Tissue regeneration method and membrane

FIELD: medicine.

SUBSTANCE: tissue regeneration or healing is stimulated when using a structure comprising a multilayer plate of a collagen membrane material, which contains a lamellated barrier material of pure collagen prepared of a natural collagen tissue; the lamellated barrier material containing a barrier layer with an outer smooth barrier surface and a fibre surface, which is opposite the outer smooth barrier surface. The structure additionally contains a matrix layer of a collagen sponge material adjoining the fibre surface.

EFFECT: matrix layer of the collagen sponge material is absorbed by an individual's body at a higher rate, than the lamellated barrier material.

20 cl, 3 dwg, 5 ex

 

Cross references to related applications

This application claims priority to provisional application U.S. No. 61/145,334, filed January 16, 2009, which is introduced in this application by reference in its entirety for all purposes.

BACKGROUND of INVENTION

The scope to which the invention relates.

The present invention in General relates to methods of regeneration, restoration or transplantation of tissue.

Discussion of the level of technology

Different types of membranes were used for repair and regeneration of several types of tissues, including the skin, mucous membrane, meniscus, cartilage, vertebral discs, ligaments and bones.

Transplantation of the skin to repair damaged skin tissue was a recognized procedure for some time. The use of skin grafts split-thickness and free from mucous membrane of skin grafts in the vestibular cavities and other types of related surgery in the oral cavity was a recognized procedure for some time. In addition, the use of free grafts, mucosa taken from the buccal mucosa was used for recovery of the attached surfaces of the mucous membrane in areas deprived of teeth, alveolar process che is justi, in particular, in combination with forming the root of the implants.

Despite the fact that such procedures transplantation are well established, the development of effective alloplastic or xenogenic replacement material for transplantation to restore and regeneration of normal skin and mucous membrane will provide a much wider use of vestibuloplasty or other surgical procedures.

U.S. patent No. .6,713,085 discloses a membrane for the regeneration of the skin and mucous membranes including a barrier layer containing outer barrier coating smooth collagen and oppositely located fibrous surface, where the matrix layer may adjoin the coating of fibrous collagen in the form of a liquid suspension.

Still there is a need in the field of technology in improving the stimulation of tissue regeneration, for example, after surgical procedures.

SUMMARY of the INVENTION

In accordance with the present invention, tissue regeneration, restoration or transplantation can be carried out using capable of resorption multilayer structure that includes a barrier plate material from purified collagen derived from natural containing collagen tissue, and additional the Loy spongy collagen. Barrier plate material includes a barrier layer containing an outer smooth barrier surface and a fibrous surface on the opposite side of the specified smooth barrier coatings. The multilayer structure further includes a matrix layer of collagen sponge material adjacent to the fibrous coating. The matrix layer of collagen sponge material is resorbed by the body at a higher speed than collagen lamellar material.

BRIEF DESCRIPTION of DRAWINGS

FIG.1 is a top view that shows the collagen patch of material covering a tissue area, which is subjected to processing in accordance with the present invention.

FIG.2 is a side view in section, which shows a collagen barrier patch is used to obtain rasskazyvaemoe multilayer structure of FIG.3.

FIG.3 is a side view in section, which shows rasskazyvaemoe a multilayer structure in accordance with the present invention.

A DETAILED DESCRIPTION of the PREFERRED EMBODIMENTS

In accordance with some embodiments of the present invention provides a composition and method for stimulating the regeneration or restoration of tissue such as mucosa (oral, urogenital the traveler, leather, meniscus, cartilage, spinal disc, bone or ligament.

In some embodiments the invention provides a composition and method for stimulating the regeneration or recovery of the mucosa. In connection with the treatment of the mucous membrane, although the method is sometimes described in connection with the stimulation of regeneration or restoration of the mucous membrane in the oral cavity after specific types of oral surgery, it will be understood that the method can be used to stimulate the regeneration or recovery of the mucosa in any part of the body, which has damaged the fabric of the mucous membrane.

Although the invention is sometimes described in connection with the restoration and regeneration of tissue of the mucous membrane in the treatment of injuries to the mucous membrane, it will be understood that the invention is also applicable to the regeneration and restoration of other types of fabrics such as leather, meniscus, cartilage, spinal disc, ligament or bone.

In some embodiments the invention provides a composition and method for stimulating the regeneration of damaged, injured, sick, wounded, deleted or missing tissue, stimulate or facilitate the healing tissue in the body of the subject.

In some embodiments of the method of promoting tissue regeneration, stimulate recovery TKA and, stimulate or facilitate engraftment of tissue or combinations thereof includes the floor area of damaged, injured, sick, wounded, deleted or missing tissue in the body of the subject using capable of resorption of the layered structure, stimulates the regeneration of tissue or promote engraftment, which includes a thin layer of barrier material from purified collagen derived from natural containing collagen tissue, where the specified thin layer of barrier material comprises an outer smooth barrier surface and further includes a fibrous surface, located opposite the specified smooth barrier surface where the specified multi-layered structure further includes a matrix layer comprising a collagen sponge material. The method further includes at least one adaptive anchoring and retaining collagen barrier plate material over a given surface, with the specified matrix layer is placed between the said surface and the fibrous surface and allows the specified surface to treat or repair the fabric where the specified matrix layer of collagen sponge material is resorbed by the body of the subject at a substantially higher speed than the plates of Aty material collagen barrier.

