Conjugate of hyaluronic acid and novocaine with amphoteric properties
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to biochemistry. What is presented is a conjugate of hyaluronic acid and novocaine of a structure as defined in the patent claim containing 20-50% residues of novocaine.
EFFECT: conjugate is water-soluble; it possess the amphoteric properties and contains no side O-acylisourea.
3 tbl, 3 ex
The invention relates to new chemical substances, namely, modified hyaluronic acid, which can be used in cosmetic, food industry, pharmacology, veterinary medicine, and the pharmaceutical industry.
Hyaluronic acid (ha) - heteropolysaccharide linear structure, belongs to the class of acidic glycosaminoglycans, is in the connective tissues of animals and humans and consists of units of D-glucuronic acid and N-acetyl-D-glucosamine. Molecular mass Ledger 104-2×106Yes.
On the basis of the civil code produces the following preparations. High-molecular GK (M=106Yes is part of gels "Provisk" (Sweden) and "Healon" (Canada), used in ophthalmic surgery operations cataract extraction, is the active substance in the films "Seprafilm" to prevent adhesive disease of the peritoneum. Low-molecular ha impregnated wipes "Gaplus", intended for the treatment of burn disease. For the treatment of venous ulcers and acne, apply a zinc salt Ledger (medicine "Curiosin" (in the form of a solution or gel), and the drug Cystistat" is intended to repair a damaged mucosa of the urinary bladder in interstitial cystitis. GK is an integral component of cosmetic sham what una, creams and tonics to stimulate hair growth. Patented application of ha in the treatment of herpes, psoriasis, and also for the manufacture of suppositories for various purposes [Peredelkino YOU, V.S. Lukin, Odinokov V.N. Acidic glycosaminoglycans and their chemical modification (review) // Bioorg. chemistry. 2008. T. No. 1. P.5-28].
Hyaluronic acid is a negatively charged polyelectrolyte. Introduction to the structure of Ledger groups with opposite charge gives the ha molecules amphoteric properties, and increase intra - and intermolecular interactions of macromolecules. The group acquires the ability to form hydrogels having hydrophilic properties. The polyampholytes based on the Ledger can be used as carriers for other molecules, such as DNA [S. Asayama, M. Nogawa, Y. Takei, Akaike T., Mamyama A. Synthesis of novel polyampholyte comb-type copolymers consisting of a poly(L-lysine) backbone and hyaluronic acid side chains for a DNA carrier // Bioconjug Chem. 1998. V.9. No. 4. P.476-81].
Among known previously synthesized derivatives of GA amphoteric structure are conjugates Ledger with carbodiimide different structures [K.P. Vercruysse, Prestwich G.D. Hyauronate derivatives in drug delivery // Therapeutic Drug Carrier Systems. 1998. V. 15. No. 5. P.513-555], with isonicotinic acid hydrazide [E.S. Lukin abstract. Diss. on saisc. step. Kida. Sciences. Ufa, 2007. 110 S(www.anrb.ru/ink that thesis. Council)] and hexamethylenediamine were [J. Yeom, Bhang, S., Kim, B-S., Seo M.S., E.J. Hwang, I.H. Cho, J.K. Park, Hahn S.K. Effect of cross-linking reagents for hyluronic acid hydrogel dermal fillers on tissue augmentation and regeneration // Bioconjugate Chem. 2010. V.21, p. 240-247]. Amphoteric properties of these conjugates have not been investigated.
One of the ways to get the Ledger with amphoteric properties is the covalent binding of GC with β-diethylaminoethyl ether of para-aminobenzoic acid (novocaine). Novocaine belongs to the class of local anesthetic drugs. In addition to anesthetic action, novocaine by direct injection into the blood stream will have an overall effect on the body: it reduces the formation of acetylcholine and reduces the sensitivity of peripheral receptors, exerts a blocking effect on the autonomic ganglia, reduces spasms of smooth muscles, the excitability of the heart muscle and motor areas of the cortex [Mashkovsky PPM Medicines. - Kharkov: Torching. 1997. Vol.2. S]. In the body novocaine relatively rapidly hydrolyzed, forming a p-aminobenzoic acid (vitamin Hi) and Diethylaminoethanol (has a moderate vasodilator action), which are themselves pharmacologically-active substances.
