CN104491003A - 加味玉屏风凝胶剂及其制备方法和用途 - Google Patents
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Abstract
本发明公开了一种加味玉屏风凝胶剂及其制备方法和用途,属于含有传统中草药的医药配制品,本发明是按重量份数比的黄芪、白术、防风、黄芩,经乙醇提取浓缩为浸膏;上述浸膏按重量体积比加入药用辅料水溶性高分子基质卡波姆,保湿剂甘油、丙二醇、促渗剂氮酮,pH调节剂三乙醇胺、防腐剂尼泊金乙酯及纯净水充分搅拌均匀而成。这样设计的本发明以“内病外治”为依据,并根据外用透皮吸收的特点,提取中药原料中的有效部位或有效组分制备成凝胶剂,直接用于紫外线损伤的皮肤,不通过肝脏的首过效应,也减少胃肠道酶对其的破坏,对光老化皮损改善明显,该凝胶剂在治疗光老化方面具有显著疗效。
Description
技术领域
本发明涉及一种含有传统中草药的医药配制品,具体是一种加味玉屏风凝胶剂及其制备方法和用途。
背景技术
皮肤和其他器官一样,也会经历衰老,并且随年龄的增长而加剧。皮肤的衰老除内源性因素外,外源性因素对皮肤的影响同样不可忽视。随着人类社会的进步,工业迅猛发展,臭氧层遭到破坏,使人类遭受过多的紫外线辐射,而成为衰老的重要外源性因素之一。人们把长期受到紫外线照射,皮肤组织、生理及形态的变化定义为光老化,即慢性UV损伤。
临床上可表现为暴露部位皮肤松弛、皱纹粗深、结节、皮革样外观,色素斑增多、毛细血管扩张,原有几何图形外观明显改变或消失,皮肤颜色改变常呈灰黄色。更重要的是过多接受紫外线照射可能导致皮肤脂溢性角化、日光性角化等良性肿瘤以及增加恶性肿瘤的发病率。
随着人们生活水平的提高,更多的患者有延缓衰老的需求,同时光老化也受到临床医师的重视,因此预防和延缓光老化进程成为近年来人们研究的热点。
随着现代医学及美容学的发展,皮肤光老化的预防多以遮光剂和外用氧化剂为主。光老化的治疗多以维甲酸和物理方法(激光、磨削、剥脱等)为主。而这些方法大多是治标不治本,并不能从根本改善光老化皮肤结构,且容易产生色素沉着或色素脱失、红斑、脱屑、瘙痒、瘢痕等副作用。
光老化组织学改变包括表皮厚度因增生(重度萎缩)明显不均匀,表皮急性损伤,角质形成细胞出现不典型增生,表皮与真皮连接境界清晰,表皮突消失;真皮炎性细胞浸润较明显,弹性纤维增粗、排列紊乱或扭结成团,弹力纤维和溶菌酶的沉淀增加;血管壁开始增厚最后变薄,炎性细胞浸润周围;黑素细胞增殖活性增强密度增加等。
弹力纤维和胶原纤维的改变与皮肤光老化的表现较为密切。弹力纤维使皮肤富有弹性,胶原纤维起到支撑和抗牵拉的作用,二者质和量的改变,均能导致皮肤外观的变化。在日光暴露部位弹力纤维增多,且形态发生异常改变,出现增粗、扭曲、聚集成团、排列不规则等,是光老化皮肤的一个组织学特征。
光老化是个长期慢性的过程,兼有皮肤自然老化时气虚阴亏的特点。传统医学对光老化的防治主要从调整阴阳、调理气血、调治脏腑和祛痰延衰着眼。
玉屏风方是中医“扶正固本”经典名方,方由黄芪、白术、防风3味药物组成。黄芪益气固表,补益肺脾之气,白术健脾兼扶正,防风可疏散风邪。黄芪能补三焦而实卫气;白术健脾,可培土生金;防风能遍行周身,可使固表不留邪,驱邪不伤正;三药合用有益气固表、敛汗之效。玉屏风正如其名,为人体抵御外邪构建了一道保护屏障。有实验研究表明,黄芪有增强表皮细胞内自身氧化酶系活力的作用,能够大幅提高SOD活性,还能加速离体表皮细胞的分裂生长,可延长表皮细胞的寿命,黄芪总黄酮是一种良好的抗氧化剂,能够清除多种自由基,通过对自由基的清除发挥对UV损伤的防护作用。