RussianPatents.com

Solid-phase method of producing bioactive nanocomposite

IPC classes for russian patent Solid-phase method of producing bioactive nanocomposite (RU 2416389):
Another patents in same IPC classes:
Method for producing viable breast cells Method for producing viable breast cells / 2409664
Solution of viable breast cells after enzymatic degradation in a collagenase solution of analysed tissue at temperature 37°C for 30-35 minutes, are applied on a biomaterial of a native form of hyaluronic acid, stored at room temperature and constant humidity 30-50 %, and cell viability is controlled by discoloration of cell monolayer.
Novel cross-linking reagents for producing chitosan-based biocompatible materials Novel cross-linking reagents for producing chitosan-based biocompatible materials / 2408618
Articles based on biologically active polymer materials can be used in surgery when treating wounds and as materials for temporary replacement of body tissue, in biotechnology for obtaining matrices for growing cell cultures, in pharmaceuticals as carriers of enzymes and other biologically active compounds. The cross-linking reagents are 2,4-derivatives of 3-oxa glutaric dialdehyde (2,2'-oxydiacetaldehyde). These compounds can be obtained via periodate oxidation of monosaccharides, nucleosides and nucleotides.
Method of obtaining polysaccharide material Method of obtaining polysaccharide material / 2392972
Invention relates to a method of obtaining polysaccharide fibre for making materials, specifically for making surgical suture materials absorbable in a human and a mammal body, absorbable and non-absorbable dressing material and absorbable textile matrix materials. The method is characterised by that 2.4-4.0 wt % solution of polysaccharide in dimethylacetamide which contains 4.56-10.00 wt % lithium chloride is mixed with 1.0-5.0 wt % poly-N-vinylpyrrolidone with molecular weight of 8-35 kDa or a metallopolymer complex - fine-grained silver stabilised by poly-N-vinylpyrrolidone in such an amount that, content of fine-grained silver relative polysaccharide dissolved in spinning solution ranges from 0.07 to 0.87 wt %. Mass ratio of polysaccharide: metallopolymer complex equals 88.0-99.0:1.0-12 wt %. The mixture is intensely stirred, held, filtered, degassed and the obtained spinning solution is extruded at room temperature into an alcohol deposition tank in form of water-soluble aliphatic C2 and C3 alcohols. The fibre is then processed in plastification and washing tanks and dried.
Taxanes covalently bonded with hyaluronic acid or hyaluronic acid derivatives Taxanes covalently bonded with hyaluronic acid or hyaluronic acid derivatives / 2384593
Invention relates to taxane, especially to paclitaxel and docetaxel covalently bonded with hyaluronic acid or a hyaluronic acid derivative, used as active substance in pharmaceutical compositions which are used in oncology, for treating tumours, autoimmune diseases and restenosis, as well as a coating for stents and medical devices. The covalent bond is formed between hydroxyl groups of taxane and carboxyl groups or hydroxyl groups of hyaluronic acid or hyaluronic acid derivatives, or amino groups of deacetylated hyaluronic acid. Bonding can take place using a linking compound (spacer compound) which bonds taxane with hyaluronic acid or hyaluronic acid derivative under the condition that, the linking compound is different from hydrazide.
Composition - osteoinducer and osteoconductor in treatment of bone pathology in dentistry and oral surgery and method of obtaining composition - osteoinducer and osteoconductor in treatment of bone pathology in dentistry and oral surgery / 2383564
Composition includes chitosan gel, which has bactericidal properties, representing matrix for including in it of water solution for "Adgelon" injection, which contains serum glycoprotein from blood of livestock, possessing biological activity in supersmall doses 10-9-10-15 mg/ml, and calcium salt - preparation "Adgelon". In obtaining composition medicine "Adgelon" is immobilised on chitosan gel.
Complex matrix for medico-biological application Complex matrix for medico-biological application / 2360928
Complex matrix consists of at least one biologically compatible polymer of natural origin, structured with sewing agent, which represents two- or multi-functional molecule, selected from epoxides, epihalohydrines and divinyl sulphone, on said polymer inoculated are chains with molecular weight less than 50000 daltons, selected from polymers of natural origin of small size, preferably, derivatives of cellulose or other biological polymer derivatives which naturally are not present in human organism, and/or non-polymerised chains with properties of oxidation inhibitors or ability to inhibit reactions of matrix decomposition, preferably, vitamins, enzymes or molecules, consisting of one or several cycles, degree of inoculation, expressed as ratio of moles of inoculated molecules and quantity of moles of polymer units, constitutes from 10 to 40%. Also described are method of obtaining such matrix and its application for separation, replacement, filling or addition of biological fluid or tissues.
Method for production of modified paper / 2355842
Invention relates to papermaking technology, precisely to production of modified paper with higher gas-proof and heat-protective properties, and can be applied in constructions, aircraft and automobile constructions, shipbuilding. The method includes treatment of paper with the mixture of 5-7% aqueous solution of polyvinyl alcohol with 5-7% aqueous solution of chitosan at their ratio 1:1 within 10-15 minutes, thereafter treatment with 15-20% aqueous solution of methyl phosphate borate and drying.
Compound for production of modified paper / 2355841
