Abstract:
A flow delivery system including a syringe that includes an outer plastic shell, a leur and a plunger; and a needle and/or a catheter that embodies a hub and a cannula which delivers a solution of a material. Various structures are included to provide locking engagements, torque sensitive connections, sufficient interfacing between components and visual conformation of connectors. The syringe assembly can also include an approach to a filter. Moreover, an approach to sterilization is provided.

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
       [0001]    This application claims the benefit of U.S. Provisional Application No. 61/003,410, filed Dec. 21, 2007; U.S. Provisional Application No. 61/004,467, filed Dec. 27, 2007; U.S. Provisional Application No. FD-PT200727, filed Dec. 27, 2007; U.S. Provisional Application No. 61/007,411, filed Jan. 3, 2008; U.S. Provisional Application No. 61/009,123, filed Jan. 18, 2008; U.S. Provisional Application No. 61/009,120, filed Jan. 18, 2008; U.S. Provisional Application No. 61/009,116, filed Jan. 18, 2008; and U.S. Provisional Application No. 61/009,122, filed Jan. 18, 2008; each of which are herein incorporated by reference in their entirety. 
     
    
     BACKGROUND 
       [0002]    This disclosure relates in general to a flow delivery system that delivers material such as a biomaterial into a body, and in particular, to a syringe body for delivery of an aqueous solution containing a biomaterial or a mixture of a biomaterial and a biocompatible fluid lubricant. 
         [0003]    This disclosure also relates to a flow delivery system, including a rotating grip or flange for the upper portion of the syringe. Needles on the syringes have a beveled distal end that creates a sharp point. The finger grips or flanges that allow the surgeon to position their index and middle finger on the body of the syringe while pushing the plunger with their thumb are commonly affixed to the syringe body. Some surgeons, including cosmetic and plastic surgeons, prefer to position the bevel in a specific direction, such as facing upward away from the skin or facing downward toward the skin depending on the procedure. When the finger grips are affixed to the syringe body, the surgeon must rotate the needle in order to configure the syringe so that the bevel on the needle is pointing in the desired direction. Many needles are engaged with the syringe body and leur by means of threads, and by rotating the needle, it is possible to loosen the connection between the needle and syringe body thus causing the needle to disengage under pressure. When disengaged while under pressure, the needle can launch from the distal end of the leur creating a sharp projectile. 
         [0004]    The present disclosure further relates to shields for syringes such as a cover/container for a needle, also known as a cannula and hub assembly having a hub portion and a cannula portion. Moreover, the present disclosure is directed to an interface between the leur and the cannula as well as to the interface between the needle hub and the leur. Often a plenum results in the area where a needle assembly (cannula and hub) meets a syringe assembly (outer shell and leur). Certain situations can develop in which pressure builds up in the plenum and can cause a needle tip to become disengaged from the leur. When caused to disengage while under pressure, the cannula and hub assembly can launch from the distal end of the leur creating a sharp projectile. 
         [0005]    Moreover, this disclosure concerns a system that includes a filter that breaks up or downsizes particles of material that are larger than desired (e.g., a relatively large agglomerated mass of the particles) for more effective delivery of the aqueous solution into the body. 
         [0006]    Medical procedures often involve the non-surgical implanting of biomaterials into the body. An example is the injecting of a dermal filler material such as collagen through the use of a syringe and needle. The biomaterial can be solid and load-bearing and is typically suspended as an aqueous solution of the biomaterial particles. The solution is then injected with a syringe through a needle. For precise placement of materials into the facial dermis, a very fine cannula, e.g. 27 gauge (0.0075″ inside diameter or ID) to 30 gauge (9.0055″ ID), is preferred. These relatively small ID cannulas limit the diameter of the suspended particles that may pass through the cannula orifice during product delivery. The diameter of the particles of a product will typically range from 1-20 microns (0.001 mm-0.02 mm) in length and less than 20 microns (0.02 mm) in width. Products including larger particles can have diameters in the range of 200-700 and up to  1000  microns. In general, smaller particles can be less deformable than larger particles. Moreover, the particles can be generally spherical initially and then assume non-spherical profiles during product delivery through a cannula. It has been determined that larger particles are desirable in some situations, such as for the containment of time release medication. The larger particles pose a problem when used with the smaller cannulas required in the facial derma. The larger particles can bridge or agglomerate, resulting in clogging of the small orifice cannula. Larger particles also result in a greater amount of force needed to translate the syringe plunger especially where the particles are relatively less deformable. Common syringes include a central vessel (or leur) engaged with an outer shell, a plunger and a needle. The needle can embody a cannula that is engaged with a cone shaped portion, (or hub) that is press-fit onto the leur. Various mechanical structures such as threading are employed to assist in the press fit of the cannula and hub on to the leur. A plenum resides between the exit orifice of the leur and the entrance orifice of the cannula. When material agglomerates in this plenum, and the user will tend to increase pressure on the plunger, this higher force has a tendency to be sufficient to cause the cannula and hub assembly to launch out of the syringe. 
