Heparin calcium compound and preparation method thereof

A compound, the technology of heparin calcium, applied in the field of medicine, can solve the problems of low purity of low molecular weight heparin calcium, achieve the effects of reducing toxic and side effects, improving clinical adverse reactions, and ensuring product quality

Inactive Publication Date: 2012-07-25
灵康药业集团股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

After long-term serious research, the present inventor unexpectedly discovered a purification method of low-molecular-weight heparin calcium compound, which solved the shortcoming of low-purity low-molecular-weight heparin calcium synthesized at present, not only simple process, convenient operation, low cost, but also improved Purity ensures the safety of medication and reduces toxic and side effects

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0047] Take 10 g of crude low-molecular-weight heparin calcium treated according to the method of CN101012289A, its HPLC purity is 93.68% after testing, dissolve it in 200 mL of water, stir well to dissolve it, and then add 1.0 M hydrochloric acid dropwise under stirring until the solution is The pH value is about 2.5; add 1g of activated carbon for adsorption, keep the temperature at 10-12°C, stir for 50 minutes, then filter with a plate frame and a 0.3μm filter membrane in turn, and then concentrate the filtrate with a 10000D ultrafiltration membrane; Calcium oxide was added to the solution and stirred vigorously until the pH of the system was about 6.8.

[0048] Add 10g of neutral alumina to the solution and stir evenly, then add to the upper end of the preparative neutral alumina chromatographic column, the stationary phase filler is Baker column chromatography special neutral alumina with a particle diameter of 50-200 μm and a pore diameter of 6 nm, pH 7.0, The pH of 0.5 ...

Embodiment 2

[0051] Take 10 g of low molecular weight heparin calcium raw material (manufactured by Shandong Bausch & Lomb Freda Pharmaceutical Co., Ltd., batch number 20100103), and its purity by HPLC is 96.52%. Dissolve it in 200mL water, stir well to dissolve it, then add 1.0M sulfuric acid dropwise under stirring until the pH value of the solution is about 3.5; add 1.5g activated carbon for adsorption, keep the temperature at 12-14°C, stir for 60min, then Filter with a plate frame and a 0.4 μm membrane in turn, and then concentrate the filtrate with a 12000D ultrafiltration membrane; add calcium hydroxide to the concentrated solution, and stir vigorously until the pH of the system is about 6.5.

[0052] Add 15g of neutral alumina to the solution and stir evenly, then add it to the upper end of the preparative neutral alumina chromatographic column. The stationary phase filler is ICN allumina N fine-pore neutral alumina with a particle size of 18-63μm and a pore size of 6nm, pH 6.5, use...

Embodiment 3

[0055] Take 10 g of expired low-molecular-weight heparin calcium crude drug, and its HPLC purity is 89.56% after testing. Dissolve it in 300mL water, stir well to dissolve it, then add 2.0M hydrochloric acid dropwise under stirring until the pH value of the solution is about 2.5; add 2.0g activated carbon for adsorption, keep the temperature at 12-14°C, stir for 120min, then Filter with a plate frame and a 0.5 μm filter membrane in turn, and then concentrate the filtrate with a 12000D ultrafiltration membrane; add calcium oxide to the concentrated solution, and stir vigorously until the pH of the system is about 6.0.

[0056] Add 20g of neutral alumina to the solution and stir evenly, then add to the upper end of the preparative neutral alumina chromatographic column, the stationary phase filler is ICN allumina N neutral alumina with a particle diameter of 18-32 μm and a pore diameter of 6 nm, pH 6.5, with Adjust the pH of the 0.8 mol / L sodium sulfate solution to 4.5 with 2.0 ...

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PUM

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Abstract

The invention discloses a heparin calcium compound and a preparation method thereof. The preparation method comprises the following steps of: dissolving a low molecular heparin calcium rough product in water; dropwise adding non-redox acid with stirring; adding active carbon to adsorb; then filtering; ultrafiltering filtrate with an ultrafiltration membrane and concentrating; adding calcium oxide or calcium hydroxide into concentrated solution and violently stirring; adding neutral aluminum oxide into the solution and uniformly stirring; adding to the upper end of a neutral aluminum oxide preparative chromatographic column to separate and purify; collecting eluent; adding ethanol into the eluent; performing gradient cooling to separate precipitate; and drying the precipitate to obtain refined low molecular heparin calcium. The method has the advantages of simple process, convenience for operation, low cost, suitability for mass production, improved purity of the low molecular heparin calcium compound and capabilities of guaranteeing the safety of the heparin calcium compound in an anti-coagulation medicament, improving the quality of a preparation product and reducing the toxic or side effect.

Description

technical field [0001] The invention relates to a heparin calcium compound, especially a low-molecular-weight heparin calcium compound, and a preparation method thereof, belonging to the technical field of medicine. Background technique [0002] Heparin calcium, that is, low molecular weight heparin calcium or low molecular weight heparin calcium, its chemical name: amino dextran sulfate calcium. 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, and among the heparins, heparin drugs dominate. Low-molecular-weight heparin calcium and low-molecular-weight heparin sodium occupy 20% and 7% of the entire antithrombotic drug market share, respectively. Although bioactive heparin has been discovered for more than 80 years, it is still one of the most important biochemical drugs because there is no produc...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08B37/10A61P7/02
Inventor 陶灵刚赵雁鸿
Owner 灵康药业集团股份有限公司
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