Conjugates of glycosaminoglycans (GAGS) (chondroitin-sulfate, heparin and oxidized primary hydroxy-group of hyaluronic acid) with novocaine are known [1-8, see references below]. They were obtained by the reaction of GAG with novocaine in the presence of a condensing reagent water-soluble 1-ethyl-3-[3-(dimethylamino)propyl]to the of bodiimide (CBI) and contained (depending on the ratio of reagents), according to NMR spectroscopic analysis, 33-38% of residues of novocaine (per 100 disaccharide glycosides of links) in a modified chondroitin sulfate, 66-90% - modified heparin, 60% in oxidized Ledger (scheme 1). References 1-8:
1. Peredelkino YOU, Odinokov V.N., V.S. Lukin, Temkina T.V., Khalilov L.M., Dzhemilev sea level Chemical modification of heparin // Bioorg. chemistry. 2006. 32. No. 5. S-529;
2. Peredelkino YU, E.S. Lukin, Odinokov V.N. Acidic glycosaminoglycans and their chemical modification (review) // Bioorg. chemistry. 2008. T. No. 1. P.5-28;
3. Peredelkino YOU, Odinokov V.N., Lukin Y.S., Dzhemilev sea level Conjugation of chondroitin sulfates with amines // Bioorg. chemistry. 2008. T. No. 5. S-710;
4. Peredelkino YOU, Odinokov V.N. Lukin Y.S., Sufijarova RS Parfenova TI, Bashkatov S.A., sibagatullin N.G., Dzhemilev sea level // Pat. Of the Russian Federation No. 2283320. Publ. 10.09.2006. BI No. 25;
5. Peredelkino YOU, Odinokov V.N. Lukin Essenially N.G., Suverov IVAN, Serik E.M., Dzhemilev sea level // Pat. Of the Russian Federation No. 2298406. Publ. 10.05.2007. BI No. 13;
6. Peredelkino YOU, Odinokov V.N., Lukin Y.S., Dzhemilev sea level, Ivanov O.V., Cathalina E.A. // Pat. Of the Russian Federation No. 2318830. Publ. 10.03.2008. BI No. 7;
7. Peredelkino YOU, Cathalina E.A., E.S. Lukin, Odinokov V.N., Dzhemilev sea level // Patent RF №2350625. Publ. 27.03.2009. BI No. 9;
8. Peredelkino YOU, Suverov IVAN, E.S. Lukin, Cathalina E.A., Odinokov V.N., Dzhemilev sea level // Pat. Of the Russian Federation No. 2343932. Publ. 20.01.2009. BI No. 2.
In addition to residues of novocaine, conjugates of chondroitin sulfates from the umbilical cord of newborns contained 3% O-utilization (products joining the CBI on carboxy-groups), conjugates of heparin-3-10%, compared dermatosurgery from pig skin is 32%.
Closest to the proposed invention is a conjugate Ledger containing, depending on the ratio of reagents, 10-53% of residues of novocaine and 18-36% urednik residues (O-utilization) [E.S. Lukin abstract. Diss. on saisc. step. Kida. Sciences. Ufa, 2007. 110 C. (www.anrb.ru/ink. thesis. Council)] (Fig.1). It was obtained according to scheme 1 and high content of O-utilization practically does not dissolve in water.
The main drawback of the above-mentioned conjugate is the presence in its composition of by-products attach carbodiimide (Fig.1), so that the solubility of the compounds was practically reduced to a minimum.
