Solid-phase method of producing water-soluble bioactive nanocomposite based on melanin-modified hyaluronic acid salt and gold nanoparticles

FIELD: chemistry.

SUBSTANCE: invention relates to natural polysaccharide polymers and can be used in medicine. The obtained water-soluble bioactive nanocomposite includes a melanin compound-modified hyaluronic acid salt as a matrix and gold nanoparticles as filler. The method includes chemical reaction of solid-phase hyaluronic acid powder, a melanin compound, aurichlorohydric acid or a gold salt in conditions of simultaneous pressure action in the range of 50 to 1000 MPa and shearing deformation in a mechanochemical reactor at temperature of -18° to 110°C.

EFFECT: invention enables to obtain a water-soluble bioactive nanocomposite with high output of the end product and high content of gold.

4 cl, 18 ex

 

The invention relates to natural polymers from the class of polysaccharides, namely solid-phase method for the production of bioactive nanocomposites nanocomposite-based salt of hyaluronic acid (ha), melanin and gold nanoparticles, which can find application in medicine, in particular the photon capture therapy (ERT), photothermal therapy, photo - and radiosensibility, chemotherapy, treatment of rheumatoid arthritis, antovic therapy, cosmetology, aesthetic dermatology and plastic surgery.

The known method of synthesis of nanoparticles gadolinia, iron, Nickel, copper, erbium, europium, prasetiya, dysprosium, holmium, chromium or manganese-based melanin in solution [patent US 5310539, 1994, Melanin-based agents for image enhancement].

A method of obtaining nanoparticles of noble metals and the manufacture of materials and devices containing nanoparticles (patent RU 2233791, S. p. Gubin, etc., publ. 2004.08.10). This method of producing nanoparticles includes forming a two-phase system - molecular layer on the surface of the aqueous phase containing the water-insoluble ORGANOMETALLIC precursor molecules (used connection-acetate, palladium, Au(P(C6H5)3)Cl), and processes for the synthesis of metal nanoparticles by chemical transformations of the source reagent precursor under the action of chemical effects or chemical and physical is such impacts, or their combinations in a monomolecular layer on the surface of the liquid phase. When the reducing agent (borohydride sodium) were introduced in the aqueous phase. The method of manufacture of materials containing nanoparticles, is the introduction of the above particles in the material.

Known solid phase method for the production of bioactive nanocomposites nanocomposite [patent RU 2416389, publ. 2011]. The disadvantages of the method include: the preliminary stage of obtaining crosslinked hyaluronic acid salt in the form of a film using a number of cross-linking agents from the class of esters, the method combines the receipt of the modified GC in a solid coated WOOFER noble metal in the gas phase; the claimed method allows to obtain a composite with a degree of filling 3·10-2up to 10-1wt.%, insufficient for solving the problems of photo - and radiosensibility, chemotherapy, treatment of rheumatoid arthritis, antovic therapy.

The prior art is not known a method of obtaining a water-soluble bioactive nanocomposites nanocomposite based on chemically modified compounds from a number of melanin CC salt and gold nanoparticles.

Object of the present invention is to provide an environmentally safe, brand-new method of obtaining water-soluble bioactive nanocomposites nanocomposite based on chemically modified compounds from the number m is larinov CC salt and gold nanoparticles in a one-step process mode in the absence of a liquid medium, without a lot of energy, labor and vadastra, and obtaining the target product with a high yield and a high gold content.

The problem is solved in that created a fundamentally new environmentally friendly method of obtaining water-soluble bioactive nanocomposites nanocomposite comprising a modified connection of a number of melanin salt of hyaluronic acid as a matrix and the gold nanoparticles as a filler, which is that carry out chemical interaction of solid-phase powders of salts of hyaluronic acid, the compounds of the number of melanin, soloconsolidation acid (SHVC) or gold salts in the simultaneous effects of pressure in the range from 50 to 1000 MPa and shear strain in mechanochemical reactor at temperatures from -18° to 110°C. And the degree of filling of the composite gold (with a degree of oxidation 0, +2, +3) is from 5·10-6-5·10-1wt.% - up to 80 wt.%. The nanoparticles have a size of from 1 to 50 nm.

