铝镁加的合成

第21卷第3期沈阳药科大学学报Vol.21No.32004年5月Journal of Shenyang Pharmaceutical UniversityMay 2004 p. 190文章编号: 1006 - 28582004 )3 - 0190- 03铝镁加的合成杨波',王国清2，吴英绵' ,伍百奇1 ,李瑞珍1(1.石家庄职业技术学院化工系河北石家庄050081 ; 2.沈阳药科大学制药系辽宁沈阳110016)摘要:目的研制新型抗酸药铝镁加的合成方法。方法采用简单易行的溶液反应合成铝镁加并运用正交设计法优化了合成工艺。结果对合成的镁加铝进行了红外光谱分析、差热分析、热重分析及X-射线粉末衍射分析确证了合成品结构。结论该方法工艺简单易于工业化生产。关键词:抗酸药;铝镁加;正交设计法中图分类号:R 923.文献标识码:A当前抗酸药的研究已从单-的含铝或镁的入CO2 ,100C反应12 ho该方法操作复杂。盐向羟基铝镁的复合物过渡,以提高抗酸效果及作者自拟方法:减少不良反应1。铝镁加( almagate),分子式为硫酸铝、硫酸镁和碳酸钠以-定浓度及摩尔AlMgd OH)( CO3); 4H2O2] ,由西班牙Amirail配比关系在-定条件下发生共沉淀置换反应制研究所研制是一种中和作用迅速,中和能力强备。大作用持久无酸反弹现象吸附胆酸制酸活性原理:A2( sO4》+ 6MgSO, + 9Na2CO3 +不随消化酶(特别是胃蛋白酶)作用而降低,不良11H2O- > Al2Mg6( OH )4( CO,》.4H2O +反应小安全性高的新型抗酸剂。作者合成了铝9Na,SO4+ 7CO2↑。镁加并运用光谱分析法确证了其结构对其稳定碳酸钠水解出氢氧根并与镁盐、铝盐发生共.性进行了考察。沉淀置换反应生成铝镁加。1仪器与试药在90C水浴电动搅拌条件下将硫酸铝、硫pHS- -3C 酸度计(上海第二分析仪器厂)多酸镁适量配比的混合液及- -定量无水碳酸钠的溶功能电子恒温水浴锅(.上海凯乐电子设备厂)精液同时缓慢滴加于适量水中约滴加1 h再继续密电动搅拌器( 100W广州富城仪器厂) ,Brucker反应20 min.将产物陈化后过滤蒸馏水充分洗IS- -55 红外分光光度计( KBr压片)热重分析仪涤后,100C干燥即得。2.2铝镁加合成影响因素考察(杜邦公司,V5. 1A、Dupont 2000、General V4. 1C、Dupont 2100，吹扫气:空气,升温速度:按照铝镁加含AlLO3为16.18%(理论值),10C min-1 升温范围:室温~ 800C ) ,D/MAX-MgO为38.39%(理论值)，制酸力为rA转旋阳极X_射线衍射仪(CuKa,50kV，28.60mEq g (理论值),考察合成中各因素水60mA石墨滤波)平变化对所得产品各种指标的影响规律。通过大所用试剂皆为分析纯,铝镁加(自制,批号.量单因素实验,确定了加料方式铝、镁盐的投料001025 ) ,铝镁加Aldrine" (对照品扬州一洋制药配比无水碳酸钠的用量是重要影响因素及其可有限公司)变动的范围。2.3铝镁加合成条件的正交设计优化2实验部分中国煤化工见定前提下,以产品产2.1 铝镁加的合成.MYTHCNMHG选用L1d40 )正交表文献3报道方法是:得16组合成条件。因素水平表(固定镁盐向Mg(OH)、A(OH)有机氨混合液中通63.5g)见表1结果见表2。收稿日期2003-11- 06作者简仿数鷯1976- )女汉族),辽宁昌图人,助教硕士,主要从事药学教育工作,Tel (0311 )3616611 - 8093 ,E - mail yb76s@ yahoo. com. cn。第3期杨波等铝镁加的合成191Table 1 The synthesis factors and the levels由直观分析法对正交实验结果的分析可见,Levels硫酸铝用量是影响产量的最主要因素。其4水平Factors3(30g )为最佳水平。Na2CO3用量是次重要的因mA(90,) 18H:o/g2:2829305052素其3水平最佳( 52g)反应温度对产量的影t/C90100 .110120响最小所以宜选择1水平( 90C )Table 2 The results of different conditionsNo.mA(S04) 18H20gmNecao./gmyidd/g127.5( 1)50(1)90(1)20.6227.5( 1 )51(2)100(2)21.052( 3)110(3)20.8427.5(1)53(4)120(4)22.6528.5(2)50(1 )20.9651(2 )22.9752(3)23.98110( 3)21.9929.5( 3)23.01029.5(3)22.01222.71330.5( 4)120(4 )22.21430.5(4)24.11524.31653(4 )90( 1)23. 9Sk185.086.7090.40Sk289.690.0088.902k390.7092.0089.80》k494.5090.20k22 .2521.6822.6022 .4022. 5022.23k322 .6823. .0022.453.6322. 5522.509.505.30 .1.802.4铝镁加的结构确证光谱、X射线粉末衍射光谱并分别进行了热分析。分别测定所合成的铝镁加及购得的铝镁加2.4.1 红外吸收光谱Aldrine* (对照品扬州一洋制药有限公司)的红外红外吸收光谱数据及解析归属见表3。，Table 3 Principal characteristic IR absorption of self-produced almagate and Aldrine"0σN0.20001025/ cmσAldrine' /cmσRerne data* / cmViberation form3 448.33 390.33400.一-OH H2O1 6251 602.3 .1 6301 4831 477.3中国煤化工1 4201 423.90O号一.1369.3.1 357.9 .Y8CNM HG1 110.41 119.3| 105* from Ref.[ 4]2.4.2 X射线粗末衍射图谱的测定 与解析X-射线衍射图谱数据对比见表4。192沈阳药科大学学报第21卷Table 4 X-ray diffraction spectral data of self- produced almagate and Aldrine *No.001025Aldrine"Reference data。d/nmI:Io[:Io7.742 21007.728 77.616.477 226.421 1 .35.824 25.771 45.76284.211 04.462 44.015 364.164 23.8603473.8670503.813.316 53.3069.3.199 73.155 33.146 6.3.099 52.909 92.897082.89242.69622.689 92.583 02.580 22.57402.300 82.308 72.29522.210 9.2. 