BG106987A - Miniaturized needleless injector - Google Patents

Abstract

Needleless injectors for liquids are known from the art is 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, and 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 At the same time the amount of the liquid required for the injection is withdrawn from the storage container (44) and transported through the hollow piston (37) to the pump chamber (43). When the lockable tensioning system is released, the amount of liquid is ejected from the pump chamber (43) through the nozzle (39). The needleless injector is easy and reliable to handle also for unpracticed people. It is used for 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. 27 claims, 4 figures

Description

TECHNICAL FIELD

The invention relates to a needle-less injector as a hand-held device, preferably in a miniature embodiment, by which an intracutaneous fluid is injected, e.g. in human or animal tissue. The invention is intended to extend the scope of application of injectors of this type.

BACKGROUND OF THE INVENTION

Liquids within the meaning of the present invention are preferably solutions, suspensions or dispersions containing the active / active / substance. The active substances may be pharmacologically active substances for the treatment of human or animal organisms, or may be substances for diagnosis or cosmetic use.

The active substances for non-pharmaceutical use may be, for example, in the field of plant protection, insecticides, fungicides, agents necessary for its growth or retardation, or artificial fertilizer. The needle-free injector according to the invention enables the ecological application of the active systemic agent, since the active substance is brought directly to the plant.

EP-0063341 and EP-0063342 are known to be a needle-less injector that contains a piston pump to expel the injected fluid, which is pumped by a working fluid from the engine. The liquid tank is positioned sideways

the piston pump. 'The amount of fluid required is sucked in when the piston is returned back through the suction duct and a non-return valve in the pump chamber. As the piston moves in the direction of the nozzle, the fluid shrinks and pushes through the outlet duct to the nozzle. The piston of the piston pump is a massive circular piston.

EP-0133471 discloses a needle-less vaccination device operated by a siphon cartridge through a special pressurized carbon dioxide valve.

EP-0347190 discloses a compressed gas vacuum injector whereby the penetration depth of the injected medicament is adjusted by gas pressure and the volume of the medicament by the piston stroke.

EP-0427457 discloses a needle-less hypodermic injector which is actuated by compression gas through a two-stage valve. The injection agent is located in an ampoule that is housed in a protective sheath attached to the injector housing. The ampoule is attached to the end of the piston rod. At the other end of the ampoule is a nozzle whose diameter decreases towards the end of the ampoule.

WO-89/08469 discloses a needle-free injector. WO-92/08508 provides a needle-less injector designed for three injections. The medicament containing the ampoule is screwed at the end of a unified actuator with the piston rod at the open end of the ampoule. The ampoule has at one end a nozzle through which the medicament is pushed. Approximately in the middle of the length of the ampoule is a moving stopper. The dose to be injected is adjusted by the screwing depth of the ampoule. After the injector is actuated, the piston rod, · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ··· coming out of the unified care   anism is retracted manually. Both appliances operate with compressed gas.

From WO-03779, a needle-less injector is known with a two-body body and a fluid reservoir located side by side. The piston actuator spring is stretched by a motor with a gearbox. The spring is released when the two body parts are slid against each other as the nozzle is pressed against the injection site. There is always a single valve in the suction duct for the liquid and at the outlet of the metering chamber.

Another needle-free injector is disclosed in WO-95/03844. It contains a fluid-filled cartridge which at one end contains a nozzle through which the fluid is forced out. At the other end, the cartridge is closed with a piston-shaped piston sliding into it. One piston loaded by a pre-stressed spring slides inwards after releasing the spring, the piston-piston to a portion in the cartridge, forcing the amount of fluid to be injected. The spring is released when the nozzle is pressed tightly enough against the injection site. This injector is intended for single or multiple use. The cartridge is located in front of the spring-loaded piston and is a fixed component of the injector. The plunger position of the injector provided for multiple applications is moved after each application by one part in the direction of the nozzle. The piston and drive spring do not return to their original position. The pre-tensioning of the spring at the beginning is large enough to expel all the fluid in the cartridge at once. The spring may again be stretched when injector · · · ·· · · · · ^r • ·· ·· ·· · · · · · · · · · • · * ··· ·· • · · · · · · ············································ méééééáééééééééééééééééééééééé биéééééáéééééééééééééééééééééééééééééééééééééééééé old rolling stockng.

