CN111655227A - 用于改变皮肤微生物组的方法和局部组合物 - Google Patents
用于改变皮肤微生物组的方法和局部组合物 Download PDFInfo
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- CN111655227A CN111655227A CN201880088122.7A CN201880088122A CN111655227A CN 111655227 A CN111655227 A CN 111655227A CN 201880088122 A CN201880088122 A CN 201880088122A CN 111655227 A CN111655227 A CN 111655227A
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Abstract
公开了一种方法。所述方法通常可用于改变皮肤微生物组。所述方法包括将局部组合物给予受试者的皮肤。还公开了一种局部组合物。所述局部组合物可用于所述方法。所述局部组合物包含微生物群体、从所述微生物群体获得的组分或其组合。所述微生物群体通常为棒杆菌属物种。所述棒杆菌属物种包含与16S rRNA序列(SEQ ID NO:1)至少约90%,任选地至少约97%的序列同一性。
Description
相关申请的交叉参考
本申请要求2017年11月29日提交的美国临时专利申请第62/592158号的优先权和所有优点,其内容特此通过参考结合。
序列表
主题申请含有序列表,该序列表已经以ASCII格式电子方式提交,并且特此通过参考以其全部结合。所述ASCII副本创建于2017年11月27日,名为WN3376_ST25.txt,并且大小为4096字节。
发明领域
本发明通常涉及用于使用局部组合物改变受试者的皮肤微生物组的方法。本发明还涉及局部组合物。局部组合物可与该方法一起使用。所述方法和局部组合物各自与具有如本文所述的特定16S rRNA序列(SEQ ID NO: 1)的棒杆菌属(Corynebacterium)物种相关。
相关技术的描述
皮肤微生物组(或菌群)一般地是指驻留于人类皮肤上的微生物。许多微生物为细菌,并且大多数见于表皮的浅层和毛囊的上部。皮肤微生物组通常为非致病性的,并且是共栖的或互惠的。细菌可提供的益处包括通过争夺营养素、分泌针对它们的化学物质或刺激皮肤的免疫***来防止短暂的病原生物定殖于皮肤表面。不幸的是,某些驻留(或天然)微生物可导致皮肤状况和/或疾病。
鉴于前述内容,仍然有机会提供改变例如改进皮肤微生物组的改进的方法。也仍然有机会提供用于改变皮肤微生物组的改进的组合物。
发明概述
提供一种方法。该方法通常可用于改变皮肤微生物组。所述方法包括给予受试者的皮肤局部组合物。还提供局部组合物。所述局部组合物可用于该方法。
所述局部组合物包含微生物群体、从微生物群体获得的组分或其组合。微生物群体通常为棒杆菌属物种。棒杆菌属物种包含与16S rRNA序列(SEQ ID NO: 1)至少约90%,任选地至少约97%的序列同一性。
通过参考当前实施方案和附图的描述,将更充分地理解和意识到本发明的这些和其他目的、优点和特征。在详细解释本发明的实施方案之前,应当理解,本发明不限于操作的细节或以下描述中阐述或附图中示出的步骤或组分的构造和布置的细节。应当理解,本文使用的措词和术语为出于描述的目的,而不应视为是限制性的。“包括”和“包含”及其变体的使用意在涵盖其后列出的项目及其等同物以及另外的项目及其等同物。进一步地,在各种实施方案的描述中可使用枚举。除非另外明确说明,否则枚举的使用不应解释为将本发明限于任何特定顺序或数量的组分。枚举的使用也不应解释为从本发明的范围排除可能与所枚举的步骤或组分组合或合并为所枚举的步骤或组分的任何另外步骤或组分。
附图简述
图1为说明受试者人口统计数据的饼状图。
图2为进一步说明受试者人口统计数据的条形图。
图3为说明如用香农指数(Shannon Index)估计的每个部位的细菌多样性的图片。图上的每个点代表样品的多样性分数。
图4为显示样品之间的细菌微生物组成相似性的排序。点代表单个微生物组,根据部位用颜色编码。
图5为盒须图,显示棒杆菌属(未分类)的前额物种水平分析。如所示的,相对丰度(y轴)随受试者年龄(x轴)而变化。
图6为盒须图,显示柯氏棒杆菌(Corynebacterium kroppenstedtii)的前额物种水平分析。如所示的,相对丰度(y轴)随受试者年龄(x轴)而变化。
图7为散点图,说明棒杆菌属(未分类)和柯氏棒杆菌如何互相排斥。
图8为热图,说明柯氏棒杆菌如何与皱纹和老年斑相关联。同样如所示的,棒杆菌属(未分类)通常与皱纹和老年斑具有低至无的相关性。
图9为盒须图,说明作为柯氏棒杆菌相对丰度的函数的发红分数分布。
图10为一系列照片,说明皮肤发红的视觉分级量表,范围从左侧的低/无发红(指定为1)到右侧的较高发红(指定为5)。
发明详述
本公开的方法可用于改变受试者的皮肤微生物组。例如,该方法可用于减少、减慢和/或预防受试者的至少一种皮肤状况。本公开的方法也可称为美容方法或治疗方法。
可经本公开的方法和/或局部组合物减少、减慢和/或预防的皮肤状况的实例包括(但不限于)炎症、发红、色素沉着、起皱纹及其组合。可经该方法减少、减慢和/或预防的其他皮肤状况包括(但不限于)痤疮、银屑病、酒渣鼻、湿疹、白癜风、皮肌炎、光化性角化病(老年斑)、脂溢性角化病、皮炎及其组合。在各种实施方案中,本公开的方法和/或局部组合物可用于舒缓和平静受试者的皮肤中的至少一种。在其他实施方案中,所述方法和/或局部组合物使受试者的皮肤保持平静。另外的皮肤状况和/或障碍描述于美国公开号2016/0271189 A1、2017/0151291 A1和2017/0228514 A1中,其公开通过参考以其全部结合至本文中。
术语“受试者”、“个体”、“宿主”和“患者”本文可互换使用,并且是指任何动物受试者,包括人类、实验动物、家畜和家庭宠物,一般地为人类。受试者可为多种微生物的宿主。受试者在其身体上和体内的各种栖息地中可具有不同的微生物组。受试者可诊断为或怀疑处于疾病的高风险下。受试者可具有助于疾病(即生态失调)的微生物组状态。在某些情况下,受试者不一定诊断为或怀疑处于疾病的高风险下。
术语“微生物组”、“微生物区系”和“微生物栖息地”本文可互换使用,并且可指生存于受试者身体上或体内的微生物的生态群落。微生物组可包括共栖、共生和/或病原微生物。微生物组可存在于受试者的许多部分(如果不是大部分)上或中。
术语“治疗(treatment)”或“治疗(treating)”本文可互换使用。这些术语可指用于获得有益或期望的结果的方法,所述结果包括(但不限于)治疗益处和/或预防益处。治疗益处可意指根除或改善所治疗的基础障碍。另外,治疗益处可通过根除或改善与基础障碍相关的一种或多种生理症状,使得尽管受试者可能仍患有基础障碍,但在受试者中观察到改善来实现。预防作用包括延迟、预防或消除疾病或病况的出现,延迟或消除疾病或病况的症状的发作,减慢、停止或逆转疾病或病况的进展,或它们的任何组合。对于预防益处,即使可能尚未做出对该疾病的诊断,处于发生特定疾病风险下的受试者或报告疾病的一种或多种生理症状的受试者也可经受治疗。
所述方法包括将局部组合物给予受试者的皮肤。在各种实施方案中,将局部组合物用手施用;然而,局部组合物也可经施用手段直接或间接地施用于皮肤,例如经涂布器、喷嘴、贴剂等。在某些实施方案中,将局部组合物在受试者的皮肤上揉搓和/或按摩。
本公开的局部组合物本文也可简称为组合物。另外,本公开的组合物可称为个人护理组合物、护肤组合物、药用组合物、美容组合物等。在某些实施方案中,组合物为美容组合物,并且可用于美容用途或美容应用。在其他实施方案中,组合物为药用组合物,并且可用于药用用途或药用应用。
组合物可根据需要、每天一次、每天几次或以任何合适的方案给予,使得获得期望的结果。在该方法中,施用频率可取决于几个因素,包括期望的预防、治疗和/或效果的水平。通常,方案包括将组合物每天一次或两次施用于皮肤以包括早上施用和/或晚上施用。在每次施用期间施用于皮肤的组合物的量可取决于几个因素,包括期望的结果水平和具体组合物。
在各种实施方案中,受试者为哺乳动物,一般地为人类,并且可包括各种年龄的雄性和雌性。在各种实施方案中,受试者为至少18岁,即为成年人。在某些实施方案中,受试者为约25-约100,任选地为约30-约80,任选地为约35-约60,任选地约40-约50岁。不受任何特定理论的束缚或限制,认为本公开的方法和组合物尤其可用于中年成年人。
组合物不限于特定的受试者或受试者上皮肤的位置。例如,个人可将组合物施用于其脸、颈、臂、手、胸、躯干、腿、脚等或其任何组合。这种皮肤区域可为正常的、干燥的、敏感的、油性的或其组合。在各种实施方案中,将组合物施用于受试者的脸部,任选地施用于至少受试者的前额。不受任何特定理论的束缚或限制,认为本公开的方法和组合物尤其可用于面部皮肤,比如受试者的前额、鼻子、面颊等。
