WO2008057976A2

WO2008057976A2 - Multiple dose syringes

Info

Publication number: WO2008057976A2
Application number: PCT/US2007/083399
Authority: WO
Inventors: Wilmer L. Sibbitt, Jr.; Randy R. Sibbitt
Original assignee: Avanca Medical Devices, Inc.
Priority date: 2006-11-03
Filing date: 2007-11-02
Publication date: 2008-05-15
Also published as: WO2008057976A3

Abstract

Multiple dose syringe apparatuses and methods suitable for use to administer multiple small doses of drugs particularly for dermatology, plastic surgery, cosmetic surgery, and neurological medicine. The multiple dose syringes can be constructed from a conventional syringe and conventional plunger with adapters, and also by individual injection mounding. The multiple dose syringe comprises a plunger with repetitive engaging structures than reversibly interact with an engaging member on the barrel where the distance between each engaging structure defines a volume or dose in the syringe. The engaging member can be flexible, semiflexible, or reversibly displaceable and as the plunger is depressed moves reversibly from one engaging structure to the next. A restraining member assures contact between the engaging member and engaging structure.

Description

Multiple Dose Syringes Technical Field

[0001] The present invention relates to syringes used to administer multiple predetermined doses of a medication or fluid specifically for the field of diagnostic, therapeutic, or preventive medicine, nursing, or pharmacy. Background Art

[0002] Common practice in medicine, nursing, and pharmacy to administer or expel multiple predetermined doses of a medication or a fluid from a syringe is to observe the plunger stopper in its relationship to the gradation scale, which is usually printed or embossed on the exterior of the syringe barrel. However, it is easy for the operator to administer too much or to little medication or fluid because it is difficult to see the gradations on the syringe barrel. This is particularly true when greater pressure must be administered to the syringe device as in percutaneous angiography when high-pressure increments must be administered with force. Similarly, in the administration of botulinum toxin and other neuromuscular blocking agents, if too much is given excessive muscle weakness or paralysis can develop. Electronic or computerized injectors have been used, but these can be expensive and awkward, and do not meet the day-to-day needs of clinics, pharmacists and nurses.

[0003] In particular, in dermatology, plastic surgery, cosmetic surgery, neurology, and neurosurgery there is a need to administer multiple small substantially identical increments of drugs in multiple anatomic sites. This type of multiple precise injections is required for botulinum toxin derivatives, hyaluronate derivatives, collagen preparations, sclerosing agents, biologic response modifier, antiinflammatory agents, and other fillers and neuromuscular blocking agents used cosmetically. Typically a patient might receive from 2 to 50 individual injections of similar or identical doses. With all these agents, administering too much or too little drug can cause an unacceptable clinical outcome. A simple device to permit administration of multiple small doses or increments of identical volume is needed. [0004] Various methods have been attempted to create multiple dose syringes. US Patent 4702737 describes a multidose syringe with a dual chamber syringe, and without substantial modifications to the plunger. US Patent 5290258 describes a multidose syringe that functions by having a rotating cap with multiple nosils, but otherwise is a rather conventional syringe. US Patents 6270482 B1 , 6558358 B2, and 7011650 B2 describe a multiple dose syringe with a bellows mechanism pushed by the plunger, but otherwise without major design changes in the plunger.

[0005] Modifications to the plunger can have particular advantages for multiple dose syringes. US Patent 5318544 describes a multiple dose syringe with a modified plunger with complex recesses that interact with a stop on the barrel, and the plunger and/or syringe must be rotated to actuate the stop. The stop surfaces are recesses in a columnar plunger. Recesses or depressions in the plunger can potentially weaken a plunger and cause breakage. Moreover, this is a complex syringe device that cannot use off- the-shelf conventional syringes and adapters in its construction, but rather requires multiple high precision dedicated molds that can be very expensive.

[0006] US Patent 5385558 describes a high-pressure angiographic syringe with a locking ring that engages recessed grooves on the plunger. The ring is pinched to release the locking so that the plunger can go to the next level. It is not intended for and does not function well for multiple small low-pressure injections as in cosmetic surgery, because the ring has to be pinched between each administration increment and the syringe is so bulky. Also, the recesses on the plunger detract from the strength of the plunger.

[0007] US Patent 6972006 B2 describes a multiple dose syringe with resistive ridges where the ridges are in the barrel itself and interact directly with the stopper on the plunger rather than the plunger. The moulds for such barrels can be very difficult to manufacture, and this type of device cannot use standard conventional syringes or barrels in its construction.

