SK12502002A3 - Miniaturized needleless injector - Google Patents

Abstract

Needleless injectors for liquids are known from the art in a variety of designs that are adapted to different conditions of application. The inventive needleless injector is designed as a hand-held device. It comprises a lockable tensioning system, an energy-storing spring (36), a hollow piston (37) displaceable within a cylinder (38), and a nozzle (39). The hollow piston is provided with a valve body on its one end. The storage container (44) for the liquid is disposed within the housing. The lockable tensioning system is tensioned by counterrotating the two housing parts (31; 32), thereby withdrawing the hollow piston (37) from the cylinder (38). At the same time the amount of liquid required for the injection is withdrawn from the storage container (44) and transported through the hollow piston to the pump chamber (34). When the lockable tensioning system is released, the amount of liquid is ejected from the pump chamber through the nozzle. The needleless injector is easy and reliable to handle also for unpracticed people. It is used for intracutaneous injections of a medical liquid into biological tissue, for injecting a liquid containing an active substance into a plant or for injecting a liquid through a membrane into the space behind said membrane.

Description

Needle-free syringe and its use

Technical field

I

The invention relates to a needle-free syringe as a hand-held device, preferably in a miniature embodiment, by means of which the fluid is injected intradermally into, for example, human or animal tissue. The purpose of the invention is to extend the field of application of such a syringe.

BACKGROUND OF THE INVENTION

The fluids within the meaning of the invention are preferably solutions, suspensions or dispersions which contain the active ingredient. The active substances may be pharmacologically active substances for the treatment of the human or animal body, or they may contain substances for diagnosis or for cosmetic use.

Substances for non-pharmaceutical use can be, for example, insecticides, fungicides, growth-promoting or growth-inhibiting agents or fertilizers in the field of plant protection. The needleless syringe of the present invention allows for an environmentally acceptable use of systemic agents, since the active ingredient is delivered directly to the plant.

From EP-0 063 341 and EP-0 063 342, a needleless syringe is known which comprises a piston pump for ejecting the fluid to be injected, which is driven by a pushing means through the engine. The fluid container is located laterally on the piston pump. The amount of fluid required for injection is sucked into the pump chamber when the piston is pulled back through the inlet channel and the non-return valve. As the piston moves in the direction of the nozzle body, the fluid is forced through the discharge channel to the nozzle and expelled. The piston of the piston pump is a massive round piston.

EP-0 133 471 discloses a needleless inoculation device which is driven from a siphon cartridge by pressurized carbon dioxide through a special valve.

EP-Ο 347 190 discloses a syringe with a vacuum-compressed gas system at which the depth of injection of the injected medicament is adjustable by gas pressure and the volume of the medicament by the stroke of the plunger.

EP 0 427 457 discloses a needleless hypodermic syringe which is driven by compressed gas through a two-stage valve. The injection device is contained in an ampoule that is inserted into a protective sheath that is attached to the syringe body. The ampoule is mounted on the end of the piston rod. At the other end of the vial is a nozzle whose diameter tapers towards the end of the vial.

WO-89/08469 discloses a disposable needle-free syringe. WO-92/08508 discloses a needleless syringe that is sized for three injections. The vial containing the medicament is screwed onto one end of the drive unit, thereby inserting the plunger rod into the open end of the vial. The ampoule contains a nozzle at one end through which the medicine is expelled. A sliding stopper is available about the middle of the ampoule length. The dose to be injected is adjustable by the insertion depth of the vial. The plunger rod that protrudes from the drive unit after actuation of the syringe is retracted by hand. Both devices are powered by compressed gas.

WO-93/03779 discloses a needleless syringe with a two-piece housing and a fluid container mounted on the side of the apparatus. The piston drive spring is tensioned by a gear motor. The spring is released as soon as the two housing parts are moved relative to each other by pressing the nozzle against the injection site. There is one valve in the liquid suction channel and at the outlet of the dosing chamber.

WO-95/03844 discloses another needleless syringe. It comprises a liquid-filled cartridge which at one end contains a nozzle through which the fluid is expelled. At the other end, the cartridge is closed by a cap-like piston which can be inserted into the cartridge. The spring loaded piston moves the cap-shaped piston by a predetermined amount into the cartridge after the spring is released, expelling the amount of fluid to be injected. The spring is released as soon as the nozzle is pressed firmly against the injection site. This syringe is for single or multiple use. The cartridge is arranged in front of the resiliently loaded plunger and is a fixed part of the injection

-3striekačky. The plunger plunger position, which is intended for multiple uses, moves a bit towards the nozzle after each use. The piston and drive spring cannot be reset. The preload of the spring is initially large enough to expel all of the fluid in the cartridge at once. The spring can only be re-tensioned when the syringe is disassembled and the syringe drive part is connected to a new, fully filled cartridge.