组合物包含微生物群体、从微生物群体获得的组分或其组合。在某些实施方案中,组合物包含微生物群体。在这些或备选实施方案中,组合物包含(或进一步包含)从微生物群体获得的组分。
微生物群体为棒杆菌属物种。棒杆菌属物种尚未分类,因此本文可简称为棒杆菌属(未分类)。也就是说,棒杆菌属物种包含与以下16S rRNA序列至少约90%、至少约91%、至少约92%、至少约93%、至少约94%、至少约95%、至少约96%、至少约97%、至少约98%、至少约99%、至少约99.5%或100%的序列同一性:
TACGTAGGGTGCGAGCGTTGTCCGGAATTACTGGGCGTAAAGGGCTCGTAGGTGGTTTGTCGCGTCGTCTGTGAAATTCCGGGGCTTAACTCCGGGCGTGCAGGCGATACGGGCATAACTTGAGTACTGTAGGGGTAACTGGAATTCCTGGTGTAGCGGTGAAATGCGCAGATATCAGGAGGAACACCGATGGCGAAGGCAGGTTACTGGGCAGTTACTGACGCTGAGGAGCGAAAGCATGGGTAGCGAACAGG (SEQ ID NO: 1)。
本文所述的序列通常基于16S rRNA基因的靶向区域,一般地为16S rRNA基因的V4区域(或子区域)。使用16S rRNA测序的方法为本领域技术人员理解的,并且本公开不限于特定的一种。
术语“16S”、“16S核糖体亚基”和“16S核糖体RNA (rRNA)”本文可互换使用,并且可指原核生物(例如细菌、古细菌)核糖体的小亚基(例如30S)的组分。不受任何特定理论的束缚或限制,认为16S rRNA在微生物物种之间在进化上高度保守。因此,对16S核糖体亚基的测序可用于鉴定和/或比较样品中存在的微生物(例如受试者的皮肤微生物组)。如本文可使用的术语“测序”是指用于确定核酸分子(例如DNA或RNA核酸分子)中核苷酸碱基A、T、C、G和U的顺序的测序方法。
如本文可使用的术语“基因组”可指以其一级DNA序列编码的全部的生物遗传信息。基因组包括基因和非编码序列两者。例如,基因组可代表微生物基因组。微生物组的遗传内容可包括:基因组DNA、RNA和核糖体RNA、表观基因组、质粒以及在组成微生物组的微生物中发现的所有其他类型的遗传信息。
如本文可使用的术语“核酸序列”和“核苷酸序列”可指寡核苷酸或多核苷酸及其片段或部分,以及指可为单链或双链并代表有义或反义链的基因组或合成来源的DNA或RNA。核酸序列可由腺嘌呤、鸟嘌呤、胞嘧啶、胸腺嘧啶和尿嘧啶(A、T、C、G和U)以及修饰形式(例如N6-甲基腺苷、5-甲基胞嘧啶等)组成。如本文关于核苷酸序列可使用的术语“同源性”和“同源的”是指与其他核苷酸序列互补的程度。可能存在部分同源性或完全同源性(即同一性)。与核酸序列部分互补(即“基本上同源”)的核苷酸序列为至少部分地抑制完全互补序列与靶核酸序列杂交的核苷酸序列。
微生物群体可以各种方式获得。在某些实施方案中,从一个或多个受试者的面部皮肤例如前额皮肤收集所述群体的样品。在各种实施方案中,受试者具有较年轻年龄,例如小于25岁,任选地小于18岁。不受任何特定理论的束缚或限制,认为本公开的棒杆菌属(未分类)在儿童、青少年和年轻人的面部皮肤上最普遍。然后可将样品群体进行培养并生长为更大的群体。微生物群体可使用本领域明白的方法浓缩、分离和/或纯化。
可使用微生物群体本身,使得组合物可类似于益生菌。如本文使用的术语“益生菌”可意指当适当给予时可赋予宿主或受试者健康益处的一种或多种微生物。
在一些实施方案中,从微生物群体获得的组分包括从微生物群体获得的上清液和/或其衍生物。在这些实施方案中,可如上所述获得群体,并然后进行后处理。例如,可分解微生物群体并且将其组分/材料分开、分离等。这些实施方案可类似于后生元(postbiotic)。
在各种实施方案中,微生物群体和/或从微生物群体获得的上清液和/或其衍生物可用于舒缓和/或平静受试者的皮肤。应当意识到,可从其获得微生物群体的受试者通常不同于经本公开的方法和/或组合物治疗的受试者。例如,前者受试者的平均年龄可能低于后者受试者的平均年龄。
通常,在给予局部组合物之前,受试者的皮肤包含天然微生物群体。一般地,天然微生物群体不同于与给予受试者皮肤的局部组合物相关的微生物群体。例如,天然微生物群体可基本上不含或完全不含棒杆菌属(未分类)。不受任何特定理论的束缚或限制,认为本公开的棒杆菌属(未分类)在中年成年人和老年人的面部皮肤上最不普遍(如果存在的话)。
在各种实施方案中,天然微生物群体包含柯氏棒杆菌。在某些实施方案中,柯氏棒杆菌包含与以下参考16S rRNA序列至少约90%、至少约91%、至少约92%、至少约93%、至少约94%、至少约95%、至少约96%、至少约97%、至少约98%、至少约99%、至少约99.5%或100%的序列同一性:
TACGTAGGGTGCGAGCGTTGTCCGGAATTACTGGGCGTAAAGAGCTCGTAGGTGGTCTGTCGCGTCATTTGTGAAAGCCCGGGGCTTAACTCCGGGTTGGCAGGTGATACGGGCATGACTGGAGTACTGTAGGGGAGACTGGAATTCCTGGTGTAGCGGTGAAATGCGCAGATATCAGGAGGAACACCGGTGGCGAAGGCGGGTCTCTGGGCAGTAACTGACGCTGAGGAGCGAAAGCATGGGTAGCGAACAGG (SEQ ID NO: 2)。
如上所介绍的,本文所述的序列通常基于16S rRNA基因的靶向区域,一般地为16SrRNA基因的V4区(或子区域)。使用16S rRNA测序的方法为本领域技术人员理解的,并且本公开不限于特定的一种。
在某些实施方案中,微生物群体和从微生物群体获得的组分中的至少一种以治疗有效量存在于局部组合物中,以减少、减慢和/或预防受试者的至少一种皮肤状况。
在各种实施方案中,微生物群体基于按组合物的重量计的100份,以按重量计约0.1-约99.9,任选地约1-约99,任选地约5-约95,任选地约10-约90,任选地约15-约85,任选地约20-约80,任选地约25-约75,任选地约30-约70,任选地约35-约65,任选地约40-约60,任选约45-约55,任选地约50份的量存在。考虑也可使用上述那些数值之间的任何和所有数值或数值范围。可将这种量归一化以考虑到包含一种或多种另外的组分。
在各种实施方案中,从微生物群体获得的组分基于按组合物的重量计的100份,以按重量计约0.1-约99.9,任选地约1-约99,任选地约5-约95,任选地约10-约90,任选地约15-约85,任选地约20-约80,任选地约25-约75,任选地约30-约70,任选地约35-约65,任选地约40-约60,任选约45-约55,任选地约50份的量存在。考虑也可使用上述那些数值之间的任何和所有数值或数值范围。可将这种量归一化以考虑到包含一种或多种另外的组分。
在特定的实施方案中,所述方法进一步定义为在需要它的受试者中治疗皮肤炎症或皮肤发红或其复发的方法。在这些实施方案中,所述方法包括给予受试者包含治疗有效量的上清液的局部药用组合物。上清液来自具有rRNA序列的微生物培养物,该rRNA序列包含与来自棒杆菌属的16S rRNA序列(未定义;SEQ ID NO: 1;V4区)至少约97%的序列同一性。上清液具有使微生物皮肤去定殖的作用,该微生物包含与来自柯氏棒杆菌的16S rRNA序列(SEQ ID NO: 2; V4区)至少约97%的序列同一性。
在其他特定的实施方案中,所述方法进一步定义为在需要它的受试者中治疗皮肤炎症或皮肤发红或其复发或者减少其发生可能性的方法。在这些实施方案中,所述方法包括给予受试者局部药用组合物,所述组合物包含治疗有效量的细菌群体,所述细菌群体由包含与参考棒杆菌属中存在的16S rDNA序列(未定义;SEQ ID NO: 1;V4区)具有至少约97%同一性的16S rDNA序列的细菌组成。在使得细菌群体对皮肤上存在的病原细菌发挥抑制或去定殖作用的条件下给予治疗组合物。病原细菌包含与来自柯氏棒杆菌的16S rRNA序列(SEQ ID NO: 2; V4区)至少约97%的序列同一性。
在仍然其他特定的实施方案中,提供一种用于诊断受试者获得或患有临床或亚临床皮肤炎症的可能性的方法。在这些实施方案中,(诊断)方法利用皮肤上存在的细菌丰度。所述细菌包含与来自柯氏棒杆菌的16S rRNA序列(SEQ ID NO: 2; V4区)至少约97%的序列同一性。
在诊断方法中,认为如果受试者在其皮肤上具有柯氏棒杆菌,那么相对于在其皮肤上没有柯氏棒杆菌的受试者,该受试者具有发生或患有临床或亚临床皮肤炎症的更高可能性。如果受试者年龄较大,则这种效果可能会加剧。另外,如果受试者在其皮肤上具有柯氏棒杆菌,则可相对于其他受试者对其群体进行定量和/或分级,从而提供何时可能发生临床或亚临床皮肤炎症和/或其严重性的估计。此外,如果受试者在其皮肤上具有柯氏棒杆菌,则可经本公开的方法和/或组合物治疗受试者。
