JP2003500118A - Needleless syringe drug capsule - Google Patents

Abstract

(57) Abstract: A clear needle-free injector drug capsule suitable for pre-filling a solution comprises a first inner layer of a drug-compatible transparent plastic defining a chamber for containing the solution, and a perimeter of the first plastic layer. And a second outer layer of transparent plastic forming a support sleeve. The first and second transparent plastic layers are each resistant to discoloration when exposed to high energy radiation. Accordingly, a low-cost, transparent needle-free injector drug capsule that can be sterilized by high energy irradiation is provided. The capsule may define a body having a main chamber for containing the liquid medication and holding the free piston in a sealed fit for subsequent use in drug release. The body further has an extension chamber with an opening for receiving the free piston in a loose fit. The initial fit of the piston allows the sterilizing fluid to penetrate, so that after assembling the drug capsule under aseptic conditions, it can be sterilized by any known method.

Description

Detailed Description of the Invention

BACKGROUND OF THE INVENTION Needleless syringes are used as an alternative to needle-type hypodermic syringes to inject a solution into the underlying tissue through the epidermis. The usual structural form is a syringe with a small injection port that contacts the skin, through which the drug is injected at a high pressure sufficient to puncture the skin. The force required to exert pressure on the drug can come from compressed coil springs, compressed gas, charge, or some other form of stored energy.

[0002] With regard to the pressure exerted on the drug during the injection cycle, it would be advantageous if there was a first stage of rapid pressure rise to peak followed by a second stage of low pressure. The first step facilitates penetration of the skin by the drug and the second step dispenses the drug through the holes formed. Usually, the pressure reached in the first stage is on the order of 300 to 400 bar, the rise time is about 50 μs and the second stage is about 1 μs.
Complete with a pressure of 00 bar. Using a 0.5 mm outlet, an injection cycle of 500 μl of drug is 30-50 ms for water or a liquid with water-like properties.

The capsule from which the drug is injected is often in the form of a cylinder containing a free piston (ie without a connecting rod), the injection opening of which is located in the end wall. The injection port may be integrally molded with the cylinder, or there may be a separate nozzle in sealed hydraulic contact with the end of the cylinder. The other end of the cylinder can be left open to accommodate the drive push rod that acts on the piston that causes the injection of the drug. The completed syringe may be a single-use, pre-filled, disposable device, or a multiple-use actuator with a replaceable drug capsule, or multiple dose-delivering continuous doses from a bulk supply. It can be provided as a dosing actuator.

Needle-free injectors place a high demand on the capsule structure due to the extremely high stresses that occur during injection. The materials used must be strong, very transparent so that the chemicals can be checked visually or by laser inspection for contamination and encapsulation gases, and chemically compatible with the chemicals they store. There is a need. The ideal material for the capsule is the so-called Type I borosilicate glass, which is very commonly used in drug-filled needle-type syringes. Although glass capsules made to the proper specifications have excellent performance, they require rigorous proof testing to eliminate glass that contains entrapped foam and foreign matter and common defects such as cracks and scratches. However, time-consuming cleaning and sterilization are also required before filling becomes possible. Generally, glass capsules are first washed to remove particulates and then heated at about 180 ° C. for at least 6 hours for dry heat sterilization and pyrogen removal. Therefore, glass capsules are expensive to manufacture.

Recently, some manufacturers have begun to use plastics instead of glass. Plastic technology allows more precise control of capsule size at high production rates. However, plastic materials raise a number of problems not present in glass, one of which is chemical compatibility. Generally, plastics are not suitable for long-term contact with chemicals. Plastics are gas permeable and contain substances that can absorb moisture and adversely affect chemicals. In addition, plastic injection molding techniques typically require release agents that are not compatible with chemicals,
Time consuming and costly cleaning and sterilization of plastic drug capsules is required. Since many chemicals are sensitive to oxygen, gas permeability should be minimized.
Absorption of water will change the concentration of the liquid agent. Finally, many transparent plastics are quite brittle and cannot withstand the extremely high stresses that occur during injection.
Moreover, little is known about the effects of high strain rates, such as occur with needleless syringes. In fact, the data sheets provided by the manufacturers only disclose mechanical properties based on standard tensile stress and impact texts performed at relatively slow strain rates.

When very low pyrogen loading is required in containers containing parenteral drugs, pyrogen-free molding techniques, usually combined with gas sterilization using ethylene oxide, are used instead of dry heat sterilization. be able to. The use of gas sterilization precludes preassembly of the free piston within the drug capsule in order to reach all surfaces. Moreover, some plastics are sensitive to germicidal gases. Due to environmental health issues, the use of ethylene oxide is banned in some countries.

