EP1032312A1

EP1032312A1 - Device for forming and delivering a mixture

Info

Publication number: EP1032312A1
Application number: EP99942979A
Authority: EP
Inventors: Philippe Gravagna; Jean-Louis Tayot
Original assignee: Imedex Biomateriaux
Current assignee: Imedex Biomateriaux
Priority date: 1998-09-18
Filing date: 1999-09-15
Publication date: 2000-09-06
Also published as: WO2000016698A1; JP2002526192A; FR2784296A1; AU5628799A; CA2310130A1; US6605066B1; BR9907117A; AU747254B2; FR2784296B1

Abstract

The invention concerns a device for forming and delivering a mixture, in particular a surgical adhesive, comprising a container (1) adapted to be hand-held by the surgeon and comprising means (5, 17, 18) for receiving two syringe bodies (2, 3) containing the constituents of the mixture, means (4) for simultaneously expelling the contents, means for maintaining the contents of the syringe (2) containing the first constituent at a set temperature higher than the physiological temperature, and a mixer (6, 7) simultaneously receiving the contents of both syringes, said mixing means further enabling cooling.

Description

DEVICE FOR FORMING AND DELIVERING A MIXTURE

Device ^" for the formation and delivery of a mixture, in particular for the surgical application of this mixture.

The present invention relates to a device for the formation and application of a mixture of two constituents, in particular the delivery of a mixture for surgical application, such as, in particular, a preparation of collagen.

Collagen preparations, intended to be applied in a fluid form, for example liquid or pasty, have already been proposed for surgical applications, in particular in the form of surgical glue.

In WO 97/29715, glues formed from a mixture of gelatin and a crosslinking agent of polyaldehyde type have therefore already been proposed in order to produce a fluid mixture to be applied at a relatively high temperature above 50 ≈C. Such temperatures are much too high for certain tissues, in particular in neural surgery, fine innervated and vascularized tissues such as the vascular and digestive walls, in particular the blood vessels, the heart, the intestine, the uterus.

It should be noted that official standards impose a temperature below 41 ° C for the product applied.

Collagen preparations are also known in the form of glue described in the application.

WO 98/15299, applied in the form of a mixture of a collagenic substance and a polyaldehyde agent, for example starch. This mixture can be applied in a fluid form at a temperature of about 37 ^o C, which is optimal. Such mixtures are characterized in particular by a substance of collagenic origin as defined in the aforementioned application, for example a collagen having at least partially lost its helical structure, not hydrolyzed, consisting mainly of alpha chains.

For these latter preparations, it is advantageous, in order to be able to easily carry out an extemporaneous mixture, that is to say at the time of the application by the surgeon of the preparation of collagenic origin and of the crosslinking agent, to bring the collagen preparation at a temperature higher than the application temperature, for example a temperature of the order of 42 ° C to 50 ° C, necessary to be sufficiently fluid. The problem is then to deliver the mixture to the receiving tissue at a temperature close to the physiological temperature of 37 ° C, or in any case below 41 ° C.

It has thus already been proposed to produce these mixtures at the last moment by having previously raised the temperature of the preparation of collagenic substance in an oven or a water bath. This method of preparation, however, has many drawbacks in hospital practice, in particular by the fact that the heated product begins to cool as soon as it leaves the thermostatically controlled enclosure, so that the temperature of the product applied is not constant and is difficult to control.

The invention therefore proposes to provide a device which makes it possible to produce an extemporaneous mixture, at the time of the application by the surgeon, of a collagenic substance and of a crosslinking agent for the delivery of the mixture at a temperature close to the physiological temperature.

It should be noted that this objective is made particularly difficult by the fact that the solutions of collagen or gelatin are very viscous, while the solutions of crosslinking agent have a low viscosity and that the mixture of fluids of very different viscosities is difficult to produce.

^" Another object of the invention is to provide such a device which has a high degree of security of delivery at the desired temperature. Another object of the invention is to provide such a device allowing several deliveries separated by time intervals likely to cause significant polymerization of the mixture.