如以下实施例部分中进一步描述的,令人惊讶地发现存在两种互相排斥的棒杆菌属物种,一种在年轻人中普遍 (棒杆菌属(未分类)),另一种在年龄较大的受试者中普遍(柯氏棒杆菌)。进一步地,发现柯氏棒杆菌与患有临床上重要的皮肤炎症和皮肤发红显著相关。
令人惊讶地,发明人发现棒杆菌属(未分类)可用于改变或调节(柯氏棒杆菌)。不受任何特定理论的束缚或限制,认为存在棒杆菌属(未分类)优于在皮肤上存在柯氏棒杆菌,因为发现后者与一种或多种不期望的皮肤状况比如发红相关。还认为柯氏棒杆菌的存在实际上可能引起这种皮肤状况。因此,棒杆菌属(未分类)可用于替换、减少和/或预防柯氏棒杆菌及其相关的皮肤状况。
组合物可包含一种或多种如本文所述的另外组分,比如一种或多种添加剂。在各种实施方案中,组合物基本上由微生物群体和从微生物群体获得的组分中的至少一种组成。本文使用的短语“基本上由……组成”通常涵盖用于特定实施方案的具体记载的要素/组分。进一步地,短语“基本上由……组成”通常涵盖和允许存在不实质性影响该特定实施方案的基本和/或新颖特征的另外或任选要素/组分。在某些实施方案中,“基本上由……组成”允许存在基于组合物的总重量≤10、≤5或≤1重量% (wt.%)的另外或任选组分。在其他实施方案中,组合物由如本文所述的微生物群体和从微生物群体获得的组分中的至少一种组成。
在各种实施方案中,组合物进一步包含至少一种美容上可接受的载体、赋形剂、添加剂或其组合。合适的添加剂包括本领域了解的那些,包括(但不限于)保湿剂、润肤剂、乳化剂、表面活性剂、油类、提取物、皮肤保护剂、消毒剂、杀菌剂、药物和药物物质、镇痛化合物、止神经痛的化合物、抗氧化剂、血液循环促进剂、抗抑郁化合物、抗焦虑化合物、抗应激化合物、防晒剂、驱虫剂、防腐剂、去角质剂、香料、色素、填充剂、溶剂、媒介物、载体、本领域技术人员已知的其他类型的添加剂及其组合。这种添加剂可单独或组合使用。各种任选的添加剂在以下更详细地描述。
应当意识到,某些组分或添加剂可按照不同的技术术语来分类,并且仅仅因为组分或添加剂按照这种术语而分类并不意指它们限于该功能。如果使用,一种或多种添加剂可以各种量存在于组合物中。
组合物可包含一种或多种保湿剂。保湿剂可赋予皮肤水分或恢复皮肤的水分。增加皮肤的含水量可使皮肤更柔软和更柔韧。保湿剂可用于模仿正常皮肤分泌物在维持皮肤柔软度方面的作用和为蒸发提供屏障。皮肤保湿剂可包括两种一般类型:封闭剂和湿润剂。封闭性保湿剂在皮肤上形成层,其可降低蒸发速率。湿润剂为非封闭性吸湿性物质,其可保留水并使水对皮肤可用。湿润剂还可通过改善皮肤的润滑性来发挥作用。封闭性和湿润性保湿剂两者均可适用于本公开的组合物。保湿剂可包含单一保湿成分,或者其可包含多种成分,这些成分可包括在内以用于多种目的,比如润肤剂、乳化剂、脂质、表面活性剂、增稠剂和防腐剂。进一步地,保湿剂可具有封闭性和非封闭性两者。水可为包括在保湿剂中的成分之一。可在没有不利地影响组合物的稳定性或其使用中特性的情况下,选择组合物中掺入的保湿剂的水平和类型。
保湿剂可包括长链C12-C22脂肪酸、液态水溶性多元醇、甘油、丙二醇、山梨醇、聚乙二醇、甲基葡萄糖的乙氧基化/丙氧基化醚、羊毛脂醇的乙氧基化/丙氧基化醚、羊毛脂醇、椰子脂肪酸、牛脂脂肪酸、非封闭性液态水溶性多元醇、芦荟胶、浓缩芦荟胶、芦荟胶冻干粉、芦荟胶油提取物、氨基酸、羊水、酪梨素(avocadin)、钙蛋白复合物、腰果油、奇亚籽油、几丁质、壳聚糖、壳聚糖PCA、胆甾醇酯、硫酸软骨素、胶原蛋白、胶原蛋白氨基酸、铜蛋白复合物、马来酸二辛酯、二季戊四醇脂肪酸酯、弹性蛋白、乙基泛醇、月见草油、甘油聚醚-12、鞘糖脂类、透明质酸、杂红花油、氢化聚异丁烯、水解胶原蛋白、水解弹性蛋白、水解纤连蛋白、水解粘多糖、水解丝、水解小麦蛋白、荷荷巴酯类、角蛋白氨基酸、猕猴桃提取物、乳酰胺MEA、脂质体、活性酵母细胞衍生物脂质体、海洋多氨基糖(marina polyaminosaccharide)、矿物油、水貂油***、粘多糖、粘多糖、美洲蒲葵提取物、泛硫乙胺、石蜡、PEG-4、PEG-6、PEG-8、PEG-12、PEG-100硬脂酸酯、全氟聚甲基异丙基醚、凡士林、石油蜡、开心果油、胎盘提取物、浮游生物提取物、多氨基酸多糖缩合物、聚丁烯、聚甲基丙烯酸甘油酯、聚季戊四醇四月桂酸酯、PPG-10丁二醇、PPG-20甲基葡萄糖醚二硬脂酸酯、蜂王浆提取物、糖类同分异构体、硒蛋白复合物、血清白蛋白、二甲基硅烷醇透明质酸酯钠、甲基硅烷醇乳酸酯钠、甲基硅烷醇甘露糖醛酸酯钠、可溶性胶原蛋白、超氧化物歧化酶、超氧化物歧化酶脂质体、组织提取物、生育酚亚油酸酯、亲脂性保湿剂(比如溶血卵磷脂、卵磷脂、胆固醇、胆固醇酯、鞘脂或神经酰胺)、低分子保湿剂(比例如丝氨酸、谷氨酰胺、山梨醇、甘露醇、甘油、吡咯烷酮羧酸钠、1,3-丁二醇、丙二醇、乳酸或乳酸盐)、高分子保湿剂(比如透明质酸、透明质酸钠、弹性蛋白、海藻酸、粘多糖、聚乙二醇、聚天冬氨酸盐或水溶性几丁质)、烃油、烃蜡、硅酮、脂肪酸衍生物、胆固醇、胆固醇衍生物、甘油二酯和三酯、植物油、植物油衍生物、液态不易消化的油类、液态易消化或不易消化的油与固态多元醇聚酯的掺混物、乙酰甘油酯、烷基酯、烯基酯、羊毛脂及其衍生物、奶甘油三酯、蜡酯、蜂蜡衍生物、固醇、磷脂或任何其他保湿剂成分。
封闭性保湿剂可为凡士林、石蜡、蜡、油脂、矿物油、蜂蜡、羊毛脂和油溶性羊毛脂衍生物、饱和和不饱和脂肪醇(比如山嵛醇)、角鲨烯、各种动植物油类,比如杏仁油、杏油、杏核油、鳄梨油、杜松油、蓖麻油、肉桂油、玉米油、棉籽油、月见草油、葡萄油、葡萄籽油、榛子油、荷荷巴油、亚麻籽油、肝油、澳洲坚果油、水貂油、牛脚油、橄榄油、棕榈仁油、棕榈坚果油、棕榈油、桃核油、花生油、松油、开心果油、罂粟籽油、菜籽油、米糠油、米胚芽油、红花油、油茶油、芝麻油、芝麻籽油、大豆油、葵花油、葵花籽油、椿花油(tsubaki oil)、核桃油、小麦胚芽油、小麦胚芽油、茶籽油、甘油三酯(triglycerine)、甘油三辛酸酯、甘油三异棕榈酸酯、可可脂、牛脂、绵羊脂、猪脂、马脂、氢化油、氢化蓖麻油、日本蜡、乳木果油、蜂蜡、小烛树蜡、棉蜡、巴西棕榈蜡、杨梅蜡、树蜡、鲸蜡、褐煤蜡、糠蜡、羊毛脂、还原羊毛脂、硬质羊毛脂、木棉蜡、甘蔗蜡、荷荷巴蜡、虫胶蜡或任何其他呈现封闭性的保湿剂。
保湿剂可包括模仿天然成分并起植物药作用的物质,包括维生素、羟基酸和类视黄醇。维生素可包括维生素A、视黄醇、视黄醇棕榈酸酯、肌醇、吡多辛氯酸盐、烟酸苄酯、烟酰胺、dl α-生育酚烟碱、抗坏血酸磷酸酯镁、维生素D2 (麦角钙化醇)、dl α-生育酚、dl-α-生育酚-2-L-抗坏血酸二酯钾、dl-α-生育酚乙酸酯、泛酸、生物素或任何其他维生素。可降低皮肤干燥严重性的一些成分为α羟基酸(AHA)和β羟基酸(BHA),包括其盐以及类视黄醇。羟基酸根据基于其构型上的羧酸数目分类。一元羧酸为乙醇酸、乳酸和扁桃酸。二元羧酸包括苹果酸和酒石酸。三元羧酸体现在柑橘类水果中存在的枸橼酸。BHA主要包括水杨酸及其衍生物。AHA已显示使去角质。因此,它们可用于过度角化的情况。它们起湿润剂的作用,对角质层具有正常化作用,增加其可塑性和柔韧性。保湿剂的其他成分可包括弹性蛋白、卵磷脂、透明质酸钠、被动皮肤过敏反应钠(sodium passive cutaneous anaphylaxis)、神经酰胺、天然存在的皮肤脂质和固醇、人造或天然油类、湿润剂、润肤剂、乳化剂、防腐剂、润滑剂、油脂、天然保湿因子(NMF),包括低分子量物质,比如氨、氨基酸、氨基葡萄糖、肌酐、枸橼酸盐和离子溶液,比如钠、钾、氯离子、磷酸根、钙和镁,吡咯烷酮羧酸钠,己二酸、乳酸、油酸、硬脂酸、异硬脂酸、肉豆蔻酸和亚油酸的十六烷基、肉豆蔻基、异癸基或异丙基酯及其相应的醇酯、异硬脂酰-2-乳酸钠和辛酰乳酸钠、甘油、聚乙二醇、丙二醇、山梨醇、甲基葡萄糖的聚乙二醇和丙二醇醚、羊毛脂醇的聚乙二醇和丙二醇醚、乳酸、L-脯氨酸和其他游离脂肪酸、椰子脂肪酸、牛脂脂肪酸、非封闭性液态水溶性多元醇和天然存在于皮肤中的必需氨基酸化合物以及硬脂酸和月桂酸。
组合物可包含一种或多种润肤剂。润肤剂可使粗糙的皮肤光滑,改变皮肤的外观,润滑、替换天然的皮肤脂质并提供封闭作用。润肤剂可包含油包水乳剂。润肤剂可使某些东西柔软或柔顺,并且也可使皮肤或粘膜光滑。润肤剂比如羊毛脂、乳木果油或凡士林可起防止水流失的屏障作用(封闭作用),并且也可起角质层柔软剂的作用。其他润肤剂可为具有不同组成的油水乳剂,并且可包括几种酯和油类,比如辛基十二烷醇、己基癸醇、油醇、油酸癸酯、硬脂酸异丙酯、棕榈酸异丙酯、肉豆蔻酸异丙酯、月桂酸己酯和二辛基环己烷。进一步地,润肤剂可包括长链酰基谷氨酸胆固醇酯、胆甾醇羟基硬脂酸酯、12-羟基硬脂酸、硬脂酸、洛定酸(rhodinic acid)、羊毛脂脂肪酸胆固醇酯、凡士林、可可脂、脂肪酸酯、甘油单、二和三酯、表皮和皮脂烃,比如胆固醇、胆固醇酯、角鲨烷、硅油和树胶、矿物油、羊毛脂及衍生物、蓖麻油、杏仁油、油酸油酯或任何其他润肤成分。
