Method of producing chitosan
SUBSTANCE: invention relates to producing chitosan from chitin and can be used in medicine, chemical, textile, paper and food industry. The method comprises crushing chitin to particle size of 1-2×2-3 mm; deacetylation of chitin in a double-neck reactor in 40% NaOH solution with in ratio to chitin of (1-3):(20-60) at 100°C, pressure of 300 mm Hg for 1-2 hours, wherein the double-neck reactor is fitted with a reflux condenser and is connected to a vacuum water-jet pump.
EFFECT: invention improves the degree of acetylation of chitosan and preserves the natural structure of the finished product.
2 tbl, 1 dwg
The invention relates to the field polymeranalogous transformations of natural macromolecular compounds, in particular the production of chitosan from chitin and can find application in medicine, chemical, textile, paper and food industries.
A method of obtaining chitosan, in which the cuticular chitin shells of insects crushed to particles of 0.2-0.3 mm, treated with 40% solution of caustic alkali at 100-110°C, liquid module 1:20, 3-3,5 hours, while the effects of ultrasound with a frequency of 15-35 kHz (Patent No. 2067588, Russia, MKI C08B 37/08. Priority from 17.09.1991,)
The main disadvantage of this method is carrying out the process at elevated temperatures, the use of additional equipment for ultrasound, increased the duration of the process.
A method of obtaining chitosan by adding chitin in 50% alkaline solution prepared by dissolving dry alkali in distilled water and cooled to room temperature 18-22°C. Chitin contribute to this solution in small portions in the ratio of chitin : the alkali solution 1:10-1:15 until a homogeneous suspension, the last stand at room temperature with periodic mixing for 5-20 days (Patent No. 2116733, Russia, IPC A23L 1/33. Priority from 07.10.1996).
The main disadvantages of this the method is the use of high alkali concentration (50%), that leads to a significant consumption of alkali and destruction of the target product, increased alkali content in the wastewater, increased time consuming process.
Closest to the present invention is a method, which provides for the grinding of chitin to a particle size of 0.05-0.2 mm, the deacetylation of 50% sodium hydroxide solution for 30-40 minutes at a temperature of 96-98°C, the separation of the target product from the alkaline solution by filtration, washing with water and drying (Patent No. 2358553, Russia, IPC A23L /33. Priority on 22.08.2007).
The main disadvantages of this method is the use of high alkali concentration (50%), which leads to a significant consumption of alkali and destruction of the target product, a high degree of pulverizing substances with a low degree of deacetylation.
The task of the invention is to develop more technological process of obtaining chitosan from chitin, a decrease in the degree of comminution of the raw materials, the preservation of the structure of the finished product close to nature, increase the degree of deacetylation (88-92%).
The technical result is an increase in the degree of grinding of the raw materials, the preservation of the natural structure of the finished product, the increase in the degree of deacetylation.
The technical result is achieved by the performance of the process of deacetylation is pre-crushed to a size of 1-2×2-3 mm of chitin in a two-neck reactor, equipped with thermometer, reflux condenser and connected to a water-jet vacuum pump, a 40% solution of NaOH at a ratio to chitin (1-3):(20-60) at 100°C, a pressure of 300 mm RT.article within 1-2 hours
The essence of the proposed method is illustrated by the following example.
Example. In a two-neck reactor equipped with a thermometer and connected to a water-jet vacuum pump, pour the pre-crushed to a size of 1-2×2-3 mm chitin, then pour a 40% NaOH solution at a ratio to chitin 1:20. The process of deacetylation (Fig.1) is carried out at 100°C for 1-2 hours
The process under vacuum water pump contributes to a significant reduction in the oxygen concentration in the reaction zone, which, as is known, increases the degree of degradation of chitin.
After this time the finished product is repeatedly washed with distilled water on a Buechner funnel to neutral pH with subsequent spin cycle.
The washed and filtered chitosan is a highly hydrated, swollen product with a water content of more than 70%. To prevent keratinization chitosan is dried in a heating Cabinet at 35-40°C to air-dry state.