FR-2 629 706 discloses two embodiments of a needleless syringe for use in dentistry with which a predetermined amount of fluid can be injected into the gum. The two syringes each consist of two parts which are coaxially folded together and releasably connected to each other. The working medium is compressed air, which is supplied to the syringe from outside. When the syringe is actuated by the trigger button, the working piston is suddenly moved by a predetermined piece by the action of the compressed air, the coil springs and the locking devices, and the amount of fluid to be injected is expelled through the nozzle. At the same time, a plurality of coil springs are tensioned to move the multiple axial sliding members within the syringe again to their initial position as soon as the used compressed air is no longer applied. The fluid to be injected is placed inside the syringe in a tubular rigid container which is provided at one end with a stopper displaceable inside the container which, via a resiliently loaded piston, holds the liquid contained in the container permanently under pressure. When a portion of the fluid is pushed from the reservoir into the fluid space inside the pump cylinder, the compression spring pushes the plug through the plunger by a corresponding piece into the fluid reservoir.

In several known embodiments of the needleless syringe, the fluid container to be injected is arranged laterally at the drive unit. The amount of liquid to be injected is sucked into the pump chamber when the massive piston of the piston pump is drawn back. The inlet channel comprises an inlet valve, the outlet channel includes an outlet valve. Both valves operate by force.

In other embodiments of the needleless syringe, the fluid container to be injected serves directly as a pump chamber and is

- exposed to the force shock that occurs when the amount of fluid to be injected is expelled.

In needleless syringes powered by pressurized gas, part of the pressurized gas escapes after each injection. The compressed gas reservoir is optionally replaceable but cannot be refilled immediately with compressed gas. For these syringes, the drive unit must be replaced as soon as the compressed gas reservoir is empty.

The object of the invention is to provide a reusable needle-free syringe with a simpler construction, which is preferably suitable for repeated expulsion of a predetermined amount of fluid. The total amount of fluid expelled after many uses should preferably be greater than the amount of fluid contained in a single reservoir. It should be possible to either collect a plurality of fluid quantities one after the other from the storage container, or to collect and expel the fluid contained in one storage container at once. The storage container should be easily replaceable. A predetermined amount of fluid must be given sufficient mechanical shock (pulse) to allow the predetermined amount of fluid to penetrate the membrane, foil or biological tissue.

The essence of the invention

The problem was solved by a needleless fluid syringe, which, as a handheld device, is arranged in a cylindrical housing and contains a fluid reservoir, which is based on the fact that

- the cover consists essentially of two parts which are releasably or non-releasably connected to each other and rotatable to one another,

the needle-free syringe comprises a locking tensioning mechanism for a spring-actuated drive which is tensioned prior to expelling a predetermined amount of fluid and is provided with a triggering device, wherein a hollow piston is mounted on the locking piece of the locking tensioning mechanism; the piston is displaceably disposed within the cylinder and protrudes from one end thereof

Preferably, a valve body, which is the sole valve body of the needle-free syringe, is disposed at the other end thereof, and a nozzle with at least one opening is located at the end of the cylinder and the space between the nozzle and the end of the hollow piston is a pump space;

- inside the housing there is a fluid reservoir which is formed as a needle-free syringe which is detachable, which is - preferably by means of a press fit - releasably connected to that end of the hollow piston which protrudes from the cylinder,

- the amount of fluid to be transported when the latch piece and the hollow piston associated therewith through the hollow piston into the pump chamber are determined by the stroke and cross-section of the hollow piston.

The locking tensioning mechanism consists of a spring-loaded driven flange as a snap piece, a spring-tensioning drive, a locking member, two stops for the driven flange between which the driven flange can be moved back and forth, and a device for releasing the locking member. The path of the driven part is precisely defined by the two stops. A transmission transmission force is arranged between the energy storage springs and the spring tension drive. The locking member has an annular shape and has sliding locking surfaces. Advantageously, a cylindrical coil spring or a plate spring or a leaf spring which acts as a tension spring or a compression spring can be used for energy storage.

