CN113209254A - 一种治疗急性脑中风的喷鼻剂及其制备方法 - Google Patents
一种治疗急性脑中风的喷鼻剂及其制备方法 Download PDFInfo
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Abstract
本发明涉及一种治疗急性脑中风的喷鼻剂及其制备方法,所述喷鼻剂由以下重量配比的中药原料药制备而成,麝香6‑9份、郁金20‑40份、栀子20‑40份、冰片0.5‑2份。
Description
技术领域
本发明涉及一种药物制剂及其制备方法,特别涉及一种治疗急性脑中风的喷鼻剂及其制备方法。
背景技术
脑中风又称脑卒中或脑血管意外,作为现代社会中常见病和高危病之一,其临床诊断为脑血栓、脑溢血、脑梗死等病症。有研究表明引发脑中风的原因多样,一些原发性中风主要是由于病患不良的生活习性所引起的。随着时代发展,医疗技术的进步,越来越多的研究证实了中风与其他疾病的相关性:有相关调查研究表明,适度的酒精摄入对心源性中风有一定保护作用,但是过度的酒精摄入则会引起卒中;脑中风与之相伴随的各类疾病如糖尿病、消化性疾病等都给卒中患者带来不同程度的负担,加之生理上的疾病往往会应发心理及精神上的疾病,这些身心疾病共同作用增加了患者死亡的风险以及治疗的难度,现医学家们也在极力探索疾病的联合治疗办法。
醒脑静注射剂,是由祖国医学传统名方“安宫牛黄丸”减味而成,处方中,麝香开窍醒神,为君药;栀子清热泻火解毒,以清心包之火,为臣药;郁金、冰片芳香辟秽,通窍开闭,以加强麝香开窍醒神之效,为佐药、使药。
临床上醒脑静注射液已在临床使用近40年,有较好的安全性与疗效性,其中麝香酮能用于中风急性期的治疗,它对神经母细胞瘤细胞的再给氧灌注损伤有着明显抑制作用,能明显抑制大鼠脑梗塞体积,减少神经细胞的损伤。同时,具有芳香开窍药物的特性,冰片,左旋龙脑,是一种小分子萜类化合物,是开窍醒脑类药物,具有“走窜上行”的作用,其能改变血脑屏障的通透性,促使药物通过血脑屏障,郁金具有非常重要的药理活性,具有对人血小板聚集的抑制作用,但日常的注射使用环境要求较高,不利于携带和后期的康复使用。目前在临床治疗中,鼻用喷雾剂作为一种全新的非注射给药方法,可提高生物利用度,避开药物的首过效应,减少药物的肝毒性,常被用于治疗如疼痛、过敏性鼻炎、糖尿病、鼻窦感染等临床疾病,正在成为局部或全身给药的重要途径,因此将疗效明确的注射剂改良为鼻喷剂,将极大方便药品的日常使用,保障人民的健康。
发明内容
本发明提供一种治疗急性脑中风的喷鼻剂,其由以下中药原料药制备而成,麝香、郁金、冰片、栀子。
本发明所述的喷鼻剂,优选的,由以下重量配比的中药原料药制备而成,麝香6-9份、郁金20-40份、栀子20-40份、冰片0.5-2份。
本发明所述的喷鼻剂,更优选的,由以下重量配比的中药原料药制备而成,麝香7-8份、郁金25-35份、栀子25-35份、冰片0.5-1.5份。
本发明所述的喷鼻剂,最优选的,由以下重量配比的中药原料药制备而成,麝香7-7.5份、郁金30份、栀子30份、冰片1份。或人工麝香7.5份、郁金30份、栀子30份、冰片1份。
本发明所述的喷鼻剂,其中含有喷鼻剂所需的任何一种药用辅料。优选的所述药用辅料,选自:吐温-80,氯化钠,司盘-80,聚乙二醇300,卵磷脂,葡萄糖。特别优选的药用辅料选自:吐温-80,氯化钠。本发明进一步包括,本发明所述的喷鼻剂在制备治疗脑栓塞、脑梗塞、颅脑外伤药物中的应用。
本发明进一步包括,本发明所述的喷鼻剂的制备方法,所述方法,步骤如下:取郁金30g,栀子30g,加水约1500ml进行蒸馏,收集蒸馏液500ml;将麝香7g加入上述蒸馏液中,并加蒸馏水500ml进行蒸馏,收集蒸馏液500ml,备用,取冰片1g,加入5g聚山梨酯-80、研匀,加入蒸馏液中,加入氯化钠4g,混匀、除菌过滤,得到500ml喷鼻剂,通过设备将喷鼻剂分装到经鼻给药的装置中,即得,其中所述经鼻给药的装置,包括喷雾装置,喷液装置,滴液装置等任意一种适合经鼻给药的装置。
