CA2114556A1 - Medicament injector and method - Google Patents

Abstract

An automatic programmable portable injection/aspiration device and injection cartridges used therewith are provided for administration of medicaments. The device includes a chamber (1219) configured for the receipt of a prepackaged disposable medicine cartridge (1217), means (1215) for operating the cartridge, means (1221) for controlling the rate, direction and extent of needle insertion, fluid injection, and needle withdrawal. Means (1221) for storing data and for programming the device to predetermine and vary the rates as desired, and sensors (1233, 1235) and indicators (1211) for detecting and indicating various rates and parameters of performance are also provided. Also provided are means (1232) for automatically interrogating an injection site to insure that the site is medically appropriate and locking means (1229) for preventing accidental discharge of the device. Injection cartridges (1217), adapted for storing and injecting single- or multiple-component medicaments are provided for use with the device, or for manual use or with mechanical actuators (1203, 1205, 1207).

Description

wo g3,02,2" 2 1 1 4 5 S ~ PCr/U592/06587 ~lEDIC~l~ INJECTOR AND NBl~OD

Backaround of the I~vention The present invention relates to an injection/aspiration device and a cartridge vial for use therewith for medical and research purposes and more particularly to a device designed for injecting medicines and other fluids into human beings and other subjects using a hollow injection needle. Both the injection/aspiration and cartridge vial components of the invention are also configured to aspirate blood and/or other fluids.
In the conv_ntional medical procedure for injecting medicines or for aspirating blood or fluids, a syringe with a hollow injection/aspiration needle, such as a standard hypodermic needle, is used. Needles are repugnant to many patients, particularly those who must have regular injections of medicine or blood samples taken. Among these are elderly patients and`people who must have daily injections of insulin or othèr drugs.
Similarly, pedi~tric patients are particularly afraid of needles. Exposed--or visible needles are undesirable because-they create fear and apprehension in many subjècts. `~
Another~problem in the medical field is that of the communication of infectious diseases caused by used needles and syringes and fluids therefrom coming int!o contact with doctors, nurses, or other medical personnel.
- Needle tips often remain exposed after aspiration of a fluid or blood from a subject, or after injection of a medicine into a subject and medical personnel are sometimes accidentally pricked with such tips. This problem is particularly acute in situations where a syringe and needle have been contaminated ` with particularly ~irulent organisms such as the AIDS virus or W093/02720 2 1 1 4 ~ 5 6 PCT/US92/06587 the hepatitis virus. The risk of puncture with a contaminated needle point is of particular concern after an injection because a finger, hand or other part of the person administering the injection is typically in close physical proximity to the needle during its removal from the subject's tissues, during replacement of a needle or the needle cover or during removal of the needle from a syringe for disposal.
There is also danger of such exposures to personnel, such as maintenance people, other than medical personnel, when a used needle and/or syringe is laid aside or discarded with a needle tip still exposed. This danger continues even when a used needle and/or syringe are placed in a disposal container. For instance, it is a routine medical procedure to use a device which cuts off the tip of an exposed needle so that it may not be re-used. However, this procedure still leaves exposed needle stubs and syringe parts which may be contaminated w~th infectious agents and with which persons may come into contact and be infected. Thus, it is not uncommon for discarded needle stubs to protrude through plastic garbage bags or other containers and present serious risk of a puncture wound to a person handling or otherwise coming into contact with the container. Similarly, even after used needles are removed from ~yringes and placed in sealed containers, the exposed syringes must also be placed in sealed containers to reduce the likelihood of infectious contact with personnel. Sanitary disposal of used needles and uséd syringes is an expensive and time consuming process and entails significant risk of exposure to infectious disease vectors.
A related problem is that of the dangers of exposing a needle to the atmosphere prior to its being used in giving an injection or withdrawing a body fluid. Not only is there danger of wounds to user personnel and patients from the exposed needle tip, but also there is the danger that the exposed needle will become contaminated by wo g3/02720 2 1 1 ~1 5 5 ~ PCT/US92/06587 airborne or aerosol borne microbial and other contaminants and infect the patient eventually injected.
This danger is particularly acute in hospitals and other medical treatment areas where strains of antibiotic-resistant microbes endemically contaminate the air andall exposed surfaces. Contact with non-sterile air is a certainty with conventional exposed needle syringe technology because, in this technology, needles are routinely exposed to the air or surfaces f-or some discrete amount of time during use. Also, in emergency use situations such as military combat, natural disasters, or industrial accidents, the unused needle may be left exposed to such contaminants by untrained, harried or inexperienced personnel.
Yet another common problem in conventional syringe/injection technology is that rela~ing to improperly given injections. The differences in the rate which a needle must travel during insertion into and withdrawal from the subject's tissues and the rate at 20- which a ~yringe piston must be operated in order to ~ inject or aspirate fluid in a painless manner are - substantial. The techniques of various medical per~onnel in using-conventional syringes are varied. Technigues - vary according to'the position of the subject, how'that 25- portion of the subject's anatomy which is to be injected' is held, and by the various' individual techniques of -- medical personnel. This problem is particularly acute with respect'to untrained or' inexperienced personnel.
When a needle' is 'inserted too slowly, needless pain 30- results. These problems are overwhelmingly due to the difficulty of operating a syringe and needle in a manner which appropriately varies the rates of needle insertion and withdrawal and the rates of fluid injection and aspiration. '' An additional problem in the field is that of dosage management.'For subjects who'give themselves injections, either because they require regular doses of injected Wos3/02720 2 1 1 4 ~ ~ ~ PCT/USg2/06587 pharmaceuticals or because medical personnel are not available, it is critical to insure that dosages are correct. Diabetic subjects often find themselves in such situations, particularly diabetics who suffer from the related condition of blindness~ Other blind people are similarly in need of a product which insures that both the type of medication and its dosage are correct for their specific needs. Similarly, soldiers in the field, travelers requiring regular injectable medications, and subjects in emergency situations where self-injection is necessary often have difficulty administering the proper dosage of a given drug and often have difficulty in using a conventional syringe. Such problems are also compounded by darkness or poor lighting conditions in battlefield, power failure, and other crisis or emergency situations.
It is well known in the medical injection field that, when administering a drug or other substance intramuscularly, an attempt is made to aspirate blood or other physiological fluid after insertion of the injection needle into a ~ite thought to be suitable. Such an attempted aspiration is mads.in.order to interrogate the injection site (i.e., essentially, as understood in the art the.volume~of tissue immediately ad~acent to and in fluid.communication with the open end.of the needle) for the presence of blood, lymph, cerebrospinal fluid, or .the like. This interrogation is made to insure.that pharmaceutical ~ubstances or other fluids are not unintentionally .injected inappropriately, e.g., into a blood vessel, lymph vessel or into cerebrospinal fluid!.
. The inappropriate administration of a drug or other ~substance into a blood vessel, lymph yessel or cerebrospinal cavity could result in any of a number of adv.erse effects including nausea, unwanted toxicity, paralysis, neurological damage or even death. Moreover, the administration of pharmaceutical substances to inappropriate sites often results in attenuation or loss of the substance's desired, specific functional W093/02720 2 1 1 ~ ~ S ~ PCT/US92/~587 characteristics or activities. Thus, it is of paramount importance to insure that a needle used in administering a drug or other substance be inserted into an appropriate injection site.
For subjects injecting themselves at home, in emergency situations, or in combat, it is virtually impossible to perform the correct procedure. Similarly, personnel who are untrained in medical injection procedures but must give injections because of crisis or ~0 emergency situations are much more likely to incorrectly administer a substance, either by administering an incorrect dosage or administering by placing the needle so that its tip is positioned at an inappropriate site (e.g., so that the substance is injected directly into the blood stream rather than intramuscularly).
An example where a pharmaceutical substance must be delivered to an exact site is in the administration of certain chemotherapeutic drugs for the treatment of cancer. It is absolutely necessary that chemotherapeutic drugs be delivered to the exact target tissue. Exposure of some of these drugs to the ckin or to the incorrect tissue or to the bloodstream may cause severe side effects. It is. thus desirable to have a means for automatically interrogating the fluids in an injection ~ device to insure that blood or other physiological fluids are not being inappropriately aspirated from a possible injection site into the-- device before drug is administered with the device. Thus, it would also be ~desirable to have a device which will automatically pre-vent injection of pharmaceuticals at an undesirable or inappropriate injection site. In other cases, however, it might be desirable or necessary to inject a drug into, for example, the bloodstream; then the interrogation would be to assure that a physiological fluid, such as blood, is aspirated into the injection device before using it to inject the drug.

W093/02720 ~ PCT/US92/~587 The present invention also relates to a two-component safety injection syringe for medical and research purposes and more particularly to a device designed to separately store a medicament and a solvent therefor until a time just prior to injection when the two substances are mixed and then injected.
It is well known in the medical field that the shelf life of particular pharmaceutically or medically active substances is increased when the active substance is stored in a dry form or in stable but non-injectable solution form prior to injection. Many drugs now being marketed or being developed for marketing are not stable in their deliverable solutions for a sufficient period of time to allow for commercial distribution or have shelf lives which are unacceptably short. Among these pharmaceuticals are epinephrine, which is used to treat severe allergic and anaphylactic reactions, and cyclophosphamide, an anti-cancer substance. Other pharmaceutically active substances such as urokinase, which is used for dissolving blood clots, and glucagon, which is used for treating hypoglycemia, are stable only in dry powder forms. Papaverine, which is optimally - stored in solution at-very acidic pH levels (in the range - - 2.0 - -2.8) must be mixed with a physiologically acceptable solvent immediately prior to injection to ~avoid the painful and destructive effects associated with acidic solutions. Other medically active substances which do not store well in forms which can be easily administered are adenosine triphosphate (available from Genentech)-and Prostaglandin-E which has a shelf life of - only 24 hours when mixed for infusion.
However, storage of a medically active substance in a stable non-injectable form necessitates~ the pre-injection mixing of the substance with a medically acceptable solvent. Therefore, separate containers for solvent and solute are generally used. However, this method of pre-injection mixing is inconvenient because it W093/02720 2 1 1 ~ PCT/US92/06587 requires more than one container. The use of more than one container is also undesirable because judgement on the part of the person mixing the medication is required to use amounts which result in an appropriate dosage and also because of the problems surrounding the difficulties in maintaining sterility when materials from two or more separate containers are mixed.
Thus, it can be seen that a need exists for injection devices which increase the shelf-life of particular pharmaceuticals by separately storing the various components of certain medicaments for a commercially acceptable period of time until a time just prior to injection. A related need is for devices which increase _ .
those shel_-li~es and which require a minimum of preparation to insure a dependable and correct dosage administration. The fulfillment of such need will permit the oommercial availability of many pharmaceuticals which have been heretofore available only directly from professional medical personnel.
In an attempt to solve these problems, a number of wet-dry syringes which incorporate both solvent and medically active solute in the same cartridge to be mixed just prior to injection have been developed. U.S. Patent 4,689,042 to Sarnoff et al. ~hows a two-barreled syringe wherein the solid medicament and liquid solvent are stored in separate container portions of the device. Pre-in~ection mixing and injection in Sarnoff are controlled by a number of biasing springs which sequentially operate by way of releasing mechanisms to propel the solvent from one compartment into a dry medicament-containing compartment via communicating passages. The entire apparatus is then agitated by the operator to mix the medicament and solvent prior to the injection. The operator then places the injection needle into target tissue and actuates an injection mechanism which propels the mixed medicament into the subject. Sarnoff is a W093~02720 2 1 1 4 5 S ~ PCT/US92/~587 complex mechanism employing many components and requiring several discrete operating steps to use.
Similarly, U.S. Patent 4,755,169, also to Sarnoff et al. discloses a multi-compartmented stacked syringe-within-a-syringe assembly wherein a biasing spring pxopels a mixing/injection piston and primary needle to rupture a seal between the respective medicament component compartments of the device. After agitation of the device and insertion of the injection needle into a target site by the operator, the biasing spring is again actuated to drive a second piston which propels the mixed medicament into ~the subject. Although somewhat simpler than the device of the '042 Sarnoff patent, the invention of the '169 patent is also a complex mechanism employing many components and requiring several discrete operating steps to use.
U.S. Patent 4,328,802 to Curley et al. discloses a wet-dry syringe and connected vial which are separated during use and w~erein the piston portion of the syringe, being biased by a spring, is actuated to inject the solvent into the solute vial whereby mixing occurs.
Manual aspiration into the syringe i5 then necessitated to charge the syringe with the mixed medicament/solvent solution. ~Removal of the syringe portion from the syringe/vial assembly is required prior to injection înto the sub~ect.
Other two-chambered syringes are marketed under the tradename Variject, manufactured by Bunder Glas GmbH.
The Bunder device is a single cylinder syringe wherein!a fluid bypass allows mixing of the medicament solvent and medicament during operation of the device.
The multiple piston assemblies of the aforementioned devices are mechanically complex and expensive to manufacture. In addition, none of the aforementioned devices provides for the withdrawal of the used injection needle to reside completely within the device to afford safe disposal and disease prevention characteristics.

W093/02720 211 d 5 S ~ PCT/US92/~587 _g_ Thus, it can be clearly seen that there is a need for injection devices which contain pre-measured dosages of particular pharmaceutical substances wherein the administration or self-administration of those doses can S be easily and dependably achieved by non-professional personnel. It can also be clearly seen that a need exists for injection devices which can be operated manually, or by mechanical means such as spring tension or gas pressure, or which can be operated automatically by means of electronic or other data processing means.

Summary and Ob~ects of the Invention It is an object of the present invention to provide concealment of an injection needle at all stages of use, thereby reducing the apprehension of the patient.
It is similarly an object of the present invention to maintain sterility of an injection needle at all stages .of use by providing means whereby the needle, prior to contact with the skin of a patient for penetration therethrough, is never exposed to any potentially conta~linating surfaces, aerosols or airborne - - particles or microbes. ~ ~ --- It- is another object of the present invention to provide-an injection vial which eliminates the dangers of infection or in~ury resulting from accidental contact ~5 with exposed needles.
It is still another object of the present invention to provide a sanitarily disposable injection vial with a needle which, after use in an injection, retracts - -completely into said vial to reduce the risk of disease transmission caused by the risk of exposure to a contaminated needle or to a contaminated syringe or to parts thereof.
It i8 yet another object of the present invention to provide a sanitarily disposable injection vial which can be safely discarded without the need for special W093/02720 2 1 1 ~ PCT/US92/06587 equipment or containers and which can be safely and sanitarily disposed of in non-hospital, rugged, or emergency environments.
It is also an object of the present invention to s provide an ampule or cartridge for dispensing fluid medication which can be filled by the use of conventional pharmaceutical packaging machinery, thus avoiding the substantial expense which would be required for the development and production of non-conventional packaging methods and machinery.
It is a further object of the present invention to reduce the risk of an improperly administered injectio~
by providing means for precisely, automatically, and programmably controlling the rate of needle insertion, the rate of needle withdrawal, the rate of medicinè
injection, and the rate of fluid aspiration.
It is also an object of the present invention to reduce the risk that an incorrect dosage of a fluid medicine will be ~dministered by injection.
Tt is a further object of the invention to reduce the risk that an incorrect drug wili be administered to a -. subject or~be self-administered by a subject.
- It is an ob~ect of the present invention to provide - means-fos-*he auto atic~ interrogation of an injection ~- 25 site to determine whether or not the injection needle tip : . is at-an appropriate.~or desired site and in the desired target tissue.
.. . It~is a further object of the present invention to provide means~ :~ for automatically scanning ah in~ection/aspiration cartridge during operation to determine if blood or other physiological fluids have - been aspirated from an actual or possible in~ection site - : into the cartridge.
It is also an object of the present invention to 35 . provide means for automatically preventing the injection of medicines or other fluids into an undesired or inappropriate tissue or site.

