BG64726B1 - Miniature needleless injector - Google Patents

Abstract

The needleless injector is designed for liquid injecting. It is a hand-held device, preferably in miniature execution and is for multiple use, suitable for repeated pushing out of preset quantity of liquids, bigger than the quantity of the liquid contained in one spare cylinder, which can be replaced in an easy way. The needleless injector has two housing parts (1, 2) interconnected with a facility for shifting, a spare liquid tank (14), fitted in the housing and connected to a hollow piston (7) displaceable within a cylinder, locking a tensioning mechanism with a shifting part, a releasing device (5) and nozzle (9). Both parts (1, 2) of the housing are positioned and formed with a facility for counter-rotation. The locking tensioning system is tensioned by counter rotation between two spacers (17), a spring-tensioning part (3), connected to the release device. The hollow piston (7) is fitted to the spring tensioning part (3), is driven by the lockable tensioning system, moves inside cylinder (8) and has a single valve (12). At the end of cylinder (8) a nozzle (9) is found with at least one hole (10), the space between the nozzle and the valve is in the form of a valve space (13). The spare liquid tank (14) is fitted in the housing, being separated from the needleless injector, and is connected to the end of the hollow piston (7), which projects out of cylinder (8). The amount of liquid which, during the drawing of the hollow piston (7) from cylinder (8) is fed across to the pumping space (13), is determined by travel (a) and the cross-section of the hollow piston (7). The position of travel (a) of the hollow piston (7) inside the needleless injector is determined by the position of the two spacers (17).

Description

The invention relates to a needle-free injector as a hand-held device, preferably in a miniature embodiment, which injects intracutaneous fluid, for example into 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 substance. The active substances may be pharmacologically active agents for the treatment of human or animal organisms, and may also 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 allows for the ecological application of the active systemic agent, since the active substance is fed directly to the plant.

EP-0063341 and EP-0063342 are known to be a needle-free injector that contains a piston pump to inject the injected fluid, which is pumped by a working fluid from the engine. The fluid reservoir is positioned laterally on the piston pump. The amount of fluid required for injection is sucked in by reciprocating the piston through the suction duct and the 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-free vaccination device that is actuated by a siphon cartridge through a special pressurized carbon dioxide valve.

EP-0347190 discloses a vacuum injector with a compressed gas in which the depth of penetration of the injected drug is adjusted by gas pressure and the volume of the drug by the stroke of the piston.

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 piston rod. At the other end of the ampoule is a nozzle whose diameter decreases towards the end of the ampoule.

WO-1989/008469 describes a needle-free injector.

WO-1992/008508 provides a needle-less injector designed for three injections. The ampoule containing the medicament 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 leaving the unified actuator is retracted manually. Both appliances operate with compressed gas.

From WO-003779, a needle-less injector with a body of two parts and a liquid reservoir located sideways to the apparatus is known. The piston actuator spring is stretched by an engine with a reducer. The spring is released when the two parts of the body slide against each other as the nozzle is pressed against the injection site. There is always one valve in the suction duct for the liquid and at the outlet of the metering chamber.

Another needle-free injector is disclosed in WO-1995/003844. It contains a fluid-filled tank which at one end contains a nozzle through which the liquid is forced out. At the other end, the tank is closed with a piston-shaped piston sliding into it. One piston loaded through the pre-stressed spring, after the spring has been released, slides inward the caliper piston to a portion of the tank, thereby displacing the amount of injection fluid. The spring is released when the nozzle is pressed tightly enough into the injection site.

This injector is intended for single or multiple use. The tank is located in front of the spring loaded piston and is a fixed component of the injector. The plunger position of the injector intended for repeated use is moved after each injection with one part toward 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 force all the fluid into the tank at once. The spring can be re-tensioned when the injector disassembles and its drive part is assembled with a new, fully filled tank.

