Intra-articular fluid simulator formulation and method for preparing intra-articular fluid additive

FIELD: medicine, pharmaceutics.

SUBSTANCE: declared group of inventions refers to an intra-articular fluid (synovial fluid) simulator formulation, and to a method for preparing an additive to said formulation. The intra-articular fluid simulator formulation contains 15% aqueous medium molecular polyvinyl pyrrolidone, (0.5-1.5)-10-3 wt % of an additive with the antimicrobial properties and 0.05-2.5% of hyaluronic acid sodium salt in deionised water at the weight relation: of polyvinyl pyrrolidone: hyaluronic acid sodium salt as 1:(0.2-0.3). The additive is prepared of silver modified silicone nanoparticles at nanoparticle size 10-40 nm and silver amount in the additive 0.8-1.1 wt %. The method for preparing the additive to intra-articular fluid simulator formulation consists in preparing silicone nanoparticles by pyrolytic laser processing of monosilane (SiH4), modifying their surfaces by nanoparticle processing in 2-5% silver nitrate in deionised water and centrifuging the solution, multiply washing the deposition and centrifuging at each washing stage.

EFFECT: group of inventions provides preparing the biologically compatible intra-articular fluid simulator formulation showing the effective rheology, antimicrobial activity, and promoting repair action on cartilaginous tissues.

6 cl, 1 tbl, 1 dwg, 4 ex

 

The technical field.

The invention relates to pharmacology and medicine and relates to a composition simulating intra-articular fluid (synovial fluid), and a method of producing an additive for a composition that is intended for the prevention and treatment of degenerative-dystrophic lesions of the large joints (knee and elbow), articular cartilage in osteoarthritis and is used for integration in the articular cavity for replacement or correction of intra-articular fluid at its pathological changes.

When osteoarthritis occurs pathological change of parameters of synovial fluid - its quantity, biochemical and cytological composition, rheology and lubricity properties, protective and regenerating properties.

The prior art.

For prevention, correction and treatment of degenerative-dystrophic diseases of joints are various compounds that mimic the composition of synovial fluid (synovial fluid), used for intra-articular introduction to improve the rheological, lubricity and other properties with pathological changes in the synovial fluid.

Known in practical medicine is a composition containing 15%aqueous solution of medium molecular polyvinylpyrrolidone. The composition is suitable for injection and t is aetsa temporary substitute synovial fluid in diseases of the joints (arthrosis) (see Rhasan, Chibalin. Experience of treatment with polyvinylpyrrolidone in patients with deforming osteoarthrosis of the knee joints. Rheumatology. 1985. No. 3. P.40-43; Amatulic, Idamante, Rgreene. New cartilage - polyvinylpyrrolidone for the treatment of patients with osteoarthritis. Therapeutic archive. 1990. T. 5. P.95-98).

However, 15%solution of polyvinylpyrrolidone having certain lubricating, immunoregulatory and exchange (glenoid cavity) properties, does not required as necessary rheology, thixotropic properties under dynamic loading (see Artificial synovial fluid for intra-articular treatment of rheumatoid arthritis and osteoarthritis (Development, clinical-experimental and biochemical study). Therapeutic archive. 1984. No. 11. S-77). The composition possesses antimicrobial properties against endogenous infection).

In the technical solution (see patent RU No. 2268052, publ. 2006; EN No. 2394552, publ. 2010; RU №2197238, publ. 2003; US No. 7485629, publ. 2009; see application RU # 2007141864, publ. 2009) provides compositions comprising aqueous solutions of biopolymer components in the form of hyaluronan (hyaluronic acid) or derivatives of hyaluronan. The compositions are intended for integration into the joint cavity in the treatment of inflammatory and degenerative joint diseases (arthritis, arthrosis).

Biopolymer is omponent in the form of hyaluronan (desulfuromonas fractions), derivatives of hyaluronan (for example, on the basis of solutions of the sodium salt of hyaluronic acid), relate to the components-analogues within the biological environment natural intra-articular (synovial) fluid, and their presence helps to improve lubricity, rheological, chondroprotective, anti-inflammatory properties of synovial fluid.

However, hyaluronan-derived hyaluronan can cause allergic reactions in acute exacerbations of osteoarthritis, arthritis inflammatory Genesis. Compositions based on them require the introduction of additional additives based preservatives to stabilize them and prevent the development of microorganisms (see patent RU No. 2268052, book authors S.ermakov, Rodnikov and other Liquid crystals in engineering and medicine. - Minsk: Asar, 2002 S-334).

In the technical solution (see patent RU No. 2002461, publ. 1993; RU №2007173, publ. 1994; RU №20331621, publ. 1995) provides compositions that mimic intra-articular (synovial) fluid containing sodium carboxymethyl cellulose (Na), compounds of esters of cholesterol and gemodez.

The presence of such components as gemodez, connections, cholesterol esters, allows to simulate the composition of synovial fluid, which contains compounds of cholesterol, reducing friction in the joint due to their orientation when sorption is and the microrelief of the cartilage in the direction of sliding of the articular surfaces (see Isoptine, S.ermakov and other Orthopaedics and traumatology. 1989. No. 10. P.7-11). The presence of known compounds Na (agent - thickener, plasticizer) improves the rheological properties of the compositions.

However, these compositions do not possess antimicrobial activity against endogenous infection, as well as strong anti-inflammatory and reparative properties.

In addition, the prior art generally shows that when playing a composition of synovial fluid developers imitated its properties through the use of components without the necessary consideration of the properties on their biocompatibility. However, from the standpoint of modern medicine it is important to develop and expand products containing biocompatible, functionally and biologically active components of synovial fluid.

The essence of the invention.

One aspect of this invention was to provide a technical result on the development of biologically compatible composition simulating intra-articular fluid, effective rheological properties, antimicrobial activity and promote the regeneration of cartilage.

To solve the technical problem, in part, on the design of the structure, simulating intra-articular fluid, as the former is further analogue of the selected composition, containing 15%aqueous solution of medium molecular polyvinylpyrrolidone, which is the substitute intra-articular fluid in diseases of the joints (arthrosis) (see Rhasan, Chibalin. Experience of treatment with polyvinylpyrrolidone in patients with deforming osteoarthrosis of the knee joints. Rheumatology. 1985. No. 3. P.40-43; Amatulic, Idamante, Rgreene. New cartilage - polyvinylpyrrolidone for the treatment of patients with osteoarthritis. Therapeutic archive. 1990. T. 5. P.95-98).

