PRODUCT ENABLING THE FORMATION OF A THERAPEUTIC IMPLANT IN A SUBJECT'S BODY - IMPLANT AND ASSOCIATED COMPOSITION

Abstract

The present invention relates to a product enabling the formation of a solid implant in the body of a subject by injection, said product comprising a pharmaceutically acceptable base composition containing at least one solvent and at least one first polysaccharide soluble in said solvent, said base composition being capable of forming a precipitate upon contact with an aqueous solution, possibly saline. Characteristically, the product further comprises a given quantity of at least one pharmaceutically acceptable active substance selected from: - ionic bactericidal / antiseptic / antifungal agents soluble or miscible in said solvent such as eosin, methylene blue, and potassium iodide;- antibiotics, growth factors, hydroxyapatite, hormones, antitumor agents, antimitotic agents, topoisomerase inhibitors, anticancer agents and mixtures of at least two of said active substances, in particular in powder form; and - contrast agents and in particular radionuclides; said quantity of active substance is mixed with said basic composition or packaged separately from said basic composition, the mixture formed by said basic composition and said quantity of active substance has a viscosity which permits the injection of said mixture and said mixture forms a precipitate on contact with an aqueous solution, possibly saline.

Description

The present invention relates to a product that, by injection, enables the formation of a solid implant in the body of a subject, a composition obtained from the product, the implant formed by injection of the product, and a method for manufacturing the product. The article entitled "Development of an alcoholic ethylcellulose sclerosing gel used for the treatment of venous malformations," published in March 2001 in the journal Pharm Clin, vol. 20, no. 1, describes a solution containing water, ethanol, and ethylcellulose. At room temperature, this solution is sufficiently fluid to be injected into a vein at the site of a venous malformation to be treated. Upon contact with blood, the solution forms a solid precipitate that seals the vessel or vein and allows the alcohol from the precipitate to pass into the vein wall, which is thus treated by the sclerosing action of ethanol, which is already known. One object of the present invention is to provide a product which makes it possible to obtain an injectable composition capable, on the one hand, of forming a solid body or implant once injected into the body of a subject and, on the other hand, of delivering an active compound or active substance. Another objective of the present invention is to provide a product which makes it possible to obtain an injectable composition capable of forming a solid body or implant once injected into the body of a subject and which has a reliable shelf life. Another objective of the present invention is to provide a product such as the above-mentioned that can be localized in the body of the subject, during injection and / or post-injection. Another object of the present invention is to provide an injectable product which forms an implant in the body of the subject into which it is injected and which has at least one therapeutic action with a reduced amount of active substance. Another objective of the invention is to provide an injectable product that forms an implant in the body of the subject into which it is injected and that releases at least one active substance over a limited area in the body of the subject. Another object of the present invention is to provide an injectable product which forms an implant in the body of the subject into which it is injected and which can take a shape adapted to the body of the subject, in particular when the implant is formed in a cavity, for example bone, and which can also serve as a filling material. Another objective of the present invention is to provide an injectable product capable of forming in the subject's body an implant whose self-forming impression conforms to the crevice or cavity to be filled into which the product has been injected. Another objective of the present invention is to provide an injectable product that forms an implant in the body of the subject into which it is injected and that exhibits several pharmacological and / or therapeutic activities. Another object of the present invention is to provide an injectable product which forms an implant in the body of the subject into which it is injected, said implant not requiring a surgical procedure to be removed. The present invention thus proposes a product enabling the formation of a solid implant in the body of a subject by injection, said product comprising a pharmaceutically acceptable basic composition, which contains at least one solvent and at least one first polysaccharide soluble in said solvent, said basic composition is capable of forming a precipitate on contact with an aqueous solution possibly saline. Characteristically, according to the invention, it comprises, in addition to a given quantity of at least one pharmaceutically acceptable active substance selected from: - ionic and soluble or miscible bactericidal / antiseptic / antifungal agents in said solvent such as eosin, methylene