Another object of the invention is to provide such an extremely practical device for use.

Another objective is to provide such a device which makes it possible to deliver the mixture in the form of a foam.

The subject of the invention is a device for the formation and delivery of a mixture, in particular for the surgical application of this mixture, characterized in that it comprises:

a receptacle suitable for gripping by the surgeon's hand and comprising means for receiving two bodies of syringes, namely a syringe containing the first constituent of the mixture, for example, a collagen solution and a syringe containing the second constituent of the mixture, for example a solution of crosslinking agent, - means for the simultaneous expulsion of the contents of the two syringes,

means for maintaining the content of the syringe of the first constituent, for example the collagen solution, at a set temperature higher than the physiological temperature, for example of the order of 45 ° C to 50 ° C,

- And a mixer simultaneously receiving the content of the two syringes during application, this mixing means further allowing cooling. The means for heating the content of the syringe advantageously comprises an electrical resistance or thermistor. This resistance can be carried by the receptacle itself.

However, it is preferred that this electrical resistance is carried permanently by the syringe body, for example in the form of a resistance embedded in a film stuck around the body of the syringe. The electrical supply of this film can be carried out, for example, by conductors connected to the film and terminating by means of connection to a source of electric current, either directly by means of an appropriate battery, or by by means of complementary connection means which are then connected to the source of electric current. In the latter case, the user, when using the device, must also connect the conductors coming from the syringe body into the complementary connection means.

Advantageously, a thermostat, preferably also fixed to the body of the syringe, controls the electrical supply to the thermistor and detects that the desired temperature has been obtained. Advantageously, this thermostat then sends a signal indicating to the surgeon that the syringe is at the desired temperature. The setting and arrangement of such a thermostat are common operations for

1 man of art.

Preferably, an additional safety thermostat is provided in the circuit, this thermostat being intended to permanently interrupt the supply of electric power to the thermistor. when a safety temperature threshold is reached or exceeded, this thermostat, in addition, authorizing a new power supply only once the temperature has dropped to a value very much lower than the set temperature, so the first thermostat will not be able to send a signal until a new correct heating cycle has occurred.

Preferably, the mixer comprises a removable connector making it possible to recover the contents of the two syringes and to bring them to the inlet of a nozzle or elongated body of the mixer containing a baffle device with obstacles gradually ensuring the homogeneity of the mixture . Preferably, this mixer body comprises elongated particles and it is particularly preferred that these particles are formed from small sections of plastic or other tube cut in half along a diametrical plane. It has been found that such an embodiment ensures a tangle allowing the desired mixture to be obtained over a short distance, of a few centimeters, while ensuring the decrease in temperature during the journey through the mixer, which constitutes one of the characteristics of the invention.

Preferably, the connector and the mixing tip are separately removable and replaceable, which makes it possible to use the content of the syringes in several successive applications, separated by long periods despite the start of polymerization of the mixture in the tip or body of the mixer which will simply be replaced.

In the preferred application of the invention to a constituent of collagen or gelatin, as defined, for example in WO 98/15299, the volume of the content expellable from the syringe of the first component, namely the collagen component, is approximately three to ten times greater, for example four times greater than that of the content of the second syringe, namely the crosslinking agent solution, such as a solution oxidized starch.

When the collagen component of the first syringe is in the form of a homogeneous liquid solution, this ratio is preferably between 3 and 6. When the collagen component of the first syringe is in the form of a liquid foam containing air as an emulsion in an aqueous solution, this ratio must be increased to a value of 6 to 10. In fact, the second syringe must be smaller to take account of the reduction in the volume of aqueous solution in the first syringe.

Preferably, the connector conduit which is connected to the first syringe is subdivided into several channels so as to produce several equidistant feeds towards the nozzle or body of the mixer, while the conduit connected to the second syringe forms only one channel single central.

Thus, for example, the single channel is disposed centrally in the connector and four equidistant channels connected to the first syringe are arranged concentrically around the single channel.