[0008] US 6579269 B1 describes a multiple dose syringe with protrusions from the barrel that engage a plunger with slotted vanes; the interaction of slots and protrusions provides resistance and an audible click. Alternatively, there is a protrusion from the plunger that interacts with a slot or protrusion from the barrel. This has the disadvantage in that the plunger must be individually injection molded or substantially machined, and conventional syringe parts cannot be used. Also, the slots on the plunger can weaken the plunger causing breakage. Another disadvantage are that the slots or protrusions must match on every vane; if each vane does not engage simultaneously the device can provide multiple sensed resistance and multiple clicks. In addition, this design does not permit easy mixing of the drug prior to administration.

[0009] US Patent Application 2003/0004467 A1 describes a cartridge syringe that can provide multiple doses including a threaded base, projections on the plunger shaft, a mechanism (position selector) for selecting the dose. This system is complex, requires special molded parts, and cannot use off the shelf- syringes and components.

[0010] Other modifications to plungers to permit sequential motion or unidirectional motion have been described previously. US Patents 5531691 , 5562623, and 5380295 describe syringes with a plunger with ratchet teeth that prevent the syringe plunger from being pulled back after an injection, and thus lock the plunger from backward motion. All of these provide an audible click and can provide multiple increments of medication, but require specially molded parts and expensive moulds. US Patent 5637092 describes a plunger with dentates that lock into the barrel at the end of a syringe cycle. This is intended to inactivate the syringe and is to be used with syringe safety systems rather than to administer multiple doses.

[0011] US Patents 4512769, 7018382 B2, Des. 297458, and 4658993 describe a plunger with ratchet teeth that interact with a ratchet so that the ratchet mechanism can mechanically advance the plunger rather than pushing on the plunger. These devices also provide an audible click. In this case the ratchet teeth can act to administer discrete doses of medication, and some are meant to permit movement of the plunger without pressing on the plunger, and to permit high-pressure injection. These devices are somewhat difficult to fill because of the ratcheting mechanism, and require specially molded parts and expensive moulds.

[0012] References that might be of interest in understanding the present invention include: US Patent 4702737. Joanne L. Pizzino. Dual dose syringe. Oct 27, 1987.

US Patent 6270482 B1. Jack P. Rosoff, Michael N. Hirsch, AIi S. Salem. Multiple-dose syringe. Aug. 7, US Patent 6558358 B2. Jack P. Rosoff, Michael N. Hirsch, AIi S. Salem. Multiple-dose syringe. May 6,

2003.

US Patent 7011650 B2. Jack P. Rosoff, Michael N. Hirsch, AIi S. Salem. Multiple-dose syringe with collapsible container. Mar. 14, 2006.

US Patent 5290258. James F. Ennis. Syringe for administering sequentially multiple doses of a medication. Mar. 1 , 1994.

US Patent 5318544. John Drypen, Charles E. Steele. Metering syringe. June. 7, 1994.

US Patent 5385558. Joseph R. Cottose, Anthonty J. Cottose. Angiographic control syringe. Jan. 31 ,

1995.

US Patent 6972006 B2. Gary William Ferguson. Syringe device with resistive ridges and methods of use. Dec. 6, 2005.

US Patent 6579269 B1. Gennady I. Kleyman. Dosage device. Jun. 17, 2003.

US Patent Application 2003/0004467 A1. James R. Musick, Jon P. Page. Multidose syringe driver. Jan.

2, 2003.

US Patent 5531691. David Shonfeld, Joel S. Schoenfeld. Single use syringe assembly. Jul.2, 1996.

US Patent 5562623. David Shonfeld, Joel S. Schoenfeld. Single use syringe assembly including spring clip lock and plunger. Oct.8, 1996.

US Patent 5380295. Rita D. Vacca. Delivery apparatus with a mechanism preventing rearward movement of a piston disposed therein. Jan 10.1995.

US Patent 5637092. Thomas J. Shaw. Syringe plunger locking assembly. Jun. 10, 1997.

US Patent 4512769. George Kozan; Pat Romanelli. Patient employed digital operated syringe device for irrigating periodontal pockets and other soft tissue spaces. Apr. 23, 1985.

US Patent 7018382 B2. Barbara L. Merboth, Arthur A. Genzman. Bone marrow mixing instrument. Mar.

28, 2006

US Patent Des. 297458. Robert D. Holewinski. Rachet syringe for composite dental materials. Aug. 30,

1998.