In view of the above, of course, the use of plastic drug capsules in needleless syringes is limited to applications where the drug capsule is filled just prior to use, and filling is generally done by pulling the drug out of a vial. This is done with the help of a transfer device that can be transferred to a syringe capsule. This is a tedious task and is prone to mistakes in filling the wrong dose and injecting air into the medication. Furthermore, sterile, pyrogen-free drug transfer is very difficult to achieve in everyday environments.

There is a growing need for single-use, prefilled, needleless syringes that are easy to use, safe to dispose of, and thus have the advantage of factory control of the drug filling process.

SUMMARY OF THE INVENTION According to a first aspect of the invention, a transparent needleless syringe drug capsule suitable for pre-filling a liquid drug is a transparent, drug-compatible plastic defining a chamber containing the liquid drug. A first inner layer and a second outer layer of transparent plastic forming a support sleeve around the first plastic layer, each of the first and second transparent plastic layers being exposed to high energy radiation. Resistant to discoloration.

The present invention is a low cost, transparent needleless syringe drug capsule using a plastic structure that overcomes the production problems associated with conventional glass and plastic drug capsules because it can be sterilized by high energy irradiation. I will provide a. Gamma irradiation causes glass and many plastics to become brownish, preventing visual inspection of the contents after filling. To the problems associated with making conventional capsules by selecting plastic materials that are combined to provide the compatibility and strength with the required chemicals and are also suitable for gamma irradiation or other high energy irradiation, A cost-effective solution is provided.

As mentioned above, the glass replacement materials proposed in the prior art are transparent plastics, but for most chemicals very few are suitable for long-term contact. Those that may be chemically compatible also have other drawbacks such as poor resistance to irradiation, strong discoloration as a result of irradiation, high water absorption, high gas or vapor permeability, or very low tensile stress. . In general, the plastics most suitable for contact with chemicals are also very brittle at the same time, in principle they can form very thick walled capsules in a single layer to provide sufficient strength, but as a result of severe molding Shrinkage and microcracks due to stress occur. However, it has been discovered that shaping or assembling a multi-layered drug capsule can take advantage of the optimal properties of one type of plastic and add to it at least one other property, whereby a finished capsule is It provides all necessary qualities, including resistance to discoloration and other harmful property changes during irradiation. Sterilization of drug capsules by gamma irradiation is much cheaper than the methods currently used to sterilize glass or other plastic drug capsules.

Preferably, the first and second plastic layers are injection molded and the second layer is joined at the interface to the first layer. One of the reasons for joining the two materials is to prevent the formation of very small voids between the layers, and when the voids are formed, an optical interference pattern (Newton ring) occurs, It adversely affects visual inspection or automatic inspection. Even small gaps will adversely affect the barrier properties of the combination. Therefore, the second plastic layer preferably has a higher melting point than the first plastic layer. These materials should have similar coefficients of expansion so that the bonding layer is not overstressed during temperature changes during and after cooling.

Preferably, the first plastic layer is a metallocene catalyzed polymer, most preferably a cyclic olefin copolymer (COC) or a cyclic olefin polymer (COP). This type of material exhibits a number of beneficial properties that make it suitable for long-term contact with chemicals, including very low water absorption, excellent water vapor barrier properties, high transparency, and low birefringence. included. This material can be sterilized by gamma irradiation without causing haze or weakening. However, this material alone is too brittle for use as a needleless drug capsule. In the present invention, the solution is to provide a strong impact resistant sleeve for support.

Preferably, the second plastic layer comprises polyester, copolyester,
It is a polymer selected from the group consisting of polyethylene naphthalate, polyamide, polycarbonate, and polyurethane. These materials are capable of providing a tough, impact resistant transparent plastic support sleeve for the first plastic layer, which materials themselves also sterilize by gamma irradiation without causing haze or weakening. can do.

Preferably, the drug capsule further comprises a P within the chamber for injecting the drug.
Equipped with a TFE piston.

Preferably, the first plastic layer is extended to form an integral fill adapter. More preferably, the fill adapter includes a bond that reveals a fragile tamper.

According to a second aspect of the invention, a needleless injector comprises a drug capsule according to the first aspect of the invention.

In a preferred example, the second or outermost plastic layer is an integral part of the needleless syringe body.

According to a third aspect of the present invention, a method of making a transparent drug capsule for a needleless syringe comprises a first layer of a drug compatible transparent plastic and a second outer support layer of a transparent plastic. Forming a multi-layer capsule having, wherein the first and second transparent plastic layers are each selected to be resistant to discoloration upon irradiation, and sterilizing the multi-layer capsule by high-energy irradiation. Equipped with.

Preferably, the first plastic layer is injection molded and then the second plastic layer is molded over the first layer such that the two layers are joined at the interface between each other. It

[0021] Preferably, the second plastic layer has a higher melting point than the first plastic layer. These materials should have similar coefficients of expansion so that the bonding layer is not overstressed during cooling and subsequent temperature fluctuations.

