements by means of costly manufacturing methods. A method for embossing a waveguide in a deformable gel layer at room temperature is disclosed in “Embossing techniques for fabricating integrated optical components in hard inorganic wave guiding materials” by W. Lukosz et al., Optical Letters, October 1983, Vol. 8, No. 10, pp. 537-539. The thin film is produced from organometallic compounds by means of a dip-drawing method. After the embossing, the film is hardened at temperatures of several 100° C. and transformed into an inorganic oxide material. During the embossing, a substrate provided with the organic sol-gel thin layer is pressed against a master grating. The master grating is coated with an aluminum layer. U.S. Pat. No. 6,591,636 B1 discloses a tool and a method for forming glass. Oxidation and corrosion processes were observed during the glass forming, particularly in the forming of glass compounds with significant alkali components and/or alkaliferous components. This leads, in particular, to undesirable dull glass surfaces. Different oxidation-resistant and corrosion-resistant compounds are suggested for coating the forming tool, wherein said compounds are applied by means of electroplating or physical vapor deposition (PVD) or chemical vapor deposition (CVD). JP 2003-342025 A discloses a master for manufacturing finely structured optical elements, for example, microlens arrays, gratings, Fresnel zoned lenses and the like. The accuracy of the structures lies below one micrometer. The structures are initially produced by means of a photolithographic process on a dummy by means of synchrotron radiation. A nickel-based alloy is applied on the thusly structured dummy by means of electroplating. After the dummy is lifted off the coating, a master for manufacturing the optical elements is obtained.

<SOH> SUMMARY OF INVENTION <EOH>It is an object of the present invention to provide a method for manufacturing a master, a master and a method for manufacturing optical elements that allow the manufacture of optical elements with structures having an optical effect in a more precise and less expensive fashion. The present invention also aims to make available an optical element that is realized in a more precise and less expensive fashion. The present invention discloses a method for manufacturing a master for the manufacture of optical elements with structures having an optical effect by moulding or hot embossing structures formed on the master on the surface of an optical substrate, wherein said method comprises the following steps: providing a substrate; coating a surface of the substrate for producing a coating on the substrate, and structuring the coating for forming the structures to be moulded or hot embossed on the surface of the optical substrate within the coating. Since the structures to be moulded or hot embossed are, according to the invention, directly produced within the coating or on a surface of the coating, respectively, their profile and accuracy is no longer impaired by an additional coating process as it is the case with the conventional application of a protective coating on an already structured master. Consequently, the invention makes it possible to achieve a finer structuring with a steeper and more precise edge steepness and a reduced roughness of the structures having the optical effect. Another advantage of the invention can be seen in the fact that a large variety of different coating techniques and/or coating materials can be used, namely because the conditions during the coating process are significantly simplified in the method according to the invention (it is no longer necessary to uniformly coat already produced structures) The quality of optical components can be additionally improved due to the fact that the invention makes it possible to realize a very uniform and homogenous coating with little surface roughness. According to the invention, it is possible, in particular, to choose nearly arbitrary materials for the coating to be applied on the substrate, particularly materials that advantageously have a low wettability with the material of the optical substrate. Many of these materials for the coating of fine structures can, if at all, only be utilized with great difficulties in methods known from the state of the art. It was determined that an ion beam etching (IBE) method, a reactive ion beam etching (RIE) method or a chemical-assisted ion beam etching (CAIBE) method is particularly suitable for structuring the coating because these methods make it possible to produce the structures within the coating in a very precise and homogenous fashion. Other aspects of the present invention pertain to a master for manufacturing optical elements, a method and a device for manufacturing optical elements and an optical element with at least one surface, on which structures having an optical effect, particularly diffractive and/or refractive structures, are at least sectionally produced.

Semiconductor device and manufacturing method of the same

The invention is directed to an improvement of reliability in a chip-size package type semiconductor device and a manufacturing method thereof. A semiconductor substrate formed with a pad electrode is prepared, and a first protection layer formed of epoxy resin is formed on a front surface of the semiconductor substrate. Then, a via hole is formed from a back surface of the semiconductor substrate to the pad electrode. A wiring layer is then formed from the via hole of the semiconductor substrate, being electrically connected with the pad electrode through the via hole. Then, a second protection layer and a conductive terminal are formed, and the semiconductor substrate is separated into individual semiconductor dies by dicing.

1. A semiconductor device comprising: a semiconductor die having a first surface and second surface; a pad electrode formed on the first surface, a via hole being formed between the pad electrode and the second surface; a first protection layer attached to the first surface so as to cover the pad electrode; an insulation film disposed on an inside wall of the via hole; and a metal portion disposed in the via hole to be in contact with the pad electrode. 2. The semiconductor device of claim 1, further comprising a conductive terminal disposed on the metal portion. 3. The semiconductor device of claim 1, further comprising a wiring layer disposed on the second surface and connected to the metal portion. 4. The semiconductor device of claim 3, further comprising a second protection layer disposed on the second surface so as to cover the metal portion and the wiring layer and a conductive terminal disposed on the metal portion or the wiring layer through an opening formed in the second protection layer. 5. The semiconductor device of claim 1, wherein the first protection layer is made of an epoxy resin. 6. The semiconductor device of claim 3, wherein the first protection layer is made of an epoxy resin 7. A method of manufacturing a semiconductor device, comprising: providing a semiconductor substrate having a first surface and a second surface, the semiconductor substrate comprising a pad electrode formed on the first surface; forming a first protection layer on the first surface to cover the pad electrode; forming a via hole from the second surface to reach the pad electrode; forming an insulation film on a sidewall of the via hole; filling at least partially the via hole having the insulation film with a metal so that the metal is contact with the pad electrode; and cutting the semiconductor substrate so as to produce a semiconductor device comprising a corresponding portion of the first protection layer as a protection element of the semiconductor device. 8. The method of claim 7, wherein the filling of the via hole comprises forming a wiring layer made of the metal on the second surface. 9. The method of claim 7, further comprising forming a conductive terminal on the filled via hole. 10. The method of claim 8, further comprising forming a conductive terminal on the wiring layer. 11. The method of claim 7, further comprising forming a second protection layer on the second surface so as to cover the filled via hole, forming an opening in the second protection layer to expose the filled via hole, and forming a conductive terminal on the exposed filled via hole. 12. The method of claim 8, further comprising forming a second protection layer on the second surface so as to cover the filled via hole and the wiring layer, forming an opening in the second protection layer to expose the wiring layer, and forming a conductive terminal on the exposed wiring layer. 13. The method of claim 7, wherein the first protection layer is made of epoxy resin. 14. The method of claim 8, wherein the first protection layer is made of epoxy resin. 15. The method of claim 7, further comprising attaching a conductive tape for holding the semiconductor substrate to the first protection layer. 16. The method of claim 8, further comprising attaching a conductive tape for holding the semiconductor substrate to the first protection layer. 17. The method of claim 7, wherein the forming of the first protection layer is performed by a coating process. 18. The method of claim 8, wherein the forming of the first protection layer is performed by a coating process.

<SOH> BACKGROUND OF THE INVENTION <EOH>1. Field of the Invention The invention relates to a semiconductor device and a manufacturing method thereof, particularly to a package type semiconductor device and a manufacturing method thereof. 2. Description of the Related Art CSP (Chip Size Package) has been pursued as a package type semiconductor device. The CSP means a small package having almost the same outside dimensions as those of a semiconductor die packaged in it. Conventionally, a BGA (Ball Grid Array) type semiconductor device has been known as a kind of CSP. In this BGA type semiconductor device, a plurality of ball-shaped conductive terminals made of a metal such as solder is arrayed in a grid pattern on one surface of the package, and electrically connected with the semiconductor die mounted on the other side of the package. A manufacturing method of the BGA type semiconductor device of the conventional art will be described with reference to drawings next. FIG. 6 is a cross-sectional view showing the manufacturing method of the semiconductor device of the conventional art. FIG. 7 is a cross-sectional view showing the semiconductor device and the manufacturing method thereof of the conventional art. First, as shown in FIG. 6 , a pad electrode 51 is formed on a front surface of a semiconductor substrate 50 formed with an electronic device (not shown), extending from the electronic device. A support substrate 60 is further formed on the front surface of the semiconductor substrate 50 . This support substrate 60 is made of, for example, a silicon substrate, a glass substrate, a ceramic substrate, or a metal substrate, supporting the semiconductor substrate 50 and preventing the semiconductor substrate 50 from cracking or warping. Then, a back surface of the semiconductor substrate 50 supported by the support substrate 60 is ground. The semiconductor substrate 50 is thinned to have a predetermined thickness by this backgrinding process. Then, the semiconductor substrate 50 is formed with a via hole 52 penetrating from its back surface to the pad electrode 51 . A wiring layer 53 is formed in the via hole 52 , being electrically connected with the pad electrode 51 . Between the semiconductor substrate 50 and the wiring layer 53 , an insulation film (not shown) is formed. A protection layer 54 is formed on the wiring layer 53 so as to partially expose the wiring layer 53 . On the exposed wiring layer 53 , a conductive terminal 55 is formed, which can be connected with an external printed circuit board and so on. Next, as shown in FIG. 7 , dicing is performed along a dicing line (not shown) to separate the semiconductor substrate 50 into semiconductor dies 50 A. Then, the support substrate 60 attached to the front surface of the semiconductor die 50 A is peeled off or removed, thereby completing the package type semiconductor device. The relevant technology is disclosed in the Japanese Patent Application Publication No. 2003-309221. In the manufacturing method of the package type semiconductor device described above, however, the support substrate 60 used for supporting the semiconductor substrate 50 in the backgrinding process or the forming process of the via hole 52 need be removed from the semiconductor die 50 A after the processes. This causes a problem of making a manufacturing method of the semiconductor device complex and increasing a manufacturing cost. Furthermore, on the front surface of the semiconductor device after the support substrate 60 is removed, the semiconductor die 50 A is not sufficiently protected (from moisture permeation from outside and the like). This causes a problem of decreasing reliability of the semiconductor die. Alternatively, the front surface of the semiconductor die 50 A (or the semiconductor substrate 50 ) is processed again for protecting the semiconductor die 50 A. This causes a problem of making the manufacturing method complex and increasing the manufacturing cost.

<SOH> SUMMARY OF THE INVENTION <EOH>The Invention provides a semiconductor device that includes a semiconductor die having a first surface and second surface, and a pad electrode formed on the first surface. A via hole is formed between the pad electrode and the second surface. The device also includes a first protection layer attached to the first surface so as to cover the pad electrode, an insulation film disposed on an inside wall of the via hole, and a metal portion disposed in the via hole to be in contact with the pad electrode. The invention also provides a method of manufacturing a semiconductor device. The method includes providing a semiconductor substrate having a first surface and a second surface and including a pad electrode formed on the first surface, forming a first protection layer on the first surface to cover the pad electrode, forming a via hole from the second surface to reach the pad electrode, forming an insulation film on a sidewall of the via hole, and filling at least partially the via hole having the insulation film with a metal so that the metal is contact with the pad electrode, and cutting the semiconductor substrate so as to produce a semiconductor device having a corresponding portion of the first protection layer as a protection element of the semiconductor device.

Test apparatus for testing an integrated circuit

Test apparatus for testing an integrated circuit The invention relates to a test apparatus for testing an integrated circuit, particularly a DDR semiconductor memory, having at least one data connection for inputting at least one data signal, at least one DQS control connection for inputting at least one unaltered-frequency DQS signal, a device for phase shifting which is designed to take the unaltered-frequency DQS signal and produce a phase-shifted DQS signal, and a combinational logic device which is connected downstream of the device and which logically combines the unaltered-frequency DQS signal with the phase-shifted DQS signal to produce an altered-frequency DQS signal which has a frequency that is increased compared with the frequency of the unaltered-frequency DQS signal and which is provided for latching the data signals or as a clock signal. The invention also relates to a method for operating a test apparatus of this type.

