CN110022848B - 包含胡椒素的抗应激组合物 - Google Patents
包含胡椒素的抗应激组合物 Download PDFInfo
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- CN110022848B CN110022848B CN201780073269.4A CN201780073269A CN110022848B CN 110022848 B CN110022848 B CN 110022848B CN 201780073269 A CN201780073269 A CN 201780073269A CN 110022848 B CN110022848 B CN 110022848B
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Abstract
本说明书描述了一种抗应激组合物，该组合物包含作为活性成分的胡椒素、其异构体、其药学上或化妆品上可接受的盐、其水合物或其溶剂化物。该组合物可以减轻或缓解由应激引起的身体和心理症状。
Description
技术领域
本说明书描述了一种抗应激组合物，该组合物包含胡椒素、其异构体、其药学上或化妆品上可接受的盐、其水合物或其溶剂化物。
背景技术
应激是指由于外部刺激或环境变化导致的人体适应不良，可导致交感神经系统过度活跃，这可能导致暂时或持续的心理和身体反应。现代人暴露于各种应激源，这些应激源与身心状态的各种变化密切相关。因此，人们对应激抗性越来越感兴趣。
使用合成化合物的用于抑郁和应激的治疗剂可能引起副作用或人体毒性。需要一种具有抗应激作用的、作为化妆品或食品而不是作为药物的物质，该物质使用天然产物。
发明内容
技术问题
在一方面，本发明的目的是提供具有提高应激抗性的效果的组合物。
另一方面，本发明的目的是提供一种组合物，该组合物具有通过使用天然产物提高应激抗性而不引起人体毒性的作用。
另一方面，本发明的目的是提供一种对糖皮质激素诱导的应激具有优异抗性的组合物。
另一方面，本发明的目的是提供一种能够通过活化催产素受体来提高应激抗性的组合物。
另一方面，本发明的目的是提供一种减轻或缓解由应激引起的身体症状的组合物。
另一方面，本发明的目的是提供一种减轻或缓解由应激引起的心理症状的组合物。
解决问题的方案
在一方面，本发明提供一种抗应激组合物，该组合物包含作为活性成分的胡椒素、其异构体、其药学上或化妆品上可接受的盐、其水合物或其溶剂化物。
发明的有益效果
在一方面，本发明实现了提高应激抗性的效果。
另一方面，本发明实现了通过使用天然产物提高应激抗性而不引起人体毒性的效果。
另一方面，本发明使得能够实现对糖皮质激素诱导的应激的优异抗性。
另一方面，本发明使得能够通过激活催产素受体来提高应激抗性。
另一方面，本发明可以减轻或缓解由应激引起的身体症状。
另一方面，本发明可以减轻或缓解由应激引起的心理症状。
附图说明
图1是展示胡椒素与催产素受体的结合的图。
图2是展示胡椒素对糖皮质激素诱导的细胞凋亡的抑制作用的图。
具体实施方式
实施方式
在下文中，将参考附图详细描述本发明的实施方式。然而，本发明中公开的技术不限于本文阐述的实施方式，并且可以以各种不同的形式实施。相反，提供这些实施方式是为了使本公开深入和完整，并向本领域技术人员充分传达本发明的精神。而且，在不脱离本发明的精神的情况下，本领域技术人员可以以各种其他形式体现本发明的精神。
如本文所用，“异构体”不仅包含光学异构体(例如，基本上纯的对映异构体、基本上纯的非对映异构体或其混合物)，还包含构象异构体(即，其中仅一个或多个化学键的角度彼此不同的异构体)、位置异构体(特别是互变异构体)或几何异构体(例如，顺反异构体)。
如本文所用，“基本上纯的”，例如针对对映异构体或非对映异构体而使用时，是指，特定化合物(例如对映异构体或非对映异构体)以约90％(w/w)或更多，优选约95％或更多，更优选约97％或更多或约98％或更多，更优选约99％或更多，甚至更优选约99.5％或更多的量存在。
如本文所用，“药学上可接受的”是指当以通常使用的药物剂量使用时没有实质的毒性作用，因此可以或已经由政府或与之相当的监管组织批准或被列入药典或被其他通用药典认可为用于动物，以及更特别地，用于人类。