         [0007]    There has been substantial research and experimentation in various mechanical methods for securing a needle tip to a syringe. U.S. Pat. No. 6,613,022 B1 is a passive needle guard that includes a body having a cavity to hold a syringe. U.S. Pat. No. 7,160,311 B2 is a compression plate apparatus that enables vessels to be joined together in various configurations. U.S. Pat. No. 7,214,207 B2 is a therapeutic infusion assembly for the subcutaneous delivery of a fluid from a remote source. U.S. Pat. No. 7,214,227 B2 is a closure member, such as a set screw and complementary receiving member included in a medical implant device. U.S. Pat. No. 7,274,966 B2 is a medical fluid delivery system including an implantable medical lead including a fixation element adapted to secure the lead to a tissue site and a fluid delivery device including a tissue piercing distal tip. U.S. Pat. No. 7,250,036 is a method for using a needle assembly for intradermal injection and a drug delivery device. U.S. Pat. No. 6,520,935 is a tip cap assembly for positive sealing engagement with a tip of syringe barrel of a syringe. U.S. patent application No. 20070255225 An intradermal needle comprising a needle cannula assembly having a limiter portion, a hub portion and a needle cannula, a protective cap having a forward and rearward cap to protect and shield a needle cannula prior to an after use, and means for engaging the needle cannula assembly and the rearward cap after use. U.S. patent application No. 20070149924 is a needle assembly including a cover, an inner shield, a needle and a hub assembly is provided. After use, the cover is placed over the distal (patient) end of the needle and the inner shield can be used to cover the proximal (non-patient) end of the needle. U.S. patent application No. 20050004552 is a passive shield system for a syringe including a body, shield, spring and ring which provide an interlock of the shield in the retracted position prior to receipt of the syringe for bulk transportation and processing and wherein the user selects the timing of the release of the shield to its extended position following injection, but which assures shielding of the syringe needle following release of the syringe plunger. U.S. patent application No. 20040102740 is a safety needle includes a needle with a sharp end and a needle shield. The needle shield includes collapsible interlocking members. U.S. patent application No. 20040097882 is a shield that protects the needle of a syringe and maintains it in a sterile condition until use. As stated, larger particles bridging or agglomerating resulting in clogging of the small orifice needle, thus resulting in a greater amount of force needed to translate the syringe plunger, the higher force may cause the surgeon to tremble and slight perturbations of the hand could result. Therefore, it is desirable to have applied forces equivalent to a low viscidity Newtonian fluid. 
         [0008]    Other applications for implanting a biomaterial into the human body include use of the biomaterial as a bulking or augmenting agent in internal body tissue, such as the tissue that defines various sphincters, for example, in the urinary tract (specifically, in the urinary outflow of the bladder into the urethra) or in the lower esophageal area connecting the esophagus to the stomach. The malfunctioning of these sphincters is usually in the form of improper or incomplete closure of the sphincters, which leads to medical conditions such as urinary incontinence and gastroesophageal reflux disease (GERD) or heartburn, respectively. Treatment of these medical conditions may include injections of a viscous material dispersed in a solution, such as collagen, in the vicinity of the associated sphincter to augment or bulk up and fortify the tissue and thereby assist in the adequate closure of the corresponding sphincter for re-establishment of normal sphincter control. Still other applications for implanting a biomaterial such as collagen into the human body include various other body passages and tissues; for example, for correcting wrinkles not only in the facial derma but in other areas of the body as well. 
         [0009]    In these applications it is known to inject the biomaterial, typically suspended in an aqueous solution, into the human body through use of a syringe together with an elongate needle and/or catheter. This type of flow delivery system may be used as a stand alone device or in combination with an appropriate medical instrument, such as a cystoscope, endoscope or gastroscope, which instruments are utilized to view the tissue in the affected area. However, as the length of the elongate needle and/or catheter increases, the amount of the force required to properly deliver the suspended mass aqueous solution of biomaterial to the desired body tissue area also increases. With known flow delivery systems, this increased amount of required force can cause problems both with the extrusion of the biomaterial through the flow delivery system and also with the intrusion of the biomaterial into the tissue. Oftentimes poor intrusion into the body tissue is the result of poor extrusion through the flow delivery system. 
         [0010]    There also has been substantial research and experimentation in various chemical compositions to reduce plunger force in a syringe and needle and/or catheter flow delivery system. An area commonly researched is the ability to introduce lubricity between the particles through use of an aqueous suspension of a particulate biocompatible material and a biocompatible fluid lubricant. The biomaterial and lubricant are typically combined in a manner that results in a homogenous mixture. It is believed that the lubricant enhances flow in part by preventing particle to particle contact. See, e.g., U.S. Pat. No. 4,803,075. However, a disadvantage of the addition of the lubricant is that can reduce the content of the active component in solution. 
         [0011]    Natural polymers or cross-linked biocompatible polysaccharide gels are used in various applications as bio implant material. Highly viscous material is often required, as it is more durable when implanted in the body. However, natural polymers can degrade under heat and light. The cross-linked biocompatible material contains particles and it has been found that it is important to create a set of uniformly sized particles. By properly placing the high intensity light sterilization process and/or an acoustic-wave heat and pressure process in the manufacturing system, it is possible to achieve the highly viscous end product with the benefits of acoustic and/or ultraviolet light sterilization and the benefits of acoustic and/or electrical-wave sizing, without the degradation of the viscosity that conventional methods cause. 
         [0012]    Various methods of sterilization are known, including for example, heat sterilization, e.g., autoclaving, irradiation sterilization, e.g., using gamma radiation, and chemical sterilization. Sterilization methods that employ heat and/or pressure require that the process be interrupted and that a sufficient amount of time and energy be employed to bring the material up to temperature and allowed to cool. Sterilization by high-intensity, short-duration pulses of incoherent, polychromatic light in a broad spectrum can be accomplished in a significantly short period of time, within a closed loop system. Most target objects are sterilized or decontaminated within less than a few minutes as only a few flashes, having durations of a few seconds to less than a minute, are required. Sterilization employing high-amplitude ultrasonic sound waves to cause cavitation in a liquid can also be achieved in a short period of time and within the closed loop system. Cavitation occurs when the high-amplitude ultrasonic sound waves create gas-bubble cavities in the liquid. When the cavities collapse they produce intense localized pressures. This cavitation may be induced to destroy liquid-borne organisms, mix fluids or slurries, promote certain chemical reactions and otherwise treat fluids or materials therein. 