1. A test apparatus for testing an integrated circuit, comprising: at least one data connection for inputting at least one data signal; at least one DQS control connection for inputting at least one unaltered-frequency DQS signal; a device for phase shifting which is designed to take the unaltered-frequency DQS signal and produce a phase-shifted DQS signal; and a combinational logic device which is connected downstream of the device and which logically combines the unaltered-frequency DQS signal with the phase-shifted DQS signal to produce an altered-frequency DQS signal which has a frequency that is increased compared with the frequency of the unaltered-frequency DQS signal and which is provided for latching the data signals or as a clock signal. 2. The test apparatus according to claim 1, wherein the combinational logic device is in a form of an XOR gate or in a form of an XNOR gate. 3. The test apparatus according to claim 1, wherein the device for phase shifting is designed to provide a 90° phase shift in the unaltered-frequency DQS signal or in an inverted DQS signal derived therefrom. 4. The test apparatus according to claim 1, wherein the altered-frequency DQS signal has a frequency which is twice the frequency of the unaltered-frequency DQS signal. 5. The test apparatus according to claim 1, wherein a latch device for latching the data signals is provided which is connected to the data connections via a data path and which is connected to the DQS control connections via a DQS control path. 6. The test apparatus according to claim 5, wherein the DQS control path has a first path with the unaltered-frequency DQS signal and a second path with the altered-frequency DQS signal. 7. The test apparatus according to claim 6, wherein the DQS control path includes a multiplexer whose output is connected downstream of the first and second paths and which can be used to select a respective one of these two paths. 8. The test apparatus according to claim 7, wherein the test apparatus has a connection for setting a mode of operation, the connection being connected to a control connection on the multiplexer and configured to be used to set a mode of operation of the test apparatus by selecting the first or second path. 9. The test apparatus according to claim 5, wherein a compensating device is provided which is arranged in the data path and which delays the data signal using a time delay which corresponds to the time delay which is obtained from producing the altered-frequency DQS signal in the DQS control path. 10. The test apparatus according to claim 9, wherein the compensating device has at least one further XOR gate and/or a further multiplexer which are in a form such that a gate transit times thereof are based on a corresponding gate transit times of the XOR gate and/or of the multiplexer in the DQS control path. 11. The test apparatus according to claim 1, wherein the data connections are in the form of write data connections which can be used to input write data signals which are configured to be written to a semiconductor memory. 12. A method for operating a test apparatus, comprising: providing a first mode of operation, in which the test apparatus is operated using an unaltered-frequency DQS signal to latch data signals; and providing a second mode of operation, in which the test apparatus is operated using the altered-frequency DQS signal at a frequency which is higher compared with the frequency of the unaltered-frequency DQS signal to latch the data signals. 13. The method according to claim 12, wherein the data signals are delayed using a delay which is based on a delay for providing the unaltered-frequency DQS signal or the altered-frequency DQS signal in the DQS control path.

<SOH> BACKGROUND OF THE INVENTION <EOH>In modern computer and software applications, there is an increasing need to process ever greater volumes of data in ever shorter times. The data are stored using large-scale-integrated memories, such as a DRAM memory. Such semiconductor memories, particularly dynamic read/write memories such as a DRAM memory, are produced in the widest variety of embodiments and variants, the individual embodiments differing from one another essentially in terms of their operating behavior. To meet the aforementioned need for ever greater speed when processing data, it is now necessary to write these data to the semiconductor memory and read them therefrom at a corresponding speed. This can firstly be done using a higher operating frequency for reading and writing the data from and to the semiconductor memory. Another option is to use semiconductor memories designed specifically for high data rates. A typical example of such a semiconductor memory is the “DDR-DRAM memory”, where DDR stands for “Double Data Rate”. Whereas, in conventional semiconductor memories, read and write operations are performed only on the rising or falling edge of a clock signal, in the aforementioned DDR semiconductor memories data are read from the semiconductor memory and written back to the memory both on the rising and falling edges of the clock signal. These semiconductor memories are thus distinguished by twice the data rate. Such semiconductor memories use a “data strobe signal”—subsequently called DQS signal for short—in order to synchronize the data which are read from the semiconductor memory and which need to be written to it. This DQS signal has a similar structure to the data signal and therefore uses data lines in the data path. The timing between the DQS signal and the data signal (I/O signal) is clearly defined in the specification of a semiconductor memory. For this reason, this timing needs to be measured in order to be able to prove that it is still within the admissible range prescribed by the specification. The read operation is uncritical in this instance, since when a semiconductor memory is read both the data signal and the DQS signal are generated by the semiconductor memory itself. By contrast, when writing (write operation) to the semiconductor memory, both the DQS signal and the data signal containing the data which need to be written to the semiconductor memory are generated externally and are input into the semiconductor memory. When such a write operation is tested, the generation and input of these signals, that is to say of the DQS signal and of the data signal, are the limiting factor. To be able to test a DDR semiconductor memory designed for an operating frequency of 500 MHz (1 Gbit/s in DDR mode) properly, for example, there need to be DQS signals at the same frequency in the DDR semiconductor memory. These DQS signals need to be provided by the test unit in question. In previous semiconductor memories, the test units in question were more powerful than the semiconductor memories to be tested. However, modern semiconductor memories, particularly the aforementioned DDR semiconductor memories, are very much faster than the aforementioned conventional test units. This is because the DDR semiconductor memories mentioned at the outset can be operated at a double data rate and hence internally at a double frequency. By way of example, future DDR semiconductor memories, such as third-generation DDR semiconductor memories, will be operated at a frequency of between 800-900 MHz. Currently available test arrangements for testing semiconductor memories are designed only for a maximum frequency of approximately 500 MHz, however. In this situation, “high-performance semiconductor memories”, such as graphics DRAM memories, reduced-latency DRAM memories etc., which are operated at a very high frequency, can no longer be tested (or can be tested only incompletely) by today's test units. This immediately leads to a situation in which relatively expensive memory products are sold without their being adequately tested. It is thus not possible to establish definitively whether or not they are now faulty, however. A semiconductor memory which is faulty or not fully functional would not be accepted by buyers of such expensive, “high-end” products, however. So as now to be able to test these semiconductor memories nevertheless, it would therefore be necessary to develop test units designed specifically for testing the semiconductor memories. The development and provision of test units designed specifically for testing such DRAM memory products therefore becomes extraordinarily cost-intensive, which likewise raises the cost of the corresponding semiconductor memories to be tested. However, this development is contrary particularly to the trend inherent in DRAM memory development for providing ever less expensive solutions and hence ever less expensive DRAM semiconductor memories. German Laid-Open Specification DE 102 00 898 A1 describes an arrangement and a method in which the read path of a semiconductor memory is tested. For the purpose of testing, the available system clock is doubled internally. Hence, in semiconductor memories whose operating frequency in normal operation is above a maximum frequency for a test unit used for a test mode, an opportunity is created for testing the full frequency range of the semiconductor memory's read path. However, the solution described in DE 102 00 898 A1 cannot be used to test a semiconductor memory's write path as well, since writing in the semiconductor memory also requires that the corresponding DQS signal and, in addition, the data signal be tested at a double frequency. In this case, although the solution described in DE 102 00 898 A1 would allow the read path to be tested at a higher frequency, the write path would remain bypassed and hence would remain untested. This is a condition which understandably needs to be avoided.

<SOH> SUMMARY OF THE INVENTION <EOH>The invention relates generally to the testing of integrated circuits which are operated at a very high frequency. Although they can be applied to any integrated circuits which need to be tested using a suitable tester arrangement, the present invention and the problems which underlie it are explained below with reference to “DDR semiconductor memories”. The present invention provides a test apparatus which can be used to test semiconductor memories which are operated at a higher frequency than the maximum frequency of the test apparatus. In particular, a better test option for the semiconductor memory's read path is intended to be provided. In several embodiments of the invention, there are: a test apparatus for testing an integrated circuit, particularly a DDR semiconductor memory, having at least one data connection for inputting at least one data signal, having at least one DQS control connection for inputting at least one unaltered-frequency DQS signal, having a device for phase shifting which is designed to take the unaltered-frequency DQS signal and produce a phase-shifted DQS signal, and having a combinational logic device which is connected downstream of the device and which logically combines the unaltered-frequency DQS signal with the phase-shifted DQS signal to produce an altered-frequency DQS signal which has a frequency that is increased compared with the frequency of the unaltered-frequency DQS signal and which is provided for latching the data signals or as a clock signal. a method for operating a test apparatus based on the invention having a first mode of operation, in which the test apparatus is operated using the unaltered-frequency DQS signal in order to latch the data signals, and having a second mode of operation, in which the test apparatus is operated using the altered-frequency DQS signal at a frequency which is higher compared with the frequency of the unaltered-frequency DQS signal in order to latch the data signals. The present invention provides testing a write path within the test apparatus by increasing the frequency of the DQS signal which is available anyway. The available DQS signal is also called the unaltered-frequency DQS signal, since it has a prescribed frequency. The clock rate of the DQS signal is increased very easily by phase-shifting the available DQS signal. This produces a DQS signal and an associated phase-shifted DQS signal, which are input into the input side of a combinational logic circuit. The signal produced at the output of the combinational logic circuit thus corresponds to a DQS signal at an increased clock frequency. In this way, it is advantageously possible to use a conventional test apparatus operated at low frequency to test a semiconductor memory which is operated at a very much higher frequency, particularly at a frequency which is twice higher. The advantages are obvious in this case: In particular, testing the read path in modern semiconductor memories, such as in the DDR semiconductor memory, which are operated at a very high frequency does not necessarily require the provision of cost-intensive test units provided specifically for testing the semiconductor memories. In this context, it is sufficient to use the previously used, conventional test units for testing, provided that they have been appropriately extended by a device for phase shifting and by a combinational logic circuit. The increased-frequency DQS signal obtained in this manner can thus be used for latching the data in the write path and hence for testing the write path. To do this, the data are written to the semiconductor memory on every rising and falling edge of the higher-frequency DQS signal obtained in this manner. Advantageously, the combinational logic device is in the form of an XOR gate. The functionality of the combinational logic circuit may naturally also be provided by an XNOR gate. However, it would also be conceivable to use any other device which has a functionality corresponding to that of an XOR gate or XNOR gate, for example an appropriate logic circuit or a program-controlled device. In one advantageous embodiment, the DQS signal phase-shifted through 90° is obtained by phase-shifting the original DQS signal. When the 90°-phase-shifted DQS signal obtained in this manner is logically combined with the original DQS signal using an XOR gate, it is thus possible to provide a DQS signal at twice the clock frequency, in which the high phases and low phases of this double DQS signal are of equal length. In an alternative refinement, a DQS signal and an associated inverted DQS signal are provided, the 90°-phase-shifted DQS signal being derived from one of these two DQS signals. The inventive test apparatus has a latch device for latching the data signals which is connected to the data connections via the data path and is connected to the DQS control connections via a DQS control path. Advantageously, the DQS control path has a first path with an unaltered-frequency DQS signal and a second path with a DQS signal which has a higher frequency, particularly twice the frequency, compared with the unaltered-frequency DQS signal. Which of these paths is used and hence which of these DQS signals is used to latch the data in the data path can be set using a multiplexer device whose output is connected downstream of the two paths. In this way, it is possible to use a conventional test apparatus, on the one hand, for operating conventional semiconductor memories which can be operated at low frequency, and additionally it is also possible to extend the functionality of this test apparatus by being able to provide a DQS signal, when selecting the second path, which (signal) can also be used to test the data paths, particularly the write paths of modern, higher-frequency semiconductor memories. To this end, the inventive test apparatus advantageously has a connection for setting a mode of operation. This connection, which is connected to a control connection on the multiplexer, can be used to set the mode of operation of the test apparatus by selecting the first or second path. The device for increasing the frequency of the DQS signal, in this case particularly the device for phase shifting, the receiver, the XOR gate and the multiplexer typically have a gate transit time which is associated with these devices. The higher-frequency DQS signal therefore has a corresponding time delay in comparison with the unaltered-frequency DQS signal at the input. The result of this time delay is that the DQS signal in the DQS control path is delayed to a greater or lesser extent compared with the corresponding data signal in the data path. In one particularly advantageous development, the data path therefore contains a compensating device which takes account of this time delay in the DQS control path and which thus delays the data signal in the data path using an appropriate time delay. In one very advantageous refinement, the data path therefore advantageously contains the same circuit parts or at least circuit parts having the same gate transit times as are responsible for the time delay in the DQS control path. Typically, the compensating device has at least one further XOR gate and/or a further multiplexer which are in a form such that the gate transit times thereof are based on the corresponding gate transit times of the XOR gate and/or of the multiplexer in the DQS control path. This makes it possible to ensure that the data path also contains a time delay which is identical to or is at least largely the same as that in the DQS control path. In one typical and also advantageous refinement, the data connections are in the form of write data connections. These write data connections can be used to input write data signals (WRITE) which are to be written to a semiconductor memory into the test apparatus. The inventive test apparatus is thus designed for testing the write path of a semiconductor memory, particularly of a DDR semiconductor memory.

Transmission

A transmission comprises a first roller having a first repeated number of first grooves on the outer circumferential surface of a first shaft body having a cross-sectional circular shape in the perimeter direction, a second roller having a second repeated number of second grooves in the perimeter direction on the outer circumferential surface of a second shaft body having a cross-sectional circular shape, and a cylinder-shaped third roller having plural grooves extending in the axial direction with intervals in the perimeter direction on the inner diameter surface. The second repeated number is different from the first repeated number. The first roller and the second roller each face the third roller via plural first rolling elements positioned in the first grooves and plural second rolling elements positioned in the second grooves.

