CN108066346A - 一种用于治疗白癜风的搽剂及其制备方法 - Google Patents
一种用于治疗白癜风的搽剂及其制备方法 Download PDFInfo
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- CN108066346A CN108066346A CN201610999009.7A CN201610999009A CN108066346A CN 108066346 A CN108066346 A CN 108066346A CN 201610999009 A CN201610999009 A CN 201610999009A CN 108066346 A CN108066346 A CN 108066346A
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明属于医药技术领域,涉及一种用于治疗白癜风的搽剂及其制备方法。本发明的搽剂包含醋酸倍他米松、低分子透明质酸钠、二甲基亚砜、助透剂、着色剂和溶剂。本发明的搽剂通过特殊的渗透促进剂实现优良的药物透皮性和色素滞留性,同时完成了白癜风的治疗和皮损部位的白斑遮盖,并且将醋酸倍他米松和他克莫司联用,起到协同增效的作用。本发明的搽剂制备工艺简单,易于生产操作,使用方便,副作用小,患者的用药顺应性得到显著改善。
Description
技术领域
本发明属于医药技术领域,涉及一种用于治疗白癜风的搽剂及其制备方法。
背景技术
白癜风是一种常见多发的色素性皮肤病,以局部或泛发性色素脱失进而形成白斑为特征,属于原发性皮肤色素脱失症,一般认为是由于皮肤和毛囊的黑素细胞内酪氨酸酶系统功能减退或丧失所致。白癜风在世界各地均有发病案例,我国患病率为1%左右,大约一半的患者在20岁之前发病。到目前为止,该病的病因仍不明确,多数学者认为与遗传、免疫及神经因素有关。白癜风易诊断但难以治愈,现有的治疗方法多种多样,其目的大都为了增加皮损部位黑素细胞的数量,使受损皮肤的颜色恢复正常。
醋酸倍他米松(Betamethasone 21-Acetate)是一种高效皮质激素类药物,具有抗炎、抗过敏和抑制免疫等多种药理作用。有学者研究发现,醋酸倍他米松促进了毛囊无色素黑素细胞黑素小体成熟,激活了酪氨酸酶的活性,并导致黑素生成增加,可用于治疗白癜风。但是,长期外用皮质激素类制剂容易引起皮肤毛囊炎、毛细血管扩张、皮肤萎缩等不良反应,并且存在停药后易复发的问题。
复方倍他米松注射液首先由先灵葆雅公司研制生产,商品名为“得宝松”。肌肉注射后,水溶性的倍他米松磷酸钠能够很快被吸收而迅速起效,而微溶性的二丙酸倍他米松可以储存起来被缓慢吸收,从而维持疗效,更长时间地控制症状等。但是,该产品的配方中使用了苯甲醇,其代谢产物苯甲醛对中枢神经系统存在毒性。中国发明专利申请CN101167730A提供了一种复方倍他米松混悬性注射液,该注射液的复方中包含低溶解性的二丙酸倍他米松和高溶解性的倍他米松磷酸钠组成,以及表面活性剂、金属螯合剂、等渗调节剂、抑菌剂、磷酸氢二钠、保护胶体等,成分工艺复杂,而且患者的用药顺应性差。
发明内容
针对现有倍他米松注射剂存在的制备工艺复杂、患者用药顺应性较差、毒副作用较大、停药后易复发等问题,本发明旨在提供一种制备工艺简单、使用方便的用于治疗白癜风的搽剂。
具体而言,本发明采用如下技术方案:
一种用于治疗白癜风的搽剂,其包含醋酸倍他米松、低分子透明质酸钠、二甲基亚砜、助透剂、着色剂和溶剂。
优选的,每1000mL搽剂中包含0.1~0.3g醋酸倍他米松、30~80g低分子透明质酸钠、100~300g二甲基亚砜、80~150g助透剂和0.01~0.05g着色剂。
在上述搽剂中,所述低分子透明质酸钠的平均分子量为40~80kDa。
在上述搽剂中,所述助透剂包括(但不限于)甘油、丙二醇、异丙醇、乙醇、液体石蜡和聚乙二醇,优选甘油。