         [0013]    The cross-linked biocompatible material contains particles, it is important to create a set of uniformly sized particles. The sizing of particles is commonly accomplished by a mechanical means, highly viscous hydrated gels contain particles of various sizes. Uniform sizing is important for the proper function of the bio-compatible material. Sizing can be accomplished within a closed loop system by the use of acoustic or electrical waves. 
         [0014]    The process of manufacturing highly viscous hydrated gels comprises: forming an aqueous solution of a water soluble, cross-linkable polysaccharide; initiating a cross-linking agent, and continuing turbulent flow and mixing of the cross-linking agent the material is degassed (air bubbles removed) and then dispensed into various vessels for medical use. 
         [0015]    Medical procedures often involve the non-surgical implanting of biomaterials. An example is the injecting of a dermal filler material such as collagen, or the use of highly viscous hydrated gels to suspend particles that carry medication. The particles of a soft tissue augmentation filler typically measure in the range of 150 micron to 800 microns. Uniform particle size is necessary for the proper function of delivery mechanisms such as a syringe. Properly hydrated particles are necessary for the performance of the biomaterial. 
         [0016]    The sterilization process of said biomaterial typically involves some form of temperature and/or pressure-based sterilization techniques such as the use of an autoclave. It has been determined that heating and cooling of the autoclave process can change particle size and level of hydration. A properly hydrated particle will not change size after it is implanted in the body. With a properly hydrated particle, injections may be done repeatedly until the desired outcome is affected. This is referred to as 100% correction. An under hydrated particle will pull moisture from surrounding cells after implanting and wills well in size. The welling can cause discomfort so the surgeon must compensate for the under hydrated material by stopping before the desired outcome is affected, this is known as less than 100% correction. 
         [0017]    Accordingly, there is a need for an improved flow delivery system for implanting a biomaterial into the human body, where the system does not allow for the needle tip (or cannula and hub assembly) to come disengaged from the leur portion of a syringe. There is also a need for interference with the axial motion of a cannula and hub assembly in the event that sufficient pressure is applied to cause the cannula and hub assembly to become disengaged from the syringe body. Moreover, there is a need for rotatably engaged finger grips for a syringe that are in mechanical engagement with the syringe body. Also, there is a need to provide a container for a cannula and hub assembly that houses the cannula in a sterile environment and covers the sharp end of the cannula while it is not in use as well as a need for providing a tactile and audible response to notify the user that a cannula and hub assembly are properly engaged. Another concern relates to needing a sufficient seal between the leur and hub as well as a seal between the exit orifice of the syringe and entrance orifice of the cannula to eliminate a plenum between the exit orifice of the leur and entrance orifice of the cannula which would otherwise allow unwanted forces to build up at the entrance orifice of the cannula. Additionally, there is a need for a visual cue to allow the user to confirm that the needle is properly engaged. There is also a need for a system that includes a filter that breaks up or downsizes particles of the biomaterial that are larger than desired, to achieve a more effective delivery of the aqueous solution into the body. Finally, there is a need for a process of sterilization of biomaterials without excessive heating and cooling and which facilitates the mixing of a cross-linking agent into a highly viscous hydrated gel as well as improves homogenous sizing of particles within the gel. 
         [0018]    The present disclosure addresses these and other needs. 
       SUMMARY 
       [0019]    Briefly and in general terms, the present disclosure is directed towards a flow delivery system which embodies a syringe. In one approach, the syringe includes an outer plastic shell, a leur and a plunger, a needle and/or a catheter having a hub, and a cannula which delivers an aqueous solution of a material. The solution can be a biomaterial or a mixture of biomaterial and a biocompatible fluid lubricant. The cannula and hub assembly can be removably engaged from the distal end of the leur of the syringe and also can be removably engaged with the outer shell or syringe body, in such a manner as to stay engaged when the fluid inside the syringe is placed under sufficient force so as to move dense material through a small diameter cannula. 
         [0020]    In another aspect, the present disclosure is directed to a flow delivery system embodying a syringe that includes a cannula and hub assembly which is removably engaged with the distal end of a leur and syringe body. The cannula and hub assembly is first engaged with the distal end of the leur and syringe body in a direction perpendicular to the central axis of the syringe body and secondly in a direction parallel to the central axis of the syringe body, in such a manner as to stay engaged when the fluid inside the syringe is placed under sufficient force so as to move dense material through a small diameter cannula. In the event that sufficient pressure is deployed so as to disengage hub from the syringe body, interference structure is provided so as to prevent the cannula and hub assembly from launching from the distal end of the syringe body. 
         [0021]    The present disclosure is also directed towards rotatably engaged finger grips for a syringe that are mechanically engaged with a syringe body that is in turn mechanically engaged with a needle tip. In one specific embodiment, there is provided a cover and container for a cannula and hub assembly engaged with a syringe body in such a manner as to protect and shield the cannula prior to, and after use and provides structure attaching the cannula and hub assembly with the syringe. The disclosure further provides structure that ensures proper engagement by providing an audible or tactile response when the proper engagement between a needle and syringe has been achieved. In one approach, material of appropriate dimension and strength is designed to break-away when sufficient torque has been employed to properly engage the hub with the syringe body. Additional disclosed features allow the user to re-engage the cover with the cannula and hub assembly so as to be able to safely remove the cannula and hub assembly from the syringe body after use and to contain it for proper disposal. 
