Way of soft tissues volume increase

FIELD: medicine.

SUBSTANCE: invention concerns medicine. Particles of the viscoelastic material chosen from group, consisting of polysaccharides and their derivatives which are suitable for injection with gel particles having the size in a range from 1 to 5 mm at action of a physiological saline solution are described. An implant for increase of volume of the soft tissues, containing particles of the viscoelastic material chosen from group, consisting of polysaccharides and their derivatives where the basic volume of the specified particles represents the gel particles, suitable for injection and having the size in a range from 1 to 5 mm at action of a physiological saline solution, is described. The way of increase of volume of soft tissues at a mammal, including a human being, including subepidermal introduction in a place of a body of the specified mammal in which it is desirable to enlarge volume of soft tissues is described.

EFFECT: augmentation of volume of soft tissues at a mammal.

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The technical FIELD TO WHICH the INVENTION RELATES

The present invention relates to the fields of aesthetic and plastic surgery including cosmetic and reconstructive surgery. More specifically, the invention describes a way to increase the volume of soft tissue in mammals, including humans. In addition, the invention is directed to the use of particles of a viscoelastic material for the production of therapeutic agents for therapeutic increase the amount of soft tissue in mammals, including humans. The invention also refers to particles of a viscoelastic material, their reception and their use as an implant.

The LEVEL of TECHNOLOGY

The material of the implant, which can be used to increase the amount of soft tissue should ideally be able to provide adequate and long-term aesthetic and/or therapeutic correction without migration or displacement; should look natural and not produmyvatsya; should easily be entered and, if necessary, be removed; must be non-immunogenic; and must be free from chronic inflammatory reactions (Krauss MC, Semin Cutan Med Surg 1999; 18:119-128). As a material to increase soft tissue, low immunogenic potential of hyaluronic acid (a naturally occurring polysaccharide), which is chemically homogeneous is all kinds and in all tissues (Larsen NE et al., J Biomed Mater Res 1993; 27:1129-1134). Stabilization (or cross-linking) of the molecules of hyaluronic acid improves their resistance to destruction by enzymes without compromising biocompatibility, at the same time the source of non-animal origin reduces the possibility of contamination antigens and subsequent allergic reactions (Friedman et al., Dermatol Surg 2002; 28:491-4).

Stabilized hyaluronic acid of non-animal origin (NASHA), U.S. patent 5827937, can be obtained from high-purity hyaluronic acid, obtained by bacterial fermentation. As dermal fillers to increase the volume of soft tissues have been developed a variety of drugs NASHA with different particle size (Restylane® Perlane, Restylane®, Restylane® Fine Lines and Restylane® Touch, all released by Q-Med AB, Uppsala, Sweden). Clinical studies show that well-known NASHA gels are effective in the augmentation of the lips (Bousquet M-T and B Agerup, Oper Techniques Ocuplast Orbit Reconstruct Surg 1999; 2:172-176), and for the correction of wrinkles and folds on the face (Olenius M. Aesth Plast Surg 1998; 22:97-101; Duranti F et al., Dermatol Surg 1998; 24:1317-25; Narins RS, et al., Dermatol Surg 2003; 29:588-95; Carruthers J, Carruthers A, Dermatol Surg 2003; 29:802-9), and that they are able to provide more long-term aesthetic improvement than bovine collagen or hylan B. Extensive clinical experience obtained during their intradermal application in approximately 1.5 million cosmetic the ski procedures on the face, confirms their safety.

According to the recommendations of RESTYLANE Touch (~500 000 particles/ml, average particle size 0.2 mm) should be injected into the upper part of the skin, RESTYLANE (~10 0000 particles/ml, an average particle size of approximately 0.4 mm) should be injected into the middle part of the skin; and RESTYLANE Perlane (~10 000 particles/ml, an average particle size of approximately 0.8 mm) should be injected into the deep layer of the skin and/or superficial layer of subcutaneous tissue.

Some known methods of increasing the volume of soft tissues, including the implantation of viscoelastic materials, suffer from the disadvantage of that is that the implant or part thereof migrates to the desired place of introduction. Another problem with some known methods of increasing the volume of tissues, including the implantation of viscoelastic materials is that the implant is displaced from the desired place of introduction. Migration and displacement are inconvenience for the patient, because they can reduce the cosmetic and/or therapeutic treatment outcome, and can also prevent the removal of the implant if necessary.

The INVENTION

The aim of the present invention to provide an implant material that is appropriate to increase the amount of soft tissue, which was devoid of the disadvantages inherent in the known implants the traditional materials. In addition, the present invention is to develop a method of producing such an implant material.

Another objective of the present invention to provide an implant that is appropriate to increase the amount of soft tissue that contains the specified implant material, which was devoid of the disadvantages of the known implants. Another objective of the present invention to provide an implant that is appropriate to increase the amount of soft tissue implant containing such material, which can be easily removed if necessary.

Another objective of the present invention is to develop a way to increase the volume of the soft tissues of mammals, including humans, which would be deprived of the disadvantages of the known methods. One of the purposes of the present invention is to develop a way to increase the volume of soft tissues of a mammal, including man, comprising the subepidermal introduction of the implant, which would avoid or reduce unwanted migration of the implant with the desired site of implantation. One of the purposes of the present invention is to develop a way to increase the volume of soft tissues of a mammal, including man, comprising the subepidermal introduction of the implant, which would avoid or reduce unwanted movement of the implant is from the desired site of implantation.

In addition, the purpose of the present invention is to develop applications of viscoelastic material for the production of therapeutic agents for therapeutic increase of the soft tissues of mammals, including humans.

With these and other objectives which will become apparent from the subsequent description, the present invention is designed particles of a viscoelastic material, which are suitable for injection gel particles having a size ranging from 1 to 5 mm under the action of physiological salt solution.

