CN101069692B - 含积雪草总甙的药物制剂及其制备方法 - Google Patents
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Abstract
本发明涉及一种含积雪草总甙的药物制剂，由积雪草总甙、渗透促进剂、乳化剂、润湿剂、增稠剂、防腐剂、碱化剂、油和水组成。其特征在于积雪草总甙占总重量的1～20％，渗透促进剂占总重量的2～10％，乳化剂占总重量的3～10％，润湿剂占总重量的2～10％、助悬、增稠剂占总重量的0.1～6％、防腐剂占总重量的0.2～2％、碱化剂占总重量的0.2～2％、油占总重量的1～20％，水占总重量的60～80％。本方法的优点提高了药物在局部的浓度，有利于更好发挥药效，治疗疾病。
Description
技术领域
本发明属于药物制剂技术领域，特别是用于治疗外伤、手术创伤、烧伤，疤痕疙瘩、硬皮病、抑郁、乳腺增生、肝肾纤维化等，含积雪草总甙的药物制剂及其制备方法。
背景技术
积雪草总甙为伞形科植物积雪草的干燥全草的水溶性有效部位。药理研究发现积雪草总甙具有激活上皮细胞，促进正常肉芽组织形成的作用，可使创伤面迅速愈合；能够抑制成纤维细胞的增殖，对无秩序的瘢痕疙瘩增生具有抑制及缓和作用，可防止粘连发生和缓解粘连的形成。临床应用于对静脉功能不良引起的长期不愈的下肢溃疡，手术或其它伤害造成的创伤面和肌腱粘连，灼烧等因素所致的伤面恢复后形成的增生性瘢痕疙瘩，炎症引起的损伤性粘连，其它因素产生的长期皮肤溃疡损伤，以及硬皮症等。此外，积雪草总甙还用于治疗子宫颈损伤、产科创伤、会阴侧切开手术、乳房裂口；窦炎、扁桃体切除术、耳炎、鼓室成形术；角膜损伤、白内障、视网膜剥离等。
已有国家标准的积雪甙霜软膏的主要成分为：甘油、十二烷硫酸钠、三乙醇胺、吐温-80、单硬脂酸甘油酯、硬脂酸、白凡士林、液状石腊、叔丁基对甲酚、羟苯乙酯。这一剂型可使积雪甙通过皮肤吸收。
公开号为CN20051000001.8的中国专利含积雪草水溶性有效组分的中药缓释制剂及其制备方法，其制剂处方包括：积雪草提取物(按积雪草总昔计)18g，羟丙基甲基纤维素30—250g，微晶纤维素20—70g，聚维酮k30醇溶液适量，硬脂酸镁适量。该发明专利申请解决了积雪草水溶性有效组分的缓释问题。
发明内容
本发明的目的是促进积雪草总甙的皮肤吸收，提高局部药物浓度，进一步增强其疗效。
已有的积雪甙霜软膏的主要成分为：甘油、十二烷硫酸钠、三乙醇胺、吐温-80、单硬脂酸甘油酯、硬脂酸、白凡士林、液状石腊、叔丁基对甲酚、羟苯乙酯。本发明在此基础上，使用了渗透增强剂以及其他促进吸收的辅料，进一步提高了皮肤对积雪草总甙的吸收。
为了达到本发明的目的，本发明采用棕榈酸异辛酯为渗透增强剂。棕榈酸异辛酯为脂肪酸酯，其化学稳定性和热稳定性好，不氧化，不变色，无刺激性，致敏性。同时还具有赋形、润滑等功效，能有效促进药物表皮渗透。
为了达到本发明的目的，本发明采用了以下的技术方案：
一种含积雪草总甙的药物制剂，由积雪草总甙、渗透促进剂、乳化剂、润湿剂、增稠剂、防腐剂、碱化剂、油和水组成。其特征在于积雪草总甙占总重量的1～20％，渗透促进剂占总重量的2～10％，乳化剂占总重量的3～10％，润湿剂占总重量的2～10％、助悬、增稠剂占总重量的0.1～6％、防腐剂占总重量的0.2～2％、碱化剂占总重量的0.2～2％、油占总重量的1～20％，水占总重量的60～80％。
作为优选，渗透促进剂主要指可有效增强积雪草总甙通过哺乳动物皮肤的脂肪酸酯，优选的为棕榈酸异辛酯、棕榈酸异丁酯中的一种。
作为优选，乳化剂主要指天然乳化剂，优选的为DRA-CE(为硬脂酸甘油酯柠檬酸盐、硬脂酸甘油酯的混合物)。
作为优选，润湿剂为甘油。
作为优选，助悬、增稠剂为高分子聚合物，优选的为丙烯酸聚合物，Carbopol934(为丙烯酸聚合物)、NovemerEC-1(为丙烯酸酯、丙烯酸酰胺共聚物、白矿油、聚山梨醇酯-85的混合物)中的一种或其混合物。
作为优选，防腐剂为Glydant Plus，其主要成分为1，3-二羟基-5，5-二甲基乙内酰脲(DMDMH)和碘代丙炔基氨基甲酸酯(IPBC)。
作为优选，碱化剂为三乙醇胺。
作为优选，油为辛酸/癸酸三甘油酯、C16-18混合醇、硅油200/100中的一种或其混合物。
作为优选，水相的配制方法为将水相的水浴加热至适宜的温度，纯化水中加入助悬、增稠剂，完全分散均匀后，加入处方量的积雪草总甙、甘油溶解成均匀物料。
作为优选，油相的配制方法为将油相的水浴加热至适宜的温度，油、渗透增强剂、乳化剂溶解成均匀物料。
作为优选，将水相物料均匀加入油相物料，直至成为匀质，冷却后加入防腐剂、碱化剂；并加入适量增稠剂。
本方法的优点提高了药物在局部的浓度，有利于发挥药效，治疗疾病。
具体实施方式
