Degradation method for acquiring dalteparin

Abstract

The invention discloses a degradation method for acquiring dalteparin and belongs to the field of dalteparin production. The method comprises the following steps: dissolving heparin sodium in water and then using hydrochloric acid for regulating pH to be acidic and adding sodium nitrite for performing degradation reaction; adjusting the pH of the degradation reaction solution to be alkali, adding sodium borohydride for reacting, and then using the hydrochloric acid for regulating pH and performing ultra-filtration; diluting and then using the hydrochloric acid for regulating pH to be acidic, performing the secondary degradation reaction, regulating the pH of the degradation reaction solution to be alkali after the reaction and then adding sodium borohydride for reacting; filtering, and then using the hydrochloric acid for regulating pH, using an ultraviolet lamp for irradiating the solution and adding ethyl alcohol for precipitating; performing column chromatography on the acquired precipitate and using ethyl alcohol for precipitating the acquired eluant; and dewatering the wet solid and drying, thereby acquiring the end product of dalteparin. According to the method disclosed by the invention, the degradation process is effectively utilized to adjust the self-molecular weight distribution, the loss of the molecular weight modification step is reduced and the yield is increased.

Description

technical field [0001] The invention relates to a degradation method for obtaining dalteparin sodium, which can effectively obtain the finished product of dalteparin sodium meeting the requirements of the Pharmacopoeia, and significantly improve the yield, and belongs to the technical field of dalteparin sodium production. Background technique [0002] Heparin sodium is the most widely used anticoagulant clinically, and it appears in the form of complexes with proteins in vivo. [0003] However, heparin sodium has a large molecular weight and high anticoagulant potency, and has many disadvantages in clinical use, such as massive bleeding, difficult dose control, poor antithrombotic effect and so on. After degrading heparin sodium into dalteparin sodium and other low-molecular-weight heparin sodium, with the decrease of molecular weight, the anticoagulant potency is also reduced, and the antithrombotic performance is improved, so that low-molecular-weight heparin sodium such ...

AI Technical Summary

Problems solved by technology

[0008] It can be clearly seen from Table 1 that using a lower concentration of sodium nitrite degradation products, the conversion ratio between 3000 and 8000 is obviously higher than that of <3000, but continue to increase the amount of sodium nitrite, and the proportion between 3000 and 8000 The increase slowed down significantly, and the proportion of <3000 increased significantly, so the degradation products formed after one-time degradation could not meet the requirements of the Pharmacopoeia, and the molecular weight must be modified by column chromatography, ultrafiltration, etc. to remove <3000 and ≥8000 molecular weight fragments, only by increasing the ratio of 3000~8000 can a more reasonable product be formed