Antimicrobial/antibacterial medical devices, coated with traditional preparations of chinese medicine

FIELD: medicine.

SUBSTANCE: antimicrobial composition for coating a medical device includes a material, which forms a polymer film, and an antimicrobial preparation from the traditional Chinese medicine, selected from a group: extract of Houttuynia cordata, sodium houttuyfonat and sodium new houttuyfonat or their mixtures. The medical device, covered with an antimicrobial composition, is made in the form of an implanted device.

EFFECT: invention provides the antimicrobial effectiveness with respect to microorganisms - causative agents of surgical infections.

19 cl, 2 dwg, 7 tbl, 4 ex

 

This invention relates to antimicrobial/antibacterial compositions and their use for coating objects such as medical devices. More specifically, antimicrobial/antibacterial compositions, which can be obtained from the funds of traditional Chinese medicine.

Each year in the United States of America is a large number of surgical procedures. According to current data per year is more than twenty-seven million of these procedures. Approximately two to three percent of cases develop or postoperative surgical wound infection (RI). The absolute number of such cases each year is estimated at 675 thousand

In the operating conditions when using medical devices possible risk of infection. The risk of infection increases dramatically when using invasive or implantable medical devices such as intravenous catheters, arterial grafts, intrathecal or intracerebral grafts and prostheses, creating the entrance gate for pathogenic microorganisms, being in direct contact with tissues and body fluids. The infection of the wound may be the result of contamination of the medical device by bacteria. For example, during surgical procedures bacteria from the surrounding atmosphere can popdata surgical wound and attached to the medical product. The bacteria can spread, getting through the implantable device into the surrounding tissue. These bacteria on medical product can lead to infection in patient morbidity and mortality. Another unfavorable aspect relates to the formation of biofilms. Bacteria living in a biofilm, usually significantly different properties from free bacteria of the same species due to the dense protective environment in the film. Such an environment can increase resistance to antibiotics as a dense extracellular matrix and the outer cell layers protect the inner layers of the microbial community. In some cases, may increase antibiotic resistance in 1000 times.

There are a number of methods to reduce the risk of infection associated with the contamination of medical devices involved in the processing of medical devices with antibiotics. Preferably, when using such devices contain an effective amount of antimicrobial drug.

Traditional Chinese medicine, or TCM, includes a range of traditional medical practices originating in China. They include such methods as the use of medicinal herbs, acupuncture, diet therapy, and massage Tiiu Kuik have conquered and shiatsu. Qigong and Taijiquan are also closely connected with TCM. Although TCM is widely recognized as the main areas of medicine in East Asia, the Western world marrow transplantation is often considered an alternative system.

Houttuynia heart-shaped, also known as herba houttuyniae, and in Japan as “dokudami” is a perennial plant, widespread in Asia, including Japan, Taiwan, the Himalayas and in Java. Houttuynia cordate - flowering plant that grows in moist shady places and is the only species of the genus Houttuynia. In China, this plant is literally called "grass with fish smell". It is used in traditional Chinese medicine. Drink dokudami cha, Japan is literally called "tea from Houttuynia sweetheart", is an infusion from the leaves of Houttuynia cordate leaf red tea and plants "cuckoo tears".

In U.S. patent publication No. 2002/0031559, we offer a suppository for the treatment of human diseases, consisting of at least one plant and inert carrier for the preparation of a suppository. Suppositories of herbs is also proposed as a means of treating unwanted symptoms of allergic rhinitis, sinusitis, nasal congestion, expiry of the nose, polyps, infections, fever, cough, cramps, dizziness, convulsions in humans. Also the methods of obtaining, implementing and reporting structures for Chinese medicine in the form of suppositories for the treatment of diseases in humans. Suppositories may include Houttuynia heart as ing is edient.

In U.S. patent publication No. 2006/0264347 described antimicrobial composition containing a cationic surface-active agent (surfactant), obtained by condensation of fatty acids and esterification of dibasic amino acids, such as laurylamine, and iodized sulfonic compound, such as diiodomethyl-p-tamilselvan. The composition can be used as an independent antimicrobial composition or in combination with medical products or medical devices.

In U.S. patent No. 7485327 features a composition comprising the extract of lemon balm leaves, known suppression of angiogenesis and activity of metalloproteinases in the matrix. Indicated that the leaf extract of Melissa suppresses angiogenesis and activity of metalloproteinases in the matrix, so it can be used for the treatment or prevention of diseases associated with angiogenesis and activity of metalloproteinases in the matrix. The composition containing the extract of the leaves of lemon balm may also contain more than one component from other antiangiogenic, anticancer, anti-inflammatory or anti-oxidant substances. This particular composition containing the extract of lemon balm leaves can be used in the pharmaceutical, dietary and/or cosmetic purposes. U.S. patent No. 7485327 offers the use of an extract of a plant-Houttuynia with davidnay together with the leaves of lemon balm as an antibacterial agent. The composition can be used together with the implant.

In the Chinese publication No. 2005-10046735 features ophthalmic preparation containing a new sodium houttuyn and the process of its receipt, and the product contains sodium new howtospot as active ingredient and a pharmaceutically acceptable auxiliary materials; it can be used for preparation of various ophthalmic medications, including eye drops, gels, opaque liquid, microspheres, microemulsions, implants and effervescent tablets.

WO9850087 offers medical device with a coating adapted for passing through narrow openings, such as catheters. The coating gives the catheter strength without significantly increasing its thickness without reducing the tensile strength.

WO0126708 offers polymer valves, instruments with valves, equipment and tools. The proposed devices include implantable device with a sufficiently long service life corresponding to therapeutic requirements of the patient and capable of delivering a certain amount of the drug in response to biological stimuli.

Despite these achievements in this area, it would be desirable to include antimicrobial/antibacterial composition in implantable medical devices reduced the I the risk of infection. In addition, it would be desirable to obtain antimicrobial/antibacterial composition of one or more of the traditional Chinese medicine, and displays its action upon contact with fluids of the human body.

In one aspect seems antimicrobial composition for coating medical devices. The antimicrobial composition includes a material that forms a polymer film, and antimicrobial drug of traditional Chinese medicine, which includes material selected from the following group: extract Houttuynia cordate, sodium houttuyn and sodium new houttuyn, or mixtures thereof.

In one form of the antimicrobial composition contains sodium howtospot or sodium new howtospot with an average particle size less than about 100 microns.

In one form of the antimicrobial composition contains sodium howtospot or sodium new howtospot with an average particle size less than about 50 microns.

In one form of the antimicrobial composition contains sodium howtospot or sodium new howtospot with an average particle size less than about 40 microns.

In another form of the antimicrobial composition contains sodium howtospot or sodium new howtospot with an average particle size less than about 40 the km and a standard deviation of particle size less than about 30 microns.

In the following form material forming the polymer film contains a biocompatible, biodegradable polymer, copolymer hydrogel or a mixture thereof.

In another form of the material forming the polymeric film is selected from aliphatic polyesters, poly(amino acids), copoly(complex-ethers), polyalkyleneglycol, polyamides, poly(ethylene glycol), poly(iminocarbonothioyl), polyarteritis, polyoxyethyl, polyamidoamine, polyoxyethyl with amine groups, poly(anhydrides), polyphosphazenes, polysaccharide gels, and their copolymers and mixtures.

In another form, the material forming the polymeric film is selected from Homo - and copolymers of lactide, glycolide, Epsilon-caprolactone, a pair of dioxanone, trimethylene carbonate, alkyl derivatives of trimethylhexanoate, polyesters of monoglyceride, hydrogels of carboxymethyl cellulose and mixtures thereof.

In one form, the material forming the polymeric film is selected from homopolymers of lactide (PL) and homopolymers of glycolide (GHG).

In another form, the material forming the polymeric film is selected from copolymers of PL and PG.

In another form the antimicrobial composition comprises calcium stearate.

In another aspect of the medical device. The medical device includes an antimicrobial composition comprising a material selected from the trail is a growing group: extract Houttuynia cordate, sodium houttuyn, sodium new houttuyn and mixtures thereof.

In one form the medical device is an implantable medical device.

In another form the medical device is in the form of fibers, mesh, powder, microspheres, flakes, sponge, foam, fabric, nonwoven material, woven material, a film, a device for securing sutures, suture material, catheter, suture brackets, stent, surgical tacks, clips, plates and screws, devices for drug delivery, barrier to prevent adhesion and adhesive for fabrics.

