CN101942039B

CN101942039B - Parnaparin production method

Info

Publication number: CN101942039B
Application number: CN2010102871329A
Authority: CN
Inventors: 郭林; 李�荣; 崔慧斐
Original assignee: DONGYING TIANDONG PHARMACEUTICAL Co Ltd; SHANDONG HI-TECH CHEMICAL GROUP Co Ltd
Current assignee: DONGYING TIANDONG PHARMACEUTICAL CO LTD; Shandong Haike Chemical Co ltd
Priority date: 2010-09-16
Filing date: 2010-09-16
Publication date: 2012-11-28
Anticipated expiration: 2030-09-16
Also published as: CN101942039A

Abstract

The invention relates to a preparation method of a biochemical medicament, in particular to a parnaparin production method. The invention adopts a technical scheme that the parnaparin production method comprises the following steps: adding sodium acetate and sodium chloride to a heparin sodium solution the concentration of which is 2-3%, adjusting the pH value to 7-8, respectively adding dissolved Cu<2+>, adding hydrogen peroxide the concentration of which is 2-3%, and keeping in a water bath at 50-55 DEG C to be subject to a degradation reaction; and removing heavy metal, decolorizing and freeze-drying to obtain the parnaparin product. The method has the advantage of simple operation and can realize industrial production. In the presence of Cu<2+>, the heparin reacts with the peroxide under alkaline conditions to degrade. However, the degradation reaction is quite random, glycosidic bonds among uronic acids or glucosamines has the possibility of being broken, and the obtained product is composed of multiple sugar chains.

Description

A kind of handkerchief heparin working method

One, technical field:

The present invention relates to a kind of preparation method of biochemical drug, particularly a kind of handkerchief heparin working method.

Two, background technology:

The handkerchief heparin is a kind of anti-freezing and antithrombotic reagent, is a kind of of Low molecular heparin, and the anti-blood with quick and lasting long-acting is fastened agent, has minimum hemorrhage risk simultaneously.The handkerchief heparin is a kind of Low molecular heparin that separates, purifies and obtained through the chemical process of patent registration, and common way is under the katalysis of cupric ion, forms through the hydrogen peroxide degradation heparin.Domestic still do not have this a kind products production that meets the European Pharmacopoeia requirement, and USP is not included this product.

Three, summary of the invention:

The object of the invention is exactly the above-mentioned defective that exists to prior art, and a kind of handkerchief heparin working method is provided, and has confirmed the top condition of hydrogen peroxide degradation, and the purifying process of handkerchief heparin has been proposed clear and definite method.The product of producing with this law is fit to suitability for industrialized production, and constant product quality.

The present invention adopts following technical scheme to realize: taking heparin sodium adds purified water and is dissolved into 2%～3% concentration; Add sodium acetate and sodium-chlor; Adjust pH to 7～8, venus crystals that the adding dissolving is good respectively and volume ratio are 2%～3% hydrogen peroxide; Put and begin reaction in 50～55 ℃ of water-baths, during control pH value and temperature; Behind the DeR 18-24h, adjust pH=9.5～10.0 add EDTA.2Na, react after 4 hours, transfer pH neutral, and 3 times of amount ethanol sedimentations are placed 21h; The gained throw out is dissolved into 10%～15% concentration, handles through strong acidic ion resin, collect effluent, and adjust pH accomplishes through plastic resin treatment to neutral, effluent adds the medicinal alcohol deposition of 3 times of amounts, places 5h; The gained throw out is dissolved into 10%～15% concentration, and adjust pH=9.5～10.0 add volume ratio and are 0.5% hydrogen peroxide oxidation 6-12h; The adding volume ratio is 1% sodium-chlor, membrane filtration, and the filtrating adjust pH is to neutral; 3 times of amount medicinal alcohol depositions are placed 6-12h; The gained throw out is dissolved into 10%～15% concentration, and lyophilize or throw out be through ethanol dehydration, dry handkerchief heparin finished product.

The invention has the beneficial effects as follows: confirmed the technical process of suitability for industrialized production, proposed the purification process that a cover is optimized, product stability is good, and yield is high.The product that this technology is produced meets the European Pharmacopoeia requirement, compares the anti-blood with quick and lasting long-acting with conventional heparin and fastens agent, has minimum hemorrhage risk simultaneously and can fill up the blank that domestic nothing meets the products production that European Pharmacopoeia requires.

Four, description of drawings:

Accompanying drawing 1 is a schematic flow sheet of the present invention.

Five, embodiment:

In conjunction with accompanying drawing 1, the present invention is done further description:

Taking heparin sodium, purified water are dissolved into 2%～3% concentration, add sodium acetate, sodium-chlor; Transfer pH7～8, the good venus crystals of adding dissolving adds 2%～3% hydrogen peroxide (v/v volume ratio, down together) respectively; Put in 50～55 ℃ of water-baths, begin the reaction, during control pH, temperature.Behind DeR 18～24h, transfer PH=9.5～10.0, add EDTA.2Na (EDTA Disodium), react after 4 hours, transfer pH neutral, 3 times of amount ethanol sedimentations are placed 21h.The gained throw out is dissolved into 10%～15% concentration, through strong acidic ion resin, handles like the 001X7 resin bed, collect effluent, and transfer pH neutral, accomplish through plastic resin treatment, effluent adds the medicinal alcohol deposition of 3 times of amounts, places 5h.The gained throw out is dissolved into 10%～15% concentration, transfers pH=9.5～10.0, add 0.5% hydrogen peroxide oxidation; Oxidation 6～12h adds 1%NaCl (v/v volume ratio), 0.65 μ m membrane filtration; Filtrating transfers pH neutral, and 3 times of amount medicinal alcohol depositions are placed 6～12h.The gained throw out is dissolved into 10%～15% concentration, lyophilize or throw out through ethanol dehydration in below 50 ℃, dry handkerchief heparin finished product below the vacuum tightness 0.095Mpa.

Claims

1. handkerchief heparin working method, it is characterized in that being processed by following technology: taking heparin sodium adds purified water and is dissolved into 2%～3% concentration, adds sodium acetate and sodium-chlor; Adjust pH to 7～8; Venus crystals that the adding dissolving is good respectively and volume ratio are 2%～3% hydrogen peroxide, put in 50～55 ℃ of water-baths; Begin reaction, during control pH value and temperature; Behind the DeR 18-24h, adjust pH=9.5～10.0 add EDTA Disodium, react after 4 hours, transfer pH neutral, and 3 times of amount ethanol sedimentations are placed 21h; The gained throw out is dissolved into 10%～15% concentration, handles through strong acidic ion resin, collect effluent, and adjust pH accomplishes through plastic resin treatment to neutral, effluent adds the medicinal alcohol deposition of 3 times of amounts, places 5h; The gained throw out is dissolved into 10%～15% concentration, and adjust pH=9.5～10.0 add volume ratio and are 0.5% hydrogen peroxide oxidation 6-12h; The adding volume ratio is 1% sodium-chlor, membrane filtration, and the filtrating adjust pH is to neutral; 3 times of amount medicinal alcohol depositions are placed 6-12h; The gained throw out is dissolved into 10%～15% concentration, and lyophilize or throw out be through ethanol dehydration, dry handkerchief heparin finished product.