The deacetylation installed potentiometric titration of a solution of 0.1 G. hydrochloric acid, is 93% (the prototype 88-92%) (table.2). The composition of the obtained chitosan from shell was determined by the method of elemental analysis. In the result of the analysis, the nitrogen content was 8.6%, hydrogen - 6,46%, carbon - 43,8%, oxygen - 40,9%.
To assess the level of quality of the obtained chitosan were used indicators set out in the technical specifications for food chitosan THAT 9289-067-00472124-03 (see tab.1).
Appearance: flakes size of 1-3 mm
Color: white with cream shade.
Taste: characteristic of the product, without foreign taste. Odour: characteristic of the product, without foreign smell.
Sources of information
1. Patent No. 2067588, Russia, MKI C08B 37/08. Priority from 17.09.1991,
2. Patent No. 2116733, Russia, IPC A23L 1/33. Priority from 07.10.1996,
3. Patent No. 2358553, Russia, IPC A23L 1/33. Priority on 22.08.2007,
|Physico-chemical properties of chitosan|
|Name of indicator||Ed. MEAs.||The norm on THE other||The results of the tests|
|Mass fraction of moisture||%||Not more than 10.0||9,4|
|Ed. pH||Not more than 7.5||3,85|
|The process conditions and the degree of deacetylation of the finished product.|
|The placeholder||The proposed method|
|The degree of crushing of chitin||0.05-0.2 mm||1-2×2-3 mm|
|Pressure||760 mm RT.article.||300 mm RT.article.|
|Duration||30-40 minutes||1-2 hours|
|Mass fraction of NaOH solution||50%||40%|
A method of producing chitosan, characterized in that the process of deacetylation pre-shredded is about 1-2×2-3 mm chitin is carried out in a two-neck reactor, equipped with reflux condenser and connected to a water-jet vacuum pump, a 40% solution of NaOH at a ratio to chitin (1-3):(20-60)) at 100°C, a pressure of 300 mm RT.article within 1-2 hours
SUBSTANCE: there are described compositions containing hyaluronic acid with a low degree of modification of functional groups, and mixtures prepared by a controlled reaction of this slightly modified hyaluronic acid with applicable difunctional or polyfunctional cross-linking agents. The compositions possess the low anti-inflammatory properties in injection in vivo and can be used as medical devices, biomedical adhesives and sealing matters.
EFFECT: targeted delivery of the bioactive substances.
49 cl, 14 dwg, 24 tbl, 45 ex
SUBSTANCE: method of production of the water-soluble bioactive nanocomposite comprising salt of hyaluronic acid modified by citric acid or salt of citric acid, as a matrix, and gold nanoparticles as the filler is carried out by chemical interaction of solid-phase powders of salt of hyaluronic acid, citric acid or salt of citric acid and aurichlorohydric acid or salt of gold under the temperature from -18° to 125°C, under conditions of simultaneous action of pressure from 50 to 1000 MPa and the shear deformation in a mechanochemical reactor.
EFFECT: invention enables to obtain water-soluble bioactive nanocomposite with reliably predictable characteristics, namely the high yield of the target product, high gold content, controlled size of gold nanoparticles, narrow distribution by size of nanoparticles of gold, significant increase in resistance of the composite during long storage the above parameters of the composite are maintained for at least one year, the method is carried out in the absence of the liquid medium and does not require the stage of purification and concentration.
20 cl, 18 ex
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
SUBSTANCE: stabiliser includes modified chitosan which is obtained by modifying chitosan particles located in an emulsion of an organic solvent - water, with pH 6.0-6.5, by first reacting a mixture consisting of a carboxylic acid in an organic solvent and a condensing agent, and then with an organic base, wherein the carboxylic acid used is either palmitic acid or stearic acid or dodecanoic acid, the condensing agent used is a mixture of hydroxysuccinimide and an aliphatic carbodiimide or formaldehyde and an aliphatic isocyanide, and the organic base used is triethylamine.
EFFECT: effective liposome composition stabiliser which can be obtained using a simple method.
