CN116997348A - 使用包含冰岛苔提取物的组合物的方法 - Google Patents
使用包含冰岛苔提取物的组合物的方法 Download PDFInfo
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- CN116997348A CN116997348A CN202280022331.8A CN202280022331A CN116997348A CN 116997348 A CN116997348 A CN 116997348A CN 202280022331 A CN202280022331 A CN 202280022331A CN 116997348 A CN116997348 A CN 116997348A
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Abstract
本发明提供了减轻疼痛或瘙痒的方法,该方法包括向有需要的患者施用治疗有效剂量的包含非极性冰岛苔提取物的组合物。
Description
技术领域
本发明涉及用于减轻疼痛和/或瘙痒的组合物。更具体地,本发明涉及用于局部或内部减轻疼痛和/或瘙痒的包含冰岛苔的提取物的组合物。
背景技术
适用于个人护理组合物的多种天然活性物质是已知的。此类活性物质的示例包括橄榄叶提取物,其被描述为表现出抗高血压和降血糖活性、针对食物和化妆品的抗自由基性质,以及当通过口服途径给予时的抗炎活性(参见例如,Leaf extract of Olea europearich in oleuropeine,products from it,their application as medicines andcompositions containing them.Combes,Georges;Escaut,Alexandre.Fr.Demande,FR2507477 A1 19821217,1982;Gonzalez M等人,橄榄叶的降血糖活性,Planta Med 1992年12月;58(6):513-515;Use of an extract from the leaves of Olea Europea as anantiradical agent.Amari,Giorgio.Eur.专利申请(1999),EP 937455A1 19990825;FehriB等人,Olea europaea L.:stimulant,anti-ulcer and anti-inflammatoryeffects.Boll Chim Farm(1996)135(1):42-49);豨莶属(Sigesbeckia)(圣草(HolyHerb)),其已被用作疟疾、风湿病、肾绞痛的治疗剂,并且与甘油结合用作癣的治疗剂;苏方木(Lignum Sappan)(苏木),其已被用于促进活血化瘀,并使得消肿止痛;以及小白菊(Feverfew),其在口服时被认为具有显著的药用性质并用作一般退热剂。其他护肤活性物质包括油提取物,诸如描述为表现出抗肿瘤和抗关节炎性质的齿叶乳香(BoswelliaSerrata)油提取物(乳香),以及描述为表现出抗刺激和抗氧化性质的燕麦油提取物。
尽管对源自天然来源的活性物质的需求日益增长,但通常难以(如果不是不可能的话)预测哪些活性物质具有诸如减轻疼痛和/或瘙痒的有益特性。因此,目前需要鉴定用于个人护理产品的新活性物质,诸如用于皮肤、眼睛和疼痛缓解。
发明内容
本发明的一个方面涉及减轻疼痛或瘙痒的方法,该方法包括向有需要的患者施用治疗有效剂量的包含非极性冰岛苔提取物的组合物。本发明的另一个方面涉及包含治疗有效剂量的非极性冰岛苔提取物的组合物,其用于减轻有需要的患者的疼痛或瘙痒。本发明的另一个方面涉及治疗有效剂量的包含非极性冰岛苔提取物的组合物用于减轻有需要的患者的疼痛或瘙痒的用途。本发明的另一个方面涉及治疗有效剂量的非极性冰岛苔提取物用于制备根据前述权利要求中任一项所述的组合物以减轻有需要的患者的疼痛或瘙痒的用途。
