CN1856293B - 多酚的无水局部用制剂 - Google Patents

多酚的无水局部用制剂 Download PDF

Info

Publication number
CN1856293B
CN1856293B CN200480027523XA CN200480027523A CN1856293B CN 1856293 B CN1856293 B CN 1856293B CN 200480027523X A CN200480027523X A CN 200480027523XA CN 200480027523 A CN200480027523 A CN 200480027523A CN 1856293 B CN1856293 B CN 1856293B
Authority
CN
China
Prior art keywords
polyphenol
mixture
carrier
conjunction
gel
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
CN200480027523XA
Other languages
English (en)
Other versions
CN1856293A (zh
Inventor
马修·巴德勒
彼得·福德
乔治·罗恩施
罗伯特·塞维利
希瑟·乔伊斯
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Origin Biomedicinals Inc
Original Assignee
Origin Biomedicinals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Origin Biomedicinals Inc filed Critical Origin Biomedicinals Inc
Publication of CN1856293A publication Critical patent/CN1856293A/zh
Application granted granted Critical
Publication of CN1856293B publication Critical patent/CN1856293B/zh
Expired - Fee Related legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/54—Lauraceae (Laurel family), e.g. cinnamon or sassafras
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/63—Oleaceae (Olive family), e.g. jasmine, lilac or ash tree
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/73—Rosaceae (Rose family), e.g. strawberry, chokeberry, blackberry, pear or firethorn
    • A61K36/736—Prunus, e.g. plum, cherry, peach, apricot or almond
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/82—Theaceae (Tea family), e.g. camellia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/886—Aloeaceae (Aloe family), e.g. aloe vera
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/889—Arecaceae, Palmae or Palmaceae (Palm family), e.g. date or coconut palm or palmetto
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/25—Silicon; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/26—Aluminium; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A61K8/27—Zinc; Compounds thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/368—Carboxylic acids; Salts or anhydrides thereof with carboxyl groups directly bound to carbon atoms of aromatic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/92—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof
    • A61K8/922—Oils, fats or waxes; Derivatives thereof, e.g. hydrogenation products thereof of vegetable origin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9706—Algae
    • A61K8/9711—Phaeophycota or Phaeophyta [brown algae], e.g. Fucus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9794—Liliopsida [monocotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/001—Preparations for care of the lips
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/20—Chemical, physico-chemical or functional or structural properties of the composition as a whole
    • A61K2800/30—Characterized by the absence of a particular group of ingredients
    • A61K2800/31—Anhydrous
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/52—Stabilizers
    • A61K2800/522—Antioxidants; Radical scavengers

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biotechnology (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Botany (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Medical Informatics (AREA)
  • Birds (AREA)
  • Inorganic Chemistry (AREA)
  • Dermatology (AREA)
  • Emergency Medicine (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Cosmetics (AREA)
  • Medicinal Preparation (AREA)
  • Medicines Containing Plant Substances (AREA)

Abstract

本发明披露了物质组合物及其配制方法，该物质组合物包括无水局部用霜、凝胶或膏基质，多酚和适当的吸附结合载体，所述载体和多酚结合以便均匀地分布在霜、凝胶或基质内并且在施用局部用混合物时该载体不抑制多酚释放至皮肤的含水环境之上和之中。所述结合载体提供了在无水介质中分散亲水多酚的能力以便局部施用至身体。具体地，本发明披露了通过使用各种结合载体分布在包含饱和或不饱和植物油或蜡的无水基质中多酚的用途，例如茶的儿茶素尤其是绿茶儿茶素的用途，所述结合载体包括但不限于滑石和粘土，藻酸盐，藻类，琼脂，树胶，明胶，纤维素，硅石，硅胶，二甲硅油，水杨酸盐，硅酸盐和硅树脂，西黄蓍胶，碳酸钙和氧化镁或氧化锌。当混合物中多酚浓度超过0.2％w/w时，该结合载体尤其有用，当多酚浓度介于1.0-20％w/w之间时，它们的用途是优选的。