Invention relates to production technology of synthetic paper, precisely to production of modified paper with higher gas-proof and heat-protective properties, and can be applied in constructions, aircraft and automobile constructions, shipbuilding. The compound contains 5-7% aqueous solution of polyvinyl alcohol, 15-20% aqueous solution of methyl phosphate borate and 5-7% aqueous solution of chitosan at the following ratio, pts. wt. polyvinyl alcohol - 5-7; chitosan - 5-7; methyl phosphate borate - 15-20; water - 275-266.
Chitosanium perchlorate, method for its preparing and power-consuming composition comprising thereof Chitosanium perchlorate, method for its preparing and power-consuming composition comprising thereof / 2315774
Invention describes chitosanium perchlorate of the following formula: C6O4H9NH3ClO4. This compound shows such properties as explosion-proof, absence of toxicity, resistance to moisture and heating, mechanical effects and possesses high oxidizing and binding properties. This allows its using in power-consuming compositions in mixture with chitosanium dodecahydro-clozododecaborate wherein it functions as a binding agent. The quantitative ratio between chitosanium dodecahydro-clozododecaborate in the composition is determined by required regimen of combustion: the more content of chitosanium perchlorate the higher activity of the composition.
Chitosan product, method for its preparing (variants) Chitosan product, method for its preparing (variants) / 2313538
Invention relates to preparing biologically active chitosan substances and their derivatives. Invention describes a modified chitosan substance showing pH-neutral reaction and plastic structure of chitosan particles as fractal chitosan particles of size of nanofractals from 1 nm, not less, and to 5000 nm, not above, or as cross-linked net-shaped polymer having multiple cavities of size from 1 nm, not less, to 50 nm, not above. Invention describes methods for their preparing. Invention provides high transdermal penetration of chitosan substance and enhanced capacity for administration of medicinal or biologically active substances into chitosan substance. Invention can be used in manufacturing cosmetic, curative-cosmetic, pharmacological preparations, biologically active food supplements and foodstuffs.
Anti-tumour bioconjugates of hyaluronic acid or its derivatives, obtained by indirect chemical conjugation Anti-tumour bioconjugates of hyaluronic acid or its derivatives, obtained by indirect chemical conjugation / 2411958
Invention relates to novel group of chemical-pharmaceutical bioconjugates, which can be obtained by indirect synthesis by means of molecular spacer between hyaluronic caid and/or its derivatives and medications with anti-tumour activity, belonging to different groups, method of their obtaining. Invention also relates to anti-tumour pharmaceutical compositions and three-dimensional biomaterials based on said conjugate.
Method of preparing agent for presowing treatment of seeds of crops and agent / 2406715
Invention relates to crop husbandry and can be used in agriculture, forestry and fruit growing in order to increase yield. The method involves ultrasonic desalination of Artemia species cyst chorions for 1-5 minutes at ultrasonic specific power of 3.9-7.0 W/cm3 and hydromodulus of 1:40, ultrasonic deacetylation of chitin contained in the desalinated chorions, in a 40% solution of potassium hydroxide with hydromodulus of 1:4 - 1:7, specific power of 4.0-7.0 W/cm3 for 3-7 minutes, neutralisation of the obtained mixture with orthophosphoric acid. Zinc sulphate, copper sulphate, boric acid, ammonium molybdate, cobalt sulphate and tilon B are added to the obtained solution.
Method of producing chitine-containing composites / 2404996
According to the method, ground biomass of hymenophores of fruiting bodies of timber fungi is treated with an aqueous solution of a surfactant and then boiled for 1 hour in a low-concentration alkali solution. After that the biomass is saturated with a 10% hydrogen peroxide solution. Repeated treatment with an alkali solution is then carried out, followed by washing with water, neutralisation with acid and treatment with acetone. Drying is carried out for 30 minutes in air.
N-2-(2-pyridyl)ethylchitosan and synthesis method thereof N-2-(2-pyridyl)ethylchitosan and synthesis method thereof / 2396281
Invention relates to organic compounds and specifically to novel N-2-(2-pyridyl)ethylchitosan and synthesis method thereof. The said compound is obtained by reacting chitosan with aqueous solution of 2-vinylpyridine in the presence of hydrochloric acid in molar ratio 2-vinylpyridine: chitosan: hydrochloric acid equal to (2-4):1:1.The reaction is carried out at room temperature until formation of a gel. The gel is then heated to 68-72°C for 24-48 hours. The cooled reaction mass is treated with aqueous hydrochloric acid solution. Deposition and subsequent hot extraction with water-soluble alcohols or ketones and drying are carried out.
Adducts of chitosanium dodecahydro-closo-dodecaborate with perchloric acid or ammonium perchlorate Adducts of chitosanium dodecahydro-closo-dodecaborate with perchloric acid or ammonium perchlorate / 2394840
Invention relates to adducts of chitosanium dodecahydro-closo-dodecaborate with perchloric acid or ammonium perchlorate with formula (C6O4H9NH3)2B12H12xnMClO4 where n is an integer equal to 1-8, and M is H+, NH4+, which can be used as energy-consuming components of different compositions, e.g. pyrotechnic compositions. The adducts with perchloric acid are obtained by reacting chitosanium dodecahydro-closo-dodecaborate with an aqueous solution of perchloric acid, taken in molar ratio of 1:n, where n is an integer equal to 1-8, with subsequent concentration of the obtained mixture and final drying to constant mass while heating. The adducts with ammonium perchlorate are obtained by reacting adducts with perchloric acid with excess ammonia gas, with concentration of the obtained mixture and drying, as for adducts with perchloric acid. Adducts with ammonium perchlorate do not become wet in air and adducts with perchloric acid exhibit some hygroscopicity, which requires their protection from moisture.