The patch may be placed on top of the fabric surface, which is subjected to treatment, for example, with the help of sutures or fibrin glue, and fabric, thus gets the opportunity to heal and regenerate.

In some embodiments mentioned multilayer structure has a thickness of approximately 0.5-8 mm

In some embodiments the layer of collagen sponge matrix includes pork S collagen, bovine collagen I/III, recombinant collagen I or III, recombinant collagen I/III or a mixture thereof. In some embodiments the layer of collagen sponge matrix also includes chitosan, elastin, or hyaluronic acid, usually in a ratio of from 0 to 30% by weight.

In some embodiments of the method in accordance with the invention includes coating the surface of damaged, injured, sick, wounded, deleted or missing tissue in the body of the subject using a collagen sponge matrix material. The collagen sponge material is then covered with collagen plate material obtained from natural containing collagen tissue, where the plate material includes a barrier layer containing an outer smooth barrier surface, and further includes a fibrous surface, located opposite the specified smooth barrier surface. Spongy Mat is Rial adjacent to the plate material purified collagen, where the matrix layer is located between the surface being treated, and fibrous face.

In some embodiments of the invention is a structure, which stimulates the regeneration/repair or engraftment to stimulate tissue regeneration, or to stimulate or facilitate the healing tissue by covering the surface of damaged, injured, sick, wounded, deleted or missing tissue in the body of a subject, comprising rasskazyvaemoe a multilayer structure that includes a barrier plate material from purified collagen derived from natural containing collagen tissue, where the barrier plate material includes a barrier layer comprising an external smooth barrier surface and further includes a fibrous surface, located opposite the specified smooth barrier surface where the specified multi-layered structure further includes a matrix layer including collagen sponge material attached to the said fibrous surface, where the specified matrix layer of collagen sponge material adapted to adhere to the surface, and the said multilayer structure is adapted so that the matrix layer is resorbed by the body of the subject p is significantly higher speed, than the plate material of the collagen barrier.

In some embodiments the matrix layer is glued or attached to the said fibrous front. In some embodiments of the multilayer structure has a thickness of approximately 0.5-8 mm In some embodiments the layer of collagen sponge matrix includes collagen of animal or human origin, as well as from a recombinant source, such as pork S collagen, bovine collagen I/III, recombinant collagen I or III, recombinant collagen I/III or a mixture thereof. In some embodiments the layer of collagen sponge matrix also includes chitosan, elastin, or hyaluronic acid, usually in a ratio of from 0 to 30% by weight. In some embodiments of the multilayer structure has at least one growth factor. In some embodiments, at least one growth factor is a selected from the group consisting of epidermal growth factor (EGF), insulin-like growth factor (IGF-1), a member of the family of fibroblast growth factor (FGF), keratinocyte growth factor (KGF), platelet growth factor (PDGF), transforming growth factor (TGF-p), CIF (factor, inducing the formation of cartilage), at least one of the BMP 1-14 (morphogenetic proteins bone), colony stimulating factor granulocyte and is of acropyga (GM-CSF), or a mixture thereof. In some embodiments the growth factor is a PDGF.

In some embodiments the matrix layer is adapted to dissolve the body of the subject at approximately the same speed, which is typical for the growth of tissue cells, in particular cells of mesenchymal and echterling origin located from the bottom of the specified layer membrane matrix on the specified plot. This speed is modified in the case of inclusion of the growth(s) factor(s). In some embodiments of the specified matrix layer is adapted to dissolve the body of the subject at approximately the same speed, which is typical for the growth of cells in the tissue adjacent to the specified membrane matrix layer on the specified site, where these cells are epithelial cells. This speed is modified in the case of inclusion of the growth(s) factor(s). In some embodiments matrix layer adapts in order to completely dissolve the specified organism within approximately 2-5 weeks after the specified coating. In some embodiments the collagen barrier plate material adapts in order to completely dissolve within approximately 6-11 weeks after the specified coating. In some embodiments of structures is adapted so that the specified collagen barrier plate material covers a given surface without complete resorption of at least approximately 50% longer than the substantially complete resorption of matrix spongy layer of the body. In some embodiments, the structure is adapted so that the collagen barrier plate material covers a given surface without resorption, at least about 100% longer than a substantially complete resorption of matrix spongy layer of the organism.

In accordance with certain embodiments of the present invention, as shown in Fig.1, the defect or the plot, which is processed in the tissue of the tissue surface M of the subject can be restored by placing the patch 10 on the defect and fixing patch on the limits of the tissue surface around the defect. Plot overlaid with plaster may then allow healing or tissue repair. In Fig.1 shows the patch 10, superimposed with the help of sutures 12 at the tissue surface M Alternative plaster may be applied over the defect by adhesive bonding of the patch with the surrounding tissue of the host or other structures surrounding the area that is treated, for example, when using organises the th adhesive (for example, fibrin glue), as is known in the field of machinery, or other acceptable method.

The patch 10 may be formed from a structure, comprising a plate material of collagen barrier with acceptable flexibility to precisely match the shape of the surface of the fabric, in relation to which it is applied. In one embodiment the collagen barrier plate material has sufficient strength to be adapted to the stitches on the injured tissue surface and to protect the surface of the tissue from trauma during the healing process.

Collagen barrier plate material for forming a patch in accordance with one embodiment of the present invention shown in Fig.2 as 14. The patch 14 includes a single collagen barrier layer 16 having a smooth barrier surface 18 on one side, textured or fibrous surface 20 on the other side, opposite the smooth surface. Smooth surface 18 may be non-porous to provide mechanical protection of the damaged site. Fibrous surface 20 allows the cells to grow on it. In the process of applying a smooth surface can be oriented away from the surface, which is exposed to the treatment, and fibrous surface can be about Antonovna to the site which is subjected to the treatment.

