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A kind of preparation method of heparin sodium

A technology of heparin sodium and sodium carbonate, applied in the preparation of heparin sodium, in the field of heparin sodium, can solve the problems of heparin destruction, adverse effects of industrialized production, lack of conditions for industrialized production, etc. high effect

Active Publication Date: 2016-01-20
YANTAI DONGCHENG PHARMA GRP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, many methods for removing serine in heparin have been published at home and abroad, among which Keiichi Takagaki (2002) reported the method of removing heparin serine by using cellulase with β-endoxylosidase activity; Yu-ki Matsuno (2007) reported The β-elimination reaction under alkaline conditions removes heparin serine, but both methods have limitations, that is, they need to first separate the heparin fragment with a specific molecular weight, and then remove the serine residue of this specific heparin fragment, so they are not available. conditions for industrial production
The patent (US2008 / 0318328A1) published by Viskov et al. (2008) reported the method of removing heparin serine with potassium permanganate, but this method will inevitably cause damage to the tetrasaccharide linking region of heparin, which has adverse effects on industrial production

Method used

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  • A kind of preparation method of heparin sodium
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Effect test

Embodiment 1

[0044] (1) Impurity removal: add crude heparin sodium (potency ≥ 50IU / mg, its 0.01% (g / mL) aqueous solution has an optical absorption value ≤ 1.0 at a wavelength of 260nm) in an amount of 20% (g / mL) In purified water, warm up to 30°C and stir until completely dissolved. Then add sodium chloride in an amount of 5% (g / mL), adjust the pH of the solution to 10.0-10.5 after the sodium chloride is completely dissolved, stir at a constant temperature for 4.0 hours, then raise the temperature to 85°C, and maintain the pH of the solution at 9.5-10.0 Keep it for 10 minutes, then quickly cool the feed liquid to 15°C, let it stand for 5 hours and filter it with a clarification plate until the feed liquid is clear, and take the filtrate;

[0045] (2) Primary enzymatic hydrolysis: raise the temperature of the above feed solution to 50°C, then adjust the pH to 9.0 with 18% (g / mL) hydrochloric acid aqueous solution or 20% (g / mL) sodium hydroxide aqueous solution, and add crude heparin sodium ...

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Abstract

The invention provides a preparation method of heparin sodium. The preparation method comprises the steps of removing impurities of crude heparin sodium, carrying out primary enzymolysis by pancreatic enzyme, performing secondary enzymolysis by cellulose, cleaning under an acid condition, grading by ethyl alcohol, performing primary oxidation with hypochlorous acid, carrying out secondary oxidation with hydrogen peroxide, freezing-drying and crushing. According to the method, serine in the heparin sodium is removed, a condition that the heparin sodium is not suitable for pharmaceutical industry production in the prior art is improved, the process is simple to operate, the produced heparin has an integral structure, and the obtained product has high valence.

Description

technical field [0001] The invention belongs to the field of biochemical medicines, and relates to a preparation method of heparin sodium, in particular to a preparation method of heparin sodium including the step of removing serine in the heparin sodium and the heparin sodium prepared by the preparation method. Background technique [0002] Heparin is a linear mucopolysaccharide consisting of repeating disaccharide units linked by uronic acid and glucosamine with 1-4 glycosidic bonds. It is widely distributed in mammalian tissues and is expressed by connective tissue mast cells. Heparin, like most mucopolysaccharides, exists in the form of heparin sodium-protein complexes in animals. During the extraction process, due to the incomplete dissociation of heparin sodium, a certain amount of covalently bonded proteins and proteins remain in heparin sodium. Positively charged proteins that bind electrostatically need to be further refined before they can be used clinically. [0...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C08B37/10
Inventor 曲涛高福凯苗伟吕惠忠仰振球由守谊
Owner YANTAI DONGCHENG PHARMA GRP
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