, W093~02720 2 1 1 ~ S ~ 6 PCT/US92/06~7 Furthermore, it is an object of the present invention to provide means to administer a drug to a pre-selected target tissue and avoid exposure of the drug to tissues which would be undesirably damaged by such exposure.
It is yet another object of the present invention to provide a means for giving or self-administering penile injections of drugs with a minimum of pain and apprehension on the part of the male.
It is an object of the present invention to provide a simplified syringe for the separate storage and pre-injection mixing of a medically active substance and a physiologically acçeptable solvent or fluid.
Another object of the present invention is to provide a disposable safety syringe adapted to be used manually or with an automatic injector for the separate storage and pre-injection mixing of a medically active substance and a physiologically acceptable solvent or fluid.
It is a similar object of the present invention to provide a syringe adapted for the pre-injection mixing of at least one liquid component with another component which has the ~afety feature of an injection needle which withdraws after use to reside completely wi~hin the closed cartridge, thus reducing the dangers of infection or injury resulting from accidental contact with exposed needles. ~^
- It is an additional object of the present invention to provide a cartridge ~yringe with means for automatically mixing medicament components immediately - prior to injection.
It is yet another object of the present invention to provide a needle agsembly housing which can be used with necked medicament containers of both conventional and non-conventional types.
In accordance with the objectives of the invention, a vial for fluid injection is provided. The injection vial is a double-ended cartridge, having a first end and a second end, the cartridge having a cylindrical bore W093/02720 ~ 5~ PCT/US92/06587 defined by a wall extending between the first end and the second end, the bore being suitable for storing a fluid charge to be expelled therefrom. A first piston and a second piston are positioned within the bore and are slidably seated against the cylindrical wall of the bore, the first piston comprising means for reversibly engaging a plunger. The cartridge is provided with a puncturable end cap which is rigidly attached and sealed to the second end of the cartridge and which comprises a needle lo guide. The cartridge is also provided with a hollow in-jection needle having an external tip and an internal tip, the internal tip being rigidly attached to and passing through the second piston, and the external tip extending toward the end cap without protruding therefrom, and means for locking the first piston and the second piston irreversibly together when the first piston and the second piston are a predetermined distance apart. It is preferred that the puncturable end cap be made of a self-sealing material, although this is not necessary for practicing the invention.
~ The vial may also be provided with a readable indicator to indicate the type of medication, patient information, the amount of medicine to be injected and ~ the various rates of needle insertion and withdrawal and of fluid injection and/or aspiration. ~
In accordance with another aspect of the invention, - a programmable automatic injection/aspiration device is provided having a housing, a chamber disposed within the housing for reversibly receiving a cartridge vial, and a cartridge vial piston operating plunger slidably disposed within the housing. Also provided are means, disposed within the housing, for propelling the plunger.
Similarly, controller means for controlling the rate, direction, and extent of movement of the plunger are provided. Control is thus provided via said propelling means, and a programmable processor for directing the controller, a sensor for detecting the rate, direction, W093/02720 - 2 1 1 ~ ~ S 6 PCT/US92/06~7 and extent of movement of the plunger, an indicator for indicating the rate, direction, and extent of movement of the plunger and for indicating the amount of fluid remaining and expelled from a fluid vial, and a sensor for detecting the presence in the vial of aspirated physiological fluids are also provided. Similarly provided are means for automatically preventing injection into an undesirable target tissue upon the detection of aspirated physiological fluid, and locking means for preventing unintentional discharge of drug from a cartridge vial disposed in the injection/aspiration device.
In accordance with the invention, a cartridge vial, containing a fluid medicine charge, may be inserted into an injection/aspiration device, which may then be used to administer the medicine by in~ection. Finally, the cartridge vial, with completely retracted needle, may be removed and discarded, while the in~ection/aspiration device may be repeatedly re-used with different cartridge vials.
- In accordance with other objects of the invention, a mixing syringe for two-compohent medic~ments is --- provided. The mixing syringe ~has a cartridge housing having a firet end -and a second end, a substantially cylindrical cartridge housing bore, a slidable cartridge - di~posed in the cartridgé housing bore having a first - end, a ~second end,^` and a temporary sealing barrier disposed between the first nd second ends separating the bore of the cartridge into a cylindrical medicament solvent charge chamber and a cylindrical medicament charge chamber.
The cartridge housing is also provided with means, fixedly attached thereto, for breaching the temporary sealing barrier, the cartridge being suitable for separately ~toring a medicament solvent charge and a medicament charge in the medicament solvent charge chamber and the medicament charge chamber, respectively, W093/02720 2 ~ PCTIUS92/06587 -14- c-~

the charges to be mixed to form a medicament to be expelled from the cartridge.
A piston is disposed within the first end of the cartridge and is slidably seated in the cartridge bore.
A retractable needle housing assembly is slidably disposed in the cartridge housing and a retractable injection needle is provided fixedly attached to the needle housing assembly and extending therethrough for injecting mixed medicament. A puncturable cartridge end stopper is provided rigidly attached to and sealing the second end of the cartridge. In some embodiments of the -invention, a puncturable end cap, the end cap sealing the second end of the cartridge housing and having a needle guide disposed therein is provided.
15Further in accordance with the objects of the invention, an operating shaft for operating the piston and the cartridge and for adapting the cartridge to other devices is provided in the piston. The operating shaft may be provided with a chamber for receiving a pushrod or 2~ injection needle portion which has punctured the piston therethrough. In some embodiments of the invention, the breachable temporary sealing barrier is so configured that the piston can pass sealably therethrough after the barrier is~-breached. In accordance with this~aspect of the invention, various valves, having substantially cylindrical openings which permit the piston of the cartridge to pass therethrough, are provided. These valves include but are not limited to stopcocks, membranes and seats therefor, iris valves, and ball and seat valves.;
In accordance with additional objects of the invention, a needle housing assembly for use with necked medicament containers which have puncturable end stoppers is provided. The assembly is provided with a needle housing, locking means disposed in the needle housing for locking the housing to the necked medicament container when the needle housing assembly and the necked cartridge W093/02720 2 1 1 4 ~ 5 6 PCT/US92/~ ~7 become a predetermined distance apart upon relative movement between the necked medicament container and the needle housing, and an injection needle.
The injection needle is provided with a hollow shaft, an internal end, an internal shaft portion, an external end, an external shaft portion, first and second apertures, and a passageway extending through the hollow shaft and connecting the first and second apertures, the needle being rigidly attached to and extending through the needle housing, the internal end and internal shaft portion of the needle being adapted to puncture a necked medicament container, and the external end and external shaft portion of the needle being adapted to expel a medicament out of the needle housing assembly.
The means for locking the housing to a necked medicament container, a needle assembly housing, comprises protrusions which are disposed in the housing and which are adapted to securely engage the neck and head portions of a medicament container. In a preferred embodiment, the needle assembly housing is provided with flanges which are disposed to capture and securely hold the neck and end- portions of a nec~ed medicament container of either a conventional or non-conventional type. The needle assembly housing of the present invention is adapted to fac~litate reduced inflamation at - an injection site by being configured to insure that the injection needle i8 inserted into the target tissue before the medicament-is injected.
The needle assembly housing of the present invention is adapted to be used within a cartridge housing of an automatic or non-automatic in~ection device having an expansion chamber which permits expansion of the needle assembly housing flanges in conjunction with a slidable cartridge for the capture thereof. It is also clear that the needle assembly housing of the present invention can be adapted to be used independently with various necked W093/0272~ PCT/US92/06~7 medicament containers which are used without an injector device.
In accordance with yet other embodiments of the invention, the means fixedly attached to the cartridge housing for breaching a temporary sealing barrier between chambers of said slidable cartridge comprises a spiral pushrod having an anchoring end and a puncturing end suitable for engaging the operating slot of a rotor valve, the anchoring end being provided fixedly attached to the cartridge housing and the spiral pushrod extending from the cartridge housing toward the cartridge puncturable end stopper, through a pushrod aperture provided in a needle assembly housing for freely guiding the pushrod therethrough so that the puncturing end of the pushrod resides in close proximity to and in alignment with the puncturable cartridge end stopper. In an additional embodiment of the invention, the spiral pushrod is adapted to operate a mixing rotor provided in ~-the cartridge for agitating the solvent/solute mixture as it passes through the cartridge to be expelled therefrom.
In accordance with still further objects of the invention, a mixing syringe for two-component medicaments is provided comprising a cartridge housing having a first end and a second. end, the.cartridge housing having a substantially cylindrical cartridge housing bore, a slidable cartridge disposed in the cartridge housing bore and having a first end, a second end, and a temporary sealing barrier disposed between the first and second ends and-separating a cartridge bore of the cartridge into a cylindrical medicament solvent charge chamber and a cylindrical medicament charge.chamber, the cartridge housing having means, fixedly attached thereto, for breaching the temporary sealing barrier, and being suitable for separately storing a medicament solven~
charge and a medicament charge in the medicament solvent charge chamber and the medicament charge chamber, W093/02720 ~ PCT/US92/065~7 respectively, the charges to be mixed to form a medicament to be expelled from the cartridge.
The cartridge is also provided with a piston disposed within the first end of the cartridge and being slidably seated in the cartridge bore, and a needle housing assembly rigidly attached to the cartridge and contained wholly within the cartridge housing. Also provide is an injection needle which is containable wholly within the cartridge housing, which can be extended to a position in which at least a portion of the needle extends outside of the cartridge housing, the needle being fixedly attached to the needle housing assembly and extending therethrough for injecting mixed medicament. The cartridge is also provided with a puncturable end cap, the end cap sealing the second end of the cartridge housing, and means for retracting the needle to reside completely within the cartridge housing after the expulsion of the medicament from the syringe is completed. The breachable temporary - sealing barrier is so configured that the piston can pass sealably therethrough after the barrier is breached being providèd with a cylindrical bore of substantially equal dimension to that of the--cartridge bore 80 that the ; piston can pass sealably therethrough after the barrier is breached. The barsier can be a valve disposed through thé cartridge having an operating cam disposed on the exterior of thè càrtridge wherein the valve operating cam is configured to be operated by a pushrod integral to the cartridge housing.
-^- Yet further in-accordance with the objects of the invention are provided an electronically or magnetically actuated pushrod contained within the cartridge and an electronic or magnetic pushrod actuator contained within the cartridge housing for breaching the temporary seal between chambers of the slidable cartridge.
Yet still further in- accordance-with additional objects of the invention, a mixing syringe is provided for the pre-injection mixing of two-component medicaments W093/02720 ~ PCT/US92/06 which comprises a cartridge housing having a first end and a second end, the cartridge housing having a substantially cylindrical cartridge housing bore and a slidable cartridge disposed in the cartridge housing bore S having a first end, a second end, and a temporary sealing barrier disposed between the first and second ends and separating the cartridge bore into a cylindrical medicament solvent charge chamber and a cylindrical medicament charge chamber, the cartridge being suitable for separately storing a medicament solvent charge and a medicament charge in the medicament solvent charge chamber and the medicament -charge chamber, respectively, the charges to be mixed to form a medicament to be expelled from the cartridge. The 1.~ cartridge is provided with a piston disposed within the first end of the cartridge and being slidably seated in the cartridge bore and a retractable needle housing assembly slidable in the cartridge housing the needle housing having means, fixedly attached thereto, for breaching the temporary sealing barrier~ The device is further provided with a retractable injection needle having a hollow shaft, an internal end, an internal shaft portion, an e~ternal end, an external shaft portion, first and second apertures, and a passageway extending through the hollow shaft and connecting-the first and , second apertures. $he needle is rigidly attached to and - extends through the.needle housing, the internal end and internal shaft portion of the needle being adapted to puncture the cartridge, and the external end and external shaft portion of the needle being adapted to expel a medicament out of the needle housing assembly, the first injection needle aperture being disposed in the internal needle shaft portion an appropriate distance from the housing to receive fluid from a punctured medicament cartridge, and the second injection needle aperture being disposed in the external needle end.

W093/02720 ~ L 1~ ~ ~ PCT/US92/06587 8rief Description of the Drawinas The invention will now be deseribed with referenee to the enelosed drawings, in whieh:
Figure 1 is a seetional elevation view of a cartridge syringe eonstrueted in aeeordanee with a first embodiment of the present invention whieh utili~es a plug as a means for separating the chambers of the eartridge.
Figures 2(a) and 2(b)-2(e) are ~eetional elevation views of a eartridge syringe eonstrueted in aceordanee with a seeond embodiment of the present invention whieh utilizes a burstable membrane as a means for separating the ehambers of the eartridge and whieh utilizes an elution eolumn for storage of the medieament solute.
Figures 3(a) and 3.(b)-3(d) are sectional elevation views of a eartridge syringe eonstrueted in aecordanee with another embodiment of the present invention wherein the means for separating the ehambers of the invention is a rotary valve operated by a spiral twist rod.
- ' Figures 4(a) and 4(b)-4(d) are seetional elevation views of a eartridge syringe eonstrueted in accordance with another embodiment of the present invention wherein the means for separating the ehambers is a stopeoek extending throu-gh th- cart~ldg- whlch i~ otuat-d ~y a pushrod and wberein means ~or automatlcally agitatlng the eomponents of the medieament during operation is provided.
Figures 5(a) and 5(b)-5(e) are seetional elevation views of a eartridge syringe eonstrueted in aeeordanee with another embodiment of the present invention wherein a stopeoek barrier means is aetuated by a pushrod integral to the e~rtridge housing and wherein the : medieament solute is disposed in a mixing maze throuqh whieh the medieament solvent must ~low.
Figures 6(a)-6(e) are seetional elevation views of a eartridge syringe eonstrueted in aeeordanee with yet another embodiment of the present invention wherein a SUBSTITUTE SHEET
IPEA/US

~u ~ u ~ ) u W093/02720 ~ PCT/US92/~

burstable membrane barrier is breached by ~n electronically or magnetically activated means and wherein the injection needle is fixedly attached to the cartridge.
Figure 7 is a sectional elevation view of a cartridge syringe constructed in accordance with another embodiment of the invention similar to that shown in Figure 1 but wherein the extended injection needle also performs the barrier breaching function of a pushrod.
Figure 8(a) is a perspective view of an embodiment of the needle housing assembly constructed in accordance the invention which can be used with various necked containers known in the art as well as with various embodiments of the cartridge syringe of the present invention.
Figure 8(b) is a plan view of the needle housing assembly of Figure 8(a).
Figure 8(cl is/~ectional view taken along the lines A-A in Figure 8~c).
Figure 8(d) is an enlarged view of Detail A of Figure 8(c).
Figure 9(a) is a sectional elevation view of a cartridge syringe constructed in accordance with the present invention ~imilar to that shown in Figures 5~a)-(e) but wherein a spherical ball valve having an aperture ~uitably configured for the passage therethrough of the piston and a solute is disposed on a grid in the necked portion to permit substantially complete evacuation of the cartridge ~re prov~ded.
Figure 9(b) is a detail view of the ball valve operating cam in the closed position of Figure 9(a).
Figure 9(c) is a sectional elevation view of the cartridge of Figure 9(a) wherein the ball valve has been opened and the piston has passed sealably therethrough to evacuate the solvent/solute mixture and to become seated at the curved abutments forming the necked portion of the cartridge.
SUBSTITUTE SHEET
IPEA/US

W093/02~20 ~ b PCT/US92/~ ~7 Figure s(d) is a detail view of the ball valve operating cam in the open position o~ Figure 9(c).
Figure lO is a longitudinal c~oss-sectional view of an injection/aspiration device showing the relative placement of tbe cartridge vial and other components;
Figure 11 is a longitudinal cross-sectional view of a cartridge vial constructed in accordance with an embodiment of the invention suitable for storing and injecting a single solution medicament;
Figure 12 illustrates another embodiment of a cartridge vial suitable for the storage and injection of a single solution medicament wherein a slidable ampule functions similarly to the first piston of the embodiment shown in Figure ll and altethnate means for needle retraction are provided which/ampule can be manufactured using conventional pharmaceutical packaging machinery.
Figure 13 illustrates an additional embodiment of the cartridge vial si~ilar to that shown in Figure 12 but for the storage and injection only of a single component medicament and wherein certain dimensional relationships are varied.

Detailed Description of the Preferred Embodiments The advantages and characteristics of the cartridge mixing syringe and needle housing of the present invent~on can be elucidated from the following detailed description of several embodiments of the mixing syringe and needle assembly to be taken as ex~mples and not aB
limitations in conjunction with the accompanying drawinqs.
From the information herein, it is also clear th~t many permutations of the present invention other than those shown in the drawings a~e possible by t~e combination of components from the various embodiments.
For example the needle assembly housing and cartridge housing shown in Figure 2 could, with slig~t SUBSTITUTE SHEET
IP~A/US

W O 93/02720 ~ 6 PC~r/US92/06587 modification, be adapted to utilize the magnetically or electronically actuated burstable membrane componentæ
shown in Figure 6.
~ith reference to Figure 1, a two-component cartridge mixing syringe comprises a double ended circularly cylindrical cartridge housing 1 constructed of a rigid material such as polyethylene and having a cartridge residence chamber 15 and a needle housing residence chamber 2 and needle housing assembly receiving.chamber 11. Cartridge housing 1 is provided with a puncturable sealing end cap 3 of re ilient material such as butyl rubber, a plastic needle guide S rigidly embedded in end cap 3 and having a needle guide aperture 7 formed therein and an injection device positioning projection 9. End cap 3 is also provided with a pushrod 60 anchored to 34 needle guide 5 at pushrod anchoring end 66 and constructed of a suitable material such as stainless steel. Pushrod 60 extends through a needle assembly housing pushrod aperture 20 toward a puncturable cartridge end stopper 39. Needle housing assembly receiving chamber 11 is further provided with curved abutments 13 of appropriate configuration to allow a needle assembly housing 18 to both enter and withdraw from needle assembly housing receiving chamber 11.
Needle assembly housing 18 and a cylindrical cartridge 31 are initially disposed within needle housing residence chamber 2 and cartridge residence chamber 15, respectively.
Cylindrical cartridge 31 is constructed of a rigiq material such as Lexan plastic, is slidably positioned within cartridge housing 1 and is provided with a three-portion chamber in which is stored a solvent charge 51 and a solute charge 63. Solvent charge 51 is stored in a first portion 33 of cartridge 31. Solvent charge 51 can consist of a single solvent or diluent, mixed solvents or diluents, a concentrated solution or one or more parts of a multiple-part medically active substance W093/02720 ~ 1 d ~ j ~ PCTJUS92/06587 .

or system. First portion 33 is separated from a second cartridge solute storage portion 35 by a plug seat 62 which is rigidly affixed to the internal walls of cartridge 31 and a plug 61.
~econd cartridge solute storage portion 35 has stored therein solute charge 63 in finely divided form on a puncturable high-surface-area solute trait grid 6~.
Solute charge C3 can consist of solid medicament, liquid medicament, a diluent for a concentrated solvent or one or more parts of a multiple-part substance or system.
Solute charge 63 is disposed across second cartridge solute storage portion 35 so that solvent charge 5~ moves through grid 64 thus dissolving solute charge 63 before the mixed solute/solvent is expelled through a hollow injection needle 23. A third cartridge injection needle portion 37 is provided with a puncturable cartridge end stopper 39 of a resilient material within a cartridge cap 38. A cartridge piston chamber abutment ~0 forms a transition between se-ond cartridge storage portion 3s and third cartridge injection needle portion 37 and forms a seat-for solute tray grid C~. The external portion of . the transition between third cartridge portion 37 and - cartridge capC38 forms a cartridge shoulder ~ Cartridge shoulder..~l functions as a flange engaging step for 25 -: engaging flanges 19 of needle assembly housing 18~during operation of the invention.~
c Cartridge 31:is further provided with a piston ~5 of a resilient material and having a piston shaft ~7 and a piston shaft head ~9 for reversibly engaging an injection/aspiration device or an adapter for manual operation. Such a cartridge could be engaged to an injection/asp:ration device or man~al adapter by any other means, other than a piston similar.to piston ~5 as shown, such as a T-shaft and keyway, a threaded rod, piston engaging barbs, or other means providing secure engagement of a cartridge to an injection/aspiration W093/02720 ~..L 1 4~ 5 ~ PCT/US92/~SB7 device. It is preferred t~at the means for engaging be reversible.
Needle assembly housing 18 is of a rigid material such as linear polypropylene and is provided ~ith a needle assembly housing bottom 16, needle housing walls 17, needle assembly housing flanges 19 and needle assembly housing lips 2~ disposed for securely engaging cartridge 31. Needle assembly housing 18 is also provided with a needle assembly housing pushrod aperture 20 having sbarpened stainless steel pushrod 60 passing therethrough. Needle assembly housing ~8 is further provided with the hollow injection needle 23 which is rigidly attached to housing 18 and whic~ passes therethrough. Injection needle 23 has an internal tip 2S
disposed toward puncturable cartridge stopper 39 and an external tip 27 for selective movement out of the housing and insertion into target tissue which passes through aperture 7 of needle guide 5 but does not protrude through sealing end cap 3 until operation of the invention.
The relative lengtbs of needle assembly housing walls 17, needle assembly housing receiving chamber 11, ~nd pushrod 60 are such that, in oper~tion of the device as described hereinbelow, ~ pushrod puncturing end 68 of pushrod ~O penetrates puncturable cartridge end stopper 39 and diclodges plug ~ from plug s-at 2 before needl-internal tip 25 contactQ punctur~ble cartridge end stopper 39. Third cartridge injection needle portion 37 is captured by the engagement of needle assembly housing flange lips 21 by cartridge shoulder ~1 of cartridge 31 when cartridge 31 has been propelled a sufficient distance toward puncturable cartridge sealing end cap 3 that needle assembly housing 18 is fully within needle assembly housing receiving chamber 11.
The above-described embodiment of the mixing syringe operates as described hereinbelow.

