Injecting ceramic-based implants for filling of crinkles, skin cavity and cicatrices and method for production thereof

FIELD: medicine.

SUBSTANCE: described are implants based on biodegradable thixotropic compound with pseudo-plastic properties and implant injected under skin or into skin in fibrous tissue. Containing microparticles of at least one biocompatible ceramic compound in suspension, in at least one liquid carrier containing at least one compound based hyaluronic acid and at least one biodegradable thixotropic compound with pseudo-plastic properties. Also disclosed is kit for preparation such implants directly before application, as well as implant production and using for filling of crinkles, and/or skin cavity, and/or cicatrices.

EFFECT: implants of simplified injection.

14 cl, 4 ex

 

The technical field to which the invention relates.

The present invention relates to implants that can be injected subcutaneously or intradermally in fibrous tissue intended for use in human or an animal in a restorative or cosmetic surgery or aesthetic dermatology to fill wrinkles, wrinkles, skin depressions and scars, including dermal defects that appear as a result of treatment, which may lead to the development of lipodystrophy, often expressed in lipoatrophy entity.

The level of technology

Until today used a certain number of means. Each tool has its advantages and disadvantages.

- Easy to use by injection were silicone oil, which is now banned. However, after injection was observed migration of the silicone droplets in the tissues beneath the point of injection, under the action of its own weight. Improperly used or used in too large quantities of silicone was the cause of siliconomas and even persistent allergic reactions. Silicone is not biodegradable substance.

- Teflon paste is a suspension of particles of polytetrafluoroethylene (diameter from 10 to 100 μm) in glycerol. In many cases, this tool was dangerous and caused chronic zeros the haunted infection, and for most patients it had to be removed from the skin and subcutaneous tissue several months after injection. It was also proved that the smallest particles of polytetrafluoroethylene hit in the liver.

In the last ten years was widely used collagen suspension. Very long collagen occupied a leading position in this field of application, as it was practically the only means permitted for distribution in the market in order to treat aging skin. Approximately 3% of patients were reported cases of allergic reactions. Most patients resorption of collagen in average is 3-5 months, which requires multiple injections per year in order to achieve a certain efficiency. Finally, it should be noted that collagen is of animal origin.

Biological sampling from the patient. The idea was interesting, but clinical experience has shown the futility of reimplantation of fat cells, which was absorbed and disappear within a few weeks. Another solution was to add a plasma in collagen gelatin of animal origin (from cattle and pigs). The results were not impressive, and the tool is of animal origin.

Hyaluronic acid used in most pharmaceutical forms is whether the majority of medical devices used in the form of a gel of sodium hyaluronate. It is widely used, because of the ease of injection and security applications, and is a good alternative due to its biocompatibility and lack of toxicity. In addition, these gels of sodium hyaluronate are widely used in eye surgery. However, their ability to Express bioresorption (typically comprising from 4 to 6 months) may disappoint some users in filling wrinkles or skin depressions, as the injection must be repeated through a small and regular intervals.

- Bioplastic materials that are polymerized microparticles (diameter from 70 to 140 μm), dispergirovannykh in polyvinylpyrrolidone. Were cases of rejection reactions.

The beads of polymethylmethacrylate (emission spectra obtained for pure) in diameter from 20 to 40 microns in suspension or solution of gelatin, or in a solution of collagen, or in a solution of hyaluronic acid. Emission spectra obtained for pure is not byroslawsky material, although widely used in the field of ophthalmology in the form of an intraocular implant. In the field of aesthetic dermatology yet sufficient experience to determine the effects of intradermal implantation after five or six years after the introduction of the implant. In addition, when the medium was a solution of collagen (stomach the CSOs origin) was registered 3% of cases of allergies.

Microparticles of polylactic acid (PLA) is a polymorphic species and diameter from 40 to 63 μm in suspension in sodium carmellose. The product, marketed under the name Newfill®has a good perspective, as it provides long-term effectiveness of the treatment while limiting the number of sessions injection. Used polymer is L-PLA 100 (100% levogyrate crystalline form PLA), which has an extremely slow kinetics of resorption (over 5 years). However, concerns about resistance of PLA crystals in the tissues, which in some cases may cause a chronic inflammatory response with repeated injections.

- The use of CMC (derived cellulose) may, on the one hand, cause allergic reactions, and, on the other hand, the body is missing an enzyme system capable of decomposing cellulose. In addition, the need to prepare immediately before use and vigorous stirring for homogenization before use, poor molding product limit its use and alienate many users. After two years, in some cases the appearance of granulomas, and cystic nodules, most of which require removal.

Disclosure of inventions

The present invention which is the elimination of the disadvantages of the known products, available on the market, and in particular such as the use of products of animal origin, in particular, from the cattle, the need for regular injections (every few months), allergic reactions, difficulty of implementation of the injection.

In this regard, in one embodiment, the implementation of the present invention use biodegradable thixotropic connection with pseudoplastic-type properties used in the injected implant in accordance with the present invention, to stabilize the suspension and, in particular, to facilitate the injection of any material, biodegradable or not, facilitate the manufacture of the above-mentioned implant and injection molding of the above-mentioned implant using thin needles typically has a size of 25-30, preferably used for dermatological and/or aesthetic purposes.

In another embodiment of the invention uses resorbed ceramic compound selected because of its safety and is already used for medical purposes, in particular in the field of implant bone tissue.