Description

多酚的无水局部用制剂
发明背景
植物多酚已知是有效的抗氧化剂并认为是饮食健康的重要组分。越来越多地，衍生自茶、葡萄和其它植物源的多酚被纯化并且因附加的有益效果可被看作食品添加物(dietary supplement)。已经开始认识到多酚可以局部施用至皮肤并且对皮肤和周围组织给予相同的局部有益效果。
然而，许多多酚，特别是绿茶儿茶素(catechin)在室温下非常不稳定并在数天内氧化和分解，尤其在水存在的情况下(1)。为了确保局部用混合物中多酚的稳定性，可以不使用水配制该混合物(无水的)，从而增加多酚的稳定性。其它抗氧化剂例如维生素C将增加这种稳定效果。饱和或不饱和的植物油通常在大量商品化的局部用混合物中用作基质，但多酚在这些油中溶解性差。许多多酚，特别是绿茶提取物，更具体地是富集多酚的绿茶提取物不能均匀地溶解或分散在主要由油或蜡组成的无水局部用混合物(topical mixture)中。
由于这一原因，设计下列方法是重要的，通过该方法多酚可以均匀地分布在无水局部用混合物中，以提供确保多酚稳定性的适当产品，同时还为局部用产品提供适当的商业吸引力。通过使用惰性吸附结合载体(absorbent binding carrier)可以在整个无水局部用混合物中实现这种均匀分布，所述载体在将该局部用混合物施用至皮肤时不抑制多酚释放至皮肤的含水环境之上和之中的能力。
在制药共混专业中吸附原理是公认的，并用于溶液脱色、吸附色谱、去垢和润湿。诸如dues、生物碱、脂肪酸和无机酸及碱等药物可以吸附在固体如炭和氧化铝上。本文描述了在用于无水混合物之前吸附多酚的新型应用。
引用文献：
1.Zhou，Q.，et al.(2003)Investigating the stability of EGCg in AqueousMedia.Current Separations 20：3.
2.Proniuk，S.，et al(2002)Preformulation study of epigallocatechin galate，a promising antioxidant for topical skin cancer prevention.J Pharm Sci 2002 Jan；91(1)：111-6
发明内容
本发明披露了物质组合物及其配制方法，该物质组合物包括无水局部用霜(cream)、凝胶或膏(oinment)基质，多酚和适当的吸附结合载体，所述载体和多酚结合以便均匀地分布在霜、凝胶或膏基质内并且在将局部用混合物施用至皮肤时该载体不抑制多酚释放至皮肤的含水环境之上和之中。所述结合载体提供了在无水介质中分散亲水多酚的能力以便局部施用至身体。特别地，本发明披露了通过使用各种结合载体分布在包含饱和或不饱和植物油或蜡的无水基质中多酚(例如绿茶儿茶素)的用途，所述结合载体包括但不限于滑石、粘土或硅石、水杨酸盐、硅酸盐和硅树脂、琼脂、藻酸盐、树胶、纤维素、西黄蓍胶、碳酸钙和氧化酶或氧化锌。当混合物中多酚浓度超过0.2％w/w时，该结合载体尤其有用，当多酚浓度介于1.0-20％w/w之间时，它们的用途是优选的。
具体实施方式
植物多酚已知是有效的抗氧化剂和抗瘤剂并认为是饮食健康的重要组分。越来越多地，衍生自茶、葡萄和其它植物源的多酚被纯化并且因附加的有益效果可被看作食品添加物。实例包括儿茶素、羟基酪醇(hydroxytyrosols)和原花色素(proanthocyanidins)。例如，绿茶含有一类多酚称为儿茶素。大量的研究显示儿茶素对减肥、口臭、多种癌症、关节炎和过敏症有益。已经开始认识到多酚可以局部施用至皮肤且对皮肤和周围组织给予相同的局部有益效果。对多酚局部施用的研究已经显示多酚对UV损伤、癌变前的皮肤病损和皮肤癌可能存在的益处，并且是通用的愈合剂(healing agent)。
然而，许多多酚，特别是绿茶儿茶素在室温下非常不稳定并在数天内氧化和分解，尤其在水存在的情况下(1)。为了确保局部用混合物中多酚的稳定性，可以不使用水而使用各种类型的合成或天然油类、蜡和乳化剂配制该混合物(无水的)，从而增加多酚的稳定性。其它抗氧化剂或保存剂(preservative)例如维生素C或EDTA将增加稳定效果。饱和或不饱和的植物油或蜡通常用于在大量商品化的局部用混合物中。实例可以包括牛油树脂、芦荟素(aloe vera)、杏仁油、橄榄油、鳄梨油、椰子油、霍霍巴油(jojoba oil)燕麦油(avena sativa oil)和其它。多酚一般是亲水性的，因此在通常用于局部用制剂的大多数油或蜡中可溶性差。一些多酚在浓缩形式或纯化形式时是树脂状的。
因此，设计下列方法是重要的，通过该方法多酚可以均匀地分布在无水局部用混合物中，特别是合成或天然油类和蜡中，以提供确保多酚稳定性的适当产品，同时为商品化局部用产品提供适合的外观、构造和吸引力。通过使用吸附结合载体可以在整个无水局部用混合物中实现这种均匀分布，所述载体在将该局部用混合物施用至皮肤时不抑制多酚释放至皮肤的含水环境之上和之中的能力。