Preferably, the pharmaceutical capsule is preassembled with a PTFE piston located in the capsule and the entire assembly is sterilized in a vacuum by high energy irradiation. Although PTFE is typically a radiation-degradable polymer, it has been found to retain sufficient strength when irradiated in vacuum, for example in a vacuum pack. Further, the PTFE piston is preferably pretreated at elevated temperature with gamma or other high energy radiation. This treatment leads to cross-linking, resulting in increased strength and resistance to further irradiation.

Preferably, the method further comprises the step of filling the sterile pharmaceutical capsules with the liquid in an automated process and then sealing the capsules in a manner suitable for shipping and long term storage.

According to a fourth aspect of the present invention, a drug capsule for a needleless syringe has a main chamber that receives a liquid drug and subsequently holds a free piston in a sealed fit for use in the injection of the drug. A body is provided, the body further having an extension chamber having an opening for loosely receiving the free piston.

In this aspect of the invention, a multichamber is provided in which the free piston, which is usually a PTFE piston, can be preassembled in a loose fit.
) Proper drug capsules are provided. The piston is initially assembled in a loose fit and is therefore not subject to mechanical stress and therefore is not degraded by normal levels of gamma radiation. In any case, the clearance provided by the initial loose fit of the piston allows the entry of the germicidal fluid. Therefore, the drug capsule can be assembled aseptically and then sterilized by any known method. After sterilization, the free piston is pushed into its pre-fill position for subsequent placement and retention in a sealed fit within the main chamber for use in drug injection.

Preferably, the drug capsule further comprises a stop for holding the free piston in the extension chamber. More preferably, this stop comprises several integral stakes formed by thermal or ultrasonic displacement of the material at the opening of the extension chamber.
) Is provided. Alternatively, this stop can be a separate mating means that is coupled to the opening of the extension chamber.

Preferably the extension chamber comprises a taper. The extension chamber may be tapered along its entire length. Alternatively, it is possible to provide a parallel section and a taper section, which taper section is provided at the transition between the main chamber and the extension chamber.

Preferably, the drug capsule is a transparent plastic drug capsule according to the first aspect of the invention.

A fifth aspect of the invention is a combination of a drug capsule and a free piston according to the fourth aspect of the invention.

[0030]   Preferably, the free piston is manufactured from PTFE.

[0031]   According to a sixth aspect of the present invention, a method of manufacturing a drug capsule comprises   Forming a drug capsule according to the fourth aspect of the present invention;   Assembling the free piston in a loose fit in the extension chamber,   Sterilizing the drug capsule assembly,   Positioning the free piston in a hermetically sealed condition within the main chamber.

Preferably, thereafter, the drug capsule is filled. The piston is pushed all the way to the ejection end and then the capsule is filled with the injection liquid, which allows the pressure of the injection liquid to bring the piston back to the other end of the main chamber. Alternatively, the injection liquid can be introduced by first evacuating the volume of the main chamber and then filling the main chamber with the injection liquid.

Sterilization can be performed using fluids. Preferably, this fluid is steam or ethylene oxide. Alternatively, the drug capsule can be sterilized by exposure to high energy radiation.

The drug capsule can be made of glass. However, preferably the drug capsule is a plastic drug capsule.

According to a seventh aspect of the invention, a needleless injector comprises a drug capsule according to the fourth aspect of the invention.

[0036]   Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings.

Detailed Description Reference is made to FIG. 1 showing a centerline cross-section through a cylindrical capsule. The capsule 1 comprises an inner liner 2 and a sleeve 3. Threads 4 are provided for attaching the capsule to the actuator, but can be replaced by snap-fitting, bayonet pins, or other widely known coupling methods. The liner 2 has at one end an injection port 5 through which the injection solution is dispensed and at 7 a fragile hydraulic connection.
lic connection) to the filling connector 6. The materials of liner 2 and connector 6 are preferably the same and are suitable for contact with chemicals. Inner hole 9 of liner 2
Are approximately parallel and have a surface treatment compatible with the piston material (see FIG. 2).

In FIG. 2, the capsule 1 is shown assembled with the piston 10 inside. The piston 10 has a quality that seals the inner hole 9 of the liner 2 and slides in the inner hole 9 to prevent contamination of chemicals by bacteria. The piston 10 is shown in a position suitable for vacuum filling, in which case the volume 11 is evacuated through the injection port 5 and then filled with the liquid agent through the injection port 5. The friction of the piston 5 in the bore 9 is sufficient to prevent movement during the vacuum. An alternative to vacuum filling is to place the piston at position 10b. In this case, the small space is first evacuated and then the chemical is introduced through the injection port 5 with sufficient pressure to push the piston 10 along the bore 9 to the required position. The structure of the connector 6 may be any suitable one for a filling machine, and a suitable filling method is described in PCT / GB96 / 03017, which is a co-pending application of the present applicant.