在上述搽剂中,所述着色剂由根据肤色进行选择的色素调配而成,所述色素包括(但不限于)胭脂红、诱惑红、苋菜红、赤藓红、酸性红、柠檬黄、日落黄、亮蓝、靛蓝、蒽醌蓝、焦糖色素、植物炭黑和钛白粉。对于黄色人种而言,所述着色剂优选采用柠檬黄、日落黄和钛白粉进行调配;对于棕色人种而言,所述着色剂优选采用焦糖色素和钛白粉进行调配;对于黑色人种而言,所述着色剂优选采用柠檬黄、日落黄、苋菜红和亮蓝进行调配。
在上述搽剂中,所述溶剂为乙醇水溶液,优选乙醇体积百分比为60%~80%的乙醇水溶液,更优选乙醇体积百分比为75%的乙醇水溶液。
在一项优选的技术方案中,上述用于治疗白癜风的搽剂还包含他克莫司。
优选的,每1000mL搽剂中包含0.05~0.2g他克莫司。
在一项优选的技术方案中,上述用于治疗白癜风的搽剂还包含芳香剂。
在上述搽剂中,所述芳香剂包括(但不限于)樱桃香精、水蜜桃香精、甜橙香精、草莓香精、苹果香精、香蕉香精、哈密瓜香精、柠檬香精、薄荷香精、玫瑰香精和茉莉香精。
一种用于治疗白癜风的搽剂的制备方法,其包括如下步骤:
1)主药溶液的制备:按照配方量称取醋酸倍他米松,将其加入到适量溶剂中,搅拌均匀后,得到主药溶液;
2)辅料溶液的制备:按照配方量称取低分子透明质酸钠、二甲基亚砜、助透剂和着色剂,将低分子透明质酸钠加入到适量溶剂中,搅拌均匀后,依次加入二甲基亚砜、助透剂和着色剂,搅拌均匀后,得到辅料溶液;
3)搽剂的制备:将步骤1)中得到的主药溶液加入到步骤2)中得到的辅料溶液中,采用溶剂定容至配方量,搅拌均匀后,得到用于治疗白癜风的搽剂。
在一项优选的技术方案中,上述制备方法的步骤1)中还包括下列操作:在将配方量的醋酸倍他米松加入到溶剂中并搅拌均匀之后,再加入配方量的他克莫司并搅拌均匀。
在一项优选的技术方案中,上述制备方法的步骤2)中还包括下列操作:在将配方量的着色剂加入到溶剂中并搅拌均匀之后,再加入配方量的芳香剂并搅拌均匀。
本发明的用于治疗白癜风的搽剂可以用于治疗各种类型的白癜风,包括(但不限于)局限型白斑、肢端型白斑、泛发型白斑等,对暴露部位面积小、病程短的皮损疗效更好。
与现有技术相比,采用上述技术方案的本发明具有下列有益效果:
1)本发明的搽剂除了具有治疗白癜风的作用以外,还通过处方中的着色剂发挥遮瑕作用(掩盖白斑),达到标本兼治的效果;
2)由于白癜风同时存在细胞和体液免疫异常的问题,因此,除了醋酸倍他米松以外,本发明的搽剂中还包含免疫调节药——他克莫司,将醋酸倍他米松和他克莫司组成复方制剂后起到协同增效作用,同时降低副作用,降低停药复发率;
3)本发明的搽剂选用二甲基亚砜和低分子透明质酸钠的组合作为渗透促进剂,不仅克服了由于着色剂的存在对药效活性成分(醋酸倍他米松和他克莫司)透皮性的影响,有效提高了药效活性成分的渗透百分比,而且具有一定的成膜性,有助于着色剂均匀滞留于皮肤表面;
4)本发明的搽剂使用方便,副作用小,显著改善了病人的用药顺应性;
5)搽剂的制备工艺简单,成本低廉,适合于工业化生产。
具体实施方式
下面将结合具体实施例对本发明的技术方案做出进一步的描述。除另有说明外,下列实施例中所使用的仪器、材料、试剂等均可通过常规商业手段获得。
实施例1-实施例9:利用色素调配着色剂。
按照表1中的色素成分及用量,将色素调配成黄色、棕色和黑色三种着色剂,以供不同肤色的白癜风患病人群使用。具体调配流程如下:在搅拌条件下,按照1mg色素:1mL水的比例,向水中依次加入各种所需的色素,目测溶解或分散均匀后继续搅拌10min,即得调配后的着色剂。
表1.着色剂调配实验结果
将相同颜色的着色剂进行比对后发现,采用1份柠檬黄、2份日落黄和1份钛白粉调配的着色剂更加接近黄色人种的肤色,采用1份焦糖色素和1份钛白粉调配的着色剂更加接近棕色人种的肤色,采用1份柠檬黄、1份日落黄、1份苋菜红和1份亮蓝调配的着色剂更加接近黑色人种的肤色,因此,以实施例1、实施例5和实施例7中的3种着色剂为例制备搽剂。
