CN112402362A - 复方水杨酸水溶型抑菌乳膏及其制备方法 - Google Patents
复方水杨酸水溶型抑菌乳膏及其制备方法 Download PDFInfo
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Abstract
本发明公开了一种复方水杨酸水溶型抑菌乳膏及其制备方法,旨在解决现有技术中水杨酸制品水溶性差,导致应用效果不良的技术问题。本发明复方水杨酸水溶型抑菌乳膏由水杨酸、康唑、十八醇、凡士林、硬脂酸、单硬脂酸甘油酯、羟苯乙酯、液体石蜡、十二烷基硫酸钠、2,6‑叔丁基对甲酚、平平加O、甘油、尿素、二甲基亚砜、水等制成。本发明先将水杨酸溶于有机溶剂,然后再制成水包油的剂型,最后乳化形成乳膏,克服了水杨酸水溶性差的问题,使水杨酸在水溶液中呈可溶性分子状态,能够直接添加到水基产品中。
Description
技术领域
本发明涉及卫生消毒技术领域,具体涉及一种复方水杨酸水溶型抑菌乳膏及其制备方法。
背景技术
水杨酸,也称为2-羟基苯甲酸,是单羟基苯甲酸,常以游离或者葡糖苷形式广泛存在于自然界中。水杨酸具有广泛抗菌消炎作用,可以用来治疗皮肤浅部真菌感染、脂溢性皮炎,痤疮、疣等多种皮肤病。
目前市场上水杨酸制品多为水杨酸软膏,传统方法是将水杨酸晶体粉碎后过100目筛,再与凡士林研磨均匀,制成软膏。该方法制得的软膏中水杨酸不能溶解,仍为细小晶体,无法充分溶解、分散于载体材料中,不利于水杨酸的生物有效性利用;因此,涂抹使用后不易渗透皮肤,抗菌治疗效果较差;并且水杨酸为脂溶性有机酸,其水溶性很差,几乎不溶于水,无法直接添加到水基产品中,因此限制了其在皮肤抑菌和化妆品生产中的普及应用。
发明内容
本发明要解决的技术问题是提供一种复方水杨酸水溶型抑菌乳膏及其制备方法,以解决现有技术中水杨酸制品中有效成分水溶性差、分散性差而导致的生物有效性不好的技术问题。
为解决上述技术问题,本发明采用如下技术方案:
研发出一种复方水杨酸水溶型抑菌乳膏,以质量百分比计,由以下原料制成:水杨酸2.5~3.5%、酮康唑0.8~1.2%、十八醇3.0~3.6%、单硬脂酸甘油酯3.0~3.6%、硬脂酸2.5~3.5%、液体石蜡4.5~6.5%、凡士林2.5~3.5%、羟苯乙酯0.18~0.22%、十二烷基硫酸钠0.18~0.22%、2,6-叔丁基对甲酚0.2~0.3%、平平加O 1.8~2.2%、甘油8~12%、湿润剂4.0~6.0%、渗透剂0.18~0.25%,余量为水。
本发明抑菌乳膏由抑菌组分(水杨酸、酮康唑)、油相组分(十八醇、单硬脂酸甘油酯、硬脂酸、液体石蜡、凡士林、羟苯乙酯)、水相组分(十二烷基硫酸钠、2,6-叔丁基对甲酚、平平加O、甘油)、渗透剂(如二甲基亚砜等)、湿润剂(如尿素等)等有机组合而成;其中,抑菌组分中的水杨酸、酮康唑均难溶于水,经本发明工艺将其制备成乳剂,有效解决了水杨酸和酮康唑生物有效差的问题;油相组分的作用:十八醇作为分散剂,硬脂酸作为稳定剂和分散剂,羟苯乙酯作为防腐剂和抑菌剂,单硬脂酸甘油酯为乳化剂,凡士林和液体石蜡作为油相以增加基质的润滑度和调节基质的稠度;水相成分的作用:十二烷基硫酸钠为水相中的乳化剂,2.6-叔丁基对甲酚BHT作为抗氧化剂,甘油对基质进行保湿并具有润滑作用,平平加O起良好的水包油的乳化作用。