Patent FR-2629706 is known, which discloses a solution most closely related to the present invention. There are two embodiments of a needle-free injector for use in dental treatment that can be used to inject a predetermined amount of fluid into the gums. Each of the two needle-free injectors consists, respectively, of a housing consisting of two parts which are coaxially connected and disassembled. They can be fixed and moved by compressed air, which serves as a working medium and is injected into the injector from outside through an external source. An injector release button is provided, whereby a working piston is displaced by pushing, in agreement between compressed air, coil springs and locking devices, to a predetermined portion whereby the amount of injection fluid is expelled through the nozzle. Several coil springs are tensioned at the same time, which return the axially moving parts to the injector to their initial position when the action of compressed air is stopped. The injection fluid is stored inside the injector in a kind of storage chamber, shaped as a tubular stable reservoir, which at one end is provided with a movable seal which, through the spring-loaded piston, permanently presses the liquid contained in the reservoir. . When a part of the liquid is forced out of the tank into the fluid space inside the pump cylinder, a pressure spring pushes inward one corresponding part of the liquid in the tank above the piston and the seal. Fluid injection is performed through a valve. At the same time as the injection takes place, the mechanical parts of the needleless injector are brought to the starting position and the injector is ready for the next injection.

In some known embodiments of the needleless injector, the injection fluid reservoir is positioned laterally to the actuator. The amount of injection fluid is sucked in when the plunger of the piston pump is returned to the pumping room. The inlet duct contains a suction valve and the outlet duct contains a discharge valve. Both valves operate by force.

In other embodiments of the needleless injector, the reservoir serves directly as a pump chamber to eject the injected fluid, which is taken as a forceful impact that occurs when the amount of injection fluid is displaced.

In compressed air non-needle injectors, a portion of the compressed gas is released after each injection. The compressed gas tank is therefore replaceable when it is not intended to be refilled directly with compressed gas. With these injectors, the drive unit must be replaced when the compressed gas tank is empty.

SUMMARY OF THE INVENTION

The invention seeks to provide a reusable, needless, simple-injection injector suitable for repetitive ejection of a predetermined amount of fluid, with the total ejected amount of fluid after many applications being greater than the amount of fluid contained in a single stock. tank.

It is another object of the invention to provide an injector design capable of taking more partial quantities of the reservoir fluid one after the other or to take and expel the amount of fluid contained in one reservoir at one time as a whole.

It is another object of the invention to make the replacement tank easy to replace.

The invention also aims at creating a large mechanical shock or impulse with a predetermined amount of fluid so that it can penetrate a membrane, foil or biological tissue.

The object of the invention is solved by a needleless fluid injector shaped as a handheld device comprising a housing of two moving parts connected to one another, a spare fluid reservoir housed in the housing and connected by a hollow piston to the cylinder. , locking mechanism with movable part, release device and nozzle.

The two body parts that are connected to each other are arranged and rotatable.

The locking mechanism has a spring-loaded part between the two stops, which has a momentary action for switching on or off and is provided with a releasing device. The hollow piston is secured to the spring portion and is actuated by a tensioning-locking mechanism. It is movable in the cylinder and protrudes at one end of the cylinder, with a valve mounted at the other end. At the end of the cylinder, a nozzle having at least one orifice is fitted and a pump space is formed in the space between the nozzle and the valve.

The replacement fluid reservoir located inside the housing is shaped as a reservoir separated by a needleless injector and connected to the end of the hollow piston projecting from the cylinder.

The predetermined amount of fluid which, when reciprocating or pulling the hollow piston from the cylinder, flows through it into the pumping space, is determined by the stroke and the cross section of the hollow piston.

The position of the hollow piston stroke inside the needleless injector is determined by the position of the two stops.

Preferably, towards the end of the hollow piston, which is located in the cylinder, is fitted with a one-piece valve, which is guided through the hollow piston and is axially movable. The valve moves with the hollow piston. It preferably has a uniaxial rotationally symmetrical shape, such as a circular cylinder shape or a truncated cone. Its diameter may be smaller than the diameter of the space in which it is axially movable. The valve can be rotated about its axis, which 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 housing is restricted by the stop. When the trap rests on the designated sealing surface, it is closed.

The space between the nozzle and the hollow piston valve is the pumping space. At the end of the pumping space, a filter can be placed on the side of the nozzle, i.e. 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 and adjusted to the particle size.

