HRP20020720A2 - Miniaturized needleless injector - Google Patents

Description

The invention relates to a needle-free injector as a hand-held device, preferably in a miniature version, with which liquid is injected intracutaneously, for example, into human or animal tissue. The aim of the invention is to expand the field of application of such an injector.

Liquids in the sense of the proposed invention are primarily solutions, suspensions or dispersions containing an active substance. The active substances can be pharmacologically active substances for the treatment of the human or animal body, or they can be substances for diagnosis or cosmetic use.

Active substances that are not for pharmaceutical use can be, for example, from the field of plant protection, insecticides, fungicides, agents that promote or inhibit growth, or fertilizers. The needleless injector according to the invention enables the environmentally friendly application of systemically effective agents, because the active substance is introduced directly into the plant.

From EP-0 063 341 and EP-0 063 342 a needleless injector is known which has a piston pump for ejecting the liquid to be injected, which is activated with the engine by means of a pressure medium. The liquid tank is mounted on the side of the piston pump. The amount of liquid required for injection is sucked into the pump chamber by pulling the piston through the exhaust channel and the check valve. When the piston moves in the direction of the nozzle body, the fluid is forced through the outlet channel into the nozzle and ejected. The piston of a reciprocating pump is a large round piston.

WO-89/08469 describes a disposable needleless injector. WO-92/08508 discloses a needle-free injector which is made for three injections. The ampoule containing the drug is screwed into one end of the activation element, with the fuse being pushed into the open end of the ampoule. At the end of the ampoule there is a nozzle through which the medicine is ejected. Approximately in the middle of the length of the ampoule, a movable stopper is provided. The dose to be injected can be adjusted using the ampoule screwing depth. The connecting rod, which protrudes from the activation element after the injector is activated, is pushed back by hand. Both devices work on compressed gas.

WO-93/03779 discloses a needle-free injector with a two-part housing and a liquid container which is inserted laterally on the apparatus. The drive spring for the piston is tensioned by a geared motor. When the spring is released, the two parts of the housing move in opposite directions, pressing the nozzle to the injection site. In each case, one valve is located on the suction channel for the liquid and in the outlet of the dosing chamber.

A further needleless injector is described in WO-95/03844. It has a cartridge filled with liquid that has a nozzle at the end through which the liquid is ejected. At the other end, the cartridge is closed with a rounded piston that can be pressed into the cartridge. After the spring is released, the spring-loaded piston pushes a predetermined portion of the rounded piston into the cartridge, expelling the amount of fluid to be injected. When the spring is unloaded, the nozzle presses firmly enough on 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 an invariable part of the injector. The position of the reusable injector piston is moved one part after each application in the direction towards the nozzle. The piston and drive spring cannot be retracted. The spring preload is initially large enough to eject the entire volume of fluid in the cartridge at once. The spring can only be re-tensioned when the injector is disassembled and the drive part of the injector is connected to a new, fully charged cartridge.

FR - 2 629 706 describes two embodiments of a non-acrylic injector for use in dental medicine, with which a predetermined amount of liquid can be injected into the gums. Both injectors consist in each case of two parts that are plugged together coaxially and are separable. The working medium is compressed air, which is supplied to the injector from the outside. When the injector is activated by means of the trigger button, the working piston is moved by the combined action of compressed air, a screw spring and a locking device by a predetermined distance, while at the same time the quantity of injection liquid is ejected through the nozzle. At the same time, several coil springs are tensioned, which pull back several axially movable parts inside the injector back to their initial position, after which the supplied air pressure is no longer effective. The liquid is fed into a tubular rigid container inside the injector, which at one end has a plug that can be moved inside the container, which constantly keeps the liquid present in the container under pressure via a spring-loaded piston. As part of the fluid is drawn from the reservoir into the fluid space inside the pump cylinder, the compression spring pushes the appropriate portion of the plug over the piston into the fluid reservoir.

In some known designs of an oxygen-free injector, the container for the liquid to be injected is located laterally on the drive part. The liquid to be injected is sucked in when the large piston of the reciprocating pump is returned to the pump chamber. In the inlet channel there is an inlet valve, and in the outlet channel there is an outlet valve. Both valves operate with auxiliary force.