Derivative of hyaluronic acid and medical agent that contains it Derivative of hyaluronic acid and medical agent that contains it / 2390529
Invention relates to derivative of hyaluronic acid, where nonsteroid anti-inflammatory medical agent is joined to hyaluronic acid by means of covalent link, which contains partial structure of disaccharide unit of hyaluronic acid, to which anti-inflammatory medical agent is joined, being represented by the following formula (1): Y-CO-NH-R1-(O-R2)n (l) where Y-CO- represents one residue of disaccharide unit of hyaluronic acid; R2 represents a residue of nonsteroid anti-inflammatory medical agent represented by group Z-CO- or atom of hydrogen, provided that all R2 are not atom of hydrogen; -NH-R1-(O-)n represents spacer residue in compound-spacer represented by the formula H2N-R1-(OH)n, having hydroxyl groups in amount of n;R1 represents linear or ramified hydrocarbon group, containing from 2 to 12 atoms of carbon, which may have a substitute;-CO-NH- represents amide link of carboxyl group of hyaluronic acid as a component of hyaluronic acid saccharide with amides of compound-spacer;-O-CO- represents ester link of hydroxyl group of compound-spacer with carboxyl group in residue of nonsteroid anti-inflammatory medical agent, and n equals integer number from 1 to 3, where derivative of hyaluronic acid has an extent of susbstitution with nonsteroid anti-inflammatory medical agent from 5 to 50% mole per repeated unit of hyaluronic acid and carbonyl group in residue of hyaluronic acid, which represents component derivative of hyaluronic acid is available as participant in formation of amide link in process of binding with spacer-binding residue of nonsteroid anti-inflammatory medical agent or as free carboxyl group that does not participate in this process, according to extent of substitution of residue of nonsteroid anti-inflammatory medical agent. Invention also relates to solution and pharmaceutical agent for suppression of pain and/or suppression of inflammation and/or treatment of arthritis, derivative of hyaluronic acid, set and medical set for injection, including solution of hyaluronic acid derivative.
Method for synthesis of cross-linked salt of hyaluronic acid, modified with vitamines / 2387671
Invention relates to methods for synthesis of new cross-linked salts of hyaluronic acid (HA) which are modified with vitamins - natural polymer from the polysaccharide family. The method involves chemical reaction of a salt of hyaluronic acid, vitamins together with at least one cross-linking agent, simultaneously subjecting the initial reagents to pressure ranging from 5 to 1000 MPa and shear deformation in a mechanochemical reactor at temperature ranging from 20°C to 50°C. The reactor used is preferably a Bridgman anvil or an auger-type device, e.g. a double-screw extruder.
Method for synthesis of cross-linked hyaluronic acid salt modified with folic acid / 2387670
Invention relates to methods for synthesis of cross-linked salts of hyaluronic acid (HA) which are modified with folic acid - a natural polymer from the polysaccharide family. The method involves chemical reaction of a salt of hyaluronic acid, folic acid together with at least one cross-linking agent, simultaneously subjecting the initial reagents to pressure ranging from 5 to 1000 MPa and shear deformation in a mechanochemical reactor at temperature ranging from 20°C to 50°C. The reactor used is preferably a Bridgman anvil or an auger-type device, e.g. a double-screw extruder.
Method for synthesis of cross-linked retinol-modified salt of hyaluronic acid / 2386641
Invention relates to synthetic polymer chemistry and more specifically to methods for synthesising cross-linked retinol-modified salts of hyaluronic acid (HA), which is a natural polymer from the polysaccharide class. The method involves chemical reaction of a salt of hyaluronic acid and retinol with at least one cross-linking agent, while subjecting the initial reagents to simultaneous reaction at pressure ranging from 5 to 1000 MPa and shear deformation in a mechanochemical reactor at temperature ranging from 20°C to 50°C. The reactor used is preferably a Bridgman anvil or an auger-type device, e.g. a double-screw extruder. The technical result is design of a universal environmentally safe method which enables production of a range of cross-linked retinol-modified salts of hyaluronic acid in a single-step process without a liquid medium, obtaining desired products with quantitative output.
Method for synthesis of cross-linked riboflavin-modified salt of hyaluronic acid / 2386640
Invention relates to synthetic polymer chemistry and more specifically to methods for synthesising cross-linked riboflavin-modified salts of hyaluronic acid (HA), which is a natural polymer from the polysaccharide class. The method involves chemical reaction of a salt of hyaluronic acid and riboflavin with at least one cross-linking agent, while subjecting the initial reagents to simultaneous reaction at pressure ranging from 5 to 1000 MPa and shear deformation in a mechanochemical reactor at temperature ranging from 20°C to 50°C. The reactor used is preferably a Bridgman anvil or an auger-type device, e.g. a double-screw extruder. The method does not require large energy, labour and water inputs, enables use of a wide variety of initial reagents, including water-insoluble salts of hyaluronic acid.
Optical nano t-flip flop Optical nano t-flip flop / 2416117
Said tasks arise when designing and making optical computing nanomachines or receive/transmit nanodevices which provide information processing in the tera- and gigahertz ranges. The optical nano T-flip flop consists of a source of constant optical signal, an optical 5-output nanofibre splitter, an optical 4-output nanofibre splitter, four optical nanofibre Y-splitters, six extensible nanofibres and five optical nanofibres.