In another aspect is provided a method of producing coatings for medical devices. The method includes a step of forming a suspension comprising a polymeric material constituting the film, and antimicrobial drug of traditional Chinese medicine, which includes material selected from the following group: extract Houttuynia cordate, sodium houttuyn and sodium new houttuyn, or mixtures thereof.

Another aspect is the method of making an antimicrobial medical device, comprising the stage of applying an antimicrobial coating on a medical device, an antimicrobial coating comprising a material forming a polymer film; and an antimicrobial drug, comprising a material selected from the following group: extract how is tuinei cordate, sodium houttuyn and sodium new houttuyn, or mixtures thereof.

In one form of the medical device with an antimicrobial coating is packaged and sterilized.

This application describes several advantages: excellent antimicrobial efficacy in vitro against organisms-pathogens surgical infections, the ability of a uniform and homogeneous distribution of these coating compounds, controlled release of substances with antimicrobial properties, and improved efficiency and stability described antimicrobial coating compounds. In addition, medical devices covered are described antimicrobial compositions are characterized by excellent stability after sterilization. In addition, possible side effects there are limited due to the nature of antimicrobial substances and coating compositions described in this application.

In Fig. 1 shows a diagram of the influence of particle size on the concentration of sodium AutoUpdate in the suture material coated with sodium autoupdator; and

In Fig. 2 graphically presents the effect of particle size on the zone of inhibition of growth in the suture material coated with sodium autoupdator.

All technical and scientific terms used herein, unless otherwise indicated, have a common value, ponat the e any specialist, working in the field, which is the ratio of the present invention. Phraseology, terminology, and notes as used in this patent application is intended to describe and should not be construed as limiting value.

In addition, all technical and scientific words, terms and phrases, introduced, defined, described or explained in the above sections, the same or similar applicable to illustrate the descriptions, examples and paragraphs of the patent application.

Used in this description and in the claims, the singular number also include the plural objects, unless explicitly from the context.

The term "biodegradable" means that the polymer is able to decompose or deteriorate in any other way in the body so that the products of its decomposition can be absorbed or excreted from the body.

Each of the following terms: "includes", "including" the "has", "with", "contains" and "contain", and their linguistic and grammatical variants, derivatives or complex forms herein shall mean "including without limitation".

In illustrating the descriptions, examples and paragraphs of the patent application the numerical value of the parameter, property, object or sizes may be specified or described in numeric format. It should be understood that indicated the p number format are presented to illustrate the application forms, described in this application, and it should not be understood as strictly limiting described in this document forms.

Accordingly, specified or described numerical range also applies to, or includes, all possible subranges and a separate numeric values (numeric value can be expressed as a whole number, fraction or decimal fraction) within the specified or described numerical range. For example, specified or described numerical range from 1 to 6 also refers to and includes all possible subranges such as from 1 to 3, 1 to 4, from 1 to 5, 2 to 4, from 2 to 6, from 3 to 6 and t p., and individual digital values, for example 1, 1,3, 2, 2,8, 3, 3,5, 4, 4,6, 5, 5,2 and 6, in a specified or described numerical range from 1 to 6. This really is regardless of the width of the numeric range, extent or size of the described numerical range.

In addition, to specify or describe a numeric value, the phrase "in the range between approximately the first value and approximately the second value is considered equivalent to and means the same thing as the phrase "in the range of from approximately the first value to approximately the second value and, thus, these two phrases are interchangeable. For example, to specify or describe the room temperature can be used as the phrase "room temperature is temperature is in the range from about 20°C to about 25°C,” and is equivalent to the phrase "room temperature refers to a temperature between approximately 20°and approximately 25°C”.

It should be understood that the various described here form is not limited in its application to the details or sequence, such as the number, stage of procedures and sub-phases of padroado, use or application forms method, details of type, composition, construction, arrangement of elements, the order and number of compositions, products, systems, subsystems, mechanisms, structures, components, elements, and configurations, and, peripheral equipment, facilities, tools and materials specified in illustrating the following descriptions and examples, unless otherwise indicated. Composition, device and methods described in this application may be practiced or implemented in accordance with various other alternative forms and different alternative ways.

In the present application is described antimicrobial composition for coating medical devices. The antimicrobial composition includes a material that forms a polymer film, and antimicrobial drug of traditional Chinese medicine (TCM), which includes material selected from the following group: extract Houttuynia cordate, sodium houttuyn and sodium new houttuyn, or mixtures thereof.

As mentioned above, the plant Houttuynia cordate widespread in Asia, including Japan, China, the Himalayas, and Java. Houttuynia cordate - flowering plant, growing in moist shady places and is the only species of the genus Houttuynia. It is also used in TCM. Drink dokudami cha, Japan is literally called "tea from Houttuynia sweetheart", is an infusion from the leaves of Houttuynia cordate leaf red tea and plants "cuckoo tears". As the extract striped bamboo extract Houttuynia cordate produced by the method of low-temperature extraction under pressure.

Raw materials from plants of the family houttuyniae consists of the fresh or dried parts of Houttuynia heart. Key antimicrobial agent is houttuinen or decanolactone, unstable and prone to polymerization. Synthesized in the present time derivative of sodium sulfite, known as sodium howtospot or new sodium houttuyn, more stable and therefore better suited for use in medical purposes.

It is shown that houttuinen has a strong suppressive effect on various bacteria and viruses. Double effect against infection by prevention and treatment of secondary infections, as well as the effect on viruses, exceeds the normal action of antibiotics. The vitro studies showed pronounced inhibitory effect Houttuynia on the microorganism Micrococcus catarrhalis, Staphylococcus aureus, Bacillus influenzae, pneumococcus, Escherichia coli, Bacillu dysenteria, Bacillus proteus, Bacillus diphtheriae and Mycobacterium, and Bacillus typhi and Leptopira.

It is shown that the broth containing houttuinen, inhibits influenza virus (Asia-Chinese origin) and the virus of epidemic hemorrhagic fever (EHFV) in vitro, and is also able to delay cytopathogenic action orphan virus strain 11 (ECHO11). It is shown that the introduction Houttuynia in oil intraperitoneally to mice contributes to the prophylactics of the disease after infection with influenza virus FM1; protection shall also be provided for the introduction of the drug through the nose and mouth.

Clinical application of Houttuynia heart is traced up to the time of the Tang; the plant described in the book “Chinese Materia Medica.”

Currently available drugs-Houttuynia cordate include water decoctions, pills, injection, syrup for the treatment of acute bronchitis, capsules for sputum drug against cough and asthma Huanglong in the form of powder for preparation of infusion solution, antitussive agent with mango and other

Sodium houttuyn, C12H23O5SNa, also known as decanolactone sodium sulfide, has a molecular mass of 302,36 and is a white or almost white needle powdery crystals with a faint odor. Suitable suppliers of sodium AutoUpdate include Hubei Yuanhe Organic Foodstuffs Co., Ltd, inkou Industrial Area, Zhifang Street, Wuhan, Zhejiang, China 430074 and Second Pharma Co., Ltd., Hangzhou Gulf Fine Chemical Zone, Shangyu, Zhejiang, China 312369.

New sodium houttuyn, C14H27NaO5S, comes in the form of needle-shaped crystals, or white crystalline powder. Its suppliers include: Hangzhou HETD Pharmaceutical & Chemical Co., Ltd., No. 8, Yi Road, Xi Yuan Xi Hu Industrial Park, Sandun Hangzhou, Zhejiang, China 310030 and Linyi Furui Fine Chemical Co., Ltd shandong china, linyi, Shandong, China 251500. New sodium howtospot is a flake or crystalline powder with a slightly unpleasant odor. It is easily soluble in hot water, slightly soluble in cold water and ethanol, and almost insoluble in chloroform and benzene. It is easily soluble in sodium hydroxide solution.

Found that favorable antimicrobial activity of TCM drugs, such as sodium AutoUpdate, may increase after grinding to reduce the average particle size of the crystalline material.

Available on the market howtospot sodium has a particle size in the range from about 1000 to about 4 μm, on average, approximately 145 μm. Such a wide distribution of particle sizes due to different measurement results of the amount of needle-shaped crystals on the long and short axis. The geometry and dimensions of the particles of sodium AutoUpdate promotes the formation of aggregates, leading to uneven distribution of coating is on the substrate. Thus, it was found that the geometry and dimensions of the crystals of raw materials and their distribution, create the need for modification and testing process to obtain acceptable coverage. Reducing the size of the particles is possible by using various well-known methods, for example, ball or jet mill. Ball mill reduces the particle size by mechanical crushing of the material when confronted with hard balls. The principle of operation of the jet mill is the acceleration of particles in the flow of air, gas or vapor, when due to the collision of the particles is their destruction. These techniques destroy the crystals AutoUpdate sodium with the formation of particles with better symmetry and a much more narrow distribution in size. In addition, the distribution of particle size can selectively be reduced even more by classification.