如本文所用，“药学上或化妆品上可接受的盐”是指在药学上或化妆品上是可接受的并且具有母体化合物的所需药理学活性的根据本发明一个方面的盐。这些盐包括：(1)由无机酸形成的酸加成盐，所述无机酸例如盐酸、氢溴酸、硫酸、硝酸、磷酸等，或由有机酸形成的酸加成盐，所述有机酸例如乙酸、丙酸、己酸、环戊烷丙酸、乙醇酸、丙酮酸、乳酸、丙二酸、琥珀酸、苹果酸、马来酸、富马酸、酒石酸、柠檬酸、苯甲酸、3-(4-羟基苯甲酰基)苯甲酸、肉桂酸、扁桃酸、甲磺酸、乙磺酸、1,2-乙烷-二磺酸、2-羟基乙磺酸、苯磺酸、4-氯苯磺酸、2-萘磺酸、4-甲苯磺酸、樟脑磺酸、4-甲基双环[2,2,2]-辛-2-烯-1-羧酸、葡庚糖酸、 3-苯基丙酸、三甲基乙酸、叔丁基乙酸、月桂基硫酸、葡萄糖酸、谷氨酸、羟基萘甲酸、水杨酸、硬脂酸和粘康酸；或(2)当母体化合物中存在的酸性质子被取代时形成的盐。
如本文所用，“水合物”是指与水键合的化合物。该术语按广义使用，包括缺乏与水的化学键合的包合物。
如本文所用，“溶剂化物”是指在溶质的分子或离子与溶剂的分子或离子之间形成的高阶化合物。
根据一种实施方式，本发明可提供一种抗应激组合物，该组合物包含作为活性成分的胡椒素、其异构体、其药学上或化妆品上可接受的盐、其水合物或其溶剂化物。
在该实施方式中，胡椒素，也称为四氢胡椒碱，是具有由下式表示的结构的胡椒碱类化合物。已知胡椒素是促进水溶性物质的渗透的物质。本发明人发现，胡椒素具有提高应激抗性的效果。因此，根据该实施方式的组合物可以表现出作为抗应激组合物的优异效果。
<式>
该组合物对糖皮质激素诱导的应激具有抗性。在一种实施方式中，该组合物可以抑制糖皮质激素诱导的细胞凋亡。对糖皮质激素诱导的细胞凋亡的抑制可导致心理或身体症状的减轻或缓解。糖皮质激素可包括选自皮质醇、可的松和皮质酮中的至少一种。
该组合物可以与催产素受体结合以活化催产素受体。催产素(OXT，OT)是从包括脊椎动物和无脊椎动物的各种动物的垂体后叶分泌的神经递质。催产素也被称为子宫收缩激素。已知催产素在分娩时参与子宫的收缩，并且当一个人看到有魅力的人时催产素也会从脑垂体分泌到血流中。催产素对缓解应激和社交能力的影响也已有报道。根据该实施方式的组合物可通过活化催产素受体实现对应激的抗性。
该组合物可以缓解或减轻由应激引起的身体症状。由应激引起的身体症状的实例包括以下症状：消化症状，例如肠易激综合征、消化不良、胃炎、胃痉挛、胃十二指肠溃疡和便秘；神经症状，例如偏头痛；泌尿症状，例如勃起功能障碍和性冷淡；心血管症状，例如高血压和心绞痛；以及皮肤症状，例如脱发和荨麻疹。持续的应激可能会使这些症状发展成疾病。
该组合物可以缓解或减轻由应激引起的心理症状。由应激引起的心理症状的实例包括抑郁、焦虑症、失眠和紧张。
在一种实施方式中，该组合物可以是化妆品组合物。
根据本发明的一种实施方式的化妆品组合物可包含占该组合物的总重量的0.0001重量％至99重量％，例如0.01重量％至60重量％的活性成分，尽管不限于此。
根据本发明的一种实施方式的化妆品组合物可以配制成含有化妆品上或皮肤病学上可接受的介质或基质。它可以被制备成适合局部应用的任何制剂，例如悬浮液、微乳液、微胶囊剂、微粒剂、离子(脂质体)或非离子囊泡分散剂、霜剂、润肤乳液、滋养乳液、粉剂、软膏剂、喷雾剂或遮瑕棒。而且，它可以以进一步含有压缩的推进剂的泡沫或气溶胶组合物的形式使用。该组合物可以根据本领域常用的方法制备。
进一步地，根据本发明实施方式的化妆品组合物可包含常规用于化妆品或皮肤病学领域的佐剂，例如粉末、脂肪、有机溶剂、溶解剂、浓缩剂、胶凝剂、软化剂、抗氧化剂、悬浮剂、稳定剂、发泡剂、香料、表面活性剂、水、离子或非离子乳化剂、填充剂、金属离子阻断剂、螯合剂、防腐剂、维生素、阻断剂、润湿剂、精油、染料、色素、亲水或疏水活化剂、脂质囊泡或化妆品中常用的其它成分。佐剂可以以化妆品或皮肤病学领域中常规使用的量使用。根据本发明实施方式的化妆品组合物还可含有皮肤吸收促进物质，以增加改善皮肤的效果。
根据本发明实施方式的组合物可被提供为各种类型的食品添加剂或功能食品。例如，它可被加工成含有该活性成分以及各种食品添加剂的发酵乳、奶酪、酸奶、果汁、益生菌、保健食品等。
根据本发明实施方式的组合物可以是用于保健食品的组合物。
根据本发明的一种实施方式的用于保健食品的组合物可以包含占组合物的总重量0.0001 重量％至99重量％，例如0.01重量％至60重量％的的活性成分，但不限于此。
在一个具体实施方式中，用于保健食品的组合物可以配制成丸剂、胶囊剂、片剂、颗粒剂、焦糖剂或饮料。在其他具体实施方式中，它可以加工成液体、粉末、颗粒剂、片剂、茶包等形式。
