Novel cross-linking reagents for producing chitosan-based biocompatible materials
SUBSTANCE: 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.
EFFECT: low toxicity and biocompatibility of chitosan-based materials is achieved by using cross-linking reagents.
2 dwg, 12 ex
The invention relates to the field of biotechnology and medicine, namely the creation of polymeric materials based on chitosan with low toxicity and high biocompatibility, in particular, films, microcapsules, hydrogels, wound coverings, scaffolds etc. products on the basis of biologically active polymeric materials can be used in surgery in the treatment of wounds and as materials for temporary replacement of body tissues, in the field of biotechnology for producing matrices for growing cell cultures, in the pharmaceutical industry as carriers of enzymes and other biologically active compounds.
As reagents for cross-linking of chitosan using phthalic and amber dianhydride, diepoxide, crown-ethers, diphenylsulfone [Sereikaite I., Bassus D., Bubnis R. and others // Bioorganic chemistry, 2003, t, No. 3, s-257] aldehydes of various structure: glutaric aldehyde (HA), genipin [F.L. Mi, Y.C. Tan, H.C. Liang e.a. // J. Biomater. Sci. Polym. Ed., 2001, v.12, No. 8, p.835-850], formaldehyde [A. Singh, S.S. Narvi, P.K. Dutta and N.D. Pandey. // Bull. Mater. Sci., 2006, V.29, №.3, p.233-238], acetaldehyde, glyoxal, oligoethyleneglycols [Ohya Y., Cai R., Nishizawa, H., Nagy, K., Ouchi T. //S.T.P. Pharma Sci., 2000, v.10., No. 1., p.77-82]. As shown by the authors [S.J. Meade et al Bioorg. Med. Chem. 11, 853-862, 2003], on the basis of comparative study of the reactivity of aldehydes most readily reacts with amino groups glutaric Aldagi the (HA). The use of HA allows cross-linking of chitosan under mild conditions (low temperature, physiological pH).
Of polymer aminecontaining media in combination with HA was used as synthetic polymers (aminoplastic modified with diamines stiroldivinilbenzol polymers, as well as the product of copolymerization of ethylene with maleic anhydride)and artificial (aminocellulose), and amino compounds, polymers of natural origin (gelatin [Draye JP, Delaey Century, Van de Voorde, A., Van Den Bulcke, A., De Reu Century, Schacht E. // Biomaterials, 1998, v.18. p.1677-1687], albumin, protein feathers, casein, collagen and others).
The most promising polymer for creating biologically active polymeric material is biocompatible and biodegradable aminopolysaccharide coated chitosan [A.J.Varma et al. Carboh. Polymers, 55, 77-93,2004; J.Berger et al. Eur. J. Pharm. Biopharm. 57, 19-34, 2004; H. Yi et al. Biomacromolecules, 6, 2881-2894 2005; K. Kurita. Marine Biotech. 8, 203-226, 2006]. The solubility of chitosan in dilute aqueous solutions of acids, along with fiber - and film-forming ability and the presence of reactive amino groups facilitates the modification of this polymer and its processing of polymer products.
Previously on the basis of chitosan - HA (RF patent 2261911) was developed biocatalyst containing immobilized organophosphorous enzyme gidrolizuemye pastefire communication, before oznaczony removal of organophosphorus compounds with different surfaces, including the skin, and subsequent detoxification, as well as for use as PPE.
The gels obtained by sequential processing of chitosan-HA and then the sulfur dioxide in aqueous solution (US Patent 4125708)and tripolyphosphate and then HA (US Patent 5322935)proposed to use as fillers in the devices column type for purification of water from dissolved compounds containing ions of chromium and manganese, and for the manufacture of highly cross-linked membranes designed for the separation of components of liquid mixtures, such as water-alcohol (US Patent 5006255). The mixture of HA and chitosan with low molecular weight is an effective flocculant in the dehydration of sewage sludge (US Patent 4609470). Films based on chitosan, crosslinked HA or containing the carbonyl group of a crosslinking reagent by genipin (Mt F.-L., HuangC.-T., Liang, H.-F. et al. // J.Agr.Food Chem., 2006, v.54, p.3290-3296), proposed as coatings of various food products; chitosan film slow down the oxidation, microbial growth, loss of moisture, absorb odors, so you can use them as edible films for high-quality food storage.
