CN112041329A - 用于预防脱发或促进毛发生长的组合物 - Google Patents
用于预防脱发或促进毛发生长的组合物 Download PDFInfo
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- CN112041329A CN112041329A CN201980021093.7A CN201980021093A CN112041329A CN 112041329 A CN112041329 A CN 112041329A CN 201980021093 A CN201980021093 A CN 201980021093A CN 112041329 A CN112041329 A CN 112041329A
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Abstract
本发明涉及用于预防脱发或促进毛发生长的组合物,并且根据本发明,Wnt蛋白衍生肽、多聚脱氧核糖核苷酸或它们的混合物通过促进毛发生长信号系统的信号转导途径的激活和细胞激活来增加β‑连环蛋白的分泌,并增加作为头发组成细胞的角质细胞、成纤维细胞和真皮乳突细胞的生长,以预防脱发和促进毛发生长,因此可将具有上述作用的Wnt蛋白衍生肽、多聚脱氧核糖核苷酸或它们的混合物用作用于预防脱发或促进毛发生长的化妆品组合物、药物组合物或保健食品组合物。
Description
技术领域
本发明涉及用于预防脱发或促进毛发生长的组合物,所述组合物包含新型Wnt蛋白衍生肽、多聚脱氧核糖核苷酸(polydeoxyribonucleotide)或它们的混合物作为活性成分。
背景技术
头发是一种由紧密粘附和角质化的上皮细胞组成的实心锥形纤维,头皮毛囊中形成约10万至15万根头发,并且已知,毛囊的数量是在出生时确定的,并且出生后不会进一步生成。每一根头发都代表着一个不同的周期:毛发生长的生长初期,毛发生长停止而毛球缩小的生长中期,真皮乳突开始活动或形成新的头发从而导致旧头发脱落的休止期,通过重复这个周期头发生长和脱落。这个周期重复3年至6年,范围为男性3-5年、女性4-6年。正常情况下,已知每天平均有50-70根头发脱落,生长初期、生长中期和休止期的头发分别约占全部头发的88%、1%和11%。
脱发是指每天至少有100根头发脱落、生长初期头发减少以及生长中期和休止期头发增多的症状。随着脱发的进行,休止期的发率迅速增加,生长初期的发率相应降低。脱发一般可包括遗传性雄性激素性脱发(秃顶)、斑秃、真菌感染引起的头癣、休止期脱发、拔毛癖、毛发生长障碍等。最常见的脱发包括秃顶(男性脱发)、女性脱发、斑秃以及休止期落发等。
脱发的原因很多。遗传因素和男性荷尔蒙(雄性激素)被认为是影响秃顶的重要因素,据估计有些女性脱发是由与男性脱发相同的途径引起的,但临床表现存在差异。斑秃被认为是由自身免疫性疾病引起的。休止期脱发是一种暂时性脱发,其发生在严重的身体和精神压力后,如内分泌疾病、营养缺乏、药物、分娩、发烧和外科手术,并且它是由于部分头发没有经过生长期而过渡到休止期而脱落所引起的。