The present invention is based on the data, according to which the subepidermal introduction of the implant containing gel particles made of a viscoelastic material, which by its size considerably exceeds previously used in implants made of viscoelastic material, applicable in order to avoid migration and/or displacement of the implant or its part with the desired area of the body, in which an increase in soft tissue. In addition, limited displacement of the implant in combination with a significant particle size facilitates easy removal of the implant if necessary.

Mentioned the size of some of the preferred particles of the present invention is in the range from 1 to 2.5 mm. In other preferred frequent the C of the present invention, the above size ranges from 2.5 to 5 mm

Mentioned viscoelastic material, the preferred particles of the present invention is selected from the group consisting of polysaccharides and derivatives thereof. In the case of the preferred particles of the present invention, the aforementioned viscoelastic material selected from the stable of glycosaminoglycans and their derivatives. For some preferred particles according to the present invention mentioned viscoelastic material selected from the group consisting of stabilized hyaluronic acid, stabilized chondroitin sulphate, stable heparin and derivatives thereof.

In the case of the preferred particles of the present invention mentioned viscoelastic material selected from the group consisting of cross-linked hyaluronic acid and its derivatives. In a particularly preferred particles according to the present invention, the concentration of the aforementioned viscoelastic material in the above-mentioned gel particles is in the range from 5 to 100 mg/ml under the action of physiological salt solution.

The preferred particles of the present invention can be administered by injection through a needle 20 or larger during the application of pressure 15-50 N.

According to another aspect of the present invention relates to a process for the preparation suitable for injection of gel particles of viscoelastic material on the waiting stages: (i) the production of a gel with the desired concentration of the specified viscoelastic material; and (ii) mechanical crushing of the specified gel in the gel particles, which when placed in a physiological saline solution have a size in the range from 1 to 5 mm

According to another aspect of the invention relates to an implant to increase the amount of soft tissue containing particles of a viscoelastic material, in which the main volume of these particles is a suitable for injection of the gel particles, which when placed in a physiological saline solution have a size in the range from 1 to 5 mm In the preferred embodiments of the implant of the above-mentioned size is in the range from 1 to 2.5 mm. In other preferred embodiments of the implant of the above-mentioned size is in the range from 2.5 to 5 mm

In accordance with one aspect of the present invention relates to a method of increasing the volume of the soft tissues of a mammal, including man, comprising the subepidermal introduction to the area of the body referred to the mammal in which it is desirable increase in the volume of soft tissue implant containing suitable for injection of the gel particles of a viscoelastic material, and the main volume of the above-mentioned particles is in the range from 1 to 5 mm when placed in a physiological saline solution. In preferred embodiments of the method of the present invention mentioned the introduction of choice and the group, consisting of subcutaneous injection, injection under the muscle and the introduction of on top of the periosteum.

In some methods of the present invention, the specified size is in the range from 1 to 2.5 mm In the preferred embodiment, this method is referred to section increase the amount of soft tissue selected from facial tissues and other tissues that covers the open skin. In other methods according to the present invention, the specified size is in the range from 2.5 to 5 mm

In preferred methods of the present invention mentioned introduction selected from the group consisting of a single introduction and multilayer injection.

According to another aspect of the invention relates to suitable for injection of the gel particles of the present invention for use as a drug. In addition, the invention relates to suitable for the injection of the implant to increase the amount of soft tissue that contains suitable for injection of the gel particles of the present invention for use as a medicine.

According to another aspect of the present invention relates to the use of suitable for injection of gel particles of a viscoelastic material according to the present invention, and the main volume of these particles has an average size in the range from 1 to 5 mm at destyatnirchenko salt solution to obtain drugs for therapeutic increase soft tissue of the mammal, including humans, where the specified drug is suitable for the subepidermal injection in accordance with the present invention in the area of the body where it is desirable therapeutic increase in soft tissue referred to a mammal.

DETAILED description of the INVENTION

According to one aspect of the present invention refers to particles of a viscoelastic material, which are suitable for injection of the gel particles having a size ranging from 1 to 5 mm under the action of physiological saline. These particles can be used in the implant to increase the amount of soft tissue containing particles of a viscoelastic material, where the main volume of the above-mentioned particles is a suitable for injection of the gel particles of the present invention, moreover, these particles under the action of physiological salt solution have a size in the range from 1 to 5 mm. In turn, the implant can be used in the method of increasing the volume of the soft tissues of mammals, including man, comprising the subepidermal introduction to the area of the body referred to a mammal, preferably an increase of the volume of soft tissue implant containing suitable for injection of the gel particles of a viscoelastic material, and the main the volume of these particles is R is setting the log file name in the range from 1 to 5 mm under the action of physiological salt solution.

The term "increase in the volume of soft tissue in the framework of the present description refers to any type of increase in the volume of soft tissues, including, but not limited to, the contouring of the face (for example, more pronounced cheeks or chin), correction of concave deformation (e.g., posttraumatic associated with HIV lipoatrophy), as well as correction of facial wrinkles associated with old age. Thus, the increase in soft tissue may be used solely for cosmetic purposes or for medical purposes, such as the consequence of an injury or degenerative disease.

The term "soft tissue" in the framework of the present description refers to tissues that connect, support or surround other structures and organs of the body. Soft tissue includes muscles, fibrous tissue and fat.

The method according to the present invention may be implemented with respect to any mammal, including humans. Preferably, the method was carried out in respect of the person.

The term "subepidermal introduction in the framework of the present description refers to the introduction into the epidermis of the skin, including the introduction in the dermis, subcutaneous tissue or deeper, for example, under the muscle or periosteum, if possible (near the bone).

The introduction can be carried out in any suitable way, for example,by injection using a standard catheter and needle of appropriate size. The introduction is carried out, if it is desirable increase in the volume of soft tissue, for example, chin, cheeks or any other designated person or body.

