FR2836921A1 - A method of preparing an injectable foam for use in creating implants, especially for the prevention of incontinence by mixing a polymer and swelling agent, heating, grinding and mixing with a support - Google Patents

Abstract

A method of preparing an injectable foam comprises: (i) mixing a compatible, non-biodegradable polymer and a foaming agent; (ii) heating the mixture to 100-250 degreesC for 30 minutes; (iii) cryogenic grinding of the polymer and (iv) mixing with a support. An Independent claim is included for an injectable foam produced by the method.

Description

<Desc / Clms Page number 1>

INJECTABLE POLYMER FOAM
The present invention relates to an injectable foam comprising discrete particles of a physiologically compatible, non-biodegradable polymer suspended in a carrier, as well as to a process for preparing this foam.

 The present invention also relates to a foam for use as an intracorporeal implant intended in particular for the reconstruction of a part of the body or the enlargement of certain tissues.

 The use of various injectable polymers for tissue augmentation or as prosthetic implants has already been proposed in the art.

 Thus, US Pat. No. 4,686,962 describes a device for the hypodermic implantation of a genitourinary prosthesis for the treatment of incontinence. This device comprises a membrane that can be inflated by injection of a material by means of a hypodermic needle.

 Urinary incontinence has also been treated by trans-oral injection of polytetrafluoroethylene (PTFE) generally in the form of a paste or encapsulated particles Transurethral polytetrafluoroethylene Injection for Post-prostatectomy Urinary Incontinence by M. Kaufman et al., The Journal of Urology, Vol.

 132, September 1984, pages 463-464.

 It has also been planned to treat urinary incontinence by implantation of a prosthesis based on a histologically compatible solid, this is for example the subject of US Pat. No. 5,922,025, and more particularly of a prosthesis based on No. 5,344,452, US 5,204,382, US 5,352,715, or a particle-based prosthesis.

<Desc / Clms Page number 2>

 carbon-coated hard solids ranging in diameter from 100 to 1000 μm (US 5,451,406).

 Non-autologous materials are commonly used in the medical field today. Paraffins, petroleum jellies, vegetable oils, lanolins, beeswaxes, silicones, PTFE and collagen have been injected into the human body as so-called soft tissue swelling agents.

 These materials have been used particularly in endoscopic treatments in orthopedics, gynecology, cosmetic surgery and urology.

 Prosthetic materials intended to be placed in the human body endoscopically, must be biocompatible, non-toxic, and they must be able to be permanently implanted.

A recent debate based on experimental studies focused on the amount of material injected, the injection site, local reactions and their potential for migration to distant organs (remote migration). While corrections of endoscopic ureteric reflux have been implemented for about ten years, it must be emphasized that no clinically significant side effect has yet been reported.

 Although the results have been encouraging, particularly in the endoscopic treatment of urinary stress incontinence and vesico-ureteral reflux, research has been pursued, they have been conducted essentially along two axes: bio-compatibility of the implanted material and that of the potential migration of said material. In particular, the migration potential of polytetrafluoroethylene (Polytef) has made professionals cautious.

<Desc / Clms Page number 3>

The problem of migration is considered in Chapter 1 of J. BUZELIN's work "Implanted and injected Materials in
Urology, "Isis Medical Media, Oxford, 1995, for each of the three most commonly used injectables: polytetrafluoroethylene (Polytef or Teflon), injectable collagen, and particulate siloxane (Macroplastique): one study, 10 and a half months after implantation, Teflon particles injected into the monkey were found in the pelvic lymph nodes, lungs, brain, kidneys and spleen, which were injectable Teflon particles with a mean diameter of between 4 and 100 μm. with more than 90% of particles smaller than
40 um.

 * Another study was to inject smaller volumes by the sub-urinary route into the monkey, local migration to the bladder and distant migration to the periaortic, pelvic and testicular nodes.

 According to Malizia A.A., Reiman H.M., Myers R.P. et al. JAMA 251: 3277-3279, 1984 "Migration and Granulomatous Reaction After Periurethral Injection of Polytef" when microparticles of PTFE (the majority of which has a diameter greater than 50 μm) are injected, they can be phagocytosed by particles likely to migrate to distance and thus form granulomas in the corresponding distant organs: the spleen, the brain, the lungs, and the liver.

