Claims for Patent: 11,566,000

Summary for Patent: 11,566,000

Title:	Crystalline form of sofpironium bromide and preparation method thereof
Abstract:	A cocrystal containing the 1′R-diastereomer and the 1'S-diastereomer of sofpironium bromide at a ratio of 1:3 (Form CO), a crystal mixture (for example, Form B) containing Form CO and a crystalline form of the 1′R-diastereomer (Form MN), and a method for preparing sofpironium bromide, which is suitable for manufacture of the crystal mixture are provided. Form CO and a crystalline form of sofpironium bromide containing Form CO (for example, Form B) have superior stability without hygroscopic property, and accordingly they can be preferably used as a raw material of medicaments.
Inventor(s):	Kazuyoshi MARUBAYASHI, Masahito Watanabe, Herbert R. Brinkman
Assignee:	Kaken Pharmaceutical Co Ltd, Botanix Sb Inc
Application Number:	US17/105,376
Patent Claims:	1. A stable co-crystal Form CO of sofpironium bromide, said co-crystal Form CO comprising in a 1:3 ratio: a) a compound shown as formula I-a and b) a compound shown as formula I-b wherein the purity of co-crystal Form CO is not less than 98% w/w based on the content of the compound (I), represented by the formula (I) wherein said co-crystal Form CO is physicochemically stable and non-hygroscopic, exhibits a single sharp endothermic peak value of 150° C. using Differential Scanning Calorimetry thermal analysis method as described in Japanese Pharmacopoeia (17th Edition), and is characterized as showing peaks at 5.9±0.2, 7.6±0.2, 11.0±0.2, and 22.2±0.2 degrees as diffraction angles 2θ in a powder X-ray diffraction spectrum. 2. The co-crystal Form CO of claim 1, wherein a content of each compound represented by formulae III, IV and V is not more than 0.5% w/w based on a content of the compound (I), wherein the compound (I) is represented by the formula (I) 3. The co-crystal Form CO of claim 1, wherein the total content of impurities is not more than 2.0% w/w based on a content of the compound (I), wherein the compound (I) is represented by the formula (I) 4. A stable topical pharmaceutical composition which is made by mixing: a pharmaceutically effective amount of sofpironium bromide co-crystal Form CO according to claim 1, and a pharmaceutically acceptable carrier. 5. The topical composition of claim 4 wherein the active pharmaceutical agent co-crystal Form CO is prepared by the steps of: preparing a suspension of sofpironium bromide in a solvent comprising ethyl acetate and methyl t-butyl ether, and stirring the suspension for at least 1 hour, and filtering the suspension to obtain the crystalline form of the active pharmaceutical agent.