优选的,以质量百分比计,由以下原料制成:水杨酸3%、酮康唑1%、十八醇3.5%、凡士林3%、硬脂酸3%、单硬脂酸甘油酯3.5%、羟苯乙酯0.2%、液体石蜡6%、十二烷基硫酸钠0.2%、2,6-叔丁基对甲酚0.25%、平平加O 2%、甘油10%、尿素5%、二甲基亚砜 0.2%,余量为水。
上述复方水杨酸水溶型抑菌乳膏的制备方法,包括以下步骤:
(1)按所述配比称取各原料备用;
(2)先将十八醇、单硬脂酸甘油酯、硬脂酸、液体石蜡、凡士林、羟苯乙酯混合后加热至完全溶解,再将2,6-二叔丁基对甲酚、酮康唑依次加入,搅拌均匀后保温,得油相制剂。
(3)将水、甘油混合后加热至86~90℃,再加入十二烷基硫酸钠、平平加O,搅拌均匀后保温,得水相制剂。
(4)先取1/4~1/2量的所述水相制剂预热,然后边搅拌边加入所述油相制剂,再加入剩余的水相制剂,搅拌均匀后得混合剂。
(5)待所述混合剂降温至60~65℃时,依次加入水杨酸、湿润剂(尿素)、渗透剂(二甲基亚砜),搅拌均质,降温后出料即成。
优选的,在所述步骤(2)中,加热温度控制为80~90℃。
优选的,在所述步骤(4)中,预热温度控制为65~70℃;加入余量的所述水相制剂后,以30~35转/min的速度搅拌15~20分钟。
优选的,在所述步骤(5)中,所述搅拌均质的时间为10~15分钟。
与现有技术相比,本发明的主要有益技术效果在于:
1. 本发明先利用抑菌成分水杨酸的脂溶性将其溶于有机溶剂中,然后再制成水包油的剂型,最后乳化形成乳膏,克服了水杨酸可溶性、分散性差的问题,使水杨酸在水溶液中呈可溶性分子状态,使其能够直接添加使用到水基产品中。
2. 本发明不仅包含溶解的水杨酸分子,还直接以水包油的形式溶解、分散于水中,其稳定性和分散性好,能够使水杨酸快速渗透皮肤,大大提高了水杨酸的生物利用度,提高水杨酸抑菌、杀菌和去除角质层的功效。
3. 本发明中的另一抑菌成分酮康唑溶于有机溶剂,几乎不溶于水,限制了其在临床上的应用,而本发明乳膏克服了局部外用几乎不经皮肤吸收的问题,能促进其发挥功效;另一方面,本发明经过长期大量的研究,摸索出了在本发明剂型下匹配合理的水杨酸和酮康唑配合比(2.5~3.5:1),其抑制细菌、真菌的效果显著。
附图说明
图1为本发明实施例中复方水杨酸水溶型抑菌乳膏的成品照片。
图2为本发明复方水杨酸水溶型抑菌乳膏于高温、低温长期放置后的状态照片。
图3 为本发明复方水杨酸水溶型抑菌乳膏分别在加水震荡离心和加油震荡后的状态照片。
图4为本发明复方水杨酸水溶型抑菌乳膏抑菌试验照片;图中,A为不同稀释浓度的乳膏抑制金黄色葡萄球菌情况,B为不同稀释浓度的乳膏抑制白色念珠菌情况。
具体实施方式
下面结合附图和实施例来说明本发明的具体实施方式,但以下实施例只是用来详细说明本发明,并不以任何方式限制本发明的范围。
在以下实施例中所涉及的仪器设备如无特别说明,均为常规仪器设备;所涉及的试剂如无特别说明,均为市售常规试剂;所涉及的试验方法,如无特别说明,均为常规方法。
实施例1:一种复方水杨酸水溶型抑菌乳膏,其由以下原料制成:
水杨酸3.6㎏、酮康唑1.2㎏、十八醇4.2 ㎏、白凡士林3.6 ㎏、硬脂酸3.6 ㎏、单硬脂酸甘油酯4.2 ㎏、羟苯乙酯0.24㎏、液体石蜡7.2 ㎏、十二烷基硫酸钠0.24 ㎏、2,6-叔丁基对甲酚0.3 ㎏、平平加O 2.4㎏、甘油12 ㎏、二甲基亚砜0.25 ㎏、尿素6㎏、纯化水70.97 ㎏。
