CA2101949A1

CA2101949A1 - Multipharmaceutical syringe

Info

Publication number: CA2101949A1
Application number: CA002101949A
Authority: CA
Inventors: Terry M. Haber; William H. Smedley; Clark B. Foster
Original assignee: Individual
Current assignee: Habley Medical Technology Corp
Priority date: 1991-03-08
Filing date: 1992-02-20
Publication date: 1992-09-09
Also published as: EP0574524A4; JPH06505411A; CN1064622A; WO1992015345A1; CN1029084C; US5286258A; AU1640592A; EP0574524A1; AU653810B2

Abstract

A multipharmaceutical delivery system, such as a syringe (2) or a topical pharmaceutical applicator, suitable for a simultaneous delivery of a mixture (124) of two or more mixed pharmaceuticals (52, 120) in selected amounts and proportions, includes a body (4, 180) with first and second variable volume reservoirs (24, 26), containing the first and second liquids or other flowable materials, such as creams and salves. The reservoirs are connected to a variable volume accumulator chamber (31) through check valves (28) to permit liquid to flow from the reservoirs into the accumulator chamber but not the reverse. A delivery head, such as a needle assembly (78) or a spray nozzle assembly (196), is selectively fluidly coupled to the accumulator chamber by an exit path (106, 202) formed in the body. After the two liquids are driven into the accumulator chamber, typically one liquid at a time, the delivery head is fluidly coupled to the accumulator chamber and the accumulator piston (30) is actuated, thus forcing the liquid mixture from the accumulator chamber, through the exit path and through the delivery head during an injection or other application of the mixture.

Description

2 1 ~ 9 P~ S 9~ ~ ~ L ~ ~ 5 IPE~ O 9 ~PK 1993 - Replacement Paqe ~E ' .~
Attorney Docket No. 11531-28PC

PHARMACEUTICAL DELIVERY SYSTEM
BAC~GROUND OF TXE INVENTION
Therapeutic in~ulin i8 of ~hree basic t~pes: fa~-acti~g, intermediate-ac~ing a~d long-acting. In~uli~ u~erQ
o~en use a combi~ation of two type~ of insulin depending on the u~er'~ hlood sugar leYel, the time of day, nouri~hme~t intake and expeeted a~ti~ity. For example, i~uli~ injected at ~he b~gin~ing of an active day mBy ha~e ~ore o~ the fast~acting insulin, while the in~ulin inje~tion given at the end of th~
day before going to bed would likely ha~e more i~termediate- or long-ac~ing i~sulin.
One of the proble~s with co~ventio~al insuli~ ;
~yringes i8 tha~ they are de~igned to inject o~ly o~e type o~
insulirl, ~ot a eombinatio~. Although in~ulin ran b~ ob~ai~ed a~ a mixture o~ the ~cwo type~, the mix~ures are ge~erally a ~e~
combination, ~uch as 70% i~termedtat~-acting aad 30~ ~as~-ac~i~g. Thu~, ~he prior are limie~ the i~ulin u~er to a prese~ mixture of ~he wo i~guli~ or ~he ~eed to make two ~eparate injec~io~.