在一个或多个实施方案中,非极性提取物用选自由以下组成的组的一种或多种溶剂提取:C1-C8烷烃、C1-C8环烷烃、C1-C8烷基醚、石油醚、C1-C8酮、二氯甲烷、乙酸乙酯、二甲苯、甲苯、氯仿、植物油、矿物油以及它们的组合。在一些实施方案中,非极性提取物用二氯甲烷提取。在一个或多个实施方案中,疼痛是TRPA1受体介导的疼痛和/或瘙痒。在一些实施方案中,疼痛是TrKA受体介导的疼痛和/或瘙痒。在一个或多个实施方案中,组合物被施涂于患者的皮肤表面。在一些实施方案中,疼痛或瘙痒与消化健康、眼部瘙痒、骨关节炎、变态反应或特应性皮炎相关。在一个或多个实施方案中,组合物还包含选自由以下组成的组的皮肤病学可接受的载体:表面活性剂、螯合剂、润肤剂、保湿剂、调理剂、防腐剂、遮光剂、芳香剂以及它们中的两种或更多种的组合。在一些实施方案中,组合物以溶液、悬浮液、洗剂、乳膏、浆液、凝胶、棒、喷雾、软膏、液体洗液、皂条、洗发剂、护发素、糊剂、泡沫、粉末、摩丝、剃须膏、水凝胶或成膜产品的形式施用。在一个或多个实施方案中,组合物经肠施用。在一些实施方案中,组合物以片剂、丸剂、胶囊、囊片、胶囊锭、锭剂、颗粒、粉末、无菌肠胃外溶液或悬浮液、计量气雾剂或液体喷雾剂、滴剂、安瓿、自动注射器装置或栓剂的形式施用。在一个或多个实施方案中,将组合物施用于眼睛。在一些实施方案中,组合物以滴眼剂溶液、眼部清洗溶液、接触镜片润滑和/或再润湿溶液、喷雾或薄雾的形式施用。在一个或多个实施方案中,非极性提取物以按总组合物的重量计约0.00001重量%至约2重量%的浓度存在于组合物中。在一些实施方案中,非极性提取物以按总组合物的重量计约0.001重量%至约0.005重量%的浓度存在于组合物中。对于本文所述的任何方面,此类实施方案可以任何组合方式结合。
本发明的另一个方面涉及减轻疼痛或瘙痒的方法,该方法包括向有需要的患者施用治疗有效剂量的包含非极性冰岛苔提取物的组合物,其中该非极性提取物用二氯甲烷提取。本发明的另一个方面涉及治疗有效剂量的包含非极性冰岛苔提取物的组合物用于减轻有需要的患者的疼痛或瘙痒的用途,其中该非极性提取物用二氯甲烷提取,用于减轻疼痛或瘙痒。
在一个或多个实施方案中,疼痛是TRPA1受体介导的疼痛和/或瘙痒。在一些实施方案中,疼痛是TrKA受体介导的疼痛和/或瘙痒。在一个或多个实施方案中,组合物被施涂于患者的皮肤表面。在一些实施方案中,疼痛或瘙痒与消化健康、眼部瘙痒、骨关节炎、变态反应或特应性皮炎相关。在一个或多个实施方案中,组合物还包含选自由以下组成的组的皮肤病学可接受的载体:表面活性剂、螯合剂、润肤剂、保湿剂、调理剂、防腐剂、遮光剂、芳香剂以及它们中的两种或更多种的组合。在一些实施方案中,组合物以溶液、悬浮液、洗剂、乳膏、浆液、凝胶、棒、喷雾、软膏、液体洗液、皂条、洗发剂、护发素、糊剂、泡沫、粉末、摩丝、剃须膏、水凝胶或成膜产品的形式施用。在一个或多个实施方案中,组合物经肠施用。在一些实施方案中,组合物以片剂、丸剂、胶囊、囊片、胶囊锭、锭剂、颗粒、粉末、无菌肠胃外溶液或悬浮液、计量气雾剂或液体喷雾剂、滴剂、安瓿、自动注射器装置或栓剂的形式施用。在一个或多个实施方案中,将组合物施用于眼睛。在一些实施方案中,组合物以滴眼剂溶液、眼部清洗溶液、接触镜片润滑和/或再润湿溶液、喷雾或薄雾的形式施用。对于本文所述的任何方面,此类实施方案可以任何组合方式结合。
通过下文对本发明的详细描述,本发明的这些和其他特征和优点将变得显而易见。
具体实施方式
如本文所用,“皮肤病学可接受的”“眼科上可接受的”“药学上可接受的”意指适合与组织(例如,皮肤或毛发)接触使用,而没有异常毒性、不相容性、不稳定性、刺激性和/或变应性应答等等。
如本文所用,术语“安全有效量”意指足以引起所需效果但低至足以避免严重副作用的量。化合物、提取物或组合物的安全且有效量将随着例如最终使用者的年龄、健康和环境暴露状况,治疗的持续时间和性质,采用的特定提取物、成分或组合物,以及所用的具体药学上可接受的载体等因素而变化。
如本文所用,“实质上不含”或“基本上不含”成分意指含有小于0.1重量%或小于0.01重量%的成分或不含成分。
为了提供更简明的描述,本文给出的一些数量表述没有用术语“约”修饰。应当理解,无论是否明确地使用了术语“约”,本文所给出的每个量都意在指代实际的给定值,并且还意在指代由本领域的普通技术人员可合理推测出的这些给定值的近似值,包括这些给定值的由实验和/或测量条件所引起的近似值。
为了提供更简洁的描述,本文中一些定量表述被叙述为约X量至约Y量的范围。应当理解,当叙述范围时,所述范围并不限制于所叙述的上下界限,而应包括约X量至约Y量的整个范围或者其中的任何量或范围。
因此,本发明的一个方面涉及一种减轻疼痛和/或瘙痒的方法,该方法包括向有需要的患者施用治疗有效剂量的包含非极性冰岛苔提取物的组合物。本发明的另一个方面涉及非极性冰岛苔提取物用于减轻疼痛和/或瘙痒的用途。令人惊奇地发现,此类包含非极性冰岛苔提取物的组合物提供了意想不到的良好的抗疼痛和/或抗瘙痒特性。疼痛或瘙痒可与多种病症相关,包括但不限于皮肤、眼睛、消化系统、肌肉骨格系统和变态反应的疾病。
在一个或多个实施方案中,疼痛和/或瘙痒可以是TRPA1受体介导的疼痛和/或瘙痒。TRPA1(也称为“瞬时受体电位锚蛋白1”和“瞬时受体电位阳离子通道,亚家族A,成员1”)是位于许多人和动物细胞的质膜上的离子通道,并且是疼痛、感冒和瘙痒的传感器。