SUB~;TITl~TE SHEET
IPEA/US

~ v ~ v ~ v ~ o u ~
W~93/02720 2 1 1 4 ~S 5 ~ PCT/US92/06587 -2s-Piston 45 is propelled toward sealable end cap 3 by the application of force to plunger shaft bead ~9 in the direction of sealing end cap 3, which force is communicated through plunger shaft ~7 to piston ~5-thus applying hydraulic pressure through solvent charge 51, plug 61 and plug seat C2, and forcing cartridge 31 and needle assembly housing 17 having injection needle 23 fixedly attached therethrough toward sealing end cap 3, this action simultaneously forces cartridge 31 onto pushrod end 68, which slides freely through needle assembly housing pushrod aperture 20, thus also propelling injection needle 23 through needle guide aperture 7 causing external needle tip 27 to puncture puncturable sealing end cap 3. The relative lengths of needle assembly housing walls 17 needle assembly housing reseiving chamber 11 and pushrod 60 are ~uch that pushrod puncturing end 68 penetrates puncturable cartridge end stopper 39 and dislodges plug Cl from plug seat C2 thus causing solvent charge 51 to enter second cartridge solute storage portion 35 before injection needle internal tip 25 contacts puncturable cartridge end stopper 39 thereby allowing the mixing of solvent charge 51 and solvent charge 63. By varying the rate at which cartridge 31 is propelled toward end cap 3 after pushrod 60 dislodges plug 61, and before internal injection needle tip 25 punctures puncturable end cap 39, the solvation time during which solvent charge 51 and solute 63 can be controlled.
Continued forc- toward puncturabl- oartr~dg- ealing end cap 3 by piston ~5 continues to propel needle 2~
outward and into the target t~ssue until needle housing 18 is stopped by sealable end cap 3, thus positioning needle assembly housing 18 within needle assembly receivi~g chamber 11 which is of a larger diameter than cartridge residence chamber 15. The positioning of needle assembly housinq 18 wit~in n~edle as~Qmbly hou~ing~
receiving chamber 11 allows flanges 19 and walls 17 of ~i~a~ E--~

W093/02720 ~ PCT/US92/06S87 ~ -26-needle assembly 18 to expand to irreversibly and securely receive and capture third cartridge injection needle portion 37 of cartridge 31. Continued pressure in the same direction causes piston ~s to move toward puncturable cartridge end stopper 39 thus causing expulsion of the 'mixed solvent charge 51/solute 63 solution through hollow injection needle 23 into the target tissue.
After injection of the mixed solvent charge 5~/solute 63 solution through hollow injection needle 23 into the target tissue, the direction of force on piston shaft ':
head ~9 is reversed, thus causing the withdrawal of irreversibly captured needle assembly housing 18 into cartridge housing 31 and the withdrawal of injection ~5 needle 23 from the target tissue 80 that injection needle external end 27 resides completely within cartridge housing 31.
Piston ~5, although slidably seated in the bore of cartridge 31, is of a slightly oversize diameter so that the frictional force required to withdraw piston ~5 back through the bore.of cartridge 31 is much greater than the force required to withdraw cartridge 31 which has been captured by, n,eedle.~assembly housing 17 and needle assembly ,housing. 17 having needle 23- attached 25 therethrough froman,injection site to reside wholly within cartridge housing 1. ' Figure 2 shows an embodiment of the invention which differs from that shown in Figure 1 by providing a burstable membrane as a barrier between the~solvent and solute portions of.the cartridge and by presenting the .:
solute in an elutable bead column. With reference to Figure 2, cylindrical cartridge 31 of rigid material such as water glass is slidably positioned within cartridge housing 1 and is provide with a three-portion chamber in which is stored solvent charge 251 and solute charge 263.
Cartridge solvent portion 33 is separated from cartridge solute storage portion 35 by a membrane seat 2~1, a ~E ~ VJ s~
W093/02720 2 1 1 4 ~ 5 ~ PCT/US92/~587 resilient circular U channel made from vulcanized rubber, wh~ch is rlgldly att~chod And sealed to the lntern_l wAll- o~ c~rtr~dge 31 either by pressure generated by oversizing the diameter o~ the wall ad~acent to the cartridge wall or an industrial adhesive known to the art, into which is fitted a burstable membrane 273 of ~
materi~l such ~s natur~l rubber or styrene film locked in by an 0-ring tnot shown].
Second solute storage portion 35 has stored therein a bead column 272 of ion exchange resins such as Rhom and Ha~s' 6 Amborl~t- c~tionic or anionic resin-. In thi~
embod~ment o~ th~ invention, the resins are saturated with the appropriate solute charge 2C3 and subsequently eluted by solvent charge 251. It should be noted that in most instances the critical factor in drug delivery is the dosage amount of solute charge 263 while a surplus of solvent charge 251 is widely tolerated. Supporting the base of the bead column 272 is a puncturable permeable grid 27S. Bead column 272 is charged into cartridge solute storage portion 35 so that in operation of the invention solvent charge 251 moves through bead column 272, dissol~inq solute charge 263 before being expelled - through hollow injection needle 23.
The relative lengths of needle ~ssembly housing walls ~7 needle assembly receiving chamber 11 and pushrod 260 are such that in operation of the device as described hereinbelow sharpened pushrod puncturing end 26~
penetrates puncturable cartridqe end stopper a39 and burstable membrane 273 before needle internal end 25 contacts puncturable end stopper 239. This cAn be best seen in Figure 2(a). By controlling the length of time between which burstable membrane 273 is punctured by pushrod 260 and needle tip 25 punctures cartridge end stopper 39 the solvation time in which solvent 251 moves through solute 263 can be varied as needed for particular solute/solvent combinations.

SuBs~ ES~E~

W093/02720 PCT/US92/~ ~7 The embodiment of the invention ~hown in Figures 2(a)-2(c) operates in ~ similar manner to that described with reference to Figure 1 above and is further illustrated in Figure 2(a)-2(e) showing the device in four positions of the injection/retraction cycle. Figure 2(a) shows the invention in its initi~l storage position.
Figure 2(b) shows the invention after force has been applied to pi6ton ~S through shaft head ~9 of shaft ~7, forcinq c~rtridge 31 and needle assembly housing 17 h~vlng in~ectlon needle 23 rigidly disposed therethrough toward puncturable cartridge housing sealing end cap 3 sufficiently far so that pushrod 2C0 anchored in pushrod base 26C has punctured cartridge end stopper 239, grid 275, and burstable membrane 273 and has expanded the flanges of needle assembly housing 17 which, in this position, is shown bottomed out in needle assembly housing residence chamber 11 but has not yet been propelled sufficiently far that the internal end of needle 23 has punctured puncturable cartridge end s~r 239.
Figure 2(b) thus shows the device in a position wherein solvent 2Sl is exposed to solute 263 but does not yet have an avenue through injection needle 23 for expulsion from cartridge 3~.
Figure 2(c) shows the device after cartridge 31 has been further propelled toward sealing end cap 3 a sufficient distance ~o that the flanges of needle assembly housing 17 have irrever~ibly captured the cap and neck portion of cartridge 31 and piston ~5 has propelled part of the solvent charge 251 through solute ~263 and into the third portion of the cbamber of cartridge 31 for injection.
Although not ~hown, it is obvious that continued force on piston 45 propels an additional amount of solvent 251 through solute 263 to inject the required amount of the medicament whereupon barbs 20~ irreversibly engage membr~ne seat 271 so that reversal of the force on piston ~S withdraws cartridge 31 needle assembly housing SU~STITUTE SHEET
IPc~/US

~ ~14 ~ ~ ~ R~o/U9S2~0 1 OCT 1992 ~7 and in~ection needle 23 to fully reside within cartridge bousing 1 ~fter the in~ection ha~ occurrQd Flgure 2(e) shows the fully witbdrawn cartridge with att~ched needle ~Qmbly hou~ing ~nd needle Rigidly anchored lnto rubb~r plung~r ~5 ar~ ~t~inless ~teQl barbs 20~
Figur~ 3 ~hows an embodim~nt of the cartridgQ of thQ
pre~nt invention having liguid con~tituents in both uppQr and lowQr portion~ of the cartridge This ~mbodim~nt i~ known a~ ~ w~t/wet c~rtridg~ Th~
temporary barriQr devic~ for ~Qpar~ting th~ portion~ of th~ c~rtridg~ rot~t~bl~ di~k ~eobly valve ~epar~tion b~rri~r and trigger therefor th~t extend~ th~
ti~ ~vail~blo for ~ixing Figur~s 3(a), 3(~), 3(c) ~nd 3(d) show thrQ~ opQrating position~ of th~ d~vice With r~fQrenc- to Figuro 3, cylindric~l cartridg~
housing 1 i~ fitt~d wit~ a shQlf 37~ that is integral with cylindrical cartridg- hou~ing 1 into which i~
iib~dded a rigid rectangular ~piral pu~hrod 332 co~xially - 20 aligned with cylindrical cartridg- 331 An in~ection n~edle 323 i~ uffici ntly off-et in nQedl~ a~e~bly hou~ing 31~ ~o a~ not to lnt rfQr- with th~ op~r~tion o~
r~ctangular piral pu hrod 3~2 Cylindrical cartridge 31 i~ d id~bly po~itlon d within cartridg~ hou~ing ~ and ~-provid d with two choib-r~ in which ~re ~tor~d a ~olvent charg ~51 and a ~olution ch~rge 363 Solv~nt ch~rg~
35~, ~uch a~ Pro~taglandin E, ~vailable fro~ Up~ohn - Ph~re~c-utic~l, a v~odilator that i~ psovided in a ~olution of ab~olute ~Icohol and ~u~t b~ diluted with aterile w~ter b~for- in~ecting, iB ~tored in f$r~t portion 333 of cartridge 3~1 and ~ol~ttion charg~ 363, such a~ th- diluont di~till~d water, i~ ~tored in ~econa cartridg portion 335 First cartridge ~olvent portion 333 i~ separat d frou ~econd ca.tLidge soiute storage portion 33~ by a di-k as~e~bly valve co~pri~lng double disk valve seat 37~, a circular ~tator di~k 377, and a circular rotor aisk ~78 Double disk valve seat 371, a SUBSTITUT~ SHEET

W093~02720 2 1 1 4 5 ~ 6 PCT/US92/~ ~7 resilient circular U channel made from castable silicone rubber, is rigidly attached to the internal walls of cartr~dge 331 either by pressure generated by oversizing the diameter of tbe wall ad~acent to the cartridge wall or an industrial adhesive known in the art, into which is permanently fitted circular stator disk 377, made from rigid rubber with alternate quarters open and circular rotor disk 378, made from stainless steel w~th alternate quarters open, which is free to rotate in double disk valve seat 371. The disks are arranged go that the open quarters do not overlap thus leaving the disk assembly valve closed. This arrangement can be seen in Figure 3(a). Rigidly attached to circular rotor disk 378 by rods 379 is a driven slotted member 381. Driven ~lotted member 381 has a rectangular slot 380 of an appropriate dimension so that a rectangular spiral pushrod 382 will cause driven spiral disk 381 to rotate as it follows the spiral of spiral rod 382. The sharpened spiral tip 388 of rectangul~r spiral pushrod 382 is of a thickness, length and rotation to cause driven spiral member 381 to rotate 90 degrees and pierce cartridge end seal 339 without c~using leakage therefrom.
The above described em~odi~ent of the wet/wet cartridge syrin~e operates as described below.
Piston 45 is propelled towards end cap 3 by the application of force to plunger shaft head ~9 in the direction of end cap 3 which force is communicated through plunger shaft ~7 to pi~ton 5 thus ~pply~ng hydraulic pressure through solvent charge 351 disk assembly valve rotor 378 ~and stator 377 th~s forcing cartr~dg- 31 and needl~ a~-mbly hou-lng ~8 havlng in~ection needle 323 fixedly attached therethrough towards end cap 3 simultaneously forcing cartridge 31 onto sharpened tip 3B8 of rectangular spiral pushrod 382 which slides freely through needle assembly housing aperture 320 thus also propelling injection needle 323 to puncture end cap 3 and thin wall 375. When the tip 388 .'`~iJ~ tJ r~ l'c~-r U V~"
~v093/0272c ~ 1 4 S 5 6 PCT/US92/~n of rectangular spiral pushrod 3~2 pas~es through rectangular slot 380 so that driven spiral di~k 3~1 turns as it follows the spir~l curve of spiral tip 388. Rigid rods 379 c~use circular disk assembly valve rotor 37~ to rotate 90 degrees, thus opening the disk assembly valve.
This is illustrated in Figure 3(b) and 3(c). It is clearly seen that the disk assembly valve opens as soon as spiral tip enters into slot 380 at the beginning of the injection cycle, allowing solution charge 363 ~nd solvent charge 351 time to mix before internal injection needle tip 25 punctures puncturable cartridge end stopper -339. End stopper339 is punctured néar the end of the injection cycle. See Figure 3(c). The remainder of rectangular spiral pushrod 382 is linear &o that no furtber rotation of valve rotor 378 occurs fixing the valve in an open position.
Figure 4(a) shows a detailed view of one embodiment of tbe invention providing a stopcock as a temporary barrier between chambers of the cartridge. The stopcock is provided with an operating cam which is actuated by a pushrod~ disposed between th- extern~l surface of the cartridge and the internal surface of the cartridge housing. This embodiment is also provided with independently actuated ~ ~ns ~or ~utomatically gitating 2S tb- ~lxlng olvent ~nd ~olut- c~rge~ during th-in~ection cycle of the invention.
With reference to ~igure 4(a), cylindrical cartridge housing 1 i5 prov~ded w~th a base shelf ~7~ t~at is integral with cylindrical cartridge bousing 1 into which is imbedded a rigid rectangular spiral pushrod ~82 formed from flat stainless steel and is disposed coaxially to cylindrical c~rtridge 1. Spiral pushrod ~82 is provided with a sharpened spiral pushrod tip 490. An injection needle ~23 is offset in a needle assembIy housing ~18 to operate without interference from rectangular spiral pushrod ~82. Needle asse~bly housing 418 is slidable in cartridge housing 1 and is provided with injection needle SUBS~I~UTE SHEET
~PEAIUS

