A kind of sustained-release microsphere preparation of osteocalcin for injection

Abstract

The invention discloses an osteocalcin slow-release microsphere preparation for injection, which comprises osteocalcin, zinc sulfate and lactic acid-glycolic acid copolymer, wherein the weight ratio of the osteocalcin to the zinc sulfate to the lactic acid-glycolic acid copolymer is (5-30):(0.1-1):100. The preparation method of the osteocalcin slow-release microsphere preparation for injection comprises the following steps: 1) dissolving the osteocalcin and the zinc sulfate in water, and using as an in-water phase; 2) dissolving lactic acid-glycolic acid copolymer in dichloromethane, and using as an oil phase; 3) mixing the in-water phase and the oil phase, and stirring to obtain a primary emulsion; 4) adding the primary emulsion into a polyvinyl alcohol water solution while stirring, thus obtaining a compound emulsion; and 5) stirring the compound emulsion at room temperature for 5 hours, centrifuging, collecting microspheres, washing the microspheres with water for injection, and carrying out freeze-drying. The preparation disclosed by the invention has good stability, high drug-loading rate and high in-vivo safety, the envelopment rate can be controlled at 82-95%, and the preparation can not be subjected to degradation, aggregation and conformational change under accelerated test conditions. The tail intravenous injection to mice shows that the bioavailability of the slow-release microsphere preparation for injection can be up to 72-76%.

Description

technical field [0001] The invention relates to a pharmaceutical preparation of osteocalcin, in particular to a sustained-release microsphere preparation of osteocalcin for injection. Background technique [0002] Osteocalcin, also known as Bone-γ-caboxyglutamic acid containing protein (BGP) or Bone vitamin K depengt protein, is a non-proliferative osteoblast specifically synthesized and secreted. Collagen. [0003] In the past, it was believed that osteocalcin was closely related to osteoporosis, and its main function was to maintain the normal mineralization of bone and inhibit the activity of osteoblasts, leading to osteoporosis. Recent studies have shown that osteocalcin has a therapeutic effect on diabetes. The research and development of osteocalcin-related pharmacology and pharmaceutical preparations has become one of the hot spots in pharmaceutical research and development. [0004] Chinese patent publication CN101674839A (application number 200880014594.4, applic...

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Problems solved by technology

[0004] Chinese patent publication CN101674839A (application number 200880014594.4, application date March 5, 2008) discloses a method for extracting osteocalcin and related compositions, which include medicines, feeds, growth promoters and oral care compositions etc., but the composition of the extract is complex and difficult to purify, and the stability of osteocalcin in the pharmaceutical composition and the safety of human administration cannot be guaranteed

However, osteocalcin is a biomacromolecule substance with extremely poor stability. It is easy to degrade or undergo conformational changes to lose biological activity. It has low solubility and is difficult to make stable injection preparations. So far, there is no injection of osteocalcin. The preparation was successfully developed

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