在一个或多个实施方案中,疼痛和/或瘙痒可以是TrKA受体介导的疼痛和/或瘙痒。TrKA是神经生长因子(NGF)的受体。TrKA负责神经元分化和生长以及避免神经细胞的细胞程序性死亡。在体内,初级传入神经纤维在背根神经节(DRG)中具有其细胞体,并且将感觉信息从外周、器官传递至脊髓,最终传递至大脑。约40%的DRG细胞是TrKA阳性的,并且支配皮肤、内脏、肌肉和骨骼。NGF/TrKA途径的抑制是急性和慢性疼痛/瘙痒的有效靶标。
冰岛苔提取物
冰岛苔(学名冰岛地衣)是在冰岛、北欧和北美洲生长的地衣。如本文所用,“冰岛苔提取物”是指整个地衣的提取物。
可以使用制备根据本发明的用于使用的提取物的任何合适的方式。合适的提取物可使用常规方法获得,这些方法包括但不限于通过碾磨、浸软、压榨、挤压、捣碎、离心和/或过程诸如冷渗滤、搅拌/蒸馏、微波辅助提取、超声处理、具有或不具有极性改性剂的超临界/亚临界CO2压缩气体提取、加压溶剂提取、加速溶剂提取、表面活性剂辅助加压热水提取、油提取、膜提取、索氏提取、金手指蒸馏/提取和/或公开于例如授予IntegratedBotanical Technologies,LLC的美国专利7442391、7473435和7537791(均以引用的方式并入本文)中的过程等,或通过其他方法诸如溶剂提取等从生物质中直接提取。具体地,根据本发明的提取物可以是通过在溶剂中研磨或浸渍地衣材料而制备的溶剂基提取物,该溶剂通常是有机溶剂,诸如二氯甲烷、醇、丙酮、具有或不具有极性调节剂的液态二氧化碳、己烷或氯仿。所得提取物主要包含有机和/或非极性化合物。地衣生物质可以与提取物完全分离,并且在提取后不使用。
产生非极性提取物的合适溶剂包括溶剂,诸如烷烃(包括C1-C8烷烃)、环烷烃(包括C1-C8烷烃)、烷基醚(包括C1-C8烷基醚)、石油醚、酮(包括C1-C8酮)、亚甲基氯(二氯甲烷)、乙酸乙酯、二甲苯、甲苯、氯仿、植物油、矿物油等。在一些实施方案中,非极性提取物通过使用上述溶剂或超临界流体萃取在有或没有极性改性剂诸如C1-C8醇、水、C1-C8多元醇/二醇或C1-C8有机酸的情况下获得。在一些实施方案中,组合物可包含来自冰岛苔的细胞培养物的提取物。在一些实施方案中,非极性冰岛苔提取物用二氯甲烷提取。在一些实施方案中,冰岛苔提取物基本上不含极性提取物,包括使用水、C1-C8醇、C1-C8多元醇、C1-C8二醇以及它们的组合提取的那些。
任何合适量的非极性冰岛苔提取物均可以用于本发明的组合物中。在一个或多个实施方案中,组合物包含安全有效量的非极性冰岛苔提取物。在一个或多个实施方案中,组合物包含约0.00001重量%、0.00005重量%、0.0001重量%、0.0005重量%、0.001重量%、0.002重量%、0.003重量%或0.004重量%至约0.005重量%、0.006重量%、0.007重量%、0.008重量%、0.009重量%、0.01重量%、0.02重量%、0.03重量%、0.04重量%、0.05重量%、0.06重量%、0.07重量%、0.08重量%、0.09重量%、0.1重量%、0.2重量%、0.3重量%、0.4重量%、0.5重量%、0.6重量%、0.7重量%、0.8重量%、0.9重量%、1重量%、1.1重量%、1.2重量%、1.3重量%、1.4重量%、1.5重量%、1.6重量%、1.7重量%、1.8重量%、1.9重量%或2重量%的非极性冰岛苔提取物。在一些实施方案中,非极性冰岛苔提取物以按总组合物的重量计约0.00001重量%至约2重量%的浓度存在于组合物中。在一些实施方案中,非极性冰岛苔提取物以按总组合物的重量计约0.0001重量%至约1.5重量%的浓度存在于组合物中。在一些实施方案中,非极性冰岛苔提取物以按总组合物的重量计约0.0005重量%至约1重量%的浓度存在于组合物中。在一些实施方案中,非极性冰岛苔提取物以按总组合物的重量计约0.0005重量%至约0.01重量%的浓度存在于组合物中。在一些实施方案中,非极性冰岛苔提取物以按总组合物的重量计约0.001重量%至约0.005重量%的浓度存在于组合物中。
皮肤病学用途
非极性冰岛苔提取物可用于皮肤上的疼痛和/或瘙痒。在一些实施方案中,组合物被施涂于患者的皮肤表面。可以治疗的相关皮肤病症包括但不限于炎性皮肤病、接触性皮炎、变应性皮炎、特应性皮炎、多形性光疹、刺激(包括由外在因素引起的疼痛/瘙痒)、痤疮炎症、牛皮癣、脂溢性皮炎、湿疹、毒藤疹、毒栎、毒漆树、昆虫咬伤、毛囊炎、脱发和继发性病况等。