In some embodiments the collagen barrier plate material 16 may preferably be a collagen I, collagen III or a mixture thereof. One acceptable material for this layer is a BioGide®from Ed. Geistlich Sohne AG fur Chemische Industrie. BioGide®the material obtained from the peritoneal membrane of the pig, he is described in U.S. patent No. 5,837,278, which is introduced in this application by reference.

Fig.3 shows a multilayer structure 14', which may be used in accordance with the present invention. This membrane includes a first collagen barrier layer 16, as shown in Fig.2, and additionally includes a second collagen matrix layer 22, which may or may not be attached or affixed to the fibrous surface 20 of the first collagen layer of the barrier plate material 16 for placement across the fabric surface for faster regeneration or transplantation of tissue. The second collagen matrix layer 22 may include or essentially consist of collagen sponge substances with a significant influence on the properties of cell adhesion, proliferation, invasion and differentiation for regeneration/recovery of cells.

In some embodiments the layer of collagen barrier plate mater is Ala, and the matrix layer of spongy collagen, are fully rassasyvanie the body of the subject.

In some embodiments the matrix layer is absorbed by the body specified subject at approximately the same speed, which is typical for the growth of cells in the tissue lying under the specified membrane matrix layer on the specified plot. This speed is modified in the case of inclusion of the growth(s) factor(s). In some embodiments, these cells are epithelial cells, endothelial cells, chondrocytes, synovial cells, cells of the spinal disks, tenacity or osteoblasts. In some embodiments, the cells are epithelial cells. In some embodiments the matrix layer is substantially completely absorbed by the specified body within approximately 2-5 weeks after the specified coating. In some embodiments the collagen barrier plate material substantially completely absorbed within approximately 6-11 weeks after the specified coating. In some embodiments, at least part of the said collagen barrier plate material covers a specified area without resorption, at least about 50% longer substantially complete resorption of the specified matrix layer specified org the mechanism. In some embodiments, at least part of the said collagen barrier plate material covers a specified area without resorption, at least about 100% longer substantially complete resorption of the specified matrix layer of the specified organism.

The collagen sponge material (e.g., product Geistlich Pharma AG, Wolhusen, Switzerland) may be formed from connective tissues of various animals and organs, such as skin tissue of a calf or pig. In some embodiments the collagen subcaste substance may primarily be a collagen I, for example more than 50% of collagen I, for example, approximately 95% of the collagen I. Collagen sponge-like material may also contain collagen III, for example, in amounts of about 5% by weight. In some embodiments the layer of collagen sponge matrix also includes chitosan, elastin, or hyaluronic acid, usually in a ratio of from 0 to 30% by weight. Collagen spongy substance can dissolve the body of the subject at approximately the same speed, which is typical for the growth of tissue cells (such as epithelial cells), lying under the structure in accordance with the invention on the area being treated. The layer of collagen sponge matrix may be included in the fibrous composition is th patterns, which supports the formation of new tissue through a significant effect on cell adhesion, proliferation, invasion and differentiation. In some embodiments the layer of collagen sponge matrix can be applied in the form of a liquid suspension and stick to the fibrous layer on the opposite side of the barrier layer by drying such as freeze drying.

In some embodiments the barrier layer remains in the body, at least about 50% longer than the spongy layer before complete resorption. In other embodiments the barrier layer remains in the body, at least about 75%, 100%, 125%, 150%, 175% or at least about 200% longer than the spongy layer before complete resolution.

The barrier layer patterns may cover the surface, which is subjected to treatment, during at least approximately 6-11 weeks or longer, for example about at least 6-8 weeks before complete resorption of the barrier layer.

In some embodiments the layer of collagen sponge matrix can be established for at least approximately 2-5 weeks or longer, the remaining material of the plate barrier within at least approximately 5-6 weeks or longer after significantly p is LEGO resorption of matrix collagen layer of the spongy substance.

In some embodiments the time resorption structure of the collagen patch can be changed by processing complex material patch with UV irradiation, dehydrothermal processing (100-160°C, vacuum, 12-240 hours), cross linking agents for chemical cross-linking of length zero or non-zero length, for example, using a carbodiimide such as EDC (N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride, CDI (N,N-carboxyphenylazo), CMC (1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide), aldehydes/dialdehyde (formaldehyde, glutaraldehyde, aldehyde hyaluronic acid), cross-linking agents of plant origin (for example, Geneina) and algos/ketosis (e.g., ribose), or the like, or combinations thereof.

BioGide®barrier material, as described above, typically has a speed of resorption in the body for approximately 6-8 weeks. Time resorption as a barrier, and a layer of collagen sponge material may be controlled by cross-linking. For example, a layer of collagen sponge material may be cross-linked so that is complete resorption within approximately 2-5 weeks in the body through the use of UV irradiation using a UV lamp In approximately 10-20 (for example, about 15 V), when the distance when listello 15-45 cm (for example, approximately 30 cm) from the surface of the collagen layer of the spongy substance of the two membrane for about 2-4 hours (approximately 3 hours). Typical wavelength represents the UV-rays in the range from about 100 nm to about 280 nm (for example, 253.7 nm). In another example, cross-linking using dehydrothermal processing can be carried out under the conditions of vacuum at <200 mbar and 100 degrees Celsius for 24 hours. Cross-linking with EDC can be carried out using an aqueous solution of approximately 0.1-0.6 g EDC approximately 0.3 to 2 g of the collagen sponge matrix (for example, approximately 0.3 g of EDC to 1.0 g of the collagen matrix). Can be used with other agents for cross-linking, such as hyaluronan, hexadecanaminium, N-hydroxysuccinimide (NHS) and glyoxal. Per gram of collagen cross-linking can be used from about 10 to 300 mg (e.g., approximately 100 mg) of the aldehyde of hyaluronic acid.