blue, and potassium iodide; - antibiotics, growth factors, hydroxyapatite, hormones, antitumor agents, antimitotic agents, topoisomerase inhibitors, anticancer agents, and mixtures of at least two of said active substances; and - contrast agents, in particular radionuclides; in that said quantity of active substance is mixed with said basic composition or packaged separately from said basic composition,in that the mixture formed by said base composition and said quantity of active substance has a viscosity that allows the injection of said mixture, and in that said mixture forms a precipitate upon contact with an aqueous solution, possibly saline. It is to the Applicant's credit that they observed that it is possible to add to the base composition a pharmaceutically active substance capable of dissolving in it and distinct from the solvent of the base composition. The mixture of the base composition and the active substance has a viscosity that makes it injectable at room temperature or after possibly being heated. Once the mixture formed by the components of the product has been injected into the body of a subject,The mixture precipitates upon contact with any hydrated tissue and any aqueous solution (blood and / or lymph) and forms a mass called an implant, which contains the active substance. This implant consists of a flocculent precipitate; it is therefore flexible and can thus form a mass that conforms to the contours of the cavity into which the mixture formed by the product has been injected. The product forms an implant whose self-forming impression conforms to the crevice or cavity to be filled into which the product has been injected. Because the implant is flexible, it does not damage the surrounding tissues. The pharmaceutical action of the implant may come from the active substance alone; it may also be at least partially conferred by the solvent. If the solvent and the active substance have the same therapeutic activity,It is possible to precisely measure the amount of active substance and the amount of solvent. The solvent will remain in the implant while the active substance will diffuse into the surrounding environment and produce a therapeutic effect over a larger area. This results in the same therapeutic activity spread over time and over a wider area. If the solvent and the active substance have different pharmaceutical activities, the implant will exhibit several pharmaceutical activities spread over time and / or over different areas of the subject's body. Preferably, the ionic bactericidal / antiseptic / antifungal agent(s) are in the form of a divided solid (powder or granules) and soluble in said solvent. The addition of such a solid does not change the viscosity of the base composition. According to a particularly advantageous embodiment, the product always comprises at least one active substance selected from bactericidal / antiseptic / antifungal agents, in particular methylene blue, eosin and potassium iodide, the latter being able to be introduced in the form of tincture of iodine. When the base composition contains ethanol, possibly mixed with 10% or less water, and ethylcellulose, and the active substance is ionic and soluble in ethanol and / or water, two therapeutic effects are obtained in two areas. Indeed, the ethylcellulose-ethanol mixture forms a stable and homogeneous mixture due to the hydrogen bonds between ethanol and ethylcellulose. The active substance is bound to this mixture only by Van der Waals forces, which are weak; it therefore diffuses into the surrounding environment. This effect is achieved, in particular, when using methylene blue and / or eosin and / or potassium iodide as active substances. These substances can be found in the form of iodine tincture, and especially methylene blue or eosin. These substances have drying and antiseptic properties and also act as dyes. The implant and necrotic target tissue together are therefore visible to the naked eye or during an ultrasound or endoscopic examination and can be easily removed, for example, surgically. The active substance diffuses out of the implant, eliminating potential germs over a larger area and also stimulating the patient's immune system. It also diffuses into the cells surrounding the implant by osmosis. The solvent remains in the implant, but when it is hydrophilic, it attracts water from the cytoplasm of cells near the implant, notably by osmosis.The first polysaccharide and the second polysaccharide, when present, amplify the migration of water from the cytoplasm of surrounding cells to the implant: the cells, depleted of their cytoplasmic water, die. Methylene blue, eosin, and potassium iodide or iodine tincture further enhance the dehydration of cells in contact with the implant. There is therefore a synergy between the polysaccharide(s) and methylene blue, eosin, potassium iodide, or iodine tincture. When the solvent is hydrophilic, as is the case with pure ethanol or ethanol in aqueous solution, synergy exists between this solvent and at least one or both of the aforementioned elements (namely the polysaccharide(s) and the aforementioned dyes). The implant will thus dehydrate the surrounding cells (empty the cytoplasm of the cells) and thereby cause sclerosis of the implanted target tissue. The same