US Patent 4658993. Richard J. Vlasich. Metering dispenser for viscous compositions. Apr.21 , 1987.

[0013] Accordingly, there is a need for methods and apparatuses that are suitable for providing a multiple dose syringe that do not suffer from the drawbacks of conventional devices mentioned above.

Disclosure of Invention

[0014] The present invention provides methods and apparatuses that are suitable for converting a largely conventional syringe or conventional reciprocating syringe into a multiple dose syringe or for making an integrated multiple dose syringe. The present invention comprises methods of modifying the plunger and barrel to permit multiple identical doses of a medication or fluid to be administered. The present invention also comprises methods for reversibly activating and inactivating the multiple dose mechanisms so that the device can function as a conventional syringe or a multiple dose syringe. The present invention also comprises components and methods for making multiple dose syringes out of conventional syringes and conventional reciprocating syringes with inexpensively produced adapters. The present invention also comprises integrated multiple dose syringes. The present invention can be used by physicians to administer multiple small, substantially identical doses of medication to a patient in one procedure, for example for the administration of botulinum toxin derivatives, neuromuscular blocking agents, hyaluronate, collagen, sclerosing agents, anti-inflammatory drugs, biological response modifiers and other medications used in dermatology, plastic surgery, cosmetic surgery, and neurologic sciences.

Brief Description of Drawings

[0015] The invention is explained by using example embodiments and corresponding drawings, which are incorporated into and form part of the specification.

Figure 1 is a schematic illustration of example plungers and plunger adapters for a multiple dose syringe.

Figure 2 is a schematic illustration of example multidose syringe barrel adapters according to the present invention.

Figure 3 is a schematic illustration of an example frame for a reciprocating mixing syringe according to the present invention.

Figure 4 is a schematic illustration of an example multidose syringe according to the present invention.

Figure 5 is a schematic illustration of example plungers and plunger adapters for a multiple dose syringe.

Figure 6 is a schematic illustration of example multidose syringe barrel adapters according to the present invention.

Figure 7 is a schematic illustration of an example multidose syringe according to the present invention.

Figure 8 is a schematic illustration of an example multidose syringe according to the present invention.

Figure 9 is a schematic illustration of an example reciprocating multidose syringe according to the present invention.

Figure 10 is a schematic illustration of example plungers and plunger adapters for a multiple dose syringe.

Figure 1 1 is a schematic illustration of an example reciprocating multidose syringe according to the present invention.

Modes for Carrying Out the Invention, and Industrial Applicability

[0016] The present invention provides apparatuses and methods for multidose syringes.

[0017] Figure 1 is a schematic illustration of the assembly of an example plunger of a multidose syringe using an adapter on a conventional syringe plunger according to the present invention, and in particular an adapter that accommodates a standard four vane plunger. The adaptor comprises a piece that fits into one of the open spaces between the vanes of the plunger, which are usually at right angles to each other. The adapter can comprise a triangular-shaped column as shown in examples 1 , 2, 3, 4, 5 so that it fits into the right angle space formed by the intersection of the plunger vanes. Example 6 is an embodiment that demonstrates that the adapter need not be a triangular column but could take other shapes as well, as long as they can fit into the potential space between the vanes. Unlike prior art designs, addition of these adapters make the plunger stronger rather than weaker. The adaptors permit engagement structures fixed to the plungers to interact reversibly with one or more engagement members on the syringe barrel. In this example embodiment the engaging structures are rigid or semi-rigid. The engagement members can be flexible, semi-flexible, compressible, or displaceable so that the engagement member can move in and out of the engagement structure as the plunger is moved up and down. The distance between each engagement structure feature can correspond to a predetermined volume in the syringe. Each high point on the engagement structure can provide resistance to mechanical movement of the engagement member in and out of the adjacent engagement structures, thus permitting the operator to feel resistance and, depending on the materials, hear an audible click. Example 1 comprises an engagement structure that defines a columnar or another geometric or curvilinear space in the adapter. The engagement structures on example 1 can interact with an engagement member that is substantially columnar, or relatively flat with an angular point that can interact with the adapter member 1. Example 2 comprises engagement structures that reside between columnar or other protuberances on the plunger adapter, and can interact with a broad flat engagement member. The adapter of example 2 can be built of flexible, semiflexible or compressible materials and the syringe member out of rigid materials. Example 3 has engagement structures that are slots; example 4 has engagement structures that are smooth depressions, and examples 5 and 6 have engagement structures that are negative teeth. Engagement structures 3 through 6 can interact reversibly with a number of engagement members including substantially columnar or relatively flat engagement members with pointed or flat surfaces. Example 7 illustrates the adapter being placed into a corresponding space on the plunger formed by the intersection of two vanes where 8 is the stopper of the plunger, 9 is a plunger vane, and 10 is the thumb rest of the plunger. Once the adapter is fitted into the plunger, and glued, welded, bonded, or affixed to the plunger by mating structures, a multidose plunger 11 results which has the adapter structures exposed to interact with the syringe structures of the barrel. Detail 13 illustrates the adapter (black structure) fitted against two plunger vanes. While the examples illustrate evenly spaced features, the invention can also provide features with different spacings for applications where predictable but nonuniform doses are desired.