The term "implant" in the framework of the present description refers in a broad sense to any type of implanted or suitable for implantation of a foreign object or material. Implants also include objects or materials, which are almost identical to the native objects and materials. The implant according to the present invention is not limited to any specific form. The decision on the final form of the implant in the body is taken by the person skilled in the art based on the treatment goals.

The term "viscoelastic material" in the context of the present description refers to a material that exhibits a combination of viscous and elastic properties. Specifically, the viscoelastic material of the present invention is suitable for injection through a needle 20 or larger, for example, 10-20 needles sizes during the application of pressure 15-50 N. In particular material or implant, or a therapeutic agent-containing material suitable for the subepidermal injection into the desired area of the body if necessary.

Viscoelastic materials of the present invention include gels, dispersions, solutions, suspensions, suspensions, and mixtures thereof. Preferably, the material was in the form of a dispersion of GE is I or gel-like particles. In a preferred embodiment, the implant according to the present invention consists of particles with a size of 1-5 mm of one or more viscoelastic materials, dispersed in physiological buffered saline or a suitable physiological saline solvent. In another preferred embodiment, the implant further comprises other suitable additives, such as local anesthetics, anti-inflammatory drugs, antibiotics or other suitable supporting medicines, for example, growth factors or bone cells. In addition, they optionally can be included in the viscoelastic material, which may be the same or different, which is not present in the form of particles or in the form of particles of size less than 0.1 mm

It is clear that the size of the gel particles of the present invention depends on the ionic strength of the buffer solution or the media, which is included in the gel particles, and/or which surrounds them.

In the scope of the present description shows the sizes of the particles suggest physiological conditions, in particular isotonic conditions. It should be noted that although it is preferable that the gel particles contain physiological saline solution and were dispersed therein, it is assumed that the gel particles of the present invention can be temporarily is shown to other sizes due to the action on the gel particles of a solution other toychest. Particles in the framework of the present invention have a size that is enclosed in the specified ranges under physiological conditions, for example when they subepidermal implanted in the body, or when they are exposed to saline or isotonic salt solution, i.e. a solution with the same onicescu that relevant biological fluids, for example isoosmotic serum.

Thus, the viscoelastic material of the present invention is, at least in the form of gel particles or gel-like particles. The main volume or more than 50% (by volume) of the particles have a size of at least 1 mm, preferably in the range of 1-5 mm in the presence of physiological salt solution. In preferred embodiments, the implementation of more than 70% (by volume), preferably more than 90% (by volume) of the particles are within the specified dimensions in physiological conditions.

In the framework of the present description saline or isotonic solution is a solution having an osmolarity in the range of 200-400 mOsm/l, preferably 250-350 mOsm/l, more preferably, about 300 mOsm/L. For practical purposes this osmolarity is easily achieved through the preparation of 0.9% (0,154 M) NaCl solution.

A suitable way to obtain particles of the desired size includes the preparation of a gel made from elm is oppose material in the desired concentration, and implementation of the physical crushing of the gel, as, for example, grinding, rubbing, or passing the gel through a filter with a suitable pore size. The obtained gel particles dispersed in a physiological saline solution, obtaining a dispersion or a suspension with particles of the desired size.

Another aspect of the present invention is the density or hardness of the gel particles. The density of the gel particles can be easily adjusted, for example, by changing the concentration of viscoelastic material, as well as the number and type of reagent carrying out cross-linking, in the case of its application. Thus, more solid particles can be obtained at higher concentration of viscoelastic material in the gel and, due to this, in the formed gel particles. More solids are generally less viscoelastic and have a longer half-life ofin vivocompared to the softer particles. For use in the present invention, the decisive factor is that the particles must retain sufficient viscoelastic properties so that they remain suitable for administration by injection.

In a preferred embodiment of the present invention, the implant is a two-component composition consisting of a softer gel particles, mixed with the firmer the gel particles. Gel particles can be obtained from the same or other viscoelastic material. The mixture of gel particles combines the desired properties of softness/hardness for use in order to increase the amount of soft tissue and prolongin vivo.

The introduction of the implant with the use of the method according to the present invention prevents or reduces migration and/or displacement of the implant, which contains or consists of particles with a size of 1-5 mm at physiological conditions. An additional advantage of the present invention lies in the fact that a large particle size in combination with prevented or reduced migration facilitates easy removal of the implant containing such particles, which should be desirable for some reason.

In a preferred embodiment of the present invention, the particles have a size in the range from 1 to 2.5 mm, such as from 1.5 to 2 mm in the presence of physiological salt solution. These particles are suitable for insertion in subcutaneous tissue and the tissue located under the muscle or over the periosteum. In particular, they are suitable for introduction into the tissue covered with skin, which is open to the views of other people, such as facial tissue, because particles and needle that are appropriate for particles of a specified size range, is likely to cause the AOC is podtekov or other color spots. In the preferred embodiment, these particles are injected into the deep subcutaneous tissue or in tissue, placed under the muscle/above the periosteum, optionally, more than one layer. Deep subcutaneous injection or introduction into muscle/on top of periosteum additionally prevents or reduces the migration of particles to the desired location. According to this variant implementation of the basic amount or more than 50% (by volume), preferably more than 70% (by volume), more preferably more than 90% (volume) of the particles are within the boundaries of the specified dimensions under physiological conditions.

In another embodiment of the invention the particles have a size in the range from 2.5 to 5 mm, for example from 3 to 4 mm, in the presence of physiological salt solution. Implants containing such particles, further prevent or reduce the migration of particles with the desired area of the body. According to this variant implementation of the basic amount or more than 50% (by volume), preferably more than 70% (by volume), more preferably more than 90% (volume) of the particles are within the boundaries of the specified dimensions under physiological conditions.