该组合物可以通过各种方法给药，例如饮用、注射、喷雾或挤压。
该组合物可包含其它能提供协同作用而不会对本发明的主要作用产生负面影响的成分。例如，为了改善性能，该组合物还可以包括添加剂，例如调味剂，色素，灭菌剂，抗氧化剂，防腐剂，保湿剂，增稠剂，无机盐，乳化剂，合成聚合物等。此外，它可以进一步包括辅助成分，如水溶性维生素、油溶性维生素、多肽、多糖、海藻提取物等。本领域技术人员可以考虑配方或用途而适当地选择和组合这些成分。这些成分的量可以在不对本发明的目的和效果产生负面影响的范围内确定。例如，所述成分的量可以为占组合物总重量的0.01重量％至5重量％，例如0.01重量％至3重量％，但不限于此。
[实施例]
在下文中，将参考实施例进一步详细描述本发明。对于本领域技术人员显而易见的是，这些实施例仅用于说明目的，并且本发明不应被解释为限于本文所述的实施例。
测试实施例1：与催产素受体的结合的确认
为了证实胡椒素与催产素受体的结合，将胡椒素(Sabina Corp，NJ)以0至400μM的浓度施用于其表面结合有催产素受体(催产素受体重组蛋白，Mybiosource,MA)的SPR芯片(Biorad，MA)，然后反应90秒。然后，使用表面等离子体共振装置(表面等离子体共振仪；Biorad，MA)测量胡椒素与催产素受体的结合模式。结果如图1所示。
根据图1的结果，发现胡椒素以浓度依赖性方式与催产素受体结合。
测试实施例2：对糖皮质激素诱导的细胞凋亡的抑制作用
为了证实胡椒素的抗应激作用，对糖皮质激素诱导的细胞凋亡进行了测试。
将PC12(神经细胞瘤细胞；KCLB21721，韩国细胞系库)以2×104个细胞/孔接种到96 孔板中，并在5％CO2和37℃下培养。培养基是补充有10％血清(热灭活的胎牛血清(FBS，Gibco))、100U/ml青霉素(Gibco)和100μg/ml链霉素(Gibco)的RPMI 1640培养基(Gibco BRL，Grand Island，NY，USA))。用400μM作为应激激素的皮质酮 (Sigma，MA)处理细胞，并在5％CO2和37℃下培养24小时以诱导应激。将400μM皮质酮和50μM作为抗抑郁药的氟西汀(盐酸氟西汀，Sigma)用作阳性对照组。对于胡椒素处理组，使用400μM皮质酮和50μM的胡椒素(Sabina Corp，NJ)。氟西汀和胡椒素各自在皮质酮施用前2小时进行预处理。向每个孔中添加10μl CCK-8溶液(Dojindo Laboratories)，然后培养2小时。接着，在540nm处进行测量。基于测量结果，图2示出了在未用皮质酮处理的组的值为1的情况下细胞的相对存活率。
从图2的结果，可以看出，胡椒素在抑制皮质酮(其为代表性应激相关糖皮质激素)诱导的细胞凋亡方面是优异的。
制剂实施例1：片剂
根据制备片剂的常规方法，将100mg本发明制备实施例1的洗脱液、400mg乳糖、400mg玉米淀粉和2mg硬脂酸镁混合并压片以制备片剂。
制剂实施例2：胶囊
根据制备胶囊的常规方法，将100mg本发明制备实施例1的洗脱液、400mg乳糖、400mg玉米淀粉和2mg硬脂酸镁混合并填充到明胶胶囊中以制备胶囊。
制剂实施例3：颗粒
将50mg本发明制备实施例1的洗脱液、250mg无水结晶葡萄糖和550mg淀粉混合，并用流化床造粒机造粒成颗粒，然后将颗粒装入小袋中。
制剂实施例4：饮料
将50mg本发明制备实施例1的洗脱液、10g葡萄糖、0.6g柠檬酸和25g液体低聚糖混合并添加300ml纯化水。在每个瓶中装入200ml所得混合物。装入瓶中后，将混合物在 130℃下灭菌4至5秒以制备饮料。
制剂实施例5：柔肤乳液(润肤乳液)
根据常规方法制备柔肤乳液，其组成如下表所示。
表1
| 成分 | 含量(重量％) |
| 胡椒素 | 0.2 |
| 甘油 | 3.0 |
| 丁二醇 | 2.0 |
| 丙二醇 | 2.0 |
| 羧乙烯基聚合物 | 0.1 |
| PEG-12壬基苯基醚 | 0.2 |
| 聚山梨醇酯80 | 0.4 |
| 乙醇 | 10.0 |
| 三乙醇胺 | 0.1 |
| 防腐剂、着色剂、香料 | q.s. |
| 纯化水 | 至100 |
制剂实施例6：滋养乳液(牛乳状乳液)
根据常规方法制备滋养乳液，其组成如下表所示。
表2
| 成分 | 含量(重量％) |
| 胡椒素 | 1.0 |
| 甘油 | 3.0 |