However, as noted above, the known composition ineffective on its rheology, thixotropic properties and does not have antimicrobial activity.

Given these circumstances, one aspect of the present invention was selection and receipt for composition, simulating intra-articular fluid, biocompatible additives, effectively affecting rheology, thixotropic properties of the composition, contributing to the improvement of regeneration (regenerating) properties of the cartilage tissue and providing an antimicrobial effect.

When choosing the admixture for a given composition were taken into account biological compatibility, applicability in pharmacology and medical practice the following materials:

1) nanoparticles of metals antimicrobial action (Ag, Zn, Cu, Au, Pt, Sn, Sb) in various solutions, including solutions of polymers medical nae is achene (for example, polyvinylpyrrolidone) (see, for example, patent RU 2131269 (WO 94046003/14), publ. 10.06.1999, medical drugs "ORGANICA", "ARGOVIT");

2) coatings with nanostructured porous polyctenium on implant surfaces, promoting regeneration of bone, cartilage tissues (see, for example, US patent No. 7186267, publ. 03.06.2007, (application US No. 2004/000313, publ. 15.01.2004,), bio-compatible porous polysilicon, the presence of cell adhesion structures, bone and formation of calcium-phosphate compounds on its surface, the absence of cytotoxicity confirmed by research, including: Bayliss, S.C., Harris, P.J. and other. Phosphate and cell growth on nanostructured semiconductors. Jornal of Materials Science Letters. 1997:16:737-740; Yangyang Lu, Fan Yang, Linto Cai. Osteoblast adhesion on porous silicon. Bulleten of Advanced Technology Research. 2009, Jan., Vol.3, No.1, 25-28; Alvarez S.D., Defrus A.M. and other. The compatibility of hepatocytes with chemically modified porous silicon with reference to in vitro biosensors. Biomaterials. 2009:30:26-34;

3) silicon nanoparticles (see, for example, patent WO 2010/096733 A2, publ. 20.02.2010. Luminescent porous silicon nanoparticles, method of making and using same; Application RU # 2003137823, publ. 27.03.2005. Frameworks for engineering of human bone tissue, methods for their manufacture and their use).

Silicon nanoparticles, as well as film nanostructured porous polysilicon, show the effect of biocompatibility with the cellular structures (see Loosenin, Anglomania, Mbongeni and others. The impact on strukturirovannogo silicon on the proliferation of stem and cancer cells. - Bulletin of experimental biology and medicine. 2011. Volume 151. No. 1. S-95; see patent WO 2010/096733 A2, publ. 20.02.2010. Luminescent porous silicon nanoparticles, method of making and using same).

The most preferred process for producing nanoparticles of silicon by laser pyrolysis of monosilane (SiH4by the dissociation of molecules of monosilane at heating water jets, surrounded by a flow of buffer gas with a CW CO2laser (laser-induced chemical vapour deposition - LICVD) (see Now, Geplugin, Anglo and others. Optical and electrical properties of thin plates made of nanocrystalline powders of silicon. Semiconductor physics and technology. 2005. Volume 39. VIP. S-873; Semiconductor Detector, Sborov, Viewstoday. Luminescence of silicon nanoparticles. General Physics Institute. Amerkhanov wounds. The book of abstracts of the Third International nanotechnology forum RUSNANOTECH. Moscow. 2008).

A characteristic feature of this process is obtaining the silicon nanoparticles with a size distribution of the nanoparticles in the range of 10-40 nm, which is optimal for hygienic regulations governing permissible ranges used nanoparticle size.

Given the level of technology, as the closest analogue for choosing and obtaining biocompatible additives that improve the properties of the synovial fluid, the selected technical is against the decision (see Now, Geplugin, Anglo and others. Optical and electrical properties of thin plates made of nanocrystalline powders of silicon. Semiconductor physics and technology. 2005. Volume 39. VIP. S-873; Semiconductor Detector, Sborov, Viewstoday. Luminescence of silicon nanoparticles. General Physics Institute. Amerkhanov wounds. The book of abstracts of the Third International nanotechnology forum RUSNANOTECH. Moscow. 2008), which consists of nanoparticles of silicon the size of 10-40 nm by laser pyrolysis of monosilane (SiH4).

To solve the technical problem, in part, on the design of the composition, a composition simulating intra-articular fluid containing 15%aqueous solution of medium molecular polyvinylpyrrolidone, and the solution contains (0.5 to 1.5)·10-3wt.% additives with antimicrobial properties based on nanoparticles of silicon modified with silver, when the particle size of 10-40 nm and the amount of silver in the addition of 0.8-1.1 wt.% and 0.05 to 2.5% aqueous solution of sodium salt of hyaluronic acid with a weight ratio of: an aqueous solution of polyvinylpyrrolidone : aqueous solution of sodium salt of hyaluronic acid, as 1:(0,2-0,3).

According to the present invention in the use composition obtained by fermentation sodium salt of hyaluronic acid with the molecular the Oh mass of 0.5-1.8 MDA.

According to the present invention the composition contains 15%aqueous solution of polyvinylpyrrolidone with a molecular weight of 35000±5000 Yes.

For the technical solution method for obtaining supplements for composition, simulating intra-articular fluid, which consists in obtaining nanoparticles of silicon the size of 10-40 nm by laser pyrolysis of monosilane (SiH4), while the surface of the silicon nanoparticles modified by processing them in a 2-5% solution of silver nitrate in deionized water at a weight ratio of: solution: nanoparticles as 1:0,02, followed by centrifugation of the solution, multiple sediment washing in deionized water by centrifugation at each washing step.

The present invention multiple sediment washing in deionized water is carried out at the initial resistivity of the water is not lower than 10 Mω·cm to achieve its specific resistance of not lower than 1 Mω·see

According to the present invention the processing of silicon nanoparticles in aqueous silver nitrate solution is carried out for 12-36 hours.

When implementing the present invention developed a biologically compatible composition simulating intra-articular fluid with effective rheology properties, having antimicrobial activity and contributing to the manifestation of regenerating action on the cartilage of the s fabric, what explains:

- use as part of a biologically compatible polymer-based agent widely used in medical practice, including for intra - articular fluids such as polyvinylpyrrolidone;

- use composition of the biocompatible additives based on nanoparticles of silicon, the surface of which is modified with silver, which composition acquires antimicrobial properties; improve the rheological properties of the composition and is manifested regenerative effect of composition on cartilage;

- the availability of polyvinylpyrrolidone (PVP) and sodium salt of hyaluronic acid (Na)forming a volumetric mesh structure of the polymer complex due to the formation of relations between the carbonyl groups (C=O) in the monomer units PVP and sodium cations in the monomer units Na, which improves the rheological properties of the composition;

- presence in the synergistic compatible polymeric agents based on polyvinylpyrrolidone and sodium salt of hyaluronic acid, forming a polymer electrolyte complexes adsorbed on the surface of nanoparticles of silicon, which leads to the structuring of the polymer matrix, to improve rheology, thixotropic properties of the composition; this increases the efficiency of interaction of intra-articular is hidcote with cartilaginous tissue of the articular cavity.

