CN107837232A - 一种七叶皂苷钠微乳滴眼液 - Google Patents
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Abstract
本发明公开了一种七叶皂苷钠微乳滴眼液,它由有效含量的七叶皂苷钠、0.5~3%的中链脂肪酸甘油三酯、0.05~0.5%的聚乙二醇、0.05~0.5%的吐温、0.1~1%的渗透压调节剂、0.1~2%的缓冲液、0.01~0.1%的防腐剂和余量的注射用水组成。本发明根据七叶皂苷钠自身的特殊性质,通过将其微乳化并制成滴眼液,有效地提高了七叶皂苷钠的质量稳定性,同时降低了眼刺激性。
Description
技术领域
本发明属于药物制剂领域,涉及七叶皂苷钠滴眼液,尤其是七叶皂苷钠微乳滴眼液。
背景技术
七叶皂苷又称七叶皂苷酸,是从七叶树科七叶树属植物种子提取得到的总皂苷、β-七叶皂苷或异七叶皂苷等的总称,属于三萜皂苷类。七叶皂苷的水溶性较差,为增加其溶解度,常将其制成盐。七叶皂苷及其盐口服或注射在临床上常用于治疗各种原因引起的脑水肿及伴发的脑功能失调、各种原因(如创伤、烧伤、手术)引起的炎症与肿胀、静脉回流障碍性疾病等,具有很强的抗炎、抗渗出作用,能明显降低急性炎症的渗出。
CN 102920722 A公开了一种眼用制剂,含有0.05~0.5%的七叶皂苷钠,可用于治疗中心性浆液性视网膜脉络膜病变、眼底出血、眼球钝挫伤、视神经损伤等眼底疾病。由于七叶皂苷钠刺激性较大,且在液体中性质不稳定,从而限制了其在眼用制剂中的应用。
发明内容
本发明的目的是提供一种七叶皂苷钠微乳滴眼液,旨在降低七叶皂苷钠对眼部的刺激性,同时提高其质量稳定性。
一种七叶皂苷钠微乳滴眼液,它由以下重量配比的成分组成:
优选地,所述成分的重量配比是:
最佳的,所述成分的重量配比是:
优选地,所述渗透压调节剂为氯化钠、氯化钾、葡萄糖、山梨醇、甘油、丙二醇中的一种或多种。
优选地,所述缓冲液为硼酸盐缓冲液或磷酸盐缓冲液。
一种七叶皂苷钠微乳滴眼液的制备方法,包括以下步骤:
1)将七叶皂苷钠、聚乙二醇、渗透压调节剂、缓冲液、防腐剂用注射用水溶解,制成水相;
2)将中链脂肪酸甘油三酯、吐温加热搅拌均匀,制成油相;
3)将油相缓缓加入到水相中,边加边搅拌,至形成澄明溶液,微孔滤膜过滤,除菌,分装,即得。
本发明的有益效果:
1)本发明根据七叶皂苷钠自身的特殊性质,通过将其微乳化并制成滴眼液,有效地提高了七叶皂苷钠的质量稳定性,同时降低了眼部刺激性。
2)本发明制备的七叶皂苷钠微乳滴眼液粒径分布均匀,平均粒径在150~180nm之间,pH在6.5~7.2之间,渗透压在290~315mOsm/kg之间,为半透明的无色均一溶液,非常适合滴眼治疗眼部疾病。
3)本发明制备的七叶皂苷钠微乳滴眼液在贮存期内不会发生破乳、絮凝和沉淀,贮存有效期可达一年。
具体实施方式
下面通过实施例对本发明进行详细地说明。
实施例1
制备方法:1)取七叶皂苷钠8g、聚乙二醇400 3g、氯化钠6g、硼酸盐缓冲液(pH7.6)9g、羟苯乙酯0.5g,用注射用水溶解,制成水相;
2)将中链脂肪酸甘油三酯12g、吐温80 2g加热搅拌均匀,制成油相;
3)将油相缓缓加入到水相中,边加边搅拌,至形成澄明溶液,0.22μm微孔滤膜过滤,除菌,分装,即得微乳滴眼液1000g。
实施例2
制备方法:1)取七叶皂苷钠12g、聚乙二醇600 2g、氯化钾9g、磷酸盐缓冲液(pH7.2)6g、苯扎溴铵0.2g,用注射用水溶解,制成水相;
2)将中链脂肪酸甘油三酯15g、吐温80 1g加热搅拌均匀,制成油相;
3)将油相缓缓加入到水相中,边加边搅拌,至形成澄明溶液,0.22μm微孔滤膜过滤,除菌,分装,即得微乳滴眼液1000g。