8 cl, 3 tbl, 5 ex, 7 dwg
SUBSTANCE: invention relates to the field of organic synthesis. A method of obtaining a water-insoluble sulphur-containing chitosan-based biopolymer includes interaction of chitosan with a thiomethylating agent, preliminarily obtained by saturation of a formaldehyde solution with gaseous H2S, with molar ratio chitosan: formaldehyde: hydrogen sulphide 1:6:4, at a temperature of 60°C for 20-25 hours.
EFFECT: invention ensures obtaining the water-insoluble sulphur-containing chitosan-based biopolymer, which possesses a complexing activity to ions of noble metals (Pd, Pt).
1 ex, 1 tbl
SUBSTANCE: skins of pond fish are flushed with cold flushing water during 10-15 minutes. They are crushed to the size of 2-3 mm. Water extraction is performed at the temperature of 40-45°C during 40-50 minutes at the ratio of crushed skins to water, which is equal to 1:1 at periodic mixing. Then, they are filtered; liquid fraction is dried in a spraying drier at the drier outlet product temperature of 60-65°C during 15-25 minutes so that hyaluronic acid is obtained. Solid fraction is subject to bleaching during 12 hours with hydrogen peroxide-salt solution that is prepared by mixing of 1 l of 3% hydrogen peroxide and 20 g of sodium chloride. Treatment of bleached solid fraction is performed with 1.0-1.2% solution of sodium hydroxide during 24 hours at the temperature of 20-25°C with further neutralisation of the obtained mixture with 3% boric acid solution. Treatment of swollen solid fraction is performed with Pancreatin ferment preparation solution taken in the quantity of 0.5-0.6% to the weight of solid fraction during 1.5-2.0 hours at the temperature of 37-40°C. Flushing of solid fraction is performed with cold flushing water for removal of Pancreatin residues so that collagen is obtained. The obtained collagen, depending on the purpose, is supplied for drying in drying chambers with forced air circulation at the temperature of 18-20°C during 12 hours and storage in dry ventilated rooms at the temperature of not higher than 20°C during 24 months or frozen to the temperature of minus 18 - minus 20°C and stored at the temperature of minus 18 - minus 20°C during 24 months. The liquid fraction dried in the spraying chamber is stored at the temperature of 0-4°C during 12 months or dissolved in physiological buffer solution.
EFFECT: improvement of the method.
2 dwg, 1 tbl, 1 ex
SUBSTANCE: production method of glucan-chitosan complex from yeast biomass of brewing waste involves mechanical and ultrasonic treatment of yeast biomass, destruction of proteins by treatment of the obtained suspension using alkali reagents with further extraction of a target product. As biomass, Saccharomyces living yeast is used. First, yeast is frozen to -15°C during 24 hours. After mechanical destruction, biomass is treated for 15 minutes at 20°C in an ultrasonic bath with frequency of an emitter of 35 kHz and voltage of 285 W. Biomass is acidified with chlorhydric acid till pH=5.5 and treated with ferment preparation in the amount of one pellet containing lipase - 3500 units of Ph.Eur., amylase - 4200 units of Ph.Eur. and protease - 250 units of Ph.Eur. per kilogramme of biomass in terms of dry substance; then, lipid components of yeast are removed. Fermentation is performed at t=20-29°C during 30-60 minutes. Destruction of proteins is performed at 55°C by means of a water bath during 60 minutes by treatment using 4% water solution of caustic soda at the ratio of yeast biomass and alkali, which is equal to 1:4. The medium is neutralised and hydrosol of glucan-chitosan complex is deposited by centrifugation during 10 minutes. The deposit is dried at t=55°C during 48 hours.
EFFECT: invention allows improving the quality of the obtained complex and its biological activity.
SUBSTANCE: invention relates to production of hydroxyalkyl derivatives of polysaccharides. The method of producing 2,3-dihydroxypropyl chitosan involves reacting chitosan with glycidol in the presence of hydrochloric acid with ratio glycidol:chitosan:hydrochloric acid = (2-6):1:1, at room temperature until a gel forms. The mixture is then heated at 55-65°C for 12-14 hours and the reaction mass is treated with water. The mixture is then deposited, subjected to hot extraction with water-soluble alcohols or ketones and dried.