206752.15142.149 41.952 11.955 3131.941.741 6.1.741 61.73111.6440.1.617 91.527 6201.527 21.52351.498 2181.50271.419 24“Values from Ref.[ 4 ]由表4所列数据对比来看,自制铝镁加的X-二氧化碳。射线粉末衍射分析所得的面间距( d值)及衍射相3结果对强度比I:10 )值与对照品基本一致,且与文献中铝镁加X射线粉末衍射所得主要数据吻合。首次采用简单易行的溶液反应合成铝镁加运2.4.3差热分析( DTA )及热重分析( TG)用正交设计法优化了其合成工艺;与铝镁加测试结果显示了2个吸热峰,见图1。Aldrine"对照品相比通过化学分析、IR光谱、X射线粉末衍射分析及热分析结构得到了确证。120-99.17%| 1727"C00-参考文献:391.67 °c-0.280[1]杨波，王国清.抗酸药研究进展[J ]沈阳药科大学学0.1.报2001 18(2):148- 151.60F1[ 2 ] Moragues J ,Beneyto JE ,Fabragas JL ret al . Characteri-zation of a new crystalline synthetic gastric antacid- al-一 J-0.1200400600magate[ J ] Arneim-Forsch/Drug Res ,1984 ,34( II ):t/°C中国煤化工. The system MgO-Al2O3-Fig.1 DAT and TG profiles of almagateYHc N M H Gate and nitrate ions on the第1吸热峰:177.27C。从100C ~phase equilibria[J]AmJ Sci ,1953 251 337- 361.177.27C样品失重11.41%(理论值11.43% ) ,证[4 ]Fabregas JL ,Cucala J. Influence of microphysical struc-ture on in vitro activity of new synthetic antacids[ J ]明本品有4个结晶水存在。第2吸热峰:Int J Pharm 1989 5x 2):173 - 178.391.67c.疵温度为本品分解点,放出结构水及(下转至第 214页)214沈阳药科大学学报第21卷Studies on the effects of the ligu capsules on pre-venting and treating the osteoporosisZHAO Ya-hong ,GONG Xian-feng ,LI Yan , WANG Min- wei( School of Pharmacy ,Shenyang Pharmaceutical University , Shenyang 110016 , China )Abstract : Objective To study the effective of ligu capsules ( traditional Chinese medicine ) in rats with os-teoporosis induced by retinoic acid. Method Osteoporosis model was established through treating withretinoic acid. Bone mineral density , bone bending strength , the level of Ca、P、Mg、Cu、Zn in serum andbone weight、bone length、bone diameter were measured. Results Femur bone mineral density , bone bend-ing strength ,the level of Ca、P、Mg in serum in ligu capsules groups were significantly increased than thosein model group. Compared with model group , level of serum- ALP and HOP/Cre were decreased ,while fe-mur weight、bone length、bone diameter were increased in ligu capsules groups. Conclusions The data indi-cated that ligu capsules could prevent and treat osteoporosis in model rats induced by retinoic acid.Key words : osteoporosis ; ligu capsules ; retinoic acid(上接第192页)Study on the synthesis and the stability of almagateYANG Bo' , WANG Guo-qing2 , WU Ying-mian' , WU Bai-qi' ,LI Rui-zhen'( 1. Department of Chemical Engineering , Shijiazhuang Vocational Technology Institute , Shijjiazhuang050081 , China ; 2. School of Pharmaceutical Engineering , Shenyang Pharmaceutical University ,Shenyang 110016 , China )Abstract : Objective To study the synthesis of almagate. Methods Applying orthogonal design method ,thesynthetic conditions of method have been optimized. Results Through determination of IR spectum ,X-raydiffraction spectrum differetial thermal analysis ,the structure of the self-prepared almagate was elucidated.Conclusions The technics of this method is simple and the method may be used for industrial production.Key words : antacid ; almagate ; orthogonal design中国煤化工MHCNM HG