CN1063184C - 甘草酸银及其制备方法和用途 - Google Patents
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Abstract
一种化合物，甘草酸银，分子式C42H60O16Ag2(1-5)H2O，由甘草酸盐与AgNO3进行反应制得，该化合物可用于制备抗菌，抗病毒的外用药物。
Description
本发明涉及一种新的化合物甘草酸银，以及该化合物的制备和药用用途，属于制药领域。
甘草酸银，分式式C42H60O16Ag2·(1-5)H2O。
银的杀菌作用早已为人类所知并加以了利用。十九世纪硝酸银就被用于治疗眼病和创伤，六十年代磺胺嘧啶银(AgSD)的出现使银化合物的应用取得了新的突破，大量的文献资料报道，银离子有如下几个方面的作用：1)具有杀灭绿脓杆菌、金葡菌、大肠杆菌、枯草杆菌的作用，被用于治疗烧伤、急慢性化脓、预防淋球菌引起的感染等；2)可杀灭白色球菌、黄黑曲霉菌、光霉白杆属真菌，被用于治疗阴道滴虫等疾病；3)可杀灭单纯性疱疹和带状疱疹病毒，肝炎病毒和梅毒螺旋体，治疗由于这些病毒和微生物引起的相关疾病。近年来的研究表明，AgSD有抗爱滋病HTV(人体免疫缺陷病毒)，LAV(淋巴结病体伴生病毒)和HILV(人体细胞白血病病毒)的作用，已初步尝试用AgSD防止爱滋病交叉感染，但目前用于治疗的银化合物如AgNO3用于临床时，由于AgNO3与体液中的氯离子起反应生成不溶的AgCl，引起体表Na+，K+和Cl的不平衡。AgSD的最大缺点是对磺胺类药过敏者不能使用，且该药长期使用会产生抗药性。
大量资料报道，甘草酸不仅具有消炎、解毒，抗癌的功效，而且有明显的抗慢性肝炎、水痘，带状疱疹病毒和白色念球菌的作用，特别引人注目的是国内外的大量研究表明，甘草甜素及其盐类具有抑制HIV-1病毒复制的作用，对由于HIV感染造成的免疫功能受损和肝脏功能失调的血友病患者，使用大量的甘草甜素可防止其发展成爱滋病。
本发明的化合物甘草酸银是由市售的甘草酸盐及硝酸银反应制得，它不仅具备甘草酸和银离子两者的抗菌抗病毒作用，而且由于其不含有磺胺嘧啶基团，因此，不会产生磺胺嘧啶药所引起的过敏反应。因此本发明的化合物可用于制备替代或部分替代AgSD的外用药物而用于治疗由于细菌、病毒感染所引起的疾病及抗爱滋病病毒和治疗爱滋病综合症。
本发明的甘草酸银的制备方法如下：
取一定量的甘草酸铵盐或钾盐，钠盐，以1∶1-1∶20比例加入乙醇(20-80％)溶液，在25-80℃温度下搅拌，使其溶解，然后缓慢加入化学计算量的AgNO3溶液(以水配制成0.05-1M浓度)，避光25-60℃下反应3-8小时，陈化8-24小时，过滤用冰水或无水乙醇洗涤，在20-80℃温度下干燥得到产品甘草酸银。
本发明的化合物甘草酸银用5-50％的蔗糖溶液与多元醇按1∶0.1-1(体积比)的比例混合的溶剂混匀制得含量1-10％的混悬液或0.5％的溶液，即可药用，直接涂覆于患处。
与目前使用的AgNO3，AgSD药物相比较，甘草酸银具有广谱的抗菌，抗病毒活性，抗菌效果与临床上广泛应用的AgSD相似，但具有优于AgSD的特点，不存在AgSD对人体的过敏反应，含银量低，但药用效果良好。
实施例1：
甘草酸铵(C42H61O16NH4.5H2O)5克，置于100ml烧杯中，加50％乙醇溶液60ml，加热至60℃，充分搅拌使溶解，取1克AgNO3，用10ml水溶解后，慢慢加入，待出现白色沉淀，停止加热，避光搅拌6小时，静置，过滤，冰水洗涤，60℃干燥，得白色产品C42H60O16Ag2·5H2O，产率47％，元素分析结果为：Ag18.82(19.16),C44.72(44.70),H6.49(6.22)，括号内为计算值。
实施例2 ：
取甘草酸钾(C42H61O16K.3H2O)100克于500ml烧杯中，加30％乙醇溶液300ml，加热到50℃，搅拌溶解，取5克AgNO3溶于40ml水中，然后慢慢加入，在40℃下避光搅拌4小时，陈化15小时，过滤，无水乙醇洗涤，40℃温度下干燥，得产品，产率62％，元素分析结果：Ag19.1，C44.08，H6.39