[0018] Figure 2 is a schematic illustration of the assembly of barrel of an example multidose syringe using an adapter placed on a conventional syringe barrel according to the present invention. One component of the barrel adapter is an engagement member that interacts with an engagement structure on the plunger (like those illustrated in Fig. 1 ). Example 14 is an example of an engagement member comprising a flat structure with a flat forward surface; example 15 is an example of an engagement member comprising a flat structure with a sharp forward structure; and example 16 is an example of an engagement member consisting of substantially columnar structure. The engagement members can be flexible, semiflexible, compressible, or displaceable so that the engagement member can move in and out of the engagement structure as the plunger is moved up and down. In one example embodiment the engagement member has a fitting that interacts reversibly or irreversibly with the barrel adapter or barrel so that the engagement member(s) can be fixed in place after the plunger has been inserted into the barrel complex. 17 is a top view of the barrel adapter with a circular structure 18 for the barrel and plunger of the syringe, and the syringe member 19, and the restraining member 20. The restraining member 20 can be shaped as a rigid right angular structure than fits into the space created by the intersecting vane of the plunger. The restraining member 20 can assure intimate contact between the engagement member of the barrel and the engagement structure of the plunger by preventing the plunger from moving away from the engagement member. 21 is a side view of a barrel adapter with the engagement member 22, the restraining member 23, and adapter structures 24 and 25 to receive and irreversibly fix the finger flanges of a conventional syringe. 26 is an oblique view of the adapter and the finger flanges 27 of a conventional syringe that fit (arrows) into the adapter structures of the barrel adaptor. 29 is the assembled barrel complex of the multiple dose syringe with finger flanges 30, restraining member 31 , and engagement member 32.

[0019] Figure 3 is a schematic illustration of the assembly of a multidose syringe by joining the barrel and plunger according to this invention. The engagement member 33 and restraining member 34 are in a position so that the plunger 35 can be freely inserted (arrow) into the barrel 36. The engagement member 38 is advanced and locks in position against the plunger, and on the opposite side 39 the restraining member is also advanced against the plunger. 40 is a top view of the assembled multidose syringe where the engagement member 41 is intimately and reversibly interacting with the engagement structures 41 of the plunger 43 which is restrained from distal movement by the restraining member 44. There can be more than one restraining member as shown in 44a, or the restraining members and the engagement member can be made in one piece or joined together with rigid or semielastic bonds to permit some movement, yet still ensure intimate contact between the engagement member and the engagement structure of the plunger. As the plunger 45 is moved up or down, the engagement member 38 interacts reversibly with the engagement structures 46. Each high point on the engagement structure provides resistance to mechanical movement of the engagement member in and out of the adjacent engagement structures, thus permitting the operator to feel resistance and, depending on the materials, to hear an audible click. The distance between each engagement structure 46 represents a predetermined volume in the syringe.

[0020] Figure 4 is a schematic illustration of the assembly of an integrated multidose syringe. In this schematic plunger 47 with engagement structures is injection molded as a single piece, and the barrel complex 48 is also individually injection molded with appropriate sliding fittings for the engagement member 49 and the restraining member 50. This device functions as described in relation to the multidose syringes in Figures 1 through 3.

