The way prolonged physiological effect of timolol to lower the intraocular pressure
(57) Abstract:The invention relates to the field of medicine, particularly, to a method of prolonging therapeutic effect of timolol drug belonging to the group nekardioselektivnym beta - blockers used to reduce intraocular pressure and treating glaucoma. The invention solves the problem of reducing the dose of timolol and prolongation of its ability to reduce intraocular pressure, this result is achieved in a method of prolonging therapeutic effect of timolol, including the use of timolol in combination with compounds that enhance its ability to reduce intraocular pressure, as compounds that enhance a specific effect of timolol, use hyaluronic acid, with timolol and hyaluronic acid take in a mass ratio of 1:2-4, and the concentration of the solution containing this combination is 0.01 to 0.05%. table 1. The way prolonged physiological effect of timolol to lower the intraocular pressure.The invention relates to the field of medicine particularly, to a method of prolonging therapeutic effect of timolol drug belonging to the group of nocardiosis>/P>It is known the use of timolol in the treatment of chronic open-angle glaucoma /2,3/. However, this drug, which is a chemical structure of (-)-1-(tert. -butylamino)-3-(4 - morpholino-1,2,5-thiadiazol-3-oxy)-2-propanol,
< / BR>itself slightly decreases the intraocular pressure elevated intraocular pressure and this effect is seen only for 1-2 hoursIn this regard, attempts were made to enhance and prolong the action of timolol by using it in combination with various miotikami (pilocarpine), agonists and carbonic anhydrase inhibitors (e.g., diakarbom) /4/. However, such combinations include the use of sufficiently high doses of ingredients that allows you to cause bronchospasm and other side effects /5/, and the duration of their therapeutic effect does not exceed 2-4 PMClosest to the claimed adopted for the prototype, is a method of prolonging therapeutic effect of timolol /6/ based on the purpose of various dosage forms containing a combination of 0.5-20 wt.h. timolol n-1 wt.h. 13,14-dihydro-15-keto-prostaglandins.The disadvantages of this method are associated with nemennym (not more than 5-6 h) decrease intra-ocular pressure.The invention solves the problem of reducing the dose of timolol and prolongation of its ability to reduce intraocular pressure.This result is achieved in a method of prolonging therapeutic effect of timolol, including the use of timolol in combination with compounds that enhance its ability to reduce intraocular pressure, as compounds that enhance specific pressure timolol use hyaluronic acid, with timolol and hyaluronic acid take in a mass ratio of 1:2 to 4, and the concentration of the solution containing this combination is 0,01-0,05%
The inventive method has advantages over known in part to the fact that the duration of intraocular pressure reduction with the introduction of the combination of timolol and hyaluronic acid (used the drug timolol company "Sigma", USA and domestic hyaluronic acid on THE 9185-00317204830-93) is 24-48 h after a single instillation in the eye. To achieve this effect, use 1-2 drops of 0.01 to 0.05% solution, i.e., 0.005 - 0.01 g of the drug per reception, while used in the known method dose of timolol 0.05-10 mg, i.e., are 10-100 times higher.The invention is illustrated by the following examples of its implementation.1. A mixture of 1 g (1 wt.h.) of timolol and 2 g of hyaluronic acid (2 wt.h.) dissolve in a small amount of water, the solution is filtered through a sterile filter paper and diluted under aseptic conditions with sterile water to a 0.01% solution (about 30L of water, which is poured into the tube-dropper 10 ml Instillation into the eyes of 1-2 drops of this solution leads to a sustainable reduction of intraocular pressure in 24-48 hours2. A mixture of 1 g (1 wt.h.) timolol 3 g hyaluronic acid (3 wt.h.) dissolve in a small amount of water and then proceed as in example 1 to obtain of 0.025% solution (about 16 liters of water), which has a similar effect.3. A mixture of 1 g of timolol (1 wt.h.) and 4 g of hyaluronan acid (4 wt.h.) dissolve in a small amount of water and then proceed as in example 1 to obtain a 0.05% aqueous solution (about 10 l of water), which has a similar effect.Comparative analysis of technical and economic indicators of the well-known SP is th dose of timolol compared with the known method and significant (5-10 times) prolongation of its ability to reduce intraocular pressure. The way prolonged physiological effect of timolol to lower the intraocular pressure, which consists in adding to the aqueous solution of timolol excipients, characterized in that as an auxiliary substance use hyaluronic acid, which is taken at the rate of 2 to 4 wt. including acid 1 wt.h. timolol, and the process is continued until reaching the concentration of the solution calculated for both components 0,01 0,05%
where R1group cyclic amide, such as 2H-3,4-dihydro-1,3-benzoxazin-2-she, 2H-3,4-dihydro-1,3-benzoxazin-2,4-dione, and 1,2,3,4-tetrahydroquinazoline-2,4-dione, and 1,2,3,4-tetrahydroquinazolin-2-it, 1,2,3,4-tetrahydropyrido(3,2-d)-pyrimidine-2,4 - dione, and 1,2,3,4-tetrahydropyrido(3,2-d)pyrimidine-2-it, 1,2,3,4-tetrahydropyrimidine-2,4-dione, pyrrolidin-2-it, 1,2,3,4 - tetrahydropyridine-2-it, 5H-6,7,8,9-tetrahydropyrido(3,2-b)azepin-6-she N-5,6,7,8-tetrahydropyrido(2,3-b)azepin - 8-she, 2H-3,4-dihydropyrido(2,3-e)-1, 3-oxazin-2-thione or 2-she pyrrolidine (3,4-b)-pyrazin-5-she 1H-2,3,4,5-tetrahydrothieno(2,3-b)indol-2-it, 8H-4,5,6,7-tetrahydrothieno(2,3-b)thiophene-7-she 4H-pyrazolo(5,4-f)benzazepin-9-it, isoindoline-1,3-dione, benzoxazolyl-2-it, unsubstituted or substituted lower alkyl, lower alkoxy, halogen, the nitro-group, carboxy, benzoyl or benzyl, n is zero or an integer from 1 to 6, Z is a group of formula (A) or (B):
N-(CH2)mR2(A) or -(CH2)p, dioxolane, furan, tetrahydrofuran, methylfuran or thiophene, m is an integer from 1 to 3; R3is lower alkyl; R4is phenyl or a radical of dioxolane, furan or thiophene, p = 1, provided that when R1radical 1,2,3,4-tetrahydrobenzo-2-or 1,2,3,4-tetrahydroquinazoline-2,4-dione, R2and R4are not phenyl or substituted by a halogen phenyl, or their pharmacologically acceptable salts with antiacetylcholinesterase activity
FIELD: organic chemistry, biochemistry.