1. A transmission comprising: a first roller having a first repeated number of first grooves on the outer circumferential surface of a first shaft body having a cross-sectional circular shape in the perimeter direction; a second roller having a second repeated number of second grooves, which is different from the first repeated number, in the perimeter direction on the outer circumferential surface of a second shaft body having a cross-sectional circular shape; and a cylinder-shaped third roller having plural grooves extending in the axial direction with intervals in the perimeter direction on the inner diameter surface; wherein said first roller and said second roller each face said third roller via plural first rolling elements positioned in said first grooves and plural second rolling elements positioned in said second grooves. 2. A transmission according to claim 1, wherein a retainer capable of sliding in said axial direction for holding said first rolling element and said second rolling element is disposed in each of the plural grooves of said third roller. 3. A transmission according to claim 2, wherein a sliding member intervenes between said retainer and said third roller. 4. A transmission according to claim 3, wherein said sliding member is a rolling unit. 5. A transmission according to claim 3, wherein said first and second rolling elements also serve as said sliding member. 6. A transmission according to claim 1, wherein when said first roller serves as an input shaft, any one of said third roller and said second roller is fixed, and the other serves as an output shaft. 7. A transmission according to claim 2, wherein said first repeated number is represented by KS, said second repeated number is represented by KS·KI, and the maximum number of said plural grooves is represented by KS·(KI±1). 8. A transmission according to claim 1, wherein said first and second rollers are configured with a hollow shape. 9. A transmission according to claim 2, wherein said first and second grooves have a symmetric shape such as a sine waveform, a triangular waveform, or the like. 10. A transmission according to claim 6, wherein said first repeated number is represented by KS, said second repeated number is represented by KS·KI, and the maximum number of said plural grooves is represented by KS·(KI+1). 11. A transmission according to claim 7, wherein said first repeated number is represented by KS, said second repeated number is represented by KS·KI, and the maximum number of said plural grooves is represented by KS·(KI±1). 12. A transmission according to claim 1, wherein said first and second rollers are configured with a hollow shape. 13. A transmission according to claim 6, wherein said first and second rollers are configured with a hollow shape. 14. A transmission according to claim 8, wherein said first and second rollers are configured with a hollow shape. 15. A transmission according to claim 1, wherein said first and second grooves have a symmetric shape such as a sine waveform, a triangular waveform, or the like. 16. A transmission according to claim 6, wherein said first and second grooves have a symmetric shape such as a sine waveform, a triangular waveform, or the like. 17. A transmission according to claim 8, wherein said first and second grooves have a symmetric shape such as a sine waveform, a triangular waveform, or the like. 18. A transmission according to claim 12, wherein said first and second grooves have a symmetric shape such as a sine waveform, a triangular waveform, or the like.

<SOH> BACKGROUND OF THE INVENTION <EOH>The present invention relates to a transmission, and particularly, relates to a ball-type transmission. Various types of transmission have been proposed for this type of transmission, and several examples thereof will be described below. A first example is a reduction gear comprising an input rotary shaft, first and second endless cam grooves formed in a periodic functionally curved manner each of which the axial center line direction is taken as a vertical axis and the circumferential direction is taken as a horizontal axis with estrangement over the outer circumferential surface of this input rotary shaft in the axial center line direction, and a cylinder body mounted on the outside of the input rotary shaft so as to rotate concentrically with the input rotary shaft. The reduction gear further comprises a third endless cam groove formed in a periodic functionally curved manner having the same amplitude value as the first endless cam groove on a portion opposing to the first endless cam groove over the inner circumferential surface of this cylinder body in the same way as the first endless cam groove, and a fourth endless cam groove formed in a periodic functionally curved manner having the same amplitude value as the second endless cam groove on a portion opposing to the second endless cam groove over the inner circumferential surface of this cylinder body in the same way as the second endless cam groove. The reduction gear still further comprises rolling elements each intervened in a position where the first endless cam groove and the third endless cam groove are intersected with each other between the first and third endless cam grooves, and also a position where the second cam groove and the fourth cam groove are intersected with each other between the second and fourth endless cam grooves. The reduction gear yet further comprises a stationary first holding member holding the rolling element positioned between the first and third cam grooves so as to move the rolling element in the axial center line direction, a second holding member holding the rolling element positioned between the second and fourth endless cam grooves so as to move the rolling element in the axial center line direction, and also so as to be rotatably supported centered on the axial center line, and an output rotary shaft connected to this second holding member. That is to say, with the first example, the first and second endless cam grooves are formed on a large diameter portion connected with the input shaft, the first endless cam groove is coupled to the first holding member via the rolling element, i.e., the ball, and the second endless groove is coupled to the second holding member connected with the output shaft via the rolling element, i.e., the ball (see Japanese Unexamined Patent Application Publication (JP-A) No. 59-180153, for example). A second example is a cap-type gearless transmission comprising two shafts each supported so as to rotate over the same axial line, an inner cylinder fixed on the end portion of one shaft, and an outer cylinder fixed on the end portion of the other shaft and facing the outer surface of the inner cylinder. The gearless transmission further comprises an endless tilting groove and plural sine wave grooves of which one is disposed on any one of the facing surfaces between the inner cylinder and outer cylinder, and the other is disposed on the other facing surfaces. The gearless transmission still further comprises a guide cylinder of which plural narrowly long windows different from the number of the sine wave grooves are opened in the isometric axial line direction inserted in a gap between the inner cylinder and outer cylinder so as to rotate, and balls each inserting in each narrowly long window so as to roll and engaging with the tilting groove and sine wave groove (see Japanese Unexamined Patent Application Publication (JP-A) No. 60-179563, for example). However, with the first example, two winding grooves need to be formed on the inner circumferential surface of the cylinder body, and even with the second example, a winding groove needs to be formed on the inner surface of the outer cylinder, so working is difficult and troublesome. On the other hand, with the second example, further entry plugs for the balls need to be disposed on the rolling surface of the balls. Steps provided on the rolling surface by the entry plugs cause the service life of the balls to be shortened.

<SOH> SUMMARY OF THE INVENTION <EOH>Accordingly, an object of the present invention is to provide a transmission of which the working is relatively simple. Another object of the present invention is to provide a transmission of which assembly is relatively simple, and also the service life of the balls can be increased. A transmission according to the present invention comprises a first roller having a first repeated number of first grooves on the outer circumferential surface of a first shaft body having a cross-sectional circular shape in the perimeter direction, a second roller having a second repeated number of second grooves, which is different from the first repeated number, in the perimeter direction on the outer circumferential surface of a second shaft body having a cross-sectional circular shape, and a cylinder-shaped third roller having plural grooves extending in the axial direction with intervals in the perimeter direction on the inner diameter surface. The first roller and the second roller each face the third roller via plural first rolling elements positioned in the first grooves and plural second rolling elements positioned in the second grooves. In the present transmission, a retainer capable of sliding in the axial direction for holding the first rolling element and the second rolling element is disposed in each of the plural grooves of the third roller. In the present transmission, a sliding member may intervene between the retainer and the third roller. In this case, the sliding member may be a rolling unit. Alternatively, the first and second rolling elements may serve as the sliding member. Also, an arrangement may be made wherein the sliding member may be realized by coating at least one of the facing portions between the retainer and the third roller with a friction reducing material, for example. In the present transmission, when the first roller serves as an input shaft, any one of the third roller and the second roller is fixed, and the other serves as an output shaft. In the present transmission, further, the first repeated number is represented by K S , the second repeated number is represented by K S ·K I , and the maximum number of the plural grooves is represented by K S ·(K I ±1). It is preferable that the first and second rollers in the transmission are configured with a hollow shape. The first and second grooves in the present transmission preferably have a symmetric shape such as a sine waveform, triangular waveform, or the like, but they may have an asymmetric shape. Also, the cross-sectional shapes of the first and second grooves are preferably any one of a simple arc shape, bearing arc shape, or triangular shape.

Process for production of highly pure donepezil hydrochloride

Disclosed is a process for production of highly pure donepezil hydrochloride in the form of polymorph I that does not involve the isolation of donepezil base. The disclosed process involves intramolecular cyclization of N-benzyl-2-(3,4-dimethoxybenzyl)-3-(4-piperidine)propionic acid followed by treatment with HCl.

1. A process for the preparation of donepezil hydrochloride in the form of polymorph I, wherein the salt is characterized by peaks expressed in degrees 2θ at approximately 9.8, 10.5, 12.6, 13.0, 13.6, 13.8, 14.8, 16.0, 16.8, 17.5, 19.8, 21.0, 21.2, 23.0 and 23.9 in a powder x-ray diffraction pattern, 4 to 6% of water content, and a LC purity of more than 99%, with a content of each individual impurity not exceeding 0.02%, which process comprises: carrying out an intramolecular cyclization of N-benzyl-2-(3,4-dimethoxybenzyl)-3-(4-piperidine)propionic acid or its salt to form donepezil base; treating the donepezil base with HCl without isolating the donepezil base to form donepezil hydrochloride; crystallizing the donepezil hydrochloride to give crystalline form I of donepezil hydrochloride; and maturing the donepezil hydrochloride form I in a damp atmosphere to give donepezil hydrochloride of desired crystalline form, water content and LC purity. 2. The process of claim 1, wherein the intramolecular cyclization is performed in the presence of a protic acid, a Lewis acid, or a mixture thereof. 3. The process of claim 2, wherein said intramolecular cyclization is performed in the presence of a protic acid selected from the group consisting of trifluoromethanesulfonic acid, methanesulfonic acid, polyphosphoric acid, fluorosulfonic acid, chlorosulfonic acid, sulfuric acid, hydrogen fluoride, and hydrogen chloride. 4. The process of claim 2, wherein said intramolecular cyclization is performed in the presence of a Lewis acid selected from the group consisting of zinc chloride, zinc bromide, aluminum chloride, aluminum bromide, titanium chloride, boron fluoride, phosphorus pentoxide, phosphorus oxychloride, phosphorus pentachloride, phosphorus trichloride, thionyl chloride, and sulfuryl chloride. 5. The process of claim 1, wherein said intramolecular cyclization is carried out in the present of a solvent. 6. The process of claim 5, wherein said solvent is a halogenated solvent. 7. The process of claim 6, wherein said halogenated solvent is selected from the group consisting of dichloromethane, chloroform, dichloroethane, tetrachloroethane, chlorobenzene, and dichlorobenzene and mixtures thereof. 8. The process of claim 5, wherein said solvent is selected from the group consisting of nitromethane, nitroethane, nitrobenzene, and ether and mixtures thereof. 9. The process of claim 1, wherein the carboxylic group of N-benzyl-2-(3,4-dimethoxybenzyl)-3-(4-piperidine)propionic acid is derivatized to a halocarbonyl group prior to carrying out the intramolecular cyclization. 10. The process of claim 1, wherein the donepezil hydrochloride has a LC purity of more than 99.5%. 11. The process of claim 1, wherein the donepezil hydrochloride has a LC purity of more than 99.8%. 12. The process of claim 1, wherein the donepezil hydrochloride has a LC purity of more than 99.9%. 13. Donepezil hydrochloride in the form of polymorph I being specified by peaks expressed in degrees 20 at approximately 9.8, 10.5, 12.6, 13.0, 13.6, 13.8, 14.8, 16.0, 16.8, 17.5, 19.8, 21.0, 21.2, 23.0 and 23.9 in a powder x-ray diffraction pattern, 4 to 6% of water content, and a LC purity of more than 99.9%, with a content of each individual impurity not exceeding 0.02%, prepared by the process of claim 1.