在本发明中，披露了大量的方法，通过这些方法将合适的结合载体和多酚一起添加至无水局部用混合物中，以获得在整个混合物中的所述分布。这些载体通常描述为化合物或复合有机化合物，其一般认为在皮肤上使用是安全的，而且还可以对皮肤有益，可能具有高的熔点，其可以或不可以吸入皮肤内，但对于吸入皮肤，当与皮肤的含水环境接触时释放吸附在载体上的药物或目标化合物。所述载体的实例包括但不限于滑石和粘土(例如绿坡缕石，埃洛石和高岭土)；藻酸盐，藻类，琼脂，树胶(gum)，明胶和纤维素；硅石，硅胶，二甲硅油(simethicone)，水杨酸盐，硅酸盐和硅树脂(例如聚甲基硅倍半氧烷)；西黄蓍胶；炭，碳酸钙；和氧化镁或氧化锌。
结合无水混合物、多酚和结合载体的重要方法为：首先粉碎多酚和结合载体直到均匀，为多酚吸附至结合载体提供机会。取决于多酚和结合载体的类型和浓度，该过程可能需要热。摩擦方法如研磨或碾磨还可有助于吸附至结合载体。然后可将多酚/载体添加至无水混合物，以获得均匀分布的局部用混合物。
该组合物和使用适当结合载体将多酚均匀分散在无水局部用混合物的方法对本领域的技术人员并不是显而易见的。至少一篇参考文献会通过涉使用甘油类混合物规避不均匀溶解和分布的问题，该甘油类混合物不是合成或天然油类和蜡，并且对于局部用制剂不具有商业价值(2)。本发明披露的所述结合载体当多酚在混合物中的浓度超过0.2％w/w时尤其有用，当多酚浓度介于1.0-20％w/w之间时，它们的用途是优选的。
实施例1：痤疮膏(acne cream)(使用水杨酸)
设计如下治疗痤疮的无水制剂，包括3％w/w纯化的绿茶提取物(包含至少70％的多酚)，其利用0.5％w/w的水杨酸作为适当的结合载体：
77.1％霍霍巴油
15.0％蜂蜡
2.0％卵磷脂
2.0％抗坏血酸棕榈酸酯(维生素C)
0.2％山梨酸
3.0％绿茶多酚提取物(70％多酚)
0.5％水杨酸
0.2％茶树油
需要在制剂过程中利用温和的热和碾磨首先粉碎多酚和结合载体直到均匀。然后在进一步混合和/或碾磨时将所述多酚/载体添加至无水混合物的余下部分，获得均匀分布的局部用混合物。
实施例2：护肤霜(使用硅胶)
设计如下治疗损伤皮肤的制剂，包括5％w/w纯化的绿茶提取物(包含至少70％的多酚)，其利用6％w/w的微粉化的硅胶作为适当的结合载体：
67.5％霍霍巴油
5.0％二甲基砜
12.0％蜂蜡
2.0％卵磷脂
6.0％硅胶(微粉化的)
5.0％绿茶多酚提取物(70％多酚)
0.2％山梨酸
2.0％抗坏血酸棕榈酸酯(维生素C)
0.2％熏衣草油
0.1％茶树油
需要在制剂过程中首先粉碎多酚和结合载体直到均匀。然后在进一步混合和/或碾磨时将所述多酚/载体添加至无水混合物的余下部分，获得均匀分布的局部用混合物。
实施例3：护肤霜(使用滑石)
设计如下治疗损伤皮肤的制剂，包括5％w/w纯化的绿茶提取物(包含至少70％的多酚)，其利用20％w/w的滑石作为适当的结合载体：
58.5％霍霍巴油
12.0％蜂蜡
2.0％卵磷脂
20.0％滑石
5.0％绿茶多酚提取物(70％多酚)
0.2％山梨酸
2.0％棕榈酸抗坏血酸酯(维生素C)
0.2％熏衣草油
0.1％茶树油
需要在制剂过程中首先粉碎多酚和结合载体直到均匀。然后在进一步混合和/或碾磨时将所述多酚/载体添加至无水混合物的余下部分，获得均匀分布的局部用混合物。
实施例4：护肤霜(使用高岭土粘土)
设计如下治疗损伤皮肤的制剂，包括5％w/w纯化的绿茶提取物(包含至少70％的多酚)，其利用6％w/w的微粉化的硅胶作为适当的结合载体：
74.5％霍霍巴油
6.0％蜂蜡
2.0％卵磷脂
10.0％高岭土陶瓷土
5.0％绿茶多酚提取物(70％多酚)
0.2％山梨酸
2.0％抗坏血酸棕榈酸酯(维生素C)
0.2％熏衣草油
0.1％茶树油
需要在制剂过程中首先粉碎多酚和结合载体直到均匀。然后在进一步混合和/或碾磨时将所述多酚/载体添加至无水混合物的余下部分，获得均匀分布的局部用混合物。
实施例5：疣霜(wart cream)(利用硅胶)
设计如下治疗疣的制剂，包括12％w/w纯化的绿茶提取物(包含至少70％的多酚)，其利用硅胶作为适当的结合载体：
62.7.0％牛油树脂
5.0％燕麦油
10.0％蜂蜡
8.0％硅胶(微粉化的)
12.0％绿茶多酚提取物(70％多酚)
2.0％抗坏血酸棕榈酸酯(vitamin C)
0.2％桉树油
0.1％茶树油
需要在制剂过程中首先粉碎多酚和结合载体直到均匀。然后在进一步混合和/或碾磨时将所述多酚/载体添加至无水混合物的余下部分，获得均匀分布的局部用混合物。
实施例6：唇膏(Lip Balm)(使用氧化锌)
设计如下治疗嘴唇的制剂，包括10％w/w纯化的绿茶提取物(包含至少70％的多酚)，其利用1％w/w氧化锌作为适当的结合载体：
10％绿茶多酚提取物(70％多酚)
0.5％尿囊素
0.2％夏枯草属提取物(prunella vulgaris extract)
0.3％香叶油(geranium oil)
0.1％茶树油
0.1％香柠檬油
1.0％氧化锌
0.1％维生素C
3i.u./gm维生素E
0.5％薄荷油香料
1％燕麦油
71.7％牛油树脂
15％蜂蜡
需要在制剂过程中首先粉碎多酚和结合载体直到均匀。然后在进一步混合和/或碾磨时将所述多酚/载体添加至无水混合物的余下部分，获得均匀分布的局部用混合物。