As the hyaluronic acid salt using salt selected from the range: tetraalkylammonium, lithium, sodium, potassium, calcium, magnesium, barium, zinc, aluminum, copper, gold or mixed salt of hyaluronic acid of the above number or Hydrosol hyaluronic acid.

In particular, the salt of hyaluronic acid is the fast sodium salt or a mixed salt or hydrometridae salt.

As connections from a number of melanin using water-soluble or insoluble pheomelanin, eumelanin, aromaland, synthetic or derived from natural sources. A distinctive feature malaysiaboleh structures is intense paramagnetic absorption in the area of the g-factor of the free electron concentration of unpaired electrons is greater than 1017spin 1 g of dry matter.

As gold reagents used soloconsolidation acid (HAuCl4·nH2O, where n=3 or 4), and gold salts - aurate: solutocapillary potassium (K[Aul4] ·nH2O, n=3 or 4), tetrachloroaurate(III) potassium (K[AuCl4]contains 52% of gold), tetrachloroaurate(III) ammonium (NH4[AuCl4]contains 52% of gold), tetrachloroaurate(III) sodium (Na[AuCl4]·n H2O, contains 49% of gold), tetrabromophenol(III) sodium (Na[AuBr4]contains 33% gold), dicyanoaurate potassium (K[Au(CN)4]contains 68.2% of gold), tetracenomycin(III) potassium (K[Au(CN)4]contains 58% gold), disulfiram(I) ammonium(NH4)3[Au(SO3)]2contains 10% gold), bis(thiosulfate)Aurat(I) sodium (Na3[Au(S2O3)2]·H2O, contains 37%), chloro(triphenylphosphine)gold(I) ([AuCl(PPh3)], contains 39% of gold).

The molar ratio of the salt of hyaluronic acid to the connection of a number of melanin is located is in the range from 100:1 to 1:100.

The molar ratio of soloconsolidation acid to the connection of a number of melanin is in the range from 1:1000 to 1:4, respectively.

The molar ratio of zolotoizvlekatelnoj potassium to the connection of a number of melanin is in the range from 1:1000 to 1:8, respectively.

The duration of the effects of pressure and shear strain, in particular, is in the range from 0.1 to 30 minutes, in particular 6 minutes at a pressure of 500 MPa. As a mechanochemical reactor can be used, in particular, Bridgman anvils or machine screw type.

In the case of the implementation process, where mechanochemical reactor are Bridgman anvils, the reaction mixture is subjected to shear by changing the angle of rotation of the lower anvil, in particular in the range from 50 to 350 degrees. For better implementation of the method, preferably the original reagents pre-homogenized in the mixer at a temperature from -18 to 5°C until a homogeneous powder mixture. In this case you can use as a mixer mill or a mixer, a screw type, for example a twin screw extruder.

In particular, mechanochemical reactor device is a screw type, for example, selected from the set: twin screw extruder with a unidirectional rotation of the screw, twin-screw the " extra " is an EP with oppositely directed rotation of the augers, twin screw extruder with a set of Cams of different types, such as transport, locking, peretiraya.

The method can be implemented sequentially, for example, first carry out a chemical reaction of the salt of hyaluronic acid together with the connection of a number of melanin, after which the product is subjected to interaction with ZHUK. When the molar ratio of SC to the connection of a number of melanin or the amount of modified agent is in the range from 100:1 to 1:100 and the ratio SHVC to the connection of a number of melanin, is in the range from 1:1000 to 1:8, respectively.

In the reaction mixture optionally, you can enter at least one stabilizing additive. As stabilizing additives used substance selected from the group of: carboxymethylcellulose (CMC), tetraalkylammonium, lithium, sodium, potassium, calcium, magnesium, barium, zinc, aluminum, copper, gold or mixed salt of CMC from the above number or Hydrosol CMC, hydroxyethyl cellulose, hydroxypropylcellulose. Moreover, the molar ratio of the salt of hyaluronic acid for stabilizing additive in the range from 100:1 to 1:1.

The conditions under which implemented the proposed method allows a simultaneous or sequential chemical interaction of the initial reagents, namely SHVC or with the and gold, restored during synthesis to nanoscale gold(0,+2,+3), on the one hand, with the hydroxyl groups of salt (salt) group with the formation of esters of the General Ledger and on the other hand - with carboxyl, amino, o-hydroxynonenal, Finansovye and semiholonomic, indolinone groups of connections from a number of melanin - formation of a stable chelate polycomplexes melanin-gold-Ledger, melanin-SC-gold, melanin-gold, CC gold, and mixtures thereof.