The use of HA in obtaining various physical forms of polymer materials based on chitosan, in particular biotechnological and medical purposes, with different types of biological activity due to its ability when interacting with the aminopolysaccharide coated to form a high water-holding capacity durable biocompatible porous structure [Vikhoreva GA, kildeeva NR, M. Ustinov, Nocevkina YU. // Chem. fibers, 2002, No. 6, S. 29-33; Vikhoreva GA, Sablikova E.A., kildeeva NR // Chem. fiber, 2001, No. 3, ñ.38-42; A.S. Acharya, Suseman L.G., J.M. Manning /A J. Biol. Chem., 1983, v.285, No. 4, p.2296-2302; Jameela S.R., Jayakrishnan A. //Biomaterials, 1995, No. 16, p.769-775].
The study of the process of cross-linking of chitosan HA showed the presence in the samples of cross-linked chitosan products crotonic condensation HA [V.Crescenzi et al. // Biomacromolecules. 2003, v.4, p.1045-1054; Pairing. Kida. Diss. Moscow, 2007], which contains the carbonyl group and the C=C-bond.
Crotonic condensation HA catalyzed by amino groups, so in the case of chitosan HA is spent not only on the stitching aminopolysaccharide coated, but also on the growth of the oligomeric chains HA, length and structure to control not possible (figure 1). Figure 1 shows the structure of the products crotonic condensation HA and products of the interaction of HA with chitosan. The presence in the composition of the resulting hydrogels reactive carbonyl group and C=C-bonds limits the use of the system chitosan - aliphatic dialdehyde in biomedical purposes.
In this regard, Wasim what is important to search for new cross-linking reagents, able, like HA, effective to react with chitosan to form hydrogels, but not forming this oligomeric products.
The objective of this invention is to provide a chitosan-based non-toxic and biocompatible materials for medical and biotechnological purposes, as well as new sorption-active materials.
This task is solved by the use of new cross-linking reagent, 2,4-derivatives of 3-oxoglutarate aldehyde (2,2'-oxadiazolidine). The introduction of the electronegative oxygen atom at the 3-position of the HA, and the presence of substituents in the 2,4-positions prevent Alderney and crotonic condensation and the formation of irregular products.
These compounds can be obtained easily controllable periodic destruction by oxidation of nucleosides, nucleotides and sugars (such as derivatives of ribose, arabinose, erythrose, glucose, galactose, arabinose). It should be noted that obtaining derivatives of 3-oxoglutarate aldehyde is carried out in aqueous solutions under mild conditions, the reaction can be monitored using TLC or NMR spectroscopy. The methodology for conducting the reaction is very simple: to a solution of compound with a diol group in the water add a small excess of NaIO4and incubated for 10-30 min at 20°C [Snikolov, Hijackable. // Chemistry of natural compounds, 1987, p.40-43; Ermolinskiy BS, Mikhailov, S.N. //Bioorgan, chemistry. 2000, t, s-504] (figure 2). 2 shows the reaction scheme for the controllable periodic destruction of oxidation, which is used to obtain derivatives of 3-oxoglutarate aldehyde. It should be noted that these derivatives can also be obtained controllable periodic destruction by oxidation of compounds with trialname groups, in this case using 2 equivalent NaIO4.
Features of the proposed use of the new cross-linking reagents are: 1) the structure dialdehyde derivatives of monosaccharides, nucleosides and nucleotides eliminates the possibility of crotonic condensation of the dialdehyde, leading to the formation of a double C=C-bonds and the formation of toxic products with unpredictable composition; 2) the presence of a crosslinking reagents additional functional groups (phosphate group and heterocyclic bases) gives the possibility of their use not only as a cross-linking reagents, and modifying connections, providing additional functionalization of chitosan; 3) the use of the reagents opens up new possibilities: a) the creation of new biocompatible materials based on chitosan; b) the implementation in the process of knitting is not only covalent, and ionic interactions; C) leads to the production of new sorption-active materials.
