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Preparation method of heparin lithium

A technology of lithium heparin and heparinase, which is applied in the field of lithium heparin preparation, can solve the problems of large investment in hardware facilities, high cost of raw materials, and large investment in hardware for the production of lithium heparin, and meets the requirements of mild dynamic ion exchange process and ambient temperature of resin method The effect of low investment and small investment in hardware facilities

Inactive Publication Date: 2012-08-01
WUHAN BORUITONG TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The preparation of lithium heparin, the current domestic patent 200510019846.0 discloses the preparation of lithium heparin by ion balance exchange method, some process steps of this method require low temperature conditions (below 10°C) operation, high requirements for material and environmental temperature control, and large investment in hardware facilities; This method adopts strongly acidic condition operation (PH1.5) in the deproteinization process link, and the heparin activity loss is bigger (heparin solution is very unstable in the environment of low pH value, easily degraded and inactivated), affecting the final activity yield and Potency, operability is not strong; this method uses ultrafiltration concentration and separation technology, ultrafiltration equipment is expensive, and hardware investment is large; the ion balance exchange method used in this method is to achieve heparin by continuously intervening high-concentration lithium ions. The conversion of sodium to lithium heparin cannot guarantee the adequacy and continuous stability of the dynamic ion balance conversion
The preparation of heparin lithium in foreign countries all adopts the ion exchange method. This method needs to use high-quality heparin sodium as a raw material, and the cost of the raw material is high. In addition, the pH may drop sharply during the ion exchange process, which seriously affects the yield and potency of the product. In addition, the exchange process requires Carried out under low-temperature extraction conditions, resulting in a large investment in hardware facilities for the production of heparin lithium, and high production costs

Method used

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  • Preparation method of heparin lithium

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020] Step 1: Stir and dissolve the crude sodium heparin raw material (commercially available raw material, potency 65-105IU / mg) with 1%-3% NaCl solution, the concentration of crude sodium heparin is 8%-16% (mass percentage concentration ), adjust the pH to 7.5-9.0 with 5M NaOH solution, heat up to 50-55°C, add heparin enzymolysis trypsin according to 0.1-0.3% of the mass of the crude product heparin sodium solution, keep warm for 4-5 hours, and use 5M NaOH Adjust the pH value of the solution to 9.0-11, heat up to 85°C-90°C, cool to room temperature, filter to remove the precipitate, and precipitate the filtrate with 0.8-1.5 times the volume of 95% ethanol for more than 4 hours, and collect the precipitate A;

[0021] Step 2: Stir and dissolve the precipitate A with pure water, the dissolved concentration is 10%-20% (mass percentage), adjust the pH to 8.5-11 with 5M NaOH solution, and press 0.1%-5% of the mass of the precipitate A aqueous solution Add protein flocculation and...

Embodiment 2

[0026] The heparin enzymolysis trypsin in step 1 is selected as compound trypsin containing trypsin;

[0027] The protein flocculation precipitant in step 2 is selected polyaluminum chloride for use;

[0028] The other steps were the same as in Example 1 to obtain the lithium heparin fine product.

Embodiment 3

[0030] The heparin enzymolysis trypsin in step 1 is selected as neutral trypsin;

[0031] The protein flocculation precipitant in step 2 is selected sodium polyacrylate for use;

[0032] The other steps were the same as in Example 1 to obtain the lithium heparin fine product.

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Abstract

The invention discloses a preparation method of heparin lithium. The method comprises the following steps of: after enzymolysis of a crude product heparin, carrying out protein removal treatment; after oxidizing and decoloring, exchanging by resin to obtain heparin lithium solution, precipitating, dehydrating and drying the heparin lithium solution to obtain a heparin lithium refined product. The preparation method of heparin lithium, provided by the invention, has the advantages of wide raw material sources, strong university, high activity yield, stable technique quality, low production cost and strong operability under an ambient temperature condition, and is convenient to achieve large-scale preparation of the heparin lithium at low investment, low cost, high yield, strong operability and stable technological quality.

Description

technical field [0001] The invention belongs to the preparation technology of an anticoagulant, in particular to a preparation technology of heparin lithium. Background technique [0002] Heparin, sodium salt and lithium salt are common in clinical blood tests, has unique application value, heparin has low chelating power, has little effect on water molecule movement, has little interference with blood components, does not affect red blood cell volume, does not cause hemolysis, Therefore, heparin is recommended as an anticoagulant in various tests using whole blood or plasma as specimens. It is suitable for red blood cell fragility test, blood gas analysis, hematocrit test, hemorheology and emergency biochemical determination. In the detection of pH value, blood gas, electrolyte and calcium ion, heparin is the only anticoagulant that can be used, and heparin lithium has the least possibility of interference when detecting non-lithium ions, so it is recommended to use hepari...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08B37/10
Inventor 蔡震山
Owner WUHAN BORUITONG TECH
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