任何合适的载体均可以根据上下文的要求用于组合物中。在一些实施方案中,载体是皮肤病学可接受的载体。如本领域的技术人员将认识到,皮肤病学可接受的载体包括适于与身体,具体地皮肤接触使用的载体,而没有不适当的毒性、不相容性、不稳定性、刺激性、变应性应答等等。皮肤病学载体的安全有效量为按组合物的重量计约50%、55%、60%、65%、70%、75%、80%、85%、90%、95%或98%至约85%、90%、95%、98%、99%、99.1、99.5%或99.9%。
皮肤病学可接受的载体可以多种形式存在。例如,包括但不限于水包油、油包水、水包油包水和硅氧烷包水包油乳液的乳液形式的皮肤病学载体均可用于本文。这些乳液可以覆盖宽范围的粘度,例如使用Brookfield RVT粘度计从约100cps至约200,000cps的粘度。
合适的皮肤病学可接受的载体的示例包括皮肤病学可接受的适于皮肤病学溶液、悬浮液、洗剂、霜膏、精华素、精华液、凝胶、调色剂、棒状物、喷剂、油膏剂、洗液和皂条、洗发剂、毛发调理剂、糊剂、泡沫、摩丝、粉末、剃须膏、擦拭物、贴片、带、强力贴片、微针贴片、绷带、水凝胶、成膜产品、面膜和皮肤贴膜、粉底、液滴等的溶剂和材料。这些产品类型可包含若干类型的皮肤病学可接受的载体,包括但不限于溶液、悬浮液、乳液诸如微乳液和纳米乳液、凝胶、固体、脂质体、其他包封技术等等。
下面是皮肤病学可接受的载体的非限制性示例。其他皮肤病学可接受的载体可由本领域的普通技术人员进行配制。在一个实施方案中,皮肤病学可接受的载体包含水。在另一个实施方案中,皮肤病学可接受的载体还可包含一种或多种水性溶剂或有机溶剂。有机溶剂的示例包括但不限于:二甲基异山梨醇;肉豆蔻酸异丙酯;阳离子、阴离子和非离子性质的表面活性剂;植物油;矿物油;蜡;树胶;合成和天然的胶凝剂;链烷醇;二醇;和多元醇。二元醇的示例包括但不限于甘油、丙二醇、丁二醇、戊二醇、己二醇、聚乙二醇、聚丙二醇、二甘醇、三甘醇、辛二醇、甘油、丁二醇和己三醇以及它们的共聚物或混合物。链烷醇的示例包括但不限于具有约2个碳原子至约12个碳原子(例如,约2个碳原子至约4个碳原子)的链烷醇,诸如异丙醇和乙醇。多元醇的示例包括但不限于具有约2个碳原子至约15个碳原子(例如,约2个碳原子至约10个碳原子)的多元醇,诸如丙二醇。基于皮肤病学可接受的载体的总重量计,有机溶剂可以约1%至约99.99%(例如,约20%至约50%)的量存在于皮肤病学可接受的载体中。基于皮肤病学可接受的载体的总重量计,水可以约5%至约95%(例如,约50%至约90%)的量存在于皮肤病学可接受的载体中(使用前)。溶液可包含任何合适量的溶剂,包括约40%至约99.99%。一些溶液含有约50至约99.9%、约60至约99%、约70至约99%、约80至约99%、或约90至99%的溶剂。
可由此类溶液制备洗剂。除了溶剂之外,洗剂通常包含至少一种润肤剂。洗剂可包含约1%至约20%(例如,约5%至约10%)的润肤剂和约50%至约90%(例如,约60%至约80%)的水。
可由溶液配制的另一类产品为霜膏。霜膏通常包含约5%至约50%(例如,约10%至约20%)的润肤剂和约45%至约85%(例如,约50%至约75%)的水。
还可由溶液配制的另一类产品是膏剂。膏剂可含有动物油、植物油或合成油或半固态10烃的简单基料。油膏剂可含有约2%至约10%的润肤剂和约0.1%至约2%的增稠剂。
可用于本发明的组合物还可作为乳液配制。如果皮肤病学可接受的载体是乳液,则约1%至约10%(例如,约2%至约5%)的皮肤病学可接受的载体包含乳化剂。乳化剂可为非离子的、阴离子的或阳离子的。
洗剂和霜膏可被配制为乳液。通常此类洗剂包含0.5%至约5%的乳化剂,而此类霜膏通常将包含约1%至约20%(例如,约5%至约10%)的润肤剂;约20%至约80%(例如30%至约70%)的水;以及约1%至约10%(例如,约2%至约5%)的乳化剂。
水包油型和油包水型单相乳液护肤制剂(诸如洗剂和霜膏)是本领域众所周知的并且可用于本主题发明。多相乳液组合物,诸如水包油包水型或油包水包油型,也可用于本主题发明。一般来讲,此类单乳液或多相乳液含有水、润肤剂和乳化剂作为主要成分。
本发明的组合物也可被配制为凝胶(例如,水性凝胶、醇凝胶、醇/水凝胶或油凝胶,使用合适的胶凝剂进行的)。用于水性凝胶和/或醇凝胶的合适胶凝剂包括但不限于天然树胶、丙烯酸和丙烯酸酯聚合物和共聚物以及纤维素衍生物(例如羟甲基纤维素和羟丙基纤维素)。适用于油(诸如矿物油)的胶凝剂包括但不限于氢化丁烯/乙烯/苯乙烯共聚物和氢化乙烯/丙烯/苯乙烯共聚物。此类凝胶通常包含约0.1重量%至5重量%的此类胶凝剂。
本发明的组合物还可配制成固体制剂(例如,蜡基棒剂、皂条组合物、粉剂或擦拭物)。本发明的组合物还可与固体、半固体或可溶解的基材(如,擦拭物、面膜、垫、手套或带)结合。
