CN1494414A - 用于保护皮肤免受太阳辐射损伤的药物和化妆品组合物 - Google Patents
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Abstract
用于保护皮肤免受太阳辐射伤害的药物和化妆品组合物，该组合物含有来自植物的组分以及常规的滤光剂和赋形剂。
Description
本发明涉及用于保护皮肤免受太阳辐射损伤的药物和化妆品组合物，该组合物含有来自植物的组分以及常规的滤光剂(sun filter)和赋形剂。
更具体地说，本发明涉及用于保护皮肤免受太阳辐射损伤的药物和化妆品组合物，该组合物含有从水飞蓟(Silybum marianum)中提取的flavanolignane磷脂复合物；葡萄(Vitis vinifera)标准提取物中的磷脂复合物和从光果甘草(Glycyrrhiza glabra)中提取的三萜磷脂复合物以及常规的滤光剂和赋形剂。
制备高保护的特效的滤光剂的制剂是护肤用品研究领域的主要部分之一。这是因为公众对太阳辐射的有害作用的了解越来越多以及大气中臭氧层减少等问题而导致市场上对该类护肤用品的需求不断增长。
对于该领域的研究使得根据不同的需要制备了多种制剂，包括针对暴露于强阳光(例如在海中或在山上)下的制剂，日常使用(抗衰老)或有特殊用途的制剂，如因为职业原因而暴露于紫外线下使用的制剂或用于色素性疾病(白化病，白癜风)的制剂。
而且，最近人们对于由于缺少对阳光的保护所造成后果的分子机理的的知识也在增长。这使得可以制备出这样的制剂，这些制剂能够抵抗任何水平的可能由于未加保护的暴露于阳光下所造成后果。
众所周知，长时间暴露于阳光以及紫外线辐射下，可能导致皮肤疾病，甚至达到严重的程度。
现在已经认识到，太阳散射部分的紫外光谱非离子化电磁辐射是皮肤改变的主要原因。到达地球表面的紫外辐射是UV-A(320到400纳米)和UV-B(290到320纳米)。
此处紫外辐射所致的疾病一般指“光线性皮肤病(photodermatosis)”。
介导的(对阳光的中毒或过敏反应)和特发性(日光性荨麻疹、多态皮肤炎、光化性类网状细胞增多症)光线性皮肤病，以及那些易于受阳光照射而恶化的光线性皮肤病(糙皮病、红斑狼疮、红斑性天疱疮、着色性干皮病、皮肌炎)可能被认为是较少有的暴露于阳光的结果。相反，直接的光线性皮肤病更常见。
光线性皮肤病可能呈现为红斑/浮肿vesiculosum反应(急性损伤)，光老化和光致癌作用(慢性损伤)。
红斑
红斑是紫外辐射引起的最常见的皮肤反应，该反应呈剂量依赖型并且其程度可能从轻度、无症状的皮肤变红到严重的红斑，同时可能伴随着疼痛、浮肿和水泡的形成。红斑因周围毛细血管扩张引起，并且是直接和血管的相互作用以及光线作用于组织发色团(芳香氨基酸、含氮碱、不饱和脂肪酸等)而引起的光化学反应的结果。许多介质显然参与这些反应：前列腺素E和D系列、白介素，并且主要是自由基。后者是由于能量由发色团转移到分子氧中而被释放出来，并且是造成大多数暴露于阳光所致血管损伤的原因。
光老化
皮肤老化是一个复杂的生物过程，影响不同的皮肤层，包括真皮。暴露于大气中的那些皮肤区域的老化过程，除了由于所谓的先天的或内在的老化(即影响皮肤和内部器官的不可逆转的退化过程)之外，还由于内在的或光决定的老化，它主要与紫外线照射有关。
根据最近的调查表明，在暴露于大气中的区域中，所有损伤的80％都和暴露于阳光中有关。然而，从化妆品和药物的观点看，显然只能对第二种类型的老化采取措施。
上面提到的氧自由基的形成依次又促进氧化胁迫，该胁迫能导致组织结构如内皮膜、蛋白质、核酸和结缔纤维的损伤。其结果是：
-过度微循环通透性，这导致组织缺氧和浮肿；
-蛋白质变性，这对于结构蛋白和酶是特别危险的；
-脂肪过氧化作用，该作用导致细胞死亡；
-结缔硬化症。
紫外辐射所致的另外一个损伤是特定DNA片段的转录和翻译过程加快，该DNA片段编码某些对胶原蛋白具高效消化活性的金属蛋白。其速度比作用于结缔基质的修复过程的速度要快的多，从而导致皮肤的损伤和皱纹的出现。
光致癌作用
现在，流行病学和临床的证据表明，太阳辐射、特别是紫外线辐射和某些癌前病情(光化性角化病)的发病有关。这些病情可能演化成肿瘤病变，例如基底细胞上皮癌、刺细胞上皮癌和最危险的黑色素瘤。
迄今为止，有三种机制明显地参与紫外辐射导致的肿瘤形成：直接和含氮碱相互作用诱导的突变，自由基和DNA的相互作用，以及紫外介导的在免疫应答中对皮肤的关键细胞的免疫抑制，所述细胞为树突细胞，它们不能继续进行有效的免疫应答以抑制癌变。
总之，很显然，能够完全保护皮肤免受紫外介导的损伤的工具应该能滤除紫外辐射，并且能对抗氧化胁迫、结缔组织粘多糖纤维的消化、突变活动和紫外介导的免疫抑制。然而，现今市场上存在的制剂不能满足所有上述要求。
本发明符合上述要求，除了常规的滤光剂和赋形剂之外，本发明提供的药物和化妆品组合物还含有至少两种下面的来自植物的成分：