黄芪能增强网状内皮系统的吞噬功能,使血白细胞数巨噬细胞吞噬指数显著升高;可增强刀豆素A 激发的T 淋巴细胞增殖反应,同时对T细胞、B细胞、DC功能具有明显的增强作用。黄芪能增加羟脯氨酸(HYP)含量,减少胶原的交链,起到延缓衰老的作用。黄芩苷可有效保护人成纤维细胞免于UVA损伤和延缓光老化进程,具体机制可能与抑制氧化损伤和调控 p53 等老化相关基因表达有关。抑制酪氨酸酶活性可阻止皮肤黑素生成,雷铁池等通过实验证明在筛选的82种中药中白术抑制酪氨酸酶活性的作用最强。白术能提高12月龄以上小鼠红细胞SOD活性,抑制小鼠脑单胺氧化酶B(MAO-B)活性,对抗细胞自氧化溶血,并且有清除氧自由基的作用,具有一定的抗衰老作用。
玉屏风散含药血清具有抗皮肤角质形成细胞和皮肤成纤维细胞光老化的作用, 其作用机理与直接促进细胞生长和增殖有关。玉屏风散对紫外线照射引起的大鼠皮肤光老化具有保护作用,机制可能是一方面玉屏风散具有清除自由基、促进表皮细胞分裂,增加真皮胶原蛋白合成的作用;另一方面玉屏风散能够减少表皮郎格罕斯细胞(LC)迁移,保护其树突状结构.人体内天然抗氧化剂SOD(超氧化物歧化酶)活力随着年龄增长逐渐降低, 而实验证明玉屏风散能改善微循环, 提高血浆TSOD 和Cu、Zn-SOD 活力, 并增加了红细胞和血红蛋白含量, 提高了血液的带氧能力, 从而促进细胞的新陈代谢, 提高机体的抗氧化能力。
回顾以往,玉屏风多以颗粒剂、胶囊剂、软胶囊、微丸、滴丸、口服液剂为主,鲜有外用制剂,尤其用于改善光老化的凝胶剂未见报道。
发明内容
本发明解释为了解决紫外线照射后的慢性UV损伤问题,而提供一种中药加味玉屏风凝胶剂及其制备方法和用途。
本发明以“内病外治”为依据,并根据外用透皮吸收的特点提取中药原料,采用有效部位或有效组分制备成凝胶剂,直接作用于UV损伤皮肤,不通过肝脏的首过效应,也减少胃肠道酶对其的破坏,对光老化皮损改善明显。
鉴于黄芩的黄酮类成分在抗氧化、抗炎和抗过敏方面有很强的药理作用,为了能加强玉屏风抗氧化作用,并预防治疗光老化所造成的炎性反应,故在玉屏风的基础上增加了黄芩一味中药,起到协同、补充作用。
本发明是按照以下技术方案实现的。
一种加味玉屏风凝胶剂,该凝胶剂按以下重量份数比的原料制成的,黄芪3~12份、白术1~6份、防风1~6份、黄芩1~2份;将上述原料的提取物按w/v比加入药用辅料水溶性高分子基质卡波姆0.5%~2%,保湿剂甘油2%~10%、丙二醇2%~10%、促渗剂氮酮0.5%~1.5%、防腐剂尼泊金乙酯0.5‰~1‰,放置24小时以上,加入pH调节剂三乙醇胺0.5%~1.5%及纯净水,配至100%,充分搅拌均匀,得到水溶性凝胶剂。
所述一种加味玉屏风凝胶剂的制备方法,其是按如下步骤制备的:
a.按重量份数比称取以下原料,黄芪3~12份、白术1~6份、防风1~6份、黄芩1~2份,加30%~90%乙醇提取2~3次,加醇量分别为药材量的5~15倍,分别提取1~2.5小时,过滤,滤液合并,回收乙醇浓缩至浸膏;
b.将上述浸膏按w/v比,依次加入甘油2%~10%、丙二醇2%~10%、氮酮0.5%~1.5%、尼泊金乙酯0.5‰~1‰、卡波姆0.5%~2%,充分搅拌,放置24小时以上;加三乙醇胺0.5%~1.5%调节pH值,加纯净水调配至100%,充分搅拌均匀即成。
所述一种加味玉屏风凝胶剂的制备方法,其是按如下步骤制备的:
a.按重量份数比称取的黄芪3~12份、黄芩1~2份,经所述乙醇提取浓缩,制成浸膏;另将白术1~6份、防风1~6份,加水5~15倍,用挥发油提取器提取挥发油2~8小时,收集挥发油,用吐温-80稀释,加入上述浸膏中;
b.将上述浸膏按w/v比,依次加入甘油2%~10%、丙二醇2%~10%、氮酮0.5%~1.5%、尼泊金乙酯0.5‰~1‰、卡波姆0.5%~2%,充分搅拌,放置24小时以上;加三乙醇胺0.5%~1.5%调节pH值,加纯净水调配至100%,充分搅拌均匀即成。
