EP1460948A1

EP1460948A1 - Apparatus for the microscopically-dosed injection of an active product by means of jets of pressurised working liquid and the method of generating a sequence of liquid jets using said apparatus

Info

Publication number: EP1460948A1
Application number: EP03712215A
Authority: EP
Inventors: Bertrand Gonon
Original assignee: Eschmann Holdings Ltd
Current assignee: Eschmann Holdings Ltd
Priority date: 2002-01-07
Filing date: 2003-01-07
Publication date: 2004-09-29
Also published as: WO2003057052A1; FR2834442B1; AU2003216790A1; US20050090778A1; FR2834442A1

Abstract

The invention relates to an injection apparatus (1) which blasts pressurised working liquid against the tissue to be treated in order to hollow out an injection channel and which subsequently injects the active product into said channel. The inventive apparatus comprises a reserve of working liquid (2) which can be pressurised and which is connected to a handpiece (5) by means of a main branch (4) of the fluid system. An active end piece (8) is disposed at the end of said handpiece comprising outlet means for a pressurised jet of working liquid. Moreover, the invention comprises a secondary branch opening (15) which is parallel to the main branch and which is fluidically isolated from same. Said secondary branch is intended to contain the active product. According to the invention, a multiplexing means (24) is used independently to control the opening and closing of the isolation valves (22, 23) of each of the two branches of the system according to pre-determined parameters.

Description

APPARATUS FOR MICRODOSE INJECTION OF AN ACTIVE PRODUCT AND METHOD

The present invention relates to a surgical, medical or diagnostic apparatus with jets of pressurized liquid making it possible to carry out one or more microdose injections of an active or treatment product. It also relates to an injection process using this device.

More generally, it also relates to a method for generating by a device a sequence of liquid jets comprising at least one pulse of working liquid under pressure followed by a microdosed pulse of active product.

In the context of medical treatment, during a surgical intervention or a diagnostic action, it is often advantageous to administer an active product, for example a drug, a product useful for surgical intervention or a diagnostic agent, directly in contact with the sick or to be treated area which is most often located inside the human body, in an organ or in the tissue thereof.

Conventionally, an injection catheter is used for this, which is inserted and pushed along a vessel inside the patient's body until its distal end, having a or several orifices or possibly extended by an injection needle, is as close as possible to the area to be treated. Then the active product is injected under pressure onto the area to be treated through the opening (s) or the needle at the end of the injection catheter.

Currently, we are witnessing the development growing gene and cell therapies requiring the use of specific active products, such as for example cells, genes, plasmids or proteins, the injection of which is delicate and poses new problems.

Indeed, these products, often based on living cells, are particularly fragile. They are for example sensitive to shocks, to pressures that are too high, to pipes of reduced diameter.

They must also be injected in very small quantities while respecting a precise dilution and dosage.

In addition, their dissemination is difficult. When injected using a conventional syringe or needle injection catheter type device, instead of gradually diffusing, these products tend to remain in a sphere located at the injection site. The effectiveness of the treatment is greatly reduced and the number of injection points must be multiplied.

The object of the invention is to provide an apparatus and a method making it possible to improve the injection, in particular of this type of product. There are also known needleless devices for injecting a treatment product under pressure. With this type of device, there is no longer any mechanical perforation of the tissue prior to injection. Penetration into the tissue is effected by the pressure force of the liquid which, after being ejected, strikes the tissue with sufficient force to perforate it and form an injection channel, then diffuses into the tissue from this channel . Thanks to the pressure with which it is injected, the treatment liquid penetrates a lot deeper than with a conventional needle injection device and its distribution is more extensive. These devices can be equipped with a catheter which makes it possible to inject inside the patient's body, directly in contact with the organ or tissue to be treated.

However, if these pressure injection devices have many advantages compared to conventional devices, they are not suitable for the injection of active products used in the context of gene or cell therapies. Indeed, these products, often containing viruses or living cells, are very fragile. When they are ejected under pressure by this type of device, they deteriorate through the violence of the shock against the treated tissue which generally causes the death of living cells and destroys the entire activity potential of the product.

The object of the invention is to teach a pressure injection device, having all the advantages of this type of device, but making it possible to inject a fragile active product, such as for example a transgenic product, without any deterioration. The inventive principle consists in dissociating the phase of producing an injection channel, harmful for fragile substances, from that of injecting the active product.

The device according to the invention makes it possible to make a shot of a working liquid under pressure against the tissue to be treated so as to hollow out an injection channel, then to inject the active product into this channel.

These two operations are carried out successively but in a short time and with the same device. The surgeon can successively perform several shots and therefore several injections of active product, in the same injection channel or in several places of the tissue to be treated, the parameters of each shot of the injection process being previously chosen and programmed by the surgeon so as to optimize the injection according to each individual case.

