Tissues adhesives

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

 

The invention relates to a flexible sheet suitable for use as a tissue adhesive and sealant material and intended for local use in therapeutic purposes on internal and external surfaces of the body. The invention also relates to a method of manufacturing such a sheet and to methods of using such a sheet. In particular, the invention relates to samokleyushcheysya, biocompatible and hydratherma polymer sheet, which can be used for therapeutic purposes, for example for wound healing, connection, sealing, and hardening the weakened tissue, and for delivery of therapeutic agents, to a method of manufacturing such a sheet and to methods of its application. In addition, the invention relates to implantable medical devices, on which a coating of a material similar to the material of the specified list.

The use of materials that are adhered to biological tissues, for a number of surgical and other therapeutic purposes, is of considerable interest because they, for example, provide an alternative to the use of mechanical fasteners, such as sutures, staples, etc. of the Composition of materials has been proposed for this purpose include viscous solutions or gels, or which are made in the specified form or prepare n is directly before application by mixing the ingredients. Such compositions are then applied to the surface of the fabric using a special device for the application, such as a syringe.

Compositions of the above type have several disadvantages. If the composition has low viscosity, it can spread in different directions from the place of application, and therefore, while I have problems with its application in a given tissue. On the other hand, if the composition has a higher viscosity, difficulties arise when it is applied. In any case, since the composition is made in hydrated form, its duration may be limited and may occur premature curing. Thus, it is necessary either to fully use all the prepared composition, or throw it away unused portion. In addition, it is obvious that the preparation of compositions immediately before use by mixing the ingredients is laborious and time-consuming, and may require the use of additional equipment. In addition to these shortcomings, the strength of adhesion between the surfaces of the fabric, which may be provided with such a composition may be less than expected.

Compositions made from materials for tissue adhesives, also applied to a suitable substrate, the art is meant to overlay the surface of the fabric. The widespread use of therapeutic materials in the form of sheet, tape or tapes for local administration in the internal or external organs of the body are widely known in medicine. However, a possible disadvantage of previously proposed products, in addition to insufficient cohesive strength is insufficient degree of adhesion to the underlying tissues, especially in long-term use. Even though the initial degree of adhesion may be satisfactory, subsequently, the sheet can keep up with tissue, often after a few minutes or seconds, for example, in the hydration of the sheet after application. In addition, the flexibility of the product may be insufficient to ensure that the product is pushed to the surface to which it is applied, which can also have a negative effect on adhesion.

Due to the inadequate strength of adhesion of these products can be necessary to provide additional reinforcement, for example, by mechanical connection with the use of sutures, staples and similar devices. Alternatively, the formation of chemical bonds between the adhesive composition and the underlying tissue and, therefore, the connection surfaces of the tissues with each other can be initiated energy effects (such as light or th is m). Obviously, this approach creates additional problems. In many cases, mechanical fastening, for example using stitches or brackets, is exactly what is required to replace or fix. In many cases, the use of such fasteners or inefficient (e.g., the lungs), or undesirable because of the introduction of various types of fasteners causes further weakening of the fabric. The use of external energy requires a supply source of such energy and its impacts. Such energy sources can be expensive, be difficult to maintain, particularly in a confined space of an operating room or similar premises. In addition, the use of external energy to create a connection may take a long time and (in some cases) to require significant attention on the part of the surgeon, who must determine the moment when the energy input is sufficient to create a strong connection, but there will be no damage to the underlying tissue.

The disadvantage of sheet products used for the purposes outlined above, is the lack of flexibility, which in many cases may be necessary or desirable. In particular, the need for flexibility in the products used in endoscopic surgery (surgery C is not minimal intervention), currently gaining importance, where often you want the product before introduction into the cavity was bent or collapsed to a compact size. Attempts to make such products more flexible, for example, by the introduction of plasticizers can degrade the adhesive capability of the product.

In accordance with the present invention proposed improvements to the sheets of tissue adhesives, or similar products, General features of which are described above, and similar items made of materials proposed for tissue adhesives that allow us to overcome or essentially to remedy the above disadvantages and/or other disadvantages of the materials used in accordance with the current level of technology.

BRIEF description of the INVENTION

In accordance with the first aspect of the present invention proposed a multi-layered sheet of tissue adhesive, comprising a structural layer or laminate, with specified structural layer or laminate includes one or more synthetic polymers having film-forming properties, and to the specified structural layer or laminate attached to a layer of material intended for contact with the tissue, wherein said material contains a group capable of reacting with the cloth.

The key is raimunda sheet, proposed according to the present invention consist in the fact that he now joins the tissues, which allows you to apply the specified worksheet in a number of medical problems. It was found that the offer sheet has superior flexibility and retains high strength adhesion. In preferred implementations, the sheet exhibits a high initial strength of adhesion to the tissue to which it is applied (and, thus, the sheet can be considered self-adhesive), and, in addition, the strength of adhesion of the sheet to the fabric stays durable for a long period of time. Without resorting to any theory, it can be assumed that the initial strength of adhesion of the sheet to the tissue due to the formation between them of electronic communications, which are then supplemented or replaced by a covalent chemical bonds between the groups of compositions capable of reacting with a cloth, and cloth, in particular, between the amino groups and/or tilenum groups located on the surface of the fabric, and functional groups worksheet, capable of reacting with the cloth.

Suppose that the initial strength of adhesion of the sheet to the surface of the fabric caused by the van der Waals and/or hydrogen bonds formed between the sheet and the surface of the fabric. Upon contact with the tissue surface of the sheet is exposed to guide the operation, causing a reaction between the functional groups capable of reacting with a cloth, and the surface of the underlying tissues. Similar reactions between functional groups capable of reacting with the tissue, and underlying tissue lead to very strong adhesion of the sheet and the surface of the fabric. The sheet can also absorb body fluids (when it is superimposed on the tissue surface emitting liquid) and any added solutions used for hydration of the sheet after its imposition on the surface (such fluid can be a solution commonly used in surgery for washing), which leads to better compliance and adhesion between the sheet and the surface of the fabric, resulting adhesive sealant becomes hemostatic and pnevmaticheskie properties.

The use of such sheets reduces or eliminates the use of additional measures, including a mechanical bond with the fabric (for example, joints or brackets), or the necessity of applying external energy in the form of heat or light, which causes the adhesion of the sheet to the underlying tissue. Another advantage of the sheet, proposed according to the present invention, is that it is applied to the fabric in the form of a pre-molded product, and is not prepared by mixing the materials used immediately before the eat.