The particle size can be determined using any suitable method, such as laser diffraction, microscopy, filtering and so on, where the size is determined by the greatest distance between the two ends of the particle. Concr the percentage form of gel particles is not critical. In the case of a spherical particle diameter corresponds to the size for this purpose. The size range can be adjusted by mechanical crushing, such as crushing, grinding, filtering, etc. of the gel with an appropriate concentration of the desired viscoelastic material.

Viscoelastic materials of the present invention include, but are not limited to, polysaccharides and their derivatives. Suitable viscoelastic materials include stabilized starch and its derivatives. In addition, suitable viscoelastic materials can be chosen from the stable of glycosaminoglycans and their derivatives, such as stabilized hyaluronic acid, stabilized chondroitin sulfate, stabilized heparin, and derivatives thereof. Suitable viscoelastic materials also include stable dextran and its derivatives, such as dextranomer. In addition, the viscoelastic material may be a combination of two or more suitable viscoelastic materials.

The term "stable" in the context of the present description, means any form of chemical stabilization, which in physiological conditions makes stable the connection is more stable to biodegradation compared to the reference compound. Not limited to, stable connection including the indicate cross-linked compounds and partially cross-linked compounds.

The term "derivative" of the polysaccharide in the present invention refers to any suitable derivative, including cross-linked polysaccharides and substituted polysaccharides, such as sulfated polysaccharides.

Viscoelastic materials of the present invention are biocompatible, sterile and represent particles that can be easily injected through a standard needles used in medicine, such as needle 20 or larger, preferably, needle sizes 10-20. Preferably, the viscoelastic material was non-animal origin. Mainly material of the present invention is stable, but not always, under physiological conditions. According to a variant implementation of the present invention is not less than 70%, preferably at least 90% of viscoelastic material is stored at least two weeksin vivomore preferably, from two weeks to two years. The viscoelastic material of the present invention preferably is destroyed after five years or morein vivo. The term "destroyed" means that the body retains less than 20%, preferably less than 10% of the material.

The viscoelastic material of the present invention is more resistant to biological degradationin vivothan natural hyaluronic acid. More continue the sustained fashion the presence of stable viscoelastic material is favorable for the patient, because it increases the time between treatment sessions.

Preferred viscoelastic material of the present invention is cross-linked hyaluronic acid, which may be obtained by cross-linking of hyaluronic acid, optional non-animal origin, using the method according to U.S. patent 5827937.

Briefly, the above method involves preparation of an aqueous solution of water-soluble, capable of cross-linking of the polysaccharide, initiating cross-linkage of the polysaccharide in the presence of polyfunctional reagent for cross-linkage; spatial braking reaction cross-linkage to terminate the reaction prior to the onset of gelation, whereby get activated polysaccharide; and the restoration of a sterically unhindered conditions for the activated polysaccharide to continue its cross-linking to obtain a viscoelastic gel.

Reagent for cross-linkage, which can be used in connection with this particular way, is any previously known reagent for cross-stitching, applicable to polysaccharides, and should be considered guarantee the necessary conditions of biocompatibility. However, it is preferable that the reagent for cross-linkage was in the bran from the group consisting of aldehydes, epoxides, polyethyelene compounds, glycidyloxy esters and diphenylsulfone. From among these compounds glycidyloxy esters are especially preferred group, and among them, preferred example can be called 1,4-potentialapplications ether.

In this particular way, the initial reaction cross-linkage in the presence of polyfunctional reagent for cross-linkage can be carried out at varying pH values, which primarily depend on whether you want a simple reaction or esters.

An example of the preferred viscoelastic material is stabilized hyaluronic acid of non-animal origin, commercially available from the company Q-Med AB, Uppsala, Sweden.

If suitable for the injection material is a material based on hyaluronic acid, the concentration of hyaluronic acid is 5 mg/ml or higher. Preferably, the concentration of hyaluronic acid was in the range of 5-100 mg/ml, more preferably 10-50 mg/ml, such as about 20 mg/ml

Cross-linked hyaluronic acid is present in the form of particles or droplets of any form. According to this variant implementation of the basic amount or more than 50% (by volume), preferably more than 70% (volume is mnih), more preferably, more than 90% (volume) of the particles have a size of at least 1 mm, preferably in the range of 1-5 mm, As stressed above, the preferred implementation includes particles in the range of 1-2 .5 mm, preferably, 1.5 to 2 mm. Another preferred implementation comprises particles in the range of 2.5-5 mm, preferably 3-4 mm

A suitable way to obtain particles of the desired size includes the preparation of a gel prepared from cross-linked hyaluronic acid to the desired concentration, and physical fragmentation of the gel, such as grinding, rubbing, or passing the gel through a filter with a suitable pore size. The obtained gel particles dispersed in a physiological saline solution, which leads to gel the dispersion or emulsion with particles of the desired size.

Another aspect of the present invention is the density or hardness of the particles. Using the method of receiving according to the present invention, it is possible to easily adjust the density of particles of cross-linked hyaluronic acid by adjusting the concentration of viscoelastic material, as well as the number and type of reagent for cross-linkage. Thus, at higher concentration of viscoelastic material in the gel and, due to this, in the resulting gel particles can be obtained more solid particles. More than the solid particles, as a rule, are less viscoelastic and have a longer half-life ofin vivocompared to the softer particles. Suitable concentrations of hyaluronic acid, resulting gel particles of different hardness equal to, for example, 20, 25, 40, 50, and 100 mg/ml For use in the present invention are of critical importance is the preservation of particles sufficient viscoelastic properties so that they were suitable for injection, as discussed above.