SUMMARY OF THE INVENTION
The pre~e~ ~ention is ~irec~ed to a variable ratio :.
multipharmaceu~ical ~eli~ery ~y~t~m, typically i~ ~he ~orm of a ~yrl~ge, ~uitabla for he ~imulta~eou~ delivery o~ ~wo or more m~xed flowabl~ phaxmaceuticals in ~elec ed amou~tq a~d ~O proportio~s. The delivery ~y~tem i~cludes f iXBt a~d ~e~o~d ~ariable volume re0~r~0irs, co~tai~i~g ~he ~ir~t ~d 0eco~d pharmaceuticals, a~d a ~ariable ~ol~m~ acc ~ lator chamber.
Th~ re0ervoir~ and ac~u~ulator chamb~r ar~ pr~rably ~ormed withi~ a c~mon bo~y. The r~ser~oir~ ar~ pre~erably con~e~ted to ~h~ accum~lator ~h~ber ~hrough check valve~ ~o p~mi~ fluid flow ~r~m the r~rvoir~ into ~h~ accumulator chamber but no~ -th~ r~v~r~e. The~ d~li~ery sy~eem alio i~clud~ a deli~ery head, typically a holIow ~eedle a~se~bly, ~lec~ively fluidly . ~ , 210t 3~i3 W092/15~5 PCT/USg2/~129~-coupled to the accumulator chclmber. After the two pharmaceuticals are dri~en from the reservoirs and into ~he accumulator chamber, typically one pharmaceutical at a time, the delivery head i.s fluldly couplecl to the accumulator chamber and the mixture is forced from the accumulator chamber and through the delivery head to permi~ administration of the mixture, typically by injection.~
One of the key features of the invention is that the first and second reservoirs and the accumulator chamber can be made as integral parts of the delivery system. By making the reservoirs and the accumulator chamber with a low-profile, preferably elliptical, configuration, the delivery ~system can be easily carried in one's pocket or purse while holding, for example, sufficient insulin for several injections. Another advanta~e of the in~ention is that, prior to a first injection, and after each injection, the accumulator piston is positioned fully within the accumulator chamber to permit the stem to be fully housed within the acc~mulator chamher region~
With the delivery system configured as a flat, rectangular product, reminiscent of a credit card, the delivery system is easy to grasp and, when configured as a syringe, quite suitable for ~elf-injection usage using one hand. When used as a self-injection syringe for insulin users, the invention reduces or eliminates the stigma of abnormality often created by the use of conventional syringes.
Another aspec~ of the invention is the use of a novel elastomeric val~e block which functions as a check valve. The valve block pre~ents liquid from flowing back into either the first or second reservoirs in a simpli~tic and economical mannex.
The invention is described with the first and second reservoirs and the accumulator chamber created using piston and cylindex arrangements. However, other ~ariable volume structures, such a~ ~lexible bags in which the volume can be reduced by 3queezi~g or other manipulation, can be u~ed ins~ead. Also, for enhanced ~terility, a flexible tubular ~kirt can be connected to the accumulator piston at one end and to the proximal end of the accumulator chamber at the other.

W092/l5~5 2 l O 1 ~ ~ 9 PCr/U5~2/0l2~s The invention, in one preferred embodiment, is con~iyured as a syxinge using a hollow needle assembly as the delivery head. However, the invention can be practiced using needle-less injectors as well. The delivery head can also be configured as a topical applicator using rollers or sprayer~ to apply a liquid pharmaceutical direc~ly onto the patient's skin or indirectly onto a bandage or patch, such bandage or patch :
being applied to the patient's skin. Spray-type delivery heads can be configured for use as an inhaler as well.
Other features and advantages of the in~ention will -appear from the followiny description in which the preferred embodiments have been set forth in detail in conjunction with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS
Fig. 1 is a partially exploded isometric view of a multipharmaceutical syringe made according to the invention;
Fig. 2 is an enlarged, partially exploded isometric view of a portion of the syringe of Fig. 1;
Figs. 2A, 2B and 2C are separate cross-sectional views of the valve body o~ Fig. 2;
Fig. 3 is a plan view of a syringe of Fig. 1 shown with the cover remo~ed, with portions of the base broken away for clarity, and in its initial, as-shipped condition;
Fig. 4 shows the syringe of Fig. 3 with the first liquid pharmaceutlcal in the first reservoir being forced into the accumulator chamber, thus moving the accumulator piston from the position of Fig. 3 to the position of Fig. 4;
Fig. 5 illustratas displacing the li~uid pharmaceutical Erom the econd reservoir into the accumulator chamber where it mixe~ with the first liquid pharmaceutical;
Fig. 6 shows the syringe of Fig. 5 with the needle assembly moved from its stored posi~ion of Fig. 5 to its extended po~ition of Fig. 6 and the expulsion of the now mixed pharmaceutical li~iid from the accumulator cha~ber, through the exlt path and through the hollow needle;
Fig. 7 is an enlarged view illustrati~g the simultaneous flow of liquid from both the first and second . . . -. ,, ~ , . . . ~ ~: .

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W092/15~5 PCr/USg2/0l29.

reservoirs, through the valve block, and into the accumulator cham~er, and then from the accumulator chamber, through the exit path, and out the hollow needle;
Fig. 8 shows the syringe of Flg. 6 in its post-use, s storage condition;
Fig. 9 is an enlarged cross-sectlonal view of an alternative needle assembly of Fig. 1 including a removable needle covered by a protective sheath;
Figs. lOA and lOB are front views of transparent dosage labels;
Figs. llA and 11~ are simplified views showing the accumulator piston and chamber of Figs. 3 and 4 used wlth a sterility skirt;
Fig. 12 shows an alternatlve embodiment of the body 15 o~ the syringe of Fig. ~ having a xeplaceable, interchangeable . .
dispenser section;
Fig. 13 shows the base portion of the dispenser section of Fig. 12 used with a spray nozzle as the delivery head;
Fig. 14 illustrates an alternati`ve embodiment of the : .
dispenser section of Fig. 13 with the spray nozzle replaced by a sponge pad-type topical pharmaceutical applicator; and Fig. 15 illustrates an alternative embodiment of the base portion of Fig. 13 in which the spray nozzle has been replaced by a roller-type topical pharmaceutical applicator.