In addition, because prior to the hydration and subsequent contact with the surface of the fabric sheet is essentially inactive, the flow of premature reaction inside of the sheet it is unlikely that increases its shelf life, which may be, for example, more than six months under appropriate conditions at room temperature.

The term "sheet" means a product whose thickness is considerably less than its other dimensions. Alternatively, such a product can be described by the term "film" or "patch".

In preferred implementations of the present invention, the structural layer or laminate is a laminate comprising two or more discrete layers connected to each other. In particularly preferred implementations, the laminate includes alternating layers of a polymer having film-forming properties, and a material containing reactive functional groups. It was found that in General, sheets, including structural laminate, has improved strength of adhesion to the tissue and/or flexibility and/or greater stability in maintaining the structural integrity compared with leaves, including one structural layer.

In this case, the sheet is offered pursuant to this invention, most prefer is Ino includes an even number of layers, and in particular, alternating layers of film-forming polymer and a material containing reactive groups. Thus, we can assume that the sheet contains a structural laminate comprising n layers of film-forming polymer and n-1 layers located between reactive material, and the layer intended for contact with the tissue and containing a material capable of reacting with the cloth. The value n may be 1 - in this case, the sheet includes only one structural layer and a layer in contact with the tissue. Alternatively, n may be 2 or 3 in this case, the sheet only includes 4 or 6 layers. Currently, the most preferred are the leaves with n=2.

The material containing reactive functional groups may be the same or be similar to the material in contact with the tissue and capable of reacting with the cloth.

Another aspect of the present invention relates to a device suitable for implantation in a human or animal, and at least part of the outer surface of the specified device, the coating comprising one or more polymers having film-forming properties, and at least part of the specified coating connected with a layer of material including a functional group capable of R is to aggravate with cloth.

In accordance with this aspect of the present invention, the coating of film-forming polymer provides a means of fastening material comprising functional groups capable of reacting with the tissue, to the device, and this material provides a means of attaching the device to the desired site within the body. Thus, this aspect of the present invention may be particularly important in regard to implantable devices that are otherwise difficult to fix in the desired position inside the body, for example, due to the fact that these devices are made of a material chemically inert and incapable of reaction with the surrounding tissue or chemical linking groups.

In the following detailed description of the invention mainly considered examples of implementation of the invention, which have the form of sheets. However, it should be understood that, where possible, similar comments can be applied to the examples of the invention include coatings applied to the implantable device.

Another aspect of the present invention relates to a method for attaching one surface of the tissue to another tissue, or to a method of sealing the surface of the fabric; however, this method includes overlaying the surface of the fabric sheet are proposed in accordance with the first aspect of the present invention.

Sheet, proposed according to the present invention can also be used to deliver one or more therapeutically active substances to the site, which imposed the specified worksheet. In such cases, the specified substance (specified substances) can be entered in the worksheet, for example, by mixing them with other ingredients that are used for the manufacture of the sheet. Alternatively, the specified substance (substances) can be linked by covalent bonds with the components of the sheet. However, in other example implementations, the sheet does not contain therapeutically active ingredients. Similarly, one or more therapeutically active substances can be introduced into the material applied to the outer surface of the implantable device proposed according to the second aspect of the present invention.

DETAILED description of the INVENTION

Abbreviations

AAS - acrylic acid

AIBN - azo-ISO-butyronitrile

DCC - dicyclohexylcarbodiimide

DCM - dichloromethane

DCU - dicyclohexylmethane

DMF - dimethylformamide (DMF)

DMSO - dimethyl sulfoxide (DMSO)

DPBS - saline phosphate buffer at Dulbecco

ENT - ear, throat, nose

LDC - hydroxypropylcellulose

IPA isopropanol

Mn- Brednikova molecular mass

Mw- bulk molecules of the RNA mass

Meon - methanol

NHS - N-hydroxysuccinimide

NVP - N-vinyl pyrrolidone

PEG - polyethylene glycol

PLG - poly(DL-lactide-co-glycolide)

poly(VP-AAc) copolymer of vinylpyrrolidone and acrylic acid

Poly(VP-AAc(NHS)) is a copolymer of vinylpyrrolidone and NHS-ester of acrylic acid

Poly(VP-AAc-AAc(NHS)) - ternary copolymer of vinylpyrrolidone, of acrylic acid NHS-ester of acrylic acid

Nature structural layer or laminate

Sheet, proposed according to the first aspect of the present invention includes a structural layer or laminate that includes at least one film-forming polymer. The structural layer or laminate may be entirely or essentially consist of a film-forming polymer. In other example implementations, the structural layer or laminate for the most part consists of a film-forming polymer. For example, the structural layer or laminate may include more than 80%, 90% or more than 95% wt. film-forming polymer.

For the manufacture of the first layer can be used in a variety suitable for this purpose, film-forming polymers, provided that they have suitable film-forming properties and are suitable for use in medical purposes, in particular, are non-toxic, biocompatible and biodegradable.

Most often, the first layer includes only one paragraph is encompassi polymer. Alternatively, the first layer may be formed from more than one film-forming polymer.

Film-forming polymer may be synthetic, or it may be a natural material, or a polymer obtained from a natural material.

The most preferred group of synthetic polymers that may be suitable for implementing the present invention are biodegradable polyesters. Specific examples of such polymers include polylactic acid and polyglycolic acid and copolymers and mixtures of these acids. Other examples include polycaprolactones and polyhydroxyalkanoate, for example, polyhydroxybutyrate, polyhydroxyvalerate and polyhydroxyalkanoate.

Currently, the most preferred polymers based on esters used according to the present invention are copolymers of the type poly(lactide-co-glycolide) (also referred to as copolymers of lactic and glycolic acids), which are typically biocompatible and biodegradable and soluble in many organic solvents.

Currently, among the particularly preferred examples of implementation of the worksheet, including structural laminate, particularly preferred are examples of implementation, including alternating layers of biodegradable material the material on the basis of complex polyester and material containing reactive functional groups. Thus, a special aspect of the present invention relates to multi-layer sheet fabric glue, including structural laminate, and the specified laminate composed of n layers of biodegradable complex polyester and n-1 layers of material containing reactive functional groups, which have between these layers of biodegradable complex of polyester and a layer of material intended for contact with the tissue and capable of reacting with the tissue; thus the values of n are 1, 2 or 3, most preferably 2.

In such implementations, the layer most remote from the layer in contact with the cloth, is a complex polyester, which essentially does not stick to the fabric. Thus, these sheets in General will stick only to the target tissue (which put the layer in contact with the tissue and containing functional groups capable of reacting with the tissue), but not to stick to the surrounding tissues (e.g., cellular or intraperitoneal walls).