211~55~ ROllJS O ~8~ 92 ~23 fixedly attached therethrough and having needle intQrnal end ~2~.
As in the embodimQnt~ ~hown in Figure~ 1, 2, 3, 4, and 7, c~rtridge hou~ing 1 i~ provided with needle a~s~mbly hou~ing re~idence chambQr 11 of appropriate dimenslon to per~it the expansion o~ neQdle a~fiembly hou~ing ~lange~ 19 when needle assembly hou~ing ~1-re~ides wholly within chaib~r ~1. Cylindrical cartridge 3~ i~ slidably po~ltion~d within cartridge housing 1.
A ~irst cartridge solvent re~ervoir portion ~33 i-~eparated fro~ cartridgQ solut~ portion ~35 by a stopcock a~ bly v~lve ~20 Stopco~k asserbly valvo ~20 i8 ~ade of ~atorial~ known in tho ~odical art- and can be of ~any difforQnt configuration- uch a~ thoso wherQin tho apQrturQ of tho valve is of an ~ppropriate diameter to por~it thQ cartridg~ p$~ton to p~ oalably thorethrough -Additional e~bod$~ent~ of tho ~topcock as~bly valvo of th- pr~ont lnvention aro mor~ fully lucidat~d in th- do~cr$ption of Figur- 5 bolow With r ~p~ct to Figur ~(a), a valv~ op~rating pu~hrod ~0 i~ ~hown ~ix~dly att~ched to b~se shQlf ~7 - ~nd i~ ~r ly di~po- d through an ap rture (not ~hown) in no dl~ bly hou~lng ~- for op ning ~topcock ~20 by pu hlng on ~topcock rot~tor ~ and i~ out~ide c ~ idg~
2S ~31 l-aving r ctangular p~ral pu~hrod ~ free to cau8-tub ~1 to continually rotat- and i~ ~or- fully ~hown in Figur~ ~(b) - ~(d) Fitt-d into th~ low r ~nd ot a tub~
~1 (al~o hown a~ dri~ n ~p~ral di~k ~
Driv n pir~l di~ 1 ha~ an oval ~lot of a di~n~ion ~o that th~ r-ctangular plral pu-hro~ --2 will cau~- driv n ~piral dl~k -1 to rotat- a- it ~ollow~ th ~piral patt n Riqidly attach~d to tub~ ~r agltatlng rotor blad~ 7 th- low~r on o~ which rQst~ on a ilicon- ring ~ which act~ a~ a b arlng for th~
~tructur- A ~Q~ annular fra~ hangs ov~r a tube top c~p ~5 that i- C108Qd and allow~ no sol~nt to ~nt~r tub~ Th- ~piral patt~rn on ~piral pu~hrod ~2 1~ of SUBSTITUTE SHEET

w093/02720 ~ S~ ~ PCT/US92/06587 ~ length to cause driven 6piral disk ~81 to rotate during the entire downward cycle of thQ ~yrlnge.
The above described embodiment of the two-component ~yringe of the invention operates as described hereinbelow.
Pi~ton ~S i~ propelled towards end cap 3 by the' ppllcatlon o~ ~oro- to plung-r ~h~t h-ad 4~ ln th~
dlrectlon o~ end cap ~, wh~ch forc- 1~ communic~ted through plunger 6ha~t ~7 to pl~ton 45 thus applying hydraulic pressure tbrough solvent charge Sl stopcock assembly valve ~20 and forcing cartridge 31 and needle assembly housing ~17 bavinq injection needle ~23 fixedly attached therethrough towards end cap 3 and simultaneously forcing cartridge 3~ onto rectangular lS spiral pushrod ~82 which sl~des freely through needle assembly housing aperturc (not shown), thus also propelling injection needle 423 to puncture end cap 3 and thin wall ~75. When the tip ~0 of rectangular spiral pushrod ~82 passes through oval Qlot ~80, driven spiral disk ~81 turns as it follows the spiral curve of the pushrod tip 490. Driven spiral disk 481 being rigidly attached to tube 491, will cause tube 4~1 to rotate continually, thus providing agitation to the mixing ~olvent and solute.
This is ~ost clearly ~een in Figure 4(b) and 4(c).
Figure 5~a) - (e) illustrate an embodiment of the invention differing from the previously described embodiments by the provision of an elution maze for the solute and a stopcock di~posed through the cartridge component of ,the invention and which is actuated by a set of ridges and grooves ,disposed within the cartridge hou~ing. In a variation thereof, the stopcock can be configured to allow sealable passage t~erethrough.
Figures 5(a), (b), (c), (d), and (e) show a two-component cartridge syringe of the present invention utilizing a two-chambered medicament cartridge slidable within a cartridge housing baving an injection needle fixedly attached to the cartridge housing and an SU~S~ E ;.~

~v ~ v~ v ~ u ~
W093/02720 2 1 1 4 5 ~ ~ PCT/US92/06~7 actuating ridge and groove integral with the cartridge housing for operating a 6topcock and guiding and positioning the cartridge.
With reference to Figures S(a), (b), (c), (d)-, and (e), a two-component cartridge syringe comprises a double ended substantially cylindricaI cartridge housing 501 having an injection end and a cartridge operating end constructed of a rigid material suitable for injection molding such as linear polypropylene or polystyrene, and having a cartridqe residence chamber S15 formed therein for slidably housing a two-chambered cartridge S31 and also having guide channel S12 and a channel ridge S10 positioned therein for operating and guiding a valve operating cam 58~ and for engaging and rotating a cam protrusion 599 and valve rotor 583. The i.njection end of cyl~ndrical cartridge housing S01 wall S16 is significantly thinned in order to allow the injection tip and shaft of hollow injection needle 523 to puncture an end w~ll 51~ t~ereof w~en cartridge ~ driv-n toward puncturable end cap 503 that also functions as a shock absorber when cartridg~ S31 ls driven toward it. End cap S03 is formulated, as is ~nown in the art, o~ a resilient material that will not core out when a needle is embedded in it or when the needle moves therethrough at high speeds and will adsorb e~ficiently an energy shock as might be transmitted by an expanding spring. One materi~l having such properties and known.in the ~rt is chlorobutyl rubb~r. Cylindrlcal o~rtrldg~
constructcd of a rigid~material such as Pyrex glass, ~
slidably position-d wlthin castridg- housln~ 0~ and ha-two chambers in which are provided a solvent charge 5-1 and a solute charge 563. Solvent charge 551 is stored in a first portion 533 of cartridge 53~ and solute charge 551 is stored in ~n elution maze S71 constructed and disposed in a second cartridge portion 535 in such a manner that solvent charge 551 is forced therethroug~
when a stopcock assembly 520 is actuated.
SUBSTITUTE SHEET
IPEAIUS

W~93/02720 ~ PCT/~'S92/~ ~7 First cartridge portion 533 is separated from second portion 53S by 6topcock assembly 520 comprising a cyllndrlc~l rotor housing/seal 58s made of a resilient material such as cast silicone rubber and provided with an apertur~ 59S that prov~des for t~e passage therethrough of solvent charge 5S1 into cartridge ~econd portion S35 after cylindrical rotor hous~ng/seal S~5 is rotated by the relative movement of cartr~dge housing 501 with respect to cartridge 531 and the interaction of cam 522 with guide channel 512 and channel ridge 510.
Cylindrical rotor housing/seal 585 and a valve rotor 583 ~re ~e~lably fitted through valve rotor Beats S2 disposed in the walls of c~rtridge 531. Rotor seats S2~
and valve rotor S83 are preferably injection molded from a general purpose lubricating nylon polymer such as Zytel lOlL.
Aperture 595 of cylindrical rotor bousing/seal 585 causes the stopcock assembly to act as a valve. This can best be seen in Figure 5(a). To the front end of cylindrical rotor cylinder 583 is attached a concentric v~ve ~cam ~ ~ with a protruding hemisphere S99 which will cause the cylindrical rotor cylinder 5~3 to rotate 90 deqrees when the cartridqe S31 slides down the circular cylindrical cartridge ~ousing past the channel ridge 510 and channel 512. This 90 deqree rotation aligns the rotor aperture 595 with the cylinder bore allowing passaqe o~ solvent charqe 551 into cylinder second portion 535. Second cartridge solute storaqe portion 535 has stored therein solute charge 563 in finely divided form on column trays 592 individually injection molded and seal~bly stacked to the. desirDd height so that solvent charge SS~ travels throuqh one tray to the next before being expelled throuqh hollow injection needle 523. Injection needle 523 made rom hollow stainless steel tubing has an external tip 527 which does not protrude through sealing end cap 503.

3Ti ~ U ~ E S~
~th!U;-~u r~,u r~ u I ~ U~
W093/02720 211~ PCT/US92~065&7 The above described embodiment of the wet/dry, wet/wet syringe operated as d~scribed herein below.
Piston 5~5 is propelled towards 6e~1able end cap S03 by the application of force to plunger ~haft head 5~9 ~n th- direct~on o~ nd cap 503, wh~ch force i- co~unicated through plunger ~haft 5~7 to plston 5~, thus applylng hydraulic pressure through 601vent charge S51 and stopcock assembly valve S20 and forcing cartridge 531 together with permanently attached needle assembly 593 towards end cap 503 causing cartridge S31 to ~l-ide down cartridge housing S01. As the hemispheric portion 59g of valve ooerat~
/cam 5B~ whrch is perpsndicular to channel ridge S10, slides down guide channel S12 its radius end S06 engages the 45 degree incline 508 at the top of channel ridge t ti va~ve o ~ ~t~n~ rotate ~his action is best seen in Figure 5~a).
The~cam~X5~8~ ~s attached to valve rotor 503 whose aperture 59S is in the horizonta~ (close~) attitude when ~a ve operatlng the hemispheric portion 599 of /cam S84 is in îts horizontal (closed) attitude.
va ve operatinq valve operating As the cam S8~ sIidès down guide channel S12 the/cam 58~ rotates 90 degrees causing slot S9S to assume a vertical (open) attitude (this action can best be seen in Figure 5(b) thus lining up with the cartridge bore.
Continued movement by piston 5~5 toward end cap 503 -propels needle S23 though puncturable cartridge end cap 503 and puncturable thin wall SlC into taxget tissue.
The force needed to in~ect the needle into target tissue is in the order of 6 oz., while the bac~pressure needed to force the ~olvent charge 55~ through thè tray column is in the order of pounds. Therefore the open stopcock assembly value will continue to aIlow the force to be translated through the piston to the cartridge. Once the cartridge 531 is seated in the down position so that needle assembly hoùsing 593 is contacting end cap 503, solvent charge S51 is forced through elution maze 571 thus eluting solute charge 563 therefrom and the mixed 8~lBsTlTuTEs HE~T

W~93/027~ ~ 55~ PCT/US92~06587 , -37-medicament is expelled through hollow injection need~e S23 into t~rget tissu~. After ln~e~tion of the mixed ,~
solvent charge SSl and solute 563 through hollow injection needle S23 into target tissue, tbe direction of S force on piston shaft head ~9 is reversed, thus c~using the withdrawal of the cartridge 531 and injection needle -~
S~3 to reside completely within cartridge housing S01.
Figure 6 shows an embodiment of the present invention differlng ~rom th- oth-r d-~cr~b~d ~bodlm~nt- in th~t the separation barrier and the separation barrier attachment groove is reces~ed past the line of descent of the piston to allow passage thereof through the breached separation barrier and wherein the barrier breaching device is activated by an electromagnet or electronically actuated pin embedded in the wall of the substantially circular cartridge housing. ~-With reference to Figure 6 two-component cartridge syringe comprises a double ended substantially cylindrical cartridge housing 601 having a conically tapered injection end constructed of a rigid material suitable for injection molding such as linear polypropylene or polystyrene. A housing is provided with cartridge residence chamber 615 and a cavity 613 for an electromagnet 618. The lower end of cartridge housinq 601, tip 616, is significantly thinned and made of easily puncturable material in order to allow a needle 623 to puncture a tip 616 when a cartridge 631 descends.
Cartridge housing 601 is provided with a puncturable end cap 603 that,also functions as a shock absorber when the cartridge 631 bottoms out.
Cylindrical cartridge 631, of rigid material such as Boron glass, is slidably positioned within cartridge housing 601 and is provided with a two-portion chamber in which is provided a solvent charge 651 and a solute charge 663. Solvent charge 651 is stored in a first portion 633 of cartridge 631, while solute charge 663 is stored in a second portion 635. A rectangular glass wall SUBST~TUTE SHEET
IPEAIUS

rCUu~ JU~S~
~114~S~ RONS 01 C)CT 1992 portion ~33 o~ cartridge 631, while ~olute charge 33 i~
~tored ln a second portion ~35 a rectangular gla~ wall protru~ion 63~ is provided in cartridge 63~ to allow a ~Qmbran~ s~at ~71 to be r~ce~ed out o~ the lin~ of descent o~ a plston ~5 First portion ~33 i- separated fro~ second portion ~35 by ~e~bran seat ~71, a re~llient circular U ch~nnel cast fro~ ~ilicone rubb r which is rigidly attach~d to attach~ nt on groov~ ~32 of gla~
wall protru~ion ~3~, ither by pr-~ur- genQrated by ovor~izing th- di~et-r of the r~bran~ ~eat wall ~3~
ad~acent to th- attach~ nt groo~ ~32 or an indu~trial adh-siv known in the art into which i~ fitted a puncturabl- ~ bran ~73 uch a- a hydrophobic coat d poly~tyren fil~ of OOS~ which fll~ ha~ th- property of b ing ~hatt-r d when pric~ d Th fil~ i~ locked in by an O ring ~not shown) A p r an nt agn t N ~37 is held in plac- on the gla~ wall of tridge ~3~ by silicone gr~- and which ha- th prop rty, in a thin layer, 005-1 000" o~ acting a~ t Jporary adh~iv Rigidly att~c~d to p~n~nt ~gn t N ~37 i~ a pin ~3- A per~Qable tray ~40 hold~ ~olut- ch~rg -3 N and S a~ u~d in ~agn~t~
ar conv ntion ~or oppo-it- agn tic charg~
Th abov d ~crib~a ~i~ nt o~ th~ ~ixing syring op~rat~ a~ d~crib~d h~r~in b~low Cartriaq ~ pro~ll d toward ~aling ~nd c~p 0 by th a~pllcation o~ ~orc to plunq r sh~t hoad ~ in th dir-ction o~ nd cap ~03 which ~orc~ i~ co~unicat d throuqtl th plwlg~r d~t to pi~ton ~5 thu~ ~pplying hy~ ulic ~r ~ur through ~olv nt ch~ 5~ and ~r~n ~ at ~n ~orcing c~rtridg ~31 and p~anQntly attach~d n~ dl- a~ bly ~3 toward ~nd cap 603 causing cartridg ~3~ to l~d down cartridg hou~ing ~0~ A~
cartridg ~3~ ~ov ~ toward nd cap 03, gla-~ wall protru-ion ~ trlp~ contact witch ~55 which clo~Q~ th~
c$rcuit (not hown) o~ batt~ry ~2 cau ing curr~nt to ~low through ~agn-tic winding~ ~3 c~u~ing elQctro~agn~t ~1~ to b~ ~agnQtic charg~d N and holding ~ir~ly in plac~

SU~STITUTE SHEET

5 i ~ Ro/Uuss902~oc6~92 relativ0 to cartridge housing 601 per~anent magnet S ~37 and attachad pin 638 A~ cartridge 631 continue~ in motion tow~rd end c~p 603 ~8 s~en in Figure 6(b), pin ~3-c~u~e~ burst~bl~ ~embr~n~ ~73 to bur~t ~llowing solut-ch~rge ~5~ to ~nter into ~0cond portion 635 o~ cartridg-63~ Piston ~5 continu0~ to propel c~rtridg~ 631 towards s0alAble 0nd cap 603 propelling needle 6~8 into targ~t tissue Wh~n cartridg~ ~31 i~ ~at0d onto end cap ~03 the ~orce toward 0nd cap ~03 on piston 6~S will cause th0 piston to ~ov~ toward ~nd cap 603 as shown in Figur~
6(c) ~orcing pQr~an~nt ~agnet S to b- ~ove down the inn-r gla~s wall o~ cartridge ~31 Th~ ~ilicon gr-a~- t~at held perman~nt ~agnet S ~37 onto th- gla-~ wall~ o~ cartridg- ~3~ act~ a~ ~ lubricant for pi~ton 6~5 and alJo a- an adhe~iv for m~gnet with a force of about 3 oz Pl~ton ~5 can pas~ the recess0d ~e-bran- ~Q~t ~71 and xp l th- ~olvated solut~ charg through hollow n~ dl- ~1~ into targ~t ti~su~
Th- ~bcdi~ent o~ th invention shown in ~igure 7 illu~trat~ a variation o~ that ~hown ln Figure 1 but having a ~odl~i~d in~-ctlon nesdl- whlch al~o functlon~
a~ a pu hrod to ~ur-t a bur-tabl~ b~rrier separating th two cartridg portion With r-~ r nc to Figuro 7 cylindrical cartridgo 31 o~ rigid ~at rial ~uch a- w~ter gla~ lidably po~itlon d ~ithin cartridg~ hou~ing ~ and i~ providQd with a thr -portion chaib~r in which i~ storod a solvont ch~rg 7~1 ~nd a olut charg 76~ A cartridg solv nt portlon h~ving ~olv~nt 7~1 th~r-in i~ ~parat~d ~ro~ tho cartridg- portion baving ~olute 7~ thoroin by a bur~tabl~ br~n~ 761 A- in th~ e~bodi~ent shown in Figur~ 2, bur~t~ble ~bran 761 i~ s~at~d in c~rtridg~
31 by a ~e~bran~ seat ~ad- fro~ vulcaniz~d rubber which i~ rigidly attached and -al d to th~ int~rnal walls o~
c~rtridge ~ ith r by pr-~-ur~ generat d by oversizing th~ di~eter of the wall ~d~acent to the cartridge wall or ~n indu~trial adh~iv ~nown to the art SU~STITUTE SHEET ~

u~ v ~
2 1 1 1 S S ~ ROll)S 0 1 OCT 1992 Ths solutQ ~torage portion o~ cartridge 31 i~
provlded with a bead colu~n of lon exchange re-ln~
similar to that shown in Figure 2 whlch ar~ saturated with th~ appropriatQ solute charge to be ~luted by S solvQnt cbarg- 7~1 Needl~ a~Qmbly bou~ing 17 i8 provided with a bollow pu~hrod/in~ection n~edl- 723 rigidly attachQd ther-through Hollow pu-hrod in~-ction n-~dle 723 i~
provided with a ~b~rpened pu-hrod in~ection needl-internal end 725 having no ap-rtur- Hollow pu~hrod in~ection n~edl- 723 i- al80 provided with a pushrod in~ection ne-dl- ap rtur- ~7~ po ition d in relation to ne-dl- a~-~bbly hou~ing 17 ~uch that pu-hrod in~ection needle ap tur- 77~ i~ not ~xpos~d to th- ~ixQd solvent 75~/~olut- 7-3 ~ixtur~ until puncturabl- cartridge end ~topp r 3~ i~ eated again t th- botto~ of nQedl-a~s-~bly hou~ing 17 during the in~ection stroke of the dsvic-T~ op ration o~ th devic hown ln Figur- 7 i-~ lar to that hown ~n th other bodi~ent~, c~rtridge31 b~ing i~p~ll d by pr --ur provid d through piJton ha~t h ad ~ ~orcing cartrldg 3~ toward puncturabl-cartridg hou~ing ~ aling na cap 3 Suc~ prQs~ure i-~uf~ici nt to br-~k br akabl- cartridg po~itloning tab 771 allowing cartridg ~ to proc-ea toward puncturabl-cartridg hou ing ~ allng ~nd cap ~ Continu d downward pr Jur on pi~ton h ad ha~t ~ cau~-~ pushrod in~ection n ~dl- int rn~l nd which ha~ no ap rtur- to punctur-- puncturabl- cartridg nd ~topp~r ~ b~ad colu~n 772 and bur~tabl- ~ bran 7~1 A- in th oth-r ~bodi~nt!
disclosQd, th br~aching o~ th barri~r b~tween th ~olv nt and ~olut- o~ cartridg 3~ p~r~it~ th- ~oining tho-- two chaib~r- and the ~ixing o~ the solut- and ~olvent Th po~ition o~ pudhrod in~Qction neQdl-ap~rtur- 773 p~r it~ acces~ o~ th ~ixed ~dica~nt only a~t~r third cartridg portion ~7 i~ co~plet~ly captur d and needle a~e-bly hou~ing 17 wlth third cartridg SUBSmUTE SHEET