FIG. 3 shows the capsule filled with the liquid drug 12 and sealed. The drug 12 is filled as described, allowing for small amounts of excess in the chamber 14 to cause volume fluctuations caused by heat. A resilient seal 13 can be placed in the bore 8 of the connector 6 or a small sealing plug can be inserted into the chamber 14 (not shown). An alternative method of sealing is to soften the cap 13a or the wall of the connector 6 by heat and provide a hermetic seal by crimping.
Other sealing methods such as ultrasonic welding and high frequency bonding of foil films can also be used, the purpose in each case being to achieve a seal that prevents bacterial contamination.

FIG. 4 shows the capsule 1 and the seal 1 assembled on the syringe actuator 15.
3 and the connector 6 broken off by the fragile joint 7 are shown, and the injection port 5 of the capsule 1 is exposed. The syringe is then ready for injection by placing the injection port 5 on the patient's skin and operating the actuator to release the energy stored therein, which in turn causes the push rod 16 to move to the piston. Acting on 10, the injection solution 12 is dispensed through the outlet 5.

The completed syringe 100 is displayed in FIG. In this example, the liner 2 is integrally formed with the main body 200, and is similar to the above-mentioned form. The energy source is a compressed carbon dioxide cartridge 101 with a fragile tube 102 (although other liquefied gases can be used). A cap 201 secured to the body 200 by welding or otherwise holds the cartridge 101 in place. This syringe is operated by removing the filling connector 6 together with the seal 13 and pressing the injection port 5 against the skin. Carbon dioxide gas is expelled from the cartridge by pushing the rod 104 against the fragile tube 102 and actuating the lever 103 to properly snap the tube 102. Piston 10
5, a push rod 16 is attached, the compressed gas acts on the piston 105 and causes it to move forward, impinging on the piston 10 first, forming a rapid pressure rise, and then continuing to push the piston 10. To inject the injection solution. The hole 107 prevents excessive back pressure which reduces the force of the piston 105, and the hole 106 is arranged so that the piston 105 just passes through it and the residual compressed carbon dioxide gas is expelled when the injection is completed. It As an alternative to compressed gas, compression coil springs or gas springs can be used and a simple energy release trigger can be replaced with a release mechanism that operates in response to the pressure of the outlet against the skin. The latter feature is desirable because it reduces the skill required to obtain a reproducible contact force on the skin, which directly affects the quality of the injection.

The material of the inner liner of the capsule must be compatible with the drug and the material of the outer sleeve must be strong and impact resistant. Both materials should be susceptible to sterilization. Furthermore, the properties of both materials should allow the formation of a bond at the interface.

A suitable material for the inner liner is a cyclic olefin copolymer (COC) known as Topaz® and manufactured by Ticona (Germany). This material is a polymer of ethylene _{(CH 2} = CH 2) and 2-norbornene catalyzed metallocene. In Topaz®, large norbornene groups cure the chains resulting in a completely amorphous structure with no observed melting point. A particularly preferred Topaz® grade is Topas 6015®, which is a transparent general purpose grade with a heat deflection temperature HDT / B of 1
It is 50 ° C. These metallocene-catalyzed cycloolefin copolymers exhibit high optical quality and have low levels of extractables. Water absorption by these ISO62 (soaking in water at 23 ° C for 24 hours) is less than 0.01%, and ISO527 part 1
And 2, the tensile stress is 66 N / mm ² , the elongation at break is 4%, and ISO 179
The notched impact strength (Charpy) by −1 eA is 2.0 kJ / m ² . This material can be stabilized by various sterilization methods known in the art such as steam, ethylene oxide gas, and gamma irradiation. Gamma irradiation 3
When used at 0 kGy, no change in mechanical properties was observed, only small changes in optical properties. The yellowness index change measured according to DIN 6187 (ΔYI) is 1 to 2, and the haze change measured according to ASTM 1003 (ΔHaze) is less than 0.4. Topaz® can be processed on conventional injection molding machines.

[0044]   A typical plastic that can be molded on the inner layer is manufactured by Eastman (USA).
Costar polyester such as Eastar GN007, polyethylene naphthalate
, Polyurethane, nylon 12, and polycarbonate. Especially good for outer layers
A suitable material is a specific grade of polycarbonate, manufactured by Bayer (Germany).
Makrolon Rx-1805 (registered trademark) containing a color additive 45/311
). This material is a transparent material based on bisphenol A with a special addition system.
It is a highly viscous polycarbonate. This material has high chemical resistance and gamma irradiation resistance
Have. This material has a tensile modulus of 2400 MPa according to ISO527,
Impact strength with IZOD notch at 23 ° C according to SO480-4A is 95 KJ / m ^Two Is. Makrolon Rx-1805® is a standard method, eg
For example, it can be sterilized by steam, ethylene oxide gas, or gamma irradiation.
Wear. This material has high color stability after gamma irradiation. This material is modern
It can be processed on any loose injection molding machine.

