CN112915176B - 一种防治脱发的草豆蔻组合物 - Google Patents
一种防治脱发的草豆蔻组合物 Download PDFInfo
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- CN112915176B CN112915176B CN202110302352.2A CN202110302352A CN112915176B CN 112915176 B CN112915176 B CN 112915176B CN 202110302352 A CN202110302352 A CN 202110302352A CN 112915176 B CN112915176 B CN 112915176B
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- alpinia katsumadai
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- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/88—Liliopsida (monocotyledons)
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Abstract
本发明涉及医药学领域，特别是涉及一种防治脱发的组合物及其用途，所述组合物由吡咯烷基二氨基嘧啶氧化物和草豆蔻提取物按重量比9:1～1:9制成，所述草豆蔻提取物可由如下方法制得：取草豆蔻药材，加10倍蒸馏水，浸泡1h，加热煎煮30min，纱布过滤，保存滤液，药渣再加6倍蒸馏水，同法浸泡、煎煮、过滤；将两次滤液混合，冷冻、干燥、粉碎。本发明的组合物可用于防治雄激素性脱发。
Description
技术领域
本发明属于医药领域。具体涉及一种防治脱发的组合物。
背景技术
脱发对个人的心理健康和生活质量产生显著影响，是许多患者自尊心低和焦虑的源头，严重者会导致抑郁症的发生。正常脱落的头发一般是处于退行期及休止期的毛发，由于进入退行期与进入生长期的毛发不断处于动态平衡，故能维持正常数量的毛发。病理性脱发是指头发异常或过度的脱落，导致病理性脱发的因素包括遗传、精神压力、自身免疫、急慢性传染病、各种皮肤病、内分泌失调、化疗毒副作用等。雄激素性脱发(androgeneticalopecia，AGA)又称脂溢性脱发，属于病理性脱发，占脱发人群的90％以上，以头皮油腻、瘙痒、头屑、脱发等为主要表现，是临床最常见的脱发类型，是由于内分泌失调造成的，不同于化疗毒副作用，多见于20-30岁的青壮年男性，以头部及顶部毛发进行性减少为特征，大多在青春期出现，随年龄症状加重。男性女性都存在雄激素性脱发，但在男性中更为常见。至今，美国FDA仅批准了两种治疗雄激素性脱发药物：适用于男女性的米诺地尔酊剂和仅适用于男性的口服非那雄胺片，二者均有显著的副作用，且停药易复发。
草豆蔻为姜科山姜属植物草豆蔻的干燥近成熟种子。具有燥湿行气，温中止呕的功效。吡咯烷基二氨基嘧啶氧化物(Pyrrolidinyl diaminopyrimidine oxide，PDO)是一种能促进头发生长的化合物，可促进毛乳头细胞的增值，恢复毛囊活力。
发明内容
本发明的目的旨在提供一种防治脱发的组合物。
具体地说，本发明提供了一种防治脱发的组合物，所述组合物由吡咯烷基二氨基嘧啶氧化物和草豆蔻提取物按重量比9:1～1:9制成，所述草豆蔻提取物可由如下方法制得：取草豆蔻药材，加10倍蒸馏水，浸泡1h，加热煎煮30min，纱布过滤，保存滤液，药渣再加6倍蒸馏水，同法浸泡、煎煮、过滤；将两次滤液混合，冷冻、干燥、粉碎。
在一优选例中，所述脱发为雄激素性脱发。
在另一优选例中，所述吡咯烷基二氨基嘧啶氧化物和草豆蔻提取物的重量比为4:1～1:4。
在另一优选例中，所述吡咯烷基二氨基嘧啶氧化物和草豆蔻提取物的重量比为7:3～3:7。
在另一优选例中，所述吡咯烷基二氨基嘧啶氧化物和草豆蔻提取物的重量比为3:2～2:3。
在另一优选例中，所述吡咯烷基二氨基嘧啶氧化物和草豆蔻提取物的重量比为1:1。
