CN113662932A - 新型纳米氨甲环酸靶向制剂及其制备方法 - Google Patents
新型纳米氨甲环酸靶向制剂及其制备方法 Download PDFInfo
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Abstract
本发明属于生物化学领域，尤其涉及一种新型纳米氨甲环酸靶向制剂及其制备方法，由以下重量百分比的原料组成：纳米脂质靶向材料5‑30％；氨甲环酸2％‑20％；乳化剂2％‑10％；增稠剂0.1％‑1％；木瓜蛋白酶0.1％‑1％；有效添加剂0.01％‑10％；余量为去离子水。本发明的氨甲环酸使用周期短，靶向作用速度快，且原料具备更舒适的肤感，更小的乳化粒径，使最终得到的纳米制剂靶向效果更明显。
Description
技术领域
本发明属于生物化学领域，尤其涉及一种新型纳米氨甲环酸靶向制剂及其制备方法。
背景技术
黑色素是决定人体皮肤颜色的一个主要因素，黑色素能有效保护皮肤抵御紫外线辐照造成的皮肤光损伤和光老化，而黑色素过度积累和分布不均匀则会导致皮肤暗沉、黄褐斑、雀斑和老年斑的产生。酪氨酸酶是黑色素合成的主要限速酶，因此对酪氨酸酶的活性进行调控是目前美白淡斑研究和应用最多的途径。氨甲环酸和酪氨酸化学结构相似，竞争性结合酪氨酸酶，从而干扰黑色素的正常形成。氨甲环酸还可以通过以下方式达到提亮肤色的作用：氨甲环酸的纤溶酶抑制作用，通过抑制纤溶酶-纤溶酶原途径，最终导致黑素生成减少，起到淡化色斑的作用；黄褐斑皮损处存在血管增生，纤溶酶释放与真皮细胞间基质结合的血管内皮生长因子。作为纤溶酶抑制的氨甲环酸可以抑制血管形成，减少红斑及血管数量。
近年来越来越多的产品含有氨甲环酸，包括口服和外用制剂。口服产品副作用较多，具体影响难以预知；外用制剂由于氨甲环酸亲水性强，难以通过皮肤角质层障碍，从而使其效果大打折扣。
然而，现有的氨甲环酸产品作用周期长，有用物质只能停留在角质层，难以深入皮肤底层。
发明内容
本发明为了解决上述现有技术中氨甲环酸产品作用周期长，有用物质只能停留在角质层，难以深入皮肤底层等问题，提供一种氨甲环酸使用周期短，靶向作用速度快，且原料具备更舒适的肤感，更小的乳化粒径，使最终得到的纳米制剂靶向效果更明显的新型纳米氨甲环酸靶向制剂及其制备方法。
本发明的技术方案：一种新型纳米氨甲环酸靶向制剂，由以下重量百分比的原料组成：
优选地，所述纳米脂质靶向材料为角鲨烷、蚕丝油、向日葵籽油、橄榄油、甜扁桃油、霍霍巴籽油、乳木果油、辛酸/癸酸甘油三酯、聚二甲基硅氧烷、环五聚二甲基硅氧烷中的一种或者几种复配使用。
角鲨烷、甜扁桃油等天然植物来源的油脂含有大量维生素、植物甾醇等有益成分。
优选地，所述乳化剂是使体系中不相溶的纳米脂质靶向材料和其他组分形成稳定纳米制剂的一组物质，乳化剂降低了体系中各组分的界面张力，并在微滴表面形成较坚固的薄膜。
优选地，所述乳化剂选自氢化卵磷脂、聚甘油-3二异硬脂酸酯、聚甘油-6聚羟基硬脂酸酯、聚甘油-6聚蓖麻油醇酸酯、PEG-8蜂蜡、三山嵛精PEG-20酯类中的一种或多种复配使用。
本发明的乳化剂属于天然绿色型或基于天然物质改造型，具有更舒适的肤感，更小的乳化粒径，使最终得到的纳米制剂靶向效果更明显。
优选地，所述增稠剂为透明质酸、黄原胶、卡波姆、纤维素类、丙烯酰二甲基牛磺酸铵/VP共聚物中的一种或多种复配使用。
纤维素类如羧甲基纤维素、羟乙基纤维素。
优选地，所述有效添加剂为抗氧剂和防腐剂，所述抗氧剂选用维生素E；防腐剂选用苯氧乙醇、1.2-己二醇、山梨酸、对羟基苯乙酮中的一种或者多种复配。
一种新型纳米氨甲环酸靶向制剂的制备方法，步骤如下：
1)称取纳米脂质靶向材料、乳化剂混合后加热至60-80℃，得到均一液态油相；同时将作为水相的氨甲环酸、增稠剂、余量水加热至60-80℃；
2)采用双水相萃取法，用10％的聚乙二醇和14％的硫酸铵组成的双水相系统获得较高纯度的木瓜蛋白酶；