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

The needle-free fluid injector according to the invention is preferably arranged so that the two parts of the housing are disassembled with one another.

It is advantageous to provide a needle-free liquid injector according to the invention, wherein the nozzle contains only one orifice with a diameter of 10 to 500 pm, preferably 50 to 150 pm.

The nozzle opening has a length of from 50 to 500 pm, preferably from 100 to 300 pm.

Preferably, a needleless fluid injector according to the invention, wherein the nozzle contains more openings whose diameter is accordingly different.

The needleless fluid injector according to another preferred embodiment of the present invention is also configured such that the nozzle contains more openings whose longitudinal axes are parallel to one another or inclined in divergence to one another.

An embodiment of the needleless fluid injector according to the invention is provided, wherein the position of the stop and the stroke of the hollow piston is variable.

The needleless fluid injector according to the present invention is preferably constructed in such a way that the locking mechanism is able to be stretched by turning the two parts of the housing by hand by hand.

It is also advisable to carry out a needleless fluid injector according to the invention, wherein the locking mechanism is able to be tensioned by a screw-sliding gear while rotating the two parts of the housing relative to each other.

The locking mechanism and the energy storage of the spring are tensioned, preferably by rotating the two parts of the housing relative to each other by a helical gear. Torque can be obtained by turning by hand or by means of a propulsion motor.

Another preferred embodiment of the needless fluid injector is one in which, according to the invention, the locking mechanism comprises a coil spring, a flat circular spring or a plate spring as an energy accumulator.

The locking mechanism consists of a drive flange, made as a spring part, one drive (thrust) for spring tension, one locking element, two restraints for the drive flange, between which the drive flange can move in a reciprocating, reciprocating manner to release the locking element. The drive flange path is precisely constrained by both stops.

A power gear is located between the energy storage spring and the spring tension actuator.

The locking element is annular and has interlocking locking surfaces. A cylindrical coil spring or a flat circular spring, or a plate spring, which acts as a tension or compression spring, may preferably be used as an energy storage.

The energy storage spring can be stretched by direct drive. For this purpose, the drive flange is displaced by an axially acting external force. In the case of high spring force, it is preferable to have a conversion gear, for example a screw-sliding gear, 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, for example, two saw blades sliding on which two saw blades formed at the top of the housing.

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

Between the two positions of the spring part of the locking mechanism, the spring force varies by about ± 10% of the average spring force.

The locking member may be a radial, elastically deformable ring or a rigid non-deformable ring with molded plate springs, or a ring that is subjected to pre-tensioning by one or more metal springs. The ring may be closed or open. It may consist of several parts.

The locking element is movable in one plane, vertically on the axis of the housing or it is deformable in this plane.

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

The hollow piston fixed in the spring part of the locking mechanism is actuated by it. The hollow piston is immersed in the cylinder and protrudes a portion of its length beyond it. It is movable and moveable.

Preferably, the implementation of a needle-free liquid injector according to the invention wherein the nozzle is made of metal, plastic, glass, silicon or a gem such as sapphire, ruby, corundum.

The nozzle may be in the form of a parallel Lepiped formed by two silicon plates, which is, for example, 1.1 mm wide, 1.5 mm long and 2.0 mm high.

The parallelepiped may have a flat triangularly shaped, approximately 400 µm wide slit in the tangent surface of the plates, which terminates in a single nozzle opening that is 50 µm wide and 200 µm long.

It is advisable for the nozzle to be enclosed throughout its periphery by a precisely fitted elastomeric profile portion. The inner contour of the elastomeric profile portion is aligned with the outer contour of the nozzle. In particular, the outer contour of the elastomeric profile portion is aligned with the inner contour of a nozzle carrier, preferably made of metal. Such a "floating reinforcement" makes the nozzle of fragile metal insensitive to impact loads that occur with a needle-less injector used for its intended purpose.

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 housing. The movable cylinder is held in its calm position by a return spring.

The two limiters for the spring part can be fixed in the housing. In addition, the position of one of these stops can be changed in the axial direction. This can change the volume of the pumping space with a constant outer diameter of the hollow piston. In the unchanged construction of the needleless injector, the amount of ejected fluid can be varied by changing the position of the stop.