Such polycomplexes stability in General do not yield covalently bound systems, as they contain recurring polychelate fragments distributed on macrocopy of macrocomplex.

About the 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 strip in the area 1650-1590 cm-1confirm the presence of a large number of conjugated systems in the studied drugs of melanin, and the changing nature of the bands in the region in 3430-3370 cm-1corresponding to the vibrations of-Oh groups in the side 418, 441, 445 cm-1the corresponding fluctuations Au-0. 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 [L.A. Dykman, V.A. Bogatyrev, HE Shchegolev, N.G. crisp Bread. GOLD IS ANCESTERY. The synthesis, properties and biomedical applications. M., Nauka. 2008, p.46].

The invention can be illustrated by the following examples.

Example 1. 6.0 g (15·10-3mole) of powdered sodium salt of hyaluronic acid, 1.0 g (1·10-2mole) of pheomelanin and 2.0 g (5·10-3mole) soloconsolidation acid (SHVC) homogenized mill at -18°C for 10-15 minutes Then the homogeneous powder mixture is fed into the power zone twin screw extruder where the material transporting capture elements and move it along the length of the cylinder during rotation. In the second and the third zone the material is subjected to shear strain due to the mixing elements consisting of Cams scored five pieces with the angle of rotation between the Cams 45°, 90° and 45° (reverse). The items are placed at different angles contributes to the formation of constipation in goods movement and as a consequence his best mixing and great physical stress.

The extruder has a measuring speed of rotation of the augers, the readings of which is proportional to the input voltage and load meter on augers, showing the value of the constant current drive.

The process is carried out with the automatic loading of material in a stream of nitrogen, the feed rate of the reaction mixture was maintained to keep the specified level Naga is narrow on the augers. The speed of the augers were chosen in the range from 20 to 200 rpm·min-1. Load (current) without load 5 a, and solid-state reaction mixture is optimally supported 10÷25 A. Temperature in the first zone of 5°C, the second 110°C, in the third zone of 5°C. the Duration of the process is 3 minutes at a pressure of 100 MPa. The product yield is 8.8 g (98,0%). 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 11.4 wt.%.

Example 2. 6.0 g (15·10-3mole) of powdered sodium salt of hyaluronic acid, 1.0 g (1·10-2mole) eumelanin and 2.0 g (25·10-4mole) zolotoizvlekatelnoj potassium (K[AuI4]·nH2O, n=3 or 4) homogenized mill at -5°C for 10-15 minutes Then the homogeneous powder mixture is fed into the power zone twin screw extruder where the material transporting capture elements and move it along the length of the cylinder during rotation. In the second and the third zone the material is subjected to shear strain due to the mixing elements consisting of Cams scored five pieces with the angle of rotation between the Cams 45°, 90° and 45° (reverse). The items are placed at different angles contributes to the formation of constipation in goods movement and as a consequence his best mixing and great physical alongside the harsh environments.

The extruder has a measuring speed of rotation of the augers, the readings of which is proportional to the input voltage and load meter on augers, showing the value of the constant current drive.

The process is carried out with the automatic loading of material in a stream of nitrogen, the feed rate of the reaction mixture was maintained to hold the specified load level on the augers. The speed of the augers were chosen in the range from 20 to 200 rpm·min-1. Load (current) without load 5 a, and solid-state reaction mixture is optimally supported 30-40 A. Temperature in the first zone 0°C, the second 110°C, in the third zone of 5°C. the Duration of the process is 3 minutes at a pressure of 200 MPa. The product yield is 8.8 g (98,0%). 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 11.4 wt.%.

Example 3. Performed analogously to example 1, but unlike him take aromaland in the amount of 2.0 g (2·10-2mol), and SHUK take in the amount of 2.0 g (5·10-3mole). The product yield is 3,76 g (94%). The maximum absorption is 522 nm, which corresponds to the value of 12 nm for the size of the gold particles. The degree of filling of the composite gold is 26.5 wt.%.

Example 4. Performed as in example 2, is however in contrast instead of the sodium salt of the Ledger taken a mixed sodium-calcium salt at a molar ratio of sodium:calcium =2:1. The product yield is 8.8 g (98,0%). 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 11.4 wt.%.