2114~5~ Roius O 1 OCT ~992 ~:

portion 37 i8 fully within needlo as~e~bly rQceivinq cha~ber 11 With reference to Figure 8, v~rious view~ ot the needle hou~ing of th~ pre~nt invent$on ~re shown Figure 8(a) shows a perspectivQ view of the needle a~e~bly hou~ing 17 show~ng needl~ as~e~bly hou~ing botto~ 1~ needle as~embly hou~ing flange~ 19 and n~edle a~so~bly hou~ing flange lip~ 2~ In~oction noedl~
apertur- S22 which i- configur~d ~or ths rigid attachm~nt therethrough or an in~ection ne~dl~ o ~hown Figure 8(b) i~ a plane view of the housing of Figuro 8(b) showing hou~ing botto~ 1~ hou~ing flanges ~9 and hou~ing flang~ lip~ 21 a~ wsll as in~ection needle apQrturs 22 Figurs 8(c) show a ~cttonal ViQW through ~ection A-A of Figur- 8(b) ~howing hou~ing botto~ 1~ housing flange~ 1~ and hou~ing flang lip~ 21 In ~ddition, an in~ction ne dle ap~rtur- ~22 1~ ~hown dispo~ed through hou-ing botto~
Flgur 8(d) 1~ a d tail d cro~ octional view o~ a portion o~ Flgur 8(c) howing in~-ctlon needl~ ap~rtur-~22 in ne~dl- a~ bly hou~ing botto~ 1-A- can b- ~- n with r f r nc- to Figure~ 8(a), (b), 2S ~c), and (d), nd ~lth ro~ r nk to Figur-~ 2, 3, ~, and 7, n dl- a~- bly hou-ing 17 havlng an in~octlon nQedl-riqidly affixod th r through op rat~ in r~lation to a n ck d ~ dic~a nt contain r ~or p cifically, when the n ck d nd of ~ ~ dlc~ nnt contain r 1~ pr~ed into contact with th curv d abut~ nt~ ot flang-~ 1~ o~ ne~dl-a~ bly hou~ing 17, th flango~ 1~ Qxpand to receive the nd of th n ck d ~ dica~ nt contaln r and contr~ct to ~-curely captur- th contaln r wh n flang llp- 21 ar-xpo~od to th narrowing rec~ or~ing th n ck o~ tho neck d ~ dlca~ent contain r as hown in Flgure~ 8(a)-8(d), n odle a~ bly housing botto~ 18 h~ in~ection ne~dlo ~perture ~22 therothroug~ for recoipt of ~n SUBSTITUTE SHEEl R~gO 1~0cbTsl~92 in~ection neQdlQ Such a n~edle can b- ~olded th~rein, thrQad~d th~rQthrough, or ~nap fit th~rQthrough or affixed in any other ~ann~r known in th- art Although a pa~-through valv~ having a b~rrel-~h~pod rotor ~ay b~ adaptabl- ~or c-rtain u~, a ball val~
h~ving a sub~tanti~lly ~ph~ric~l rotor and ~eat ther~for i~ anoth~r pref-rr-d bodi~ nt of th- temporary br~achabl- b~rrier o~ th in~Qntion Th- ball valvQ
rotor i~ provid~d with a cylindrical apertur~
th~rethrough of appropriat- di~ n~ion ~o that, when the val~ rotor i- rotat d to align th rotor apertur- with th- bor- of th c~rtridg- cylind, th cartrldg~ pi-ton can pa~- -alably th r~through Thi~ can b ~ccompli~h d by pro~iding the val~ rotor with a cylindrical bor~
~ub tanti~lly id ntical to th cartridg bor~ through which tho pi-ton uov Alt rnativ~ly, by providing a c~rtridgo pi~ton of ~ tically d-for~abl- n~t~rial such a~ ~ilicon pla-ti¢ or rubb r- which can co~pr 8~ or ~xpand to pa~- -alably through th~ v~lv~ rotor, th~ ~
contont of th cartridg can b~ ~ora co~pl~t~ly xp~ll d Th b~ll valv ~ at i~ pr~f rably int~gral to tho cartridg wall- an~ r c ~od -al~bly th~r in ~ufficl ntly far to p~r~it th- cartridge pi~ton to pas~
~alably th r througb Figur-~ g(a), (b), ~c), and (d) illu~trat an addition~ bodi nt of th inv ntion wb r~in th~ a an~
for ~ p~ratlng th two cb~ b r of th ¢artridg i~ a ball ~lv op rat-d in ~NCh tb ~aa- ~ann r a- th ~to~cock b~wn in Figur S A k~y a-p-ct of thi-~bodi~nt of th inv ntion i~ th pa ~tbrough f-atur- of the valv~ which p r~it- th cartridg piston to pa~
s~ bly tb r~through, thu- v~cu~ting th~ c~rtridg~ ~or co pl~t~ly ~itb r f r nc~ to Figur - 9(a), ~b), ~c) and (d), 3S a cartridg hou~ing ~0~ ha a c~rtridg- ~ lidably di~po~-d tb r-in A ¢artridg hou~ing ~0~ also ha~ a n~dl- a~ bly hou~ing ~2~ ~lidably dispos~d ther~in SIJBSTITUTE SHEET - ;

t~uS92~06s8 7 ,5 ~ RO/US O 1 OCT 1992 between a cartridg~ 98~ and a puncturabl- cartridg~
housing se~ling Qnd cap 937 A cartridg~ 9~1 co~pris~
a gla~s cylindrical top ~ Qnt 9~9 having a first cartridgQ solv nt r-s~rvoir portion ~07 th~r~in and also S having a pi~ton ~05 d idably ~-ated th~r~in A cartridge urthor provid d witb a ball valv ca-t hou~ing ~11 having a ub~tantlally ~pherlcal ball valv~ ~3 s~at~d ther~in. A ball valv ~13 al~o has a cylindrical chann~l 15 of a dia~t~r great-r than the bor~ of a cartridg A cartrld~ furthQr provid~d with a gla~
~le~ nt ~25 which i~ attach~d to th in~ction ~nd of ball valv cast hou~ing 11. A gla~ ~lQ~ent 25 co~pri~ a cartridg- n ck ~27 and a puncturabl~
cartridg- ~nd stopp r n ~ A ball valv~ ~13 i~ furthQr provid d, through ~haft ~17, with an op~rating ca~ ~19 di~po~ d to rotatably ngag a guid~ ridg~ ~23 having ~n inclin~d plan ~21 and a guid chann l ~ di~po~ed th~r-in for guiding and op-rating a c~rtridg- ~81 and a ball valv ~1~, r ~p ctiv ly Th op ration of tho -bodi~ nt of th~ pr~s~nt inv ntion bown in Figur ~ 9~a), (b), (c) ~nd (d) i- v ry i ilar to th oP ration of th ~bodin nt of th inv ntion hown in ~igur ~ S(a), (b), (¢), (d) and (-) ~or -~¢lfically, for¢ tran ~itt-d through a pi~ton dh~t h ad ~01, a pi~ton ~haft ~03, a rubb r pi~ton ~05 ~n~ a ~olv nt charg ~0~ forc-~ a cartsidg ~-1 toward a puncturabl- cartridg~ hou-ing aling ~nd ¢~p ~7 Th v n nt o~ a ¢artridg~ ~1 causQ~ a rotatabl- ¢a~
~l~D nt ~1~ to ngag an in¢lin~d plan ~2~ of a guid ridg ~23, thu- cau~ing a 90 d gr - rotatlon of a rotatabl- caa 1 _ nt ~1~ and of a ball valv ~13 whlch i~ fix dly attach d th~r~to, and cau-ing th aligna nt of cylindrical ap rtur ~15 with th bor- of a f~r~t cartridg- ~olv nt r---rvoir portion ~07 and with a bor-o~ ~¢ond ¢~rtrldg~ ~olut~ portion ~7~ to 8uch ~n Qxtent that a rubb~r pi~ton ~05 can pas~ ~alably through a ball SUBSTITUTE SHEET

2114 5 5 6 RO/US oi OCT i992 valve 913 forcing a solvQnt charge 906 into a second cartridg~ ~olut~ portion 97~ and through a solute grid 9~ having a medically activ~ ~ubstanc~ dispos~d th~r~in The medically activ~ substanc~ i~ elut~d by ~olvent s charge 906 as it pa~se~ through a solute grid ~8S
recessed into the neck portion of a cartridge ~81 to permit a pi~ton ~05 to almost completely evacuat~ -~
cartridge ~81 Si~ultaneou~ly with th- downward ~ovement of a cartridg~ 9~1 is the ~ove~ent of a needle a~embly hou~ing 929 into a needl- a~sQmbly housing expan~ion charber 933 ~llowing the oxpan~ion of the needl- a~e~bly housing flange~ g2~ and the capture of a cartridge neck 927 by a ne~dle a~e~bly hou~ing ~2~ and the puncturing of puncturablQ cartrldg- end ~topp~r n - by an ln~ectlon needle internal end ~31 Continued pres~ure on a rubbQr pi~ton ~OS cauJeJ the compl~te xpul~ion of a solvent charg- ~0~ ~nd the lutod ~olute contained therein Reversing the direction of force placed on a rubber pi~ton ~05 cause~ retraction o~ a cartridge ~81 and an irr-v~r~ibly captured needle hou~ing a~e~bly i29 80 that a cartridge ~ ne-dle hou~ing a~-~bly 92~, ~nd an in~ection needle ~-~ re~ido wholly within a cartridg~
~0~. :

SUBSTI~UTE SHEET

WO 93/02720 2 1 1 ~ 5 ~ ~ PCr/US92/06587 --45-- .

able 1 .
~.,. .,,.",~ ~ ~

, ,~....... , .-~ ... , . Wo~ ~_I T~ N~o ,,',.. ,~.~"',.' .
S , . ~ ~ ~ ~ ~ ~ d ~ . c . ~ ~ d _ .~ ,.. ;
~ ~ ~ ~ ~ ~ ~ d ''''`.~ ,"'........ ,.',' to~ P~t '`., .. ,'. ,'... ,.... ' .'': .:": ~ ' ~1 ~rod Dou~us~ ~ ~llc~
',,-...' . ,j.,'. ,',~ .. -.. ,: ' :..,'..''...
. . s-.- :.S~ :S : ~ ~d ..... . , .. : .
... :.'';.'''".. ".. "''.
.,",,.,,,..~ . _ ~' ~_ ~

s,':, ;S.':::''-::' .. ...s..
,... : . :.. :., .: :~: -.. :
~ sS.~s~ jS jSS ~ s Ibnl~k ~ lltd_ ~p_cd ~v . .. ,?: ~ _ _ :,SS~ .s:jSjS..: S :, ". ,~ :' SS .
.~ .,, . - . . s ~s ~ .. ~ _~ ~ ~ ;- ~0 ~_ d .*,.' . .~ ~ , ~ , ~ . . . ~ . . .~

:.
Table 1 lists some major characteristics of the eight embodiments of the cartridge shown in Figures 1-7 and 9. ::
.. . . .
The listed combinations of elements are illustrative only and are intended to demonstrate some of the permutations of the invention. For example, although not shown in the ; drawings or table, it is obvious from the description herein that a passthrough stopcock can be ~ubstituted for the stopcock in Embodiment No. 5. Similarly, an elution maze can be substituted for the bead columns of Embodiment Nos. 7 or 2.
Thus, with reference to Figures 1-9, it can be clearly seen that by performing only the simple operation of applying downward pressure on the operating piston of any of the various embodiments of the present invention, that joining of the solvent and solute chambers, mixing of the two medicament components, and the injection of W093/02720 2 1 1 4 5 ~ ~ PCT/U$92/~ ~7 the medically active substance is achieved. It can a~80 be clearly seen that the simple operation of reversing the direction of force on the operating piston, that the injection needle is both withdrawn from the injection site and withdrawn to reside wholly within the cartridge housing of the invention.
Thus the present invention provides a series of embodiments wherein the relative motion of a prepackaged cartridge containing at least one medicall~ active substance and a housing for the cartridge triggers the breaching of a barrier between a cartridge chamber having the medically active substance therein and another cartridge chamber containing a physiologically acceptable solvent or diluent.
Preferred methods of using the two-component syringes of the types described above are both with an adaptor for manual use and with an automatic injection/aspiration device of the type described herein. Another preferred method is to provide a plunger handle in place of the piston operating shaft of any of the described syringe embodiment~. Thus, the syringes can be used manually without need for other actuating ~ower.
With reference to the resilient materials disclosed herein, such materials are those standard in the medical and den*al packaginq and hypodermic syringe art such as rubber, plastics,-and other synthetic and non-synthetic materials known in the art for use in fulfilling similar - and related objectives. It is also clear that all of the embodiments of the invention disclosed herein are adapted to- be manufactured by standard medical and dental container and device manufacturing equipment.
Also, the cartridges of the present invention are adapted to contain standard amounts of solvent and appropriate amounts of solute for standard dosages of the particular medically active substance to be administered.
"Cylindrical" means having a shape or cavity described by a line which always has a point in common wo g3/02,20 2 1 1 ~ ~ 5 6 PCT~US92/06~7 with a given closed curve, and which line moves so that it is always parallel with a given line not in the plane of the closed curve. Thus, a right circular cylinder i8 one having two equal parallel circular bases and a perpendicular axis, and a right elliptical cylinder ls one having two equal parallel elliptical bases and a perpendicular axis. In the context of the invention, it can be seen that the relationship between the various cartridge embodiments and their corresponding cartridge housings is that of a piston fitted to a cylinder. That is, the cartridge housing bore (cylinder) acts as both container and guide for the cartridge (piston) as the device operates. With respect to the various pistons of the cartridges, each operates much the same as a standard '' syringe plunger known in the art. ~'-By "substantially cylindrical" it is meant that the housing and corresponding cartridge and needle housing :
assembly of a particular embodiment of the invention are of appropriate relative configuration, though not precisely cylinder~, that -the relative movement of the various components approximates the action of a piston or -pistons within a cylinder. -' - - By "sealably~ with rQgard to piston movement through a breachable~ temporary barrier means is meant sealQd sufficiently while moving through the breachablQ barrier that fluid is driven therethrough by the piston.'-The advantages and~ characteristics of the injection/aspiration device and cartridge vial for the storage and injection of single-component medicaments of the present invention -can be elucidated from the following detailed description of a preferred embodiment of the injection/aspiration device and cartridge vial, to be taken as exnmples and not as limitations in conjunction with the accompanying drawings.
The injection/aspiration device, illustrated in Figure 10, comprises: a housing 1201 for disposition of the various components ~having a chamber 1219 for 2 1 ~ 5 ~
W~93/02720 PCT/US92/~587 reversibly receiving a cartridge vial of a type as described below and in Figures 11 and 12, a d.c. motor 1203, a lead screw 1205, a linear bearing 1207 for holding a lead nut, a lead nut 1213 surrounding the lead screw, and armed/safety injector ~witch 1209, indicating light emitting diodes 1211, a plunger 1215 attached to lead screw 1205, a cartridge vial 1217 disposed within chamber 1219, an electronic control unit 1221, an injector trigger button 1223, a d.c. power source 1225, an on/off switch 1227, a cartridge/ampule position locking solenoid 1229 having cartridge/ampule position locking solenoid shaft 1231, aspirated fluid sensor 1233, and plunger shaft rate/position/direction sensor 1235.
The injection/aspiration device of the invention operates in conjunction with cartridge vials as described hereinbelow. All of the components of the device are energized by d.c. power source 1225 through the operation of switch 1227. D.c. motor 1203 propels lead screw 1205 which is attached to lead nut 1213 and plunger shaft 1215 which is reversibly attached to cartridge vial shaft end 1216 by means-of a mechanical keyway provided at the end of plunger shaft 121S. Linear bearing 1207 is provided for smooth ope~ation of lead screw 1205 and plunger shaft ~215. Lead screw nut 1213 is provided as an attachment means for connecting lead screw 1205 to plunger shaft 1215.- Electronic control unit 1221 is a programmable electronic processor connected by means of -wires not shown to DC motor 1203 to control the rate, direction, and extent of movement of lead screw 1205, plunger shaft 1215 and, thereby, the rate, extent of movement, and direction of movement of cartridge vial shaft end 1216.
Cartridge vial shaft end 1216 can be of any type configured to securely but reversibly attach to plunger shaft 1215.
Similarly, as described below, plunger shaft 1215 can be adapted to operate other types of cartridge vials such as those designed to be used with a spear type shaft of W093/02720 ~ PCT/US92/o6587 a type known in the dental cartridge field. The electronic control unit 1221 is programmed by means of a programmable read-only memory (PRO~), and a programmable array logic (PAL) which, depending on the application of the device, can be interchanged to adapt the device to the age or sex of the patient, the location paramet~..rs of the injection, (such as intramuscular, subcutane~us or intravenous) for the rate of needle withdrawal and insertion, and for the rate of medicinal- charge injection. The electronic control unit ~. 30 comprises electronic timers which control the o~era~l timing and specific rates during the injection process. A set of programmed instructions are stored in a replaceable and interchangeable memory chip (not shown) in electronic control unit 1221. By either interchanging memory chips or by reprogramming programmab~e memory chips, the various functions of the injection/aspiration device can be controllably varied. Cartridge/ampule position locking mechanism 1229 is a solenoid which can be activated to lock a cartridge vial in a particular position by means - : of cartridge/ampule position locking solenoid shaft 1231 80 that blood or other fluids can be aspirated. Although -a solenoid and.solenoid shaft are described herein as a locking mechanism,.it can be clearly seen that many other 25 . means for accomplishing the objective of the device to lock any type of cartridge vial in a particular position . in.the injection/aspiration devic~. housing can be used.
-Similarly, although programmable - and/or interchangea~le. memory chips are described examples herein, it can be clearly seen that many other means for - programming the stated functions could be used to accomplish the objectives of the inventionc It is also clear that although a d.c. motor and power - source and electronic components are described herein as means for controlling the various rates of operation of the various components of the invention that other means such as compressed gas and valves could also be used.