其他皮肤病学可接受的添加剂
本发明的组合物还可包含多种另外的皮肤病学可接受的活性剂中的任一种。合适的附加的可接受的皮肤病学活性剂的示例包括:亮肤剂、深色剂、另外的抗老化剂、弹性蛋白原促进剂、胶原促进剂、抗痤疮剂、控油光剂、抗微生物剂(诸如抗酵母剂、抗真菌剂和抗细菌剂)、抗炎剂、抗寄生虫剂、外用止痛剂、防晒剂、光照保护剂、抗氧化剂、角质层分离剂、洗涤剂/表面活性剂、保湿剂、营养物质、维生素、能量增强剂、止汗剂、收敛剂、除臭剂、脱毛剂、毛发生长增强剂、毛发生长延缓剂、固化剂、补水剂、增效剂、抗硬结剂、皮肤调理剂、抗蜂窝炎剂、气味控制剂诸如气味遮盖剂或pH调节剂等。
各种合适的另外的皮肤病学可接受的活性物质的示例包括羟基酸;过氧化苯甲酰;D-泛醇;UV滤光剂诸如但不限于阿伏苯宗(Parsol 1789)、苯基二苯并咪唑四磺酸酯二钠(Neo Heliopan AP)、二乙氨基羟基苯甲酰基苯甲酸己酯(Uvinul A Plus)、依莰舒(Mexoryl SX)、氨茴酸甲酯、4-氨基苯甲酸(PABA)、西诺沙酯、乙基己基三嗪酮(Uvinul T150)、胡莫柳酯、4-甲基亚苄基樟脑(Parsol 5000)、甲氧基肉桂酸辛酯(Octinoxate)、水杨酸辛酯(Octisalate)、帕地马酯O(Escalol 507)、苯基苯并咪唑磺酸(Ensulizole)、聚硅氧烷-15(Parsol SLX)、水杨酸三乙醇胺、双-乙基己氧苯酚甲氧苯基三嗪(Tinosorb S)、二苯酮1-12、二羟苯宗、甲酚曲唑三烷氧烷(Mexoryl XL)、二乙基己基丁酰胺基三嗪酮(UvasorbHEB)、奥克立林、氧苯酮(Eusolex4360)、舒利苯酮、亚甲基二苯并三唑四甲基丁酚(Tinosorb M)、二氧化钛、氧化锌;类胡萝卜素;自由基清除剂;自旋捕捉剂;类视黄醇和类维生素A前体,如视黄醇/视黄酸和棕榈酸视黄酯;神经酰胺;多不饱和脂肪酸;必需脂肪酸;酶;酶抑制剂;矿物质;激素,诸如雌激素;类固醇,诸如氢化可的松;2-二甲氨基乙醇;铜盐如氯化铜;含有铜的肽,诸如Cu:Gly-His-Lys、辅酶Q10;氨基酸,诸如脯氨酸;维生素;乳糖酸;乙酰辅酶A;烟酸;核黄素;硫胺;核糖;电子转运蛋白,诸如NADH和FADH2;以及其他植物提取物,诸如燕麦、芦荟、龙牙草、大豆、香菇提取物,以及它们的衍生物和混合物。
如果存在,任何附加的皮肤病学可接受的活性剂可以任何合适的量存在于组合物中,例如按组合物的重量计,以约0.0001%至约20%,例如约0.001%至约10%诸如约0.01%至约5%的量存在于组合物中。在一些实施方案中,该量为0.1%至5%,并且在其他实施方案中为1%至2%。
本发明的组合物可包含皮肤病学可接受的有效量的一种或多种附加的抗炎化合物。合适的抗炎剂的示例包括取代的间苯二酚、(E)-3-(4-甲基苯磺酰基)-2-丙烯腈(诸如Sigma-Aldrich,St.Louis,Missouri商购获得的“Bay11-7082”)、四氢姜黄素(诸如可从Sabinsa Corporation,Piscataway,NJ商购获得的四氢姜黄素CG)、得自以下的提取物和材料:黄柏(Phellodendron amurense)皮层提取物(PCE)、非变性大豆(大豆(Glycine max))、野甘菊(小白菊(Tanacetum parthenium))、姜(生姜(Zingiber officinale))、银杏(Ginkgo biloba)、羟基积雪草苷(雷公根(Centella asiatica)提取物成分)、黄栌(Cotinus coggygria)、蜂斗菜提取物(紫蜂斗菜(Petasites hybridus))、枸杞莓(宁夏枸杞(Lycium barbarum))、奶蓟草提取物(水飞蓟(Silybum marianum))、金银花(忍冬(Lonicera japonica))、秘鲁凤仙花(秘鲁香树(Myroxylon pereirae))、鼠尾草(Salviaofficinalis)、蔓越莓提取物(红莓苔子(Vaccinium oxycoccos))、苋菜油(繁穗苋(Amaranthus cruentus)、石榴(Punica granatum)、巴拉圭茶(巴拉圭冬青(Ilexparaguariensis)叶提取物)、白百合花提取物(圣母百合(Lilium candidum))、橄榄叶提取物(油橄榄(Olea europaea))、根皮素(苹果提取物)、燕麦粉(燕麦(Aveena sativa))、Lifenol(啤酒花:蛇麻(Humulus lupulus))提取物、Bugrane P(红芒柄花(Ononisspinosa))、甘草查尔酮(欧亚甘草:胀果甘草(Glycyrrhiza inflate)提取物成分)、Symrelief(红没药醇和姜提取物)、它们中的两种或更多种的组合等。