In some embodiments in a liquid suspension of collagen sponge substances included heparin oligosaccharides derived from heparin, hyaluronic acid, glucosaminoglycans (for example, chondroitin-4-sulfate) or their mixture (1-30% by weight, for example 2-10% by weight).

In addition, the combination of the PE the first and second layers 16 and 22 increases the thickness of the membrane 14' for ease of circulation and accelerate healing. The thickness of the membrane may vary depending on the application, but will typically range from approximately 0.5 mm to approximately 8 mm, with a possible range from approximately 2 mm to approximately 5 mm, a thickness of approximately 3 mm is one of the possibilities.

The first layer 16 in the embodiments shown in Figures 2 and 3, can be obtained in a variety of ways, including, but without limitation as such, the process described in U.S. patent No. 5,837,278; when using other animal tissue (pleura, mesentery, pericardium, Dura mater, intestine) and/or membranes by deaeration and drying in air liquid suspension (like the film is transparent membrane); by deaeration and drying in vacuum liquid suspension (like the film is transparent membrane); or when using the compacted substance. The first layer 16 can be made of collagen I, II, III, IV, IX, X and XI pigs, cows, horses or can be obtained using recombinant technology, or combinations of these types of collagen.

The second collagen sponge matrix layer 22 in one embodiment, as shown in Fig.3 represents, for example, dried by freezing a liquid suspension of collagen.

The second collagen sponge layer 22 can be formed from the skin of cows, pigs or from recombine the spas skin material and can be formed of the skin material pig, bovine collagen I/III or recombinant collagen I and recombinant collagen I/III, and may optionally include chitosan, elastin, or hyaluronic acid is usually in a ratio of from 0 to 30% by weight.

In the embodiment shown in Fig.3, the first and second membrane layers 16 and 22 can be connected to each other or combined in any suitable manner. Examples of three acceptable ways combinations include: attaching a first membrane layer to the second membrane layer by using fibrin glue or any other type of adhesive; attaching the first membrane layer to the second membrane layer when using the collagen suspension; or the coating of the first membrane layer using suspension spongy collagen, and then freeze drying the combination.

Is it possible to use the combined first and second layers without any additional materials like growth factor.

In some embodiments, at least one growth factor, such as EGF (epidermal growth factor), IGF-1 (insulin-like growth factor), member of the family of fibroblast growth factor (FGF), keratinocyte growth factor (KGF), PDGF (platelet-derived growth factor AA, AB, BB), TGF-β (family of transforming growth factor - β1, β2, β3), CIF (factor, inducing the formation of cartilage), at least one of BP 1-14 (morphogenetic proteins bone), colony-stimulating factor for granulocytes and macrophages (GM-CSF), or mixtures thereof, which can accelerate tissue regeneration, may be introduced into the structure in accordance with the invention, and/or added to the surface of the membrane, which can be placed opposite the tissue that is being treated. In some embodiments the growth factor is a PDGF.

Is it possible to deliver pharmacologically and/or biologically active substances such as growth factors, in the system release, for example in the form of releasing the substance in time, such as microspheres, gelatinous balls and the like. Such forms can be loaded into the structure in accordance with the invention, for example, be enclosed or encapsulated in it.

The invention additionally relates to the use of the structure, as defined in this application or its components for regeneration or transplantation of tissue, and for applying patterns, as defined in this application or its components in the manufacture of a pharmaceutical preparation to stimulate regeneration or healing tissue.

In some embodiments of the multi-layer patch in accordance with the invention can be obtained as described below:

(A) A First membrane layer can be obtained in accordance with the procedure described in U.S. patent No. 5,837,278, it contains olonilua surface (for example, Bio Gide®membrane from Geistlich Pharma AG, Wolhusen, Switzerland).

(B) Collagen sponge-like material may be obtained from Geistlich Pharma AG, Wolhusen, Switzerland and formed into a liquid suspension. Liquid suspension may be used in the form of a substantially homogeneous layer to the fibrous surface of the first membrane, which optionally contains chitosan, elastin, or hyaluronic acid, and dried, preferably freeze dried, to obtain a multilayer structure in accordance with the present invention.

Non-limiting examples:

Example 1

The patch with collagen sponge part

1. Soaking a pure collagen sponge substances (derived from pig skin, 95% collagen I, 5% collagen III) in water (30 minutes, with constant stirring).

2. The first dispersion soaked collagen using a colloid mill in the same water (100 kg liquid collagen suspension, 2%).

3. Bringing the pH to 3.3 with hydrochloric acid.

4. The second collagen dispersion of clay suspension by using a colloid mill.

5. Re bringing the pH to 3.3 with hydrochloric acid.

6. Making clay suspension in trays for drying freezing to level 5 mm.

7. Application of collagen liquid suspension of fibrous part of the Bio Gide®collagen member the N.

8. Drying freeze.

Example 2

The patch with the spongy part of the collagen/elastin

1. Soaking a pure collagen sponge substances (derived from pig skin, 95% collagen I, 5% collagen III) in water (30 minutes, with constant stirring).