实施例10-实施例12:搽剂的制备。
表2.搽剂的处方组成
按照表2中的用量称取醋酸倍他米松或者醋酸倍他米松和他克莫司,加入到适量75%乙醇中,搅拌均匀后,得到主药溶液;按照表2中的用量称取低分子透明质酸钠(平均分子量为40~80kDa)、二甲基亚砜、助透剂和着色剂(按照实施例1、实施例5和实施例7中的处方进行调配),将低分子透明质酸钠加入到适量75%乙醇中,搅拌均匀后,依次加入二甲基亚砜、助透剂和着色剂,并有选择地加入芳香剂,搅拌均匀后,得到辅料溶液;将主药溶液加入到辅料溶液中,采用75%乙醇定容至1000mL,搅拌均匀后,得到用于治疗白癜风的搽剂。
实验例1:用于治疗白癜风的搽剂的皮肤刺激实验。
采用实施例10至实施例14中的搽剂进行皮肤刺激实验,具体实验过程如下:选取体重为2.0~2.5kg的家兔作为实验动物,于实验前24h用剪刀及电动剃毛刀在家兔背部脊柱两侧各剃出一块区域,尺寸约为10cm×5cm,其中上半部分为完整皮肤试验区,下半部分为破损皮肤试验区,左侧涂受试药物或阳性对照物(品名:百点零搽剂,批号:151204,生产厂家:江苏灵豹药业股份有限公司),涂药量为1.0mL,右侧为自身空白对照;破损皮肤试验区左右两侧皮肤在给药前用手术刀划破皮肤,形成“井”字型(以渗血为准),破损面积为2×2cm2,涂药15min后用温水去除残留受试药物或阳性对照物。同法每天给药1次,连续30d,并在去除药物后的3、7、30d观察涂药处皮肤有无红斑和水肿现象,若有明显损伤,取皮肤作病理组织学检查。
按照表3对实验动物进行皮肤刺激反应评分,计算出平均分值后,按照表4进行刺激强度评价。
表3.皮肤刺激反应评分
表4.皮肤刺激强度评价
强度 | 分值 |
无刺激性 | <0.5 |
轻度刺激性 | <2.09 |
中度刺激性 | <6.0 |
强刺激性 | >6.0 |
表5.皮肤刺激实验结果
由表5中的结果可知,本发明的搽剂在药物去除后7d时对家兔的皮肤刺激为阴性(即无刺激性),而此时阳性对照物在家兔的破损皮肤区已经产生了轻度刺激;在药物去除后30d时,本发明的搽剂对家兔的完整皮肤区仍未产生任何刺激,对破损皮肤区也仅仅产生了轻度刺激,而此时阳性对照物在家兔的破损及完整皮肤区都产生了中度刺激。相比而言,本发明的搽剂的皮肤刺激副作用更低。
实验例2:搽剂的皮肤渗透实验。
采用实施例10至实施例14中的搽剂和阳性对照物(品名:百点零搽剂,批号:151204,生产厂家:江苏灵豹药业股份有限公司)进行皮肤渗透实验,具体实验过程如下:选取200~250g的Wistar大鼠,断颈处死,固定四肢,电动剃除大鼠腹毛,剥离腹部皮肤,剪除皮下组织以及脂肪,选用无破损者浸泡于生理盐水中,备用。采用改良的Franz扩散池法,将鼠皮装在Franz扩散池的供给池和接收室之间,鼠皮外侧朝向供给池,在接收池中加入pH=7.4的磷酸盐缓冲液(PBS)作为接收液,转速保持在200rpm,温度保持在37℃,在供给池中加入1mL搽剂(实施例10至实施例14中的产品)或阳性对照物,分别在1、3、5、7、9、12h取样,采用高效液相色谱法测定接收液中的药物含量,计算累积透皮量(mean±SD)和和实验结束时(12h取样后)的渗透百分比,其结果如表6所示。
表6.皮肤渗透实验结果
结果显示:在实验结束时,本发明的搽剂比市售品具有较高的渗透百分比,表明采用二甲基亚砜和低分子透明质酸钠的组合作为渗透促进剂时,即使处方中存在由色素调配的着色剂,也不会影响两种活性药物的吸收。
实验例3:搽剂的体外药效学实验。
采用实施例10和实施例13中的搽剂和阳性对照物(品名:百点零搽剂,批号:151204,生产厂家:江苏灵豹药业股份有限公司)进行体外药效学评价。
1.白癜风动物模型的构建:
取豚鼠50只,剪去背部长毛,电动剃净短毛,备皮约4cm*4cm。随机分为5组,分别为I组(正常组)、II组(白癜风模型组)、III组(实施例10搽剂治疗组)、IV组(实施例13搽剂治疗组)和V组(阳性对照物治疗组),II组~V组在脱毛后涂7%过氧化氢,0.8mL/次,2次/d,连续50d,建立白癜风动物模型。在此期间,受试豚鼠3d剃毛1次,III组~V组每天分别采用实施例10和实施例13中的搽剂和阳性对照物涂抹脱毛区,每天早晚各1次,连续50d。治疗期间观察皮肤色素保留时间,治疗结束后肉眼观察治疗白癜风的疗效。
2.具体实验方法:
豚鼠末次给药禁食12小时后,用乙醚麻醉,经腹部主动脉取血,制备血清,采用血酪氨酸酶检测试剂盒,按照说明书进行,用紫外分光光度计测定475nm波长处吸光值,计算酪氨酸酶含量。
剪取患病皮肤组织,用10%福尔马林溶液固定,病理切片,HE染色,光镜下观察表皮黑色素囊,计算黑色素毛囊数。
3.实验结果:
3.1 一般观察:
实验过程中:正常组的皮肤和毛色不变,呈黑色;白癜风模型组的皮肤颜色慢慢变淡,有的长出白斑,有的黑毛变成黄毛,有的甚至长出白毛。实施例10和13搽剂组的皮肤和毛色和正常组无差别,对照组在给药过程中可以看到肤色由正常到白斑可见再到和正常组无差别,表明实施例10和13搽剂组能够在治疗过程中对皮损部位发挥有效的遮盖作用。
实验结束后:正常组的皮肤和毛色不变,呈黑色;白癜风模型组的皮肤颜色最淡,呈白色,有的出现白斑,有的黑毛变成黄毛,有的甚至长出白毛。实施例10和13搽剂组和阳性对照物组的皮肤和毛色和正常组无差别。
3.2 对黑色素毛囊数的影响:
表7.对黑色素毛囊数的影响结果(mean±SD)
组别 | 实验动物数(只) | 黑色素毛囊数(个) |
正常组 | 10 | 39.7±1.39 |
白癜风模型组 | 10 | 20.9±2.05** |
实施例10搽剂组 | 10 | 31.5±3.21* |
实施例13搽剂组 | 10 | 29.1±3.78* |
阳性对照物组 | 10 | 28.6±3.92* |
注:与正常组相比,**P<0.05,与模型组相:*P<0.05
由表7可知,与正常组相比,白癜风模型组豚鼠的黑色素毛囊数明显减少,具有显著性差异(P<0.05),说明该白癜风模型造模成功。与模型组相比,实施例10搽剂组和阳性对照物组豚鼠的黑色素毛囊数显著增多(P<0.05)。由此可知,实施例10和13搽剂组和阳性对照物组对豚鼠白癜风模型黑色素毛囊数均有显著的改善作用,并且联用醋酸倍他米松和他克莫司的实施例10搽剂效果更佳。
3.3 对血浆中酪氨酸酶含量的影响:
表8.对酪氨酸酶含量的影响(mean±SD)
组别 | 实验动物数(只) | 酪氨酸酶含量(nmol/L) |
正常组 | 10 | 0.0789±0.0215 |
白癜风模型组 | 10 | 0.0315±0.0259** |
实施例10搽剂组 | 10 | 0.0542±0.0263 |
实施例13搽剂组 | 10 | 0.0474±0.0227 |
阳性对照物组 | 10 | 0.0461±0.0211 |
注:与正常组相比:**P<0.05
由表8可知,与正常组相比,白癜风模型组豚鼠的酪氨酸酶含量明显减少,具有显著性差异(P<0.05),说明该白癜风模型造模成功。与模型组相比,实施例10和13搽剂组和阳性对照物组豚鼠的血浆酪氨酸酶含量呈现出增高趋势。由此可知,实施例10搽剂组和阳性对照物组对豚鼠白癜风模型血浆酪氨酸酶含量均具有一定的提升作用,并且联用醋酸倍他米松和他克莫司的实施例10搽剂效果更佳。
Claims (10)
1.一种用于治疗白癜风的搽剂,其包含醋酸倍他米松、低分子透明质酸钠、二甲基亚砜、助透剂、着色剂和溶剂;
其中:每1000mL搽剂中包含0.1~0.3g醋酸倍他米松、30~80g低分子透明质酸钠、100~300g二甲基亚砜、80~150g助透剂和0.01~0.05g着色剂。
2.根据权利要求1所述的用于治疗白癜风的搽剂,其特征在于:
所述低分子透明质酸钠的平均分子量为40~80kDa。