为了测试本发明制备的无水局部用制剂中多酚儿茶素的稳定性，选择使用滑石(实施例3)作为吸附结合载体的护肤霜制剂用于多酚的稳定性测试。当所述护肤霜在室温和35℃下存储5个月时使用标准色谱技术测量儿茶素的含量。结果如下所示。
表1：在室温和35℃下存储的护肤霜(滑石载体)中儿茶素的含量
室温
          没食子                                                          儿茶素 
日期             EGC    GC     EC     C      EGCg   GCg    ECg    Cg     
          酸                                                              总量
04Jan26   0.0    0.9    0.3    0.4    0.1    1.5    0.1    0.5    0.0     3.8
04Feb12   0.0    0.9    0.3    0.4    0.1    1.6    0.2    0.5    0.0     3.8
04Feb25   0.0    0.9    0.3    0.4    0.1    1.6    0.2    0.5    0.0     4.1
04Mar11   0.0    0.8    0.3    0.4    0.1    1.5    0.1    0.5    0.0     3.7
04Mar25   0.0    0.9    0.3    0.4    0.1    1.5    0.1    0.5    0.0     3.8
04Apr08   0.0    0.8    0.3    0.4    0.1    1.5    0.1    0.4    0.0     3.6
04apr23   0.0    0.8    0.3    0.4    0.1    1.5    0.2    0.5    0.0     3.7
04May20   0.0    0.8    0.3    0.4    0.1    1.5    0.2    0.5    0.0     3.8
35°温度
          没食子                                                儿茶素
日期            EGC   GC    EC    C     EGCg  GCg   ECg   Cg   
          酸                                                    总量
04Jan26   0.0   0.9   0.3   0.4   0.1   1.5   0.1   0.5   0.0   3.8
04Feb12   0.0   0.8   0.3   0.4   0.1   1.5   0.1   0.5   0.0   3.7
04Feb25   0.0   0.8   0.3   0.4   0.1   1.5   0.1   0.5   0.0   3.7
04Mar11   0.0   0.8   0.2   0.3   0.1   1.4   0.1   0.4   0.0   3.5
04Mar25   0.0   0.6   0.2   0.2   0.1   1.0   0.1   0.3   0.0   2.5
04Apr08   0.0   0.8   0.2   0.3   0.1   1.4   0.1   0.4   0.0   3.3
04Apr23   0.0   0.8   0.2   0.3   0.1   1.4   0.1   0.4   0.0   3.5
04May20   0.0   0.8   0.3   0.4   0.1   1.5   0.2   0.5   0.0   3.7
儿茶素(多酚)符号：
EGC：表没食子儿茶素
GC：没食子儿茶素
EC：表儿茶素
C：儿茶素
EGCg：表没食子儿荼素桔酸盐
GCg：没食子儿茶素桔酸盐
Ecg：表儿茶素桔酸盐
Cg：儿茶素桔酸盐
正如儿茶素含量随时间的关系所示(表1，图1)，护肤霜中的多酚浓度随测试时间不明显下降，即使在作为加速老化测试的较高温度下也是如此。该数据表明本发明所描述的制剂长时间持续稳定。
相反，在几种可商品购买的护肤霜制剂上进行的相同测试表明，当购买的测试产品通过常规出口时不能检测到儿茶素。这些护肤霜包括商品名为″Green Beaver′s Green tea″和″Jason′s Tea Time″的那些。这些护肤霜不含无水制剂或不使用适当的吸附结合载体。
尽管特别参考其提到的实施方案详细描述了本发明，但应认识到，本发明能够采用其它不同的实施方案，其细节在各种明显的方面能够修改。对于本领域的技术人员显而易见的是，在本发明的精神和范围内，可以进行变化和修改。因此，上述公开内容和描述仅仅用于说明，而不以任何方式限制本发明，本发明仅由权利要求书限定。

