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Shandong Binzhou Zhiyuan Biotechnology Co., Ltd.
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Propyl betaclodextrin is an ether derivative of betaclodextrin.The introduction of hydroxypropyl group opened the hydrogen bonds within the betacyclodextrin molecule, forming an amorphous mixture, greatly improving the water solubility, proving high safety, and even being used for intravenous injection.Therefore, it is considered as a potential substitute for maternal cyclodextrin.Betacyclodextrin reacts with epoxypropane under alkaline conditions. Under the catalysis of base, betacyclodextrin alkoxy anions attack the carbon atoms with the least substituents on the oxygen ring, where the steric hindrance is the least.Cyclodextrin and epoxypropane react easily to form 6 substituents in strong alkaline environment, and 2 substituents in weak alkaline condition.The hydroxyl groups at the 2, 3 and 6 sites are activated under strong alkaline conditions, and the steric resistance at the 6 sites is the least, and the substituents are easy to enter.Under the condition of weak alkalinity, the hydroxyl group in the 2 position is the most acidic and easy to be activated, so the 2 position is the main substitute.Cyclodextrins and their derivatives have long been thought to have rigid structures, an assumption that does not accord with their ability to form complex structures easily.The structure of cyclodextrins is relatively flexible. Experiments show that cyclodextrins are flexible not only in solution, but also in solid state through non-covalent bonding.The introduction of hydroxypropyl group opened the internal hydrogen bond of betacyclodextrin, making the framework flexible and the substituents have some room to move.This relatively flexible structure can better explain the improvement of its complex formation ability and its complex reaction kinetics.At present, shandong binzhou zhiyuan biotechnology co., ltd. is the largest manufacturer of cyclodextrin derivatives in China. The product quality is first-class in China and the product types are the most in the same industry.
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Shandong Binzhou Zhiyuan Biotechnology Co., Ltd.
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Pharmaceutical Intermediate: Hydroxypropyl-beta-cyclodextrin - HPBCD - News - Shandong Binzhou Zhiyuan Biotechnology Co.,Ltd
Hydroxypropyl-beta-cyclodextrin is an ether derivative of beta-cyclodextrin. The introduction of hydroxypropyl groups opens the hydrogen bonds in the beta-cyclodextrin molecule, forming an amorphous mixture, which greatly improves the water solubility. It has been proved to be highly safe and can even be used for intravenous injection. Hydroxypropyl-beta-cyclodextrin is therefore considered to be a potential alternative to the parent cyclodextrin. The cyclodextrin is condensed with propylene oxide under alkaline conditions. Under the base catalysis, the cyclodextrin alkoxy anion attacks the carbon atom with the least substituent on the oxygen ring, and the steric hindrance is the smallest. Cyclodextrin and propylene oxide react easily in a strong alkaline environment to form a 6-substituent, and under weak alkaline conditions, a 2-substituent is easily formed. The hydroxyl groups at positions 2, 3, and 6 are activated under strong alkaline conditions, and the steric hindrance at the 6 position is the smallest, and the substituent is easily accessible. Under the weak alkaline condition, the hydroxyl group at the 2 position is the strongest and easy to activate, so the substitution is mainly in the 2 position. It has long been believed that the structure of cyclodextrin and its derivatives is rigid, a hypothesis that does not conform to the nature of the complexes they can easily form. Its structure is relatively flexible, and experiments have shown that cyclodextrin forms a complex by non-covalent bonding not only in solution, but also in a solid state. The introduction of hydroxypropyl opens the internal hydrogen bond of beta-cyclodextrin, making the backbone flexible and the substituents also have some activity space. This relatively flexible structure can better explain the improvement of the composite forming ability and the composite reaction kinetics.
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Shandong Binzhou Zhiyuan Biotechnology Co., Ltd.
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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.
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Pharma Sources Insight June 2024: Globalization on the Go