The hollow piston is placed movably inside the cylinder. One end of it sticks out of the cylinder. At its other end, there is primarily a valve body, which is the only valve body of an oxygen-free injector. At the end of the cylinder there is a nozzle with at least one opening. The space between the nozzle and the end of the hollow piston is the pump space. There is a liquid container inside the case. The tank is made as a tank separate from the oxygen-free injector, which - primarily by means of a pressure fitting - is connected releasably to the end of the hollow piston that protrudes from the cylinder. The previously determined amount of liquid, which is transported through the hollow piston into the pump space by the return of the rebound part and the hollow piston connected to it, is determined by the stroke and cross-section of the hollow piston.

The locking tensioning device consists of a drive flange loaded with a spring as a rebound part, a drive for spring tension, a locking element, two stops for the driving flange, between which the flange can move back and forth, and a device for relieving the locking element. The path of the drive part is precisely limited by two stops. Between the spring with stored energy and the drive for tensioning the spring is a transmission for transmitting the force. The locking element has the shape of a ring and it has an included locking surface. For energy storage, a cylindrical screw spring or a plate spring or a feather spring can be used, which acts as a tension spring or as a compression spring.

The energy storage spring can be tensioned by direct drive. For this purpose, the drive flange is pushed with an external force acting axially. For higher spring forces, a transmission is useful for transmitting the force, for example a screw-driven transmission, with which the spring is tensioned with an external torque. A transmission of this type is a single-stroke or multi-stroke transmission located between the spring and the spring-tensioning drive.

The drive flange can be made in the shape of a pot. The collar of the drive flange may have, for example, two toothed depressions on which the two teeth in the upper part of the housing slide.

The mean spring force can be 10 N to 150 N. Between the two positions of the rebound part of the locking tension device, the spring force changes by approximately +/-10% of the mean spring force.

The locking element can be a ring that can be deformed radially elastically inward, or a rigid ring with an upgraded feather spring, or a ring obtained by prestressing one or more metal springs. The ring can be closed or open; it can consist of several parts. The locking part is placed movably in a plane perpendicular to the housing, or it can be deformed in that plane.

Further details of the spring-actuated locking tension device are described in DE-195 45 226.

A hollow piston is fixed in the rebound part of the locking tensioning device, which is actuated by the locking tensioning device. The hollow piston is immersed in the cylinder and it protrudes part of its length out of the cylinder; it can be moved inside the cylinder.

At the end of the cylinder there is a nozzle. The nozzle opening can have a hydraulic diameter of 10 μm to 500 μm, preferably from 50 μm to 150 μm. The nozzle opening can have a length from 50 μm to 500 μm, preferably from 100 μm to 300 μm. If the nozzle has several openings of their longitudinal the axes can be parallel to each other or they can be inclined to each other so that they move away from each other.If the nozzle has several openings they can have different hydraulic diameters.

The nozzle can be made from two silicon wafers that together form a cuboid, which has, for example, a width of 1.1 mm, a length of 1.5 mm and a height of 2.0 mm. At the contact surface of the two plates, the cube may have a flat triangular depression approximately 400 µm thick, ending in a single nozzle opening 50 μm wide, 50 μm thick, and 200 μm long. It may be expedient to surround the nozzle around its entire circumference with an elastomeric product which exactly matches it. The internal shape of the elastomeric workpiece is adapted to the external shape of the nozzle, and the external shape of the elastomeric workpiece is adapted to the internal shape of the nozzle holder, which is made primarily of metal. Such a "floating holder" makes the nozzle made of brittle material insensitive to shock loads that occur with the proper use of the glycol-free injector.

First of all, at the end of the hollow piston, which is inside the cylinder, there is a valve body that is made primarily in one part, which goes through the hollow piston and can be moved axially in relation to the hollow piston. The valve body moves mainly with the hollow piston. The valve body preferably has a uniaxial, rotationally symmetrical shape, such as a circular cylinder or a truncated cone. Its diameter can be smaller than the diameter of the space in which the movable body of the valve is located. The valve body can rotate around its axis. The axis of the valve body remains constantly parallel to the axis of the hollow piston. In this way, a defined sealing surface is obtained on the inlet side of the valve body. The way the valve body can move relative to the hollow piston is limited by a stop. In the position where the valve body rests on the defined sealing surface, the valve is closed.

The space between the nozzle and the valve body mounted on the hollow piston is the pump space. In front of the end of the pump space on the nozzle side, i.e. in the outlet channel for the liquid, a filter can be placed, which is conveniently made as a deep filter. If the liquid to be injected contains suspended particles, the pore width of the filter should be adjusted to the size of the particles.

