AU2011205069A1 - Multi-site injection system - Google Patents

Abstract

MULTI-SITE INJECTION SYSTEM A multi-site injection system in accordance with the present invention generally includes a plurality of medicament delivering needles/microprotrusions along with a support therefore. A supply of medicament is provided and a means provided for supplying the medicament to the plurality of needles/microprotrusions in order to effect delivery into a stratum corneum of a user. C\NRFPonbI\DCC\TZM\3781404_I.DOC - 28/7/l1

Description

Australian Patents Act 1990 - Regulation 3.2 ORIGINAL COMPLETE SPECIFICATION STANDARD PATENT Invention Title: Multi-site injection system The following statement is a full description of this invention, including the best method of performing it known to me: P/00/0 1 I 5951 WO 2005/110525 PCTUS2005/012122 MULTI-SITE INJECTION SYSTEM The present invention is generally directed to the administration of a medicament and is more particularly 5 directed to a multi-site injection system for dermal delivery of a medicament. Topical delivery of medicament is a very useful method for achieving both systemic and localized 10 pharmalogical effects. A problem in such transcutaneous drug, delivery is providing sufficient drug penetration across the skin. As is well know, the skin consists of multiple 15 layers, starting with a stratum corneum layer of about 20 microns for humans, a viable epidermal tissue layer of about 70 microns and a dermal layer of about 2 mm in thickness. 20 As such, the stratum corneum represents a major barrier for chemical penetration through the skin being responsible for the majority of the skin barrier property. This is, of course, dependent upon the medicament water solubility and molecular weight. 25 Delivering medicament through the skin may be attained by piercing the stratum corneum and delivering a drug to the skin in or below the stratum corneum. Such devices for piercing the stratum corneum may 30 include a plurality of micron-sized needles or blades having lengths sufficient to pierce the stratum corneum without passing completely through the epidermis. Once WO 2005/110525 PCT/US2005/012122 a medicament is passed through the stratum corneum, there typically is no major hindrance to penetration of the remaining epidermal layers or the dermis. 5 Do to sometimes painful use of individual needle penetration of the stratum corneum, it is desirable to provide a plurality of micro needles or protrusions for simultaneous delivery of a medicament through a larger area of stratum corneum. 10 Accordingly, the present invention provides for a multi-site injection system utilizing a plurality of microprotrusions or needles for piercing the stratum corneum of the skin to a depth sufficient for delivering 15 a medicament through the skin of a patient. SUMMARY OF THE INVENTION A multi-site injection system in accordance with 20 the present invention generally includes a plurality of medicament delivering needles/microprotrusions along with a support therefore. A supply of medicament is provided and a means provided for supplying the medicament to the plurality of needles/microprotrusions 25 in order to effect delivery into a stratum corneum of a user. One embodiment of the present invention generally includes a rotatable drum having an outer surface with 30 the microprotrusions thereon. 2 WO 2005/110525 PCT/US2005/012122 The microprotrusions may include passages, or lumens, therethrough for enabling transport of the medicament therethrough from an inner surface of the rotatable drum and into the stratum corneum of a user. 5 Alternatively the microprotrusions may be solid and coated with the medicament. A fixed inner drum may be provided for supporting the rotatable drum and includes at least one radial 10 opening therein for providing the medicament to the microprotrusions. The supply of medicament is disposed within the inner drum and a housing is provided for supporting the 15 rotatable drum and the inner drum. The housing includes an opening for exposing an arcuate portion of the rotatable drum in order to enable rotation of the rotatable drum by rolling the rotatable drum against a users -skin. 20 While not shown, a blatter may be provided for containing the medicament with the blatter being in fluid comunication with the radial opening in a fixed inner drum for providing the medicament to the 25 microprotrusion passages. An alternative embodiment of a multi-site injection system in accordance with the present invention generally includes a guide plate having a plurality of 30 openings therethrough and needle plate having a plurality of needles projecting therethrough with each 3 WO 2005/110525 PCT/US2005/012122 needle being aligned with a corresponding opening and a guide plate. The needle plate is movable from a first position 5 with the needles position behind a top surface of the guide plate to a second position with the needles projecting from the top plate through the openings. A plunger base is provided for moving the needle plate from the first to the second position. 