         [0022]    Further, in one preferred embodiment, a cannula and hub assembly are engaged such that there is a seal between the leur and cannula as well as a seal between the hub and leur. To ensure that the needle is properly engaged, a visual indicator can be provided to indicate that the needle has been inserted far enough to ensure proper engagement. 
         [0023]    In yet another approach, a filter is located within the body of the syringe. The filter includes a plurality of openings, each of a predetermined size. As the aqueous solution containing the suspended biomaterial particles travels through the body of the syringe under an applied force, the solution encounters the openings in the filter which break up or downsize any particles of the biomaterial within the solution that are larger than the size of the openings. At the same time, the openings in the filter allow any particles of the biomaterial that are smaller than the size of the openings to pass without any downsizing. The size of the openings in the filter may vary and preferably is selected in dependence on the size of the opening or orifice in the needle and/or catheter. The downsized particles then pass together with any other non-downsized particles in a relatively unobstructed manner through the needle and/or catheter and its orifice and into the body. 
         [0024]    The filter breaks up any agglomerated biomaterial particle matter or mass into smaller particles of a specific size (i.e., that of the openings in the filter). This reduces the resistance to the flow of the aqueous solution through a flow delivery system that includes the filter, which also reduces the amount of force necessary to transport and expel the aqueous solution through the system and into a body. 
         [0025]    The present disclosure is also directed to a manufacturing system which includes the forming of an aqueous solution of a water soluble, cross-linkable polysaccharide; sterilizing the material with one or both of either; high-intensity, short-duration pulses of incoherent, polychromatic light in a broad spectrum, or by the use of high-amplitude ultrasonic sound waves. The process further involves the initiating a cross-linking of said polysaccharide in the presence of a poly-functional cross-linking agent, and continuing turbulent flow and mixing of the cross-linking agent the material is degassed and then sized before it is dispensed into various vessels for medical use. Natural polymers degrade under heat and light thus decreasing their viscosity. Although decreased viscosity renders the material less durable as a bio-implant, it does render the material more susceptible to homogenous mixing. In the manufacturing process it is often difficult to combine a cross-linking agent in a highly viscous gel. By locating either of the proposed sterilization processes, after the formation of an aqueous solution and before the cross-linking agent is added, the cross-linking agent may be added and thoroughly mixed while the viscosity is low. Acoustic and/or electrical waves may also be employed to create a homogeneous mix of properly sized particles within the highly viscous gel. The viscosity can be regained in the cross linking and de-gassing processes, therefore attaining the benefits of the short-duration sterilization process and retaining the high viscosity of the finished product. 
         [0026]    These and other objects, features and advantages of the present invention will become more apparent in light of the following detailed description of preferred embodiments thereof, as illustrated in the accompanying drawings. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWING 
         [0027]      FIG. 1  including  FIGS. 1A-1B , is a perspective and detailed view of a first iteration of a locking tip for a syringe. 
           [0028]      FIG. 2  including  FIGS. 2A-2B , is a detail section view of the first iteration of the locking tip. 
           [0029]      FIG. 3  including  FIGS. 3A-3B , is a detailed view of a second iteration of a locking tip. 
           [0030]      FIG. 4  including  FIGS. 4A-4B , is a detailed section view of the second iteration of the locking tip. 
           [0031]      FIG. 5  including  FIGS. 5A-5B , is a detailed view of a third iteration of a locking tip. 
           [0032]      FIG. 6  including  FIGS. 6A-6B , is a detailed view of a syringe with a lateral lock. 
           [0033]      FIG. 7  including  FIGS. 7A-7B , is a detailed view of a second iteration of a lateral lock. 
           [0034]      FIG. 8  is a perspective view of a syringe with a rotating finger grip. 
           [0035]      FIG. 9  is an exploded view of the assembly of  FIG. 8 . 
           [0036]      FIG. 10  including  FIGS. 10A-10B  is a section view of the assembly of  FIG. 8 . 
           [0037]      FIG. 11  is a perspective, exploded view of a torque sensitive cannula engaged with a syringe 
           [0038]      FIG. 12  is a perspective view of the cannula and hub assembly of  FIG. 11 . 
           [0039]      FIG. 13  is a perspective view of the cannula. 
           [0040]      FIG. 14  is a detail view of the cannula of  FIG. 11 . 
           [0041]      FIG. 15  is a section view of the cannula of  FIG. 14 . 
           [0042]      FIG. 16  is a top view of the cannula of  FIG. 15 . 
           [0043]      FIG. 17  is a side view of another embodiment of a syringe assembly. 
           [0044]      FIG. 18  including  FIGS. 18A-FIG .  18 B, is an enlarged section view of the interface structure of the syringe assembly of  FIG. 17 . 
           [0045]      FIG. 19  including  FIGS. 19A-19B , is a perspective and detailed view of one approach to a visual indicator. 
           [0046]      FIG. 20  including  FIGS. 20A-20B , is a detail view of the visual indicator. 
           [0047]      FIG. 21  including  FIGS. 21A-21B , is a detailed section view of the visual indicator. 
           [0048]      FIG. 22  including  FIGS. 22A-22B , are various views of a syringe and needle/catheter flow delivery system that includes a filter located inside the body of the syringe according to the present invention; 
           [0049]      FIG. 23  is a perspective view of one embodiment of the filter of  FIG. 22 . 
           [0050]      FIG. 24  is a perspective view of a bundle of glass rods prior to slicing the bundle to form a second embodiment of the filter of  FIG. 22 . 