In a preferred embodiment of the present invention softer gel particles, for example, contains 15-22 mg/ml cross-linked hyaluronic acid, mixed with a more solid gel particles, for example, contains 22-30 mg/ml cross-linked hyaluronic acid. The resulting mixture of gel particles combines the desired properties of softness/hardness for use in increasing the amount of soft tissue with prolonged stabilityin vivo.

According to the present invention, the viscoelastic material is injected, preferably injected under the epidermis in any suitable way. As an example, can be made in the skin incision with a scalpel or sharp needle for injection to facilitate passage through the skin of the catheter is larger for the introduction of the implant according to the present invention in the desired area of the body. Site is preferably, the introduction was carried out subcutaneously and under the muscle or over the periosteum.

The implant is composed of particles of a viscoelastic material and, optionally, other suitable ingredients may be administered as a single aliquot or in the form of multiple layers of aliquot. The viscoelastic material may not necessarily be replaced, re-enacted or supplemented by a subsequent injection of the same or other viscoelastic material. Injected volume is determined by the desired increase in the volume of tissue. In a typical increase in the volume of tissue, the injection volume is in the range of 1-500 ml, depending on the purpose and tissue exposed.

According to another aspect of the invention relates to a new use of the particles according to the present invention, and the main volume of the above-mentioned particles has an average size in the range from 1 to 5 mm, to obtain drugs for therapeutic increase the amount of soft tissue in a mammal, including humans, and referred to a drug suitable for the subepidermal injection according to the present invention in the area of the body referred to the mammal in which it is desirable therapeutic increase in soft tissue.

According to this aspect, it is preferable that the administration was performed subcutaneously and under we the hospitals or on top of the periosteum. Described earlier in this description, the discussion of suitable particle sizes are also applicable to this aspect of the invention.

In the framework of the present description, the term "therapeutic" includes any kind of prevention that facilitate or corrective treatment. But not limited to, this aspect of the invention encompasses that the drug is intended for reconstructive increase resulting from the medical condition, and is part of the medical treatment of this condition. Thus, therapeutic application differs from non-medical or cosmetic use in that they are aimed at different groups of patients. Specifically, therapeutic application of directed only to patients who need reconstructive increase arising from a medical condition, and therapeutic applications is part of the drug treatment of this condition in these patients.

Hereinafter the present invention will be further illustrated by means of examples, without limiting its scope given examples.

EXAMPLES

Example 1. Getting gel particles stabilized hyaluronic acid of non-animal origin

In accordance with previously shown, for example, in U.S. patent 5827937, 10g of hyaluronic acid, obtained by fermentation of Streptococcus, was dissolved in 100 ml of 1% NaOH, pH>9. Added reagent for cross-linkage, which represents a 1,4-potentialapplications ether to a concentration of 0.2%. The solution was kept at 40 C for 4 hours.

Seasoned solution was diluted aqueous acid solution with stirring to achieve a neutral pH value, receiving a final concentration of hyaluronic acid 20 mg/ml, and again kept for 12 h at 70 C. Then viscoelastic suspension, the resulting second-keeping, cooled to room temperature and triturated to the final particle size of approximately 1.5-2 mm.

Example 2. The increase in the volume of the cheeks and chin

Materials

Transparent viscoelastic gel composed of stabilized hyaluronic acid (20 mg/ml) of non-animal origin, was dispersible in physiological saline. This gel can be obtained, for example, by the method of example 1. Sterilized the investigated material (2 ml) were placed in a 3 ml glass syringe and was injected with subcutaneous and/or on top of the periosteum, using sterilized 16G x 7 or 9 cm infiltration catheter Coleman with a blunt tip (Byron Medical Inc., Tucson, Arizona, USA).

Selection of patients and the research plan

Adult outpatient patients (aged >18 years old) of both sexes who are interested in those who piticescu increase the volume of the cheeks and/or chin with aesthetic purposes. For inclusion in this study from the patient's consent was required to abstain from other cosmetic procedures (e.g., additional therapy to increase, injections of botulinum toxin, laser or chemical update the skin surface or procedures facelift) during the whole study. Patients who have undergone therapy to increase facial tissues or procedures laser/chemical peels in the past 6 months, or aesthetic surgery of the face during the preceding 12 months, were excluded from the study. In addition, patients with skin disease in the active phase or inflammation affecting the scope of the proposed treatment, patients with an established Allergy/hypersensitivity to local anesthetics of the actions or previous adverse reactions to NASHA, as well as patients taking anticoagulants or antithrombotic drugs, were excluded from participation in the study. The use of anticoagulants, aspirin, and nonsteroidal anti-inflammatory drugs was prohibited until complete healing of the site of injection.

Method injection

The area of the body for the planned treatment was cleansed with an antiseptic solution and, if needed local anesthesia was administered lidocaine (0.5 or %)/adrenaline in place of the planned incision. If necessary, provide additional anesthesia, regional nerve blockade, or subcutaneous administration of lidocaine/epinephrine at the site of the proposed implantation. Carried out a skin incision of 1-2 mm in length with a scalpel (11 blade) or acute injection needle to facilitate insertion through the skin 16G catheter with a blunt tip to inject the gel into the subcutaneous adipose tissue, and adipose tissue located under the muscle or over the periosteum. The gel was injected with a small aliquot, and not a single mass, the plot is the desired increase by manual movement of the catheter in a different place after each injection, using a tunneling technique. During each session of treatment was administered up to 10 ml (5 syringes) gel max 3 single anatomic area (chin and both cheeks). Upon completion of the injection, the treated area is massaged to bring it into conformity with the shape of the surrounding tissue and, if necessary, applying ice for a short time to reduce any swelling.

This method achieved a satisfactory increase in the volume of the cheeks and/or chin, at least 3 months. In particular, deep subcutaneous injection, and injection on top of the periosteum additionally prevent migration of the implant.