Example 5. Performed analogously to example 1, however in contrast instead of the sodium salt of the Ledger taken mixed sodium-aluminum salt at a molar ratio of sodium:aluminum =3:1. The product yield is 8.6 g (95.0%). 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 11.6 wt.%.

Example 6. Performed analogously to example 2, however in contrast instead of the sodium salt of the Ledger taken mixed sodium-zinc salt at a molar ratio of sodium:zinc =2:1. The product yield is 8.8 g (97,0%). 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 11.4 wt.%.

Example 7. Performed analogously to example 2, however in contrast instead of the sodium salt of the Ledger taken mixed sodium-copper salt at a molar ratio of sodium:copper =2:1. The product yield is 8.6 g (96,0%), 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 11.6 wt.%.

Example 8. Made an is logical to example 2, however in contrast instead of the sodium salt of the Ledger taken hydrometridae salt at a molar ratio of sodium:hydrogen =1:1. The product yield is 8.8 g (98,0%). 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 11.4 wt.%.

Example 9. Performed analogously to example 1, however in contrast instead of the sodium salt of the Ledger taken mixed sodium-gold salt at a molar ratio of sodium : gold =3:1. The composition is homogenized in the mill at 5°C for 10-15 min Speed of rotation of the augers in the range from 60 to 200 rpm·min-1. Load (current) without load 5 a, and solid-state reaction mixture is optimally supported 30÷35 A. the Temperature in the first zone of 5°C, the second 110°C, in the third zone of 5°C. the Duration of the process is 3 minutes at a pressure of 500 MPa. The product yield is 8.8 g (98,0%). 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 11.4 wt.%.

Example 10. Performed as in example 2, but unlike him take of 300.0 g (75·10-2mole) of powdered sodium salt of hyaluronic acid, 50.0 g (5·10-1mole) eumelanin and 100.0 g (125·10-3mole) zolotoizvlekatelnoj potassium (K[Aul4]·nH2O, n=3 or 4), 50.0 g (21·10 -2mole) of sodium salt of CMC. The composition is homogenized in the mill at 5°C for 10-15 min Speed of rotation of the augers in the range from 30 to 100 rpm·min-1. Load (current) without load 5 a, and solid-state reaction mixture is optimally supported 25÷30 A. the Temperature in the first, second and third zone of 5°C. the Cycle is repeated 3 times. The temperature for the 4th run is in the first zone of 5°C, in the second 105°C, in the third zone of 5°C. the Duration of the process is ~15 minutes at a pressure of 300 MPa. The product yield is 499,5 g (~100,0%). The maximum absorption is 504 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 wt.%.

Example 11. Performed as in example 2, but unlike him take of 300.0 g (75·10-2mole) of powdered sodium salt SC, 100.0 g (5·10-1mole) eumelanin, 25,0 g (10,5·10-2mole) of sodium salt of CMC, 25,0 g of sodium salt of the GOC (5,5·10-3mole), homogenizers in the mill at 20°C for 10-15 min Speed of rotation of the augers in the range from 20 to 100 rpm·min-1. Load (current) without load 5 a, and solid-state reaction mixture is optimally supported 40÷45 A. the Temperature in the first, second and third zone 50°C. the Cycle is repeated 3 times. The temperature for the 4th run is in the first zone 15°C, the second is 15°C, in the third zone is 15°C. On the 4th run to the reaction mixture is added DMSO to 10% by weight of the composition and dosed solutocapillary potassium (K[AuI4]·nH2O, n=3 or 4) in an amount of 100.0 g (125·10-3mole). The cycle is repeated 4 times. The temperature regime in the next two cycles is in the first area 105°C, the second - 110°C, in the third zone is 15°C. the Total duration of 30 minutes at a pressure of 400 MPa. The product yield is 544,5 g (~100,0%). The maximum absorption is 510 nm, which corresponds to the value of 5 nm for the size of the gold particles. The degree of filling of the composite gold amounted to 9.2 wt.%.

Example 12. to 120.0 mg (3·10-4mole) of powdered sodium salt of hyaluronic acid, 20.0 mg (2·10-4mole) holomelaena and 40.0 mg (1·10-4mole) soloconsolidation acid (SHVC) homogenized mill at 10°C for 10-15 minutes Then the homogeneous powder mixture 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 200 MPa at 20°C when the angle of rotation of the lower anvil 250° during 1 min. Then relieve pressure, remove the anvil from the press. The product yield is 176,4 mg (98,0%), 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 11.4 wt.%.