<SOH> BACKGROUND OF THE INVENTION <EOH>1. Field of the Invention The present invention relates to a process for the preparation of highly pure donepezil hydrochloride in the form of polymorph I. 2. Related Art 5,6-Dimethoxy-2-(1-benzyl-4-piperidinylmethyl)-1-indanone, known under the international nonproprietary name (INN) donepezil, is an acetylcholinesterase inhibitor (The Merck Index, 13th Ed., 2001, Monograph #3453). Tablets containing the hydrochloride salt of donepezil are marketed in the United States of America under the proprietary name ARICEPT (Eisai). This product is orally administrated and clinically used as a therapeutic and ameliorating agent for Alzheimer's-type senile dementia, particularly as a prophylactic treatment. Donepezil hydrochloride in the forms of polymorphs II, IV and V is claimed in U.S. Pat. No. 6,140,321. Donepezil hydrochloride form III is claimed in U.S. Pat. No. 5,985,864. Donepezil hydrochloride in the form of polymorph I was described in the same patents and earlier in Example 4 of U.S. Pat. No. 4,895,841. Donepezil hydrochloride in the form of polymorph I is substantially stable under storage conditions for 1 month at 60° C. (FIG. 18 of U.S. Pat. No. 6,140,321). Polymorph I preserved water content in a narrow range of 4.5 to 5.9% when it was stored at 25° C. under an atmosphere with a relative humidity of 10 to 96% (see FIG. 20 of U.S. Pat. No. 6,140,321). The crystalline donepezil hydrochloride form I is characterized by a x-ray power diffraction spectrum having peaks expressed in degrees 2θ at 9.94, 10.60, 12.66, 13.12, 13.66, 13.86, 14.92, 15.26, 16.08, 16.86, 17.50, 17.58, 18.42, 19.28, 19.80, 19.94, 21.22, 22.00, 22.54, 22.98, 23.60, 23.78, 23.92, 26.46, 28.02 and 29.50 (Claim 12 of U.S. Pat. No. 6,140,321). FIGS. 1 and 21 of U.S. Pat. No. 5,985,864 show a x-ray powder diffraction spectrum of crystalline donepezil hydrochloride form I. Donepezil hydrochloride is produced by first producing donepezil, which is a free base, and then converting it into a hydrochloride. In other words, donepezil base is used as a precursor for the production of donepezil hydrochloride. A synthetic route to donepezil is shown in Scheme 1 and comprises the condensation of 5,6-dimethoxy-1-indanone with N-benzyl-4-piperidinecarboxaldehyde followed by reduction of the obtained N-benzyl-5,6-dimethoxy-2-(4-piperidinylmethylene)-1-indanone [III] and column chromatography of the crude donepezil base on silica gel. Donepezil hydrochloride is prepared from the resulting purified donepezil base by treating the base with hydrogen chloride and re-crystallizing the resulting solid from MeOH/i-Pr 2 O (Sugimoto et al., J. Med. Chem. 38:481 (1995); U.S. Pat. No. 4,895,841). Recently it was proposed to use crystallization for purification of crude donepezil base obtained after the reduction of compound [III] (U.S. Pat. No. 6,245,911). An alternative process disclosed in WO 00/09483 for preparing donepezil is shown in Scheme 2 and comprises the steps of (a) carrying out the intramolecular cyclization of N-benzyl-2-(3,4-dimethoxybenzyl)-3-(4-piperidine)propionic acid to yield donepezil base and (b) isolating the resulting donepezil base by chromatography or crystallization. An additional process for production of donepezil hydrochloride involves reacting a donepezil intermediate with halogenated benzyl to obtain a donepezil quaternary ammonium salt, hydrogenation of the quaternary ammonium salt to produce donepezil base, followed by addition of hydrogen chloride to produce donepezil hydrochloride (U.S. Pat. No. 6,252,081). It should be noted that all of the known procedures for preparing donepezil hydrochloride form I involve the isolation and handling of the intermediate donepezil base prior to converting it into donepezil hydrochloride. There are several disadvantages in such two-step processes. These include increased cycle time due to increased handling requirements, increased air emissions if drying of the donepezil base is required, and increased total volume of solvent needed. Further, in the prior art, the desired compound is purified by column chromatography, which requires a large amount of solvent and the column is discarded after use, and is thus very disadvantageous in production cost. In addition, a large amount of used solvent is evaporated into the atmosphere. Therefore, column chromatography is preferably not used from the viewpoint of working environment and environmental protection.

<SOH> SUMMARY OF THE INVENTION <EOH>In view of the foregoing, there is a need in the art to provide a scalable industrial process for synthesizing highly pure donepezil hydrochloride form I hydrate, without the need for isolation, chromatography and re-crystallization of the intermediate donepezil base. It is a further need in the art to provide a process for synthesizing donepezil hydrochloride form I hydrate having a liquid chromatography (LC) purity (by area under a LC peak) of more than 99% and a content of each individual impurity not exceeding 0.02% (by area). Thus, the present invention provides a process for preparing crystalline donepezil hydrochloride form I hydrate, wherein the obtained salt is characterized by 4 to 6% of water content, a LC purity (by area) of more than 99% and a content of each individual impurity not exceeding 0.02% (by area), which process comprises: carrying out an intramolecular cyclization of N-benzyl-2-(3,4-dimethoxybenzyl)-3-(4-piperidine)propionic acid or its salt to form donepezil base; treating the donepezil base with HCl without isolating the donepezil base to form donepezil hydrochloride; crystallizing the donepezil hydrochloride to give crystalline form I of donepezil hydrochloride; and maturing the donepezil hydrochloride form I in a damp atmosphere to give donepezil hydrochloride hydrate form I of desired LC purity.

Accelerated healing with intraoperative combination of suture and autogenous blood components

A suture combined intraoperatively with autogenous blood components. At least one strand of suture is placed into a sterile container. Blood obtained from a patient is separated, using a centrifuge, for example, to retrieve certain healing components such as autogenous growth factors, to obtain an autogenous blood suspension. The autogenous blood suspension is added to the sterile container containing the strand of suture. The suture wicks up biologic components of the autogenous blood suspension to produce an enhanced suture. Surgical repairs using the enhanced suture are conducted by suturing a tear to itself or to bone, for example. Post-operatively, the biologic components leach from the suture to accelerate healing of the repair.

1. A method of suturing comprising: obtaining an autogenous blood component from a patient; and intraoperatively combining the autogenous blood component with a length of suture. 2. The method of claim 1, further comprising suturing tissue of the patient using the length of suture combined with the autogenous blood component 3. The method of claim 1, wherein the autogenous blood component comprises a growth factor. 4. The method of claim 3, wherein the growth factor is platelet-rich plasma. 5. The method of claim 1, wherein the autogenous blood component is obtained by centrifuging the patient's blood. 6. A surgical method comprising: providing at least one strand of suture into a container; obtaining an autogenous blood suspension from a patient; combining the autogenous blood suspension with the at least one strand of suture in the container; and suturing tissue of the patient using the at least one strand of suture combined with the autogenous blood suspension. 7. The method of claim 6, wherein the autogenous blood suspension includes a component selected from the group consisting of autogenous growth factors, hyaluronic acid, anticoagulants, antiseptics, antibiotics, and vitamins. 8. The method of claim 6, wherein the autogenous blood suspension comprises platelet-rich plasma. 9. The method of claim 6, wherein the at least one strand of suture comprises a material selected from the group consisting of collagen, surgical gut, silk, cotton, polyolefins, polyamides, polyesters, polyglycolic acid and glycolide-lactide copolymer. 10. The method of claim 6, wherein the autogenous blood suspension is obtained by centrifugation. 11. A surgical suture comprising: a length of suture prepared for surgical use in a patient; and autogeneous blood material obtained from the patient combined with the suture prior to surgical use.

<SOH> BACKGROUND OF THE INVENTION <EOH>Surgical suturing is used to repair torn tissue. It is known to provide packaged suture to surgeons with medically useful materials included in the suture, such as human epidermal growth factor. Limitations of the known methods include the storage stability of the materials included in the suture and patient immunological compatibility.

<SOH> SUMMARY OF THE INVENTION <EOH>The present invention provides a suture that is combined intraoperatively with autogenous blood components. At least a strand of suture is placed into a sterile container. Blood obtained from a patient is separated, using a centrifuge, for example, to retrieve certain healing components such as autogenous growth factors, to obtain an autogenous blood suspension. The autogenous blood suspension is added to the sterile container containing the strand of suture. The suture wicks up biologic components of the autogenous blood suspension to produce an enhanced suture. The surgeon effects surgical repairs using the enhanced suture by suturing a tear to itself or torn tissue to bone, for example. Post-operatively, the biologic components leach from the suture to accelerate healing of the repair, for example. The invention also provides a method of conducting suturing by employing a suture that is combined intraoperatively with autogenous blood components such as platelet-rich-plasma. The method comprises the steps of: (i) providing at least a strand of suture into a sterile container; (ii) obtaining an autogenous blood suspension comprising healing components such as growth factors from blood obtained from a patient; (iii) adding the autogenous blood suspension to the sterile container containing the suture to allow the suture to soak in the autogenous blood suspension and to produce an enhanced suture; and (iv) effecting a surgical repair employing the enhanced suture. Other features and advantages of the present invention will become apparent from the following description of the invention, which refers to the accompanying drawing.

Music instrument system and methods

A system and methods which allow even a novice performer to easily play music which is not disharmonious and which is pleasing to the performer and his or her audience. The music is preferably created by a performer breaking one or more beams of light, which are emitted by one or more beam emitters and received, or detected, by one or more beam detectors. When a beam detector determines that a beam has been broken, a trigger is sent to a synthesizer, with such synthesizer preferably being a computer interfaced to the beam detectors via a Universal Serial Bus connection. The synthesizer selects from one or more electronic sounds, based on a pre-programmed collection of sounds, and a sound generator, such as an amplifier and speakers, plays the sound.

1. A sound scene creation method comprising: developing an underpinning; writing a first melody using a scale that fits sympathetically with the underpinning; writing a counterpoint that is sympathetic to the melody; creating a transpose matrix; and, writing at least one additional melody using alternate chords that fit sympathetically with the underpinning. 2. The sound scene creation method of claim 1, wherein the first melody is between sixteen and one hundred twenty-eight notes long. 3. The sound scene creation method of claim 1, wherein the at least one additional melody contains up to one hundred twenty-eight notes. 4. A music instrument wherein the music elements which can be produced by the instrument are limited to a set of between three and seven different sounds, including octaves of such sounds, wherein the sounds are sympathetic. 5. The music instrument of claim 4, wherein the music instrument allows transposition of the music elements. 6. A method of composing an electronic instrument program comprising: selecting at least one first sympathetic scale; selecting at least one first background composition, wherein substantially all notes are included in the first sympathetic scale; selecting at least one first melody composition, wherein substantially all notes are included in the first sympathetic scale; assigning the first background composition to at least one first trigger; assigning the first melody composition to at least one second trigger; and, arranging operation of the first and second triggers such that at least one performer may operate the first and second control switches to play the compositions assigned thereto. 7. The electronic instrument program composition method of claim 6, further comprising: selecting a transpose operation to transpose the first background composition and the first melody composition from the first sympathetic scale to a second sympathetic scale; assigning such transpose operation to at least one third trigger; arranging operation of the at least one third trigger such that at least one performer may operate the at least one third trigger to transpose the background composition and the melody composition from the first sympathetic scale to the second sympathetic scale. 8. The electronic instrument program composition method of claim 7, wherein the transpose operation comprises: selecting a transposition; and, selecting a first note to be played upon execution of the transposition. 9. The electronic instrument program composition method of claim 6, further comprising: selecting a series of transpose mappings; assigning the series of transpose mappings to at least one third trigger; and, arranging operation of the at least one third trigger such that a performer causes the first background composition and the first melody composition to be transposed from the first sympathetic scale to a subsequent sympathetic scale according to the series of transpose operations each time the at least one third trigger is operated. 10. The electronic instrument program composition method of claim 6, wherein the first sympathetic scale comprises a major scale. 11. The electronic instrument program composition method of claim 10, wherein the first note of the first sympathetic scale comprises a root note of the first sympathetic scale. 12. A method of configuring and performing an electronic musical instrument comprising: assigning at least one sound element into at least one first program; assigning at least one sound element to at least one second program; assigning the first program to at least one first trigger; assigning the second program to at least one second trigger; assigning at least one function to at least one third trigger; and, activating the triggers in a desired order to produce a musical performance. 13. The electronic musical instrument configuring and performing method of claim 46, wherein the first program is a background sound. 14. The electronic musical instrument configuring and performing method of claim 46, wherein the second program is comprised of a chord that fits against the predominant scale of the first program. 15. The electronic musical instrument configuring and performing method of claim 46, wherein the function is a transpose mapping. 16. A method of configuring and performing an electronic musical instrument comprising: assigning at least one sound element to at least one first program to create a background sound; assigning at least one sound element into at least one second program, wherein the sound elements assigned are comprised of a chord that fits against the predominant scale of the first program; assigning the first program to at least one first trigger; assigning the second program to at least one second trigger; assigning at least one transpose mapping to at least one third trigger; and, activating the triggers in a desired order to produce a musical performance. 17. A portable, light beam based musical instrument comprising a plurality of beam emitters and beam detectors, a plurality of trigger circuits, a plurality of sounds, and at least one audible sound generator for playing the sounds, wherein the musical instrument is played by interacting with the beams emitted by the beam emitters. 18. The music instrument of claim 17, wherein the plurality of sounds are sympathetic. 19. A portable light beam based musical instrument comprising a plurality of beam emitters and beam detectors, a plurality of trigger circuits, a plurality of sounds, and at least one audible sound generator for playing the sounds, wherein the musical instrument is played by interacting with the beams emitted by the beam emitters, and wherein prolonged activation of one of the beams emitted by the beam emitters causes successive sounds to be played. 20. The music instrument of claim 19, wherein the plurality of sounds are sympathetic.

