Production method of dalteparin sodium fine product

Abstract

The invention discloses a production method of dalteparin sodium. According to the production method, a heparin sodium coarse product is taken as a raw material, a low-molecular-weight heparin sodium coarse product is obtained through degradation, reduction and ethanol precipitation; compared with a method taking a heparin sodium fine product as the raw material, the method is wider in application range and can better control the quality of a dalteparin sodium fine product from the source. Innovatively, molecular weight and distribution of the low-molecular-weight heparin sodium coarse product before chromatography are tested through HPLC (high performance liquid chromatography), corresponding required-to-be-removed areas of macromolecules and micromolecules and corresponding volumes are calculated according to the formula, filtrate in the chromatography process is collected, a low-molecular-weight heparin sodium fine product liquid which meets the requirements is accurately and quantitatively obtained, and use of an expensive molecular weight interception filtering membrane is avoided; a one-pot process is achieved through oxidation, sterilization filtration and sediment dehydration, the operation is simplified, and time and labor cost are saved; and a new method for preparing a raw dalteparin sodium material is developed on the basis of the prior art, and industrial production of dalteparin sodium is realized.

Description

technical field [0001] The invention relates to the field of biomedicine, in particular to a preparation and purification process of high-quality dalteparin sodium. Background technique [0002] Heparin Sodium is a mucopolysaccharide sulfate anticoagulant. Heparin sodium is the sodium salt of aminodextran sulfate extracted from the intestinal mucosa of pigs or cattle, and belongs to mucopolysaccharides. It has anticoagulant effect both in vivo and in vitro, and is currently the mainstream anticoagulant drug. However, the bioavailability of unfractionated heparin sodium is low and the side effects are large. Later, it was discovered that the sodium salt of aminodextran sulfate fragment obtained by cleavage of heparin sodium has an average molecular weight of 4000-6000 Daltons, which is called low molecular weight heparin sodium. Low molecular weight heparin sodium injection, like heparin sodium injection, is an antithrombin Ⅲ (AT Ⅲ) dependent thrombin inhibitor. However, c...

AI Technical Summary

Problems solved by technology

This patent also uses high-quality heparin sodium as raw material, so the acquisition of raw materials in production is limited, and the cost is increased. At the same time, it is difficult to control the production process and product quality of dalteparin sodium from the source

At the same time, an expensive molecular weight cut-off filter membrane is used, and the molecular weight cut-off filter membrane is frequently used, which increases the cost of technological production

Images