Example 13. to 120.0 mg (3·10-4mole) of powdered sodium salt of hyaluronic acid, 20.0 mg (2·10-4mole) holomelaena and 40.0 mg (5·10-5mole) zolotayadolina akin potassium (K[AuI4]·nH2O, n=3 or 4) homogenize in the mill at 5°C for 10-15 minutes Then the homogeneous powder mixture 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 450 MPa at 90°C when the angle of rotation of the lower anvil 200° for 30 sec. Further relieve pressure, remove the anvil from the press. The product yield is 176,4 mg (98,0%). 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 11.4 wt.%.

Example 14. Performed analogously to example 12, however, in contrast holomelaena take in quantity 2,00 mg (2·10-5mol), and SHUK take in quantity 2,00 mg (5·10-6mole). The product yield is 124,00 mg (100%). The maximum absorption at 490 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 0.8 wt.%.

Example 15. Performed analogously to example 13, however in contrast instead of the sodium salt of the Ledger taken a mixed sodium-calcium salt at a molar ratio of sodium:calcium =2:wiht product is 176,4 mg (98,0%). 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 11.4 wt.%.

Example 16. Performed analogously to example 12, however in contrast instead of the sodium salt of the Ledger taken mixed sodium-aluminum salt at a molar ratio of sodium:aluminum =3:1. The product yield is 171,0 mg (95,0%). The maximum absorption is 517 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 11.7 wt.%.

Example 17. Performed analogously to example 13, however in contrast instead of the sodium salt of the Ledger taken mixed sodium-zinc salt at a molar ratio of sodium:zinc =2:1. The product yield is 174,6 mg (97,0%). The maximum absorption is 514 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 11.5 wt.%.

Example 18. Performed analogously to example 12, however in contrast instead of the sodium salt of the Ledger taken mixed sodium-copper salt at a molar ratio of sodium:copper =2:1. The product yield is to 172.8 mg (96,0%). The maximum absorption is 515 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 11.6 wt.%.

The examples clearly show, who then created a universal environmentally safe way, allowing to obtain water-soluble bioactive nanocomposite comprising a modified connection of a number of melanin salt of hyaluronic acid as a matrix and the gold nanoparticles as a filler, in one technological mode 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 bioactive nanocomposites nanocomposite, in particular non-toxicity, tumorotropic, low viscosity with intravenous administration commensurate with the viscosity of blood of a healthy person 3-5 MPa·s, has high stability, with accurately known concentration of major components. Also achieved a high concentration of gold (>10 mg/g-tissue) bioactive nanocomposites nanocomposite, which allows implementing the principle of ERT, photothermal therapy, photo - and radiosensibility, chemotherapy, treatment of rheumatoid arthritis, antovic therapy.

1. The method of obtaining water-soluble bioactive nanocomposites nanocomposite comprising a modified connection of a number of melanin salt of hyaluronic acid as a matrix and the gold nanoparticles as a filler, zakluchali the Xia is what does the chemical interaction of solid powders, salts of hyaluronic acid, the compounds of the number of melanin, soloconsolidation acid or salt of gold in the simultaneous effects of pressure in the range from 50 to 1000 MPa and shear strain in mechanochemical reactor at temperatures from -18° to 110°C.

2. 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.

3. The method according to claim 2, characterized in that the salt of hyaluronic acid is sodium salt.

4. The method according to claim 2, characterized in that the salt of hyaluronic acid is mixed salt.

5. The method according to claim 1, characterized in that the connection of a number of melanin selected from the group of pheomelanin, eumelanin, aromaland.

6. The method according to claim 1, characterized in that the salt of gold is solutocapillary potassium.

7. The method according to claim 2, characterized in that the molar ratio of the salt of hyaluronic acid to the connection of a number of melanin is in the range from 100:1 to 1:100.

8. The method according to claim 1, characterized in that the molar ratio of soloconsolidation acid to soybean is inniu from a number of melanin is in the range from 1:1000 to 1:4, respectively.

