Nikolaeva Ludmila, Oborotova Natalia, Bunyatyan Natalia, Zhang Xi, Sanarova Ekaterina, Lantsova Anna, Orlova Olga, Polozkova Alevtina
Ministry of Health of Russian Federation, I.M. Sechenov First Moscow State Medical University, Moscow 119991, Russia.
Ministry of Health of Russian Federation, Federal State Budgetary Scientific Institution, N.N. Blokhin Russian Cancer Research Center, Moscow 115478, Russia.
Pharmaceuticals (Basel). 2016 Nov 1;9(4):68. doi: 10.3390/ph9040068.
Despite the rapid development of medical technologies, chemotherapy treatment still occupies an important place in clinical oncology. In this regard, the current research in this area focuses on the synthesis of new highly effective antitumor substances that have minimal side effects and the development of stable pharmaceutical formulations (PF) on their basis. In order to solve this problem, the I. Ya. Postovsky Institute of Organic Synthesis of the Ural Branch of the Russian Academy of Sciences actively sought for original substances, namely, nitrosourea (NU) derivatives, one of the most promising classes of anticancer drugs. As a result of this research, a novel NU derivative was synthesized, namely ormustine, which showed high antitumor activity in preliminary preclinical trials. It is now crucial to develop an ormustine pharmaceutical formulation. Conducted technological studies showed that the most suitable solvent for the drug substance is 0.1 M hydrochloric acid, which ensures its rapid dissolution by ultrasonic treatment. A significant reduction in the concentration of the active ingredient during the storage of the solution required the development of a technique of its lyophilization and the selection of a shaper such as a Kollidon 17 PF. Upon completion of the development of a pharmaceutical formulation of ormustine, its stability after lyophilization was demonstrated, and a sufficient amount of the drug has been acquired for preclinical research.
尽管医学技术迅速发展，但化疗在临床肿瘤学中仍占据重要地位。在这方面，该领域目前的研究集中在合成副作用最小的新型高效抗肿瘤物质，并在此基础上开发稳定的药物制剂（PF）。为了解决这个问题，俄罗斯科学院乌拉尔分院I. Ya. 波斯托夫斯基有机合成研究所积极寻找原始物质，即亚硝基脲（NU）衍生物，这是最有前景的抗癌药物类别之一。这项研究的结果是合成了一种新型NU衍生物，即奥氮芥，它在初步临床前试验中显示出高抗肿瘤活性。现在开发奥氮芥药物制剂至关重要。进行的工艺研究表明，最适合该药物的溶剂是0.1 M盐酸，通过超声处理可确保其快速溶解。溶液储存期间活性成分浓度的显著降低要求开发其冻干技术并选择如聚乙烯吡咯烷酮17 PF这样的成型剂。奥氮芥药物制剂开发完成后，证明了其冻干后的稳定性，并获得了足够量的药物用于临床前研究。