实施例3：
用50％蔗糖溶液与丙三醇按1∶1(体积)混合制成溶剂A，称取40mg甘草酸银置于量并中，滴入少量溶剂A使其充分乳化后，补足溶剂到10ml，摇匀后即可药用。
实施例4：
甘草酸银的抗菌活性实验
一、材料
细菌：金黄色葡萄球菌(S.auceus)，枯草杆菌(B.Subtilis)，大肠杆菌(E.COli)、绿脓杆菌(P.aeruginosa)，真菌黑曲霉菌(A.niger)，白色念球菌(C.albicoms)。
培养基：用营养琼脂培养细菌，PDA琼脂培养黑曲霉菌，YPD琼脂培养白色念球菌。
菌悬液制备：分别取活化后的新鲜菌种一杯，接种于5ml相应的培养液中，温度28℃，培养20小时。
方法：采用平板扩散法
评定标准：抑菌圈直径φ＜10mm，不敏感；φ为10-15mm，敏感，φ＞15mm极度敏感。实验结果：
Claims (4)
1、一种化合物，其特征在于这种化合物为甘草酸银，分子式为C42H60O16Ag2(1-5)H2O。
2、一种制备如权利要求1所述的化合物甘草酸银的方法，其特征在于方法的具体操作为：
取一定置的甘草酸盐以1∶1-1∶20的比例，加入30-80％的乙醇溶液，在25-80℃下搅拌，使其溶解，缓慢加入化学计量的以水配成0.05-1M浓度的硝酸银溶液，避光，在25-60℃下反应3-8小时，陈化8-24小时，过滤，用冰水或无水乙醇洗涤，在20-80℃下干燥即得产品。
3、一种如权利要求1所述的化合物甘草酸银的制备方法，其特征在于所说的甘草酸盐为铵盐，钾盐，钠盐。
4、一种如权利要求1所述的化合物甘草酸银的用途，其特征在于这种化合物可用于制备抗菌，抗病毒感染的外用药物。
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| CN1169435A CN1169435A (zh) | 1998-01-07 |
| CN1063184C true CN1063184C (zh) | 2001-03-14 |
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| CN1827634B (zh) * | 2005-03-04 | 2010-09-29 | 北京美倍他药物研究有限公司 | 甘草酸及甘草次酸的硝酸酯衍生物及其医药用途 |
| CN103242391B (zh) * | 2012-02-13 | 2016-04-13 | 南京华狮化工有限公司 | 一种制备甘草酸锶化合物的方法及其产品和应用 |
| CN103242392B (zh) * | 2012-02-13 | 2016-04-13 | 南京华狮化工有限公司 | 一种甘草酸复盐及其制备与应用 |
| CN104861016A (zh) * | 2015-03-01 | 2015-08-26 | 李玉山 | 一种甘草酸金属络合物的制备方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1004354B (zh) * | 1985-06-25 | 1989-05-31 | 江苏省植物研究所 | 高纯度甘草酸结晶的分离精制法 |
| CN1026983C (zh) * | 1988-06-30 | 1994-12-14 | 兰州大学 | 食用甘草甜素的制造方法 |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1004354B (zh) * | 1985-06-25 | 1989-05-31 | 江苏省植物研究所 | 高纯度甘草酸结晶的分离精制法 |
| CN1026983C (zh) * | 1988-06-30 | 1994-12-14 | 兰州大学 | 食用甘草甜素的制造方法 |
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