a)水飞蓟中提取的flavanolignane磷脂复合物 0.1-5％
b)葡萄标准提取物的磷脂复合物 0.1-5％
c)从光果甘草中提取的三萜磷脂复合物 0.1-5％
本发明的药物和化妆品组合物优选含有至少两种下面的来自植物的成分以及常规的滤光剂和赋形剂，其百分比如下：
a)水飞蓟中提取的flavanolignane磷脂复合物 0.5％
b)葡萄标准提取物的磷脂复合物 1.5％
c)从光果甘草中提取的三萜磷脂复合物 1.5％
从水飞蓟中提取的flavanolignane磷脂复合物(也叫做“组分a”)公开于EP 0.209.038中。
它们的特点是具有优良的抗氧化和抗炎作用。在用CCl4作为氧化前刺激物、肝脏微粒体作为目标进行的试验中，组分a)的LC50(毫克/毫升)为25.0，而维生素E(作为参照化合物)的LC50为30.0。对于抗炎活性而言，证实组分a)能够抑制75％的对实验动物爪接种巴豆油诱导的浮肿。在人中，对20个健康志愿者进行试验，相对于安慰剂，证实组分a)能够抑制25％的通过将皮肤暴露于紫外辐射所产生的红斑反应。
葡萄标准提取物中的磷脂复合物(也叫做“组分b”)公开于EP 0.275.224中。
体外分析表明，组分b)具有非常强的抗氧化活性。试验中，用Fe+++/ADP作为刺激物、脂质体制剂作为氧化的目标，证实组分b)比儿茶酸活力强35倍，比维生素E活力强50倍。还需要强调的是，这些复合物浓度即使低到10毫摩尔，也能够抑制95％的紫外辐射诱导的脂肪过氧化作用。
也已证实组分b)能够抑制发炎组织中的任一弹性蛋白酶、胶原酶和透明质酸酶，尽管是以非竞争性的方式，这个特点对于开发抗皮肤光老化的产品非常有用。
在最近的诱变分析中，显示组分b)具有优良的抗突变特性。对酿酒酵母(酵母菌，真核细胞)进行的自发突变试验表明，这些复合物能够逆转线粒体和核DNA突变，分别为60％和90％(0.5毫克/毫升)。
也对组分b)的抗免疫抑制特性进行了评估。将组分b)对裸鼠皮肤局部用药，并以安慰剂作为对照，发现组分b)能抑制紫外介导的皮肤免疫抑制约50％。在人中，对18名健康志愿者进行的试验表明能抑制30％的将皮肤暴露于紫外辐射所致的红斑反应。
从光果甘草中提取的三萜磷脂复合物(也叫做“组分c”)公开于EP0.283.713中。
局部给药时，它们具有很强的抗炎作用，通过抑制组织11-β羟基类固醇脱氢酶而抑制皮质醇从活性形态转化成失活形态，从而延长炎症刺激后所释放的皮质醇的抗炎作用。证实复合物c)能够抑制95％的对实验动物爪接种巴豆油诱导的浮肿，显示比通常的非-甾类抗炎药(该情况下为吲哚美辛)更加有效。
也对组分a)，b)和c)进行了毒理学试验。将在大鼠中进行的急性毒性试验总结于下表。
组分 口服LD50 腹膜内LD50
毫克/千克 毫克/千克
a) ＞3.000 ＞2.000
b) ＞5.000 ＞2.221
c) ＞2.000 ＞4.432
此外，对家兔进行的眼的急性和慢性皮肤刺激试验证明，组分a)，b)和c)没有刺激作用。
对健康志愿者进行的皮肤试验中既没有观察到过敏也没有观察到不耐性症状。
将本发明的组合物进行局部给药，所述组合物为适当的制剂形式，既可以是液态(比如胶凝剂、洗剂、乳状物、乳剂、泡沫剂等等)，也可以是固态或半固态(比如乳膏剂、膏剂、唇膏等等)。可以根据传统方法制备上述制剂，比如根据“Remington’s Pharmaceutical Handbook”，MackPublishing Co，NY，USA中所描述的方法，同时加入合适的赋形剂，比如润肤剂、润湿剂、增稠剂、乳化剂、染料、矫味剂等等。
Claims (3)
1.保护皮肤免受太阳辐射伤害的药物和化妆品组合物，该组合物含有至少两种下面的来自植物的组分以及常规的滤光剂和赋形剂：
a)水飞蓟中提取的flavanolignane磷脂复合物 0.1-5％
b)葡萄标准提取物中的磷脂复合物 0.1-5％
c)从光果甘草中提取的三萜磷脂复合物 0.1-5％。
2.权利要求1中的药物和化妆品组合物，该组合物含有至少两种下面的来自植物的组分以及常规的滤光剂和赋形剂：
a)水飞蓟中提取的flavanolignane磷脂复合物 0.5％
b)葡萄标准提取物中的磷脂复合物 1.5％
c)从光果甘草中提取的三萜磷脂复合物 1.5％。
3.至少两种下面的组分在制备用于保护皮肤免受阳光辐射所致损伤的药物和化妆品组合物中的用途：
a)从水飞蓟中提取的flavanolignane磷脂复合物；
b)葡萄多酚成分的磷脂复合物；
c)光果甘草中提取的三萜磷脂复合物。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IT2001MI000429A ITMI20010429A1 (it) | 2001-03-02 | 2001-03-02 | Composizioni farmaceutiche e cosmetiche per la protezione della pelledai danni indotti dalle radiazioni solari |