2. The first dispersion soaked collagen using a colloid mill in the same water (100 kg liquid collagen suspension, 2%).

3. Bringing the pH to 3.3 with hydrochloric acid.

4. The addition of the suspension of elastin.

Obtaining suspensions:

A. Deletion of the elastin (dried, Sigma) through a sieve 4000 mesh to obtain particles of elastin, less than 40 microns;

b. Swelling of elastin within 24 hours at 10-15°C in water pH to 3.3 with hydrochloric acid;

C. the Suspension of elastin in a blender to obtain a homogeneous suspension (10 kg suspension elastin 5%).

5. Second, the dispersion of clay suspension collagen/elastin using a colloid mill.

6. Re bringing the pH to 3.3 with hydrochloric acid.

7. Introducing a liquid suspension in trays for drying freezing to level 5 mm.

8. The use of liquid suspensions of collagen/elastin to the fibrous part of the Bio Gide®collagen membranes.

9. Drying by freezing (the spongy part of the final combination product: 20% elastin, 80% collagen).

The patch with the spongy part of the collagen/chitosan

1. Soaking a pure collagen sponge substances (derived from pig skin, 95% collagen I, 5% collagen III) in water (30 minutes, with constant stirring).

2. The first dispersion soaked collagen using a colloid mill in the same water (100 kg collagen clay suspension, 2%).

3. Bringing the pH to 3.3 with hydrochloric acid.

4. The addition of chitosan solution.

Obtaining a solution.

A. Chitosan was dispersible in deionized water;

b. Added 8% acetic acid;

C. was Dissolved chitosan by stirring for 1 hour at room temperature (10 kg of a solution of acetic acid 4%, chitosan 2,5%).

5. The second dispersion liquid suspension of collagen/chitosan.

6. Re bringing the pH to 3.3.

7. Introducing a liquid suspension in trays for drying freezing to level 5 mm.

8. The use of clay suspension collagen/chitosan to the fibrous part of the Bio Gide®collagen membranes.

9. Drying by freezing (the spongy part of the final combination product: 11% chitosan, 89% collagen).

Example 4

The patch with the spongy part of the collagen/hyaluronic acid

1. Soaking a pure collagen sponge substances (derived from pig skin, 95% collagen I, 5% to the of Laguna III) in water (30 minutes, constant stirring).

2. The first dispersion soaked collagen using a colloid mill to obtain a 2% collagen liquid suspension.

3. Bringing the pH to 3.3 with hydrochloric acid.

4. The addition of hyaluronic acid gel.

Preparation of a gel

A. The dissolution of sodium hyaluronate (molecular weight: 2×106Yes) in deionized water;

b. Bringing the pH to 3.3 with 1N hydrochloric acid (20 kg of gel, hyaluronic acid 1%).

5. The second dispersion liquid suspension collagen/hyaluronic acid.

6. Re bringing the pH to 3.3 with hydrochloric acid.

7. Introducing a liquid suspension in trays for drying freezing to level 5 mm.

8. The use of liquid suspension collagen/hyaluronic acid to the fibrous part of the Bio Gide®collagen membranes.

9. Drying by freezing (the spongy part of the final combination product: 9% hyaluronic acid, 91% collagen).

Example 5

The man who was bitten by dog ear skin were subjected to treatment using the structure in accordance with the invention. The membrane was sewn over the wound with sutures and left the wound to heal. Unexpectedly found that the wound had formed a new skin, including hair follicles.

Oskolkov the above-described embodiment may be made of a large number of modifications variations and modifications, it is understood that all materials in the above description and represented in the accompanying drawings shall be interpreted as illustrative and not in a limiting sense.

1. The method of promoting tissue regeneration, stimulates healing tissue or stimulate or facilitate engraftment of tissue, or a combination comprising coating the surface of damaged, injured, sick, wounded, deleted or missing body tissue of the subject using rasskazyvaemoe multilayer structure to stimulate regeneration or healing of tissue that includes a barrier plate material from purified collagen derived from natural containing collagen tissue, where specified collagen barrier plate material includes a barrier layer comprising an external smooth barrier surface, and additionally comprising a fibrous surface, located opposite the specified smooth barrier surface where the specified multi-layered structure further includes a matrix layer, containing collagen sponge material; the method further includes at least one adaptive anchoring and retaining collagen barrier plate material over a given surface, with the specified matrix layer places the I between the said surface and the fibrous surface and allows the specified surface to treat or repair the fabric, where the specified matrix layer of collagen sponge material is resorbed by the body of the subject at a substantially higher speed than the specified collagen barrier plate material, in which the specified multi-layer structure is adapted so that the matrix layer is resorbed by the body within about 2-5 weeks after the specified coverage, as specified collagen barrier plate material is resorbed within about 6-11 weeks after this coating, and the specified multilayer structure adapted using a method selected from the application of UV irradiation using a UV lamp, approximately 10-20 B at a distance of approximately 15-45 cm from the surface of the collagen layer of the spongy substance of the membrane for about 2-4 hours cross-linking with dehydrothermal processing under conditions of vacuum at <200 mbar and 100 degrees Celsius within 24 hours of cross-linking with EDC when using an aqueous solution of approximately 0.1-0.6 g EDC approximately 0.3 to 2 g of the collagen sponge matrix, the use of other agents for cross-linking such as hyaluronan, hexadecanaminium, N-hydroxysuccinimide (NHS) and glyoxal, and where the matrix layer includes gobch the initial collagen pig from pig skin.