- DESCRIPTION OF THE PREFERRED EM~ODIMENTS
Referring the reader to Figs. 1-3, a multiphar~aceutical syringe 2, especially useful fcr dispensing insulin, includes a body 4 made up of a base 6 and a cover 8.
Ba~e 6 and cover 8 are pre~erably made of clPar, phar~aceutically compatible plastic, such as polypropylene or acrylic, and are joined, such as by ultrasonic weIding techniques or using suitable adhesive. Base 6 has three 35 elongate, flattened elliptical cutouts 10, 12, 14 separated by walls 16, 18. Fir~t and second pistons 20, 22 are sli~ably moun~ed within cutouts 10, 12 and define first a~d second vaxiable volume reser~oirs 24, 26. A valve body ~8 is mounted W092~15~5 2 ~ 9 PCTIUS92/01295 :
in a cutout 27 formed ln base 6 at the distal end of elongate cutout 14 for the reasons to be discussed below. An accumulator pi.ston 30 is slidably molmted within cutout 14 to define a variable ~olume accumulator chamber 31 bounded by base 6, valve body 28, body supports 33 formed at the distal end of cutout 14 and accumulator piston 30. Pistons 20, 22 and 30 can each be made from one piece of an elastomeric material, such as silicone rubber. If desired, pistons 20, 22 and 30 can be multi-component parts having a leading edge of a resillent material, to provide a good seal, and a trailing edge OL a low friction material, to provide guidance to keep the pis~ons from skewing within their respective cutouts.
Syringe 2 also includes a stem 32 sized to fi' substantially fully within cutout 14 when accumulator piston 30 is adjacent body supports 33 as shown in Fig. 3. Stem 32 has raised finger grips 34 at its proximal end 36, proximal end 36 being enlarged to provide a good surface for the user to press against. The proximal edge 38 of body 4 has a scalloped shape to accommodate the arcuate shape of proximal end 36 to permi~ a generally flush appearance a~ suggested in Fig. 3. Stem 32 also has a longitudinal guide slot 42 and a transverse guide slot 44, guide slot 44 being positioned near the dis~al end 46 of stem 32. Slots 42, 44 are made to receive cylindrical gulde pegs 48 which extend from the underside of that portion of base 25 6 overlying cutouts 10, 12, 14 along proximal edge 38. Guide pegs 48 are best illustrated in Fig. 12 but are also ~hown in dashed lines Fiy. 1; their positions are suggested in Fig. 3 by broken circles. The guide pegs 4~ ~hat are aligned with cutouts 10-14 travel alo~g guide slot 42 as stem 32 moves along 30 cutouts 10-14. Transverse guide slot 44 is used, as discussed below, after stem 32 has been substantially remo~ed from body 4 and moved laterally to another cutout. The use of guide pegs 48 and guide slots 42, 44 both keeps stem 32 properly aligned within the cutouts during use and also prevents stem 32 from being completely removed fxom body 4 to both prevent its loss and to maintain distal end 46 within accumulator chamber 31 for enhanced qanitation.

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W092/15345 PCT/US92/0129' The inner surfaces of elliptical cutouts 10, 12, 14 may be coated with a pharmaceutically compatible, low friction material, such as PTFE sold by the DuPont Corporation of Wilmington, Delaware under the trademark TEFLON. Other coatings, which are ideally hard, low friction and inert, can be used as well. For example, a thi.n coating may be deposited onto the surfaces of cutouts 10, 12, 14 by appropriate vapor deposition processes.
Referring now primarily to Figs. 2, 2A-2C and 4, valve body 28 is made of an elastomerlc material, preferably a silicon elastomer such as that made by Dow Chemical Company of Midland, ~ichigan as Q7-4765. Valve body 28 iæ illustrated ln ~hese figures as it would exist when s~em 32 is pressing first piston 20 thus forcing flrst liquid 52 within the first 15 re~ervoir 24 through a first flow path 54, formed in base 6, through valve body 28 and into accumulator chc~mber 31. To do so, valve body 28 includes first and second blind flow paths 56, 58. Blind flow pa~hs 56, 58 are preferably circular blind holes formed in valve body 28. Valve body 28 also includes first and second normally closed slits 60, 62 formed in valve body 28 after valve body has been formed. Slits 60, 62, which are in the pre~erred embodiment 0.100" wide, can be made by forcing a thin blade, 0.006" thick and 0.100" wide, into the face 64 of ~alve body 28 at positio~s chosen to intersect flow paths 56, 58.
The thickness of valve body 28 at edges 66, 6a is abuut 0.062" and is pre~erably ~lightly greater than the depth of cutout 27; the width of ~ace 64 is preferably equal to or slightly longer ~han the width of cutout 27. Thus, when cover 8 is mounted to base 6, ~alve body ~8 acts to seal accumulator chamber 31 from first and second reservoirs 24, 26 except for the flow paths fo~ed by blind flow paths 56, 58 and ælits 60, 62.
Valve b].ock 2a also includes a cu~out region 70 35 spaced apart from edges 66, 68. Cutout region 70 is about 0.010" deep and permits the opening of slits 60, 62 when first and ~econd re~ervoirs 24, 26 are pressurized by the use of stem 32. Fig 2, 2B and 2C illustrate, in a æomewhat exaggerated , ." ' .,., ~ ~ ' , '' ' ~ :