The location of the coil spring and thus the hollow piston stroke inside the needleless injector is limited by both stops. Given the position of the limiters, the location of the coil spring path and thus the hollow piston stroke at each injector is constant.

Through the release device, the locking member slides parallel to or deforms radially in the plane of the ring. With the cylinder fixed in the housing, 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 housing, the releasing device is actuated by pushing the cylinder inwards against the force of the return spring, and the blocking element is disconnected by disconnecting the connection.

Preferably, a needle-free liquid injector according to the invention, in which the reservoir of the liquid reservoir discharged from the injector is connected in a detachable manner by a press assembly to the end of the hollow piston, which extends from the cylinder.

In an alternative embodiment of the needless fluid injector according to the invention, the separate fluid reservoir is connected in a detachable manner to the hollow piston and is capable of being moved internally to the housing by the stroke of the hollow piston.

The end of the hollow piston is covered by the liquid contained in the reservoir.

The needle-less liquid injector according to the invention is configured so that the separate reservoir for the liquid is formed as an interchangeable spare reservoir and a spring-loaded part is installed to accommodate the separate reservoir.

It is advantageous to carry out the needless fluid injector according to the invention, wherein the separate fluid reservoir is connected in a detachable manner to the hollow piston and the spring portion.

The spring portion is provided with locking hooks that are secured to a annular groove formed in the reservoir.

This connection may be a detachable or non-detachable plug-in connection, with the plurality of hooks being gripped into the annulus of the reservoir after it has been inserted into the needle-less injector.

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

It is advantageous for the needless liquid injector according to the invention to be arranged so that its end on the nozzle side is provided with a removable cap to protect the nozzle opening from contamination and evaporation of the liquid during storage of the needleless injector and during its use.

The needleless liquid injector according to the invention is preferably constructed in such a way that a filter is mounted in front of the nozzle facing the pumping room.

It is advantageous to carry out a needleless fluid injector according to the present invention, wherein the separate reservoir for the fluid is filled with a liquid drug, preferably from the group of analgesics, vaccines, antidiabetic drugs, hormones, pregnancy protection agents, vitamins, antibiotics agents, antimicrobials, amino acids, coronary agents.

The two body parts, the locking mechanism, the cylinder and the reservoir are preferably made of plastic, for example polybutylene terephthalate.

The hollow piston is made of metal, such as high quality special steel.

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

The nozzle can be made of metal, plastic, glass, silicon or a gem such as sapphire, ruby, corundum.

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

It is preferred to have a needle-free fluid injector according to the invention which is shaped as a hand-held device with one housing and one spare fluid reservoir in which the locking mechanism comprises a coil spring and is able to be tensioned by a single screw-sliding gear. rotating the two body parts relative to one another, the locking mechanism being provided with a releasing device.

At the end of the cylinder there is a nozzle with a single opening.

The replacement reservoir is attached by means of a press assembly with the end of the hollow piston and is connected to the spring part by means of locking hooks, which are engaged in a circular groove formed in the replacement reservoir.

The spare tank is filled with liquid medicine.

The needleless injector according to this embodiment of the invention is, where appropriate, such that a filter is located in front of the nozzle facing the pumping compartment.

When injected, the manual injector can be held with one hand and serviced. The cylinder, hollow piston, valve, nozzle and filter respectively are miniature elements of the injector structure according to the present invention.

Preferably, the use of a needleless injector according to the invention for injecting a fluid containing a biologically active substance into plant tissue.

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

- It has a shape that is comfortable to grasp. The liquid reservoir is located in the injector housing.

- It is applicable for many - up 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, the ease of use of the injector by untrained people, and it is tensioned with a relatively small amount of force through a single-screw gear.

- The locking mechanism can be released manually by pushing one finger on the start button or by pushing the 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.

- The mechanical impulse 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 for many 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 many 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.

