Univerzita Karlova V Praze, Prirodovedecka Fakulta

Univerzita Palackeho V Olomouci

I.q.a., A.s.

Univerzita Palackeho V Olomouci and I.q.a., A.s.

Michal Svoboda

Marian Hajduch

Jan Sarek

Katerina Novakova

Tomas Kubelka

David Biedermann

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 &#x2014;OC&#x2014;R&#x2014;COOH, substituents of general formula Xa bound to the amino group of the terpenoid, wherein Xa is &#x2014;OC&#x2014;R&#x2014;COOH, quarternary ammonium substituents of general formula Xb bound to the carboxy group of the terpenoid, wherein Xb is &#x2014;(CH2)nN+R3Y&#x2014;, quarternary ammonium substituents of general formula Xc bound to the carboxy group of the terpenoid, wherein Xc je &#x2014;(CH2)nR+Y&#x2014;, substituents of general formula Xd bound to the carboxy group of the terpenoid, wherein Xd represents &#x2014;R&#x2014;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.

Method of preparation of a soluble formulation of water-insoluble pentacyclic and tetracyclic terpenoids, a soluble formulation of a pentacyclic or tetracyclic terpenoid and a pharmaceutical composition containing this soluble formulation

The invention relates to a method of preparation and isolation of betulin diacetate from birch bark from paper mills and its optional processing to betulin, wherein the birch bark is ground, mixed with two- to twenty-fold excess volume of water and is stirred so that all birch bark is dipped, then the fraction of the birch bark which floats on the surface is collected, said collected fraction is dried at the temperature in the range of from 50 to 85&#xb0; C. and the betulin contained in the dried birch bark is then subjected to an acetylation reaction, after the acetylation the birch bark is dried at the temperature of from 50 to 100&#xb0; C. and the formed betulin diacetate is then isolated from the birch bark by supercritical extraction of the birch bark with carbon dioxide at the pressure of 28-35 MPa and the temperature of from 50 to 100&#xb0; C. and subsequently, the supercritical extract is recrystallized for direct use or for further processing. The further processing can be basic hydrolysis of the re-crystallized betulin diacetate to betulin.

Method of preparation and isolation of betulin diacetate from birch bark from paper mills and its optical processing to betulin

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Praha, Czechia

Michal Svoboda