本发明进一步提供所述的喷鼻剂在制备治疗脑卒中、颅脑外伤治疗中的应用,本发明所述的应用,是所述组合物可以改善脑缺血-再灌注引起的损伤。
本发明所述的喷鼻剂还含有溶剂或增溶剂,所述溶剂选自注射用水,增溶剂有司盘-80,聚乙二醇300,吐温-80、卵磷脂等,最优选的为吐温-80。
本发明所述的喷鼻剂还含有渗透压调节剂,主要为氯化钠,葡萄糖中的一种,最佳为氯化钠,加入量为8g/L。
本发明所述的喷鼻剂可以应用于治疗脑血管病的药物或者后期康复治疗使用。其中,脑血管病优选缺血性脑血管病,进一步优选为脑梗塞,同时对颅脑外伤有一定治疗效果。
以下通过实验数据进一步说明本发明的有益效果。
喷鼻剂配方筛选实验:
增溶剂的筛选,吐温-80作为优选增溶剂及其用量的筛选
通过:取郁金30g,栀子30g,加水约1500ml进行蒸馏,收集蒸馏液500ml;将麝香7g加入上述蒸馏液中,并加蒸馏水500ml进行蒸馏,收集蒸馏液500ml,备用,各取100ml蒸馏液3份,取冰片0.2g,分别加入0.5g、1g、2g聚山梨酯-80、研匀,分别加入上述100ml蒸馏液中,f分别加入氯化钠4g,混匀、除菌过滤,得到3份约100ml喷鼻剂,观察鼻喷剂澄清度,其中2g约1天澄清,1g约3天澄清、0.5g需15天澄清,综合吐温的毒理情况使用冰片:吐温=1:5的配方比例。氯化钠作为添加剂的筛选:经氯化钠和葡萄糖对比实验,氯化钠效果更好。
喷鼻剂制备方法筛选实验:
鼻喷剂为保证期热原以及无菌的条件,考察了不同提取方法,最终确定以使用蒸馏方式进行药材的提取方法效果最好。
经过以上筛选过程,得到本发明的以下配方及制备方法:
取郁金30g,栀子30g,加水约1500ml进行蒸馏,收集蒸馏液500ml;将麝香7g加入上述蒸馏液中,并加蒸馏水500ml进行蒸馏,收集蒸馏液500ml,备用,取冰片1g,加入5g聚山梨酯-80、研匀,加入蒸馏液中,加入氯化钠4g,混匀、除菌过滤,得到500ml喷鼻剂,通过设备将喷鼻剂分装到经鼻给药的装置中,即得。
本发明喷鼻剂在脑部缺血模型的药效研究
实验动物:C57雄性小鼠21-22g分为模型组、给药组和空白对照组组,共三个组别,其中:
模型组:大鼠脑缺血再灌注手术组,给与生理盐水
给药组:大鼠脑缺血再灌注给与鼻喷剂治疗的的组别
空白对照组:空白对照组正常大鼠,给与生理盐水。
供试品溶液的制备
A为模型组(生理盐水),B为本发明实施例所述的喷鼻剂,C组为空白对照组,A,B,C组按照同一剂量组各样品等体积给药。给药方式:大鼠脑缺血损伤造模方法为大鼠以用3%水合氯醛(溶剂为生理盐水)1.5ml/100g剂量腹腔注射,麻醉小鼠。沿小鼠颈部正中剪开皮肤,分离暴露两侧颈总动脉并穿线,并分别置线备用,用动脉夹夹闭两侧颈总动脉,将小鼠放入37℃恒温放置1小时后进行再灌注,缝合伤口,术前1h各组分别经鼻给予各自组别的供试品一次,再灌注后再一次经鼻给予各自组别的供试品一次;24h后存活的小鼠按照颈椎脱臼处死小鼠,快速取出脑组织后,经生理盐水洗涤后置于-20℃冰箱短暂冰冻,将每一个大脑横向切6片,将切片置于TTC染色剂中,在37℃的水浴中避光孵育,此间用弯镊将脑片的上下面翻转至少一次,以便两面染色一致。正常组织呈红色,梗死组织呈白色,完全显色后用4%多聚甲醛固定24小时,最后拍照运用Photoshop计算梗死面积。实验结果:
1、梗死面积百分比统计
空白对照组 | 模型组 | 鼻喷剂组 | |
0.00% | 28.86% | 16.92% | |
0.00% | 27.77% | 24.02% | |
0.00% | 25.32% | 20.35% | |