The energy storage spring can be tensioned by direct drive. Thereafter, the driven flange is displaced by an axially acting external force. At a high spring force, a force transforming the gear, for example a helical-sliding gear, by means of which the spring is tensioned by external torque, is advantageous. Such a transmission is a single or multi-stage transmission which is arranged between the spring and the spring tensioning drive.

The driven flange may be pot-shaped. For example, the flange of the driven flange may comprise two sawtooth-shaped recesses on which two sawtooths slide on the upper housing part.

The mean spring force may be 10 N to 150 N. Between the two positions of the latch piece of the locking tensioning mechanism, the spring force varies by about ± 10% of the mean spring force.

The locking member may be a radially elastically deformable ring or a rigid ring with sliding cams, or a rigid ring with shaped leaf springs, or a ring which is biased by one or more metal springs. The ring may be open or closed; it may consist of several parts. The locking member is displaceably disposed in a plane perpendicular to, or deformable in, the axis of the housing.

Further details of the locking tensioning mechanism for the spring-actuated drive are described in DE-195 45 226.

A hollow piston is mounted in the latching member of the locking tensioning mechanism, which is driven by the locking tensioning mechanism. The hollow piston plunges into the cylinder and protrudes from the cylinder over a portion of its length; it is displaceable in the cylinder.

A nozzle is located at the end of the cylinder. The orifice opening may have a hydraulic diameter of from 10 µm to 500 µm, preferably from 50 µm to 150 µm. The nozzle orifice may have a length of from 50 pm to 500 pm, preferably from 100 pm to 300 pm.

In the case of a plurality of nozzle openings, the longitudinal axes of these openings may extend parallel to each other or may be inclined relative to one another so as to divide. With several orifice holes, their hydraulic diameter may vary.

The nozzle may be a prism composed of two silicon plates, for example 1.1 mm wide, 1.5 mm long and 2.0 mm high. The prism may comprise a flat, triangular, about 400 pm thick recess in the contact surface of the plates, which terminates in a single nozzle orifice that is 50 pm wide, 50 pm thick and 200 pm long. It may be expedient to enclose the nozzle over its entire circumference with a precision mating elastomer molding. The inner contour of the elastomer molding is adapted to the outer contour of the nozzle, the outer contour of the elastomer molding is adapted to the inner contour of the nozzle holder, which preferably consists of metal. Such floating clamping makes the nozzle of brittle material insensitive to shock

-7 the applied loads that occur when using the needle-free syringe for the purposes for which it is intended.

At the end of the hollow piston located within the cylinder there is preferably a valve body, preferably made in one piece, which is guided through the hollow piston and which is axially displaceable relative to the hollow piston. The valve body preferably has a uniaxial rotational symmetrical shape, such as a circular cylinder or truncated cone. Its diameter may be smaller than the diameter of the space in which the valve body is slidably arranged. The valve body can rotate about its axis. The axis of the valve body remains permanently parallel to the axis of the hollow piston. This creates a defined sealing surface on the inlet side of the valve body. The path along which the valve body can slide relative to the hollow piston is limited by a stop. In the position in which the valve body abuts the defined sealing surface, the valve is closed.

The space between the nozzle and the valve body located on the hollow piston is the pump space. A filter, which is preferably designed as a depth filter, may be located upstream of the end of the pump chamber from the nozzle side, i.e. in the fluid outlet channel. If the fluid to be injected contains suspended particles, the pore width of the filter must be adapted to the particle size.

Further details on the hollow piston and the valve body are given in DE 195 36 902.

The locking tensioning mechanism and the energy storing springs are preferably tensioned by rotating the two housing parts relative to each other, preferably by a helical-shift transmission. Torque can be generated by hand or by motor.

The diameter of the cylinder preferably practically coincides over its entire length with the outer diameter of the hollow cylinder. The roller may be fixedly fixed in one housing part. Furthermore, the cylinder can be displaceably disposed in this one housing part. The sliding cylinder is brought to its rest position by a return spring.

The two stops for the snap-in piece can be fixed in the cover. Furthermore, the position of one of these stops can be changed in the axial direction. Thus, the volume of the pump chamber can be varied at a constant outer diameter of the hollow piston. With an otherwise unchanged needle-free syringe design, the amount of fluid ejected can be changed by changing the stop position.

The position of the latch path and hence the stroke of the hollow plunger within the needle-free syringe is limited by both stops. At a given stop position, the position of the track of the snap piece and thus the stroke of the hollow piston is constant with each injection.