Example 3. Getting gel particles stabilized the ow of hyaluronic acid of non-animal origin with a longer life

Ten grams of hyaluronic acid obtained by fermentationStreptococcus, was dissolved in 100 ml of 1% NaOH, pH>9. Added reagent for cross-linkage, which represents a 1,4-potentialapplications ether to a concentration of 0.2%. The solution was kept at 40°C for 4 hours.

Alkaline gel was divided into two portions, each of which individually diluted acid aqueous solution with stirring to achieve a neutral pH value, receiving a final concentration of hyaluronic acid 20 mg/ml and 25 mg/ml, respectively. The gel was kept for 12 h at 70°C and cooled to room temperature. Two portions of the gel were combined and triturated to the final particle size of approximately 3-4 mm

Example 4. The increase in the volume of breast tissue

Women with smaller Breasts were injected with the gel, which can be obtained, for example, by the method of example 3. In each breast was introduced 100 ml of gel, implanted under the scope glands, directly on the pectoral muscle, using a blunt 12G needle in the form of a small aliquot. Pay attention not to disturb the natural fabric. 12 months after implantation of the breast is still kept in good shape with thin nodular implants. The implant does not interfere with mammographic analysis.

One of the women changed their minds about the necessity of the presence of gel in it g the UDI and asked to remove the implant. For back-extraction of the gel used blunt catheter (12G). Almost the entire implant was removed in the form of pure transparent gel-like fluid. The analysis showed that the gel retains its volume, but its concentration decreased slightly compared to the baseline (75% of original), showing thereby that life of the implant is approximately 2-3 years.

1. Particles of a viscoelastic material selected from the group consisting of polysaccharides and derivatives thereof, which are suitable for injection gel particles having a size ranging from 1 to 5 mm under the action of physiological salt solution.

2. Particles according to claim 1, for which the specified size is in the range from 1 to 2.5 mm

3. Particles according to claim 1, for which the specified size is in the range from 2.5 to 5 mm

4. Particles according to any one of claims 1 to 3, where specified viscoelastic material selected from the stable of glycosaminoglycans and their derivatives.

5. Particles according to any one of claims 1 to 3, where specified viscoelastic material selected from the group consisting of stabilized hyaluronic acid, stabilized chondroitin sulphate, stable heparin and derivatives thereof.

6. Particles according to any one of claims 1 to 3, where specified viscoelastic material selected from the group consisting of cross-linked hyaluronic acid and its derivatives.

7. Part of the s 6, where the concentration of the specified viscoelastic material in said gel particles is in the range from 5 to 100 mg/ml under the action of physiological salt solution.

8. Particles according to any one of claims 1 to 3, which is suitable for injection through a needle 20 or larger during the application of pressure 15-50 N.

9. Way to obtain is suitable for injection of gel particles of a viscoelastic material, comprising the stages of (i) preparation of a gel with the desired concentration of the specified viscoelastic material, and (ii) the mechanical crushing of the specified gel on gel particles having a size ranging from 1 to 5 mm under the action of physiological salt solution.

10. The implant to increase the amount of soft tissue containing particles of a viscoelastic material selected from the group consisting of polysaccharides and their derivatives, where the main volume of these particles is a suitable for injection of the gel particles having a size ranging from 1 to 5 mm under the action of physiological salt solution.

11. The implant to increase the amount of soft tissue of claim 10, wherein said size is in the range from 1 to 2.5 mm

12. The implant to increase the amount of soft tissue of claim 10, wherein said size is in the range from 2.5 to 5 mm

13. The way to increase the volume of soft tissues in a mammal, including man, including the subepidermal introduction to body area specified mammal in which it is desirable to increase the amount of soft tissue implant containing suitable for injection of the gel particles viscoelastic material selected from the group consisting of polysaccharides and derivatives thereof, and the main volume of these particles has a size in the range from 1 to 5 mm under the action of physiological salt solution.

14. The method according to item 13, in which the specified introduction is subcutaneous injection.

15. The method according to item 13, which specified the introduction is the introduction of muscle.

16. The method according to item 13, in which the specified introduction is an introduction on top of the periosteum.

17. The method according to any of p-16, wherein said size is in the range from 1 to 2.5 mm

18. The method according to any of p-16, wherein said size is in the range from 2.5 to 5 mm

19. The method according to 17, wherein said area of increased volume of soft tissue selected from the facial tissues and other tissues, covered with open skin.

20. The method according to any of p-16, which specified the introduction is only the introduction.

21. The method according to any of p-16, which specified the introduction is a multilayer introduction.

22. Suitable for injection of the gel particles according to any one of claims 1 to 8 for use as a medicine.

<> 23. Suitable for the injection of the implant to increase the amount of soft tissue that contains suitable for injection of the gel particles according to any one of claims 1 to 8, for use as pharmaceuticals.

24. Application suitable for injection of gel particles of a viscoelastic material according to any one of claims 1 to 8, where the main volume of these particles has an average size in the range from 1 to 5 mm under the action of physiological saline to obtain drugs for therapeutic increase the amount of soft tissue of a mammal, including humans, with the specified drug is suitable for the subepidermal injection according to any one of p-21 in the area of the body specified mammal in which it is desirable therapeutic increase in soft tissue.