For example, in one form of the antimicrobial composition contains sodium howtospot or new sodium howtospot or a mixture with an average particle size less than about 100 microns. In another form of implementation of the antimicrobial composition comprises sodium howtospot or new sodium howtospot or a mixture with an average particle size less than about 50 microns. In one form of the antimicrobial composition soderzhaniya howtospot or new sodium howtospot or a mixture with an average particle size less than about 40 microns. In another form of the antimicrobial composition contains sodium howtospot or new sodium howtospot or a mixture with an average particle size less than about 40 μm and a standard deviation of particle size less than about 30 microns.

The advantage of the described in this application antimicrobial compositions is that they can serve compositions for coating, using the carrier medium for the delivery of antimicrobial drug on the surface of the medical device. Specialists in this field it is known that coatings traditionally used in the manufacture of certain medical devices, such as, for example, absorbable and non-absorbable multi-fiber suture materials. Examples of medical devices and coatings that can be inflicted on them, can be found in U.S. patents№№ 4201216, 4027676, 4105034, 4126221, 4185637, 3839297, 6260699, 5230424, 5555976, 5868244 and 5972008, each of which is fully incorporated herein. As described in U.S. patent No. 4201216, the coating may contain a film-forming polymer and essentially water-insoluble salt of a fatty acid with a number of carbon atoms C6or higher. As another example, absorbable coating that may be used in absorbable medical device may include poly(alkylene oxalates),where alkylene groups are derived from diols C 6or a mixture of diols from C4to C12that are applied to a medical device from a solution as described in U.S. patent No. 4105034. In the coating composition may include a polymer or copolymer, which may include lactide and glycolide as a bonding agent. The composition may also include calcium stearate as a lubricant. The coating is usually not included in the manufacturing process of medical devices, however, at last it is possible to apply the coating of the antimicrobial composition comprising an antimicrobial agent from the TCM.

Examples of suitable biocompatible, biodegradable polymers that can be used in accordance with the present invention include, without limitation, polymers, selected from the following groups: aliphatic polyesters, poly(amino acids), copoly(complex-ethers), polyalkylacrylate, polyamides, poly(ethylene glycol) poly(aminocarbonyl), polyarteritis, poloxamer, polyamidoamine, polyoxyethyl with amine groups, poly(anhydrides), polyphosphazenes, biopolymers, and copolymers and mixtures thereof.

Applicable aliphatic polyesters include, without limitation, homopolymers and copolymers of lactide (including lactic acid, D-,L - and mesolectal), glycolide (including glycolic acid), Epsilon-caprolactone, para-dioxanone (1,4-dioxane-2-one), trimethylenebis (1,dioxan-2-one), alkyl derivatives of trimethylhexanoate, polyesters of monoglyceride and polymer mixture.

Preferred polymers include homopolymers of lactide (PL) and homopolymers of glycolide (GHG)emissions. More preferred are copolymers of PL and PG (MRO), for example, copolymers containing from about 80 to about 99 molar percent of the SQUARE.

In one form, the material forming the polymer film contains a biocompatible, biodegradable polymer, copolymer hydrogel or mixture of hydrogels. The material forming the polymer film may be selected from aliphatic polyesters, poly(amino acids), copoly(complex-ethers), polyalkyleneglycol, polyamides, poly(ethylene glycol), poly(iminocarbonothioyl), polyarteritis, polyoxyethyl, polyamidoamine, polyoxyethyl with amine groups, poly(anhydrides), polyphosphazenes, polysaccharide gels, and their copolymers and mixtures.

In another form, the material forming the polymeric film is selected from Homo - and copolymers of lactide, glycolide, Epsilon-caprolactone, a pair of dioxanone, trimethylene carbonate, alkyl derivatives of trimethylhexanoate, polyesters of monoglyceride, hydrogels of carboxymethyl cellulose and mixtures thereof. The material forming the polymeric film is selected from homopolymers of lactide (PL) and homopolymers of glycolide (GHG)emissions. In one of the Orme material, forming a polymer film is selected from copolymers of PL and PG.

In another aspect, the antimicrobial composition may further contain other components that improve the efficiency of antimicrobial action of compositions, or otherwise to act as the active substance, giving other benefits. These compounds include, without limitation, additional antimicrobial drugs, additional salt or other auxiliary or active substances, giving the songs the best properties or enhance their antimicrobial activity. Such components include, without limitation, antimicrobial drugs, such as triclosan, triclocarban, 2-Phenoxyethanol, chlorhexidine salt, hexetidine and cetylpyridinium; antibiotics; and other active ingredients.

Antimicrobial compositions described in this application can be used for coating materials of the substrate. In addition, they can be a part of the coating that are described here antimicrobial composition. These coatings may include one or more layers. In another form of the antimicrobial composition may also be applied to the already formed device or part in the form of a coating. The device with the coating may be performed, for example, by immersing the device in the composition, sextravaganza, cable is about coating or spraying the composition onto the device and subsequent drying.

Described here antimicrobial compositions are used separately or in combination with other polymer coating to make the surface of the substrate favorable properties. These compositions can also be used for delivery of pharmaceuticals, for example, antimicrobial, anticoagulant, healing, antiviral, antifungal, anti-platelet or possessing other properties of substances on a substrate.

Antimicrobial compositions can also be used to inhibit the growth of algae, fungi, molluscs or microorganisms on the surface. Described in this application of the antimicrobial composition can be used as herbicides, anti-fogging, drugs for the diagnosis and preliminary studies, as well as antifolates.

Dispersions for coatings can be prepared preferably by transferring all water-soluble components into a form that is soluble in an organic solvent or solvent mixture, and then adding insoluble compounds to the solution. Disperse system is obtained by combining the above-mentioned compounds in the vessel, preventing the evaporation of the solvent, and subsequent mixing with a mechanical stirrer. The mixer must have sufficient energy to create a homogeneous dispersion systemiii suspension without aggregation of insoluble compounds. Suitable devices include high-speed blade mixer, homogenizer, ultrasonic baths, faucets type "vortex" or other devices for mixing, usually used to produce dispersions, suspensions or emulsions.

Antimicrobial drugs described in this application, may be present in the form of compositions for coating in a concentration of from about 1 to about 15 mass %, or from about 1.5 mass % to about 7.5 mass %, or from about 2.0 to about a 5.0 mass %. In one form of antimicrobial drugs from TCM described in this application are present in a concentration of approximately 2.5 mass %. In another form of antimicrobial drugs from TCM described in this application are present in a concentration of approximately 5 mass %.

In the coating containing the antimicrobial agent in TCM, such as disperse systems sodium AutoUpdate, medical device, it is necessary to control the volume and distribution of material to cover, which is applied to the medical device. The operation of the coating may be produced by conventional dipping and wiping as described in U.S. patent No 5817129, the contents of which are incorporated herein by reference, when the substrate is passed is via the vessel, containing a suspension or dispersion system, and then through a series of wheels to remove excess coating; then it passes through the drying system to remove solvent. Coatings can also be applied to the medical device by spraying, unearth, dipping, coating tape and other methods of coating, known in the industry.

In another aspect described in the present application relates to the production of medical devices containing antimicrobial compositions described in this application. In another form of implementation of the medical device is in the form of fibers, mesh, powder, microspheres, flakes, sponge, foam, nonwoven material, woven material, a film, a device for securing sutures, suture material, catheter, suture brackets, stent, surgical tacks, clips, plates and screws, devices for drug delivery, barrier to prevent adhesion and adhesive for fabrics. The medical device may be coated with one or more antimicrobial compositions described in this application. In one form the medical device can be coated or impregnated antimicrobial composition by dipping, unearth, spraying or coating a medical device, an antimicrobial composition, as mentioned above, and the show is on in the examples below.