Other examples could be used synthetic polymers include aminirovanie polymers, for example aminirovanie the glycols (including glycols, commercially available under the trademark JEFFAMINE) and the floor is allylamine.

Others may be used in accordance with the present invention, film-forming polymers include polysaccharides and, in particular, the main polysaccharides.

The nature of a layer in contact with fabric

Sheet, proposed according to the first aspect of the present invention includes the layer in contact with the tissue, which includes material, containing functional groups capable of reacting with the cloth. Such material preferably includes one or more polymers containing functional groups capable of reacting with the cloth.

The term "functional group capable of reacting with the tissue" means a functional group capable of reacting with other functional groups present on the surface of the tissue, with the formation of covalent bonds with the fabric. Usually tissue partially consist of proteins that typically contain fragments of thiols and fragments of primary amines. Many functional groups, such as aminoether, n-nitrophenylarsonic, NHS-esters, epoxides, isocyanates, acrylates, vinylsulfonic, orthopaedic-disulfide, maleimide, aldehyde groups, todatetime and other groups that can react with thiols and primary inorganic salts and, thus, to form a functional group capable of reacting with the tissue". In accordance with the present description, the term NHS NHS-ester includes not only the N-hydroxysuccinimide, but and its derivatives containing substituted Succinimidyl cycle. An example of such a derivative is N-hydroxycarbonylmethyl and its salts, particularly the sodium salt, which can increase the solubility of the material capable of reacting with the cloth.

Possibly used in accordance with the present invention the functional group capable of reacting with the tissue, represent any functional group capable of reacting (in the most commonly used terms that are used when applying the composition to the fabric, i.e. in the aquatic environment and without the use of significant quantities of heat or other energy supplied from the outside) with functional groups located on the surface of the fabric. Functional groups located on the surface of the fabric include tirinya groups and amino groups, and, thus, functional groups capable of reacting with the tissue, include groups reactive towards tilenum and/or amino groups. Their examples include:

aminoether;

n-nitrophenylarsonic;

NHS-esters;

epoxide;

isocyanate;

acrylate;

vinylsulfonic;

orthopaedic-disulfide;

maleimide;

aldehyde group, and

todatetime.

The most preferred functional group capable of reacting with a cloth, is NHS-slojnoe the IRNA group.

In addition to the functional groups capable of reacting with a cloth, a polymer (polymers)of the material of the second layer may contain a functional group, is not able by themselves to react with the fabric, which is applied to the sheet, but provides a good strength of adhesion of the sheet to the fabric. In accordance with the present description of such functional groups are called "no reactive functional groups". Examples of reactive functional groups include hydroxyl group, heterocyclic amines and amides (for example, in residual vinylpyrrolidone) and, in particular, carboxyl group (e.g., contained in the residues of acrylic acid).

Particularly preferably, if the functional group capable of reacting with a cloth, are activated derivatives not reactive functional groups. In some implementations, not all reactive functional groups can be activated, with the result that they form a functional group capable of reacting with the cloth. In other examples of implementation, not just some reactive functional groups can be activated and form a functional group capable of reacting with the cloth. In the latter case, the initial strength of the contact is about sticking of the sheet to the tissue, to which it is applied, and strength over the long-term adhesion, formed due to the formation of covalent linkages by the reaction of functional groups capable of reacting with the tissue, with the functional groups of the fabric can be different and may change due to the proportion of non-reactive groups that are in an activated form.

The NHS-ester group is particularly preferable functional group capable of reacting with the tissue, and therefore, the preferred polymers capable of reacting with a cloth, are polymers enriched NHS-ester groups. In particular, the preferred polymers capable of reacting with a cloth, are ternary copolymers of poly(VP-AAC(NHS)) and poly(VP-AAC-AAC(NHS)).

The adequacy of the initial strength of adhesion of the sheet to the tissue in the case bookieboo polymer (polymers) can be quantified in vitro, for example, through testing the strength of adhesion. This test is carried out, allowing the sheet to stick to a suitable substrate (secured in a fixed position), while another section of the sheet is physically attached to the load device for tensile testing, located in such a way that before the test sheet is not under load. The load sensor can move along an axis essentially perpendicular to the longitudinal axis, along which the substrate. The test involves the movement of the load cell in the direction opposite from the substrate, with a constant, predetermined speed as long as the sheet will not become detached from the substrate. The output value of this test is a quantitative measure of the energy required for adhesion of the test sheet, i.e. the cumulative energy required to break the interaction between the sheet and the substrate to which it is glued. Fit cumulative energy of adhesion of the sheet, proposed according to the present invention should be not less than 0.5 MJ.

In some implementations of the present invention, the preferred polymer capable of reacting with the cloth, is a ternary copolymer of poly(VP-AAC-AAC(NHS)). The carboxyl group of a fragment of poly(VP-AAC) can be transformed into the NHS-ester groups by reaction with NHS in the presence of dicyclohexylcarbodiimide (see Example 9). If the content of the acid in the poly(VP-AAc) is defined (in moles), the proportion of acid groups converted into a group capable of reacting with a cloth, can be adjusted by adding the molar percentage of the NHS.

Another possible used polymer capable of reacting with the tissue and containing a hydroxyl group is an activated form of succinate hydroxypropylcellulose (LDCs), e.g. the succinate-NHS hydroxypropylcellulose. In this case, some of the hydroxyl group of the polymer is activated NHS through bridges formed succinic acid (see Example 11).

The properties sheet of tissue glue can be optimized by including other polymers and additives.

Additives that improve the properties of the

Despite the fact that the sheet is offered according to the first aspect of the present invention, has adequate flexibility, it is sometimes desirable to increase the flexibility, elasticity and/or the strength of the sheet in the wet state by adding to the structural layer or laminate and/or a layer in contact with the tissue, one or more plasticizers and elastomers. In particular, the need for greater flexibility in the composition can be introduced low-molecular-weight particles, such as glycerol and low molecular weight polyethylene glycol. Examples of suitable elastomers that may be introduced into the product, include poly(caprolactone), poly(urethanes) and poly(silicones). Such materials can increase the flexibility and/or elasticity of the sheet when added in concentrations that constitute up to 30% wt. from the mass of ingredients that make up the sheet.

However, the introduction of high concentrations of such materials may have a negative effect on the bond strength of the sheet. To overcome this drawback, the additive can be functionalized and VK is ucati group, capable of reacting with the tissue, which can contribute to bond strength.

Buffer agents

The reaction between the functional groups of the sheet, capable of reacting with the tissue, and functional groups located on the surface of the fabric may be different depending on pH. Thus, it may be preferable to the introduction of buffer agents before applying or, more preferably, the inclusion of the buffer agent in the composition used to prepare the sheet, in particular in the layer of the sheet in contact with the tissue. The average clutch of some leaves, proposed according to the present invention, applied to explantion liver pig, can be improved by coating the surface of the fabric phosphate/carbonate buffer having a pH of 10.5.