2. The method according to p. 1, where the specified collagen barrier plate material fit so that it substantially completely dissolved within approximately 6-8 weeks after the specified coverage.

3. The method according to p. 1, where this structure is adapted so that said collagen barrier plate material covered given surface without complete resorption of at least approximately 50% longer substantially complete resorption of the specified matrix spongy layer of the organism.

4. The method according to p. 1, where this structure is adapted so that said collagen barrier plate material covered given surface without complete resorption of at least about 100% longer substantially complete resorption of the specified matrix spongy layer of the organism.

5. The method according to p. 1, where this multilayer structure is subjected to chemical cross-linking using a chemical agent for cross-stitching, selected from the group consisting of carbodiimide, aldehyde, formaldehyde, genipin, an aldose, ketose, or combinations thereof.

6. The method according to p. 1, where the specified matrix layer is adapted to dissolve the body of the subject at approximately the same speed that the character is and for the growth of tissue cells, which lie below the membrane matrix layer on the specified section.

7. The method according to p. 6, where the specified matrix layer is adapted to dissolve the body of the subject at approximately the same speed, which is typical for the growth of tissue cells that lie under the specified membrane matrix layer on the specified site, and where these cells are cells of mesenchymal or ectodermal origin.

8. The method according to p. 1, where the specified matrix layer is glued or attached to the said fibrous surface.

9. The method according to p. 1, where the specified collagen barrier plate material obtained from animal tissue (pleura, mesentery, pericardium, Dura mater, intestines).

10. The method according to p. 9, where the specified barrier plate material includes peritoneal membrane pigs.

11. The method according to p. 1, where the specified multi-layered structure has a thickness of approximately 0.5-8 mm

12. The method according to p. 1, where the layer of collagen sponge matrix includes pork collagen, bovine collagen I/III, recombinant collagen I or III, recombinant collagen I/III or a mixture.

13. The method according to p. 12, where the specified collagen sponge matrix layer further includes chitosan, elastin, or hyaluronic acid.

14. The method according to p. 1, g is e a multilayered structure carries at least one growth factor.

15. The method according to p. 14, where the specified at least one growth factor is selected from the group consisting of epidermal growth factor (EGF), insulin-like growth factor (IGF-1), a member of the family of fibroblast growth factor (FGF), keratinocyte growth factor (KGF), platelet-derived growth factor (PDGF-AA, AB, BB), transforming growth factor (TGF-β1, β2, β3), CIF (factor, inducing the formation of cartilage) at least one of the BMP 1-14 (morphogenetic proteins bone), colony stimulating factor of granulocytes and macrophages (GM-CSF), or a mixture thereof.

16. The method according to p. 15, where the specified growth factor is a PDGF.

17. The method according to p. 14, where the specified growth factor is present as a form of prolonged action.

18. The method according to p. 17, where this form of prolonged action is included in the microspheres.

19. The method according to p. 8, where the specified collagen sponge material attached to the said fibrous surface by applying to the specified fibrous surface in the form of clay suspension and then dried.

20. The method according to p. 19, where the specified collagen sponge matrix layer further includes chitosan, elastin, or hyaluronic acid.



 

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3 cl, 3 tbl, 12 ex

FIELD: medicine.

SUBSTANCE: group of inventions refers to surgery and may be used for making external osteosynthesis implants. An osteosynthesis system comprises a piece part on an external surface of which there is a layer of a polymer film in the electret state with the layer of the polymer film made of a fusible element. The group of inventions refers to a method for making the osteosynthesis system involving preparation the layer of the polymer film on an external surface of the piece part by coating the surface of the piece system with a fine fusible polymer powder, fusion thereof on the surface of the piece part and electrostatic charging of the prepared film.

EFFECT: group of invention provides making a uniform coating of the electret layer on the surface of the piece part of the osteosynthesis system firmly attached to the surface of the piece part that enables faster fusion of bone fragments due to electric stimulation and prevented implant corrosion.

10 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to N-substituted monomers and polymers, methods of producing such monomers and polymers and methods for their use for different medical purposes, e.g., in medical devices. Disclosed is a polymer which contains a repeating unit of formula (I), where X1 and X2 are independently selected from Br and I; y1 and y2 are equal to zero or an integer from 1 to 4, A1 is selected from a group consisting of , , , and , R3 is selected from C1-C30 alkyl, and C1-C30 heteroalkyl, C5-C30 aryl, C6-C30 alkylaryl and C2-C30 heteroaryl; R4 is selected from H, C1-C30 alkyl and C1-C30 heteroalkyl; R1 is (A) or (B); Z is O or S; R5 and R6 are selected from -CH=CH-, -CHJ1-CHJ2- and -(CH2)a-; a equals zero or an integer from 1 to 8; J1 and J2 are independently selected from H, Br and I; Q is a group which contains 20 or more carbon atoms; Rx is selected from optionally substituted branched or straight C7-C30 alkyl and optionally substituted C6-C30 aryl; and Ry is selected from hydrogen, optionally substituted branched or straight C1-C30 alkyl and optionally substituted C6-C30 aryl. Also disclosed are versions of said polymer, methods of producing said polymers and a medical device containing the disclosed polymers. The medical device is preferably a stent.

EFFECT: disclosed polymer has improved physical and chemical properties and is suitable for use in implantable medical devices.