The outlet of the four channels enters the beginning of the mixer tip where the mixing will be done homogeneously. For the application of such a collagen mixture, it is preferred that the contents of the first syringe, containing the constituent of collagen origin, be brought, by means of electric heating, to a constant temperature chosen from the range of 42 ° C. at 57 C and: preferably from 44 ° C to 50 ° C, the other constituent, namely the crosslinking agent, being at ambient temperature, generally the temperature of the operating room; the length of the mixing tip is then preferably of the order of 2 to 4 cm and it is found that it is possible to obtain, at the outlet, an extremely homogeneous mixture at a temperature of about 37 ° C, and less than 41 ° C; or, preferably from 48 ° C to 54 ° C, the other constituent being at room temperature, the length of the mixing tip being 2 to 4 cm and extended by a tube for laparoscopy, preferably of the order from 25 to 35 cm.

The mixture which is delivered using the device according to the invention can be a mixture which is delivered in the form of a liquid or a fluid gel, or also in the form of a foam resulting from the emulsion with a gaseous component, preferably sterile, for example air.

The foam can be formed in situ in the mixer by opening a source of gas in the mixer, for example at the inlet or in its path. This gas source can be a third syringe containing the gas and the content of which is expelled at the same time as that of the other two syringes to pass simultaneously through the mixer.

Still in the case of a mixture in the form of a foam, the first constituent of the mixture can itself be a foam, which can either be formed in the body of the first syringe, or introduced into this body, by being brought in, if necessary, and maintained in this body at the set temperature, which also makes it possible to keep the foam in stable form.

The first frothy component can be prepared, either in the body of the syringe, or outside, for example in another syringe connected to the first, by mixing the gas with the constituent in liquid form. As a variant, it is possible, advantageously, to produce the foam by mixing a dry powder comprising the protein element of the first constituent, and a gas, for example air, with the solvent, for example a physiological serum. So ^'3' very advantageously, the gas used may be one that is naturally contained, or incorporated into the void volume of a powder of the protein member in proportion to the degree of expansion of this powder, the solvent being subsequently introduced into this gaseous solid two-phase mixture.

These various variants of the formation of the first frothy component can advantageously use the body of the first syringe, namely the syringe capable of being heated, and another syringe, each of these syringes containing one or more elements of the constituent which, when they are mixed form the foam, preferably by repeated successive transfers from one syringe to the other, the foam formed being finally contained in the first syringe provided with the heating means.

Alternatively, instead of an additional syringe, the heating syringe can be connected to a vial of suitable volume such that the injection of the contents of the syringe into the vial causes an overpressure which pushes the contents back into the syringe when the syringe is released. push on the syringe plunger.

The subject of the invention is also a set, or kit comprising a receptacle as defined in the present invention, a first syringe body containing a first component, and closed by a cap, a second syringe body containing the second component, and closed by a cap, a connector, and a mixer tip containing entangled particles 0/16698

very.

Preferably, the first component is a collagen solution as defined in application WO 98/15299, or an aqueous collagen foam emulsified with a gas, for example air, and the second component is a polyaldehyde solution, especially oxidized starch.

The invention also relates to the methods for producing liquid or foam mixtures described above.

The invention also relates to a syringe comprising means for maintaining its content at a set temperature, for example close to physiological temperature, or much higher, for example, of the order of 45 ° C to 50 ° C.

This syringe can be used in the device or kit described above, but it can also be used individually for the implementation of its content in any other application. Among these applications, one consists in heating the syringe containing a viscous product in order to reduce its viscosity and to facilitate its administration, for example for hyaluronic acid or gelatin or collagen, for example for intraocular administration.

Another application is used to heat a previously frozen product to speed up and facilitate its use.

The means for maintaining the temperature may advantageously be the means described above.