Known patents and/or patent applications, of which we can mention the patent EP-B1-0627899, which describes the composition of the injected implant containing biocompatible ceramic matrix presets is existing in a liquid pharmaceutically acceptable carrier, selected from the group of biocompatible organic polymers in the buffer the aquatic environment, spreading from the injection site into the fabric, and mixtures thereof, in which a ceramic matrix contains particles with a size distribution in the range from 50 μm to 250 μm. The implant according to this patent is designed to be filled fibrous cavities mainly near the bone or hard tissue. If it is mentioned that the described implant can be injected into the soft tissue through needles larger than 20, more preferably 22, together with this (and in contrast) indicates that it is preferable that the injection, which should contribute to the growth of tissues, should be carried out using needles size 20 and less than and close to the bone or cartilage for treatment of the nose or treatment of sphincter. On the other hand, specifies that the size of the ceramic material constituting from 50 μm to 250 μm, preferably from 100 μm to 200 μm, should allow injection by using thin needles. When the amount is more than 50 μm, as indicated, the ceramic particles will be unduly subjected to phagocytosis. When the amount is more than 200 μm, as indicated, is difficult for the injection of particles. In the example implementation, injected and analyzed implants containing hydroxyapatite (ON) in a mixture of collagen. All of them are characterized by the beginning of the om calcification. None of the examples do not only use ceramics. Indeed, in the introductory part of the patent specifies that the collagen acts on filling under the skin surface, while the ceramic particles are used for the regeneration of the nearby bone and cartilage. However, as mentioned above, the presence of collagen is undesirable.

Also known documents, registered in the name of William G. Hubbard, a it WO-A-93/15721, and in the name of Bioform Inc., namely, WO-A-01/12247 and EP-A-1080698. They describe biocompatible and permanent, that is not resorbed (not absorbed), materials containing a matrix of ceramic particles to increase the amount of soft tissue (or "soft tissue" in English terminology). The said particles have a spherical shape and size adjustable, typically from 35 to 150 μm, however, this size may be less than 35 μm, preferably from 10 to 35 μm. In documents WO-A-93/15721 and WO-A-01/12247 preferred ceramic material is hydroxyapatite or NAR, but for this purpose you can also use the tricalcium phosphate. The bearer of these particles is biocompatible and resorbed idcompany material containing polysaccharide. In the document WO-A-93/15721 among the possible polysaccharides indicated carboxymethylcellulose (CMC) sodium and glycerin, the most preferred is a combination of them. The document WO-A-01/12247 among the possible polysaccharides indicated hyaluronic acid, but above all, carboxymethylcellulose (CMC) sodium and glycerin, the most preferred is a combination of them. The main difference of these implants from implant in accordance with the present invention is a permanent implant of the prior art.

Injected implants in accordance with the present invention allows to eliminate the disadvantages of the known solutions. In particular, they allow you to fill in wrinkles, wrinkles, scars and/or skin depressions using a simple and effective product that is capable of almost total bioresorption.

First and foremost object of the present invention is the manner in which the implant can be injected subcutaneously or intradermally into fibrous tissue, preferably at least one biodegradable thixotropic connection with pseudoplastic-type properties, preferably, at least one bioresorbable thixotropic connection with pseudoplastic-type properties, and more preferably at least one thixotropic connection with pseudoplastic-type properties based on xanthene resin.

Such biodegradable thixotropic connection with pseudoplastic-type properties used in the injected implant in accordance with this izobreteny is m, allows you to stabilize the suspension and greatly facilitate the injection of any material, biodegradable or nonbiodegradable, simplifies the manufacture of the above-mentioned implant and injection molding of the above-mentioned implant using thin needles typically has a size of 25-30, preferably used for dermatological and/or aesthetic purposes.

The second object of the present invention is an implant that can be injected subcutaneously or intradermally in fibrous tissue containing at least one biodegradable thixotropic connection with pseudoplastic-type properties, preferably, at least one bioresorbables thixotropic connection with pseudoplastic-type properties, and more preferably at least one thixotropic connection with pseudoplastic-type properties based on xanthene resin.

In particular, the present invention relates to a variant the execution of the said implant is an implant that can be injected subcutaneously or intradermally, containing microparticles of at least one biocompatible ceramic compounds in suspension in at least one liquid carrier, with the said implant is characterized by the fact that these microparticles are biodegradable, preferably bioresorbability, and have a size of from 10 to 8 μm, preferably from 10 to 50 μm, more preferably from 10 to 45 μm, and most preferably from 15 to 40 microns. These ceramic compound contains at least one element selected from the group comprising tricalcium phosphate (βTCP) and biphasic products (HRV), includes DRUG and βTCP in varying proportions, with preferably the mentioned element is βTCP, and the fact that the said liquid medium contains at least one connection based on hyaluronic acid and at least one biodegradable thixotropic connection with pseudoplastic-type properties, preferably at least one bioresorbables thixotropic connection with pseudoplastic-type properties, and more preferably, at least one thixotropic connection with pseudoplastic-type properties based on xanthene resin.

Under the "implant" in accordance with the present invention should be understood as intended for implantation of the composition, and the composition, which has already been implanted in the body of man or animal. Under "liquid media" in accordance with the present invention should be understood the connection that transports ceramic compound which is in liquid form. The term "liquid" means in this case that the same gel, for example, visco-plastic gel. Under the "gel" in the framework of the present invention should be understood three-dimensional physical structure, having a viscosity, rheological (viscoplasticity) and thixotropic (mistakemate) properties. This gel means having at least one thixotropic connection with pseudoplastic-type properties. Under "fibrous tissue" in the framework of the present invention should be understood subcutaneous space mainly of a fibrous nature, which can be filled with fibers. The term "subcutaneous" in the framework of the present invention should be understood as "hypodermic"that is "under the skin layer. The term "intradermal" in the framework of the present invention should be understood "thicker skin". Under "suspension" in the framework of the present invention should be understood condition powder, dispersed in a liquid not dissolving in said liquid.