 It has also been shown in this study that small particles have been localized in different sites at a distance from the injection, these particles result from the direct transformation of the material into emboli generated by extrusion from the treated tissues caused by the high pressure. injection.

<Desc / Clms Page number 4>

particules est comprise entre 50 et 450um et que la taille des particules moyennes est de 171um. Il a également été compté que 29% du nombre total des particules présentent un diamètre inférieur à lOOum et que 99% du volume total des particules est constitué de particules de diamètre supérieur à lOOum. A study on the size of siloxane particles used by Macroplastique, showed that the size distribution of

particles is between 50 and 450um and that the average particle size is 171um. It has also been reckoned that 29% of the total number of particles have a diameter of less than 100 μm and that 99% of the total particle volume consists of particles of diameter greater than 100 μm.

 The particles are deposited along the perimeter of the injected material. Smaller particles can be located in the center of the injected bowl, surrounded by larger particles, and are thus more likely to migrate at a distance. This has also been shown with Teflon.

 In addition, because of the textured nature of the siloxane particles, there is an increase in particle surface area and a higher potential for anchoring by foreign collagen. Two recent studies have shown that the larger particles of Macroplastique siloxane-based implants have low potential for migration. The migration of some isolated particles is attributed to the injection technique, that is to say that they are implanted extra-vesicularly.

 Thus, according to Henly D.R., Barret D.M., Weiland T.L., Malizia A.A., O'Connor M.K., Wein A.J., J. Urol. 1995 Jun; 153 (6): 2039-43: "Particulate Silicone for Use in Periurethral Injections: Local Effects and Search for Migration" when performing perirurethral injection of Macroplastic paste (the particles of the pulp having an average 73go) we observe a local and remote migration.

 Polyvinylpyrrolidone (PVP) hydrogel, which is used as a vehicle and lubricant by Macroplastique, is commonly

<Desc / Clms Page number 5>

 used in the fields of pharmacy, cosmetic, diet.

Low molecular weight PVP (about 9800) is biocompatible, and is completely excreted by normal glomerular filtration. There appears to be a significant difference in potential for the migration between the slowly excreted PVP used by Macroplastique and the vasodilatory properties of the glycerin-based medium used by Polytef. This difference can be explained by the difference in functions performed. by each of these vehicles.

 In order to overcome the problem of migration, it has been proposed to use polymers of higher particle size.

 Patent applications EP 636,014, US 5,258,028 and US 5,336,263 describe the use of textured microparticles in the manufacture of a composition for the long-term treatment of urological disorders, such as incontinence. Said microparticles are dispersed in a physiologically acceptable vehicle and have a mean particle size of between 30 and 3000 nm, preferably between 80 and 600 m. The surface of these microparticles comprises indentations, cavities and pores, of dimensions between 10 and 500 μm, a minimum distance between the indentations being maintained so that the microparticles can be injectable by means of a hypodermic needle.

 EP 402 031 relates to an injectable composition, comprising a plurality of discrete, physiologically compatible, non-biodegradable, polymeric particles of average diameter between 0.027 and 5.08 mm, and having a lubricated surface. These microparticles are reversibly deformable, about 20 to 75% of their outer diameter, preferably they are polyacrylonitrile microparticles in the form of spheres or macrodisks.

<Desc / Clms Page number 6>

 It is clear that the larger the particles used, the lower the risk of migration of these particles. However the larger the size of the particles used, the more difficult their extrusion by means of a needle.

 Surprisingly and advantageously, the inventors of the present application have found an injectable composition (foam) which makes it possible to overcome the drawbacks of the compositions of the prior art both in terms of biocompatibility and migration of the injected implant. The composition according to the invention has a very high compressive capacity.

 This composition consists of an injectable foam comprising discrete particles of a physiologically compatible, non-biodegradable polymer, suspended in a support, such that the essential (99% v / v) of said particles has a diameter of between 30 and 5000 μm. and such that said foam has a reversible compressibility of between 300 and 420%.

 This foam can be prepared according to the process according to the present application.

This method according to the present application implements the following steps: mixing a physiologically compatible, non-biodegradable polymer and a swelling agent, preferably such that the weight percent of swelling agent in the polymer is between 0.5% and 10%, preferably about
10%,. heating said mixture to a temperature between
100 and 250 C, preferably about 200 C for a period of about 30 minutes, this heating makes it possible to obtain a spongy material,

<Desc / Clms Page number 7>

 . cryogenic grinding of this polymer, mixing the ground polymer and a support.