目前,仅有两种FDA批准的脱发处理产品:非那雄胺(Finasteride)和米诺地尔(Minoxidil)。非那雄胺是一种男性脱发治疗药物,作为男性脱发处理剂,它通过抑制5α-还原酶的机制来抑制脱发,5α-还原酶是将男性荷尔蒙转化为脱发诱导因子二氢睾酮(DHT)的酶。米诺地尔通过增加头皮血流量来抑制脱发。然而,这些疗法经常被报道有一些副作用,而且它们的治疗效果是暂时和有限的。脱发是多种因素综合造成的而不是任一种因素,并且某些因素的解决也不能完全治愈它。
因此,西方医学和东方医学对脱发进行了各种研究,并尝试了各种治疗方法。天然产物、类固醇、自身免疫抑制等方面的研究正在进行,并且采用激光治疗、自体富血小板血浆应用、微针滚轮(derma roller)或干细胞等治疗也已开展。然而,这些治疗也不能以复杂的方式解决各种脱发的原因,并且未经科学检验的医疗程序具有的缺点在于,与价格相比,它们并不起作用。因此,迫切需要开发经科学验证的且在成本方面更经济的针对脱发的新型药物。
发明内容
技术问题
本发明的目的在于提供用于预防脱发或促进毛发生长的肽。
本发明的另一个目的在于提供用于预防脱发或促进毛发生长的化妆品组合物。
本发明的第三个目的在于提供用于预防脱发或促进毛发生长的药物组合物。
本发明的第四个目的在于提供用于预防脱发或促进毛发生长的保健食品组合物。
技术方案
为了实现上述目的,本发明提供了包含选自于由SEQ ID NO:1和SEQ ID NO:2组成的组中的至少任一种氨基酸序列的肽。
此外,本发明还提供了用于预防脱发或促进毛发生长的化妆品组合物,所述化妆品组合物含有如下作为活性成分:包含选自于由SEQ ID NO:1和SEQ ID NO:2组成的组中的至少任一种氨基酸序列的肽、多聚脱氧核糖核苷酸或它们的混合物。
此外,本发明还提供了用于预防脱发或促进毛发生长的药物组合物,所述药物组合物含有如下作为活性成分:包含选自于由SEQ ID NO:1和SEQ ID NO:2组成的组中的至少任一种氨基酸序列的肽、多聚脱氧核糖核苷酸或它们的混合物。
此外,本发明提供了用于预防脱发或促进毛发生长的保健食品组合物,所述保健食品组合物含有如下作为活性成分:包含选自于由SEQ ID NO:1和SEQ ID NO:2组成的组中的至少任一种氨基酸序列的肽、多聚脱氧核糖核苷酸或它们的混合物。
有益效果
根据本发明,Wnt蛋白衍生肽、多聚脱氧核糖核苷酸或其混合物通过促进毛发生长信号系统的信号转导途径的激活和细胞激活来增加β-连环蛋白的分泌,并增加作为头发组成细胞的角质细胞、成纤维细胞和真皮乳突细胞的生长,以预防脱发和促进毛发生长,因此可将具有上述作用的Wnt蛋白衍生肽、多聚脱氧核糖核苷酸或它们的混合物用作用于预防脱发或促进毛发生长的化妆品组合物、药物组合物或保健食品组合物。
附图说明
图1示出了衍生自Wnt蛋白的新型肽-1(Wnt-1,SEQ ID NO:1)和肽-2(Wnt-2,SEQID NO:2)的高效液相色谱分析的结果。
图2示出了使用真皮乳突细胞通过多聚脱氧核糖核苷酸(PDRN)促进细胞生长的效果及其显微图像。
图3示出了使用(A)角质细胞、(B)成纤维细胞和(C)真皮乳突细胞通过Wnt-1或Wnt-2促进细胞生长的效果及其显微图像。
图4示出了使用角质细胞通过(A)Wnt-1+PDRN或(B)Wnt-2+PDRN促进细胞生长的效果及其显微图像。
图5示出了使用真皮乳突细胞通过Wnt-1+Wnt-2+PDRN促进细胞生长的效果及其显微图像。
图6示出了使用真皮乳突细胞通过(A)PDRN;(B)Wnt-1、Wnt-2、Wnt-1和Wnt-2;(C)Wnt-1和Wnt-2来增加β-连环蛋白活性的效果。