The active product, not being used to dig the conduit, does not undergo a violent shock and is perfectly preserved. It can however be sent under pressure and deep into the targeted tissue. Its diffusion is therefore greatly improved compared to a conventional injection device.

By patent application WO 00/56232 in the name of SAPHIR MEDICAL PRODUCTS GMBH, there is known an apparatus for dissection by pressurized liquid also making it possible to inject a treatment liquid by pressure spraying.

This device provides either for direct mixing of the treatment product in the reserve of working liquid, or for having a reserve of working liquid and an independent reserve of treatment product, both being pressurized by a generator. pressure.

In the first case, the active product is diluted in the working liquid and is used at the same time as this. Such a scenario cannot be suitable for the fragile products targeted by the invention. Indeed, they would then be destroyed by digging the injection channel. In addition, the working liquid, most often physiological saline, is generally packaged in flexible plastic bags of large capacity, conventionally one liter. The active product, expensive and difficult to manufacture, is generally in the form of small quantities and would be very strongly diluted in the reserve of working liquid, which would lead to a concentration in the injected form incompatible with the desired applications.

In the second case, a reserve of treatment product is pressurized by the pressurized liquid generator. The surgeon triggers the firing of the active product by means of a switching or mixing device which is not described.

Application WO 00/56232 also generally envisages the production of combinations of pulses of working liquid and of treatment product within a discontinuous train of pulses constituting a pulsed jet, using a multiplexing means not described. These different variants are envisaged in a very general way, without a precise embodiment being described and therefore remain on a purely theoretical level.

The invention makes it possible to provide a concrete embodiment of this general principle by teaching a bypass device playing the role of this mixing, switching or multiplexing member.

The injection device according to the invention comprises, like the device described in this previous application, a reserve of working liquid which can be pressurized by a pressurized liquid generator, a handpiece ending in one end. active comprising means for outputting a jet of pressure, continuous or pulsed, working liquid and a jet of active product.

According to the invention, the apparatus further comprises: - a main branch of the fluid circuit, connecting the reserve of working liquid to the handpiece, and in which the flow is controlled by the state of a first valve;

- A secondary branch branch, parallel to the main branch and fluidly isolated from the latter, intended to contain the active product, and in which the flow is controlled by the state of a second valve; and

a multiplexing means making it possible to independently control the opening and closing of the valves of each of the two branches of the circuit according to predetermined parameters.

These parameters are arbitrary and are previously chosen and recorded by the surgeon according to the particular case to be treated.

By varying the opening parameters of the two valves of the two branches of the circuit, the surgeon can obtain with the device according to the invention very numerous injection possibilities.

The invention thus teaches for example a method of generating a sequence of liquid jets by means of a similar device in which the two valves of the two branches of the circuit are simultaneously opened in order to produce this mixture in the active end of the 'apparatus and generate a jet consisting of a mixture of active product and working liquid whose proportions are precisely fixed by adjusting the opening time of each valve.

The invention also teaches an injection method using this device in which an injection channel is dug by firing a jet of working liquid under pressure, then in a subsequent phase, the active product is injected into this channel injection.

The injection channel being hollowed out firstly by firing the jet of pressurized working liquid, the active product injected in a second time is perfectly preserved.

More generally, it teaches a process for generating a sequence of liquid jets by means of an apparatus comprising a reserve of working liquid pressurized by a pressurized liquid generator, a handpiece ending in an active end. which comprises means for outputting a pressurized jet of working liquid and a jet of an active product, a main branch of the fluid circuit, connecting the reserve of working liquid to the handpiece, in which the flow is controlled by the open or closed state of an isolation valve, a secondary branch branch, parallel to the main branch and fluidly isolated from the latter, intended to contain an active product and in which the flow is controlled by the open or closed state of an isolation valve, and a multiplexing means for independently controlling the opening and closing of the isolation valves according to parameters. very predetermined. This process is characterized in that one generates a sequence comprising at least one pulse of working liquid under pressure, followed by a microdosed pulse of active product. According to this process, the valve of the main branch of the circuit is first opened in order to generate a pulse formed of an appropriate quantity of working liquid under pressure, then in a next step the valve of the branch branch is opened in order to generate a pulse formed by the desired amount of active product.

Here again, the quantities of liquid forming the pulses of working liquid and of active product can be precisely established by fixing the opening times of each of the valves.

The active product pulse can possibly be followed by a new pulse of pressurized working liquid. This new impulse can for example serve to push the active product deeper into the heart of the tissue to be treated. The pulse of active product can also be generated under high pressure, that is to say with a pressure corresponding substantially to that of the working liquid.

However, certain particularly fragile products cannot withstand being subjected to such pressure. In a particularly advantageous manner, the pulse of active product can also be generated at a pressure lower than that of the working liquid and preferably at low pressure.