Other advantages and characteristics of the invention will appear on reading the following description, given by way of nonlimiting example and referring to the appended drawing in which: - Figure 1 is a schematic view of a device according to the invention

- Figure 2 is a schematic view of a syringe body with its thermistor and its thermostat - Figure 3 is a cross section in elevation of a receptacle of the device

- Figure 4 is a top view of this receptacle

- Figure 5 is a cross-sectional view of this receptacle at the syringe bodies

- Figure 6 is an enlarged view of a complementary part of this receptacle for thermal insulation

- Figure 7 is a longitudinal sectional view of the connector

- Figure 8 is a cross-sectional view of this connector at the channels

- Figure 9 is a longitudinal sectional view of the mixing tip - Figure 10 is an enlarged view of an internal holding spider for the tip

- Figure 11 is a top view of this spider - Figure 12 is a very enlarged view of a particle intended to be contained in the mixer

Referring to Figures 1 and 2, we see that the device according to the invention comprises a receptacle 1 provided with two parallel housings capable of receiving two syringe bodies 2, 3 of different diameters, the device comprising a plunger 4 allowing simultaneously expel the contents of the two syringes. A complementary part 5, in the form of a double stirrup, makes it possible to thermally insulate the two syringe bodies contained in their respective housings. The outlet tips of the two syringes receive a connector 6 which continues with an elongated body or mixing tip 7. The body of the first syringe 2 which contains the constituent of collagen origin to be heated is surrounded by a plastic film 8, glued to the body 2 and containing a resistance (not visible). This resistance is supplied with electric current by means of a thermostat 9 pressed against the film 8 by a metallic adhesive 10 and adjusted to a set temperature, for example 48 ° C. This thermostat 9 controls the electrical supply which comes from two conductors 11 which terminate in an interface box 12 provided with a switch 13, a power-on indicator 14 and a reference temperature indicator lamp 15 , which lights up when the thermostat has reached the set temperature and maintains this temperature. The housing 12 is connected by suitable conductors to a transformer-adapter block capable of being connected to the network.

Referring to FIGS. 3 to 6, it can be seen that the receptacle or box 1, which includes finger rests facilitating its gripping and its use by the surgeon, has two housings in the form of open cylinders 17, 18 of different diameters adapted to the diameters of the two syringes 2 and 3 whose internal sections are in a fixed ratio which can be chosen between the values 3 to 1 and 10 to 1 depending on the characteristics of the adhesive mixture to be produced, for example in a ratio of 4 to 1. The syringe bodies are held in the housing by clipping, in the housing 1. The syringe bodies are thus immobilized. Naturally, the housing 17 is shaped so that it can also accommodate the presence of the thermostat 9 and to allow the passage of the conductors 11 supplying the resistor. The plunger 4 has a conformation which allows it to simultaneously push the two plunger rods 19, 20 of the two syringes 2, ^• 3 to ensure simultaneous expulsion of the contents of the two syringe bodies, the flow expelled from the syringe 2 being naturally three to ten times greater, for example four times greater than that expelled from the syringe 3. Thanks to the shape of the receptacle 1 and of the plunger 4, the surgeon can proceed to the expulsion of the desired quantities using the fingers of 'one hand.

When the syringes are stored, they have their tip covered with a cap 21 maintaining sterility.

The invention is particularly applicable to the adhesives defined in application WO 98/15299, the content of which is incorporated herein by reference.

The invention is also applicable to other products for which heating to 37 ° C. or more is necessary or preferable, such as adhesives or viscoelastic solutions containing highly concentrated macromolecular solutions whose high viscosity is reduced to a temperature close to 37 at 50 ° C and in particular preparations containing partially or completely fibrinogen, albumin, gelatin or collagen, hyaluronic acid, or polysaccharides.

For mounting the device, the caps of the two syringes are removed and the connector 6, the shape of which is shown in FIGS. 7 and 8, is fitted onto the parallel tips of the two syringes. connector 6 has, for this purpose, two tubes 22, 23 which are fitted onto the nozzles of the syringe bodies and, on the other side, a central connector 24 on which the mixer nozzle 7 can be fitted. the interior of the tube 22 is conical and continues through a channel 25, which then divides into four thinner channels 26, distributed equidistantly around the central axis of the end piece 24. The conical tube 23 extends, for its part, by a single channel 27 which opens at the center of the end piece 24, the channels 26 and 27 having the same diameter.