 In the context of the present invention, all the polymers that can be used in the field of the present invention (plastic surgery, soft tissue enlargement in the treatment of incontinence and vesico-ureteral reflux or gastric reflux) can be used to prepare the composition in the form of foam according to the invention. Preferably, these will be silicones, polyurethanes, polyacrylonitriles, polyvinyl alcohols (PVA) and even more preferably silicones, especially silicones comprising alkyl and / or aromatic groups.

 Said polymer is suspended in a carrier which is a physiologically compatible vehicle, since this vehicle reacts with the tissues of the human body in a minimal or no way, moreover this support is eliminated or metabolized without any cytotoxicity.

 As support in the foam according to the present invention, it is possible to use saline solutions, starches, hydrogels, polyvinylpyrrolidones, polysaccharides, fats, organic oils, as well as any polymers that can be used for this purpose.

 Preferably, polyvinylpyrrolidones (PVP) will be used.

 The weight percentage of polymer relative to the total weight of the foam is between 25 and 50%, it is preferably about 30%, the complement to 100% consisting essentially of the support.

 The present application also relates to the process for preparing said foam defined above, as well as the use of this foam for the manufacture of an implant, particularly for

<Desc / Clms Page number 8>

 increase the volume of a part of the body, for example for the reconstruction of a part of the body.

 The foam according to the invention comprises discrete particles of a physiologically compatible, non-biodegradable polymer having a reversible compressibility of between 300% and 420%. It is thus understood that large-diameter foam particles, that is greater than about 2000 μm, have a compressive capacity of between 300% and 420%. The smaller sized particles do not have such a capacity because their (bubble) structure was destroyed during the preparation of the injectable foam during the cryogenic milling step. The ability to compress the large diameter particles of the foam according to the invention makes it possible to inject said foam by means of a hypodermic needle. Smaller diameter particles, even if they have a lower compressive capacity, can also be injected by means of a hypodermic needle.

As the compression capacity of the particles is reversible, once injected into the human body, the composition returns to its original properties, it is in no way impaired.

 By compression capacity (C) in the sense of the present invention is meant the percentage of the difference between the diameter of the particles not subjected to compression (not understood diameter) and the diameter of the particles subjected to compression (diam. on the diameter of the particles subjected to compression. The diameter of the particles subjected to compression will generally be considered to be equal to the internal diameter of the needle used to inject said composition.

 C = [(noncompressed diameter) / diam. compr.] x 100

<Desc / Clms Page number 9>

By way of example, the compression capacity of the silicone foam particles according to the present invention can reach 420%, in fact this foam which comprises particles of diameter 5 mm dispersed in a solution of PVP can be injected by means of 18 gauge needle (0.863 mm internal diameter).

 Of course, these values can vary depending on the support used, the concentration of the particles in the injected fluid, and the possible sieving during the preparation of the composition.

 Said foam comprises crosslinked silicone particles which have a structure called honeycomb. It is an alveolar cross-linked silicone, comprising hollow spaces and inter-articular holes.

 The silicone particles that form the foam have a cellular crosslinked structure essentially composed of inter-reticular holes and holes. The internal structure of these particles, and in particular that of large diameter particles, also includes closed pores and bubbles.

 The walls separating the cavities, holes, bubbles and pores have a generally smooth surface including some cavities of equally smooth appearance, the thickness of these walls is about 10 to 100 Lm.

 These polymer particles are suspended in a support, which is preferably a polyvinylpyrrolidone. The size distribution of these particles depends on their use.

 Figure 1 is a photograph taken by means of an optical microscope.

 Figures 2 and 3 are SEM photographs (taken under a scanning electron microscope) of particles forming the foam according to the invention. According to this technique, only the surface of the particles is visible, the internal structure of the particles does not appear.

<Desc / Clms Page number 10>

 Figure 1 is an enlargement (x 13) of a particle, it is a particle of large diameter in which, the structure of honeycomb cells, internal bubbles and those and holes distributed in a manner random are clearly visible.