31 cl, 1 dwg, 2 tbl, 3 ex

Tissues adhesives // 2443435

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine. What is described is a multilayer tissue adhesive sheet which contains a structure layer or a laminated plastic attached to a layer supposed to contact with tissue. The structure layer or the laminated plastic contains one or more synthetic polymers showing film-forming properties, while the tissue contact layer contains tercopolymer poly(VP-AAc-AAc(NHS)). The synthetic polymers showing film-forming properties are preferentially biodegradable polyesters, while the tissue reactive groups are most preferentially NHS-polyester groups.

EFFECT: sheet shows better flexibility and herewith keeps high adhesive strength.

26 cl, 2 dwg, 8 ex

FIELD: medicine.

SUBSTANCE: compositions, methods and sets applied to sealing of injured tissues are described herein; the compositions are produced by combining of the first transversally cross-linked component with the second transversally cross-linked component to the effect of formation of the porous matrix with spans, and combining of the porous matrix with the hydrocarbon gel forming component applied to filling-in at least some of the spans.

EFFECT: compositions have minimal turgescing properties.

15 cl, 15 tbl, 14 dwg, 26 ex

Implants with fk506 // 2332959

FIELD: medicine.

SUBSTANCE: invention refers to implants, in particular, to intracavernous or intravascular implants, and is preferable for treatment or preventive maintenance of coronary or peripheric narrowings or occlusions of vessels, in particular, narrowings, or stenosis or restenosis respectively, preferably for prevention of restenosis which, in chemically covalent or incovalent to the bound or physically fixed form, contain FK506, to the method of their obtaining and application.

EFFECT: reduction of inflammation centres.

52 cl, 7 dwg, 10 tbl, 9 ex

FIELD: medicine, plastic and reconstructive surgery.

SUBSTANCE: the present innovation deals with the ways for obtaining spongiform material out of biological tissues applied for treating contour skin deformations in plastic surgery or filling in volumetric defects of organs and soft tissues in reconstructive surgery. It is important to obtain spongiform material of wide functional properties and clinical efficiency. The method deals with mechanical purification of allogeneic connective-tissue neoplasms against the residues of adjacent tissues and foreign contaminations followed by washing in running water, treatment with 3%-hydrogen peroxide solution, rinsing in 0.9%-sodium chloride solution, homogenization till obtaining the homogeneous viscous mass to form the body of the required geometrical shape and size to subject it for frosting-defrosting cycles at the quantity of 2-7, moreover, frosting should be fulfilled steadily at the rate of about 0.1-1°C/min up to -40...-45°C to be kept at the temperature mentioned for 24 h followed by complete defrosting of biomaterial at +4°C, and in the course of the last cycle after frosting up to the desired temperature it is necessary to subject biomaterial for vacuum freeze drying to achieve the constant weight, then it should be hermetically sealed and sterilized with gamma-irradiation at the dosage of 2.5 MRad.

EFFECT: higher efficiency.

FIELD: medicine, thoracic surgery.

SUBSTANCE: the present innovation deals with treating the main bronchus stump during pneumonectomy and repeated operations on postoperational bronchial fistulas. One should apply an elastic hollow conductor under the bronchus, moreover, it is necessary to introduce one branch of pre-cooled clamp for soft tissues made of the fusion with a shape-memory effect. Then this conductor should be withdrawn out of operation wound, moreover, another branch should be applied onto opposite side of the bronchus. Then one should cover bronchial stump, tracheal bifurcation and adjacent tissues with granules out of porous titanium nickelide at particles size being ,1-1,0 mm at the quantity of 0.03-0.06 g/sq. cm. The innovation enables to decrease the number of postoperational complications, shorten the terms for healing bronchial stump and duration of operation due to proper applying the clamp for soft tissues.

EFFECT: higher reliability of sealing bronchial stump.

8 dwg, 3 ex

FIELD: medicine.

SUBSTANCE: method involves placing cell-free dermal matrix into antibiotic solution before transplantation. The cell-free dermal matrix is poured with acetone cooled to -20°C in 1:10 proportion the day before transplantation. Desiccation and degreasing being done, the matrix is placed into antibiotic or antiseptic solution or their combination.

EFFECT: enhanced effectiveness in suppressing pathogenic microflora.

FIELD: medicine.

SUBSTANCE: medical material is processed by ionising radiation at radiation dose 5 to 100 kGy and contains a biodegradable resin and a polycarbodiimide compound in the amount of 0.1 to 10 wt % of resin. Biodegradable resin contains at least one resin specified in a group consisting of polybutylene succinate, and a polybutylene succinate copolymer, and polylactic acid or poly(3-hydroxyalkanoate) in the amount of 0 to 50 wt % of said polybutylene succinate resin. Group of inventions refers to a sterilised medical instrument made of said material, and to methods for making the medical material and the medical instrument which involve formation of said material and its processing by ionising radiation at radiation dose 5 to 100 kGy.

EFFECT: improved thermal stability, reduced tensile elongation and maintained strength and impact resistance after ionising radiation in the made medical material and instrument.

7 cl, 3 tbl, 16 ex

Tissues adhesives // 2443435

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine. What is described is a multilayer tissue adhesive sheet which contains a structure layer or a laminated plastic attached to a layer supposed to contact with tissue. The structure layer or the laminated plastic contains one or more synthetic polymers showing film-forming properties, while the tissue contact layer contains tercopolymer poly(VP-AAc-AAc(NHS)). The synthetic polymers showing film-forming properties are preferentially biodegradable polyesters, while the tissue reactive groups are most preferentially NHS-polyester groups.