所述一种加味玉屏风凝胶剂的制备方法,其是按如下步骤制备的:
a.按重量份数比称取以下原料,黄芪3~12份、黄芩1~2份、白术1~6份和防风1~6份,加水提取2~3次,加水量分别为药材量的5~15倍,分别提取1~2.5小时,过滤,滤液合并,浓缩至比重1.1~1.3的浸膏,加入95%乙醇使含醇量为50%~80%,使其沉淀,离心或过滤,将上清液或滤液回收乙醇,并继续浓缩至浸膏;
b.将上述浸膏按w/v比,依次加入甘油2%~10%、丙二醇2%~10%、氮酮0.5%~1.5%、尼泊金乙酯0.5‰~1‰、卡波姆0.5%~2%,充分搅拌,放置24小时以上;加三乙醇胺0.5%~1.5%调节pH值,加纯净水调配至100%,充分搅拌均匀即成。
所述一种加味玉屏风凝胶剂的制备方法,其是按如下步骤制备的:
所述黄芪是黄芪总皂苷,所述黄芩是黄芩苷,所述白术是白术挥发油,所述防风是防风挥发油,
所述a.按重量份数比称取的黄芪总皂苷45~160份和黄芩苷40~80份,加纯净水溶解,另将白术挥发油6~36份和防风挥发油0.5~6份用吐温-80稀释,混合成浸膏;其中所述纯净水为浸膏重量的45~90%,吐温-80为浸膏重量的0.5~3%。
所述的加味玉屏风凝胶剂在制备防治光老化外用药物中的应用。
这样设计的本发明以“内病外治”为依据,并根据外用透皮吸收的特点提取中药原料,采用有效部位或有效组分制备成凝胶剂,直接作用于UV损伤皮肤,不通过肝脏的首过效应,也减少胃肠道酶对其的破坏,对光老化皮损改善明显,该凝胶剂在治疗光老化方面具有显著疗效。
附图说明
图1是造模后小鼠皮肤组织学HE染色观察;
图2是造模后小鼠皮肤弹力纤维Weigert染色观察;
图3是加味玉屏风组小鼠皮肤组织学HE染色观察;
图4 是加味玉屏风组小鼠皮肤弹力纤维、胶原纤维Weigert染色观察;
图5是自然恢复组小鼠皮肤组织学HE染色观察;
图6是自然恢复组小鼠皮肤弹力纤维、胶原纤维Weigert染色观察;
图7是凝胶空白基质组HE染色图;
图8是凝胶空白基质组E.V.G染色图;
图9是造模后CK5的表达图;
图10是造模后CK14的表达图;
图11是加味玉屏风组CK5的表达图;
图12是加味玉屏风组CK14的表达图;
图13是自然恢复组CK5的表达图;
图14是自然恢复组CK14的表达图;
图15是凝胶空白基质组CK5的表达图;
图16是凝胶空白基质组 CK14的表达
图17是造模后CK1表达图;
图18是造模后CK10表达图;
图19是加味玉屏风凝胶干预后CK1表达图;
图20是加味玉屏风凝胶干预后CK10表达图;
图21是自然恢复组CK1表达图;
图22是自然恢复组CK10表达图。
具体实施方式:
下面结合附图及实施例对本发明进行详细的说明。
一. 实施例
实施例1:
一种加味玉屏风凝胶剂,称取黄芪60g、黄芩20g、白术30g和防风30g,混合,加80%乙醇提取2次,加醇量分别为药材量的10倍(W/V)计1400mL,分别提取2小时,过滤,滤液合并,回收乙醇浓缩至浸膏68g。
将上述浸膏,加甘油4.25g、丙二醇4.25g,氮酮0.85g,搅拌,加卡波姆-980 0.85g ,含0.05g尼泊金乙酯的乙醇溶液1mL,搅拌,放置24小时以上,加三乙醇胺0.85g,加纯净水配至85g,充分搅拌均匀而成。
实施例2:
一种加味玉屏风凝胶剂,先称取黄芪60g、黄芩15g,混合,加70%乙醇提取2次,加醇量分别为药材量的8倍(W/V)计600mL,分别提取1.5小时,过滤,滤液合并,回收乙醇浓缩至浸膏38g。