By means of the lowering device, the locking member is displaced parallel to the plane of the ring or radially deformed in the plane of the ring. With the cylinder fixed in the housing, the lowering device is actuated by the finger-pushable lowering button and the locking member is released. With the cylinder sliding in the housing, the lowering device is actuated by pushing the cylinder against the force of the return spring and the locking member is extended.

A fluid storage container is formed within the housing. The reservoir is formed as a reservoir separate from the needleless syringe; is connected to that end of the hollow piston which is opposite the pump chamber. This end of the hollow piston is covered with the liquid contained in the reservoir.

The supply container connected to the hollow piston may additionally be connected to the snap-in member. This connection may be a releasable or non-releasable engagement connection in which the latch member is provided with a plurality of latch hooks that extend into the peripheral groove on the reservoir after insertion of the reservoir into the needle-free syringe.

The amount of fluid to be expelled is determined by the stroke and cross-section of the hollow piston. The stroke of the hollow piston is limited by both stops for the driven flange.

It is expedient to provide a removable closure cap prior to the nozzle to protect the nozzle opening during storage of the needleless syringe before and during its shelf life against contamination and evaporation of the fluid.

The two housing parts, the locking tensioning mechanism, the cylinder and the storage container, preferably consist of plastic, for example polybutylene terephthalate. The hollow piston preferably consists of metal, for example stainless steel.

The valve body may consist of metal, ceramic, glass, gem, plastic or elastomer.

The nozzle may consist of metal, plastic, glass, silicon or gem, such as sapphire, ruby, corundum.

The filter preferably consists of sintered metal or sintered plastic.

The needle-free syringe is preferably designed as a hand-held device. It can be held and operated with one hand during the injection. The cylinder, hollow piston, valve body, nozzle and possibly filter are miniaturized parts.

The operation of the needle-free syringe will now be described.

The needle-free syringe is at rest during storage of the unused or just used needle-free syringe as well as between the two injections. The energy storage spring is preloaded. The latch piece abuts against a stop that limits the path of the latch member at rest. The hollow piston is deep in the cylinder. There is only a very small distance between the end of the hollow piston and the inside of the nozzle. The locking member is in the extended position.

When the two housing parts are rotated relative to each other, the locking tensioning mechanism is tensioned. The snap piece moves in the axial direction away from the cylinder, increasing the tension of the energy storing spring. At the same time, the hollow piston is pulled out of the cylinder a little and the pump space is increased. The hollow piston continues to extend part of its length into the cylinder. At the same time, a portion of the fluid contained in the storage container is transported through the hollow piston and beside the valve body to the pump chamber and the pump chamber is filled with fluid. The amount of fluid in the pump chamber practically coincides with the amount of fluid expelled upon injection. The latch piece is moved until the latch member snaps into its retracted position. With the needle-free syringe with the trigger button, this button protrudes a little from the cover.

The tip of the needle-free syringe from the nozzle side is inserted into the injection site and pushed. With a needle-free syringe with a trigger button, the trigger button is pressed with one finger and pressed into the housing. This moves the locking member to the extended position and actuates the injection. In a needleless syringe with a displaceably arranged cylinder, the syringe is pushed into the injection site with increasing force against the return spring force by its end on the nozzle side. In this case, the cylinder is inserted into the housing, the locking member being moved into

-10 position and injection starts. When the needle-free syringe is removed from the injection site, the return spring pushes the cylinder back to its rest position.

As soon as the locking member assumes the extended position, the force K of the tensioned, energy-storing spring acts through the latch member, the hollow piston and the closed valve at the end of the hollow piston during the time interval At thus the mechanical pulse K At = m · Av, with high velocity, emerges from the nozzle and intradermally penetrates the tissue. After the injection, the needle-free syringe is restored again.

The needleless syringe of the present invention can be used in human medicine and veterinary medicine to inject intra-cutaneously a preparation of an active substance existing in the form of a liquid, for example a medicament, into human or animal tissue. Examples of suitable pharmaceutical preparations are, inter alia, analgesics, vaccines, antidiabetics, hormones, contraceptives, vitamins, antibiotics, sedatives, antimicrobials, amino acids, coronary agents.

The drug preparation may exist in the form of a solution, suspension or emulsion. For suspensions, the average particle size should not exceed 15 µm, preferably 10 µm.