10 The needles may be coated with a medicament or the needles may include lumens in communication with a medicament reservoir, or supply, disposed in the plunger base for delivery of the medicament into a stratum 15 corneum of a users skin. The needles and openings may be arranged in order to applicate the medicament to a users skin in a definite pattern which, may be a symmetrical radial 20 pattern, an asymmetrical radial pattern or a concentric pattern which may or may not be circular. A rectilinear pattern of needles may be utilized in accordance with the present invention and the medicament preferably comprises botulinum toxin. 25 A further embodiment of a multi-site injection system in accordance with the present invention generally includes a needle plate and a plurality of hollow needles fixed to an outside of the needle plate, 30 for transport of a medicament from an inside of the needle plate and into a stratum corneum of a user. 4 WO 2005/110525 PCT/US2005/012122 A pressurizer is provided and disposed over an inside of the needle plate to form a cavity therebetween in communication with the hollow needles. 5 In addition, an injection port is disposed in the pressurizer for introducing the medicament into the cavity. More particularly, in accordance with the present 10 invention, the pressurizer is flexible for causing uniform transport of the medicament through the needles. Accordingly, the pressurizer provides a means for forcing the medicament from the cavity through needle 15 lumens. A still further embodiment of a multi-site manifold injection system in accordance with the present invention generally includes a handle along with a 20 syringe supported by the handle and including a plunger for dispensing a fluid medicament from the syringe. A manifold is attached to one end of the handle and in fluid communication with a syringe and a plurality of 25 needles, protruding from the manifold, are provided for delivery of the fluid medicament from the manifold and into the stratum corneum of a user. In accordance with one embodiment of the present 30 invention, the manifold may be disposed perpendicular to the handle and further comprise a plurality of concentric conduits interconnected with radial conduits. 5 WO 2005/110525 PCT/US2005/012122 The concentric conduits may be circular and radially spaced apart from one another. 5 In addition, a transparent sheet may be provided and interconnecting a concentric and radial conduits for enabling visual orientation of the manifold onto a patients' skin by manipulation of a handle. 10 Alternatively, the manifold may comprise a plurality of concentric conduits and a plurality of radial ribs supporting the plurality of concentric conduits. Preferably, the medicament utilized in combination with the syringe manifold and needle is 15 botulinum toxin. Yet another embodiment of the present invention includes a multi-site blister injection system having a carrier sheet including a plurality of medicament filled 20 rupturable blister disposed on an inside surface thereof. A plurality of needles extending from the outside of the carrier stream may be provided with each needle 25 being aligned with a corresponding blister and having a lumen for transport of the medicament into the stratum corneum of the user. Each of the needles is positioned for traversing 30 the carrier sheet and rupturing the corresponding blister. 6 WO 2005/110525 PCT/US2005/012122 A pressure plate is disposed on the carrier sheet inside surface for forcing a blister against the needles for causing rupture thereof and forcing a medicament through the needle lumens. 5 The pressure plate may be fixed to the carrier sheet and a foam pad may be disposed on the carrier sheet outside. Preferably, the foam pad covers the needles extending the carrier sheet outside and is 10 penetrable by the needles. The foam pad may be adhered to the pressure plate along a perimeter thereof for securing the carrier sheet between the foam pad and the pressure plate. 15 Preferably, the medicament in accordance with the present invention comprises botulinum toxin. Still another embodiment of a multi-site injection system in accordance with the present invention 20 generally includes a shell including a top and a bottom and a plurality of needles protruding from the shell bottom. Each of the needles include a lumen extending through the shell bottom. 25 A membrane is provided and disposed between the shell top and the shell bottom and an inlet is provided for introducing a fluid between the shell top and the shell bottom. 30 A diverter is also provided for selectively directing fluid between the membrane and the shell bottom and between the membrane and the shell top. 7 WO 2005/110525 PCT/US2005/012122 The diverter may include a manually operated valve and the system may further include the supply of medicament, preferably botulinum toxin, for introduction 5 between the membrane and the shell bottom. An inert fluid supply may also be provided for introduction between the membrane and the shell top. 10 Also in accordance with the present invention, a method of multi-site injection comprises providing a shell between the top and a bottom with bottom having a plurality of needles protruding therefrom with each needle including a lumen therethrough and extending 15 through the shell bottom. The method also includes providing a membrane between the shell top and the shell bottom. 