[发明专利]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)9.942410.601912.666913.125513.664413.864014.924915.261716.083516.863417.503417.584218.422019.282719.804519.944521.2210022.003222.543122.984923.605623.787523.927826.463328.022529.5037.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)7.4089.8810012.361315.544016.103816.223816.483517.301718.042018.441718.841919.341919.844721.162422.401923.183324.022224.922525.722726.401827.2214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)6.56309.94813.001715.004715.261415.74616.483517.42418.102118.505619.501720.103220.942121.6610022.322522.921723.921924.681726.004427.202328.022928.224028.6013.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)6.24159.661211.042212.122412.546712.766113.982714.421514.881116.341217.4610018.122518.603219.061519.987420.424120.623421.304821.806322.587823.044624.003224.544925.149025.369926.063428.104128.58399.303129.4428.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.