Due to their inventive design, the apparatus and the method according to the invention make it possible to easily use very small quantities of active product and to carry out microdoses thereof.

The apparatus and method according to the invention are therefore particularly well suited for the injection of transgenic active products. They can however be used in all kinds of other surgical, medical, therapeutic or diagnostic applications, as well as in applications relating to different technical fields.

Other characteristics and advantages of the invention will appear on reading the detailed description which follows, description made with reference to the appended drawings, in which:

. Figure 1 is a general schematic view of the injection apparatus according to the invention; . FIG. 2 is a schematic view of a part of the injection apparatus according to the invention corresponding to the main branch and to the branch of the hydraulic circuit;

. Figure 3 is a schematic view similar to that of Figure 2, showing the part of the injection device according to the invention corresponding to the main branch and the branch branch of the circuit, with a small diameter conduit;

. FIG. 4 is a view of another variant of the part of the injection device according to the invention corresponding to the main branch and to the branch branch of the circuit, not comprising a valve for introducing the active product but in which the bypass tubing serves as a metered reserve of active product; . FIG. 5 is a graph representing the nature and the quantity of liquid delivered by the apparatus over time, during a particular example of its application to two successive microdose injections of active product. . FIGS. 6 to 12 are schematic views of a part of the injection device according to the invention, corresponding to the main branch and to the branch branch of the circuit and to the catheter, in various configurations corresponding to different times, referenced from

VI to XII on the graph of FIG. 5, during the example of application represented in FIG. 5.

The injection device according to the present invention will now be described in detail with reference to Figures 1 to 12. The equivalent elements shown in the different figures will have the same reference numerals.

In Figure 1, there is shown schematically an injection device 1 according to the invention capable of sending one or more jets of sterile working liquid under pressure and inject one or more microdose quantities of active product.

This device comprises a reserve 2 of working liquid, for example a flexible plastic bag containing the working liquid, connected to a generator 3 of pressurized liquid.

According to a preferred embodiment, the generator 3 of pressurized liquid is an enclosure in which the reserve 2 of working liquid is enclosed and which is filled with a neutral gas under pressure in order to compress the bag and put the liquid under pressure.

The pressure of the jet of liquid generated can be adjustable in order to adapt it to the needs. The pressure inside the enclosure is preferably between 0.3 and 200 bars and preferably between 0.3 and 100 bars.

The enclosure can also be thermostatically heated to a temperature close to or slightly above 37 ° C so that the working liquid reaching the intervention site is approximately the same temperature as the patient's body. The working liquid used is preferably sterile physiological serum used at an appropriate pressure depending on the application. A suitable high pressure value of the working liquid cited here only by way of example is around 20 bars.

Other sterile liquids can obviously be used as sterile working fluid such as for example a saline solution, a solution of glucose, of Ringer-lactate, of hydroxyethyl starch or a mixture of these solutions.

The sterile working liquid is supplied by through a tube forming the main branch 4 of the hydraulic circuit, to a handpiece 5 which allows the user to control the triggering of the jet of working liquid and / or active product and to direct it.

The handpiece 5 has an ergonomic body 6, allowing easy gripping and handling and may have control members such as for example push buttons 7. The handpiece 5 is extended by an active end 8. It s 'Acts in this variant of a catheter 9. It is conventionally in the form of a flexible conduit 10 in and along which passes the sterile working liquid under pressure as well as the active or treatment product.

The catheter 9 includes a proximal end 11 manipulated by the surgeon and a distal end 12 inserted inside the patient's body. The distal end 12 of the catheter has one or more orifices through which the working liquid and the active product are ejected.

The catheter 9 may include known navigation and orientation means which, not forming part of the invention, have not been shown in the figures. Its distal end 12 is articulated and may further include a locating system in order to be able to position itself at the appropriate place and at a preferential inclination, the assembly being controlled from the handpiece 5.

The catheter 9 may also include an anchoring system in order to ensure immobilization of the active distal end during fluid shots, thereby improving the precision of the interventions. It can be any mechanical anchoring means or a means using suction. In this case, the injection device 1 comprises a suction system 13 connected to a vacuum source 14, for example a vacuum pump or the general vacuum circuit of the hospital. These optional means have been shown in broken lines in FIG. 1.

One can then imagine a variant of catheter 9 which comprises a suction conduit surrounding the conduit 10 concentrically and flaring at the distal end 12 of the catheter to form a skirt.

Thus, after positioning the distal end 12 of the catheter near a zone of tissue or wall of an organ to be treated, the surgeon can press the distal end against this zone by triggering the suction at the level of the skirt which then behaves like a suction cup.

Advantageously, the skirt physically isolates the injection site from the blood circulation and from the rest of the patient's body.