20 More particularly, in accordance with the present invention, the method includes introducing a medicament between the membrane and the shell bottom and introducing' a pressurized fluid between the membrane and the shell top for forcing the medicament through the 25 needle lumens. The medicament in accordance with the present invention preferably comprises botulinum toxin. 30 8 WO 2005/110525 PCT/US2005/012122 BRIEF DESCRIPTION OF THE DRAWINGS 5 The advantages and features of the present invention will be better understood by the following description when considered in conjunction with the accompanying drawings in which: 10 Figure 1 is a perspective view of a multi-site injection system in accordance with the present invention generally showing a housing, or shell, for supporting a rotatable drum along with a rotatable drum having an outer surface with microprotrusions therein, a 15 port is also shown which provides an access for charging the system with a medicament to be injected, such as, for example botulinum toxin; Figure 2 is a partial cross section of the system 20 shown in Figure 1 more clearly illustrating a fixed inner drum for containing a medicament and at least one radial opening therein for providing medicament to a plurality of microprotrusions affixed to and rotatable with the rotatable drum, the rotatable drum is rotated 25 by rolling the drum against a users skin, not shown, and the housing supporting the rotatable drum and the inner drum includes an opening for exposing an arcuate portion of the rotatable drum for enabling rotation thereof; 30 Figure 3 is a cross sectional view taken along line 3-3 of Figure 2 more clearly showing operation of the system; 9 WO 2005/110525 PCT/US2005/012122 Figure 4 is a perspective view of a multi-site injection system in accordance with the present invention generally showing a guide plate having a 5 plurality of openings therethrough, a plunger base and a plurality of needles projecting from the guide plate; Figure 5 is a partial cross section of one embodiment of the present invention showing a reservoir 10 of medicament disposed in the plunger base with needle lumens in fluid communication therewith and disposed with needle points generally flush with a top surface of the guide plate; 15 Figure 6 is a cross sectional view similar to that shown in Figure 5 illustrating movement of the plunger base for protruding the needles from the top surface of the guide plate and into a stratum corneum of a users skin; 20 Figure 7 illustrates continued pressure on the plunger base for forcing medicament through the needle lumens and into the stratum corneum of the users skin; 25 Figures 8 and 9 illustrate various needle patterns which may be suitable for various applications and areas of treatment on a users skin; Figure 10 is a perspective view of a multi-site 30 injection system in accordance with the present invention generally showing a needle plate with a 10 WO 2005/110525 PCT/US2005/012122 plurality of needles projecting therefrom and fixed to an outside surface of the needle plate; Figure 11 is a perspective view of the multi-site 5 injection system shown in Figure .1 showing a reverse side with a pressurizer disposed over an inside of the needle plate along with an injection port and a pressurized reservoir of medicament interconnected to the port via a tube; 10 Figure 12 is a partial cross section of the injection system shown in Figures 10 and 11 illustrating a cavity for and between the pressure plate and an inside surface of the needle plate illustrating 15 medicament flow from the pressure reservoir through the tube into the cavity and through hollow needles for transport of the medicament into a stratum corneum of a user; 20 Figure 13 is a perspective view of the multi-site manifold injection system in accordance with the present invention generally showing a handle, a manifold attached to one end of the handle and a plurality of needles protruding from the manifold for delivery of 25 fluid medicament from the manifold into a stratum corneum of a user, not shown; Figure 14 is a cross sectional view of the system shown in Figure 13 more clearly shown a syringe 30 supported by the handle and including a plunger for dispensing the fluid medicament from the syringe; 11 WO 2005/110525 PCT/US2005/012122 Figure 15 is a perspective view of a multi-site blister injection system in accordance with the present invention generally showing a carrier sheet and a pressure plate disposed on an inside surface of the 5 carrier sheet; Figure 16 is an exploded perspective view of the system more clearly illustrating a carrier sheet with medicament filled blisters and a foam pad; 10 Figure 17 is a cross sectional view of the embodiments shown in Figures 15 and 16 more clearly