Preparation process of nadroparin calcium

A preparation technology of nadroparin calcium, which is applied in the preparation technology of high-quality nadroparin calcium and the field of preparation of medicinal chemicals, can solve the problems of low yield, low degree of automation, and high cost of separation methods, and achieve operational Convenience, high degree of automation, and the effect of improving production capacity

Active Publication Date: 2014-10-08
CHANGZHOU QIANHONG BIOPHARMA
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] The purpose of the present invention is to provide a preparation process of nadroparin calcium, which controls the molecular weight of low molecular weight heparin calcium through anion exchange chromatography, so that the molecular weight can be accurately controlled within 1%, and the yiel

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  • Preparation process of nadroparin calcium

Examples

Experimental program
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Effect test

Embodiment 1

[0022] Example 1: Preparation of Nadroparin Calcium

[0023] Degradation of heparin sodium: feed 30kg heparin sodium, dissolve it in purified water with 21 to 30 times the weight of heparin sodium, adjust pH to 5.5 to 6, add 4.5% to 5% of sodium nitrite, and keep at 10°C to 30°C. The degraded solution was stirred for 3 to 6 hours.

[0024] Reduction of the degradation solution: adjust the pH of the degradation solution to neutrality, add 1.5% to 2% of sodium borohydride of the heparin sodium feeding amount, and stir and react at 10°C to 30°C for 12 to 24 hours to obtain a degradation reduction solution.

[0025] Ultraviolet irradiation: 254nm wavelength ultraviolet lamp is inserted into the reducing solution and irradiated for 45 to 90 minutes at room temperature to eliminate the residual nitroso compounds in the solution and reduce the content of N-NO groups.

[0026] Calcium transfer and concentration: The reducing solution is ultrafiltered with a 5% calcium chloride soluti...

Embodiment 2

[0029] Example 2: Preparation of Nadroparin Calcium

[0030] Degradation of heparin sodium: feed 30kg heparin sodium, dissolve in purified water with 15 to 20 times the weight of heparin sodium, adjust the pH to 4.5, add 2% to 2.3% of sodium nitrite in the feeding amount, keep the temperature at 15°C to 30°C and stir the reaction 3 to 6 hours of degradation solution.

[0031] Reduction of the degradation solution: adjust the pH of the degradation solution to neutrality, add 0.6% to 1% of sodium borohydride of the heparin sodium feeding amount, and stir and react at 15°C to 20°C for 12 to 24 hours to obtain a degradation reduction solution.

[0032] Ultraviolet irradiation: 254nm wavelength ultraviolet lamp is inserted into the reducing solution and irradiated for 45 to 90 minutes at room temperature to eliminate the residual nitroso compounds in the solution and reduce the content of N-NO groups.

[0033] Calcium transfer and concentration: The reducing solution is ultrafilte...

Embodiment 3

[0036] Example 3: Preparation of Nadroparin Calcium

[0037] Degradation of heparin sodium: feed 30kg heparin sodium, dissolve it in purified water with 10 to 14 times the weight of heparin sodium, adjust pH to 5, add 3% to 4% of sodium nitrite in the feeding amount, keep at 20°C to 30°C and stir the reaction 3 to 6 hours of degradation solution.

[0038] Reduction of the degradation solution: adjust the pH of the degradation solution to neutrality, add 0.5% to 0.8% of sodium borohydride of the heparin sodium feeding amount, and stir and react at 10°C to 30°C for 12 to 24 hours to obtain a degradation reduction solution.

[0039] Ultraviolet irradiation: 254nm wavelength ultraviolet lamp is inserted into the reducing solution and irradiated for 45 to 90 minutes at room temperature to eliminate the residual nitroso compounds in the solution and reduce the content of N-NO groups.

[0040] Calcium transfer and concentration: The reducing solution is ultrafiltered with 17-20 time...

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Abstract

The invention relates to a preparation process of nadroparin calcium. The preparation process comprises the following steps: S1, degrading heparin sodium; S2, reducing degradation liquid; S3, performing ultraviolet radiation, namely radiating reduction liquid by using an ultraviolet lamp to remove residual nitro compounds from the reduction liquid and reduce the content of N-NO groups; S4, performing calcium conversion and concentration, namely performing ultrafiltration on an ultrafiltration membrane by using a 5% calcium chloride solution, and concentrating the reduction liquid until the solid-liquid ratio is 1:10; S5, performing anion exchange chromatography, namely performing chromatography by adopting anion exchange resin, and collecting elution liquid; S6, freeze-drying to obtain nadroparin calcium. According to the process, the molecular weight of low-molecular-weight heparin calcium is controlled through the anion exchange chromatography, so that the molecular weight can be accurately controlled within 1% and the yield can be increased to more than 50%; moreover, the automation degree is high and the operation is convenient, so that a powerful guarantee is provided for increasing the production capacity.

Description

technical field [0001] The invention relates to the preparation of a medicinal chemical in the field of medicine and chemistry, in particular to a preparation process of a high-quality and high-purity fine nadroparin calcium. Background technique [0002] Unfractionated heparin is a mixture of various glucosamines. Calcium heparin can delay or prevent blood clotting in vitro and in vivo. Its anticoagulation mechanism is complex, and it has effects on all aspects of coagulation, including inhibiting the conversion of prothrombin into thrombin, inhibiting thrombin activity, preventing the conversion of fibrinogen into fibrin, and preventing platelet aggregation. Heparin calcium can also lower blood lipids, lower LDL and VLDL, increase HDL, change blood viscosity, protect vascular endothelial cells, prevent atherosclerosis, promote blood flow, and improve coronary circulation. [0003] The anti-F II a effect of heparin calcium is stronger than that of heparin sodium, and its ...

Claims

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Application Information

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IPC IPC(8): C08B37/10A61P7/02A61P35/00A61P29/00A61P37/08
Inventor 周翔金晶陶翎费清清
Owner CHANGZHOU QIANHONG BIOPHARMA
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