           [0051]      FIG. 25  is a perspective view of the second embodiment of the filter of  FIG. 22 . 
           [0052]      FIG. 26  is a schematic view, depicting a sterilization process. 
       
    
    
     DETAILED DESCRIPTION  
       [0053]    The present disclosure is directed towards a flow delivery system for implanting biomaterial into the human body. The system can include structure prohibiting a needle tip (or cannula and hub assembly) to become disengaged from a leur portion of a syringe. The system can also include structure interfering with the axial motion of a cannula and hub assembly in the event that sufficient pressure is applied to cause the cannula and hub assembly to become disengaged with the syringe body under such force. Rotatably engaged finger grips for a syringe that are in mechanical engagement with the syringe body are also disclosed as is a container for a cannula and hub assembly that contains the cannula in a sterile environment and covers the sharp end of the cannula while it is not in use. In one approach, the system can include a tactile and audible response to notify the user that a cannula and hub assembly are properly engaged. Moreover, there is disclosed a seal between the leur and hub as well as a seal between the exit orifice of the syringe and entrance orifice of the cannula to eliminate a plenum between the exit orifice of the leur and entrance orifice of the cannula. Additionally, where desirable, there is provided a visual cue to allow the user to confirm that the needle is properly engaged as well as a system that includes a filter that breaks up or downsizes particles of the biomaterial. 
         [0054]    In the figures, like reference numerals refer to like elements. Referring to  FIGS. 1A and 1B , in a first iteration of a syringe assembly  31 , a feature is added to a syringe body  21  that provides a locking mechanism that prevents the cannula and hub assembly  20  from dislodging or becoming disengaged from the syringe body  21 . The feature is embodied in a cut  10  in the surface of the syringe body  21  that creates a flexible portion  11  that has a protrusion  12  (See  FIG. 2 ,  FIG. 2B ). A cross section of the first iteration is shown in  FIGS. 2A and 2B . The cannula and hub assembly  20  is engaged with the syringe body  21  by threads  23 . Clockwise motion of the hub  20  into threads  23  engages the cannula and hub assembly  20  with syringe body  21 . In the previous approaches, counterclockwise motion of the cannula and hub assembly  20  in threads  23  disengages the cannula and hub assembly  20 . The protrusion  12  is ramp-shaped, as the ridge  13  is engaged in a clockwise direction through the threads  23 , the flexible portion  11  flexes outward as the ridge  13  moves along the ramp portion of the protrusion  12 . As the ridge drops off the high end of the ramp, the flexible portion  11  flexes back to a normal position in which the protrusion  12  interferes with the passage in a counterclockwise direction of the ridge  13  and thus retains the cannula and hub assembly  20  engaged with the syringe body  21 . 
         [0055]    The second iteration of the syringe assembly  32  is illustrated in  FIGS. 3A ,  3 B,  4 A and  4 B. In the second iteration of the syringe assembly  32 , a similar system to the first iteration is proposed in which the cut  10  and flexible portion  11  function in a similar manner to the first iteration except that there is a 90 degree alteration in the orientation of the feature. The protrusion  26  also functions in a similar manner so as to interfere with the passage in a counterclockwise direction of the ridge  13 . 
         [0056]    The third iteration of the syringe assembly,  33  is illustrated in  FIGS. 5A and 5B . A series of ramp shaped protrusions  24  are positioned along threads  23  in the syringe body  21 . The ramp shaped protrusions  24  cause a decrease in the inside diameter of the syringe body and therefore increased pressure on the ridge  13 . As the ridge  13  on the cannula and hub assembly  20  is engaged in a clockwise direction with the threads  23  on the syringe body  21 , the ridge  13  meets gradually increasing interference from the ramp-shaped protrusions  24  followed by a decrease in interference after dropping of the high end of the ramp. The high end of the ramp-shaped protrusions  24  prevent counterclockwise movement of the ridge  13 . The interference caused by the ramp shape protrusions  24  prevent the cannula and hub assembly  20  from moving in a counterclockwise direction after having been engaged with the syringe body  21  in a clockwise direction. 
         [0057]    Other features of the contemplated syringe assembly is presented in  FIGS. 6 and 7  including  6 A,  6 B,  7 A and  7 B. The syringe assembly includes an outer housing, a cannula and hub assembly  120  and a leur. The outer housing has a central axis  125 . The syringe assembly includes structure which, in combination the cannula and hub assembly  120  and the syringe body  121  are engaged in first a lateral direction  126 , perpendicular to the central axis  125  of the syringe assembly and then in an axial direction  127 , parallel to the central axis  125  of the syringe body (See  FIGS. 6A ,  6 B). The cannula and hub assembly  120  has a rotatably tapered ridge  115  that engages with a similarly tapered slot  116  after it is moved laterally into position. The tapered ridge  115  moves along the similarly tapered slot  116  in such a manner as to move the cannula hub assembly  120  along the central axis  125  in a direction  127  so as to create a seal between the hub assembly  120  and the leur  124 . The cannula and hub assembly  120  has a conical shape that meets the conical shape of the distal end  128  of the leur so as to create a liquid tight seal. Such a seal as is created by two conical sections meeting, is a common method of creating a liquid tight seal. 
