SOLID SITOSTANOL FORMULATIONS INHIBIT CHOLESTEROL UPTAKE

植物甾醇，如谷甾醇，通过抑制人体从小肠吸收胆固醇来降低人体血清胆固醇水平。尽管谷甾醇毒性最小，本身不被吸收，但以前使用这种植物甾醇降低胆固醇的尝试因其在水和食用油中的低溶解度而变得复杂。使用一种创新的质谱学方法取代传统的长期临床试验，一种新的谷甾醇水溶液配方已被证明可将人类对胆固醇的吸收减少37%。重要的是，只需300毫克的谷甾醇就能实现这一点，这一数量比之前报道的有效剂量少了5-10倍。为了开发一种商业制剂的成分和剂量大小，本研究将通过质谱学评估各种固体谷甾醇制剂作为人类胆固醇吸收的抑制剂。这里描述的工作将产生一种灵活的固体配方，可以用在片剂中作为膳食补充剂或作为食品成分的固体添加剂。这种制剂的多功能性和公认的谷甾醇安全性将为血清胆固醇轻度升高的患者提供更好的治疗方法，而这一群体目前还没有得到传统药物的治疗。拟议的商业应用：植物类固醇可以作为胆固醇吸收的抑制剂，因为它们是安全和耐受性很好的。这项建议描述了制备可用作膳食补充剂或食品配料的固体谷甾醇配方的研究。

Plant sterols, such as sitostanol, lower the level of human serum cholesterol by inhibiting its absorption from the small intestine. Even though sitostanol has minimal toxicity and is not absorbed itself, previous attempts to use this plant stanol for cholesterol lowering have been complicated by its low solubility in water and dietary oils. Using an innovative mass spectrometry method to replace conventional long-term clinical trials, a new aqueous sitostanol formulation has been shown to reduce human cholesterol absorption by 37%. Importantly, this was achieved with only 300 mg of sitostanol, an amount that is 5- to 10-fold less than that previously reported to be effective. In order to develop a composition and dose size for a commercial preparation, this study will evaluate by mass spectrometry various solid sitostanol formulations as inhibitors of human cholesterol absorption. The work described here will produce a flexible solid formulation that can be used in a tablet for a dietary supplement or as a solid additive for a food ingredient. The versatility of this formulation and the acknowledged safety of sitostanol will provide better therapy for individuals with mildly elevated serum cholesterol, a group that is currently not served by conventional pharmaceuticals. PROPOSED COMMERCIAL APPLICATIONS: Plant sterols can serve as cholesterol absorption inhibitors since they are safe and well tolerated. This proposal describes studies to prepare a solid sitostanol formulation that can be used as a dietary supplement or as a food ingredient.