By "biodegradable" or "decomposition" in the framework of the present invention should be understood decay in the biological environment of the material, resulting cellular, enzymatic, bacterial or viral activity. Biodegradation corresponds to the loss of physical properties. Under the "bioresorbable" or "resorption" in the framework of the present invention should be understood biodegradation, which is oversheets complete disappearance of the material, the products of biodegradation are excreted by the kidney or metabolic means.

The implant in accordance with the present invention in the preferred embodiment, or in another embodiment, contains at least one biodegradable thixotropic connection with pseudoplastic-type properties, preferably, at least one bioresorbables thixotropic connection with pseudoplastic-type properties, and more preferably at least one thixotropic connection with pseudoplastic-type properties based on xanthene resin. For example, this connection is cantoral 180®produced by CPKELCO Inc.

In a preferred embodiment of an implant in accordance with the present invention microparticles of ceramic compounds, as a rule, are resorbed (or almost resorbed after implantation in fibrous tissue in the period from 2 to 36 months, preferably from 3 to 24 months and more preferably from 4 to 18 months. In this case we are talking about resorbed ceramic material. Of course, that the carrier liquid is chosen so, that he himself was also biodegradable and preferably bioresorbables, and is also compatible with resorption of the ceramic compounds. In all cases, as a rule, in the accordance with the present invention avoid the use of native animal such as bovine collagen.

The size of the microparticles is an average size, measured by sieving (usually by suction through a sieve or vibration sieve in accordance with the standards AFNOR) or by laser granulometry. The percentage errors of the approximate and usually is about 10% at screening, and about 2% by laser granulometry. Preferably, the particles generally have a size in the range of 10 to 80 μm, preferably from 10 to 50 μm. More preferably the particulates have a size of from 10 to 45 μm, and more preferably from 15 to 40 microns.

In the framework of the present invention, the microparticles can be of any shape. According to a variant of execution of the microparticles essentially can be in the form of beads. Under the "particles" in the context of the present invention should be understood microparticles, containing or not containing a coating of biocompatible excipient known to specialists in this field.

Thus, in accordance with the present invention resorbed ceramic microparticles are inorganic and non-metallic material, usually having passed through the processing by annealing at high temperature and under pressure (sintering). The basic structure of ceramic materials is two-phase: vitreous phase (Matri is a) and the crystalline phase (crystalline needles). Traditional ceramic materials are burnt clay, porcelain, faience, glass, etc. New ceramic materials are preferred in accordance with the present invention, have the General properties, such as high corrosion resistance, mechanical properties for dense ceramic materials and ionic electrical properties for industrial applications. There are different collections of ceramic materials, depending on their composition, from which you can specify the calcium phosphates, which are bioactive ceramic materials.

The objective of the implant can be injected into the body of the implant is the formation of the fabric of new collagen fibers, which is usually called the Genesis of the new collagen and which is responsible for filling in wrinkles or skin depressions. It is necessary to start the mechanism, i.e. the synthesis of new collagen fibers, however, the implant should not remain in the body of the ingot for a long time. Indeed, any foreign body implanted in the body, causes nonspecific inflammatory response to a foreign body, so the period of his stay in the body should be medium. The choice of ceramic compounds with defined above for a period of resorption preferably should allow to combine maximum efficiency with a minimum of R is taken.

Indeed, as a rule, it is not desirable to use any preservision implant. So, preferably in accordance with the present invention a ceramic compound, which represents the mineral phase, which is almost completely decomposes or dissolves after subcutaneous or intradermal injection, and then almost completely removed from the body by natural processes.

In addition, the implant in accordance with the present invention preferably should meet the requirements of ease of use, resorption in a controlled period of time as the media, and ceramic compounds, lack of allergenicity of the product (due to the absence of compounds of animal origin) and does not require any preliminary tests.

According to the invention, a ceramic compound, usually has a specific surface area of 0.5 m2/g to 100 m2/g, preferably from 2 m2/g to 27 m2/, As a rule, the specific surface area measured by the BET method.

The present invention also concerns the injected implant, in which the microparticles are present in the liquid medium at the ratio of weight/volume, is strictly greater than 0% and smaller than 15%, preferably comprising from 2% to 12%.

In accordance with the present invention, the ceramic is e connection as a rule, contains at least one element selected from the group comprising tricalcium phosphate (βTCP) and biphasic products (HRV)containing hydroxyapatite (NAR) and βTCP in varying proportions, preferably this element is βTCP, provided that these particles are biorenewable, preferably bioresorbability. Thus, microparticles of a DRUG excluded from the present invention.

Hydroxyapatite (NAR) of General formula CA10(PO4)6(OH)2is closest to the crystals of biological Apatite. Generally, the atomic ratio CA/P (1,67) is less than the atomic ratio in the bone. Tricalcium phosphate (βTCP) has the formula CA3(PO4)2. The ratio of CA/P, as a rule, is 1.5. Two-phase products (HRV) join NAR and βTCP with varying degrees of respect. It should be noted that these products requires consideration of many variables contributing to their biological behavior: elementary composition, the nature of mineral phases, micro - and macroporosity, the presence of impurities.