The task of the invention is to obtain having amphoteric properties of water-soluble conjugate Ledger with novocaine, not containing by-products. This is achieved as follows. The reaction of GA with novocaine is carried out in the presence of the OED and N-hydroxybenzotriazole (HOBt) as an additive that prevents the formation of side O-utilization. Synthesis of OS the effect in the aquatic environment (pH 4.7-4.8) at room temperature for 30-60 min at a ratio of chemicals VOC:novocaine:t:CBI=1:1-2:0.5-2:0.75-2 and get a water-soluble products with 20-50% of residues of novocaine, not containing O-utilization (scheme 2). It should be noted that, HOBt is used in peptide synthesis and is sometimes used in the carbodiimide synthesis of some derivatives of GA (1-5-fold excess relative to the COOH-group of the substrate) [Kurisawa, M., J.E. Chung, Y.Y. Yang, Gaoa Sh.J., H. Uyama Injectable biodegradable hydrogels composed of hyaluronic acid-tyramine conjugates for drug delivery and tissue engineering // Chem. Commun. 2005. P. 4312-4314; Bulpitt, P., Aeschlimann D. New strategy for chemical modification of hyaluronic acid: preparation of functionalized derivatives and their use in the formation of novel biocompatible hydrogels // J. Biomed. Mater. Res. 1999. V.47. P.152-169; Crescenzi V., Francescangeli, A., A. Taglienti, D. Capitani, L. Mannina Synthesis and partial characterization of hydrogels obtained via glutaraldehyde crosslinked of acetylated chitosan and of hyaluronan derivatives // Biomacromolecules. 2003. V.4. P.1045-1054; Crescenzi V., Francescangeli, A., A. Taglienti New gelatin-based hydrogels via enzymatic net working // Biomacromolecules. 2002. V.3. P.1384-1391].
All samples conjugates Ledger with 20-50% of residues of novocaine showed properties of polyampholytes [S. Asayama, M. Nogawa, Y. Takei, Akaike T., Maruyama A. // Bioconjug. Chem. 1998. V.9. No. 4. P.476-481.], i.e. measured at 500 nm turbidity their aqueous solutions (concentration 4 mg/ml) was changed by varying the pH from 2 to 11. Maximum absorption of solutions of the samples was observed at pH 2-5 .5 (table 1).
The invention is illustrated by the following examples.
Example 1. 0.1 g (0.25 mmol) of GC, 0.07 g (0.25 mmol) of novocaine, 0.016 g (0.125 mmol) of HOBt are placed in a glass container with a volume of 100 cm3equipped with magnetic what esilkoy. Then add 25 ml of distilled water. All components are mixed at room temperature until complete dissolution. Bring the solution to pH 4.75 with 0.1 M NaOH, was added 0.036 g (0.19 mmol) of water-soluble CBI and intensively stirred the reaction mass over a period of 0.5 h, keeping pH 4.7-4.8 titration with 0.1 M Hcl. Then it was cooled to 0-5°C. the reaction mass is added 0.1 M NaOH (to pH 7), 3-5 ml of saturated NaCl solution and 75 ml of ethyl alcohol. The precipitate centrifuged at 3000 rpm for 2-5 minutes the precipitate is dissolved in 15 ml of 6% NaCl and add 45 ml of ethanol. The newly formed precipitate centrifuged at 3000 rpm for 2-5 min, washed with ethanol and then diethyl ether and dried in vacuum. So get modified GC with novocaine with a degree of substitution of carboxyl groups of the polymer 20 mol%. (scheme 2).
To obtain conjugates with novocaine used a CC with a molecular weight of 40 kDa [Peredelkino YOU, Odinokov V.N., Vakhrusheva B.C., Golikova M.L., Khalilov L.M., Dzhemilev sea level Modification of hyaluronic acid aromatic amino acids // Bioorgan. chemistry. 2005, 31 So. No. 1. S-95]) and higher.
Conversion of the carboxylic groups of ha in amide was determined according to the1H-NMR spectroscopy using the integrated intensity of the characteristic signals about the ones residue novocaine (signal with δ 1.4 ppm (t, J=14.1 and 7.0 H2NCF2CH3)) in relation to the intensity of the signal of the methyl protons acetamide group GK in the field 5 2 ppm as an internal standard. Spectra1H-NMR and13C-NMR were recorded for solutions in D2O spectrometer Bruker AMX-400 (operating frequency for1H-NMR 400 MHz), as the standard used acetone. Spectra in the visible region (500 nm) were obtained using the spectrophotometer Specord M-40. Control the pH of the solutions was performed using a pH meter pH-340".