In a preferred embodiment of the invention, the drug capsule comprises Topaz6 as the inner layer.
015 (registered trademark), and Makrolon Rx-1805 (
Is manufactured using a registered trademark. Any conventional injection molding machine can be used. However, the preferred processing parameters are: Topaz
For 6015 (R), injection molding requires a tool temperature of 110-150 ° C,
Injection speed 5 to 40 cm ³ / s, shot volume 27 to 30 cm ³ , injection time 0
． It should be carried out at 80 s, holding pressure 200 to 600 bar, holding time 2 to 3.5 s, and counterpressure 50 bar. For Makrolon Rx-1805®, suitable process parameters are barrel temperature 240-300 ° C., molding temperature 80-120 ° C., injection pressure 500-1000 bar, injection time 0.5.
To 1.0 s, back pressure 20 to 100 bar, holding pressure 150 to 450 bar,
And the holding time is 1.5 to 3.0 s.

Usually, the liner is molded first, allowing slight cooling, and then the outer layer is molded around it. The liner is usually 1-2 mm thick, preferably 1.5 mm,
The outer layer has a thickness of 2 to 4 mm, preferably 3 mm. Preferably, the temperature should be selected so that the second molding melts slightly and a bond with the first inner liner is subsequently formed. Of course, it is also possible in the design of the capsule or syringe to prescribe the external molding first. Again, it is important that the expansion coefficients of the two materials are in the correct range so that no large stresses are created as a result of the different thermal expansions. Additional layers or features can be molded onto the capsule, such as plastics that change color upon irradiation to visually indicate that the device has been sterilized.

The inner layer can also be formed by a liquid crystal polymer or poly-para-xylylene (parylene). These materials are suitable for long term contact with chemicals and become opaque or translucent when formed into thin layers.

A suitable liquid crystal polymer is Vectra® (Hoechst-Celanese)
, Xydan® (Amoco Performance Products), HX type liquid crystal polymer (DuPont), Eikonol® and Sumika.
super (registered trademark) (Sumitomo Chemical), Rodrun (registered trademark) (Unitika)
, Granlar®, and the like, selected from aromatic copolyesters, such as commercial products. The thin layer of liquid crystal polymer can be obtained by making the liquid crystal polymer as wide as the plastic material forming the outer layer of the drug capsule, such as polycarbonate. This results in an annular morphology that is thermoformed to the desired shape.

The parylene coating is formed by the active monomer gas polymerizable on the surface of the preformed outer sleeve. It is typically formed from a few molecules to a layer 75 microns thick.

A preferred material for the piston is polytetrafluoroethylene (PTFE), which has low stiction (similar coefficients of kinetic and traction) and excellent chemical resistance. Due to its ease of deformation, pistons made of this material can be inserted to provide an interference fit within the inner bore of the capsule, and also at the high strain rates that occur during the first part of the injection. Has elastic modulus. Due to the latter property,
A high coefficient of restitution and maximum energy transfer from the actuator to the drug are ensured. It should be noted that many prior art syringes specify the use of "O" ring seals on the piston, which has a number of drawbacks. As one of them,
"O" ring seals are known to "weld" to the inner bore of the capsule upon prolonged contact with no lubricant or release agent at the interface. In a conventional method of improvement, the capsule body is coated with a silicone emulsion and baked to form a very thin film of lubricant. Alternatively, the "O" ring can be siliconized. In this case, the only option is to use treated "O" rings, as the baking process is not suitable for plastics. Highly transparent plastics are amorphous, the most suitable type for storing chemicals is very sensitive to contact with oil and cracks on contamination. Another problem with the "O" ring is
The small movement of the ring in the groove at the start of injection is due to the pressure pulse within the drug.
re pulse) is to increase the rise time. A potential disadvantage of using PTFE is 25 kGy (2
． Most of the intensity is lost when irradiated with 5 Mrad). Furthermore, P
It has been discovered that TFE, when exposed to irradiation under mechanical stress, deforms to reduce that stress. Therefore, the piston irradiated in the inner hole may be released, or the sealing in the inner hole may be insufficient. Therefore, the PTFE piston is preferably pretreated at elevated temperature with gamma or other high energy radiation. It has been found that this treatment causes crosslinking, resulting in increased strength and resistance to further irradiation.

FIG. 6 shows another example of the drug capsule. The capsule 2 has an inner hole 9 which expands at the open end of 9A. The inner bore 9A is shown as a taper that facilitates manufacturing, but can be a parallel inner bore that is joined to the inner bore 9 by a short taper. The piston 10 is loosely fitted in the inner hole 9A, and the capsule 2
It is held in this position by staking the rim 2A of the stake. Alternatively, other holding means can be used. The pile enclosure 20 can be formed by thermal displacement or ultrasonic displacement of the rim 2A.