In the most preferred implementation of the present invention, the ceramic compound is bioactive and therefore has the property chemical exchange with living tissues. By "biological activity" within this is of subramania should understand the property, providing specific chemical reactions in the area of interface between implant and tissue-receptor. It depends on the chemical and physico-chemical properties of the material and the opposite bioinertness (property biocompatible, but inert materials). After implantation, injection connection, as a rule, is a region of the extracellular dissolution and decomposition of the cell of origin, depending on the chemical structure (βTCP, HRV), physical structure (pores) and environmental material. Biological fluid, including liquid medium filling the micropores of the ceramic compounds, calcium fortified.

Decomposition, which preferably is the resorption of the implant in accordance with the present invention, as a rule, should not be too quick to let go of nonspecific inflammatory response to a foreign body, responsible for the synthesis of new collagen fibers. NAR is very little soluble, and the degree of its decomposition, as a rule, is very low in vivo, but varies with pH. βTCP is much more soluble and, as a rule, has a fairly high degree of decomposition in vivo. Two-phase products have properties that vary depending on the relationship between NAR and βTCP. Thus, most always the result of implantation depends on the kinetics of colonization and resorption, which is usually caused by chemical and physico-chemical characteristics of the injected implant in accordance with the present invention; preferably these criteria are monitored, due to the nature of the implant in accordance with the present invention.

For example, ceramic particles are particles Biosorb®sold as particles βTCP SBM.

Typically, the carrier liquid has a limited bioresorption ability, component, usually from about one to four months.

Preferably the liquid carrier of the implant is biocompatible gel, preferably bioresorbables gel.

In a preferred implementation of the present invention carrier liquid is such that the connection on the basis of hyaluronic acid mainly contain hyaluronic acid. The phrase "based on" in the framework of the present invention should be understood that at least the main part of the above-mentioned connection is hyaluronic acid, cross stitched or no, or one of its salts or one of its polysaccharide derivatives.

In a preferred implementation of the present invention mentioned the connection on the basis of hyaluronic acid hyaluronic acid with a molecular weight higher than the surrounding one million daltons, preferably in the range of one million to five million daltons.

The liquid medium may also optionally contain at least one element selected from the group comprising cellulose derivatives such as CMC (carboxymethylcellulose), a receiver array (hypromellose), HPC (hydroxypropylcellulose) and other glucosaminoglycans, in addition to hyaluronic acid.

The implant in accordance with the present invention has the form of microparticles, if necessary, the shape of the beads in suspension in the liquid medium carrying the said microparticles. These particles should have a diameter exceeding 10 μm, in order to avoid rapid or instant phagocytosis by macrophages. They should have a diameter less than 45 microns, so that they can be injected using a very fine needle (usually ranging in size from 25 to 30). Preferably, according to the invention, the carrier liquid is chosen so that it had its own viscosity sufficient for injection through a needle ranging in size from 25 to 30, for example, from 1500 to 4000 m3/kg at 25°and to maintain the homogeneity of the mineral phase, which is a ceramic compound in suspension in the liquid phase, which is the carrier liquid.

Ceramic connection in accordance with the present invention can be obtained Liu is a diversified known specialist way. There are two types of ways, depending on whether the ceramic compound of synthetic or natural (biological). Getting on the first type of method used for ceramic compounds of synthetic origin, are described below. Basic products obtained by chemical synthesis in the form of a powder. Formation for use by subcutaneous or intradermal injection (porosity and shape) requires various operations after firing at a temperature generally below 900°C. Thus, the powder can be sealed under pressure, then heated to a temperature typically in the range of 1100 to 1500°that results in at least partial sintering of the components of the powder. Is melting the above-mentioned components, then the agglomeration of micro-crystals formed upon cooling and remaining in the United state. Internode these microcrystals determine microporosity, i.e., the size of microparticles, at least partially, average size, typically less than 5 microns. Microporosity simultaneously depends on pressure and temperature. Adding to the powder, for example, naphthalene balls preferably can create macroporosity, that is, the size of the microparticles, at least partially, typically exceeding 100 microns. The diameter of the macropores is determined is by the diameter mentioned balls, which they are sublimated at a high temperature.

As for the second type of method used to obtain ceramic compounds of natural origin, it is generally similar to the first type of receipt, that is using the same heat treatment, but on the basis of already existing porous biological structures, often phosphocalcic (corals, bones). Mentioned heat treatment destroys organic elements and leads to ceramization postchallenge basis.

Determination of physico-chemical characteristics of ceramic compounds in accordance with this invention, generally known to the specialist. It can be done by elementary analysis, for example, by quantifying [calcium (CA), phosphorus (P) and trace element(s)], determine whether it is possible audience of heavy elements (pollution) and/or determine the ratio Sa/R. It can also be implemented, in addition to elemental analysis or separately, by using the diffraction of x-rays, for example, in the determination of mineral phases (NAR, βTCP), by determining the degree of crystallinity (size, shape crystals) and/or detection of crystal defects. It can also be implemented, in addition to elemental analysis and/iLike x-ray diffraction or separately, using infrared spectrometry, for example, by defining functional groups (carbonates, the presence of water, organic compounds, ionic substitution, etc.)by structure determination (determination of the surface condition, micro - and macro porosity).

The present invention concerns also a method of obtaining injectable implant in accordance with the present invention, containing the following steps:

- at the preliminary stage get biocompatible ceramic compound as defined above microparticles;

on another stage, regardless of previous preliminary step, get a solution of a liquid medium containing at least one connection based on hyaluronic acid and at least one biodegradable thixotropic connection with pseudoplastic-type properties;

after this ceramic compound obtained in the preliminary stage, injected into the carrier liquid, obtained at different stages during the final stage with the purpose of obtaining a mostly homogeneous suspension, usually by using the homogenization type mixer.