FR-2629706 describes two embodiments of a needle-free injector for use in dentistry, by which a predetermined amount of fluid in the gums can be injected. The two injectors consist of two parts, respectively, which are coaxially connected and disassembled. The working medium is compressed air that is injected into the injector from outside. When the injector is released via one start button, one piston is displaced by pushing, in agreement between the compressed air, the coil springs and the locking devices, to a predetermined part, whereby the amount of injection fluid is pushed through a nozzle. Several coil springs are tensioned at the same time, which returns a few axially moving parts to the injector when their compressed air is no longer effective. The injection fluid is placed inside the injector in a tubular stable tank, which at one end is provided with a seal that moves into the tank, which, by means of a spring-loaded piston, presses the liquid permanently inside the tank. When a part of the fluid is pushed out of the reservoir into the fluid space inside the pump cylinder, the pressure spring pushes inward one corresponding part in the fluid reservoir above the piston and the seal.

In some known embodiments of the needleless injector, the reservoir for the injection fluid is positioned laterally to the actuator. The amount of injection fluid is sucked in when the massive piston is returned

the piston pump in the pump gfostInSTKb. The inlet duct contains a suction valve, the outlet duct contains a discharge valve. Both valves operate with one auxiliary force.

In other embodiments of the needleless injector, the reservoir serves directly as a pump chamber for the injected fluid and is taken as a forceful blow that occurs when the amount of injection fluid is displaced.

With compressed gas non-needle injectors, a portion of the compressed gas is released after each injection. The compressed gas reservoir is replaceable, but it does not refill directly with compressed gas. With these injectors, the drive unit must be replaced when the compressed gas tank is empty.

The invention seeks to provide a reusable, needless, simple-injector, which is preferably suitable for repeated ejection of a predetermined amount of fluid. The total amount of fluid expelled after many applications should preferably be greater than the amount of liquid contained in a single reservoir. It must be possible to take more partial quantities of liquid from the tank one after the other or to take and expel the quantity of liquid contained in one tank as a whole, at a time. The replacement tank must be easily replaceable. A given amount of fluid should give a sufficiently large mechanical impact (impulse) so that this amount of fluid can penetrate a membrane, foil or biological tissue.

SUMMARY OF THE INVENTION

This task eg | 50 | pia, "obG'las} u1iz © bret ^ ncetB, through a single needleless fluid injector, which is arranged as a handheld device in a cylindrical body and contains one spare fluid tank. The body consists mainly of two parts. The two parts are connected to each other detachably or individually and are arranged to rotate relative to each other. The needle-less injector comprises a locking-actuating mechanism by actuating a spring which, prior to pushing a predetermined amount of fluid, is tensioned and provided with a releasing device. A hollow piston is mounted in the part with a momentary action (on or off) of the locking mechanism, which is actuated by the locking mechanism. The hollow piston is movable in one cylinder. It protrudes from one end of the cylinder. Preferably at its other end is a valve, which is the only valve of the needleless injector. At the end of the cylinder, a nozzle with at least one opening is fitted. The space between the nozzle and the end of the hollow piston is the pumping space. Inside the body is a fluid reservoir. The replacement tank is shaped as a separate tank from

That the needleless injector, which you prefer through a press assembly, is connected detachably to the end of the hollow piston, which ends protruding from the cylinder. The set amount of fluid, which, in the reverse motion of the instantaneous part and the associated hollow piston, is fed through the hollow piston into the pumping space, is determined by the stroke and the cross section of the hollow piston.

The locking mechanism consists of a spring-loaded actuating flange as part with a momentary action, one • ·

drive / thrust / tension tension, one blocking element, two actuators for the drive flange, between which the actuating flange can move further, and one device for releasing the blocking element. The drive flange path is precisely constrained by both stops. A power transmission is located between the energy storage spring and the spring tension drive. The locking element is annular and has adhesive locking surfaces. As a battery of energy, it may be preferable to use a Q cylindrical coil spring or a flat circular spring, or a plate spring that acts as a tension or compression spring.

The energy storage spring can be stretched by direct drive. For this purpose, the drive flange is moved by an axially acting external force. At high spring force, a power-transmitting gear, e.g. a helical-gear drive by which the spring is tensioned by an external torque. One such gear is a single or multi-gear which is located between the spring and the spring tension actuator.

The drive flange can be shaped cup-shaped. The annular edge of the drive flange may comprise e.g. two saw blades sliding two saw blades into the upper body.

The average spring force can range from 10N to 150N.

Between the two positions of the torque-locking part of the locking mechanism, the spring force changes by about + 10% of the average spring force.