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

The locking tensioning device and the spring with stored energy are primarily tensioned by turning the two parts of the housing in opposite directions primarily via a screw-thrust transmission. The torque can be produced manually or by means of a motor.

The diameter of the cylinder is in accordance primarily along its entire length with the outer diameter of the hollow piston. The cylinder can be fixed in part of the housing. Furthermore, the cylinder can be positioned so that it can be moved axially in the housing part. In the rest position, the movable cylinder is held by a return spring.

Two stops for the rebound part can be fixed in the housing. Furthermore, the position of one of these stops in the axial direction can be variable. This allows the volume of the pump space to be changed at a constant outer diameter of the hollow piston. With the otherwise unchanging design of the carbonless injector, the amount of ejected liquid can be changed by changing the position of one limiter.

The position of the path of the rebound part and thus the stroke of the hollow piston inside the carbonless injector is limited by both stops. At the given position of the stop, the position of the path of the rebound part and thus the stroke of the hollow piston is constant with each injection.

By means of the actuation device, the locking element is moved parallel to the plane of the ring or deformed radially in the plane of the ring. If the cylinder is mounted stationary in the housing, the actuation device is actuated by a trigger button that can be pressed with a finger and the locking element is released. If the cylinder is mounted in a movable housing, then the actuating device is actuated by pressing the cylinder inward against the force of the return spring and the locking element is raised.

There is a liquid container inside the case. This tank is made as a tank that is separate from the oxygen-free injector; it is connected to the end of the hollow piston, which is located opposite the pump chamber. The end of the hollow piston is covered with the liquid in the tank.

The container connected to the hollow piston can be additionally connected to the rebound element. This connection can be a detachable or non-detachable plug connection, with the pop-up part having a number of snap-on tabs that engage in the bypass groove on the canister when the canister is pushed into the needleless injector.

The previously determined amount of ejected liquid is determined by the stroke and cross-section of the hollow piston. The stroke of the hollow piston is limited by two stops for the drive flange.

It is expedient to provide a removable cap in front of the nozzle, to protect the nozzle opening during storage of the carbon-free injector and against contamination and evaporation of the liquid during its use.

Both parts of the housing, the locking tension device, the cylinder and the container are made primarily of plastic, for example polybutylene terephthalate. The hollow piston is primarily made of metal, for example stainless steel.

The valve body can be made of metal, ceramic, glass, precious stone, plastic or elastomer.

The nozzle can be made of plastic, glass, silicon or precious stone, such as sapphire, ruby, corundum.

The filter is primarily made of sintered metal or sintered plastic.

The needleless injector is primarily used as a hand-held device. When injecting, it can be held and activated with one hand. The cylinder, the hollow piston, the valve body, the nozzle and, if necessary, the filter are integral parts of the miniature design.

Below is a description of how the oxygen-free injector works.

During the disposal of the unused or already used needle-free injector, as well as between two injections, the needle-free injector is in a state of rest. The spring with stored energy is tensioned. The rebound part rests on a stop that limits the path of the rebound part in the rest state. The hollow piston sinks deep into the cylinder. There is only a small gap between the end of the hollow piston and the inside of the nozzle. The locking element is in the raised position.

The locking tensioning device is tightened by turning the two housing parts in opposite directions. The rebound part moves in the axial direction out of the cylinder, increasing the tension of the spring with stored energy. At the same time, the hollow piston is partially pulled out of the cylinder, and the pump space increases. The hollow piston protrudes part of its length out of the cylinder. At the same time, part of the liquid, which is in the tank, is transported with the hollow piston and past the valve body into the pump space, and the pump space is filled with liquid. The amount of liquid in the pump space practically corresponds to the amount of liquid expelled with one injection. The rebound part is moved so far, until the snap-in element snaps into its depressed position. In the case of a silicone-free injector with a trigger button, the button protrudes slightly from the housing.

The end of the needle-free injector, on the nozzle side, is placed at the injection site and pressed. In the case of a needleless injector with a trigger button, the trigger button is activated with a finger and pressed into the housing. This moves the locking part to the raised position and ejects the injection. With a needleless injector with a movable cylinder, the injector with its end on the nozzle side is pressed by hand with an increasing force against the action of the return spring force at the injection site. In doing so, the cylinder is pushed into the housing, the locking element is moved to its raised position and the injection is ejected. When lifting the needleless injector from the injection site, the return spring pushes the cylinder back to its rest position.