| 丁二醇 | 3.0 |
| 丙二醇 | 3.0 |
| 羧乙烯基聚合物 | 0.1 |
| 蜡 | 4.0 |
| 聚山梨醇酯60 | 1.5 |
| 辛酸/癸酸甘油三酯 | 5.0 |
| 角鲨烷 | 5.0 |
| 脱水山梨醇倍半油酸酯 | 1.5 |
| 液体石蜡 | 0.5 |
| 鲸蜡硬脂醇 | 1.0 |
| 三乙醇胺 | 0.2 |
| 防腐剂、着色剂、香料 | q.s. |
| 纯化水 | 至100 |
制剂实施例7：按摩霜
根据常规方法制备按摩霜，其组成如下表所示。
表3
制剂实施例8：头发乳液的制备
根据常规方法制备头发乳液，其组成如下表所示。
表4
| 成分 | 含量(重量％) |
| 胡椒素 | 2.0 |
| 纯化水 | 至100 |
| 甘油 | 3.0 |
| 丁二醇 | 3.0 |
| 液体石蜡 | 7.0 |
| β-葡聚糖 | 7.0 |
| 卡波姆 | 0.1 |
| 雪绒花提取物 | 2.0 |
| 辛酸/癸酸甘油三酯 | 3.0 |
| 角鲨烯 | 5.0 |
| 鲸蜡硬脂基葡糖苷 | 1.5 |
| 脱水山梨糖醇硬脂酸酯 | 0.4 |
| 聚山梨酯 | 1.2 |
| 防腐剂 | q.s. |
| 香料 | q.s. |
| 着色剂 | q.s. |
| 三乙醇胺 | 0.1 |
制剂实施例9：洗发剂组合物的制备
根据常规方法制备洗发剂组合物，其组成如下表所示。
表5
| 成分 | 含量(重量％) |
| 聚季铵盐-10 | 0.5 |
| 月桂基醚硫酸钠 | 20 |
| 胡椒素 | 0.3 |
| 香料 | 1.0 |
| 对羟基苯甲酸甲酯 | 0.1 |
| 鲸蜡醇 | 0.5 |
| 氯化钠 | 0.8 |
| 纯化水 | 至100 |
制剂实施例10：头发处理剂的制备
根据常规方法制备头发处理剂，其组成如下表所示。
表6
| 成分 | 含量(重量％) |
| 胡椒素 | 0.5 |
| 硬脂酰胺丙基二甲胺 | 2 |
| 甘油 | 0.5 |
| 香料 | 0.5 |
| 防腐剂 | 0.03 |
| 十六十八醇 | 5 |
| 乳酸 | 1 |
| 蒸馏水 | 至100 |
Claims (6)
1.胡椒素或其药学上或化妆品上可接受的盐在制备用于抑制糖皮质激素诱导的细胞凋亡的组合物中的用途，其中，所述糖皮质激素包括选自皮质醇、可的松和皮质酮中的至少一种。
2.根据权利要求1所述的用途，其特征在于，所述胡椒素是具有由下式表示的结构的化合物：
3.根据权利要求1所述的用途，其特征在于，所述组合物是化妆品组合物。
4.根据权利要求3所述的用途，其特征在于，所述胡椒素或其药学上或化妆品上可接受的盐的含量为占所述组合物的总重量的0.01重量％至99重量％。
5.根据权利要求1所述的用途，其特征在于，所述组合物是用于保健食品的组合物。
6.根据权利要求5所述的用途，其特征在于，所述胡椒素或其药学上或化妆品上可接受的盐的含量为占所述组合物的总重量的0.01重量％至99重量％。
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| US6849645B2 (en) * | 2000-05-19 | 2005-02-01 | Sabinsa Corporation | Method of increased bioavailability of nutrients and pharmaceutical preparations with tetrahydropiperine and its analogues and derivatives |
| WO2004089110A3 (en) * | 2003-03-31 | 2005-06-09 | Breakthru Products Llc | Hydration beverage and method of delivering nutrients |
| CN104288002A (zh) * | 2014-09-13 | 2015-01-21 | 上海梦之队国际贸易有限公司 | 一种用于化妆品的能量补充复合物的制备方法 |