Claims (11)

1.无水局部用混合物，其包括无水混合物中的吸附结合载体和多酚，其中所述多酚吸附在所述结合载体上，并且所述混合物是通过包括以下步骤的方法配制的：粉碎吸附结合载体和多酚直到均匀，接着添加至混合物的余下部分。
2.混合物，其包括无水局部用霜、凝胶或膏，其中吸附在所述吸附结合载体上的多酚均匀地分布在霜、凝胶或膏内，并且其中在将霜、凝胶或膏施用至皮肤时所述多酚将释放在皮肤上或皮肤中，并且所述混合物是通过包括以下步骤的方法配制的：(a)粉碎吸附结合载体和多酚直到均匀；以及(b)接着添加至无水局部用霜、凝胶或膏基质中。
3.权利要求1或2的混合物，其中多酚包括衍生自茶属科的多酚。
4.权利要求1或2的混合物，其中多酚包括衍生自绿茶的多酚。
5.权利要求1或2的混合物，其中结合载体选自滑石，粘土，藻酸盐，藻类，琼脂，树胶，明胶，纤维素，硅石，硅胶，二甲硅油，水杨酸盐，硅酸盐，硅树脂，西黄蓍胶，碳酸钙，氧化镁和氧化锌。
6.权利要求5的混合物，其中结合载体为硅石或硅胶。
7.权利要求5的混合物，其中结合载体为水杨酸盐或硅酸盐。
8.权利要求5的混合物，其中结合载体为氧化镁或氧化锌。
9.权利要求2的混合物，其中无水局部用霜、凝胶或膏包括饱和或不饱和的植物油或蜡。
10.权利要求9的混合物，其中所述油或蜡为天然植物油或蜡。
11.权利要求10的混合物，其中所述天然植物油或蜡为牛油树脂，芦荟素，杏仁油，橄榄油，鳄梨油，椰子油，霍霍巴油和燕麦油。
CN200480027523XA 2003-09-23 2004-09-21 多酚的无水局部用制剂 Expired - Fee Related CN1856293B (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US50497203P 2003-09-23 2003-09-23
US60/504,972 2003-09-23
PCT/CA2004/001659 WO2005027867A1 (en) 2003-09-23 2004-09-21 Anhydrous topical formulation for polyphenols