另将白术、防风各20g,混合粉碎过1号药典筛,加水8倍量计320mL,用挥发油提取器提取挥发油8小时,收集挥发油0.15mL,用吐温-80稀释至0.65mL,加入到上述浸膏中。
最后在上述浸膏中,加甘油2g、丙二醇2g、氮酮0.65g、含0.02g尼泊金乙酯的乙醇溶液0.4mL,搅拌,加卡波姆-980 0.7g,搅拌,放置24小时以上,加三乙醇胺0.7g,加纯净水配至46g,充分搅拌均匀而成。
实施例3:
一种加味玉屏风凝胶剂,称取黄芪60g、白术20g、防风20g、黄芩10g,加水提取3次,加水量分别为药材量的12倍(W/V)计1320mL,分别提取1.5小时,过滤,滤液合并,浓缩至比重1.25的浸膏,加入95%乙醇使含醇量达到70%,使其沉淀,离心或过滤,将上清液或滤液回收乙醇,并继续浓缩至浸膏95g。
在上述浸膏中,加甘油3.3g、丙二醇3.3g、氮酮1g、含0.1g尼泊金乙酯的乙醇溶液2mL,搅拌,加卡波姆-980 0.66g 搅拌,放置24小时以上,加三乙醇胺1.1g,加纯净水配至110g,充分搅拌均匀而成。
实施例4:
一种加味玉屏风凝胶剂,称取白术、防风各30g,混合粉碎过1号筛,加水量为药材量的6倍(W/V)计360mL,用挥发油提取器提取挥发油6小时,收集挥发油0.2mL,用吐温-80稀释至0.8 mL,备用。
黄芪皂苷1.6g、黄芩苷1.0g加入纯净水85mL,搅匀溶解,加入上述稀释后挥发油,再依次加入甘油5g、丙二醇5g、氮酮0.5g、含0.1g尼泊金乙酯的乙醇溶液2mL,加卡波姆1.0g,搅拌,放置24小时以上;加三乙醇胺1.0g,加纯水配至100g,充分搅拌均匀而成。
所述黄芪总皂苷、黄芩苷系南京狄尔格医药科技有限公司市售商品,所述白术挥发油,防风挥发油系自行制备。
实施例5:
黄芪60g加60%乙醇提取两次,加醇量分别为药材量的8倍(W/V)计480mL,分别提取1.5小时,过滤,滤液合并,得黄芪醇提液备用。
白术20 g、防风20 g,加水量为药材量的8倍(W/V)计320mL,用挥发油提取器提取挥发油4小时,收集挥发油0.12 mL,用吐温-80稀释至0.6 mL,备用,其过滤水煎液作为第一煎,第二煎加水8倍即320mL,提取40分钟,过滤,合并滤液,浓缩至40g,加入95%乙醇使含醇量达到60%,使其沉淀,离心或过滤,将上清液或滤液加入上述黄芪醇提液一起回收乙醇,并继续浓缩至浸膏46g。
将上述浸膏加丙二醇5.5g、黄芩苷0.5g、上述稀释后挥发油,搅拌均匀,加卡波姆0.82g充分搅拌,放置24小时以上,加三乙醇胺0.82g,加适量纯净水配至55g,继续搅拌均匀而成。
本发明所用水溶性凝胶基质包括药学上允许的所有适宜药用辅料。并且除水溶性凝胶外,还包括乳膏剂、巴布剂等其它外用剂型。
二.疗效观察
外用加味玉屏风凝胶对皮肤慢性UV损伤小鼠模型的治疗疗效观察
1 材料
1.1实验动物
普通健康清洁级昆明种小鼠40只,雌雄各半,鼠龄6周(18-22g),由天津市山川红实验动物科技有限公司提供,生产许可证:scxk(津)2013-0001。
1.2 实验主要仪器
SS-03AB型紫外线光疗仪上(购于海希格玛高技术有限公司)(UVB发射光谱260~350mn,峰值311nm;UVA发射光谱340~400nm,峰值365nm);National NN-5250型一按感应微波炉(National公司);YT-6生物组织拷片机(湖北孝感亚光医用电子技术研究所);SHANDON-AS325切片机; KMY-103型电热干燥箱;OLYMPUS双目生物显微镜。
1.3 实验主要试剂
弹力纤维EVG染色液 4×20ml(高锰酸钾溶液、草酸溶液、Elastin溶液、Van Gieson染液) 购于珠海贝索生物技术有限公司(生产批号:610111);