图7示出了使用真皮乳突细胞通过(A)PDRN;(B)Wnt-1、Wnt-2、Wnt-1+Wnt-2、Wnt-1+PDRN、Wnt-2+PDRN、Wnt-1+Wnt-2+PDRN来增加c-myc活性的效果。
图8示出了使用去除毛发的C57BL/6小鼠通过Wnt-1+Wnt-2+PDNR的毛发生长效果。
具体实施方式
本发明的发明人证实,新型Wnt蛋白衍生肽(Wnt-1或/和Wnt-2)、多聚脱氧核糖核苷酸或它们的混合物激活Wnt信号系统,以增加β-连环蛋白的分泌和活性,促进对毛根产生而言重要的角质细胞、成纤维细胞和真皮乳突细胞的生长,并在生长初期诱导毛发分化,完成了本发明。
因此,本发明提供了包含选自于由SEQ ID NO:1和SEQ ID NO:2组成的组中的至少任一种氨基酸序列的肽。
所述肽可在氨基酸序列的N端被乙酰化。
所述肽可以是衍生自Wnt蛋白的肽。Wnt蛋白衍生肽是发挥与天然Wnt蛋白的功能类似的功能的肽,并且与受体结合以发挥诸如生长因子功能的功能。
所述肽可预防脱发和促进毛发生长。
本发明还提供了用于预防脱发或促进毛发生长的化妆品组合物,所述化妆品组合物含有如下作为活性成分:包含选自于由SEQ ID NO:1和SEQ ID NO:2组成的组中的至少任一种氨基酸序列的肽、多聚脱氧核糖核苷酸或它们的混合物。
所述肽可在氨基酸序列的N端被乙酰化。
所述肽可以是衍生自Wnt蛋白的肽。Wnt蛋白衍生肽是发挥与天然Wnt蛋白的功能类似的功能的肽,并且与受体结合以发挥诸如生长因子功能的功能。
多聚脱氧核糖核苷酸分离自鱼的精巢,所述鱼可以选自于由鲑鱼(salmon)、鳟鱼、鲱鱼、青鳕(pollock)和鳕鱼(cod)组成的组,但不限于此。
多聚脱氧核糖核苷酸可具有350kDa至2000kDa的数均分子量。
此外,该组合物增加β-连环蛋白的分泌,以促进角质细胞、成纤维细胞和真皮乳突细胞的生长并增加c-myc的表达,从而预防脱发和促进毛发生长。
可将该组合物配制成选自于由如下组成的组中的制剂:生发液(hair tonic)、护发素(hair conditioner)、亮发素(hair essence)、头发洗剂(hair lotion)、头发营养洗剂(hair nutrition lotion)、洗发香波、润发精(hair rinse)、焗油膏(hair treatment)、发乳(hair cream)、头发营养霜、头发保湿霜、头发按摩霜、发蜡、头发气雾剂(hairaerosol)、发膜、头发营养膜、发皂(hair soap)、洗发乳(hair cleansing foam)、发油、头发干洗剂(hair drying agent)、护发护理剂(hair preservation treatment)、染发剂、卷发剂、头发去色剂、发胶(hair gel)、发釉、美发剂(hair dressinger)、粘发剂、润发膏(hair moisturizer)、发用摩丝(hair mousse)和头发喷雾剂(hair spray),但不限于此。
当本发明的组合物是化妆品组合物时,除了活性成分外,化妆品组合物还可以包含常规助剂,例如稳定剂、增溶剂、维生素、色素和香料以及载体。此外,化妆品组合物可进一步包含皮肤吸收增强剂,以增强效果。