皮肤病学可接受的抗炎剂的一个示例是间苯二酚。特别合适的取代的间苯二酚包括4-己基间苯二酚和4-辛基间苯二酚,特别是4-己基间苯二酚。4-己基间苯二酚可以“SYNOVEA HR”从Sytheon(Lincoln Park,NJ)商购获得。4-辛基间苯二酚可从CityChemical LLC(West Haven,Connecticut)商购获得。
所谓“小白菊的提取物”意指植物“解热菊”的提取物,诸如可根据名称为“PARTHENOLIDE FREE BIOACTIVE INGREDIENTS FROM FEVERFEW(TANACETUM PARTHENIUM)AND PROCESSES FOR THEIR PRODUCTION”的美国专利7,537,791中列出的详细内容制备。一种特别合适的小白菊提取物可以约20%活性小白菊从Integrated BotanicalTechnologies公司(Ossining,NY)商购获得。
多种其他皮肤病学可接受的物质也可存在于本发明的组合物中。在一个或多个实施方案中,组合物包含一种或多种选自由以下组成的组的局部用成分:表面活性剂、螯合剂、润肤剂、湿润剂、调理剂、防腐剂、遮光剂、芳香剂等。
润肤剂意指帮助维持皮肤的柔软、光滑和柔韧外观的化合物(例如,通过保留在皮肤表面上或角质层中以充当润滑剂)。合适的润肤剂的示例包括在Handbook of CosmeticScience and Technology(由A.Barel,M.Paye和H.Maibach编辑,由Marcel Dekker,Inc(New York,NY)于2001年出版)中的第35章,第399-415页(由G Zocchi的Skin Feel Agent)中所见的润肤剂,并且包括但不限于凡士林、己基癸醇硬脂酸酯以及植物、坚果和植物油,诸如澳洲坚果油、米糠油、葡萄籽油、棕榈油、月见草油、氢化花生油和鳄梨油。
湿润剂意指旨在提高皮肤顶层的水含量的化合物(例如,吸湿化合物)。合适的保湿剂的示例包括在保湿剂(由A.Barel、M.Paye和H.Maibach编辑,由Marcel Dekker(IncNew York,NY)于2001年出版)中的第35章,第399-415页(G Zocchi的Skin Feel Agents)中所见的那些,并且包括但不限于甘油、山梨糖醇或海藻糖(例如,α,α-海藻糖、β,β-海藻糖、α,β-海藻糖)或它们的盐或酯(例如,海藻糖6-磷酸酯)。
表面活性剂意指旨在进行清洗或乳化的表面活性剂。合适的表面活性剂的示例包括在Handbook of Cosmetic Science and Technology(由A.Barel,M.Paye和H.Maibach编辑,由Marcel Dekker,Inc.,New York,NY于2001年出版)中的第37章,第431-450页(L.Oldenhove de Guertechin的表面活性剂分类(Classification of surfactants))中所见的表面活性剂,并且包括但不限于阴离子表面活性剂诸如硫酸酯和椰油酰甘氨酸钠、阳离子表面活性剂、两性表面活性剂诸如甜菜碱、非离子表面活性剂诸如烷基多聚糖苷。
合适的皮肤病学可接受的防腐剂的示例包括能够保护和保留本发明的组合物的那些。在一个或多个实施方案中,螯合剂为乙二胺四乙酸(“EDTA”),并且更具体地为EDTA四钠,其可以商品名“Versene100XL”从Dow Chemical Company,Midland,Michigan商购获得。
合适的皮肤病学可接受的防腐剂包括例如,对羟基苯甲酸酯、季铵类物质、苯氧基乙醇、苯甲酸盐、DMDM乙内酰脲、有机酸,并且基于组合物的总重量,以约0%至约1%,或约0.05%至约0.5%的量存在于组合物中。
赋予毛发另外的属性诸如光泽的多种调理剂中的任一种适用于本发明中。示例包括但不限于挥发性有机硅调理剂,其在大气压下具有小于约220℃的沸点。合适的挥发性有机硅的示例非排它性地包括聚二甲基硅氧烷、聚二甲基环硅氧烷、六甲基二硅氧烷、环聚甲基硅氧烷流体、诸如以商品名“DC-345”从Dow Corning Corporation(Midland,Michigan)商购获得的聚二甲基环硅氧烷、以及它们的混合物,并且具体地包括环聚甲基硅氧烷流体。其他合适的调理剂包括阳离子聚合物,该阳离子聚合物包括聚季铵盐、阳离子瓜尔胶等。
