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Application of holothuria atra glycosaminoglcan in preparation of medicine for preventing and treating thromboembolism disease

A technology of glycosaminoglycan and thromboembolism, which is applied in the application field of black sea cucumber glycosaminoglycan in the preparation of drugs for the prevention and treatment of thromboembolism, can solve problems that have not been reported, and achieve high safety and good development and research value Effect

Inactive Publication Date: 2014-11-19
SHANGHAI KAIRUN BIOLOGY MEDICINE LIMITED LIABILITY +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] Sea cucumber glycosaminoglycans have significant biological activities such as anticoagulant, antiplatelet aggregation, reducing blood viscosity, fibrinolysis, and regulating blood lipids, and can be used to treat thromboembolic diseases. Experimental studies have found that different molecular weight segments of sea cucumber glycosaminoglycans have activities Further experiments found that the activity of glycosaminoglycans in black sea cucumbers was higher than that reported so far, but there is no research on the anticoagulant activities of glycosaminoglycans and depolymerized glycosaminoglycans in black sea cucumbers. See the literature reports, especially for the anticoagulant activity of the natural molecular fragment samples of black sea cucumber and the degradation products injected subcutaneously.

Method used

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  • Application of holothuria atra glycosaminoglcan in preparation of medicine for preventing and treating thromboembolism disease
  • Application of holothuria atra glycosaminoglcan in preparation of medicine for preventing and treating thromboembolism disease
  • Application of holothuria atra glycosaminoglcan in preparation of medicine for preventing and treating thromboembolism disease

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0064] Extraction of sea cucumber glycosaminoglycans:

[0065] Extraction of sea cucumber glycosaminoglycans:

[0066] Weigh 0.5 kg of black sea cucumber medicinal material and soak in water for 16 hours. Drain the water from the body wall of the sea cucumber, mince it, weigh it and add water to 4kg, put it in a water bath at 60°C, add 6mol / L sodium hydroxide to adjust the pH to 8.2±0.2, add 20ml of protease Alcalase (Novozymes (Shenyang) Biotechnology Co., Ltd.) stirring, enzymatic hydrolysis for 4 hours, inactivation at 85°C for 10 minutes, and cooling. Centrifuge at 5°C, collect the supernatant, add 6mol / L hydrochloric acid to adjust the pH to 2.5±0.2, refrigerate at 4°C for 2 hours, centrifuge, collect the supernatant, add 6mol / L sodium hydroxide to adjust the pH to 7.5±0.2, add 0.8 Double the volume of ethanol, let stand at 4°C for 12h.

[0067] Centrifuge, collect the precipitate and weigh it, add 10 times the weight of distilled water, heat to 85°C±2°C, after it is c...

Embodiment 2

[0074] Preparation of Depolymerized Sea Cucumber Glycosaminoglycans

Embodiment 2-1

[0076] The pure sea cucumber glycosaminoglycan in Example 1 above was prepared into a 5% solution with 5% acetic acid, 30% hydrogen peroxide was added to make the concentration of hydrogen peroxide in the solution 3%, and controlled depolymerization was carried out at 40°C for 42 hours. The solution was neutralized to neutral with 0.1 mol / l sodium hydroxide, 3 times the volume of absolute ethanol was added for alcohol precipitation, left to stand, and centrifuged to obtain a crude product of depolymerized sea cucumber glycosaminoglycan.

[0077] The crude product is dried, dissolved in 5 times the weight of water, passed through a sephadex-G75 column, and eluted with 0.5 mol / l sodium chloride to remove salt and small molecular impurities, and freeze-dry the desalted sample to obtain 55 g of depolymerized sea cucumber Glycosaminoglycans have a molecular weight of 20,000Da to 22,000Da, a D value of <1.5, and a purity of more than 98%.

[0078] The depolymerized sea cucumber glyc...

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Abstract

The present invention discloses the use of black sea cucumber glycosaminoglycan in preparing medicine for the prevention and treatment of thromboembolic disease. animal testing has shown that for a weight average molecular weight exceeding 20,000Da of black sea cucumber depolymerized sea cucumber glycosaminoglycan or of one or more segments of natural molecular segments of black sea cucumber sea cucumber glucosaminoglycan, the anti-coagulant activity thereof shows dose-dependency; in contrast to heparin and low molecular weight heparin, the dose-dependency thereof increases the incremental easing of blood coagulation, and, with an identical dose size, as weight average molecular weight increases, the onset time is delayed while the duration of efficacy is increased. For certain dosages, natural molecular segment sea cucumber glycosaminoglycan can have a duration of efficacy of up to 16 hours. The present invention has a higher level of safety when compared with heparin-type drugs and vitamin K antagonist-type drugs. In clinical use, the present invention has a wide treatment window for thromboembolic disease, has a high level of safety, and has good research and development value.

Description

technical field [0001] The present invention relates to the medical use of sea cucumber glycosaminoglycans of black sea cucumbers, in particular to the use of depolymerized sea cucumber glycosaminoglycans with a weight average molecular weight greater than 20,000 Da or sea cucumber glycosaminoglycans of natural molecular segments in the preparation of drugs for thromboembolic diseases Thromboembolic diseases include atherosclerotic thromboembolic diseases, venous thromboembolic diseases, blood hypercoagulability, and prevention of postoperative thrombosis or treatment of postoperative thrombosis. Background technique [0002] The blood viscosity of middle-aged and elderly people gradually increases, and the possibility of platelet aggregation leading to thrombus (such as coronary artery and cerebral artery) increases. Thromboembolic disease has become a common disease that seriously threatens the health of human beings, especially middle-aged and elderly people. . Thrombosi...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/726A61P7/02A61P9/10
CPCA61K9/0019A61K9/19A61K31/726A61K35/616A61P7/02A61P9/10
Inventor 王志国刘全海董玉琼
Owner SHANGHAI KAIRUN BIOLOGY MEDICINE LIMITED LIABILITY
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