 Figure 2 is an enlargement (x 80) of a particle, a line of the broken line corresponds to 100um. References (1) have depressions and holes and references (2) the walls between these recesses and holes. Some of these walls were destroyed during grinding, bubbles that formed the internal structure before grinding now appear as open pores or holes.

 Figure 3 is an enlargement (x 80) of a particle, a line of the broken line corresponds to 100um. the alveolar lattice structure (4) of a particle partially destroyed during a grinding step is presented. The recesses and holes (1) and the walls (2) between these recesses and holes also appear in this figure. Slight depressions (3) appearing as craters randomly distributed on the walls (2) are also visible.

 Another advantage of the foam according to the present invention is that the pores of the polymer particles will serve as anchoring during healing or tissue regeneration. Indeed, thanks to the inherent ability of fibroblasts to form tissue in and around the surface irregularities of the polymer (honeycomb structure), such an anchoring of the polymer particles takes place, which further reduces the risks of migration. said polymer.

 In addition, the use of high diameter particles to increase soft tissue volume minimizes the risk of migration from the injection site. Where we inject particulate materials (by means of a needle), a small amount of material

<Desc / Clms Page number 11>

 crosses the injection site through the puncture orifice. This phenomenon is explained by the increase of the internal pressure of the tissues generated by the injection of material (see the reference Malazia et al cited above). The smaller the particles, the greater the migration will be.

 According to the present invention, because of the particle size, the risk of migration is minimized.

 After injection of the composition, the support is absorbed by body fluids a few days after implantation. Next, connective tissues, proteins, collagen and fibroblasts infiltrate the pores of the polymer. Thus, each particle or each small group of particles is surrounded by a collagen protein matrix, the result being the encapsulation of particles or groups of particles.

 The process for preparing the injectable foam according to the invention comprises the following steps: mixing a polymer and a swelling agent, heating (vulcanizing) the mixture until a spongy material is obtained, cryogenic grinding of this polymer, a mixture of the ground polymer and a support.

 The present application also relates to this method of manufacturing an injectable foam and the injectable foam obtainable by this method.

 The first step of this process consists essentially in mixing a polymer selected from the polymers that can be used in the composition according to the present invention, preferably it will be a silicone or a polyurethane with a swelling agent. All conventional blowing agents used in the field of the present invention may be employed. In particular, it will be hydrogen, nitrogen.

<Desc / Clms Page number 12>

 The inventors of the present application have shown that the use of water which is not known as a conventional blowing agent in the field of the present invention can be advantageously employed.

 The mixing of the first step is carried out in a preheated container at a temperature of between 100 and 250 ° C. and even more preferably preheated to a temperature of the order of 200 ° C.

 During the second step, heating, at a temperature between 100 and 250 ° C., preferably about 200 ° C. for a period of about 30 minutes, allows the evaporation of the swelling agent, which has as a result the swelling of the mixture. This gives a spongy material, a silicone foam after a period of about 30 minutes.

 During the third step, the amorphous silicone sponges obtained are crushed by cryogenic grinding. The cryogenic grinding is carried out at atmospheric pressure, at a temperature below -50 C. These temperatures are obtained using liquid nitrogen, liquid air or liquid helium.

 Indeed, at temperatures below 0 C, polymers and in particular silicones become harder and therefore more fragile. The grinding step followed by a possible sieving step are carried out under these conditions.

 At the end of the grinding step, particle size is obtained in a broad spectrum, between 50 and 5000 u. m, the subsequent sieving step makes it possible to select the desired particles according to their diameter. Depending on the use that will be made of this foam, the size of the particles can be of great importance.

<Desc / Clms Page number 13>

 The optionally sieved crushed polymer is then mixed with a carrier, which is preferably a solution of polyvinylpyrrolidone (PVP). Preferably, the composition of the mixture will comprise about 33% by weight of ground polymer and 67% by weight of carrier.

 The carrier solution (PVP solution) is prepared using water, preferably at a PVP / water ratio of 1.5.

 Advantageously, the injectable foam will then be placed in syringes, these syringes then being stored in bags intended to be sterilized. Sterilization may be performed using gamma radiation.

 The foam according to the present invention can be used for the manufacture of an intracorporeal implant, in particular to increase the volume of a part of the body. Thanks to the anchoring properties of the polymer particles, the foam once injected will remain near the injection zone, it will not migrate.