实施例2:一种复方水杨酸水溶型抑菌乳膏,其由以下原料制成:
水杨酸3.6 ㎏、酮康唑1.2㎏、十八醇4.1㎏、白凡士林3.5 ㎏、硬脂酸3.5 ㎏、单硬脂酸甘油酯4.1㎏、羟苯乙酯0.23 ㎏、液体石蜡7.1 ㎏、十二烷基硫酸钠0.23 ㎏、2,6-叔丁基对甲酚0.25 ㎏、平平加O 2.3 ㎏、甘油11.5 ㎏、尿素5.8㎏、二甲基亚砜0.24 ㎏,纯化水72.35 ㎏。
实施例3:复方水杨酸水溶型抑菌乳膏的制备方法,包括如下步骤:
(1)按实施例1所述配比配置各项原料备用;
(2)油相制备
先将十八醇、单硬脂酸甘油酯、硬脂酸、液体石蜡、白凡士林、羟苯乙酯混合后加热85℃±2℃至完全溶解,将2,6-二叔丁基对甲酚(BHT)、酮康唑依次加入油相,搅拌均匀,保温,得油相制剂。
(3)水相制备
再将纯化水、甘油混合后加热至88℃±2℃,再加入十二烷基硫酸钠、平平加O,继续加热至88℃±2℃,搅拌均匀,保温,得水相制剂。
(4)乳化
① 取1/3水相制剂转移到已预热到65℃的乳化搅拌锅内,边搅拌边快速将油相制剂加入乳化罐中,再将余量的水相制剂加入到乳化搅拌锅内,以35转/min持续搅拌混合20分钟,开启乳化罐的冷却水降温;
② 待降温至60℃时,再依次加入水杨酸、二甲基亚砜、尿素,继续搅拌均质20分钟;
③ 当温度降至40℃时,关闭冷却水、关闭搅拌,开启出料阀出料。
制得的复方水杨酸水溶型抑菌乳膏如图1所示,乳膏色泽呈白色,为质地均匀的膏体,无异味,无肉眼可见的杂质;检测其pH值为5.5。
实施例4:复方水杨酸水溶型抑菌乳膏的制备方法,包括如下步骤:
(1)先按实施例2所述配比配置各原料备用
(2)油相制备
先将十八醇、单硬脂酸甘油酯、硬脂酸、液体石蜡、白凡士林、羟苯乙酯混合加热85℃±2℃至完全溶化,将2,6-二叔丁基对甲酚(BHT)、酮康唑依次加入油相,搅拌均匀,保温,得油相制剂。
(3)水相制备
再将纯化水、甘油加温至88℃±2℃,再加入十二烷基硫酸钠、平平加O,搅拌均匀,保温,得水相制剂。
(4)乳化
① 取1/3水相制剂转移到已预热到68℃的乳化搅拌锅内,边搅拌边快速将油相制剂加入乳化罐中,再将余量的水相制剂加入到乳化搅拌锅内,以30转/min持续搅拌混合15分钟,开启乳化罐的冷却水降温;
② 以2600转/min搅拌5分钟,再均质15分钟;
③ 待降温至65℃时,依次加入实施例1所述配比的水杨酸、尿素、二甲基亚砜,继续搅拌均质15分钟;
④ 当温度降至40℃时,关闭冷却水、关闭搅拌,开启出料阀出料。
制得的复方水杨酸水溶型抑菌乳膏色泽呈白色、质地均匀,无异味,无肉眼可见的杂质;检测其pH值为5.6。
试验例1:
(1)稳定性试验:取实施例3所制备得到的复方水杨酸水溶型抑菌乳膏分别在-20℃和30℃下放置保存1个月,取出观察分析乳膏的稳定性状态,结果参见图2。由图2中可以看出,经过1个月低温(-20℃)和高温(30℃)保存后,水杨酸乳膏无分层、破乳现象,均一性和分散性仍保持较好。
(2)亲水性试验:
取实施例4所制备得到的复方水杨酸抑菌乳膏,加入1倍体积水后,于震荡悬浮器上中频震荡5 min,之后以3000 rpm离心10 min,取出观察可见:乳膏未出现分层、破乳现象,说明其亲水性较好,稳定性好(见图3中左图);
