PSEUDOPOLIMORPHIC FORM OF DESLORATADINE WITH CARBON DIOXIDE, PROCESS FOR ITS PREPARATION , ITS USE AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME

摘要

#CMT# #/CMT# Pseudopolymorph of a desloratadine compound (I) formed with carbon dioxide, is new. #CMT# : #/CMT# Pseudopolymorph of a desloratadine compound of formula (I) formed with carbon dioxide (1/2CO 2) exhibiting X-ray diffraction peaks (having a angle of 2-theta value from 9.38 to 33.01 corresponding d value angstrom from 9.4201 to 2.7114, intensity(Cps) value from 369 to 22.9 and intensity(%) value from 100 to 6.2) and their relative intensities (great than 5%) of the X-ray diffractogram of the desloratadine 1/2 CO 2and exhibiting IR spectrum values (wave number vs % of transmittance) at e.g. 1300, 1400, 1500, 2800 and 2900 cm -1>, is new. Independent claims are also included for: (1) the preparation of (I); (2) preparation of salts of desloratadine compound of formula (VI) (where X is anion; and n is 1-2) comprises reacting the solution of (I) in an organic solvent with a solution of the corresponding acid formed with an organic solvent; (3) pharmaceutical composition comprising as active ingredient (I) in admixture with carriers and/or auxiliary agents; and (4) the preparation of pharmaceutical composition comprising admixing (I) with carriers and/or auxiliary agents. #CMT#[Image]#/CMT# #CMT#[Image]#/CMT# #CMT#ACTIVITY : #/CMT# Antiallergic. #CMT#MECHANISM OF ACTION : #/CMT# None given. #CMT#USE : #/CMT# (I) is useful as pharmaceutical ingredient (particularly an anti-allergic ingredient). (I) is useful for the treatment of allergy. (I) is useful for the preparation of salts of desloratadine (all claimed). No biological data given. #CMT#ADVANTAGE : #/CMT# (IV and VI) is prepared with high purity. #CMT#ORGANIC CHEMISTRY : #/CMT# Preparation (Claimed): Preparation of (I) comprises: (A) either reacting a decarbethoxylating loratadine compound of formula (V) with an alkali metal hydroxide in the presence of in 2-methoxyethanol or 2-ethoxyethanol to give a desloratadine compound of formula (IV); and (B) reacting (IV) with carbon dioxide in an organic solvent. Preferred Components: In step (b) is carried in an ester, ether, or a lower aliphatic alcohol and/or an ester, or an ether and/or a lower aliphatic alcohol (preferably ethyl acetate (preferred), tetrahydrofuran, diethyl ether, dioxane, or ethyl acetate and/or methanol, ethyl acetate and/or ethanol, tetrahydrofuran and/or methanol, tetrahydrofuran and/or ethanol, diethyl ether and/or ethanol, or diethyl ether and/or methanol. In step (b) comprises carbon dioxide or adding dry ice to a solution of (IV) formed with an organic solvent. In step (a) comprises distilling off the 2-methoxyethanol or 2-ethoxyethanol, dissolving the residue in an organic solvent and carbon dioxide or adding dry ice to the solution. In step (a) is carried in ethyl acetate as organic solvent. In the step of preparing of (I and VI) comprises carrying out the reaction at room temperature to 40 [deg]C (preferably room temperature). In step (a) removing the 2-methoxyethanol or 2-ethoxyethanol from the reaction mixture, dissolving the residue in an organic solvent and evaporating the solution. In step (a) is carried out the reaction under heating (preferably at the boiling point of solvent used). In the step of preparing (VI) comprises using hydrochloric acid, hydrobromic acid, sulfuric acid, methanesulfonic acid, benzenesulfonic acid, maleic acid or fumaric acid. In the step of preparing (VI): (where n is 1) comprises using the acid in an approximately equimolecular amount, related to (I); and (where n is 2) comprises using the acid in at least a molar ratio of 2:1 (preferably in a molar ratio of 2:1-3:1), related to (I). #CMT#[Image]#/CMT# #CMT#ADMINISTRATION : #/CMT# Administration of (I) is oral or parenteral. No dosage given. #CMT#EXAMPLE : #/CMT# Ethyl acetate (500 ml) were placed in a vessel equipped vigorous stirrer, then a solution of desloratadine (29 g) in ethanol (120 ml) was added drop wise during an hour. During the addition and the crystallization steps carbon dioxide developed from dry ice (20 g) was introduced continuously into the suspension. The reaction mixture was worked up to give pseudopolymorph of desloratadine with half mole of carbon dioxide (28.42 g, 92.5%).