21~5~6 W093/02720 PCT/US92/~587 Although not shown in Figure 10, the various electronic and electrical components of the invention are connected electrical circuitry.
It should also be clear that many different means for 5securely connecting to and easily disengaging a cartridge vial to and from plunger shaft 1215 are possible. As an example and not described as a limitation, Figure 12 shows plunger shaft 1047 of an injection/aspiration device having pointed barbed plunger shaft head ~0~9 10similar to pointed shafts known in the dental injection cartridge field which is driven a sufficient distance into piston 10~5 during operation of the invention that a sufficiently secure connection is made to operate piston ~045 in both directions. Disconnection of barbed 15head 10~9 from piston lo~5 is achieved by the retraction of plunger shaft 10~7 and plunger shaft head ~049 a sufficient distance into lead nut ~213 which is of an appropriate internal diameter to accomplish the aisconnection.
20The cartridge vial portion of the invention includes a hollow injection/aspiration needle attached to one piston with its external pointed end initially disposed -within a sealed end cap for sanitary purposes. A second piston- is also provided in the cylindrical bore to 25operate in conjunction with the first piston to impel the injection needle and the inject~on fluid into the subject -`
and then withdraw the injection needle and first piston from the subject through the sealed end cap sufficiently so that the-point of the needle need not be exposed to 30the atmosphere before, during, or after operation of the invention. The present invention provides a means for withdrawing the needle tip into a disposable cartridge immediately after the injection and before the injector device is withdrawn from contact with the subject. This 35reduces the risk of unintentional exposure to a used needle tip by both users and non-users because the needle tip need never be exposed.

Wos3/02720 2 1 1 ~ 5 S 6 PCT/USg2/06587 The programmable automatic injector portion of the invention includes a chamber for insertion of a vial, a piston operating plunger for operation of the vial! and a power source for operating the plunger. The injector 5also includes a controller invention can be used to aspirate blood or other fluids.

Cartridge Vial Embodiments:

The advantages and characteristics of the cartridge vial and injection/aspiration device according to the 10present invention can be elucidated from the following detailed description of one embodiment of the injection/aspiration device and three embodiments of the cartridge vial, to be taken as examples and not as limitations in conjunction with the accompanying 15drawings.
With reference to Figure 12, a cartridge vial comprises a double-ended circularly cylindrical housing 1001 constructed of rigid material and having a cartridge/ampule position locking solenoid shaft aperture 201053, aspirated ~luid sensor apertures ~0~2 an ampule residence chamber 1015 and. cylindrical needle housing -assembly receiving chamber 1011. Cartridge housing loO1 i~lprovided with a puncturable sealing end cap 1003 of ~resilient material, a plastic needle guide 1005 rigidly 25embedded in the end cap 1003 and having needle guide - ~aperture 1007 formed therein and an injection device - positioning projection 1009. The needle assembly : receiving chamber 1011 is further provided with curved abutments 1013 of appropriate configuration to allow the 30needle assembly housing 1016 to.both enter and withdraw from néedle assembly housing receiving chamber 1011.
Needle assembly housing 10 6 and ampule 1031 are both initially disposed within ampule residence chamber lOlS.
A glass ampule 1031, positioned within the cartridge, is - provided with a three portion chamber in which is stored W093/02~0 2 1 1 4 ~ ~ 6 PCT/USg2/06587 a fluid charge 1051. The first portion 1033 of ampule 1031 freely communicates with ~econd portion 10~5 and third portion ~037. Third portion S037 is provided with a puncturable ampule stopper 1039 of a resilient material. An ampule piston chamber abutment lo~0 forms the transition between first ampule portion 1033 and second ampule portion 1035 and forms a stop for a piston 10~5 during operation of the invention. The external portion of the transition between first ampule portion 101033 and second ampule portion 1035 forms an ampule shoulder lo~1. Ampule 1031 is further provided with flange engaging lips 1043 which are formed by the narrowing transition area between second chamber portion 1035 and third chamber portion 1037.
15Ampule 1031 is further provided with a piston 10~5 of resilient material for reversibly engaging a pointed plunger shaft head 10~9 having a plunger shaft ~0~7 of an injection/aspiration device. Such an ampule could be reversibly engaged to the in~ection/aspiration device by many other means, other than a piston like piston 10~5 as - shown, such as a T-shaft and keyway or any other means providing secure reversible engagement of a cartridge device to an injection/aspiration device.
Needle assembly housing 1016 is provided ;with a needle assembly housing bcttom 1018, needle housing walls 1017, needle assembly housing flanges 1019 and, needle assembly housing lips 1021 disposed for securely engaging ampule 1031. Needle assembly housing 1016 is further provided with a hollow injection needle 1023'which passes therethrough and has an internal tip 1025 disposed toward puncturable ampule stopper 1039 and an external tip 1027 which passes through aperture 1007 of needle guide 1005 but does not protrude through sealing end cap 1003.
Needle assembly housing walls 1017 are o~ sufficient length so that, in operation of the cartridge as described hereinbelow, third ampule portion 1037 is captured by the engagement of needle assembly housing Wo 93/027~0 _53_ Pcr/US92/o6587 flange lips 1021 by flange engaging step 10~3 of ampule 1~31 before needle internal end 1025 contacts puncturable a~pule end stopper 1039 and when ampule 1031 has been propelled a sufficient distance toward puncturable Scartridge sealing end cap 1003 that needle assembly housing 1016 is fully within needle assembly housing receiving chamber loll.
Although a bar code indicator is seen as an efficient means for labeling both the cartridge vial and 10injector/aspirator components of the invention, any other means or multiple means could be employed to label the invention for machine readable purposes and for human readable purposes. For instance, both components of the invention could be labeled concurrently with readable 15magnetic strips, braille bumps and alphanumeric symbols.
The above-described embodiment of the ampule type cartridge vial of the invention operates as described hereinbelow.
Piston 10~5 is propelled toward sealable end cap 1003 20by the application of force to plunger shaft 10~7 which force i8 communicated through plunger shaft head 1049 to piston 10~5 thus applying hydraulic pressure through fluid charge 1051 and forcing ampule 103~ onto needle assembly 1016. Continued pressure on plunger shaft head 2510~7 is communicated through needle housing flanges 1019 needle housing walls 1017 and needle housing bottom 1016 to needle 1023, thus propelling needle 1023 through needle guide aperture 1007 causing external needle tip 1027 to puncture puncturable end cap 1003. Continued 30force toward puncturable cartridge sealing end cap 1003 by piston 10~5 continues to propel needle 1023 outward until needle housing 1016 is stopped by sealable end cap 1003, thus positioning needle assembly housing 1016 within needle assembly receiving chamber loll which is of 35a larger diameter than ampule residence chamber 1015.
The positioning of needle assembly 1016 within the needle assembly receiving chamber allows flanges lolg and walls ~D~BA~72D ~114SS~ PCT/~S92/06587 1~17 of needle assembly 1016 to expand to irreversibly and securely receive and capture the third portion 1037 of ampule 1031. Continued pressure in the same direction ca~ses puncturable ampule stopper 1039 on ampule 1031 to be driven into internal needle tip 1025 thus puncturing ampule stopper 1039 and causing ampule stopper 1039 to contact needle assembly housing bottom 1018. At this time in the operation of the invention, cartridge/ampule position locking solenoid 1029 (shown in Figure 10 but not shown in Figure 12) is energized causing cartridge/ampule position locking solenoid shaft 1031 (also shown in Figure 11 but not shown in Figure 12) to extend through cartridge/ampule position loc~ing solenoid aperture 1053 thus locking ampule ~031 and needle assembly 1017 tightly against needle guide lOOS.
The direction of force on plunger shaft head 1049 may then be reversed causing a slight withdrawal of piston 10~5 away Srom end cap 1003, thus causing aspiration into fluid 1051 in ampule 1031 of physio-logical fluid~s) if needle tip 1027, now located at a possible injection site in tissue, is in communication with such fluid. An aspirated fluid sensor 1233 and light source, such as a photodiode or photocell 1232 in the injection/aspiration component of the invention (shown in Figure 10 but not in Figure 12), then scan the fluid in ampule 1031 through aspiraeed fluid -nsor Apertures 10~2 to spectrophotometrically - detect the presence of physiological fluid(s). -If no fluids are detected and it i5 regarded as desirable or appropriate that none be aspiratable from an injection site for the drug being administered, or if fluid(s) that are detected do not indicate that the possible injection site, at which needle tip 1027 is located is undesirable or inappropriate, the injection cycle continues and the site at which needle tip 1027 is located, is employed as the injection site. Continued force in the same direction toward end cap 1003 on piston .. . .. . .. . . .

o g3nmno 2 1 1 ~ 5 5 G PCT/US92/06587 -~5-~0~5 causes the expulsion of fluid charge 1051 through needle 1023 into the subject. In operation of the invention, with respect to an automatic injection/aspiration device of the type discussed above, 5the rate of propulsion of piston shaft head 10~9 is varied to control the rate of insertion of needle 1023 and the rate of injection of fluid charge 1051. Also in the operation of the invention, a typical time fos this seguence of inserting hollow in~ection needle 1023 is on 10the order of 100 milliseconds. After the in~ection of fluid charge 1051 the operational sequence is continued into the retraction/needle capture stage by the reversal of force on piston shaft head lo~9 thus causing pressure on piston 10~5 to be directed away from sealing cap 1003.
15The partial vacuum created by the withdrawal of piston 10~5 causes ampule 103~ to retract from needle 1023 a sufficient distance so that internal needle tip 1025 no longer penetrates puncturable ampule end stopper 1039.
The retraction of ampule 1031 from needle tip 1025 i8 20assisted by the biasing force caused by the contact between curved needle assembly housing flanges 1019 and curved àmpule shoulders 10~1. Thus, needle assembly housing flanges 1021 are then engaged to flange engaging ~ `~tep~ 10~3 on ampule 1031. Locking solenoid shaft 1231 : 2S(~hown in Figurè 10 but not in~Figure 12) i~ then withdrawn allowing further retention of the connected ampule/neediè assembly. The ampule and needle assembly, thus irreversibly engaged, is withdrawn as piston 10~5 is withdrawn by continued force in the direction awày from 30puncturable sealing end cap 1003 thus withdrawing needle 1023 from the in~ection site a sufficient distance so that external needle tip 1027 is captured completely within needle assembly receiving chamber 1011. Thus, no part of needle 1023 need. e~er be exposed to any 35environment other than the subject's tissues or the inside of the cartridge ~ial. A typical time for W093/02720 2 1 1 4 5 ~ 5 PCT/US92/06587~
-s6-operation of the withdrawal/needle capture sequence is on the order of 200 milliseconds.
During operation of the invention, if an undesirable or inappropriate physiological fluid (e.g. blood) or lack of physiological fluid (e.g., lack of blood if an intravenous injection is intended) is detected by aspirated fluid sensor 1033, the injection sequence may be automatically stopped, thus preventing the injection of medicine or other fluids into an undesi~able or inappropriate injection site.
With reference to Figure 13, an embGdiment of the cartridge vial of the present invention intended for injections where no aspiration is necessary is illustrated. Cartridge ~01 is provided with slidable ampule 1~31 having piston 14~5 for the receipt of a barbed plunger shaft head known in the dental injection cartridge field and having a ~econd ampule portion 1~35 which is smaller than third ampule portion 1~37 the transition area therebetween forming an engaging surface for engaging flanges 1~19 of needle housing assembly 1~18. Needle assembly housing 1~18 is provided with needle assembly housing walls 1417 of sufficient length that~ when the flanges capture third portion 1~37 of ampule 1~31 needle tip 1~25 has already punctured puncturable ampule end stopper 1~39. It can thus clearly be seen that the retraction of needle assembly housing 1~18 and needle 1~23 are accomplished without permitting the withdrawal of needle tip 1~25 from puncturable end cap 1~39.
The additional advantages and characteristic~ of a non-ampule type embodiment according to the present invention can also be elucidated from the following detailed description of a second embodiment of the cartridge vial component, to be taken as an example and not as a limitation in conjunction with the accompanying drawings.

4 ~ U~ ,7~
W~93/02~ PCT/US92/06587 The cartridge type vial illustrated in Figure 11 comprises: a double-ended circularly cylindrical glass tube 1101 provided with a puncturable sealing end c~p 1103 of resilient materi~l, a rigid plastic needle guide 5 ~lOS riqidly embedded in the puncturable end cap, and first piston ~17 ~lid~bly seated within the bore ~118 of th~ cartrid~. First pi~ton 1117 is provided with ~n operatlng rod eng~gc~ent sh~t ll~9 h~vlng s~t end 1120. The cartridge also comprises ~ second piston 1115 which is ~lso slidably disposed within the bore 1118 of the cartridge. An intern~l end 1111 of hollow injection needle 1107 passing through piston 1115 and is rigidly att~ched thereto by a needle anchoring washer 1113.
Hollow injection needle 1107 also has an external end 1109 which extends through a cylindrical aperture 1104 in needle guide 1105 so that tip llo9 at the external end does not pass through puncturable end cap 1103.
Cylindrical aperture llo~ is of sufficient diameter to allow the expulsion of air from chamber 1125 during operation of the device. Second piston lllS is also rigidly fitted with a ~ta~nless steel engaging barb 1121 which extends toward first piston 1117. Medicinal fluid charge 1123 is disposed between piston 1117 and piston lllS.
The c~rtridge vi~l of the invention operates as described hereinbelow.
- The space in bore lllB between piston 1117 and piston 1115 is filled with ~ charge of fluid medicine 1123 to be injected into ~ subject. Piston 1117 is propelled by means of a rigidly connected piston rod 1119 toward piston 1115 forcing piston 1117 toward piston lllS thus applying hydraulic pressure through fluid charge 1123 to piston 1115 which forces piston 1115 longitudinally through the bore 1118 of the cartridge. This in turn drives hollow injection needle 1107 which is guided by needle guide 1105 through puncturable end cap 1~03.
Continued pressure on piston shaft head 1120 ?