EFFECT: invention simplifies the method of production and output of the end product and improves sorption properties of the compound.
1 tbl, 3 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: there are presented: using benzophenanthridine alkaloid salts for preparing therapeutic agents for treating tumours, wherein the alkaloid salt is found in the form luteic, phosphatidic or hyaluronic acid, the benzophenanthridine alkaloid salt with phosphatidic acid or hyaluronic acid, and a based pharmaceutical composition for treating tumours.
EFFECT: what is shown is cytotoxic activity of the sanguinarine salts according to the invention at least twice increased in all studied tumour cell lines in relation to the chloride salt; it is suggested to be caused by higher absorption by the tumour cells.
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: fish industry.
SUBSTANCE: method involves providing deacetylation of raw material with the use of preliminarily cooled alkaline solution; washing and drying. Deacetylation process is performed in three stages, first stage being performed for 7 days and subsequent two stages being performed for 2 hours each, combined with thermal processing at temperature of 55-590C. Washing process is provided after each deacetylation stage.
EFFECT: provision for producing of chitosan from chitin of cancerous with increased extent of deacetylation, while native properties of natural polymer being kept, without breaking of glycoside binding chain.
FIELD: organic chemistry.
SUBSTANCE: claimed method includes subsequent chitosane-containing raw material with non-polar liquefied gas, water, alkali, water, acid, water, alkali, and water to produce target product in form of solid residue, wherein in at least first extraction step pressure in reaction mixture is periodically released to provide extractant boiling, and than increased up to starting value.
EFFECT: method with reduced energy consumption.
FIELD: chemical technology of natural compounds.
SUBSTANCE: invention describes a method for preparing water-soluble derivatives of chitosan. Method involves treatment of chitosan with acid medium up to its swelling wherein vapor medium water-acid is used as acid medium. Treatment of chitosan is carried out with vapor of monobasic acid aqueous solution taken among the group including hydrochloric acid, formic acid and acetic acid. Method allows simplifying technology in preparing water-soluble derivatives of chitosan.
EFFECT: improved preparing method.
4 cl, 1 tbl, 9 ex
FIELD: chemistry and technology of derivatives of polysaccharides, chemical technology.
SUBSTANCE: invention relates to methods for preparing chitosan esters. Invention describes a method for preparing chitosan polyethylene glycol ester that involves dissolving chitosan in acetic acid followed by alkalization. Then the reaction mixture is subjected for effect of ethylene oxide under pressure 1-3 atm and temperature 60-100°C, and the concentration of reaction mass is corrected by addition of distilled water up to the density value of solution 1.030-1.032 g/cm3. Then the reaction mass is purified by electrodialysis at the rate value of solution in treatment chambers 3.0 cm/s, not less, temperature 20-45°C, the current density value 0.25-0.75 A/dm2 and the constant volume of the reaction mass. Method provides enhancing the effectiveness of purification by electrodialysis due to reducing energy consumptions. Chitosan esters can be used in medicine, cosmetics, food and chemical industry.
EFFECT: improved preparing method.
FIELD: organic chemistry of natural compounds, chemical technology, medicine.
SUBSTANCE: invention relates to the group of chitosan-containing compounds. Invention relates to synthesis of modified chitosan of the following structure: wherein n = 150-1400. The modified chitosan possesses the bactericidal activity, in particular, antituberculosis activity.
EFFECT: valuable medicinal properties of modified chitosan.
1 tbl, 1 dwg, 3 ex
FIELD: natural compounds technology.
