第21卷第3期沈陽藥科大學學報Vol.21No.32004年5月Journal of Shenyang Pharmaceutical UniversityMay 2004 p. 190文章編號: 1006 - 28582004 )3 - 0190- 03鋁鎂加的合成楊波',王國清2，吳英綿' ,伍百奇1 ,李瑞珍1(1.石家莊職業(yè)技術學院化工系河北石家莊050081 ; 2.沈陽藥科大學制藥系遼寧沈陽110016)摘要:目的研制新型抗酸藥鋁鎂加的合成方法。方法采用簡單易行的溶液反應合成鋁鎂加并運用正交設計法優(yōu)化了合成工藝。結果對合成的鎂加鋁進行了紅外光譜分析、差熱分析、熱重分析及X-射線粉末衍射分析確證了合成品結構。結論該方法工藝簡單易于工業(yè)化生產。關鍵詞:抗酸藥;鋁鎂加;正交設計法中圖分類號:R 923.文獻標識碼:A當前抗酸藥的研究已從單-的含鋁或鎂的入CO2 ,100C反應12 ho該方法操作復雜。鹽向羥基鋁鎂的復合物過渡,以提高抗酸效果及作者自擬方法:減少不良反應1。鋁鎂加( almagate),分子式為硫酸鋁、硫酸鎂和碳酸鈉以-定濃度及摩爾AlMgd OH)( CO3); 4H2O2] ,由西班牙Amirail配比關系在-定條件下發(fā)生共沉淀置換反應制研究所研制是一種中和作用迅速,中和能力強備。大作用持久無酸反彈現(xiàn)象吸附膽酸制酸活性原理:A2( sO4》+ 6MgSO, + 9Na2CO3 +不隨消化酶(特別是胃蛋白酶)作用而降低,不良11H2O- > Al2Mg6( OH )4( CO,》.4H2O +反應小安全性高的新型抗酸劑。作者合成了鋁9Na,SO4+ 7CO2↑。鎂加并運用光譜分析法確證了其結構對其穩(wěn)定碳酸鈉水解出氫氧根并與鎂鹽、鋁鹽發(fā)生共.性進行了考察。沉淀置換反應生成鋁鎂加。1儀器與試藥在90C水浴電動攪拌條件下將硫酸鋁、硫pHS- -3C 酸度計(上海第二分析儀器廠)多酸鎂適量配比的混合液及- -定量無水碳酸鈉的溶功能電子恒溫水浴鍋(.上海凱樂電子設備廠)精液同時緩慢滴加于適量水中約滴加1 h再繼續(xù)密電動攪拌器( 100W廣州富城儀器廠) ,Brucker反應20 min.將產物陳化后過濾蒸餾水充分洗IS- -55 紅外分光光度計( KBr壓片)熱重分析儀滌后,100C干燥即得。2.2鋁鎂加合成影響因素考察(杜邦公司,V5. 1A、Dupont 2000、General V4. 1C、Dupont 2100，吹掃氣:空氣,升溫速度:按照鋁鎂加含AlLO3為16.18%(理論值),10C min-1 升溫范圍:室溫~ 800C ) ,D/MAX-MgO為38.39%(理論值)，制酸力為rA轉旋陽極X_射線衍射儀(CuKa,50kV，28.60mEq g (理論值),考察合成中各因素水60mA石墨濾波)平變化對所得產品各種指標的影響規(guī)律。通過大所用試劑皆為分析純,鋁鎂加(自制,批號.量單因素實驗,確定了加料方式鋁、鎂鹽的投料001025 ) ,鋁鎂加Aldrine" (對照品揚州一洋制藥配比無水碳酸鈉的用量是重要影響因素及其可有限公司)變動的范圍。2.3鋁鎂加合成條件的正交設計優(yōu)化2實驗部分中國煤化工見定前提下,以產品產2.1 鋁鎂加的合成.MYTHCNMHG選用L1d40 )正交表文獻3報道方法是:得16組合成條件。因素水平表(固定鎂鹽向Mg(OH)、A(OH)有機氨混合液中通63.5g)見表1結果見表2。收稿日期2003-11- 06作者簡仿數(shù)鷯1976- )女漢族),遼寧昌圖人,助教碩士,主要從事藥學教育工作,Tel (0311 )3616611 - 8093 ,E - mail yb76s@ yahoo. com. cn。第3期楊波等鋁鎂加的合成191Table 1 The synthesis factors and the levels由直觀分析法對正交實驗結果的分析可見,Levels硫酸鋁用量是影響產量的最主要因素。其4水平Factors3(30g )為最佳水平。Na2CO3用量是次重要的因mA(90,) 18H:o/g2:2829305052素其3水平最佳( 52g)反應溫度對產量的影t/C90100 .110120響最小所以宜選擇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鋁鎂加的結構確證光譜、X射線粉末衍射光譜并分別進行了熱分析。分別測定所合成的鋁鎂加及購得的鋁鎂加2.4.1 紅外吸收光譜Aldrine* (對照品揚州一洋制藥有限公司)的紅外紅外吸收光譜數(shù)據及解析歸屬見表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中國煤化工1 4201 423.90O號一.1369.3.1 357.9 .Y8CNM HG1 110.41 119.3| 105* from Ref.[ 4]2.4.2 X射線粗末衍射圖譜的測定 與解析X-射線衍射圖譜數(shù)據對比見表4。192沈陽藥科大學學報第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所列數(shù)據對比來看,自制鋁鎂加的X-二氧化碳。射線粉末衍射分析所得的面間距( d值)及衍射相3結果對強度比I:10 )值與對照品基本一致,且與文獻中鋁鎂加X射線粉末衍射所得主要數(shù)據吻合。首次采用簡單易行的溶液反應合成鋁鎂加運2.4.3差熱分析( DTA )及熱重分析( TG)用正交設計法優(yōu)化了其合成工藝;與鋁鎂加測試結果顯示了2個吸熱峰,見圖1。Aldrine"對照品相比通過化學分析、IR光譜、X射線粉末衍射分析及熱分析結構得到了確證。120-99.17%| 1727"C00-參考文獻:391.67 °c-0.280[1]楊波，王國清.抗酸藥研究進展[J ]沈陽藥科大學學0.1.報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中國煤化工. The system MgO-Al2O3-Fig.1 DAT and TG profiles of almagateYHc N M H Gate and nitrate ions on the第1吸熱峰:177.27C。從100C ~phase equilibria[J]AmJ Sci ,1953 251 337- 361.177.27C樣品失重11.41%(理論值11.43% ) ,證[4 ]Fabregas JL ,Cucala J. Influence of microphysical struc-ture on in vitro activity of new synthetic antacids[ J ]明本品有4個結晶水存在。第2吸熱峰:Int J Pharm 1989 5x 2):173 - 178.391.67c.疵溫度為本品分解點,放出結構水及(下轉至第 214頁)214沈陽藥科大學學報第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頁)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中國煤化工MHCNM HG