~U n~U r~llr~U I ~ Ul,l 177J
WO 93/02720 2 1 1 4 ~ S ~ PCT/US92/~587 communicated through piston ~haft 1119 drives piston 1115 onto n~ guld- ~05 whl~h top- pl~ton lllS.
CartridgQ/ampule position loc~ng solenoid 1229 (not ~hown ln Figure 11, see Figure 10) is then operatëd to insert solenoid shaft 1231 (not shown in Figure 11, ~ee Fi~u~- 10) thu- loc~ng oylinde~ 1101 a~ain-t ond cap 110~ .
The direction of force on piston plunger 6haft head ~120 may then be reversed to cause a slight wlthdr~wal of p~ston ~7 aw~y ~ro~ nd c~p llO~ thu- ~auslng a~p~ratlon o~ physiologi~ luld(s), lnto ~luld charge 1123, if needle tip 1109, now located at a possible injection site in tissue, is in communication with such fluid. Aspirated fluid sensor 1233 and light source ~5 (photodiode or photocell 1232) (shown in Figure 10 but not in Figure 11) in the injection/aspiration component of the invention (shown in Figure 11 but not in Figure 10) then ~cans the fluid in the bore between piston 1117 and piston 1118 to detect the presence of physiological fluid(s). If no fluids are detected and it is regarded as desirable or appropriate that none be aspiratable at the possible injection ~ite at which needle tip 1109 is located, or if the fluid(s) that are detected do not indicate that the possible injection site is undesirable or inappropriate, the injection cycle continues with the possible site used ~s the actual injection site or in~ection of the ~edicinal charge.
Continued force on piston 1117 througb piston shaft '~9 then causes expulsion of the medicinal fluid charge ~23 through hollow injection needle 1107 and into the subject. Continued force on piston sbaft 1~19 impels piston 1117 to be within a predetermined distance fro~
piston 1115 ~ufficiently onto barb 1121 to irreversibly lock needle 1~07 and piston ~117 to piston ~1 5 as a last portion of medicinal fluid charge 1123 is expelled from the bore. Locking sol,enoid shaft ~231 (not shown in Figure 11, see Figure 10) is then withdrawn allowing SUBSTITUTE SHEET
IPFA/I 1.~:

' ` ' `. . .,' ~'. . '!;: ~
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W093/02720 ~ S S~ PCT/US92/~587 withdrawal of the cartridge. When the direction of the force on piston sha~t 1119 is reversed, piston 1117 withdraws away from end cap 1~03 through th~ cartridge bor- draw~ng pl-ton l~S which h~- be-n lock~d to piston ~117 by means o~ stalnless steel locking barb ~12i away from needle guide 1105 thus withdrawing needle ~07 which is rigidly attached by anchor washer 11 3 to piston lllS.
Continued force in this withdrawal direction on piston 1119 withdraws point 1109 of needle 1107 through 10puncturable end cap 1103 and needle guide 110~ so that needle end 1109 is captured within the cylindrical bore of the cartridge, thus the entirety of needle 1107 is disposed completely within bore 1118 of the cartridge after the injection cycle is completed.
15During operation of this embodiment, if an undesirable or inappropriate physiological fluid (e.g.
blood) or lack of physiological fluid (e.g., lack of blood if an intravenous injection is intended) is detected by aspirated fluid sensor ~233 the injection sequence is autom~tically stopped, thus preventinq the injection of medicine or other fluids into an undesirable or inappropriate injection site.
Although a preferred method of using the cartridge vials or mixing syringes of the type~ described above is with a powered automatic injection/aspiration device also as described above, it can be clearly seen that a manually or mechanically powered injection device, such as one powered with ~pring tension, could be configured to operate such cartridge vials. It is also clear that any of the cartridge vials or mixing syringes described herein can ~e adapted for manual use without need for additional apparatus to actuate the syringe or vial.
For example, by providing an actuator rod functionally similar to that of a conventional syringe plunger in place of operatinq rod engagement shaft 1120, shown in Figure 11, a cartridge or syringe to insert the injection needle into a subject, inject the medicament, B3 1 ~ ?~
I rJ t ' 'I ;~

5 5 ~

and withdraw the needle, is easily achieved. It is also clear that, in those embodiments adapted for retrieving the injection needle to reside wholly within the cartridge or syringe walls, can also be easily achieved.
With reference to the resilient materials disclosed herein, such materials are those standard in the medical and dental packaging and hypodermic syringe art such as rubber, plastics, and other synthetic and non-synthetic materials known in the art for accomplishing similar and related objectives. Also, all of the embodiments of the cartridge vials disclosed herein are adapted to be manufactured by standard medical and dental ampule and container manufacturing equipment.
Similarly, the cartridge vials disclosed herein are adapted to contain, when fully charged, from 0.1 to 100 milliliters of fluid. However, more typically such vials will contain, when fully charged, from 0.5 to 10 milliliters of fluid.
The needles will have lengths and guages, and will be made of materials, that are standard in the hypodermic syringe/needle art. :~

'`- ' ' '' --;;~.

Claims (133)

What Is Claimed Is:

1. A cartridge vial for fluid injection, comprising:
(A) a cartridge having a first end and a second end, said cartridge having a cylindrical bore defined by a wall extending between said first end and said second end, said bore being suitable for storing a fluid charge to be expelled therefrom;
(B) a first piston and a second piston positioned within said bore and being slidably seated against said cylindrical wall of said bore, said first piston comprising means for reversibly engaging a plunger, (C) a puncturable end cap which is immovably attached to said second end of said cartridge and which comprises a needle guide, (D) a hollow injection needle having an external tip and an internal tip, said internal tip being rigidly attached to and passing through said second piston, and said external tip extending toward said end cap without protruding therefrom, (E) means for locking said first piston and said second piston irreversibly together when said first piston and said second piston are a predetermined distance apart.

2. A cartridge vial according to claim 1 wherein said puncturable end cap attached to said second end of said cartridge, said puncturable end cap being self-sealing.

3. A cartridge vial according to claim 1 wherein said cartridge further comprises a readable indicator.

4. A cartridge vial as in claim 1 wherein said means for irreversibly locking said first and second pistons together comprises barbs attached to at least one of the slidably disposed pistons.

5. A device as in claim 1 wherein said means for irreversibly locking said first and second pistons together comprises hook and loop connectors disposed respectively on the two said pistons.

6. A programmable automatic injection/aspiration device comprising:
(A) a housing, (B) a chamber disposed within said housing for reversibly receiving a cartridge vial, (C) a piston operating plunger slidably disposed within said housing, (D) means, disposed within said housing, for -propelling said plunger, (E) programmable controller means for adjustably controlling the rate of movement of said plunger via said propelling means.

7. A device as in claim 6 wherein said controller means includes means for controlling the direction of said plunger.

8. A device as in claim 6 wherein said controller means includes means for controlling the extent of movement of said plunger.

9. A device as in claim 6 further comprising a programmable processor for directing said controller

10. A device as in claim 6 further comprising sensor means for detecting the rate of movement of said plunger.

11. A device as in claim 6 further comprising sensor means for sensing the direction of movement of said plunger.

12. A device as in claim 6 further comprising sensor means for sensing the extent of movement of said plunger.

13. A device as in claim 6 further comprising indicator means for indicating the rate, direction, and extent of movement of said plunger and for indicating the amount of fluid remaining and expelled from a fluid vial.

14. A device as in claim 6 further comprising locking means operably connected to said propelling means for preventing unintentional discharge of said device.

15. A device as in claim 6 further compris means for locking said cartridge vial in a particular position in relation to said injection/aspiration device housing so that said first piston can operate to aspirate fluids into said vial.

16. A device as in Claim 6 wherein said cartridge further comprises a readable indicator for matching cartridge vials and ampules to said device and for indicating patient information.

17. A device as in claim 6 further comprising aspirated fluid sensor means for detecting aspirated fluids.

18. A device as in claim 17 wherein said sensor means is a photoelectric cell.

19. A method of administering fluid medication, comprising :

(A) Providing a cartridge vial for fluid injection, said cartridge vial comprising:
(i) a cartridge having a first end and a second end, said cartridge having a cylindrical bore defined by a wall extending between said first end and said second end, said bore being suitable for storing a fluid charge to be expelled therefrom;
(ii) a first piston and a second piston positioned within said bore and being slidably seated against said cylindrical wall of said bore, said first piston comprising means for reversibly engaging a plunger, (iii) a puncturable end cap which is attached to said second end of said cartridge and which comprises a needle guide, (iv) a hollow injection needle having an external tip and an internal tip, said internal tip being rigidly attached to and passing through said second piston, and said external tip extending toward said end cap without protruding therefrom, (v) means for locking said first piston and said second piston irreversibly together when said first piston and said second piston are a predetermined distance apart, and (vi) means for locking said vial in a particular position in relation to said cartridge so that said first piston can be operated to aspirate fluid, (B) propelling said plunger shaft to insert said needle into a subject; then (C) locking said vial in a particular position in relation to said cartridge so that said vial can be operated to aspirate; then (D) propelling said plunger shaft in a reverse direction to interrogate by aspiration an injection site; then (E) automatically scanning said vial to insure the absence of blood or other physiological fluids; then (F) propelling said plunger shaft to inject fluid through said needle; then (G) withdrawing said needle from said injection site;
then (H) retracting said needle a sufficient distance 80 that said needle thereafter resides completely within said cartridge, and (I) controlling said propelling of said plunger shaft as to rate, direction, and extent of movement.

20. A method as in claim 19 further comprising the step of retracting said needle a sufficient distance so that said needle thereafter resides completely within said cartridge after said step (E) when blood or other physiological fluid is detected by said aspirated fluid sensor.

21. A cartridge vial for fluid injection comprising:

(A) a cartridge, having a first end and a second end, said cartridge having a cylindrical bore which is widened at said second end of said cartridge to form a cylindrical needle housing assembly residence chamber for reversibly receiving a needle housing assembly, and a puncturable end cap, said end cap sealing said second end of said cartridge and having a needle guide disposed therein;
(B) an ampule disposed within said cartridge bore having a first cylindrical portion, a second cylindrical portion adjacent to and narrower than said first portion, and a third cylindrical portion adjacent to said second portion and being adjacent to and wider than said second portion, said ampule being suitable for storing a fluid charge to be expelled therefrom;
(C) a piston within said first portion of said ampule and being slidably seated in said ampule, said piston comprising means for reversibly engaging a plunger;
(D) a puncturable ampule end stopper rigidly attached to and sealing said third portion of said ampule; and (E) a needle housing assembly disposed in said cylindrical bore of said cartridge said needle housing assembly comprising a housing, a hollow injection needle rigidly attached to said housing and having an internal end and an external end, said internal end of said needle extending through said needle assembly housing toward said puncturable ampule end stopper, and said external end of said hollow injection needle extending toward said puncturable end cap of said cartridge without protruding therefrom, said housing having locking means for irreversibly locking said needle assembly housing to said ampule when said needle cap assembly and said ampule are a predetermined distance apart.
wherein said cartridge

22. A cartridge vial according to Claim 21 wherein said cartridge further comprises a readable indicator.

23. A cartridge vial according to claim 21 wherein said cartridge vial is provided with an aperture for engaging said housing locking means.

24. A mixing syringe for two-component medicaments comprising:
(A) a cartridge housing having a first end and a second end, said cartridge housing having a substantially cylindrical cartridge housing bore; (B) a slidable cartridge disposed in said cartridge housing bore and having a first end, a second end, and a temporary sealing barrier disposed between said first and second ends and separating a cartridge bore of said cartridge into a cylindrical medicament solvent charge chamber and a cylindrical medicament charge chamber, said cartridge housing having means, fixedly attached thereto, for breaching said temporary sealing barrier, said cartridge being suitable for separately storing a medicament solvent charge and a medicament charge in said medicament solvent charge chamber and said medicament charge chamber, respectively, said charges to be mixed to form a medicament to be expelled from said cartridge;
(C) a piston disposed within said first end of said cartridge and being slidably seated in said cartridge bore;
(D) a retractable needle housing assembly slidable in said cartridge housing;
(E) a retractable injection needle fixedly attached to said needle housing assembly and extending therethrough for injecting mixed medicament; and (F) a puncturable cartridge end stopper rigidly attached to and sealing said second end of said cartridge.

25. The device of claim 24 wherein said cartridge housing further comprises (G) a puncturable end cap, said end cap sealing said second end of said cartridge housing and having a needle guide disposed therein.

26. The device of claim 24 wherein said piston further comprises (H) an operating shaft for operating said piston and said cartridge and for adapting said cartridge to other devices.

27. The device of claim 24 wherein said breachable temporary sealing barrier is so configured that said piston can pass sealably therethrough after said barrier is breached.

28. The device of claim 27 wherein said breachable temporary sealing barrier is provided with a cylindrical bore of substantially equal dimension to that of said cartridge bore so that said piston can pass sealably therethrough after said barrier is breached.

29. The device of claim 27 wherein said breachable temporary sealing barrier comprises a valve.

30. The device of claim 27 wherein said breachable temporary sealing barrier comprises a stopcock.

31. The device of claim 27 wherein said breachable temporary sealing barrier comprises a stopcock and operating cam, said operating cam being disposed within said cartridge chamber.

32. The device of claim 27 wherein said breachable temporary sealing barrier comprises a stopcock and operating cam, said operating cam being disposed on the outside of said cartridge.

33. The device of claim 27 wherein said breachable temporary sealing barrier comprises a membrane and seat therefor.

34. The device of claim 33 wherein said membrane seat is recessed into the wall of said cartridge cylinder bore a sufficient distance so that said cartridge piston slides sealably therethrough.

35. The device of claim 24 wherein said needle housing assembly is slidably disposed in said cylindrical bore of said cartridge housing and comprises (A) a needle housing, (B) an injection needle having a hollow shaft, an internal end, an internal shaft portion, an external end, an external shaft portion, first and second apertures, and a passageway extending through said hollow shaft and connecting said first and second apertures, said needle being rigidly attached to and extending through said needle housing, said internal end of said needle extending through said needle assembly housing toward said puncturable cartridge end stopper, said external end of said needle extending toward said puncturable end cap of said cartridge housing without protruding therefrom, said needle being adapted to expel a medicament from said cartridge, said housing having locking means for irreversibly locking said needle assembly housing to said cartridge when said needle cap assembly and said cartridge are predetermined distance apart.

36. The device of claim 35 wherein said first injection needle aperture is disposed in said internal needle shaft portion an appropriate distance from said housing to receive fluid from a punctured medicament cartridge, and said second injection needle aperture is disposed in said external needle end.

37. The device of claim 35 wherein said first injection needle aperture is disposed in said internal needle shaft end, and said second injection needle aperture is disposed in said external needle end.

38. The device of claim 24 wherein said means fixedly attached to said cartridge housing for breaching a temporary sealing barrier between chambers of said slidable cartridge comprises a pushrod.

39. The device of claim 24 wherein said means fixedly attached to said cartridge housing for breaching a temporary sealing barrier between chambers of said slidable cartridge comprises (A) a pushrod having an anchoring end and a puncturing end wherein said anchoring end is fixedly attached to said cartridge housing said pushrod extending from said cartridge housing toward said cartridge puncturable end stopper, and (B) a needle assembly housing having a pushrod aperture for freely guiding said pushrod therethrough so that said puncturing end of said pushrod resides in close proximity to and in alignment with said puncturable cartridge end stopper.

40. The device of claim 24 wherein said means fixedly attached to said cartridge housing for breaching a temporary sealing barrier between chambers of said slidable cartridge comprises (A) a pushrod having an anchoring end and a cam-engaging end wherein said anchoring end is fixedly attached to said cartridge housing, said pushrod extending from said cartridge housing toward a cartridge stopcock operating cam, and (B) a needle assembly housing having a pushrod aperture for freely guiding said pushrod therethrough so that said cam-engaging end of said pushrod resides in close proximity to and in alignment with said cartridge stopcock operating cam disposed between said cartridge and said cartridge housing.

41. The device of claim 24 wherein said temporary sealing barrier comprises a valve having an operating slot for engaging a spiral pushrod.

42. The device of claim 24 wherein said cartridge further comprises a mixing rotor adapted to be operated by a spiral pushrod.

43. The device of claims 41 or 42 wherein said means fixedly attached to said cartridge housing for breaching a temporary sealing barrier between chambers of said slidable cartridge comprises (A) a spiral pushrod having an anchoring end and a puncturing end suitable for engaging the operating slot of a rotor, wherein said anchoring end is fixedly attached to said cartridge housing said pushrod extending from said cartridge housing toward said cartridge puncturable end stopper, and (B) a needle assembly housing having a pushrod aperture for freely guiding said pushrod therethrough so that said puncturing end of said pushrod resides in close proximity to and in alignment with said puncturable cartridge end stopper.

44. The device of claim 24 wherein said breachable temporary sealing barrier comprises a plug.

45. The device of claim 43 wherein said barrier comprises a truncated cone and seat therefor.

46. The device of claim 43 wherein said barrier comprises a truncated pyramid and seat therefor.

47. The device of claim 43 wherein said barrier comprises a ball and seat therefor.

48. The device of claim 43 wherein said barrier comprises a flap.

49. The device of claim 43 wherein said barrier comprises a trapdoor.

50. The device of claim 24 wherein said breachable temporary sealing barrier comprises a membrane.

51. The device of claim 49 wherein said membrane comprises a synthetic polymer.

52. The device of claim 49 wherein said polymer is polystyrene.

53. The device of claim 49 wherein said polymer is polyethylene.

54. The device of claim 49 wherein said membrane comprises rubber.

55. The device of claim 24 wherein said breachable temporary sealing barrier comprises a disk.

56. The device of claim 55 wherein said disk is circular.

57. The device of claim 55 wherein said disk is ovoid.

58. The device of claim 55 wherein said disk is polygonal.

59. The device of claim 55 wherein said disk comprises a synthetic polymer.

60. The device of claim 55 wherein said polymer is polystyrene.

61. The device of claim 55 wherein said polymer is polyethylene.

62. The device of claim 55 wherein said disk comprises polyethylene.

63. The device of claim 55 wherein said disk comprises rubber.

64. The device of claim 24 wherein said breachable temporary sealing barrier comprises a valve.

65. The device of claim 64 wherein said valve is a rotary valve.

66. The device of claim 64 wherein said valve is an iris valve.

67. The device of claim 64 wherein said valve is a stopcock.

68. The device of claim 64 wherein said valve is a ball valve.

69. The device of claim 68 wherein said ball valve has an aperture suitable for the sealable passage therethrough of a piston.