9. The method according to claim 6, characterized in that the molar ratio of solutocapillary potassium to the connection of a number of melanin is in the range from 1:1000 to 1:8, respectively.

10. The method according to claim 1, characterized in that the duration of the effects of pressure and shear strain is in the range from 0.1 to 30 minutes.

11. The method according to claim 1, characterized in that it further introduce a stabilizing additive selected from the group of: carboxymethylcellulose (CMC), tetraalkylammonium, lithium, sodium, potassium, calcium, magnesium, barium, zinc, aluminum, copper, gold or mixed salt of CMC from the above number or Hydrosol CMC, hydroxyethyl cellulose, hydroxypropylcellulose.

12. The method according to claim 11, characterized in that the molar ratio of the salt of hyaluronic acid for stabilizing additive in the range from 100:1 to 1:1.

13. The method according to claim 1, characterized in that the mechanochemical reaction is: twin screw extruder with a unidirectional rotating screw or twin-screw extruder with oppositely directed rotation of the screw or twin-screw extruder with a set of transport or locking or peretyagin Cams.

14. The method according to claim 1, characterized in that the mechanochemical reaction are Bridgman anvils, while the shear deformation is carried out by changing the angle turning parts, all specifications is and the lower anvil.



 

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12 cl, 8 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a recovered imidised biologically compatible polymer functionalised by an imide group. The above polymer is selected from the group consisting of polyethylene oxide, partially or completely hydrolysed by polyvinyl alcohol, polyvinylpyrrolidone, polyethyloxazoline, polyoxypropylene oxide block copolymers (poloxamers and meroxapol), polyethylene oxide and poloxamine copolymer, carboxymethyl cellulose and hydroxyalkylated cellulose, polypeptides, polysaccharides, carbohydrates, polysaccharose, hyaluronic acid, dextran, heparin sulphate, keratan sulphate, chondroitin sulphate, heparin, alginate, gelatin, collagen, albumin, ovalbumin, complex polyphosphoesters, polylactides, polyglycolides, polycaprolactones, polyamides, polyurethanes, polyesteramides, polyorthoesters, polydioxanones, polyacetals, polyketals, polycarbonates, polyorthocarbonates, polyphosphazenes, polyhydroxybutyrates, polyhydroxyvalerates, polyalkylene oxalates, polyalkylene succinates, polymaleic acids, polyamino acids, polyvinyl alcohol, polyvinylpyrrolidone, polyhydroxy cellulose, chitin, chitosan, and copolymers, ternary copolymers, or combinations or mixtures of the aforementioned materials. Also, the invention refers to a composition for a tissue adhesive, a medical device and a pharmaceutical composition.

EFFECT: invention represents additionally modified or functionalised imidised polymers.

9 cl, 2 ex, 20 dwg

FIELD: biotechnologies.

SUBSTANCE: fish roe is homogenised. Fish roe hydrolysis is carried out with a ferment preparation "Collagenase" in presence of an inhibitor for 10-12 hours. Chitosan is added to the produced hydrolysate at the ratio of 0.5-1.0:1.0. Components are mixed.

EFFECT: invention makes it possible to accelerate process of chitosan-nucleic complex production.

1 dwg, 1 tbl, 3 ex

FIELD: biotechnologies.

SUBSTANCE: method includes depolymerisation of a high-molecular chitosan with hydrogen peroxide. The process of chitosan depolymerisation is carried out in a double-phase system. The solid phase is activated chitosan with Mav = 450-650 kDa and the average particle size of 0.05-0.20 mm. The liquid phase is a water solution of H2O2 with concentration of H2O2 in a reaction system equal to 1-7%. The reaction is carried out for 120-180 minutes at 70°C. Then phase separation of produced chitosan homologs is carried out by means of filtration via paper or textile surface of the produced reaction mixture. The produced filtrate contains water-soluble chitosan oligomers.

EFFECT: invention makes it possible to quantitatively control extent of conversion of an initial high-molecular chitosam into oligomer and low-molecular structures of its homologs.

1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of purifying chondroitin sulphate and can be used in food and cosmetic industry and in medicine. The method involves electrochemical deposition to obtain a hydrogel of chondroitin sulphate, stabilisation, removal from the electrode, washing and drying. The chondroitin sulphate is dissolved in a 0.01-0.1 n alkali solution in ratio of 1:50-1:200 and deposited in an alkaline medium with constant cooling and stirring. The solution is stirred at a rate of 10-20 rpm. Current density is equal to 1-10 A/m2. Voltage is preferably not lower than 2.7 V. The hydrogel of chondroitin sulphate is stabilised in a 0.05-0.5 n HCl solution.