Blocker! the element may be (a radial elastically deformable ring or a rigid non-deformable ring with movable supports, or a rigid ring with shaped plate springs, or a ring that is subjected to pre-tensioning by one or more metal springs. The ring may be closed or open; the locking element is movable in one plane, vertically on the axis of the body, or it is deformable in that plane.

Further details of the spring-actuated locking mechanism are described in DE 19545226.

A hollow piston is mounted in the torque portion of the locking mechanism, which is actuated by the locking mechanism. The hollow piston is immersed in the cylinder and protrudes a portion of its length outside the cylinder; it is located in the cylinder movable / movable /.

A nozzle is fitted at the end of the cylinder. The nozzle opening may have a hydraulic diameter of from 10pm to 500m, preferably from 50µm to 150m. The nozzle opening can have a length of 50μπι to 500µm, preferably from ОО до to ЗОртрт.

With more openings in the nozzle, the longitudinal axes of the nozzle openings may be parallel to each other or inclined in a divergent manner. With more nozzle openings, their hydraulic diameters may be different.

The nozzle may be a parallelepiped formed of two silicon plates, e.g. 1.1mm wide, 1.5mm long and 2.0mm high. The parallelepiped may have a flat, triangular shaped, approximately 400 pth thick grog, which terminates in a nozzle opening, 50 pound wide, 50 pound thick and 200 pound long in the contact surface of the plates. It is advisable for the nozzle to be enclosed throughout its periphery with a precisely fitted, elastomeric profile portion. The inner contour of the elastomeric profile portion is aligned with the outer contour of the nozzle, the outer contour of the elastomeric profile portion is aligned with the inner contour of a nozzle carrier, preferably consisting of metal. Such a "floating reinforcement" renders the nozzle of fragile material insensitive to impact loads that occur with the needless injector used for its intended purpose.

^w Preferably, at the end of the hollow piston located in the cylinder is a one-piece valve which is guided by the hollow piston and is axially movable relative to the hollow piston. The valve moves mainly with the hollow piston. The valve preferably has a uniaxially rotary-symmetrical shape, such as e.g. circular cylinder or truncated cone. Its diameter may be smaller than the diameter of the space in which the valve is axially movable. The valve can rotate around its axis. The axis of the valve remains always parallel to the axis of the hollow body. In this way, there is a certain sealing surface on the suction side of the valve. The way in which the valve can be moved relative to the hollow body is limited by one stop. In the position where the valve fits on the designated sealing surface, the valve is closed.

The space between the nozzle and the hollow piston valve is the pumping space. Before the end of the pumping area on the nozzle side, i. one filter can be placed in the fluid outlet, which is preferably shaped like a depth filter. If the injected fluid contains suspending particles, the filter pore width must be adjusted to match the particle size.

Further details of the hollow piston and valve are given in DE 19536902.

The locking mechanism and the energy storage spring are tensioned, preferably by rotating the two body parts against each other by means of a screw-sliding gear. Torque can be obtained by hand or by means of an engine.

The diameter of the cylinder preferably coincides along its entire length with the outer diameter of the hollow piston. The cylinder can be fixed in one part of the body. In addition, the cylinder can be axially movable in one part of the body. The movable cylinder is held in its calm position by a return spring.

The two moment-limiting part restraints can be fixed in the body. In addition, the position of one of these stops can be changed in the axial direction.

^h 'thus may vary the volume of the pump chamber at a constant outer diameter of the hollow piston. In the unchanged construction of the needleless injector, the amount of fluid expelled can be varied by changing the position of the stop.

The position of the path of the instantaneous part and thus of the hollow piston stroke inside the needleless injector is limited by the two stops. Given the position of the limiters, the location of the path of the part with • · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·· ·· ··· · 9 instantaneous action of her * with this * a * stroke * of the * hollow piston at each injector is constant.

By means of a release device, the locking element slides parallel to or deforms radially in the plane of the ring. With the cylinder fixed in the body, the release device is actuated by a trigger button pressed with the finger and the locking element released. In the case of a cylinder mounted movably in the body, the releasing device is actuated by pushing the cylinder inwards, against the force of the return spring, and the blocking element is switched off and disconnected.

Inside the body is a spare fluid tank. This spare tank is shaped as a separate tank from the needleless injector; it is connected to the end of the hollow piston, which is opposite the pumping room. The end of the hollow piston is covered by the liquid contained in the reservoir.

The hollow piston spare tank can be further connected to the instant action part. This connection may be a detachable or non-detachable plug-in connection, wherein the instant action portion is provided with a plurality of locking hooks which are engaged in a annular groove in the reservoir after the reservoir is inserted into the needle-less injector.

