Abstract:
An injection device has a housing ( 34 ), and a carpule container ( 44 ) for receiving a carpule ( 50 ) having a fluid ( 52 ) to be injected and having a piston ( 48 ) displaceable in said carpule ( 50 ). It further has a piston rod ( 38 ) with end plate ( 46 ′) which serves, in the context of an injection, to displace the piston ( 48 ) of a carpule ( 50 ) inserted into the carpule container ( 44 ) and thereby to eject fluid ( 52 ) from the carpule ( 50 ). In order to minimize patient error in adjusting the amount of fluid medication ( 52 ) to be injected, the mechanism includes a first component ( 68 ) and a second component ( 92 ) which link ( 98 ) and interact with each other, to control when the carpule container ( 44 ) can rotate with respect to the housing ( 34 ), and to prevent creation of an axial gap ( 62 ) between end plate ( 46 ′) and piston ( 48 ).

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application is a section 371 of PCT/EP10/05762, filed Sep. 9, 2010 published Mar. 31, 2011 as WO-2011-035 877-A2, and further claims priority from application DE 10 2009 048 497.3 filed Sep. 26, 2009 the entire disclosure of which is hereby incorporated by reference. 
     
    
     FIELD OF THE INVENTION 
       [0002]    The invention relates to an injection device that preferably serves to perform one or more injections, depending on the medication demand of the patient, from a medication reservoir that is also referred to as a “carpule”. The injections occur through an injection needle that can also be referred to as a “hollow needle.” 
       BACKGROUND 
       [0003]    A carpule has a displaceable piston, usually made of an elastomer, and this piston is also referred to as a “plunger.” Upon injection, the plunger is pushed forward, i.e. toward the patient, by a piston rod that is also referred to as a “dosing piston,” in order to expel medication through the injection needle. 
         [0004]    In usual embodiments of such injection devices, the desired motion of the piston can be adjusted in 0.14-mm steps. It is thus necessary, in order to achieve the desired precision in terms of the quantity of medication injected, for the position of the piston at the beginning of an injection to be accurately known. 
         [0005]    With many injection devices the carpule is replaceable, i.e. when the contents of a carpule are exhausted, a new one is inserted into the injection device. After insertion of a new carpule, the location of the piston in it is not accurately known. Even in the case of carpules that are filled automatically with a consistent volume, the location of the piston can fluctuate by approximately +/−0.5 mm. 
         [0006]    In the case of a pen injector in which the carpule can be replaced, it is therefore necessary, after a carpule change, to “preset” the piston rod against the piston of the carpule, i.e. after presetting, a clearance must no longer exist between the piston rod and piston. 
         [0007]    Presetting usually occurs by the fact that the patient, after inserting the carpule and after threading on an injection needle, repeatedly sets a small injection dose and performs “injections” into the air until the piston rod is resting snugly against the piston and medication emerges for the first time from the injection needle. This procedure is called “priming.” In practice, it is important that this operation be as simple and intuitive as possible, since it will otherwise easily be overlooked. 
         [0008]    Pen injectors usually have a holder into which the carpule is inserted and which is mounted on the pen injector. This holder, which can also be referred to as a “carpule container,” is configured on its patient-side, i.e. front, end so that an injection needle can be attached, for example by means of a bayonet connection or a screw thread. 
       SUMMARY OF THE INVENTION 
       [0009]    It is therefore an object of the invention to make available a novel injection device whose structure minimizes any need for priming. 
         [0010]    According to the invention, this object is achieved by structuring the injection mechanism with a linkage including a first component and a second component. The first component is arranged rotatable but not axially displaceable with respect to the housing. The second component is arranged non-rotatable but axially displaceable with respect to the piston rod. The first and second components interact in such a way that, once the end plate of the piston rod abuts against the piston, rotation of the carpule with respect to the housing is blocked, and no axial gap can be inadvertently created between the end plate and the piston. 
     
    
     
       BRIEF FIGURE DESCRIPTION 
         [0011]    Further details and advantageous refinements of the invention are evident from the exemplifying embodiments, in no way to be understood as a limitation, that are described and depicted below. 
