Method of preparation of a soluble formulation of water-insoluble pentacyclic and tetracyclic terpeniods, a soluble formulation of a pentacyclic or tetracyclic terpenoid and a pharmaceutical composition containing this soluble formulation
Abstract
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 fonnula Xa bound to the hydroxy group of the terpenoid, wherein Xa is -DC-R--COOH, substituents of general formula Xa bound to the amino group of the terpenoid, wherein Xa is -DC-R--COOH, quarternary ammonium substituents of general fonnula Xb bound to the carboxy group of the terpenoid, whereinXb 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 fonnula 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, rhanmosyl, lactosyl, cellobiosyl, maltosyl and the 2-deoxyanalogues thereof, and subsequently, the prepared derivative is dissolved in the solution containing water, a cyclodextrin and optionally phannaceutically acceptable auxiliary substances, fonning an inclusion derivative with the cyclodextrin. Object of the invention is filrther a soluble fonnulation 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 phannaceutical composition containing the soluble fornlUlation.