| ITMI2001A000429 | 2001-03-02 |
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| CN1494414A true CN1494414A (zh) | 2004-05-05 |
| CN1248677C CN1248677C (zh) | 2006-04-05 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ITMI20010429A1 (it) * | 2001-03-02 | 2002-09-02 | Indena Spa | Composizioni farmaceutiche e cosmetiche per la protezione della pelledai danni indotti dalle radiazioni solari |
| ES2325291B1 (es) * | 2007-10-04 | 2010-04-22 | Madaus S A | "uso de un extracto de silybum marianum" |
| FR2986154B1 (fr) * | 2012-01-31 | 2017-08-04 | Pierre Fabre Dermo-Cosmetique | Nouveau systeme photoprotecteur |
| US8877259B2 (en) | 2012-02-09 | 2014-11-04 | Mary Kay Inc. | Cosmetic formulation |
| US9056063B2 (en) | 2012-03-13 | 2015-06-16 | James E. Hanson | Natural sunscreen composition |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US764508A (en) * | 1904-03-25 | 1904-07-05 | Thomas Harrison Symington | Dust-guard for journal-boxes. |
| IT1215291B (it) * | 1985-07-17 | 1990-01-31 | Inverni Della Beffa Spa | Complessi di flavanolignani con fosfolipidi, loro preparazione e relative composizioni farmaceutiche. |
| IT1201151B (it) * | 1987-01-14 | 1989-01-27 | Indena Spa | Complessi fosfolipidici con estratti da vitis vinifera,procedimento per la loro preparazione e composizioni che li cntengono |
| IT1203515B (it) * | 1987-02-26 | 1989-02-15 | Indena Spa | Complessi di saponine con fosfolipidi e composizioni farmaceutiche e cosmetiche che li contengono |
| IT1253431B (it) * | 1991-12-02 | 1995-08-08 | Valetudo S R L | Preparati farmaceutici per uso topico destinati al trattamento della psoriasi e della dermatite atopica |
| IT1288257B1 (it) * | 1996-11-29 | 1998-09-11 | Paoli Ambrosi Gianfranco De | Composizione per uso cosmetico,farmaceutico o dietetico a base di un aminozucchero e/o di un acido poliidrossilico |
| JP3763075B2 (ja) * | 1998-04-24 | 2006-04-05 | サンスター株式会社 | 歯周病の予防又は治療用の食品組成物、口腔用組成物及び医薬組成物 |
| WO2000064472A1 (en) * | 1999-04-22 | 2000-11-02 | Howard Murad | Methods and compositions for treating dermatological disorders with fruit extracts |