Amphoteric properties of the conjugate of ha with 20% residual novocaine, depending on the pH (from 2 to 11) was investigated according to the method described in S. Asayama, M. Nogawa, Y. Takei, Akaike T., Maruyama A. // Bioconjug. Chem. 1998. V.9. No. 4. P.476-481. Prepared several sample solutions with a concentration of 4 mg/ml, pH of each solution was brought to a desired value and measured the absorbance (turbidity) at 500 nm. Maximum absorption of solutions of the samples was observed at pH 2-5 .5.
|pH||A (λ500 nm)||pH||A (λ500 nm)|
Example 2. Conjugate GC content of residues of novocaine 35 mol%. is obtained analogously to Example 1, but the ratio of chemicals VOC:novocaine:t:CBI=1:1.5:1.5:1.5.
|pH||A (λ500 nm)||PH||A (λ500 nm)|
Example 3. Conjugate GC content of residues of novocaine 50 mol%. is obtained analogously to Example 1, but the ratio of chemicals VOC:novocaine:t:CBI=1:1:2:2.
|pH||A (λ500 nm)||pH||A (λ500 nm)|
As can be seen from the results (table 1-3), increasing the degree of substitution of carboxyl groups of the polysaccharide on the remains of novocaine from 20% to 50 mol%. the optical density (turbidity) of solutions of the samples proportionally increases and the maximum value is at pH 2-5 .5. At pH 6-11 absorbance value was almost unchanged.
Water-soluble conjugates Ledger with novocaine, having amphoteric properties, can be used as a biomaterial with reparative-regenerative properties in medicine, a carrier for other molecules (such as acids and bases by nature), as well as in cosmetic products.
Conjugate of hyaluronic acid with novocaine formula
where n=20-50%, m=50-80%,
having amphoteric properties.
SUBSTANCE: disclosed are versions of a method of producing cross-linked polysaccharides, involving reaction of at least one polysaccharide selected from amino-polysaccharide, amino-functionalised polysaccharide containing one or more amino groups which can be cross-linked by reducing sugar, and combinations thereof, with at least one reducing sugar. The invention also discloses polysaccharides obtained using the disclosed method, a method of producing cross-linked matrices based on polysaccharides and matrices obtained using this method. The obtained matrices may include polysaccharide matrices and composite cross-linked matrices, including polysaccharides cross-linked with proteins and/or polypeptides.
EFFECT: obtained polysaccharides have satisfactory resistance to enzymatic degradation coupled with rheological properties of the preparation for injection, obtained matrices exhibit various physical, chemical and biological properties.
29 cl, 12 dwg, 6 tbl, 11 ex
SUBSTANCE: chitosan is dissolved in an organic acid: 4-6% citric acid or 2-8% lactic acid in the relation of the ingredients chitosan: the organic acid 1:2-1:4 to prepare a forming solution. Chitosan has molecular weight 80-500 kDa. The forming solution is added with vitamin B1 in the amount of max. 0.5 wt %. The prepared forming solution is applied on a substrate in the amount of 0.2-0.25 ml/cm2 and kept to achieve a film structure. Said method is used to form the chitosan film coating having the thickness of 50-250 mcm and the breaking elongation of 42 to 470%.
EFFECT: group of inventions allows preparing high-elastic chitosan citrate or lactate films possessing bactericidal action.
2 cl, 1 tbl, 13 ex
SUBSTANCE: method involves preparation of material for enzymatic hydrolysis. Alkaline hydrolysis is carried out with proteolytic enzyme preparations with neutralisation of the obtained solution to pH=7. A salt is added to the obtained enzymatic hydrolysate to a value of not less than 0.1 mol/l. Successive ultrafiltration is carried out, first on a membrane with maximum retention of 50 kD with separation of high-molecular weight impurities, and then on a membrane with maximum retention of 5 kD with separation of low-molecular weight substances. The chondroitin sulphate solution retained at the membrane is washed on the same membrane with distilled water until complete removal of salts. Final washing with distilled water is carried out on a membrane with maxim retention of 50 kD.
EFFECT: invention enables to obtain a chondroitin sulphate preparation with weight ratio of the basic substance.
SUBSTANCE: method involves activation of hyaluronic acid using a cross-linking agent and an auxiliary cross-linking agent. The activated hyaluronic acid then reacts with a nucleophilic cross-linking agent. The pH of the reaction medium ranges from 8 to 12. The nucleophilic cross-linking agent contains at least 50 wt % oligopeptide or polypeptide. Further, pH of the reaction medium is regulated to 5-7 and cross-linked hyaluronic acid is precipitated in the organic solvent. The invention also relates to use of the cross-linked hyaluronic acid obtained using this method in plastic surgery to make implants and to a hedrogel containing said cross-linked hyaluronic acid in a buffer aqueous solvent.