By "liquid media" in the context of the present invention should be understood mixture of a liquid medium, it is possible, in a solvent, preferably in an aqueous solvent.

The injected implant is in accordance with the present invention can be used in ready to use form in a pre-filled syringe, in ready to use form in a pre-filled vial or in the form of dried substances that require pre-cooking prior to use.

The present invention concerns also set for the preliminary preparation of the implant in accordance with the present invention, containing at least one biocompatible ceramic compound and at least one carrier liquid.

Set in accordance with the present invention typically contains in the first part of the ceramic compound and in the second part of the carrier, and allows the application to prepare injectable implant in accordance with the present invention immediately prior to use.

The present invention relates to the use of the injected implant in accordance with the invention, designed to fill wrinkles and/or wrinkles and/or skin depressions and/or scars, containing subcutaneous injection of the implant. It applies to both the human body and an animal body. Thus, this use relates primarily to the field of reconstructive or plastic surgery or to the field of aesthetic dermatology.

The implementation of the invention

Examples 1-4

These examples and included in our products various connections:

p> βTCP

Sodium hyaluronate

Xanthan gum

They were selected due to resorption capacity, viscosity and stabilizing properties in suspensions.

Examples of compositions (%, weight/volume):

Ceramic microparticles, which were used in these examples are particles Biosorb®sold by SBM.

They are well tolerated by the body and, therefore, are biocompatible.

Studies of cytotoxicity, sensitization, irritation, and implantation on the animal, carried out according to ISO 10993, showed excellent tolerance of the compounds given as examples of implementation of the present invention. The study of the acute toxicity intraperitoneal injection showed that the lethal dose for a mouse exceed 10 ml/kg, tested product (βTCP in suspension in the gel hialuronowy acid and xanthan gum) has no toxicity and meets the test according to ISO 10993. Unlike bioinert ceramic materials (alumina, zircon), βTCP is a bioactive ceramic material and, therefore, has the ability to chemical exchange with living tissues.

Unlike hydroxyapatite (NAR) βTCP has a much higher solubility and significant degradability in vivo.

Resorption of the implant in accordance with the present invention should not be too quick to colonize microparticles macroparasite. Thus begins a nonspecific inflammatory reaction is as a foreign body, which leads to its encapsulation fibrous tissue.

Thus, the clinical outcome depends on the kinetics of colonization and resorption, which is due to chemical and physico-chemical criteria of the implant; these criteria should be well monitored.

Not yet been produced estimates βTCP in the process of filling wrinkles (intradermal injection). However, numerous examples of applications in soft tissues (periodontia, guided tissue regeneration and bone tissue clearly showed good tolerance βTCP as the animal and in humans. Compositions for topical application were tested on the rat. It is not apparent phenomena of irritation and sensitization.

After implantation, the material becomes a place of extracellular dissolution and decomposition of cellular origin.

Studies of implantation in the rat was conducted during three months, to assess the effects of compounds in accordance with the present invention intradermal injection. They showed absolute safety of the product during and after injection (no pain, no irritation). Upon expiration of 3 months after implantation, histological examination showed the absence of any macroscopic damage, regardless used the end is crazy β The TCP.

Nonspecific inflammatory response to the foreign body was observed in accordance with the data sources. In addition, these reactions are manifested locally only at the site of contact with the material showed excellent tolerance of the studied material. Around these implants were not observed no abstsedirovaniya or necrotic tissue.

After one month there is the appearance of the connective tissue capsule is penetrated by blood vessels and surrounding the implant. This capsule consists mainly of connective cells, macroparasites, lymphocytes, giant cells of foreign bodies and fat cells.

- After 3 months reported a significant decrease in cell density of the connective capsule, as well as its thickness, which reflects the decrease in the intensity of the inflammatory response upon decomposition of the implant (approximately 50% in three months, which proves the complete disappearance of the product for the period from 8 to 16 months, depending on known models of decomposition). Remains unchanged only the number of fat cells. But the increase of deposition of collagen fibers.

Was the evaluation of different formulations with and without xanthan gum xanthan gum, which were subjected to treatment in an autoclave (121°C, 20 min)in order to evaluate the influence of xanthan gum to stabilize the suspension. Some of these compositions was prigotovlena on the basis of water for injection, the other is based on a 0.9% solution of sodium chloride to measure the effect of salt solution on the viscosity of the prepared gels after steam sterilization cycles. These studies have revealed a good suspension ability of xanthan gum and a higher resistance in the presence of a salt solution with a concentration of 0.9%. Registered data of the current stability or preliminary stability confirm the stability autoclaved suspensions obtained with 0.5% and 0.6% xanthan gum gel 2% hyaluronic acid.

Xanthan gum prevents deposition dispersions due to its ultra-threshold stress (or shear). This characteristic, as well as purchased the viscosity significantly exceed these same characteristics in a plant resins (guar, caruba)grafted cellulose or alginates.

The main property of xanthan gum is its action regulation rheology of aqueous systems and its stabilizing effect on water multiphase systems, whether for stabilization of liquid (emulsion), solids (slurry) or gas (foam).

In addition, the rheological properties of xanthan gum is elevated pseudoplasticity, i.e. reversible viscosity and crystallization of exceeding this characteristic of polysaccharides, such as the aforementioned hyaluronic acid.