实施例3
制备方法:1)取七叶皂苷钠6g、聚乙二醇200 1g、葡萄糖7g、硼酸盐缓冲液(pH8.0)5g、苯甲醇0.8g,用注射用水溶解,制成水相;
2)将中链脂肪酸甘油三酯20g、吐温80 0.8g加热搅拌均匀,制成油相;
3)将油相缓缓加入到水相中,边加边搅拌,至形成澄明溶液,0.22μm微孔滤膜过滤,除菌,分装,即得微乳滴眼液1000g。
实施例4
制备方法:1)取七叶皂苷钠15g、聚乙二醇400 4g、甘油2g、硼酸盐缓冲液(pH7.6)15g、羟苯乙酯0.5g,用注射用水溶解,制成水相;
2)将中链脂肪酸甘油三酯8g、吐温80 4g加热搅拌均匀,制成油相;
3)将油相缓缓加入到水相中,边加边搅拌,至形成澄明溶液,0.22μm微孔滤膜过滤除菌,分装,即得微乳滴眼液1000g。
试验例
对比例(普通七叶皂苷钠滴眼液)的制备:按CN 102920722A实施例2的方法制备。
1.稳定性试验
各组样品置于40±2℃、相对湿度为75±5%条件下观察6个月,分别于1、2、3、6个月取样检测七叶皂苷钠的含量,结果见表1。
表1稳定性试验结果
结果显示,随着贮存期的延长,七叶皂苷钠的含量有下降的趋势,但实施例1-4的下降幅度很小,观察6个月后含量仍在可控的范围内,而对比例的含量下降幅度很大,说明本发明提供的微乳制剂能提高七叶皂苷钠在滴眼液中的质量稳定性。
2.刺激性性试验
选用健康家兔20只,随机分为5组,实施例1-4组和对比例组,每组4只。给药前检查家兔眼部角膜、虹膜及结膜,无病变或炎症。每只家兔左眼的眼结膜囊滴入七叶皂苷钠微乳滴眼液或七叶皂苷钠滴眼液2滴,被动闭合10s,同法右眼给予同量生理盐水,每日2次,连续给药7天。每天给药前及最后一次给药后观察并记录眼部变化。按“眼刺激反应评分标准”判定受试药物的眼刺激性程度,无刺激性0-3.9分,轻度刺激性4-8.9分,中度刺激性9-12.9,强度刺激性13-16分,评分结果见表2。
表2七叶皂苷及其盐对家兔眼刺激性的影响
结果显示,七叶皂苷钠微乳滴眼液的眼刺激性评分均在3.9分以内,判定为无刺激性。而对比例仅有两只家兔的评分在3.9分以内,另两只均有轻度刺激性,从评分结果来看,本发明具有更好的安全性。
Claims (5)
1.一种七叶皂苷钠微乳滴眼液,其特征在于由以下重量配比的成分组成:
2.如权利要求1所述的七叶皂苷钠微乳滴眼液,其特征在于由以下重量配比的成分组成:
3.如权利要求1所述的七叶皂苷钠微乳滴眼液,其特征在于:所述渗透压调节剂为氯化钠、氯化钾、葡萄糖、山梨醇、甘油、丙二醇中的一种或多种。
4.如权利要求1所述的七叶皂苷钠微乳滴眼液,其特征在于:所述缓冲液为硼酸盐缓冲液或磷酸盐缓冲液。
5.如权利要求1-4任何一项所述的七叶皂苷钠微乳滴眼液的制备方法,其特征在于包括以下步骤:
1)将七叶皂苷钠、聚乙二醇、渗透压调节剂、缓冲液、防腐剂用注射用水溶解,制成水相;
2)将中链脂肪酸甘油三酯、吐温加热搅拌均匀,制成油相;
3)将油相缓缓加入到水相中,边加边搅拌,至形成澄明溶液,微孔滤膜过滤,除菌,分装,即得。
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CN102920722A (zh) * | 2012-11-23 | 2013-02-13 | 广州花海药业股份有限公司 | 治疗眼底病的眼用制剂 |
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刘美欣等: "微乳型0.05%环孢素滴眼液的质量控制及稳定性的初步研究", 《中国医院药学杂志》 * |
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