applies to any ionic active substance or any combination of ionic active substances. Any active substance or any mixture of active substances is preferably used in the form of a powder which is mixed with the basic composition to form a solution or a suspension or kept separate from the latter so as to avoid its possible degradation due to reaction with the other constituents of the basic composition. When the product includes hydroxyapatite, the latter can form a suspension with the base composition. The Applicant has indeed demonstrated that hydroxyapatite forms a stable solution in a base composition containing ethanol possibly mixed with water as described later, and ethylcellulose. Finally, certain components of the product of the invention can confer several functions on the implant formed. Thus, the aforementioned ionic bactericidal / antiseptic / antifungal agents are also dyes; they are considered to be contrast agents because they allow the implant to be located during an ultrasound or a laparoscopy. Similarly, some anticancer drugs can also serve as contrast agents when they remain in the implant. The same is true of radionuclides, which can both have a therapeutic / pharmacological action and serve as contrast agents. The quantity of active substance is not limited according to the invention; for example, it may represent more than 50% by mass of the basic composition. This results in an implant that exhibits a homogeneous concentration of active substance throughout its volume. The implant can be formed in any cavity or in any organ or tissue, soft or hard, accessible by a needle or catheter. Thus, the mixture resulting from the constituents of the product of the invention can be injected, for example, into a vein or blood vessel, into a potentially cancerous tumor, a cyst, or into a bone cavity so as to fill it and / or promote its reconstruction by the formation of new bone tissue. The size of the implant is easy to control because it depends directly on the amount of composition according to the invention injected into the subject's body. In the case of a tumor, particularly a cancerous one, injecting the mixture obtained from the product of the invention at the periphery of the tumor makes it possible to sclerose the blood vessels supplying it. This produces a first therapeutic effect due to the active substance, which may be an anticancer drug, and a second therapeutic effect through the drying (destruction) of the vessels and tumor cells by contact, for example, when the solvent is ethanol or a water-ethanol mixture and the product also contains methylene blue, eosin, or potassium iodide in sufficient quantity to achieve a desiccating, sclerosing, and destructive effect. Furthermore, a colored implant is obtained that also stains the tissue into which it has been implanted (the implanted tumor, for example). The entire system is visible to the naked eye, allowing for the localization of both the implant and the tumor, when the implant has formed within a tumor. Advantageously, the said first polysaccharide is chosen from cellulose, cellulose derivatives insoluble in aqueous solutions, in particular, ethylcellulose. Particularly stable sclerosing gels are obtained with pure ethanol or in solution with water as described below. Advantageously, the solvent is chosen from among non-polar and pharmaceutically acceptable organic solvents and mixtures of at least two of these solvents, and in particular from ethanol, possibly anhydrous, toluene, water-ethanol mixtures containing at least 50% by volume of ethanol and preferably at least 90% by volume of ethanol, ethanol-toluene mixtures, and mixtures of toluene with water-ethanol mixtures containing at least 50% by volume of ethanol and preferably at least 90% by volume of ethanol. Stable gels with the sclerosing action of ethanol are thus obtained with ethylcellulose. According to a particular embodiment, the product further comprises a second polysaccharide selected from mucilages, including agar-agar and pectins, and preferably from pectins, and furthermore, at least one radionuclide usable in therapy, preferably in an amount such that the entire radionuclide is trapped in said second polysaccharide, the mixture of said base composition, said active substance, said second polysaccharide and said radionuclide has a viscosity which permits the injection of said mixture and said mixture forms a precipitate on contact with an aqueous solution, possibly saline. When the product contains a radionuclide or a contrast agent, these are preferably in divided form (powder or granules) so as not to alter the viscosity of the mixture used to form the implant. The radionuclide may also be present even in the absence of the second polysaccharide. Indeed, the Applicant demonstrated that the precipitate formed constitutes a three-dimensional network similar to that of absorbent cotton. A radionuclide or any other active substance in powder form is immobilized within the network formed by the precipitate, which prevents its migration within the subject's body and concentrates its activity around the area near the implant. The presence of the second polysaccharide nevertheless helps to ensure the radionuclide remains within the implant. Preferably, a basic composition of ethylcellulose