In another form of implementation described here antimicrobial agents can be mixed with the polymer or mixture of polymers used for the manufacture of medical devices, and then molded or pressoffice in the form of medical devices. Antimicrobial drugs described in this application, may be present in the form of a polymer or polymer mixture is from about 1 to about 15 mass %, or from about 1.5 to about 7.5 mass %, or from about 2.0 to about a 5.0 mass %. In one form of implementation of antimicrobial drugs from TCM described in this application are present in a concentration of approximately 2.5 mass %. In another form of antimicrobial drugs from TCM described in this application are present in a concentration of approximately 5 mass %. As is well known to specialists in this field, the initial mixture of antimicrobial drug and polymer may be formed and then mixed with a balanced amount of polymer or polymer mixture to obtain the desired concentration of antimicrobial drug related to TCM.

In another aspect is provided a method of obtaining coatings for medical devices. The method includes a step of forming a slurry containing polymer material forming the film, and antimicrobial drug and the traditional Chinese medicine, comprising a material selected from the following group: extract Houttuynia cordate, sodium houttuyn and sodium new houttuyn, or mixtures thereof.

Another aspect is the method of making an antimicrobial medical device, comprising the stage of applying an antimicrobial coating on a medical device, an antimicrobial coating comprising a material forming a polymer film; and an antimicrobial drug, comprising a material selected from the following group: extract Houttuynia cordate, sodium houttuyn and sodium new houttuyn, or mixtures thereof.

As you know, medical devices are usually sterilized so that they are on microorganisms have lost viability. In particular, the sterility in the industry is considered to be the minimum level of guaranteed sterility 10-6. Examples of sterilization processes described in U.S. patents№№ 3815315, 3068864, 3767362, 5464580, 5128101 and 5868244, each of which is fully incorporated herein. In particular, absorbable medical devices can be sensitive to radiation and heat. Accordingly, it may be desirable to carry out the sterilization of such products using commonly used sterilizing gases or agents, such as gaseous ethylene oxide.

Absorbable medical the disorder are sensitive to moisture, and consequently, they are often packaged in a sealed foil packaging. However, a sealed foil packaging also impermeable and for sterilizing gas. To compensate for this phenomenon and to be able to use the packaging foil when sterilized with gaseous ethylene oxide, were developed processes, which use foil packaging with ventilation devices for the transmission of gases (for example, non-woven Tyvek®, manufactured by E. I. du Pont de Nemours and Company, Wilmington, Delaware, USA). Ventilation devices are installed on the open end of the packing and leak air, water vapor and ethylene oxide inside the package. After completion of the sterilization process packing seal near the ventilation device, and the device is separated from the sealed package, and then cut off or removed in any other way, resulting in hermetically sealed packaging. Another type of packaging foil having a ventilation hole is packaging type bag having a ventilation device installed near one end of the packing, and the ventilation device is hermetically secured to one of the sides of the package, forming a vented portion. After completion of the sterilization process UPA is ovcu seal near the ventilated part, and sealed packaging cut off vented side.

Below described specific forms as examples. Although the following examples illustrate certain embodiments of the present invention should not be interpreted as limiting the scope of the invention, but rather as an additional tool for a complete description of the invention.

EXAMPLES

Research method used to measure the sodium AutoUpdate

As stated above, the antimicrobial compositions for coating medical devices described in this application, may include material to obtain a polymer film; and an antimicrobial agent containing material selected from the following groups: plants extract Houttuynia cordate, sodium houttuyn and sodium new houttuyn, and mixtures thereof. In one form of the composition may also include calcium stearate, a copolymer of lactide and glycolide. To accurately determine the concentration of sodium AutoUpdate (NC) in the medical product is coated, for example rassassyvesa suture material was developed by the following method.

Research methods previously available for the determination of HX, includes titration of iodine and method for measuring absorption in the UV range. When using such methods to opredelyaemaya in NC absorbable suture material is a tendency to interact with the filament material, therefore, such methods are inefficient for quality control of the product. For example, the basic solution used in the titration of iodine that reacts with the polymer, which is made of suture material. In addition, for each study requires several tens of grams of suture material to achieve sufficient sensitivity titration method. Method UV spectroscopy is more sensitive; however, the coating can prevent the UV-range.

Thus, a method was developed for the determination of sodium AutoUpdate using high-performance liquid chromatography (HPLC). This method is applicable to both non-sterile and sterile absorbable medical devices, including suture material.

The developed method consists of two stages: 1) removal of sodium AutoUpdate of absorbable suture material in an appropriate solvent system and (2) the detection and quantitative determination of sodium AutoUpdate by HPLC with UV detector.

The solubility of sodium AutoUpdate in cold water and most organic solvents, such as acetonitrile and methanol, a minor. Sodium howtospot must be completely removed from the coating of medical devices, which, as shown, may also contain calcium stearate and sprinklers which measures lactide/glycolide and be dissolved in the solution for extraction to quantify. It was found that the mixed system of solvents of different polarity and with the appropriate pH allows to achieve the desired efficiency of extraction. The solvent system consists of 70% of the phosphate buffer in water pH to 10.8% and 30% acetonitrile. The extraction procedure involves placing a sample of medical devices in the solvent and shaken for 30 minutes at room temperature. Analysis of the efficiency of extraction indicates that more than 99% extraction of sodium AutoUpdate.

For analysis by HPLC as described below, the system was used Agilent 1100 column Phenomenex, Gemini-NX C18, 250 × 4.6 mm, 5 μm. As the mobile phase used 70% phosphate buffer pH to 10.8% and 30% acetonitrile. Sodium howtospot was determined using a UV detector at a wavelength of λ=283 nm. The conditions of HPLC were as follows:

Column: Gemini-NX 5 ám, 110A°, 4.6×250 mm, Phenomenex

Mobile phase: CH3CN: buffer* 300: 700

* 0,017M K2HPO4, an aqueous solution of pH=10,8

Rate of flow: 2.0 ml/min

The column temperature: 55°C

Volume of sample: 10 μl

Analysis duration: 8 minutes

Example 1. The manufacture of suture material with a coating of funds TCM

Copolymers of L(-) lactide/glycolide containing 65 mole % lactide and 35 molar% of glycolide, was dissolved in uksousdimitilovom feeds 45 wt.%. To the solution was added sodium houttuyn (Second Pharm Co LTD steam the Oia# 071213) in an amount of 2.5 and 5 wt.%. Then to the solution was added calcium stearate in the amount of 4.5 wt.%. The solution was stirred at the "vortex" at room temperature until a uniform suspension. Colored braided suture 2/0, Polyglactin 910 covered with slurry by dipping. Then suture material was dried at room temperature. Suture material, covered by means of TCM, cut into fragments of length 68,9 cm and sterilized by ethylene oxide.

Made so suture material coated investigated to determine the physical properties. Suture material with a coating of tools TCM has normal physical test, indicating a preservation of normal physical properties of the original thread. Suture material with a coating of sodium AutoUpdate, as discussed above, was identified as the prototype of the TCM-1.

Example 2. Stability after sterilization by ethylene oxide

Suture material TCM-1, prepared as described in example 1 were analyzed by HPLC and determination of activity in vitro before and after sterilization with ethylene oxide. The results presented in tables 3 and 4 below indicate acceptable stability suture material coated after sterilization by ethylene oxide.

Example 3.

The effectiveness of antimicrobial activity was evaluated in vitro by zones of inhibition of growth and logarithmic SN is the position number of cells. The data in tables 1 and 2 indicate that the suture material TCM-1 is effective in vitro against Staphylococcus Aureus, methicillin-resistant (MRSA)and Staphylococcus Epidermidis, methicillin-resistant (MRSE).

The results of the evaluation of the effectiveness of suture material TCM-1 in vitro indicate that although it is less effective than commercially available antibacterial suture material Polyglactin 910 (measured by zone of inhibition of growth), it is more effective than commercially available antibacterial suture material Polyglactin 910 measured on a logarithmic decrease in the number of cells, suggesting a different mechanism of action. Apparently, TCM-1 has a rapid bactericidal effect on susceptible microorganisms. This differs from predominantly bacteriostatic activity of triclosan, which is used for coating a commercially available antibacterial suture material Polyglactin 910.