| US9289374B2 (en) * | 2014-04-23 | 2016-03-22 | Lifevantage Corporation | Topical compositions and methods for reducing oxidative stress |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1902755A1 (en) * | 2006-09-19 | 2008-03-26 | Cognis IP Management GmbH | Cosmetic compositions decreasing GM-CSF release induced by nickel salts |
| KR101077018B1 (ko) | 2009-03-23 | 2011-10-26 | (주)아모레퍼시픽 | 스트레스 완화 및 진정 효과를 갖는 화장료 조성물 |
-
2016
- 2016-09-27 KR KR1020160124253A patent/KR102655937B1/ko active IP Right Grant
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2017
- 2017-09-26 US US16/336,749 patent/US20210275422A1/en not_active Abandoned
- 2017-09-26 CN CN201780073269.4A patent/CN110022848B/zh active Active
- 2017-09-26 EP EP17856687.3A patent/EP3520771A4/en active Pending
- 2017-09-26 WO PCT/KR2017/010586 patent/WO2018062801A1/ko unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6849645B2 (en) * | 2000-05-19 | 2005-02-01 | Sabinsa Corporation | Method of increased bioavailability of nutrients and pharmaceutical preparations with tetrahydropiperine and its analogues and derivatives |
| WO2004089110A3 (en) * | 2003-03-31 | 2005-06-09 | Breakthru Products Llc | Hydration beverage and method of delivering nutrients |
| US9289374B2 (en) * | 2014-04-23 | 2016-03-22 | Lifevantage Corporation | Topical compositions and methods for reducing oxidative stress |
| CN104288002A (zh) * | 2014-09-13 | 2015-01-21 | 上海梦之队国际贸易有限公司 | 一种用于化妆品的能量补充复合物的制备方法 |
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| Title |
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| "四氢胡椒碱对辣椒碱软膏透皮渗透性的影响";师伯省等;《中国药物经济学》;20141231(第7期);第21、35页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| KR102655937B1 (ko) | 2024-04-11 |
| KR20180034124A (ko) | 2018-04-04 |
| CN110022848A (zh) | 2019-07-16 |
| US20210275422A1 (en) | 2021-09-09 |
| WO2018062801A1 (ko) | 2018-04-05 |
| EP3520771A4 (en) | 2020-06-17 |
| EP3520771A1 (en) | 2019-08-07 |
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