70. The device of claim 64 wherein said valve is a gate valve.

71. A mixing syringe for two-component medicaments comprising:

(A) a cartridge housing having a first end and a second end, said cartridge housing having a substantially cylindrical cartridge housing bore; (B) a slidable cartridge disposed in said cartridge housing bore and having a first end, a second end, and a temporary sealing barrier disposed between said first and second ends and separating a cartridge bore of said cartridge into a cylindrical medicament solvent charge chamber and a cylindrical medicament charge chamber, said cartridge housing having means, fixedly attached thereto, for breaching said temporary sealing barrier, said cartridge being suitable for separately storing a medicament solvent charge and a medicament charge in said medicament solvent charge chamber and said medicament charge chamber, respectively, said charges to be mixed to form a medicament to be expelled from said cartridge;
(C) a piston disposed within said first end of said cartridge and being slidably seated in said cartridge bore;
(D) a needle housing assembly rigidly attached to said cartridge and contained wholly within said cartridge housing;
(E) an injection needle which is containable wholly within said cartridge housing, which can be extended to a position in which at least a portion of said needle extends outside of said cartridge housing, said needle being fixedly attached to said needle housing assembly and extending therethrough for injecting mixed medicament;
(F) a puncturable end cap, said end cap sealing said second end of said cartridge housing; and (G) means for retracting said needle to reside completely within said cartridge housing after the expulsion of said medicament from said syringe.

72. The device of claim 71 wherein said breachable temporary sealing barrier is so configured that said piston can pass sealably therethrough after said barrier is breached.

73. The device of claim 72 wherein said breachable temporary sealing barrier is provided with a cylindrical bore of substantially equal dimension to that of said cartridge bore so that said piston can pass sealably therethrough after said barrier is breached.

74. The device of claim 71 wherein said temporary sealing barrier comprises a rotating valve disposed through said cartridge and a valve operating cam disposed on the exterior of said cartridge, said valve operating cam being configured to be operated by a pushrod.

75. The device of claim 71 wherein said means fixedly attached to said cartridge housing for breaching a temporary sealing barrier between chambers of said slidable cartridge comprises a valve cam operating pushrod.

76. The device of claim 74 wherein said valve cam operating pushrod is integral to said housing.

77. The device of claims 24 or 71 wherein said means fixedly attached to said cartridge housing for breaching a temporary sealing barrier between chambers of said slidable cartridge comprises (A) an electronically actuated pushrod contained within said cartridge; and (B) an electronic pushrod actuator contained within said cartridge housing.

78. The device of claims 24 or 71 wherein said means fixedly attached to said cartridge housing for breaching a temporary sealing barrier between chambers of said slidable cartridge comprises (A) a magnetically actuated pushrod contained within said cartridge; and (B) a magnetic pushrod actuator contained within said cartridge housing.

79. A mixing cartridge for two-component medicaments comprising:
(A) a cartridge having a first end, a second end, and a breachable temporary sealing barrier dividing a cylindrical cartridge bore of said cartridge into a medicament solvent charge chamber and a medicament charge chamber, said breachable temporary sealing barrier being so configured that a piston can pass sealably therethrough after said barrier is breached, said cartridge being suitable for separately storing a medicament solvent charge and a medicament charge in said medicament solvent charge chamber and said medicament charge chamber, respectively, said charges to be mixed to form a medicament to be expelled from said cartridge, said cartridge second end being adaptable for receiving an injection needle;
(B) a piston disposed within said first end of said cartridge and being slidably seated in said cartridge bore; and (C) a puncturable cartridge end stopper rigidly attached to and sealing said second end of said cartridge.

80. The device of claim 79 wherein said piston further comprises (D) an operating shaft for operating said piston and for adapting said cartridge to other devices.

81. The device of claim 79 wherein said breachable temporary sealing barrier is provided with a cylindrical bore of substantially equal dimension to that of said cartridge bore so that said piston can pass sealably therethrough after said barrier is breached.

82. The device of claim 81 wherein said breachable temporary sealing barrier comprises a valve.

83. The device of claim 81 wherein said breachable temporary sealing barrier comprises a stopcock.

84. The device of claim 81 wherein said breachable temporary sealing barrier comprises a membrane and seat therefor.

85. The device of claim 84 wherein said membrane seat is recessed into the wall of said cartridge cylinder bore.

86. The device of claim 79 wherein said cartridge further comprises (D) an injection needle fixedly attached to said second end of said cartridge and extending sufficiently through said puncturable cartridge end stopper to permit injection of said mixed medicament.

87. The device of claim 79 wherein said cartridge second end further comprises means for securely and reversibly receiving an injection needle.

88. The device of claim 87 wherein said means comprises indentations on the outside surface of said cartridge second end said indentations being adaptable for receipt of a needle assembly housing.

89. The device of claim 87 wherein said means comprises at least one groove on the outside surface of said cartridge second end said groove being adaptable for receipt of a needle assembly housing.

90. The device of claim 89 wherein said groove is formed by a narrowing transition between said puncturable cartridge end stopper and said cartridge.

91. A needle housing assembly for use with a necked medicament container having a puncturable end stopper comprising:
(A) a needle housing;
(B) locking means, disposed in said needle housing, for locking said housing to said necked medicament container when said needle housing assembly and said necked cartridge become a predetermined distance apart upon relative movement between said necked medicament container and said needle housing; and (C) an injection needle having a hollow shaft, an internal end, an internal shaft portion, an external end, an external shaft portion, first and second apertures, and a passageway extending through said hollow shaft and connecting said first and second apertures, said needle being rigidly attached to and extending through said needle housing, I
said internal end and internal shaft portion of said needle being adapted to puncture a necked medicament container, and said external end and external shaft portion of said needle being adapted to expel a medicament out of said needle housing assembly.

92. The device of claim 68 wherein said means for locking said housing to a necked medicament container comprises protrusions which are disposed in said housing and which are adapted to securely engage the neck and head portions of a medicament container.

93. The device of claim 92 wherein said means for locking said housing to a necked medicament container comprises at least one flange disposed in said housing for securely engaging the neck and head portions of a medicament container.

94. The device of claim 93 wherein said means for locking said housing to a necked medicament container comprises a multiplicity of flanges, disposed in said housing, for securely engaging the neck and head portions of a medicament container.

95. The device of claim 91 wherein said injection needle further comprises a pushrod for breaching a temporary sealing barrier between chambers of a medicament cartridge.

96. The device of claims 91 or 72 wherein said first injection needle aperture is disposed in said internal needle shaft portion an appropriate distance from said housing to receive fluid from a punctured medicament cartridge, and said second injection needle aperture is disposed in said external needle end.

97. The device of claims 91 or 95 wherein said first injection needle aperture is disposed in said internal needle shaft end, and said second injection needle aperture is disposed in said external needle end.

98. The device of claim 91 further comprising means, fixedly attached to said needle housing, for breaching a temporary sealing barrier between the chambers of a two-chambered medicament container.

99. The device of claim 91 further comprising means, fixedly attached to said needle housing, for sterilely enclosing said injection needle until use.

100. The device of claim 99 wherein said means further comprises removable sheaths disposed around said internal and said external needle ends and portions.

101. The device of claim 91 further comprising means, fixedly attached to said needle housing, for sterilely enclosing said injection needle during use.

102. The device of claim 101 wherein said means further comprises puncturable sheaths.

103. The device of claim 101 wherein said means further comprises compressible sheaths disposed around said internal and said external needle ends and portions.

104. The device of claim 102 wherein said sheaths are pleated.

105. The device of claim 91 wherein said locking means is configured to reversibly lock said housing to said necked medicament container.

106. The device of claim 91 wherein said locking means is configured to irreversibly lock said housing to said necked medicament container.

107. A mixing syringe for two-component medicaments comprising:

(A) a cartridge housing having a first end and a second end, said cartridge housing having a substantially cylindrical cartridge housing bore;
(B) a slidable cartridge disposed in said cartridge housing bore and having a first end, a second end, and a temporary sealing barrier disposed between said first and second ends and separating a cartridge bore of said cartridge into a cylindrical medicament solvent charge chamber and a cylindrical medicament charge chamber, said cartridge being suitable for separately storing a medicament solvent charge and a medicament charge in said medicament solvent charge chamber and said medicament charge chamber, respectively, said charges to be mixed to form a medicament to be expelled from said cartridge;
(C) a piston disposed within said first end of said cartridge and being slidably seated in said cartridge bore;
(D) a retractable needle housing assembly slidable in said cartridge housing said needle housing having means, fixedly attached thereto, for breaching said temporary sealing barrier;
(E) a retractable injection needle having a hollow shaft, an internal end, an internal shaft portion, an external end, an external shaft portion, first and second apertures, and a passageway extending through said hollow shaft and connecting said first and second apertures, said needle being rigidly attached to and extending through said needle housing, said internal end and internal shaft portion of said needle being adapted to puncture said cartridge, and said external end and external shaft portion of said needle being adapted to expel a medicament out of said needle housing assembly, said first injection needle aperture being disposed in said internal needle shaft portion an appropriate distance from said housing to receive fluid from a punctured medicament cartridge, and said second injection needle aperture being disposed in said external needle end;
(F) a puncturable cartridge end stopper rigidly attached to and sealing said second end of said cartridge.

108. The device of claim 107 wherein said cartridge further comprises (G) a puncturable end cap, said end cap sealing said second end of said cartridge housing and having a needle guide disposed therein.

109. The device of claim 107 wherein said piston further comprises (H) a piston shaft for operating said piston and said cartridge and for adapting said cartridge to other devices.

110. The device of claim 107 wherein said internal end of said injection needle comprises said means for breaching said temporary sealing barrier.

111. The device of claim 107 wherein said breachable temporary sealing barrier is so configured that said piston can pass sealably therethrough after said barrier is breached.

112. The device of claim 110 wherein said breachable temporary sealing barrier is provided with a cylindrical bore of substantially equal dimension to that of said cartridge bore so that said piston can pass sealably therethrough after said barrier is breached.

113. The device of claim 110 wherein said breachable temporary sealing barrier comprises a valve.

114. The device of claim 110 wherein said breachable temporary sealing barrier comprises a stopcock.

115. The device of claim 110 wherein said breachable temporary sealing barrier comprises a stopcock and operating cam, said operating cam being disposed within said cartridge chamber.

116. The device of claim 110 wherein said breachable temporary sealing barrier comprises a stopcock and operating cam, said operating cam being disposed on the outside of said cartridge.

117. The device of claim 110 wherein said breachable temporary sealing barrier comprises a membrane and seat therefor.

118. The device of claim 116 wherein said membrane seat is recessed into the wall of said cartridge cylinder bore a sufficient distance so that said cartridge piston slides sealably therethrough.

119. The device of claim 109 wherein said piston is puncturable by said injection needle internal end and said piston shaft is chambered so that said needle internal end can penetrate said piston and said piston shaft chamber to permit said piston to pass sealably through said temporary barrier.

120. The device of claims 24, 71, 79 or 107 wherein said cartridge further comprises one or more medically active substances.

121. The device of claim 120 wherein said medically active substances are selected from the group comprising glucagon, human growth hormone, papaverine, morphine.

122. A fluid injector comprising:
(A) a tubular cartridge, having a first end and a second end, said cartridge having an interior bore which is widened at said second end of said cartridge to form a cylindrical needle housing assembly residence chamber for reversibly receiving a needle housing assembly, and a puncturable end cap, said end cap sealing said second end of said cartridge and having a needle guide disposed therein;
(B) an ampule disposed within said cartridge bore wall, said ampule having a first elongated cylindrical portion, a second cylindrical portion adjacent to and narrower than said first portion, and a third cylindrical portion adjacent to [said second portion and being adjacent to] and wider than said second portion, said ampule being suitable for storing a fluid charge to be expelled therefrom;
(C) a piston slidably seated within said first portion of said ampule ;
(D) a plunger engageable with said piston for exerting a force against said piston;
(E) a puncturable ampule end stopper rigidly attached to and sealing the outwardly facing end of said third portion of said ampule; and (F) a needle housing assembly disposed in said cylindrical bore of said cartridge said needle housing assembly comprising:
a housing, a hollow injection needle rigidly attached to said housing and having an internal end and an external end, said internal end of said needle extending through said needle housing assembly toward said puncturable ampule end stopper, and said external end of said hollow injection needle extending toward said puncturable end cap of said cartridge without protruding therefrom, said housing having locking means for irreversibly locking said needle housing assembly to said ampule when said needle housing assembly and said ampule are brought together.

123. A fluid injector actuated by a plunger, said fluid injector comprising:
(A) a tubular cartridge having an upper end and a lower end, said cartridge having an interior bore wall which widens at said lower end of said cartridge to form a needle housing assembly residence chamber for receiving a needle housing assembly;
(B) a puncturable end cap sealing said lower end of said cartridge;
(C) an ampule slidably disposed within the upper end of said cartridge bore wall, said ampule having an upper end and a lower end and being suitable for storing a fluid charge to be expelled therefrom;
(D) a piston slidably seated within said ampule and engageable by said plunger from said upper end of said ampule;
(E) a puncturable ampule end stopper rigidly attached to and sealing said lower end of said ampule; and (F) a needle housing assembly slidably disposed within said upper end of said cartridge below said ampule, said needle housing assembly comprising:
a generally cup-shaped housing having a housing bottom and flexible upstanding housing wall sections attached to the periphery of said housing bottom, said housing walls extending toward said lower end of said ampule, a hollow injection needle extending through and rigidly engaged by said housing bottom and having an internal section, and an external section, said internal section of said hollow injection needle extending from said housing bottom, upwardly within said housing walls, toward said puncturable ampule end stopper, and said external section of said hollow injection needle extending from said housing bottom downwardly toward aid puncturable end cap of said cartridge without protruding from said puncturable end cap, the upper edges of said housing wall sections being engageable with said lower end of said ampule as said ampule slides downwardly within said cartridge bore, whereby actuation by said plunger moves said ampule downwardly within said cartridge bore wall in said upper end of said cartridge toward said lower end of said cartridge thus engaging said upper edges of said housing wall sections and moving said needle housing assembly from said upper end of said cartridge into said needle housing assembly residence chamber at said lower end of said cartridge causing said external section of said hollow injection needle to protrude through said puncturable end cap and allowing said flexible housing wall sections to expand outwardly in said needle housing assembly residence chamber, the further downward movement of said ampule causing the internal section of said hollow injection needle to pass through said puncturable ampule end stopper thereby allowing fluid to be injected outwardly through said hollow injection needle.

124. A fluid injector in accordance with Claim 123 wherein said interior bore wall is cylindrical.

125. A fluid injector in accordance with Claim 124 further comprising a needle guide disposed in said puncturable end cap.

126. A fluid injector in accordance with Claim 123 wherein said ampule has a circumferential recess or groove located adjacent its lower end for engagement with inwardly extending sections of the upper edges of said cup-shaped housing wall sections.

127. A fluid injector in accordance with Claim 123 wherein said ampule further comprises a first cylindrical portion, a second cylindrical portion adjacent to and narrower than said first portion, and a third cylindrical portion adjacent to and wider than said second portion.

128. A fluid injector in accordance with Claim 127 wherein said upper ends of said housing walls engageable with said ampule further comprises locking means for irreversibly locking said needle housing assembly to said ampule at said third cylindrical portion of said ampule when said needle housing assembly and said ampule are engaged.

129. A fluid injector in accordance with Claim 128 wherein said housing walls further comprise needle assembly housing lips at said upper ends of said housing walls, said lips engageable with said ampule.

130. A fluid injector in accordance with Claim 123 wherein said piston further comprises means for reversibly engaging said plunger.

131. A fluid injector in accordance with Claim 123 wherein said upper end of said tubular cartridge receives an assembly which spring loads said plunger for actuation.

132. A method for injecting a fluid to a preselected internal target tissue while avoiding fluid exposure to surface tissues which would be undesirably damaged by such exposure, comprising the steps of:
positioning a hollow injection needle axially within the lower section of a tubular cartridge;
inserting an ampule containing said fluid into said cartridge above said hollow injection needle, said ampule having a puncturable end stopper facing the inwardly positioned end of said hollow injection needle;
positioning said cartridge on surface tissue over internal target tissues;
propelling said hollow injection needle together with said ampule within said cartridge in the direction of said surface tissue causing said external end to puncture and extend outward from said cartridge and through surface tissue into said internal target tissue;
then propelling said ampule within said cartridge toward said hollow injection needle causing said puncturable end stopper on said ampule to be punctured by said inwardly positioned end of said hollow injection needle allowing said end to extend into said ampule; and expelling said fluid from said ampule through said external end of said hollow injection needle into said internal target tissue.

133. An injector positionable on external tissue for delivering fluid into a preselected internal target tissue while avoiding fluid exposure to the surface tissue comprising:
a hollow injection needle axially within the lower section of a tubular cartridge;
an ampule containing said fluid positioned in said cartridge above said hollow injection needle, said ampule having a puncturable end stopper facing the inwardly positioned end of said hollow injection needle;

means for propelling said hollow injection needle together with said ampule within said cartridge causing said external end of said needle to puncture and extend outward from said cartridge and through the surface tissue into the target tissue;
means for further propelling said ampule within said cartridge in the direction of said hollow injection needle causing said puncturable end stopper on said ampule to be punctured by said inwardly positioned end of said hollow injection needle allowing said end to extend into said ampule;
and means for expelling said fluid from said ampule through said external end of said hollow injection needle into said internal target tissue.