当本发明的组合物是化妆品组合物时,化妆品组合物的制剂可以以本领域通常制备的任意制剂来制备,例如,化妆品组合物可以是面部洗剂(face lotion)、乳剂、皮肤洗剂(skin lotion)、化妆水(toner)、洗剂(lotion)、精华(essence)、防晒霜、霜剂、隔离霜、粉底、散剂、膜、凝胶、软膏(ointment)、贴剂(patch)、棒(stick)、洗发水、冲洗剂(rinse)、喷雾剂(spray)、卸妆水和清洁剂等,但不限于此。
当所述制剂为糊剂、霜剂或凝胶时,其可使用动物油、植物油、蜡、石蜡、淀粉、黄芪胶、纤维素衍生物、聚乙二醇、硅酮、膨润土、二氧化硅、滑石粉或氧化锌等作为载体组分。
当所述制剂是散剂或喷雾剂时,其可使用乳糖、滑石粉、二氧化硅、氢氧化铝、硅酸钙或聚酰胺粉末作为载体组分,并且特别地,喷雾剂可额外包含推进剂,例如氯氟烃、丙烷/丁烷或二甲醚。
当所述制剂是溶液或乳剂时,使用溶剂、增溶剂或乳化剂作为载体组分,例如水、乙醇、异丙醇、碳酸乙酯、乙酸乙酯、苄醇、苯甲酸苄酯、丙二醇、1,3-丁二醇油(1,3-butylglycol oil)、甘油脂肪酸酯(glycerol aliphatic ester)、聚乙二醇或失水山梨醇的脂肪酸酯。
当所述制剂是混悬剂时,其可使用如下作为载体组分:液体稀释剂,例如水、乙醇或丙二醇;助悬剂,例如乙氧基化的异硬脂醇、聚氧乙烯山梨醇酯和聚氧乙烯失水山梨醇酯、微晶纤维素、偏氢氧化铝(aluminummetahydroxide)、膨润土、琼脂或黄芪胶。
本发明还提供用于预防脱发或促进毛发生长的药物组合物,所述药物组合物含有如下作为活性成分:包含选自于由SEQ ID NO:1和SEQ ID NO:2组成的组中的至少任一种氨基酸序列的肽、多聚脱氧核糖核苷酸或它们的混合物。
所述肽可在氨基酸序列的N端被乙酰化。
当本发明所述的组合物为药物组合物时,对于给予,除了上述活性成分外,所述组合物可包含药学上可接受的载体、赋形剂或稀释剂。载体、赋形剂和稀释剂可包括乳糖、葡萄糖、蔗糖、山梨醇、甘露醇、木糖醇、赤藓糖醇、麦芽糖醇、淀粉、阿拉伯树胶、海藻酸盐、明胶、磷酸钙、硅酸钙、纤维素、甲基纤维素、微晶纤维素、聚乙烯吡咯烷酮、水、羟基苯甲酸甲酯、羟基苯甲酸丙酯、滑石粉、硬脂酸镁和矿物油。
本发明所述的药物组合物可根据各自的常规方法以口服制剂的形式配制,所述口服制剂例如散剂、颗粒剂、片剂、胶囊剂、混悬剂、乳剂、糖浆剂或气雾剂(aerosol)、外部制剂、栓剂或无菌注射溶液。具体而言,当配制时,其可使用常用的稀释剂或赋形剂制备,例如填充剂、膨胀剂、粘合剂、润湿剂、崩解剂和表面活性剂。用于口服给予的固体制剂包括片剂、丸剂、散剂、颗粒剂、胶囊剂等,但不限于这些。除了活性成分之外,此种固体制剂可通过混合将至少一种赋形剂(例如淀粉、碳酸钙、蔗糖、乳糖、明胶等)来制备。此外,除了简单的赋形剂外,还可以使用例如硬脂酸镁和滑石粉的润滑剂。除了口服使用的液体和液体石蜡外,固体制剂还可以通过添加各种赋形剂(例如润湿剂、甜味剂、芳香剂、防腐剂等)来制备。用于肠胃外给予的制剂包括无菌水性溶液、非水性溶剂、混悬剂、乳剂、冻干制剂和栓剂。作为非水性溶剂和混悬剂,可使用丙二醇、聚乙二醇、植物油(如橄榄油)、可注射酯(例如油酸乙酯)等。作为栓剂的基质,可使用witepsol、聚乙二醇(macrogol)、吐温61、可可脂、月桂酯(laurinum)、甘油明胶等。