[0021] Figure 5 is a schematic illustration of the assembly of the plunger of a multidose syringe using an adapter on a conventional syringe plunger according to the present invention, and in particular an adapter that accommodates a standard four vane plunger. The adaptor comprises a piece that fits onto one of vanes of the plunger, which are usually at right angles to each other. A complex sleeve as shown in examples 51 through 55 can fit over a plunger vane. Example 56 is an embodiment that demonstrates the adapter comprising a simple sleeve. Unlike prior art designs, addition of adapters as shown in the figure can make the plunger stronger rather than weaker, and need only to be on one vane. The adaptors permit the engagement structures fixed to the plungers to interact reversibly with engagement element(s) on the syringe barrel. The engagement structures can be rigid or semirigid. The engagement members can be flexible, semiflexible, compressible, or displaceable so that the engagement member can move in and out of the engagement structure as the plunger is moved up and down. The distance between each engagement structure can represent a predetermined volume in the syringe. Each high point on the engagement structure can provide resistance to mechanical movement of the engagement member in and out of the engagement adapter structures, thus permitting the operator to feel resistance and, depending on the materials, hear an audible click. Example 51 comprises an engagement structure that has a columnar or other geometric or curvilinear space in the adapter. The engagement structures on example 1 can interact with an engagement member that is substantially columnar or relatively flat with an angular point. Example 52 illustrates engagement structures that reside between columnar or other protuberances on the plunger adapter, and can interact with a broad flat engagement member. The adaptor of example 52 can be built of flexible, semiflexible or compressible materials and the engagement member can comprise rigid materials. Example 53 comprises engagement structures that are slots; example 54 comprises engagement structures that are smooth depressions, and examples 55 and 56 comprises engagement structures that are negative teeth. Engagement structures 53 through 56 can interact reversibly with a number of engagement members including substantially columnar or relatively flat engagement members with pointed or flat surfaces. Example 57 illustrates as adapter being placed (arrows) onto the corresponding plunger vane 58, where 59 is the stopper of the plunger, and 60 is the thumb rest of the plunger. Once the adapter is fitted into the plunger, and glued, welded, bonded, or affixed to the plunger by mating structures, a multidose plunger is created 61 , which has the engagement structures 62 exposed to interact with the engagement element of the barrel. 63 shows an adapter (black structure) fitted over the plunger vane in cross-section. 64 shows a simple sleeve (also in 56) fitted over the plunger vane.

[0022] Figure 6 is a schematic illustration of the assembly of barrel of a multidose syringe using an adapter placed on a conventional syringe barrel according to the present invention. The barrel adapter comprises an engagement member that interacts with an engagement structure on the plunger. In the figure, the engagement member is situated on the surface of the vane. 65 is an example of an engagement member consisting of a flat structure with a flat forward surface; 66 is an example of an engagement member consisting of a flat structure with a notch which engages the engagement structures on the vane; and 67 is an example of this same type of notch by containing a engagement member consisting of substantially columnar structure. The engagement members can be flexible, semiflexible, compressible, or displaceable so that the syringe member can move in and out of the engagement structure as the plunger is moved up and down. In one embodiment the engagement member has a fitting that interacts reversibly or irreversibly with the barrel adapter or barrel so that the engagement members can be fixed in place after the plunger has been inserted into the barrel complex. 68 is a top view of the barrel adapter with a circular structure 69 for the barrel and plunger of the syringe, and the syringe member 70, and the restraining member 71 (in this example slotted). The restraining member 71 can be shaped as a rigid rectangular structure with a slot to accommodate and stabilize the syringe. The restraining member 71 can assure intimate contact between the engagement member of the barrel and the engagement structure of the plunger by preventing the plunger from moving away from the engagement member. 72 is a side view of the barrel adapter with the engagement member 73, the restraining member 74, and adapter structures 75 and 76 to receive and irreversibly fix the finger flanges of a conventional syringe. 77 is an oblique view of the adapter and the finger flanges 78 of a conventional syringe which fit (arrows) into the 79 adapter structures of the barrel adaptor. 80 is the assembled barrel complex of the multiple dose syringe with finger flanges 81 , restraining member 82, and engagement member 83.

[0023] Figure 7 is a schematic illustration of an assembled multidose syringe using an adapter placed on a conventional syringe barrel according to the present invention. 84 is a top view of the finger flanges showing a slotted engagement member 85 intimately interacting with an engagement structure 86 (shown as a black structure) on the corresponding vane, the next vane 87, a slotted restraining member 88 abutting all three opposing vanes. The structure of the engagement member keeps pressure on the contact point with the engagement structure, while the restraining member contacts the opposite side of the plunger and keeps the plunger from moving away. 89 is an oblique view of the completely assembled device. The engagement structures and plunger can be injection molded as a single piece, and the barrel complex can also be individually injection molded with appropriate sliding fittings for the engagement member and the restraining member.