illustrating a plurality of needles extending from the carrier sheet, a plurality of rupturable blisters filled 15 with a medicament, such as botulinum toxin, along with the pressure plate positioned for forcing the blisters against corresponding needles for causing rupture thereof and forcing medicament through needle lumens; 20 Figure 18 is a cross sectional view similar to that shown in Figure 17 in which the pressure plate has been forced against the blisters and medicament is forced into the stratum corneum of a users skin; 25 Figure 19 is a perspective view of a multi-site injection system in accordance with the present invention generally illustrating a shell having a top and a bottom with a plurality of needles protruding from the shell bottom. An inlet for introducing fluid 30 between the shell top and bottom is shown along with a diverter; 12 WO 2005/110525 PCT/US2005/012122 Figure 20 is a cross sectional view of the system shown in Figure 19 more clearly illustrating the shell top, bottom and a membrane disposed between the shell top and the shell bottom along with a diverter valve for 5 selectively directing fluid between the membrane and the shell bottom and between the membrane and the shell top, Figure 20 showing a filling cycle with medication being injected into a reservoir; 10 Figure 21 is a cross sectional view similar to Figure 20 showing the diverter selectively directing fluid between the membrane and top shell during an injection cycle in order to pressurize the reservoir of medicament thereby forcing the medicament through needle 15 lumens; and Figure 22 is an enlarged view of the needles illustrating a lumen therethrough for injection of the medicament into the stratum corneum of a users skin (not 20 shown) . DETAILED DESCRIPTION With reference to Figure 1, there is shown a multi 25 site injection system 10 which includes a rotatable drum 12 including an outer surface having a plurality of microprotrusions, or needles, affixed thereto. The microprotrusions may have lumens, or passages, therethrough. 30 A housing 20 is provided for supporting the rotatable drum along with a fixed inner drum 24, see 13 WO 2005/110525 PCT/US2005/012122 Figures 2 and 3. An arcuate opening 28 in the housing 20 is provided for exposing the drum surface 14 which enables rotation of the drum 12 by rolling the drum 12 against a users skin 42. 5 Also shown in Figure 1 is an access 34 which is provided for introducing a medicament, such as botulinum toxin into the system via a syringe, not shown, or other suitable conveyance. 10 As more clearly shown in Figures 2 and 3, an inner drum, fixed to the housing, or shell, 20, is provided for containing a supply of medicament instilled through the access port 30 as hereinabove noted. 15 This nonrotating inner drum, or reservoir, 36 includes a plurality of radial passages, or openings, 38 for providing the medicament 36 to the needles 18. 20 Preferably, a sponge-like material 40 is disposed on the rotatable drum 12 for both distributing medicament provided through the radial openings 18 and enabling application of the medicament via the needles 18 without excess medicament being deposited on the 25 users skin 42. In operation, rotation of the drum 12 on the users skin 42 causes rotation of the drum as indicated by the arrow 44 and medicament flows into the sponge and is 30 applied to the users skin 42. The needles penetrate the stratum - corneum, or skin, 42 of the user, thus introducing the medicament thereinto. 14 WO 2005/110525 PCT/US2005/012122 Alternatively, the protrusions, or needles may include lumens therethrough for direct transport of medicament 36 from the inner drum 34 upon rotation of 5 the drum 12 against the users skin 42. With reference to Figure 4, there is shown an injection system 110 generally including a guide plate 112 having a plurality of openings therethrough along 10 with a needle plate 120 including a plurality of needles 124 shown extending through the openings 116 and projecting from a top surface 128 of the guide plate 112. Also shown is a plunger base 130 for moving the needle plate from a first position with the needles 124 15 positioned generally behind the top surface 128, see Figure 5 to a second position with the needles 124 projecting from the top surface 128 as shown in Figures 4, 5, and 6. 20 The needles 124 may be coated with a medicament, such as, for example, botulinum toxin. The guide plate 112, needle plate 120, needles 124, and base 130 may be made form any suitable material and 25 the needles preferably are about 128 gauge and 1mm in length. Use of the multi-site injection system 110 for delivery of a medicament into the stratum corneum of a users skin is illustrated in Figures 5-7. 30 As shown, the needle plate is configured in any suitable manner for being moveable from a first position shown in Figure 5 with the needles positioned behind, or 15 WO 2005/110525 PCT/US2005/012122 flush with the top surface 128 of the needle plate 120 to a second position shown in Figures 6 and 7 with the needles 124 projecting from the top surface 128 through the openings 116. 