Method for preparing high-quality LMW (low molecular weight) heparins

A molecular weight, high-quality technology, applied in the field of biomedicine, can solve the problems of harsh reaction conditions of ultra-low molecular weight heparin, low anti-FXa factor titer, and high anti-FIIa titer, achieving no thrombocytopenia and no bleeding. , The effect of low anti-FIIa titer

Inactive Publication Date: 2012-08-15
雷晓刚
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Among them, the process of extracting ultra-low molecular weight heparin from heparin sodium by enzymatic degradation has disadvantages such as harsh reaction conditions, high cost, too many impurities, and difficult purification of the product.
However, the ultra-low molecular weight heparin prepared by the β-elimination degradation method also has problems such as low anti-FXa factor titer, high anti-FIIa potency, and a certain probability of bleeding, mainly due to insufficient sample purity and excessive impurity content. , accumulation of small molecule heparin and other factors, these are problems that cannot be solved by the current extraction process

Method used

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  • Method for preparing high-quality LMW (low molecular weight) heparins

Examples

Experimental program
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Effect test

Embodiment 1

[0021] Example 1: Weigh 1 kg of heparin sodium and 2.5 kg of benzethonium chloride salt for later use.

[0022] 1. Gradually add the weighed heparin sodium into 9 liters of distilled water until it is completely dissolved.

[0023] 2. Synthesis of heparin benzethonium chloride salt: 2.5 kg benzethonium chloride salt was added into distilled water and stirred until completely dissolved. Then add the benzethonium chloride salt solution slowly into the heparin sodium solution under stirring, continue to stir for 2 hours, then stop stirring, and let stand for a period of time. The supernatant was removed, and the remaining pellet suspension was centrifuged to collect the pellet.

[0024] 3. Pretreatment of heparin benzethonium chloride salt: add 10 L of distilled water to the precipitate obtained by centrifugation, stir, and soak for not less than 1 hour. Centrifuge at high speed, spread the sediment obtained from the final centrifugation evenly on stainless steel plates, the th...

Embodiment 2

[0038] Example 2: The difference between this example and Example 1 is that heparin sodium is 6 kg, benzethonium chloride is 15 kg, and benzyl chloride is 20 L.

[0039] Product testing results: average molecular weight is 2200 Da, molecular weight distribution: 20% of 4500 Da; anti-FXa titer: 162 IU / mg, anti-FIIa titer: 3.0 IU / mg , anti-FXa / anti-FIIa=54.

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Abstract

The invention discloses a method for preparing high-quality LMW (low molecular weight) heparins. Based on an improved beta-elimination and degradation method, through innovatively adding a heavy salinization method, a polyphosphazene alkaline hydrolysis method and a saponification method and the like, the key problems that in feed liquid, more macromolecular heparins exist, and micromolecular heparins are accumulated, and the like are solved, thereby preparing super small molecular fragments. The average molecular weight of ultralow molecular heparin sodium prepared by using the method above is 2000-3000, the molecular weight distribution of the heparin sodium is as follows: the proportion of the molecular weight less than 1600 is less than or equal to 40.0%; and the proportion of the molecular weight greater than 4500 is less than or equal to 11.0%; the rate of the resistant FXa / FIIa is greater than 30, wherein the valence of the resistant FXa is 145-180 IU / mg, and the valence of the resistant FIIa is less than 5.0 IU / mg. Compared with low molecular heparin sodium and ultralow molecular heparin sodium, the high-quality LMW heparin sodium has an extremely good antithrombotic activity, a smaller bleeding risk and a lower influence on platelets, therefore, the high-quality LMW heparin sodium is expected to be a new-generation heparin antithrombotic medicament.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a method for preparing high-quality ultra-low molecular weight heparin. Background technique [0002] Heparin (unfractionated heparin) is a highly sulfated glycosaminoglycan that has anticoagulant effects both in vivo and in vitro. It is mainly used clinically for hemodialysis, thromboembolic diseases, cardiovascular surgery, cardiac catheterization, extracorporeal circulation, etc. Its biggest side effect is to cause bleeding, and sometimes even lead to hemorrhagic death. According to statistics, the incidence of bleeding is as high as 35%. Nonetheless, it remains the drug of choice for the prevention of thrombosis, pulmonary embolism, disseminated intravascular coagulation, and certain thromboembolic complications. Although people take various methods, such as reducing the dose, local medication, etc., to reduce the risk of bleeding, they cannot fundamentally solve the problem. Th...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08B37/10A61P7/02
Inventor 雷晓刚周霞郭维
Owner 雷晓刚
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