Listed below are the specific instances of implementation of the proposed technical solution.
Example 1. Controllable periodic destruction oxidation uridine
0.899 g (4.2 mmol) of periodate sodium was dissolved in 8 ml of water was then added with stirring 0.976 g (4 mmol) uridine and the solution kept at room temperature. According to TLC in the system chloroform - ethanol 4:1, the reaction ends after 1 hour. Reactional the mixture was left in the refrigerator for 20 hours at 0°C, the precipitated white crystalline precipitate NaIO3was filtered and received a 0.5 M solution dialdehyde derivative of uridine (oxUrd), which ispolzovali the crosslinking of chitosan. The solution dialdehyde derivative of uridine is stable when stored in the refrigerator for several months.
Example 2. Controllable periodic destruction oxidation disodium salt of adenosine-5'-monophosphate
To a solution of 0.782 g (2 mmol) of disodium salt of adenosine-5'-monophosphate in 2.5 ml of water was added under stirring 4.2 ml of a 0.5 M solution of periodate sodium (2.1 mmol) at room temperature. The mixture was stirred 2 hours at room temperature and the mixture was left in the refrigerator for 20 hours at 0°C. the Precipitated white crystalline precipitate NaIO3was filtered and received a 0.3 M solution dialdehydes derived adenosine-5'-monophosphate (oxAMP). The solution dialdehydes derived stable when stored in the refrigerator for months.
Example 3. Controllable periodic destruction oxidation of methyl β-D-ribofuranoside
0.899 g (4. mmol) periodate sodium was dissolved in 8 ml of water, then added with stirring 0.648 g (4 mmol) of methyl β-D-ribofuranoside and the solution kept at room temperature. According to TLC in the system chloroform - ethanol 4:1, the reaction ends after 1 hour. Reactional the mixture was left in the refrigerator for 20 hours at 0°C, the precipitated white crystalline precipitate NaIO3was filtered and received a 0.5 M solution dialdehydes derived methyl β-D-ribofuranoside, which is used for the crosslinking of chitosan. The solution dialdehydes derived stable when stored in the refrigerator for several months.
Example 4. Obtaining a solution of 3-oxoglutarate aldehyde (2,2'-oxadiazolidine)
0.450 g (2.1 mmol) of periodate sodium was dissolved in 5 ml of water, then added with stirring 0.208 g (2 mmol) of 1,4-anhydromannitol and the solution kept at room temperature. According to TLC in the system chloroform - ethanol 5:1, the reaction ends after 1 hour. Reactional the mixture was left in the refrigerator for 20 hours at 0°C, the precipitated white crystalline precipitate NaIO3was filtered and received a 0.4 M solution of 3-oxoglutarate aldehyde, which ispolzovali the crosslinking of chitosan. A solution of 3-oxoglutarate aldehyde stable when stored in the refrigerator for several months.
Example 5. Obtaining a hydrogel of chitosan
To 2.5 g of 3%-aqueous solution of chitosan with molecules of the nuclear biological chemical (NBC weight of 460 kDa in 2%acetic acid (pH 4,1) add 0.4 ml of 0.5m oxUrd. The resulting gel has the following composition, wt. %: chitosan - 2,43, oxUrd - 1,54, the rest to 100%. The ratio oxUrd/NH2is 0.67 mol/mol. Gelation is completed within 120 minutes.
Example 6. Obtaining a hydrogel of chitosan
3%solution of chitosan (molecular weight of 460 kDa) in 2%acetic acid titrated 10M NaOH to pH 5.0. To 2.5 g of this solution was added 0.4 ml of 0.5m oxUrd. The resulting gel has the following composition, wt. %: chitosan - 2,43, oxUrd - 1,54, the rest to 100%. The ratio oxUrd/NH2is 0.67 mol/mol. Gelation is completed within 60 minutes.