It is resistant to enzymatic hydrolysis, including galactomannan, amylases, cellulases, pectinases, proteases, etc.

All these characteristics make it possible to give preference to xanthan gum for use as an additive in the injected compositions for aesthetic and dermatological purposes.

The present invention provides the use of xanthan gum for use in injectable formulations in aesthetic and dermatological purposes and in General as an agent in the injected compositions in the field of medicine and veterinary medicine.

1. The implant is injected by subcutaneous or intradermal injection of fibrous tissue and containing microparticles of at least one biocompatible ceramic compounds in suspension in at least one liquid carrier, characterized in that the microparticles are biodegradable and have a size of from 10 to 80 μm, preferably from 15 to 50 μm, the specified ceramic compound contains at least one component selected from the group consisting of tricalcium phosphate (βTCP) and biphasic products (HRV), which include DRUG and βTCP variable in the relationship, with the specified component is βTCP, and the fact that the said liquid medium contains at least one connection based on hyaluronic acid and at m is re, one biodegradable thixotropic connection with pseudoplastic-type properties.

2. The implant according to claim 1, characterized in that the ceramic compound in most cases has a specific surface area of 0.5 to 100 m2/g, preferably from 2 to 27 m2/year

3. The implant according to claim 1, characterized in that the microparticles are capable of bioresorbability after implantation in fibrous tissue in the period from 2 to 36 months, preferably from 3 to 24 months, and more preferably from 4 to 18 months.

4. The implant according to claim 1, characterized in that the microparticles are present in the liquid medium in the ratio (wt./about.) from 0 to 15%, preferably from 2 to 12%.

5. The implant according to claim 1, characterized in that the carrier liquid for the implant is a biocompatible gel and preferably capable of bioresorbability gel.

6. The implant according to claim 1, characterized in that the connection on the basis of hyaluronic acid contains mainly hyaluronic acid.

7. The implant according to claim 1, characterized in that the connection specified on the basis of hyaluronic acid hyaluronic acid with molecular weight of more than 1 million daltons, and preferably from 1 to 5 million daltons.

8. The implant according to claim 1, characterized in that the liquid medium contains at least one derivative of cellulose.

9. They who Lancet of claim 8, characterized in that a derivative of cellulose selected from the CMC (carboxymethylcellulose), a receiver array (hydroxypropylmethylcellulose) and LDCs (hydroxypropylcellulose).

10. The implant according to claim 9, characterized in that the derivative of cellulose is a carboxymethyl cellulose.

11. The implant according to any one of claims 1 to 10, characterized in that it has the form of ready-to-use pre-filled syringe, ready-to-use pre-filled vial or requiring restoration of the lyophilisate.

12. Cooking method introduced by injection of the implant according to any one of claims 1 to 11, comprising the following stages:

preparation of biocompatible ceramic compounds in the form of microparticles, characterized according to claim 1,

preparation of a solution of a liquid medium containing at least one connection based on hyaluronic acid and at least one biodegradable thixotropic connection with pseudoplastic-type properties

the introduction of ceramic compounds in the carrier liquid so that turned out to be mainly a homogeneous suspension.

13. The ready set for immediate use introduced by injection of the implant according to any one of claims 1 to 11, containing a ceramic compound in the first part and the carrier liquid in the second part.

14. The application input is about by injection of the implant according to any one of claims 1 to 11 for filling wrinkles, and/or wrinkles and/or skin depressions, and/or scar tissue, including subcutaneous injection of the specified implant.



 

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False hair // 2257231

FIELD: cosmetic medicine.

SUBSTANCE: false hair is made from titanium nickelide-based biologically inert alloy in the form of threads bearing on their middle part, serving as intracutaneous portion, surface layer of porous permeable titanium nickelide-based alloy. Each individual hair is implanted by sticking followed by closely located extraction and traction to location of porous layer un skin and under skin toward aponeurosis.

EFFECT: improved inert properties of false hair, increased reliability, mechanical wear resistance, and lifetime.

2 dwg

The invention relates to medicine, namely to surgery, and may be applicable to eliminate wrinkles

FIELD: medicine, orthopedics, oral surgery, surgical stomatology.

SUBSTANCE: the present innovation refers to the system of delivering medicinal preparations and could be applied for filling in osseous defects or as a matrix for cell cultures. Porous hydroxyapatite ceramics with bimodal distribution of pores contains thin intragranular (under 10 mcm diameter) and large-scale interpenetrating intergranular pores, the size being above 100 mcm, at total quantity of about 41-70 rot.%. The method deals with manufacturing spherical granules of about 400-600 mcm diameter that contain hydroxyapatite powder and gelatin, pressing these spherical granules under 10-100 MPa pressure and thermal treatment at about 900-1250°C at keeping from 30 to 300 min. The innovation enables to create ceramics with bimodal distribution of pores.

EFFECT: higher efficiency of manufacturing.

2 cl, 1 tbl

Transplant mixture // 2301684

FIELD: medicine.

SUBSTANCE: transplant mixture has liophylized allogenic bone tissue and allogenic hydroxyapatite and patient autoblood platelets gel with Metronidazole, taken in the following components proportions (%): liophylized allogenic bone tissue - 65; allogenic hydroxyapatite - 10; patient autoblood platelets gel - 20; Metronidazole - 5.

EFFECT: enhanced effectiveness of treatment; no clamps required; reliably and tightly closed bone tissue defect; accelerated regenerate reorganization; improved antiseptic and immunomodulating action.

