Sulfobutyl beta cyclodextrin sodium for injection in Temozolomide

Gliomas originate from the ectoderm and are the most common primary tumors of the nervous system, accounting for more than 50% of intracranial primary tumors. Although surgical treatment has significantly improved the survival of patients with glioma, drug therapy is still one of the important means for the treatment of glioma because of the difficulty in radical treatment. According to the 2012 NCCN guidelines, chemotherapy should be adopted except for low-grade, complete resection of gliomas without high-risk factors. Temozolamide, as a new imidazolium tetrazine alkylating agent, easily enters the blood-brain barrier, and its concentration in brain tissue can reach 30%-40% of the blood concentration. It has been widely used in the chemotherapy of central nervous system tumors, especially malignant glioma, and has become a "milestone" in the progress of glioma chemotherapy. It has become a first-line chemotherapeutic drug for malignant glioma. Temozolamide has low solubility (about 3mg/ml) and poor stability in aqueous solution, which makes it difficult to develop intravenous injection. The original research company disclosed a pharmaceutical preparation in the patent CN 03804363. The technical scheme has successfully realized the solubilization of temozolomide in aqueous solution and made intravenous injection possible. However, there are some problems, such as slow dissolution rate and re-dissolution rate, long time of liquid mixing and re-dissolution, and high impurity content, which cause potential safety hazards to patients. Because of the high content of impurities, the appearance of the original developer is light pink powder, while the low content of impurities in Temozolomide freeze-dried powder is white powder. In addition, crystallization is easy to precipitate in the process of liquid mixing. If the temporary storage time of solution exceeds 8 hours, it needs to be filtered again, which brings great trouble to GMP production. The present invention uses glycine and sulfobutyl beta cyclodextrin sodium as solvents, which can remarkably improve the dissolution rate without adding organic solvent, reduce the time of temozolomide existing in solution state in industrial production, and reduce the level of related substances. At the same time, the resolving speed and stability during storage can be improved.