         [0058]    In the second iteration of the contemplated syringe assembly ( FIGS. 7A and 7B ), threads  123  engage with ridge  115 . The cannula and hub assembly  120  engages in a direction  126  perpendicular to the central axis  125  of the syringe body, at which point the threads  123  engage with the ridge  15 . By rotating the cannula and hub assembly  120  in a clockwise direction, the cannula and hub assembly  120  moves in a direction  127  parallel to the central axis  125  of the syringe body  121 . Movement of the cannula and hub assembly  120  in the direction  127 , engages the conical shape of the cannula and hub assembly  120  with the distal end  128  of the leur  124 , thus creating a liquid tight seal. The assembly further includes a smaller opening  117  ( FIG. 6 ,  FIG. 7 ) at the distal end of the syringe body that provides interference with the ridge on the hub  115 , in the event that the cannula and hub assembly  120  become disengaged from the syringe body and leur. The open end  117  of the syringe body  121  is too small for the ridge  115  to pass. Under considerable pressure, the cannula and hub assembly  120  may be forced in such a manner as to come disengaged with the syringe  121 , however, motion in the axial direction will be stopped by the smaller opening  117  thus preventing the cannula and hub assembly from being launched from the distal end of the syringe assembly. 
         [0059]    Turning now to  FIG. 8  through  FIG. 10 , a syringe assembly with a central axis  219  includes an outer shell (or syringe body)  210  with an interior leur  213  and a plunger  211  that is moveably engaged with the leur  213 . The syringe body has a proximal and distal end and is wider at the proximal end and narrower at the distal end. The proximal end of the needle  212  is removably engaged with the distal end of the leur  213  and the syringe body  210 . The needle is engaged with the syringe body by threads  217  in such a manner that when the needle is rotated it moves upward along the syringe body  210  and firmly engages with the distal end of the leur  213 . 
         [0060]    The leur  211  is engaged with the syringe body  210  along the central axis  219  and fits inside the syringe body  210 . Protrusions  215  flex outward as the leur is positioned and snap into place to hold the leur  211  in the syringe body  210 . Finger grips  214  embody a form that is engaged along the central axis  219  of the syringe body. The finger grips are engaged from the distal end of the syringe and moved toward the proximal end of the syringe body  210  and are engaged with the larger proximal end of the syringe body  210  in such a manner as not to allow the finger grips to slide off of the proximal end of the syringe body. A protrusion  216  on the finger grips  14  is engaged with a detent  218  ( FIG. 9 ) on the syringe body  210 . The protrusions  216  and detent  218  prevent the finger grips from sliding downward along the syringe body  210 . 
         [0061]    The finger grips  214  are rotatably engaged with the syringe body  210 . Notably, the syringe body  210  is in direct mechanical engagement with both the finger grips  214  and the needle  212  in such a manner that allows rotation of the finger grips  214 . 
         [0062]    In the embodiments of the present invention described above, it will be recognized that individual elements and/or features thereof are not necessarily limited to a particular embodiment but, where applicable, are interchangeable and can be used in any selected embodiment even though such may not be specifically shown. 
         [0063]    Referring to  FIG. 11  through  FIG. 16 , a single use syringe with a removable tip is described. The syringe assembly embodies an outer shell  322  with an interior leur  323  and a plunger  324  that is moveably engaged with the leur  323 . The needle is comprised of a cannula  325  engaged with a hub  320 . The cannula  325  and hub  320  are permanently engaged and make up the cannula and hub assembly  332  ( FIG. 12 ). The hub  320  ( FIG. 11 ) is removably engaged with the leur  323  and the outer plastic shell  322 . The interior surface of the hub  28  is engaged with the distal end of the leur  323 . The outer surface of the hub is flared at the top  326  to engage with threads  321  in the outer shell  322 . As the flange  326  on the hub  320  is engaged with the threads  321  of the outer shell  322  it moves upward and thus engages the interior surface of the hub  328  with the distal end of the leur  323 . The conical shape of the hub  20  provides a seal with the distal end of the leur  323  when sufficient torque is exerted on the hub  320  to properly thread the flared ridge  326  into the threads  321  of the syringe body  322 . The cannula and hub assembly  332  is stored in the cap  331 . The cap  331  provides a sterile container for the cannula and hub assembly  332  and also protects the user from being pricked by the cannula  325  while assembling the syringe  330 . 
         [0064]    To assemble the syringe the user inserts the cannula and hub assembly  332  into the syringe  330 , the cannula and hub assembly  332  is left inside the cap  331  while threading the ridge  326  of the hub  320  into the threads  321  of the syringe body  322 . Ribs  316  ( FIG. 13 ) along the longitudinal axis of the container  310  provide a grip for the user&#39;s finger tips. Fin-like protrusions  327  on the hub  320  engage with the rectangular shaped portion  312  of the container  310 , thus not permitting the hub  320  to rotate inside the cap  331 . When the hub  320  is sufficiently engaged with both the syringe body  322  and the distal end of the leur  323  the cap  331  is removed and the syringe is ready for use. If the cannula and hub assembly  332  is not sufficiently engaged with the syringe body  322 , it can become disengaged during use and, when under sufficient pressure, can become a sharp projectile. 