Suitable means for dissolving, suspending or emulsifying the active substances and, if necessary, the necessary auxiliaries are, for example, water, alcohols, alcohol-water mixtures, as well as oil-in-water or water-in-oil emulsions. These include purified, sterilized water, ethanol, propanediol, benzyl alcohols, ethanol mixtures, oils (such as coconut oil, peanut oil, soybean oil, castor oil, sunflower oil), fatty acid esters (such as isopropyl myristate, isopropyl palmitate, ethyl oleate), triglycerides, triacetin, solketal, propylene glycol. Further, these formulations may contain excipients such as preservatives as well as acids and bases for adjusting the pH.

The determined amount of fluid can be injected into the leaf or stalk of the plant or through the membrane into the space behind the membrane using a needleless syringe.

The needleless syringe of the present invention has the following advantages:

-11 - It has a suitable shape. The fluid reservoir is located in the syringe cover.

- Can be used for many - up to several hundred - injections, which can be taken from one or more reservoirs.

- There are no valves other than the valve at the end of the hollow piston.

- Even with high spring forces, the locking tensioning mechanism can be easily operated even by untrained persons and is tensioned by means of a screw-sliding transmission with relatively little force.

- The locking tensioning mechanism is manually actuated by pressing the trigger button with one finger or by pressing the needle-free syringe onto the injection site.

- The drive unit is not replaced, only the fluid reservoir is replaced.

- The valve, located at the end of the hollow piston, operates without auxiliary force and closes very quickly.

- The volume of the pump compartment can be changed by changing the position of one of the two stops.

- The mechanical pulse of the amount of fluid to be injected can be adapted to the desired depth of penetration into the tissue or the thickness of the membrane to penetrate.

- The fluid reservoir is adapted to the conditions of - and possibly multiannual - storage of the reservoir as well as its connection to the syringe. Its design is independent of the requirements of the pump chamber before the nozzle.

- The fluid reservoir is not exposed to the force of the injection.

- The fluid reservoir can be easily replaced.

The amount of fluid to be administered in the intended use can be easily administered in several partial amounts in succession at different points in the injection area.

- The needle-free syringe affects the injection site considerably less than a conventional syringe injection.

The invention will be explained in more detail by means of figures.

-12Overview of figures in drawings

In FIG. 1 is a longitudinal cross-sectional view of the needle-free syringe with the trigger button at rest, in which the cylinder is rigidly arranged in one housing part.

Fig. 2 shows a longitudinal section of the needle-free syringe without the trigger button in the tensioned state of the energy storage spring in which the cylinder is displaceably arranged in one housing part.

Fig. Figures 3 and 4 illustrate said one end of a storage container and a latch piece in another embodiment.

DETAILED DESCRIPTION OF THE INVENTION

In FIG. 1, the two housing parts 1 and 2 are shown which are releasably connected to one another and are rotatable relative to each other. The locking tensioning mechanism, which is in the rest state, shows the latching piece 3, the locking member 4 in the extended state, the trigger button 5 acting on the locking member, and the energy storing coil spring 6 in the form of a compression spring. A hollow piston 7 is mounted in the snap-in piece 3 and is inserted into the cylinder

8. A nozzle 9 with a nozzle aperture 10 is disposed at the end of the cylinder

11. The end of the hollow piston on the nozzle side is provided with a valve body 12. Between the valve body and the filter there is a pump space 13. The storage container 14 is arranged in a different free space inside the coil spring; The cage 16, which surrounds the coil spring, is connected to the housing part 1 by positive fit. The locking member 3 abuts against the stop 17. The nozzle is protected by a removable closing cap 18.

In FIG. 2, the two housing parts 31 and 32 are shown which are detachably connected to each other and rotatable relative to each other. From the locking tensioning mechanism in the tensioned state, there is shown a snap piece 33, the locking member 34 in the retracted state and the energy storing coil spring 36 in the tensioned state. A hollow piston 37, which is inserted into the cylinder 38, is fixed in the snap-in piece 33.

A nozzle 39 with a nozzle opening 40 is disposed at the end of the cylinder. The end of the hollow piston on the nozzle side is provided with a valve body 42. Between the valve body and the nozzle is a pump space 43. The reservoir 44 is arranged in a different space inside the coil spring; The cage 46, which surrounds the coil spring, is connected to the housing part 31 by positive fit. The latch member 33 abuts the inserted latch member 34 at the stop 47. The cylinder 38 is arranged axially displaceably in the part 31; is held in its rest position by a helical return spring 48 which acts as a compression spring. The cylinder 38 is provided with a lowering device (not shown) that extends the locking member 34 as soon as the cylinder 38 is pushed against the return spring force into the housing part 31 when the needle-free syringe is pushed onto the injection site. The path a of the driven part between the two stops is indicated by a. The stroke of the hollow piston agrees with this path.