Table 1
The efficiency of in vitro by zones of inhibition of growth
Suture materialThe zone of inhibition of growth (mm)
MRSAMRSE
Suture material TCM-1 2,5% 1,61,8
Suture material TCM-1 5%2,43,0

Table 2
The efficiency of in vitro on a logarithmic reduction
Suture materialLogarithmic reduction
MRSAMRSEE. coli
Suture material TCM-1 2,5%4,04,00,7
Suture material TCM-1 5%4,04,01,0
Antibacterial suture material Polyglactin 910*1,72,00
The control suture material (Polyglactin without antimicrobial additives*)000
* Commercially available

Table 3
Stability after sterilization by ethylene oxide
MRSA
Suture materialZone of inhibition (mm)Logarithmic reduction
Suture material TCM-1 2,5%1,64,0
Suture material TCM-1, 2,5% MA1,34,0
Suture material TCM-1 5%2,44,0
Suture material TCM-1, 5% MA2,04,0

Table 4
The effect of sterilization MA and storage on the content AutoUpdate Na in the suture material TCM-1
Sodium AutoUpdate
Sample suture materialparts per million*% loss
Suture of 2.5% TCM-1, without the MA, the original d is installed 1968No data
Suture material TCM-1 to 2.5% TCM-1 MA168514.4V
Suture 5% TCM-1, without the MA, the source data4282No data
Suture material TCM-1 5% TCM-1 MA330722,8
% loss = (ppm in the suture material, not treated MA - ppm in the suture material treated EC/ppm in the suture material is not processed EA 100%)

Absorbable suture material was covered with a mixture of selected tools TCM, absorbable polymers and other additives in acetic acid ethyl ester by immersion. After coating the suture material was dried, sterilized and Packed. Found that the products possess the desired physical, mechanical and antibacterial properties.

Example 4. The influence of particle size and distribution of particle size on stability and antimicrobial efficacy of the coating.

Conducted research with suture material coated with sodium autoupdator, with a coating of sodium AutoUpdate prepared using crushed iliasmarinos sodium AutoUpdate. The coating was applied at two levels using the method described above. Particle size was determined by laser diffraction analyzer particle size Beckman Coulter model LS 320. The results of these studies are presented below in tables 5-7 and graphically in figure 1 and 2.

As described below, the coating made using crushed material, provided greater efficiency and a greater amount of sodium AutoUpdate on the suture material with an equal volume of a suspension for coating, and much more sodium AutoUpdate on the surface of the suture and a slight decrease in the percentage of TOC. In addition, when using powdered sodium AutoUpdate not found a significant reduction in the concentration or zones of inhibition of growth when stored at a temperature of 25 and 50°C for 4 weeks. Crushed sodium howtospot created a large zone of inhibition of growth of Staph aureus after sterilization by ethylene oxide. Discovered that powdered sodium howtospot provides more logarithmic decrease in the number of Staph aureus after sterilization by ethylene oxide during storage at a temperature of from 25°to 50 ° C for four weeks.

tr>
Table 5
The influence of particle size and coating on the performance of sodium AutoUpdate (NC)
DescriptionUnground NC
(as received from the supplier)
Crushed NC
(smaller particle size)
The advantages of grinding sodium AutoUpdate
The average particle size (µm)144,737,4
The standard deviation of the particle size (µm)140,125,8
% of particles less than 100 micronsa 50.599,4
% of particles less than 10 microns1,818,2

The content of the NC in ppm in sterile source 5%coverage20846407Grinding NC provides the best cost efficiency, higher content of NC on the surface of the suture material with the same amount of suspension to cover
The content of the NC in ppm in sterile original floor of 7.5%48619436
The TOC content of the NC in ppm in sterile source 5%coverage20,60,9Grinding GC provides more stability to its content on the surface of the suture - % CCA is significantly reduced
The TOC content of the NC in ppm in sterile original floor of 7.5%17,40,2
The content of the NC in ppm after 4 weeks aging at 50°C (5% coverage)1137470When chopping, NH was not observed a significant decrease in the concentration in ppm when stored at 50°C for 4 weeks

The content of the NC in ppm after 4 weeks aging at 50°C (7.5% floor)90510469
The size of zones of inhibition of growth of Staph aureus after sterilization (5% coverage)1,32,5When chopping, NC observed an increase in the size of zones of inhibition of growth of Staph aureus after sterilization by ethylene oxide
The size of zones of inhibition of growth of Staph aureus using sterile 7.5 percent cover2,03,5
0,22,8When chopping, NH was not observed a significant reduction of the zones of inhibition of growth after storage at 50°C for 4 weeks

Zone of inhibition of growth of Staph aureus after 4 weeks storage at 50°C (7.5% floor)1,0a 3.9
Logarithmic growth Staph aureus after sterilization (5%coverage)1,1the 3.8Grinding NC promotes greater logarithmic reduction of Staph aureus after sterilization by ethylene oxide
Logarithmic reduction in the number of Staph aureus after sterilization (floor of 7.5%)3,6the 3.8
Logarithmic reduction in the number of Staph aureus after 4 weeks at 50°C (5% coverage)0,2 3,6When chopping, NH was not observed a significant reduction in logarithmic decrease after storage at 50°C for 4 weeks

Logarithmic reduction in the number of Staph aureus after 4 weeks at 50°C (floor of 7.5%)1,03,6

Table 6
The influence of particle size, coating and storage conditions
Crushed in the laboratory NCUnground NC
The content of the NC in the suture material (ppm)The content of the NC in the suture material (ppm)
Floor
Content (%)
Storage
Condition
123AVG.Stan-dart-ing the disturbances of%
CCA
%
Change-out
123AVG.Stan-dart-ing the disturbances of%
CCA
%
Change-out
5.0Sterile, original value6477637163746407600.9%181125791862208442920,6%-
7,5Sterile, original value9442941694509436180,2%580941784597486184717,4%-
that 0 4 weeks at 25°C88138088793582794695,7%29%264020732112227531713,9%9%

7.54 weeks at 25°C118171091911116112844724,2%20%4161238221842909108937,4%-40%
5.04 weeks at 50°C76147309748674701532,1%17%57601139583,8%-95%
7.54 weeks at 50°C107011058710119104693082,9%11%2841170126290554059,7%-81%

Table 7
The influence of particle size, amount of coating and storage conditions
Crushed in the laboratory NCUnground NC
These microbiological studiesThese microbiological studies
br/> Content (%)Storage
Condition
SA
1
SA
2
SA
3
Zone filing-ing
AVG.
Area-AVL-ing
Factory, disturbances of
SA
LR
EC
LR
SA
1
SA
2
SA
3
Zone filing-ing
AVG.
Area
filing-
ing
Factory of disturbances-
out
SA
LR
EC
LR
5,0Sterile, original value2,42,72,52,50,2the 3.80.31,3-1.1-
7,5Sterile, original value3,53,6 3,53,50,1the 3.80.32,0-3.6-
5,04 weeks at 25°C3,63,63,53,60,13,6-1,61.6
7,54 weeks at 25°C3,64,1the 3.8the 3.80,33,6-2,23.6
5,0 4 weeks at 50°C2,82,92,82,80,13,6-0,00.2
7,54 weeks at 50°Ca 3.94a 3.9a 3.90,13,6-0,91.0

Another aspect of the present invention includes a medical device with an antimicrobial composition comprising an antimicrobial agent selected from the following group: extract Houttuynia cordate, sodium houttuyn, a new sodium houttuyn and mixtures thereof. In one form of implementation of the antimicrobial agent contains a new sodium houttuyn. In another form of the antimicrobial agent contains the sodium houttuyn. In another form of implementation of the antimicrobial composition comprises sodium howtospot or sodium new howtospot with an average particle size less than about 100 microns. In another form of the antimicrobial agent has an average particle size of less than 50 microns. In another form of the antimicrobial agent has an average particle size less than 40 microns. In another form the antimicrobial composition has an average particle size less than about 40 μm and the standard deviation of particle size less than about 30 microns. In another form of the antimicrobial composition is applied on at least one surface of the medical device and contains a polymeric material to form a film. In one form of implementation of the material forming the polymer film contains a biocompatible, biodegradable polymer, copolymer hydrogel or a mixture thereof. In another form of the antimicrobial agent is present in a concentration of from about 1 to about 15% by weight. In another form of the antimicrobial agent is present in a concentration of from about 1.5 to about 7.5% by weight. In another form of the antimicrobial agent is present in a concentration of from about 2.0 to about 5.0 percent by weight. In one form of the antimicrobial agent characterized the tsya average particle size, enhancing the antimicrobial efficacy of the substance. In another form the medical device is in the form of fibers, mesh, powder, microspheres, flakes, sponge, foam, fabric, nonwoven material, woven material, a film, a device for fixing seams, joints, catheter, suture brackets, stent, surgical tacks, clips, plates and screws, devices for drug delivery, barrier to prevent adhesion and adhesive for fabrics.

