CN101942039A

CN101942039A - Parnaparin production method

Info

Publication number: CN101942039A
Application number: CN 201010287132
Authority: CN
Inventors: 刘伟; 张岩岩; 于合新
Original assignee: 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: 2011-01-12
Anticipated expiration: 2030-09-16
Also published as: CN101942039B

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 production method

One, technical field:

The present invention relates to a kind of preparation method of biochemical drug, particularly a kind of handkerchief heparin production 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 by the chemical process of patent registration, and common way is under the katalysis of cupric ion, forms by the hydrogen peroxide degradation heparin.Domestic still do not have this a kind products production that meets the European Pharmacopoeia requirement, and American Pharmacopeia is not included this product.

Three, summary of the invention:

Purpose of the present invention is exactly the above-mentioned defective that exists at prior art, and a kind of handkerchief heparin production method is provided, and has determined 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.

Its technical scheme is: in heparin sodium aqua 2%～3% concentration, add sodium acetate, sodium-chlor is transferred pH7～8, adds the good Cu of dissolving respectively ²⁺, add 2%～3% hydrogen peroxide, put in 50～55 ℃ of water-baths, DeR takes place; By removing heavy metals, obtain handkerchief heparin product through the decolouring freeze-drying.

Taking heparin sodium adds purified water and is dissolved into 2%～3% concentration, adds sodium acetate, and sodium-chlor is transferred pH to 7～8, adds the good venus crystals of dissolving respectively, adds 2%～3% hydrogen peroxide, puts in 50～55 ℃ of water-baths, begins reaction; DeR is transferred PH=9.5～10.0 after for some time, adds EDTA.2Na (disodium ethylene diamine tetraacetate), after reaction for some time, transfers pH neutrality, and 3 times of amount ethanol sedimentations are placed for some time; The gained throw out is dissolved into 10%～15% concentration, handles through strong acidic ion resin, collect effluent liquid, and transfer pH to neutral, finish through plastic resin treatment, effluent liquid adds the medicinal alcohol precipitation of 3 times of amounts, places; The gained throw out is dissolved into 10%～15% concentration, transfers pH=9.5～10.0, add hydrogen peroxide oxidation after, add 1% NaCl, membrane filtration, filtrate is transferred pH neutrality, 3 times of amount medicinal alcohols precipitations are placed; 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: determined the technical process of suitability for industrialized production, proposed the purification process that a cover is optimized, product stability is good, the yield height.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 the accompanying drawings 1, the invention will be further described:

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 (disodium ethylene diamine tetraacetate), react after 4 hours, transfer pH neutrality, 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 as the 001X7 resin bed, collect effluent liquid, and transfer pH neutrality, finish through plastic resin treatment, effluent liquid adds the medicinal alcohol precipitation 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, filtrate is transferred pH neutrality, and 3 times of amount medicinal alcohol precipitations are placed 6～12h.The gained throw out is dissolved into 10%～15% concentration, lyophilize or throw out through ethanol dehydration in below 50 ℃, following dry the handkerchief heparin finished product of vacuum tightness 0.095Mpa.

Claims

1. handkerchief heparin production method is characterized in that being made by following technology:

In heparin sodium aqua 2%～3% concentration, add sodium acetate, sodium-chlor is transferred pH7～8, adds the good Cu of dissolving respectively ²⁺, add 2%～3% hydrogen peroxide, put in 50～55 ℃ of water-baths, DeR takes place; By removing heavy metals, obtain handkerchief heparin product through the decolouring freeze-drying.

2. handkerchief heparin production method according to claim 1, it is characterized in that being made by following detailed process: taking heparin sodium adds purified water and is dissolved into 2%～3% concentration, add sodium acetate, sodium-chlor, transfer pH to 7～8, add the good venus crystals of dissolving respectively, add 2%～3% hydrogen peroxide, put in 50～55 ℃ of water-baths, begin reaction; DeR is transferred PH=9.5～10.0 after for some time, adds EDTA.2Na, after reaction for some time, transfers pH neutrality, and 3 times of amount ethanol sedimentations are placed for some time; The gained throw out is dissolved into 10%～15% concentration, handles through strong acidic ion resin, collect effluent liquid, and transfer pH to neutral, finish through plastic resin treatment, effluent liquid adds the medicinal alcohol precipitation of 3 times of amounts, places; The gained throw out is dissolved into 10%～15% concentration, transfers pH=9.5～10.0, add hydrogen peroxide oxidation after, add sodium-chlor, membrane filtration, filtrate is transferred pH neutrality, 3 times of amount medicinal alcohols precipitations are placed; The gained throw out is dissolved into 10%～15% concentration, and lyophilize or throw out be through ethanol dehydration, dry handkerchief heparin finished product.