The body of the mixer proper, which forms the elongated tip 7, is shown in FIG. 9. It has an enlarged proximal end 28 followed by a long cylindrical part 29 ending in a more narrowed distal end 30. The central volume of the end 28 makes it possible to receive the end-piece 24 of the connector and continues through a central channel of large diameter 31, which at its other end continues through a channel of smaller section 32 opening at the outlet of the end 30.

Most of the channel 31 is filled with particles intended to form a large number of baffles to ensure the homogenization of the mixture. For example, such an enlarged particle is shown in Figure 12 consists of a section of a thin plastic tube cut in half by a diametrical plane. The dimensions of such a particle are preferably as follows: length: 0.8 mm, external radius: 0.8 mm, internal radius: 0.4 mm

The entanglement of these particles forms a mass which is maintained inside the channel 31 by a plug formed by an elongated spider 33 shown in FIGS. 10 and 11 and the branches of which are provided with small ribs, the spider 33 being forced into the nozzle 7 above the entanglement of particles, the dimensions of the spider being such that it offers no resistance to the flow of the constituents coming from the syringe bodies but that it keeps the particles 34 in place. Example 1:

The implementation is carried out as follows: during preparations for an operation including the application of surgical glue, the conductor 11 is connected to the interface box 12 and heating is carried out. When the heating indicator light comes on, the device is ready for use. The surgeon can then expel the desired amount of mixture by pushing back the piston plunger 4. The collagen component and the polyaldehyde component are expelled in a proportion of volumes of approximately 4 to 1, if it is a solution homogeneous collagen and, separately crossing the channels 26 and 27, end in the central channel 31 where they come into contact with the entanglement of particles 34. The gradual homogenization of the mixture of the two constituents causes a lowering of the temperature of the collagen constituent which meets the unheated polyaldehyde component. The course of these constituents and then of the mixture in the nozzle 7 completes the lowering of the temperature, so that the homogenized mixture leaves the channel 32 at a temperature very close to the physiological temperature of 37 ° C. In a variant, the implementation of the electric syringe is added to a preliminary step to manufacture a liquid foam of collagen or any other protein to be used for the preparation of the adhesive mixture. Example 2; The electric syringe 2 contains a volume of sterile protein solution half the maximum volume. It is gradually heated by the electrical resistance to the desired temperature. This syringe 2 is then connected by a simple connection, face to face with a syringe containing the same volume of air s,> _?

Successive round trips by pressing the pistons of the two syringes allow the respective contents of the two syringes to be mixed homogeneously. After approximately 10 round trips, the foam is stored in syringe 2, of which it occupies the maximum volume. This is disconnected. Then, the syringe 2 is placed in the receptacle 1 and the process for producing the adhesive mixture is carried out as in the previous example. In this case, the preheated protein component and the crosslinking agent are expelled in a volume proportion of approximately 8 to 1, increased to take account of the volume of air in the foam.

Example 3:

Syringe 2 contains a volume of sterile water half the maximum volume. It is gradually heated by the electrical resistance to the desired temperature. This water syringe is then connected, by a simple face-to-face connection, with a syringe containing the necessary quantity of protein in the form of sterile powder at neutral pH, as well as an amount of air with a total volume equal to that of the electric water syringe.

The content of the 2 syringes is mixed by successive round trips by pressing on the pistons of the two syringes to prepare a homogeneous liquid protein foam and, after having placed the syringe 2 in the receptacle 1, the method of setting in work is done as in example 2. Example 4:

The heating syringe 2 contains a volume of sterile protein solution, half the maximum volume, added to the same volume of sterile air.

The biphasic content of this syringe is gradually heated by the electrical resistance to the desired temperature. The electric syringe is then connected by a simple connector, face to face with an empty sterile syringe, of zero initial volume and of sufficient potential volume.