FIELD: chemistry.

SUBSTANCE: invention relates to synthetic polymer chemistry. The nanocomposite contains a matrix in form of a cross-linked salt of hyaluronic acid which is modified with sulphur-containing compounds and nanoparticles of a noble metal as filler. A film of the cross-linked salt of hyaluronic acid which is modified with sulphur-containing compounds is obtained through chemical reaction of the salt of hyaluronic acid with a mixture of two sulphur-containing compounds and with a cross-linking agent, under conditions with pressure between 50 and 300 MPa and shear deformation in a mechanical reactor at temperature between 20 and 30°C. The reactor used to obtain the film is a Bridgman anvil.

EFFECT: invention enables to obtain a range of new bioactive nanocomposites with quantitative output and in the absence of a liquid medium, where the method does not require high energy, labour and water consumption and significantly increases efficiency of the composite; in particular, resistance to decomposition in the presence of hydroxyl radicals is 2-3 times higher compared to the control result.

16 cl, 7 ex

 

The invention relates to natural polymers from the class of polysaccharides, namely solid-phase method for the production of bioactive nanocomposites nanocomposite based on chemically modified sulfur-containing compounds stitched salt of hyaluronic acid (ha) and nanoparticles of noble metals, and can find application in various fields of medicine, in cosmetics, for example, in aesthetic dermatology and plastic surgery.

Unknown solid-phase methods for the production of bioactive nanocomposites nanocomposite based on chemically modified sulfur-containing compounds stitched salts and nanoparticles of noble metals. However, the known solid phase method of obtaining a crosslinked hyaluronic acid salt (patent RF 2366665), as well as a method of obtaining a crosslinked hyaluronic acid salt in solution (patent RF 2366666).