0.00% | 29.71% | 15.05% | |
0.00% | 26.01% | 19.89% | |
0.00% | 26.85% | 20.16% | |
0.00% | 30.95% | 17.38% | |
平均值 | 0.00% | 27.92% | 19.11% |
SD值 | 0.00% | 2.03% | 2.93% |
RSD值 | 7.29% | 15.35% |
结论:模型对照组脑梗死面积与正常对照组0%比较差异明显,说明小鼠脑缺血再灌注模型建立成功。与模型对照组相比,给药组合能降低脑梗死面积,说明制剂治疗效果明显。
具体实施方式
下述实施例加以举例说明制备过程,不应该认为是对本发明的限制。
实施例1
取郁金30g,栀子30g,加水约1500ml进行蒸馏,收集蒸馏液500ml;将麝香7g加入上述蒸馏液中,并加蒸馏水500ml进行蒸馏,收集蒸馏液500ml,备用。取冰片1g,加入5g聚山梨酯-80(供注射用)、研匀,加入蒸馏液中,加入氯化钠4g,混匀、除菌过滤,分装即得。
实施例2
取郁金30g,栀子30g,加水约1500ml进行蒸馏,收集蒸馏液500ml;将麝香3g加入上述蒸馏液中,并加蒸馏水500ml进行蒸馏,收集蒸馏液500ml,备用。取冰片1g,加入6g聚乙二醇300(供注射用)、研匀,加入蒸馏液中,加入葡萄糖4g,混匀、除菌过滤,分装即得。
实施例3
取郁金30g,栀子30g,加水约1500ml进行蒸馏,收集蒸馏液500ml;将麝香3g加入上述蒸馏液中,并加蒸馏水500ml进行蒸馏,收集蒸馏液500ml,备用。取冰片2g,加入5g聚山梨酯-80(供注射用)、研匀,加入蒸馏液中,加入氯化钠4g,混匀、除菌过滤,分装即得。
实施例4
取郁金30g,栀子30g,加水约1500ml进行蒸馏,收集蒸馏液500ml;将麝香7g加入上述蒸馏液中,并加蒸馏水500ml进行蒸馏,收集蒸馏液500ml,备用。取冰片2g,加入5g聚山梨酯-80(供注射用)、研匀,加入蒸馏液中,加入氯化钠4g,混匀、除菌过滤,分装即得。
Claims (10)
1.一种治疗急性脑中风的喷鼻剂,其特征在于,由以下中药原料药制备而成,麝香、郁金、冰片、栀子。
2.根据权利要求1所述的喷鼻剂,其特征在于,由以下重量配比的中药原料药制备而成,麝香6-9份、郁金20-40份、栀子20-40份、冰片0.5-2份。
3.根据权利要求1所述的喷鼻剂,其特征在于,由以下重量配比的中药原料药制备而成,麝香7-8份、郁金25-35份、栀子25-35份、冰片0.5-1.5份。
4.根据权利要求1所述的喷鼻剂,其特征在于,由以下重量配比的中药原料药制备而成,麝香7-7.5份、郁金30份、栀子30份、冰片1份。
5.根据权利要求1所述的喷鼻剂,其特征在于,由以下重量配比的中药原料药制备而成,人工麝香7.5份、郁金30份、栀子30份、冰片1份。
6.根据权利要求1所述的喷鼻剂,其特征在于,含有喷鼻剂所需的药用辅料。
7.根据权利要求6所述的喷鼻剂,其特征在于,所述药用辅料,选自:水,吐温-80,氯化钠,司盘-80,聚乙二醇300,卵磷脂,葡萄糖。
8.根据权利要求7所述的喷鼻剂,其特征在于,所述药用辅料,选自:水,吐温-80,氯化钠。
9.权利要求1所述的喷鼻剂在制备治疗脑栓塞、脑梗塞、颅脑外伤药物中的应用。
10.权利要求1所述的喷鼻剂的制备方法,其特征在于,所述方法,步骤如下:取郁金30g,栀子30g,加水约1500ml进行蒸馏,收集蒸馏液500ml;将麝香7g加入上述蒸馏液中,并加蒸馏水500ml进行蒸馏,收集蒸馏液500ml,备用,取冰片1g,加入5g聚山梨酯-80、研匀,加入蒸馏液中,加入氯化钠4g,混匀、除菌过滤,分装即得。
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