<SOH> BACKGROUND OF THE INVENTION <EOH>There have been several attempts to design an area/device wherein a person or people may, by moving within this area in certain ways, cause a sound system to generate various sounds. Some of these attempts include setting up various electromagnetic beams/patterns in the area whereby movement of a person/people interferes with these beams/patterns and causes sound generation. However, sound generation has typically been controlled by such systems in either of two ways. One sound generation control system used in the prior art monitors a performer's movements and consistently generates exactly the same sound or sounds every time a specific movement occurs. With such systems, even slight movement variations can cause undesirable changes in pitch, tone, volume, or the like. While such systems permit a highly-trained person to “play” the system and generate exactly certain sounds at each “performance” in a more-or-less “professional” manner, these systems are not likely to produce pleasing or entertaining sounds or results if a novice attempts to perform on them. A second sound generation control method has focused on the “power” given, say, to children in a museum setting to produce, for example, sounds by “playing” randomly in a designated area, thus permitting them to play and experiment but with little heed given to production of pleasing sounds. Additionally, such prior art systems generally comprise relatively large areas around which are placed the light beams used for playing music or producing sounds. See for example U.S. Pat. No. 5,081,896 by Hiyosji; U.S. Pat. No. 3,749,810 by Dow; U.S. Pat. No. 5,045,687 by Gurner; and U.S. Pat. No. 5,017,770 by Sigalov, the teachings of which are incorporated herein by reference in their entirety. The light beams in such prior art systems generally are substantially vertical in orientation, or are arranged such that the triggering motion is substantially horizontal. Such prior art systems are also relatively large and cage-like. Thus, a player of such systems must run, jump, etc. as in Hiyosji, and/or trigger a cage of vertical beams as in Sigalov. Furthermore, such systems generally require that the beam or sensor have interaction with either a substantial part of the user's body, or at least that the beam or sensor be interrupted by an arm or a full hand. Thus, such systems also require relatively gross movements for their operation. Such systems therefore are not adapted for fine, precise, and economical user movements. Moreover, such systems are generally fairly large and require permanent or semi-permanent installations. While permanent installation is certainly desirable in many cases, equally desirable is a portable system which even a single person may disassemble, move, and re-assemble quickly and with little effort.

<SOH> SUMMARY OF THE INVENTION <EOH>A preferred embodiment of the present invention provides a music instrument, operable by at least one performer, capable of creating a real-time performance. Such a music instrument can comprise independently-controllable computer programs, each such computer program comprising musical elements; a plurality of independently-controllable switches, structured and arranged so that at least one switch controls at least one computer program; a plurality of interruptible electromagnetic beams, structured and arranged so that interruption of at least one respective such beam by a performer will affect operation of at least one switch; wherein operation of the music instrument will permit a plurality of the musical elements to be sounded during a performance period. Each of the musical elements used by the music instrument may be sounded during a performance period, and are preferably comprised of sound vibrations whose relative frequencies are sympathetically compatible to a performer's audience. The net result is a music instrument which allows even a novice performer, by a group of willful interruptions of the beams, to perform music consistently pleasing to the audience. The music instrument is preferably comprised of several sub-components, including a music synthesizer in which the programs are stored and which is capable of playing one or more programs simultaneously; a plurality of independently-controllable switches, structured and arranged such that at least one of the switches controls at least one of the programs; and a plurality of electromagnetic beams, structured and arranged so that interruption of at least one beam affects operation of at least one switch. In a preferred embodiment, the electromagnetic beams are arranged substantially horizontally, and all electromagnetic beams are located within approximately a limb-length from the performer. The electromagnetic beams may also be preferably arranged such that a performer is only surrounded thereby on three sides. The beam emitters and beam detectors used in creating and detecting the presence or absence of the electromagnetic beams of the present invention are preferably configured such that a member having a cross section not substantially more than the diameter of a human finger or a thin conductor-type baton, can be used to interact with the beams. The present invention may restrict the number of music elements available to a performer at any given time to a set of about seven different music elements, plus octaves of the musical elements, with the music elements related to each other such that sounding together of any combination of the music elements would ordinarily not be perceived as disharmonious by a performer's audience. While such restrictions may appear to significantly limit a performance, the present invention also allows a performer to switch from music element set to music element set, thereby providing a performer with a wider range of sound capabilities while still producing music which is not disharmonious. In addition to providing a music instrument through which programs can be played by a performer, the present invention also preferably includes a software control system through which a performer or other programs-writer can compose their own programs. Such a software control system preferably includes a graphical interface for selecting a music element scale which serves as the basis upon which the program is built. A programs-writer can then select desired music elements to serve as a background composition and assign a tempo to the background composition. In a preferred embodiment, the music elements chosen for the background composition are notes from the selected music element scale, although the present invention may permit a programs-writer to select music elements which are not from the selected music element scale. One or more melodies, comprised of one or more music elements, preferably selected from the selected music element scale, are next created by the programs-writer. In a preferred embodiment, the programs-writer next assigns the background composition and melodies to one or more beams. By assigning a melody comprised of multiple music elements to a beam, a programs-creator can allow a performer to play an entire melody, in some cases comprising as many as one hundred twenty-eight sequential music elements, simply by breaking a single beam for an extended period of time. Programs created in such a manner can allow even a novice performer to compose and play/perform music which is not disharmonious and which is pleasing to an audience. A preferred software control system allows a programs-creator to not only create programs containing melodies and background compositions, but also to create transposition tables. Transposition tables allow a performer to add another dimension to a performance while keeping the sounds produced during the performance harmonious. Transposition tables allow a programs-creator to define how one or more music elements are to be modified during a performance. The transpose table creation process preferably comprises selecting a particular transposition and selecting at least one first note to be played when performing the transposition is undertaken, thereby signaling to the performer that the transposition has occurred. Thus, for example, a programs creator can use a transposition table to specify that all music elements of all melodies currently being played should be shifted up one octave, while the background composition should remain unchanged. The software control system preferably allows a programs-writer to assign a transposition table, or series of transposition tables, to at least one beam, foot switch, or other switch associated with the present invention, such that a performer effect a transposition when desired. Alternatively, the software control system can allow a programs-writer to force a transposition to occur at a certain time after the program has begun. Such a system may be more entertaining in some of the embodiments described below, such as those for rehabilitation, especially those used for rehabilitating children. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory and are intended to provide further explanation of the invention as claimed.

Water purification apparatus and method of using the same

A water purification apparatus, comprising a water pump, wherein the water pump inlet port receives water from an external source, a nonreturn valve in fluid communication with the water pump outlet port, and an ionizer chamber in fluid communication with the nonreturn valve output end, wherein the ionizer chamber doses a bacteriacide into water contained in the ionizer chamber. The apparatus also includes a filter, wherein the input end of the filter is in fluid communication with the output end of the ionizer chamber.

1. A water purification apparatus, comprising: a water pump, wherein the water pump has an inlet port and an outlet port, and wherein the water pump inlet port receives water from an external source; a nonreturn valve, wherein the nonreturn valve has an input end and an output end, wherein the nonreturn valve inlet port is in fluid communication with the water pump outlet port; an ionizer chamber, wherein the ionizer chamber has an inlet port and an outlet port, wherein the ionizer chamber inlet port is in fluid communication with the nonreturn valve output end, and wherein the ionizer chamber doses a bacteriacide into water contained in the ionizer chamber; and, a filter, wherein the filter has an input end and an output end, wherein the input end of the filter is in fluid communication with the output end of the ionizer chamber. 2. The apparatus of claim 1, wherein the water pump is hand operated. 3. The apparatus of claim 1, further comprising an ionizer control means which controls dosing of the bacteriacide into the water contained in the ionizer chamber. 4. The apparatus of claim 3, wherein the ionizer control means controls dosing of the bacteriacide by applying an electrical current to the bacteriacide. 5. The apparatus of claim 3, wherein the ionizer control means determines the amount of bacteriacide to be dosed into the water based on the impedance of the water. 6. The apparatus of claim 3, wherein the ionizer control means determines the amount of bacteriacide to be dosed into the water based on the average pump volume per stroke. 7. The apparatus of claim 3, wherein the ionizer control means controls dosing of the bacteriacide by applying an electrical current to the bacteriacide, and wherein the ionizer control means determines the amount of bacteriacide to be dosed into the water based on the impedance of the water. 8. The apparatus of claim 1, wherein the bacteriacide is colloidal silver. 9. The apparatus of claim 3, wherein the bacteriacide is colloidal silver. 10. The apparatus of claim 9, wherein the ionizer control means controls dosing of the colloidal silver by applying an electrical current to at least one silver bar. 11. The apparatus of claim 9, wherein the ionizer control means determines the amount of colloidal silver to be dosed into the water based on the impedance of the water. 12. The apparatus of claim 9, wherein the ionizer control means determines the amount of colloidal silver to be dosed into the water based on the average pump volume per stroke. 13. The apparatus of claim 9, wherein the ionizer control means controls dosing of the colloidal silver by applying an electrical current to at least one silver bar, and wherein the ionizer control means determines the amount of colloidal silver to be dosed into the water based on the impedance of the water. 14. The apparatus of claim 3, wherein the water pump has a rotatable handle. 15. The apparatus of claim 14, further comprising a power supply, and wherein the position of the water pump handle determines whether power from the power supply is applied to the ionizer control means. 16. The apparatus of claim 1, wherein the filter is a multi-stage filter. 17. The apparatus of claim 1, wherein the filter is a two stage filter. 18. The apparatus of claim 16, wherein the multi-stage filter has a sub-micron rating. 19. The apparatus of claim 16, wherein at least one stage of multi-stage filter is comprised of a ceramic filter. 20. The apparatus of claim 16, at least one stage of the multi-stage filter is comprised of a charcoal filter. 21. The apparatus of claim 16, wherein the multi-stage filter has a sub-micron rating, wherein at least one stage of the multi-stage filter is comprised of a ceramic filter, and wherein at least one stage of the multi-stage filter is comprised of a charcoal filter. 22. The apparatus of claim 17, wherein a first stage of the two stage filter is a ceramic filter, and a second stage of the two stage filter is a charcoal filter. 23. The apparatus of claim 22, wherein the charcoal filter stage is located nearest the outlet end of the filter. 24. The apparatus of claim 1 further comprising a strainer, wherein the strainer has a first end and a second end, and a tube, wherein the tube has a first end and a second end, wherein the first end of the tube is connected to the water pump input port and the second end of the tube is connected to the first end of the strainer. 25. A method for operating a portable water purification apparatus, comprising: rotating a handle associated with a water pump from a stowage position to an operating position; operating the water pump to cause water to enter the portable water purification apparatus; monitoring the impedance of the water within the water purification apparatus; dosing a bacteriacide into the water within the water purification apparatus based on the monitored impedance; filtering the dosed water; and, outputting the filtered water. 26. The method of claim 25, wherein the bacteriacide is colloidal silver. 27. The method of claim 25, wherein rotating the handle from a stowage position to an operating position causes a magnet within the water pump to be able to trigger an electrical circuit that monitors the impedance of the water.

<SOH> BACKGROUND OF THE INVENTION <EOH>The steady growth of tourism in remote areas has placed an undesirable burden on government authorities to provide facilities in such areas for the benefit of tourists and vacationers. By way of example, one facility frequently required by visitors is clean drinking water. Unfortunately, most water treatment apparatii are large and can have a significant impact on the local environment, both from a physical perspective and an aesthetic perspective. Clearly, the provision of such facilities can decrease the appeal of the wilderness and the ability of tourists and other visitors to visit these sites. Additionally, there are many areas which are so little used and so remote that government authorities are unable to provide and maintain the necessary facilities. Such facilities would also be subject to destruction and/or damage, such as by natural occurrences, vandals, and the like. It is relatively well known that Ag+ ions, also referred to as “colloidal silver”, in measured doses are toxic to lower life forms such as bacteria, but are not toxic to humans. In fact there is evidence available that colloidal silver provides significant benefits to the functioning of the human body and offers particular benefits to the immune system. Various apparatii have been used for dosing water with silver ions to take advantage of the bactericide effects of silver. However, in general, such apparatii have been used only in reticulated water systems, for example, where town water is connected.