Known liquid-phase multi-stage method for the production of bioactive nanocomposites nanocomposite based on chemically modified sulfur-containing compounds and oligomeric polypeptides, hyaluronic acid (molecular weight 3000-8000) and nanoparticles (16 nm) gold [H.Lee, K.R.Lee, I.Kim, T.Park. "Synthesis, Characterization and in vivo Diagnostic Application H.A. immobilized Gold Nanoparticles". Biomaterials, 2008, 29, No. 35, 4709-4718]. Bioactive nanocomposite was prepared as follows: in the aquatic environment modify oligomeric hyaluronic acid applied, nitrobenzimidazole and di is matricola, then activate 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide, and then add the polypeptide with the dye, Hilyte Fluor 647. The resulting composite product is added to the aqueous colloidal solution of gold nanoparticles. Thus formed nanocomposite containing one particle of gold as at 31 oligomeric molecule of hyaluronic acid. Information about consumer properties of the nanocomposites nanocomposite is not given.

The disadvantages of this method are multi-stage, a longer duration of chemical processes, high cost of organic reagents, time-consuming purification of the final products.

The objective of the invention is the creation of environmentally safe fundamentally new solid-phase method, which allows to obtain not previously known bioactive nanocomposites in the absence of a liquid medium, without large energy labor and vadastra, thus to obtain the target products in high yield, to increase the efficiency of composites, in particular to improve the resistance to degradation in the presence of hydroxyl radicals, and use a variety of source reagents for obtaining matrices, including water-insoluble salt Ledger, and various fillers and thereby to expand the range of the obtained composites.

The problem is solved in that it is designed principally n the new environmentally safe solid-phase method for the production of bioactive nanocomposites nanocomposite, includes a modified sulfur-containing compounds stitched salt of hyaluronic acid as a matrix and nanoparticles of a noble metal as a filler, which consists in the fact that the film-modified sulfur-containing compounds crosslinked hyaluronic acid salt, obtained by a chemical interaction of the salt of hyaluronic acid with a mixture of two serosoderjaschei compounds and cross-linking agent in the simultaneous effects of pressure in the range from 50 to 300 MPa and shear strain in mechanochemical reactor at a temperature of from 20° to 30°With handle pairs of noble metal by cathodic sputtering, the degree of filling of the composite metal is 3·10-2up to 10-1wt.%.

The film thickness of the modified crosslinked hyaluronic acid salt is in the range from 40 to 80 μm. The noble metal is a metal from a number of: gold, silver, platinum, palladium. The filler nanoparticles have a size of from 1 to 10 nm.

As serosoderjaschei connections connections can be used from a number of: Biotin, thiamine, L-cysteine, cystine, methionine, glutathione, methylmethanesulfonate chloride, 1-thioglycerol, 2-mercaptoethanol, 2-mercaptobenzthiazole, thiourea, 1,4-dimercapto-2,3-diol, acid number: thioglycolate, 2,3-dimercaptopropane, lipoic. In particular, Caruso is containing a series connection is: a mixture of glutathione and 1,4-dimercapto-2,3-diol.

As the salts of hyaluronic acid, you can use salt from the series: tetraalkylammonium, lithium, sodium, potassium, calcium, magnesium, barium, zinc, aluminum, copper, gold, or a mixed salt of hyaluronic acid of the above number or Hydrosol hyaluronic acid. In particular, the salt of hyaluronic acid is sodium or mixed gold-sodium salt.

As a cross-linking agent can be used ether from the series: diglycidyl ether of ethylene glycol, diglycidyl ether of diethylene glycol, diglycidyl ether of triethylene glycol, diglycidyl ether of polyethylene glycol, diglycidyl ether of propylene glycol, diglycidyl ether of 1,4-butanediol, diglycidyl ether of 1,6-hexandiol. In particular, cross-linking agent is diglycidyl ether of diethylene glycol.

The molar ratio of the salt of hyaluronic acid to the amount of serosoderjaschei compounds is in the range from 1000:1 to 100:1.

The molar ratio of the salt of hyaluronic acid to the cross-linking agent is in the range from 500:1 to 50:1. The molar ratio of the amount of serosoderjaschei connections to the cross-linking agent is in the range from 1:10 to 1:2.

The duration of the effects of pressure and shear strain ranges from 6 to 40 seconds.

Mechanochemical reactor, in particular, are the Bridgman anvils. is iformatio shift osushestvliayut by changing the angle of rotation of the lower anvil Bridgman in the range from 50 to 350 degrees.