Explanation of the annexed figures

The invention is explained in more detail with the aid of the accompanying figures, of which:

Figure 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 housing;

Figure 2 is a longitudinal section through a needle-less injector in a stressed state of energy storage, a spring in which the cylinder is movably disposed in one portion of the housing;

Figure 3 shows one end of the spare tank and the spring part in another embodiment of the invention;

Figure 4 shows one end of the storage tank and the spring section in another embodiment of the invention.

Examples of carrying out the invention

Figure 1 shows a needle-less injector comprising a housing with two parts 1 and 2 which are detachably connected to one another and arranged to rotate relative to one another. A spring-loaded spring-loaded part 3 with a momentary action on or off, a locking element 4 off, a disconnected state, a start button 5 acting on the locking element 4 and an energy-spiral spring 6 are placed in front of the locking or starting mechanism in rest. in the form of a pressure spring.

A coil piston 7 is mounted in the spring part 3 and placed in a cylinder 8. At the end of the cylinder 8 there is a nozzle 9 with an opening 10. A filter 11 is placed in front of the nozzle 9.

The end of the hollow piston 7, on the side of the nozzle 9, is provided with a valve 12. A pump space 13 is formed between the valve 12 and the filter lie.

A spare tank 14 is housed in the free space formed inside the coil spring 6. The spare tank 14 is secured by a flange 15 to the hollow piston 7 and is held thereon by a press assembly 19.

The coil spring 6 is enclosed by a separator 16 which is connected to the housing part 1 by its shape and thanks to it. The spring part 3 rests on the stop 17. The nozzle is protected by a detachable cap 18.

Figure 2 shows two parts of the housing 31 and 32, which are detachably connected to each other and arranged to rotate relative to each other. The spring-loaded locking mechanism is provided with a spring-loaded part 33 for switching on and off, a locking element 34 in the engaged, engaged state and energy-storing coil spring 36 in a stressed state.

A hollow piston 37 is mounted in the spring portion 33 and housed in a cylinder 38. At the end of the cylinder 38 there is a nozzle 39 with an opening 40. The end of the hollow piston 37, on the side of the nozzle 39, is provided with a valve 42. Between the valve 42 and the nozzle. 39 there is a pumping room 43.

The spare tank 44 is located in the free space formed inside the coil spring 36. It is gripped by a flange 45 on the hollow piston 37 and is held thereon by a press assembly 49.

The separator 46, which encloses the coil spring 36, is connected to the housing part 31 due to its shape.

The spring portion 33 lies adjacent to the stop 47 of the locking element 34.

The cylinder 38 is located in the housing portion 31 with axial displacement capability. 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 housing portion 31 against the force of the return spring 48 by pushing the needleless injector at the injection site.

The figure shows that the path of the driven part between the two stops is indicated by "a" or the stroke of the hollow piston 37 corresponds to this path "a".

Figure 2 shows the injectionless needle injector. The nozzle 39 is pressed against the schematically represented stretched skin 35. Upon further pinching at the injection site, the needle-less injector is released and the fluid is injected from the pumping space 43 into the skin 35.

Figures 3 and 4 show one end of the storage tank 54 and the spring portion 53 in other embodiments.

In Figure 3, the hollow piston 57 is inserted into the reservoir 54, but is not yet connected thereto.

In Figure 3, the storage tank 54 is represented by three partial longitudinal sections. 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 with a press assembly 59 into the submerged nozzle 58.

In a longitudinal section, a portion of the spring portion 53 is provided with a hollow piston 57 inserted therein. The spring portion 53 is provided with a plurality of retaining hooks 51 formed on its side facing the spare tank 54.

In Figure 4, the spare tank 54 is connected to the hollow piston 57 and the spring portion 53, with the hollow piston 57 connected to the press assembly 59 and to the spring part 53 by means of the retaining hooks 51, which are engaged in the annular groove 52 of the spare tank. 54.

The connection shown in Figures 3 and 4 between the spare tank 54 and the spring 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 52 with a triangular cross-section.