The connection components of the sheet during manufacture

Materials structural layer or laminate and/or a layer in contact with the tissue, can be connected at the time of manufacture. This connection can increase the physical strength of the sheet and can optimize the properties of the sheet, in particular the time required for biodegradation of the sheet after its imposition.

The connection can be made in various ways, including casting of the component layers of the common solvents. Another method includes manufacturing the pressure of the composition, in this method of preparing a structural layer or laminate and/or a layer in contact with the tissue, comprising at least two functional groups capable of reacting with functional groups in the attached material. Thus, the component acts as a crosslinking agent. Preferably, the crosslinking agent contains at least two functional groups in the same form. Thus, the crosslinking agent is most preferably represents homobifunctional or geopolitically crosslinking agent.

Physical form sheet

Typically, the total thickness of the sheet can range from 0.01 to 1 mm, usually from 0.01 to 0.5 mm, most typically between 0.015 to 0.2 mm or between 0.015 to 0.1 mm, for example between 0.015 to 0.05 mm

In the preferred currently, implementations of the thickness of the layer in contact with the cloth, larger than the thickness of the structural layer or laminate. For example, the thickness of the layer in contact with the tissue, may be more than 50% of the total thickness of the sheet or more than 60%.

The sizes that can be manufactured sheet, or dimensions, which may be a cut sheet, range from a few square millimeters to several tens of square centimeters.

Manufacturing sheet

The most convenient method of making sheet, proposed according to the present izobreteny is, includes step-by-step formation of the individual layers that make up the sheet.

First, it may be prepared structural layer or (preferably) a structural layer of the laminate, the most remote from the layer in contact with the tissue, for example, by casting a solution of the material which forms the layer, in a suitable solvent, or by a suitable plate or form, or on a suitable release paper, such as a release paper coated with silicone. Poured the solution is then dried or allowed to dry, possibly in conditions including elevated temperature and/or reduced pressure.

Then successive layers of structural laminate can be poured onto a pre-formed first layer, followed by drying each new layer to remove the solvent and, if necessary, curing the purpose of obtaining the desired number of cross-links. Most preferably, the curing is performed under high temperatures (typically in a period of time up to one hour or more at temperatures of components up to 60°C or above).

Finally, the structural layer or laminate can be diffused layer intended for contact with the tissue. In this case, after casting preferably produce drying to remove solvent and the stated purpose of obtaining the desired number of cross-links. Preferably the curing is produced at least partially under the influence of high temperatures (typically over a time of ten minutes to one hour or more at temperatures of components up to 60°C).

The casting of each layer of the sheet can be produced in a separate operation. In the alternative case, in particular in the case of relatively thick layers (i.e. relatively thick compared to the other layers of the sheet), the layer can be made consistent casting thinner sublayers.

The water content of the sheet, proposed according to the present invention, after manufacture, but prior to use is usually less than 10% wt. and more often less than 5% wt.

At the time of manufacture to the surface of individual layers of the sheet may be caused to the image or alphanumeric mark. This mark can be used to distinguish surface designed to stick to fabric, from nucleases surfaces; alternatively, it can be used to indicate the brand of the product or manufacturer. The chromophores that may be used as substances for applying marks include methylene blue.

Typically, the implantable device proposed according to the present invention, can be manufactured is s any conventional method of applying a coating to the device. For example, coatings can be applied to the device in a manner analogous to the method of application materials by the casting on the structural layer or laminate layer in contact with the tissue, as described above. Alternatively the coating may be applied by immersing the device in a liquid composition or by spraying the liquid composition on the device.

Therapeutic application sheet

Sheet, proposed according to the present invention is suitable for application on both external and internal surfaces of the body, i.e. it can be imposed locally on the external surface of the body (e.g., skin) or on the inner surface, for example the surface of internal organs, obrazuemyh during surgical procedures, including traditional surgery and surgery of minimum intervention.

Sheet, proposed according to the present invention, particularly suitable for use in the following surgical procedures:

Thoracic (chest) region/cardiovascular operations

General surgery

Ear, nose and throat

Urologic operations

Oral/maxillofacial operations

Orthopedic operations

Neurological operations

Gastroenterological operations

Eye operations

Gynecologic operations/obstetrician is TBE

Possible use cases are described in more detail below.

Wound healing

The ability of the sheet to dissolve means that the sheet can be used to support tissue and wound healing of internal organs and superficial wounds. As soon as the sheet begins to decompose, is tributary to him fibroblasts, which begin to besiege the components of the intercellular matrix. Thus, the sheet can be used as a dressing tool both external and internal surfaces of the body. In addition, to accelerate the healing process, the composition can be added such factors as growth factor and camp (cyclic amp), which are known to promote proliferation of skin cells. The sheet can be manufactured in such a way that it allows you to control the penetration of moisture and infectious agents, and thus, such a sheet can be, in particular, used in the treatment of burns.

The accretion of the skin

The sheet may be imposed locally with the aim of accretion of the wound edges (as an alternative to surgical suture). The advantages of such use may include the reduction of scar formation, and, thus, the proposed composition and the sheet can be used to hold cosmetic "small" (outpatient) operations (for example, held at priem the x emergency). Self-adhesive properties of the sheet can facilitate very fast application.

Healing hernia

Offer sheet may be used to provide hardening operations healing hernia. Self-adhesive attachment allows you to overcome the potential disadvantages of surgical mesh products, traditionally used for reinforcing the wall of the peritoneum, the use of which is associated with stitches or staples on the already weak plot. Sheet design for this application and may not disappear in the short or long period of time, depending on the time required for healing of damaged tissue. The sheet may also be imposed to ensure that the fabric was designed to resist the imposition of parentheses.

The invention can also be applied to create the adhesive coating on mesh products used for the treatment of hernias.

Anastomosis

Offer sheet is a tool for quick sealing and prevent holes in the United tubular systems, such as blood vessels, vascular implants, and implants, bladder, and gastrointestinal tract. The property sheet to promote the healing of tissue may represent a valuable device used saulenienes tissue.

Sealing of large areas of tissue

Good sealing and technological properties of the sheet in combination with self-adhesive properties and the ability to cover a large surface area means that the sheet can be a great success applied to the sealing surfaces of the resected tissue, in particular areas that are prone to diffuse bleeding (e.g., liver). Offer sheet also provides an ideal support matrix for healing tissue in these areas. It may also help to limit the expiration of the cerebrospinal fluid after conducting a neurological intervention.