In another aspect, a method of obtaining coatings of medical devices includes a step of forming a suspension comprising a polymeric material to form a film of antimicrobial drug that includes a material selected from the following group: Houttuynia cordate, sodium houttuyn, sodium new houttuyn and mixtures thereof. In one form of implementation of the antimicrobial agent contains a new sodium houttuyn. In another form of the antimicrobial agent contains sodium houttuyn. In another form of the antimicrobial agent has an average particle size of less than 100 microns. In another form of the antimicrobial agent has an average particle size of less than 50 microns. In another form of the antimicrobial agent has an average particle size less than 40 microns. In another form the antimicrobial composition has an average size of the particles less than approximately 40 μm and the standard deviation of particle size less than about 30 microns. In another form of implementation, the material forming the polymer film contains a biocompatible, biodegradable polymer, copolymer hydrogel or a mixture thereof.

Another aspect is the method of making an antimicrobial medical device, comprising the stage of applying an antimicrobial coating on a medical device, an antimicrobial coating comprising a material forming a polymer film; and an antimicrobial drug, comprising a material selected from the following group: extract Houttuynia cordate, sodium houttuyn and sodium new houttuyn, or mixtures thereof. In one form of implementation of the antimicrobial agent contains a new sodium houttuyn. In another form of the antimicrobial agent contains sodium houttuyn. In another form of the antimicrobial agent has an average particle size of less than 100 microns. In another form of the antimicrobial agent has an average particle size of less than 50 microns. In another form of the antimicrobial agent has an average particle size less than 40 microns. In another form of the antimicrobial agent is present in a concentration of from about 1 to about 15% by weight. In another form of the antimicrobial agent is present in a concentration of from about 1.5 to AP is sustained fashion to 7.5% by weight. In another form of implementation, the method further includes the stage of antimicrobial sterilization of medical devices.

Although the subject invention is illustrated in detail and described in the drawings and descriptions of the described modes of implementation are given for the purpose of illustration and are not limiting. All changes or modifications within the invention are protected.

1. Antimicrobial composition for coating a medical device, including:
(a) the material for the formation of the polymer film, where the material comprises a biocompatible, biodegradable polymer, copolymer or their mixture; and
(b) an antimicrobial agent comprising a material selected from the following group: extract Houttuynia cordate, sodium houttuyn, a new sodium houttuyn and mixtures thereof.

2. The antimicrobial composition according to claim 1, in which the antimicrobial agent includes sodium new houttuyn.

3. The antimicrobial composition according to claim 1, in which the antimicrobial agent includes sodium houttuyn.

4. The antimicrobial composition according to claim 2 or 3, in which the antimicrobial agent has an average particle size less than about 100 microns.

5. The antimicrobial composition according to claim 4, in which the antimicrobial agent has an average particle size less than about 50 microns.

6. The antimicrobial composition according to claim 4, in which the antimicrobial agent has an average size of the portion is less than approximately 40 microns.

7. The antimicrobial composition according to claim 5, in which the antimicrobial agent has an average particle size less than about 40 μm and the standard deviation of particle size less than about 30 microns.

8. The antimicrobial composition according to claim 1, in which the material forming the polymeric film is selected from aliphatic polyesters, poly(amino acids), copoly(broadcast alkoxylate), polyalkyleneglycol, polyamides, poly(ethylene glycol), poly(iminocarbonothioyl), polyarteritis, polyoxyethyl, polyamidoamine, polyoxyethyl with amine groups, poly(anhydrides), polyphosphazenes, polysaccharide gels, and their copolymers and mixtures.

9. The antimicrobial composition of claim 8 in which the material forming the polymeric film is selected from Homo - and copolymers of lactide, glycolide, Epsilon-caprolactone, a pair of dioxanone, trimethylene carbonate, alkyl derivatives of trimethylhexanoate, polyesters of monoglyceride, hydrogels of carboxymethyl cellulose and mixtures thereof.

10. The antimicrobial composition according to claim 1, in which the antimicrobial agent is present in amount, effectively overwhelming the growth of bacteria.

11. The antimicrobial composition according to claim 1, in which the antimicrobial agent is present in a concentration of at least 100 ppm.

12. The antimicrobial composition according to claim 1, in which the antimicrobial agent has an average particle size, the effective surface is superior antimicrobial efficacy of the antimicrobial agent.

13. The antimicrobial composition according to claim 1, additionally containing calcium stearate.

14. Medical device coated with an antimicrobial composition according to any one of claims 1 to 14, where the device is made in the form of the implantable device.

15. Medical device 14, in which the antimicrobial agent has an average particle size less than about 40 μm and the standard deviation of particle size less than about 30 microns.

16. Medical device 14, in which the antimicrobial composition is applied at least on one surface of the medical device, and further provides a material for formation of the polymer film.

17. Medical device 14 having the form of a fiber, mesh, powder, microspheres, flakes, sponge, foam, fabric, nonwoven material, woven material, a film, a device for fixing seams, joints, catheter, suture brackets, stent, surgical tacks, clips, plates and screws, devices for drug delivery, barrier to prevent adhesion and adhesive for fabrics.

18. Method of coating a medical device, comprising a stage of forming a suspension comprising the material for the formation of the polymer film; the antimicrobial agent comprising a material selected from the following group: Houttuynia cordate, sodium houttuyn, sodium new houttuyn and mixtures thereof.

19. A method of obtaining a medical device according to any one of p-17, including the stage of applying the antimicrobial composition for coating according to any one of claims 1 to 13.



 

Same patents:

FIELD: medicine.

SUBSTANCE: invention concerns a stabilised antimicrobial gel compound containing hydrogen peroxide (H2O2) and other additives. As the additives, the compound contains the thickener cellulose ester, the stabiliser dipotassium hydrogenphosphate (K2HPO4) and disodium salt ethylenediamine-N,N,N1,N1-tetraacetic acid (Na2EDTA), glycerol and water in certain proportions.

EFFECT: preparing the antimicrobial compound with stabilised hydrogen peroxide with no toxic components used, applicable as skin antiseptics, eg for hand cleaning.

2 cl, 21 tbl, 12 ex

FIELD: medicine.

SUBSTANCE: after a colocolonic anastomosis is created 10-12 cm in a proximal direction from the anastomosis, a double tube is inserted into an intestinal lumen. After a transanal insertion of the tube, an infusion pump is used for dosed introduction of a rifaximin suspension at 0.01 mcg of an active substance per 1 kg of a patient's body weight a minute through one channel and a passive outflow through the second channel. The rifaximin suspension is introduced continuously for the first days, then 3 times a day for 3 hours until observing active intestinal peristalsis.

EFFECT: method provides effective prevention of colocolonic anastomotic leakage, reduces a probability of postoperative complications ensured by avoiding microbial contamination, infection and development of anastomositis, as well as promotes reducing the length of treatment and postoperative stay in hospital.

2 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: group of inventions refers to medicine, namely to veterinary science, and can be applicable for using a composition for protection against an infection caused by Lawsonia intracellularis. That is ensured by using a non-living composition containing carbohydrate which is also found in living cells of Lawsonia intracellularis in association with an external cell membrane of the above cells. The vaccine is presented in the form applicable for intramuscular introduction, and contains an oil-in-water adjuvant containing oil drops with an average size of 400 nm.

EFFECT: using the given non-living composition leads to effective immunisation in intramuscular introduction with using small drops of the oil-in-water adjuvant which provides protection of animals against Lawsonia intracellularis.

7 cl, 9 tbl, 4 ex

FIELD: biotechnology.

SUBSTANCE: invention relates to compositions and polymeric materials for biomedical use, comprising silver nanoparticles (0.0005-0.02 wt %) stabilised by amphiphilic copolymers of maleic acid (0.0008-0.05 wt %), low molecular weight organic amines (0.0002-0.04 wt %) and water. In addition, the said composition may additionally comprise the polymeric structure-forming agent.

EFFECT: introduction to the composition of the polymer structure-forming agent enables to obtain the macroporous structured hydrogel materials having prolonged bactericidal and antifungal action.

3 cl, 2 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: inorganic clay, represented by sodium-calcium, and/or calcium and/or ferrous forms of montmorillonite, is modified with a water solution of silver nitrate with a concentration 0.16-9.9 wt % in a weight ratio clay:water solution of silver nitrate 1:5. Modification is carried out with mixing from 3 to 7 hours at a temperature in the interval from 10°C to the temperature of boiling. The obtained material is washed with distilled water to pH ≈6-5, until excess of silver nitrate is removed, stood at room temperature and decanted. The material is dried at a temperature of 20-160°C.