组合物可包含一种或多种乳化剂。乳化剂可为能够降低油与水相之间的界面张力的物质,并因此可助于油(在水包油乳剂的情况下)和水(在油包水乳剂的情况下)分别分散成小尺寸的液滴和助于将颗粒保持在分散状态。乳化剂可一般地分为:i) 蛋白或碳水化合物聚合物,其通过包覆分散的脂肪或油颗粒的表面,从而防止其聚结而起作用;这种乳化剂有时也称为保护性胶体,和ii) 长链醇和脂肪酸,由于其分子的溶解性,它们能够降低悬浮颗粒界面处的表面张力。当皂通过乳化污物的油性成分而发挥清洁作用时,其以这种方式发挥作用。
组合物可包含一种或多种表面活性剂。表面活性剂可为洗涤剂、皂基、月桂酸钠、棕榈酸钠或任何其他脂肪酸皂、月桂基硫酸酯钠、月桂基硫酸酯钾或任何其他高级烷基硫酸酯盐、POE月桂基硫酸酯三乙醇胺、POE月桂基硫酸酯钠或任何其他烷基酯硫酸酯盐、月桂酰肌氨酸钠或任何其他N-酰基肌氨酸、N-肉豆蔻酰基-N-甲基牛磺酸钠、N-椰油酰基-N-甲基牛磺酸钠、月桂酰基甲基牛磺酸钠或任何其他高级脂肪酸酰胺磺酸盐、POE油基醚磷酸酯钠、POE硬脂基醚磷酸酯或任何其他磷酸酯盐、二-2-乙基己基磺基琥珀酸钠、单月桂酰基单乙醇酰胺聚氧乙烯磺基琥珀酸钠、月桂基聚丙二醇磺基琥珀酸钠或任何其他磺基琥珀酸盐、线性十二烷基苯磺酸钠、线性十二烷基苯磺酸三乙醇胺、线性十二烷基苯磺酸盐或任何其他烷基苯磺酸盐、N-月桂酰基谷氨酸钠、N-硬脂酰基谷氨酸二钠、N-肉豆蔻酰基-L-谷氨酸单钠或任何其他N-酰基谷氨酸盐、氢化蓖麻油脂肪酸甘氨酸硫酸酯钠或任何其他高级脂肪酸酯硫酸酯盐、土耳其红油或任何其他硫酸化油、POE烷基醚羧酸、POE烷基芳基醚羧酸盐、α-烯烃硫酸盐、高级脂肪酸酯磺酸盐、仲醇硫酸酯盐、高级脂肪酸烷醇酰胺硫酸酯盐、月桂酰基单乙醇酰胺琥珀酸钠、N-棕榈酰基天冬氨酸二-三乙醇胺、酪蛋白钠或任何其他阴离子表面活性剂、硬脂基三甲基氯化铵、月桂基三甲基氯化铵或任何其他烷基三甲基铵盐、二硬脂基二甲基氯化铵、二烷基二甲基氯化铵盐、聚(N,N'-二甲基-3,5-亚甲基哌啶鎓)氯化物、氯化鲸蜡基吡啶鎓或任何其他烷基吡啶鎓盐、烷基季铵盐、烷基二甲基苄基铵盐、烷基异喹啉鎓盐、二烷基吗啉鎓盐、POE烷基胺、烷基胺盐、聚胺脂肪酸衍生物、戊醇脂肪酸衍生物、苯扎氯铵、苄索氯铵或任何其他阳离子表面活性剂、2-十一烷基-N,N,N-(羟乙基羧甲基)-2-咪唑啉钠、2-椰油酰基-2-咪唑啉鎓氢氧化物-1-羧基乙氧基-2-钠盐或任何其他咪唑啉类双极性表面活性剂、2-十七烷基-N-羧甲基-N-羟乙基咪唑啉鎓甜菜碱、月桂基二甲基氨基乙酸甜菜碱、烷基甜菜碱、酰胺甜菜碱、磺基甜菜碱或任何其他甜菜碱类表面活性剂、或任何其他双极性表面活性剂、失水山梨醇单油酸酯、失水山梨醇单异硬脂酸酯、失水山梨醇单月桂酸酯、失水山梨醇单棕榈酸酯、失水山梨醇单硬脂酸酯、失水山梨醇倍半油酸酯、失水山梨醇三油酸酯、二甘油失水山梨醇五辛酸酯、二甘油失水山梨醇四辛酸酯或任何其他失水山梨醇脂肪酸酯、甘油单棉籽油脂肪酸、甘油单芥酸酯、甘油倍半油酸酯、甘油单硬脂酸酯、甘油α,α-油酸酯焦谷氨酸酯、单硬脂酸甘油酯苹果酸或任何其他甘油或聚甘油脂肪酸酯、丙二醇单硬脂酸酯或任何其他丙二醇脂肪酸酯、氢化蓖麻油衍生物、甘油烷基醚、聚氧乙烯甲基聚硅氧烷共聚物或任何其他亲液性非离子表面活性剂、POE失水山梨醇单油酸酯、PO-失水山梨醇单硬脂酸酯、POE失水山梨醇单油酸酯、POE-失水山梨醇四油酸酯或任何其他POE失水山梨醇脂肪酸酯、POE-山梨醇单月桂酸酯、POE-失水山梨醇单油酸酯、POE-山梨醇五油酸酯、POE-失水山梨醇单硬脂酸酯或任何其他POE失水山梨醇脂肪酸酯、POE-甘油单硬脂酸酯、POE-甘油单异硬脂酸酯、POE-甘油三异硬脂酸酯或任何其他POE甘油脂肪酸酯、POE单油酸酯、POE二硬脂酸酯、POE单-二油酸酯、二硬脂酸乙二醇酯或任何其他POE脂肪酸酯、POE月桂基醚、POE油基醚、POE硬脂基醚、POE山嵛基醚、POE2-辛基十二烷基醚、POE胆甾烷醇醚或任何其他POE烷基醚、POE辛基苯基醚、POE壬基苯基醚、POE二壬基苯基醚或任何其他POE烷基苯基醚、Pluronic或任何其他泊洛沙姆、POE.POP鲸蜡基醚、POE.POP-2-癸基十四烷基醚、POE.POP单丁基醚、POE.POP水合羊毛脂、POE.POP甘油醚或任何其他POE-POP烷基醚、Tetronic或任何其他四-POE.四-POP乙二胺缩合产物、POE蓖麻油、POE氢化蓖麻油、POE氢化蓖麻油单异硬脂酸酯、POE氢化蓖麻油三异硬脂酸酯、POE氢化蓖麻油单焦谷氨酸单异硬脂酸二酯、POE氢化蓖麻油马来酸或任何其他POE蓖麻油氢化蓖麻油衍生物、POE失水山梨醇蜂蜡或任何其他POE蜂蜡羊毛脂衍生物、椰子油脂肪酸二乙醇酰胺、月桂酸单乙醇酰胺、脂肪酸异丙醇酰胺或任何其他链烷醇酰胺、POE丙二醇脂肪酸酯、POE烷基胺、POE脂肪酸酰胺、蔗糖脂肪酸酯、POE壬基苯基甲醛缩合产物、烷基乙氧基二甲基胺氧化物、三油基磷酸或任何其他亲水性非离子表面活性剂或任何其他表面活性剂。
组合物可包含一种或多种油。油可用作渗透性透皮载体,其快速渗透皮肤并助于转运本发明组合物中存在的其他组分。可使用的油的实例包括杏仁油(almond oil)、茴香油、杏仁油(apricot kernel oil)、杏油、鳄梨油、香脂薄荷油、罗勒油、蜂香油、佛手柑、佛手柑油、桦木油、苦杏仁油、苦橙油、葛缕子油、小豆蔻油、蓖麻油、雪松油、肉桂油、黏土油、丁香油、丁香叶油、椰子油、分馏椰子油、棉籽油、柏木油、桉树油、月见草油、小茴香油、栀子花油、天竺葵油、生姜油、葡萄柚油、葡萄籽油、榛子油、啤酒花油、山香油、靛蓝灌木油、茉莉油、荷荷巴油、刺柏油、猕猴桃油、夏威夷果油、月桂油、薰衣草油、柠檬油、柠檬草油、菩提油、亚麻籽油、独活草油、澳洲坚果油、玉米油、母菊油、麝香玫瑰油、橙花油、肉豆蔻油、乳香、橄榄油、橙花油、橙油、棕榈油、广霍香油、桃仁油、花生油、山核桃油、胡薄荷油、薄荷油、杏仁油(persic oil)、松油、松焦油、罂粟籽油、菜籽油、玫瑰油、玫瑰果油、迷迭香油、芸香油、鼠尾草油、接骨木油、檀香木油、黄樟油、芝麻油、银枞油、大豆油、留兰香油、葵花油、甜杏仁油、甜马郁兰油、甜紫罗兰油、焦油、茶树油、百里香油、小麦胚芽油、野薄荷油、欧耆草油、依兰油、核桃油、妥尔油、蓟籽油、氢化植物油或任何其他合适的油。
组合物可包含精油、提取物及其组合。精油一般地为含有来自植物的挥发性香气化合物的浓缩液体。精油也可称为挥发油(volatile oil)、香精油(ethereal oil)、挥发油(aetherolea),或简称为从其中提取它们的植物的油。从其含有植物香料的精华——其所源自的植物的特征性香料这个意义上说,油一般地为“精华的”。
植物的各个段或部分可用于获得精油和提取物,比如树皮、浆果、花朵、果实、树叶、果皮、树脂、根茎、根部、种子和/或树木。精油可通过许多方法获得,比如通过蒸馏(例如使用蒸汽)、压榨、溶剂提取、净油提取、树脂采收和/或冷压。
可使用许多不同的提取方法来获得适合于本公开的提取物。这些提取方法包括(但不限于)在授予Rana等的美国专利7897184中公开的提取方法,其特此通过参考以其全部结合。尽管所描述的提取溶剂具体提及乙醇,但是应当理解,除乙醇之外或作为乙醇的备选,可使用其他醇,比如(但不限于)异丙醇、乙醇和/或甲醇。示例性的醇溶剂包括(但不限于) C1-C4醇,比如甲醇、乙醇、丙醇、异丙醇和丁醇;水-醇或醇与水的混合物,包括水-乙醇;多元醇,比如丙二醇和丁二醇;和脂肪醇。任何这些醇溶剂均可使用。其他溶剂(比如(但不限于)丙酮)也可用作提取溶剂。也可使用任何比率的溶剂-水混合物例如醇-水和/或丙酮-水混合物。在各种实施方案中,溶剂为其中所得提取物和/或其后续形式(例如提取物粉末)适合于摄入的溶剂。例如,溶剂为水或乙醇。
在一个实例中,提取物可使用有机溶剂提取技术获得。在另一个实例中,可使用溶剂依序分级分离来获得提取物。总的水-乙醇提取技术也可用于获得提取物。通常,这称为一次性提取(lump-sum extraction)。以该方法产生的提取物将含有存在于提取材料中的广泛种类的植物化学物质,包括脂肪和水溶性植物化学物质。收集提取溶液后,将溶剂蒸发,得到提取物。
也可使用总乙醇提取。该技术使用乙醇作为溶剂。该提取技术产生的提取物除水溶性化合物之外还可包含脂溶性和/或亲脂性化合物。总甲醇提取也可以类似的方式使用,具有类似的结果。
可用于获得提取物的提取技术的另一个实例为超临界流体二氧化碳提取(SFE)。在该提取程序中,要提取的材料不会暴露于任何有机溶剂。而是提取溶剂为在超临界条件下(例如> 31.3℃和> 73.8巴)含或不含改性剂的二氧化碳(CO2)。本领域的技术人员将意识到,可改变温度和压力条件以获得最佳提取收率。该技术产生脂溶性和/或亲脂性化合物的提取物,类似于也可使用的总己烷和乙酸乙酯提取技术。