Sealing air leaks

In addition to the properties of the adhesive described above, high tensile strength and good own elasticity of the sheet (after hydration and reactions of functional groups capable of reacting with a cloth) make it particularly suitable for sealing the openings through which leaks the air trapped in the lungs, especially after lung resection. In this case, after the sealing sheet is an ideal support matrix for healing tissue in these areas.

Hemostasis

Offer sheet may be imposed on the bleeding site on which it is actuat as a physical barrier. The sheet material capable of reacting with the tissue, can immobilizative proteins and, thus, to promote hemostasis.

The introduction of therapeutic agents

In solution (solutions)used for the preparation of components of the sheet can be added medicines, disinfectants and other therapeutic agents (including biologically active substances such as growth factors, and even cells and cell components), or they can be covalently associated with the specified components in the manufacture of sheet before use. Once the sheet is in place, after blending to the desired location, there is a slow release drug or under the influence of diffusion, or caused by the design of the sheet, for example, is controlled by the density of cross-links into a sheet, which determines the speed of resorption over time and, consequently, release of the drug. The rate of release can be controlled by selecting appropriate design of the sheet. Thus, the sheet can be a means to deliver a known quantity of drug or in the organism as a whole, or just a specific area. The drug may be directly associated with a component of the solution used for the manufacture of the sheet, or it can simply be dispersed through the Academy of Sciences in solution.

Prevention of postoperative adhesions

The formation of postoperative adhesions, i.e. undesirable connective tissue between adjacent tissues, is a serious problem, causing a large part of postoperative complications. This problem is particularly common during operations on the intestines, after which the spikes can cause, for example, twisting of the intestine, which can further lead to the need for repeat surgery. The use of sheet material according to the present invention, when the operation can effectively prevent the formation of postoperative adhesions between the operated tissue and surrounding tissues.

Procedures minimum intervention

The use of minimum intervention techniques for sampling tissue for biopsy, injection devices, delivery of therapeutic agents, and perform surgical procedures is a rapidly developing branch of surgery alternative to traditional "open" surgical procedures. Treatments using minimal intervention is usually less painful, lead to the formation of smaller scars, promotes the fast recovery and cause fewer postoperative complications in patients is now, and reduce the cost of medical care. The procedure is done using specially designed instruments are inserted through small keyhole incisions. The sheet may be introduced into the body by using existing and specially designed surgical instruments for minimally invasive and Tokarov, and the sheet can be given in an appropriate form, or the size and configuration of the sheet can be prepared later, including stops for suturing clips tools. The flexible sheet can give it the shape that reduces the overall size of, for example, by folding or collapse that promotes the use of sheet operations minimum intervention and/or other procedures with limited access to the processing area. High initial strength of adhesion of the sheet to the tissue to which it is applied, can also be considered an advantage when carrying out such procedures.

Brief description of drawings

Figure 1 schematically and not to scale depicts an example implementation of a sheet of tissue glue, proposed according to the present invention.

Figure 2 shows the scheme for synthesis of copolymer of N-vinylpyrrolidone50/ acrylic acid25/ of ester N-hydroxysuccinimide and acrylic acid 25).

Detailed description of preferred implementations

The following more detailed description of the present invention with reference to the Examples given are for illustrative purposes. In Examples 1 and 2 described the manufacture of sheets of tissue glue, proposed according to the present invention. In Examples 3-5 specified operational and technical characteristics of such sheets. In Examples 6 and 7 described the synthesis of a material containing a group capable of reacting with a cloth, which is used for manufacture of materials of Examples 1 and 2. Example 8 describes the synthesis of alternative types of material capable of reacting with the cloth.

Example 1

Preparation of multilayer sheet

Multi-layer sheet fabric glue, proposed according to the present invention, is shown schematically in figure 1. The sheet includes a structural laminate layer intended for contact with the cloth.

Structural laminate has the following structure:

a) the first layer 1 consisting of PLGA;

b) a second layer 2 consisting of poly(VP-AAC-AAC(NHS)); and

c) a third layer 3, consisting of PLGA.

Layer 4, which is intended for contact with tissue, is connected with the third layer 3, and includes a poly(VP-AAC-AAC(NHS)).

The thickness of the first and third layers 1, 3 is approximately 4 μm, the thickness of the second layer 2 is approximately 3 μm. The thickness of the layer 4, the pre is assigned to the contact with the tissue, approximately 22 microns; this layer consists of three sublayers 4A, having approximately equal thickness.

The sheet is prepared as follows:

1.1. Preparation of solutions

The following way to prepare three solutions:

the solution contains 10 g PLG dissolved in 100 ml of dichloromethane.

The solution includes 7.5 g of poly(VP-AAC-AAC(NHS)), dissolved in 100 ml of a mixture of dichloromethane /Meon 15/4.

The solution includes 2.5 g of methylene blue dissolved in 50 ml of water.

1.2. The casting layer 1

The solution is poured onto a release paper coated with silicone, using a device called "K-bar". The film is dried for 30 minutes at 20°C./atmospheric pressure. The film is not removed from the release paper.

1.3. The casting layer 2

The solution is poured on Layer 1, using the device "K-bar". The film is dried for 30 minutes at 20°C./atmospheric pressure. The film is not removed from the release paper.

1.4. The logo

On the surface Layer 2 is applied by solution brand/visual logotip.

1.5. The casting layer 3

The solution is poured on a Layer 2 using device "K-bar". The film is dried for 30 minutes at 20°C./atmospheric pressure. The film is not removed from the release paper.

1.6. The casting layer 4 a-C

The solution is poured on a Layer 3 using the unit "K-bar". The film is dried for 30 minutes at 20°Prov./atmospheric pressure. The film is not removed from the release paper.

The solution is poured on a Layer 4A by using device "K-bar", the Film is dried for 30 minutes at 20°C./atmospheric pressure. The film is not removed from the release paper.

The solution is poured on a Layer 4b, using the device "K-bar". The film is dried for 16 hours at 20°C/low pressure. The film is not removed from the release paper.

1.7. Cutting

The product is cut to the desired size using a specially designed cutters and removed from the release paper.

1.8. Final drying

The product is dried for 24 hours at 20°C/reduced pressure.

Example 2

Alternative preparation of multilayer sheet

Two-layer sheet fabric glue, proposed according to the present invention includes a structural layer and a layer intended for contact with the cloth.

The structural layer is made in the form of only the first layer 1 made of PLGA.

Layer 2, which is intended for contact with tissue, is connected to the first layer 1 and includes a poly(VP-AAc-AAc(NHS)).