and ethanol, as described above, is used, with pectin as the second polysaccharide. Pectin is capable of trapping radionuclides, so its presence reinforces the mechanical trapping action of the network formed by the precipitate / implant. According to one embodiment, the mass ratio of active substance to base composition is substantially equal to or greater than 0.15. In the case of eosin or methylene blue in an ethylcellulose-ethanol base composition, satisfactory diffusion of eosin or methylene blue is obtained in the environment surrounding the implant, the latter remaining colored and therefore easily localizable. According to an embodiment that can be combined with any of the aforementioned embodiments, the product further comprises an injection device, said quantity of active substance and / or said second polysaccharide optionally mixed with said radionuclide is / are packaged separately from said basic composition, preferably in powder form and are suitable for being mixed with the latter in said injection device. The radionuclide serves as a contrast agent and makes it possible to treat, for example, cancers due to the radiation it emits. For the purposes of this invention, an injection device means, for example, a syringe on which is mounted a needle of length and diameter suitable for the injection site, a catheter on which is mounted a needle, or a brachytherapy device. The mass ratio of second polysaccharide to first polysaccharide is not limited according to the invention; for example, it is less than or equal to 1 / 20. According to another embodiment which can be combined with any of the aforementioned embodiments, the product further comprises a gas that is chemically inert with respect to said base composition and said active substance, said gas forms a two-phase mixture with said base composition, said active substance, the optional second polysaccharide and the optional radionuclide, the mixture of said gas, said base composition, said active substance, said optional second polysaccharide and said optional radionuclide or contrast agent has a viscosity which permits the injection of said mixture and said mixture forms a precipitate on contact with an aqueous solution, possibly saline. The gas forms bubbles that can be detected by ultrasound, for example. When the basic composition contains hydroxyapatite, the amount of the latter is not limited. Advantageously, the product contains an amount of hydroxyapatite substantially equal to or less than the amount of the first polysaccharide. The hydroxyapatite forms a suspension with the basic composition and any other components of the product. When the product precipitates to form the implant, the hydroxyapatite is distributed throughout the precipitate, which forms a three-dimensional network suitable for colonization by osteoblasts, among other things. This type of implant is suitable for bone reconstruction. The present invention also relates to a pharmaceutically acceptable composition comprising a pharmaceutically acceptable base composition which contains at least one solvent, at least one first polysaccharide soluble in said solvent, said base composition is capable of forming a precipitate on contact with an aqueous solution possibly saline and which characteristically contains - a given quantity of at least one active substance, which is selected from: - ionic bactericidal / antiseptic / fungal agents soluble in said solvent such as eosin and methylene blue and potassium iodide;- antibiotics, growth factors, hydroxyapatite, hormones, antitumor agents, antimitotic agents, topoisomerase inhibitors, anticancer agents and mixtures of at least two of said active substances, possibly a second polysaccharide chosen from mucilages, including in particular agar-agar and pectins and preferably from pectins and possibly, in addition, at least one radionuclide usable in therapy, and possibly a contrast agent, in that said pharmaceutical composition has a viscosity which allows its injection and in that it forms a precipitate on contact with an aqueous solution, possibly saline.; Advantageously, all active substances, including antibiotics, anti-tumor agents and anti-cancer agents, are anionic so as to be able to escape from the precipitate formed by the implant. The present invention also relates to an implant obtained by total or partial precipitation of the aforementioned composition. The present invention also relates to a method of manufacturing a pharmaceutically acceptable composition according to which - said basic composition is prepared; - said active substance which is in powder form and / or said second polysaccharide in powder form optionally mixed with said radionuclide in powder form is dissolved under stirring at room temperature in said basic composition. Throughout this application, by way of example, anticancer agents may be cited platinum salts such as, for example, cis-diaminedichloroplatin(ll) or cisplatin, (R,R)-1,2-diaminocyclohexane (ethanedioate-0,0) platinum or oxaliplatin, cyclobutane-dicarboxyloplatin or carboplatin, [2-(aminomethyl)cyclobutyl]methanamine;2-oxidopropanoate;platinum(4+) or lobaplatin, which are also opaque to X-rays and can therefore also serve as a contrast agent. We can also mention, particularly as anticancer