基于未变性胶原生物表面活性剂的可控制备及性能研究

The native collagen, because of its excellent bioactivity and being used in many fields such as medicine and cosmetics, has been more and more important. However, the undenatured collagen extracted from animal tissue exists stably only under the acidic condition, limiting its application under physiological conditions.Therefore, the chemical modification on the side chains of native collagen has become significant. In order to improve the thermal stability and the resistance to enzyme, the study on modifying collagen is mainly based on chemical crosslinking around the world. This project aims at preparing a kind of biosurfactant, which is based on undenatured collagen by grafting and has the properties of good water-solubility and excellent emulsification, dispersion, solubilization and stabilization with drugs in the multiphase dispersing system. Hydrophobic long chain and hydrophilic short chain are introduced into the amino groups of the side chains of collagen without changing the collagen natural structure and biological activities. By graft modification,the influences of different grafting conditions on the structure, biological properties and surface activity of collagen-based biosurfactant is obtained. Also, the controlled method and principle of preparing the undenatured collagen-based surfactant, which has surface activity as well as biological activities, is established. Consequently, a scientific basis can be provided for the use of natural collagen in biological and other fields.

未变性天然胶原因具有优良的生物学活性用于医药、美容护肤等领域已受日益重视。从动物组织提取得到的未变性胶原只能在酸性条件下稳定存在，使其在生理条件下的应用受到局限，因而对未变性胶原侧链修饰化学改性研究意义重大。目前国内外针对胶原的化学改性研究主要基于化学交联改性以提高天然胶原的热稳定性和耐酶降解性能，为了赋予胶原良好的水溶性和在多相分散体系中对药物等能具有乳化、分散、增溶、保护稳定等作用，本项目拟通过接枝改性制备未变性胶原基表面活性剂。在不改变胶原螺旋结构和生物活性的前提下，在胶原侧链氨基处引入疏水长链和亲水短链，研究接枝改性与胶原基表面活性剂的结构、胶原生物学性质以及表面活性性能之间的关系，获得不同接枝改性条件对天然胶原表面活性剂的结构与胶原生物活性的影响规律，建立同时具有表面活性和生物活性的未变性胶原生物表面活性剂的可控制备方法和原理，为天然胶原更好地应用于生物医药等领域提供科学依据。

通过研究进一步优化得到月桂酸酐的制备工艺，将月桂酸酐作为疏水长链，丁二酸酐作为亲水短链接枝改性未变性胶原，获得不同接枝改性条件对天然胶原表面活性剂的结构与胶原生物活性的影响规律。通过调控加入的疏水长链（月桂酸酐、月桂酰氯或月桂醛）和亲水短链（丁二酸酐）的配比达到人为调控胶原表面活性剂表面活性的性能，获得接枝改性天然胶原表面活性剂的可控制备方法和原理。项目按上述计划执行完成了申报书中的所有研究内容。本项目通过接枝改性制备了未变性胶原基表面活性剂，在不改变胶原螺旋结构和生物活性的前提下，在胶原侧链氨基处引入疏水长链和亲水短链，研究不同疏水长链接枝改性方法、疏水长链和亲水短链的接枝比等因素与胶原基表面活性剂的结构、胶原生物学性质以及表面活性性能之间的关系，找到了不同接枝改性条件与天然胶原表面活性剂的结构、胶原生物活性之间的关系，得到了同时具有表面活性和生物活性的未变性胶原生物表面活性剂的可控制备方法。该研究结果为天然胶原用于美容护肤增强与油相的混溶或作为药物载体用于生物医药等领域提供了科学依据。. 在本项目执行期间，共发表学术论文35篇，其中SCI收录论文24篇，EI收录论文4篇，北大中文核心期刊4篇，其它杂志3篇。参加国际学术会议发表论文1篇，出版学术专著1部，授权中国发明专利3项。此外，培养博士研究生毕业6人，硕士研究生毕业10人。