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
The invention relates to the field of chemical technology, namely the group of compounds containing chitosan. The resulting modified chitosan can be used in medicine, cosmetics, agriculture, veterinary, food and light industry.
Chitosan is a physiologically active compound of natural origin, widely used in cosmetics and medicines. It is produced by hydrolysis of chitin, the main component of the outer skeleton of arthropods:
Chitin (from the French "chitine" and the Greek "chitone", which means "skin", "shell") is widely distributed in nature, it is part of the cell walls of fungi and bacteria, where does the support and a protective function.
According to the chemical structure of chitosan is a high molecular weight polymers (MM˜30000-260000 USD) from the group of polysaccharides built from the remnants of glucosamine (acetylglucosamine), interconnected β(1→4) glycosidic bonds. In its structure, physicochemical properties and biological role of chitosan is similar to the cellulose of plants.
In recent years in various fields of medicine and cosmetology has emerged a heightened interest in the use of chitosan as a mild remedy, obladayushzuyu antiseptic effect. Especially valuable is that chitosan, being a product of vital activity of living organisms are harmless to humans.
Known to be an effective antibacterial antibiotic streptomycin, which molecule is a tricyclic carbohydrate containing one of the two cycles guanidine groups [encyclopedia of medicine. 8th ed., edited Ufraw, M., "radar", 2001, str].
The structural formula of streptomycin has the following form:
Streptomycin by their chemical nature, as chitosan refers to the aminoglycosides, is an effective broad-spectrum antibiotic, active against Mycobacterium tuberculosis, the causative agents of plague, tularemia, brucellosis, dysentery, strepto-, fees and meningococci, produces radiant fungus (genus Streptomyces).
However, streptomycin is toxic enough and with long-term use affects the auditory nerve.
Closest to the proposed solution is the drug carboxymethylchitosan, obtained by the reaction of chitosan with monochloracetic acid (U.S. Pat. Of the Russian Federation No. 2185387, class 08 In 37/08, 2000).
The disadvantages of this drug include lack of bactericidal activity and complex method of receipt.
The technical purpose of this invention is to increase the bactericidal activity and the drug.
To solve the technical problem of the synthesized modified chitosan of the following structure:
Since the polymer forms of medications are generally preferred due to the strengthening effect due to the presence of many active groups located at the molecular distances, lower toxicity, and the effect of Deposit (longer therapeutic effect of the drug, it was considered useful to carry out guanidine amine groups of chitosan, turning them from inactive amine in high-performance guanidine.
The modified chitosan was obtained as follows. Due to the low thermal stability of chitosan as a soft guanidinium tool was selected carbodiimide (NH=C=NH) - tautomer Monomeric cyanamide (NH2CN).
As a source of chitosan materials have served two commercial sample of chitosan succinate companies CJSC "Bioprogress" and "Hemmed", freeze-dried method. Their molecular masses are according to ultrafiltration (osmosis on the membranes) 30000 26000 and; the degree of polymerization, respectively, n=150 and n=1400. The reaction was carried out with swollen chitosan succinate in a solution of acetonitrile containing the estimated quantity of 50% aqueous carbodiimide:
To complete the process the reaction mixture after 24 hours of exposure under normal conditions was heated for 10 hours at 40°C. the Modified chitosan differs from the original by more friable structure.
IR-spectroscopic study of the obtained polymer (see drawing) shows the appearance of the structure of the modified chitosan (curve 1) a significant number guanidino groups: intensive bandsandwhen ˜3350 and 1600-1650 cm-1. For comparison, the drawing shows a range of grandravine polyethylenimine containing guanidine band (curve 2). The IR spectrum of initial chitosan bands at 3350 and 1600 cm-1does not contain [chitin and chitosan]. Since we had no method osmoticheskogo the determination of molecular mass to determine the molecular weight of the modified chitosan was used the following method. Sample source modified chitosan was dissolved in 2% acetic acid and determined their characteristic viscosity. The equality of the obtained values (ηRef=0,41 DL/l; ηmod=0,43 DL/l) indicates that during the reaction, the degradation of the polymer chains of chitosan did not take place. In turn, a small increase in the molecular is Arnau mass due to modifications of about 20%, also not so much to affect the characteristic viscosity.
The emergence of guanidino groups in the chitosan is logged chemical analysis: colorimetry with eosin.
By the method of serial dilution of the antibacterial activity grandravine chitosan. Bacteriostatic activity on the strain of Pseudomonas aeruginosa was 0,075%, bactericidal 0,15%.
Due to the proximity grandravine chitosan to streptomycin drug was also tested for anti-TB activity. It also noted increased efficiency, due to the polymeric nature of the drug (compared with streptomycin) and compared to the unmodified chitosan.
