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Application of depolymerized holothuria glycosaminoglcan in preparing medicine for preventing and controlling thrombotic diseases

A technology for thrombotic diseases and glycosaminoglycans, which is applied in the application field of depolymerizing sea cucumber glycosaminoglycans in the preparation of drugs for the prevention and treatment of thrombotic diseases, which can solve the large individual differences in pharmacokinetics, potential safety hazards, and the risk of fatal bleeding And other issues

Inactive Publication Date: 2014-06-04
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 influence of diet, and the complex drug interactions, it is difficult to use optimal doses of warfarin in clinical practice. In addition, heparin and low molecular weight heparin drugs, Clinical use can easily lead to bleeding, and people with different constitutions need to be monitored closely
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 depolymerized holothuria glycosaminoglcan in preparing medicine for preventing and controlling thrombotic diseases
  • Application of depolymerized holothuria glycosaminoglcan in preparing medicine for preventing and controlling thrombotic diseases
  • Application of depolymerized holothuria glycosaminoglcan in preparing medicine for preventing and controlling thrombotic diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] 1. Extraction of Sea Cucumber Glycosaminoglycans

[0041] Weigh 2 kg of Yuzu sea cucumber medicinal material and soak in water overnight. Drain the water from the body wall of the sea cucumber, mince it, weigh it and add water to 18Kg, put it in a water bath at 60°C, adjust the pH to 7.8±0.2, add 60ml of protease Alcalase (Novozymes (Shenyang) Biotechnology) with 2% of the weight of the feed Co., Ltd.) stirring, enzymatic hydrolysis for 4.5 hours, inactivation above 84°C for 6 minutes, cooling to 48°C±2°C, adding sodium hydroxide to adjust the pH to 7.8±0.2, and adding 0.2-0.25% compound trypsin ( Wuxi Xuemei Enzyme Preparation Technology Co., Ltd. (Xuemei Brand) stirred for 4.5 hours, boiled for 6 minutes, and cooled. Centrifuge at 4°C, collect the supernatant, add hydrochloric acid to adjust the pH to 2.4±0.2, refrigerate at 4°C for 2.5 hours, centrifuge, collect the supernatant, add sodium hydroxide to adjust the pH to 6.8±0.2, add 0.8 times (v / v) Ethanol, stand o...

Embodiment 2

[0052] The extraction of sea cucumber glycosaminoglycans is the same as in Example 1.

[0053] The preparation method of depolymerized sea cucumber glycosaminoglycan is as follows:

[0054] Dissolve the above sea cucumber glycosaminoglycan product with 5.1% acetic acid, add hydrogen peroxide with a weight concentration of 30%, so that the weight concentration of hydrogen peroxide in the solution is 5.1%, and depolymerize at 60°C for 1 hour;

[0055] Neutralize the depolymerization solution to neutral with sodium hydroxide, add ethanol with 4 times the volume of the depolymerization solution for alcohol precipitation, let stand, centrifuge, collect the precipitate, and obtain the crude product of depolymerized sea cucumber glycosaminoglycan;

[0056] Dry the crude product, dissolve it in water with 5 times the weight of the crude product, pass it through a sephadex-G100 column, elute with 0.05mol / l sodium chloride for 5 column volumes, collect the eluate with a molecular weight...

Embodiment 3

[0060] The extraction of sea cucumber glycosaminoglycans is the same as in Example 1.

[0061] The preparation method of depolymerized sea cucumber glycosaminoglycan is as follows:

[0062] Dissolve the above sea cucumber glycosaminoglycan product with 4.9% acetic acid, add hydrogen peroxide with a weight concentration of 30%, so that the weight concentration of hydrogen peroxide in the solution is 5.3%, and depolymerize at 58°C for 45 minutes;

[0063] Neutralize the depolymerization solution to neutral with sodium hydroxide, add ethanol with 4 times the volume of the depolymerization solution for alcohol precipitation, let stand, centrifuge, collect the precipitate, and obtain the crude product of depolymerized sea cucumber glycosaminoglycan;

[0064] Dry the crude product, dissolve it in water with 5 times the weight of the crude product, pass it through a sephadex-G100 column, elute with 0.05mol / l sodium chloride for 5 column volumes, collect the eluate with a molecular we...

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Abstract

The invention discloses an application of depolymerized holothuria glycosaminoglcan in preparing a medicine for preventing and controlling thrombotic diseases. The weight-average molecular weight of the depolymerized holothuria glycosaminoglcan is 45,500-49,000Da. Animal experiments prove that a certain dosage of depolymerized holothuria glycosaminoglcan with weight-average molecular weight of 45,500-49,000Da has obvious anti-coagulation activity through hypodermic injection (3-100mg / kg). Experimental results indicate that the anti-coagulation activity of the depolymerized holothuria glycosaminoglcan is dosage-dependent; compared with heparin and low-molecular heparin, the blood coagulation effect is slowly improved along with the increase of dosage. The depolymerized holothuria glycosaminoglcan can be safely and effectively used for preventing and controlling thrombotic diseases, including the prevention and control of deep venous thrombosis and thrombophilia; the product is suitable for pregnant women suffering venous blood embolism; the depolymerized holothuria glycosaminoglcan also can be used for preventing the blood clot formation and the like in hemodialysis.

Description

technical field [0001] The invention relates to a medical application of depolymerized sea cucumber glycosaminoglycan, in particular to the application of depolymerized sea cucumber glycosaminoglycan with a weight average molecular weight of 45,500Da to 49,000Da in the preparation of drugs for preventing and treating thrombotic diseases, including the treatment of deep Venous thrombosis, and its application in the prevention of thrombosis during hemodialysis treatment and the prevention and treatment of thrombosis after surgery. Background technique [0002] The diseases caused by the two pathological processes of thrombosis and thromboembolism are clinically called thrombotic diseases. Thrombotic disease is a serious threat to human life and health, and its incidence rate ranks first among various diseases, and it has gradually increased in recent years. It is one of the focuses and hotspots of contemporary medical research. [0003] Thrombosis refers to the pathological p...

Claims

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Application Information

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IPC IPC(8): A61K31/726A61P7/02
Inventor 王志国刘全海董玉琼
Owner SHANGHAI KAIRUN BIOLOGY MEDICINE LIMITED LIABILITY
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