           [0012]      FIG. 1  shows an injection device  28  in the form of a so-called pen injector, viewed in the direction of arrow I of  FIG. 2 ; 
           [0013]      FIG. 2  shows the injection device of  FIG. 1  viewed in the direction of arrow II of  FIG. 1 , the cartridge being partly filled with the medication; 
           [0014]      FIG. 3  shows the injection device according to  FIGS. 1 and 2 , in which device the stock of medication is exhausted, and in which the empty carpule must therefore be replaced with a full carpule; 
           [0015]      FIG. 4  shows the same injection device, in which the piston rod has been screwed back, by rotation of the carpule container in the direction of an arrow  58 , in order to enable replacement of the empty carpule; 
           [0016]      FIG. 5  shows the injection device of  FIG. 4 , in which device the carpule container (which still contains the empty carpule) has been removed; 
           [0017]      FIG. 6  shows the injection device of  FIG. 5 , in which device the old carpule has been removed from the carpule container and substituted with a new one; 
           [0018]      FIG. 7  shows the injection device of  FIG. 6 , in which device the carpule container is mounted on the housing of the injection device; 
           [0019]      FIG. 8  shows the injection device of  FIG. 7 , in which device the piston rod has been brought, by rotation of the carpule container, against the piston in the new carpule and is abutting against it with no clearance; 
           [0020]      FIG. 9  is a depiction analogous to  FIG. 8  but at enlarged scale; this figure serves to explain that there must be no air gap present between the piston in the carpule and a plate mounted on the piston rod; 
           [0021]      FIG. 10  is a side view of a carpule container  44 , viewed in the direction of arrow X of  FIG. 11 ; 
           [0022]      FIG. 11  is a longitudinal section viewed along line XI-XI of  FIG. 10 , a filled carpule  50  being located in carpule container  44 ; 
           [0023]      FIG. 12  is a three-dimensional depiction of carpule container  44  of  FIGS. 10 and 11 ; 
           [0024]      FIG. 13  is a three-dimensional depiction of a first component  68  that serves for mounting carpule container  44  on housing  34  and that here carries three ramps that serve to assist priming; 
           [0025]      FIG. 14  is a three-dimensional depiction of component  68  of  FIG. 13 , but viewed from the side of the ramps; 
           [0026]      FIG. 15  is a plan view of component  68  of  FIGS. 13 and 14 , viewed in the direction of arrow XV of  FIG. 14 ; 
           [0027]      FIG. 16  is a three-dimensional depiction of a second component  92  that likewise carries three ramps which interact with the ramps of the component of  FIGS. 13 to 15 ; 
           [0028]      FIG. 17  is a plan view from below of second component  92 , viewed in the direction of arrow XVII of  FIG. 18 ; 
           [0029]      FIG. 18  is a side view looking in the direction of arrow XVIII of  FIG. 17 ; 
           [0030]      FIG. 19  is a plan view of component  92  of  FIG. 16 , viewed in the direction of arrow XIX of  FIGS. 16 and 18 ; 
           [0031]      FIG. 20  is a three-dimensional depiction of second component  92  in accordance with  FIGS. 16 to 19 , and of a compression spring acting on said component; 
           [0032]      FIG. 21  is a depiction analogous to  FIG. 20  but in a side view; the depiction of second component  92  corresponds approximately to the depiction in accordance with  FIG. 18 ; 
           [0033]      FIG. 22  is a plan view of housing  34 , viewed in the direction of arrow XXII of  FIG. 21 ; 
           [0034]      FIG. 23  is an exploded view to explain the interaction of the parts depicted in the preceding figures; 
           [0035]      FIG. 24  is a three-dimensional depiction analogous to  FIG. 23 ; 
           [0036]      FIG. 25  is a depiction which serves to explain the presetting of piston rod  38  ( FIG. 9 ) against piston  48  of a carpule  50 , and the simultaneous locking of second component  92  to prevent rotation; 
           [0037]      FIG. 26  is a depiction showing the locked state of second component  92 , as a result of which piston rod  38  ( FIG. 9 ) is also blocked in terms of twisting but can be moved in an axial direction; 
           [0038]      FIG. 27  is a depiction showing release of the locking of second component  92  before a carpule change, carpule container  44  being rotated in this context in the direction of arrow  58  as depicted; 