agents, radionuclides chosen from among Phosphorus 32, Thallium, Technetium, Strontium 89, Indium, Yttrium 90, Iodine 131, Holmium 166, Rhenium 186 and 188, Copper 67, Samarium 153, Lutetium 177, Dysprosium 165, Gallium and Cesium and compounds whose molecules contain a radioactive atom chosen in particular from the aforementioned radionuclides. These substances can also serve as contrast agents. Other examples of growth factors include erythropoietin, GM-CSF (Granulocyte Macrophage Colony Stimulating Factor), and GCSF (Granulocyte Colony Stimulating Factor). Examples of antibiotics include ethanol-soluble penicillin compounds such as benzylpenicillin (Penicillin G), benzathine benzylpenicillin, phenoxymethylpenicillin (Penicillin V), aminopenicillins (Penicillin A), penicillinase-resistant penicillins (Penicillin M), carboxypenicillins, ureidopenicillins, and amidinopenicillins.Examples of antibiotics that can be used in the context of the present invention include tetracyclines, aminoglycosides, macrolides, quinolones, fucidin (against staphylococci), lincosamides, phenicol antibiotics, sulfonamides, combinations of sulfonamides and trimethoprim, synergistins, and forsfomycin. These substances will preferably be in powder form to obtain a stable mixture. The product of the invention, the composition of the invention, and the implant of the invention can thus be used for the treatment of blood vessels (destruction of low-flow vessels), the treatment of herniated discs, the treatment of cancers such as thyroid cancer and prostate cancer, bone reconstruction, the treatment of benign cysts, and the treatment of well-isolated benign or malignant tumors. For example, when the product of the invention includes a radionucleotide, the latter is present in an effective quantity to have a therapeutic effect. The maximum volume of the injected mixture can be 5 ml, for example. This results in an implant that exhibits therapeutic activity due to the gamma rays it emits and that is easily localized. Polysaccharides, particularly cellulose and its derivatives, have known antibacterial properties that can enhance or complement the activity of the active substance and / or solvent. Furthermore, the Applicant has observed that mucilages, particularly pectins, are capable of sequestering heavy metals and radionuclides. The presence of pectin(s) or other mucilage allows for the formation of an implant that possesses anti-cancer activity due to the gamma radiation from the radionuclide(s) trapped within the pectin or other mucilage; radionuclides also act as contrast agents. The implant's area of ​​action can be easily limited by its volume, which is directly determined by the quantity of the pharmaceutical composition according to the invention injected into the subject's body. The implant is placed simultaneously with its formation, i.e., by injection; it is less invasive than microcapsules containing a radionuclide, notably due to the formation of the flocculent and therefore flexible precipitate, as previously explained.Furthermore, an implant can be developed that fills and dries out the cyst, making it more easily detectable or detectable by other methods. Alternatively, an implant can be developed that forms around the periphery of the cyst or tumor, creating an outgrowth. The therapeutic action is then primarily achieved at the point of contact between the implant and the cyst / tumor. In the case of a tumor, the presence of the implant will mobilize the immune system to promote its destruction. The Applicant also demonstrated that pectins mixed with ethyl cellulose solutions can be sterilized without significant destruction of the pectin network, as the latter intertwines with that formed by the ethyl cellulose. Definitions The term "injectable" refers to a composition having a viscosity measured with a rotary rheometer as indicated below at 25°C of substantially equal to or less than 600 Pa.s, preferably substantially equal to or less than 300 Pa.s. The term "active substance" refers to a pharmaceutically acceptable substance that has a medical effect on a living organism. This effect may be therapeutic (curative treatment of a disease) or prophylactic; a substance that can simply improve a condition related to a disease, such as pain; a substance that can restore, correct, or modify a physiological function by exerting a pharmacological, immune, or metabolic action; and a substance that can be used for diagnosis. Derived terms such as "therapeutic treatment" refer to the administration, particularly by injection, of an active substance. The term "amount of active substance" does not necessarily refer to an amount suitable for producing a medical effect but preferably corresponds to that amount. The term "aqueous solution possibly saline" refers in particular to blood, lymph, serum, plasma, intracellular environment and any solution of the "physiological saline" type. The term "contrast agent" refers to any substance or mixture of substances that can be detected by the eye or by a known medical imaging technique where energetic particles can generate images and highlight certain tissues, organs, or parts of the human or animal body, such as, for example, radiography, ultrasound, MRI, scintigraphy, positron emission tomography (PET), single-photon emission computed tomography (SPECT). Dyes can thus allow the implant to be located when it is formed / placed under the skin, for example. The term "mucilage" refers to any substance naturally secreted by a living organism of plant, animal or micro-bacterial origin which swells upon contact with water, taking on a viscous consistency at room temperature (25°C). Examples of mucilage include pectins, mucilage obtained from flax or plantain seeds, mucilages produced by white seaweed, agar-agar and agarose. Throughout this application, the viscosity indicated is the value obtained by measurement at 25°C using an ARES rotary rheometer marketed by TA Instruments and equipped with a coaxial stainless steel geometry. The diameter of the inner cylinder is 16.5 mm, the diameter of the outer cylinder is 17 mm, and the height is 13 mm. The measurements are taken at 25°C, the rheometer having been brought to this temperature prior to the measurements. The values ​​indicated allow for obtaining a composition suitable for injection into the body of a subject, possibly after heating the composition to make it more fluid. The term "pectins" refers to polysaccharides comprising a D-galacturonic acid backbone and small amounts of more or less branched L-rhamnose. It encompasses polysaccharides in which the carboxyl group of the D-galacturonic acid is in its acidic, ionized form, for example with calcium, or forms an ester, for example with methanol, and polysaccharides in which the galacturonic acids are acetylated. Thus, according to the invention, the term "pectins" includes pectic acids with a degree of methylation less than 5% (DM < 5), weakly methylated pectins with a degree of methylation less than 50% (DM < 50), and highly methylated pectins with a degree of methylation greater than 50%. The molecular weight is not limited according to the invention, nor is the origin of the pectins. For example, they may be apple pectin, lemon pectin, or... beet. The term "subject" refers to an animal or a human being, adult or not, and more particularly an animal or a human being whose state of health requires therapeutic treatment. The term "pharmaceutically acceptable" refers to a substance which, when introduced into the body of the subject, does not cause toxic effects and / or side effects of an intensity comparable to or greater than the medical effect obtained by using the active substance. In the case of cancer treatment, a pharmaceutically acceptable composition makes it possible to kill cancer cells without the side effects outweighing the therapeutic benefits provided by the administration of the composition. The term "injection" covers subcutaneous, intravenous, intramuscular, intraosseous, percutaneous (subcutaneous intradermal) and intra (specific organ or tissue) injections. The term "eosin" encompasses both the Y and B forms of eosin as well as their mixtures. Figures The present invention, its features and the various advantages it provides will become clearer upon reading the following description and referring to the accompanying drawings in which: - Fig. 1 represents, on the upper curve, the viscosity of 96° ethanol and ethylcellulose gels as a function of the ethanol concentration, the lower curve represents the mass percentage of ethanol in the gel; - Fig. 2 is a photograph which represents the experimental device used to measure the passage of ethanol and eosin or methylene blue to the outside of the precipitate which will partially form the implant after injection of the product of the invention; - Fig. 3a is a photograph of the precipitate obtained with eosin and Fig. 3b of that obtained with methylene blue; and - Fig. 4 is a photograph of the precipitate obtained from a basic composition which is a suspension of a metal powder in the basic composition of 96° ethanol-ethylcellulose. EXAMPLES Preparation of the basic composition Ingredients: Ethylcellulose reference Aqualon N100F, pharmaceutical grade, % ethoxy = 49.2; intrinsic viscosity at 25°C = 94 cP in ethanol according to the standard method of the European Pharmacopoeia marketed by the company ASHLAND / SPCI. 96° Ethanol (solution containing water and ethanol) 96% Ethanol, pharmaceutical grade, D= 0.81 Kg / L, marketed by Fisher Chemicals. Several gels of 96° ethanol and ethylcellulose were prepared by diluting with 96° ethanol a stock composition consisting of 1600 ml of 96° ethanol and 94.25 g of ethylcellulose. The viscosity of these solutions was measured at 25°C using the aforementioned rheometer. Figure 1 shows the viscosity of these solutions as a function of the mass concentration of ethylcellulose (mass of ethylcellulose / (mass of ethylcellulose + mass of 96% ethanol)). All these solutions have a viscosity that makes them injectable. Addition of an active substance in powder form In 10 ml of each of the gels prepared in the previous step, 1.5g of eosin Y powder (marketed by RAL diagnostic) or 1.5g of methylene blue powder (marketed by Reag Ph. Eur) was dissolved at room temperature under gentle stirring. It was verified that the viscosity of these compositions remained in the same range as that of the base gels. Physiological saline (9 / 1000 saline, i.e., 9 g / L) was prepared. Since the concentration of blood serum is 6 g / L, the additional 3 g / L was used to compensate for the osmolarity of other blood ions present. The gel containing the aforementioned methylene blue or eosin was placed in a reverse osmosis unit mounted on a stand and equipped with a semipermeable membrane. The semipermeable membrane was placed in a graduated cylinder containing 400 mL of the aforementioned physiological saline. Using a spectrophotometer set to the wavelength corresponding to the highest absorbance peak of methylene blue (A=668 nm) or to the wavelength corresponding to the highest absorbance peak of eosin Y (A=525 nm), the transfer of eosin or methylene blue from the gel to the physiological saline was determined.Similarly, using a 0 to 100% alcoholmeter equipped with a thermometer and marketed by the company "AlAmbik®", we measured the passage of ethanol from the gel to the serum through the semipermeable membrane. The hemipermeable membrane is a behavioral model of the cell plasma membrane. The cells constitute the vascular walls, cysts, tumors, or any other tissue to be treated by the implant according to the invention. When a substance passes through the hemipermeable membrane, this means that on the one hand, this substance leaves the precipitate formed by the product and that on the other hand, it can pass by osmosis through the cell membrane. We first observed the formation of a precipitate at the level of the hemipermeable membrane. The gel containing eosin or methylene blue does indeed form a precipitate, like the base composition, upon contact with the aforementioned physiological saline. Above the precipitate, the composition remains in gel form. The implant formed in situ is therefore flexible and deformable. It will not cause mechanical damage to the surrounding tissues. Furthermore, the osmometer indicates an osmotic pressure, which confirms the diffusion of certain compounds through the hemipermeable membrane. The diffusion of eosin into physiological saline was then observed. As shown in Fig. 2, eosin crosses the semipermeable membrane and passes into the physiological saline, as evidenced by its red color. The diffusion of eosin or methylene blue begins 30 minutes after the semipermeable membrane comes into contact with the physiological saline. 12 hours after this contact, the osmotic pressure is almost zero, indicating the end of the passage of eosin or methylene blue into the physiological saline. Fig.3 clearly shows that the precipitate obtained contains eosin which gives it its red color. The passage of ethanol from the gel through the semipermeable membrane was then determined using an alcoholmeter placed in a graduated cylinder. After 30 minutes from the immersion of the osmometer in physiological saline, no change in the ethanol concentration was observed in the graduated cylinder. The same was true after 12 hours. The same phenomenon was observed with methylene blue. Furthermore, the precipitate obtained remained colored even after eosin or methylene blue was passed through physiological saline. The Applicant thus demonstrated that the ethanol remained in the precipitate, giving it a lasting sclerosing action, and that the methylene blue or eosin diffused out of the precipitate, thus disinfecting the environment of the implant. Example 1: Preparation of a pharmaceutically acceptable composition according to the invention for use in the treatment of osteomyelitis Preparation of the basic composition: 100 ml of 96° ethanol is mixed with 10 grams of ethylcellulose at 20°C. Next, 0.1 d of methylene blue or eosin powder and 5 grams of hydroxyapatite powder (hydroxyapatite in powder form with a purity >95%, marketed by the company MIDICOAT; powder BTE / 5-183) are added to the aforementioned basic composition. The resulting composition has a viscosity identical to that of the basic composition containing rethylcellulose and 96° ethanol. The resulting mixture can be injected into a bone cyst. The bactericidal ethanol contributes to the disinfection of the injection site. A synergistic bactericidal action is observed with the dye. The ethylcellulose precipitate then forms a matrix within the bone cyst, which will allow colonization by osteoblasts necessary for bone formation. Example 2: Preparation of a pharmaceutically acceptable composition according to the invention for use in bone reconstruction A basic composition is prepared as explained in Example 1 above. A growth factor as above and 5 g of hydroxyapatite are added to this basic composition. The resulting mixture can be placed in a cavity formed in bone tissue. The growth factor and hydroxyapatite allow the colonization of the cancellous implant by osteoblasts, which contributes to the formation of bone material. Example 3: Preparation of a pharmaceutically acceptable composition according to the invention for use in the treatment of benign cysts or benign tumors A basic composition is prepared as described in Example 1. A dye (methylene blue) is then added. The ethanol has a therapeutic effect here because it dries out the cyst, initiating necrosis. The dye allows the contours of the cyst to be localized, as the precipitate has formed around it, thus enabling its removal. Ethylcellulose forms a localized solid implant that traps the solvent and dye, thereby limiting their diffusion within the body. Example 