Publications (2)

Publication Number Publication Date
CN1856293A CN1856293A (zh) 2006-11-01
CN1856293B true CN1856293B (zh) 2010-12-15

Family

ID=34375547

Family Applications (1)

Application Number Title Priority Date Filing Date
CN200480027523XA Expired - Fee Related CN1856293B (zh) 2003-09-23 2004-09-21 多酚的无水局部用制剂

Country Status (9)

Country Link
US (1) US20090017078A1 (zh)
EP (1) EP1663132A4 (zh)
JP (1) JP2007505838A (zh)
KR (1) KR20070029623A (zh)
CN (1) CN1856293B (zh)
AU (1) AU2004273552B2 (zh)
CA (1) CA2536609A1 (zh)
NZ (1) NZ545609A (zh)
WO (1) WO2005027867A1 (zh)

Families Citing this family (22)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8541438B2 (en) 2004-06-18 2013-09-24 3M Innovative Properties Company Substituted imidazoquinolines, imidazopyridines, and imidazonaphthyridines
JP2007308426A (ja) * 2006-05-19 2007-11-29 Ito En Ltd 口腔内腫瘍改善又は治療用軟膏剤
WO2008034703A1 (en) * 2006-09-20 2008-03-27 L'oreal Obtaining a controlled coloured effect from a vegetable extract
FR2905866B1 (fr) * 2006-09-20 2008-11-28 Oreal Procede de preparation d'un extrait vegetal stable
JP2008169120A (ja) * 2007-01-05 2008-07-24 Nippon Shikizai Inc 口唇用油性組成物
EP2082736A1 (fr) 2008-01-23 2009-07-29 Jean Hilaire Saurat Composition pharmaceutique à usage topique
US20090263518A1 (en) 2008-04-17 2009-10-22 Barry Callebaut Ag Composition and Uses Thereof
FR2951082B1 (fr) * 2009-10-12 2011-11-11 Coroebos Composition cosmetique de protection de la peau et/ou des cheveux avant immersion
CA2683258C (en) * 2009-10-20 2011-08-09 Asa Bullion Investment Limited Lotion for cleaning human anorectal area
CA2684258A1 (en) 2009-11-03 2011-05-03 Guy Chamberland Compositions comprising plant extracts and methods of treating wounds, burns and skin injuries therewith
FR2969496B1 (fr) * 2010-12-22 2013-11-08 Expanscience Lab Extrait de pulpe et/ou de peau d'avocat riche en polyphenols et compositions cosmetiques, dermatologiques et nutraceutiques le comprenant
US20120276030A1 (en) * 2011-04-29 2012-11-01 Garden Art Innovations, Llc Cosmetic composition
US9987218B2 (en) 2011-05-04 2018-06-05 Elc Management, Llc Mud mask with real leaf and method for making the same
US8784909B2 (en) 2011-05-04 2014-07-22 Glamglow, Inc. Mud mask with real tea leaf and method for making the same
JP5900978B2 (ja) * 2012-10-31 2016-04-06 公立大学法人福岡県立大学 皮膚創傷部治癒用組成物及び同皮膚創傷部治癒用組成物の製造方法
WO2014110096A1 (en) * 2013-01-11 2014-07-17 The Procter & Gamble Company Lotions comprising emollients of a renewable resource and an immobilizing agent
DE102013214843A1 (de) * 2013-07-30 2015-02-05 Henkel Ag & Co. Kgaa Wasserfreie Zusammensetzungen leichter Textur
CN103505394B (zh) * 2013-10-11 2016-06-22 金红叶纸业集团有限公司 含抗过敏组合物的纸
EP3651727B1 (en) * 2017-07-12 2021-10-13 Unilever IP Holdings B.V. Skin composition booster oil
CN111194219B (zh) * 2017-08-09 2023-09-15 保利益私人有限公司 包含甘蔗提取物的多酚在预防、改善或治疗皮肤问题的用途
US11638759B2 (en) * 2019-08-13 2023-05-02 Darlene E. McCord Non-activated, amorphous, pH neutral, two-part bedside-ready clay delivery system that treats pathogen infections in humans and animals
CN111514097B (zh) * 2020-05-14 2022-02-11 燕山大学 一种核桃壳多酚的pH响应型纳米水凝胶的制备方法