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form, the opening of first slit 60 due to pressurization of liquid 52 within ~irst variable vol~ne reservoir 24 by stem 32 as illustrated in Fig. 4. As seen in Figs. 2B and 2C, surface 72 created by cutout region 70 lying above first slit 60 is permitted to bo~ upwardly thus permitting first sli~ 62 to open thus opening a fluid path between first reservoir 24 and accumulator chamber 32. However, second slit 62 acts as a check valve, partially due to the pressurized fluid within accumulator chamber 31 pressing on its overlyi.ng surface 74, to prevent flow from accumulator chamber 31 to second reservolr 26 during this operation.
Syringe 2 further includes a rota~able needle - asse~bly 78 mounted to body 4. Needle assembly 78 includes a hub assembly having a hub 82 and end flanges 84, 86. Hub 82 has a bore ~8 formed therethrough ror receipt of one end 9o of a hollow needle 92. Needle 92 is secured within base 88 by an epoxy adhesive 93. Cover 8 and base 6 include holes 94, 96 sized for receipt of hub 82. The axial length of hub 82 is about equal to the combined thickness of base 6 and cover 8.
With end flange R4 resting agai~st the outer surface ~02 of cover a and end ~lange 86 resting against the outer surface 98 of base 6, flange 86 is secured to hub 82, such as with an adhesi~e, to securely mount needle assembly 78 to body 4.
The pivotal movement of needle assembly 78 between the stored or retracted position of Figs. 3-5 and the extended position of Fig. 6 is limi~ed by the engagement of a cylindrical peg 105, extending frQm end flange 8~, which rides within a slot 100 formed in outer surface of 102 of cover 8.
As sugge~ted in Fig. 2, slot 100 narrows somewhat near i~s ends to proYide a detent:ing action with peg 94 to help keep needle assembly 78 from lnadvertently pivotin~ when in its re~racted or ex~ended posi~ions. ~ase 6 has a cu~out 10~ intersecting hole 96 to provide a safe place for receipt of needle 92 when syringe 2 is not in u~e~ A removable protective 3heath may be u9ed with needle a~sembly 78, if desired.
An exit path 106 is farmed in base 5 and intersects elongate cutout 14 at a position adjacent cutout region 70 of ~alve body 28. Pal:h 106 fluidly couples accumulator chamber 31 . ,. ~ ;., . . , : . .

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21~19~
WO92/15345 PCT/US92/01295 ~