5 The plunger base .130 preferably includes and defines a reservoir 142 between the needle plate 120 and the base 130 for containing the medicament 134. 10 Incompressibility of the medicament 134 enables movement of the plunger base 130 to move the needle plate 120 from the first to the second position as indicated by the arrows 146. 15 Continued movement of the plunger base 130 forces medicament 134 through needle lumens 150 and collapse of the reservoir 142. The guide plate 112, needle plate 120, and plunger based 130 may be integrally formed with a diaphragm arrangement, not shown, for enabling the 20 relative motion hereinabove described. Other suitable configurations should be considered to be within the scope of the present invention. It should be appreciated that while the system 110 25 shown in Figure 4 illustrates, holds, or openings 116 and needles arranged in a generally symmetrical radial pattern, other patterns may be utilized for delivery of a medicament to body areas requiring different patterns of application. Figures 8 and 9 illustrate systems 154, 30 156 showing an asymmetrical radial pattern and a rectilinear pattern respectively. 16 WO 2005/110525 PCT/US2005/012122 With reference now to Figures 10 and 11, there is shown a multi-site injection system 208 in accordance with the present invention generally including a flexible needle plate 210 having a plurality of hollow 5 needles 212 fixed to an outside surface 216 of the needle plate 210. The needle plate 210 may be formed from any suitable material and the needles may be formed thereinto or affixed thereto in any conventional manner. 10 As more clearly shown in Figure 11, the system 208 may include a pressurizer 220, which may be in the form of a flexible blatter or the like, for causing uniform pressure across an inside surface 224 of the needle plate 210. 15 As shown in Figure 12, the pressurizer 220 establishes a cavity 226 between the pressurizer 220 and the inside surface 224 of the needle plate 210. 20 As shown in Figure 12, the- inside surface 224 of the needle plate 210 may include a separate containment element 228 to facilitate construction of the system 208. Thus, as illustrated the pressurizer 220 provides a means for forcing medicament, which is preferably 25 botulinum toxin from the cavity 226 through needle lumens 232. Spacing and orientation of the needles on the needle plate 210 is determined by the intended use of the needle plate 210 .on specific user body parts, not shown. 30 An injection port 234 is preferably interconnected to a pressure reservoir 236 through a tube 240. Control 17 WO 2005/110525 PCT/US2005/012122 of medicament flow from the pressure reservoir 236 through the tube and. into the cavity 226 may be controlled in any conventional manner. 5 Pressure medicament in the cavity 226 thus forces the medicament into a stratum corneum 242 of a user, not shown. Pressure provided by the flexible pressurizer as 10 indicated by the arrows 244, 246 enable uniform flow of medicament as indicated by arrows 248, 250 through the needle lumens 232 as indicated by arrows 252, 254. With reference to Figures 13 and 14, there is shown 15 a multi-site injection system 310 including a handle 312, a syringe 316, which includes a plunger 318 for dispensing a fluid medicament from the syringe and into a manifold 322, as illustrated by arrows 326 in Figure 14. 20 The handle 312, syringe 316, plunger 318, and manifold 322 may be formed by any suitable materials. As shown in Figures 13 and 14, the manifold 322 may be disposed in a generally perpendicular relationship with 25 the handle 312 and plunger 318 and a plurality of needles 330 protruding from the manifold 322 for delivery of fluid medicament from the manifold 322 into a stratum corneum of a user (not shown). 30 The needles may be affixed to the manifold 322 in any conventional manner may be approximately 328 gauge with a length of approximately 1mm and include needle 18 WO 2005/110525 PCT/US2005/012122 lumens 334 in fluid communication with conduits 338 of the manifold 322. The conduits may be concentric and in fluid communication with radial members 342. 5 In one embodiment of the present invention, the radial members may be hollow for providing fluid communication of medicament or alternatively in another embodiment of the present invention may be solid ribs for supporting the conduits 338. 10 A transparent sheet 346 may interconnect the conduits 338, 342 for enabling a constant pressure to be exerted over the entire area presented by the manifold 322. while enabling visual orientation of the manifold 15 322 onto a patients' skin (not shown) by manipulation of the handle 312. In operation, finger pressure on the plunger 318 drives, or otherwise ratchets, a piston 350 disposed 20 within the syringe for forcing medicament 354 downwardly through an exit port 356 and into the manifold conduits 338, as hereinabove noted, forcing medicament through the needle lumens 334 as indicated by the arrows 360. It should be appreciated that any suitable plunger, 25 syringe, which may be fitted into the handle of the present invention is to be considered within the scope of the present invention. With reference to Figures 15 and 16, there is shown 30 a multi-site injection system 410 in accordance with the present invention showing a carrier sheet 412 along with a foam pad 414, see Figure 16. A pressure plate 416 is 19 WO 2005/110525 PCTUS2005/012122 disposed on a carrier sheet inside surface 420 and the foam pad 414 may include an adhesive for holding the carrier sheet 412 against the pressure plate 416. 