以上每种提取方法还可包括本领域了解的一个或多个另外处理步骤和/或与之组合使用。例如,可将植物材料粉碎、打碎、磨碎等。也可存在一个或多个过滤步骤以去除例如纤维素/纤维或其他固体材料。也可存在一个或多个纯化步骤以去除例如某些成分和/或污染物。这种纯化可例如通过蒸馏、蒸发、离心等来完成。还可存在一个或多个浓缩和/或干燥步骤以去除水和/或其他挥发物,例如醇、较轻的化合物、VOC等。此外,可添加酸和/或碱以调节pH或中和。取决于最后/最终提取物的期望形式,还可利用本领域了解的各种另外步骤,比如筛选、压制、研磨、磨碎、混合、分散等。应当意识到,还可考虑这些另外处理步骤以重复和/或不同顺序的组合。还应当意识到,如果在有香味成分中使用或用作有香味成分,则本公开的方法不限于获得精油或提取物的特定方法。
可使用的精油的实例包括(但不限于)沉香油(Agar oil)或Oodh油、沉香木油、Ajwain油、多香果油、当归油、茴香油、杏仁油、阿魏油、香脂薄荷油、苦配巴香脂油(BalsamCopaiba oil)、香脂油、罗勒油、月桂树油、月桂油、安息香油、佛手柑油、桦木油、黑胡椒油、血橙油、布枯油、Calamodin油或卡四季橘油(Calamansi Oil)、白菖油、樟脑油、***油、葛缕子籽油、小豆蔻籽油、胡萝卜油、胡萝卜籽油、桂皮油、猫薄荷油、雪松油或雪松木油、芹菜油、积雪草油、洋甘菊油、肉桂油、枸橼油、香茅油、快乐鼠尾草油、丁香油、椰子油、咖啡油、苦配巴油、芫荽油、艾菊油或圣经叶油(Bible leaf oil)、木香根油、蔓越莓籽油、荜澄茄油、孜然油或黑种草籽油、咖哩叶油、柏木油、香附油、印蒿油、莳萝油、土木香油、榄香油、桉树油、小茴香油、胡芦巴油、冷杉油、亚麻油、乳香油、高良姜油、格蓬油、天竺葵油、生姜油、一枝黄花油(Goldenrod oil)、葡萄柚油、番石榴油、蜡菊油、山核桃油、啤酒花油、辣根油、牛膝草油、茉莉油、刺柏油、岩玫瑰油、月桂油、薰衣草油、杜香油、柠檬油、柠檬草油、白柠檬油、芳樟油、山苍子油、莲花油、木兰油、橘子油、麦卢卡油、马郁兰油、茶树精油、蜂花油或柠檬香脂油、薄荷油、薄荷油、辣木油、山香薄荷油、艾蒿油、芥末油、没药油、桃金娘油、苦楝油、橙花油、绿花白千层油、肉豆蔻油、橄榄油、橙油、牛至油、菖蒲油、玫瑰草油、玉檀香油(Palo Santo oil)、欧芹油、广霍香油、天竺葵油、胡薄荷油、薄荷油、紫苏油、苦橙叶油、松油、鸡蛋花油、辐射油、罗文沙叶油、红雪松油、罗马洋甘菊油、玫瑰油、玫瑰果油、迷迭香油、玫瑰木油、鼠尾草油、檀香木油、黄樟油、香薄荷油或香薄荷油、五味子油、留兰香油、甘松油、云杉油、八角茴香油、甜安妮油、红橘油、艾菊油、龙蒿油、茶树油、百里香油、姜黄油、缬草油、马鞭草油、香根草油或香根草油、Warionia油、冬青油、苦艾油、欧耆草油、依兰油、蓬莪术油及其组合。
可使用的提取物的实例包括但不限于***胶提取物、紫花苜蓿提取物、藻类提取物、杏仁提取物、库拉索芦荟(aloe barbadensis)提取物、芦荟提取物、药蜀葵提取物、茴香提取物、苹果提取物、杏提取物、山金车(arnica)提取物、蒙大拿山金车(arnicamontana)提取物、朝鲜蓟提取物、阿魏提取物、鳄梨提取物、甘菊环提取物、香脂薄荷提取物、香脂薄荷提取物、竹提取物、香蕉提取物、大麦提取物、熊果提取物、蜂花粉提取物、甜菜提取物、越橘提取物、桦树叶提取物、黑升麻提取物、黑加仑子提取物、黑胡桃提取物、黑莓提取物、黑莓叶提取物、墨角藻提取物、蓝莓提取物、玻璃苣提取物、植物提取物、荞麦提取物、牛蒡提取物、地榆提取物、假叶树提取物、金盏花提取物、茶树(camellia sinensis)提取物、甘菊提取物、刺山柑提取物、小米椒提取物、角叉菜胶提取物、胡萝卜提取物、毛叶番荔枝提取物、樱桃树皮提取物、樱桃提取物、金鸡纳提取物、委陵菜提取物、柑橘花提取物、苜蓿花提取物、款冬提取物、锥花提取物、玉米须提取物、矢车菊提取物、聚合草(cornfrey)提取物、偃麦草提取物、山楂提取物、单子山楂提取物、黄瓜提取物、柏树提取物、蒲公英提取物、狗玫瑰果提取物、接骨木花提取物、eleuterococcus提取物、榆树皮提取物、英国橡树提取物、桉树提取物、蜡菊提取物、小茴香提取物、胡芦巴提取物、蕨类提取物、无花果提取物、栀子花提取物、大蒜提取物、龙胆提取物、生姜提取物、银杏gingko biloba)提取物、银杏(ginkgo)提取物、银杏(ginko)提取物、人参提取物、葡萄提取物、葡萄叶提取物、葡萄籽提取物、葡萄皮提取物、枸杞提取物、瓜拉纳(guarana)提取物、夏威夷生姜提取物、干草花提取物、蜡菊提取物、指甲花提取物、芙蓉花提取物、啤酒花提取物、七叶树提取物、问荆提取物、金丝桃属提取物、印度水芹提取物、常春藤提取物、薏苡提取物、荷荷巴油、枣提取物、刺柏提取物、欧刺柏提取物、卡力特树(Karite)提取物、海带提取物、猕猴桃提取物、秘鲁拉坦尼(krameria triandra)提取物、斗篷草提取物、掌状海带(laminaria digitata)提取物、海带(laminaria)提取物、薰衣草提取物、柠檬香脂提取物、柠檬提取物、柠檬皮提取物、生菜提取物、甘草提取物、菩提树提取物、白果紫草提取物、茜草提取物、锦葵提取物、芒果提取物、药蜀葵(marshmallow)提取物、母菊属提取物、瓜类提取物、西洋耆草提取物、细花含羞草树皮提取物、槲寄生提取物、罗汉果提取物、蘑菇提取物、没药提取物、荨麻提取物、橡树根提取物、燕麦提取物、油树脂提取物、洋葱提取物、橙花(orange blossom)提取物、橙花(orange flower)提取物、牡蛎壳提取物、三色堇提取物、欧芹提取物、木瓜提取物、百香果提取物、桃子提取物、墙草属植物(pellitory)提取物、胡薄荷提取物、薄荷提取物、蔓长春花提取物、松针提取物、菠萝提取物、开心果提取物、车前草提取物、花粉提取物、皂树(quillaja saponaria)提取物、榅桲籽提取物、覆盆子提取物、萝芙木提取物、匍匐芒柄花提取物、豆科灌木提取物、大黄根提取物、米糠提取物、玫瑰果提取物、迷迭香提取物、鼠尾草提取物、接骨木属(sambucus)提取物、血根草根提取物、肥皂草属(saponaria)提取物、海草提取物、肥皂草提取物、大豆提取物、留兰香提取物、圣约翰草(St. John's wort)提取物、荨麻提取物、草莓提取物、甘蔗提取物、葵花提取物、甜苜蓿提取物、茶提取物、蓟提取物、百里香提取物、番茄提取物、直立委陵菜(tormentill)提取物、缬草提取物、香草提取物、紫罗兰提取物、核桃提取物、西洋菜提取物、小麦麸提取物、小麦胚芽提取物、白荨麻提取物、白橡树皮提取物、白柳树皮提取物、野生靛蓝提取物、柳树皮提取物、金缕梅提取物、欧耆草提取物及其组合。
组合物可包含一种或多种皮肤保护剂。可使用的合适的皮肤保护剂的实例包括尿囊素、芦荟胶、茴香提取物、鳄梨油不皂化物、羧甲基几丁质、硫酸软骨素、胶原蛋白、胶原蛋白氨基酸、胚提取物、蓖麻油酸甘油酯、水解动物弹性蛋白、水解乳蛋白、水解植物蛋白、亚油酸(和)亚麻酸(和)花生四烯酸、脂质体、全氟聚甲基异丙基醚、浮游生物提取物和脊髓提取物。
组合物可包含一种或多种药物物质。将药物物质掺入组合物中可用于预防或治疗各种皮肤障碍或将药物物质递送至皮肤,将其有利地局部给予以进行经皮吸收。药物物质可为任何化合物或其混合物,其可对已给予该药物物质的人产生有益作用。药物物质可为在包括人在内的哺乳动物中产生局部或全身作用的任何生理学或药理学物质。可使用的合适药物物质的实例包括抗炎化合物、镇痛药、镇静剂、强心苷类、***拮抗剂、抗帕金森病药、抗抑郁药、抗肿瘤药、免疫抑制剂、抗病毒药、抗生素、食欲抑制剂、抗呕吐剂、抗组胺药、抗偏头痛药、冠状动脉、脑或外周血管扩张剂、抗心绞痛药、钙通道阻滞剂、激素药物、避孕药、抗血栓药、抗高血压药、化学依赖性药、局部***、皮质类固醇类、皮肤病学药物等、维生素(如维生素A (比如全反式视黄醇、视黄醇乙酸酯、视黄醇棕榈酸酯、视黄醇丙酸酯、β-胡萝卜素、比目鱼肝油、鲨鱼肝油)、维生素B1 (比如盐酸硫胺、苯磷硫胺、双苯酰硫胺、双丁硫胺、舒布硫胺、betoiamine盐酸盐、盐酸西托硫胺、羧化辅酶、赛可硫胺、呋喃硫胺)、维生素B2 (比如核黄素、核黄素四丁酸酯、黄素腺嘌呤二核苷酸)、维生素B6、维生素B12 (比如钴胺素、B12 TAM、腺苷钴胺、氰钴胺、甲钴胺)、其他B族维生素、维生素C (比如抗坏血酸)、维生素D (比如麦角钙化醇(维生素D2)、胆钙化固醇(维生素D3)、骨化二醇、骨化三醇、阿法骨化三醇(alfacalcitriol)、二氢速甾醇、阿法骨化醇、骨化二醇、骨化三醇、胆钙化醇、鳕鱼肝油、二氢速甾醇、麦角骨化醇)、维生素E、α-生育酚、生育酚烟酸酯、生育醌、小麦胚芽油、维生素K (比如植物甲萘醌(phytomenadione)、氢化甲萘醌二磷酸酯钠、甲萘醌)、维生素P、蔗糖硫酸酯(比如硫糖铝(sucralfate)、蔗糖八硫酸酯及其盐、酯和复合物)、抗菌药(比如苯氧乙醇)或任何其他药物物质。