Fig. 2 shows a needleless syringe mounted for injection. Nozzle 39 is pressed against schematically shown, tightly stretched skin 35; upon further pressing on the injection site, the needle-free syringe is lowered and the fluid from the pump chamber 43 is injected into the skin 39.

Fig. Figures 3 and 4 illustrate said one end of a storage container and a latch piece in another embodiment. In FIG. 3, the hollow piston is introduced into the storage container but not yet connected to the hollow piston.

In FIG. 3, the (three-layer) storage container 54 is shown partially in longitudinal section. The outer layer of the reservoir is a rigid sleeve 55, which is provided with a peripheral groove 52. The reservoir is closed by a plug 56 that passes into the immersion throat 58 by a press fit 59. the piece is provided on its side facing the storage container with a plurality of snap hooks 51.

In FIG. 4, the storage container is connected to the hollow piston and the latch piece, i.e. the hollow piston through a press fit 59 and to the latch piece through the latching hooks 51 that extend into the peripheral groove 52 of the storage container.

The connection between the supply container and the latch piece shown in FIG. 3 and FIG. 4, consists of snap hooks 51 with round arms and a peripheral groove 52 with a semicircular cross-section. This connection is a releasable plug-in connection.

For non-releasable plug-in connections, snap hooks with sawtooth-shaped arms and a circumferential groove with a triangular cross-section can be selected.

Example 1

A needle-free syringe construction according to the present invention

The needle-free syringe for intradermal injection into biological tissue has the following features:

The cover has an outer diameter of about 20 mm and a length of about 70 mm. Both housing parts, locking mechanism and spring cage are made of polybutylene terephthalate. The cylinder also consists of polybutylene terephthalate; it has an outer diameter of 5 mm and an inner diameter of 1.60 mm. The nozzle consists of quartz. The orifice has a diameter of 140 µm and a length of 220 gm. The stainless steel hollow piston has an outside diameter

1.59 mm and internal diameter 0.35 mm. The piston stroke is 12 mm. The valve body comprises an elastomer; It takes the form of a 2 mm thick disc with an outside diameter

1.60 mm. The disc is provided with axial recesses on its housing through which fluid can flow into the pump chamber alongside the valve body. The end of the hollow piston is provided with a groove into which the valve body extends. The expelled amount of fluid is about 23 mm ³ . The replaceable storage container has a volume of about 11

Example 2

Intra-skin application of fluid

An injectable solution of 20 g dextran-fluorescein (UW 3000) per liter of distilled water was injected into two narcotized dogs using the needle-free syringe of the invention through the skin. 4.5 ml of dextranfluorescein solution was then filled into a needle-free syringe reservoir and

The 15-reservoir was connected to the hollow plunger of the syringe. The syringe was actuated by multiple tensioning and releasing the locking tensioning mechanism to expel air from the hollow piston, pump chamber and nozzle. Subsequently, the needle-free syringe was pre-mounted

I shaved the skin in the area of the abdomen of the dogs and got into action. This procedure was repeated several times.

Blood samples were taken at regular intervals and the dextran-fluorescein content in blood plasma was determined. The results demonstrate the functional capability of the needleless syringe of the present invention.

Example 3

In vitro assay of viral suspension

Laboratory investigations using a needle-free syringe have determined whether the viability of suspended live viruses is reduced when the suspension is expelled through a needle-free syringe nozzle.

Only about 1 log ₁₀ PFU (plaque forming units) of relatively large DNA viruses (test virus: Vaccinia virus) and less (about 0 log) were detected from the virus suspension recovered after expulsion from the needle-free syringe. , 5 log-ιο PFU) for small RNA-viruses (test virus: bovine viral diarrhea virus).

Example 4

In vivo administration of a vaccine with modified live viruses

In an animal experiment, the applicability of a needleless syringe to administer a vaccine suspension with modified live viruses was investigated. In this study, both the safety and tolerability of vaccination with a needleless syringe and the efficacy of this route of administration were investigated.