一抗 兔抗鼠CK5单克隆抗体(克隆号bs-1060R)浓缩液、兔抗鼠 CK14单克隆抗体(克隆号bs-1792R)浓缩液均购自于北京中杉金桥生物技术有限公司;
兔抗鼠 CK1单克隆抗体(克隆号bs-1244R)浓缩液、兔抗鼠CK10单克隆抗体(克隆号bs-2700R)浓缩液均购于北京博奥森生物技术有限公司;
SABC免疫组化染色试剂盒(5%BSA封闭液、二抗、SABC)购于武汉博士德生物技术有限公司;
液体DAB酶底物显色试剂盒(3ml 批号:911882A)由A(浓缩缓冲液)、B(DAB溶液)、C(浓缩H2O2溶液)三种溶液组成;
抗原修复液:柠檬酸抗原修复缓冲液粉剂,购于北京中杉金桥生物技术有限公司。
2 方法
2.1 慢性UV损伤小鼠模型的建立
将30只昆明小鼠,先用清水浸湿小鼠背部预脱毛部位,约3cm×5cm,用眼科小剪扩大范围粗略剪去长毛,用刀片将其余背毛尽量剃除干净,以确保小鼠皮肤与UV充分接触。脱毛时应避免损伤小鼠皮肤,以免影响实验结果。由于小鼠背毛生长较快,所以在UV照射期间隔天剃毛一次。
将小鼠固定于自制塑料固定盒内,黑布遮挡头部,背部照射部位充分暴露,置于SS-03AB型紫外线光疗仪正下方30cm处,UVB 强度为0.45mW/cm2,UVA 强度为6.7mW/cm2;UVB的辐照剂量为0.07J/cm2,UVA为10倍UVB辐照剂量即0.7J/cm2,每天照射1次,每周照射5天,每周增加0.5个红斑量,共照射9周完成光老化模型建立。UVB累计照射剂量达9.45J/cm2,UVA累计照射剂量达94.5J/cm2。
照射期间严格执行实验计划照射剂量及时间,每天肉眼观察小鼠皮肤变化情况,如有水疱、糜烂等出现,立即剔除,以免影响实验结果。
2.2 小鼠分组及给药
待光老化模型成功建立后,将小鼠随机分成3组,每组10只,按性别分笼饲养。即凝胶基质空白组、自然恢复组、加味玉屏风组。自然恢复组不予处理自然恢复,其他干预4周,加味玉屏风组每日分别外涂相同剂量的加味玉屏风凝胶(以20g小鼠为例,约为3.3g/d),4周干预结束后取老鼠背部皮肤,并断椎处死小鼠。用10 %水合氯醛(0.3 ml/ 100 g) 腹腔麻醉,固定于自制处置台,背部皮肤充分暴露。常规消毒后切取小鼠背部照射部位脊柱右侧的皮肤组织,并用10%福尔马林溶液固定后进行石蜡包埋、切片、贴片与烤片,HE染色、EVG染色,SABC免疫组化判定CK5、CK14及 CK1、CK10的表达。
2.3 结果
2.3.1实验小鼠皮肤肉眼观察
造模后小鼠皮肤明显增厚且粗糙,干燥,弹性减退,光泽感下降,皮纹加深,可见粗大的皮沟。自然恢复组小鼠皮肤外观较慢性UV损伤后改善不明显。在加味玉屏风凝胶干预慢性UV损伤小鼠模型4周后,小鼠皮肤光泽度有所提升,干燥明显改善,皮肤弹性有所恢复,加深的皮纹略变浅。
2.3.2HE染色及EVG染色
本实验采用间苯二酚-碱性品红染色(Weigert染色法),用于皮肤的组织结构及弹力纤维、胶原纤维变化的检测。染色后胶原纤维呈红色,弹力纤维呈蓝黑色,肌纤维、红细胞呈黄色。
造模后小鼠表皮薄厚不一,伴有角化过度及角化不全,角质形成细胞变大,轮廓不清,部分核深染,形态不规则;真皮层明显变厚,真皮浅层结构疏松,真皮层微血管扩张,附属器不规则增生,大量炎性细胞浸润;胶原纤维束明显肿胀变性,均质化,形成片状、块状,并可见无定型物质沉积;真皮层弹力纤维增粗、变多,部分增生的弹力纤维断裂、破碎、卷曲扭结、聚集成团、排列紊乱,无定形,毛囊周围最为明显,有的甚至消失(图1-2)。
加味玉屏风凝胶干预4周后小鼠表皮薄厚一致,细胞大小排列均匀一致,细胞层数与造模后相比明显减少,真皮层结构较为致密,可见表皮突,仅可见少量炎性细胞;真皮内弹力纤维和胶原纤维与造模后比较明显变细,并且排列整齐有序,与皮肤表面平行,呈波浪状,无卷曲扭结(图3-4)。