5 With reference to Figure 17 and 18, the carrier sheet 412 may be of conventional design and include blisters 424 filled with a medicament 426 as well as a plurality of protruding needles 430 extending from an outside surface 432 of the carrier sheet 412. Each of 10 the needles which may be, for example, 428 gauge and having 2mm length and include lumens 436 for transport of medicament therethrough. Each of the needles 430 is aligned with a 15 corresponding blister 424 and each needle including a point 438 for rupturing of corresponding blisters 424. As shown, the pressure plate preferably includes a plurality of berms 440 for providing enhanced pressure 20. against blisters as the pressure plate 416 is forced against the blisters 424. The foam pad 414 preferably has a depth equal to or slightly greater than the length of the needles 430 in 25 order to prevent inadvertent contact with the needles before use. In operation, as shown in Figure 18, when the pressure plate 416 is forced downwardly as indicated by 30 the arrows 444, the needle points 438 are rupture the blisters 424 and continued pressure by the pressure plate 416 collapses the blisters 424 and forces 20 WO 2005/110525 PCT/US2005/012122 medicament through the needle lumens 436 as indicated by the arrows 442. This pressure also compresses the foam pad 414 as 5 shown against a users skin 444 and into the stratum corneum 446. It should be appreciated that the drawings are not to scale but rather enlarged to illustrate the operation of the multi-site injection system 410. 10 With reference to Figures 19-22, there is shown a multi-site injection system 510 in accordance with the present invention generally including a shell 512 having a top 516 and a bottom 518. A plurality of needles 522 protrude from the shell bottom 518 with each needle 522 15 including a lumen 524 (see Figure 22) communicating with a reservoir 526 established by a membrane 528 disposed between the shell top 516 and the shell bottom 518. It should be appreciated that the shell, membrane 20 and needles may be made from any suitable material. Preferably, the needles have a gauge of about 528 and a length in the order of 2mm. An inlet 530 including a tube 532 and passageway 534 provide a means for introducing a fluid between the shell top 516 and shell 25 bottom 518. A diverter 538 includes a manually operated valve 540 for selectively directing fluid between the membrane 528 and shell bottom 518 into the reservoir 526. 30 As shown by the arrow 544 during a filling cycle the inlet, or supply line, introduces a medicament, 21 WO 2005/110525 PCT/US2005/012122 preferably botulinum toxin, into the reservoir by alignment with a dip tube 548 with the passageway 534 for filling of the reservoir 526. 5 Thereafter, the diverter 538 by way of the valve 540 aligns the passageway 534 for introducing a fluid, such as saline solution, between the membrane 528 and the top shell as illustrated by the arrows 552, 554. This provides a pressure above the membrane 528 which 10 forces the medicament from the reservoir 526 through the needle lumens 524 as illustrated by the arrows 558. Although there has been hereinabove described various multi-site remotely pressurized injection 15 systems in accordance with the present invention for the purpose of illustrating the manner in which the invention may be used to advantage, it should be appreciated that the invention is not limited thereto. That is, the present invention may suitably comprise, 20 consist of, or consist essentiAlly of the recited elements. Further, the invention illustratively disclosed herein suitably may be practiced in the absence of any element which is not specifically disclosed herein. Accordingly, any and all 25 modifications, variations or equivalent arrangements which may occur to those skilled in the art, should be considered to be within the scope of the present invention as defined in the appended claims. 22 C:\NRPortbl\DCC\TZM\3471259_1.DOC - 28/07/2011 Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" or "comprising", will be understood to imply the inclusion of a 5 stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps. The reference in this specification to any prior publication (or information derived from it), or to any 10 matter which is known, is not, and should not be taken as an acknowledgment or admission or any form of suggestion that the prior publication (or information derived from it) or known matter forms part of the common general knowledge in the field of endeavour to which this specification relates. 22a