组合物可包含一种或多种镇痛化合物。可使用的合适的镇痛化合物的实例包括芦荟、MSM、鸸鹋油、薄荷醇、氨基葡萄糖、软骨素、辣椒素、山金车提取物、芫荽油、罗马洋甘菊油、柳树皮提取物、小白菊提取物、圣约翰草提取物、卡瓦(kava kava)提取物、荨麻叶、乙酰水杨酸、巴拉(Bala)、黑升麻、黑蛇根、美洲升麻、美洲黄麟草、柴胡属(bupleurum)、金盏花、樟脑、辣椒(cayenne)、魔爪根、月见草油、生姜、积雪草、银杏、刺柏、薰衣草油、甘草、马郁兰、绣线菊、薄荷醇、西番莲、槲皮素、salicinum、野山药、冬青、红纹马先蒿、苦艾或任何其他镇痛药。
组合物可包含一种或多种抗炎化合物。可使用的合适的抗炎化合物的实例包括芦荟、MSM、鸸鹋油、软骨素、氨基葡萄糖、辣椒素、山金车提取物、葡萄籽提取物、芫荽油、万寿菊提取物、荨麻叶提取物、罗马洋甘菊油、矢车菊提取物、圣约翰草、柳树皮提取物、金缕梅提取物、小白菊提取物、大麦草、黑升麻、黑蛇根、美洲升麻、美洲黄麟草、乳香属(Boswellia)、玻璃苣、菠萝蛋白酶、牛蒡、金盏花、辣椒、蒲公英、魔爪根、DHEA (去氢表雄酮)、紫锥菊(Echinacea)、接骨木花、月见草油、亚麻籽、银杏、生姜、人参、山楂(Hawthorne)、山柰酚、甘草、活根草(life root)、金色千里光(golden Senecio)、美类叶升麻草(squaw weed)、金色千里光(golden groundsel)、北美紫菀草(cocash weed)、coughweed、狗舌草(ragwort)、金色狗舌草(golden ragwort)、grundy swallow、菩提树、马郁兰、绣线菊、NDGA、苦楝、Padma 28、槲皮素、乳木果油、姜黄、野山药、苦艾、丝兰(yucca)、红没药醇、硫糖铝、LIPACIDE、愈创蓝油烃(gauaiazulene)、必需脂肪酸、来自植物籽油和其他植物来源的多不饱和脂肪酸衍生物或任何其他抗炎药。必需脂肪酸(EFA)可包括ω-3和ω-6脂肪酸,比如亚麻酸和α亚麻酸。另外,组合物中可包含含有EFA的任何已知的草药或各种化合物。这种草药的实例包括亚麻籽和月见草油。
组合物可包含一种或多种止神经痛的化合物。具有止神经痛作用的化合物通常沿神经线路或在神经分布区域内提供减轻疼痛或不适。可使用的合适的止神经痛药包括辣椒素、罗马洋甘菊油、芫荽油或任何其他止神经痛的化合物。
组合物可包含一种或多种抗氧化剂。具有抗氧化活性的化合物通常防止组织的损伤或恶化。可使用的合适的抗氧化剂的实例包括软骨素、抗坏血酸、维生素C、可可脂、葡萄籽提取物、圣约翰草提取物、芫荽油、半胱氨酸、大麦草、越橘、紫锥菊(Echinacea)、大蒜、生姜、银杏、人参、葡萄籽原花青素提取物、绿茶、山楂(Hawthorne)、柠檬香脂、水飞蓟、牛至、薄荷、石榴汁、马齿苋、碧萝芷、红酒、迷迭香、五味子(schizandra)、无味子(wuweizi)、五仁醇、三亚油酸甘油酯、三七、酒石酸、姜黄、α-生育酚或任何其他生育酚、二丁基羟基甲苯丁基羟基茴香醚或任何其他抗氧化剂。
组合物可包含一种或多种血液循环促进剂。血液循环促进剂通常向施用组合物的区域提供增加的血液循环。可使用的合适的血液循环促进剂的实例包括MSM (甲基磺酰甲烷)、山金车提取物、罗马洋甘菊油、荨麻提取物、万寿菊提取物、葡萄籽提取物、矢车菊提取物、芫荽油、欧椴树提取物、万寿菊提取物、小白菊提取物、圣约翰草提取物、金缕梅提取物、阿顺那树(arjuna)、巴拉(Bala)、安息香、越橘、黑胡椒、蓝胶桉树、蓝花马鞭草、冰片、假叶树、辣椒、柏树、天竺葵、生姜、银杏、葡萄籽原花青素提取物、山楂(Hawthorne)、L-精氨酸、柠檬、柠檬草、菩提树花、绿花白千层、燕麦秸秆、橙花、西番莲、秘鲁香脂、松树、秦椒皮、玫瑰油、迷迭香、西班牙鼠尾草、云杉、田七人参、百里香、紫罗兰、白桦树、育亨宾(yohimbe)或任何其他血液循环促进剂。
组合物可包含一种或多种具有抗抑郁、抗焦虑或抗应激活性的化合物。可使用的合适的抗抑郁、抗焦虑或抗应激化合物的实例包括MSM、卡瓦(kava kava)提取物、罗马洋甘菊油、小白菊提取物、圣约翰草提取物、蜂花粉、佛手柑、黑升麻、臭夏至草、夏枯草、加州罂粟、快乐鼠尾草、西洋樱草(cowslip)、特纳草(damiana)、DHEA (去氢表雄酮)、天竺葵、人参、积雪草、葡萄柚、牛膝草、牙买加山茱萸、兜兰、薰衣草、柠檬香脂、甘草、菩提树、半边莲属(lobelia)、巴拉圭茶(mate)、槲寄生、益母草、艾蒿、燕麦秸秆、西番莲、薄荷、迷迭香、并头草属、缬草根、马鞭草属(vervain)、野生生菜、红纹马先蒿或任何其他抗抑郁、抗焦虑或抗应激化合物。
组合物可进一步包含任何减轻疼痛、抗炎、抗氧化剂、血液循环促进剂、抗抑郁、抗焦虑或抗应激类型的草药。可使用的合适的草药的实例包括阿顺那树(arjuna)、巴拉(Bala)、大麦草、蜂花粉、安息香、佛手柑、越橘、黑升麻、臭夏至草、黑胡椒、蓝胶桉树、蓝花马鞭草、玻璃苣、冰片、乳香属(Boswellia)、菠萝蛋白酶、夏枯草、柴胡属(bupleurum)、牛蒡、假叶树、加州罂粟、樟脑、辣椒、快乐鼠尾草、北美紫菀草、西洋樱草、coughweed、柏树、特纳草、蒲公英、魔爪根、DHEA、紫锥菊、接骨木花、月见草油、亚麻籽、大蒜、天竺葵、生姜、银杏、人参、金色千里光(golden groundsel)、金色狗舌草(golden ragwort)、金色千里光(golden Senecio)、积雪草、葡萄柚、葡萄籽原花青素提取物、绿茶、grundy swallow、山楂(Hawthorne)、欧石楠、牛膝草、牙买加山茱萸、刺柏、山柰酚、L-精氨酸、兜兰、薰衣草、柠檬、柠檬香脂、柠檬草、甘草、活根草、菩提树、半边莲属(lobelia)、马郁兰、巴拉圭茶(mate)、绣线菊、水飞蓟、槲寄生、益母草、艾蒿、NDGA (去甲二氢愈创木酸)、苦楝、绿花白千层、燕麦秸秆、橙花、牛至、Padma 28、西番莲、薄荷、秘鲁香脂、松树、石榴汁、秦椒皮、马齿苋、碧萝芷、槲皮素、狗舌草、红酒、玫瑰油、迷迭香、salicinum、五味子、酸模(sharp sorrel)、并头草属(skullcap)、西班牙鼠尾草、云杉、美类叶升麻草、田七人参、百里香、三亚油酸甘油酯、姜黄、缬草根、马鞭草属(vervain)、紫罗兰、白桦树、野生生菜、野山药、冬青、红纹马先蒿、苦艾、育亨宾、丝兰或任何其他减轻疼痛、抗炎、抗氧化剂、血液循环促进、抗抑郁、抗焦虑或抗应激类型的草药。
组合物可包含一种或多种药用提取物。药用提取物可具有多种药用作用。可使用的合适的药用提取物的实例包括芦荟提取物、睡莲提取物、胡萝卜提取物、金鸡纳提取物、苜蓿提取物、小茴香提取物、矢车菊提取物、虎耳草提取物、黄瓜提取物、丝瓜提取物、桉树提取物、野生问荆提取物、金缕梅属(hamamelis)提取物、芍药提取物、七叶树提取物、鱼腥草(Houttuynia cordate)提取物、鸢尾根茎提取物、柠檬提取物、甘草根提取物、紫草(Lithospermum erythrorhizon)提取物、草木犀提取物、蜂花提取物、桑椹提取物、桃子提取物、桃叶提取物、黄檗(Phellonden dronamurense Rupr)提取物、胎盘提取物、樱草花提取物、覆盆子提取物、玫瑰提取物、地黄(Rehmannia glutinosa)提取物、鼠尾草提取物、海草提取物、丝提取物、肥皂草提取物、苦参(Sophora angustifolia)提取物、茶提取物、百里香提取物、胸腺提取物、白荨麻提取物或任何其他药用提取物。
可包含在组合物中的药物和药用成分不受上述成分的限制。可根据目的将药物和药用成分单独配制成组合物,或者可将两种或更多种类型的药用成分组合并适当地配制。进一步地,药物和药用成分不仅可以游离形式使用,而且当能够形成盐时,还可以酸或碱的盐的形式配制成组合物,或者当具有羧酸基时,还可以酯的形式配制成组合物。
组合物可包含一种或多种防晒剂。可使用的合适的防晒剂的实例包括尿囊素、PABA、对氨基苯甲酸酯类、二苯甲酮-2、二苯甲酮-6、苯酰间苯二酚、水杨酸苄酯、西诺沙酯、二羟苯宗、七叶苷糖、4-双(羟丙基)氨基苯甲酸乙酯、对甲氧基肉桂酸乙基己酯、依托立林(etocrylen)、氨基苯甲酸甘油酯、胡莫柳酯、水杨酸甲酯、邻氨基苯甲酸甲酯、甲基丁香酚、3-(4-甲基亚苄基)硼烷-2-酮、美克西酮(mexenoe)、octabenxone、奥克立林、羟苯甲酮、帕地马酯、2-苯基-1H-苯并咪唑-5-磺酸、舒利苯酮、3-亚苄基樟脑、咖啡提取物、水杨酸乙酯、甘油基PABA、胡莫柳酯、异丙基苄基水杨酸酯、邻氨基苯甲酸薄荷酯、尼龙12 (和)二氧化钛、辛基二甲基PABA、甲氧基肉桂酸辛酯、水杨酸辛酯、辛基三嗪酮、谷维素、PEG-25 PABA、TEA水杨酸盐、二氧化钛、氧化锌、二苯甲酮-1、二苯甲酮-3、二苯甲酮-4、二苯甲酮-8、二苯甲酮-9、二苯甲酮-11、二苯甲酮-12、丁基甲氧基二苯甲酰基甲烷、4-异丙基二苯甲酰基甲烷、酪梨素、阿甘油(argana oil)、DEA甲氧基肉桂酸盐、甲酚曲唑、乙基二羟丙基对氨基苯甲酸、依托立林(etocrylene)、甲氧基肉桂酸异丙酯、3-(4-甲基亚苄基)樟脑、奥克立林、辛酚***、辛基二甲基PAB、甲氧基肉桂酸辛酯、水杨酸辛酯、辛基三嗪酮、PABA、乳木果油、TEA水杨酸盐、三-PABA泛醇或任何其他防晒剂。