多种可商购获得的珠光剂或遮光剂中的任一种适用于组合物。适用的珠光剂或遮光剂的示例包括但不限于以下两项的单酯或二酯:(a)具有约16至约22个碳原子的脂肪酸和(b)乙烯或丙二醇;(a)具有约16至约22个碳原子的脂肪酸和(b)式:HO-(JO)a-H的聚亚烷基二醇的单酯或二酯,其中J为具有约2至约3个碳原子的亚烷基基团;并且a为2或3;含有约16个至约22个碳原子的脂肪醇;式:KCOOCH2L的脂肪酸酯,其中K和L独立地含有约15个至约21个碳原子;不溶于洗发剂组合物的无机固体;以及它们的混合物。
适于在皮肤上使用的任何芳香剂组合物均可用于根据本发明的组合物中。
皮肤病学产品形式
组合物可以是局部施用的。这样的局部施用可以是针对身体上需要治疗的任何皮肤,例如面部、嘴唇、颈部、胸部、背部、臀部、手臂、腋窝和/或腿部的皮肤。还可以将组合物施用至粘膜(即,在口腔中)。
在一些实施方案中,本发明的形式为包含本发明组合物的基材。可使用任何合适的基材。例如,在US7452547和US2009/0241242中公开了合适的基材和基材材料的示例,这些文献全文以引用方式并入本文。在一些实施方案中,组合物为片剂、丸剂或胶囊的形式。在一个或多个实施方案中,组合物为溶液、悬浮液、乳液、洗剂、乳膏、浆液、凝胶、棒、喷雾、软膏、液体洗液、皂条、洗发剂、护发素、糊剂、泡沫、粉末、摩丝、剃须膏、水凝胶或成膜产品的形式。在一个或多个实施方案中,组合物为溶液、悬浮液、乳液、洗剂、乳膏、浆液、凝胶、棒、喷雾、软膏、液体洗液、皂条、洗发剂、护发素、糊剂、泡沫、粉末、摩丝、剃须膏、水凝胶或成膜产品的形式。
可使用向有需要的皮肤施用组合物的任何合适方法。例如,可通过用手将组合物从包装直接施用于有需要的皮肤而施用于有需要的皮肤,或可从基材诸如擦拭物或面膜处转移,或它们中的两种或更多种的组合。在其他实施方案中,组合物可经由点滴器、管、滚筒、喷雾器和贴片来施用,或添加到浴缸中或者以其他方式添加到水中以施用于皮肤等。组合物可以多种方式或形式施用,包括但不限于作为免洗型霜、面膜和/或精华素。
眼科用途
非极性冰岛苔提取物可用于眼睛里的疼痛和/或瘙痒。在此类实施方案中,将组合物施用于患者。可以治疗的相关眼睛病症包括但不限于由外在因素诱导的眼部瘙痒、结膜炎、变态反应和疼痛/瘙痒。
对于眼科应用,提取物可以用眼科上可接受的载体配制。可用的水包油载体和油包水载体可见于美国专利公布20030165545A1和美国专利9,480,645、8,828,412和8,496,976中,这些专利文献中的每一者均全文以引用方式并入本文。
眼科上可接受的载体(或本发明的组合物)可任选地包含一种或多种附加的赋形剂和/或一种或多种附加的活性成分。下文描述了此类任选组分的示例。
眼科组合物中通常使用的赋形剂包括但不限于缓和剂、张度剂、防腐剂、螯合剂、缓冲剂(不是本发明的有机酸且除其以外)和表面活性剂。其他赋形剂包括增溶剂,稳定剂、舒适增强剂、聚合物、润肤剂、pH调节剂(不是本发明的有机酸且除其以外)和/或润滑剂。多种赋形剂中的任何一种都可以用于本发明的组合物中,包括水、水和水混溶性溶剂的混合物,诸如包含0.5%至5%的无毒水溶性聚合物的植物油或矿物油、天然产物诸如琼脂和阿拉伯树胶、淀粉衍生物诸如淀粉乙酸酯和羟丙基淀粉,以及其他合成产物诸如聚乙烯醇、聚乙烯吡咯烷酮、聚乙烯基甲醚、聚环氧乙烷,以及优选地交联聚丙烯酸以及它们的混合物。
与本发明的实施方案一起使用的缓和剂或抚慰剂包括但不限于纤维素衍生物(诸如羟乙基纤维素、甲基纤维素、羟丙甲纤维素或它们的混合物)、透明质酸、罗望子籽提取物、甘油、聚乙烯吡咯烷酮、聚环氧乙烷、聚乙二醇、丙二醇和聚丙烯酸以及它们的混合物。在一些实施方案中,透明质酸、丙二醇、罗望子籽提取物、甘油和/或聚乙二醇400中的一种或多种是缓和剂或抚慰剂。在一个或多个实施方案中,缓和剂或抚慰剂选自透明质酸、罗望子籽提取物或它们的混合物。
在一些实施方案中,本发明的组合物在眼科上适合施用于受试者的眼睛。术语“水性”通常表示水性制剂,其中赋形剂按重量计大于约50%,更优选大于约75%,具体地讲大于约90%的水。在一个或多个实施方案中,本发明的组合物基本上不含刺激眼睛的化合物。在一些实施方案中,本发明的组合物基本上不含游离脂肪酸和C1至C4醇类。在一个或多个实施方案中,本发明的组合物包含按总组合物的重量计小于40%(或约40%),任选地小于35%(或约35%),任选地小于30%(或约30%),任选地小于25%(或约25%),任选地小于20%(或约20%),任选地小于15%(或约15%),任选地小于10%(或约10%)或任选地小于5%(或约5%)的非醇、有机赋形剂或溶剂。这些滴剂可以用优选为无菌的单剂量安瓿输送,因此制剂中无需抑菌组分。另选地,滴剂可以用多剂量瓶递送,该多剂量瓶可以优选地包括在组合物递送时从组合物中提取任何防腐剂的装置,这样的装置为本领域已知。