3)将油相和水相混合后，在真空均质机中均质5-15min，速度为1000-2000rpm；
4)真空均质后，开启搅拌降温至40℃，加入木瓜蛋白酶、有效添加剂，继续搅拌得到初乳；
5)初乳转入高压均质机循环5-15周，压力为500-1500bar，得到液体精华乳；
6)精华乳进一步进行喷雾干燥处理得到纳米氨甲环酸微囊。
本发明的氨甲环酸使用周期短，靶向作用速度快，且原料具备更舒适的肤感，更小的乳化粒径，使最终得到的纳米制剂靶向效果更明显。
采用本发明方法制备新型纳米氨甲环酸靶向制剂，与现有氨甲环酸制剂相比，具有很多有益之处：
1.制备过程简单，粒径更小，纳米靶向制剂中的平均粒径不超过0.1μm，有效成分在靶向部位逐步缓释；
2.添加木瓜蛋白酶，采用双水相萃取法，用10％的聚乙二醇和14％的硫酸铵组成的双水相系统获得较高纯度的木瓜蛋白酶。木瓜蛋白酶分解角质，加快移除靶向部位的老化角质细胞，与氨甲环酸联合使用，大大提高靶向淡化色素的效果；纳米脂质材料选取与皮肤角质层有良好相容性的成分；
3.乳化剂选取天然或基于天然改性的，具有更舒适的肤感，更小的乳化粒径，使最终得到的纳米制剂靶向效果更明显；
4.纳米制剂产品形式多样，经过真空均质和高压均质之后得到纳米精华液；经过真空均质、高压均质和喷雾干燥得到纳米微囊。
具体实施方式
下面结合实施例对本发明作进一步详细的说明，但并不是对本发明保护范围的限制。
实施例1
一种新型纳米氨甲环酸靶向制剂，其原料重量百分比如下：
上述新型纳米氨甲环酸靶向制剂的制备方法，步骤如下：
(1)称取角鲨烷、辛酸/癸酸甘油三酯、氢化卵磷脂加热至60-80℃
得到油相；称取去离子水、氨甲环酸、透明质酸加热至60-80℃
得到水相；
(2)将油相和水相混合，在真空均质机中均质5-15min，速度为1000-2000rpm；
(3)真空均质后，开启搅拌降温至40℃，加入木瓜蛋白酶、维生素E、苯氧乙醇，继续搅拌得到初乳；
(4)初乳转入高压均质机循环5-15周，压力为500-1500bar，得到液体精华乳。
实施例2
一种新型纳米氨甲环酸靶向制剂，其原料重量百分比如下：
上述新型纳米氨甲环酸靶向制剂的制备方法，步骤如下：
(1)称取橄榄油、环五聚二甲基硅氧烷、氢化卵磷脂、聚甘油-6聚羟基硬脂酸酯加热至60-80℃得到油相；称取去离子水、氨甲环酸、卡波姆、对羟基苯乙酮加热至60-80℃得到水相。
(2)将油相和水相混合，在真空均质机中均质5-15min，速度为1000-2000rpm。
(3)真空均质后，开启搅拌降温至40℃，加入木瓜蛋白酶、维生素E、1.2-己二醇，继续搅拌得到初乳。
(4)初乳转入高压均质机循环5-15周，压力为500-1500bar，得到液体精华乳。
实施例3：
一种新型纳米氨甲环酸靶向制剂，其原料重量百分比如下：
上述新型纳米氨甲环酸靶向制剂的制备方法，步骤如下：
(1)称取甜扁桃油、聚二甲基硅氧烷、氢化卵磷脂、聚甘油-6聚蓖麻油醇酸酯加热至60-80℃得到油相；称取去离子水、氨甲环酸、羟乙基纤维素、山梨酸加热至60-80℃得到水相。
(2)将油相和水相混合，在真空均质机中均质5-15min，速度为1000-2000rpm。
(3)真空均质后，开启搅拌降温至40℃，加入木瓜蛋白酶、维生素E继续搅拌得到初乳。
(4)初乳转入高压均质机循环5-15周，压力为500-1500bar，得到液体精华乳。
实施例4：
一种新型纳米氨甲环酸靶向制剂，其原料重量百分比如下：
上述新型纳米氨甲环酸靶向制剂的制备方法，步骤如下：
(1)称取乳木果油、辛酸/癸酸甘油三酯、氢化卵磷脂、PEG-8蜂蜡加热至60-80℃得到油相；称取去离子水、氨甲环酸、黄原胶加热至60-80℃得到水相。
(2)将油相和水相混合，在真空均质机中均质5-15min，速度为1000-2000rpm。