本发明还提供了上述组合物在制备防治脱发的药物、保健品、化妆品或洗护品中的用途。
本发明各个方面的细节将在随后的章节中得以详尽描述。通过下文的描述，本发明的特点、目的和优势将更为明显。
具体实施方式
本发明的问世部分是基于这样一个意外发现：吡咯烷基二氨基嘧啶氧化物与草豆蔻提取物组合物外用涂剂可促进睾酮诱导的雄激素性脱发小鼠模型的毛发生长，且比单用吡咯烷基二氨基嘧啶氧化物或单用草豆蔻效果更好。因此，吡咯烷基二氨基嘧啶氧化物与草豆蔻提取物组合物外用涂剂可用于制备防治脱发，特别是雄激素性脱发的药物、保健品、化妆品、洗护品等。
本发明的吡咯烷基二氨基嘧啶氧化物可通过商业途径从北京沃凯生物科技有限公司等处购买获得。本发明的草豆蔻提取物可用本领域的常规方法制备获得，如取草豆蔻药材，加10倍蒸馏水，浸泡1h，加热煎煮30min，纱布过滤，保存滤液，药渣再加6倍蒸馏水，同法浸泡、煎煮、过滤；将两次滤液混合，冷冻、干燥、粉碎即得。其亦可通过商业途径从上海源叶生物有限公司处购买获得，其纯度均符合药用标准。本发明的吡咯烷基二氨基嘧啶氧化物和草豆蔻提取物组合物外用涂剂中的吡咯烷基二氨基嘧啶氧化物，建议浓度不超过3.5％，使用剂量2次/天(1ml/次)。
组合物中“可药用载体”不会破坏本发明的吡咯烷基二氨基嘧啶氧化物及草豆蔻提取物提取物的药学活性，同时其有效用量，即能发挥药物载体作用时的用量对人体无毒。
所述可药用载体包括但不限于：软磷脂、硬脂酸铝、氧化铝、离子交换材料、自乳化药物传递系统、吐温或其他表面活化剂、血清蛋白、缓冲物质如磷酸盐、氨基乙酸、山梨酸、水、盐、电解质如硫酸盐精蛋白、磷酸氢二钠、磷酸氢钾、氯化钠、锌盐、硅酸镁、饱和脂肪酸部分甘油酯混合物等。
其他常用的药物辅料如粘合剂(如微晶纤维素)、填充剂(如淀粉、葡萄糖、无水乳糖和乳糖珠粒)、崩解剂(如交联PVP、交联羧甲基淀粉钠、交联羧甲基纤维素钠、低取代羟丙基纤维素)、润滑剂(如硬脂酸镁)以及吸收促进剂、吸附载体、香味剂、甜味剂、赋形剂、稀释剂、润湿剂等。
本发明的吡咯烷基二氨基嘧啶氧化物及草豆蔻提取物组合物按本领域的常规方法制成药物、保健品、化妆品、洗护品等。
所述化妆品或洗护品可以选自生发油、护发素、护发精华、毛发洗剂、毛发营养洗液、洗发香波、染发液、煽油膏、发乳、毛发营养霜、毛发滋润霜、毛发按摩霜、发蜡、毛发气、雾剂、发膜、毛发营养膜、洗发皂、毛发清洁泡沫、发油、毛发干燥剂、毛发护理剂、染发剂、毛发卷曲制剂、毛发漂白剂、发胶、毛发釉、美发用品、粘发剂、毛发保湿剂、毛发摩丝及喷发定型剂组成的剂型。
下面结合具体实施例，进一步阐述本发明。应理解，这些实施例仅用于说明本发明而不用于限制本发明的范围。下列实施例中未注明具体条件的实验方法，通常按照常规条件或按照制造厂商所建议的条件。除非另外说明，否则所有的百分数、比率、比例、或份数按重量计。
除非另行定义，文中所使用的所有专业与科学用语与本领域熟练人员所熟悉的意义相同。此外，任何与所记载内容相似或均等的方法及材料皆可应用于本发明方法中。文中所述的较佳实施方法与材料仅作示范之用。
本发明提到的上述特征，或实施例提到的特征可以任意组合。本专利说明书所揭示的所有特征可与任何组合物形式并用，说明书中所揭示的各个特征，可以任何可提供相同、均等或相似目的的替代性特征取代。因此除有特别说明，所揭示的特征仅为均等或相似特征的一般性例子。
实施例一
1.实验材料
1.1药材
睾酮(CAS：58-22-0，分子量288.42，HPLC纯度≥98％，由美国Sigma-Aldrich公司生产)；草豆蔻提取物；吡咯烷基二氨基嘧啶氧化物(简写PDO，CAS:55921-65-8，分子式C8H13N5O，分子量195.22，HPLC纯度≥98％，北京沃凯生物科技有限公司)
1.2实验动物
体重20±2g的C57BL/6雄性小鼠(8周)，由上海中医药大学实验动物中心提供，动物合格证号：SYXK(沪)2009-0069。置于常规饲养环境，自由进食和饮水。
2.实验方法
2.1吡咯烷基二氨基嘧啶氧化物及草豆蔻提取物组合物外用涂剂的配制
(1)草豆蔻提取物制备方法：取草豆蔻药材，加10倍蒸馏水，浸泡1h，加热煎煮30min，纱布过滤，保存滤液，药渣再加6倍蒸馏水，同法浸泡、煎煮、过滤；将两次滤液混合，冷冻干燥得浸膏，浸膏粉碎，过筛，即得提取物粉末；