3.根据权利要求1所述的用于治疗白癜风的搽剂,其特征在于:
所述助透剂选自甘油、丙二醇、异丙醇、乙醇、液体石蜡和聚乙二醇中的任意一种或多种以任意比例形成的混合物。
4.根据权利要求1所述的用于治疗白癜风的搽剂,其特征在于:
所述着色剂由根据肤色进行选择的色素调配而成,所述色素包括胭脂红、诱惑红、苋菜红、赤藓红、酸性红、柠檬黄、日落黄、亮蓝、靛蓝、蒽醌蓝、焦糖色素、植物炭黑和钛白粉。
5.根据权利要求4所述的用于治疗白癜风的搽剂,其特征在于:
当所述肤色为黄色时,所述着色剂由柠檬黄、日落黄和钛白粉调配而成;
当所述肤色为棕色时,所述着色剂由焦糖色素和钛白粉调配而成;
当所述肤色为黑色时,所述着色剂由柠檬黄、日落黄、苋菜红和亮蓝调配而成。
6.根据权利要求1所述的用于治疗白癜风的搽剂,其特征在于:
所述溶剂为乙醇水溶液。
7.根据权利要求1所述的用于治疗白癜风的搽剂,其特征在于:
所述用于治疗白癜风的搽剂还包含他克莫司。
8.根据权利要求7所述的用于治疗白癜风的搽剂,其特征在于:
每1000mL搽剂中包含0.05~0.2g他克莫司。
9.根据权利要求1所述的用于治疗白癜风的搽剂,其特征在于:
所述用于治疗白癜风的搽剂还包含芳香剂。
10.一种权利要求1至6中任一项所述的用于治疗白癜风的搽剂的制备方法,其包括如下步骤:
1)主药溶液的制备:按照配方量称取醋酸倍他米松,将其加入到适量溶剂中,搅拌均匀后,得到主药溶液;
2)辅料溶液的制备:按照配方量称取低分子透明质酸钠、二甲基亚砜、助透剂和着色剂,将低分子透明质酸钠加入到适量溶剂中,搅拌均匀后,依次加入二甲基亚砜、助透剂和着色剂,搅拌均匀后,得到辅料溶液;
3)搽剂的制备:将步骤1)中得到的主药溶液加入到步骤2)中得到的辅料溶液中,采用溶剂定容至配方量,搅拌均匀后,得到用于治疗白癜风的搽剂。
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CN110711244A (zh) * | 2019-11-19 | 2020-01-21 | 四川大学华西医院 | 一种神经导向因子Sema在制备治疗骨关节炎搽剂中的应用 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103127140A (zh) * | 2013-01-25 | 2013-06-05 | 江苏圣宝罗药业有限公司 | 一种治疗银屑病的复方外用药物 |
-
2016
- 2016-11-14 CN CN201610999009.7A patent/CN108066346A/zh active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN103127140A (zh) * | 2013-01-25 | 2013-06-05 | 江苏圣宝罗药业有限公司 | 一种治疗银屑病的复方外用药物 |
Non-Patent Citations (2)
Title |
---|
姚静主编: "《药用辅料应用指南》", 31 August 2011, 中国医药科技出版社 * |
王爱琴等主编: "《临床皮肤性病学》", 31 May 2014, 科学技术文献出版社 * |
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110711244A (zh) * | 2019-11-19 | 2020-01-21 | 四川大学华西医院 | 一种神经导向因子Sema在制备治疗骨关节炎搽剂中的应用 |
CN110711244B (zh) * | 2019-11-19 | 2023-08-01 | 四川大学华西医院 | 一种神经导向因子Sema在制备治疗骨关节炎搽剂中的应用 |
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