Provide examples illustrate the practical implementation of the synthesis grandravine chitosan.
A portion of 25 g (0.1 mole) of chitosan succinate (n=150) was ground in a coffee mill in a fine yellow powder and was mixed in a flask with 100 ml of acetonitrile, containing 4.5 g (0.1 mole) carbodiimide. After swelling of chitosan in a solution of acetonitrile during the day the reaction mixture to complete the reaction was heated with occasional stirring at a temperature of 40°C. the Modified chitosan was separated by filtration, then washed with 50 ml distillirovanna the water on the filter and dried in air.
Received guanidine of modificat chitosan is a volumetric light powder light yellow color, it is difficult soluble in water and slightly better in 2% acetic acid solution.
A portion of 25 g of commercial chitosan succinate (n=150) was purified by presidenial. To this end it was dissolved in 1.5 liters of 2% aqueous solution of acetic acid. Complete dissolution of the sample chitosan requires at periodic stirring ˜48 hours. The obtained homogeneous solution of chitosan acetate decantation from a small residue, which may include nephrolitiasis chitin and protein impurities. A clear solution was added with vigorous stirring to 2 liters of a 15% aqueous solution of ammonia. The reaction mixture was left for a day and then gently decantation of the upper clear solution. To the precipitate, having a form of white wool was added 1.5 l of distilled water, thoroughly mixed, and again left for the day. The operation of the washing and decanting was repeated three times until the complete disappearance of the smell of ammonia. After that sediment base of chitosan was obezvozhivani on the centrifuge and neutralized by adding dropwise 5 g glacial acetic acid, thorough mixing in a mortar and drying in air to constant weight. Exit 20,
The obtained chitosan acetate used in the reaction with the carb what diimides by the method of example 1. The degree of guanidine purified chitosan higher (75%)than neprevzojdennogo (60%), according to the colorimetric determination with eosin.
Sample of 0.5 g of the modified and the original chitosan was dissolved in 100 ml of 2% aqueous solution of acetic acid and measured the results of the specific viscosity of the obtained solutions. Close values obtained viscosities ηRef=0.4 ηmod=0,3 indicates the absence of destruction of the chain of chitosan at grandravine.
Portion 5 g of the commercial chitosan succinate (n=1400) modified by treatment of 1 g of the carbodiimide in 20 ml of acetonitrile by the method of example 1. The modified chitosan was washed on the filter and dried to constant weight.
Weighed to 0.1 g of the modified and the original chitosan was dissolved in 100 ml of 2% aqueous solution of acetic acid and measured the results of the specific viscosity of the obtained solutions. Close values obtained viscosities ηRef=1,0 ηmod=0,9 indicates the absence of destruction of the chain of chitosan at grandravine.
|Antitubercular activity grandravine chitosan|
|30 min||1 hour||24 hours|
|Succinate grandravine chitosan||0,5||+||-||-|
|Acetate grandravine chitosan||0,5||-||-||-|
The modified chitosan of the following structure:
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: 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: 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: 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.
SUBSTANCE: the present innovation deals with technique of revaccination in adults against diphtheria and tetanus under conditions of Far North. For this purpose one should form a group of people vaccinated more than 10 years ago to vaccinate them in February. The method leads to increased efficiency of vaccination due to decreased duration of vaccination period.
EFFECT: higher efficiency of revaccination.
FIELD: medicine, obstetrics.
SUBSTANCE: one should conduct antibacterial therapy 3 mo before planned pregnancy consisting of preparations of tetracyclinic group or macrolides in combination with nystatin and metronidasol to continue it since the first day of menstrual cycle and, also, it is necessary to perform correction of vaginal biocenosis, and about 3-4 wk after therapy carried out for 2 next mo before planned pregnancy starting, also, since the first day of menstrual cycle - metabolic therapy; At the onset of pregnancy one should conduct courses for preventing placental deficiency dealing with introduction of preparations that improve uterine-placental circulation, and preparations that improve rheological properties of blood and vitamin-metabolic therapy or the same preparations, and additionally - introduction of macrolides ad viferon rectally in case of activation of chlamydial infection. The present innovation enables to sanitize uterine cavity, improve uterine-placental circulation, restoration of placental tissue structure that, in its turn favors the birth of healthy generation.
EFFECT: higher efficiency of prophylaxis.
1 cl, 9 tbl
FIELD: medicine, pharmacy.