凝胶空白基质组与自然恢复组的小鼠皮肤组织在干预4周后组织结构未发生变化。表皮仍薄厚不一,伴有角化过度及角化不全。真皮层仍较空白组增厚明显,大量炎性细胞浸润;胶原纤维、弹力纤维仍较粗,仍有部分卷曲扭结、聚集成团(图5-8)。
2.2.3 CK5和CK14的表达
照射紫外线后CK5、CK14在表皮内呈弥漫性表达,几乎全层表达见图9、 图10,阳性率均为95%。
加味玉屏风组CK5的表达呈阴性或弱阳性表达,表达接近表皮上层见图11,阳性率为50%,与用药前表达情况相比t=5.339,P=0.000,P<0.05,有统计学意义见表1;CK14的表达呈弱阳性,多数仍表达在基底层,偶见表达于基底层上部见图12,阳性率为70%,与用药前表达情况相比t=5.480,P=0.000,P<0.05,有统计学意义见表2。
自然恢复组与凝胶空白基质组的小鼠皮肤组织在干预4周后角蛋白的表达仍呈阳性反应见图13-16, 阳性率仍为95%,与干预前相比,CK14 t均=1.000,P均=0.330, P>0.05无统计学意义;CK5自然恢复组t=1.453,P=0.163,P>0.05无统计学意义;凝胶空白基质组t=1.000,P=0.330,P>0.05无统计学意义。
2.2.4 CK1及CK10的表达
照射紫外线后CK1、CK10在表皮内呈弥漫性表达,几乎全层表达见图17、图18,阳性率均为95%。
用加味玉屏风凝胶干预4周后,CK1的表达呈阴性或弱阳性(图19)。与用药前相比,t=21.73,P<0.01,有显著意义。说明加味玉屏风凝胶可以使光老化小鼠皮肤CK1的表达量降低。干预后CK10表达也呈阴性或弱阳性(图20)。与用药前相比,t=28.50,P<0.01,有显著意义。说明加味玉屏风凝胶可以降低光老化小鼠皮肤CK10的表达量。
自然恢复组在4周后,CK1及CK10仍呈阳性表达(图21、图22)。CK1表达与4周前相比,t=0.22,P>0.05,无统计意义,说明自然恢复组小鼠皮肤CK1的表达量无明显变化。CK10表达,t=-0.28,P>0.05,无统计意义,提示CK10表达量亦无明显变化。
加味玉屏风组、自然恢复组CK1、CK10的表达及P值的比较见表3、表4。
采用单因素方差分析,比较加味玉屏风组及自然恢复组在干预4周后CK1及CK10的表达情况,P<0.01,意义显著;说明加味玉屏风凝胶能降低小鼠皮肤CK1的表达量且明显优于自然恢复组。提示加味玉屏风凝胶能降低小鼠皮肤CK10的表达量且明显优于自然恢复组。
本发明证实,在慢性UV损伤的小鼠背部皮肤涂抹加味玉屏风凝胶后,小鼠皮肤组织结构与造模前接近,弹力纤维和胶原纤维排列渐为整齐有序,CK5、CK14及CK1、CK10阳性表达程度显著降低,呈阴性或弱阳性表达;而自然恢复组无论角蛋白的表达还是组织结构均未发生改变。推测外用加味玉屏风凝胶对皮肤慢性UV损伤有明显的改善作用。
本发明从弹力纤维和胶原纤维的变化和细胞角蛋白CK1、CK5、CK10、CK14的表达方面证实加味玉屏风凝胶的作用,不仅找到一种能防治光老化的药物,丰富了有关光老化的机制研究,还拓展了玉屏风散的临床应用范围,为促进玉屏风散的开发利用打下了基础。
Claims (6)
1. 一种加味玉屏风凝胶剂,其特征在于:该凝胶剂按以下重量份数比的原料制成的,黄芪3~12份、白术1~6份、防风1~6份、黄芩1~2份;将上述原料的提取物按w/v比加入药用辅料水溶性高分子基质卡波姆0.5%~2%,保湿剂甘油2%~10%、丙二醇2%~10%、促渗剂氮酮0.5%~1.5%、防腐剂尼泊金乙酯0.5‰~1‰,放置24小时以上,加入pH调节剂三乙醇胺0.5%~1.5%及纯净水,配至100%,充分搅拌均匀,得到水溶性凝胶剂。