           [0039]      FIG. 28  is a longitudinal section viewed in the direction of arrows XXVIII-XXVIII of  FIG. 25 ; 
           [0040]      FIG. 29  is a longitudinal section viewed in the direction of arrows XXIX-XXIX of  FIG. 26 ; 
           [0041]      FIG. 30  is a plan view of housing  34 , viewed in the direction of arrow XXX of  FIG. 31 ; 
           [0042]      FIG. 31  is an exploded view of a simplified embodiment of the injection device; 
           [0043]      FIG. 32  is a depiction analogous to  FIG. 31  but as a three-dimensional view; 
           [0044]      FIG. 33  shows a variant of  FIG. 16  (of the embodiment according to  FIGS. 16 to 29 ) which seems particularly suitable for injection devices in which a replacement of carpules is not possible, namely a component having three ramps  124  that interact with the ramps of the component of  FIGS. 13 to 15 ; 
           [0045]      FIG. 34  is a plan view from below of second component  92 , viewed in the direction of arrow XXXIV of  FIG. 35 ; 
           [0046]      FIG. 35  is a side view looking in the direction of arrow XXXV of  FIG. 34 ; 
           [0047]      FIG. 36  is a plan view of the component of  FIGS. 33 to 35 , viewed in the direction of arrow XXXVI of  FIG. 35 ; 
           [0048]      FIG. 37  shows a variant of second component  92 , having a thread pitch of its ramps  124 ′ that is reduced as compared with  FIG. 35 ; 
           [0049]      FIG. 38  is a plan view of part  92 , viewed in the direction of arrow XXXVIII of  FIG. 37 ; 
           [0050]      FIG. 39  is a highly schematic depiction of parts of the injection device that are important here in the “presetting” procedure after a carpule change; 
           [0051]      FIG. 40  shows the completion of presetting, plate  46 ′ of piston rod  38  abutting against piston  48 , and piston rod  38  being blocked in terms of rotation; and 
           [0052]      FIG. 41  shows a procedure in the context of carpule changing, in which carpule container  44  is rotated in the direction of an arrow  58 , in order to move plate  46 ′ downward. 
       
    
    
     DETAILED DESCRIPTION 
       [0053]      FIGS. 1 and 2  show an injection device  28  that, because of its small size, is also referred to as a “pen injector.” At the rear, i.e. at its end facing away from the patient, it has an adjusting knob  30  for setting a desired injection dose (by rotating knob  30 ), the dose that is set being displayed in a window  32 . During setting, knob  30  is rotated out of housing  34 , and during an injection the patient pushes on knob  30  in the direction of an arrow  36 , i.e. toward the patient. The result is that a piston rod  38 , which is equipped with an external thread  40 , is moved forward in the direction of an arrow  42  toward the patient (who is to be thought of as being at the top in  FIGS. 1 to 12  and  23  to  32 ). External thread  40  is depicted as a left-hand thread. 
         [0054]    In  FIGS. 2 and 3 , piston rod  38  is located in a carpule container  44  that is equipped with two oppositely located windows  46 . 
         [0055]      FIG. 3  shows pen injector  28  with an empty carpule  50  whose shape can best be gathered from  FIG. 11 . The injection fluid  52  ( FIGS. 2 ,  6 ,  7 ,  8 ,  9 ,  11 ) is exhausted, and piston rod  38  is in its maximally forward position. Before a completely filled carpule  50  can be inserted, as shown by  FIG. 11 , piston rod  38  must now be brought into its maximally rearward position. 
         [0056]    In many pen injectors this is done by unscrewing carpule container  44  and then turning piston rod  38  back by turning a separate component that is referred to as a “return ring.” In other pen injectors piston rod  38  is simply pushed manually into housing  34  after carpule container  44  is removed. 
         [0057]    In the case of the injection device depicted, piston rod  38  is screwed back by rotating carpule container  44 , in this case by turning it counterclockwise (see arrow  58  in  FIG. 4 ). (The rotation direction is indicated from the viewpoint of the front end of injector  28 , i.e. as viewed from above.) 
         [0058]    When piston rod  38  has reached its maximally rearward position, carpule container  44  can be removed ( FIG. 5 ) and the empty carpule  50  can be replaced by a full one (see  FIG. 6 ). Carpule container  44  can then be remounted onto housing  34  (see  FIG. 7 ). Piston rod  38  is screwed forward by a rotation opposite to direction  58  ( FIG. 4 ), i.e. in this case by a clockwise rotation (see arrow  60  of  FIG. 8 ). 