SUBSTANCE: medicinal formulation possessing the bacteristatic effect consists of a core comprising the following components, wt.-%: clarithromycin, 40.0-80.0; polyvinylpyrrolidone, 3.0-10.0; sodium lauryl sulfate, 2.0-5.0; sodium croscarmelose, 4.0-10.0; aerosil, 0.5-2.0; magnesium stearate, 0.5-2.0, and microcrystalline cellulose, 10.0-31.0. Also, the medicinal formulation consists of envelope comprising the following components, wt.-%: hydroxypropylmethylcellulose, 30.0-70.0; polyethylene glycol, 12.0-22.0; titanium dioxide, 11.0-20.0, hydroxypropylcellulose, 2.0-10.0, dye yellow quinoline, 1.0-4.0, and vanillin, 1.0-4.0. Also, invention describes a method for preparing the medicinal formulation by wet granulation followed by tableting and applying the envelope from an aqueous suspension. Prepared tablets show the necessary mechanical strength, insignificant scattering index by mass (± 3.5%) and dissolving 88-91% for 30 min.
EFFECT: improved and valuable properties of medicinal formulation.
3 cl, 2 tbl
FIELD: medicine, gynecology, surgery.
SUBSTANCE: one should introduce 3.5%-chitosan ascorbate gel into fistulous channel that contains metronidasol at the dosage of 2 mg/ml, at the volume up to 20 ml once/2 d till complete fistula's closing. The present innovation enables to activate reparative processes and fistulous epithelization that favors for closing fistulous channel in earlier terms.
EFFECT: higher efficiency of therapy conducted.
FIELD: medicine, surgery.
SUBSTANCE: one should apply a polycompositional film onto donor's wounds after autodermoplasty performed. This film contains the following components in weight proportions: chitosan 78.3-89.4; polyvinyl alcohol 9.8-19.8; antibiotic of aminoglycoside group 0.5-2.0; anesthetic 0.1-0.2. It is perforated at tension coefficient being 1:4. The innovation enables to decrease wound's traumatization, improves prophylaxis of suppuration and increases cosmetic effect even at a single application of the film suggested.
EFFECT: higher efficiency of therapy.
SUBSTANCE: the present innovation deals with application of pleuromutilin derivatives, that is valnemulin and thiamulin, for transdermal treatment of bacterial diseases, in particular those induced by Dichelobacter nodosus, Fusobacterium necrophorum, Bacteriodes nodosus and Bacteriodes melamnogenicus, for manufacturing medicinal preparation or as an active ingredient of medicinal preparation of the same indication and corresponding method for transdermal treatment of diseases, for example foot rot. It has been detected the capacity of antibiotics to penetrate skin and enter either plasma or blood at concentrations being efficient against systemic bacterial infections, so, medicinal preparation could be designed in the form of ointment, cream, solution, shampoo, powder and spray.
EFFECT: higher efficiency of application.
9 cl, 1 tbl
FIELD: biotechnology, immunology.
SUBSTANCE: invention proposes preparation that comprises the immunoelectrophoretically pure secretory immunoglobulin A isolated from whey milk and/or colostrum of immunized ungulate animals and pharmaceutically acceptable vehicles. The base preparation (substance) comprises 6-12% of secretory immunoglobulin A at pH 4-8, an anti-complementary activity at least 10 mg of protein, not activating 2 CH50, protects in >70% against corresponding infections (in infection macroorganism in doses ≥10 ID50), shows areactogenic property in intravenous administration, can comprise stabilizing additives in the total concentration 4%, not above. The preparation possesses high purity, low anti-complementary activity, stable in storage, useful for oral, parenteral and topical using and possesses therapeutic activity with respect to microorganisms and viruses against which humans and animals immunization have been carried out. Invention can be used in treatment and prophylaxis of immunodeficiency states, bacterial and viral infections in humans and animals.
EFFECT: valuable medicinal and veterinary properties of preparation.
9 cl, 1 tbl, 10 ex
FIELD: organic chemistry, chemical technology, medicine, pharmacy.
SUBSTANCE: invention relates to novel heterocyclic compounds comprising 2-aminopyridin-3-sulfonic fragment of the general formula (1) or their pharmaceutically acceptable salts, N-oxides or hydrates possessing properties of antagonists of glutamate-induced calcium ions transport, in particular, neuroprotective effect. Also, invention relates to the focused library for the search of biologically active leader-compounds comprising at least one heterocyclic compound of the general formula (1) and to pharmaceutical composition if form of tablets, capsules or injections placed into pharmaceutically acceptable package containing compounds of invention as an active substance. In compound of the general formula (1) R1 represents hydrogen atom; R2 represents chlorine atom, optionally substituted hydroxyl group, optionally substituted amino-group, optionally substituted azaheterocyclyl; or R1 and R2 in common with nitrogen and sulfur atoms to which they are bound form optionally substituted and optionally condensed with other cycles 1,1-dioxo-4H-pyrido[2,3-e][1,2,4]thiadiazine or optionally substituted and optionally condensed with other cycles 5,5-dioxo-5,6,7,9-tetrahydro-5-thia-1,6,9-triazabenzocyclohepten-8-one. Also, invention discloses methods for preparing different compounds of the general formula (1).