The set amount of ejected fluid is determined by stroke and e.g. section of the hollow piston. The hollow piston stroke is limited by the two actuators of the driven flange.

It is appropriate for the nozzle to be provided with a removable cap to protect the nozzle opening while storing the nozzle. · 4 · · 4 · 4 · needle-free Injector Tb K during its use against contamination and evaporation of the liquid.

The two body parts, the locking mechanism, the cylinder and the reservoir are preferably made of plastic, e.g. polybutylene terephthalate. The hollow piston is made of metal, e.g. high quality special steel.

The valve may be made of metal, ceramics, glass, gem, plastic or elastomer.

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

The filter preferably consists of sintered metal or sintered plastic.

The needle-free injector is preferably manufactured as a hand-held device. When injected, it can be held with one hand and serviced. The cylinder, hollow piston, valve, nozzle and filter respectively are miniature elements of the structure.

The mode of action of the needleless injector is described below.

During storage of the unused or already used needle-less injector, as well as between two injections, the needle-free injector is in a quiet state. The energy storage spring is in a stressed state. The instant action portion is attached to the stop which restricts its path in a quiet state. The hollow piston is immersed deep in the cylinder. There is only a short distance between the end of the hollow piston and the inside of the nozzle. The locking element is in the off, disengaged position.

When the two body parts are rotated against each other, the locking mechanism is tensioned. The part with the moment · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · • the action slides in an axial direction ^ 'away from the cylinder, whereby the tension of the energy accumulating spring increases. At the same time, the hollow piston removes one part from the cylinder and the pumping space increases. The hollow piston, one part of its length, extends further into the cylinder. At the same time, one part of the fluid contained in the reservoir is forced out by the hollow piston and passing along the valve into the pump space and the pump space filled with liquid. The amount of fluid in the pumping room is practically equivalent to the amount of fluid discharged for one injection. The momentary action portion slides as far as the locking member is in its engaged, engaged position. With a needle-less injector with a start button, this button exits slightly from the body.

The end of the needleless injector on the nozzle side is placed on the injection site and pressed. With a needle-less injector with a trigger button, the trigger button is actuated by a finger and pressed inward into the body. In this way, the locking element moves to the off, disengaged position and the injection is performed. In the case of a needleless injector with a movable cylinder, the injector with its end on the side of the nozzle is pressed by hand with increasing force against the force of the return spring on the injection site. Thus the cylinder slides inwards into the body, the locking member is moved to its off, disengaged position and injection is performed. When the needle is removed from the injection site, the return spring compresses the cylinder back to its rest position.

• .. · · · · · · · · • · · · · · ·

While the locking element has taken an off position, the force K of the tensile, energy-saving spring acts, via the torque portion, the hollow piston and the closed valve at the end of the hollow piston during the interval At, on the fluid located in the pumping space, whereby the mass of fluid m receives velocity Δν and thus a mechanical impulse K .At = m .Αν, flows at a higher velocity than the nozzle and enters the tissue intracutaneously. After injection, the needle-free injector is at rest again.

The needle-free injector according to the invention can be used in human and veterinary medicine for the intracutaneous injection of a biologically active substance, e.g. drug, in human or animal tissue. Examples of suitable pharmaceutical compositions are e.g. analgesics, vaccines, antidiabetic drugs, hormones, pregnancy protection agents, vitamins, antibiotics, sedatives, antimicrobials, amino acids, coronary agents.

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

Suitable means for dissolving, suspending or emulsifying biologically active substances and, accordingly, the necessary excipients are e.g. water, alcohol, alcoholic mixtures, and emulsions of oil in water or water in oil. These include purified sterilized water, ethanol, propanediol benzyl alcohol, ethanol water mixture, oils / such as coconut oil, peanut, soybean, castor, sunflower oil /, esters of ···· ···· · · · ···· · ··· ·· · • ·· ··· ·· ··· · · ···· ··· · ·· Fatty Acid / KJo and ^ bpr * 0pild Myristate, Isopropyl Palmitate, Ethyl oleate /, Triglyceride, Triacetin , ketal sol, propylene glycol. The formulations of the excipients, such as e.g. preservatives such as acids or bases to determine pH values.

The desired amount of fluid can be injected by a needle-free injector into the leaf or stem of a plant or through a membrane into the space behind the membrane.

The needle-free injector according to the invention has the following advantages:

- It has a shape that is comfortable to grasp. The spare fluid tank is located in the body of the injector.