with an end 110 of bore 88 when needle assembly 78 is in the extended position of Figs. 6 and 7. Exit path 106 is created by an open top groove fo~med in base 6 for most of its length.
However, a portion 103, shown in Fig. 7A, is formed in base 6 and opens into hole 96 to connect end 110 of bore ~8 to exit path 106. An O-ring 112 is positioned at the terminal end 114 of portion 108 of exit path 106 to crea~e a seal against hub 82. Other types of seals can be used as well.
The amount of liquids 52, 120 forced into accumulator chamber 31 can be gauged through the use of ~ransparent dosage labels 150, 152 shown in FIGS. 10A and 10~3. ~abel 150 includes accumulator calibrations 154. Labels 150, 152 are transparent except ~or the marking shown in FIGS. 10A and 10B to provide an unimpeded view of the con~ents of reservoirs 24, 26 and accumulator chamber 31. Th~ space between each calibration 154 equals one unit of medication. Label 150 also include first and second pharmaceutical calibrations 156, 158. Calibrations 156, 158 are each spaced apart by distances equal to one-half of a unit of medicine. Therefore, if the user moves pistons 20, 22 from one calibra~ion 15~, 158 to the next calibration 156, 15R, equal amounts (one-half unit each) of liquids 52, 120 will be rorced into accumulator chamber 31 ~o move piston 30 a distance equal tc the distance between successive caIibrations 154.
~abel 152, mounted to the opposite side of body 4 as label 150, is used when the proportion of first liquid 52 to ~econd liquid 120 is 7 to 3. The distance between successive first and ~econd pharmaceutical calibrations 160, 162 coxresponds to 70~ of a unit and 30~ of a unit respectively.
No~e that succeseive calibrations 162 are staggered - otherwise they could be too clo~e together for easy reading. Labels 150, 152 are preferably removable ~o that label3 ha~ing other calibrations ~or other propoxtions and dosages can be used as well.
In u~e, syringe 2 is preferably obtained in the initial, as-shipped condition of Fig. 3. 5tem 32 is withdrawn from cutout 14, moved to the left to into alignment wi~h elongate cutout 10 and pushed in the direction of arrow 116.

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~~ W0~2t15~S ~Cr/US~2/01295 Doing so forces liquid 52 into variable volu~e accumulator chamber 31 and causes accumulator piston 30 to move in the direction of arrow 118. After a suf~icient amount of l1quid 52 has been forced into accumulator cha~ber 31 from firs~
reservoir 24, stem 32 is moved in the direction opposite arrow 116 and then moved laterally until it is aligned with elongate cutout 12. Stem 32 is then dri~en in. the direction of arrow 116 forcing second li~uid 20 within second variable volume region 26 along a second flow path 122, through valve body 28 and into accumulator cha~ber 31 to create a mixed liquid 124 as shown in Fig. 5.
Next, needle assembly 78 is moved in the direction of arrow 126 to the extended positlon of Fig. 6. This is preferably accomplished by grasping the outer grooved surfaces 15 128 formed in hub assembly 80. Stem 32 is used to drive accumulator piston 30 in the direction of arrow 116 to force mixed liquid 124 past cutout region 70, through exit path 106, through bore R8 and through hollow needle 92. At the end of the injection, stem 32 is in the position of Fig. 8 and needle assembly 78 is rotated back to its stowed position as shown in Fig. 8.
Fig. 9 illustrates an alternative embodiment of needle assembly 78. Needle assembly 132 includes a needle 134 mounted to a threaded adapter 136 by an epoxy adhesive 138.
Adapter 136 mounts to a threaded hole 140 formed in hub 142 to permit needle 134 to be easily and quickly replaced when needed. Assembly 132 also includes a safety sheath 1~ which snaps onto an end of adapter 136 to help prevent inadvertent . needle sticks and to help keep needle 134 clean.
Figs. llA and llB illustrate, in simplified form, an accumulator chamb~r 166 housing an accumulator piston 168 and a sterility skirt 170. Skirt 170 is a lightweight, fluid impervious, flexible tubular material, such as silicone rubber, secured to piston 168 at one end 172 of skirt 170 and to ~he 35 proximal end 174 of chamber 166 at the other end 176 of skirt 170. Skirt 170 is in its extended condition of Fig. llA when piston 168 is ~ully within chamber 166 and is in itB compressed condition of Fig. 11~ when piston 168 is near proximal end 174.

.