EFFECT: improved preparing methods, valuable medicinal properties of compounds.
10 cl, 4 sch, 4 tbl, 9 ex
FIELD: organic chemistry, biochemistry, pharmacy.
SUBSTANCE: invention relates to new heterocyclylsulfonyl alkylcarboxylic acids and their derivatives of the general formula (1): or their pharmaceutically acceptable salts, N-oxides or hydrates possessing the inhibitory effect on kinase activity and to the focused library for search of active leader-compounds comprising at least abovementioned compound. In the general formula 91) W represents optionally substituted heterocyclic radical, among them: pyrrole-3-yl, thiophene-2-yl, isooxazole-4-yl, pyrazole-4-yl, imidazole-4-yl, pyridine-3-yl, 1H-2,4-dioxopyrimidine-5-yl, 2,3-dihydro-1H-indole-5-yl, 2,3-dihydro-1H-indole-7-yl, 1,3-dihydro-2-oxoindole-5-yl, 2,3-dioxo-1H-indole-5-yl, 2-oxo-3H-benzoxazole-6-yl, benzothiazole-6-yl, 1H-benzimidazole-5-yl, benzo[1,2,5]oxadiazole-4-yl, benzo[1,2,5]thiadiazole-4-yl, 1,2,3,4-tetrahydroquinoline-6-yl, 3,4-dihydro-2-oxo-1H-quinoline-6-yl, quinoline-8-yl, 1,4-dihydro-2,3-dioxoquinoxaline-6-yl, 3-oxo-4H-benzo[1,4]oxazine-7-yl, 3-oxo-4H-benzo[1,4]thiazine-7-yl, 2,4-dioxo-1H-quinazoline-6-yl, 2,4-dioxo-1,5-dihydrobenzo[b][1,4]diazepine-7-yl or 2,5-dioxo-3,4-dihydrobenzo[b][1,4]diazepine-7-yl; Y represents optionally substituted methylene group; R1 represents chlorine atom, optionally substituted hydroxyl group, optionally substituted amino-group, optionally substituted azaheterocyclyl; n = 1, 2 or 3; or Yn represents carbon atom of optionally substituted (C3-C7)-cycloalkyl or optionally substituted (C4-C7)-heterocyclyl. Also, invention relates to a pharmaceutical composition in form of tablets, capsules or injections placed into pharmaceutically acceptable package.
EFFECT: valuable properties of compounds.
5 cl, 3 sch, 5 tbl, 6 ex
FIELD: organic chemistry, chemical technology, antibiotics.
SUBSTANCE: derivative of 9-deoxo-9a-aza-9a-homoerythromycin A of the formula (3) wherein R4 represents hydroxyl protecting group is prepared by protection of 2'-hydroxy-group of compound of the formula (5) to form compound of the formula (4)
and by oxidation of C-4''-hydroxy-group of compound of the formula (4) that is carried out by addition of dimethylsulfoxide to solution containing compound of the formula (4) and a solvent followed by cooling the mixture up to about -70°C, activation of dimethylsulfoxide in situ and defoaming the reaction mixture. Compound of the formula (4) is converted to the oxidation stage directly without its isolation. Also, invention proposes additive salt of trifluoroacetic acid of compound of the formula (3) and a method for its preparing by treatment of compound of the formula (3) with trifluoroacetic acid. Invention provides increasing yield and improving purity of the end product.
EFFECT: improved preparing method.
11 cl, 6 ex
FIELD: biotechnology, medicine, infectious diseases, medicinal microbiology.
SUBSTANCE: invention relates to a composition designated for treatment and prophylaxis of infections caused by Neisseria microorganism that comprises the following components: (a) protein with amino acid sequence similar by 65% and above with the natural Neisseria protein of a single species (the first group of amino acid sequences is given in the text) and/or its fragment consisting of 10 and more amino acids and eliciting antigen properties; (b) the second protein with amino acid sequence similar by 65% and above with the natural Neisseria protein of another species (the second group of amino acid sequences with even numbers is given in the text), and/or its fragment consisting of 10 or more amino acids and eliciting antigen properties; in particular, the second protein represents NspA. The composition comprises additionally adjuvant. The composition is used both a medicinal agent and for manufacturing the medicinal agent. Applying the invention provides enhancing the effectiveness of prophylaxis or treatment due to the universal effect of the composition (vaccine). Invention can be used in medicine for treatment of infections.
EFFECT: valuable medicinal properties of composition.
8 cl, 137 dwg, 5 tbl, 12 ex