[0024] Figure 8 is a schematic illustration of a multidose syringe that can be reversibly converted to a conventional syringe and back again. This can be accomplished with a modification of the plunger. Many plungers have a break-off mechanism comprising a narrowed section of the plunger. This narrowing can be used to rotate the plunger to a position where the engagement structures are not in contact with the engagement members, e.g., being rotated 90° to the side. 90 is the syringe plunger with the engagement structures and 91 a narrowing of the plunger body. The plunger is pulled 92 back so that the narrowing is aligned with the engagement member and the restraining member, and rotated. This rotates 93 the engagement structures 90° away from the engagement member and thus there is no interaction between them and 94 the syringe functions now as a regular syringe. The schematic 95 shows the engagement structures at 90° to the engagement members 96 and not in contact with the restraining member 97. [0025] Figure 9 is a schematic illustration of a multidose syringe that is also a reciprocating syringe using a multidose mechanism as described herein. The plungers on reciprocating syringes are mechanically bound together by a mechanical reciprocating mechanism, so the plungers on reciprocating syringes actively reciprocate with each other whether there is mixture in the syringe or not. Typically the mechanical reciprocating mechanism is a pulley, gear, or hydraulic link between the two plungers. US Patents applications 20060184130A1 and 20050192543A1 , and US Patents 6245046, 6962576, and 7118554 describe reciprocating syringes, but none of them are multidose reciprocating syringes. 98 is the dominant plunger with the engagement structures, 99 is the engagement member, 100 is the accessory plunger, and 101 is the reciprocating mechanism, in this case a pulley system. This permits one-handed operation of the multidose syringe. All of the previous embodiments for the multidose syringe also apply to the reciprocating multidose syringe. In the case of the reciprocating syringe the multidose mechanism can be placed on either the dominant or accessory plunger and barrel and each would function equally well since they are mechanically bound together. Predetermined syringe motions can thereby be provided on both injection and aspiration operations.

[0026] Figure 10 a schematic illustration of a plunger for a multidose syringe according to the present invention. A special problem arises when a symmetrical columnar plunger is used on a syringe, which is typical for the 1 ml syringe and smaller, but can be used on any sized syringe instead of the standard four vane plunger as noted in the prior embodiments. To convert a conventional syringe with a columnar plunger to a multidose syringe, the plunger can be replaced with a four vane version as previously described with the engagement structures, or the engagement structures can be integrated within the columnar plunger itself. Because most columnar plungers do not give adequate space for adapters, in the example in the figure, a special columnar plunger can be used to convert the conventional syringe to a multidose syringe. 102 consists of a substantially columnar plunger with angular geometric repetitive engagement structures on its surface; 103 consists of a substantially columnar plunger consisting of stacked plates of different diameters with right angled edges, 104 consists of a substantially columnar plunger consisting of stacked plates of different diameters with curved edges; and 105 consists of a an undulating cylinder of repetitively different diameters. In each case the smaller diameter portion creates the engagement structure. These plungers can be individually formed, and can also be constructed of a columnar sleeve that is placed over the conventional cylindrical plunger, space permitting. [0027] Figure 11 a schematic illustration of a multidose syringe according to the present invention. Because a columnar plunger can tend to rotate with pressure, the engagement structures can be shaped to be functional over a range of rotational positions. The engagement member configuration in the figure accommodates such a columnar structure. In a top view of a multidose syringe with a columnar plunger of varying diameters between the engagement structures and greater diameter structures, 106 is the finger flanges, 107 is the engagement member and 108 is the restraining member. In this case, the engagement member and restraining member can be identical or mirror images of each other in properties and construction. The engagement and restraining members provide resistance moving from 109 the smaller diameter adapter structure to 1 10 larger diameter structure. The engagement member and restraining member can be flexible, semiflexible, or rigid with the ability to be reversible displaced along the plane of the finger flanges. 111 shows the fully assembled device. With symmetric columnar plungers with engagement surfaces, a combined engagement and restraining member 112 can be constructed. In this case it can be a reversibly deformable membrane, sheet or plate, metal or plastic clips, or a reversibly deformable mounted annular ring all constructed of reversibly deformable elastomeric materials. 1 15 shows this fully assembled device.

[0028] All of the above devices can be constructed and assembled from many components, or can be injection molded in a few components. It is anticipated the construction materials can comprise plastic, polymers, metal, and glass or combinations of these materials with appropriate biologically compatible lubricants and surface treatments as is known to the art. [0029] Applications

[0030] Multidose syringes according to the present invention can be used to administer multiple small substantially identical doses (increments) of drugs and substances in multiple anatomic sites, especially for botulinum toxin derivatives, other neuromuscular blocking agents, hyaluronate derivatives, collagen preparations and derivatives, skin fillers, corticosteroids, anti-inflammatory agents, hormones, sclerosing agents, tattooing and coloration agents, anti-aging agents, chemotherapy, radioactive substances, antibiotics, preservatives and biologic response modifiers.