EFFECT: invention enables to obtain cross-linked hyaluronic acid in dry form, having high resistance to decomposition factors such as temperature, free radicals and enzymes.
18 cl, 3 tbl, 3 ex
SUBSTANCE: disclosed is a method of determining antibacterial properties of chitosan by estimating its minimum bacteriostatic and/or bactericidal concentration. Complex buffer solutions based on three organic acids MES, ACES and TES with different pH values are prepared. The ready buffer solutions are poured into a vessel. Double dilutions of chitosan are then prepared in vessels with the buffer solutions. Aliquots of a bacterial suspension in a fluid medium are added to the chitosan solutions in the buffer. The solutions are incubated for 24 hours at temperature which is optimum for bacterial growth. The minimum bacteriostatic and/or minimum bactericidal concentration of chitosan is then determined after incubation by determining growth of the culture or a drop in the number of living cells, respectively.
EFFECT: invention enables to determine antibacterial properties of chitosan in a wide pH range from 5,50 to 8,00 without the need to use buffers of different chemical composition.
5 dwg, 2 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to a method for preparing sodium salt of hyaluronic acid modified by boron compounds with no fluid medium added. The method consists in the fact that powdered sodium salt of hyaluronic acid together with a modifying agent and mixed modifying agents is pre-homogenised in a mixer at temperature ranging within 20° to 50°C; thereafter the prepared homogenous powder mixture is simultaneously exposed to pressure and shearing deformation in a mechanochemical reactor at temperature ranging within 20° to 50°C and pressure 5-1000 MPa.
EFFECT: invention provides preparing boron-containing sodium salt of hyaluronic acid applied in boron neutron capture therapy in one-stage process parameters with no fluid medium added which requires low power, labour and water consumptions.
13 cl, 15 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to medicine, more specifically to producing chitosan oligomers possessing biological activity and applicable in food industry and medicine. In a method for producing chitosan oligomers, a chitosan solution is taken in the concentration of 0.025-0.075% (weight/volume) and exposed to low-frequency ultrasound of the intensity of 92-460 Wt/cm2 for 5-30 minutes.
EFFECT: reduction in price of the chitosan oligomers production combined with promotion of higher medium viscosity molecular weight of the product within the range 25 ÷ 120 kDa.
3 tbl, 3 ex
SUBSTANCE: method involves preliminary acetylation of chitin with acetic anhydride, washing and drying the acetylated chitin in order to reduce degree of deacetylation thereof and, as a result, increase output of the desired product - D(+)-glucosamine hydrochloride when obtaining said product through hydrolysis of acetylated chitin with concentrated hydrochloric acid while heating, followed by evaporation, crystallisation, separation, washing and drying the desired product.
EFFECT: high output of the desired product while maintaining its high quality; method is more environmentally friendly since pre-treatment of chitin reduces the amount of processing wastes.
1 cl, 2 ex
SUBSTANCE: method of producing chitosan chromate involves reaction of soluble chitosan salts with metal chromates in ratio of 2 moles of the chitosan cation to 1 mole of chromate anion or with metal bichromates in ratio of 4 moles of the chitosan cation to 1 mole of the bichromate anion. The solid chitosan chromate residue formed is then separated and dried at temperature not higher than 150°C. The invention discloses an energy-intensive composition based on chitosan dodecahydro-closo-dodecaborate containing an effective amount of chitosan chromate. The quantitative ratio in the energy-intensive composition is by the required combustion mode: the higher the content of chitosan chromate, the higher the activity of the composition.
EFFECT: invention enables to obtain a chemical compound having sufficiently high oxidative properties and suitable for use in energy-intensive compositions which burn without emitting harmful gaseous products.