<SOH> SUMMARY OF THE INVENTION <EOH>The present invention is directed to a water purification apparatus and methods of using the same that substantially obviates one or more of the problems due to limitations and disadvantages of the related art. One embodiment of the present invention provides a light weight, compact, self contained, portable water treatment apparatus. Such an embodiment is particularly well suited for use by the military and/or first responders, both in the field and post incident. The water purification apparatus can also allow travelers and adventurers to sterilize and filter water from streams, water holes, puddles, dams and the like, thus converting it to potable water for drinking and living. The invention has particular application to the treatment of water for human consumption and the destruction or removal of bacteria and microorganisms which are dangerous to human health. The invention can also remove terrorist introduced bacteria such as Anthrax, and viruses with a pore size greater than or approximately equal to that of small pox, such as, but not limited to, faecal coliform. In one embodiment water from external sources enters the unit by way of a flexible tube, one end of which is connected to a hand pump associated with the unit. The water leaves the hand pump chamber and passes through a colloidal silver ionizer where effectively all the pathogenic bacteria are killed. The water can also pass through a filter, such as, but not limited to, a combination dual filter with sub-micronic rating. Such a filter should capable of stopping Anthrax spores and bacteria, faecal coliform bacteria, and virus groups with a pore size greater than or similar to small pox from passing through the filter. Such filtering can preferably be accomplished even at a flow rate in excess of 500 ml per minute. Although such a filter arrangement is preferred, it should be apparent to one skilled in the art that alternative filter arrangements, including increasing the number of filters or layers of filtering material, may be substituted therefor without departing from the spirit or the scope of the invention. Light weight and small, one embodiment of the unit fits in a space smaller than two water bottles in a standard backpack, and offers a net weight decrease. An embodiment of the unit is also capable of operating at least two months without battery replacement. In still another embodiment, the filter assembly can be easily removed for cleaning after operating with dirty water sources. Additional features and advantages of the invention will be set forth in the description which follows, and in part will be apparent from the description, or may be learned by practice of the invention. The objectives and other advantages of the invention will be realized and attained by the structure particularly pointed out in this written description as well as the appended drawings. It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory and are intended to provide further explanation of the invention.

Apparatus, system, and methods for status monitoring and control of cable television network components

Apparatus, systems, and methods to cost effectively monitor and control distributed devices within a cable television network are disclosed. In particular, a gateway transponder and a device transponder are provided. A device transponder can be associated with a device other than a power supply located in a cable television network. The device transponder provides an efficient mechanism for exchanging control messages between a device where the transponder resides and a network operator management system. A gateway transponder can be associated with a network power supply. A gateway transponder serves as a gateway between a network operator management system and a set of device transponders. In a further feature of the present invention, a very simplified management protocol is provided that simplifies Simple Network Management Protocol (SNMP) messaging and reduces the size of management messages that are exchanged between a gateway transponder and a device transponder.

1. A system for status monitoring and control of cable television network components with a cable television network, comprising: a plurality of cable television network components; at least one device transponder associated with a cable television network component within said plurality of cable television network components, wherein said at least one device transponder facilitates monitoring and management of the cable television network component; and at least one gateway transponder associated with one of the cable television network components, wherein said at least one gateway transponder serves as a gateway between a cable operator's management system and a set of said at least one device transponders. 2. The system of claim 1, wherein said at least one device transponder, comprises: a controller that manages operation of said at least one device transponder; an X10 interface that provides an interface between said controller and the at least one gateway transponder; a protocol translator that translates control messages received from the cable operator's management system into messages having a simplified management protocol; and a device interface coupled to said controller and the cable television network component that the device transponder is associated with for monitoring and managing the cable television network component. 3. The system of claim 1, wherein said at least one gateway transponder, comprises: a controller that manages operation of said at least one gateway transponder; an X10 interface that provides an interface between said controller and communication paths to device transponders within said at least one device transponder; a DOCSIS interface that provides an interface between the cable operator's management system and said controller; a protocol translator that translates control messages received from the cable operator's management system into messages having a simplified management protocol; and a device interface coupled to said controller and the cable television network component with which the gateway transponder is associated. 4. The system of claim 3, wherein the simplified management protocol comprises vSNMP, wherein the vSNMP protocol operates in a poll mode, wherein vSNMP messages are constructed using the SNMPv1, SMIv1 specification with the following changes: All Messages The initial Tag and Length are omitted, since the message length is provided by the MAC layer. The Version field is omitted, since it is not required by the transponders. The Community String field is omitted, since security is not an issue. GetRequest The error-status field is omitted, since it is always null. The error-index field is omitted, since it is always null. The variable-bindings field is omitted, since only a single VarBind is supported. The value field is omitted, since it is always null. GetResponse The error-index field is omitted, since it is always null. The variable-bindings field is omitted, since only a single VarBind is supported. The identity field is omitted, since it is always the same as the request. SetRequest The error-status is omitted since it is always null. The error-index is omitted, since it is always null. The variable-bindings field is omitted, since only a single VarBind is supported. SetResponse The error-index is omitted, since there is only a single VarBind. The variable-bindings field is omitted, since only a single VarBind is supported. The VarBind is omitted, since a response with no error indicates the value was set correctly and there is only a single gateway to each transponder. The identity field is omitted, since it is always the same as the request. The value is omitted. Traps The agent address is omitted, since the IP address can be supplied only by the gateway. The time-stamp is omitted since the time is supplied by the gateway transponder. 5. The system of claim 1, wherein each gateway transponder within said at least one gateway transponder is associated with a network power supply. 6. A method to transmit control messages to a cable TV network device, comprising: (a) receiving a DOCSIS command message; (b) determining whether the DOCSIS command is for a network power supply associated with a gateway transponder or for another device; (c) when the DOCSIS command is for a device other than a network power supply, converting the DOCSIS command to a vSNMP command; (d) formatting the vSNMP command using an X10 protocol; and (e) transmitting the vSNMP command with the X10 protocol to a device transponder. 7. A method to receive control messages from a cable TV network device received by a gateway transponder from a device transponder, comprising: (a) receiving a vSNMP message using an X10 protocol; (b) translating the vSNMP message into a DOCSIS command; (c) formatting a DOCSIS message based on the DOCSIS command; and (d) transmitting the DOCSIS message to a network operator's management system.

<SOH> BACKGROUND OF THE INVENTION <EOH>1. Field of Invention The present invention relates to communication transmission networks, and more particularly to cable television transmission networks. 2. Related Art In a cable television transmission network, radio frequency signals are transmitted bi-directionally between a plurality of subscriber premises and a central headend facility. The bi-directional capability is achieved using a frequency division multiplexing method wherein signals higher than approximately 50 MHz propagate toward subscriber homes and signals lower than approximately 40 MHz propagate toward the headend. These transmission networks commonly employ a hybrid fiber-coax (HFC) architecture, with fiber optic cables used for long distance trunks, and coaxial cable employed for the feeders that run through the neighborhoods served by the network. The coaxial cables also carry a low frequency AC voltage that powers the active network elements that are installed in the coaxial distribution network. Specifically, 60 to 90 volt power signals are carried within a coaxial cable to provide power in cable television networks. Network power supplies that are distributed throughout a cable television network provide this power to amplifiers, optical nodes and other components. Power blocks or other means are used to segment the power, such that each power supply powers only a portion of the network equipment and is isolated from other network power supplies. Within a cable television network, there are often many power segments. Transponders have been developed and deployed to monitor and control cable television network power supplies. A transponder is a telemetry device used to exchange management and control information between a management system and a managed device. Transponders are generally located within network power supplies, and employ a variety of communication protocols that allow cable operators to monitor the power supplies from an operations office, typically located at a cable headend. The protocols used include proprietary protocols, a Hybrid Management Sublayer (HMS) protocol, and Data Over Cable Service Interface Specification (DOCSIS). HMS is a set of protocols, management information bases (MIBs), and other specifications standardized by the Society of Cable Telecommunications Engineers to provide remote management of cable television network equipment. DOCSIS is a collection of specifications developed by Cable Television Laboratories that describe protocols and procedures for providing Internet, telephony, video on demand, and other data services over a cable television network. DOCSIS and HMS standards are in wide use throughout the cable industry. Similarly, a wide range of transponders have been developed and deployed for monitoring amplifiers, optical nodes, and other active devices within a cable television network. These transponders use proprietary legacy communications protocols, as well as standards-based status monitoring protocols, such as HMS. The use of these legacy proprietary and HMS status monitoring protocols in amplifiers and optical nodes has several significant drawbacks that make their use unattractive to network operators, including the need for expensive headend controllers, slow data communications performance, and high cost. Moreover, network providers have widely deployed DOCSIS capabilities in their networks. A status monitoring transponder that interoperates with the existing DOCSIS infrastructure can be developed. However, deployment of such a transponder throughout all components within a cable network would result in larger device size, increased power consumption, and higher network costs. While cost effective to place a DOCSIS status monitoring transponder in network power supplies, it is not cost effective to deploy a DOCSIS status monitoring transponder in each of the amplifiers, optical nodes and other components that are distributed throughout a cable network. What is needed is a cost effective apparatus, system, and methods for active monitoring and control of network components distributed throughout a cable television network.

<SOH> SUMMARY OF THE INVENTION <EOH>The present invention provides apparatus, systems, and methods to cost effectively monitor and control distributed devices within a cable television network. In particular, a gateway transponder and a device transponder are provided. A device transponder can be associated with a device other than a power supply located in a cable television network. The device transponder provides an efficient mechanism for exchanging control messages between a device where the transponder resides and a network operator management system. A gateway transponder can be associated with a network power supply. A gateway transponder serves as a gateway between a network operator management system and a set of device transponders. A gateway transponder serves to receive messages using the DOCSIS protocol from a network operator's management system and translate those messages using a management layer protocol and a protocol for low frequency signaling on power lines, such as X10, for transmittal to a device transponder. Similarly, a gateway transponder can receive messages from a device transponder using the X10 protocol and translate those messages into a DOCSIS format for transmittal to a network operator's management system. In other embodiments, power line protocols supporting low frequency signaling, other than the X10 protocol, can be used. In further embodiments, messages could be transmitted on the radio frequency (RF) channel of the cable TV coaxial cable using an RF signaling protocol. In a further feature of the present invention, a very simplified management protocol is provided that simplifies Simple Network Management Protocol (SNMP) messaging. This protocol, referred to herein as vSNMP for very simplified network management protocol, reduces the size of management messages that are exchanged between a gateway transponder and a device transponder. There are numerous advantages to the present invention. One advantage is the reduction or elimination of expensive and complex proprietary monitoring system headend controllers that currently support transponders in cable television networks. Furthermore, the present invention supports complete cable television network monitoring via existing DOCSIS infrastructure without the need for specialized proprietary software. Finally, inexpensive power line carrier technology can be used with device transponders, where cost, space and power are restricted. Thereby, enabling network operators to deploy DOCSIS hardware and technology—which is typically more expensive and complex—only where needed. Further embodiments, features, and advantages of the present inventions, as well as the structure and operation of the various embodiments of the present invention, are described in detail below with reference to the accompanying drawings.

Release agent and release sheet

A release agent comprising (A) an olefin-based elastomer having a density of not less than 0.855 g/cc and less than 0.868 g/cc, and (B) an ethylene-α-olefin copolymer having a density of from 0.868 g/cc to 0.970 g/cc as main components, wherein the difference in average density between the components (A) and (B) is not less than 0.005 g/cc and the mixing weight ratio of the component (A) to the component (B) is from 90:10 to 10:90. Such a release agent contains no silicone-based components generating undesired gasses, can exhibit not only a good releasability to various adhesives but also a less fluctuation in peeling force, and can maintain a low peeling force even when the release agent is bonded to an adhesive and preserved under a heating condition.

1. A release agent comprising (A) an olefin-based elastomer having a density of not less than 0.855 g/cc and less than 0.868 g/cc, and (B) an ethylene-α-olefin copolymer having a density of from 0.868 g/cc to 0.970 g/cc as main components, wherein the difference in average density between said components (A) and (B) is not less than 0.005 g/cc and the mixing weight ratio of the component (A) to the component (B) is from 90:10 to 10:90. 2. A release agent according to claim 1, wherein said component (A) is a copolymer of ethylene with at least one comonomer selected from a group consisting of propylene, butene and hexene. 3. A release agent according to claim 1, wherein said component (A) and/or said component (B) have a functional group. 4. A release agent according to claim 1, wherein said component (A) and said component (B) exhibit an endothermic peak of not less than 1 J/g as measured at the temperature of from 0 to 200° C. using a differential scanning calorimeter. 5. A release sheet comprising a sheet-like substrate and a release layer formed at least one surface of the substrate, which is composed of the release agent as defined in claim 1. 6. A release sheet according to claim 5, wherein the release layer is composed of the release agent obtained by cross-linking the component (A) or (B) with a reactive compound capable of reacting with the functional group contained therein.