组合物可包含一种或多种驱虫剂。可使用的合适的驱虫剂的实例包括避蚊酮、丁基乙基丙二醇、邻苯二甲酸二丁酯、二乙基甲苯甲酰胺、邻苯二甲酸二甲酯、乙基己二醇、香茅、樟脑或任何其他驱虫剂。
组合物可包含一种或多种防腐剂。可使用的合适的防腐剂的实例包括葡萄籽提取物、可可脂、对羟基苯甲酸甲酯、对羟基苯甲酸丙酯、重氮咪唑烷基脲(diazolindinylurea)、山梨酸、苯氧乙醇、对羟基苯甲酸乙酯、对羟基苯甲酸丁酯、对羟基苯甲酸丁酯钠、辛二醇、脱氢乙酸或任何其他防腐剂。组合物可以包含或可以不包含防腐剂,并且可包含多种防腐剂。防腐剂可助于防止不期望的细菌和真菌在组合物中形成。防腐剂也可增加组合物的保存期限。保存期限可指从产生组合物到将组合物施用于皮肤表面之间的时间。防腐剂可用于本领域技术人员已知的不同目的。
组合物可进一步包含糖(例如白糖、红糖等)或糖等同物,或者其他助于去角质的去角质剂或粒状材料。可使用的合适的去角质剂的实例包括pumus、杏粉、燕麦粉、核桃壳粉和杏仁粉。组合物的一个实施方案包含白糖。
组合物可包含一种或多种香料和/或色素(例如颜料、染料等)。可使用任何类型的天然或合成香料,比如花、草药或果实香料。香料的使用在美容领域中和在非处方药物制剂领域中为众所周知的,并且许多合适的香料为本领域已知的。组合物的稳定性和功能通常不会因存在或不存在香料而改变。小苍兰精油可用作天然香料。其他精油也可用作天然香料。可以省略香料,并且在其中组合物旨在用于敏感个体或可能对香料发生过敏反应的个体的情况下,可能期望省略香料。可使用任何类型的天然或FD&C着色剂,比如FD&C蓝色1号。任选地,组合物可为无色的,或具有由其中存在的一种或多种化合物提供的颜色。
组合物可进一步包含各种药学上或美容上可接受的赋形剂或添加剂,比如通常在美容或药用组合物中使用的那些。赋形剂或添加剂可为pH调节剂、稳定剂、着色剂、发泡剂、粘度调节剂、亮肤剂(比如熊果苷)、填充剂或增稠剂(比如海藻酸盐和Carbomer-940)、铺展剂、珍珠光泽剂、保护皮肤免受水、大气中和固体表面上的侵蚀性物质(比如盐、颜料、脂肪和酯)的侵蚀的试剂、保护剂(比如壳聚糖、盐、蜡和长链醇)。其他添加剂包括乳酸、枸橼酸、乙醇酸、琥珀酸、酒石酸、dl-苹果酸、碳酸钾、碳酸氢钠、碳酸氢铵和其他pH调节剂。应当意识到,在本公开的组合物中可使用上述添加剂的各种组合。此外,组合物可基本上不含或完全不含这种组分。
可将组合物配制成包含美容上可接受的载体(或媒介物)。美容上可接受的载体的实例包括(但不限于)水、甘油、蜡、各种醇(比如乙醇、丙醇)、植物油、矿物油、硅酮(比如硅油)、脂肪酯、脂肪醇、二醇、聚二醇或其任何组合。在以上的任选添加剂中描述了其他实例。
本公开的组合物可使用本领域了解的各种方法来制备。在制备组合物的一个实例中,制备方法包括以下步骤:组合微生物群体和从微生物群体中获得的组分中的至少一种以及任选地如上所述的一种或多种另外的组分(例如载体和/或添加剂),以获得组合物。组分可使用常规制备方法和装置(例如混合器、搅拌机等)来组合。
成品组合物可呈适合于局部施用于皮肤的任何形式,比如(但不限于)气溶胶喷雾剂、凝胶剂、乳膏剂、分散体、乳剂、泡沫剂、液体、洗剂、保湿剂、摩丝、贴剂、润发油、粉剂、泵式喷雾剂、固体、溶液剂、棒剂(stick)、丝华芙(suave)或小毛巾。乳剂可包括水包油乳剂、油包水乳剂和硅酮包水乳剂。在各种实施方案中,组合物可以药物、准药物或化妆品的形式使用。其可采取洗剂、乳膏剂、软膏剂、粉剂、凝胶剂、气雾剂、泡沫剂、洗面奶(facialcleanser)、香脂(balm)、凝胶剂、洗发剂(shampoo)、护发素(conditioner)、洗涤液(wash)、漂洗液(rinse)、小毛巾、美容液(beauty liquid)、剥撕式面膜(pack)、面膜、粉底液(makeup)、粉底(foundation)、磨砂膏、去角质霜、皂、口红、毛发化妆品、身体化妆品的形式或任何其他合适的用于施用于身体外表面的形式。然而,组合物能够采用的形式不限于这些形式。在某些实施方案中,组合物呈局部组合物的形式,任选地呈局部洗剂、局部洗涤液、局部乳膏剂、局部用块剂、局部用棒剂或其组合的形式。
工业应用性
本公开的本发明可用于用后生元和/或益生菌调节皮肤微生物组,特别是柯氏棒杆菌物种的组成。皮肤上柯氏棒杆菌物种的丰度也可用作获得或患有皮肤炎症(临床可见或亚临床)的可能性的诊断标志物。
说明本公开的方法和组合物的以下实施例,旨在说明而非限制本发明。
实施例
进行了两项代表性观察研究。在第一项研究中,观察495名受试者。这项研究为在秋初的密歇根州中部进行的一项未经预约的自愿性代表性研究。受试者的年龄在10到超过70岁范围内。微生物组拭子采样在5个身体部位进行:前额、头皮、前臂、鼻子和嘴巴。为每名受试者收集了300多个变量。在第二项研究中,在春末的密歇根州中部观察155名受试者。
参照附图,图1为说明第一项研究的受试者人口统计数据的饼状图。图2为进一步说明第一项研究的受试者人口统计数据的条形图。
图3为说明如用香农指数估计的每个部位的细菌多样性的图片。图上的每个点代表样品的多样性分数。图4为显示样品之间的细菌微生物组成相似性的排序。点代表单个微生物组,根据部位用颜色编码。
图5为盒须图,显示棒杆菌属(未分类)的前额物种水平分析。图6为盒须图,显示柯氏棒杆菌的前额物种水平分析。使用寡核苷酸分型管线鉴定棒杆菌属内的物种水平变化。通过显现其相对丰度(y轴)如何随年龄(x轴)而变化,将物种水平的变化与棒杆菌属(未分类)和柯氏棒杆菌相关联。根据其高度互相排斥,柯氏棒杆菌倾向于在中年成年人(40-49岁)中替换棒杆菌属(未分类) (图7)。图7为散点图,说明棒杆菌属(未分类)和柯氏棒杆菌如何互相排斥。
图8为热图,说明柯氏棒杆菌如何与皱纹和老年斑相关联。同样如所示的,棒杆菌属(未分类)通常与皱纹和老年斑具有低至无的相关性。图9为盒须图,说明作为柯氏棒杆菌相对丰度的函数的发红分数分布。图10为一系列照片,说明皮肤发红的视觉分级量表,范围从左侧的低/无发红(指定为1)到右侧的较高发红(指定为5)。
令人惊讶地,发现棒杆菌属(未分类)与年轻人相关,而柯氏棒杆菌与老年人相关。另外,还发现棒杆菌属(未分类)和柯氏棒杆菌互相排斥。当一种存在时,另一种不存在(即它们不共存)。令人惊讶地,发现柯氏棒杆菌与皮肤发红显著相关(r2> 0.4,见图9)。由于棒杆菌属(未分类)和柯氏棒杆菌互相排斥,因此棒杆菌属(未分类)可用作调节柯氏棒杆菌的工具(例如经培养上清液和/或用生物本身)。
提供以下另外的实施方案,其编号不应解释为指定重要性水平。
另外的实施方案
实施方案1涉及一种改变皮肤微生物组的方法,所述方法包括:将局部组合物给予受试者的皮肤;其中局部组合物包含微生物群体、从微生物群体获得的组分或其组合;其中微生物群体为棒杆菌属物种;和其中棒杆菌属物种包含与16S rRNA序列(SEQ ID NO: 1)至少约90%,任选地至少约97%的序列同一性。
实施方案2涉及实施方案1,其中局部组合物包含微生物群体。
实施方案3涉及实施方案1或2,其中局部组合物包含从微生物群体获得的组分。
实施方案4涉及实施方案3,其中所述组分包含从微生物群体获得的上清液和/或其衍生物。
实施方案5涉及前述实施方案中的任何一项,其中微生物群体和从微生物群体获得的组分中的至少一种以治疗有效量存在于局部组合物中,以减少、减慢和/或预防受试者的至少一种皮肤状况。
实施方案6涉及实施方案5,其中受试者的皮肤状况包括炎症、发红、色素沉着、起皱纹或其组合。
实施方案7涉及前述实施方案中的任何一项,其中局部组合物呈局部药用组合物或局部美容组合物的形式。
实施方案8涉及前述实施方案中的任何一项,其中局部组合物进一步包含至少一种美容上可接受的载体、赋形剂、添加剂或其组合。
实施方案9涉及前述实施方案中的任何一项,其中受试者为人类,并且为至少18岁,任选地为约30-约80岁。
实施方案10涉及前述实施方案中的任何一项,其中在给予局部组合物之前,受试者的皮肤包含天然微生物群体,和其中天然微生物群体不同于与给予受试者皮肤的局部组合物相关的微生物群体。
实施方案11涉及实施方案10,其中天然微生物群体包含柯氏棒杆菌,任选地其中柯氏棒杆菌包含与参考16S rRNA序列(SEQ ID NO: 2)至少约90%,任选地至少约97%的序列同一性。
实施方案12涉及前述实施方案中的任何一项,其中将局部组合物用手施用于受试者的皮肤,任选地其中将局部组合物在受试者的皮肤上揉搓和/或按摩。
实施方案13涉及前述实施方案中的任何一项,其中受试者的皮肤进一步定义为受试者的脸部,任选地进一步定义为至少受试者的前额。
实施方案14涉及用于改变受试者的皮肤微生物组的局部组合物,所述局部组合物包含:微生物群体、从微生物群体获得的组分或其组合;其中微生物群体为棒杆菌属物种;和其中棒杆菌属物种包含与16S rRNA序列(SEQ ID NO: 1)至少约90%,任选地至少约97%的序列同一性。
实施方案15涉及实施方案14,其中局部组合物包含微生物群体。
