Collagen Gel Delivery System for The Percutaneous Application of Prostaglandins

• Main Author: 林倫輝
• Other Authors: 許明照
• Format: Others
• Language: zh-TW
• Published: 1995
• Online Access: http://ndltd.ncl.edu.tw/handle/07266140394326746987

碩士 === 台北醫學大學 === 藥學研究所 === 83 === Natural polymer oftelopeptide-poor collagen by the treatment of pepsin is low antigenic, biocompatible, biodegradable and is less toxic than synthetic polymers. With the possible formation of inter- and intra-molecular crosslinkmgs during purification and reconstituted process, the properties of collagen usually were found to be poorly reproducible. After a system survey of reported methods of purification used by various labs, a detailed examination of how digestion medium and its temperature, the ratio of collagen to pepsin, and the freeze-drying conditions affecting the properties of collagen was initiated. The morphological characteristics examined by scanning electron microscopy reveals that fibril collagen, porous fibril membrane or dense membrane is all possible formed dependent on the pretreatment and freeze-drying conditions. The helical structure (α, β, γ) , the content of monomers and oligomers in each collagen sample obtained by various conditions were analyzed by the SDS-PAGE electrophoresis and size exclusion HPLC. Both methods show that the collagen sample obtained by the pretreatment with pepsin under pH 2.5 HCl solution and freeze-drying in 0.5 M acetic acid give less oligomers. Its fibril characters and easy hydration also expresses that the method to obtain this collagen sample is the best choice for the purification. Transdermal delivery system for prostaglandin (PGE1) to achieve therapeutic effect has less been one of major research nowadays. But the chemical instability and low penetration rate limit the clinical application. Therefore, a methylester derivative of PGE1 with more lipophilic character to enhance the penetration rate would be valuable. In this study, in vitro transdermal delivery on hairless mouse skin of PGE1 and its methylester from buffer solution with various content of alcohol was investigated. In the initial stability studies, it was found that PGE1 methylester was mainly degraded to PGA1 methylester and then PGB1 methylester, but the hydrolysis of methylester to PGE1 was minor. During penetration, it was found that PGE1 methylester was converted to PGE1 in the skin. There showed a maximal penetration rate for PGE1 methylester from buffer solution with 40 % alcohol content. PGE1 methylester also penetrate faster than that PGE1 from all three alcohol content examined. When 1 % collagen was used as gelling agent, PGE1 methylester still shows a similar pattern of penetration but with a slower penetration rate.