2. 如权利要求1所述一种加味玉屏风凝胶剂的制备方法,其特征在于:
a.按重量份数比称取以下原料,黄芪3~12份、白术1~6份、防风1~6份、黄芩1~2份,加30%~90%乙醇提取2~3次,加醇量分别为药材量的5~15倍,分别提取1~2.5小时,过滤,滤液合并,回收乙醇浓缩至浸膏;
b.将上述浸膏按w/v比,依次加入甘油2%~10%、丙二醇2%~10%、氮酮0.5%~1.5%、尼泊金乙酯0.5‰~1‰、卡波姆0.5%~2%,充分搅拌,放置24小时以上;加三乙醇胺0.5%~1.5%调节pH值,加纯净水调配至100%,充分搅拌均匀即成。
3. 如权利要求2所述一种加味玉屏风凝胶剂的制备方法,其特征在于:
所述a.按重量份数比称取的黄芪3~12份、黄芩1~2份,经所述乙醇提取浓缩,制成浸膏;另将白术1~6份、防风1~6份,加水5~15倍,用挥发油提取器提取挥发油2~8小时,收集挥发油,用吐温-80稀释,加入上述浸膏中。
4. 如权利要求2所述一种加味玉屏风凝胶剂的制备方法,其特征在于:
所述a.按重量份数比称取以下原料,黄芪3~12份、黄芩1~2份、白术1~6份和防风1~6份,加水提取2~3次,加水量分别为药材量的5~15倍,分别提取1~2.5小时,过滤,滤液合并,浓缩至比重1.1~1.3的浸膏,加入95%乙醇使含醇量为50%~80%,使其沉淀,离心或过滤,将上清液或滤液回收乙醇,并继续浓缩至浸膏。
5. 根据权利要求2所述一种加味玉屏风凝胶剂的制备方法,其特征在于:
所述黄芪是黄芪总皂苷,所述黄芩是黄芩苷,所述白术是白术挥发油,所述防风是防风挥发油,
所述a.按重量份数比称取的黄芪总皂苷45~160份和黄芩苷40~80份,加纯净水溶解,另将白术挥发油6~36份和防风挥发油0.5~6份用吐温-80稀释,混合成浸膏。
6. 如权利要求1-5中任意一项所述的加味玉屏风凝胶剂在制备防治光老化外用药物中的应用。
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Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
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CN104825824A (zh) * | 2015-05-25 | 2015-08-12 | 济南新斯诺生物技术有限公司 | 一种抗辐射的中药外用凝胶剂及其制备方法 |
CN104983633A (zh) * | 2015-07-10 | 2015-10-21 | 北京国济众芳中医药研究所 | 具有止痒固发清除自由基功效的外用中药组合物、制剂及其制备方法 |
CN104983633B (zh) * | 2015-07-10 | 2018-02-09 | 北京国济众芳中医药研究所 | 具有止痒固发清除自由基功效的外用中药组合物、制剂及其制备方法 |
CN106727884A (zh) * | 2016-12-23 | 2017-05-31 | 江苏大学 | 玉屏风散在制备抗衰老或老年性痴呆症药物中的用途 |
CN109700790A (zh) * | 2018-12-28 | 2019-05-03 | 中南大学湘雅医院 | 一种靶向AQP3的抗皮肤衰老药物Butein |
CN116920013A (zh) * | 2023-08-03 | 2023-10-24 | 阜阳师范大学 | 一种治疗或预防子痫前期的中药组合物 |
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