3 cl, 5 ex
SUBSTANCE: method involves taking a certain weighed amount of chitosanium chromate which is first purified from extraneous impurities and reduced to constant weight. The weighed amount is then turned into a stable weighted form through thermal treatment on air at temperature 800-900°C to form chromium oxide Cr2O3. The weight of the formed chromium oxide is then determined. Content of chromic acid in the initial weighed amount of chitosanium chromate is then calculated from the weight of chromium oxide. The degree of deacetylation of chitosan is calculated using defined formulae.
EFFECT: invention enables to increase accuracy of determining degree of deacetylation of chitosan.
FIELD: medicine, pharmaceutics.
SUBSTANCE: present invention refers to medicine, namely to a pharmaceutical composition for local application. The composition contains chondroitin sulphate, hyaluronidase, glucosamine hydrochloride, liposome and pharmaceutically acceptable carriers and excipients in the amounts specified in the patent claim. The composition may additionally contain capsaicin.
EFFECT: pharmaceutical composition according to the invention is characterised by fast skin penetration of the ingredients.
3 cl, 4 ex
SUBSTANCE: invention refers to medicine, namely traumatology, orthopaedics and rehabilitation, and may be used for treating inflammatory-degenerative arthropathies. The therapy is three-staged. The first stage involves at least one course of the integrated therapy aiming at inflammatory response suppression and pain syndrome arrest. The second stage involves at least one session of focused extracorporeal shock wave therapy to create microcavities buried in a interarticular cartilage. At the third stage, the created microcavities buried in the interarticular cartilage are filled with a modelling compound by interarticular electrophoresis followed by stabilising the modelling compound. The modelling compound is represented by a mixture of 15 portions of fine biopolymer gel, 65 portions of hyaluronic acid, 15 portions of animal's articular cartilage extracts and 5 portions of Dimexidum solution. The modelling compound is stabilised by non-invasive exposure to pulse high-power IR laser at wave length 785 nm and heated to 44 Celsius degree.
EFFECT: method provides high clinical effectiveness to be implemented in outpatient care that enables avoiding a surgical intervention, including joint replacement, and ensuring complete removal ensured by possibility of recovery of shape, volume and normal consistence of the interarticular cartilage.
SUBSTANCE: invention relates to medicine, in particular to ophthalmology, and deals with treatment of "dry eye" syndrome. Method includes obturation of respective lachrymal duct. For this purpose into lower lachrymal duct on 1/3-1/2 of its depth introduced is medication based on stabilised hyaluronic acid in dose 0.2-0.4 ml. Introduction can be performed by means of syringe, provided with metal blunt pointed cannula with internal diameter 1 m, 1 cm long, curved in the middle at 45 degrees. As medication based on hyaluronic acid, mainly Restilane (Restilane Sab-Q) is used.
EFFECT: method makes it possible to obdurate lachrymal ducts in efficient, dosed and atraumatic way with simplification and price reduction of treatment.
3 cl, 2 ex
SUBSTANCE: what is offered is using hyaluronidase immobilised by electron-beam synthesis as an anti-inflammatory agent.
EFFECT: invention enables extending the indications for using hyaluronidase immobilised by electron-beam synthesis.
SUBSTANCE: invention refers to medicine, namely physiotherapy, and may be used for laserophoresis of biologically active substances of higher molecular weight. What is used is a low-intensity laser emission (LILE) by alternating various wave lengths and power densities every second day. At wave length 632-638 nm, power density makes 10-40 mWt/cm2. At wave length 780-785 nm, power density makes 20-90 mWt/cm2. Length of the exposure on one area makes 0.5-1 minute. Length of one session does not exceed 15 minutes.
EFFECT: implementing the method provides higher volumes of the substance of higher molecular weight introduced by laserophoresis in treating various dermatological diseases and eliminating cosmetic defects ensure by more optimal distribution of the introduced substance in biotissues.
3 cl, 3 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to pharmacology, and represents a sterile injectable water-based composition in the form of gel for iintra-articular injection containing hyaluronic acid of molecular weight 0.1 to 10×106 Da in the amount of 1-100 mg/ml of water or one of its salts and optionally one or more other natural polysaccharides specified in a group consisting of chondroitin sulphate, keratan, keratan sulphate, heparin, heparan sulphate, cellulose and its derivatives, chitosan, xanthan, alginate and their salts, and also one or more polyalcohols in the amount of 0.0001-100 mg/ml of water, prepared by making a water-based formulation containing hyaluronic acid or one of its salts, optionally one or more other natural polysaccharides, and also one or more polyalcohols, sterilising it with wet steam; the prepared gel shows a coincidence frequency of the elasticity modulus G' and the viscosity modulus G" within the range 0 to 10 Hz preferentially 0.41 Hz ±0.41 Hz with G" exceeding G' if the coincidence frequency is found to be high.