         [0059]    As soon as plate  46 ′ of piston rod  38  reaches piston  48  (see  FIG. 8 ), the system automatically locks, i.e. a further rotation of carpule container  44  in a clockwise direction  60  becomes impossible. An elevated torque must now be exerted in order to rotate the carpule container counterclockwise (see arrow  58  of  FIG. 4 ). 
         [0060]    This prevents the patient from inadvertently rotating carpule container  44  counterclockwise even though he or she still wishes to withdraw injections from carpule  50  that is presently inserted. The reason is that a gap  62  ( FIG. 9 ) would thereby be produced between plate  46 ′ and piston  48 , so that the distance over which the latter would be moved forward during a subsequent injection, by plate  46 ′ of piston rod  38 , is too small by an amount equal to the size of said gap  62 , so that the fluid quantity injected in the context of the injection would correspondingly be too small. Correct “presetting” of plate  46 ′ against piston  48  is therefore very important. 
         [0061]    In the locked state ( FIG. 8 ), carpule container  44  can therefore be rotated counterclockwise only with an elevated torque. This provides protection against inadvertent initiation of a carpule change ( FIG. 4 ), similar in effect to the protection that is usual with comparable pen injectors. 
         [0062]    Once carpule container  44  is locked, as will be described below, the patient can begin with injections without needing to specifically prime the pen injector again. This results in very intuitive and easily understandable operation. 
         [0063]      FIGS. 10 to 12  serve to explain carpule container  44 . The latter has at its end  63  remote from the patient a peg  64  that serves for bayonet connection with a corresponding opening  66  of a first component  68  that is depicted in  FIGS. 13 to 15  and  23  to  32 . 
         [0064]    For latching (as shown in  FIG. 25 ), peg  64  is introduced from above along a track  70  into opening  66 , and then brought, by rotation (to the left) over a latching lug  74  along a distance  72 , into the latched position depicted in  FIGS. 25 ,  26 , and  27 . Lower boundary  78  ( FIG. 26 ) of opening  66  is elastically resilient as a result of an axially extending opening  76  ( FIG. 26 ), in order to enable a latching connection. 
         [0065]    Component  68  has a hollow-cylindrical outer wall  80 , and recessed into said wall are elastically resilient guidance members  82  that have associated with them, in housing  34 , an annular groove  84  ( FIGS. 20 ,  24 ,  28 ,  29 ). Upon assembly, guidance members  82  latch into this annular groove  84 , and component  68  is then rotatably guided by guidance members  82  in annular groove  84  of housing  34  but cannot be displaced axially relative to housing  34 . Component  68  is in turn connected fixedly, but disengageably, to carpule container  44  via bayonet connection  64 ,  66 . 
         [0066]    As  FIG. 14  shows, component  68  has, adjacently to the cylindrical outer wall  80 , a base  86  at whose center is located an opening  88  into which projects (as shown in  FIGS. 28 ,  29 ) a collar  90  of a second component  92 , so that components  68  and  92  are rotatable and also axially displaceable relative to one another. 
         [0067]    Collar  90  has an opening  94 , extending in an axial direction, that serves for axial guidance of piston rod  38  and is therefore adapted to the latter&#39;s cross-sectional shape (as is shown, for example, by  FIGS. 16 ,  17 , and  19 ) so that piston rod  38  and second component  92  can rotate only together, but can shift axially relative to one another. 
         [0068]    In contrast thereto, first component  68  can rotate relative to housing  34  but cannot shift axially. The same is then true of carpule container  44  when it is latched in on part  68 . 
         [0069]    First component  68  and second component  92  together form a linkage  98  whose function will be described below with reference to  FIGS. 25 to 27 . It serves to convert a relative rotation between components  68  and  92  into an axial motion of second component  92 , which motion has the function of immobilizing second component  92  and piston rod  38  guided therein, for example by positive engagement of component  92  with housing  34  (see  FIGS. 21 to 23  and  25  to  27 ) or by generating a strong friction between second component  92  and housing  34  (as depicted in  FIGS. 32 to 36 ). 
         [0070]    As  FIGS. 13 to 36  show, first component  68  and second component  92  are equipped with ramps  104  and  118 , respectively. 
         [0071]      FIGS. 14 and 15  show, by way of example, three ramps  104  that are arranged on base  86  of first component  68  at equal spacings of 120°. 