本发明的药物组合物的适宜剂量根据患者的条件和体重、疾病的严重程度、药物的形式和时间而变化,但可由本领域技术人员适当地进行选择。因此,该组合物的日剂量优选为0.001mg/kg至50mg/kg,并且可根据需要给予一次或分成数次进行给予。
本发明提供了用于预防脱发或促进毛发生长的保健食品组合物,所述保健食品组合物含有如下作为活性成分:包含选自于由SEQ ID NO:1和SEQ ID NO:2组成的组中的至少任一种氨基酸序列的肽、多聚脱氧核糖核苷酸或它们的混合物。
所述肽可在氨基酸序列的N端被乙酰化。
当本发明所述的组合物是保健食品组合物时,其可包含各种营养素、维生素、矿物质(电解质)、诸如合成香料和天然香料等的香料、着色剂和填充剂(奶酪、巧克力等)、果胶酸及其盐、褐藻酸及其盐、有机酸、保护性胶体增稠剂、pH调节剂、稳定剂、防腐剂、甘油、醇类、碳酸饮料中使用的碳酸剂(carbonating agent)等。此外,该组合物也可含有用于生产天然果汁、合成果汁和蔬菜饮料的果肉。这些成分可单独使用或组合使用。另外,保健功能性食品组合物可处于肉、香肠、面包、巧克力、糖果、点心、糕点、披萨、拉面、口香糖、冰淇淋、汤、饮料、茶、功能性水、饮品、酒精和维生素复合物中的任一种的形式。
此外,保健功能性食品组合物可进一步包含食品添加剂,并且除非另有规定,其作为食品添加剂的合规性通过由食品和药品安全部(Ministry of Food and Drug Safety)批准的韩国食品添加剂法典的总则和一般测试方法(General Regulations and GeneralTest Methods of Korean Food Additives Codex)的可适用项目的标准来确定。
上述“韩国食品添加剂法典”中公布的项目的实例包括:化学合成物,例如酮类、甘氨酸、柠檬酸钾、烟酸和肉桂酸等;天然添加剂,例如柿子提取物、甘草提取物、结晶纤维素、高粱色素和瓜尔胶等;混合制剂,例如L-谷氨酸钠制剂、面条的碱性制剂、防腐剂制剂和焦油色素制剂等。
此时,在制备保健功能性食品组合物的过程中添加到食品中的本发明所述的组合物的含量可根据需要适当地增加或减少。
实施例
以下,将对实施例进行详细描述以帮助理解本发明。然而,以下实施例仅仅是为了说明本发明的内容,并且本发明的范围不受这些实施例的限制。为了向本领域技术人员更全面地解释本发明,提供了本发明的实施方式。
实施例1:衍生自Wnt蛋白的新型肽的制备
为了生产本发明的衍生自Wnt蛋白的新型肽,对Wnt蛋白家族进行了检测,并使用BlastP程序预测了Wnt蛋白的每个部分的功能。其中,探索了与受体蛋白的潜在结合,并优化了预测位点的氨基酸序列以选择和构建本发明的肽。
由Peptron合成了肽。在肽自动合成仪(PeptrEX-R48)中,用Fmoc固相法合成了所需肽,并将合成肽从树脂中分离出来。使用Shiseido capcell pak C18分析RP柱,通过反相HPLC(Prominence LC-20AB,岛津(Shimadzu),日本)对肽进行完全分离和分析。所述肽由下表1的氨基酸序列表示,并且氨基酸序列的N端被乙酰化(图1)。
[表1]
氨基酸序列 | |
Wnt-1 | MCCGRGYDQF |
Wnt-2 | MCCGRGYNYH |
实施例2:通过多聚脱氧核糖核苷酸对细胞生长的分析
,使用含有10%胎牛血清(FBS)和1%青霉素/链霉素的DMEM培养基(Dulbeco’sModified Eagle’s Medium),在37℃、5%CO2的培养箱中对真皮乳突细胞(Promocells)进行培养。