EFFECT: invention provides higher degradation resistance of the gel, and also makes the gel visco-elastic.
11 cl, 8 ex, 11 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions refers to pharmaceutics, more specifically to a pharmaceutical product of hyaluronic acid for damages of epithelium and connecting tissue. The pharmaceutical product contains 0.001 % to less than 100 %, at least one physiologically acceptable hyaluronic acid salt having viscosity to equal 0 (zero) mPa·s in the concentration equal to 1 weight/volume in water at 20°C and less 10 mPa·s in the concentration equal to 6 weight/volume % in water at 20°C. What is also presented is using physiologically acceptable hyaluronic acid salt having specified viscosity values for preparing the given pharmaceutical product.
EFFECT: group of inventions provides improved therapeutic efficacy of the pharmaceutical product ensued by using hyaluronic acid salts having very low viscosity and thereby having no effect on the rheological characteristic of the product.
4 cl, 5 ex
SUBSTANCE: invention relates to medicine, particularly to ophthalmology. An ophthalmic device comprises a polymer matrix which in turn contains a biologically active agent and a carrier. The ophthalmic device is applicable for release of the biologically active agent induced by one or more amounts of lachrymal components from the polymer matrix in contact with tears in an eye. A method for making the ophthalmic device involves mixing a matrix-forming substance, the carrier and the biologically active agent, introducing a mixture into a cast for making the device and polymerising the matrix-forming substance in the cast. A method for biologically active agent delivery to a subject involves subject's eye contact with the device wherein one or more amounts of the lachrymal components release the biologically active agent from the device.
EFFECT: invention provides the stable ophthalmic device which is effective to deliver the biologically active agents into patient's eyes for long periods of time.
19 cl, 4 dwg
FIELD: medicine, pharmaceutics.
SUBSTANCE: group of inventions refers to medicine, particularly to ophthalmology. An aqueous liquid ophthalmic composition contains hyaluronic acid in the concentration of 0.05-0.4% or its pharmaceutically acceptable salt, and additionally contains gluconic acid and its salt with a metal, but does not contain chlorhexidine or its salt. A method for improving the viscosity stability of the aqueous eye-drop ophthalmic composition containing hyaluronic acid is conditioned by introducing gluconic acid and its salt with the metal.
EFFECT: invention provides slowed-down viscosity reduction of the aqueous ophthalmic composition.
6 cl, 6 tbl, 6 ex
FIELD: medicine, pharmaceutics.
SUBSTANCE: invention refers to preparing a pharmaceutical composition in the form of a suspension for preventing and treating disturbed physiological and reparative regeneration of locomotor tissues - bone tissue and articular cartilage. Pharmaceutical compositions stimulating supporting tissue and articular cartilage regeneration contain the substance Micellate of calcium carbonate and magnesium carbonate. The studies have proved that the offered pharmaceutical compositions showed manifested reparative-regenerative action and caused no manifested general toxic action in various doses and routes of administration in experimental animals.
EFFECT: composition has no irritant action; sensibilising action is not observed; pharmaceutical compositions are effective agents for preventing and treating disturbed physiological and reparative regeneration of locomotor tissues - bone tissue and articular cartilage.
2 cl, 2 ex, 1 tbl, 3 dwg
FIELD: medicine, surgery.
SUBSTANCE: one should apply a hemostatic film onto damaged spleen, moreover, as hemostatic material one should apply hyaluronic acid-based film (HA) being chemically associated with 5-aminosalicylic acid and impregnated with ferrum of the following total structural formula:
. Moreover, substitution degree of carboxylic groups with 5-aminosalicylic acid corresponds to 30-50% M. The innovation provides stimulation of fibroblastic activity and accelerated formation of granulations.
EFFECT: higher efficiency of therapy.