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5665367A (en) * 1996-09-27 1997-09-09 Chesebrough-Pond's Usa Co., Division Of Conopco, Inc. Skin care compositions containing naringenin and/or quercetin and a retinoid
US5703041A (en) * 1995-07-25 1997-12-30 L'oreal Stable composition containing a water-sensitive cosmetic and/or dermatological active agent
CN1178467A (zh) * 1995-03-14 1998-04-08 因迪纳有限公司 茶的多酚提取物、其用途和含有它们的制剂
CN1190888A (zh) * 1995-05-16 1998-08-19 阿奇发展公司 抑制5α－还原酶活性的方法和组合物
CA2353071A1 (en) * 1998-11-25 2000-06-02 Sembiosys Genetics Inc. Oil bodies as topical delivery vehicles for active agents
US6150422A (en) * 1996-03-12 2000-11-21 L'oreal Stable gelled composition containing lipophilic active agents sensitive to oxygen and/or water
WO2001013955A1 (en) * 1999-08-19 2001-03-01 Lavipharm S.A. Film forming polymers, methods of use, and devices and applications thereof
WO2003066016A1 (en) * 2002-02-08 2003-08-14 The Procter & Gamble Company Rinse-off skin conditioning compositions

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2738346A (en) * 1952-12-01 1956-03-13 Simon H Wender Method for the separation of flavonoid compounds
JPH0753658B2 (ja) * 1990-06-15 1995-06-07 昌市 桜下 粒状緑茶浴用剤の製造方法
JPH07255419A (ja) * 1994-03-17 1995-10-09 Nonogawa Shoji Kk （＋）カテキンを配合した健康食品および医薬品
US5948439A (en) * 1997-10-31 1999-09-07 Farmo-Nat Ltd. Effervescent granules
JP4201898B2 (ja) * 1998-10-21 2008-12-24 株式会社ロッテ 抗菌製剤
US6299925B1 (en) * 1999-06-29 2001-10-09 Xel Herbaceuticals, Inc. Effervescent green tea extract formulation
JP2002080358A (ja) * 2000-09-07 2002-03-19 Noevir Co Ltd 皮膚外用剤
JP2003183143A (ja) * 2001-12-18 2003-07-03 Nonogawa Shoji Kk 消臭粉末化粧料
US20040062779A1 (en) * 2002-09-26 2004-04-01 Jerry Whittemore Dermatologic composition using ultra-fine/micronized 1-ascorbic acid and other antioxidant ingredients in a stabilized anhydrous vehicle

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1178467A (zh) * 1995-03-14 1998-04-08 因迪纳有限公司 茶的多酚提取物、其用途和含有它们的制剂
CN1190888A (zh) * 1995-05-16 1998-08-19 阿奇发展公司 抑制5α－还原酶活性的方法和组合物
US5703041A (en) * 1995-07-25 1997-12-30 L'oreal Stable composition containing a water-sensitive cosmetic and/or dermatological active agent
US6150422A (en) * 1996-03-12 2000-11-21 L'oreal Stable gelled composition containing lipophilic active agents sensitive to oxygen and/or water
US5665367A (en) * 1996-09-27 1997-09-09 Chesebrough-Pond's Usa Co., Division Of Conopco, Inc. Skin care compositions containing naringenin and/or quercetin and a retinoid
CA2353071A1 (en) * 1998-11-25 2000-06-02 Sembiosys Genetics Inc. Oil bodies as topical delivery vehicles for active agents
WO2001013955A1 (en) * 1999-08-19 2001-03-01 Lavipharm S.A. Film forming polymers, methods of use, and devices and applications thereof
WO2003066016A1 (en) * 2002-02-08 2003-08-14 The Procter & Gamble Company Rinse-off skin conditioning compositions