         [0072]    Proceeding, in  FIG. 15 , from a point  105  that would correspond on a clock to approximately three o&#39;clock, this is followed clockwise firstly by a ramp-free portion  106  having an angular extent of approximately 50°. This is followed by a portion  108  (e.g. 30°) having a ramp portion  110  that usually rises to a maximum in portion  108 . 
         [0073]    There then follows a flat portion  112  (e.g. 40°) in which the height of ramp  104  does not substantially change further, and at the end  114  of this portion  112  the height of ramp  104  drops abruptly to zero, i.e. point  114  represents a shoulder of ramp  104 . First component  68  thus has a total of three ramps  104 , three shoulders  114 , and three ramp portions  110 . 
         [0074]    The above-described configuration repeats after shoulder  114 , i.e. the next ramp portion  110  begins to rise at an angular spacing  106  from shoulder  114 , as is clearly evident from  FIGS. 14 and 15 . 
         [0075]    Second component  92  ( FIGS. 16 to 19 ) has a configuration largely complementary thereto, as shown by a comparison of  FIGS. 15 and 19 . It likewise has three ramps  118 . 
         [0076]    Beginning at a shoulder  120  ( FIG. 19 ) at a location corresponding approximately to four o&#39;clock there comes first (viewed clockwise) a flat region  122  (e.g. 50°) adjacent to which is a rising region  124  of the lower (in  FIG. 19 ) ramp  118 . This ramp region  124  has in this example an angular extent  126  of approximately 30°, and it ends in a flat roof region having an angular extent  128  of, for example, 40°, at the end of which a shoulder  120  is again located. 
         [0077]    Ramps  118  are located around collar  90 , and located inside collar  90  is opening  94  in which piston rod  38  is guided. When second component  92  rotates, piston rod  38  therefore also rotates, and the latter can shift freely in an axial direction in opening  94  as is necessary, for example, when priming. 
         [0078]    On its side facing away from ramps  118 , second component  92  has a coupling projection  130  that tapers frustoconically at its free end  132  and is equipped with longitudinal grooves  134  for engagement into corresponding longitudinal grooves  136  of housing  34 , so that projection  130 , upon engagement into longitudinal grooves  136 , is prevented by positive engagement from rotating. This effect can optionally also, in accordance with  FIGS. 30 to 36 , be achieved without the projection by the fact that second component  92  is simply pressed against a surface  140  ( FIG. 32 ) of housing  34  and secured there by friction to prevent rotation. 
         [0079]    Second component  92  is pressed by a spring  142  in a direction toward first component  68 , which latter is guided in the housing rotatably, but (because of guidance members  82  and annular groove  84 ) axially nondisplaceably. 
       Mode of Operation  
       [0080]    As  FIG. 25  shows, upon a clockwise rotation  60  such as that which occurs after insertion of a new carpule  50  (see  FIG. 8 ), ramps  104  of first component  68  are located between ramps  118  of second component  92 , since the latter is pressed by spring  142  ( FIG. 24 ) against first component  68 . As a result, coupling part  130  is out of engagement with coupling part  136  provided in housing  34 , so that when the patient rotates carpule container  44  clockwise (arrow  60 ), first component  68  with its ramps  104  also rotates along with carpule container  44 , and said ramps  104  engage (as shown in  FIG. 25 ) between ramps  118  of second component  92  and thereby also transfer said rotary motion  60  to second component  92  and to piston rod  38  guided therein. 
         [0081]    The latter is guided in housing  34  in a threaded part  150  ( FIGS. 28 ,  29 ) that, for example, can be part of the dosing apparatus of the injector and that does not rotate during a carpule change. Piston rod  38  is therefore moved in an upward direction in  FIG. 28 , i.e. toward the patient, in the context of a rotation  60  ( FIG. 25 ). 
         [0082]    As depicted in  FIG. 9 , piston rod  38  thereby comes into contact by means of its plate  46 ′ against piston  48  in carpule  50 , i.e. injector  28  is now primed, i.e. correctly prepared for an injection. 
         [0083]    Piston rod  38  therefore cannot move any farther upward, i.e. the torque in the direction of arrow  60  ( FIG. 25 ) continues to act because the patient is continuing to turn carpule container  44  as depicted in  FIG. 26 , but the rotation of second component  92  is now blocked because piston rod  38  is abutting against piston  48  (see  FIG. 8 ). 