EFFECT: obtaining an efficient antibacterial material for traditional and veterinary medicine.

2 tbl, 5 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: given invention refers to a compound of formula its stereoisomers, including R and S isomers, wherein: 'A' represents N; Y and Y' represent O; '---' is absent; R1 and R2 are identical or different, and independently represent hydrogen or C1-12 alkyl; R3 represents hydrogen; R4 represents heteroaryl which can be optionally substituted in any acceptable position by one or more substitutes Ra; Z represents -(CH2)n-heteroaryl which can be optionally substituted in any acceptable position by one or more substitutes Ra; T, U, V and W are identical or different, and independently represent hydrogen or halogen; Ra is independently specified in hydrogen, halogen, C1-12 alkyl, C1-12 haloalkyl, -C(=Y)OR7, -(CH2)nYR7, each of which can be optionally substituted in any acceptable position by halogen; R7 represents hydrogen or C1-12 alkyl; m represents 1; m′ represents 0; n represents 1; wherein: the above heteroaryl is specified in 1,2,3-triazolyl, pyridinyl, 1-oxypyridinyl (pyridinyl-N-oxide), pyrazinyl, isoxazolyl, imidazo[1,2-α]pyrimidinyl, imidazo[1,2-α]pyrazinyl. The compounds of the given invention are applicable to prevent, relieve and/or treat bacterial infections in an individual. The bacterial infection is caused by the drug-resistant species Staphylococcus, Streptococcus, Enterococcus, Bacterioides, Clostridia, H. influenza, Moraxella, acid-resistant species like Mycobacterium tuberculosis, as well as linezolid-resistant species Staphylococcus and Enterococcus.

EFFECT: phenyloxazolidinone compounds as antimicrobial agents.

12 cl, 8 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: claimed is a cocrystalline form of fenbufen with pyrazinamide, where molar ratio of fenbufen with pyrazinamide constitutes 1:1, which has an endothermal peak from 148 to 152°C by the data of measurements by means of differential scanning calorimetry and peaks at 2θ(°) 7.38, 10.43, 11.04, 21.67 by the data of measurement of polycrystal X-ray radiation diffraction.

EFFECT: increased rate and level of solubility of the crystalline form of fenbufen and its suitability for application in the pharmaceutical industry.

2 ex, 7 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to immunology, molecular biology and genetic engineering. There are presented an immunogenic composition containing a mixture of staphylococcal proteins, and comprising a staphylococcal protein binding an extracellular component, and a staphylococcal transport protein, or the staphylococcal protein binding the extracellular component, and a staphylococcal virulence regulator or a toxin, or the staphylococcal transport protein and the staphylococcal virulence regulator or the toxin. There are also presented vaccines, methods of treating, using and methods for preparing a staphylococcus vaccine.

EFFECT: invention may be used in medicine for treating and preventing a staphylococcal infection.

23 cl, 8 tbl, 7 dwg, 8 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to pharmaceutical formulations and is applicable for providing bactericidal efficacy. A pharmaceutical formulation contains two various antibiotics as active ingredients in the form of a synergetic combination of a fixed dose in a parenteral dosage form. The first antibiotic represents carbapenem or its pharmaceutically acceptable salts, while the second antibiotic represents aminoglycoside which represents etimycin or its pharmaceutically acceptable salts. The above first antibiotic and the above second antibiotic are found in weight ratio of 6:1 to 13:1. Besides, the pharmaceutical formulation contains one or more additives specified from a group of synthetic/natural amino acids/vitamins/stabilisers/polymers/antioxidants/micronutrient elements.

EFFECT: pharmaceutical formulation used in the very low concentrations, provides higher clinical effectiveness in the patients suffering from or sensitive to mixed multibacterial lethal infections, with a low tolerance to drugs and disease, and having a risk of potential toxicity, wherein potential toxicity caused by high doses provides a cause for concern.

8 cl, 3 tbl, 6 dwg, 1 ex

FIELD: chemistry.

SUBSTANCE: composition includes a bactericidal substance - catapol - in amount of 2.1-2.5 wt %, zosterin in amount of 1.1-5.0 wt % and distilled water.

EFFECT: providing a composition which stimulates a reparative process in external protective tissue, having anti-inflammatory and radioprotective action.

1 tbl, 1 ex

FIELD: medicine.

SUBSTANCE: group of inventions relates to medicine. An implanted medical device for delivery of a number of medications to a place of intervention in accordance with the first version contains in fact a cylindrical intraluminal framework, a primer layer, the first and second coatings and, at least, one therapeutic preparation. The cylindrical intraluminal framework is expandable from the first diameter for delivery into a vessel to the second diameter for the vessel expansion. The intraluminal framework has a luminal surface and an abluminal surface. The distance between the luminal surface and the abluminal surface specifies a thickness of the intraluminal framework wall. The intraluminal framework also contains a multitude of holes, extending from the luminal to abluminal surface. The primer layer includes a multitude of layers and covers the luminal surface, the abluminal surface and surfaces of the multitude of holes. The first coating contains a material, which has the first electric charge, and is fixed to the primer layer. The second coating contains a material, which has the second electric charge and is fixed to the first coating only in the multitude of holes. The second electric charge is opposite to the first electric charge. The therapeutic preparation is placed in, at least, one of the multitude of holes. The second coating is made in the form of an intermediate layer between the first coating and, at least, one therapeutic preparation. The implanted medical device in accordance with the second version contains a cylindrical intraluminal framework, a layer of first coating, a layer of second coating and, at least, one therapeutic preparation. The cylindrical intraluminal framework is expandable from the first diameter for delivery into a vessel to the second diameter for the vessel expansion and has a luminal surface and an abluminal surface. The distance between the luminal surface and the abluminal surface specifies a thickness of the intraluminal framework wall. The intraluminal framework also contains a multitude of holes, extending from the luminal to abluminal surface. The first coating contains a material with the first electric charge, fixed on at least, a part of the abluminal surface, the luminal surface and surfaces of the multitude of holes. The layer of the second coating contains a material with the second electric charge, fixed on, at least, a part of the layer of the first coating. The second electric charge is opposite to the first electric charge. The therapeutic preparation is placed in, at least, one of the multitude of holes. The layer of the second coating is made in the form of an intermediate binding layer between the layer of the first coating and, at least, one therapeutic preparation, resulting in obtaining a layered configuration, in which the layer of the second coating is located between the layer of the first coating and, at least, one therapeutic agent, applied in, at least, one of the multitude of holes. The method of the coating application on the intraluminal framework, containing the multitude of holes, made in it, has the following stages: application of the layer of the first coating, containing the material, which has the first electric charge on, at least, a part of the surface of the intraluminal framework and the surface of the multitude of holes; application of the layer of the second coating, containing the material, which has the second electric charge, on, at least, a part of the first coating, with the second electric charge being opposite to the first electric charge; and application of, at least, one therapeutic preparation into, at least, one of the multitude of holes to form the layered configuration, in which the layer of the second coating is located between the layer of the first coating and, at least, one therapeutic agent, applied in, at least, one of the multitude of holes.

EFFECT: inventions ensure prevention of thrombosis and separation of the coating from the underlying surface of a stent.

13 cl, 11 dwg, 2 tbl

FIELD: medicine.

SUBSTANCE: invention refers to medicine. What is described is a bioresorbable hydrogel polymer composition for cardiovascular surgery in the form of a film prepared by a reaction of natural polymers, biologically active substances, a solvent and a softening agent wherein the polymers are presented by cross-linked bioresorbable polymers - gelatin, chitosan or a mixture of chitosan and gelatin, chitosan and polyhydroxybutyrate; the biologically active substance or mixtures thereof are presented by the antioxidant L-carnosine, the anticoagulant heparin, the antiaggregant dipyridamole, acetylsalicylic acid, the non-steroid anti-inflammatory preparation acetylsalicylic acid, the antimicrobial preparations - ciprofloxacin, metronidazole; mechanical strength of the film is not less than 1.2 MPa, the relative elongation is no more than 160%, and the elasticity modulus is 0.4-5 MPa.

EFFECT: there are used hydrogel polymer compositions with the control bioresorption period, prolonged length of biologically active substance release, having biocompatible and thrombus-resistant properties and improved mechanical characteristics - higher softness and elasticity.

