盐酸多奈哌齐的多晶型物及其制备方法

摘要

提供了以四种多晶型物形式的盐酸多奈哌齐、即盐酸1－苄基－4－[(5,6－二甲氧基－1－二氢茚酮)－2－基]甲基－哌啶,该多晶型物在药物用途中对热和潮湿是稳定的。它们可用工业方法制备。它们是由X射线粉末衍射图案中的峰和在溴化钾中的红外吸收光谱中的吸收峰来规定的。

主权项

1．盐酸多奈哌齐，即盐酸1-苄基-4-[(5,6-二甲氧基-1-二氢茚酮)-2- 基]甲基-哌啶，以选自由(Ⅰ)、(Ⅱ)、(Ⅲ)和(Ⅳ)组成的组的多晶型物形式 存在，每种多晶型物是由粉末X射线衍射图案中在如下所示衍射度下 因如下以I/I₀表示的强度而得到的峰以及在溴化钾中的红外吸收光谱 中如下所示以厘米倒数表示的吸收峰来规定的： (1)多晶型物(Ⅰ) 粉末X射线衍射图案中的峰为： 衍射角度强度 (2θ,°)(I/I₀) 9.9424 10.6019 12.6669 13.1255 13.6644 13.8640 14.9249 15.2617 16.0835 16.8634 17.5034 17.5842 18.4220 19.2827 19.8045 19.9445 21.22100 22.0032 22.5431 22.9849 23.6056 23.7875 23.9278 26.4633 28.0225 29.5037. 溴化钾中的红外吸收光谱波数(cm^-1)为： 463,502,563,589,604,701,750,759,799,860,922,947,972, 1012,1038,1104,1120,1128,1175,1192,1218,1250,1267,1316, 1368,1410,1433,1440,1455,1472,1502,1591,1606,1644,1684, 2412,2530,2559,2595,2620,2717,2840,2858,2924,3004,3074, 3259,3373,3547,3589cm^-1. (2)多晶型物(Ⅱ) 粉末X射线衍射图案中的峰为： 衍射角度强度 (2θ,°)(I/I₀) 7.408 9.88100 12.3613 15.5440 16.1038 16.2238 16.4835 17.3017 18.0420 18.4417 18.8419 19.3419 19.8447 21.1624 22.4019 23.1833 24.0222 24.9225 25.7227 26.4018 27.2214 溴化钾中的红外吸收光谱波数(cm^-1)为： 699,748,762,845,947,1009,1035,1067,1103,1118,1129,1174, 1193,1206,1222,1247,1267,1317,1365,1422,1436,1456,1465, 1502,1592,1607,1688,2412,2489,2627,2846,2868,2913,2928, 3435cm^-1. (3)多晶型物(Ⅲ) 粉末X射线衍射图案中的峰为： 衍射角度强度 (2θ,°)(I/I₀) 6.5630 9.948 13.0017 15.0047 15.2614 15.746 16.4835 17.424 18.1021 18.5056 19.5017 20.1032 20.9421 21.66100 22.3225 22.9217 23.9219 24.6817 26.0044 27.2023 28.0229 28.2240 28.6013. 溴化钾中的红外吸收光谱波数(cm^-1)为： 559,641,648,702,749,765,786,807,851,872,927,949,966, 975,982,1007,1034,1071,1080,1111,1119,1131,1177,1190, 1205,1217,1230,1250,1265,1292,1313,1367,1389,1420,1438, 1453,1461,1470,1500,1589,1605,1697,2407,2419,2461,2624, 2641,2651,2667,2837,2848,2873,2924,2954,2961,2993,3007, 3377,3433cm^-1. (4)多晶型物(Ⅳ) 粉末X射线衍射图案中的峰为： 衍射角度强度 (2θ,°)(I/I₀) 6.2415 9.6612 11.0422 12.1224 12.5467 12.7661 13.9827 14.4215 14.8811 16.3412 17.46100 18.1225 18.6032 19.0615 19.9874 20.4241 20.6234 21.3048 21.8063 22.5878 23.0446 24.0032 24.5449 25.1490 25.3699 26.0634 28.1041 28.5839 9.3031 29.4428. 溴化钾中的红外吸收光谱波数(cm^-1)为： 401,431,459,467,490,506,518,561,586,606,631,651,709, 758,766,857,944,1009,1041,1106,1119,1132,1213,1225, 1265,1304,1318,1429,1458,1470,1500,1589,1605,1630,1647, 1683,2562,2577,2608,2634,2689,2717,2836,2924,2949,2989, 3007,3032,3061,3322,3376,3422cm^-1.