PROCÉDÉ D'ÉLABORATION D'UNE PRÉPARATION SOLUBLE DE TERPÉNOÏDES TÉTRA- ET PENTACYCLIQUES INSOLUBLES DANS L'EAU, PRÉPARATION SOLUBLE D'UN TERPÉNOÏDE TÉTRA- OU PENTACYCLIQUE ET COMPOSITION PHARMACEUTIQUE CONTENANT CETTE PRÉPARATION SOLUBLE
Univerzita Karlova v Praze, Prírodovedecká fakulta;Univerzita palackeho V Olomouci;I.Q.A., A.S.
发明人:
申请号：
EP07801129.3
公开号：
EP2068882B1
申请日:
2007.09.25
申请国别(地区):
EP
年份:
2017
代理人:
摘要：
The invention relates to a method of preparation of a soluble formulation of water-insoluble pentacyclic and tetracyclic terpenoids, wherein the water-insoluble terpenoid having a free carboxylic, hydroxy or amino functional group is derivatized on this functional group with a substituent selected from the group comprising substituents of general formula Xa bound to the hydroxy group of the terpenoid, wherein Xa is -OC-R-COOH, substituents of general formula Xa bound to the amino group of the terpenoid, wherein Xa is -OC-R-COOH, quarternary ammonium substituents of general formula Xb bound to the carboxy group of the terpenoid, wherein Xb is -(CH2)nN+R3Y-, quarternary ammonium substituents of general formula Xc bound to the carboxy group of the terpenoid, wherein Xc je -(CH2)nR+Y-, substituents of general formula Xd bound to the carboxy group of the terpenoid, wherein Xd represents -R-COOH, glycosylic substituents Xe bound by alpha or beta glycosidic bond to the hydroxy group or to the carboxy group of the terpenoid, wherein Xe is selected from the group comprising glucosyl, galactosyl, arabinosyl, rhamnosyl, lactosyl, cellobiosyl, maltosyl and the 2-deoxyanalogues thereof, and subsequently, the prepared derivative is dissolved in the solution containing water, a cyclodextrin and optionally pharmaceutically acceptable auxiliary substances, forming an inclusion derivative with the cyclodextrin. Object of the invention is further a soluble formulation of a pentacyclic or tetracyclic triterpenoid, containing an inclusion complex of the derivatized pentacyclic or tetracyclic terpenoid with a cyclodextrin, and optionally water and pharmaceutically acceptable auxiliary substances and further a pharmaceutical composition containing the soluble formulation.