 Thus, the foam according to the present invention can be used to increase the area of the part of the body where said foam is injected.

 The foam according to the present invention can thus be used in cosmetic surgery, especially for the reconstruction of breasts, buttocks, lips. The amount of foam (composition) injected will depend on the desired volume increase.

 It can still be used for scar reconstruction when the soft tissues, following an injury, have depressions.

 The foam according to the present invention can still be used for expanding so-called soft tissues, in particular in the treatment of urinary incontinence and in particular of urinary incontinence.

<Desc / Clms Page number 14>

 effort, vesical-ureteral reflux, reflux of gastric fluid.

Thus, under local, regional or general anesthesia, the composition is injected by endoscopic injection into the area that is to be enlarged.

 All the techniques known to those skilled in the art for installing an injectable implant can be used to inject the composition according to the present invention. Thus, we can use mechanical guns, pneumatic, electric. The syringe containing the injection foam is placed in the gun and so is ready to be injected, a cytoscope can be used to observe the injection site (neck of the bladder or ureter). Preferably a catheter is used to connect the needle to the syringe, the foam passes through this catheter (extrusion) before being injected where the needle is positioned.

By way of example, a foam according to the invention which can be used in urology, for example, for the treatment of urinary incontinence and more particularly of urinary stress incontinence, vesico-ureteral reflux, and also reflux of gastric fluids will usually have particles of diameter generally between
100 and 2000 μm (95% v / v), preferably it will have a mean particle diameter of between 600 and 1000 μm, preferably about 900 μm. A suitable sieve will be used to obtain such a particle size.

A typical distribution of the particles of a foam that can be used in urology is presented in FIG. 4. This curve of the percentage (%) of particles as a function of their diameter (μm) is obtained by means of a "Mastersizer" type laser diffractometer. of the society
Malvern. This is a LALLS method "low angle light scattering" for light scattering at small angles. Particles with

<Desc / Clms Page number 15>

 diameter is within this range (between 100 and 2000 μm) do not exhibit a closed bubble structure. As a result, the compression capacity of this structure is lower than that of the larger diameter particles.

 Indeed, the honeycomb structure is mainly observed on large particles of which only the surface has been damaged in the cryogenic grinding step.

 The present invention also relates to an injectable foam comprising discrete particles of a physiologically compatible, non-biodegradable polymer suspended in a support, characterized in that the foam has a reversible compression capacity of between 300% and 420%, The bulk of said particles has a diameter of between 1000 and 5000 nm, this foam being obtainable by the claimed process.

1000 et 5000um (95% v/v). Le diamètre moyen de ces particules est préférentiellement compris entre 1500 et 2500um, de préférence d'environ 2000um. Un tamis adéquat sera utilisé pour obtenir une telle taille des particules. A foam according to the invention that can be used in reconstructive surgery, for example for the reconstruction of a part of the body such as breasts, buttocks, lips, scars, generally has particles of larger diameter, between

1000 and 5000um (95% v / v). The average diameter of these particles is preferably between 1500 and 2500um, preferably about 2000um. A suitable sieve will be used to obtain such a particle size.

pourcentage de particules en fonction de leur diamètre (lam) est obtenue au moyen d'un diffractomètre laser de type"Mastersizer"de la société Malvern. A typical distribution of the particles of a foam that can be used in reconstructive surgery is presented in FIG.

percentage of particles as a function of their diameter (lam) is obtained by means of a "Mastersizer" type laser diffractometer from Malvern.

<Desc / Clms Page number 16>

 These particles are highly compressible, their compression capacity can reach 420%, it is essentially due to the closed porosity structure.

 The examples which follow illustrate the invention without limiting its scope.

EXAMPLES
Example 1: Example of composition according to the invention more particularly intended for use in urology or to increase soft tissue (sub-mucosal implants).

 Injectable compositions intended for urology, are most commonly used for the treatment of pathologies such as vesico-ureteral reflux and urinary stress incontinence. The compositions according to the present invention which can be used in urology consist of a particulate system in which 95% of the particles (v / v) are between 100 and 2000 μm.

 In Figure 4 is shown the curve of the particle distribution of such a foam according to their diameter, the average particle diameter shown in Figure 4 is 900 um.