- It is applicable to many to several hundred injections that can be taken from one or more storage tanks.

- It has no valves other than the valve at the end of the hollow piston.

- The locking mechanism allows, even at high spring forces, its ease of use by untrained people, and it is tensioned with a relatively small amount of force through a single screw-sliding gear.

- The locking mechanism can be released manually by pushing one finger on the start button or by pushing the needle-less injector on the injection site.

- Do not replace the unified actuator, only the fluid reservoir.

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

- The volume of the pumping room is variable by changing the position of one of the two stops.

'Chim'

- The mechanical pulse of the injected amount of fluid can be matched to the desired depth of penetration into the tissue or to the thickness of the membrane through which it passes.

- The liquid storage tank agrees to the conditions - respectively long years - for storage of the tank and to its attachment to the injector. Its design is independent of the requirements that apply to the pumping room before the nozzle.

- The fluid reservoir is not exposed to force when injected.

- The replacement fluid reservoir is easily changed.

- The required amount of medicated fluid for a given application can be injected easily in a number of separate quantities one after the other at different points in the injection area.

- Needless injection injures significantly less the injection site than injection via a single syringe.

EXPLANATIONS OF THE FIGURES Attached

The invention will be explained in more detail with reference to the accompanying drawings, in which:

FIG. 1 is a longitudinal section through a needle-less injector with a start button, presented in a resting position in which the cylinder is stationary in one part of the body;

FIG. 2 is a longitudinal section through a needle-less injector without a push-button in a tensioned state of energy storage, wherein the cylinder is movably disposed in one part of the body;

Figs. 3 and 4 show one end of the storage tank and the momentary part in other embodiments.

EXAMPLES FOR THE IMPLEMENTATION OF THE INVENTION

In FIG. 1 depicts two body parts 1 and 2 which are detachably connected to one another and are rotatable. Part of instantaneous action / on or off / 3, locking element 4 off, disengaged, starting actuator are shown in front of the stationary / initial state / locking / tensioning mechanism.

That button 5 acting on the locking element 4 and energy-saving coil spring 6 in the form of a pressure spring. A hollow piston 7 is secured in the part of instantaneous action 3, which is immersed in a cylinder 8. At the end of the cylinder there is a nozzle 9 with a nozzle opening 10. A filter 11 is placed in front of the nozzle 11. The end of the hollow piston 7 is on the nozzle side. is provided with a valve 12. There is a pumping space between the valve 12 and the filter 11. The storage tank 14 is located in the free space inside the coil spring 6; it is ^w seated in a flange 15 on the hollow piston 7 and is retained on the hollow piston 7 by a press assembly 19. The separator 16 that encloses the coil spring 6 is connected to the body part 1 by virtue of its shape. The torque portion 3 lies on the stop 17. The nozzle 9 is protected by a detachable cap 18.

Figure 2 shows the two body parts 31 and 32 which are detachably connected to each other and are rotatable. The tensile locking mechanism is provided with a torque actuation part / on or off / 33, a locking element 34 in the engaged, recessed state and an energy accumulating coil spring 36 in the tensed state. A hollow piston 37 is attached to the torque portion 33, which is immersed in the cylinder 38. At the end of the cylinder there is a nozzle 39 with a nozzle opening 40. The end of the hollow piston 37 is provided with a valve 42 on the side of the nozzle. 42 and a nozzle there is a pumping space 43. The spare tank 44 is located in the free space inside the coil spring 36; it is clamped in a flange 45 on the hollow piston 37 and retained on the hollow piston 37 by a press fit 49. The separator 46 which encloses the coil spring 36 is connected to the body part 31 by virtue of its shape. The torque portion 33 lies adjacent to the locking element 34 on the stop 47. The cylinder 38 is disposed in the part of the body 31 with the possibility of axial displacement; it is held in rest by a spiral return spring 48 which acts as a pressure spring. The cylinder 38 is provided with not shown in the drawing a releasing device which disengages the locking element 34, while the cylinder 38 is inserted into the part of the body 31 against the force of the return spring 48 by pushing the needleless injector on the injection site. "A" indicates the path of the actuated part between the two stops. The hollow piston stroke is consistent with this path.

Figure 2 shows the needle-less injector placed for injection. The nozzle 39 is pressed against the schematically represented stretched skin 35; upon further pressing on the injection site, the needle-free injector is released and the fluid is injected from the pump space 43 into the skin 35.

• · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

Figs. 3 and 4 show one end * of? the spare tank and the instantaneous part in other embodiments. In FIG. 3, the hollow piston 57 is inserted into the reservoir, but is not yet connected to the hollow piston 57.

In Fig. 3 is shown a spare tank 54 with three shells in partial longitudinal section. The outermost shell of the spare tank 54 is a rigid sleeve 55 that is provided with a circumferential groove 52. The replacement reservoir 54 is closed with a stopper 56 which passes through a press assembly 59 into the submerged nozzle 58. In the longitudinal section, a portion of the torque portion 53 with the hollow piston 57 attached thereto. The torque portion 53 is provided on its side, facing the replacement tank 54 with a plurality of locking hooks 51.

In Fig. 4, the storage tank 54 is connected to the hollow piston 57 and the torque portion 53, namely, the hollow piston 57 through the press assembly 59 and the torque portion 53 via the retaining hooks 51, which are engaged in the annular groove 52 of the spare tank 54.

The connection shown in FIGS. 3 and 4 between the reserve tank 54 and the torque portion 53 consists of locking hooks 51 with circular projections and a circular groove 52 with a semicircular cross section. This connection is a detachable plug connection.

For a non-detachable plug connection, the retaining hooks 51 can be selected with saw blades and the annular groove with a triangular cross-section.

Example 1: Construction of a needle-free injector according to the invention • M · · · · · · · · · · · · · · · · · · · · · · ·

The needle-free injector for intradermal injection into biological tissue has the following characteristics:

The body has an outer diameter of about 20mm and a length of about 70mm. The two body parts, the locking mechanism and the spring separator are made of polybutylene terephthalate. The cylinder also consists of polybutylene terephthalate; it has an outside diameter of 5mm and an inside diameter of 1.60mm. The nozzle is made of quartz. The nozzle opening has a diameter of 140m and a length of 220μητ The hollow piston of stainless steel has an outer diameter of 1.59mm and an inner diameter of 0.35mm. The piston stroke is 12mm. The valve consists of an elastomer; it has the form of a washer 2mm thick and an outer diameter of 1.60mm. The washer is provided on its lateral surface with axial openings through which the fluid can flow along the valve into the pump space. The end of the hollow piston is provided with a groove in which the valve is engaged. The displaced amount of liquid amounts to 23mm ³ . The interchangeable spare tank has a capacity of about 11mm ³ .

Example 2: Intradermal injection of fluid

Injection solution of 20g of dextrin-fluorescein (UW3000) per liter of distilled water is injected through the skin onto two anesthetized dogs using a needle-free injector according to the invention. To this end, 4.5ml of dextrinfluorescein solution was filled into the needle injector spare tank and the needleless injector was connected to the injector hollow piston. The injector was actuated by repeatedly stretching and releasing the locking mechanism to push out the air from the hollow piston, pumping the pump. Space and nozzle. The NaFIAZyluZeigg injector was placed on the pre-shaved area in the dog's stomach area and put into operation. The process was repeated many times.

Blood samples were taken from dogs at regular intervals and the dextrin-fluorescein content of the blood plasma was determined. The results confirmed the functionality of the needle-free injectors according to the invention.

Example 3: In-vitro assay of viral suspension

The use of needle-free injectors in laboratory tests has determined whether the viability of suspended live viruses is reduced when the suspension is pushed through the needle-injector nozzle.

When collected, after vomiting out of the needle-free injector viral suspension, a decrease of only about 1 logio PFU was observed in relatively large DNA viruses (test virus: Vaccinia virus) and about less than about 0.51ogi ₀ PFU. / for small RNA viruses / test virus: Bovine viral darrhea virus /.

Example 4: In vivo administration of a live virus modified vaccine

The feasibility of needle-free injectors for the administration of modified live virus vaccine suspension was investigated in animal experiments. In this study, both the safety and tolerability of vaccination by needle-free injectors and the efficacy of this vaccination were established.

e · · · · · * ♦ · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · ·

Six healthy, same age coats were divided into two groups. Group 1 comprised 2 dogs, group 2 four dogs. Dogs from both groups were vaccinated at three weeks intervals, respectively, three times with a modified live canine adeno virus vaccine.

In group 1, 1 millimeter of the canine vaccine adeno-virus / CAV-1 / / Galaxy DA2ppvL + Cv, SNo 610041 was given as a drug; Solvay Animal Health Inc./ intramuscularly, as recommended by the manufacturer, via a syringe. In group 2, an experimental canine vaccine, adeno-virus, was administered as a drug without a needle.