Claims (50)

1. A multi-site injection system comprising: a plurality of medicament delivering 5 needles/microprotrusions; a needle/microprotrusion support; a supply of medicament; and means for providing the medicament to the plurality of needles/microprotrusions in order to effect 10 delivery into a stratum corneum of a user.

2. The system according to claim 1 wherein the support comprises a rotatable drum. 15

3. The system according to claim 1 wherein the support comprises a guide plate.

4. The system according to claim 1 wherein the support comprises a needle plate. 20

5. The system according to claim 1 wherein the support comprises a manifold.

6. The system according to claim 1 wherein the 25 support comprises a carrier sheet.

7. The system according to claim 1 wherein the support comprises a shell. 30

8. A multi-site injection system comprising: a rotatable drum having an outer surface with microprotrusions thereon, said microprotrusions having 23 WO 20051110525 PCT/US2005/012122 lumens therethrough for enabling transport of a medicament therethrough from an inner surface of said rotatable drum and into a stratum corneum of a user; a fixed inner drum for supporting said 5 rotatable drum and having at least one radial opening therein for providing said medicament to the microprotrusion lumens; a supply of said medicament disposed within the inner drum; and 10 a housing for supporting the rotatable drum and the inner drum, said housing having an opening for exposing an arcuate portion of said rotatable drum in order to enable rotation of said rotatable drum by rolling said rotatable drum against a user's skin. 15

9. A multi-site injection system comprising: a rotatable drum having an outer surface with microprotrusions thereon and radial opening for transport of a medicament therethrough; 20 a fixed inner reservoir for storing the . medicament and for supporting said rotatable drum, the reservoir having at least one radial opening therein for release of the medicament; a sponge layer covering said rotatable drum 25 for receiving medicament as the rotated drum is pressed and rotated across a user's skin and enabling said microprotrusions to 'deliver the medicament by penetrating of the stratum corneum of the user. 30

10. The system according to claim 9 wherein said sponge layer is fixed to said rotatable drum. 24 WO 2005/110525 PCT/US2005/012122

11. The system according to any one of claims 8-10 wherein said medicament comprises botulinum toxin.

12. A multi-site injection system comprising: 5 a guide plate having a plurality of openings therethrough; a needle plate having a plurality of needles projecting therefrom, each needle being aligned with a corresponding opening in said guide plate, said needle 10 -plate being movable from a first position with the needles positioned behind a top surface of said guide plate to a second position with the needles projecting from the top surface through the openings; and. a plunger base for moving said needle plate 15 from the first to the second position.

13. The system according to claim 12 wherein said needles are coated with a medicament. 20

14. The system according to claim 12 wherein said plunger bore includes a reservoir for medicament and needles include lumen therethrough in communication with said reservoir for delivery of the medicament into a stratum corneum of a users skin. 25

15. The system according to any one of claims 12 14 wherein the needles and opening are arranged in a symmetric radial pattern. 30

16. The system according to any one of claims 12 14 wherein the needles and opening are arranged in an asymmetric radial pattern. 25 WO 2005/110525 PCT/US2005/012122

17. The system according to any one of claims 12 14 wherein the needles and openings are arranged in a concentric pattern. 5

18. The system according to claim 17 wherein said concentric pattern is circular.

19. The system according to any one of claim 12-14 10 wherein the needles and opening are arranged in a rectilinear pattern.

20. The system according to any one of claims 12 14 said medicament comprises botulinum toxin. 15

21. A multi-site injection system comprising: a needle plate having a plurality of needles projecting therefrom; and botulinum toxin disposed with the needles for 20 delivery to a stratum corneum of a user.

22. A multi-site injection system comprising: a needle plate; a plurality of hollow needles, fixed to an 25 outside of said needle plate, for transport of a medicament from an inside of said needle plate and into a stratum corneum of a user; a pressurizer disposed over an inside of said needle plate to form a cavity therebetween in 30 communication with the needles; and an injection port disposed in said pressurizer for introducing the medicament into said cavity. 26 WO 2005/110525 PCT/US2005/012122

23. The system according to claim 21 wherein said pressurizer is flexible for causing uniform transport of the medicament through the. needles. 5

24. A multi-site injection system comprising: a needle plate having an inside and an outside; a pressurizer disposed an the needle plate 10 inside to form a cavity therebetween; a medicament disposed in said cavity; a plurality of needles disposed on the needle plate outside each needle having a lumen in fluid communication with said cavity for transport of the 15 medicament into a stratum corneum of a user; and means for forcing medicament from said cavity through needle lumens.