<SOH> BACKGROUND ART <EOH>Release films include a substrate and a release layer formed on at least one surface of the substrate, and have been extensively used for protecting an adhesive surface or a bonding surface. Release agents used for forming the release layer are generally classified into silicone-based release agents and non-silicone-based release agents. The silicone-based release agents are excellent in releasability, but cause problems such as failure (corrosion, contact troubles, etc.) due to a trace amount of siloxane-based gases generated therefrom especially in the application fields such as electronic equipments and electric equipments. As the non-silicone-based release agents, there have been proposed release agents which are lessened in surface energy by using halogen compounds such as fluorides therein, release agents composed of polyvinyl carbamate (reaction product of PVA and C 18 H 37 NCO) as a long chain alkyl-containing polymer, release agents composed of a reaction product of polyethylene imine and C 18 H 37 NCO, release agents composed of a copolymer containing perfluoroalkylvinyl as a main component, release agents composed of a polyethylene-based resin composition, etc. The non-silicone-based release agents are free from generation of the siloxane-based gases, require no use of combination of special catalysts nor operations such as heat treatments, attain a good releasability only by drying after its application, and have advantages such as long pot life. However, in general, the non-silicone-based release agents need a larger peeling force and tend to be deteriorated in heat resistance as compared to that of the silicone-based release agents, thereby causing problems such as increase in peeling force when the release agents are bonded to an adhesive and preserved under a heating condition. Further, the non-silicone-based release agents have the following peculiar problems depending upon materials used therefor. For example, the release agents which are lessened in surface energy by using halogen compounds such as fluorides therein, cannot meet a current demand of dehalogenation for decreasing environmental burden upon disposal of wastes. The release agents composed of a copolymer containing perfluoroalkylvinyl as a main component exhibit an excellent releasability, but are usually insoluble in organic solvents and dissolved only in specific and expensive solvents such as FR thinners, resulting in considerably limited applications. Also, as the release agents composed of a polyethylene-based resin composition, there are known release agents containing a low-density polyethylene-based resin as a main component (for example, refer to Japanese Patent Publication (KOKOKU) No. 51-20205 (1976) and Japanese Patent Application Laid-Open (KOHYO) 11-508958 (1999)), and release agents containing a high-density polyethylene-based resin as a main component (for example, refer to Japanese Patent Application Laid-Open (KOKAI) Nos. 2000-239624 and 2000-119411). The release agents containing a low-density polyethylene-based resin as a main component require a large peeling force, and tend to cause such a problem that when used as a protective film for a pressure-sensitive adhesive layer, a part of the adhesive layer is transferred to the surface of the release layer upon peeling, or the surface of the adhesive layer after peeling is undesirably peeled and suffers from a pulse-like shape called “stick slip”. Whereas, the release agents containing a high-density polyethylene-based resin as a main component tend to have problems such as deteriorated adhesion strength to a substrate composed of a polar polymer and a large peeling force.

<SOH> BRIEF DESCRIPTION OF THE DRAWING <EOH>FIG. 1 is an explanatory view showing a method of drawing a base line relative to an endothermic peak obtained by DSC measurement. detailed-description description="Detailed Description" end="lead"?

Sustained-release tramadol formulations with 24-hour efficacy

A sustained-release tramadol formulation oral administration is provided which, upon initial administration of one dose, provides an analgesic effect within 2 hours, which analgesic effect continues for at least 24 hours after administration

1. A once daily oral pharmaceutical composition for controlled release of tramadol or a salt thereof, in which the composition, upon initial administration of one dose, provides an onset of analgesic effect within 2 hours, which analgesic effect continues for at least 24 hours after administration. 2. A once daily oral pharmaceutical composition for controlled release of tramadol or a salt thereof, wherein the composition, upon initial administration of one dose, provides a mean plasma concentration of at least 100 ng/mL within 2 hours of administration and continues to provide a mean plasma concentration of at least 100 ng/ml for at least 22 hours after administration. 3. A once daily oral pharmaceutical composition of claim 2 which continues to provide a mean plasma concentration of at least 100 ng/mL for at least 23 hours after administration. 4. A once daily oral pharmaceutical composition of claim 2 which continues to provide a mean plasma concentration of at least 100 ng/mL for at least 24 hours after administration. 5. The once daily oral pharmaceutical composition of claim 1, wherein said pharmaceutical composition comprises about 200 mg of tramadol or a salt thereof. 6. A once daily oral pharmaceutical composition for controlled release of tramadol or a salt thereof comprising 100 mg of tramadol or a salt thereof, wherein the composition, upon initial administration of one dose, provides a mean plasma concentration of at least 50 ng/mL within 2 hours of administration and continues to provide a mean plasma concentration of at least 50 ng/mL for at least 22 hours after administration. 7. A once daily oral pharmaceutical composition of claim 6 which continues to provide a mean plasma concentration of at least 50 ng/mL for at least 23 hours after administration. 8. A once daily oral pharmaceutical composition of claim 6 comprising 300 mg of tramadol or a salt thereof, wherein the composition, upon initial administration of one dose, provides a mean plasma concentration of at least 150 ng/mL within 2 hours of administration and continues to provide a mean plasma concentration of at least 150 ng/mL for at least 22 hours after administration. 9. A once daily oral pharmaceutical composition of claim 8 which continues to provide a mean plasma concentration of at least 150 ng/mL for at least 23 hours after administration. 10. A once daily oral pharmaceutical composition of claim 8 which continues to provide a mean plasma concentration of at least 150 ng/mL for at least 24 hours after administration. 11. A one daily oral pharmaceutical composition for controlled release of tramadol or a salt thereof comprising 200 mg of tramadol or a salt thereof, wherein upon initial administration of 400 mg, the composition provides a mean plasma concentration of at least 200 ng/mL for at least 22 hours after administration. 12. A once daily oral pharmaceutical composition of claim 11 which upon said administration provides a mean plasma concentration of at least 190 ng/mL for at least 23 hours after administration. 13. A once daily oral pharmaceutical composition of claim 11 which upon said administration provides a mean plasma concentration of at least 180 ng/mL for at least 24 hours after administration. 14. The once daily oral pharmaceutical composition of claim 6 wherein the mean maximum plasma concentration (Cmax) is less than 100 ng/mL. 15. The once daily oral pharmaceutical composition of claim 2 wherein the mean maximum plasma concentration (Cmax) is less than 300 ng/mL. 16. The once daily oral pharmaceutical composition of claim 2 wherein the mean maximum plasma concentration (Cmax) is less than 200 ng/mL. 17. The once daily oral pharmaceutical composition of claim 2 wherein the mean maximum plasma concentration (Cmax) is less than 2.2 times the mean plasma concentration obtained 24 hours after administration (C24h). 18. The once daily oral pharmaceutical composition of claim 8 wherein the mean maximum plasma concentration (Cmax) is less than 300 ng/mL. 19. The once daily oral pharmaceutical composition of claim 8 wherein the mean maximum plasma concentration (Cmax) is less than two times the mean plasma concentration obtained 24 hours after administration (C24h). 20. The once daily oral pharmaceutical composition of claim 11 wherein the mean maximum plasma concentration (Cmax) is less than 2.3 times the mean plasma concentration obtained 24 hours after administration (C24). 21. The once daily oral pharmaceutical composition of claim 2, wherein the median time to the mean maximum plasma concentration (tmax) is between 2 and 10 hours. 22. The once daily oral pharmaceutical composition of claim 21 wherein the tmax is between 3 and 6 hours. 23. The once dailhy oral pharmaceutical composition of claim 22 wherein the tmax is between 5 and 6 hours. 24. A once daily oral pharmaceutical composition for controlled release of tramadol or a salt thereof comprising 100 mg of tramadol or a salt thereof, wherein the composition, upon initial administration of one dose, provides an O-desmethyltramadol mean plasma concentration of at least 11 ng/mL within 2 hours of administration and continues to provide an O-desmethyltramadol mean plasma concentration of at least 12 ng/mL for at least 24 hours after administration. 25. A once daily oral pharmaceutical composition of claim 24 comprising 200 mg of tramadol or a salt thereof, wherein the composition, upon initial administration of one dose, provides an O-desmethyltramadol mean plasma concentration of at least 24 ng/mL within 2 hours of administration and continues to provide an O-desmethyltramadol mean plasma concentration of at least 25 ng/mL for at least 24 hours after administration. 26. A once daily oral pharmaceutical composition of claim 24 comprising 300 mg of tramadol or a salt thereof, wherein the composition, upon initial administration of one dose, provides an O-desmethyltramadol mean plasma concentration of at least 32 ng/ml within 2 hours of administration and continues to provide an O-desmethyltramadol mean plasma concentration of at least 32 ng/mL for at least 24 hours after administration. 27. A once daily oral pharmaceutical composition of claim 25 wherein upon initial administration of 400 mg, the composition provides an O-desmethyltramadol mean plasma concentration of at least 50 ng/mL within 2 hours of administration and continues to provide an O-desmethyltramadol mean plasma concentration of at least 50 ng/mL for at least 24 hours after administration. 28. The once daily oral pharmaceutical composition of claim 1, wherein said composition is a tablet. 29. The formulation of claim 1, wherein between 10% and 40% of the agent is released from the formulation between 0 and about 2 hours of measurement, between about 30% and 60% of the agent is released from the formulation between 2 and about 7 hours of the measurement, between about 50% and 80% of the agent is released from the formulation between 7 and about 12 hours of measurement, and between about 80% and 100% of the agent is released from the formulation after about 20 hours of measurement. 30. A once daily oral pharmaceutical composition of claim 1 having a dissolution rate in vitro when measured with HPLC-USP apparatus Type 1 at 100 rpm in 50 mM sodium phosphate buffer at pH 6.8, from about 5% to about 30% after 1 hour; from about 15% to about 40% after 2 hours; from about 20% to about 50% after 4 hours, from about 30% to about 70% after 8 hours; from about 40% to about 90% after 12 hours; from about 50% to about 100% after 16 hours; from 60% to about 100% after 24 hours. 31. A once daily oral pharmaceutical composition of claim 1 having a dissolution rate in vitro when measured with HPLC-USP apparatus Type 1 at 100 rpm in 50 mM sodium phosphate buffer at pH 6.8, from about 10% to about 25% after 1 hour; from about 15% to about 30% after 2 hours; from about 25% to about 40% after 4 hours, from about 40% to about 55% after 8 hours; from about 60% to about 75% after 12 hours; from about 70% to about 90% after 16 hours; from about 90% to about 100% after 24 hours. 32. The once daily oral pharmaceutical composition of claim 30 wherein the composition comprises 200 mg of tramadol or a salt thereof. 33. The once daily oral pharmaceutical composition of claim 31 wherein the composition comprises 200 mg of tramadol or a salt thereof. 34. The once daily oral pharmaceutical composition of claim 2 wherein said pharmaceutical composition comprises about 200 mg of tramadol or a salt thereof. 35. The once daily oral pharmaceutical composition of claim 3 wherein said pharmaceutical composition comprises about 200 mg of tramadol or a salt thereof. 36. The once daily oral pharmaceutical composition of claim 4 wherein said pharmaceutical composition comprises about 200 mg of tramadol or a salt thereof. 37. The once daily oral composition of claim 2 wherein said composition is a tablet. 38. The once daily oral composition of claim 6 wherein said composition is a tablet. 39. The once daily oral composition of claim 11 wherein said composition is a tablet. 40. The once daily oral composition of claim 24 wherein said composition is a tablet.