实施方案16涉及实施方案14或15,其中局部组合物包含从微生物群体获得的组分。
实施方案17涉及实施方案16,其中所述组分包含从微生物群体获得的上清液和/或其衍生物。
实施方案18涉及实施方案14-17中的任何一项,其中微生物群体和从微生物群体获得的组分中的至少一种以治疗有效量存在于局部组合物中,以减少、减慢和/或预防受试者的至少一种皮肤状况。
实施方案19涉及实施方案14-18中的任何一项,其中局部组合物呈局部药用组合物或局部美容组合物的形式。
实施方案20涉及实施方案14-19中的任何一项,其中局部组合物进一步包含至少一种美容上可接受的载体、赋形剂、添加剂或其组合。
实施方案21涉及实施方案14-20中任何一项的局部组合物用于受试者的皮肤的用途。
实施方案22涉及实施方案14-20中任何一项的局部组合物用于处理选自炎症、发红、色素沉着、起皱纹及其组合的皮肤状况的用途。
术语“包含”或“含有”本文以其最广义使用,以意指和涵盖“包括(including)”、“包括(include)”、“基本上由...组成”和“由...组成”的概念。使用“例如(for example)”、“例如(e.g.)”、“比如”和“包括”来列出说明性实例并不限于仅仅所列实例。因此,“例如”或“比如”意指“例如(但不限于)”或“比如(但不限于)”并且涵盖其他相似或等同的实例。如本文使用的术语“约”用于合理地涵盖或描述通过仪器分析测量的或由于样品处理所致的数值的微小变化。这种微小变化可为大约数值的±0-10%、±0-5%或±0-2.5%。进一步地,术语“约”在与数值范围相关联时适用于两个数值。此外,即使当没有明确说明时,术语“约”也可适用于数值。
通常,本文使用的在数值范围内的连字符“-”或破折号“-”为“至”或“直到”;“>”为“高于”或“大于”;“≥”为“至少”或“大于或等于”;“<”为“低于”或“小于”;和“≤”为“至多”或“小于或等于”。基于个体,一个专利、多个专利和/或专利申请公开的每个上述申请均在一个或多个非限制性实施方案中通过参考以其全部明确地结合至本文中。
应当理解,所附权利要求不限于在详述中描述的明确和特定的化合物、组合物或方法,其可在落入所附权利要求范围内的特定实施方案之间变化。关于本文用来描述各种实施方案的特定特征或方面所依赖的任何马库什组,应当意识到,可从独立于所有其他马库什成员的各马库什组的每个成员获得不同、特殊和/或意外的结果。可单独和/或组合地依赖于马库什组的每个成员,并在所附权利要求的范围内为具体实施方案提供足够的支持。
还应当理解,独立地和共同地描述本发明的各种实施方案时所依赖的任何范围和子范围均落入所附权利要求的范围内,并且应理解为描述和考虑其中包括整数和/或分数值的所有范围,即使本文没有明确写明这种值。本领域技术人员易于认识到,所枚举的范围和子范围足以描述和能够实现本发明的各种实施方案,并且可将这种范围和子范围进一步描述为相关的一半、三分之一、四分之一、五分之一等等。仅作为一个实例,范围“从0.1到0.9”可进一步描述为下三分之一(即从0.1到0.3)、中三分之一(即从0.4到0.6)和上三分之一(即从0.7到0.9),其单独地和共同地处于所附权利要求的范围内,并且可单独地和/或共同地被依赖,并为所附权利要求范围内的具体实施方案提供足够的支持。另外,关于定义或修饰范围的语言,比如“至少”、“大于”、“小于”、“不大于”等,应理解为这种语言包括子范围和/或上限或下限。作为另一个实例,范围“至少10”固有地包括至少10到35的子范围、至少10到25的子范围、25到35的子范围等等,并且每个子范围可单独地和/或共同地被依赖,并为所附权利要求范围内的具体实施方案提供足够的支持。最后,可依赖于所公开范围内的单个数字,并为所附权利要求范围内的具体实施方案提供足够的支持。例如,范围“1到9”包括各种单个整数(比如3)以及包含小数点(或小数)的单个数字(比如4.1),可依赖于这些数并为所附权利要求范围内的具体实施方案提供足够的支持。
本文已经以说明性的方式描述了本发明,并且应当理解,已经使用的术语旨在具有描述性而不是限制性的词语的性质。鉴于以上教导,本发明的许多改变和变化是可能的。在所附权利要求的范围内,可以不同于具体描述的方式来实践本发明。本文明确地考虑独立和从属权利要求(包括单项和多项从属两者)的所有组合的主题。
Claims (22)
1.一种改变皮肤微生物组的方法,所述方法包括:
将局部组合物给予受试者的皮肤;
其中所述局部组合物包含微生物群体、从所述微生物群体获得的组分或其组合;
其中所述微生物群体为棒杆菌属物种;和
其中所述棒杆菌属物种包含与16S rRNA序列(SEQ ID NO: 1)至少约90%,任选地至少约97%的序列同一性。
2.权利要求1的方法,其中所述局部组合物包含所述微生物群体。
3.权利要求1或2的方法,其中所述局部组合物包含所述从所述微生物群体获得的组分。
4.权利要求3的方法,其中所述组分包含从所述微生物群体获得的上清液和/或其衍生物。
5.权利要求1-4中任何一项的方法,其中所述微生物群体和所述从所述微生物群体获得的组分中的至少一种以治疗有效量存在于所述局部组合物中,以减少、减慢和/或预防所述受试者的至少一种皮肤状况。
6.权利要求5的方法,其中所述受试者的皮肤状况包括炎症、发红、色素沉着、起皱纹或其组合。
7.权利要求1-6中任何一项的方法,其中所述局部组合物呈局部药用组合物或局部美容组合物的形式。
8.权利要求1-7中任何一项的方法,其中所述局部组合物进一步包含至少一种美容上可接受的载体、赋形剂、添加剂或其组合。
9.权利要求1-8中任何一项的方法,其中所述受试者为人类,并且为至少18岁,任选地为约30-约80岁。
10.权利要求1-9中任何一项的方法,其中在给予所述局部组合物之前,所述受试者的皮肤包含天然微生物群体,和其中所述天然微生物群体不同于与给予受试者皮肤的所述局部组合物相关的所述微生物群体。
11.权利要求10的方法,其中所述天然微生物群体包含柯氏棒杆菌,任选地其中所述柯氏棒杆菌包含与参考16S rRNA序列(SEQ ID NO: 2)至少约90%,任选地至少约97%的序列同一性。
12.权利要求1-11中任何一项的方法,其中将所述局部组合物用手施用于所述受试者的皮肤,任选地其中将所述局部组合物在所述受试者的皮肤上揉搓和/或按摩。
13.权利要求1-12中任何一项的方法,其中所述受试者的皮肤进一步定义为所述受试者的脸部,任选地进一步定义为至少所述受试者的前额。
14.一种用于改变受试者的皮肤微生物组的局部组合物,所述局部组合物包含:
微生物群体、从所述微生物群体获得的组分或其组合;
其中所述微生物群体为棒杆菌属物种;和
其中所述棒杆菌属物种包含与16S rRNA序列(SEQ ID NO: 1)至少约90%,任选地至少约97%的序列同一性。
15.权利要求14的局部组合物,其中所述局部组合物包含所述微生物群体。
16.权利要求14或15的局部组合物,其中所述局部组合物包含所述从所述微生物群体获得的组分。
17.权利要求16的局部组合物,其中所述组分包含从所述微生物群体获得的上清液和/或其衍生物。
18.权利要求14-17中任何一项的局部组合物,其中所述微生物群体和所述从所述微生物群体获得的组分中的至少一种以治疗有效量存在于所述局部组合物中,以减少、减慢和/或预防所述受试者的至少一种皮肤状况。
19.权利要求14-18中任何一项的局部组合物,其中所述局部组合物呈局部药用组合物或局部美容组合物的形式。
20.权利要求14-19中任何一项的局部组合物,其中所述局部组合物进一步包含至少一种美容上可接受的载体、赋形剂、添加剂或其组合。
21.权利要求14-20中任何一项的局部组合物用于受试者的皮肤的用途。
22.权利要求14-20中任何一项的局部组合物用于处理选自炎症、发红、色素沉着、起皱纹及其组合的皮肤状况的用途。
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN114469926A (zh) * | 2022-01-28 | 2022-05-13 | 吉林省健维天然生物科技有限公司 | 二氢槲皮素的新用途及二氢槲皮素水凝胶的制备方法 |
CN114469926B (zh) * | 2022-01-28 | 2023-06-27 | 吉林省健维天然生物科技有限公司 | 二氢槲皮素的新用途及二氢槲皮素水凝胶的制备方法 |
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KR20200094178A (ko) | 2020-08-06 |
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WO2019108715A1 (en) | 2019-06-06 |
US20190160117A1 (en) | 2019-05-30 |
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