[0031] Multidose syringes according to the present invention can be used for administration of cosmetic pharmaceuticals as used in dermatology, plastic surgery, and cosmetic medicine. Multidose syringes according to the present invention can be used for administration of neuroactive pharmaceuticals as used in neurology, plastic surgery, neurosurgery, pain clinics, anesthesiology and other specialties. Multidose syringes according to the present invention can be used for delivering multiple identical or integral multiples of any drug or substance. Multidose syringes according to the present invention can be used to administer identical aliquots of a drug or reagent for pharmacy or nursing. Multidose syringes according to the present invention can be used for patient administration of drugs. Multidose syringes according to the present invention can be used first to mix or resuspend or draw up a pharmaceutical and then used as multidose syringe. Multidose syringes according to the present invention can be converted to a conventional syringe with the multidose mechanism inactivated by rotating the plunger, used to mix like a conventional syringe, and then rotated back to convert back to a multidose syringe. [0032] The particular sizes and equipment discussed above are cited merely to illustrate particular embodiments of the invention. It is contemplated that the use of the invention can involve components having different sizes and characteristics. It is intended that the scope of the invention be defined by the claims appended hereto.

Claims

We claim:

1 ) A syringe comprising: a) A plunger having a plurality of engagement features spaced along the actuation axis of the plunger; b) A barrel configured to slidably engage the plunger, and having a engagement feature mounted with the barrel such that the barrel engagement feature engages in sequence the plurality of engagement features on the plunger providing a mechanical resistance to motion that varies as the barrel engagement features engages each plunger engagement feature.

2) A syringe as in Claim 1 , wherein the barrel engagement features comprise one or more of repetitive columnar depressions, repetitive space and pegs, slots, undulating surfaces, and teeth.

3) A syringe as in Claim 1 , wherein the plunger engagement features are spaced such that plunger motion equal to the distance between two adjacent plunger engagement features substantially corresponds to a predetermined volume displacement in the barrel.

4) A syringe as in Claim 1 , wherein the plunger comprises a four vane plunger, and wherein the plunger engagement features comprise an adaptor mounted with the four vane plunger.

5) A syringe as in Claim 4, wherein the adaptor comprises an elongated member, having two adjacent sides forming approximately a right angle and sized to fit in between two vanes of the plunger, and having a third side having engagement features.

6) A syringe as in Claim 5, wherein the engagement features comprise one or more of repetitive columnar depressions, repetitive space and pegs, slots, undulating surfaces, and teeth.

7) A syringe as in Claim 4, wherein the adaptor comprises an elongated member shaped to fit over a vane of the plunger.

8) A syringe as in Claim 4, wherein the plunger has a narrowed portion such that, when the narrowed portion is adjacent the barrel engagement feature, the plunger can be rotated, and wherein the plunger engagement features engage the barrel engagement feature when the plunger is at a first rotational relationship to the barrel but do not engage the barrel mechanical features when the plunger is at a second rotations relationship to the barrel.

9) A syringe as in Claim 1 , wherein the plunger comprises a columnar portion having a cross-sectional area that varies along the axis of the columnar portion.

10) A syringe as in Claim 1 , further comprising a restraining member mounted with the barrel such that the restraining member urges contact between the barrel engagement feature and the plunger engagement features.

11 ) A syringe adaptor kit, comprising: a) A plunger adaptor that is mountable with a plunger of a syringe and provides a plurality of engagement features spaced along the actuation axis of the plunger when mounted with the plunger; b) A barrel adaptor that is mountable with a barrel of a syringe and provides an engagement feature that engages with the engagement features on the plunger adapter when the plunger and plunger adaptor move along the barrel axis.

12) A syringe adaptor kit as in Claim 11 , wherein the barrel adaptor further comprises a restraining member that is mountable with the barrel of the syringe and that urges the plunger engagement features to engage with the barrel engagement feature.

13) A syringe adaptor kit as in Claim 1 1 , wherein the plunger engagement features comprise one or more of repetitive columnar depressions, repetitive space and pegs, slots, undulating surfaces, and teeth.