In the analysis of the prior art are not identified technical solutions with a set of features of the present invention described above and provides the result.

The analysis of the prior art demonstrates compliance with the proposed technical solution criteria invention of "novelty", "inventive step".

The present invention can be industrially realized by using known manufacturing processes, equipment and materials used in pharmacology and medicine.

The implementation of the invention.

The invention is illustrated:

- figure 1 shows a photograph of a silicon nanoparticles obtained using scanning electron microscope (SEM);

table 1, which shows the rheological properties of samples of compounds that mimic the intra-articular fluid.

To implement the invention using known industry equipment and materials:

- 15%-aqueous solution of medium molecular polyvinylpyrrolidone and preferably with a molecular weight of 35000±5000 Yes; this solution is used for injection as an artificial substitute for intra-articular (synovial) fluid in diseases of the joints, accompanied by her lack of the glenoid cavity (gap);

sodium with the l hyaluronic acid ([(C 14H20NO11)Na]n) with a molecular weight of 0.5-1.8 MDA, which is obtained by the method of bacterial (cell) fermentation, which is the most optimal therapeutic effect (no in preparation alien protein, particularly animal protein); the specified molecular weight component of the optimal therapeutic effect, which is confirmed by studies of intra-articular structures of liquids "Ostenil" (TRB Chemedica AG, Germany, http://www.trbchemedica.com; http://www.ostenil.ru/and Synocrom" (Croma Pharma GmbH, Austria, http://www.croma.at; http://www.synocrom.com.ua/croma-pharma.htm)containing sodium salt of hyaluronic acid; the invention preferably using sodium hyaluronate with a molecular weight of 1.6 MDA.

To obtain a composition that simulates intra-articular fluid, use of 0.05-2.5% solution of sodium salt of hyaluronic acid in deionized water. The solution of sodium salt of hyaluronic acid in deionized water get when mixing, preferably at a temperature of 40-50°C.

In the composition according to the invention use:

- aqueous solutions of polyvinylpyrrolidone and sodium salt of hyaluronic acid with a weight ratio of them as 1: (0,2 - 0,3), which is optimal in terms of obtaining physiologically active composition, simulating intra-articular fluid, as evidenced by the following studies;

- add the with antimicrobial properties based on nanoparticles of silicon, modified silver (Ag), when the particle size of 10-40 nm.

To obtain use of this additive process, in accordance with which implement the following stages of its receipt.

step 1 - obtaining nanoparticles of silicon.

For the implementation of this phase, use the technology of synthesis described in the works: Now, Geplugin, Anglo and others. Optical and electrical properties of thin plates made of nanocrystalline powders of silicon. Semiconductor physics and technology. 2005. Volume 39. VIP. S-873; Semiconductor Detector, Sborov, Viewstoday. Luminescence of silicon nanoparticles. General Physics Institute. Amerkhanov wounds. The book of abstracts of the Third International nanotechnology forum RUSNANOTECH. Moscow. 2008).

The synthesis of nanoparticles of silicon is carried out at a laser pyrolysis of monosilane (SiH4); the process is conducted in a flow reactor at a heating jet monosilane, surrounded by a flow of inert buffer gas (such as Ar), a CW CO2laser (laser-induced chemical vapour deposition - LICVD). For nanoparticles with the given parameters size govern the capacity of a CO2laser flow rate of the buffer gas and monosilane (SiH4).

Specifically, the process of obtaining nanoparticles of silicon was carried out under the following synthesis parameters (n is rolisa) monosilane: the flow rate of monosilane - 0.2 l/min; the flow rate of the buffer gas is 12.5 l/min; temperature 650°C; the pressure in the chamber 200 Torr; power CO2laser 600 W.

A characteristic feature of this process is obtaining the silicon nanoparticles with a size distribution of the nanoparticles in the range of 10-40 nm, which is confirmed by their study by scanning electron microscope (see figure 1).

stage 2 - surface modification of nanoparticles of silicon.

This stage was carried out in the following sequence.

1. Use a solution of silver nitrate (AgNO3) in deionized water. Ion-exchange properties of this salt solutions are widely used in medical practice to obtain drugs with antimicrobial properties.

Obtained at the first stage, the nanoparticles of silicon is treated in an aqueous solution of silver nitrate (AgNO3).

When the recovery of silver on silicon thermodynamic equilibrium between the two redox pairs is determined by the difference of the standard potentials, it performs the following rule: coupled pair with a relatively high (more positive) potential attaches electrons from conjugate pairs with relatively low (more negative) potential. Mating pair for Ag when restoring on the surface of nanoparticles of silicon-pair: SiHx- (4)e=Si+(4-x)N+. Potential Yes the Noah electrode reaction is 0,148 Century The value of the potential is determined based on the value of the activation energy for thermal desorption SiHxgroups from the silicon surface. This higher capacity allows the deposition of other substances whose potential recovery above - 0,148 Century, the Silver recovered in aqueous solutions: Ag++e-=Agφ°. The standard electrode potential of Ag is 0,799 (see Wasabisabi and other "Quick chemical Handbook". ISD. Leningrad. "Chemistry". Leningrad branch. 1991 S.353, 363).

For the deposition process nonvalence silver on the surface of the silicon nanoparticles according to the invention using 2-5% aqueous silver nitrate solution at a weight ratio of solution to the modified nanoparticles as 1:0,02, and the processing of the nanoparticles specified solution within 12-36 hours.

Specified according to the invention an aqueous solution of silver nitrate, the quantitative ratio between the solution and the nanoparticles, the processing mode of the silicon nanoparticles in the solution is optimal. Changes in these technological regimes and parameters leads either to reduce the amount of silver on the modified surface of the nanoparticles of silicon, which reduces the antimicrobial activity of synovial fluid, or to increase the amount of silver on the surface of nanoparticles of silicon, whutcha the t biocompatibility of the nanoparticles.