 

Same patents:

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine. Claimed is composition with hyaluronic acid (HA), which includes gel particles of bound water-insoluble hydrated HA. HA includes bindings, represented with the following structural formula: HK'-U-R2-U-TK'. Where each group HA' represents the same or other molecule of bound HA'; each U independently represents optionally substituted 0-acylisourea or N-acylurea; and R2 represents optionally substituted alkyl, alkenyl, alkinyl, alkoxy, cycloalkyl, cycloalkenyl, cycloalkinyl, aryl, heteroaryl, heterocyclic radical, cycloaliphatic alkyl, aralkyl, heteroaralkyl or heterocyclolalkyl. Also claimed is method of developing tissues in individual, including introduction of needle into individual in place where development of tissues is necessary, needle is connected to syringe filled with composition with HA, and applying force to syringe in order to supply composition with HA to individual. Method of obtaining composition with HA includes formation of water-insoluble dehydrated particles of bound HA, separating insoluble in water particles by their average diameter, selection of subset of particles by average diameter and hydration of subset of dehydrated particles by means of physiologically compatible water solution. Other method of obtaining composition with bound HA includes binding precursor of bound HA by means of bis-carbodiimide in presence of pH buffer and dehydration of bound HA. Also included is method of developing tissues in individual that needs tissue development. Method of stabilisation of bound HA includes hydration of water-insoluble dehydrated bound HA by means of physiologically compatible water solution which includes local anesthetic, so that value of elasticity module G' for stabilised composition constitutes not less than approximately 110% from value G' for non-stabilised composition.

EFFECT: claimed composition of hyaluronic acid and method of preparation and application of HA composition are efficient for development of tissue and/or drug delivery.

27 cl, 22 ex, 2 tbl, 7 dwg

FIELD: medicine.

SUBSTANCE: invention concerns medicine, namely to reconstructive surgery, traumatology-orthopedy, maxillofacial surgery, stomatology and can be applied at osteo-plastic operations. For delivery of medical products immediately in a zone of defect and their prolonged influence in the centre of a lesion medicinal preparations are dissolved in a normal saline solution in a dose providing local effect, collagen-containing component is added to a solution in the ratio 9-20 g: 100 ml of a solution also admix with the carrier from dispersed allotransplants in the ratio of 1:1-3.

EFFECT: method allows lowering a dose necessary for reception of medical effect in 10 times, and also allows accelerating reparative processes in a defect zone.

3 dwg

FIELD: medicine.

SUBSTANCE: method of antibiotics fixation within porous implants is described. Result of method application lies in possibility of reliable fixation of antibiotic solution within porous implant and arrangement of favourable conditions for haemostasis in operative wound due to application of 10% gelatine solution as antibiotic carrier. Specified result is achieved by filling porous implants with antibiotic solution in liquid gel. For this purpose implant is dipped in solution by 3/4. Filling occurs under the influence of capillary forces. After solution cooled to form dense gel, antibiotic is fixed in implant pores and gradually released after installation to bone defect area.

EFFECT: reliable fixation of antibiotic solution within porous implant and arrangement of favourable conditions for haemostasis in operative wound.

3 cl, 1 ex

FIELD: medicine-destination polymers.

SUBSTANCE: invention relates to biologically stable hydrogels to be employed as endoprosthesis consisting essentially of following components: polyacrylamide including acrylamide, crosslinked methylene-bis-acrylamide, wherein acrylamide and methylene-bis-acrylamide are linked at molar ratio from 150:1 to 1000:1. Hydrogel is rinsed with water or physiologic solution so that it contains about 0.5-3.5% polyacrylamide and less than 50 ppm acrylamide and methylene-bis-acrylamide monomers, while modulus of elasticity of hydrogel is approximately 10 to 700 Pa and its complex viscosity about 2 to 90 Pa*sec. Rinsing stage allows removal of nearly all amounts (even trace amounts) of above-indicated monomers resulting in lower toxicity and higher stability of hydrogel. Biologically stable hydrogel is used as injectable prosthesis to fill soft tissues and also to treat or prevent urinary incontinence or anal incontinence. Hydrogel, obtained in a few stages including combining acrylamide and methylene-bis-acrylamide, initiating radical polymerization, and rinsing with apyrogenic water or physiologic solution, is also useful in treatment or prevention of bladder-ureter reflux in mammalians. In all these cases biologically stable hydrogels contain between 0.5 and 25% polyacrylamide.

EFFECT: enlarged resource for manufacturing endoprostheses.

10 cl, 3 dwg, 7 tbl

The invention relates to medicine, in particular to plastic surgery
The invention relates to medicine, namely to a method for producing compositions for injection, for use in reconstructive and cosmetic surgery

The invention relates to medicine, namely to molecular-linked gel containing a variety of biological and non-biological polymers such as proteins, polysaccharides and synthetic polymers

The invention relates to a formulation and method for producing a biocompatible hydrogel based on cross-linked copolymer of acrylamide with cross-linking agents that can be used as a material for medical purposes, for example:

- when the endoprosthesis through targeted injections hydrogel for plastics soft tissues of the face, breast, penis, calf muscles, vocal cords and other tissues, the density of which corresponds to the density of the hydrogel;

- as a filler in the manufacture of implants, including implants breast;

- as a depot for drugs with long-term medication, such as tumors or abscesses;

- as a carrier for culturing human cells and animals with subsequent implantation of hydrogel containing cells in the mammalian organism
The invention relates to medicine, namely to surgery, and may be applicable to eliminate wrinkles

FIELD: medical equipment.

SUBSTANCE: adhesive substance contains, wt %: polymer base 30.0-60.0; hydrocolloid 25.0-40.0; fluorine polymer 0.2-10.0. In addition, the composition can contain also softening agents 0.1-15.0 wt %; adhesiveness agents 0.1-8.0 wt %; filling compounds 0.1-10.0 wt % and elastomer 0.1-3.0 wt %.

EFFECT: preparation of adhesive substance with improved water absorption, maintaining integrity and strength after water saturation.

8 cl, 2 tbl, 1 dwg

FIELD: medical equipment.

SUBSTANCE: adhesive composition contains, wt %: copolymer of butylmethacrylate with methacrylic acid 20.0-30.0; hydrocolloid 21.0-46.0; plastificator 20.0-35.0; fluorine-containing polymer 1.0-5.0. Composition can also additionally contain adhesive agents and fillers 1.0-10.0 and 1.0-20.0 wt % respectively.