2i~l9l~9 WO92/l5~5 PCT/US92/01295 Therefore, skirt 170 and piston 168 help to keep the inner walls of chamber 166 sterile during use and between uses.
Other methods for insuring sterility is main~ained can be used as well.
Fig. 12 illustrates an alternative embodiment of syringe body 4. Syringe body 180 includes a base 182 and a dispenser section 184. Base 182 includes a hinged end 186 shown in an open configuration prior to mountlng stem 32 into cutout 12. ~inged end la6 is pi~o~ed downwardly until surfaces 188, 190 meet and are secured together, such as through ultrasonic welding techniques, to secure stem 32 within body - 180.
Dlspenser ~ection 184 includes a base portion 192 and a cover portion 194. Dispenser section 184 can include the structure shown with respect to the embodiment of Figs. 1-8.
Other dispenser sections can be made to be interchangeable with the same ba~e 182 to permit flowable pharmaceu~icals to be dispen~ed in different ways.
Fig. 13 illu~trates a ba~e portion 192A so~figured for use with a di~penser section oE the type including a spray nozzle assembly 196 instead of needle as~embly 78. Valve block 28A is modified to eliminate cutout 70; instead of cutou~ 70, a similarly positioned cutout (not shown) is formed in the inner surface of the overlying cover portion 1~4 to permit slits 60A, 62A to open when subjected tc pressure ~rom reservoirs 24, 26.
A cutout 70, or its equivalent formed in cover portion 194, is not needed if the pressure needed to open slits 60, 62 is sufficiently greater than the pres~ure required to push actuator piston 30 along cutout 14 90 that piston 30 wi.ll move along cutout 14, thu~ enlarging actuator ch~mber 31, before opening the other, non-pre~surized ~lit 62, 60. Also, valve block 28A includes a bore 210 to provide a fluid flow path between accumulator chamber 31 and exit bore 106. Otherwise the structure o~ base portion 192A is ~imilar to the co~responding structure vf ~yringe 2 shown in Fig. 2.
Fig. 14 illustrates a ba~e portio~ 192B having a pharmaceutical dispensing sponge pad 198 mounted within a cutout 104B. The ~low of mixed pharmaceutical i~ controlled by . ; .
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WO~2/lS~ PC-r/US~2/012~5 11 ' a valve 200 mounted to the dispenser section and through a bore 212 formed in valve body 28~ Bore Z12 lntersects bore 210 so valve 200 controls fluid flow from accumulator chamber 31, through bore 210, along an exit pa~h 202 and ~o sponge pad 19~.
This embodiment permits the user to mix two pharmaceuticals within chamber 31 and then deliver the mixed pharmaceuticals to sponge pad 198 for topical application, typically directly to a patient or indirectly through a bandage, pad or patch.
Fig. 15 illuscrates a further base portion 192C which is similar to base portion 192~ with the exception that a pair of cutouts 204 are formed therein to accommodate the tips 206 of an application roller 208. Sponge pad 198C is smaller than sponge pad 198 to leave room within cutout 104C for roller 208.
This dispensing section embodiment is also used for the topical applica.tion of a mixed pharmaceutical.
Other modifications and variation can be made to the disclosed embodiment~ without departing from the subject o~ the invention as defined in the following claims. For example, instead of using check valve structures to the prevent the reverse flow of fluid back into reservoirs 24, ~6, pistons 20, 22 could be made so that they are one way pistons, that is so that they move only in the direction oE arrow 116. More than two reservoirs may be used; an additional ~eser~olr could be used to house a sterile saline solution used to flush out the syringe between uses. Also, the physical axrangement of the reservoirs relative to the accumulator chamber can be changed.
Instead of having the reservoirs be integrally made with body 4, ~hey could be separately con~tructed containers, such as conventional syringe cartridge~ of the type having a septum at -!
30 one end, an exposed pis~on at the other and filled with a liquid pharmaceutical. Valve block 2~ could be constructed with slits 60, 62 passing completely through the valve block;
this would permit the slits to open directly i.nto reco~figured flow paths 54, 122 so to elimi~ate the need for blind flow paths 56, 58. The needle as~embly could be in a fixed orientation relative to the body or slidably mounted to the body. Different types of val~es and flow paths could be used to selectively fluidly couple needle 92 to accumula~or cha~ber .. . . ...

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W09~/lS345 PCr/US92/0129~ ' 3~. The invention generally has been described w.ith respec~ to liquid pharmaceuticals; the invention is intended to cover both readily flowable llquids and flowable, but more viscous, creams and sal~es as well.

Claims

13 Replacement Page WHAT IS CLAIMED IS:

1. A variable ratio, liquid pharmaceutical dispensing system comprising:
first and second variable volume liquid reservoirs containing first and second liquids;
a variable volume accumulator chamber, means for permitting fluid flow from the first and second reservoirs into the variable volume accumulator chamber while preventing backflow;
a pharmaceutical delivery head;
means for fluidly coupling the pharmaceutical delivery head to the variable volume accumulator chamber;
means for forcing first and second volumes of the first and second liquids from the first and second reservoirs, respectively, to the variable volume accumulator chamber via the fluid flow permitting means, so that the volume of the variable volume accumulator chamber increases by an amount equal to the first and second volumes combined, and the first and second volumes of the first and second liquids creates a liquid mixture in the variable volume accumulator chamber; and means for expulsing the liquid mixture from the variable volume accumulator chamber through the pharmaceutical delivery head via the fluidly coupling means.

2. The system of claim 1 wherein the first and second variable volume reservoirs are elongate with generally constant cross-sectional shapes.

3. The system of claim 2 wherein the first and second variable volume reservoirs each has an elliptical cross-sectional shape.