The experimental vaccine (CAV-2) used for the injection of animals in the second group was obtained from a weakened strain of the canine adeno virus. The tiger amounts to 712 logio TCO50 for 60 microliters (TSP) = tissue infectious dose /. Six single doses were given for each vaccination time (six times 10 micrograms = 60 microliters for each vaccination). The injection area at the back of the dogs was selected and the six injection sites were marked using a marker pen.

Vaccination efficacy was determined by determining the number of virus neutralizing antibodies in the dog's serum, respectively, three weeks after each injection.

Tolerance was determined by monitoring the injection sites six hours after vaccination and then every day until the completion of the animal experiment. The injected areas were photographed and the result of the test after the injection sites were noted.

This experience showed:

· · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · 9

In animals' From rpytia 2'has a very small redness at the injection site during the first 2 to 3 days. Only by tingling, a persistent 1 to 2 days and a passing bump was detected. This small and acceptable local response is highly likely to depend on the site of injection of the modified live viruses and is therefore considered to be a necessity for good vaccine efficacy. This explanation is supported by the fact that after injection of saline with cooking salt using a needle-less injector, almost no staining and no or only a small bump was observed.

Efficacy was determined by a virus neutralization test. The results are shown in Table 1. The highest titers are still able to neutralize canine adeno viruses.

Virus neutralizing antibodies were demonstrated in the serum of all animals in both groups three weeks after the first vaccination. After the second and third vaccinations, a small enhancing effect was obtained.

Vaccination with the experimental canine adeno vaccine using a needle-free injector is just as effective as muscle vaccination with the usual vaccine using a syringe.

• · · · · ·

24.

· · · · · · · · · · · ·

Table 1: canine - adeno - virus; virus neutralizing titer of canine serum

DOGS VN - titer of canine serum Number _ha p p _{Acte Istika} 21 ^g experience days after the first 21 days after the second 21 days after the third vaccination vaccination vaccination CAV-1 - a common vaccine intramuscularly via a syringe 1 ΛΛζ ...... 1024 1024 4096 14Y0 1 400 1024 1024 512 CAV-2 - an experimental vaccine subcutaneously with a needle-free injector 1494 TTK9 4096 4096 8192 1495 USK9 4096 4096 8192 1497 UVL9 4096 8192 4096 1499 TVL9 2048 2048 2048

Y

Claims (27)

