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Process for preparing low moledule heparin calcium of low nitrite content

A low-molecular-weight heparin calcium and low-nitrite technology, which is applied in the directions of medical preparations containing active ingredients, pharmaceutical formulations, organic active ingredients, etc., can solve the problems of complex process, many steps and large quantities of low-molecular-weight heparin calcium, etc. To achieve the effect of simple process, convenient operation and low cost

Active Publication Date: 2004-12-15
ZHAOKE PHARMA HEFEI
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In addition, this patent has many steps for preparing low-molecular-weight heparin calcium, and there are many types and quantities of chemical reagents used. To prepare low-molecular-weight heparin calcium, it is first necessary to make heparin sodium, and then use high-concentration calcium chloride hexahydrate (9.63g / g Low molecular weight heparin sodium) is replaced by low molecular weight heparin calcium, the process is more complicated
[0007] The preparations of domestic low molecular heparin calcium manufacturers all contain 20-30ppm of nitrite, and there are no patents and literature reports on the removal of nitrite in low molecular heparin calcium in China

Method used

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  • Process for preparing low moledule heparin calcium of low nitrite content

Examples

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Embodiment 1

[0033] Dissolve 800 grams of refined heparin sodium in 20 liters of acetic acid aqueous solution at pH 3.0, add 20 grams of sodium nitrite to the solution, and crack at 25°C for 4 hours to obtain a cracking solution; neutralize the solution with calcium hydroxide to obtain pH 5 .5 solution; filter, discard the insoluble matter, the filtrate precipitates with saturated calcium chloride ethanol solution, collects the precipitate and dissolves it in water for injection, adjusts the pH of the solution with hydrochloric acid, and obtains a solution of pH 0.3; Neutralize the solution to obtain a solution with a pH of 6.0; filter, discard the insoluble matter, precipitate the filtrate with a saturated calcium chloride ethanol solution, collect the precipitate, and dry it under reduced pressure to obtain the finished low-molecular-weight heparin calcium.

Embodiment 2

[0035] Dissolve 800 grams of refined heparin sodium in 20 liters of acetic acid aqueous solution of pH 3.4, add 28 grams of sodium nitrite to the solution, and crack at 27 ° C for 4.5 hours to obtain a lysis solution; neutralize the solution with calcium hydroxide to obtain a pH 6 .0 solution; filter, discard the insolubles, precipitate the filtrate with saturated calcium chloride ethanol solution, collect the precipitate and dissolve it in water for injection, adjust the pH of the solution with hydrochloric acid to obtain a solution of pH 1.0; use calcium hydroxide Neutralize the solution to obtain a solution with a pH of 6.5; filter, discard the insoluble matter, precipitate the filtrate with a saturated calcium chloride ethanol solution, collect the precipitate, and dry it under reduced pressure to obtain the finished low-molecular-weight heparin calcium.

Embodiment 3

[0037] Dissolve 800 grams of refined heparin sodium in 22 liters of acetic acid aqueous solution at pH 3.2, add 28 grams of sodium nitrite to the solution, and crack at 23°C for 5 hours to obtain a lysis solution; neutralize the solution with calcium hydroxide to obtain pH 5 .8 solution; filter, discard the insoluble matter, and the filtrate is precipitated with saturated calcium chloride ethanol solution, collects the precipitate and dissolves it in water for injection, adjusts the pH of the solution with hydrochloric acid, and obtains a solution of pH 0.5; Neutralize the solution to obtain a solution with a pH of 6.2; filter, discard the insoluble matter, precipitate the filtrate with a saturated calcium chloride ethanol solution, collect the precipitate, and dry it under reduced pressure to obtain the finished low-molecular-weight heparin calcium.

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Abstract

The preparation process of low molecular weight heparin calcium includes the following steps: dissolving refined heparin sodium in acetic acid aqua and adding sodium nitrite to the solution for cracking for 4-6 hr to obtain cracked solution; neutralizing the solution with calcium hydroxide to pH 5.5-6.0; filtering to eliminate insoluble matter, precipitating the solution with saturated ethanol solution of calcium chloride and collecting the precipitate; dissolving the precipitate in injection water and regulate pH with hydrochloric acid to 0.3-1.0; neutralizing the solution to pH 6.0-6.5; filtering to eliminate insoluble matter, precipitating the filtrate with saturated ethanol solution of calcium chloride and collecting the precipitate; and conventional decompression drying to obtain low molecular weight heparin calcium product. The product has average molecular weight of 3000-5000 D, Xa resisting activity not lower than 90 IU / mg, Xa resistance / IIa resistance ratio of 3-5 and nitrite content lower than 2 ppm.

Description

technical field [0001] The invention relates to a preparation method of low-molecular-weight heparin calcium, in particular to a preparation method of low-molecular-weight heparin calcium with low nitrite content. Background technique [0002] Antithrombotic drugs include heparin, non-heparin antiplatelet aggregation drugs, enzymes and four other small subclasses. Heparin and enzymes are basically biochemical drugs. Among them, heparins occupy the largest market share. Among the heparins, low-molecular-weight heparins dominate. Low-molecular-weight heparin calcium and low-molecular-weight heparin sodium account for 20% and 7% of the total antithrombotic drugs market share, respectively. [0003] Although bioactive heparin has been discovered for more than 80 years, it is still one of the most important biochemical drugs and one of the main export drugs in my country because there is no product that can completely replace it. . The clinical application of heparin has a histo...

Claims

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Application Information

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IPC IPC(8): A61K31/727A61P7/02C08B37/10
Inventor 王贤舜
Owner ZHAOKE PHARMA HEFEI
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