EFFECT: composition is not destructed under influence of intestinal liquids, is resistant to cold-fluidity, can be stored for long time and γ-sterilised.

6 cl, 3 tbl, 2 ex

FIELD: medicine.

SUBSTANCE: method of inhibiting polyresistant bacteria growth includes local introduction of pharmaceutical composition, containing 15 wt % or more of pentan-1,5-diol and pharmaceutically acceptable carrier. Method of disinfecting bacteria-contaminated surface includes obtaining disinfecting composition, which contains 15 wt % or more of pentan-1,5-diol and water carrier, application of said composition onto said surface; possibly, keeping it in contact with said surface for time period from 5 minutes to 24 hours at environment temperature and washing said surface with water or water composition with detergent.

EFFECT: inhibiting polyresistant bacteria and eliminating risk of further selection of poliresistant bacterial strains.

18 cl, 2 tbl, 3 ex

FIELD: medicine.

SUBSTANCE: invention describes a glue composition contacting skin, with improved original and lasting adhesion properties, water absorption and light permeability, which can be obtained by a melt extrusion. The compositions can be applied in wound dressing.

EFFECT: improved composition.

97 cl

FIELD: medicine, in particular, production of medicinal articles such as therapeutic band-plasters capable of recovering continuity function of skin and invaded subdermal tissues.

SUBSTANCE: therapeutic band-plaster has matrix made from biologically inert materials and adapted for dosed releasing of medicinal drugs. Band-plaster of such structure does not require utilization of retention layer.

EFFECT: increased efficiency in recovering of invaded subdermal tissues and skin continuity function, simplified and reliable structure of band-plaster and minimum drug losses.

1 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: invention describes a bioadhesive composition useful for medicinal agents applied on skin or other patient body surfaces and comprising hydrophobic phase and hydrophilic phase. Hydrophobic phase comprises cross-linked butyl rubber or butyl rubber cross-linked with polyisobutylene and hydrophilic phase comprises a mixture of hydrophilic polymer and complementary oligomer able for cross-linking of hydrophilic polymer. Hydrophilic polymer is chosen from the group comprising poly-(N-vinyllactames), poly-(N-vinylamides), poly-(N-alkylacrylamides), polyacrylic acid, polymethacrylic acid, polyvinyl alcohol, polyvinylamide, their copolymers and mixtures. Complementary oligomer is chosen from the group comprising polyhydric alcohols, monomeric and oligomeric alkylene glycols, polyalkylene glycols, polyalkylene glycols with terminal carboxyl-groups, polyalkylene glycols with terminal amino-groups, incomplete polyhydric alcohol esters, alkanediols and carboxylic diacids. Adhesive has no irritating, comedogenous and sensitizing properties, it sticks to skin at insignificant pressure.

EFFECT: valuable medicinal properties of compositions.

27 cl, 2 tbl, 10 dwg, 4 ex

FIELD: medical engineering; bandaging means; absorbent articles.

SUBSTANCE: device has composite material plate having nonwoven substrate of three-dimensional structure. Hard absorbing cartridge is partially built-in into inside of the three-dimensional structure, the rest being arranged on the nonwoven substrate surface. Fusible member is hot melt adhesive. The hot melt adhesive builds reticular fiber structure covering the hard absorbing cartridge and small cellulose fibers engageable with the hard absorbing cartridge. Ordinary or double-layer reticular structure holds the hard absorbing cartridge in given position. The hot melt adhesive shows no clamminess.

EFFECT: high absorbing properties.

23 cl, 18 dwg, 5 tbl

FIELD: veterinary science, surgery.

SUBSTANCE: method involves applying the application of mixture comprising glue base with ligfol and Novocain on infected surface taken in the ratio, wt.-%: ligfol, 70; Novocain, 30. Method allows decreasing time for treatment of suppurative wounds by 1.5-2 times, economy of dressing material and time that improved labor conditions of veterinary expert. Invention can be used in treatment of suppurative wounds both aerobic and anaerobic etiology.

EFFECT: improved treatment method.

1 ex

FIELD: hygienic facilities.

SUBSTANCE: invention provides nonwoven material, such as fibrous linen or plastic film, manufactured by applying glue in the form of drawing on one side of material followed by perforating nonwoven material. The latter comprising a combination of perforations best serves as a component of absorbing articles and exhibits a variety of functional properties.

EFFECT: extended resource for manufacturing functional absorbing articles.

9 cl, 4 dwg

Fixer for mustard // 2222351
The invention relates to pharmaceutical industry and relates fixer for mustard plasters containing emulsifying substance as an adhesive component in the amount of 1.0-30.0 wt.h., the filler in the amount of 1.0-30.0 wt.h., water as solvent a to 100 wt.h

FIELD: medicine.

SUBSTANCE: invention relates to medicine, more specifically to cardiosurgery. Distal and proximal parts are exected, as well as a valved device with corresponding valves, commissural zones, atriums and free edges for their subsequent stitching in compliance with the design size of the circle of the reconstructed output section. A virtual three-dimensional model of the prosthetic device is made and displayed on a plane. All elements are exected. The length of the arc of the elements along the line of attachment is the same. The exected valves and distal part are juxtaposed by the visceral side to each other such that, the centres of the atriums and the base of the valve coincide. The proximal part is attached to the base of the valve and all elements are stitched using continuous twisted suture with formation of commissural rods. Atriums in the distal part of the prosthetic device are formed by joining the proximal part with the smallest and the distal part with the largest radius of curvature, measured on the displays. An extra commissural rod is formed when stitching the edges of the distal part of the prosthetic device.

EFFECT: improved haemodynamic characteristics of the prosthetic device, reduced risk of fatigue wear of biomaterial and thrombosis on the valved device.

2 cl, 8 dwg

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