The successive round trips by pressing on the pistons of the two syringes make it possible to prepare and homogenize the protein foam within the syringe 2.

After about 10 round trips, the protein foam is kept at the required temperature in the electric syringe, of which it occupies the maximum volume. The empty syringe is disconnected. Then, the process for producing the final adhesive mixture is carried out as described above. In this case, the preheated protein component and the crosslinking agent are expelled in a volume proportion of about 8 to 1, increased to take into account the volume of air in the foam.

Example 5:

Syringe 2 contains a volume of sterile water half the maximum volume, added to the same volume of sterile air. The biphasic content of this syringe is gradually heated by the electrical resistance to the desired temperature. The electric syringe is then connected by a simple connection, face to face with a syringe of sufficient potential volume, containing the necessary quantity of protein in the form of sterile dry powder at neutral pH. The content of the two syringes is mixed by successive round trips by pressing on the pistons of the two syringes to prepare a homogeneous liquid protein foam and the mode of implementation is as in the previous example.

Example 6: _j _ The syringe 2 contains the required amount of the form of dry powder protein, sterile, at neutral pH, after addition of a volume of air equal to half the maximum volume of the syringe.

The electric syringe is immediately connected by a simple connector, face to face with a second sterile syringe containing a volume of sterile water equal to half the volume of the electric syringe.

Sterile water is injected into the electric syringe where it gradually wets the dry powder.

The content of this syringe is then gradually heated by the electrical resistance to the desired temperature. Successive round trips by pressing the pistons of the two syringes make it possible to prepare and homogenize the protein foam within syringe 2. After approximately 10 round trips, the foam is kept at the required temperature in the electric syringe. The empty syringe is disconnected. Then, the process for producing the final adhesive mixture is done as in the previous examples. Example 7: Device 1 with two parallel syringes

2 and 3 of the present invention is added a third air syringe which opens through a special tubing added, at the inlet of the mixer 7 so that the air is automatically incorporated into the adhesive mixture in formation, from the moment when the operator simultaneously pushes the contents of the three sterile syringes, using a special holding device such as a receptacle with three syringe housings and a suitable plunger.

Claims

1- Device for the formation and delivery of a mixture, in particular for the surgical application of this mixture, characterized in that it comprises:.> - a receptacle (1) suitable for gripping by the hand of the surgeon and comprising means (5, 17, 18) for receiving two syringe bodies (2, 3), namely a syringe containing the first component of the mixture, and a syringe containing the second component of the mixture, means (4) for the simultaneous expulsion of the contents of the two syringes, - means (8, 9) for maintaining the contents of the syringe (2) of the first constituent, at a set temperature above the physiological temperature, and a mixer (6, 7) receiving the contents of the two syringes simultaneously during application, this mixing means also allowing cooling.

2- Device according to claim 1, characterized in that the means for heating the contents of the syringe comprises an electrical resistance or thermistor.

3- Device according to claim 2, characterized in that said electrical resistance or thermistor is permanently carried by the syringe body (2) containing the first component of the mixture.

4- Device according to claim 3, characterized in that said resistance or thermistor is carried by a film (8) surrounding the syringe body. 5- Device according to one of claims 1 to 4, characterized in that it comprises a first thermostat (9) controlling the electrical supply of said heating means (8) and detecting the obtaining of the set temperature for the maintaining this temperature, as well as the means for this thermostat to send a signal indicating that the set temperature has been reached.

6- Device according to claim 5 characterized in that said thermostat is carried by said syringe body (2) containing the first component.

7- Device according to any one of claims 1 to 6 characterized in that it comprises a second safety thermostat arranged to permanently interrupt the supply of the thermistor or resistance in electric current, when a higher safety temperature threshold at the set temperature is reached or exceeded, and to not authorize a new supply until the temperature has dropped to a value lower than the set temperature.

8- Device according to one of claims 1 to 7 characterized in that it comprises an elongated mixer body (7) simultaneously receiving the two constituents by one of its two ends when the operator expels the content of said syringes ( 2, 3).