取实施例4所制备得到的复方水杨酸抑菌乳膏,加入油剂中并于震荡悬浮器上中频震荡5 min后,取出观察可见:乳膏仍团聚成团并未分散,说明与油不相溶,为水包油剂型(见图3中右图)。
(3)抑菌性试验:取实施例4所制备得到的水杨酸乳膏用无菌水依次稀释2倍、4倍、6倍和8倍浓度后,用管碟法分别检测其抑制金黄色葡萄球菌和白色念珠菌情况,结果见图4,从中可以看出:稀释6倍后,本发明水杨酸乳膏仍对细菌和真菌有较好抑制作用。
上面结合附图和实施例对本发明作了详细的说明;但是,所属技术领域的技术人员能够理解,在不脱离本发明构思的前提下,还可以对上述实施例中的各个具体参数进行变更,或者是对相关材料及进行等同替代,从而形成多个具体的实施例,均为本发明的常见变化范围,在此不再一一详述。
Claims (9)
1.一种复方水杨酸水溶型抑菌乳膏,其特征在于,以质量百分比计,其由以下原料制成:
水杨酸2.5~3.5%、酮康唑0.8~1.2%、十八醇3.0~3.6%、单硬脂酸甘油酯3.0~3.6%、硬脂酸2.5~3.5%、液体石蜡4.5~6.5%、凡士林2.5~3.5%、羟苯乙酯0.18~0.22%、十二烷基硫酸钠0.18~0.22%、2,6-叔丁基对甲酚0.2~0.3%、平平加O 1.8~2.2%、甘油8~12%、湿润剂4.0~6.0%、渗透剂0.18~0.25%,余量为水。
2.根据权利要求1所述的复方水杨酸水溶型抑菌乳膏,其特征在于,它由以下原料制成:
水杨酸3%、酮康唑1%、十八醇3.5%、单硬脂酸甘油酯3.5%、硬脂酸3%、液体石蜡6%、凡士林3%、羟苯乙酯0.2%、十二烷基硫酸钠0.2%、2,6-叔丁基对甲酚0.25%、平平加O 2%、甘油10%、湿润剂5%、渗透剂 0.2%,余量为水。
3.根据权利要求1或2所述的复方水杨酸水溶型抑菌乳膏,其特征在于,所述湿润剂为尿素。
4.根据权利要求1或2所述的复方水杨酸水溶型抑菌乳膏,其特征在于,所述渗透剂为二甲基亚砜。
5.权利要求1所述复方水杨酸水溶型抑菌乳膏的制备方法,其特征在于,包括以下步骤:
(1)按权利要求1所述原料配比配置各原料备用;
(2)先将十八醇、单硬脂酸甘油酯、硬脂酸、液体石蜡、凡士林、羟苯乙酯混合后加热至完全融化,再依次加入2,6-二叔丁基对甲酚、酮康唑,搅拌均匀后保温,得油相制剂;
(3)将水、甘油混合后加热至85~90℃,再加入十二烷基硫酸钠、平平加O,搅拌均匀后保温,得水相制剂;
(4)先取1/4至1/2量的所述水相制剂预热,然后边搅拌边加入所述油相制剂,再加入剩余的水相制剂,搅拌均匀后得混合剂;
(5)待所述混合剂降温至60~65℃时,再加入水杨酸、湿润剂、渗透剂,搅拌均质,降温后出料即成。
6.根据权利要求5所述复方水杨酸水溶型抑菌乳膏的制备方法,其特征在于,在所述步骤(2)中,加热温度控制为80~90℃。
7.根据权利要求5所述复方水杨酸水溶型抑菌乳膏的制备方法,其特征在于,在所述步骤(4)中,预热温度控制为65~70℃。
8.根据权利要求5所述复方水杨酸水溶型抑菌乳膏的制备方法,其特征在于,在所述步骤(4)中,加入余量的所述水相制剂后,以30~35转/min的速度搅拌15~20分钟。
9.根据权利要求5所述复方水杨酸水溶型抑菌乳膏的制备方法,其特征在于,在所述步骤(5)中,搅拌均质的时间为10~15分钟。
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