2. Spend centrifugation of a suspension of an aqueous solution with silicon nanoparticles. The suspension is separated into components using multifunction centrifuges Thermo Scientific SL40. The maximum number of revolutions 15200 rpm the silver nitrate Solution is poured, receive precipitate the nanoparticles of silicon.

3. The precipitate nanoparticles of silicon repeatedly washed with deionized water by centrifugation at each washing step.

For washing use deionized water in the initial resistivity not lower than 1 Mω·cm - OST 11 029.003-80 "electronics Products. Water used in production. Marks, technical requirements, methods of purification and control".

The process of washing and centrifugation is completed when the specific resistance of water is not less than 1 Mω·see

To control the resistivity of the water is used, the control unit BCVR-24-003.

The result is a silicon nanoparticles, the surface of which is modified restored to her silver.

The process of centrifugation in the implementation of phase 2 of the optimal processing technology and nanoparticles from aqueous solutions.

Specifically for the implementation of this phase was used:

3%solution of silver nitrate (AgNO3) in deionized water in the amount of 50 ml per 1 g of nanoparticles of silicon; the processing of the suspension within 24 hours;centrifuging the suspension an aqueous solution with silicon nanoparticles after they are processed in an aqueous solution of silver nitrate; repeated washing and centrifugation.

The resulting precipitate the nanoparticles of silicon in the amount of 0.98,

Obtained by carrying out this process the silicon nanoparticles were investigated for determination of amount of silver.

Research method was quantitative analysis based on measuring the volume or mass of reagent required for the reaction with the test substance - titrimetric analysis. Titrimetric analysis to determine the amount of silver was carried out by using indicators that secures the equivalence point of the titration.

When conducting titrimetric analysis, by definition, wt.% silver content were used reagents: a mixture of sulfuric and nitric acids; titrant based on the solution of thiocyanate ammonium (or potassium); as indicator solution salesonline alum.

As a result of the research it was found that in the investigated number of nanoparticles of silicon contained 0.9 wt.% silver (9,0·10-3g).

Obtained in the second stage, the silicon nanoparticles, the surface of which is modified with silver, was used to obtain a composition that simulates intra-articular fluid.

For preparation of the composition according to the invention were used in 15%aqueous solution srednemolekularnah the polyvinylpyrrolidone and, preferably, the molecular weight of 35000±5000 and silicon nanoparticles obtained in step 2.

The suspending components was performed using ultrasonic treatment.

To obtain the composition according to the invention in a 15%aqueous solution of medium molecular polyvinylpyrrolidone injected (0.5 to 1.5)·10-3wt.% additives with antimicrobial properties based on nanoparticles of silicon modified with silver, when the particle size of 10-40 nm and Soderini silver nanoparticles of silicon, 0.8 to 1.1 wt.%.

Specified according to the invention the content of additives with antimicrobial properties based on nanoparticles of silicon modified with silver, at the specified size of the nanoparticles, the amount of silver in silicon nanoparticles optimally and complies with sanitary standards on the concentration of nanoparticles in aqueous solutions (GN 1.2.2633-10. Hygienic standards of the contents of the priority of nanomaterials in the environment approved 25.05.2010, Chief state sanitary inspector of the RF).

The increase or decrease of these parameters will either lead to a deterioration of the antimicrobial activity of the composition, or to reduce the level of its biocompatibility with tissue in the joints, or to increase the cost to obtain a composition.

Specified according to the invention the quantitative content of the additive on the basis of nanochemistry, modified silver, at the specified size of the nanoparticles, the amount of silver in silicon nanoparticles optimally under conditions of a composition having effective rheology, thixotropic properties.

There were prepared the following compounds that mimic the intra-articular fluid.

Example 1 (control).

The composition contains 10 ml of aqueous 15% solution of polyvinylpyrrolidone with a molecular weight of 35000 MDA and 1.5·10-3wt.% the silicon nanoparticles modified with silver, with the particle size of 10-40 nm, when the amount of silver in silicon nanoparticles with 0.9 wt.%.

The suspension was mixed using ultrasonic treatment.

Example 2 (invention).

The composition contains 8 ml of aqueous 15% solution of polyvinylpyrrolidone with a molecular weight of 35000 MDA, 2 ml aqueous 0.1% solution of sodium salt of hyaluronic acid obtained by fermentation with a molecular mass of 1.6 MPa and 1.0·10-3wt.% the silicon nanoparticles modified with silver, with the particle size of 10-40 nm, when the amount of silver in silicon nanoparticles with 0.9 wt.%.

Aqueous solutions of polyvinylpyrrolidone and sodium salt of hyaluronic acid before introducing nanoparticles of silicon pre-mixed using ultrasonic treatment.

Example 3 (control).

The composition contains 10 ml of aqueous 5% solution of polyvinylpyrrolidone with a molecular weight of 35000 Hmm.

Example 4 (control).

The composition contains 8 ml of aqueous 15% solution of polyvinylpyrolidone with molecular weight of 35000 MDA, 2 ml aqueous 0.1% solution of sodium salt of hyaluronic acid obtained by fermentation with a molecular mass of 1.6 MDA.

The compositions of examples 1-4 were tested to assess their rheological and antimicrobial properties.

Evaluation of the antimicrobial properties of the compositions according to examples 1-4 were carried out on the basis of decodifying method using guidelines (MUK 4.2.1890-04) "Determination of the sensitivity of microorganisms to antibiotics", approved 04.03.2004, Chief state sanitary doctor of the Russian Federation (Ministry of health)).

Desctiption method (DDM) determining the sensitivity of microorganisms (bacteria and fungi) based on the ability of antimicrobial agents included in the composition to diffuse into the nutrient medium of impregnated their cardboard (paper) disks, inhibiting the growth of microorganisms, sown on the surface of the nutrient medium.

Inflammatory lesions of the joints characterized by specific changes detected by physico-chemical, biochemical and cytological study of synovial effusion (synovial fluid), resulting from the puncture of a cavity of a joint.

Synovial zhidkosti inflammatory, degenerative-dystrophic diseases of joints contains microflora and may contain various endogenous infection, bacteria. The color and transparency of the articular effusion depend on the content of the pathological admixtures and their character.

Given these circumstances for evaluation of antimicrobial activity of the compositions according to examples 1-4 as test microorganisms used strains of bacteria: Staphylococcus aureus ATCC 25923; Staphylococcus aureus ATCC 43300 MRSA; Pseudomonas aeruginosa.

