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

A technology of glycosaminoglycans and thromboembolism, which is applied in the application field of sea cucumber glycosaminoglycans in the preparation of drugs for the prevention and treatment of thromboembolic diseases, can solve problems such as potential safety hazards, fatal bleeding risks, side effects, etc., and achieve wide window and good development Research value, high safety 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

However, while highly effective, warfarin carries a risk of serious and even fatal bleeding
In addition, due to the large individual differences in pharmacokinetics and the susceptibility to the influence of diet, and the complex drug interactions, it is difficult to use optimal doses of warfarin in clinical practice. It is easy to cause bleeding, and people with different constitutions need to use it with strong monitoring
Therefore, the anticoagulant drugs currently used clinically all have certain side effects. In view of the aging population, the increase in the incidence of thrombotic diseases, and the widespread use of existing anticoagulant drugs in the clinical prevention and treatment of thrombotic diseases and the seriousness of its security risks

Method used

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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0070] Extraction of sea cucumber glycosaminoglycans:

[0071] Weigh 4.5 kg of Yuzu sea cucumber medicinal material and soak in water for 16 hours. Drain the body wall of the sea cucumber, mince it, weigh it and add water to 36kg, put it in a water bath at 60°C, add 6mol / L sodium hydroxide to adjust the pH to 8.2±0.2, add 90ml of protease Alcalase (Novozymes (Shenyang) Biotechnology Co., Ltd.) stirring, enzymatic hydrolysis for 4 hours, inactivation above 85°C for 10 minutes, cooling to 49°C±2°C, adding 6mol / L sodium hydroxide to adjust the pH to 8.2±0.2, and then adding 9g of compound trypsin (Wuxi City Xuemei Enzyme Preparation Technology Co., Ltd., Xuemei Brand) stirred for 4 hours, boiled for 15 minutes, and cooled. 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 et...

Embodiment 2

[0079] Preparation of depolymerized sea cucumber glycosaminoglycan

Embodiment 2-1

[0081] 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 4h50min. The solution was neutralized to neutral with 0.1 mol / l sodium hydroxide, 3 times the volume of ethanol was added for alcohol precipitation, allowed to stand, and centrifuged to obtain a crude product of depolymerized sea cucumber glycosaminoglycan.

[0082] 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 54,500Da to 57,000Da, a D value of <1.5, and a purity of over 98%.

[0083] The depolymerized sea cucumber glycosaminoglyca...

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Abstract

The present invention discloses the use of sea cucumber glycosaminoglycan in preparing medicine; animal testing has shown that for a weight average molecular weight exceeding 54,500Da of depolymerized sea cucumber glycosaminoglycan or of one or more segments of natural molecular segments of 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, and can be used for preparing medicine for preventing and treating arterial thromboembolic diseases. 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, in particular to the application of depolymerized sea cucumber glycosaminoglycans with a weight average molecular weight greater than 54,500 Da or sea cucumber glycosaminoglycans with natural molecular segments in the preparation of drugs for preventing and treating thromboembolic diseases , Thromboembolic diseases include atherosclerotic thromboembolic diseases, venous thromboembolic diseases, hypercoagulable states, and postoperative thrombosis or postoperative thrombosis. Background technique [0002] With the development of society and the process of population aging, the blood vessels of the elderly are aging, the blood vessel walls are damaged, and they are prone to hypertension, arteriosclerosis, and diabetes. After the vascular endothelial cells are damaged, the production of thromboplastin increases, which promotes the formation of thrombin, and the thrombin A...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/726A61P9/10A61P7/02
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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