SOLVENT FREE PROTEIN COMMINUTION

药物控释系统在过去十年中受到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。通过使患者体内的药物水平保持在接近恒定的水平，可以大大提高治疗效果。在控释治疗制剂中，通常需要将物质分散成非常细小、均匀的颗粒。在蛋白质疗法中，这种细颗粒的产生尤其成问题。现有的方法难以达到期望的粒度分布，将蛋白质暴露在变性条件下，如热或空气，或留下残留的产品污染，这需要较少的处理。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过程。该工艺使用无毒的液化气体、压缩气体或临界流体（具有介于气体和液体之间的特性）来形成小的（l-5 μ m）、单分散的蛋白质颗粒，而无需先将材料溶解在液体溶剂中。期望产品材料保持充分的活性，并且没有残留的加工化学品，如溶剂、盐或表面活性剂。拟议的商业应用：拟议的工艺可以通过产生更少残留污染的治疗产品来提高疗效，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大小，也可用于控释制剂，如微球或气溶胶输送系统。

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.