INJECTABLE CALCIUM SULFATE MICROSPHERES FOR PROTEINS

Biotek开发了一种新工艺，使用硫酸钙制造可注射的可生物降解的微球和微胶囊，非常适合于多肽和蛋白质等水溶性药物的仓库输送。初步测试表明，丁酰胆碱酯酶可以活性形式结合和释放，最近的改进使高产率地常规制备可注射的75-100微米微球成为可能。拟议的第一阶段工作将研究成分、加工、装载和疏水处理的变化对溶解和释放的影响。第一阶段的重点将是阐明保持和释放蛋白质的机制，该计划包括基于两种技术的微球内蛋白质分布的研究：银染结合能量色散X射线光谱和受控表面磨损结合去除材料的蛋白质分析。第二阶段将使用第一阶段的数据来开发用于人类生长激素等药用蛋白质的可注射微球库，然后将通过展示重复性、原型制造、质量评估、稳定性测试、IND提交和初步的人类临床研究来进行产品开发。拟议的商业应用：新的多孔硫酸钙微球旨在最终开发成通用蛋白库输送系统，在该系统中，空的微球可以在一个设施中制造，然后分发到其他设施，使用不太可能导致变性或活性丧失的温和加工条件装载专利蛋白药物。

BIOTEK has developed a new process which uses calcium sulfate to make injectable biodegradable microspheres and microcapsules well suited for depot delivery of water soluble drugs such as peptides and proteins. Preliminary testing has shown that butyrylcholinesterase can be incorporated and released in active form, and recent improvements have made possible routine preparation of injectable 75 - 100 microm microspheres in high yield. The proposed Phase I work will study the effect of variations in composition, processing, loading and hydrophobic treatment on dissolution and delivery. The emphasis in Phase I will be on elucidating the mechanisms by which protein is held and released, and the program includes a study of protein distribution inside microspheres based on two techniques: silver staining combined with Energy Dispersive X- Ray Spectroscopy and controlled surface abrasion combined with protein analysis of the removal material. Phase II will use the data from Phase I to develop an injectable microsphere depot for a medicinal protein such as human growth hormone and will then pursue product development through demonstration of reproducibility, prototype manufacturing, quality assessment, stability testing, IND submission, and an initial human clinical study. PROPOSED COMMERCIAL APPLICATION: The new porous calcium sulfate microspheres are intended for eventual development into a generic protein depot delivery system in which empty microspheres could be manufactured at one facility and then distribute to other facilities for loading with proprietary protein drugs using mild processing conditions unlikely to lead to denaturation or loss of activity.