Indeed, the active product, useful and beneficial on the targeted area, can be harmful, even toxic if it is applied to other organs of the patient not concerned by the treatment. This is in particular often the case in gene therapies, during which it is possible, for example, to administer to the target organ genes, cells, nucleic acids or genetically modified proteins, applied in isolation or by means of a vector for example a virus.

It is therefore very important that the administered product, developed for a specific application, remains localized at the site of its injection and is not carried away from the treatment site by the flow of the blood circulation in order to avoid it ending up inadvertently. other non-target organs. With the device according to the invention, the active product is injected deep into the heart of the tissue to be treated, which greatly reduces the probability that it will come out of the injection channel and lead to an organ not concerned by the treatment.

If the distal end 12 of the catheter is provided with a suction skirt, the injection site is completely isolated from the patient's blood circulation, until a complete diffusion of the active product in the tissue concerned has occurred. The risks of accidental dispersion are thus further reduced.

To further limit the risks, these active ingredients are often formulated in the form of a particularly viscous liquid in order to prevent it from flowing out of the injection channel. Advantageously, the device according to the invention is perfectly suited for injecting products whatever their viscosity.

According to a preferred variant not shown, the catheter 9 may comprise at its distal end a retractable puncturing or pricking tool, preferably of the retractable needle type, movable between a working exit position and a retracted safety position inside the catheter, allowing to perform a puncture work initiating the digging of the injection channel by a mechanical perforation. According to an originality patented moreover, the exit of the end tool can be caused automatically by the pressure of the liquid escaping from the catheter, the end tool being automatically retracted inside the catheter in the absence liquid or if its pressure is below a threshold value. The injection device 1 also includes a secondary branch branch 15 intended to contain the active product to be injected.

This secondary tubing 15 is preferably connected to a reserve of active product or of treatment 16 by means of communication 17.

The reserve of active product 16 can be of any kind. It is for example a self-piercing system of a precise dose of active product. It can also be a simple syringe in which the surgeon has placed the active product and which he uses to introduce the active product into the injection device via the communication means 17.

The communication means 17 can for example be a three-way charge valve 18 as shown in the figures. In order to avoid handling errors, the charging valve 18 is preferably a two-way valve.

By a simple opening of the valve 18, the surgeon can initially put the reserve of active product 16 in communication with the secondary branch 15 of the device in order to load the latter with active product. The charging valve is then placed in the configuration shown in FIG. 3. The surgeon can thus, for example, fill the secondary tubing 15 with the contents of a syringe. Then in a second step, it can put the secondary branch branch 15 in communication with the main branch 4, the device then being ready for injection. The tap is in the configuration of Figures 1 and 2. Those skilled in the art can easily imagine a variant of the device according to the invention in which these steps would be automated.

The secondary branch branch 15 is isolated from the main branch 4 of the fluid circuit by two non-return valves 19 and 20 positioned at the two ends of the branch manifold, respectively at the inlet and at the outlet thereof.

A non-return valve 21 is preferably disposed at the outlet of the main pipe 4 so as to avoid any return of working liquid or active product which may cause contamination upstream of the fluid circuit.

The fluid circulation in each of the branches of the circuit depends on the open or closed state of two isolation valves 22 and 23 respectively equipping the main branch and the secondary branch of the circuit.

According to a preferred embodiment, at least one of these isolation valves 22 or 23, and preferably both, comprises or each comprise, a roller with a cam profile which in the closed position crushes the tubing from the outside .

For technical reasons related to the nature of the conduits, the two isolation valves 22 and 23 are mounted in the immediate vicinity of the non-return valves 20 and 21. If the technical or technological possibilities allow it, the non-return valves 20 and 21 are or will be integrated into the isolation valves 22 and 23 or vice versa.

According to an advantageous embodiment, these two valves are controlled, preferably electronically, by a multiplexing means 24. According to an essential characteristic of the invention, these two isolation valves 22 and 23 are actuated independently of one of the 'other. The multiplexer 24 controls the opening and closing of the isolation valves 22 and 23 in function of time and duration parameters, previously recorded by the surgeon and which may be any, in order to achieve an optimal injection sequence for the particular case to be treated.

It is conceivable to modify the opening times of the isolation valves 22 and 23 as a function of the viscosity of the liquids whose passage is controlled. When the isolation valve 22 is open and the isolation valve 23 closed, a jet of pressurized working liquid is ejected from the distal end 12 of the catheter 9.

This firing of working liquid under pressure can for example make it possible to dig an injection channel. It can also be used for any other appropriate cutting or dissection application, before or after the injection.

For better efficiency, the working fluid under pressure can be fired according to a practice known in this field.

When the isolation valve 22 is closed and the isolation valve 23 open, the pressurized working liquid circulates in the branch branch 15 and pushes the active product present in the secondary branch. In this way, the active product is propelled by the working liquid under pressure to the distal end of the catheter and is injected into the previously dug injection line.