FIELD: medical-destination materials and products.

SUBSTANCE: preparation of hydroxyapatite-based porous ceramic granules, which can be used to fill bone defects in traumatology, orthopedics, maxillofacial surgery, and surgical stomatology, comprises preliminary synthesis of calcium phosphate powder with Ca/P ratio 1.5-1.67 and preparing suspension with 10% gelatin solution in proportion of 0.5-3 mL solution per 1 g powder at solution temperature 10 to 39° C. Suspension of hydroxyapatite in aqueous gelatin solution is then dispersed in neutral liquid vegetable oil, resulting mixture is stirred by blade stirrer at rotation speed 100 to 1500 rpm. Under effect of surface tension, spherical granules are formed, which are washed, dried, and subjected to heat treatment at 900-1250° C.

EFFECT: enabled preparation of granules with controlled size and open porosity occupying 20 to 80% of the volume.

1 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: mixture has lyophilized allogenic bone tissue and additionally has allogenic hydroxyapatite and patient autoplasma enriched in blood platelets. The components are taken in ratio in %: lyophilized allogenic bone tissue - 60; allogenic hydroxyapatite - 20; patient autoplasma enriched in blood platelets - 20.

EFFECT: provided increase in transplantation mixture plasticity; usability for modeling transplant from the given mixture of required form; tightly closed bone tissue defect.

4 dwg

FIELD: medical technologies; production of the carbonate hydroxyapatite ceramics.

SUBSTANCE: the invention is pertaining to the charge for the carbonate hydroxyapatite ceramics. The charge for production of the ceramic material on the basis of the carbonate of hydroxyapatite may be used for filling-up the osteal defects in traumatology and orthopedics, the maxillofacial surgery and the surgical stomatology. The charge of the carbonate hydroxyapatite additionally contains 2-20 mass % of the potassium carbonate. The technical result of the invention is production of the dense ceramic material and reduction of the temperature of its sintering. At that its kilning may be conducted in the air medium in the ordinary kilns without application of the special cost intensive inventory maintaining the set humidity and the gas medium.

EFFECT: the invention ensures production of the dense ceramic material and reduction of the temperature of its sintering.

1 ex, 1 tbl

FIELD: medicine.

SUBSTANCE: method involves applying hydroxyapatite collagen material plate so that plate size is selected to be by 5-8 mm greater than trepanation opening.

EFFECT: enhanced effectiveness in making plastic repair of maxillary sinus; excluded allergic responses.

The invention relates to the field of medicine and relates to a method of forming a bone implant, which can be used for plastic bone as in the treatment and prosthetics areas of bone affected by degeneration, when bone defects resulting from congenital or acquired diseases

The invention relates to medicine, namely to orthopedics and traumatology, and can be used for bone grafting
The invention relates to medicine, namely to traumatology in the treatment of hip fractures

FIELD: medical equipment; surgical instruments.

SUBSTANCE: intravenous anti-embolic filter can be used for catching grums. Filter has catheter in form of hollow tube. There are thread-like members at one end of tube; members are oriented radial to hold grum. Catheter is also provided with flat radial directed members and with support member in form of ring made for rest of its external surface against wall of vein. Ring is mounted with concentricity to tube at one end of tube; ring is connected with tube by mentioned radial directed thread-like members. Flat radial oriented members are attached to external surface of tube in front of ring at side of other end of tube; flat members have cutting edge along their lengths. Cutting edge is turned to other end of tube, which end is closed at its edge. Through openings are made along length of tube I its sidewall in part disposed from closed edge to flat members provided with cutting edge. Anti-embolic device prevents migration of thrombotic masses and helps to crush the mass to separate components.

EFFECT: higher reliability of catching grums; higher efficiency of grum crushing; provision of normal blood current in vein.

1 dwg

FIELD: medical engineering.

SUBSTANCE: method involves using titanium alloy casing coated with alumina. First, the casing is etched with hydrofluoric acid, washed with distilled water, covered with calcium ions over external casing surface. Then, alumina layer is sprayed by atomizing sapphire target with argon ions in vacuum. Alumina layer thickness is equal to 0.11-0.2 mcm. Next, calcium ions are introduced into alumina layer.

EFFECT: high quality of implant.

1 dwg

FIELD: medicine.

SUBSTANCE: endovascular bifurcation implanted prosthetic appliance can be used in X-ray-endovascular surgery for restoration of changed parts of clearings of blood vessels, for example, of aneurysm of thoracic part of aorta or abdominal aneurysm. Prosthetic appliance has main case provided with bifurcation in distal part and two legs form of extended polytetrafluoroethylene and strengthened from outside by self-widened metal stenter made of zigzag-curved wire, which form cylindrical surfaces. Prosthetic appliance is made integral and it is provided with envelope of extended polytetrafluoroethylene, which covers metal stenter by two guiding branches - shorter and longer ones, as well as fixing threads for shorter and longer branches. Shorter branch has ring at its proximal end to let longer branch go. There is thread-extender onto distal end. Shorter and longer branches are attached to prosthetic appliance by fixing threads for shorter and longer branches correspondingly by means of loop-shaped easily loosing seam. Fixing thread for longer branch has one its end attached to distal end of leg and it reaches proximal end of main case. Fixing thread of shorter branch is attached close to distal end of leg and it attaches shorter branch until point of bifurcation. Branches are connected higher than point of bifurcation of main case.

EFFECT: prevention of replacement of prosthetic appliance due to complications; simplicity and high comfort of implantation operation.

8 cl, 10 dwg

FIELD: medical equipment.