Example 1: Design of a needle-free injector according to the invention

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

The housing has an outer diameter of about 20 mm and a length of about 70 mm. The two parts of the housing 1, 2, 31, 32, the locking mechanism and the spring separator 16,46 are made of polybugene terephthalate. The cylinder 8, 38 is also made of polybutylene terephthalate. It has an outer diameter of 5 mm and an inner diameter of 1.60 mm. The nozzle 9.39 is made of quartz. The opening 10, 40 of the nozzle 9, 39 has a diameter of 140 µm and a length of 220 µm. The hollow piston 7, 37 made of stainless steel has an outer diameter of 1.59 mm and an inner diameter of 0.35 mm. The hollow piston stroke 7, 37 is 12 mm. The valve 12, 42 is made of an elastomer. It is in the form of a washer 2 mm thick and an outer diameter of 1.60 mm. The washer is provided with axial openings on its lateral surface through which the fluid can flow past the valve 12,42 into the pumping space 13,43. The end of the hollow piston 7, 37 is provided with a groove in which the valve 12,42 is engaged.

The displaced amount of liquid amounts to 23 mm ³ .

The interchangeable spare tank 14, 44 has a volume of about 11 mm ³ .

Example 2. Intradermal injection of fluid

A solution of 20 g of dextrin fluorescein (UW / 3000) 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, 4.5 ml of dextrin-fluorescein solution was filled into the needle injector spare tank and connected to the injector hollow piston. The injector was actuated by repeatedly stretching and releasing the locking mechanism to expel the air from the hollow piston, pump space and nozzle.

Finally, the needle-free injector was placed on a pre-shaved area in the dog's stomach area and put into action. The process was repeated repeatedly on different dogs.

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 vivo assay of live virus modified vaccine

The feasibility of needle-free injectors for the administration of a modified live virus vaccine suspension was investigated in animal experiments. This study established both the safety and tolerability of vaccination with needle-free injectors and the efficacy of this vaccination route.

Six healthy, same-age dogs were divided into two groups.

Group 1 consisted of two dogs and group 2 four dogs. Dogs from both groups were vaccinated at three weeks intervals, respectively, three times with a modified live canine vaccine (canine adeno virus).

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./ intramuscularHo, as recommended by the manufacturer, by syringe.

In group 2, adenovirus was administered by needle-free injector.

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 log ₁₀ TCID _W for 60 L (TLC = tissue infectious dose). Six single doses were given for each vaccination time (six times 10 μ1 = 60 μΐ 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:

Group 2 animals show very little redness at the injection site during the first 2 to 3 days. Only by tingling, a continuation of 1 to 2 days and a bifurcation afterwards were 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 given 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-virus vaccine using a needle-free injector is just as effective as muscle vaccination with the usual vaccine using a syringe.

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

DOGS

-------------------------------------- ₅ ----------- --------- ------ Number 21 write the first 21 days after the second 21 days drop the third

Characteristics tried vaccinated vaccinated vaccinated

CAV-1 is a common intramuscular vaccine through a syringe 1486 1024 1024 4086 1486 1024 1024 512 CAV-2 —Expression vaccine ™ γψ ™ *** Ί Through a needle-free injector 1484 TTKS 4086 4086 8162 1485 USK9 4086 4086 8182 1487 UVL8 4086 8182 4086 I486 TVL9 2048 2048 2048

Application of the invention

During storage of the unused or already used needle-free injector, as well as between two injections, it is at rest.

The energy accumulating spring 6.36 is in a stressed state.

The spring on and off portion 3,33,53 is clamped to the stop 17,47, which limits its resting state. The hollow piston 7,37,57 is immersed deep in the cylinder 8, 38. There is only a small distance between the end of the hollow piston 7,37,57 and the inside of the nozzle 9, 39. The locking element 4.34 is in the off, disengaged position.

When rotating the two parts 1,2,31,32 of the housing relative to each other, the locking mechanism is tensioned. The spring portion 3, 33, 53 slides in an axial direction, moving away from the cylinder 8,38, whereby the energy storage spring 6, 36 stumbles.

At the same time, the hollow piston 7,37,57 removes one part from the cylinder 8,38 and the pumping space 13,43 increases. The hollow piston 7, 37, 57 with one part of its length goes further into the cylinder 8,38. At the same time, a portion of the fluid contained in the reservoir 14,44,54 is expelled25 through the hollow piston 7,37,57 and is filled with fluid 12 through 42 into the pumping space 13, 43. The amount of fluid in the pumping compartment 13, 43 practically corresponds to the amount of fluid discharged for one injection.