4. The system of claim 2 wherein the first and second variable volume reservoirs are partially defined by first and second pistons.

5. The system of claim 28 further comprising a collapsible sterility skirt connected to the accumulator Replacement Page piston and to the variable volume accumulator chamber to aid keeping the variable volume accumulator chamber sterile.

6. The system of claim 27 wherein the expulsing means includes said stem.

7. The system of claim 1 wherein the first and second reservoirs and the variable volume accumulator chamber are defined by a common body.

8. The system of claim 7 further comprising calibration markings on the common body.

9. The system of claim 1 wherein the pharmaceutical delivery head includes a hollow hypodermic needle having a tip.

10. The system of claim 9 wherein:
the common body has a needle storage region sized to house the needle therein; and the hollow needle is movably mounted to the common body for movement between a storage position, with the needle within the needle storage region, and a use position, with the tip of the needle external of the needle storage region.

11. The system of claim 10 wherein the hollow needle is pivotally mounted to the common body.

12. The system of claim 1 wherein the permitting means includes first and second check valves operably positioned between the first and second reservoirs and the variable volume accumulator chamber.

13. The system of claim 25 wherein the maintaining means includes first and second deflectable surfaces formed on the valve body and aligned with the first and second slits so that applying a pressurized flowable material to one of the Replacement Page reservoir ends causes the corresponding first or second deflectable region to deflect.

14. The system of claim 13 wherein the first and second deflectable surfaces are in fluid communication with the variable volume accumulator chamber so that the presence of pressurized flowable material in the variable volume accumulator chamber tends to seal the other of the first and second slits.

15. The system of claim 14 wherein the delivery head coupling means includes a fluid path segment across the first and second deflectable surfaces.

16. The system of claim 1 wherein the flowable material delivery head includes a spray nozzle assembly.

17. The delivery system of claim 1 wherein the flowable material delivery head includes a topical applicator.

18. The delivery system of claim 17 wherein the topical applicator includes a roller applicator.

19. The system of claim 1 further comprising means for keeping the accumulator chamber sterile.

20. A syringe comprising:
first and second liquid reservoirs containing first and second liquids, each of said reservoirs having a length and first and second ends and a generally constant cross-sectional shape along at least a part of the length;
first and second pistons mounted within the first and second reservoirs and movable towards the first ends thereof;
an accumulator chamber having a length and first and second ends, at least part of the length of the accumulator chamber having a generally constant cross-sectional shape;

Replacement Page an accumulator piston mounted within the accumulator chamber and movable along the length of the accumulator chamber;
a flow path fluidly coupling the first ends of the first and second reservoirs to the accumulator chamber;
a stem for selectively driving the first piston, the second piston and the accumulator piston towards the respective first ends of the first reservoir, the second reservoir and the accumulator chamber;
means for preventing fluid flow from the accumulator chamber into either of the first and second reservoirs so that when the first piston is driven towards the first end of the first reservoir by the stem, liquid in the first reservoir flows into the accumulator chamber so to tend to force the accumulator piston towards the second end of the accumulator chamber;
a hollow needle; and means for selectively fluidly coupling the accumulator chamber to the hollow needle so that when fluidly connected, any liquid in the accumulator chamber can be forced through the fluidly coupling means and to the hollow needle by driving the accumulator piston towards the first end of the accumulator chamber by the stem.

21. A check valve for coupling first and second pressurized fluid sources to a common region, comprising:
an elastomeric valve body having first and second normally closed slits, said slits having inlets fluidly coupled to the first and second pressurized fluid sources and outlets fluidly coupled to the common region; and means for maintaining the. second slit closed when the inlet of the first slit is subjected to a fluid pressure sufficient to open the first, normally closed slit to permit the pressurized fluid to pass through the opened first slit and into he common region.

22. The check valve of claim 21 wherein the maintaining means includes first and second deflectable 17 Replacement Page surfaces aligned with the first and second slits so that applying a pressurized fluid to the inlet of the first slit causes the first deflectable surface to deflect.

23. (Restricted out) The check valve of claim 22 wherein the first and second deflectable surfaces are in fluid communication with the common region so that the presence of pressurized fluid in the common region tends to seal the second slit.

