A kind of production method of nadroparin calcium

A production method and heparin calcium technology, applied in the field of biomedicine, can solve the problems of poor product stability, uncontrollable product yield of raw materials, etc., and achieve the effects of improving product yield, shortening preparation cycle, and reducing cost input.

Active Publication Date: 2015-08-26
山东辰龙药业有限公司
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  • Abstract
  • Description
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  • Application Information

AI Technical Summary

Problems solved by technology

This method overcomes the defects of uncontrollable raw materials, low product yield and poor product stability in the traditional process

Method used

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  • A kind of production method of nadroparin calcium
  • A kind of production method of nadroparin calcium

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Experimental program
Comparison scheme
Effect test

preparation Embodiment 1

[0034] Specific steps:

[0035]a) Enzymolysis: Take 1000g of crude heparin sodium, add 10kg of water to dissolve it, adjust the pH value of the feed solution to 8.2 with 20% (w / v) calcium hydroxide solution, adjust the temperature of the feed solution to 37°C, and add papaya respectively 7g of protease and 4g of ribonuclease II were stirred and reacted for 10 hours, centrifuged to remove the precipitate, and the supernatant was filtered with a plate and frame filter to collect 10 L of filtrate. ;

[0036] b) Oxidation: Control the temperature of the filtrate obtained in step a) to 37° C., adjust the pH value of the filtrate to 10.1 with 20% (w / v) calcium hydroxide solution, add 30 ml of hydrogen peroxide, and stir and react at room temperature for 8 hours to obtain a purified solution;

[0037] c) Ultrafiltration to remove impurities: adjust the purified solution obtained in step b to pH 7.2 with 4 mol / L hydrochloric acid, then perform tangential flow ultrafiltration, and sel...

preparation Embodiment 2

[0048] Specific steps:

[0049] a) Enzymolysis: Take 1000g of crude heparin sodium, add 11kg of water to dissolve it, adjust the pH value of the feed solution to 8.3 with 20% (w / v) calcium hydroxide solution, adjust the temperature of the feed solution to 38°C, and add papaya respectively 6g of protease and 5g of ribonuclease II were stirred and reacted for 10 hours, centrifuged to remove the precipitate, and the supernatant was filtered with a plate and frame filter to collect 11 L of filtrate. ;

[0050] b) Oxidation: Control the temperature of the filtrate obtained in step a) to 39° C., adjust the pH value of the filtrate to 9.5 with 20% (w / v) calcium hydroxide solution, add 35 ml of hydrogen peroxide, and stir and react at room temperature for 7 hours to obtain a purified solution;

[0051] c) Ultrafiltration to remove impurities: adjust the pH of the purified solution obtained in step b to 6.8 with 4 mol / L hydrochloric acid, then perform tangential flow ultrafiltration, ...

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Abstract

The invention discloses a production method of nadroparin calcium and belongs to the field of biomedicine. According to the method, crude heparin sodium is taken as raw material. Basing on enzymolysis and improved nitrite degradation method, nadroparin calcium high-quality product with particular average molecular weight (3800 to 5000Da) is prepared by enzymolysis, oxidative decolorization, ultrafiltration and impurity removal, ethanol precipitation and impurity removal, degradation, reduction, ultraviolet radiation, oxidation, Calcium replacement, nanofiltration, Ultrafiltration and refining, freeze-drying and other steps. The method provided by the invention has advantages of simple preparation technology, high bioavailability of the product, long half life in vivo, small hemorrhagic tendency and the like.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a method for producing Nadroparin calcium (Nadroparin). Background technique [0002] Heparin (unfractionated heparin) is a highly sulfated glycosaminoglycan that has anticoagulant effects both in vivo and in vitro. However, unfractionated heparin has defects such as low bioavailability, large side effects, and frequent administration, and its replacement product, low-molecular-weight heparin such as nadroparin calcium, not only has better antithrombotic effect than unfractionated heparin, but also has high bioavailability, long half-life in vivo, Small bleeding tendency and other advantages. The anticoagulant activity of heparin is divided into two categories: antithrombotic activity (FXa) and anticoagulant (FIIa) activity. In the process of antithrombosis, both anti-FXa activity and anti-FIIa activity are necessary. The measuring standard of FXa / FIIa is expressed by the value of an...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08B37/10
Inventor 周霞雷晓刚乔德强郭维林勇郭恩中
Owner 山东辰龙药业有限公司
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