If the two isolation valves are open simultaneously, a mixture is formed at the union of the two branches of the circuit and a diluted active product is ejected from the catheter. As mentioned in the introductory part of this application, the surgeon can obtain numerous injection possibilities by varying the opening and closing parameters of the isolation valves 22 and 23.

The injection device according to the invention ensures the perfect sterility required for surgical type interventions. Indeed, all the elements of the fluidic circuit, likely to be contaminated, are disposable sterile elements and for single use: from the sterile bag containing the working liquid, to the reserve of active product, to the various pipes, valves, valves , fittings and other hydraulic components, up to the handpiece and catheter.

In FIG. 1, all the disposable elements of the injection device intended for single use have been shown in gray. The elements intended to be kept have been shown in black.

Figure 4 shows in more detail another embodiment of the invention. According to this variant, the main 4 and secondary 15 branches of the circuit are arranged in parallel and connected at their ends by the bifurcations 25 and 26.

The main branch 4 decomposes respectively, from the bifurcation 25 and in the direction of flow of the fluid, into a tube 27 which can be crushed, preferably at its end, by the cam of the isolation valve 22, a non-return valve 21 and a tube 28 leading to the bifurcation 26.

The secondary branch 15 decomposes respectively, from the bifurcation 25 and in the direction of flow of the fluid, into a tube 29, a non-return valve 19, a tube 30 which can be crushed, preferably at its end, by the cam of the isolation valve 23, a non-return valve 20 and a tube 31 leading to the bifurcation 26. After the bifurcation 26, a tube 32 common to the two branches will supply the handpiece 5. According to the variant of FIG. 4, the injection device may not include any active liquid charging valve. In this embodiment, the tubing 30 directly plays the role of the reserve of active product 16. The portion of tubing 30 serves as a calibrated reserve for a precise dose of active product.

It can be of variable length and diameter depending on the volume of active product to be injected. Such a system advantageously makes it possible to inject very small amounts of active product. It is thus possible, by using a tubing 30 of suitable length, to obtain for example a metered reserve of 1 or 2 ml of active product.

Such a characteristic perfectly meets the concerns encountered in the context of gene or cell therapies during which there are generally very small volumes of active product to be injected. Because of these small volumes, the use of conventional injection systems becomes problematic and the usual containers such as flexible plastic bags prove to be unsuitable.

The device according to the invention allows injections of micro-amounts of active product to be carried out in a simple and effective manner according to a precise dosage.

However, when the active product contains living cells, it is important to use tubing with a sufficient diameter. In fact, with pipes of too small diameters, the cells die causing the injection completely without effect.

According to a preferred embodiment, an internal diameter suitable for the pipes is for example close to 1.5 mm. In order to reduce the volume of the reserve of active product while ensuring its good conservation, it is then possible to reduce the length of the calibrated tubing 30.

Tubing, non-return valves, valves and other elements of the fluid circuit are made of materials resistant to high pressure. It is thus possible, for example, to use high-pressure tubing made of braided polyamide.

Certain active products are moreover sensitive to high pressure and cannot be injected under a pressure identical to that of the working liquid without risking deterioration detrimental to their effectiveness.

In this case and according to a variant of the apparatus according to the invention shown in FIG. 3, the secondary branch branch 15 may comprise a portion of tubing 33 of reduced internal diameter, serving to greatly reduce the pressure of the liquid passing through it . This portion of tubing 33 of reduced internal diameter preferably replaces the portion of tubing 29, located at the inlet of the secondary branch branch 15 before the non-return valve 19. When the isolation valve 23 is open, the liquid of working under pressure, coming from the reserve 2 and the generator of liquid under pressure 3, enters the portion of tubing or restriction 33 having a greatly reduced diameter. This constriction causes a significant decrease in its pressure before it comes into contact with the active product. present in the tubing 30 of the branch branch.

The active product can thus be ejected with a pressure much lower than that of the working liquid, which advantageously preserves the most fragile substances.

This pressure reduction can be modulated by varying the diameter and the length of the restriction 33. According to a preferred variant, the tubing or restriction 33 has for example an internal diameter close to 0.3 mm.

Since the working liquid is the only one to pass through the portion of tubing 33, it is possible to greatly reduce its diameter without risking damaging the living cells of the active product.

Thus and according to an essential characteristic of the invention, the injection device advantageously makes it possible to produce an injection channel under high pressure and then to inject an active product at low pressure.

Furthermore, the use of a portion of tubing with reduced diameter or restriction 33 can also make it possible to inject micro-amounts of active product.

Indeed, for technical reasons, the opening time of the isolation valve 23 cannot be reduced below a minimum duration limit imposed by the characteristics of the device. This minimum opening time causes the injection of a minimum quantity of active product which cannot be reduced for the same injection pressure.