9- Device according to claim 8, characterized in that this body (7) has a channel

(31) filled with particles (34) entangled.

10- Device according to claim 9 characterized in that said particles (34) are formed of tube sections cut along a diametrical plane. 11- Device according to claim 10 characterized in that said tube sections have substantially the following dimensions: length 0.8 mm, external radius: 0.8 mm, internal radius: 0.4 mm 12- Device according to one of claims 9 to 11, characterized in that said particles are ιtîa.ntenues inside said elongated member by a cross (33) forced down.

13- Device according to claims 9 to 12, characterized in that the length of said body or mixer tip (7) is between 2 and 4 cm.

14- Device according to any one of claims 1 to 13, characterized in that said mixing means comprises a connector (6) capable of being fixed on the syringe body tips by means of two conical tubes (22, 23) and an elongated mixer body (7) capable of being fixed on a tip (24) of the connector (6).

15- Device according to claim 14 characterized in that said connector (6) has a central channel (27) in communication with said second syringe body (3) and a plurality of equidistant channels (26) in communication with said first body syringe (2). 16- Device according to one of claims 1 to 15, characterized in that the receptacle (1) has two housings (17, 18) capable of receiving said syringe body (2, 3) and a complementary part (5) having complementary stirrup shapes for thermal insulation of the syringe bodies in said housings, and in that it is associated with a piston plunger (4) allowing the simultaneous actuation of two piston rods (19, 20) syringe. 17- Device according to one of claims 1 to 16, characterized in that the ratio of the sections, and therefore of the volumes, of the first and second syringe body is 3 to 10, and in particular 3 to 6 for a liquid mixture and from 6 to 10 for a frothy mixture.

^* • '. " 18- Device according to claim 17, characterized in that, for the production of a liquid mixture, said ratio is of the order of 4. 19- Device according to any one of claims 1 to 17, characterized in that the first syringe body (2) contains a substance of collagenic origin and the second syringe body (3) contains a crosslinking agent, in particular polyaldehyde. 20- Device according to claim 19, characterized in that the substance of collagen origin is a collagen solution having lost at least partially its helical structure, not hydrolysed, consisting mainly of alpha chains 21- Device according to one of claims 1 to 20, characterized in that the crosslinking agent is a solution of oxidized starch.

22- Device according to any one of claims 1 to 21, characterized in that the set temperature at which the first component is maintained is between 42 ° C and 57 ° C.

23- Device according to claim 22, characterized in that the set temperature at which the first component is maintained is between 44 ° C and 50 ° C for direct application at the outlet of the mixer. 24- Device according to claim 22, characterized in that the set temperature at which the first component is maintained is between 48 ° C and 54 ° C for application by a tube.

25- Syringe capable of being implemented in a device according to one of claims 1 to 24 and comprising means for maintaining its content at a set temperature above the physiological temperature.

26- Syringe according to claim 25, characterized in that said means for maintaining the content of the syringe at said set temperature are the means defined in any one of claims 2 to 7 and 22 to 24.

27- Process for the manufacture of a mixture intended to be formed and delivered by implementing a device according to any one of claims 1 to 24 or a syringe according to either of claims 25 and 26, in which one forms, in the body of said syringe, said first constituent of the mixture, or else this first constituent is introduced into said syringe.

28- A method according to claim 27, characterized in that to produce a mixture in the form of foam, a gas is brought into the mixer at the time of mixing the first and second constituents.

29- A method according to claim 27, characterized in that to produce a mixture in the form of foam, is introduced into said syringe provided with temperature maintenance means, or is formed in this syringe, a first constituent in the form of foam containing components of the first constituent and a gas. 30- A method according to claim 29, characterized in that the foam is produced by connecting to the body of said syringe, provided with temperature maintenance means, another syringe, the components of said first constituent, namely a liquid phase and a gas, or a liquid phase, a powdery solid phase ¹ and a gas, being distributed, either in one of the syringes, or between the two syringes, and the foam is produced by successive transfers from a syringe into the 'other.