Cathode spraying was carried out the spraying installation JFC-II00 E firm "JEOL", Japan) in a vacuum of 10-1PA, the voltage of 100 V, a current of 5 a and a frequency of 50 Hz.

In contrast to the known method, the claimed method of obtaining nanocomposites nanocomposite includes the step of obtaining the matrix of the modified sulfur-containing compounds crosslinked hyaluronic acid salt in the form of a film by the chemical interaction of the salt of hyaluronic acid with a mixture of two serosoderjaschei compounds and cross-linking agent, without solvent, in the simultaneous effects of pressure in the range from 50 to 300 MPa and shear strain in mechanochemical reactor at a temperature of from 20° to 30°C, whereas in the known method the matrix is to be based on chemically modified sulfur-containing compounds and oligomeric polypeptides, hyaluronic acid (molecular weight 3000-8000) in several stages in the water environment.

Another significant difference is that the introduction of the matrix filler is carried out by processing the obtained film pairs noble metal by cathodic sputtering, as in the known method to the resulting aqueous colloidal solution of the compound modified oligomeric hyaluronic acid applied, nitrobenzimidazole and dithiothreitol, and then activated 1-ethyl-3-(3-d is methylaminopropyl) carbodiimide are added to the Hydrosol of gold nanoparticles. The degree of filling of the composite gold is unknown, however, in relation to the oligomeric PS gold is 1-2%, while in the proposed method, the degree of filling of the composite metal is 3·10-2up to 10-1wt.%. Besides gold filler are and other precious metals.

Thus reached a new technical result, namely, that the simplified method (Maastricht), allows you to extend the range of the obtained composites due to the possibility to use a variety, including water-insoluble salt of ha. Resistance to degradation in the presence of hydroxyl radicals produced composites increased 2-3 times compared with the control result. In addition, it should be noted that the solution of this problem was made possible thanks to the fact that the process is carried out by interaction of initial reagents in solid powdered state with the simultaneous action of pressure and shear strain. The method essentially is unique, environmentally safe, does not require much energy, labor and vadastra, target products are obtained with high yield

Quantitative output of products depends on the degree of interaction glycidyloxy groups of the crosslinking agent with the hydroxyl groups of salts Ledger and hydroxyl is or carboxyl groups, serosoderjaschei compounds. Therefore, a quantitative yield of the target products were judged according to FTIR spectral analysis of the initial reagents and reaction products. It is established that in the spectra of these products are completely absent characteristic bands glycidyloxy groups cross-linking agents (850-860 and 900-920 cm-1and present resulting from the interaction glycidyloxy groups of the crosslinking agent with the hydroxyl groups of salts GC and sulfur-containing compounds. Output modified crosslinked salts Ledger was determined by the results of extraction of the aqueous or alcoholic solution of the final products of the reaction at 50°C. were isolated from extracts of the products of interaction deg-1 serosoderzhashchimi compounds, unreacted salts Ledger was 1-3 wt.% the number of initial components, which corresponds to almost quantitative (97-99%increase) the output of the modified crosslinked salts Ledger. The size of nanoparticles of noble metals was evaluated according to the position of the maximum absorption of dilute colloidal solutions (hydrogels) in the UV spectra [Laakmann, Washeteria, Soumerai, Nghiem. GOLD NANOPARTICLES. The synthesis, properties and biomedical applications. M., Nauka. 2008, p.46]. Resistance to degradation in the presence of hydroxyl radicals is estimated by the value of half of reducing the viscosity of the hydrogels obtained and the final products, as described by Wong et al. in Inorganic Biochemistry, V. 14, R (1981) and in the patent of Russian Federation №2174985. Control the size of half of reducing the viscosity of the hydrogel of the nanocomposites nanocomposite obtained from the same source components, but the liquid-phase method is 55 hours (see comparative example 7).

The invention can be illustrated by the following examples:

Obtaining bioactive nanocomposites nanocomposite

Example 1. A powder mixture of 160,0 mg (4·10-4mole) of sodium salt SC (mol. weight 2300000), 0.65 mg (2·10-6mole) of glutathione, 0.4 mg (8·10-6mole) 1,4-dimercapto-2,3-diol, 2,7 mg (8·10-6mole) diglycidylether ether of diethylene glycol (deg-1) is placed on the lower anvil Bridgman (the diameter of the working surface =3 cm), cover the top of the anvil, the anvil put under a press and subjected to pressure of 300 MPa at 20°C, at an angle of rotation of the lower anvil 350° for 40 sec. Further relieve pressure, remove the anvil from the press. The formed film thickness of 80 μm of the modified sulfur-containing compounds, crosslinked sodium salt SC is placed in a sputtering device with a gold cathode and sprayed gold for 40 sec. The maximum absorption is 513 nm, which corresponds to the value of 5 nm for the size of the gold particles. The degree of filling of the composite gold is 5·10-2%. The magnitude of the half-cycle reduction wask the STI hydrogel, obtained from the final product, is 160 hours.