         [0084]    Oblique surfaces  110  ( FIGS. 14 to 16 ) of ramps  104  of first component  68  therefore now produce an axial force on oblique surfaces  124  of ramps  118  of second component  92  and displace the latter, as depicted in  FIG. 26 , against the force of spring  142  ( FIG. 21 ) away from first component  68 . This results in a coupling between projection  130  ( FIG. 21 ) and longitudinal grooves  136  in housing  34  ( FIG. 22 ), so that second component  92  cannot rotate any farther in a clockwise direction  60 . 
         [0085]    Injection device  28  is thus now ready to use, i.e. the patient can, in normal fashion, set his or her individual injection dose and give him- or herself injections until the contents of carpule  50  are exhausted. 
         [0086]    Carpule container  44  must then be removed. For this, it is rotated counterclockwise in direction  58 , as shown in  FIG. 27 . This causes the previous coupling between first component  68  and second component  92  to disengage; the latter is displaced upward by spring  142 ; and shoulders  114  of first component  68  come into abutment against shoulders  120  of second component  92  so that the latter is likewise driven in counterclockwise direction  58 . 
         [0087]    As a result, piston rod  38  is rotated into housing  34  until it comes to a stop, and at the end of this procedure bayonet closure  64 ,  66  is disengaged, so that carpule container  44  can be taken off in order to remove the exhausted carpule and insert a new carpule  50 , as has already been described with reference to  FIGS. 1 to 9 . 
         [0088]    The above-described procedure is then repeated in order to prime the new carpule  50  again, and once again prepare injection device  28  for reliable use. 
         [0089]    In order to optimize the present invention, the slope of the ramps was also modified. 
         [0090]    Each of these ramps can be imagined as part of a thread whose (notional) flights have a specific pitch. This thread pitch is the spacing from one flight to the next, and in this case is preferably approximately 10 to 20 mm. 
         [0091]    The inside diameter a and outside diameter b of ramps  124 ′ of part  92  are plotted in  FIG. 38 . Practical values can be, for example,
   a=6 mm   b=11.5 mm   
 
         [0094]    One ramp  124 ′ extends here over an angle beta that is equal, for example, to 40°. 
         [0095]    If parts  68  and  92  rotate during presetting through an angle of 36° relative to one another, their spacing h then changes by a value 
         [0000]        h= 360°/36°*thread pitch   (1).
 
         [0096]    If the thread pitch is equal to 15 mm, h therefore has a value of approximately 1.5 mm, which experiments have shown to be a favorable value. 
         [0097]    Ramps  104  on part  68  have the same shape as ramps  124 ′ of part  92 , and are therefore shown only in  FIGS. 39 to 41 . Part  68  and its ramps  104  are shown therein in gray in order to facilitate comprehension. 
         [0098]      FIGS. 39 to 41  are highly schematic depictions of the adjusting procedures.  FIG. 39  shows the presetting of plate  46 ′ against piston  48 . Ramps  118  are rotated in the direction of arrow  60  so that they initially move plate  46 ′ upward toward piston  48 . In  FIG. 40 , plate  46 ′ has reached piston  48 . Upper ramps  110  therefore now shift relative to lower ramps  124 ′ and displace part  92  downward, so that the latter is now at a spacing h′ from part  68 , and part  92  is blocked in terms of rotation in the manner described. The injection device is now primed. 
         [0099]      FIG. 41  shows the procedure in the context of a cartridge change. Carpule container  44  is rotated in the direction of arrow  58 , with the result that ramps  104  disengage from ramps  124 ′ and the spacing between parts  68  and  92  once again becomes h. Part  92  is pressed by its spring  142  (see  FIG. 31 ) toward part  68 . Ramps  104  now press with their steep flanks  114  against the corresponding flanks  120  ( FIG. 40 ) of ramps  110 . 
         [0100]    Because part  68  is rotating together with part  92  in the direction of arrow  58 , plate  46 ′ is moved downward; and at the end of this movement, part  68  disengages from dosing part  44 , as depicted in  FIG. 5 . Operation is therefore very simple and intuitive, and dosing accuracy is correspondingly increased. 
         [0101]    Numerous variants and modifications are, of course, possible within the scope of the present invention.