         [0065]    The present structure provides a tactile and/or an audible response to alert the user that the hub  320  is properly engaged with the syringe body  322  and the distal end of the leur  323 . The syringe assembly includes a body portion  310  that houses the cannula and hub assembly  332 , and further comprises ridges  316  along the longitudinal axis of the body  310 , protrusions  317 , a cut  314  in the surface of the body  310 , a partial cut  313  and a flexible portion  311  ( FIGS. 13-16 ). When the cannula and hub assembly  332  is engaged with the cap  331  the protrusions  17  ( FIG. 16 ), engage with the fin-like protrusions  327  on the hub  320 . The protrusion  317  are formed as part of the flexible portion  311 , within the boundary created by the cuts  314  and the partial cut  313  are located on the inner surface of the flexible portion  311  ( FIGS. 15 ,  16 ). The partial cut  313  is configured so as to break through when a specified amount of torque is applied to the cap  331  as the fin-like protrusion  327  bear against the protrusion  317 . When the partial  313  breaks, an audible response is provided. The protrusion  317  are attached to the flexible portion  311  and thus will flex outward as they engage with the fin-like protrusion  327 . When the protrusion  317  flex outward, there is no longer enough interference with the fin-like protrusion  327  to continue rotating the cannula and hub assembly  332 . Furthermore, as the flexible portions  311  flex outward, they press against the user&#39;s fingertips, providing a tactile response. When the user wishes to remove the cannula and hub assembly  332  from the syringe body  322 , the flexible portion  311  may be depressed, thus engaging the protrusions  317  with the fin-like protrusion  327  so as to provide sufficient grip to remove the cannula and hub assembly from syringe body. 
         [0066]    Again, in the embodiments of the present invention described above, it will be recognized that individual elements and/or features thereof are not necessarily limited to a particular embodiment but, where applicable, are interchangeable and can be used in any selected embodiment even through such may not be specifically shown. 
         [0067]    In yet another approach, an useful interface between the cannula and leur as well as an interface between the leur and hub is provided. Here the syringe assembly embodies an outer shell  410  and plunger  411 , with a unique leur  434  that has a contoured outer surface at its distal end  435  ( FIG. 18 ). A hub  432  has a contoured inner surface  431 . A cannula  439  has a contoured proximal end  423  that engages with a contoured distal end  422  of the leur  434 . The interior surface of the leur comprises a gradual taper  436  that, at the small end of the taper, approaches the diameter of the cannula  423 . The hub  432  has an inner surface  431  that is contoured to fit the end  435  of the leur  434 . The proximal end of the cannula  423  is tapered so as to fit into, and create a tight seal with the tapered distal tip  422  of the leur  432 . The tight seal between the proximal end of the cannula and the leur  435 , eliminates an undesirable plenum  420 . The material inside the leur is forced through the gradually tapered contour  436 . Pressure created by the force of the plunger along the interior of the leur  434  is exerted against the inner walls of the leur and does not build up in a manner that has the potential to dislodge the hub  432  from the end  435  of the leur  434 . 
         [0068]    Referring to  FIGS. 19A and 19B , a syringe assembly  531 , can include a syringe body  521  that provides a visual indicator  511  to show that the needle  520  is properly engaged with the syringe body  521 . The feature can be defined by a tinted portion of the syringe body  511  that interacts with the colored needle  520  to show that the needle is properly engaged with the syringe body  521 . A cross section of the first iteration is shown in  FIGS. 21A and 21B  the needle body  520  is engaged with the syringe body  521  by threads  523 . Clockwise motion of the needle  520  into threads  523  engages the needle  520  with syringe body  521 , also seen in  FIGS. 20A and 20B . An opaque portion of the syringe body  510  prevents the user from seeing the needle  520  in the visual indicator  511 . When the needle  520  is visible through the transparent, tinted visual indicator  511 , the needle is threaded far enough into the syringe body so as to be properly engaged with the syringe body  521 . The needle  520  is made of a colored material, of a contrasting color to the transparent, tinted visual indicator  511  so as to create a visual effect such as a color change. If, for example, the needle  520  were blue and the transparent, tinted visual indicator  511  were yellow, when the needle were threaded into the syringe body  521  far enough to pass the opaque portion  510 , there would be a visible green tint in the area where the needle  520  were seen through the visual indicator  511 . 
         [0069]    Referring to  FIG. 22 , including  FIGS. 22A and 22B , there illustrated is one embodiment of a flow delivery system  630  which reduces the amount of force required to transport and expel an aqueous solution of a biomaterial or a mixture of a biomaterial and a biocompatible fluid lubricant into a body at a desired location, such as, for example, the facial derma or a sphincter (i.e., urinary tract or with the esophageal tract). The biomaterial may embody collaged or other known materials used as bulking agents to augment or build up the tissue in the desired area to correct for improper sphincter operation or to cure cosmetic defects (e.g., wrinkles). The biocompatible fluid lubricant may include a non cross-linked collaged or other known materials that forma homogeneous mixture with the preferred biomaterial. Typically the amount of lubricant required in the mixture with the biomaterial is that what provides for proper intrudability of the biomaterial into the internal body tissue at the desired location and which also provides for proper extrudability of the biomaterial through and out from the flow delivery system  630 . 
         [0070]    The flow delivery system  630  may include the syringe  612 , plunger  614  and needle and/or catheter  620 , along with some or all of the other structural components of the previously described flow delivery systems described in detail above. In one preferred embodiment, the flow delivery system  630  also includes a filter  650  located in the flow path inside the syringe  612  such that the filter  640  covers the entire cross-sectional area of the flow path inside the syringe  612 . Also, the filter is illustrated as being located in the lower portion of the syringe  612  near the tapered end  616  of the syringe  612 . However, the filter  640  may be located anywhere within the flow path in the inside of the syringe  612 . The filter  640  may be adhered to the inner surface of the syringe  612 , or may be press fit therein. It suffices that the filter  640  be placed within the inside of the syringe  612  such that it does not move when the aqueous solution is forced through the syringe  612  by, e.g., the plunger  614 . 