Six healthy dogs of the same age were divided into two groups. Group 1 included two dogs, group 2 included four dogs. Animals of both groups

They were vaccinated with a three-weekly modified live canine adeno virus vaccine at three weeks intervals.

In Group 1, 1 milliliter of canine adenovirus (CAV-1) vaccine (Galaxy DA2ppvL + Cv, SNo 610041; Solvay Animal Health Inc.) was administered intramuscularly according to the manufacturer's recommendations using a classical syringe. In Group 2, the canine adenovirus experimental vaccine was administered using a needleless syringe.

The experimental vaccine (CAV-2) used to vaccinate Group 2 animals was produced from an attenuated canine adenovirus strain. The titer was 7.2 log 10 TCID 50 per 60 microliters (TCID = tissue culture infective dose). Six single doses were administered at each vaccination time (six times 10 microliters = 60 microliters for each vaccination). The injection area on the back of the dogs was shaved and the six injection sites were each marked with a ballpoint pen.

Vaccination efficacy was determined by determining the number of virus-neutralizing antibodies in the sera of dogs three weeks after each vaccination.

Tolerance was assessed by observing injection sites six hours after vaccination and daily thereafter until the end of the animal experiment. Injection areas were photographed and the finding was recorded after the injection sites were palpated.

This experiment showed:

In Group 2 animals, only a very small redness of injection sites was detected during the first 2 to 3 days. A transient swelling of 1-2 days was detectable only by palpation. This small and quite acceptable local reaction is very likely to be related to the local enhancement of the administered modified live virus and should therefore be viewed as essential for good efficacy. This explanation is supported by the fact that after injection of physiological saline solution using a needle-free syringe, no or even minor transient swelling was observed.

Efficacy was determined by virus neutralization assay. The results are shown in Table 1. The highest titers are still uptake to neutralize canine adenoviruses.

-17 In the sera of all animals from both groups, virus neutralizing antibodies were detected three weeks after the first vaccination. After the second and third vaccinations, a moderate booster effect was shown.

Vaccination with an experimental canine, adenovirus vaccine with a needle-free syringe is exactly as effective as intramuscular vaccination with a commercially available vaccine with a classical syringe.

Table 1: Canine adenovirus; neutralizing virus titer in dog serum

The dog VN-titer in dog serum Number experiment mark 21 days after the first vaccinations 21 days after the second vaccinations 21 days after the third vaccinations CAV-1 Commercial Vaccine Int shots by muscular injection <BRA DAD 1496 - 1024 1024 4096 1498 - 1024 1024 512 CAV-2 experimental vaccine subcutaneously by needle-free injection syringes 1494 TTK9 4096 4096 8192 1495 USK9 4096 4096 8192 1497 UVL9 4096 8192 4096 1499 TYL9 2048 2048 2048

Claims (25)