通过用胰蛋白酶/EDTA对培养的细胞进行处理来回收细胞,然后使用血细胞计数器测量细胞数量。以3×103个细胞/200μL/孔将细胞接种在96孔板中,然后稳定至少4小时。此后,去除培养基,在DEME培养基中稀释以使多聚脱氧核糖核苷酸(PDRN)浓度为50μg/mL、100μg/mL、200μg/mL,然后用细胞处理并在37℃、5%CO2的培养箱中培养72小时。
随后,通过用胰蛋白酶/EDTA对细胞进行处理来回收细胞,然后使用血细胞计数器测量细胞数量。基于未用PDRN处理的对照组,通过计算百分比来分析细胞生长率。
作为结果,如图2所示,证实了真皮乳突细胞的生长率随着PDRN处理浓度的增加而增加。
实施例3:通过Wnt衍生肽对细胞生长的分析
为了证实细胞的形态变化和增殖率,在含有10%胎牛血清和1%青霉素/链霉素的DMEM培养基中培养角质细胞T0020001(AddexBio)、成纤维细胞(ATCC)和真皮乳突细胞。
在通过用胰蛋白酶/EDTA对培养的细胞进行来回收细胞之后,用血细胞计数器测量细胞数量。以3×103个细胞/200μL/孔将细胞接种于96孔板中,并稳定至少4小时。
此后,去除培养基,用DEME培养基稀释以使Wnt肽(Wnt-1、Wnt-2)为10ng/mL、100ng/mL、1000ng/mL和10000ng/mL,然后用细胞处理并在37℃、5%CO2的培养箱中培养72小时。细胞随后用显微镜观察来分析细胞形态和生长率。
作为结果,如图3所示,在角质细胞中,随着Wnt-1肽浓度的增加,细胞的生长率增加,并且浓度为100ng/mL的Wnt-2肽显示出最高的细胞生长率(图3A)。此外,成纤维细胞在10ng/mL浓度的Wnt-1肽下表现出生长效应,并且在高浓度下表现出类似的细胞生长率,然而与对照组相比,在Wnt-2肽中未观察到变化(图3B)。最后,在真皮乳突细胞中,Wnt-1肽和Wnt-2肽在100ng/mL下均显示出最高的细胞生长率(图3C)。
实施例4:通过Wnt肽与PDRN联合处理对细胞生长的分析
如实施例1中,将真皮乳突细胞以3×103个细胞/200μL/孔接种于96孔板中,并稳定至少4小时。此后,去除培养基,用DEME培养基稀释以使多聚脱氧核糖核苷酸(PDRN,BRPharm Co.Ltd.)为25μg/mL、50μg/mL、100μg/mL且Wnt-1肽+Wnt-2肽为0.1μg/mL(各自0.05μg/mL),然后用细胞处理并在37℃、5%CO2的培养箱中培养72小时。
随后,通过用胰蛋白酶/EDTA对细胞进行处理来回收细胞,然后用血细胞计数器测量细胞数量。基于未用PDRN处理的对照组,通过计算百分比来分析细胞生长率。
作为结果,如图5所示,与单独使用Wnt-1+Wnt-2处理相比,当与PDRN联合进行处理时,细胞的生长率增加,并且,随着PDRN的处理浓度的增加,真皮乳突细胞的生长率增加。
实施例5:β-连环蛋白和c-myc的表达分析
如实施例1中,在以4×104个细胞/孔接种于6孔板后,使真皮乳突细胞稳定至少4小时。此后,去除培养基,用不同浓度的PDRN、Wnt-1肽和Wnt-2肽单独或组合对细胞进行处理,并在37℃、5%CO2的培养箱中培养72小时。