The thickness of the first layer 1 is approximately 15 μm. The thickness of the layer 2, which is intended for contact with tissue, approximately 22 microns.

The sheet is prepared as follows:

2.1. Preparation of solutions

The following way to prepare three solutions:

solution And including the et 10 g PLG, dissolved in 100 ml of dichloromethane.

The solution contains 10 g of poly(VP-AAC-AAC(NHS)), dissolved in 100 ml of a mixture of dichloromethane /Meon 15/4.

The solution includes 2.5 g of methylene blue dissolved in 50 ml of water.

2.2. The casting layer 1

The solution is poured onto a release paper coated with silicone, using a device called "K-bar". The film is dried for 30 minutes at 20°C./atmospheric pressure. The film is not removed from the release paper.

2.3. The casting layer 2

The solution is poured on Layer 1, using the device "K-bar". The film is dried for 30 minutes at 20°C./atmospheric pressure. The film is not removed from the release paper.

2.4. The logo

On the surface Layer 2 is applied by solution brand/visual logotip.

2.5 Cutting

The product is cut to the desired size using a specially designed cutters and removed from the release paper.

2.6. Final drying

The product is dried for 24 hours at 20°C/reduced pressure.

Example 3

The strength of adhesion in vitro

In vitro strength of the bonding sheet, proposed according to the present invention, the liver is quantitatively evaluated using universal install the Zwick test (Zwick universal testing machine). The average clutch after 5 minutes soaking in saline solution with FOSFA is important buffer for Dulbecco (DPBS) is usually from 7 to 14 MJ.

Example 4

Physical characteristics

The product is a transparent/opaque film that is visible logo. Ultimate tensile strength, determined using universal installation of Zwick testing, typically ranges from 2 to 9 MPa.

Example 5

The strength of adhesion in vivo

Sheets as shown in Example 1, was used to stop bleeding, leakage of the fluid and air from wounds received in the standard biopsy tissue of the lungs and liver. After applying the sheet firmly adheres to the surface of the fabric, resulting in immediate stabilization of the damaged site and satisfactory hemostasis and/or pneumostat.

Healing was assessed by macroscopic method and by means of histological examination of tissue. After 14 days after the application has found a good degree of healing and sealing sections of the initial damage and the formation of normal tissue around the remains of the sheet. These remains were enclosure (thin fibrous coating. The remaining material was subjected to continuous resorbtive macrophages involving cellular infiltrate, and the process is usually completed within 50 days.

Example 6

Synthesis of ternary copolymer (VP-AAc-AAc(NHS))

The reaction is shown schematically in figure 2.

2000 ml obeskislorozhennaja what about the DMSO was heated to 80°C. Then in DMSO was added 121,3 g (of 1.09 mol) of N-vinylpyrrolidone and to 78.7 g (of 1.09 mol) of acrylic acid, and then 0.04 g (2,44×10-4mol) azo-ISO-butyronitrile. The reaction mixture was stirred at 80°C for 17-19 hours and then left to cool to room temperature. In the solution of the obtained polymer was dissolved 125,6 g (1,09 mol) NHS, and then added 112,6 g (0,545 mol) dicyclohexylcarbodiimide dissolved in 225 ml of DMF. The reaction mixture was stirred at room temperature for 96 hours. A byproduct of the reaction, dicyclohexylamine was filtered under reduced pressure on a glass filter. The polymer was isolated by mixing with 2000 ml of isopropanol, followed by deposition of 13000 ml of diethyl ether, after which the precipitate was filtered. The polymer is washed three times in 2500 ml of diethyl ether and then dried at 40°C under reduced pressure.

Next, to remove trace amounts of contaminants, the polymer was purified in a Soxhlet extraction apparatus using isopropanol.

After extraction in the Soxhlet extraction apparatus, the polymer was further purified by preparing a 6% (wt./about.) the solution of polymer in a mixture of dichloromethane /Meon (15/4.vol.), and then besieged from 50-fold excess of diethyl ether, then washed with diethyl ether. The purified polymer was dried at 40°C under reduced pressure.

Approximate molecular masses of the polymer amounted to: M n=2000-5000, Mw=10000-30000.

Example 7

Alternative synthesis of ternary copolymer (VP-AAc-AAc(NHS))

400 ml obeskislorozhennaja of toluene was heated to 80°C. Then, toluene was added to 31.6 g (0.28 mol) of N-vinylpyrrolidone and 20.6 g (0.28 mol) of acrylic acid, and then immediately added to 0.1 g (6.1×10-4mol) azo-ISO-butyronitrile. The reaction mixture was stirred at 80°C for 17 to 19 hours. The polymer was isolated planting of 2000 ml 1/1 (vol./about.) a mixture of hexane/ diethyl ether, and then filtered under reduced pressure. The polymer is washed three times with 300 ml of diethyl ether and then dried in vacuum at 40°C.

The acid content in the copolymer (VP-AAc) was determined by titration of a 1.0 M solution of sodium hydroxide. Then 50 mol%. acid groups turned in the NHS-ester groups by reaction with NHS in the presence of dicyclohexylcarbodiimide. Then 33,7 g of polymer (VP-AAc)containing 0.77 mole of functional groups of acrylic acid and 44,54 g (0.38 mol) NHS was dissolved in 1000 ml of DMF at 25°C. After that, 79,77 g (0.38 mol) of dicyclohexylcarbodiimide dissolved in 137 ml of DMF and added to the polymer solution and the reaction mixture was stirred at 25°C for 96 hours. A byproduct of the reaction, dicyclohexylamine was filtered under reduced pressure on a glass filter. The polymer was isolated by addition of 1250 ml isopropanol, followed by deposition of the C 5000 ml of diethyl ether, then the precipitate was filtered. The polymer is washed three times in 1000 ml of diethyl ether and then dried at 40°C under reduced pressure.

Next, to remove trace amounts of contaminants, the polymer can be purified using a number of known methods, for example extraction of socket, dialysis or washing with a suitable solvent, such as isopropanol. In addition, drying at elevated temperature and reduced pressure also helps to remove the trace amounts of solvents and other volatile substances.

Next, to remove trace amounts of contaminants, the polymer was purified in a Soxhlet extraction apparatus using isopropanol.

After extraction in the Soxhlet extraction apparatus, the polymer was further purified by preparing a 6% (wt./about.) the solution of polymer in a mixture of dichloromethane /Meon (15/4.vol.), and then besieged from 50-fold excess of diethyl ether, then washed with diethyl ether. The purified polymer was dried at 40°C under reduced pressure.

