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Method for extraction of ultra-low molecular weight heparin sodium by nadroparin calcium waste

A technology of nadroparin calcium and heparin sodium, which is applied in the field of producing ultra-low molecular weight heparin, can solve the problems of low raw material utilization rate of heparin sodium, increase of production cost, loss of heparin sodium, etc., and achieve high synthesis difficulty, high cost and high yield low effect

Inactive Publication Date: 2020-03-17
TIANJIN BIOCHEM PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] At present, as long as ultra-low molecular weight heparin is directly produced using unfractionated heparin sodium as a raw material (enzymatic hydrolysis method, hydrogen peroxide method), the problem of the prior art is that the raw material utilization rate of heparin sodium is low, and part of heparin sodium will be lost during the production process. thus increasing production costs

Method used

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  • Method for extraction of ultra-low molecular weight heparin sodium by nadroparin calcium waste
  • Method for extraction of ultra-low molecular weight heparin sodium by nadroparin calcium waste

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Cleavage: Weigh 1 kg of heparin sodium, dissolve it with purified water, adjust the pH to 1.5, add 20 g of sodium nitrite, stir and react for 0.5 hours, during which the pH is maintained at 1.5, and the starch-KI reagent is used to judge the cleavage at the end of the reaction. When the starch-KI reagent is negative, the cleavage reaction ends. get lysate

[0027] Reduction: Adjust the pH of the lysing liquid to neutral, add 10 g of sodium borohydride, and stir and react at 20°C for 20 hours; adjust the pH of the liquid to 2.5, and stir for 2 hours. Get the recovery solution.

[0028] 1st classification: Add 3 times the amount of ethanol to the reducing drug solution, add ethanol and stir evenly, a precipitate will be obtained, separate the supernatant from the precipitate, and discard the separated supernatant.

[0029] Secondary fractionation: dissolve the precipitate with purified water, adjust the pH to 5.0, add 300 g of sodium chloride and dissolve. Add 1 times ...

Embodiment 2

[0035] Cleavage: Weigh 1 kg of heparin sodium, dissolve it with purified water, adjust the pH to 3.0, add 30 g of sodium nitrite, stir and react for 0.7 hours, during which the pH is maintained at 3.0, and the starch-KI reagent is used to judge the cleavage at the end of the reaction. When the starch-KI reagent is negative, the cleavage reaction ends. get lysate

[0036] Reduction: adjust the pH of the lysing liquid to neutral, add 20 g of sodium borohydride, stir and react at 30°C for 22 hours; adjust the pH of the liquid to 2.8, and stir for 2 hours. Get the recovery solution.

[0037] 1st classification: Add 3 times the amount of ethanol to the reducing drug solution, add ethanol and stir evenly, a precipitate will be obtained, separate the supernatant from the precipitate, and discard the separated supernatant.

[0038] Secondary fractionation: dissolve the precipitate with purified water, adjust the pH to 5.5, add 400g of sodium chloride and dissolve. Add 1 times the a...

Embodiment 3

[0044] Cleavage: Weigh 1 kg of heparin sodium, dissolve it with purified water, adjust the pH to 4.0, add 40 g of sodium nitrite, stir and react for 1.0 hour, during which the pH is maintained at 4.0, and the starch-KI reagent is used to judge the cleavage at the end of the reaction. When the starch-KI reagent is negative, the cleavage reaction ends. get lysate

[0045] Reduction: Adjust the pH of the lysing liquid to neutral, add 30 g of sodium borohydride, and stir and react at 40°C for 24 hours; adjust the pH of the liquid to 3.0, and stir for 2 hours. Get the recovery solution.

[0046] 1st classification: Add 3 times the amount of ethanol to the reducing drug solution, add ethanol and stir evenly, a precipitate will be obtained, separate the supernatant from the precipitate, and discard the separated supernatant.

[0047] Secondary fractionation: dissolve the precipitate with purified water, adjust the pH to 6.0, add 500 g of sodium chloride and dissolve. Add 1 times t...

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PUM

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Abstract

The invention discloses a method for extraction of ultra-low molecular weight heparin sodium by nadroparin calcium waste. The method mainly includes the steps of cracking, reduction, 1-2 grading, crystallization, purification, fine screening and the like. Nadroparin calcium belongs to one of low molecular weight heparin drugs. While nadroparin calcium is produced, nadroparin calcium waste is collected and is reprocessed to produce ultra-low molecular weight heparin, thus increasing the utilization rate of the initial raw material common heparin sodium up to 90% or above, the anti-Xa titer is 32-35 IU / mg, and the weight-average molecular weight is 1400-1600 Daltons, therefore the purposes of saving resources, reducing the production cost and protecting the ecological environment are achieved.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical production, and relates to a production method for producing ultra-low molecular weight heparin by reprocessing the production waste of nadroparin calcium. Background technique [0002] Ultra-low molecular weight heparin sodium has been found to have neuroprotective and antiasthmatic effects in recent years. The potency range is 10-50IU / mg, and the molecular weight range is 1000-2000. The efficacy of ultra-low molecular weight heparin sodium is not possessed by unfractionated heparin. Ultra-low molecular weight heparin sodium is a new drug in the research and development stage, and its therapeutic efficacy is still under research and development. [0003] At present, as long as ultra-low molecular weight heparin is directly produced using unfractionated heparin sodium as a raw material (enzymatic hydrolysis method, hydrogen peroxide method), the problem of the prior art is that the raw mat...

Claims

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Application Information

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IPC IPC(8): C08B37/10
CPCC08B37/0075
Inventor 高鑫郭彬
Owner TIANJIN BIOCHEM PHARMA
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