然后,通过向每个细胞中添加裂解缓冲液(1M Tris-HCl,0.5M EDTA,1%TritonX-100,100mM PMSF)来裂解细胞,并使用BCA(二喹啉甲酸(Bicinchoninic acid))试剂盒对蛋白进行定量。将20μg蛋白装载在10%SDS-聚丙烯酰胺上,并在125V下进行电泳。通过使用转移缓冲液(20%甲醇、25mM Tris-HCl、192mM甘氨酸)在50mA下电泳120分钟,将经电泳分离的蛋白转移到PVDF膜(止动剂-P转移膜(Immobilon-P transfermembrane))。
为防止非特异性结合,用5%脱脂乳对膜进行封闭,然后用在TTBS溶液(137mMTris-Cl,pH 7.4;20mM NaCl;0.05%吐温-20)中稀释至1:1000的一级抗体(β-连环蛋白,c-myc,Santa Cruz Biotechnology,Inc.),在4℃下进行反应12小时。随后,用TTBS洗涤膜三次,并与稀释至1:2000的二级抗体(HRP缀合的抗兔IgG)在室温下反应2小时。然后用TTBS冲洗膜三次,然后用ECL诊断试剂盒在X射线胶片上确认蛋白表达。
作为结果,如图6所示,当组合Wnt-1+Wnt-2进行处理时,β-连环蛋白的表达比Wnt-1或Wnt-2单独处理时增加,并且当经PDRN额外处理时,证实了β-连环蛋白的表达呈浓度依赖性方式增加。
此外,如图7所示,c-myc的表达随着PDRN处理浓度的增加而增加,并且当Wnt与PDRN联合进行处理时,证实了c-myc的表达增加。
实施例6:对C57BL/6小鼠中Wnt肽与PDRN联合处理的促进毛发生长的效果的分析
为了分析Wnt肽(Wnt-1+Wnt-2)与PDRN联合处理对促进毛发生长的效果,使用最常用于毛发生长测验的C57BL/6小鼠进行了体内毛发生长实验。
将各自体重相近的7周龄雌性C57BL/6小鼠(Orient Bio Co.,Ltd.)在25℃和50%湿度下驯化1周后,在8周龄时进行实验。将小鼠置于含有乙醚的干燥器中,麻醉1分钟,用脱毛膏除去老鼠背部的毛发。从脱毛当天起,将Wnt肽(Wnt-1+Wnt-2,5μg/mL或15μg/mL)和PDRN(2.5mg/mL或7.5mg/mL)经皮施用于背部区域,每天施用200μL样品一次。在施用15天之后,拍摄照片,通过检查施用部位的颜色变化来确认毛发生长的程度。将3%的米诺地尔用作阳性对照,磷酸盐缓冲液用作阴性对照。
作为结果,如图8所示,与阴性对照组相比,Wnt肽(Wnt-1+Wnt-2)与PDRN联合处理的组显著增加了毛发生长,并且显示出与阳性对照水平相似的毛发生长效果。
根据本发明,Wnt蛋白衍生肽、多聚脱氧核糖核苷酸或它们的混合物通过促进毛发生长信号系统的信号转导途径的激活和细胞激活来增加β-连环蛋白的分泌,并增加作为头发组成细胞的角质细胞、成纤维细胞和真皮乳突细胞的生长,以预防脱发和促进毛发生长,因此可将具有上述作用的Wnt蛋白衍生肽、多聚脱氧核糖核苷酸或它们的混合物用作用于预防脱发或促进毛发生长的化妆品组合物、药物组合物或保健食品组合物。
如上文详细描述的本发明的具体部分,对于本领域技术人员来说显而易见的是,这些具体描述仅仅是优选的实施方式,并且本发明的范围不限于此。因此,本发明的实质范围将由所附权利要求及其等同物限定。
本发明的范围由所附权利要求表示,并且应当理解,根据权利要求及其等同物的含义和范围而产生的所有变化或修改都包括在本发明的范围内。
<110> 碧睿制封有限公司(BR PHARM Co.,Ltd.)