EFFECT: sheet shows better flexibility and herewith keeps high adhesive strength.

26 cl, 2 dwg, 8 ex

FIELD: medicine.

SUBSTANCE: compositions, methods and sets applied to sealing of injured tissues are described herein; the compositions are produced by combining of the first transversally cross-linked component with the second transversally cross-linked component to the effect of formation of the porous matrix with spans, and combining of the porous matrix with the hydrocarbon gel forming component applied to filling-in at least some of the spans.

EFFECT: compositions have minimal turgescing properties.

15 cl, 15 tbl, 14 dwg, 26 ex

FIELD: medicine.

SUBSTANCE: inventions relate to medicine, namely to cell transplantology, and deal with method and transplant for treatment of liver failure. For this purpose autologous progenitor cells of bone marrow are isolated and cultivated in vitro. Also realised is sampling of autologous liver cells. After that, immobilisation of autologous liver cells and progenitor cells of bone marrow on carrier - biodegradable biocompatible three-dimensional matrix is performed. After that, transplantation of carrier with cells is performed by its introduction into mesentery of small intestine. Transplant includes biodegradable biocompatible three-dimensional porous matrix with pore size 2-500 mcm and total porosity 50-97%, ensuring total concentration of liver cells and progenitor bone marrow cells 2×106-15×106 cells per 1 cm3 of matrix and ratio of progenitor bone marrow cells to liver cells from 1:1 to 1:4. Total volume of matrix constitutes not less than 0.05 cm3, its smallest linear size being not less than 0.2 mm.

EFFECT: inventions make it possible to improve results of liver failure treatment due to prolongation of terms of hepatocyte survival and activisation of their proliferation, creation of conditions for growing of vessels into creates carcass, diffusion of nutrients, oxygen and factors of tissue differentiation, make it possible to avoid application of immunosuppressive therapy.

6 cl, 6 dwg

FIELD: medicine.

SUBSTANCE: there is described composition, which includes thermoplastic polymer, speed modifying agent and biologically active agent, which is suitable as implant for medication delivery with slow release into human or animal organism and which can be introduced in organism in liquid form.

EFFECT: characteristics of release and biodegradation of polymeric system with slow release are considerably improved.

2 tbl, 2 ex, 9 cl

Balloon catheter // 2327489

FIELD: medicine.

SUBSTANCE: given invention refers to balloon for medicinal equipment, specifically for catheter used within angioplasty containing polyamide copolymer material, characterised by the fact that specified polyamide copolymer material is presented with general formula (I), HO-(PF-OOC-PA-COO-PF-COO-PA)n-COOH, where PA is polyamide segment, PF is diol segment containing dimeric diol and/or corresponding diol polyester with end OH groups and n is number within 5 to 20.

EFFECT: improved plasticity performance.

25 cl, 1 dwg, 3 tbl, 2 ex

FIELD: polymer materials.

SUBSTANCE: invention concerns amorphous light-sensitive cross-linked polymeric structure and provides structure including (i) amorphous cross-linked structure formed from matrix based on acrylate and/or methacrylate compound and cross-linking agent and (ii) photoreactive component capable of undergoing reversible photodimerization reaction. Cross-linked structures are characterized by good properties with shape-memory effect.

EFFECT: increased mechanical strength of material with desired property profile.

21 cl, 4 dwg, 2 tbl, 12 ex

FIELD: medicine.

SUBSTANCE: method involves producing and transplanting and implantable segment containing mature cartilage tissue cells fixed on absorbable supporting matrix for repairing animal cartilage. The implantable segment has absorbable elastic supporting matrix for culturing and fixing living cells thereon. Instrument for introducing the implantable segment, having mature cartilage tissue cells on supporting matrix, into defective animal cartilage area, has clamps and external tubular envelope. The envelope has an end holdable by user and an end for making introduction into defective cartilage area. Holder and telescopic member are available in the envelope end holdable by user. Injection canal is partially embedded into the holder and projects beyond the holdable envelope end towards the end for making introduction. The clamps are attached to the telescopic member. They are well adapted for catching and releasing the implantable segment when telescopically moving the holder in the envelope.

EFFECT: enhanced effectiveness in arranging and fixing implantable segment in the implantation place.

47 cl, 11 dwg

The invention relates to the field of medicine and related material for medical purposes, in particular the drive for human and animal cells, implanted in the body of a mammal, or depot for drugs, representing multifunctional biocompatible hydrogel containing cross-linked copolymer of acrylamide, methacrylamide, and a cross-linking agent is 2-hydroxyethyl methacrylate and N,N'-methylene-bis-acrylamide and water, and method of its production by copolymerize these monomers in three stages

The invention relates to a biodegradable and biocompatible polymer compositions with a memory of its own form, which can find application in medical devices and as carriers of therapeutic or diagnostic agents

FIELD: medicine.

SUBSTANCE: invention refers to medicine. There are described methods for making implantable medical devices, preferentially of PEEK, having antimicrobial properties. The antimicrobial action is ensured by implantation of ceramic particles containing antimicrobial metal cations into the molten PEEK resin to be cooled and finally shaped by injection moulding, cutting and mechanical treatment or by other processing methods.

EFFECT: implants possess effective antimicrobial action for reducing a bacterial growth and a risk of infection.

12 cl, 1 dwg, 3 tbl

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