下面结合实施例对本发明作进一步描述，但本发明并不为实施例所限制。
实施例1：
方法：将水相的水浴加热至70-80℃后，纯化水中加入Carbopol934，搅拌使之完全分散均匀，再加入处方量的积雪草总甙、甘油溶解成均匀物料。将油相的夹层水加热至70-80℃，棕榈酸异辛酯、天然乳化剂、辛酸/葵酸三甘油脂、C16-18混合醇、硅油200/100溶解成均匀物料。然后将油相的物料抽到主锅中搅拌，缓缓将水相成分加入，搅拌成匀质后，冷却后加入防腐剂Glydant Plus，使用碱化剂三乙醇胺调节pH值至人体可接受的弱酸性至中性范围；并视制剂稠薄程度，加入适量增稠剂Novemer EC-1。
经机器罐装成12g或者20g/支的软膏剂
实施例2：
方法：将水相的水浴加热至70-80℃后，纯化水中加入Carbopol934，搅拌使之完全分散均匀，再加入处方量的积雪草总甙、甘油溶解成均匀物料。将油相的夹层水加热至70-80℃，辛酸/葵酸三甘油脂、棕榈酸异辛酯、天然乳化剂、C16-18混合醇、硅油200/100溶解成均匀物料。然后将油相的物料抽到主锅中搅拌，缓缓将水相成分加入，搅拌成匀质后，冷却后加入防腐剂Glydant Plus，使用碱化剂三乙醇胺调节pH值至人体可接受的弱酸性和中性范围；并视制剂稠薄程度，加入适量增稠剂Novemer EC-1。
经机器罐装成12g或者20g/支的软膏剂
实施例3：
积雪草总甙软膏长期稳定性试验结果
注：积雪甙含量的测定方法为高效液相法，因为本品辅料峰保留时间、积雪草甙、羟基积雪草甙保留时间都不同，辅料与主药峰分离良好，说明辅料、羟基积雪甙对积雪甙含量测定无干扰。
实验结果表明，本发明的软膏，在为期24月的稳定性考察中，能保持均一的油水乳化性状。采用精密的高效液相测定法对主要有效成分：积雪甙的研究发现，积雪甙能够维持其含量。
实施例4：
透皮吸收实验
根据《中国药典》2005版第二部附录XC“溶出度测定法”、附录XD“释放度测定法”中的方法测定。
大鼠处死，脱毛取皮剪成直径5厘米左右的圆形，精确称取4g积雪草总甙软膏(含积雪草总甙100mg)，涂于鼠皮外层。将鼠皮固定于溶出度测定仪的碟桨装置的网碟中，测定0.5、1、2、4、8、12小时各时间点内层鼠皮溶出的积雪甙量。采用容量法测定积雪草总甙含量。
| 时间(h) | 累计释药量 | 累积释药百分率 |
| 0 | 0 | 0 |
| 0.5 | 18.7 | 18.7 |
| 1 | 27.5 | 27.5 |
| 2 | 35.7 | 35.7 |
| 4 | 42.3 | 42.3 |
| 8 | 47.8 | 47.8 |
| 12 | 52.1 | 52.1 |
实验结果表明，本发明的软膏，有效的促进了积雪草总甙的透皮吸收，提高了局部药物浓度。
Claims (10)
1.一种含积雪草总甙的药物制剂，由积雪草总甙、渗透促进剂、乳化剂、润湿剂、增稠剂、防腐剂、碱化剂、油和水组成，其特征在于积雪草总甙占总重量的1～20％，渗透促进剂占总重量的2～10％，乳化剂占总重量的3～10％，湿润剂占总重量的2～10％、增稠剂占总重量的0.1～6％、防腐剂占总重量的0.2～2％、碱化剂占总重量的0.2～2％、油占总重量的1～20％，水占总重量的60～80％，其中所述的渗透促进剂为棕榈酸异辛酯、棕榈酸异丁酯中的一种，各组分重量百分比之和为100％。
2.根据权利要求1所述的含积雪草总甙的药物制剂，其特征在于乳化剂为硬脂酸甘油酯柠檬酸盐和硬脂酸甘油酯的混合物。
3.根据权利要求1所述的含积雪草总甙的药物制剂，其特征在于润湿剂为甘油。
4.根据权利要求1所述的含积雪草总甙的药物制剂，其特征在于增稠剂为丙烯酸聚合物、NovemerEC-1中的一种或其混合物。
5.根据权利要求1所述的含积雪草总甙的药物制剂，其特征在于防腐剂为1，3-二羟基-5，5-二甲基乙内酰脲。
6.根据权利要求1所述的含积雪草总甙的药物制剂，其特征在于碱化剂为三乙醇胺。
7.根据权利要求1所述的含积雪草总甙的药物制剂，其特征在于油为辛酸/癸酸三甘油酯、C16-18混合醇、硅油200/100中的一种或其混合。
8.根据权利要求1所述的含积雪草总甙的药物制剂，其特征在于水相的配置方法为将水相的水浴加热至适宜的温度，纯化水中加入增稠剂，完全分散均匀后，加入处方量的积雪草总甙、甘油溶解成均匀物料。
9.根据权利要求1所述的含积雪草总甙的药物制剂，其特征在于油相配置方法为将油相的水浴加热至适宜的温度，油、渗透促进剂、乳化剂溶解成均匀物料。
10.根据权利要求1或10所述的含积雪草总甙的药物制剂，其特征在于将水相物料均匀加入油相物料，直至成为均质，冷却后加入防腐剂、碱化剂；并加入适量增稠剂。
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