RESEARCH IN THE DEVELOPMENT OF DOSAGE FORMS OF NEW ANTITUMOR DRUGS

抗肿瘤新药剂型开发研究

• 批准号: 4692073
• 负责人: J C CRADOCK
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/4692073
• 关键词: alkylating agents; analgesics; anthracyclines; antiemetics; biological products; camptothecin; cannabinoids; dosage forms; drug administration routes; drug metabolism; drug vehicle; gas chromatography; heroin; high performance liquid chromatography; hydantoins; liposomes; neoplasm /cancer chemotherapy; neoplasm /cancer pharmacology; pharmacokinetics; prodrugs; quinones; radioimmunoassay; ultraviolet spectrometry

This project describes the activities of the formulation laboratory of the Pharmaceutical Resources Branch. These studies are directed toward resolving problems in the intravenous delivery of antitumor agents and involve methods to evaluate and then improve drug solubility and stability. Pharmaceutical aspects of the new platinum analogue, tetraplatin, were examined. Stability-indicating HPLC methods were devloped and applied to an evaluation of this compound under a variety of conditions and a freeze dried dosage form was developed. The safety of certain antitumor agents has been a topic of considerable concern to personnel involved with the handling and administration of these compounds. Procedures to decompose (two-three log reduction) fourteen compounds have been developed using simple procedures: base, hydrogen peroxide, and/or heat. These compounds represent most of the chemical categories of clinically active antitumor agents. Methods to improve drug solubility have also been evaluated. Several water soluble prodrugs of camptothecin have been prepared and evaluated in suitable tumor models. The N,N-diethyl glycine deriviative exhibited activity and potency similar to that demonstrated by camptothecin. Also the influence of the polymer, poly 1-methionine sulfoxide on the solubility of several antitumor agents was studied.

本项目描述了美国食品和药物管理局配方实验室的活动。 药物资源科。这些研究针对的是 解决抗肿瘤药物静脉给药中存在的问题及对策 涉及评估和改善药物溶解度的方法和 稳定性。新的铂类似物的药学方面， 四铂，进行了检查。指示稳定性的高效液相色谱方法是 开发并应用于该化合物在各种条件下的评价 并开发了冻干剂型。 某些抗肿瘤药物的安全性一直是一个相当重要的话题 对参与处理和管理这些问题的人员的关注 化合物。程序分解(二三对数化)十四 使用简单的程序开发了化合物：碱、氢 过氧化氢，和/或加热。这些化合物代表了大多数化学物质 临床活性抗肿瘤药物的分类。 并对提高药物溶解度的方法进行了评价。几杯水 喜树碱可溶前药的制备和评价 合适的肿瘤模型。N，N-二乙基甘氨酸衍生物展示 活性和效力与喜树碱相似。也是 聚合物聚1-甲硫氨酸亚砜对溶解度的影响 对几种抗肿瘤药物进行了比较研究。