<SOH> BACKGROUND OF THE INVENTION <EOH>Tramadol Pharmaceutical Formulations Tramadol hydrochloride (HCl) was developed by GrOnenthal GmbH, Germany. It has been marketed in Germany since 1977 (eg. Tramal™), and in the United States as Ultram® since 1995. The efficacy and safety profile of tramadol HCl make it highly suitable as a long-term treatment for chronic pain. Tramadol HCl is a synthetic, centrally acting analgesic that has been shown to be effective in a variety of acute and chronic pain states. In particular, tramadol HCl, in both immediate and slow-release formulations, in conjunction with non-steroidal anti-inflammatory drugs (NSAIDs) (Roth SH “Efficacy and safety of tramadol HCl in breakthrough musculoskeletal pain attributed to osteoarthritis”. J. Rheumatol 1998; 25:1358-1363. Wilder-Smith CH et al. “Treatment of severe pain from osteoarthritis with slow-release tramadol or dihydrocodeine in combination with NSAID's: a randomized study comparing analgesia, antinociception and gastrointestinal effects”. Pain 2001; 91:23-31.), has been demonstrated to reduce pain attributed to osteoarthritis (OA). After oral administration, tramadol HCl is rapidly and almost completely absorbed, and it is extensively metabolized. The major metabolic pathways appear to be N- and O-demethylation and glucuronidation or sulfonation in the liver. Only one metabolite, mono-O-desmethyltramadol (M1), is pharmacologically active, which has an approximate 200-fold higher affinity for the μ-opioid receptor than racemic tramadol (DeJong R. “Comment on the hypoalgesic effect of tramadol in relation to CYP2D6” (comment) Pain Dig 1997; 7:245; Kogel B. et al “Involvement of metabolites in the analgesic action of tramadol” Proc. 9 th World Congress on Pain, Vienna, 1999). In healthy humans, tramadol is demethylated by the polymorphic enzyme cytochrome P450 2D6 (CYP2D6) to the M1 metabolite. The mechanism of action of tramadol HCl is not completely understood. Animal models indicate that the drug (and its active M1 metabolite) acts as an opiate agonist, apparently by selective activity at the μ-receptor. In addition to opiate agonist activity, tramadol HCl inhibits re-uptake of certain monoamines (norepinephrine, serotonin) which appears to contribute to the drug's analgesic effect. The antinociceptic effect of tramadol HCl is only partially antagonized by naloxone in some tests in animals and humans. In addition, because of the drug's opiate agonist activity, it has been suggested that tramadol HCl may produce dependence; however, its abuse potential appears to be low, and tramadol HCl is not “subject to control” under the United States Federal Controlled Substances Act of 1970 as a scheduled drug. Immediate release formulations of tramadol HCl are well known in the art. Such formulations, however, require frequent dosing in order to provide effective pain relief. Lack of compliance with high frequency dosing regimens can result in inconsistent plasma drug concentrations and accordingly less consistent analgesia. Twice daily formulations are available and are desirable over immediate release formulations as they provide longer periods of analgesia after administration and require less frequent dosing. A once daily formulation is even more desirable for increased effectiveness, safety and convenience. A critical factor influencing the rate of absorption, and thereby the safety and efficacy, of an active pharmaceutical ingredient by the body following oral administration in a tablet or other solid dosage form is the rate of release of the active pharmaceutical ingredient from that dosage form post ingestion. It is thus the ability of the dosage form components to control the release rate that constitutes the basis for the so-called controlled-release, extended-release, sustained-release or prolonged-action pharmaceutical preparations that are designed to produce slow, uniform release and absorption of active pharmaceutical ingredients over a period of hours, days, weeks or months. The advantages of such controlled-release formulations include: a reduction in the required administration frequency of the drug as compared to conventional immediate release dosage forms, often resulting in improved patient compliance; the maintenance of a stable concentration of the drug in the body and thereby a sustained therapeutic effect over a set period of time; and a decreased incidence and intensity of undesired side effects of the active agent caused by the high plasma concentrations that occur after administration of immediate-release dosage forms. Many materials have been proposed and developed as matrices for the controlled release of active pharmaceutical ingredients. These include, for example, polymeric materials such as polyvinyl chloride, polyethylene amides, ethyl cellulose, silicone and poly (hydroxymethyl methacrylate). See e.g., U.S. Pat. No. 3,087,860 to Endicott et al; U.S. Pat. No. 2,987,445 to Levesque et al.; Salomon et al. Pharm. Acta Helv., 55, 174-182 (1980); Korsmeyer, Diffusion Controlled Systems: Hydrogels, Chap. 2, pp 15-37 in Polymers for Controlled Drug Delivery, Ed Tarcha, CRC Press, Boca Raton, Fla. USA (1991); and Buri et al., Pharm. Acta Helv. 55, 189 197 (1980). High amylose starch has also been used for controlled-release purposes and, in particular, recent advances have been made using cross-linked high amylose starch. For example, U.S. Pat. No. 6,284,273 (Lenaerts et al.), which issued Sep. 4, 2001, and No. 6,419,957 (Lenaerts et al.), which issued Jul. 16, 2002, teach a solid controlled release oral pharmaceutical dosage unit in the form of tablets comprising a dry powder of a pharmaceutical product and a dry powder of cross-linked high amylose starch, wherein said cross-linked high amylose starch is a matrix comprising a mixture of about 10-60% by weight of amylopectin and about 40-90% amylose. U.S. Pat. No. 6,607,748 (Lenaerts et al.) which issued on Aug. 19, 2003 describes a process for making a cross-linked high amylose starch which is known under the name Contramid®. Extended Release Formulations Known in the Art Extended and controlled release formulations relating to tramadol HCl have been suggested, examples being described in: United States Patent Application Publication No. 2003/0143270, (Deboeck et al.) published Jul. 31, 2003; U.S. Pat. No. 6,254,887 (Miller et al.) issued Jul. 3, 2001; United States Patent Application Publication No. 2001/0036477 (Miller et al.) published Nov. 1, 2001; U.S. Pat. No. 6,326,027 (Miller et al.) issued Dec. 4, 2001; and U.S. Pat. No. 5,591,452 (Miller et al) issued Jan. 7, 1997; and European Patent No. 1 190 712 (Vanderbist) published Mar. 27, 2002. Although there are some controlled release tramadol HCl formulations on the market which purport to be once-daily formulations, none of these has successfully replaced twice-daily tramadol HCl formulations. Articles have been published in which comparative data between putative “once-daily” tramadol HCl formulations and immediate release tramadol HCl formulations are presented. Adler et al., “A Comparison of Once-Daily Tramadol with Normal Release Tramadol in the Treatment of Pain in Osteoarthritis,” The Journal of Rheumatology (2002) 29(10): 2195-2199; and Bodalia et al., “A Comparison of the Pharmacokinetics, Clinical Efficacy, and Tolerability of Once-Daily Tramadol Tablets with Normal Release Tramadol Capsules,” Journal of Pain and Symptom Management (2003) 25(2): 142-149. Adverse Events from Administration of Tramadol HCl The most frequently reported side effects of tramadol observed in clinical trials in the United States are constipation, nausea, dizziness/vertigo, headache, somnolence and vomiting. These are typical adverse effects of opiate drugs. Seizures and anaphylactoid reactions have also been reported, though the estimated incidence of seizures in patients receiving tramadol HCl is less than 1% (Kazmierczak, R., and Coley, K.: “Doctor letters on prescribing: evaluation of the use of tramadol HCl.” Formulary 32: 977-978, 1997). Adler et al., supra, reports on the results of a clinical study comparing a once daily tramadol formulation to immediate release tramadol in the treatment of pain in osteoarthritis. The authors report similar adverse event profiles for individuals in both treatment groups. Table 2 of Adler et al. indicates that a greater percentage of people who were in the once daily treatment group withdrew due to adverse events than did those in the other treatment group. In Bodalia et al., supra, the authors report comparable tolerability with a 150 mg once daily dose, a 200 mg once daily dose and three doses of a 50 mg normal release tramadol formulation. This article does not however include any information on how to make the formulations which are purported to be “once daily” nor does the article disclose any pharmacokinetic data after a single dose. Citation or identification of any reference in this section shall not be construed as an admission that such reference is available as prior art to the present invention.

<SOH> SUMMARY OF THE INVENTION <EOH>An object of the present invention is to provide an improved sustained-release tramadol formulation with 24-hour effective analgesia. In accordance with one aspect of the present invention, there is provided a once daily oral pharmaceutical composition for controlled release of tramadol or a salt thereof, in which the composition, upon initial administration, provides an onset of analgesic effect within 2 hours, which analgesic effect continues for at least 24 hours after administration. In accordance with another aspect of the present invention, there is provided a once daily oral pharmaceutical composition for controlled release of tramadol or a salt thereof, wherein the composition, upon initial administration of one dose, provides a mean plasma concentration of at least 100 ng/mL within 2 hours of administration and continues to provide a mean plasma concentration of at least 100 ng/mL for at least 22 hours after administration. In an embodiment of the present invention, there is provided a once daily oral pharmaceutical composition for controlled release of tramadol or a salt thereof, wherein the composition, upon initial administration of one dose, provides a mean plasma concentration of at least 100 ng/mL within 2 hours of administration and continues to provide a mean plasma concentration of at least 100 ng/mL for at least 22 hours after administration and wherein the mean maximum plasma concentration (C max ) is less than 2.2 times the mean plasma concentration obtained 24 hours after administration (C 24h ). The term “λ z ” is the apparent terminal elimination rate constant, determined by the slope of the regression during the log-linear phase. The term “AUC 0-Tmax ” is the mean area under the plasma concentration-time curve from time 0 to T max and is used as an indicator of the rate of drug absorption, or metabolite formation. It is calculated as the arithmetic mean of the area under the plasma concentration-time curve from time 0 to T max calculated for each individual participating in the bioavailability study. The term “AUC 0-∞ ” is the mean area under the plasma concentration-time curve extrapolated to infinity It is calculated as the arithmetic mean of the area under the plasma concentration-time curve from time 0 extrapolated to infinity, calculated for each individual participating in the bioavailability study. The term “analgesic effect” is defined for the purposes of the present invention as providing a mean blood plasma concentration of at least about 100 ng/mL of tramadol. The term “C′ max ” is the maximum observed plasma concentration, calculated as the mean of the individual maximum blood plasma concentrations. The term “controlled release” is defined for purposes of the present invention as a method of oral drug delivery where the rate of release of the active pharmaceutical ingredient from the formulation is not solely dependent on the concentration of active pharmaceutical ingredient remaining in the formulation and/or the solubility of the active pharmaceutical ingredient in the medium surrounding the formulation, and where the time course and/or location of release of an active ingredient from a pharmaceutical formulation are chosen to accomplish therapeutic or convenience objectives not offered by conventional dosage forms. The term “half-life” is the apparent terminal elimination half-life. The term “HVD” is the half value duration, that is, the time during which tramadol concentrations are above one half the C′ max . This parameter is an indicator of the shape of the plasma concentration time curve. The term “immediate release” is defined for purposes of the present invention as the release of an active ingredient from a pharmaceutical formulation where the rate of release of the active pharmaceutical ingredient from the pharmaceutical formulation is not retarded by means of a controlled release matrix and where the components of the pharmaceutical formulation are designed such that, upon ingestion, maximum exposure of said active pharmaceutical ingredient to body tissues occurs in the minimum period of time. The term “initial administration” is defined for purposes of the present invention as the first single dose of a formulation containing an active ingredient administered to a patient or subject or the first dose administered to a patient or subject after a suitable washout period. The term “MRT” is the mean residence time, which is an estimate of the average time that a tramadol molecule resides in the body following oral administration. The term “mean maximum plasma concentration” (C max ) is defined for the purposes of the present invention as the maximum mean plasma concentration. The term “mean plasma concentration” is defined for purposes of the present invention as the arithmetic mean blood plasma concentration. 0026a] The term “t max ” is the time at which C max is achieved. The term “T max ” is the time at which the maximum blood plasma concentration is observed for each individual participating in the bioavailability study. The term “Rstart” is the time at which plasma concentrations begin to decline in a log-linear fashion, that is, the time at which either drug absorption or metabolite formation is complete. The word “tramadol”, as used herein shall refer to tramadol, its stereoisomers and its pharmaceutically acceptable salts. The term “steady qtate” is defined for purposes of the present invention as the state, following multiple dose administration, where the rate of drug elimination matches the rate of input and the plasma drug concentrations at a given time within a dosing interval are approximately the same from one dosing interval to another.

Artificial grass lawn for sports fields

The invention relates to an artificial grass lawn suitable for sports fields, which artificial grass lawn consists of a base layer, on which first artificial grass fibres are disposed. In accordance with the invention, the artificial grass lawn is characterized in that said base layer comprises a material having damping properties, which is present thereon and/or therein. Thus the properties of a natural grass field are approximated very closely, and also the style of play on the sports field is positively affected. Furthermore, the artificial grass field thus obtained is substantially free of maintenance and of injury.

1. Artificial grass lawn suitable for sports fields, which artificial grass lawn consists of a base layer, on which first artificial grass fibres are disposed, as well as further artificial grass fibres, which are worked into said base layer, characterized in that said further artificial grass fibres are arranged in such a way as to exhibit damping properties in order to absorb shocks exerted on the lawn during play and to transmit the shocks to the base layer. 2. Artificial grass lawn according to claim 1, characterized in that said further artificial grass fibres exhibite moisture-regulating properties. 3. (canceled) 4. Artificial grass lawn according to claim 1, characterized in that said further artificial grass fibres are smaller in length than said first artificial grass fibres. 5. Artificial grass lawn according to claim 4, characterized in that the length of said further artificial grass fibres is approximately 10%-50% of the length of said first artificial grass fibres. 6. Artificial grass lawn according to claim 1, characterized in that said further artificial grass fibres are monofilaments. 7. Artificial grass lawn according to claim 1, characterized in that said further artificial grass fibres are composed of twisted fibres. 8. Artificial grass lawn according to claim 1, characterized in that said further artificial grass fibres have a helical shape. 9. Artificial grass lawn according to claim 1, characterized in that said further artificial grass fibres have a spiral shape. 10. Artificial grass lawn according to claim 1, characterized in that said further artificial grass fibres are hollow. 11. Artificial grass lawn according to claim 10, characterized in that said further artificial grass fibres are configured as bellows. 12-15. (canceled) 16. Artificial grass lawn according to claim 1, characterized in that said base layer has a closed structure. 17. Artificial grass lawn according to claim 1, characterized in that said base layer has an open structure. 18. Artificial grass lawn according to claim 1, characterized in that said further grass fibres are manufactured from rubber. 19. Artificial grass lawn according to claim 1, characterized in that said further grass fibres are manufactured from a synthetic foam product. 20. Artificial grass lawn according to claim 19, characterized in that said synthetic foam product is an open foam product.