 Among the products of the prior art that can be used in urology are Macroplastique and Polytef, both permanent synthetic injectables.

J. BUZELIN's book "Implanted and injected Materials in
Urology ", Ed. Isis Medical Media, Oxford, 1995 presents the distribution curve of Macroplastic and Polytef particles according to their size.

<Desc / Clms Page number 17>

In the following table, the average particle sizes of Macroplastique TM, Polytef and the foam according to the invention are listed.

<Tb>
<Tb>

Product <SEP> Injection <SEP> Size <SEP> of <SEP> Particles <SEP> Medium
<tb> Polytef <SEP> 90% <SEP> of <SEP> particles <40m <SEP> (*)
<tb> Macroplastic <SEP> 171Am <SEP> (*)
<tb> Product <SEP> according to <SEP> the invention <SEP> 900m
<Tb>
(*) "Implanted and injected Materials in Urology", J.

BUZELIN Ed. Isis Medical Media, Oxford, 1995
In addition, as recalled on the preceding pages, the small particles tend to migrate and the large particles have the disadvantage of being weakly compressible, it is generally necessary to use large needles (higher at 18Gauge) to inject them. The above mentioned products are generally used in urology, they are conventionally injected with needles of 18 or 20 Gauge.

 The size of the particles according to the present invention makes it possible to minimize the risks of migration, which is the major problem of injectable products in urology.

 Although these particles are larger in size than the particles usually used for the same applications, they can be injected using the needles usually used by gynecologists and urologists (18 and 20 Gauge). For some applications such as vesicoureteral reflux treatment, 21 Gauge needles can also be used.

<Desc / Clms Page number 18>

* Vulcanisation du mélange dans un four à convection à température d'environ 200 C pendant environ 30 minutes, Broyage cryogénique en utilisant un agent pour refroidir, de préférence de l'azote liquide. Le broyage et le tamisage sont effectués au cours de la même étape, les particules obtenues ont un diamètre inférieur ou égal à 2000lim, * Mélange de la mousse de silicone broyée avec une solution de PVP, la PVP de masse moléculaire moyenne comprise entre 2000 et 35000 est utilisée, de préférence, on utilisera un PVP de masse moléculaire moyenne comprise entre 7000 et 11000. De préférence, on utilisera une composition constituée d'un mélange de 33% de mousse de silicone et de
67% d'une solution de PVP, cette solution de PVP peut être préparée en utilisant de l'eau, de préférence selon un rapport
PVP/eau de 1,5.

These compositions according to the present invention may be prepared according to the following process: Mixing silicone with a swelling agent, preferably water in a ratio of 90% silicone and 10% water,

* Vulcanization of the mixture in a convection oven at a temperature of about 200 ° C. for about 30 minutes. Cryogenic grinding using an agent for cooling, preferably liquid nitrogen. The grinding and sieving are carried out during the same step, the particles obtained have a diameter of less than or equal to 2000 μm. * Mixture of the silicone foam ground with a solution of PVP, the PVP of average molecular mass between 2000 and 35000 is preferably used a PVP of average molecular weight between 7000 and 11000. Preferably, use will be made of a composition consisting of a mixture of 33% silicone foam and
67% of a PVP solution, this PVP solution can be prepared using water, preferably in a ratio of
PVP / water of 1.5.

Putting in syringe of the mixture obtained, Sterilization by irradiation by means of γ-rays.

Example 2 Example of Composition According to the Invention More Specifically for the Manufacture of Subcutaneous Implants (Reconstructive Surgery)
Injectable (foam) compositions for reconstructive surgery are most commonly used to clear scars and / or to increase soft tissue volume

<Desc / Clms Page number 19>

 subcutaneous. The compositions according to the present invention which can be used in reconstructive surgery consist of a particulate system whose particles are less than zum and preferably of between 1000 and 5000 μm (95% v / v).

 The typical distribution curve of the compositions according to Example 2 is shown in FIG. 5. The average particle size is between 1500 and 2500 μm, and is preferably about 2000 μm.

 The injection of these particles can be carried out using 14 or 16 gauge needles, however 18 gauge needles can also be used.