         [0071]    Referring to  FIG. 23 , there illustrated in perspective is another embodiment of the filter  640 . The filter  640  comprises a disk  642  having a plurality of through holes  644  of a predetermined shape formed in the disk  642  by, e.g., an etching process. In the exemplary embodiment of  FIG. 23 , the disk  642  may comprise a sterile material such as stainless steel, glass or other suitable material, and the plurality of through holes  644  all have a honeycomb shape and are of equal size. In the alternative, the size of the holes  644  may vary between one another. The size of the holes  644  is preferably selected in dependence on the size of the opening or orifice in the needle and/or catheter  620  utilized in the flow delivery system  630 . The holes  644  will break up or downsize any biomaterial particles within the aqueous solution which are larger than the size of the holes  644  as these particles encounter the holes when the solution travels through the syringe  612  under an applied force (e.g., from the action of the plunger  614 ). The downsized particles then pass through the holes  644  and through the remainder of the flow delivery system  630  and out of the needle/catheter  620  unobstructed and into a body. Also, for any particles smaller than the size of the holes, these particles pass through the holes  644  without any downsizing taking place. 
         [0072]    Referring to  FIGS. 24-25 , there illustrated is an alternative embodiment of the filter  640 . In  FIG. 24 , a plurality of sterile solid glass rods  646  are bundled together and held bundled together by an outer sheath  648 . The sheathed bundle of rods  646  may then be sliced perpendicular to the axis of the rods  646  to form the filter  640  of  FIG. 25 . The spaces  650  between the glass rods function as the holes of the filter  640  for downsizing of the particles within the aqueous solution. In the alternative, some or all of the glass rods  646  comprising the filter  640  may not be solid but instead may be hollow, thereby creating an opening  652  within each of the hollow rods  646 . In this alternative embodiment, the openings  652  within the hollow rods  646  are of a predetermined size for downsizing of the particles within the aqueous solution and work in conjunction with the spaces  50  between the rods  646  for downsizing of the particles. 
         [0073]    In operation, the filter  640  within the flow delivery system  630  of the present invention breaks up any agglomerated biomaterial particle matter or mass within the aqueous solution into smaller particles of a specific size or smaller (i.e., that of the openings  644  in the filter  640  of  FIG. 23 ). Since the size of the openings in the filter  640  is selected in dependence on the size of the orifice of the needle/catheter  620  utilized, the size of the particles suspended in the aqueous solution and transported through the syringe  612  do not clog up the needle/catheter orifice. Instead, the solution is expelled without obstruction out of the orifice of the needle/catheter  620 . Thus, the flow delivery system  630  of the present invention sizes the particulate matter within the syringe  612  before it reaches the needle  620 . this reduces the resistance to the flow of the aqueous solution through the flow delivery system  630 , which also reduces the amount of force necessary to transport and expel the aqueous solution through the system  30  and into a body, even with systems  630  that utilize an elongate needle/catheter  20 . 
         [0074]    The flow delivery system  630  has been described for use with a conventional syringe and needle/catheter configuration that also contains a plunger  614  to supply a force to push the aqueous solution through the syringe  612  and out of the needle/catheter  620 . However, the broadest scope of the present invention is not limited as such. The plunger  614  may be omitted and other means for forcing the aqueous solution through the syringe  612  may be utilized such as, for example, an acoustic transducer. Also, the syringe  612  may omit the plenum  24  ( FIG. 21 ) and instead my employ various means for facilitating the flow of the aqueous solution out of the syringe and into and through the needles/catheter  620 . For example, a contoured lower portion of the syringe  612  may be utilized. 
         [0075]    As shown in  FIG. 26 , water soluble, cross-linkable polysaccharide is combined with water  710  when mixed the material is initially of high viscosity  711 . The following stage of the process involves one of either or both sterilization methods  712  high-intensity, short-duration pulses of incoherent, polychromatic light in a broad spectrum; or high-amplitude ultrasonic sound waves to cause cavitation in a liquid  712  to sterilize the flowing material  713 . After the sterilization process the viscosity of the material is lowered  715 . While the viscosity is low, a cross-linking agent is added  714  the low viscosity permits homogenous mixing  716 . The material is then sized  719  by a means of electrical and/or acoustic wave sizing  718 . In order to remove air bubbles, or to de-gas the material it is placed in a vacuum and centrifuge  717 , in this stage the viscosity is raised to the level prior to the sterilization. The material is then dispensed in various vessels for medical use  720 . 
         [0076]    Thus, the sterilization and sizing of biomaterial, and in particular to the sterilization and sizing of said biomaterial without the interruption of flow within the production system is provided. The same accomplishes improving the speed of the production system and the quality of the end product. The sterilization of the biomaterial can be accomplished by ultraviolet radiation and by acoustic wave. The processes may employ ultraviolet radiation, acoustic wave or both ultraviolet radiation and acoustic wave. High intensity short duration pulses of light for deactivating microorganisms may be employed along a sealed system so as to allow the process to flow without interruption or contamination. Acoustic waves may be employed as an efficient means of delivering energy into a substance. The energy may be directed in such a manner as to provide heat and pressure within a closed loop system. Acoustic and/or electrical waves may also be employed in such a manner as to provide uniform particle sizing within a bio-compatible gel. Thus, a manufacturing system can include the forming of an aqueous solution of a water soluble, cross-linkable polysaccharide; sterilizing the material with high-intensity pulses of polychromatic light and/or by the use of high-amplitude ultrasonic sound waves; initiating a cross-linking of said polysaccharide with a cross-linking agent and sizing the particles. The process continues with mixing of the cross-linking agent with the material which is then de-gassed and dispensed for medical use. 
         [0077]    Although the present invention has been illustrated and described with respect to several preferred embodiments thereof, various changes, omissions and additions to the form and detail thereof, may be made therein, without departing from the spirit and scope of the invention.