The preferred material for the piston 10 is PTFE, and because the piston 10 is loosely fitted in the bore 9A and is not mechanically stressed, the piston 10 is exposed to normal levels, ie up to 40 kGy of gamma radiation. Does not deteriorate. In any case, the gap between the piston 10 and the inner hole 9A is capable of steam infiltration for high-pressure steam sterilization or gas sterilization with ethylene oxide. Both of these are common choices for sterilizing devices that deliver drugs parenterally. Therefore, the piston and capsule can be assembled clean and then sterilized by any known method.

After sterilization, the capsules are filled. As shown in FIG. 7, the piston 10 is pushed into the substantially parallel inner hole 9 from the enlarged inner hole 9A, and the rib 10b comes into contact with the inner hole 9 in a sealed state. Alternatively, the piston can be pushed to the ejection end of the capsule and placed at 10A. Thereafter, the capsule is filled with the injection solution 12 as shown in FIG. 8 and sealed by the plug 13 or the cap 13A. The plug 13 can have a protrusion 13 </ b> B that seals the filling port 21.

In the present application, the term “plastic” refers to a specific organic substance, which is mainly a synthetic or semi-synthetic (casein and cellulose derivative) condensation or polymerization product, and a plastic by heating and pressurization, and then molding, Certain natural materials that can be cast or extruded in molds (shellac, bitumen, except natural rubber)
Is used in the general sense of and.

[Brief description of drawings]

[Figure 1]   It is a figure which shows the 1st example of the plastic chemical | medical agent capsule by this invention.

2 and 3   It is a figure which shows filling of the chemical | medical agent capsule of FIG.

[Figure 4]   FIG. 2 shows the drug capsule of FIG. 1 assembled on the body of a needleless syringe.

FIG. 5 is a diagram showing an example of a needle-free injector incorporating a second example of the plastic drug capsule according to the present invention.

[Figure 6]   It is a figure which shows the 3rd example of the medicine capsule by this invention.

7 and 8   It is a figure which shows filling of the chemical | medical agent capsule of FIG.

[Procedure for Amendment] Submission for translation of Article 34 Amendment of Patent Cooperation Treaty

[Submission date] July 6, 2001 (2001.7.6)

[Procedure Amendment 1]

[Document name to be amended] Statement

[Name of item to be amended] Claims

[Correction method] Change

[Contents of correction]

[Claims]

26. the stop is claim 25 chemicals capsule according comprising several integral Kuikakomi formed by thermal distortion or ultrasonic displacement of the material at the opening of the extension chamber (stake).

27. the stop is medicine capsule of claim 25, further comprising a separate fitting means coupled to the opening of the extension chamber.

28. Pharmaceutical capsule according to claim 25, wherein the extension chamber comprises a tapered portion.

29. extension chamber, drug capsule according to claim 28, wherein being tapered over its entire length.

30. The drug capsule of claim 28 , wherein the extension comprises a parallel portion and a taper portion, the taper portion being provided at a transition between the main chamber and the extension chamber.

It comprises a first inner layer of 31. Drug compatible transparent plastic defining a chamber for containing a liquid, and a second outer layer of transparent plastic for forming the support sleeve around the first plastic layer 26. The transparent needleless syringe drug capsule of claim 25 , wherein the first and second transparent plastic layers each have resistance to discoloration when exposed to high-energy radiation and are suitable for pre-filling with a liquid agent. .

32. The needleless syringe according to claim 31 , wherein the first and second plastic layers are injection molded and the first layer is joined to the second layer at the interface.

33. The needleless syringe drug capsule of claim 31, wherein the second plastic layer has a higher melting point than the first plastic layer.

34. The needleless syringe drug capsule of claim 31, wherein the first plastic layer is a metallocene catalyzed polymer.

35. A needle-less injector drug capsule as claimed in claim 31, wherein the first plastic layer is a cyclic olefin copolymer.

36. The needleless syringe drug capsule of claim 31, wherein the second plastic layer is a polymer selected from the group consisting of polyester, copolyester, polyethylene naphthalate, polyamide, and polyurethane.

37. The needleless syringe drug capsule of claim 31 , further comprising a piston of polytetrafluoroethylene in the chamber for injecting the drug.

38. The needleless syringe drug capsule of claim 31, wherein the first plastic layer is extended to form an integral fill adapter.

39. The needleless syringe drug capsule of claim 31 , wherein the fill adapter includes a fragile, tamper evident coupling.