Vulcanisation du mélange dans un four à convection à température d'environ 200 C pendant environ 30 minutes Broyage cryogénique en utilisant un agent pour refroidir, de préférence de l'azote liquide. Le broyage et le tamisage des particules pour obtenir des particules de diamètre inférieur ou égal à 5000gm sont effectués au cours de la même étape,

Tamisage des particules pour obtenir des particules de diamètre supérieur ou égal à lOOOjm, Mélange de la mousse de silicone broyée avec une solution aqueuse de PVP, de préférence selon un rapport PVP/eau de 1,5. Une PVP de masse moléculaire moyenne comprise entre 2000 et 35000 est utilisée, de préférence, on utilisera un These compositions according to the present invention may be prepared according to the following process: Mixing silicone with a swelling agent, preferably water in a ratio of 90% silicone and 10% water,

Vulcanization of the mixture in a convection oven at a temperature of about 200 ° C. for about 30 minutes Cryogenic grinding using an agent for cooling, preferably liquid nitrogen. Grinding and sieving the particles to obtain particles of diameter less than or equal to 5000 gm are carried out during the same step,

Sieving the particles to obtain particles of diameter greater than or equal to 1000 μm, Mixing the ground silicone foam with an aqueous solution of PVP, preferably in a PVP / water ratio of 1.5. A PVP of average molecular weight between 2000 and 35000 is used, preferably one will use a

<Desc / Clms Page number 20>

PVP of average molecular weight between 7000 and
11000. Preferably, a composition consisting of a mixture of 33% silicone foam and
67% of a PVP solution. Other silicone foam concentrating compositions of between 20 and
50% can be used; Putting the mixture into syringes Irradiation sterilization using y-rays.

Claims (17)

1-Process for preparing an injectable foam, characterized in that the following steps are carried out: mixture of a physiologically compatible, non-biodegradable polymer and a swelling agent, heating said mixture to a temperature between 100 and 250 C for a period of about 30 minutes,. cryogenic grinding of this polymer, mixing the polymer and a support.  2-Process according to claim 1, wherein the polymer is chosen from silicones, polyurethanes, polyacrylonitriles and polyvinyl alcohols (PVA).  3-Process according to claim 2 such that the polymer is a silicone.  4-Process according to claim 3 such that the polymer is a silicone comprising alkyl and / or aromatic groups.  5-Process according to one of the preceding claims such that said support is selected from saline solutions, starches, hydrogels, polyvinylpyrrolidones, polysaccharides, fats, organic oils.  6-Process according to claim 5 such that said support is a polyvinylpyrrolidone.  7-Process according to one of the preceding claims such that the swelling agent is selected from hydrogen, nitrogen, water.  8-Process according to claim 7 such that the swelling agent is water.  9-Process according to one of the preceding claims such that the mixture of the ground polymer and the support is carried out in the <Desc / Clms Page number 22>  proportions by weight: 33% of polymer and 67% of support.  10-Process according to one of the preceding claims such that it implements a sieving step after the cryogenic grinding step of the polymer.  11-Injectable foam comprising discrete particles of a physiologically compatible polymer, non-biodegradable suspended in a support, characterized in that the foam has a reversible compressibility of between 300% and 420%, the bulk of said particles a diameter of between 30 and 5000 μm, this foam being obtainable by the method according to one of claims 1 to 10.  12-Injectable foam according to claim 11 as it comprises crosslinked silicone particles, these particles having a structure called honeycomb.  13-Injectable foam comprising discrete particles of a physiologically compatible polymer, non-biodegradable suspension in a support, characterized in that most of said particles has a diameter between 100 and 2000 nm, this foam being obtainable by the process according to the claim 10.  14-Injectable foam comprising discrete particles of a physiologically compatible, non-biodegradable polymer suspended in a support, characterized in that the foam has a reversible compressibility of between 300% and 420%, most of said particles has a diameter of between 1000 and 5000 μm, this foam being obtainable by the process according to claim 10.  15-Use of the injectable foam according to one of claims 11 to 14 for the manufacture of an intracorporeal implant.  16-Use of the injectable foam according to claim 13 for the manufacture of an intracorporeal implant for the treatment of <Desc / Clms Page number 23>  urinary incontinence and more particularly urinary stress incontinence, vesico-ureteral reflux, reflux of gastric fluids.  17-Use of the injectable foam according to claim 14 for the manufacture of an intracorporeal implant for the reconstruction of a body part such as breasts, buttocks, lips, scars.