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Drug compastion with thrombolysis, anti-inflammatory and cell protective function

A technology of water-soluble polymers and compositions, applied in the field of blood fibrin and medicine

Inactive Publication Date: 2004-08-04
SCI FUTURE MANAGEMENT SFM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Compounds containing non-toxic thrombolytics and substances with hemorheological correction functions for comprehensive treatment of ischemic heart disease, hypertension, and rheumatoid diseases have not been successfully synthesized so far

Method used

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  • Drug compastion with thrombolysis, anti-inflammatory and cell protective function
  • Drug compastion with thrombolysis, anti-inflammatory and cell protective function
  • Drug compastion with thrombolysis, anti-inflammatory and cell protective function

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Prepare the pharmaceutical composition of the present invention by the following method

[0039] The method for preparing the reaction mixture is to dissolve protosubtilin (protosubtilin) ​​in 0.025M sodium phosphate buffer solution (its pH value is 7.5-8.2) in a dextran (molecular weight is 40-70kDa, preferably 40kDa) solution, Preference is given to prosubtilisin G3Kh and polyethylene oxide (PEO) (with a molecular mass of 400-20000 Da, preferably 1500 Da). The resulting mixture was purified by removal of inert and useless proteins by salt precipitation followed by filtration. The resulting solution was irradiated with γ-rays or accelerated electron beams (energy 2.0 MeV) at a dose of 0.5-1.5 Mrad. After irradiation the solution was sterile filtered and dispensed in 10 ml portions into vials with a capacity of 15 ml each. Then the solution was dried by lyophilization until the residual moisture was not more than 2%.

[0040] The result was a composition containing a...

Embodiment 2

[0043] The composition of the present invention can be prepared by another method, that is, to prepare respectively the active component (the first component) containing the protease complex immobilized on polyoxyethylene and dextran and the solvent—polyoxyethylene solution ( Component 2). By changing the ratio of active component / solvent, the two components of the composition can change the activity of the pharmaceutical composition of the present invention, so that various individual treatment schemes can be selected.

[0044] Adopt following way to prepare above-mentioned two-component composition:

[0045] Component 1 (active substance)

[0046] The reaction mixture was prepared by dissolving prosubtilin (preferably prosubtilin) ​​in 0.025 M sodium phosphate buffer solution (pH 7.5-8.2) of dextran (molecular weight 40-70 kDa, preferably 40 kDa) G3Kh) and polyethylene oxide (PEO) with a molecular weight of 400-20000 Da (preferably 1500 Da). The resulting mixture is purifi...

Embodiment 3

[0054] 15g polyoxyethylene PE0-1500 is dissolved in the 0.025M phosphate buffer (pH is 7.5) solution of the dextran of 300ml 10%, the molecular weight of dextran is 40kDa, adds 6.3g prosubtilin G3Kh, at 18 -20°C, the mixture was stirred for 30 minutes. Salt precipitation is then used to precipitate inert and useless proteins. To this end, 1.3 g of Sodium phosphate disubstituted were sequentially added to the mixture to dissolve completely and to a final concentration of 0.45% and 1.9 g of calcium chloride to a final concentration of 0.63%. After calcium chloride is dissolved in the reaction mixture, an insoluble calcium phosphate precipitate settles out, which adsorbs inert and useless proteins. The mixture was kept at 4-8°C for 12 hours to completely precipitate inert and useless proteins. The reaction mixture was then filtered through filter paper (white band). The filtrate volume was 300ml. The resulting solution was irradiated with gamma rays at a dose of 1.0 Mard. Af...

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PUM

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Abstract

A pharmaceutical composition having thrombolytic, anti-inflammatory and cytoprotective properties is described. The composition contains active proteases attached to a gel or to a mixture of a gel with a water-soluble polymer, said attachment being achieved with the help of radiation, preferably with the help of gamma-radiation or a flow of accelerated electrons. As the proteases the composition contains proteases which are stable at a temperature of up to 70 DEG C, preferably at 30-40 DEG C, for instance such as subtilysine, trypsin, chemotrypsin, papain or streptokinase. The gel is preferably polyethylene glycol gel, dextran gel, or polyglycane gel, and the water-soluble polymer is polyethylene glycol, polyvinyl alcohol, dextran or polyglycane. The method of preparing said composition and its use are also disclosed. <??>Advantages: the claimed composition is noted for a broad range of application and can be used in cardiology, nephrology, surgery, rheumatology, gynecology and gastroenterology.

Description

technical field [0001] The present invention relates to the field of medicine, in particular to pharmacology and agents based on enzyme preparations, which may be used for comprehensive treatment of ischemic heart disease, ischemic stroke, rheumatoid disease and other diseases associated with local ischemia, Diseases such as thrombosis and nonspecific inflammation. [0002] The invention encompasses the field of enzymatic hydrolysis of thrombus-forming proteins, mainly fibrin, which is the structure-forming protein of all thrombus, and is independent of the position and size of the peptides. The present invention more particularly relates to compounds containing proteolytic enzymes immobilized (attached) to hydrophilic water-soluble polymers and having fibrin-dissolving properties. The present invention also relates to methods of fibrinolytic therapy using the above-mentioned compounds in the treatment of acute myocardial infarction and ischemic stroke, as well as to the trea...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K9/00A61K9/06A61K38/48A61K41/00A61K47/02A61K47/26A61K47/32A61K47/48A61P7/02A61P9/10A61P17/02C12N11/00C12N11/08
CPCA61K9/0019A61K47/48784A61K47/32A61K38/482A61K47/02A61K47/26A61K9/06A61K41/00C12N11/08A61K47/6903A61P17/02A61P29/00A61P37/02A61P7/02A61P9/10C12N11/089
Inventor A·V·阿塔默诺夫E·I·维利思查津O·V·格里施因A·V·特罗伊特斯基
Owner SCI FUTURE MANAGEMENT SFM
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