EFFECT: invention enables to obtain chondroitin sulphate with high weight ratio of the basic substance and increases output of the end product.

5 cl, 1 ex

FIELD: chemistry.

SUBSTANCE: to endow various materials with hydrophilic properties, a modifier is deposited on the surface of said materials. A coating is formed by successively depositing aqueous solution of an oligo(aminopropyl)ethoxysilane of a general formula shown on fig 1, and subsequently depositing aqueous solution of nitrilotrimethylene phosphonic acid of a general formula shown on fig 2. After deposition, each solution is dried on air and heat treated.

EFFECT: invention enables to endow various materials with improved hydrophilic properties.

8 dwg, 6 ex

FIELD: chemistry.

SUBSTANCE: device for synthesis of composite coatings contains a working vacuum chamber 1, an emission net 2 from a precipitated metal, a hollow cathode 3, limited by the emission net 2, an anode 4 inside the hollow cathode 3, a source 5 of an electric discharge supply, with a positive pole connected to the anode 4, and with a negative pole connected to the hollow cathode 4, a target 6, installed on the bottom of the hollow cathode 3 opposite to the emission net 2, a source 7 of high voltage, with a positive pole connected to the hollow cathode 3, and with a negative pole connected to the target 6, a source 8 of net voltage, with a positive pole connected to the anode 4 and with a negative pole connected via a high voltage diode 9 to the emission net 2, and a generator 10 of high voltage impulses, with a positive pole connected to the anode 4 and with a negative pole connected to the emission net 2.

EFFECT: creation of a device for synthesis of both conductive and dielectric coatings on products from conductive and dielectric materials, which would ensure the reduction to zero of current of accelerated ions on the surface of the product and impulse-periodical bombing of a synthesised on it coating by molecules of gas with energy of tens of keV.

1 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to agriculture. A nanostructured water-phosphorite suspension, which consists of nanoparticles with the size less than 100 nm and which is obtained from natural phosphorites as a phosphorus fertiliser for corn.

EFFECT: invention makes it possible to create the phosphorus fertiliser for corn, based on natural phosphorites, with considerably smaller consumption per a unit of the sown area with the preservation of high yield of the said culture.

1 tbl, 16 ex

FIELD: chemistry.

SUBSTANCE: group of inventions can be used in the production of catalysts, in particular, for the selective NOx reduction. A catalytic composition contains at least one oxide on a carrier, consisting of zirconium oxide, or titanium oxide, or mixed zirconium and titanium oxide, or of zirconium oxide and an oxide of at least one oxide of other element, selected from praseodymium, lanthanum, neodymium and yttrium, applied on a silicon oxide-based carrier. After burning at 900°C for 4 hours the oxide on the carrier has a shape of particles applied on the carrier. The size of the said particles constitutes not more than 5 nm, if the oxide on the carrier is obtained on the basis of zirconium oxide, not more than 10 nm, if the oxide on the carrier is obtained on the basis of titanium oxide, and not more than 8 nm, if the oxide on the carrier is obtained on the basis of mixed zirconium and titanium oxide. After burning at 1000°C for 4 hours the size of the particles constitutes not more than 7 nm, if the oxide on the carrier is obtained on the basis of zirconium oxide, not more than 19 nm, if the oxide on the carrier is obtained on the basis of titanium oxide, and not more than 10 nm, if the oxide on the carrier is obtained on the basis of mixed zirconium and titanium oxide.

EFFECT: invention makes it possible to reduce the size of the particles in the catalytic composition, their aggregation and sintering at high temperature.

10 cl, 1 tbl, 9 ex

FIELD: chemistry.

SUBSTANCE: invention relates to the field of plasmochemistry and can be applied for production of fullerenes and nanotubes. A carbon-containing raw material is decomposed in a gas discharge. For this purpose, first, inflamed is a volume glow discharge in a mixture of gaseous hydrocarbons and inert gas under pressure of 20-80 Torr. Then, under visual observation burning of the glow discharge with a constricted cathode area and diffuse positive column is obtained. Products of decomposition are precipitated in the form of soot.