When the locking element takes the raised position, the force K of the tensioned spring with stored energy acts through the rebound part, the hollow piston and the closed valve at the end of the hollow piston during the time section Δt on the liquid located in the pump space, whereby the liquid mass m acquires a velocity Δv and thus mechanical impulse K·Δt = m·Δv, so it leaves the nozzle with a higher speed and penetrates into the tissue intracutaneously. After the injection, the needle-free injector is again in the idle state.

The needleless injector according to the invention can be used in human medicine and in veterinary medicine for intracutaneous injection of a liquid containing an active ingredient preparation, for example a drug, into the skin or animal tissue. Examples of suitable pharmaceutical compositions are, among others, analgesics, vaccines, antidiabetics, hormones, contraceptives, vitamins, antibiotics, sedatives, antimicrobials, amino acids, coronary agents.

The drug preparation can be in the form of a solution, suspension or emulsion. In the case of suspension, the mean particle size of 15 μm, preferably 10 μm, must not be exceeded.

Suitable agents for dissolving, suspending or emulsifying the active substances and, if necessary, necessary auxiliary substances are, for example, water, alcohols, mixtures of alcohol and water, as well as oil-in-water or water-in-oil emulsions. This includes purified, sterilized water, ethanol, propanediol, benzyl alcohol, ethanol-water mixtures, oil (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. Furthermore, the formulations may contain excipients such as preservatives, as well as acids or bases to adjust the pH value.

A pre-determined amount of liquid can be injected into the leaf or stem of the plant through the membrane into the space behind the membrane using an oxygen-free injector.

The needleless injector according to the invention has the following advantages:

• It has a suitable shape. The fluid reservoir is located in the injector housing.

• It can be used for many - up to several hundred - injections, which can be taken from one or more containers.

• Apart from the valve at the end of the hollow piston, it has no further valves.

• The locking tension device is activated manually by pressing the trigger button with your finger or by pressing the needle-free injector to the injection site.

• The drive unit is not replaced, only the fluid tank is replaced.

• The valve located at the end of the hollow body works without auxiliary force and closes very quickly.

• The volume of the pump space can be changed by changing the position of one or both stops.

• The mechanical impulse of the amount of liquid to be injected can be adapted to the desired depth of penetration into the tissue or the thickness of the membrane through which it must be penetrated.

• The liquid tank is adapted to the conditions - if necessary long-term - when storing the tank as well as its connection to the injector.

Its construction is independent of the requirements placed on the pump chamber in front of the nozzle.

• During injection, the liquid container is not exposed to impact force.

• The liquid tank can be replaced easily.

• The amount of liquid required for the application for a predetermined application case can be injected in a simple way in several partial amounts successively at different points of the injection area.

• A needleless injector injures the injection site significantly less than an injection given with a conventional injection needle.

The invention is further explained in more detail with the help of figures. Figure 1 shows a longitudinal section through a needleless injector with a trigger button in the idle state, in which the cylinder is stationary in the housing part. Figure 2 shows a longitudinal section through a needleless injector without a trigger button in the tensioned state of the spring with stored energy, the cylinder being movable in the housing.

Figure 1 shows both parts of the housing (1) and (2), which are connected to each other separately and can be rotated in opposite directions. From the locking tensioning device, which is in a state of rest, the rebound part (3), the locking element (4) in the raised state, the trigger button (5) that acts on the locking part and the spring (6) with stored energy in the form of compression are shown. springs. A hollow piston (7) is fixed in the rebound element (3), which sinks into the cylinder (8). A nozzle (9) with a nozzle opening (10) is placed at the end of the cylinder. There is a filter (11) in front of the nozzle. At the end of the hollow piston on the nozzle side is the valve body (12). Between the valve body and the filter is the pump space (13). The tank (14) is located in the otherwise free space inside the coil spring; it is wedged into the flange (15) on the hollow piston and is held on the hollow piston with a pressure fit (19). The cage (16), which surrounds the coil spring, is tightly connected to part (1) of the housing. The rebound part (3) rests on the stop (17). The nozzle is protected with a cap (18) that can be removed.