Also Published As

Publication number Publication date
JP2007505838A (ja) 2007-03-15
KR20070029623A (ko) 2007-03-14
US20090017078A1 (en) 2009-01-15
EP1663132A4 (en) 2009-05-20
CN1856293A (zh) 2006-11-01
CA2536609A1 (en) 2005-03-31
WO2005027867A1 (en) 2005-03-31
AU2004273552A1 (en) 2005-03-31
AU2004273552B2 (en) 2010-12-16
NZ545609A (en) 2009-08-28
EP1663132A1 (en) 2006-06-07

Similar Documents

Publication Publication Date Title
CN1856293B (zh) 多酚的无水局部用制剂
Brown et al. Polyphenol composition and antioxidant potential of mint leaves
Singh et al. Comparative determination of phytochemicals and antioxidant activity from leaf and fruit of Sapindus mukorrossi Gaertn.–A valuable medicinal tree
Premanath et al. Studies on anti-oxidant activity of Tinospora cordifolia (Miers.) leaves using in vitro models
Rao et al. Evaluation of anti-oxidant activities and total phenolic content of Chromolaena odorata
Yin et al. Antioxidant and antidiabetic activities of extracts from Cirsium japonicum roots
Dureja et al. Free radical scavenging potential and total phenolic and flavonoid content of Ziziphus mauritiana and Ziziphus nummularia fruit extracts
Shahat et al. Antioxidant capacity and polyphenolic content of seven Saudi Arabian medicinal herbs traditionally used in Saudi Arabia
Srivastava et al. Correlation of antioxidant activity and phytochemical profile in native plants
Pattanayak et al. Total phenolic content, flavonoid content and in vitro antioxidant activities of Dendrophthoe falcata (Lf) Ettingsh
Lahlou et al. Antioxidant activity phenolics flavonoids and proanthocyanidins content of Senecio anteuphorbium
JP2017112935A (ja) 粉末青汁飲料
Meena et al. Acute toxicity and genotoxic activity of Hibiscus rosa-sinensis flower extract
TW201622738A (zh) 到手香萃取物於製備改善痤瘡之組成物之用途
Akbar et al. Antioxidant capacity of Piper longum and Piper nigrum fruits grown in Bangladesh
Krishnamoorthy et al. Quantification of phytochemicals and in vitro antioxidant potential of various solvent extracts of certain species of Acanthaceae
Peng et al. Antioxidant and nitrite-scavenging activities of Zanthoxylum bungeanum maxim. and Capsicum annuum L.: a synergistic, additive or antagonistic effect of the extracts?
Deshpande et al. In-vitro antioxidant activity of different fraction of roots of Cassia auriculata Linn.
Rahim et al. Synergistic effect of polyherbal formulations on DPPH radical scavenging activity
Khan et al. Comparative antioxidant scavenging and lipid peroxidation activity of rutin and gallic acid
Molehin et al. Antioxidant and inhibitory effects of aqueous and ethanolic extract of Tapinanthus bangwensis leaves on Fe 2+-induced lipid peroxidation in pancreas (in vitro).
Hossain et al. In vitro studies on antibacterial, thrombolytic and antioxidant activities of green tea or Camellia sinensis
Uysal et al. Studies on in vitro antioxidant activities of nine diff erent fruit tree leaves collected from Mediterranean region of Turkey
Dushing Yogesh et al. Antioxidant Assessment of Ashokarishta, A Fermented Polyherbal Ayurvedic formulation
Srivastava et al. Principal phenolic phytochemicals and antioxidant property in Eucalyptus bark

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
C10 Entry into substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant
C17 Cessation of patent right
CF01 Termination of patent right due to non-payment of annual fee

Granted publication date: 20101215

Termination date: 20110921