(2)取3g PDO粉末加入100ml 1,2丙二醇搅拌混匀，制成3％PDO溶液；
(3)取3g草豆蔻提取物粉末加入100m l1,2丙二醇搅拌混匀，制成3％草豆蔻提取物溶液；
(4)各取3％PDO溶液和3％草豆蔻提取物溶液按照9:1，8:2，7:3，6:4，5:5，4:6，3:7，2:8，1:9的比例搅拌混匀得到不同浓度的PDO提取物+草豆蔻提取物组合物外用涂剂(分别为2.7％PDO+0.3％草豆蔻提取物，2.4％PDO+0.6％草豆蔻提取物，2.1％PDO+0.9％草豆蔻提取物，1.8％PDO+1.2％草豆蔻提取物，1.5％PDO+1.5％草豆蔻提取物，1.2％PDO+1.8％草豆蔻提取物，0.9％PDO+2.1％草豆蔻提取物，0.6％PDO+2.4％草豆蔻提取物，0.3％PDO+2.7％草豆蔻提取物)，即下面的组合物组。
2.2雄激素性脱发小鼠模型的建立及分组涂样
雄激素性脱发小鼠模型的建立参照文献(鹰嘴豆素A对病理脱发模型小鼠毛发生长影响的初步研究.天然产物研究与开发.2014,26:613～618)。选择体重均一的C57BL/6雄性小鼠(20±2g)适应饲养1周，用松香、石蜡混合加热溶化冷却后涂于小鼠背部去除毛发，诱导小鼠毛囊由静止期进入生长期，此时毛囊与自发形成的生长期毛囊在形态上无差别，皮肤呈粉红色。脱毛第二天各组小鼠背部试验区域按以下方法进行动物分组及涂样：
空白对照组：涂抹溶剂30min后，涂抹空白基质；
模型组：涂抹0.1％睾酮30min后，涂抹空白基质；
PDO组：涂抹0.1％睾酮30min后，涂抹3％PDO(制备方法见2.1)；
草豆蔻提取物组：涂抹0.1％睾酮30min后，涂抹3％草豆蔻提取物(制备方法见2.1)；
组合物组：涂抹0.1％睾酮30min后，涂抹组合物(制备方法见2.1)；
2.3评价指标
2.3.1毛长测量：涂药第15d，18d和21d，分别拔去脱毛区域前、中、后部各3搓毛发，测量其长度，取平均值。
2.3.2毛重测量：第21天后处死小鼠，在脱毛区域沿毛发根部剪下3*3cm面积的毛发，分析天平称重，求其平均值。
2.3.3协同分数：协同分数通过Clarke R.Issues in experimental design andendpoint analysis in the study of experimental cytotoxic agents in vivo inbreast cancer and other models[J].Breast Cancer Research&Treatment,1997,46(2-3):255-278描述的公式计算，其全文通过引用并入本文：
协同分数＝((A/C)×(B/C))/(AB/C)；
其中A为药物PDO的毛长或毛重值；B为药物草豆蔻提取物的毛长或毛重值；C为模型组的毛长或毛重值；AB为PDO、草豆蔻提取物联合疗法的毛长或毛重值。协同分数：>1表示协同效应，＝1为叠加效应，<1为拮抗效应(参照Gould SE等，Translational value ofmouse models in oncology drug development.Nature medicine.201521,431-439)。
2.4统计分析
所有实验数据均重复3次，结果以平均值±标准差表示，采用SPSS 16.0统计软件对实验数据采用单向方差分析(One-way ANOVA)及LSD检验，P<0.05为统计学上差异有显著性。
3.结果
3.1吡咯烷基二氨基嘧啶氧化物及草豆蔻提取物组合物对睾酮诱导的雄激素脱发小鼠的治疗作用
3.1.1吡咯烷基二氨基嘧啶氧化物及草豆蔻提取物组合物对毛长的影响
