首页> 外国专利> HIGHLY STABLE COMPOSITIONS OF ORALLY ACTIVE NUCLEOTIDE ANALOGUES OR ORALLY ACTIVE NUCLEOTIDE ANALOGUE PRODRUGS

HIGHLY STABLE COMPOSITIONS OF ORALLY ACTIVE NUCLEOTIDE ANALOGUES OR ORALLY ACTIVE NUCLEOTIDE ANALOGUE PRODRUGS

机译:口服活性核苷酸类似物或口服活性核苷酸类似物的高度稳定的组成

摘要

Disclosed are highly stable compositions having outstanding storage stability and/or demonstrating exceptional resistance to aqueous degradation, the composition including an orally active nucleotide analogue or an orally active nucleotide analogue prodrug, which is orally bioavailable, such as adefovir dipivoxil and tenofovir disoproxil. In particular molecular dispersions of adefovir dipivoxil in copovidone are disclosed. For example, when a composition of the invention is stored for 1 month or for 18 months at 25 ° C and 60% relative humidity, its orally active nucleotide analogue or orally active nucleotide analogue prodrug degrades to provide a composition containing no more than 0. 2% or no more than 0. 7% by weight of a less orally bioavailable impurity, respectively. Also disclosed are a container/closure package system including the composition and a package insert and methods of manufacturing the composition and treating a patient for a disease or condition, for example, a viral disease or cancer, with the use of the composition.
机译:公开了具有优异的储存稳定性和/或表现出优异的抗水降解性的高度稳定的组合物,该组合物包括可口服生物利用的口服活性核苷酸类似物或口服活性核苷酸类似物前药,例如阿德福韦酯和替诺福韦二甲酚。特别地,公开了阿德福韦酯在共聚维酮中的分子分散体。例如,当本发明的组合物在25°C和60%相对湿度下保存1个月或18个月时,其口服活性核苷酸类似物或口服活性核苷酸类似物前药会降解以提供不超过0的组合物。 2%或不超过0. 7%(按重量计)的口服生物利用度较低的杂质。还公开了一种包括组合物和包装插页的容器/密闭包装系统,以及使用该组合物制造该组合物并治疗患者的疾病或病症例如病毒性疾病或癌症的方法。

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