SUBSTANCE: invention relates to epothilones with modified thiazole substituent, methods for production thereof and pharmaceutical composition capable of cell growth inhibiting containing the same. Claimed compounds have general formula I , wherein P-Q represents double carbon bond or epoxy; R represents H, C1-C6-alkyl; G represents ; R1 represents and ; G1 and G2 represent hydrogen; G3 represents O, S, and NZ1; G4 represents H, optionally substituted C1-C6-alkyl, OZ2, Z2C=O and Z4SO2; G5 represents halogen, N3, CN, NC, heteroaryl containing nitrogen or oxygen, and heterocycle; G6 represents H, C1-C6-alkyl, or OZ5, wherein Z5 represents H, C1-C6-alkyl; G9 represents oxygen; Z1 represents H, optionally substituted C1-C6-alkyl, optionally substituted acyl; Z2 represents optionally substituted C1-C6-alkyl or aryl; Z4 represents optionally substituted aryl.
EFFECT: new epothilones capable of cell growth inhibiting.
19 cl, 39 ex
FIELD: medicine, gastroenterology, pharmacy.
SUBSTANCE: invention relates to a solid composition eliciting with an anti-ulcer activity and to a method for its preparing. Pharmaceutical composition consists of a core containing famotidine as an active component and starch, aerosil, stearic acid salt as accessory inert substances wherein a core is covered by polymeric envelope. Core comprises glucose and stearic acid as an accessory inert substance and magnesium stearate as a stearic acid salt. Polymeric envelope comprises oxypropylmethylcellulose, propylene glycol, castor oil, talc and titanium dioxide taken in the definite ratio of all components in the composition. Method for preparing pharmaceutical composition involves preparing raw, mixing therapeutically effective amount of famotidine with glucose and starch, moistening the mixture with starch paste, granulation, drying wetted granulate, repeated granulation, powdering dry granules, tableting and applying polymeric envelope containing oxypropylmethylcellulose on prepared cores with addition of titanium dioxide, propylene glycol, castor oil and talc. Invention provides enhancement of degradability, solubility and stability in storing.
EFFECT: improved method for preparing, valuable pharmaceutical properties of composition.
3 cl, 1 ex
FIELD: organic chemistry, biochemistry, medicine, pharmacy.
SUBSTANCE: invention relates to methods for treatment of diseases or syndromes associated with metabolism of fatty acids and glucose and to new compounds and their pharmaceutically acceptable salts. Invention relates to applying new compounds and pharmaceutical compositions for treatment of cardiovascular diseases, diabetes mellitus, cancer diseases, acidosis and obesity by inhibition of activity of enzyme malonyl-CoA-decarboxylase. Indicated compounds correspond to formulae (I) and (II) wherein Y, C, R1, R2, R6 and R7 have values given in the invention claim.
EFFECT: valuable medicinal and biochemical properties of azoles.
27 cl, 8 tbl
FIELD: medicine, therapy, gastroenterology.
SUBSTANCE: method involves preliminary assay of the disorder type in gallbladder motor contraction and bile-excretion ways followed by prescribing thermal low-mineralized hydrocarbonate-sodium-sulfate-calcium-magnesium mineral water in the dose by 200-300 ml, 3 times per a day, 1 h before eating, tubages № 3 with mineral water, bathes and shower with mineral water every day for 10-14 days. In the hypotonic type of motor activity method involves mineral water at temperature 25-30°C, and in the hypertonic type - at temperature 38-40°C. Method provides accelerating in scars formation of ulcers and epithelization of erosions in gastroduodenal system, to prevent frequent exacerbations and to reduce activity of Chelicobacter-induced inflammation.
EFFECT: improved therapy method.
4 tbl, 2 ex
FIELD: medicine, endocrinology.
SUBSTANCE: invention relates to treatment of diabetes mellitus in mammals. Invention proposes applying inhibitors of enzyme dipeptidyl peptidase IV as an active component in manufacturing a medicinal agent, and in a method for treatment of diabetes mellitus. Invention provides enhancing the functional activity of insulin-producing cells in animal and differentiation of epithelial cells of the pancreas.
EFFECT: improved method for insulin producing and diabetes treatment.
20 cl, 5 dwg, 2 tbl, 2 ex