(3)真空均质后，开启搅拌降温至40℃，加入木瓜蛋白酶、维生素E、苯氧乙醇、1.2-己二醇，继续搅拌得到初乳。
(4)初乳转入高压均质机循环5-15周，压力为500-1500bar，得到液体精华乳。
本发明4个实施例的测试效果如下：
选择实施例1-4制得的新型纳米氨甲环酸靶向制剂。
受试人群：150人，年龄介于25至40岁之间，均为室内工作者，受试者皮肤健康，符合受试者志愿入选标准。
测试指标：
①皮肤黑色素含量(MI值)，MI值表征黑色素指数,通过测定特定波长的光照在人体皮肤上的反射量来确定皮肤中黑色素的含量。
②皮肤白度(亮度)(L*值)，值越大颜色越偏向白色，反之偏向黑色。
③皮肤明亮度(暗黄度)(ITA°值)，值越大，皮肤越明亮，反之皮肤越暗沉。
测试方法：分别使用实施例1-4制得的新型纳米氨甲环酸靶向制剂，对照组为空白对照组。每天洁面后，使用实施例样品涂敷于测试部位(大约2μL/cm2)。使用0、2、4周后进行检测，检测时控制温度(20±2)℃，测试者面部稍作清洁后，在此环境下静坐25min后进行测试，用皮肤黑色素和血红素测试探头检测受试者使用样品前后的MI值；用皮肤色差测试探头测试受试者使用样品前后L*值和ITA°值。根据0周的数据将150人进行分组，分为5组，每组30人。
检测结果如表1：
表1：受试者使用0、2、4周的MI值、L*值和ITA°值的平均值。
实施例1-4在第2周、第4周的结果均显著高于对照组(p＜0.05)，结果显示新型纳米氨甲环酸靶向制剂可以达到良好的抑制黑色素，显著提亮肤色的作用。
Claims (7)
1.一种新型纳米氨甲环酸靶向制剂，其特征在于：其由以下重量百分比的原料组成：
2.根据权利要求1所述的一种新型纳米氨甲环酸靶向制剂，其特征在于：所述纳米脂质靶向材料为角鲨烷、蚕丝油、向日葵籽油、橄榄油、甜扁桃油、霍霍巴籽油、乳木果油、辛酸/癸酸甘油三酯、聚二甲基硅氧烷、环五聚二甲基硅氧烷中的一种或者几种复配使用。
3.根据权利要求1所述的一种新型纳米氨甲环酸靶向制剂，其特征在于：所述乳化剂是使体系中不相溶的纳米脂质靶向材料和其他组分形成稳定纳米制剂的一组物质，乳化剂降低了体系中各组分的界面张力，并在微滴表面形成较坚固的薄膜。
4.根据权利要求3所述的一种新型纳米氨甲环酸靶向制剂，其特征在于：所述乳化剂选自氢化卵磷脂、聚甘油-3二异硬脂酸酯、聚甘油-6聚羟基硬脂酸酯、聚甘油-6聚蓖麻油醇酸酯、PEG-8蜂蜡、三山嵛精PEG-20酯类中的一种或多种复配使用。
5.根据权利要求1所述的一种新型纳米氨甲环酸靶向制剂，其特征在于：所述增稠剂为透明质酸、黄原胶、卡波姆、纤维素类、丙烯酰二甲基牛磺酸铵/VP共聚物中的一种或多种复配使用。
6.根据权利要求1所述的一种新型纳米氨甲环酸靶向制剂，其特征在于：所述有效添加剂为抗氧剂和防腐剂，所述抗氧剂选用维生素E；防腐剂选用苯氧乙醇、1.2-己二醇、山梨酸、对羟基苯乙酮中的一种或者多种复配。
7.一种如权利要求1所述的新型纳米氨甲环酸靶向制剂的制备方法，其特征在于：其步骤如下：
1)称取纳米脂质靶向材料、乳化剂混合后加热至60-80℃，得到均一液态油相；同时将作为水相的氨甲环酸、增稠剂、余量水加热至60-80℃；
2)采用双水相萃取法，用10％的聚乙二醇和14％的硫酸铵组成的双水相系统获得较高纯度的木瓜蛋白酶；
3)将油相和水相混合后，在真空均质机中均质5-15min，速度为1000-2000rpm；
4)真空均质后，开启搅拌降温至40℃，加入木瓜蛋白酶、有效添加剂，继续搅拌得到初乳；
5)初乳转入高压均质机循环5-15周，压力为500-1500bar，得到液体精华乳；
6)精华乳进一步进行喷雾干燥处理得到纳米氨甲环酸微囊。
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Application publication date: 20211119 |