表1体现了吡咯烷基二氨基嘧啶氧化物及草豆蔻提取物组合物对毛发长度的影响。选取造模第15、18、21天的毛发长度来分析，空白对照组毛发生长较多，和脱发模型组相比有显著差异，说明睾酮可抑制毛发生长，模型建立成功；PDO组、草豆蔻提取物组和组合物组均可促进毛发生长，与脱发模型组相比有显著的差异(P＜0.05或P＜0.01或P<0.001)。其中不同比例的组合物组(PDO与草豆蔻提取物9:1，8:2，7:3，6:4，5:5，4:6，3:7，2:8，1:9)对毛发生长的促进作用最强，与单用PDO组及单用草豆蔻提取物组相比均有显著差异(第15天，组合物组vs PDO组：P＜0.05，组合物组vs草豆蔻提取物组：P＜0.05，协同分数均＞1；第18天，组合物组vs PDO组：P＜0.05，组合物组vs草豆蔻提取物组：P＜0.05，协同分数均＞1；第21天，组合物组vs PDO组：P＜0.05，组合物组vs草豆蔻提取物组：P＜0.05，协同分数均＞1)。表明组合物在刺激毛发生长方面显著优于单用PDO或单用草豆蔻提取物。
3.1.2吡咯烷基二氨基嘧啶氧化物及草豆蔻提取物组合物对毛重的影响
表2体现了吡咯烷基二氨基嘧啶氧化物及草豆蔻提取物组合物对小鼠毛重的影响。在第21天处死小鼠，选取脱毛区域，剪下2*2cm面积的毛发，分析天平称重发现空白对照组毛重是83.74±18.48mg，脱发模型组毛重是14.29±3.46mg，PDO组毛重是30.69±3.59mg，草豆蔻提取物组毛重是27.97±2.63mg，组合物组毛重是48.70±6.32mg。说明PDO组、草豆蔻提取物组和组合物组均可促进毛发生长，且与脱发模型组相比均有显著性差异(P＜0.05或P＜0.01或P<0.001)。其中不同比例的组合物组(PDO与草豆蔻提取物9:1，8:2，7:3，6:4，5:5，4:6，3:7，2:8，1:9)对毛发生长的促进作用最强，与单用PDO组及单用草豆蔻提取物组相比均有显著差异(组合物组vs PDO组：P＜0.05，组合物组vs草豆蔻提取物组：P＜0.01，协同分数均＞1)。表明组合物在刺激毛发生长方面显著优于单用PDO或单用草豆蔻提取物。
表1
表2
综上研究结果表明，吡咯烷基二氨基嘧啶氧化物与草豆蔻提取物外用涂剂可刺激毛发的生长，治疗雄激素性脱发，作用效果优于单用吡咯烷基二氨基嘧啶氧化物或单用草豆蔻提取物。
本发明所涉及的多个方面已做如上阐述。然而，应理解的是，在不偏离本发明精神之前提下，本领域专业人员可对其进行等同改变和修饰，所述改变和修饰同样落入本申请所附权利要求的覆盖范围。
Claims (7)
1.一种防治脱发的组合物，其特征在于，所述组合物由吡咯烷基二氨基嘧啶氧化物和草豆蔻提取物按重量比9 : 1 ~ 1 : 9制成，所述草豆蔻提取物由如下方法制得：取草豆蔻药材，加10倍蒸馏水，浸泡1 h，加热煎煮30 min，纱布过滤，保存滤液，药渣再加6倍蒸馏水，同法浸泡、煎煮、过滤；将两次滤液混合，冷冻、干燥、粉碎。
2.如权利要求1所述的组合物，其特征在于，所述脱发为雄激素性脱发。
3.如权利要求1或2所述的组合物，其特征在于，所述吡咯烷基二氨基嘧啶氧化物和草豆蔻提取物的重量比为4 : 1 ~ 1 : 4。
4.如权利要求1或2所述的组合物，其特征在于，所述吡咯烷基二氨基嘧啶氧化物和草豆蔻提取物的重量比为7 : 3 ~ 3 : 7。
5.如权利要求1或2所述的组合物，其特征在于，所述吡咯烷基二氨基嘧啶氧化物和草豆蔻提取物的重量比为3 : 2 ~ 2 : 3。
6.如权利要求1或2所述的组合物，其特征在于，所述吡咯烷基二氨基嘧啶氧化物和草豆蔻提取物的重量比为1 : 1。
7.如权利要求1或2所述的组合物在制备防治脱发的药物中的用途。
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| CN108272781A (zh) * | 2017-11-22 | 2018-07-13 | 上海中医药大学 | 豆蔻明在制备防治脱发的药物中的应用 |
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| CN107550749A (zh) * | 2017-10-15 | 2018-01-09 | 广州汀兰生物科技有限公司 | 一种生发组合物及其应用 |
| CN108272781A (zh) * | 2017-11-22 | 2018-07-13 | 上海中医药大学 | 豆蔻明在制备防治脱发的药物中的应用 |
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