Figure 2 shows both parts of the housing (31) and (32), which are connected to each other separately and are placed so that they can rotate in opposite directions. The rebound part (33), the locking element (34) in the compressed state and the coil spring with stored energy (36) in the tensioned state are shown from the locking tensioning device in the tensioned state. A hollow piston (37) is fixed in the rebound part (33) and sinks into the cylinder (38). At the end of the cylinder there is a nozzle (39) with a nozzle opening (40). At the end of the hollow piston on the nozzle side is the valve body (42). Between the valve body and the nozzle is the pump space (43). The container (44) is located in the otherwise free space inside the coil spring; it is inserted into the flange (45) on the hollow piston and is held on the hollow piston by means of a pressure washer (49). The cage (46), which surrounds the coil spring, is hermetically connected to the housing part (31). The rebound part (33) rests on the raised locking element (34) on the stop (47). The cylinder (38) is located in part of the housing (31) and it is movable axially; it is held in its resting position by means of a return spring (48) which has the shape of a screw and which acts as a compression spring. The cylinder (38) has an actuation device, not shown, which raises the stop part (34) when the cylinder (38) is retracted into the housing part (31) against the force of the return spring when the carbonless injector is pressed against the injection site. The path is marked with (a).

of the drive part between two stops. The stroke of the hollow piston corresponds to that path.

Figures 3 and 4 show the end of the container and the rebound part in a further embodiment. Figure 3 shows the hollow piston inserted into the tank, but not yet connected to the hollow piston.

Figure 3 shows the container (54) (which has three shells) partially in longitudinal section. The outer shell of the container is a rigid sleeve (55) which has a circumferential groove (52). The container is closed with a plug that passes into the submerged extension (58) with a pressure fitting (59). The section (53) with the hollow piston (57), which is fixed there, is shown in longitudinal section. The spring part on its side facing the tank has several snap-in catches (51).

Figure 4 shows a container that is connected to a hollow piston and a rebound part, and to the hollow piston by means of a pressure fitting (59), and to the rebound part via snap-on clips (51) that engage in the circulating groove (52) of the container.

The connection between the container and the rebound part, which is shown in figures 3 and 4, consists of snap-on hooks (51) with a round supporting part and a circular groove (52) with a semicircular section. This connection is a detachable plug connection.

Snap-in hooks with a supporting part in the form of saw teeth and a circular groove with a triangular cross-section can be selected for an inseparable plug-in connection.

Example 1

Construction of the needle-free injector according to the invention

The needleless injector for intracutaneous injection into biological tissue has the following features:

The case has an outer diameter of approximately 20 mm and a length of approximately 70 mm. Both parts of the housing, the locking tension device and the spring cage are made of polybutylene terephthalate. The cylinder is also made of polybutylene terephthalate; it has an outer diameter of 5 mm and an inner diameter of 1.60 mm. The nozzle is made of quartz. The nozzle opening has a diameter of 140 μm and a length of 220 nm. The hollow stainless steel piston has an outer diameter of 1.59 mm and an inner diameter of 0.35 mm. The stroke of the piston is 12 mm. The valve body is made of elastomer; it has the form of a 2 mm thick plate with an outer diameter of 1.60 mm. On its surface, the plate cover has an axial recess through which liquid can flow along the valve body into the pump space. A groove is provided at the end of the hollow piston into which the valve body engages. The ejected amount of liquid is approximately 23 mm3. The replaceable tank has a volume of approximately 11 cm3.

Example 2

Intracutaneous application of liquid

An injection solution of 20 g of dextran-fluorescein (UW 3000) per liter of distilled water was injected into two anesthetized dogs through the skin using a carbonless injector according to the invention. For this purpose, 4.5 ml of dextran-fluorescein solution was placed in the reservoir of the carbon-free injector and the reservoir was connected to the hollow plunger of the injector. The injector is activated by repeatedly tightening and releasing the locking tension device to draw air from the hollow piston, pump chamber and nozzle. The needle-free injector is then placed on the pre-shaved area of the skin in the dog's belly area and activated. This procedure was repeated several times.

At regular intervals, blood samples were taken from the dogs and the content of dextran-fluorescein was determined in the blood plasma. The results confirm the functionality of the oxygen-free injector according to the invention.

Example 3

In vitro tests of viral suspension

In laboratory research with the use of an oxygen-free injector, it was determined whether the viability of suspended live viruses is reduced if the suspension is ejected through the nozzle of an oxygen-free injector.

A reduction of approximately 1 logio PFU (e. plaque forming units) was found on the viral suspension captured after ejection from the aglycone injector for relatively large DNA viruses (the test virus is a vaccine virus) and less approximately 0.5 logio PFU) for smaller RNA viruses ( test virus: Bovine viral diarrhea virus).