Bacteria of the species Staphylococcus aureus is one of the most resistant of representatives of gram-positive microflora of man, are the causative agents of pustular infections.

Bacteria of the species Pseudomonas aeruginosa is one of the most resistant of representatives of gram-negative microflora, are highly resistant to physical and chemical factors. Often they are resistant to multiple drugs and disinfectants.

Testing used a dense nutrient medium - tripcase-soy agar (Trypcase-soy agar).

Preparation of Petri dishes with nutrient dense environment was performed in accordance with the instructions of the manufacturer of the nutrient medium and guidelines MUK 4.2.1890-04.

As a diagnostic disks used were standard discs with a diameter of 6 mm from the special filter cardboard (paper).

Dis is and was subjected to a single treatment (impregnation) examinees compositions (Examples 1-4).

Suspension (inoculum) of each test bacterial cultures in sterile physiological solutions were prepared with density (turbidity) of 0.5-0.6 standard Mac-Farland. The suspension contained approximately (1,5-2,0)·108CFU/ml (colony forming units/ml).

Inoculum (within 15 minutes after preparation) was used for inoculation dense nutrient media in Petri dishes (above).

Inoculum was applied by pipette to the surface of a nutrient medium in a volume of 1-3 ml and distributed evenly on the surface. Agape Petri dishes were dried at room temperature for 15-20 minutes.

After inoculation on the surface of the medium (with the help of sterile forceps) put the disks treated with test compounds (Example 1-4). Ensured uniform and intimate contact of the disks with the surface environment.

Directly after application disks in Petri dishes were placed in a thermostat, and incubated at a temperature of 25-35°C for 18-72 hours After the end of the incubation was measuring the diameter of zones of growth inhibition of the test organisms (drive around) with an accuracy of 1 mm When the measurement is focused on the zone of complete suppression of visible growth.

To increase the validity of the studies testing the drives with the test compound (Example 1-4) for each test microorganism was repeated three times, OTS who were nivalis the average diameter of the zone of growth inhibition. As a result of researches it is established that:

the diameters of zones of growth inhibition of the test organisms around the disks treated with the compositions of examples 1 and 2, respectively - 17 mm and 15 mm;

the diameters of zones of growth inhibition of the test organisms around the disks treated with compositions according to examples 3 and 4, respectively 2 mm and 3 mm

Measurement of the rheological characteristics of the sample compounds that mimic the intra-articular fluid was carried out using a rotational viscometer Rheotest RN4.1 (production PCG "GRENADE")intended for quality control in production and laboratory research products: oils, pastes, solutions, suspensions, emulsions.

Measurements were taken of the dynamic viscosity of the following sample compositions in accordance with examples 1-3.

Dynamic viscosity (mPas/mPas) was carried out at a temperature of sample composition 25°C, when the velocity gradients) shift: 1.0-1; 10-1; 100-1.

The results of measurements of the dynamic viscosity of the sample composition are presented in table 1, "Rheological properties of samples of compounds that mimic the intra-articular fluid.

The measurement results show that the addition of the composition, simulating intra-articular fluid, nanoparticles of silica (as in example 1) and the silicon nanoparticles and the aqueous solution is freeway hyaluronic acid salt (example 2) increases (improves) the dynamic viscosity and thixotropic properties of the composition, inherent in native articular (synovial) fluid.

The obtained values of dynamic viscosity composition samples correspond to the region of permissible values of dynamic viscosity of native articular (synovial) fluid.

According to the biological and rheological studies of the dynamic viscosity of native articular (synovial) fluid may be (depending on the condition of the joint of the patient, loads and shift gradient, chemical and biological factors) in a wide range of values from 10 mPas to 1000 mPas (see for example Dan Mazzucco, Gareth McKinley and other. Rheology of joint fluid in total knee arthroplasty patients. Journal of a French Brasserie Research. 2002: 20:1157-1163; Schurz J, Ribitsch V. Rheology of synovial fluid. Biorheology. 1987: 24:385-399; Fama H, Bryant JT, Kontopoulou M. Rheological properties of synovial fuids. Biorheology. 2007: 44: 59-74; Bryan Preston Conrad. The effects of glucosamine and chondroitin on the viscosity of synovia).

Patients (as indicated) for the prevention and treatment of degenerative-dystrophic lesions of the large joints (knee and elbow), articular cartilage in osteoarthritis are encouraged to integrate (to enter) in the articular cavity (for replacement or correction synovial fluid) from 1.0 to 3.0 ml of the composition according to the invention one or two times a week. The average duration of preventive treatment course of 3-4 weeks. Structure for storing ampoliros 3.0 ml, followed by sterilization, prepact the positive gamma radiation.

Practical application of the composition according to the invention is illustrated on animals in terms of the veterinary clinic. Used dogs: German shepherd dog (5 years, male, weight-35 kg); German shepherd (6 years old, male, weight - 37 kg). Signs of degenerative changes in the knee joints of dogs diagnosed based on clinical examination and radiography. During the clinical examination were visually evaluated the production of limb movement, the degree of extension of the knee joint, lameness was defined periarticular muscle groups and determined their tone, was diagnosed with pain. Dogs could step on the patients limb, the knee joints of dogs the degree of extension was one - to 145°, and the other up to 160°, at the rate of 170°-180°. The amplitude of movements in the joint had one dog is 70°, and another 85° at the rate of 100°-115°. On x-rays was observed irregular narrowing of joint cracks, small bone growths on the edges of the articular surfaces, some formation of bone layers (seals). Diagnosed with degenerative changes in the knee joints of dogs traumatic nature. In order to achieve the rheological (lubricating) effect, pain relief, reduce inflammation in the joints of dogs, to improve the regeneration of HRA is of evich tissues dogs directly into the cavity of the knee twice a week for 4 weeks were injected with 1.5 ml of the composition according to the invention. Applied composition prepared according to Example 2 (see above). After 4 weeks the animals were able to load the limbs, the degree of extension in the knee joint and range of motion they reached respectively 165°-170° and 95°-105°, in dogs decreased lameness and pain, neuromuscular tone of the joints and limbs has increased.

Thus, studies generally confirm that the claimed invention composition simulating intra-articular fluid, has a biocompatible properties, has an effective rheological properties, possesses antimicrobial activity and contributes to the manifestation of regenerating action on cartilage.

The feasibility of using the composition according to the invention supplements based on nanoparticles of silicon justified known properties of silicon that is involved in protein and carbohydrate metabolism of the tissues of living organisms, in immunological processes in the processes of mineralization of bone tissue, regeneration of cartilage tissue, which is confirmed by including the above studies mentioned in the description.