Example 2. Performed analogously to example 1, but in contrast, the film of the modified sulfur-containing compounds, crosslinked sodium salt SC sprayed gold for 80 sec. The maximum absorption is 516 nm, which corresponds to the value of 10 nm for the size of the gold particles. The degree of filling of the composite gold is 10-1%. The magnitude of the half-cycle reduce the viscosity of the hydrogel obtained from the final product, is 170 hours.

Example 3. Performed analogously to example 1, but in contrast, the film of the modified sulfur-containing compounds, crosslinked sodium salt SC sprayed gold for 8 sec. The maximum absorption is 510 nm, which corresponds to the value of 1 nm for the size of the gold particles. The degree of filling of the composite gold is 3·10-2%. The magnitude of the half-cycle reduce the viscosity of the hydrogel obtained from the final product, is 150 hours.

Example 4. A powder mixture of 174,0 mg (4·10-4mole) of the mixed sodium-gold salt at a molar ratio of sodium: gold =12:1, 0,065 mg (2·10-7mole) of glutathione, 0.04 mg (8·10-7mole) 1,4-dimercapto-2,3-diol, 0.27 mg (8·10-7mole) diglycidylether ether of diethylene glycol (deg-1) is placed on the lower anvil Bridgman (the diameter of the working surface is STI =3 cm), cover with the top anvil, anvils put under a press and subjected to pressure of 50 MPa at 20°C, at an angle of rotation of the lower anvil 50° for 6 sec. Further relieve pressure, remove the anvil from the press. The formed film thickness of 80 μm of the modified sulfur-containing compounds stitched mixed sodium-gold CC salt is placed in a sputtering device with a silver cathode and sprayed silver for 30 sec. The maximum absorption at 410 nm, which corresponds to the size of 7 nm size particles of silver. The degree of filling of the composite silver is 7·10-2%. The magnitude of the half-cycle reduce the viscosity of the hydrogel obtained from the final product, is 110 hours.

Example 5. Performed analogously to example 1, but in contrast, the formed film thickness of 80 μm of the modified sulfur-containing compounds, crosslinked sodium salt SC is placed in a sputtering device with a platinum cathode and sprayed with platinum for 30 sec. The maximum absorption is 245 nm, which corresponds to the value of 8 nm for the size of the platinum particles. The degree of filling of the composite platinum is 8·10-2%. The magnitude of the half-cycle reduce the viscosity of the hydrogel obtained from the final product, is 250 hours.

Example 6. Performed analogously to example 1, but in contrast to the negatives is the weight of the starting components is reduced by two times, and the temperature of the anvils 30°C. in Addition, the formed film thickness of 40 μm of the modified sulfur-containing compounds, crosslinked sodium salt SC is placed in a sputtering device with a palladium cathode and sprayed palladium for 25 sec. The maximum absorption at 230 nm, which corresponds to the value of 5 nm for the particle size of palladium. The degree of filling of a composite palladium is 4·10-2%. The magnitude of the half-cycle reduce the viscosity of the hydrogel obtained from the final product is 240 hours.

Example 7. Comparative example. 160,0 mg (4·10-4mole) of powdered sodium salt SC (mol. weight 2300000), 0.65 mg (2·10-6mole) of glutathione, 0.4 mg (8·10-6mole) 1,4-dimercapto-2,3-diol, 2,7 mg (8·10-6mole) diglycidylether ether of diethylene glycol (deg-1) dissolved in 20 ml of bidistilled water and leave to stand in a Petri dish at room temperature until complete evaporation of water. The formed film of the modified sulfur-containing compounds, crosslinked sodium salt SC transferred to the hydrogel by adding 5 ml of bidistilled water. Next to this hydrogel was added 1 ml of Hydrosol of gold, containing 0.16 mg of gold nanoparticles with a size of 10 nm, prepared according to the method of Frens [Laakmann, Washeteria, Soumerai, Nghiem. GOLD NANOPARTICLES. Synthetic is, properties for biomedical application. M., Nauka. 2008, p.39]. Stir the mixture until odnorodnogo state. The maximum absorption is 516 nm, which corresponds to the value of 10 nm for the size of the gold particles. The degree of filling of the composite gold is 10-1%. The magnitude of the half-cycle reduce the viscosity of the hydrogel obtained from the final product is 55 hours.