40. A needle-free injector comprising the drug capsule according to claim 25 .

41. A combination of the drug capsule of claim 25 and a free piston.

42. The combination of claim 41, wherein the free piston is made of PTFE.

43. A method of manufacturing a drug capsule, comprising a needleless syringe comprising a body having a main chamber for containing a liquid agent and thereafter retaining a free piston in a hermetically sealed condition for use in injection of the drug. Forming a drug capsule, wherein the body further comprises an extension chamber having an opening for accommodating the free piston, and assembling the free piston in a loose fit within the extension chamber; Sterilizing, and placing a free piston in a hermetically sealed condition within the main chamber.

44. The method of claim 43 , further comprising the step of filling a drug capsule.

45. The method of claim 43 , wherein after pushing the piston to the ejection end, the capsule is filled with the injectable solution, whereby the pressure of the injectable solution returns the piston to the other end of the main chamber.

46. The method of claim 43 , wherein the injection solution is introduced by first evacuating the volume of the main chamber and then filling the main chamber with the injection solution.

47. The method of claim 43, wherein the sterilizing step comprises fluid sterilization.

48. The method of claim 4 7, wherein fluids for sterilization is steam or ethylene oxide.

49. The method of claim 43, wherein the sterilizing step comprises exposing to high energy radiation.

50. The method of claim 43 , wherein the capsule is formed of glass.

51. The method of claim 43 , wherein the capsule is formed of plastic.

─────────────────────────────────────────────────── ─── Continued front page    (81) Designated countries EP (AT, BE, CH, CY, DE, DK, ES, FI, FR, GB, GR, IE, I T, LU, MC, NL, PT, SE), OA (BF, BJ , CF, CG, CI, CM, GA, GN, GW, ML, MR, NE, SN, TD, TG), AP (GH, GM, K E, LS, MW, MZ, SD, SL, SZ, TZ, UG , ZW), EA (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM), AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BY, CA, C H, CN, CR, CU, CZ, DE, DK, DM, DZ , EE, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE, K G, KP, KR, KZ, LC, LK, LR, LS, LT , LU, LV, MA, MD, MG, MK, MN, MW, MX, MZ, NO, NZ, PL, PT, RO, RU, S D, SE, SG, SI, SK, SL, TJ, TM, TR , TT, TZ, UA, UG, US, UZ, VN, YU, ZA, ZW

Claims (52)