The composition simulating intra-articular fluid, and method for producing the additive to the composition.

Table 1
geologicheskiy properties of samples of the compositions, simulating intra-articular fluid.
Test specimens of the compositionsDynamic viscosity, mPas, at a temperature of 25°C, shear rate, with-1
1,010,0100,0
15%aqueous solution of polyvinylpyrrolidone (PVP) with the addition of nanoparticles of silicon modified with silver, example 1 (control)24,7a 21.516,3
15%solution of PVP with the addition of an aqueous solution of sodium salt of hyaluronic acid and silicon nanoparticles modified with silver, example 2 (invention)157,398,655,2
15%aqueous solution of PVP, example 3 (control).9,59,58,6

1. The composition simulating intra-articular fluid containing 15%aqueous solution of medium molecular polyvinylpyrrolidone, and the solution contains (0.5 to 1.5)·10-3wt.% additives with antimicrobial properties based on nanoparticles of silicon modified with silver, when the size of the re nanoparticles 10-40 nm and the amount of silver in the addition of 0.8-1.1 wt.% and 0.05-2.5% solution of sodium salt of hyaluronic acid in deionized water at a weight ratio of: a solution of polyvinylpyrrolidone : a solution of sodium salt of hyaluronic acid, as 1:(0,2-0,3).

2. The composition simulating intra-articular fluid according to claim 1, characterized in that use is obtained by fermentation sodium salt of hyaluronic acid with a molecular weight of 0.5-1.8 MDA.

3. The composition simulating intra-articular fluid according to claim 1, characterized in that use the 15%aqueous solution of polyvinylpyrrolidone with a molecular weight of 35000±5000 Yes.

4. The method of obtaining the additive to the composition according to claim 1, consisting in obtaining nanoparticles of silicon the size of 10-40 nm by laser pyrolysis of monosilane (SiH4), while the surface of the silicon nanoparticles modified by processing them in a 2-5% solution of silver nitrate in deionized water at a weight ratio of: solution : nanoparticles as 1:0,02, followed by centrifugation of the solution, multiple sediment washing in deionized water by centrifugation at each washing step.

5. The method according to claim 4, characterized in that multiple sediment washing in deionized water is carried out at the initial resistivity of the water is not lower than 10 Mω·cm to achieve its specific resistance of not lower than 1 Mω·see

6. The method according to claim 4, characterized in that the processing of silicon nanoparticles in aqueous silver nitrate solution is carried out for 12-36 hours



 

Same patents:

FIELD: oil and gas industry.

SUBSTANCE: as an additive to increase the processing depth of hydrocarbon-containing raw materials, in thermocatalytic processes there used is organic salt having the following formula: M(OOC-R)n, or M(SOC-R)n, or M(SSC-R)n, where R means alkyl, aryl, isoalkyl, tert-alkyl, alkylaryl, possibly containing hydroxylic, keto-, amino-, carboxylic, thiocarbamic groups, n 1-3, and M means transition metal from the elements of the Mendeleyev's Classification Table. Also, invention refers to the method for increasing the processing depth of hydrocarbon-containing raw materials, in which the above additive is used.

EFFECT: use of the described invention allows increasing the processing depth of hydrocarbon-containing raw materials in thermocatalytic processes.

14 cl, 8 ex, 12 tbl

FIELD: chemistry.

SUBSTANCE: invention can be used when producing titanium dioxide based catalysts for photocatalytic treatment of water and air from organic compounds. The method of producing titanium dioxide involves feeding reactants into a reactor continuously, hydrolysis of titanium tetrachloride solution with an alkaline agent while stirring, separating residue from solution, washing, drying and calcining the residue. Titanium tetrachloride is hydrolysed with aqueous suspension of calcium hydroxide, and after hydrolysis, the fine fraction of the end product is separated from the suspension and the coarse fraction is returned into the reactor. The end product is washed after the step for calcination of titanium hydroxide with pure hydrochloric acid at pH=1-2, and the product is re-dried. The size of calcium hydroxide particles fed into the reactor for hydrolysis is not less than 3 mcm, and concentration of titanium tetrachloride is kept not more than 2%.

EFFECT: invention enables to obtain pure nanodispersed titanium dioxide.

9 cl, 1 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to nanoparticles for drug delivery with the nanoparticles consisting of a metal-chelating polymer, and an active agent representing a related TNF ligand inducing apoptosis (TRAIL) wherein the active agent is covalently bond with the polymer. The invention also refers to the pharmaceutical composition for inducing apoptosis in a cancer cell, reducing tumour growth and/or tumour growth inhibition which involves said nanoparticles and a pharmaceutically acceptable carrier. What is also declared is a method for preparing the nanoparticles which involves mixing the aqueous solution of the metal-chelating polymer with a soluble metal salt, oxidation of metal ions and formation of the nanoparticles by reducing pH to a basic level. Then the stages of metal addition, oxidation and reduction to basic pH are performed again. They are followed by nanoparticle functionalisation and contact with TRAIL, and blocking of the rest active sites on the surface of the nanoparticles.

EFFECT: invention provides reducing the effective apoptosis ensured by TRAIL stabilisation, prevented splitting and reduced TRAIL amount required for apoptosis.

27 cl, 30 dwg, 8 ex

FIELD: chemistry.

SUBSTANCE: invention relates to nanotechnologies in field of chemistry. Method includes interaction of silicon compound of tetraethylorthosilicate with reducing agent - sodium borohydride in presence of ionic liquid, containing dialkyl imidazolium cation, in organic solvent medium and separation of silicon nanoparticles that are formed. As ionic liquid 1,3-dimethylimidazolium iodide can be used, diglyme being used as organic solvent. Interaction is carried out in inert gas atmosphere. Invention ensures obtaining nanocrystalline silicon in absence of silicon halogenides and metallic sodium in conditions of homogenous reaction.

EFFECT: method is technological and easily reproducible.

4 cl, 3 dwg, 1 ex

FIELD: nanotechnologies.

SUBSTANCE: invention relates to nanotechnology. The device for producing arrays of carbon nanotubes (CNTs) on metal substrates comprises two electrodes 7 and 8 located coaxially and moved toward each other by water-cooled rods 8 and 9, sliding graphite current leads 11 and 12 made in the form of rings. The electrodes 7 and 8 are electrically insulated from rods 8 and 9. On the cathode 1 the replacement inserts 2 of electrotechnical non alloyed steel are mounted, fixed with graphite screws 3 and which are the substrates for sedimentation of dense ordered arrays of CNTs.