<120> 用于预防脱发或促进毛发生长的组合物
<130> OP-2019-0048
<160> 2
<170> KoPatentIn 3.0
<210> 1
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> Wnt-1
<400> 1
Met Cys Cys Gly Arg Gly Tyr Asp Gln Phe
1 5 10
<210> 2
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> Wnt-2
<400> 2
Met Cys Cys Gly Arg Gly Tyr Asn Tyr His
1 5 10
Claims (17)
1.一种包含选自于由SEQ ID NO:1和SEQ ID NO:2组成的组中的至少任一种氨基酸序列的肽。
2.如权利要求1所述的肽,其中,所述肽在所述氨基酸序列的N端被乙酰化。
3.如权利要求1所述的肽,其中,所述肽是衍生自Wnt蛋白的肽。
4.如权利要求1所述的肽,其中,所述肽是用于预防脱发或促进毛发生长的肽。
5.一种用于预防脱发或促进毛发生长的化妆品组合物,所述化妆品组合物含有如下作为活性成分:包含选自于由SEQ ID NO:1和SEQ ID NO:2组成的组中的至少任一种氨基酸序列的肽、多聚脱氧核糖核苷酸或它们的混合物。
6.如权利要求5所述的用于预防脱发或促进毛发生长的化妆品组合物,其中,所述肽在所述氨基酸序列的N端被乙酰化。
7.如权利要求5所述的用于预防脱发或促进毛发生长的化妆品组合物,其中,所述肽是衍生自Wnt蛋白的肽。
8.如权利要求5所述的用于预防脱发或促进毛发生长的化妆品组合物,其中,所述多聚脱氧核糖核苷酸分离自鱼精巢。
9.如权利要求8所述的用于预防脱发或促进毛发生长的化妆品组合物,其中,所述鱼选自于由鲑鱼、鳟鱼、鲱鱼、青鳕和鳕鱼组成的组。
10.如权利要求5所述的用于预防脱发或促进毛发生长的化妆品组合物,其中,所述多聚脱氧核糖核苷酸具有350kDa至2000kDa的数均分子量。
11.如权利要求5所述的用于预防脱发或促进毛发生长的化妆品组合物,其中,所述组合物通过增加β-连环蛋白的分泌来促进角质细胞、成纤维细胞和真皮乳突细胞的生长。
12.如权利要求5所述的用于预防脱发或促进毛发生长的化妆品组合物,其中,所述组合物增加c-myc表达。
13.如权利要求5所述的用于预防脱发或促进毛发生长的化妆品组合物,其中,将所述组合物配制成选自于由如下组成的组中的制剂:生发液、护发素、亮发素、头发洗剂、头发营养洗剂、洗发香波、润发精、焗油膏、发乳、头发营养霜、头发保湿霜、头发按摩霜、发蜡、头发气雾剂、发膜、头发营养膜、发皂、洗发乳、发油、头发干洗剂、护发护理剂、染发剂、卷发剂、头发去色剂、发胶、发釉、美发剂、粘发剂、润发膏、发用摩丝和头发喷雾剂。
14.一种用于预防脱发或促进毛发生长的药物组合物,所述药物组合物含有如下作为活性成分:包含选自于由SEQ ID NO:1和SEQ ID NO:2组成的组中的至少任一种氨基酸序列的肽、多聚脱氧核糖核苷酸或它们的混合物。
15.如权利要求14所述的用于预防脱发或促进毛发生长的药物组合物,其中,所述肽在所述氨基酸序列的N端被乙酰化。
16.一种用于预防脱发或促进毛发生长的保健食品组合物,所述保健食品组合物含有如下作为活性成分:包含选自于由SEQ ID NO:1和SEQ ID NO:2组成的组中的至少任一种氨基酸序列的肽、多聚脱氧核糖核苷酸或它们的混合物。
17.如权利要求16所述的用于预防脱发或促进毛发生长的保健食品组合物,其中,所述肽在所述氨基酸序列的N端被乙酰化。
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