| ITMI20010429A1 (it) * | 2001-03-02 | 2002-09-02 | Indena Spa | Composizioni farmaceutiche e cosmetiche per la protezione della pelledai danni indotti dalle radiazioni solari |
-
2001
- 2001-03-02 IT IT2001MI000429A patent/ITMI20010429A1/it unknown
-
2002
- 2002-02-26 EP EP02703604A patent/EP1363588B1/en not_active Expired - Lifetime
- 2002-02-26 WO PCT/EP2002/002027 patent/WO2002072051A2/en active IP Right Grant
- 2002-02-26 PL PL363649A patent/PL204103B1/pl unknown
- 2002-02-26 SI SI200230247T patent/SI1363588T1/sl unknown
- 2002-02-26 KR KR1020037010928A patent/KR100894581B1/ko active IP Right Grant
- 2002-02-26 AU AU2002237310A patent/AU2002237310B2/en not_active Ceased
- 2002-02-26 ES ES02703604T patent/ES2254647T3/es not_active Expired - Lifetime
- 2002-02-26 SK SK1088-2003A patent/SK285876B6/sk not_active IP Right Cessation
- 2002-02-26 CZ CZ20032336A patent/CZ299436B6/cs not_active IP Right Cessation
- 2002-02-26 IL IL15763002A patent/IL157630A0/xx active IP Right Grant
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- 2002-02-26 CN CNB028057481A patent/CN1248677C/zh not_active Expired - Fee Related
- 2002-02-26 DK DK02703604T patent/DK1363588T3/da active
- 2002-02-26 HU HU0303375A patent/HU230038B1/hu not_active IP Right Cessation
- 2002-02-26 JP JP2002571010A patent/JP4351447B2/ja not_active Expired - Fee Related
- 2002-02-26 US US10/469,300 patent/US7374748B2/en not_active Expired - Lifetime
- 2002-02-26 AT AT02703604T patent/ATE314050T1/de active
- 2002-02-26 CA CA2439685A patent/CA2439685C/en not_active Expired - Lifetime
- 2002-02-26 RU RU2003126481/15A patent/RU2284191C2/ru not_active IP Right Cessation
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2003
- 2003-08-28 IL IL157630A patent/IL157630A/en unknown
- 2003-08-29 NO NO20033847A patent/NO333511B1/no not_active IP Right Cessation
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2004
- 2004-06-03 HK HK04103980A patent/HK1060975A1/xx not_active IP Right Cessation
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