[Claims] 1. A transparent needleless syringe drug capsule suitable for prefilling a liquid drug, comprising: a first inner layer of a drug compatible transparent plastic defining a chamber for containing the liquid drug; A second outer layer of transparent plastic forming a support sleeve around the plastic layer, the first and second transparent plastic layers each being resistant to discoloration when exposed to high energy radiation. Needleless syringe drug capsule. 2. The needleless syringe of claim 1, wherein the first and second plastic layers are injection molded and the first layer is interfaced to the second layer. 3. The needleless syringe drug capsule of claim 1, wherein the second plastic layer has a higher melting point than the first plastic layer. 4. The needleless syringe drug capsule of claim 1, wherein the first plastic layer is a metallocene catalyzed polymer. 5. The needleless syringe drug capsule of claim 1, wherein the first plastic layer is a cyclic olefin copolymer. 6. The needleless syringe drug capsule of claim 1, wherein the second plastic layer is a polymer selected from the group consisting of polyester, copolyester, polyethylene naphthalate, polyamide, and polyurethane. 7. The needleless syringe drug capsule of claim 1 further comprising a polytetrafluoroethylene piston in the chamber for injecting the drug. 8. The needleless syringe drug capsule of claim 1, wherein the first plastic layer is extended to form an integral fill adapter. 9. The needleless syringe drug capsule of claim 8, wherein the fill adapter includes a fragile, tamper evident coupling. 10. A body having a main chamber for containing a liquid agent and thereafter holding a free piston in a hermetically sealed condition for use in injection of a medicament, the body further comprising a free piston in the loosely fitted state. The needleless syringe drug capsule of claim 1 having an extension chamber having an opening for receiving. 11. The needleless syringe drug capsule of claim 10, further comprising a stop for retaining the free piston within the extension chamber. 12. The needleless syringe drug capsule of claim 11, wherein the stop comprises a number of integral stakes formed by thermal or ultrasonic displacement of material at the opening of the extension chamber. . 13. The needleless syringe drug capsule according to claim 11, wherein said stop comprises a separate mating means coupled to the opening of the extension chamber. 14. The needleless syringe drug capsule of claim 10, wherein the extension chamber comprises a taper. 15. The needleless syringe drug capsule of claim 14, wherein the extension chamber is tapered along its entire length. 16. The needleless syringe drug capsule of claim 14, wherein the extension comprises a parallel portion and a taper portion, the taper portion being provided at a transition between the main chamber and the extension chamber. 17. A needle-free injector comprising the drug capsule according to claim 1. 18. The needleless syringe according to claim 17, wherein the second or outermost plastic layer is an integral part of the body of the needleless syringe. 19. A method of making a transparent drug capsule for a needleless syringe, the method comprising forming a multi-layer capsule having a first inner layer of drug compatible transparent plastic and a second outer support layer of transparent plastic. And wherein the first and second transparent plastic layers are each selected to be resistant to discoloration upon irradiation, and sterilizing the multilayer capsule by high energy irradiation. 20. The method of claim 19, wherein the first and second plastic layers are injection molded such that the two layers are joined at the interface between each other. 21. The method of claim 19, wherein the second plastic layer has a higher melting point than the first plastic layer. 22. The method of claim 19, wherein the drug capsule is preassembled with a piston of polytetrafluoroethylene located within the capsule. 23. The method of claim 22, wherein the polytetrafluoroethylene piston is pretreated by exposure to high energy radiation at elevated temperatures. 24. The method of claim 19, further comprising the step of filling the sterilized chemical capsules with the liquid in an automated filling process and then sealing the capsules in a manner suitable for shipping and long term storage. 25. A drug capsule for a needleless syringe, comprising a body having a main chamber for containing a liquid agent and subsequently holding a free piston in a hermetically sealed condition for use in injection of the drug, said body comprising: Further, the drug capsule having an extension chamber having an opening that accommodates the free piston in a loose fit. 26. The drug capsule of claim 25, further comprising a stop for retaining the free piston within the extension chamber. 27. The drug capsule of claim 26, wherein the stop comprises a number of integral stakes formed by thermal or ultrasonic displacement of material at the opening of the extension chamber. 28. The drug capsule of claim 26, wherein the stop comprises a separate mating means coupled to the opening of the extension chamber. 29. The drug capsule of claim 25, wherein the extension chamber comprises a taper. 30. The drug capsule of claim 29, wherein the extension chamber is tapered along its entire length. 31. The drug capsule of claim 29, wherein the extension comprises a parallel portion and a taper portion, the taper portion being provided at a transition between the main chamber and the extension chamber. 32. A first inner layer of chemically compatible transparent plastic defining a chamber for containing a liquid agent, and a second outer layer of transparent plastic forming a support sleeve around the first plastic layer. 26. The transparent needleless syringe drug capsule of claim 25, wherein the first and second transparent plastic layers each have resistance to discoloration when exposed to high-energy radiation and are suitable for pre-filling with a liquid agent. . 33. The needleless syringe of claim 32, wherein the first and second plastic layers are injection molded and the first layer is interfaced to the second layer. 34. The needleless syringe drug capsule of claim 32, wherein the second plastic layer has a higher melting point than the first plastic layer. 35. The needleless syringe drug capsule of claim 32, wherein the first plastic layer is a metallocene catalyzed polymer. 36. The needleless syringe drug capsule of claim 32, wherein the first plastic layer is a cyclic olefin copolymer. 37. The needleless syringe drug capsule of claim 32, wherein the second plastic layer is a polymer selected from the group consisting of polyester, copolyester, polyethylene naphthalate, polyamide, and polyurethane. 38. The needleless syringe drug capsule of claim 32, further comprising a piston of polytetrafluoroethylene in the chamber for injecting the drug. 39. The needleless syringe drug capsule of claim 32, wherein the first plastic layer is extended to form an integral fill adapter. 40. The needleless syringe drug capsule of claim 32, wherein the fill adapter includes a fragile, tamper evident coupling. 41. A needleless syringe comprising the drug capsule of claim 25. 42. A combination of the drug capsule of claim 25 and a free piston. 43. The combination according to claim 42, wherein the free piston is made of PTFE. 44. A method of manufacturing a drug capsule, comprising: a needleless syringe comprising a body having a main chamber for containing a liquid agent and subsequently holding a free piston in a sealed fit for use in injection of the drug. Forming a drug capsule, wherein the body further comprises an extension chamber having an opening for accommodating the free piston, and assembling the free piston in a loose fit within the extension chamber; Sterilizing, and placing a free piston in a hermetically sealed condition within the main chamber. 45. The method of claim 44, further comprising the step of filling a drug capsule.
The method described. 46. The method of claim 44, wherein after pushing the piston to the ejection end, the capsule is filled with the injectable solution, whereby the pressure of the injectable solution causes the piston to return to the other end of the main chamber. 47. The method of claim 44, wherein the injection solution is introduced by first evacuating the volume of the main chamber and then filling the main chamber with the injection solution. 48. The method of claim 44, wherein said sterilizing step comprises fluid sterilization. 49. The sterilizing fluid is steam or ethylene oxide.
8. The method according to 8. 50. The method of claim 44, wherein said sterilizing step comprises exposing to high energy radiation. 51. The method of claim 44, wherein the capsule is formed of glass. 52. The method of claim 44, wherein the capsule is made of plastic.