EFFECT: invention provides electrically conductive structures "substrate-CNT array" by a simple and economical method.

5 dwg

FIELD: chemistry.

SUBSTANCE: invention can be used in non-linear optics and pyroelectric devices. Before film precipitation padding is prepared by separation of thin layer from highly oriented pyrographite by means of double-sided adhesive tape. C60F18 powder is loaded into evaporation cell, placed into vacuum chamber, container with prepared padding is installed at the distance from 10 to 40 mm from it. Evaporation of C60F18 powder is performed by heating of evaporation cell to 120-170 °C, supporting padding temperature 18-25 °C. Device of padding introduction into vacuum includes vacuum chamber, sluice device with straight through valve and flange-window for replacement and loading of paddings, rod, made with possibility of reciprocating movement and rotation, holder with padding. Device for fluorofullerene evaporation includes means of mechanical and thermal protection, control and regulation of heating temperature, mounting and positioning of constituting elements, tubular heater and means for placement of evaporated substance. Tubular heater is made in form of quartz tube 8 with coiled outside wire heater 7. Means of mounting and positioning are made in form of stud 4 for console fixation of cell, screw with nut 9 and clamp, located on ceramic pole 11, installed in round base of evaporation cell. Means of positioning include alundum dual channel tube 6 for thermocouple 5.

EFFECT: invention makes it possible to simplify film obtaining, as well as servicing and repair of equipment, reduce energy consumption and increase reliability.

12 cl, 2 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to an X-ray agent for X-ray diagnosing of various organs. The declared agent contains 2.0-9.0 wt % of tantalate in the form of nanoparticles of average size 5 nm of at least one element specified in a group consisting of yttrium, lanthanum, cerium, praseodymium, neodymium, samarium, europium, gadolinium, terbium, dysprosium, holmium, erbium, thulium, ytterbium, lutetium, or bismuth, 0.3-1.2 wt % of natural polysaccharide and water.

EFFECT: invention provides high contrast ratio within the whole range of X-ray powers applied in medical X-ray diagnosing (10-100 keV) and having high sedimentation stability.

2 cl

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a galvanic particle consisting of zinc, partially copper-plated. A galvanic particle size is equal to nm to 100 mcm, while copper weight therein makes 0.01-10 % of particle weight. The galvanic particles under the invention may be prepared by contact of the zinc particles and a copper salt solution. The invention also refers to a pharmaceutical composition which contains an effective amount of said galvanic particles and a bioabsorbed polymer, and to an oral dosage form containing an effective amount of the galvanic particles under the invention, and a pharmaceutically acceptable carrier. The invention also refers to a method for destruction of drug-resistant microorganisms involving contact of a microorganism and the composition containing the carrier and said galvanic particles.

EFFECT: invention provides preparing galvanic pairs applicable for drug delivery.

16 cl, 19 tbl, 20 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a pharmaceutical composition for treating cytostatic myelosuppression. The declared composition containing 0.4-4 wt % of oxidised dextran of molecular weight 35-70 kDa as a leukopoiesis stimulator, a liposome-forming agent - phosphatidyl choline in the amount of 1.0-4.0 wt %, a liposome stabiliser representing polyethylene glycol of molecular weight 1500-4000 Da in the amount of 0.4-4 wt % and a pharmaceutically acceptable excipient. The pharmaceutical composition may be presented in the form of a nanoliposome emulsion of liposome size 150-800 nm.

EFFECT: invention provides preparing the pharmaceutical composition for more effective and earlier prevention of cytostatic myelosuppression.

3 cl, 1 tbl, 3 ex

FIELD: metallurgy.

SUBSTANCE: manufacturing method of high-strength steel reinforcement involves melting of steel of the specified chemical composition, in which total content of Cr+Ni+Cu<0.14 is maintained, and ratio of aluminium to boron (Al/B) is within 10 - 20; heat treatment of hot-rolled rod is performed by heating in the furnace up to 900-940°C with further isothermal hardening during 85-110 seconds in molten lead at temperature of 530-560°C and final water cooling, and drawing of hot-rolled rod is performed with total shrinkage of 57-62%. Invention will allow obtaining metal nanostructure after heat treatment, which consists of ferrite-carbide mixture with interlamellar distance of 80-180 nm and small quantity of structurally free ferrite in the form of islands along grain boundaries. Strength of not less than 1570 N/mm2, yield strength of not less than 1400 N/mm2 and relative breaking elongation of not less than 6% is provided in cold deformed high-strength reinforcement.

EFFECT: improving strength.

1 dwg

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention includes compositions and methods for obtaining activated polymer nanoparticles for targeted delivery of medication. Nanoparticle includes biocompatible polymer and amphiphilic stabilising agent, non-covalently bound with linker, which includes, at least, one elecrophile, selectively reacting with any nucleophile on targeting substance, and places targeting substance on external surface of biodegradable nanoenvelope, active substance being loaded into nanoenvelope. Biocompatible po;ymer includes one or several polyesters, selected from group, containing polylactic acid, polyglycolic acid, copolymer of lactic and glycolic acids and their combinations. Amphiphilic stabilising agent includes polyol. Active substance represents anti-cancer medication, preferably, curcumin.

EFFECT: invention ensures delivery of therapeutic substance to the place of its action.

27 cl, 11 dwg, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to method of obtaining modeling mass with biocidal properties. Organosiloxane is mixed with boric acid and Lewis's acid, obtained mixture is heated, biocidal additive and, at least, one additive, selected from group, which includes filling agent, pigment, plasticiser, are introduced. Boric acid is taken in amount 4-40 wt.f. per 100 wt.f. of organosiloxane, Lewis's acid is taken in amount 0.001-3 wt.f. per 100 wt.f. of organociloxane, as biocidal additiove silver nanoparticles in amount 0.00001-0.1 wt.f. per 100 wt.f. of organosiloxane are taken. Silver nanoparticles are introduced under heating, heating being performed by superhigh-frequency irradiation to temperature 100-50°C for 10-90 minutes.

EFFECT: invention makes it possible to simplify known method of obtaining modeling mass for and increase its biocidal properties by 40-70 times.

1 tbl, 18 ex

FIELD: chemistry.

SUBSTANCE: invention relates to filler materials made of nanoparticles for use in composite materials, including dental composite materials. The filler materials contain clusters of silica and zirconium dioxide nanoparticles. The filler materials can be obtained by mixing a sol of silica nanoparticles with a sol of pre-formed crystalline particles of zirconium nano-oxide.