Example 8

Synthesis of succinate-NHS hydroxypropylcellulose

10 g hydroxypropylcellulose (Mwapproximately equal 370000) was dissolved in 350 ml of anhydrous N-methylpyrrolidone at 80°C. Then, to the mixture was added 1.4 g (0.014 mol) of succinic acid anhydride and 1.71 g (0.014 mol) of 4-dimethylaminopyridine. The reaction mixture is left overnight at 80°C. a Solution of the cooling gap is Ali to room temperature and was added 400 ml of isopropanol. The polymer was besieged from 3000 ml of diethyl ether, was filtered and successively washed with 300 ml of diethyl ether. Finally, the polymer was dried in vacuum at 40°C.

Then the polymer was dissolved in DMF and was introduced into the reaction with NHS in the presence of dicyclohexylcarbodiimide, which received the compound that contains NHS-ester groups capable of reacting with amino groups and thiol groups.

1. A multi-layered sheet of tissue adhesive, comprising a structural layer or laminate, with specified structural layer or laminate includes one or more synthetic polymers having film-forming properties, and to the specified structural layer or laminate attached to a layer of material intended for contact with tissue, including ternary copolymer of poly(V-AAC-AAC(NS)).

2. The sheet according to claim 1, which includes a structural laminate comprising two or more discrete layers connected to each other.

3. The sheet according to claim 2, in which the laminate includes alternating layers of a polymer having film-forming properties, and a material containing reactive functional groups.

4. The sheet according to claim 3, which includes a structural laminate comprising two layers of film-forming polymer and located between the layer of reactive material, and the layer intended for to the beat with a cloth.

5. The sheet according to claim 4, in which the reactive material includes a ternary copolymer of poly(VP-AAc-AAc(NHS)).

6. The sheet according to claim 1, in which one or more polymers having film-forming properties, are polyesters.

7. The sheet according to claim 6, in which polyesters selected from the group consisting of polylactic acid, polyglycolic acid, polycaprolactones, polyhydroxyalkanoates and copolymers and mixtures of any of these substances.

8. The sheet according to claim 7, in which polyesters selected from the group consisting of polylactic acid, polyglycolic acid and copolymers and mixtures of these acids.

9. Sheet of claim 8, in which complex the polyester is a poly(lactide-co-glycolide).

10. The sheet according to claim 3, in which the reactive functional group selected from the group consisting of imidapril, p-nitrophenylarsonic, NHS-esters, epoxides, isocyanates, acrylates, vinylsulfonic, orthopaedic-disulfide, maleimide, aldehyde groups and iodated.

11. Sheet of claim 10, in which reactive functional groups are NHS-ester groups.

12. The sheet according to claim 1, the total thickness of which ranges from 0.01 to 1 mm.

13. The sheet 12, the total thickness of which is between 0.015 to 0.05 mm

14. The sheet according to claim 1, in which the layer intended for contact with tissue, the leaves more than 50% of the total thickness of the sheet.

15. The sheet according to claim 1, which includes a structural laminate, and the specified laminate composed of n layers of film-forming polymer and n-1 layers of material containing reactive functional groups, which are located between these layers of film-forming polymer, and a layer of material intended for contact with tissue, including ternary copolymer of poly(V-AAC-AAc(NHS)); the value of n is 1, 2 or 3.

16. The sheet 15 in which the film-forming polymer is a biodegradable polymer.

17. The sheet according to claim 1, which includes a structural laminate, and the specified laminate composed of n layers of biodegradable complex polyester and n-1 layers of material containing reactive functional groups, which have between these layers of biodegradable complex of polyester and a layer of material intended for contact with tissue, including ternary copolymer of poly(V-AAC-AAC(NS)); the value of n is 1, 2 or 3.

18. The sheet 17, in which a complex polyester selected from the group consisting of polylactic acid, polyglycolic acid, polycaprolactones, polyhydroxyalkanoates and copolymers and mixtures of any of these substances.

19. Sheet p, in which complex polyester selected from the group consisting of polylactic acid, polyglycolic acid and FOSS is Kerov and mixtures of these acids.

20. The sheet according to claim 19, in which complex the polyester is a poly(lactide-co-glycolide).

21. The sheet 15, in which the material containing reactive functional groups, is a ternary copolymer of poly(V-AAC-AAC(NHS)).

22. The sheet according to any one of p-21, in which the value of n is 2.

23. Sheet according to article 22, in which the material intended for contact with the tissue, is more than 50% of the total thickness of the sheet.

24. Sheet according to item 23, in which the material intended for contact with the tissue, is more than 60% of the total thickness of the sheet.

25. A method of manufacturing a sheet according to any of the preceding paragraphs, and the method includes the step forming layer (s) of the structural layer or laminate with the subsequent formation of the layer intended for contact with the cloth.

26. The method for attaching one surface of the fabric to another fabric, or a method of sealing the surface of the fabric; however, this method includes overlaying the surface of the fabric sheet made in accordance with any of claims 1 to 24.



 

Same patents:

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.

The invention relates to medicine, namely to surgery

FIELD: medicine.

SUBSTANCE: invention refers to medicine, more specifically to stents and bag catheters with improved rapamycin release coating, and also to methods for producing such coatings.

EFFECT: production of stents and bag catheters with improved rapamycin release coating.

10 dwg, 24 ex

FIELD: medicine.

SUBSTANCE: group of inventions refers to medicine, and can be used for making an implanted prostheses and blood compatible coating for such prostheses. A process of making a blood compatible product (6) involves the following stages: making a mould (7) having a product configuration (6); adjusting a polytetrafluoroethylene membrane to the product configuration (6) by heating of the membrane and attaching it to the mould (7) be exposing to differential pressure generated between two membrane surfaces; cooling of the membrane adjusted in such a way with simultaneously keeping it in a condition of attaching to the mould (7); and removing the adjusted membrane from the mould (7). The membrane is made of a porous polytetrafluorethylene which was not thermostabilised to adjust the membrane to the product configuration (6), and membrane fibres have no preferential orientation, and heating of the membrane when adjusting the membrane to the product configuration (6) is performed at gel point of said porous polytetrafluorethylene. The invention also refers to a cardiac prosthesis in which at least one of its portions comprises a blood compatible coating generated by implementing said process.

EFFECT: group of inventions allows making the blood compatible irregular products made of polytetrafluorethylene.

9 cl, 9 dwg

FIELD: medicine.