By reducing the injection pressure by means of the restriction 33, it is possible to reduce the quantity of active product injected for the same opening time of the isolation valve 23. The apparatus according to the invention thus advantageously allows injections of microquantities of active product.

The operation of the apparatus according to the invention will be better understood from the description of a specific example of operation corresponding to FIGS. 5 to 12. It must however be understood that this is only a specific case of 'use of the device according to the invention, intended to illustrate one of the many possibilities of application offered by this injection device and not to limit protection in any way.

In this example, we want to perform an injection consisting of two successive shots of 160 μl of active product, each of these shots being preceded by a shot of 140 μl of working liquid under pressure in order to dig the injection channel.

There is a reserve of active product, for example 500 μl. The injection device used comprises a catheter containing a volume of 600 μl and a calibrated bypass tube of 500 μl.

In the various figures, the working liquid has been symbolized by hatching in black and the active product by inverted hatching in gray.

First, the surgeon first purges the injection device in order to expel the air it contains to fill it with working liquid. To do this, it opens the isolation valves 22 and 23 and triggers the flow of the working liquid.

The charging valve 18 must be placed in the configuration of FIGS. 1 and 2, putting the secondary branch 15 into communication with the main branch 4. The working liquid gradually fills the main branch 4, the bypass branch 15 and the catheter 9. At time t _{ι r} working liquid begins to exit at the distal end of the catheter. At time t ₂ , the surgeon closes the isolation valves 22 and 23. The flow of working liquid at the outlet of the catheter stops. The entire internal hydraulic circuit of the injection device is filled with working liquid. The device is then in the configuration shown in FIG. 6.

The surgeon then performs the loading of the device with active product. For this, it opens the charging valve 18, as in FIG. 3, so as to put the bypass line 15 into communication with the reserve of active product 16. It can be, for example, a syringe filled with product. active which it places at the inlet of valve 18.

At time t ₃ , it opens the valve 23 and begins to fill the line 15 with the active product. This expels the working liquid initially present. An amount of working liquid equivalent to the amount of active product introduced flows out of the catheter. In the example illustrated, this quantity is 500 μl.

At time t ₄ , the introduction of active product is complete. The surgeon closes the isolation valve 23 and replaces the charging valve 18 in the position shown in FIG. 2 in order to put the two branches of the circuit back into communication. The device is then in the configuration shown in FIG. 7.

The shots are then prepared by successively arranging the fluid packets in an appropriate order and quantities and placing them in the firing position at the end of the catheter just before the outlet.

To do this, the isolation valve 23 is open at time t ₅ for a period corresponding to a flow through this valve of 160 μl of active product pushed by the entry of 160 μl of working liquid under pressure into the branch of bypass 15.

A corresponding quantity of working liquid escapes from the catheter 9. The apparatus is then in the configuration of FIG. 8.

At time t ₆ , the isolation valve 23 is closed and the isolation valve 22 is open until time t ₇ . This opening time corresponds to the flow of 140 μl of working liquid under pressure through the valve 22. 140 μl of working liquid are expelled simultaneously from the catheter.

The apparatus is then in the situation of FIG. 9.

At time t ₇ , the isolation valve 22 is closed and the isolation valve 23 is open until time t ₈ . This opening time corresponds to the flow of 160 μl of active product through the valve 23, pushed by the working liquid under pressure. 160 μl of working liquid are expelled simultaneously from the catheter.

At time t ₈ , the two isolation valves are closed so as to stop the flow. The device is then in the situation in FIG. 10. It is ready to carry out the injections. The surgeon places the active distal end of the catheter, in the firing position, in contact with the wall area of the organ or tissue to be treated.

At time t ₉ , it triggers the first shot. The isolation valve 22 is open from t ₉ to t ₁₀ , which corresponds to the duration of ejection of the first shot at the distal end of the catheter. This shot is composed a first pulse of 140 μl of pressurized working liquid used to dig the injection channel, followed by a second pulse of 160 μl of active product injected in a second time into this channel.

At time t ₁₀ , the two valves are closed. The device is then in the situation in FIG. 11. The surgeon can move the active end of the catheter to a second firing position. At time t _n , it triggers the second shot. The valve 22 is open from t _n to t ₁₂ , corresponding to the time necessary for the ejection of the second shot at the distal end of the catheter. This shot is, like the previous one, composed of a first pulse of 140 μl of pressurized working liquid used to dig the injection channel, followed by a second pulse of 160 μl of active product injected in a second step in this channel.

At time t ₁₂ , the two valves are closed. The device is then in the final configuration of FIG. 12.

The two shots can possibly be carried out successively in the same place. In this case, the time interval t ₁₀ -t _n during which the two isolation valves are closed becomes superfluous and can be eliminated, the two shots then succeeding each other without interruption.

According to a particular feature of the process, the opening times of the isolation valves 22 and 23 are modified as a function of the viscosity of the liquids used.