EFFECT: filler materials provide the desired optical properties, such as opalescence, and are useful in dental compositions.

25 cl, 4 tbl, 2 dwg

FIELD: chemistry.

SUBSTANCE: invention can be used when producing titanium dioxide based catalysts for photocatalytic treatment of water and air from organic compounds. The method of producing titanium dioxide involves feeding reactants into a reactor continuously, hydrolysis of titanium tetrachloride solution with an alkaline agent while stirring, separating residue from solution, washing, drying and calcining the residue. Titanium tetrachloride is hydrolysed with aqueous suspension of calcium hydroxide, and after hydrolysis, the fine fraction of the end product is separated from the suspension and the coarse fraction is returned into the reactor. The end product is washed after the step for calcination of titanium hydroxide with pure hydrochloric acid at pH=1-2, and the product is re-dried. The size of calcium hydroxide particles fed into the reactor for hydrolysis is not less than 3 mcm, and concentration of titanium tetrachloride is kept not more than 2%.

EFFECT: invention enables to obtain pure nanodispersed titanium dioxide.

9 cl, 1 tbl, 1 ex

FIELD: process engineering.

SUBSTANCE: invention relates to machining jet-forming channels in nozzle diamond insert for gas- and hydroabrasive machining. Nozzle insert channel is roughed by coarse diamond powder. Then, channel surface is finished by polishing using the mix containing nanodiamond powder, powder of iron and alloy of aluminium with copper or nickel the following ratio of components in wt %: nanodiamond powder 2.0-3.0, powder of iron 10-13.0 and alloy of aluminium with copper or nickel 0 85.0-88.0.

EFFECT: decreased labor input, higher wear resistance, higher efficiency of blasting.

FIELD: electricity.

SUBSTANCE: device comprises an active layer arranged between two current-conducting layers, being in electric contact with them and representing an oxide of the type ABOx, where the element B is titanium, or zirconium, or hafnium, and the element A - a trivalent metal with ion radius, equal to 0.7-1.2 of ion radius of titanium, or zirconium, or hafnium. If the element B is titanium, then A is selected as aluminium or scandium, if the element B is zirconium or hafnium, then A is selected as scandium or ittrium or lutecium.

EFFECT: increased stability and recurrence of switching voltage, resistance in low and high resistance conditions.

3 cl, 2 dwg

FIELD: instrument making.

SUBSTANCE: heating of resistance strain gauges by pulse electric current is carried out after sealing of the inner cavity of the sensor system with simultaneous action at its receiving pressure cavity, exceeding the maximum permissible overload pressure 1.05 times, and minimum permissible lower temperature during operation, and also pressure that exceeds maximum permissible overload pressure 1.05 times and higher temperature exceeding 1.05 times the maximum permissible higher temperature during operation. Thermal stabilisation is carried out at the temperature that exceeds 1.05 times the maximum permissible higher temperature during operation. Measurements of initial output signals during thermal stabilisation are carried out under higher supply voltage. Control of initial output signal variation speed is carried out by ratios of speed of variation of given values of initial output signals in the last and last but one measurement of the initial output signal during thermal stabilisation.

EFFECT: higher stability of an initial and a nominal output signal of sensors, detection of hidden defects of resistance strain gauges at early stages of manufacturing.

FIELD: instrument making.

SUBSTANCE: pressure sensor with a thin-film nano- and microelectromechanical system (NaMEMS) is designed for use when exposed to non-stationary temperatures and higher vibration accelerations. The pressure sensor of strain gauge type with a thin-film nano- and microelectromechanical system (NaMEMS) comprises a body, a NaMEMS installed in it, comprising a round membrane, arranged as a whole with a peripheral base, a heterogeneous structure from thin films of materials formed on it, where resistance strain gages are formed, arranged as identical square strain gauge elements connected by thin-film links of identical quantity. Strain gauge elements of the first pair of resistance strain gauges are arranged as symmetrical between each other relative to mutually perpendicular axes of a membrane, stretching via centres of resistance strain gauges, and symmetrical to appropriate strain gauge elements of the second pair of resistance strain gauges, relative to mutually perpendicular axes of the membrane, stretching via centres of contact sites, arranged symmetrically relative to mutually perpendicular axes of the membrane stretching via centres of resistance strain gauges. Distances between strain gauge elements of the first pair of resistance strain gauges are equal to each other and are equal to distances between strain gauge elements of the second pair of resistance strain gauges. Centres of all strain gage elements are arranged along a circumference, radius of which is defined in accordance with the appropriate ratio.

EFFECT: reduced error of measurements in pressure sensors of strain gauge type and also increased long-term stability and reduced non-linearity of a calibration characteristic.

3 dwg

FIELD: chemistry.

SUBSTANCE: present invention relates to composites comprising inorganic micropigments and/or filler in form of surface-phosphated microparticles, whose surface is at least partially coated with finely ground alkali-earth carbonate nanoparticles by means of binders based on copolymers comprising as the monomers one or more dicarboxylic acids and one or more monomers from a group of diamines, triamines, dialkanolamines or trialkanolamines and epichlorohydrin, a method of producing such composites, aqueous suspensions thereof and use thereof in papermaking or in production of paints and plastics as well as the use of the binders for coating of microparticles with nano alkali-earth carbonate.

EFFECT: providing pigment or filler composites and aqueous suspensions thereof, which have good optical properties, good printing properties and have low solvent absorption.

47 cl, 9 tbl, 11 dwg

FIELD: chemistry.

SUBSTANCE: elastomeric composition contains a combination of polymers, filler, plasticising additives, vulcanising agents in form of sulphur and sulphur-containing compounds and a mixture of nanostructured modifiers. The polymer combination consists of a mixture of synthetic isoprene rubber and stereoregular butadiene rubber, filler - combination of technical carbons, plasticising additives - stabilising system consisting of naphtham-2 and paraffin.

EFFECT: longer life of the working part of shock-absorbers - material made from the disclosed elastomeric composition.

1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to medicine, namely to a pharmaceutical composition for local application. The composition contains chondroitin sulphate, hyaluronidase, glucosamine hydrochloride, liposome and pharmaceutically acceptable carriers and excipients in the amounts specified in the patent claim. The composition may additionally contain capsaicin.

EFFECT: pharmaceutical composition according to the invention is characterised by fast skin penetration of the ingredients.

3 cl, 4 ex

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