4: Preparation of a pharmaceutically acceptable composition according to the invention containing pectin A basic composition is prepared by mixing 4.2500 g of ethylcellulose with 67.4105 g of 96% ethanol. The ingredients are identical to those listed in Fig. 1. Five grams of pharmaceutical-grade pectin, marketed by the French pharmaceutical company Coopération Pharmaceutique Française, are added to this mixture. It is observed that upon stirring at 18°C, a homogeneous mixture is obtained. This mixture is a gel whose viscosity, measured as shown in Fig. 1, is very close to that of the 96% ethanol and ethylcellulose gel. This gel is therefore injectable. Upon contact with a saline solution such as physiological serum as previously described, a cottony, deformable and slightly elastic precipitate is obtained which is not degraded when heated to a temperature of 40 °C. After 5 days, the resulting mixture becomes heterogeneous and it is observed that the pectin settles at the bottom of the container holding the mixture. Tests dissolving pectin in 96% ethanol showed that it was not soluble in 96% ethanol. Determination of the maximum amount of pectin added to obtain a stable gel We have developed a range of gels (A, B and C) obtained by mixing 96° ethanol with ethylcellulose, each of the gels having a different viscosity and density. Table II lists the different compositions of the gels. Table II The three gels have a viscosity that allows them to be injected into a subject's body. Pectin appears in stable suspension in gel D and in gel E. This is not the case for gels B and C, for which the pectin separates from the gel after 24 hours. It therefore appears that for 96° ethanol-ethylcellulose gels with a viscosity greater than 340cP (and optimal gel density) pectin is more easily in stable suspension without however exceeding the experimental Mass (Pectin) / Mass (ethylcellulose) ratio of 1 / 20. The powdered pectin particles used in this series of experiments can be even finer, which can further increase the stability of their suspension in the mixture. Vigorous stirring (using a vortex-type eccentric stirrer) allows for resuspension of the gelled ethanol + pectin mixture. A person skilled in the art can choose the most appropriate particle size. The incorporation of eosin Y powder or methylene blue into the gelled ethanol + pectin mixture is carried out at room temperature without any difficulty. The colored mixture is obtained quickly and is stable. Heating the different mixtures obtained shows that they resist heat. The gel appears to have elastic behavior; that is to say, the viscosity before heating is obtained again once the gel has cooled to its initial temperature. Bringing this colored gel (ethylcellulose / ethanol with 967pectin) into contact with an aqueous medium causes immediate precipitation. The diffusion of ethanol and eosin or methylene blue is the same as that observed for the experiment referred to in Fig.2. Example 5: Preparation according to the invention for the treatment of cancerous tumors A basic composition containing ethylcellulose, 96% ethanol, and pectin is prepared as described in Example 4, with a pectin / ethylcellulose mass ratio of 1 / 20. A dye (methylene blue) and a powdered radionuclide are then added. The ethanol also has a therapeutic effect because it will cause necrosis of the tumor. The radionuclide serves both as an active substance due to the gamma rays it emits and also allows for the localization of the implant formed by precipitation. The pectin will enhance the action of the ethylcellulose by trapping the radionuclide. Example 6: Preparation according to the invention allowing the treatment of cancerous tumors without pectin A basic composition was prepared by mixing 130 mg of ethyl cellulose with 2095.6 mg of 96% ethanol. 300 mg of a metallic powder simulating a radionuclide was added to this basic composition. As can be seen in Fig. 4, the precipitate is a three-dimensional mass forming a network of fibers like cotton, which completely traps the metallic powder. This example shows that the radionuclide can be used without pectin.

Claims

10. Pharmaceutically acceptable composition comprising a pharmaceutically acceptable basic composition which contains at least one solvent, at least one first polysaccharide soluble in said solvent, said basic composition being capable of forming a precipitate on contact with an aqueous solution, possibly saline; characterized in that it comprises - a given quantity of at least one active substance, which is selected from: - ionic bactericidal / antiseptic / fungal agents soluble in said solvent such as eosin and methylene blue and potassium iodide;- antibiotics, growth factors, hydroxyapatite, hormones, - anti-tumor agents, anti-mitotic agents, topoisomerase inhibitors, anti-cancer agents and mixtures of at least two of said active substances, possibly a second polysaccharide chosen from mucilages, including in particular agar-agar and pectins and preferably from pectins and possibly, in addition, at least one radionuclide usable in therapy, and possibly a contrast agent, in that said pharmaceutical composition has a viscosity which allows its injection and in that it forms a precipitate on contact with an aqueous solution, possibly saline.;