7 cl, 12 dwg, 2 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: invention refers to medical products, and to a method for making medical products. A carrier material is treated by electrolytic oxidation for pulse current feed at frequency of 50 to 10000 Hz onto the carrier material in an acidic bath or an alkaline bath to form a film having micropores and/or microroughnesses of the density of 5×104/mm2 or more on the surface of the carrier material, and then the carrier material is treated by iodine impregnation for impregnating the film with iodine or iodine compounds. The iodine compound preferentially represents iodine polyvinyl pyrrolidone, iodine β-cyclodextrine or silver iodide. The carrier material represents a material of Ti or a Ti alloy, stainless steel or a Co-Cr alloy. The film may be formed by using any of the chemical treatment, thermal treatment and mechanical treatment, or a combination of these treatments instead of electrolytic oxidation.

EFFECT: saving costs for preparing medical products with high microbial activity and long-time antimicrobial activity, and biological compatibility.

16 cl, 5 tbl, 3 dwg, 4 ex

FIELD: medicine.

SUBSTANCE: invention relates to chemical and pharmaceutical industry and represents implanted medical device, which contains: intra-lumen implanted construction; first coating, containing combination of rapamycin and probucol in therapeutic doses, enclosed in first polymer material, first coating being connected to the surface of intra-lumen implanted construction; and second coating, containing second polymer coating, containing second polymer material, connected to first coating, for regulation of rate of rapamycin and probucol eluting, second polymer material containing fluoropolymer.

EFFECT: invention provides treatment and prevention of disease and minimisation of organism response to introduction of medical device, stimulates healing and endoepithelisation, as well as provides control over rates of drug eluting from implanted medical devices and prevents restenosis.

49 cl, 7 ex, 97 dwg

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to textile treatment for cardiovascular surgery. A method involves textile treatment with a composition containing gelatin and intermolecular cross-linking of gelatin by an aqueous solution of glutaric dialdehyde, an antibiotic and 0.9% sodium chloride in certain proportions.

EFFECT: method enables make textiles hermetic and antimicrobial, reduced postoperative chemotherapeutic load on the patient.

5 cl, 11 tbl, 11 ex

FIELD: medicine.

SUBSTANCE: invention relates to medicine. Described is membrane envelope of implanted dosing system, which is suitable for hypodermic application. Membrane envelope contains first half and second half, and both halves contain continuous locking edge and are made with possibility of connection to each other by means of lockable connection. Locking edges of halves contain, at least, one hollow and/or, at least, one projection, made as continuous or discontinuous, and membrane envelope is made with possibility of locking in such a way, that, at least, one projection and/or, at least, one hollow of second half became opposite to, at least, one hollow and/or, at least one projection of first half by means of locking connection.

EFFECT: membrane envelope is suitable for hypodermic application aimed at separation of active agent in constant quantity during increased time interval.

10 cl, 2 dwg, 1 ex

FIELD: medicine.

SUBSTANCE: present invention refers to medicine, more specifically to a biodegradable stents consisting of an internal biodegradable metal frame and an external polymer coating. The biodegradable coating consists of biodegradable polymers and can additionally contain at least one pharmacologically active substance, such as an anti-inflammatory, cytostatic, cytotoxic, antiproliferative agent, an anti-microtubule agent, an antiangiogenic, anti-restenosis (for restenosis), antifungicidal, anti-cancer, anti-migration, hypocoagulation and/or anti-thrombosis agent. The stent has a function of vessel lumen maintenance only during a period of time before repaired tissue is able to perform this function again.

EFFECT: making the biodegradable stent.

12 cl, 24 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to medicine, namely a medical composition used for drug storage and delivery, particularly coatings for medical devices, self-contained films, cell cultivation matrixes, etc. The composition contains 3-hydroxybutyrate and 3-hydroxyvalerate (3-PHB/3-PHV) copolymer, and at least one biologically active substance selected from a group of antibiotics or nonsteroid anti-inflammatory preparations in the following proportions, wt %: 3-PHB/3-PHV copolymer 1-6; biologically active substance 1-5; solvent the rest. Additionally, the composition contains a surfactant or polyethylene glycol or gelatin. The composition is presented in the form of microparticles or film.

EFFECT: creation of the biologically active polymeric medical composition of wide spectrum of action and application showing biological compatibility and haematological compatibility, optimal physical-chemical properties, as well as an ability for slow biological resorption in vivo with making no toxic products and negative reactions in use.

18 cl, 8 dwg, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a method for coating a catheter with a certain amount of a pharmacological biologically active substance with the method for coating having used a coating device provided with a dispenser for release of the measured amount of a coating solution by a release device purposefully on a surface of the catheter.

EFFECT: within a short period of contact time the catheter provides controlled and optimal transfer of the biologically active substance on the vascular wall and therein to make the therapeutic process flowing positively.

12 cl, 3 tbl, 5 dwg, 32 ex

FIELD: medicine.

SUBSTANCE: invention refers to medicine, and can be used in oncology (oncogynaecology, oncoproctology), abdominal surgeries, urology, otolaryngology, proctology (hemorrhoids, proctitis, anal fissures), gynaecology (erosion, colpitis, vulvovaginitis), and also active drainage in surgery. A bioactive-coated drainage system for treating abdominal diseases represents a hollow shape element in the form of a cylinder made of silicon elastomers. A cylinder exterior comprises a bioactive coating tissue made of a hydrophilic textile material coated with at least one layer of a complex bioactive substance and biocompatible biodegradable polymer. The bioactive coating is attached to the shape element with a medical-grade polymer adhesive, and at least one end of the bioactive coating is sutured.

EFFECT: invention is easy-to-manufacture, practically feasible, exhibits prolonged medical action and less traumatic.

11 cl, 6 dwg

FIELD: medicine.

SUBSTANCE: group of inventions relates to medicine. An implanted medical device for delivery of a number of medications to a place of intervention in accordance with the first version contains in fact a cylindrical intraluminal framework, a primer layer, the first and second coatings and, at least, one therapeutic preparation. The cylindrical intraluminal framework is expandable from the first diameter for delivery into a vessel to the second diameter for the vessel expansion. The intraluminal framework has a luminal surface and an abluminal surface. The distance between the luminal surface and the abluminal surface specifies a thickness of the intraluminal framework wall. The intraluminal framework also contains a multitude of holes, extending from the luminal to abluminal surface. The primer layer includes a multitude of layers and covers the luminal surface, the abluminal surface and surfaces of the multitude of holes. The first coating contains a material, which has the first electric charge, and is fixed to the primer layer. The second coating contains a material, which has the second electric charge and is fixed to the first coating only in the multitude of holes. The second electric charge is opposite to the first electric charge. The therapeutic preparation is placed in, at least, one of the multitude of holes. The second coating is made in the form of an intermediate layer between the first coating and, at least, one therapeutic preparation. The implanted medical device in accordance with the second version contains a cylindrical intraluminal framework, a layer of first coating, a layer of second coating and, at least, one therapeutic preparation. The cylindrical intraluminal framework is expandable from the first diameter for delivery into a vessel to the second diameter for the vessel expansion and has a luminal surface and an abluminal surface. The distance between the luminal surface and the abluminal surface specifies a thickness of the intraluminal framework wall. The intraluminal framework also contains a multitude of holes, extending from the luminal to abluminal surface. The first coating contains a material with the first electric charge, fixed on at least, a part of the abluminal surface, the luminal surface and surfaces of the multitude of holes. The layer of the second coating contains a material with the second electric charge, fixed on, at least, a part of the layer of the first coating. The second electric charge is opposite to the first electric charge. The therapeutic preparation is placed in, at least, one of the multitude of holes. The layer of the second coating is made in the form of an intermediate binding layer between the layer of the first coating and, at least, one therapeutic preparation, resulting in obtaining a layered configuration, in which the layer of the second coating is located between the layer of the first coating and, at least, one therapeutic agent, applied in, at least, one of the multitude of holes. The method of the coating application on the intraluminal framework, containing the multitude of holes, made in it, has the following stages: application of the layer of the first coating, containing the material, which has the first electric charge on, at least, a part of the surface of the intraluminal framework and the surface of the multitude of holes; application of the layer of the second coating, containing the material, which has the second electric charge, on, at least, a part of the first coating, with the second electric charge being opposite to the first electric charge; and application of, at least, one therapeutic preparation into, at least, one of the multitude of holes to form the layered configuration, in which the layer of the second coating is located between the layer of the first coating and, at least, one therapeutic agent, applied in, at least, one of the multitude of holes.

EFFECT: inventions ensure prevention of thrombosis and separation of the coating from the underlying surface of a stent.

13 cl, 11 dwg, 2 tbl

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