PATENT CLAIMS 1. A needle-free fluid syringe, which is designed as a hand-held device, with a cover and a reservoir for said fluid, characterized in that: - the housing has two parts (1, 2), (31, 32) which are connected to each other and rotatable relative to each other, and - the needle-free syringe comprises a locking tensioning mechanism with a latch piece (3, 33, 53) slidable between two stops (17, 47), which is provided with a triggering device, as well as a hollow piston (7, 37, 57) mounted in a locking piece (3, 33, 53), and which is driven by a locking tensioning mechanism, wherein the hollow piston is displaceably disposed within the cylinder (8, 38) and comprises a single valve body (12, 42), and a nozzle located at the end of the cylinder (9, 39) with at least one opening (10, 40), and the space between the nozzle and the valve body forms a pump space (13, 43), and - the fluid storage container (14, 44, 54) is arranged inside the housing and is formed as a container separate from the needle-free syringe and is connected to the end of the hollow piston that protrudes from the cylinder, and - the amount of fluid that is transported through the hollow piston to the pump chamber (43) when the hollow piston (7) is removed from the cylinder (8) is determined by the stroke (a) and the cross-section of the hollow piston, - the stroke position (a) of the hollow piston inside the needle-free syringe is determined by the position of both stops (17, 47). Needle-free syringe according to claim 1, characterized in that the two housing parts (1, 2, 31, 32) are releasably connected to each other. Needle-free syringe according to claims 1 and 2, characterized in that - the nozzle (9, 39) comprises only one opening (10, 40) with a hydraulic diameter of from 10 pm to 500 pm, preferably from 50 pm to 150 pm, and The 19-orifice (10, 40) has a length of from 50 µm to 500 µηη, preferably from 100 µιτι to 300 µιτι. Needle-free syringe according to claims 1 and 2, characterized in that the nozzle (9, 39) comprises a plurality of nozzle openings, the hydraulic diameters of which may be different. Needle-free syringe according to claims 1 and 2, characterized in that the nozzle (9, 39) comprises a plurality of nozzle orifices whose longitudinal axes extend parallel to one another or are inclined relative to one another. Needle-free syringe according to claims 1 to 5, characterized in that the position of the stop and thus the stroke (a) of the hollow piston are variable. Needle-free syringe according to claims 1 to 6, characterized in that the locking tensioning mechanism can be tensioned by rotating the two housing parts (1, 2), (31, 32) relative to each other by hand. Needle-free syringe according to claims 1 to 7, characterized in that the locking tensioning mechanism can be tensioned by rotating the two housing parts (1,2), (31, 32) with each other by a screw-sliding transmission. Needle-free syringe according to claims 1 to 8, characterized in that the locking tensioning mechanism comprises a coil spring (6, 36), a disc spring or a leaf spring as an energy storage device. Needle-free syringe according to claims 1 to 9, characterized in that the nozzle (9, 39) consists of metal, plastic, glass, silicon or gemstone such as sapphire, ruby, corundum. Needle-free syringe according to claims 1 to 10, characterized in that the separate fluid container (14, 44, 54) is releasably connected to the end of the hollow piston by means of a press fit (19, 49, 59). that protrudes from the cylinder. Needle-free syringe according to claims 1 to 11, characterized in that the separate fluid container (14, 44, 54) is releasably connected to the hollow piston (7, 37, 57) and is movable within the hollow piston stroke. cover. Needle-free syringe according to claims 1 to 12, characterized in that the separate fluid container (14, 44, 54) is designed as a replaceable storage container, and that the snap-in piece (53) is adapted to receive said separate container. . 14. A needle-free syringe according to claims 1a13, characterized in that - the separate fluid storage container (54) is releasably connected to the hollow piston (57) and the snap-fit piece (53), and - the catch piece (53) is provided with catch hooks (51) which extend into the peripheral groove (52) on the supply container. Needle-free syringe according to claims 1 to 14, characterized in that the nozzle-side end of the needle-free syringe is provided with a closure cap (18). Needle-free syringe according to claims 1 to 15, characterized in that a filter (11) is arranged in front of the nozzle side facing the pump chamber. Needle-free syringe according to claims 1 to 16, characterized in that the separate fluid container (14, 44, 54) is filled with a liquid medicament, preferably from the group consisting of analgesics, vaccines, anti-21 diabetics, hormones, contraceptives, vitamins, antibiotics, sedatives, antimicrobials, amino acids, coronary agents. Needle-free syringe according to claims 1 to 3, which is designed as a hand-held device, with a cover and a fluid reservoir, characterized in that: - the locking tensioning mechanism comprises a coil spring (6, 36), and the locking tensioning mechanism can be tensioned by a screw-sliding transmission by rotating both parts (1, 2), (31, 32) relative to each other, and the locking tensioning mechanism is provided with a lowering device , and a nozzle (9, 39) with a single opening (10, 40) is provided at the end of the cylinder, and - the reservoir (14, 44, 54) is connected by means of a press fit (59) to the end of the hollow piston, and is connected to the latch piece (53) by latching hooks (51) which extend into the peripheral groove (52) of the reservoir, and - the separate reservoir (14, 44, 54) is filled with a liquid medicament. Needle-free syringe according to claim 18, characterized in that a filter (11) is arranged in front of the nozzle side facing the pump chamber. Use of a needleless syringe according to claims 1 to 19 for injecting an active substance-containing fluid into biological tissue. Use of a needleless syringe according to claims 1 to 19 for injecting an active substance-containing fluid into plant tissue. Use of a needleless syringe according to claims 1 to 19 for injecting active substance-containing fluids into animal tissue. Use of a needleless syringe according to claims 1 to 19 for intra-skin injection of vaccines to an animal. -2224. Using a needleless syringe inject subcutaneous injection of vaccines into an animal. according to claims up to 19 on Use of a needleless syringe according to the claims by intravermal injection of vaccines to a human. Use of a needleless syringe according to claims subcutaneous injection of vaccines to a human. Use of a needleless syringe according to claims injecting fluid through a membrane into a space downstream of the membrane.