Preparation Of NTCD Acid-CTS Complex And Solid Dispersion

Objective: To prepare the complex and solid dispersion(SD) of norcantharidin acid and chitosan, in order to obtain a new compound with lesser acute toxicity than norcantharidin; to prepare the sodium salt of 11-Deoxyglycyrrhetinic acid so as to lower its side effects and enhance its water-solublity.Methods: The chitosan samples with high degree of deacetylation were prepared by intermittent alkaline hydrolysis,then norcantharidin in acid solution was heated to form norcantharidin acid by means of acid hydrolysis,subsequently,the acid reacted with chitosan in alcohol-water system to obtain the complex; on the other hand, norcantharidin acid and chitosan were dissolved in 1% acetic acid aqueous solution.These solutions were spray dried to obtain solid dispersions, on the other hand, they were mixed and then formed physical mixtures by grinding method.The Physicochemical properties of the solid dispersions and physical mixtures obtained were investigated by FT-IR analysis,powder X-ray diffraction,differential scanning calorimetry,etc. The acute toxicity of mice treated with vena caudalis injection and gavage was observed between the SD and norcantharidin.The median lethal dose (LD50) was calculated by Bliss software;11-Deoxyglycyrrhetinic acid is obtained through Clemmensen reaction so as to reduce side effects of glycyrrhetinic acid, and then the corresponding sodium salts were obtained by the simple method.Results: When treated with gavage and vena caudalis injection, LD50 of SD is 3.80 times and 10.33 times of that of norcantharidin. The water solubility and absorbability of Glycyrrhetinic acid was increased to a certain extent by structural modification of water-soluble sodium salt,and the pharmacological actions could be improved accordingly. the better anti-inflammatory effect may correlate with the ability to inhibit the synthesis of PEG2 and NO as well as anti-lipid peroxidationConclusion: The spray drying method could make the drug utterly dispersed.The ultimate products can not only increase the water-solubility, but also reduce side effects, and enhance the curative effect.