The spring portion 3, 33, 53 slides as far as the locking member 4, 34 is in its engaged, engaged position. With a needle-less injector with trigger 5, it enters the housing slightly.

The end of the needleless injector on the nozzle side 9.39 is placed on the injection site and pressed. With a needle-less injector with trigger 5, it is triggered by a finger and pressed inward into the housing. In this way, the locking element 4 moves to the off, disengaged position and the injection is performed.

In the case of a needle-free injector with a movable cylinder 38, the injector with its end on the side of the nozzle 39 is pressed by hand with increasing force against the force of the return spring 36 on the injection site 35. Thus, the cylinder 38 slides inwards into the body, the blocking element 34 is moved in its off, uncoupled position and injection is performed.

When the needle is removed from the injection site, the return spring 36 presses the cylinder 38 back to its rest position.

While the locking element 4.34 is off, the force K of the tensile, energy-saving spring acts through the spring portion 3,33,53 of the hollow piston 7, 37, 57 and the closed valve 12, 42 at the end of the hollow piston 7, 37, 57 during the interval At, on the fluid located in the pumping space 13,43, where the mass of fluid m receives velocity Αν and thus a mechanical impulse K. At = m.Av, expires at a higher velocity than nozzle 9, 39 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, such as a drug, into human or animal tissue, in the liquid state.

Examples of suitable pharmaceutical compositions are, for example, 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 agents for dissolving, suspending or emulsifying biologically active substances and the necessary excipients are, for example, water, alcohol, alcohol-water mixtures, as well as oil-in-water emulsions, ethanol, propanediol benzyl alcohol, ethanol aqueous mixtures, oils (such as coconut oil, peanut, soybean, castor, sunflower oil), fatty acid esters (such as isopropyl myristate, isopropyl palmitate, ethyl oleate), triglyceride, triacetin, sol-ketal, propylene glycol.

Further formulations of excipients, such as preservatives such as acids or bases, can be obtained to establish 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 in the space behind it.

Claims

Claims (20)