Example 4

In vitro application of vaccines with modified live viruses

In an experiment on animals, the usability of a glycol-free injector for administering a vaccine suspension with modified live viruses was tested. This test determined both the safety and tolerability of the vaccine administered using an oxygen-free injector, as well as the effectiveness of this method of administering the vaccine.

Six healthy dogs of the same age were divided into two groups. There were two dogs in group 1, and 4 dogs in group 2. The animals of both groups were vaccinated over a three-week period, in each case three times with a modified live canine adenovirus vaccine.

In group 1, 1 ml of canine adenovirus vaccine (CAV-1) (Galaxy DA2ppvL+Cv, Sno 610041; Solvay Animal Health Inc.) was given intramuscularly according to the manufacturer's recommendations using an injection needle. In group 2, the experimental canine adenovirus vaccine was given with a needle-free injector.

The experimental vaccine (CAV-1) that was used to vaccinate animals was produced from a weakened type of canine adenovirus. The titer was 7.2 logio TCID50 per 60 microliters (TCID = tissue culture infective dose). At each vaccination, six individual doses were given (six times of 10 microliters = 60 microliters for each vaccination). The injection area on the dog's back was shaved and six injection sites were marked with a ballpoint pen.

The effectiveness of the vaccination was determined by determining the number of antibodies in the dog's serum that were neutralized with the virus in each case three weeks after each vaccination.

Tolerability was determined by observation of the injection site six hours after vaccination and then daily until the conclusion of the animal experiments. The injection area was photographed and the finding was recorded after palpation of the injection site.

This experiment showed the following:

In group 2 animals, slight redness could be seen at the injection site for 2 to 3 days. Transient swelling that lasted 1 to 2 days could be determined by palpation. This slight and completely acceptable local reaction is most likely related to the local multiplication of the given modified live virus and is therefore considered important for good vaccine efficacy. This explanation is supported by the fact that after injection of sodium chloride saline using a glycol-free injector, no staining and also no swelling or no or only slight transient swelling can be observed.

The effectiveness was determined by a virus neutralization experiment. The results are shown in Table 1. The highest titers can still neutralize canine adenovirus.

Virus-neutralizing antibodies were detected in the serum of all animals from both groups three weeks after the first vaccination. After the second and third vaccination, a smaller strengthening effect was shown.

Vaccination with an experimental canine adenovirus vaccine with a needleless injector is as effective as intramuscular vaccination with a conventional vaccine using an injection needle.

Table 1. Canine adenovirus; virus neutralization titer from dog serum.

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Claims (27)