Example 7. Obtaining a hydrogel of chitosan
To 2.5 g of 2%solution of chitosan with molecular weight of 460 kDa in 2%acetic acid (pH 4,1) type of 0.64 ml of 4 mm oxUMP. The resulting gel has the following composition, wt.%: chitosan - 1,60, oxUMP was 0.026, the rest to 100%. The ratio oxUMP/NH2is 0.01 mol/mol. Gelation is completed within 10 minutes.
Example 8. Obtaining a hydrogel of chitosan.
To 2.5 g of 2%solution of chitosan with a molecular mass of 190 kDa in 2%acetic acid (pH 4,1) type of 0.64 ml of 4 mm ohmr. The resulting gel has the following composition, wt. %: chitosan - 1,60, kamr - 0,028, the rest to 100%. The ratio ohmr/NH2is 0.01 mol/mol. Gelation is completed in 14 hours.
Example 9. Obtaining a hydrogel containing immobilized trypsin/p>
To 2.5 g of 3%-aqueous solution of chitosan with a molecular mass of 190 kDa in 2%acetic acid (pH 4,1) add 0.2 ml of an aqueous solution of trypsin (5 mg/ml) and 0.4 ml of 0.5m oxUrd. The resulting gel has the following composition, wt. %: chitosan - 2,43, oxUrd - 1,54, trypsin - 0,032, the rest to 100%. The ratio Urd/NH2chitosan is 0.67 mol/mol. Gelation is completed within 120 minutes. The gel has activity equal to 90 units/g of dried gel.
Example 10. Obtaining microcapsules based on chitosan
Microcapsules were obtained by means of high-frequency (200 Hz) breaker jet molding composition is a joint solution of chitosan with a molecular mass of 300 kDa and oxUrd, in warm (60°C) vegetable oil. The ratio oxUrd/NH2were 0.4 and 2 mol/mol. To complete the process of gelation capsules kept in oil for 5-10 minutes under stirring. The obtained microcapsules with a diameter of 300-500 μm, had a spherical shape. The degree of swelling in water of the microcapsules obtained when the ratio oxUrd/NH2=2.0 mol/mol, 300%, and at oxUrd/NH2=0.4 mol/mol - 2000%.
Example 11. The receiving space of the modified films based on chitosan
To 45 g of 2%solution of chitosan with molecular weight of 460 kDa in 2%acetic acid (pH 4,1) type of 11.26 ml of 2 mm dialdehydes derived METI the β-D-ribofuranoside. After mixing, the solution was poured into a Petri dish with a diameter of 10 cm and left overnight at 40°C. the Obtained film has the following composition, wt.%: chitosan - 95,40, dialdehydes derived methyl β-D-ribofuranoside - 0,80, the rest to 100%. The ratio dialdehydes derived methyl β-D-ribofuranoside /NH2was 0.005 mol/mol. The thickness of the laminated film 50 μm, the degree of swelling in water of 800%.
Example 12. Having surface modified films based on chitosan
A solution of chitosan (2%) by weight of 45 g with molecular weight of 467 kDa in 2%acetic acid (pH of 4.1) was poured into a Petri dish of 10 cm diameter and leave for 5 days at 25°C. the thickness of the formed film was 50 μm. Molded film was filled with 20 ml of 0.1 M aqueous solution of NaOH to neutralize the acetic acid, and then after washing with distilled water and placed 11.3 ml of 4 mm 3-oxoglutarate aldehyde for 2 hours. The thickness of the obtained film is 83 μm, the degree of swelling in water of 1000%.
Example 13. Obtaining fibrous biocatalyst based on chitosan
Woven cellulosic material (cotton calico) weight 1.2 g were placed in a 3%solution of chitosan with a molecular mass of 190 kDa (2.55 g)containing 0.2 ml of an aqueous solution of α-chymotrypsin (5 mg/ml) and 0.40 ml of 0.5m oxUrd. Calico was pressed and held in the air in techenie minutes. The resulting biocatalyst had the following composition, wt. %: protein - 2,05, chitosan - 12,92 insoluble carrier -51,37, oxUrd - 0,032, the rest to 100%. The activity of the biocatalyst was 87%/year
Cross-linking reagents to obtain chitosan-based biocompatible and non-toxic materials for biomedical and biotechnological purposes, as well as new sorption-active materials constituting 2,4-derived 3-oxoglutarate aldehyde (2,2'-oxadiazolidine).