SUBSTANCE: chitosan preparation process comprises breaking naturally occurring chitin-containing material, charging it into reactor, demineralization with 6-7% aqueous hydrochloric acid, deproteination with sodium hydroxide solution at 85-95°C, deacetylation with sodium hydroxide solution on heating, decoloration, and washing with water after each stage to pH 6.5. Process is characterized by that chitin-containing material broken to achieve fraction 0.5-6 mm is fed simultaneously into a number of reactors, wherein demineralization is effected with aqueous hydrochloric acid stream at 85-95°C for 1.5 h while controlling pH in each reactor exit to achieve acid concentration in each reactor exit the same as concentration of the initial acid by way of feeding it in a continuous manner. In addition, deproteination is carried out with 6-7% sodium hydroxide solution stream for 1.5 h followed by discharging treated material into autoclave to perform deacetylation simultaneously with decoloration using 50% sodium hydroxide solution at 130-140°C in inert gas environment and in presence of 3-5% hydrogen peroxide solution used in amount 3-5% of the total volume of mixture.
EFFECT: enhanced process efficiency.
FIELD: chemical technology.
SUBSTANCE: invention relates to methods for preparing water-soluble saline complexes (associates) of hyaluronic acid with d-metals of IV, V and VI periods of Mendeleyev's periodic system of elements that can be used in pharmacology and cosmetology. Invention describes a method for preparing water-soluble saline complexes of hyaluronic acid involving preparing an aqueous solution of salt of d-metal of IV, V and VI periods of periodic system and its mixing with hyaluronic acid sodium salt, holding the mixture, its stirring, dilution with water and isolation of the end product. For mixing method involves using the amount of aqueous salt of abovementioned d-metal that is equivalent to the amount of carboxy-groups of hyaluronic acid sodium salt or in the limit from 0.95 to 1.10. After dilution with water the solution mixture is subjected for ultrafiltration on separating membranes with simultaneous washing out with aqueous salt solution of abovementioned d-metal firstly and then with deionized water followed by concentrating the product. By another variant for mixing the method involves the amount of aqueous solution of d-metal salt lesser of the equivalent amount of carboxy-groups in hyaluronic acid sodium salt. After dilution with water the mixture is subjected for ultrafiltration on separating membranes with simultaneous washing out with deionized water followed by concentrating the product also. Method is characterized by the decreased time of processes and simplicity.
EFFECT: improved preparing method.
2 cl, 1 tbl
FIELD: medicine, food processing industry, in particular production of depolymerized chitosane and products based on the same.
SUBSTANCE: claimed method is based on using of chitosanase in acetic acid medium and spray drying of and depolymerized chitosane and is characterized in that obtained depolymerized chitosane is preliminary converted in non-ionized form by neutralizing of bound acetic acid with ammonium hydroxide followed by precipitation in ethanol and air drying. Further interaction is carried out with ammonium lipoate or glutathione in aqueous medium. Claimed products may be used individually or in combination with other components.
EFFECT: new products for food processing industry and medicine.
4 cl, 2 ex
FIELD: organic chemistry, chemical technology.
SUBSTANCE: invention relates to a method for preparing modified glycosaminoglycans possessing analgesic properties. Method involves interaction of glycosaminoglycans with 1-phenyl-2,3-dimethyl-4-aminopyrazolone-5-(4-aminoantipyrine) in aqueous medium at pH = 4.7-4.8 in the presence water-soluble 1-ethyl-3-[3-(dimethlamino)propyl]carbodiimide as a condensing agent at room temperature followed by purification from low-molecular reagents. Method involves a single step that simplifies technology in preparing modified glycosaminoglycans.
EFFECT: improved preparing method.
FIELD: natural substances, chemical technology.
SUBSTANCE: invention relates to a method for preparing chitosan and purification from components of the reaction mixture - low-molecular products of deacetylation and alkali excess. Invention relates to a method for purifying chitosan prepared by solid-state method involving treatment of reaction mass with extractant consisting of 3.3-20.0% of water, 32.2-57.1% of ethyl acetate and 24.6-64.5% of ethanol at the extractant boiling point. Also, invention relates to a method for purifying chitosan prepared by suspension method and involving treatment of the reaction mass with ethyl acetate and the following treatment with extractant consisting of 6.2-25.0% of water, 12.5-62.5% of ethyl acetate and 31.3-62.5% of ethanol at the extractant boiling point.
EFFECT: improved isolating and preparing method.
3 cl, 2 tbl, 1 dwg