Patent Claims 1. Needless liquid injector shaped like a handheld device with one body and one spare fluid reservoir, characterized in that -the body comprises two parts / 1,2 /, / 31,32 /, which are connected to each other and are rotatable relative to each other and the needleless injector comprises a locking and tensioning mechanism, which moves between two stops (17,47) with a torque actuator (3,33,53), which is provided with one release device and a hollow piston / 7,37, 57 /, which is fixed in the part with instantaneous action / 3,33,53 / and is actuated by a locking-tensioning mechanism, wherein the hollow piston is movable in a single cylinder / 8,38 / and contains a single valve / 12, 42 /, and at the end of the cylinder one nozzle / 9,39 / with at least one opening / 10,40 / is inserted and the space between the nozzle and the valve forms is but pumped space / 13,43 / s the spare tank / 14,44,54 / for the fluid is located inside the body, is shaped like a tank separated from the needleless injector and is connected to the end of the piston, which end protrudes from the cylinder and -the amount of liquid which, when the hollow piston (7) is withdrawn from the cylinder (8), is fed through the hollow piston into the pumping space (43), is determined by the stroke (a) and the cross section of the hollow piston 111 ·, ·· · · · · · · · · · · the position of the stroke (s) of the hollow piston (7) inside the needleless injector is determined by the position of the two stops (17,47). A needle-free injector according to claim 1, characterized in that -the two parts / 1,2 /, / 31,32 / of the body are disassembled with one another. A needle-free injector according to claims 1 and 2, characterized in that the nozzle / 9,39 / contains only one opening / 10,40 / with hydraulic diameter from ΙΟμηι to 500μπι, preferably from 50μπι to 150μπι and the nozzle opening / 10.40 / has a length from 50μπι to 500μιη, preferably from ΙΟΟμηι to PPL. A needle-free injector according to claims 1 and 2, characterized in that -the nozzle / 9,39 / contains more nozzle openings whose hydraulic diameter is accordingly different. A needle-free injector according to claims 1 and 2, characterized in that -the nozzle / 9,39 / contains more apertures of the nozzle whose longitudinal axes are parallel to each other or inclined in a divergent relation to each other. A needle-free injector according to claims 1 to 5, characterized in that the position of the stop and thus of the stroke (s) of the hollow piston is variable. A needle-free injector according to claims 1 to 6, characterized in that it is •• e · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · - the locking-tensioning mechanism is capable of stretching by turning the two body parts (1,2), / 31,32 / relative to each other by hand. A needle-free injector according to claims 1 to 7, CHARACTERIZING THAT - the locking-tensioning mechanism is able to be tensioned by a screw-sliding gear while rotating the two parts of the body / 1,2 /, / 31,32 / relative to each other. 9. The needle-less injector according to claims 1 to 8, _w characterized thereby, that the locking mechanism comprises one coil spring (6.36), one flat circular spring or one plate spring as an energy storage. A needle-free injector according to claims 1 to 9, CHARACTERIZING THAT -the nozzle / 9,39 / consists of metal, plastic, glass, silicon or precious stone such as sapphire, ruby, corundum. A needle-free injector according to claims 1 to 10, characterized in that - the separate spare tank / 14,44,54 / for the fluid is connected in a detachable way by a press assembly / 19,49,59 / to the end of the hollow piston, which ends protruding from the cylinder. A needle-free injector according to claims 1 to 11, characterized in that the separate reservoir (14,44,54) for the fluid is connected to the hollow piston (7,37,57) and is movable with the hollow piston in the body. A needle-free injector according to claims 1 to 12, CHARACTERIZING WITH THAT · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · The single orifice tank0ar714 * 44>, 54 / for the liquid is shaped as an interchangeable spare tank and a moment action part / 53 / is installed to receive the separate spare tank. A needle-free injector according to claims 1 to 13, characterized in that the separate liquid reservoir / 54 / is connected to the hollow piston / 57 / and the torque portion / 53 / the instant action portion (53) is provided with locking hooks (51) which are engaged in a annular channel (52) in the storage tank. A needle-free injector according to claims 1 to 14, characterized in that the end of the needleless injector on the nozzle side is provided with one cap / 18 /. A needle-free injector according to claims 1 to 15, characterized in that - one filter (11) is located in front of the nozzle side facing the pumping room. A needle-free injector according to claims 1 to 16, characterized in that -the separate reservoir (14,44,54) for the fluid is filled with a liquid medicine, preferably from the group of analgesics, vaccines, antidiabetic drugs, hormones, anti-pregnancy agents, vitamins, antibiotics, sedatives, antimicrobial substances, amino acids, amino acids, amino acids coronary agents. A needle-free injector according to claims 1 to 3 for a liquid shaped like a handheld device with one body and one spare fluid reservoir, characterized in that the locking-tensioning mechanism comprises one coil spring / 6,36 / and the locking-tensioning mechanism is able to be tensioned by a screw-sliding gear when rotating the two body parts / 1,2 /, / 31,32 / one relative to another, the locking mechanism being provided with one release device and - one nozzle / 9,39 / with a single opening / 10,40 / is fitted at the end of the cylinder the spare tank / 14,44,54 / is connected by a press assembly / 59 / to the end of the hollow piston and is connected to the part by a momentary action / 53 / by means of locking hooks / 51 /, which are engaged in the annular channel / 52 / in the spare tank and The spare tank (14,44,54) is filled with liquid medicine. A needle-free injector according to claim 18, CHARACTERIZING THAT - one filter (11) is located in front of the nozzle side facing the pumping room. Use of a needle-free injector according to claims 1 to 19 for injecting a liquid containing a biologically active substance into biological tissue. Use of a needle-free injector according to claims 1 to 19 for injecting a fluid containing a biologically active substance into plant tissue. Use of a needle-free injector according to claims 1 to 19 for injecting a fluid containing a biologically active substance into an animal tissue. · · · · · · · · · · · · · · · · · · · · · · · 9 9 · · · · · · · · · · · · · 9 9 9 9 9 9 · · ·· «* ·· _- ·· 9999 9 9 ww - - - ···· Use of the needle-free injector according to claims 1 to 19 for intracutaneous injection of a vaccine into an animal. Use of the needle-free injector according to claims 1 to 19 for the subcutaneous injection of a vaccine into an animal. Use of the needle-free injector according to claims 1 to 19 for the intracutaneous injection of a vaccine into a human. Use of the needle-free injector according to claims 1 to 19 for the subcutaneous injection of a vaccine into a human. Use of a needle-free injector according to claims 1 to 19 for injecting fluid through a membrane into the space behind the membrane.