SUBSTANCE: luminescent biocatalyst contains immobilised cells of luminescent bacteria which are included in a polyvinyl alcohol based cryogenic gel at given ratio of components.
EFFECT: prolonged possible use of the biocatalyst, simplification of its composition and production technology.
1 dwg, 2 tbl, 6 ex
FIELD: food industry.
SUBSTANCE: method includes preparation of yeast water suspension, addition of potassium alginate into it. The potassium alginate is preliminary kept in water solution of ethyl alcohol with concentration of 50 - 85 vol. %. Exopolysaccharide with molecular mass of 0.5×106-2×107 Da, obtained from Paracoccus denitrificans VKPM B-8617 bacteria strain is added into the obtained mixture with the following obtaining of pH mixture values till 4.2-6.5. The mass ratio of the exopolysaccharide is: alginate is 0.1-0.9:3.5-4.5. Obtained technological solution is treated by coupling solution of calcium chloride.
EFFECT: increase of life time of biocatalyst work with preservation of high activity.
2 tbl, 3 ex
SUBSTANCE: immobilised biocatalyst contains cells of filamentous fungi, which produce pectinases and are included into matrix of gel carrier containing polyvinyl alcohol. Gel carrier represents cryogel of polyvinyl alcohol with macropores of 0.5-5.0 mcm section. Immobilised biocatalyst is produced on the basis of the following components, taken in the following ratio (wt %): cells of filamentous fungi (by dry mass) - 0.001-0.1, polyvinyl alcohol - 8.4÷12.5; aqueous phase - up to 100. Time of biocatalyst application makes 572-744 parts, average productivity of process by pectolytic activity makes 1.05-1.45 Units.ml-1part-1, and maximum pectolytic activity makes 104160-830000 Units.
EFFECT: invention provides for durable preservation of high mechanical strength by immobilised biocatalyst and vitality of filamentous fungi cells having pectolytic activity.
FIELD: food products; alcoholic beverages.
SUBSTANCE: method of obtaining biocatalyst for alcoholic fermentation comprises increasing biomass of yeast Saccharomyces cerevisiae and immobilising it by including it in helium matrix by way of mixing with gelling material solution with its subsequent curing by ions Ca++. Gelling material is represented by mixture of exopolysaccharide with molecular weight 1.5·105-2.5·105 Da, derived from Paracoccus denitrificans All-Russian collection of industrial microorganisms B-8617 bacteria strain and sodium alginate in mass ratio 0.1-0.9:3.5.-4.5.
EFFECT: obtaining highly active biocatalyst with long work period for alcoholic fermentation basing on free yeast cells for industrial production of ethanol as chemical while using it as fuel.
1 tbl, 2 ex
SUBSTANCE: invention represents a biocatalyst containing immobilised bacteria cells included in polyvinyl alcohol cryogel, used to decompose methylphosphonic acid and its esters. The biocatalyst contains the following components (wt %): bacterial cells biomass - 0.125÷0.725, polyvinyl alcohol cryogel - 7.6÷12.8, aqueous phase - up to 100. Polyvinyl alcohol cryogel is formed in air. As individual bacterial cultures, Pseudomonas species 78G, Escherichia coli BN5α/pTrcTE-OPH, Escherichia coli SG13009 [pREP4]/pTES-His-OPH are used as able to degrade organophosphorous compounds with C-P-bonding. Methylphosphonic acid decomposition rate is 7.3-18 mg/l/h, while its esters are decomposed at 9.6-21.4 mg/l/h throughout 245-310 days.
EFFECT: biocatalyst is characterised with high rate of methylphosphonic acid and its esters decomposition over a long period of time.