1. Needleless fluid injector shaped as a handheld device comprising a housing of two movable parts connected to one another, a spare fluid reservoir located in the housing and connected to a displacement cylinder, hollow piston, blocking-tensioning device a mechanism with a movable part, a releasing device and a nozzle, characterized in that - the two parts (1, 2), (31, 32) of the housing which are connected to each other are arranged and rotatable relative to each other, such as - the locking mechanism is movable between two stops (17,47) a spring portion (3,33,53) which is connected to the release device and the hollow piston (7,37,57) is fixed in the spring part ( 3,33,53) and is actuated by a tensioning-locking mechanism, the hollow piston (7,37, 57) being movable in the cylinder (8, 38) and containing a single valve (12,42) and at the end a nozzle (9, 39) with at least one opening (10, 40) is mounted on the cylinder (8, 38), forming a pumping space (13,43) between the nozzle (9,39) and the valve (12, 42). , in that - the reservoir (14, 44, 54) for the fluid is located inside the housing, is shaped as a reservoir separated from the needleless injector and connected to the end of the hollow piston (7, 37, 57) projecting from the cylinder ( 8, 38) - the amount of fluid which, when the hollow piston (7) is withdrawn from the cylinder (8), is fed through the hollow piston (7) into the pumping space (43), is determined by the stroke (a) and the cross-section of the hollow piston (7), whereby - the position (h) of the hollow piston (7) inside the needleless injector is limited by the position of the two stops (17,47). A needle free liquid injector according to claim 1, characterized in that - the two parts (1,2), (31,32) of the housing are detachably connected to each other. A needle-free liquid injector according to claims 1 and 2, characterized in that - the nozzle (9, 39) contains only one opening (10.40) with a diameter of 10 µm to 500 µm, preferably from 50 µm to 150 µm, and the nozzle opening (10, 40) (9, 39) has a length of 50 to 500 µm, preferably 100 to 300 µm. A needle-free liquid injector according to claims 1 and 2, characterized in that - the nozzle (9, 39) contains more openings (10.40) whose diameter is different. A needle-free liquid injector according to claims 1 and 2, characterized in that - the nozzle (9, 39) comprises a plurality of openings (10.40) whose longitudinal axes are parallel to one another or inclined in a divergent manner. A needle-free liquid injector according to claims 1 to 5, characterized in that - the position of the stop (17) and that of the stroke (a) of the hollow piston (7) is variable. A needle-free liquid injector according to claims 1 to 6, characterized in that - the locking mechanism is capable of being stretched by turning the two parts of the housing (1,2), (31, 32) against each other by hand. A needle-free liquid injector according to claims 1 to 7, characterized in that - the locking mechanism is able to be tensioned by a screw-sliding gear for rotating the two parts (1,2), (31, 32) of the housing relative to each other. A needle-free liquid injector according to claims 1 to 8, characterized in that the locking mechanism comprises a coil spring (6, 36) or a flat circular spring or a plate spring as an energy storage. A needle-free liquid injector according to claims 1 to 9, characterized in that - the nozzle (9, 39) is made of metal, plastic, glass, silicon or a gem such as sapphire, ruby, corundum. A needle-free liquid injector according to claims 1 to 10, characterized in that - the separate liquid reservoir (14, 44, 54) discharged from the injector is disassembled by means of a press assembly (19, 49, 59) with the end of the hollow piston (7, 37, 57) projecting from the cylinder (8, 38). A needle-free liquid injector according to claims 1 to 11, characterized in that - the separate reservoir (14,44,54) for the liquid is detachably connected to the hollow piston (7, 37, 57) and is capable of being moved in the housing of the hollow piston (7, 37, 57). A needle-free liquid injector according to claims 1 to 12, characterized in that - the separate spare tank (14,44,54) for the liquid is shaped as an interchangeable spare tank, with the spring part (53) installed and adapted to receive the separate spare tank (14,44, 54). A needle-free liquid injector according to claims 1 to 13, characterized in that - the separate reservoir (54) for the liquid is detachably connected to the hollow piston (57) and the spring part (53), and - the spring portion (53) is provided with locking hooks (51) which are engaged in a annular groove (52) formed in the storage tank (54). A needle-free liquid injector according to claims 1 to 14, characterized in that - the end of the needleless injector on the nozzle side (9) is provided with a cap (18). A needle-free liquid injector according to claims 1 to 15, characterized in that - one filter (11) is mounted in front of the nozzle side (9) facing the pumping room (13). A needle-free liquid injector according to claims 1 to 16, characterized in that - the separate fluid reservoir (14,44,54) is filled with a liquid medicine, preferably from the group of analgesics, vaccines, antidiabetic drugs, hormones, anti-pregnancy agents, vitamins, antibiotics, sedatives, antimicrobials, amino acids, amino acids, amino acids coronary agents. A needle-free liquid injector according to any one of claims 1 to 3, which is configured as a handheld device with one housing and one spare fluid tank, characterized in that - the locking mechanism comprises a coil spring (6, 36) and is capable of being tensioned by a screw-sliding gear for rotating the two parts (1,2), (31,32) of the housing relative to each other, the locking mechanism being fitted with one release device and - one nozzle (9, 39) with a single opening (10, 40) is fitted at the end of the cylinder (8,38), and - the spare tank (14,44,54) is connected by a press assembly (19,59) to the end of the hollow piston (7, 37) and is connected to the spring part (53) by means of locking hooks (51) which are engaged in annular groove (52) formed in the storage tank (14,44, 54), wherein 5 - The spare tank (14, 44, 54) is filled with liquid medicine. A needle-free injector according to claim 18, characterized in that - a filter (11) is mounted in front of the nozzle side (9) facing the pumping room (13). Use of a needle-free injector according to claims 1 to 19 for injecting a fluid containing biologically 15 active substance in plant tissue. Attachment: 4 figures Publication of the Patent Office of the Republic of Bulgaria 1113 Sofia, 52-B Dr. GM Dimitrov Blvd.