In summary, the method for generating a sequence of liquid jets according to the invention can comprise the following steps: - purging the device in order to expel the air it contains to fill it with working liquid; - loading the device with active product;

- preparation of the shot (s) by successively placing the fluid packets in an appropriate order and quantities and placing them in the firing position at the active distal end of the device just before the outlet orifice;

- positioning of the active distal end of the device in the firing position;

- performing at least one shot of a sequence of liquid jets.

The apparatus according to the invention may be suitable in the context of a wide variety of medical, surgical or diagnostic interventions on all the organs of the body of a living being or in ex situ surgery.

The surgical device according to the invention is for example particularly suitable for performing interventions such as transmyocardial or myocardial revascularization, because it allows the realization of revascularization ducts in the ischemic zone of the myocardium then the injection into these ducts of angiogenic substances for example of the growth factor type.

The device according to the invention makes it possible to inject the most diverse substances such as for example therapeutic products, products having an action linked to the intervention in progress or diagnostic, contrast products. These can be conventional chemical molecules or products from biotechnology and genetic engineering.

The invention is obviously not limited to an apparatus which can inject only one active product. It is possible to imagine, in accordance with the principle of the invention, an injection device comprising several branch branches, arranged in series or in parallel, and allowing the application of various active products, mixed or successively according to previously programmed characteristics.

Likewise, the apparatus and method previously described are not limited to applications in the surgical, medical or diagnostic field. The method for generating a sequence of liquid jets according to the invention is a general method which can find application in many other fields such as, for example, construction, agriculture, food industry, chemical laboratories or biology, engraving and drawing, tattooing, cleaning or other.

Thus by way of non-exhaustive illustration, one can for example imagine using the apparatus and / or the method according to the invention:

- in the building sector for example for the treatment of wood, the injection of hardening, treating or drying products in walls and walls; - in the laboratory, for the microdose injection of reagents inside basic products intended for example to be analyzed or to be used for the preparation of vaccines or drugs;

- In the food industry, in particular to inject a flavor, taste, preservative, color or other product into a food product such as meat or another product with firm flesh;

- To inject colored products such as inks into human or animal skin, in order to carry out decorative or identification tattoos, or on other types of support for marking, drawing or engraving.

Claims

1. Apparatus for injecting an active product comprising a reserve (2) of working liquid pressurized by a pressurized liquid generator (3), a handpiece (5) ending in an active end (8 ) which comprises means for outputting a pressurized jet of working liquid and a jet of active product, characterized in that it comprises:

- a main branch (4) of the fluid circuit, connecting the reserve of working liquid (2) to the handpiece (5), in which the flow is controlled by the open or closed state of a valve isolation (22);

- A secondary branch branch (15), parallel to the main branch (4) and fluidly isolated from the latter, intended to contain the active product, and in which the flow is controlled by the open or closed state of an isolation valve (23); and

- Multiplexing means (24) for independently controlling the opening and closing of the isolation valves (22, 23) according to predetermined parameters.

2. Apparatus according to claim 1 characterized in that it comprises a multiplexing means (24) for independently controlling the opening and closing of the isolation valves (22, 23) according to any predetermined parameters, beforehand chosen and recorded by the surgeon according to the particular case to be treated.

3. Apparatus according to any one of the preceding claims, characterized in that the reserve (2) of working liquid is a flexible plastic bag containing the working liquid and in that the generator (3) of pressurized liquid is an enclosure in which the reserve (2) of working liquid is enclosed and which is filled sufficiently with a neutral gas to put it under pressure in order to compress the pocket and pressurize the liquid.

4. Apparatus according to any one of the preceding claims, characterized in that the active end (8) is a catheter (9).

5. Apparatus according to the preceding claim characterized in that the catheter (9) comprises at its distal end a retractable puncture or puncture tool, movable between a working position and a retracted safety position inside the catheter.

6. Apparatus according to the preceding claim characterized in that the catheter (9) comprises at its distal end a retractable puncture or puncture tool, mobile of the retractable needle type.

7. Apparatus according to any one of the preceding claims characterized in that it comprises a suction system (13) connected to a source of vacuum (14).

8. Apparatus according to any one of the preceding claims, characterized in that a non-return valve (21) is arranged at the outlet of the main branch (4).

9. Apparatus according to any one of the preceding claims, characterized in that the secondary branch branch (15) is isolated from the main branch (4) by means of two non-return valves (19, 20) mounted at the two ends of the tube. bypass.

10 Apparatus according to any one of the preceding claims 1 or 8 or 9 characterized in that the isolation valves (22) and (23) are mounted in the immediate vicinity of the non-return valves (21) and (20) respectively.

11. Apparatus according to the preceding claim characterized in that the non-return valves (20) and (21) are integrated with the isolation valves respectively (23) and (22).