SUBSTANCE: biocatalyst for obtaining glucose-fructose syrups in process of isomerization of glucose or fructose, which contains bacterial cells with glucose isomerase activity, silicon dioxide and salts of magnesium and divalent cobalt, ratio of bacterial cells and silicon dioxide being from 1:6 to 1:10 in weight fractions by dry substances. Silicon dioxide is used in form of hydro-gel with the following set of properties: humidity 60-95%, value of specific surface of product, obtained after hydro-gel drying at 105-120°C, equals 30-550 m2/g, bulk density of product, obtained after hydro-gel drying at 105-120°C, equals 0.1-0.7 g/cm3.
EFFECT: acceleration and simplification of process of immobilisation of bacterial cells, possessing glucose isomerase activity, preservation of fermentative activity of cells at high level after immobilisation.
10 cl, 13 ex, 3 tbl
FIELD: medicine; pharmacology.
SUBSTANCE: carrying out of treatment of disease, in particular, diabetes, by implantation of the encapsulated devices containing a covering and cells, thus density of cells makes 100000 cells/ml, and the covering contains acrylate polyethylene alcohol (PEG) high density with molecular mass from 900 to 3000 Dalton, and also a sulfonated comonomer.
EFFECT: minimisation of the tissue response, augmentation of concentration of cells and augmentation of time of viability of cells in the specified devices.
83 cl, 33 dwg, 8 tbl, 20 ex
SUBSTANCE: invention concerns biotechnology. Capsules with liquid center are obtained by drop introduction of sodium alginate solution with concentration of 1.0÷1.5% and microbe cells into calcium chloride solution with concentration of 2.0÷2.5%. Conditioning time for the obtained capsules in calcium chloride solution is set at 4-5 minutes.
EFFECT: obtaining capsules with liquid centre characterised by small intra-diffusion resistance which allows for accelerating metabolic processes between immobilised cell and external medium in fluid phase cultivation.
2 cl, 3 dwg, 2 ex
SUBSTANCE: method includes revival of pure culture Klyuveromyces marxianus Y-303 by Koch's method, seeding in Petri dish with 2% wort agar at temperature 48-50°C. Dishes are turned upside-down and kept for 2-3 days in thermostat at temperature 28-30°C. Grown colonies are moved to Petri dish with wort agar for biomass growth, then to bevels with wort agar. Submerged yeast cultivation is carried out in flask of capacity 500 cm, each containing 50 cm of beer wort during 47.5-48.5 h at temperature 30°C. Grown biomass is mixed with distilled water in ratio 1:5, autolysis is carried out at temperature 38-42°C during 59.5-60.5 h. Produced enzyme-containing mixture is deposited with ethyl alcohol at pH 5.0 or with acetone at pH 5,5. β-fructofuranozidase is purified within 3 steps: removal of low-molecular additives by gel filtration on column with sephadex G-25, increasing enzyme preparation purity by ion-exchange chromatography on column with DEAE-cellulose, fractionation on column with sephadex G-150. Concentration on membrane Amicon PM-30 is carried out up to 5 cm3, followed with lyophilisation at t=-30°C. β-ructofuranozidase is immobilised on polymer fibre sorbent (anionite). Before immobilisation, sorbent is processed with 5% hydrochloric acid, distilled water, 5% caustic soda solution and water again. Each process step takes 12 h. Washed sorbent is additionally processed with 95% ethyl alcohol and water again. Aqueous solution of β-fructofuranosidase is made of content 0.018-0.098 mole/dm3, processed sorbent is incubated. Method enables to produce immobilised enzyme in amount 0.005-0.025 mg/g.
EFFECT: provided purity of end product.
2 tbl, 3 ex
FIELD: production methods.
SUBSTANCE: biocatalyst is made on the base of immobilized cells of photosynthetic bacteria, includes to the matrix of criogel polyvenial alcohol, thanks to which it is produced the hydrogen production. Biocatalist has long time of service, obtain seriously modified productivity and can be used for hydrogen producing in reactors of different types.
EFFECT: it is increased the productivity of using.
SUBSTANCE: 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.
EFFECT: obtaining fibre with good deformation and strength properties.
1 dwg, 4 tbl, 29 ex
SUBSTANCE: 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.