SUBSTANCE: structure of intraparietal reinforcing assembly allows integrating into biological prosthetic appliance. Intraparietal reinforcing assembly for introduction into biological prosthetic appliance is made for mounting inside organic tissue of biological prosthetic appliance and for reinforcement of its structure to keep shape of prosthetic appliance after implantation. Reinforcing assembly has intraparietal rod made for introduction into organic tissue of biological prosthetic appliance, and tenon attached to first end of rod.

EFFECT: higher strength of prosthetic appliance; ability of keeping necessary shape; usage of maximal part of surface area and available volume.

14 cl, 4 dwg

FIELD: medical equipment.

SUBSTANCE: when treating surface of implant intended for implantation into bone tissue, microscopic roughness is provided, which roughness has pores and peaks. Diameter of pores is smaller or equal to 1 micron, depth of pores equals to 500 nm maximum, width of peak at level of half of pores equals to 15-150% diameter of pores.

EFFECT: higher reliability of attachment of implant.

21 cl, 3 tbl, 10 dwg, 2 ex

FIELD: medicine.

SUBSTANCE: tissues are connected together by means of implants, or tissue connects with aids supporting or replacing tissue either with other auxiliary therapeutic devices. Implant is characterized by the fact that at least part of it is made of material turning to liquid state under effect of mechanical energy. Material, turning to liquid state, is placed onto implant in such a way that it can make contact with tissue and is capable of turning to excited state under effect of mechanical oscillations and be simultaneously pressed into tissue to liquefy at least part of material, which turns into liquid state, and is pressed into openings of tissue. Device for implanting implants 7 has oscillator 2, oscillation member and resonator 6. Oscillator 2 intends for excitation of mechanical oscillations in oscillation member. Resonator 6 and oscillation member form oscillation module 3. Resonator 6 actively connects with implant 7 to transmit mechanical oscillations and it intends for pressing implant 7 into tissue. Device also has guide of implant; casing or transmitting member has to be support for guide. Set is composed of oscillator 2, oscillation member and resonator 6. Oscillator 2 intends for exciting mechanical oscillations in oscillation member. Additional set with single implant or with more number of implants 7 has structures for implanting implants by means of energy of mechanical oscillations. Method of implantation of implants 7 by means of implantation device consists of following steps: positioning of implant onto tissue in such a way that areas of implants, made of material being capable of turning into liquid state, make contact or can make contact with tissue n point where there roughness or openings onto surface of tissue, which openings provide motionless connection, or in point where those roughness or openings can be formed by hydrostatic pressure; implant is subject to influence of mechanical oscillations followed by simultaneous pressing implant into tissue until at least part of material, being capable of turning into liquid state, is liquefied and pressed into mentioned surface defects or openings; repeated hardening of material, being capable of turning into liquid state, when implant is pressed into tissue.

EFFECT: reliable, at least partially motionless connections with tissue of human or animal's body, namely, with skeleton.

47 cl, 30 deg, 1 ex

FIELD: medicine.

SUBSTANCE: tissues are connected together by means of implants, or tissue connects with aids supporting or replacing tissue either with other auxiliary therapeutic devices. Implant is characterized by the fact that at least part of it is made of material turning to liquid state under effect of mechanical energy. Material, turning to liquid state, is placed onto implant in such a way that it can make contact with tissue and is capable of turning to excited state under effect of mechanical oscillations and be simultaneously pressed into tissue to liquefy at least part of material, which turns into liquid state, and is pressed into openings of tissue. Device for implanting implants 7 has oscillator 2, oscillation member and resonator 6. Oscillator 2 intends for excitation of mechanical oscillations in oscillation member. Resonator 6 and oscillation member form oscillation module 3. Resonator 6 actively connects with implant 7 to transmit mechanical oscillations and it intends for pressing implant 7 into tissue. Device also has guide of implant; casing or transmitting member has to be support for guide. Set is composed of oscillator 2, oscillation member and resonator 6. Oscillator 2 intends for exciting mechanical oscillations in oscillation member. Additional set with single implant or with more number of implants 7 has structures for implanting implants by means of energy of mechanical oscillations. Method of implantation of implants 7 by means of implantation device consists of following steps: positioning of implant onto tissue in such a way that areas of implants, made of material being capable of turning into liquid state, make contact or can make contact with tissue n point where there roughness or openings onto surface of tissue, which openings provide motionless connection, or in point where those roughness or openings can be formed by hydrostatic pressure; implant is subject to influence of mechanical oscillations followed by simultaneous pressing implant into tissue until at least part of material, being capable of turning into liquid state, is liquefied and pressed into mentioned surface defects or openings; repeated hardening of material, being capable of turning into liquid state, when implant is pressed into tissue.

EFFECT: reliable, at least partially motionless connections with tissue of human or animal's body, namely, with skeleton.

47 cl, 30 deg, 1 ex

Up!
βTCP10%βTCP7%
Sodium hyaluronate2%Sodium hyaluronate2,2%
Xanthan gum0,5%Xanthan gum0,5%
βTCP10%βTCP7%
Sodium hyaluronate2,2%Sodium hyaluronate2,2%
Xanthan gum0,6%Xanthan gum0,6%
βTCP10%βTCP7%
Sodium hyaluronate1,8%Sodium hyaluronate1,8%
Xanthan gum1%Xanthan gum1%
βTCP10%βTCP7%
Sodium hyaluronate1,6%Sodium hyaluronate1,6%
Xanthan gum0,8%Xanthan gum0,8%