Method for producing nadroparin calcium by using crude sodium heparin products

A technology of nadroparin calcium and heparin sodium, which is applied in the field of biochemical raw material medicine production, can solve the problems that it is difficult to guarantee the quality of heparin sodium, the safety of the final product is difficult to guarantee, and the pressure on environmental protection is increased, so as to ensure product quality and low energy consumption , The effect of simple preparation process

Active Publication Date: 2015-04-29
NORTH CHINA PHARMA HUAKUN HEBEI BIOTECH
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  • Abstract
  • Description
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  • Application Information

AI Technical Summary

Problems solved by technology

The heparin sodium removal step in the method is not easy to ensure the quality of heparin sodium used to prepare nadroparin calcium, and barium chloride is also used when preparing nadroparin calcium from heparin sodium, which is highly toxic. If there is residue, the safety of the final product is difficult. Guarantee, and increase environmental pressure

Method used

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  • Method for producing nadroparin calcium by using crude sodium heparin products

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Effect test

Embodiment 1

[0036] Take 1kg of crude heparin sodium, dissolve it in 8L of purified water, add 80g of sodium chloride, raise the temperature to 50°C, and at the same time adjust the pH value to 8.5 with 1mol / L sodium hydroxide solution, and perform salt hydrolysis for 2 hours under this condition. The salt solution was centrifuged to obtain heparin sodium pretreatment solution. Lower the temperature of the heparin sodium pretreatment solution to 28°C, add hydrogen peroxide, the volume of which is 1% of the volume of the heparin sodium pretreatment solution, stir evenly, add to a resin column equipped with 15L OC1074 resin for adsorption, and control the adsorption rate to 0.05 BV / h, the resin after adsorption is first washed with 5.5% sodium chloride solution, the flow rate is 0.5BV / h, and washed to absorbance A 260nm ≤0.20,A 280nmWhen ≤0.20, use 12% sodium chloride solution to elute, the elution rate is 0.05BV / h, detect the refraction of the column liquid, start collecting the eluate whe...

Embodiment 2

[0038] Take 1kg of crude heparin sodium, dissolve it in 10L of purified water, add 200g of sodium chloride, raise the temperature to 60°C, and adjust the pH value to 9.0 with 3mol / L sodium hydroxide solution, and perform salt solution for 3 hours under this condition , and the salt solution was centrifuged to obtain a heparin sodium pretreatment solution. The temperature of the sodium heparin pretreatment solution is down to 32 DEG C, add hydrogen peroxide, its volume is 2% (of the volume of the sodium heparin pretreatment solution, after stirring, add to the resin column that 15L FPA98 resin is housed and carry out adsorption, the control adsorption speed is 0.06BV / h, the resin after adsorption is first washed with 6% sodium chloride solution, the flow rate is 0.5BV / h, and washed to absorbance A 260nm ≤0.20,A 280nm When ≤0.20, elute with 12% sodium chloride solution, the elution rate is 0.06BV / h, detect the refraction of the column liquid, and start collecting the eluate whe...

Embodiment 3

[0040] Take 1kg of crude heparin sodium, dissolve it in 10L of purified water, add 200g of sodium chloride, raise the temperature to 50°C, and at the same time adjust the pH value to 8.5 with 6mol / L sodium hydroxide solution, and perform salt hydrolysis for 2 hours under this condition. The salt solution was centrifuged to obtain heparin sodium pretreatment solution. Lower the temperature of the heparin sodium pretreatment solution to 30°C, add hydrogen peroxide, the volume of which is 1.5% of the volume of the heparin sodium pretreatment solution, stir evenly, add to a resin column equipped with 15L FPA98 resin for adsorption, and control the adsorption rate to 0.05 BV / h, the resin after adsorption is first washed with 5.5% sodium chloride solution, the flow rate is 0.5BV / h, and washed to absorbance A 260nm ≤0.20,A 280nm When ≤0.20, use 12% sodium chloride solution to elute, the elution rate is 0.05BV / h, detect the refraction of the column liquid, start collecting the eluate...

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Abstract

The invention discloses a method for producing nadroparin calcium by using crude sodium heparin products. The method is implemented by taking crude sodium heparin products as a raw material through the steps of pretreating the crude sodium heparin products by using a salt hydrolysis process; sequentially carrying out oxidation, ion exchange resin adsorption, washing and elution on the obtained object; sequentially carrying out ultrafiltration and freeze-drying on the obtained product so as to obtain a fine sodium heparin product; and sequentially carrying out depolymerization, reduction, grading-alcoholic precipitation, calcium transfer, and freeze-drying treatment on the fine sodium heparin product, so that nadroparin calcium is obtained. The method disclosed by the invention has the advantages that the quality of nadroparin calcium is controlled from the aspects of source and process, the production cycle is short, the energy consumption of production is low, and the quality of products is high, therefore, the method is suitable for large-scale industrial production.

Description

technical field [0001] The invention belongs to the technical field of production of biochemical raw materials, in particular to a method for producing nadroparin calcium from crude heparin sodium. Background technique [0002] Nadroparin calcium is a low-molecular-weight heparin calcium salt, which is obtained by depolymerizing heparin derived from porcine intestinal mucosa and then grading it with nitrous acid, and selectively removing most sugar chains with a molecular weight less than 2000. It consists of a series of complex oligosaccharides that have not been fully characterized. The non-reducing end is mainly composed of 2-O-thio-α-L-iduronic acid, and the reducing end is mainly composed of 6-O-thio-2,5-anhydro -D-mannitol composition. Its weight average molecular weight should be 3600-5000. Calculated on dry basis, the anti-Xa factor activity is 95IU / mg-130IU / mg, and the ratio of anti-Xa factor potency to anti-IIa factor potency is 2.5-4.0. Nadroparin calcium can b...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08B37/10
Inventor 段宝玲任风芝张雪霞陈书红高任龙魏松波刘建芬李宁李丽红米文强
Owner NORTH CHINA PHARMA HUAKUN HEBEI BIOTECH
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