24. A variable ratio, liquid pharmaceutical dispensing system comprising:
first and second pistons;
an accumulator piston;
first and second variable volume reservoirs containing first and second liquids, wherein the first and second variable volume reservoirs are elongate with generally constant cross-sectional shapes, and the first and second variable volume reservoirs are partially defined by the first and second pistons;
a variable volume accumulator chamber, wherein the variable volume accumulator chamber is partially defined by the accumulator piston housed within the variable volume accumulator chamber;
means for permitting fluid flow from the first and second reservoirs into the variable volume accumulator chamber while preventing backflow;
a pharmaceutical delivery head;
means for fluidly coupling the hypodermic liquid to the variable volume accumulator chamber;
means for forcing first and second volumes of the first and second liquids from the first and second reservoirs, respectively, to the variable volume accumulator chamber via the fluid flow permitting means, so that the volume of the variable volume accumulator chamber increases by an amount equal to the first and second volumes combined, and the first and second volumes of the first and second liquids creates a liquid mixture in the variable volume accumulator chamber; and 18 Replacement Page means for expulsing the liquid mixture from the variable volume accumulator chamber through the pharmaceutical delivery head via the fluidly coupling means, the expulsing means including the accumulator piston.

25. A variable ratio multipharmaceutical delivery system comprising:
first and second variable volume reservoirs containing first and second flowable materials;
a variable volume accumulator chamber;
means for permitting fluid flow from the first and second reservoirs into the variable volume accumulator chamber while preventing backflow;
a flowable material delivery head;
means for fluidly coupling the delivery head to the variable volume accumulator chamber;
means for forcing first and second volumes of the first and second flowable materials from the first and second reservoirs, respectively, to the variable volume accumulator chamber via the fluid flow permitting means, so that the volume of the variable volume accumulator chamber increases by an amount equal to the first and second volumes combined, the first and second volumes of flowable materials forced into the variable volume accumulator chamber creates a flowable material mixture therein; and the permitting means including an elastomeric valve body having first and second normally closed slits, said slits having reservoir ends fluidly coupled to the first and second reservoirs respectively, and each of said slits having accumulator ends fluidly coupled to the variable volume accumulator chamber;
means for maintaining the second slit closed when the reservoir end of the first slit is subjected to a fluid pressure sufficient to open the first slit to permit the pressurized flowable material to pass through the opened slit and into the variable volume accumulator chamber; and 19 Replacement Page means for expulsing the flowable material mixture from the variable volume accumulator chamber through the delivery head via the fluidly coupling means.

26. A pharmaceutical delivery system comprising:
first and second liquid reservoirs containing first and second liquids, each of said reservoirs having a length and first and second ends and a generally constant cross-sectional shape along at least a part of the length;
first and second pistons mounted within the first and second reservoirs and movable towards the first ends thereof;
an accumulator chamber having a length and first and second ends, at least part of the length of the accumulator chamber having a generally constant cross-sectional shape;
an accumulator piston mounted within the accumulator chamber and movable along the length of the accumulator chamber;
a flow path fluidly coupling the first ends of the first and second reservoirs to the accumulator chamber;
a stem for selectively driving the first piston, the second piston and the accumulator piston towards the respective first ends of the first reservoir, the second reservoir and the accumulator chamber;
means for preventing fluid flow from the accumulator chamber into either of the first and second reservoirs so that when the first piston is driven towards the first end of the first reservoir by the stem, liquid in the first reservoir flows into the accumulator chamber so to tend to force the accumulator piston towards the second end of the accumulator chamber;
a pharmaceutical delivery head; and means for selectively fluidly coupling the accumulator chamber to the pharmaceutical delivery head so that when fluidly connected, any liquid in the accumulator chamber can be forced through the fluidly coupling means and to the pharmaceutical delivery head by driving the accumulator Replacement Page piston towards the first end of the accumulator chamber by the stem.

27. A variable ratio, liquid pharmaceutical dispensing syringe comprising:
first and second pistons;
an accumulator piston;
first and second variable volume reservoirs containing first and second liquids, wherein the first and second variable volume reservoirs are elongate with generally constant cross-sectional shapes, and the first and second variable volume reservoirs are partially defined by the first and second pistons;
a variable volume accumulator chamber, wherein the accumulator chamber is partially defined by the accumulator piston housed within the accumulator chamber;
means for permitting fluid flow from the first and second reservoirs into the accumulator chamber while preventing backflow;
a flowable material liquid delivery head including a hollow hypodermic needle;
means for fluidly coupling the hypodermic liquid to the accumulator chamber;
means for forcing the first and second liquids from the first and second reservoirs to the accumulator chamber via the fluid flow permitting means, so that selected amounts of the first and second liquids are forced into the accumulator chamber to create a liquid mixture therein, the forcing means including a stem engageable with the first and second pistons;
and means for expulsing the liquid mixture from the accumulator chamber through the delivery head via the fluidly coupling means, the expulsing means including the accumulator piston.