EFFECT: proposed taxane has high therapeutic effectiveness when treating oncological diseases, autoimmune diseases and restenosis, dissolves in water without reduction of its pharmacological activity and is not toxic, which leads to overcoming hypersensitivity and anaphylaxis.
46 cl, 20 ex, 4 dwg
SUBSTANCE: 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.
EFFECT: composition provides increased ability to stimulate proliferation of osteoblasts, reparative processes of osteoformation with recovery by means of morphologically normal bone matrix.
2 cl, 3 ex
FIELD: chemistry, medicine.
SUBSTANCE: 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.
EFFECT: increase of application efficiency.
20 cl, 7 ex, 2 tbl, 1 dwg
FIELD: textile, paper.
SUBSTANCE: 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.
EFFECT: prepared modified paper has increased gas-proof and heat-protective properties, and resistance to thermal-oxidative degradation.
1 tbl, 6 ex
FIELD: textile, paper.
SUBSTANCE: 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.
EFFECT: increase of gas-proof and heat-protective properties, and resistance to thermal-oxidative degradation of modified paper.
2 tbl, 6 ex
FIELD: organic chemistry, chemical technology.
SUBSTANCE: 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.
EFFECT: improved preparing method, valuable properties of composition.
3 cl, 1 dwg, 4 ex
FIELD: derivatives of chitosan.
SUBSTANCE: 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.
EFFECT: improved and valuable properties of chitosan substances.
14 cl, 4 tbl, 7 dwg, 9 ex
SUBSTANCE: invention describes a chitosan-base composition reducing the content of nitrates in plant growing production. The composition comprises chitosan of molecular mass 20-150 kDa, organic acids - mixture of succinic, ascorbic and sorbic acids in the mass ratio = 2:1:1, respectively, activating agents of nitrate and nitrite reductases - iron nitrate, ammonium molybdate, indolyl acetic acid and ethylenediaminetetraacetic acid in the mass ratio = 20:5:1:1, respectively; or iron nitrate, ammonium molybdate, indolyl acetic acid and N,N-dicarboxymethylglutamic acid in the mass ratio = 20:5:1:1, respectively, and substances enhancing synthesis of chlorophyll - 2-oxoglutaric acid and L-glutamic acid in the mass ratio = 30:1, and a surface-active substance also in the following ratio of above indicated components, wt.-%: chitosan, 15-25; organic acids, 15-25; activators of nitrate and nitrite reductases, 25-30; enhancers of chlorophyll synthesis, 29-35, and surface-active substance, 1-3. The composition provides enhancing assimilation of inorganic nitrogen in plant and reduces the content of nitrates in plant growing productions.
EFFECT: valuable properties of composition.
FIELD: production of new materials.
SUBSTANCE: proposed nanocomposite can be used as component contributing to charges of consumer properties of materials made on its base. Nanocomposite includes fibrils of filler-chitin individualized to nanosizes with distance between fibrils from 709 to 20-22 nm and water-soluble polymeric matrix in interfibril space. Degree of filling of nanocomposite is 0.05-0.25% mass. Fibrils are arranged in parallel and they have cross size of 4 nm. Method of production of nanocomposite comes to the following: free-radical polymerization in water medium of at least one monomer of row of acrylic acid, salt of acrylic acid, acrylamide is carried out in presence of filler. Initiator is chosen from the row of water-soluble peroxides, hydroperoxides or their salts, potassium persulfate. Individualization to nanosizes of fibrils is done simultaneously with process of polymerization and/or with combination of said process with mechanical disintegrating action by disintegrating or pressing, or pressing with abrasion shift. Nanocomposite is obtained in form of film, being pervaporation membrane.
EFFECT: enlarged range of filling, ease of production.
22 cl, 1 tbl, 9 ex, 2 dwg
SUBSTANCE: composite contains a reactive ceramic phase of triple-substituted calcium phosphate and an organic phase containing polyvinyl alcohol hydrogel. The mechanical properties and injectability of said material can be adjusted by varying the concentration of two phases.
EFFECT: preparation of the new injectable composite applicable as a bone filler.
9 cl, 2 tbl