EFFECT: carrying out process in a strongly non-equilibrium electric discharge makes it possible to increase the speed of soot obtaining and 9,6 times increase the output of nanotubes and fullerenes per unit of put in energy.

1 dwg

FIELD: chemistry.

SUBSTANCE: invention can be used in manufacturing polymer-based composites. Carbon nanotubes are functionalised by carboxyl and/or hydroxyl groups and processed by ultrasound in an organic solvent in the presence of products of reaction of tetrabutyltitanate with stearic or oleic acid at a temperature from 40oC to the temperature of the solvent boiling.

EFFECT: obtained dispersions of the carbon nanotubes are stable in non-polar organic solvents.

2 cl, 6 ex

FIELD: chemistry.

SUBSTANCE: invention can be used in manufacturing composites, containing organic polymers. A dispersion of carbon nanotubes contains 1 wt.p. of oxidised carbon nanotubes and 0.25-10 wt.p. of a product of interaction of organic amine, which contains in a molecule at least one hydroxyl group and at least one amino group, with tetraalkyltitanate.

EFFECT: dispersion is stable with the high content of nanotubes and minimal content of ballast substances.

8 ex

Fuel composition // 2531146

FIELD: chemistry.

SUBSTANCE: invention relates to a fuel composition, which contains hydrocarbon fuel, components, which arise at a high-voltage electric discharge, additional carbon-containing additives and a disperse phase. As the carbon-containing additives the composition includes nanoparticles in the form of carbon nanotubes, obtained by catalytic pyrolysis of acetylene on nanoclusters of iron and cobalt in an aluminium oxide matrix and having a structure of twisted balls with a diameter over 2 mcm with an average external diameter ~20-30 nm, or nanoparticles in the form of graphene, which has a layered structure with the granule size ~ 400 nm and obtained by a chemical method, consisting in oxidation of graphite layers with the following reduction and obtaining nanometer layers of a carbon product. The quantitative ratio of components, included in the composition, constitutes: hydrocarbon fuel - 100 g; carbon nanotubes or graphene - 0.5 g, remaining part - disperse phase.

EFFECT: composition makes it possible to reduce the time of delay of fuel ignition and increase stability of the flame burning.

4 cl, 3 dwg

FIELD: machine building.

SUBSTANCE: part is rotated and its surface is processed by an ultrasonic finish processing device with a deforming element. The ultrasonic finish processing device with a deforming element is moved along the part, is imparted with ultrasonic vibrations and multiple shock treatment by the deforming element is carried out with the ultrasonic frequency of 20 kHz and amplitude of 5-40 mcm. Herewith the deforming element and the part are partially immersed in the bath with kerosene to cool the processed part surface thus providing for the creation of gradient submicro- and nanocrystalline structures on it.

EFFECT: high strength and hardness of the part surface.

4 cl, 6 dwg, 1 ex

FIELD: chemistry.

SUBSTANCE: method includes forming a film with thickness of not more than 200 nm from semiconductor nanoparticles of SnO2 with size of not more than 50 nm. The film of SnO2 nanoparticles is then annealed at temperature of 330±20 K or 500±20 K for at least 15 min in an oxygen-containing atmosphere, followed by cooling to room temperature at a rate of at least 10 K/s.

EFFECT: broader functional capabilities of the material.

2 cl, 4 dwg

FIELD: carbon materials.

SUBSTANCE: weighed quantity of diamonds with average particle size 4 nm are placed into press mold and compacted into tablet. Tablet is then placed into vacuum chamber as target. The latter is evacuated and after introduction of cushion gas, target is cooled to -100оС and kept until its mass increases by a factor of 2-4. Direct voltage is then applied to electrodes of vacuum chamber and target is exposed to pulse laser emission with power providing heating of particles not higher than 900оС. Atomized target material form microfibers between electrodes. In order to reduce fragility of microfibers, vapors of nonionic-type polymer, e.g. polyvinyl alcohol, polyvinylbutyral or polyacrylamide, are added into chamber to pressure 10-2 to 10-4 gauge atm immediately after laser irradiation. Resulting microfibers have diamond structure and content of non-diamond phase therein does not exceed 6.22%.

EFFECT: increased proportion of diamond structure in product and increased its storage stability.

2 cl

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