25. The system according to claim 24 wherein the 20 means for forcing medicament comprises on injection port disposed in said pressurizer.

26. The system according to claim 25 wherein said pressurizer is flexible for causing transport of the 25 medicament through the needle lumen.

27. The system according to any one of claims 22 26 wherein said medicament comprises botulinum toxin. 30

28. A multi-site injection system comprising: a handle; 27 WO 2005/110525 PCT/US2005/012122 a syringe supported by said handle and including a plunger for dispensing a fluid medicament from said syringe; a manifold attached to one end of said handle 5 and in fluid communication with said syringe; a plurality of needles, protruding from said manifold, for delivery of said fluid medicament from said manifold and into a stratum corneum of a user. 10

29. The system according to claim 28 wherein said manifold is disposed perpendicular to said handle.

30. The system according to claim 28 wherein said manifold comprises a plurality of concentric conduits 15 interconnected with radial conduits.

31. The system according to claim 30 wherein said concentric conduits are circular. 20

32. The system according to claim 30 wherein the concentric conduits are radially spaced apart from one another.

33. The system according to claim 32 further 25 comprising a transparent sheet interconnecting the concentric and radial conduits for enabling visual orientation of said manifold onto a patients skin by manipulation of said handle. 30

34. The system according to claim 28 wherein said manifold comprises a plurality of radial conduits. 28 WO 2005/110525 PCT/US2005/012122

35. The system according to claim 34 further comprising a plurality of concentric ribs supporting said plurality of radial conduits. 5

36. The system according to claim 35 wherein the concentric conduits are circular.

37. The system according to any one of claims 28 36 wherein the medicament comprises botulinum toxin. 10

38. A multi-site injection system comprising: a carrier sheet including a plurality of medicament filled rupturable blisters disposed on an inside surface thereof; 15 a plurality of needles extending from an outside surface of said carrier sheet, each needle being aligned with a corresponding blister and having a lumen for transport of the medicament into a stratum corneum of a user, each needle traversing said carrier sheet and 20 positioned for rupturing the corresponding blister; and a pressure plate disposed on the carrier sheet inside surface for forcing the blister against the needles for causing rupture thereof and forcing the medicament through the needle lumens. 25

39. The system according to claim 38 wherein said pressure plate is fixed to said carrier sheet.

40. The system according to claim 39 further 30 comprising a foam pad disposed on the carrier sheet outside. 29 WO 2005/110525 PCT/US2005/012122

41. The system according to claim 40 wherein said foam pad covers the needle extending from the carrier sheet outside and is penetrable by said needle. 5

42. The system according to claim 41 wherein said foam pad is adhered to said pressure plate along a perimeter thereof for securing the carrier sheet between said foam pad and said pressure plate. 10

43. The system according to any one of claim 38-42 wherein said medicament comprises botulinum toxin.

44. A multi-site injection system comprising: a shell including a top and a bottom; 15 a plurality of needles protruding from the shell bottom, each needle including a lumen extending through the shell bottom; a membrane disposed between the shell top and shell bottom; 20 an inlet for introducing a fluid between the shell top and the shell bottom; and a diverter for selectively directing fluid between the membrane and the shell bottom and between the membrane and the shell top. 25

45. The system according to claim 44 wherein said diverter includes a manually operated valve.

46. The system according to claim 45 further 30 comprising a supply of medicament for introduction between the membrane and the shell bottom. 30 WO 2005/110525 PCTUS2005/012122

47. The system according to claim 46 further comprises a supply of inert fluid for introduction between the membrane and the shell top. 5

48. The system according to claim 47 wherein said medicament comprises botulinum toxin and said inert fluid comprises a saline solution.

49. A method of multi-site injection comprises: 10 providing a shell including a top and a bottom, said bottom having a plurality of needles protruding therefrom with each needle including a lumen therethrough and extending through the shell bottom; providing a membrane between the shell top and 15 the shell bottom; introducing a medicament between the membrane and the shell bottom; and introducing a pressurized fluid between the membrane and the shell top for forcing the medicament 20 through the needle lumen.

50. The method according to claim 49 wherein said medicament comprises botulinum toxin. 31