12. Apparatus according to any one of the preceding claims characterized in that the secondary branch of bypass (15) is connected to a reserve of active product (16) by a means of communication (17).

13. Apparatus according to the preceding claim characterized in that the communication means (17) is a charge valve (18) two or three ways.

14. Apparatus according to any one of claims 1 to 11 characterized in that the branch branch (15) comprises a portion of tubing (30) serving as calibrated reserve for a precise dose of active product.

15. Apparatus according to any one of the preceding claims characterized in that the secondary branch branch (15) comprises a portion of tubing or restriction (33) of reduced internal diameter, serving to break the pressure of the liquid passing through.

16. Apparatus according to the preceding claim characterized in that the portion of tubing or restriction (33) of reduced internal diameter is located at the entrance of the secondary branch branch (15) before the non-return valve (19).

17. Apparatus according to any one of the preceding claims, characterized in that at least one of the valves (22, 23) of the two branches of the circuit comprises a roller with a cam profile which closed position crushes the tubing from the outside.

18. Apparatus according to any one of the preceding claims, characterized in that all the elements of the fluid circuit liable to be contaminated are disposable sterile elements, for single use.

19. Injection method by means of an injection device according to any one of the preceding claims, characterized in that an injection channel is dug by firing a jet of pressurized working liquid, then in a next step, the active product is injected into this injection channel.

20. Method for generating a sequence of liquid jets, by means of an apparatus comprising a reserve (2) of working liquid pressurized by a pressurized liquid generator (3), a handpiece (5) ending with an active end (8) which comprises means for outputting a pressurized jet of working liquid and a jet of an active product, a main branch (4) of fluid circuit, connecting the reserve of working liquid (2) to the handpiece (5), in which the flow is controlled by the open or closed state of an isolation valve (22), a secondary branch branch (15), parallel to the main branch (4) and fluidly isolated from it, intended to contain an active product and in which the flow is controlled by the open or closed state of an isolation valve (23), and a means multiplexer (24) for independently controlling the opening and closing of the isolation valves t (22, 23) according to predetermined parameters, characterized in that a sequence is generated comprising at least one pulse of working liquid under pressure, followed by a pulse microdose of active product.

21. Method for generating a sequence of liquid jets according to the preceding claim, characterized in that the valve (22) of the main branch (4) of the circuit is opened in order to generate a pulse formed of an appropriate quantity of working liquid under pressure, then in a later phase the valve (23) of the branch branch (15) is opened in order to generate a pulse formed of the desired quantity of the active product.

22. A method of generating a sequence of liquid jets according to claim 20 or 21 characterized in that the pulse of active product is generated with a pressure corresponding substantially to that of the pulse of working liquid.

23. A method of generating a sequence of liquid jets according to claim 20 or 21 characterized in that the pulse of active product is generated with a pressure lower than that of the working liquid and preferably at low pressure.

24. A method of generating a sequence of liquid jets according to any one of claims 20 to 23 characterized in that the pulse of active product is followed by a new pulse of the working liquid under pressure.

25. A method of generating a sequence of liquid jets according to any one of claims 20 to 24 characterized in that the quantities of liquid forming the pulses of working liquid and active product are precisely established by fixing the times of opening of each of the valves (22, 23).

26. Method for generating a sequence of liquid jets according to the preceding claim, characterized in that the opening times of the valves (22, 23) vary as a function of the viscosity of the liquids.

27. Method for generating a sequence of liquid jets, by means of an apparatus comprising a reserve (2) of working liquid pressurized by a pressurized liquid generator (3), a handpiece (5) ending with an active end (8) which comprises means for outputting a pressurized jet of working liquid and a jet of an active product, a main branch (4) of fluid circuit, connecting the reserve of working liquid (2) to the handpiece (5), in which the flow is controlled by the open or closed state of an isolation valve (22), a secondary branch branch (15), parallel to the main branch (4) and fluidly isolated from it, intended to contain an active product and in which the flow is controlled by the open or closed state of an isolation valve (23), and a means multiplexer (24) for independently controlling the opening and closing of the isolation valves t (22, 23) according to predetermined parameters, characterized in that the two valves (22, 23) of the two branches (4, 15) of the circuit are simultaneously opened in order to generate a jet consisting of a mixture of the product active and working liquid, the proportions of which are precisely set by adjusting the opening time of each of the valves (22, 23).

28. A method of generating a sequence of liquid jets according to any one of claims 20 to 27 characterized in that a very small amount of active product is used and that a microdosing thereof is carried out.

29. Method for generating a sequence of liquid jets according to any one of claims 20 to 28, characterized in that it comprises the following steps: - purging the device to expel the air it contains to fill it with working liquid;

- loading the device with active product;

- positioning of the active distal end of the device in the firing position;

- performing at least one shot of a sequence of liquid jets.