SUBSTANCE: invention refers to medicine and follow-up care (medical rehabilitation), and can be used for antiseptic surface preparation of medical devices made of polymeric materials used in minor orthopaedics. A method consists in forming on a device surface an antiseptic coating of a preparation containing biocide based on a nanodispersed powder of bentonite intercalated by silver or/and copper ions in a plastic binder solution. The particle size of the bentonite powder is no more than 150 nm. The antiseptic coating process is executed in two stages. At the first stage, a surface of the device made of a polymeric material based on silicon rubbers of molecular weight 2·105-6·105 is modified in low-temperature oxygen plasma at oxygen (O2) consumption 0.8-7 l/h, working pressure equal to (70-135)±5 Pa, at high-frequency electromagnetic radiation of frequency 13.56 MHz and power 20-40 Wt, during (2-3)±1 minutes. At the second stage, the modified surface of the device is treated with the antiseptic preparation wherein the plastic binder is fluoracrylic polymer in solvent based on perfluoroisobutylmethyl and perfluorobutylmethyl esters in the ratio, wt %: fluoracrylic polymer - 1-3, solvent - the rest, with perfluoroisobutylmethyl ester - 20-80 wt % and perfluorobutylmethyl ester - 20-80 wt %. The antiseptic preparation has the following proportions: biocide: plastic binder in solvent, as 1:(50-100) weight parts.

EFFECT: use of the invention enables forming a coating with antiseptic and service effective properties on the surface of the devices made of organosilicon polymers of molecular weight 2·105-6·105.

2 cl, 3 ex

Stent coating // 2380059

FIELD: medicine.

SUBSTANCE: invention concerns medicine and is intended for cardiovascular surgery in stenting of arteries. In a stent coating containing a polymer material with an active antiproliferative substance, said polymer material presents a copolymer of butyric and valeric acids, while the active antiproliferative substance is rubomycinum. The amount of the copolymer of butyric and valeric acids per one stent is 2-15 mg/stent, while rubomycinum composes a polymer layer in amount 0.002-0.025 mg/stent.

EFFECT: creation of simpler stent coating expressing biocompatibility and haemocompatibility, with optimal physical-mechanical properties, and also slow bioresorbility in vivo without production of toxic products and negative reactions from a vascular wall while in service.

3 cl, 3 dwg, 1 tbl, 5 ex

FIELD: medicine.

SUBSTANCE: invention concerns medicine. The device implanted into a human body or an animal is described, containing the bioblasted polymer including units of ethylene carbonate of the formula (A): -(-C(O)-CH2-CH2-O-)- (A), in number of 70-100 molar % which possesses internal viscosity 0.4-4.0 dl/g at determination in chloroform at 20°C in concentration of 1 g/dl and 5-50°C vitrification temperature, blasted at the expense of superficial erosion which is supervised on the mechanism of non-hydrolytic scission.

EFFECT: restoration of normal blood flow and keeping an artery opened after installation of a balloon catheter.

13 cl, 1 dwg, 2 ex

FIELD: medicine.

SUBSTANCE: invention relates to method of manufacturing medication-releasing medical device, selected from group consisting of vascular devices, prostheses, probes, catheters, tooth implants or similar, applied in treatment an/or prevention of vessel restenosis, which leads to acute circulatory collapse , conditioned by reduction of circulating blood weight. Claimed method includes application on device by means of submerging into suitable solution or by means of dispersion, of at least one medication layer, when necessary introduced into polymer able to release said medication; polymer which has active functional groups, selected from group consisting of amino groups and sulphhydryl groups capable of chemical binding of biological molecules in one step by means of cold plasma methods; and biological molecules on said polymer surface. Also described is medication-releasing medical device, obtained by said method and application of polymers with reactive functional groups for covering medical devices, preferably vessel stents, by means of cold plasma application.

EFFECT: due to application of definite class of polymers using cold plasma, claimed method is more technological, namely facilitates application of polymer without destroying its functional groups properties and better polymer binding with biomolecules resulting in slower, controlled release of medication from medical device.

36 cl, 1 tbl, 5 ex, 2 dwg

FIELD: medicine.

SUBSTANCE: are described medical implants which release anthracycline, fluoropyrimidine, antagonist of folic acid, podophyllotoxin, camptotecine, hydroxyurea or platinum complex.

EFFECT: suppressed or reduced rate of implant-associated infections.

83 cl, 1 dwg, 2 tbl, 25 ex

Vascular stent // 2325193

FIELD: medicine.

SUBSTANCE: stent includes hyaluronic acid polymer-based coating, and mentioned hyaluronic acid polymer is ester derivative of hyaluronic acid.

EFFECT: effective prevention of restenosis phenomenon.

40 cl, 3 dwg, 7 tbl, 9 ex

FIELD: chemistry of polymers, medicine.

SUBSTANCE: invention describes covers for medicinal device made of metal. Cover comprises polymerized derivative of alkoxysilane bound covalently with surface of medicinal device, lactone polymer bound covalently with functional groups of polymerized derivative of alkoxysilane by the in situ polymerization process accompanying with the cycle opening, and at least one layer of polyester applied on bound lactone. Biologically active agents can be applied together with layers of polyester. Such cover-containing surfaces can be used in medicinal devices, in particular, in stents. Cover is biocompatible and provides prolonged release of biologically active agents for from some weeks to some months.

EFFECT: improved and valuable properties of cover.

49 cl, 8 dwg, 7 tbl, 15 ex

FIELD: surgical facilities.

SUBSTANCE: invention provides material suitable as hemostatic and wound-healing remedy in low-invasive internal surgery involving endoscopic techniques. Allogenic connective-tissue formations (tendons, fascias, dermis) are subjected to mechanical cleaning to remove the rests of adjoining tissues and foreign bodies, washed with running water during 5-10 min, degreased by cold (+4оС) acetone, placed for 5-10 min in 3% hydrogen peroxide solution to remove blood, and thrice rinsed with 0.9% sodium chloride solution. Treated tissues are frozen in cryogenic chamber at -45оС and dried in vacuo to constant weight using liophilic drying technique. Dried material is then wetted at 1:5 weight ratio in solution containing calculated quantities of hemostatic (fibrinogen), fibrinolysis inhibitor (aminocapronic acid), and antibiotic (cephalexin) for 10-20 min until biomaterial structure is completely and uniformly impregnated. Solution id prepared at +4оС by consecutively dissolving 0.2 g cephalexin and 1 g fibrinogen in 10 ml of 5% aminocapronic acid solution. Thereafter, biomaterial is once again frozen and subjected to liophilic drying, then ground on blade-type mill (e.g. "Cyclotec", Foss Tecator) to particle size 0.1-0.25 mm, which are packaged by 0.5 g doses into glass 20-ml bottles, tightly sealed, and sterilized by gamma radiation in dose 2.5 MRad (25 kGr).

EFFECT: simplified technology, improved quality and structure of material.

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

Up!