14) A syringe adaptor kit as in Claim 1 1 , wherein the plunger adaptor comprises an elongated member, having two adjacent sides forming approximately a right angle and sized to fit in between two vanes of the plunger, and having a third side having engagement features.

15) A syringe adaptor kit as in Claim 1 1 , wherein the plunger adaptor comprises an elongated member shaped to fit over a vane of a four vane syringe plunger or to fit within the space between two adjacent vanes of a four vane syringe plunger.

16) A syringe adaptor kit as in Claim 15, wherein the plunger adaptor has along the axis collinear to the plunger length engagement structures comprised of one or more of repetitive columnar depressions, repetitive space and pegs, slots, undulating surfaces, teeth, or smooth teeth; the distance between features of the engagement structure representing a corresponding volume in the syringe, and is constructed of rigid or semirigid materials; and is adapted to be fitted into or bonded to the plunger.

17) A syringe adaptor kit as in Claim 1 1 , wherein the barrel adaptor comprises a flexible, semiflexible, compressible, or displaceable engagement member that interacts intimately and reversibly with the engagement structures on the plunger adaptor so that each engagement feature on the plunger adaptor provides resistances to mechanical movement of the engagement member in and out of the adjacent plunger engagement structures, thus permitting the operator to feel resistance to motion, hear an audible click, or both, in positions where the engagement member is of a shape that favorably mates with a corresponding plunger engagement structure.

18) A syringe adaptor kit as in Claim 1 1 , wherein the barrel adaptor further comprises a restraining member adapted to mount with the barrel and urge the plunger engagement features into intimate contact with the barrel engagement feature.

19) A syringe adaptor kit as in Claim 1 1 , wherein the barrel engagement feature mounts to engage the plunger adaptor engagement features on a first side of the plunger, and wherein the restraining member mounts to urge the plunger on the opposite side of the plunger.

20) A syringe adaptor kit as in Claim 1 1 , wherein the barrel adaptor mounts with the barrel such that the engagement feature can be selectively positioned to engage or not to engage the plunger adaptor engagement features.

21 ) A syringe adaptor kit as in Claim 11 , wherein the barrel adaptor comprises fittings adapted to mount with finger flanges of a syringe. 22) A syringe as in Claim 9, wherein the plunger has one or more of angular geometric engagement features on its surface; stacked plates of different diameters with right angled edges, stacked plates of different diameters with curved edges; and an undulating repetitively different diameters.

23) A syringe as in Claim 9, wherein the barrel engagement feature comprises one or more of a membrane, sheet, plate, spring, or annular ring of reversibly deformable and elastomeric properties.

24) A syringe as in Claim 23, wherein the barrel engagement feature further urges the plunger engagement features into intimate contact with the barrel engagement member.

25) A method of making a syringe, comprising: a) supplying an adaptor kit as in Claim 11 ; b) supplying a syringe having a barrel and a plunger' c) mounting the plunger adaptor with the plunger; d) mounting the barrel adaptor with the barrel; e) disposing the plunger with mounted plunger adaptor in the barrel with mounted barrel adaptor.

26) Multidose syringes, methods of using multidose syringes, methods of making multidose syringes, and multidose syringe adapters substantially as described.

27) A method of using administering predictable amounts of a material, comprising: a) Providing a syringe as in Claim 1 , b) Placing a quantity of the material in the barrel of the syringe; c) Moving the plunger into the barrel until a predetermined number of engagement feature interactions have occurred.

28) A method as in Claim 27, further comprising repeating step c until a second predetermined number of engagement feature interactions have occurred.

29) A method as in Claim 27, wherein the material comprises one or more of botulinum toxin derivatives, neuromuscular blocking agents, hyaluronate derivatives, collagen preparations and derivatives, skin fillers, corticosteroids, anti-inflammatory agents, hormones, sclerosing agents, tattooing and coloration agents, anti-aging agents, chemotherapy, radioactive substances, antibiotics, preservatives and biologic response modifiers.

30) A method as in Claim 27, wherein the material comprises a cosmetic pharmaceutical used in dermatology, plastic surgery, or cosmetic medicine.

31 ) A method as in Claim 27, wherein the material comprises a neuroactive pharmaceutical used in neurology, plastic surgery, neurosurgery, pain clinics, or anesthesiology.

32) The above multidose syringes for administration of neuroactive pharmaceuticals as used in neurology, plastic surgery, neurosurgery, pain clinics, anesthesiology and other specialties.

33) A method as in Claim 27 wherein the first and second predetermined number of interactions are the same, such that the volume of material supplied is substantially identical.