SOLVENT FREE PROTEIN COMMINUTION

在过去的十年里，药物控制释放系统受到了越来越多的关注和应用，因为它们经常提供明显优于传统技术的给药方案。通过允许患者体内维持几乎恒定的药物水平，可以极大地提高治疗效果。在控释治疗药物的配方中，通常希望将材料分散成非常细小、均匀的颗粒。在蛋白质疗法中，这种细小颗粒的产生尤其成问题。现有的做法难以实现所需的粒度分布，使蛋白质暴露在热或空气等变性条件下，或留下残留的产品污染，这需要较少的加工。本提案的具体目的是开发一种避免上述困难的蛋白质粉碎工艺。建议的工艺使用无毒的液化气、压缩气体或临界流体(其性质介于气体和液体之间)来形成小的(L-5微米)单分散蛋白质颗粒，而无需首先将材料溶解在液体溶剂中。产品材料应保持全部活性，不含残留的加工化学品，如溶剂、盐或表面活性剂。拟议的商业应用：拟议的工艺可以提高治疗产品的疗效，减少残留污染，从而使制药和生物技术行业受益，该技术可用于在药物制造中获得所需的颗粒尺寸，也可用于微球或气雾剂输送系统等控释制剂。

Controlled release systems for drugs have received increased attention and application over the past decade, as they frequently provide a dosing regimen significantly superior to conventional techniques. By allowing a near constant level of drug to be maintained within the patient, treatment efficacy can be greatly improved. In the formulation of controlled release therapeutics, it is frequently desirable to disperse the material into very fine, uniform particles. With proteinaceous therapeutics, the generation of such fine particles is particularly problematic. Existing practices have difficulty achieving the desired particle size distribution, expose the protein to denaturing conditions such as heat or air, or leave residual product contamination, which necessitates fewer processing. The specific aim of the present proposal is to develop a protein comminution process that avoids the aforementioned difficulties. The proposed process uses nontoxic liquefied gases, compressed gases, or critical fluids (which have properties intermediate to gases and liquids) to form small (l-5 mu m), monodisperse protein particles 'without first dissolving the material in a liquid solvent. The product material is expected to retain full activity and be devoid of residual processing chemicals such as solvents, salts, or surfactants. PROPOSED COMMERCIAL APPLICATIONS: The proposed process can benefit the pharmaceutical and biotech industries by yielding improved efficacy of therapeutic products with less residual contamination, The technique can be useful in obtaining a desired particle size in drug manufacture, and may also prove useful in terms of controlled release formulations such as microspheres or aerosol delivery systems.