1. A needleless liquid injector, which is made as a hand-held device, with a housing and a liquid container, characterized in that • the housing has two parts (1; 2), (31; 32) which are interconnected and are positioned so that they can rotate in opposite directions, and • the needleless injector has a locking tensioning device with a rebound part (3; 33; 53) that can be moved between two stops (17; 47), on which there is an activation device, as well as a hollow piston (7; 37; 57), which is fixed in the rebound part (3; 33; 53), and which is actuated by means of a locking tension device, the hollow piston being positioned so that it can be moved inside the cylinder (8; 38) and having a single valve body (12; 42), and at the end of the cylinder there is a nozzle (9; 39) with at least one opening (10; 40), and the space between the nozzle and the valve body forms the pump space (13; 43), and • the reservoir (14; 44; 54) for the fluid is located inside the housing and is made as a reservoir separate from the carbonless injector and is connected to the end of the hollow piston protruding from the cylinder, and • the amount of liquid, which when pulling out the hollow piston (7) from the cylinder (8) is transported with the hollow piston into the pump space (43), is determined by the stroke (a) and the section of the hollow piston, • the stroke position of the hollow piston (a) inside the needleless injector is determined by the position of the two stops (17; 47). 2. Needleless injector according to claim 1, characterized by the fact that the two parts (1; 2), (31; 32) of the housing are releasably connected to each other. 3. Needleless injector according to claims 1 and 2, characterized in that • the nozzle (9; 39) has only one orifice (10; 40) with a hydraulic diameter of from 10 pm to 500 pm, preferably from 50 μm to 150 μm, and • the nozzle opening (10; 40) has a length of from 50 μm to 500 μm, preferably from 100 μm to 300 μm. 4. Needleless injector according to claims 1 and 3, characterized in that the nozzle (9; 39) has several openings, the hydraulic diameters of which are different as needed. 5. Needleless injector according to claims 1 and 2, characterized in that • the nozzle (9; 39) has several openings, the longitudinal axes of which run parallel to each other or are inclined so that they move away from each other. 6. Needleless injector according to claims 1 to 5, characterized in that • the position of one stop, and thus the stroke of the hollow piston (a), can be changed. 7. Needleless injector according to claims 1 to 6, characterized in that • the clamping device can be tightened by manually turning two parts of the housing (1; 2), (31; 32) in opposite directions. 8. Needleless injector according to claims 1 to 7, characterized in that • the locking tensioning device can tighten over the screw-push transmission by turning the two housing parts (1; 2), (31; 32) in opposite directions. 9. Needleless injector according to claims 1 to 8, characterized in that • the locking tension device contains a screw spring (6; 36), a plate spring or a feather spring as stored energy. 10. Needleless injector according to claims 1 to 9, characterized in that • the nozzle (9; 39) is made of metal, plastic, glass, silicon or a precious stone such as sapphire, ruby, corundum. 11. Needleless injector according to claims 1 to 10, characterized in that • a separate container (14; 44; 54) for liquid is releasably connected to the end of the hollow body protruding from the cylinder by means of a pressure fitting (19; 49; 59). 12. Needleless injector according to claims 1 to 11, characterized in that • a separate container (14; 44; 54) for the liquid is releasably connected to the hollow piston (7; 37; 57) and can be moved inside the housing with the stroke of the hollow piston. 13. Needleless injector according to claims 1 to 12, characterized in that • the separate container (54) for the liquid is made as a replaceable container, and the spring part (53) is made to accept the separate container. 14. Needleless injector according to claims 1 to 13, characterized in that • the separate container (54) for the liquid is releasably connected to the hollow piston (57) and the rebound part (53), and • the spring part (53) has snap-in hooks (51) that engage in the circulation groove (52) on the tank. 15. Needleless injector according to claims 1 to 14, characterized in that • the end of the carbonless injector on the nozzle side has a closing cap (18). 16. Needleless injector according to claims 1 to 15, characterized in that • there is a filter (11) in front of the side of the nozzle facing the pump area. 17. Needleless injector according to claims 1 to 16, characterized in that • a separate container (14; 44; 54)) for liquid is filled with a liquid drug primarily from the group of analgesics, vaccines, antidiabetics, hormones, contraceptives, vitamins, antibiotics, sedatives, anti-microbial substances, amino acids, coronary agents . 18. A needleless injector according to claims 1 to 3, for liquid, which is made as a hand-held device, with a housing and a container for liquid, characterized in that • the locking tensioning device contains a screw spring (6; 36), and the locking tensioning device can be tightened via a screw-push transmission by turning two parts of the housing (1; 2) (31; 32) in opposite directions, and on the locking tensioning device there is activation device, i • at the end of the cylinder there is a nozzle (9; 39) with a single opening (10; 40) and • the container (14; 44; 54) is connected to the end of the hollow piston by means of a pressure fitting (59), and which is connected to the rebound part (53) by means of snap-on hooks (51) that engage in the circulation groove (52) on the container, and • a separate container (14; 44; 54) is filled with liquid medicine. 19. Needleless injector according to claims 1 to 18, characterized in that • there is a filter (11) in front of the side of the nozzle facing the pump area. 20. The use of a non-acrylic injector according to claims 1 to 19, characterized in that it is used for injecting a liquid containing an active substance into biological tissue. 21. The use of a non-acrylic injector according to claims 1 to 19, characterized in that it is used for injecting a liquid containing an active substance into plant tissue. 22. The use of a glycol-free injector according to claims 1 to 19, characterized in that it is used for injecting a liquid containing an active substance into animal tissue. 23. The use of a glycol-free injector according to claims 1 to 19, characterized in that it is used for intracutaneous injection of a vaccine into an animal. 24. The use of a glycol-free injector according to claims 1 to 19, characterized in that it is used for subcutaneous injection of a vaccine into an animal. 25. Use of a glycol-free injector according to claims 1 to 19, characterized in that it is used for intracutaneous injection of a vaccine into a human. 26. The use of a glycol-free injector according to claims 1 to 19, characterized in that it is used for subcutaneous injection of a vaccine into a human. 27. The use of an oxygen-free injector according to claims 1 to 19, characterized in that it is used to inject liquid through the membrane into the space behind the membrane.