The examples clearly show that created a fundamentally new, environmentally friendly way to get a number of new bioactive nanocomposites in the absence of a liquid medium, to obtain the desired products in high yields. The method does not require large energy, labor and vadastra, allows it to be used as the source of a variety of reagents, including water-insoluble, salt Ledger. Achieved a significant increase in the effectiveness of composites, in particular resistance to degradation in the presence of hydroxyl radicals increased 2-3 times compared with the control value of the half period reduce the viscosity of the hydrogel, of the nanocomposites nanocomposite obtained by liquid-phase method.

1. Method for the production of bioactive nanocomposites nanocomposite comprising a modified sulfur-containing compounds stitched salt of hyaluronic acid as a matrix and nanoparticles of a noble metal as a filler, allcauses is that film modified sulfur-containing compounds crosslinked hyaluronic acid salt, obtained by a chemical interaction of the salt of hyaluronic acid with a mixture of the two sulfur-containing compounds and cross-linking agent, in the simultaneous effects of pressure in the range from 50 to 300 MPa and shear strain in mechanochemical reactor at a temperature of from 20 to 30°With handle pairs of noble metal by cathodic sputtering, the degree of filling of the composite metal is 31·10-2up to 10-1wt.%.

2. The method according to claim 1, characterized in that the film thickness of the modified crosslinked hyaluronic acid salt is in the range from 40 to 80 microns.

3. The method according to claim 1, characterized in that the noble metal is a metal from a number of: gold, silver, platinum, palladium.

4. The method according to claim 1, characterized in that the filler nanoparticles have a size of from 1 to 10 nm.

5. The method according to claim 1, characterized in that the mixture of sulfur-containing compounds selected from the range of: Biotin, thiamine, L-cysteine, cystine, methionine, glutathione, methylmethanesulfonate chloride, 1-thioglycerol, 2-mercaptoethanol, 2-mercaptobenzthiazole, thiourea, 1,4-dimercapto-2,3-diol, acid number: thioglycolate, 2,3-dimercaptopropane, lipoic.

6. The method according to claim 5, characterized in that a mixture of sulfur-containing compounds is the tsya mixture of glutathione and 1,4-dimercapto-2,3-diol.

7. The method according to claim 1, characterized in that the salt of hyaluronic acid is a salt of a number: tetraalkylammonium, lithium, sodium, potassium, calcium, magnesium, barium, zinc, aluminum, copper, gold, or a mixed salt of hyaluronic acid of the above number, or Hydrosol hyaluronic acid.

8. The method according to claim 7, characterized in that the salt of hyaluronic acid is sodium or mixed gold-sodium salt.

9. The method according to claim 1, characterized in that the crosslinking agent is an ester of a number: diglycidyl ether of ethylene glycol, diglycidyl ether of diethylene glycol, diglycidyl ether of triethylene glycol, diglycidyl ether of polyethylene glycol, diglycidyl ether of propylene glycol, diglycidyl ether of 1,4-butanediol, diglycidyl ether of 1,6-hexandiol.

10. The method according to claim 9, characterized in that the crosslinking agent is diglycidyl ether of diethylene glycol.

11. The method according to claim 1, characterized in that the molar ratio of the salt of hyaluronic acid to the amount of sulfur-containing compounds is in the range from 1000: 1 to 100:1.

12. The method according to claim 1, characterized in that the molar ratio of the salt of hyaluronic acid to the cross-linking agent is in the range from 500:1 to 50:1.

13. The method according to claim 1, characterized in that the molar ratio of the amount of sulfur-containing compounds to cross-linking Agay the Tu is in the range from 1:10 to 1:2.

14. The method according to claim 1, characterized in that the duration of the effects of pressure and shear strain ranges from 6 to 40 C.

15. The method according to claim 1, characterized in that the mechanochemical reactor are Bridgman anvils.

16. The method according to item 15, wherein the shear deformation is carried out by changing the angle of rotation of the lower anvil Bridgman in the range from 50 to 350°.

 

© 2013-2015 Russian business network RussianPatents.com - Special Russian commercial information project for world wide. Foreign filing in English.