Views:0 Author:Site Editor Publish Time: 2021-05-19 Origin:Site
Butylphthalide (NBP) can increase the levels of nitric oxide (no) and prostaglandin (PGI2) in cerebral vascular endothelium, reduce the vascular resistance of internal carotid artery, increase its blood flow, promote the increase of the number of microvessels around the infarcted area, and significantly improve the microcirculation and blood flow of cerebral ischemic area; In addition, it can also improve mitochondrial membrane fluidity, restore mitochondrial membrane potential, increase mitochondrial ATPase activity, increase mitochondrial respiratory chain complex enzyme IV activity, improve antioxidant enzyme activity, protect mitochondria and reduce neuronal apoptosis.
Butylphthalide preparation is clinically used for acute ischemic stroke, but it is almost insoluble in water, and its solubility will affect the bioavailability in vivo, thus limiting its clinical application. Sulfobutyl beta cyclodextrin sodium is a more water-soluble pharmaceutical excipient than hydroxypropyl beta cyclodextrin, less nephrotoxicity and safer for injection. The solubility of butylphthalide can be effectively improved and the safety of injection can be improved by wrapping butylphthalide in sodium sulfobutylphthalide cyclodextrin.
In order to obtain a stable preparation process of butylphthalide sulfobutyl beta cyclodextrin sodium inclusion complex, central composite design response surface methodology was used to optimize the inclusion process. As a new pharmaceutical excipient, sulfobutyl betacyclodextrin sodium has incomparable advantages over other cyclodextrin derivatives: good water solubility, low binding rate of plasma protein, no association in vivo, and rapid prototype clearance; The hemolysis is reduced, the nephrotoxicity is very low, and the irritation to mucous membrane is also small. Sulfobutyl beta cyclodextrin sodium used for injection can improve the solubility of drug, make the drug quickly reach the required dosage during injection, reduce the irritation of injection to the drug delivery site, improve the stability of drug in solution state, alleviate the hemolysis effect, and improve the safety of drug use. The successful preparation of butylphthalide sulfonated butylbetacyclodextrin sodium inclusion complex provides the basis for the development of butylphthalide preparation.