在一个或多个实施方案中,为了对抗由蒸发和/或疾病引起的眼泪的高渗性,本发明的组合物是等渗的或略微低渗的。这可能需要张度剂使制剂的渗透度达到或接近210-320毫摩尔每千克(mOsm/kg)的水平。在一些实施方案中,本发明的组合物通常具有220-320mOsm/kg范围内的渗透度,或者任选地具有235-300mOsm/kg范围内的渗透度。眼科组合物通常将配制成无菌水溶液。
眼科组合物的渗透度可用张度剂调节至与组合物的预期用途相容的值。例如,可调节眼科组合物的渗透度以接近正常泪液的渗透压,这相当于水中约0.9w/v%的氯化钠。合适的张度调节剂的示例包括但不限于氯化钠、氯化钾、氯化钙和氯化镁;右旋糖;甘油;丙二醇;甘露糖醇;山梨醇等以及它们的混合物。在一个实施方案中,使用氯化钠和氯化钾的组合来调节组合物的张度。
眼科组合物也可用于施用药物活性化合物。此类化合物包括但不限于青光眼治疗剂、止痛剂、抗炎和抗过敏药物以及抗微生物剂。药物活性化合物的更具体的示例包括倍他洛尔、噻吗洛尔、毛果芸香碱、碳酸酐酶抑制剂和前列腺素;多巴胺能拮抗剂;手术后抗高血压剂,诸如对氨基可乐定(阿拉可乐定);抗感染剂,诸如环丙沙星、莫西沙星和妥布霉素;非甾体和甾体抗炎剂,诸如萘普生、双氯芬酸、奈帕芬胺、舒洛芬、酮咯酸、四氢皮质醇和地塞米松;干眼治疗剂,例如,PDE4抑制剂;以及抗过敏药物,诸如H1/H4抑制剂、H4抑制剂、奥洛他定或它们的混合物。
在一些实施方案中,眼科组合物可具有与预期用途相容的pH,并且通常在4(或约4)至10(或约10)的范围内,任选地在6(或约6)至8(至约8)之间,任选地在6.5(或约6.5)至7.5(或约7.5)之间,或任选地在6.8(或约6.8)至7.2(或约7.2)之间。
在一个或多个实施方案中,可采用多种常规缓冲剂,诸如磷酸盐、硼酸盐、柠檬酸盐、乙酸盐、组氨酸、tris、bis-tris等以及它们的混合物。硼酸盐缓冲剂包括硼酸及其盐,诸如硼酸钠或硼酸钾。也可采用四硼酸钾或偏硼酸钾,四硼酸钾或偏硼酸钾在溶液中产生硼酸或硼酸盐。还可使用水合盐,诸如硼酸钠十水合物。磷酸盐缓冲剂包括磷酸及其盐;例如,M2HPO4和MH2PO4,其中M是碱金属诸如钠和钾。也可使用水合盐。在本发明的一个实施方案中,使用Na2HPO4.7H2O和NaH2PO2.H2O作为缓冲剂。术语磷酸盐还包括在溶液中产生磷酸或磷酸盐的化合物。另外,还可使用上述缓冲剂的有机抗衡离子。缓冲剂的浓度通常在约0.01w/v%至2.5w/v%之间变化,更优选地在约0.05w/v%至约0.5w/v%之间变化。
在一个或多个实施方案中,当使用TA Instrument AR 2000流变仪测量时,本发明组合物的粘度范围为约1cps至约500cps,任选地为约10cps至约200cps,或任选地为约10cps至约100cps。TA Instrument AR 2000流变仪应当与TA Rheological Advantage软件的AR2000流量测试方法一起使用,所述流变仪具有40mm钢板的几何形状;应当通过测量稳态流量来获得粘度范围,所述稳态流量控制剪切速率为0秒-1至200秒-1。
在一个或多个实施方案中,组合物可以以滴眼剂溶液、眼部清洗溶液、接触镜片润滑和/或再润湿溶液、喷雾、薄雾或任何其他形式将组合物施用于眼睛。
本发明的组合物可以是用于接触镜片的包装溶液的形式。在一个或多个实施方案中,作为润湿溶液,本发明的组合物可密封在泡罩包装中,并且还适于经历灭菌过程。
泡罩包装件和灭菌技术的示例公开于以下参考文献中,这些参考文献全文以引用方式并入本文:美国专利号D435,966;4,691,820;5,467,868;5,704,468;5,823,327;6,050,398;5,696,686;6,018,931;5,577,367;以及5,488,815。该部分制造过程提供了使用抗过敏剂处理眼科装置的另一种方法,即在密封包装之前向溶液中加入抗过敏剂,随后对包装进行灭菌。这是使用抗过敏剂处理眼科装置的优选方法。
可在不同的温度和时间段下进行灭菌。优选的灭菌条件的范围是约100℃持续约8小时至约150℃持续约0.5分钟。优选的灭菌条件的范围是约115℃持续约2.5小时至约130℃持续约5.0分钟。最优选的灭菌条件为约124℃持续约18分钟。
当用作润湿溶液时,本发明的组合物可以是水基溶液。典型的润湿溶液包括但不限于盐水溶液、其他缓冲液和去离子水。在一个或多个实施方案中,润湿溶液为去离子水的水溶液或含盐的盐水溶液,所述盐包括但不限于氯化钠、硼酸钠、磷酸钠、磷酸氢钠、磷酸二氢钠或它们的对应钾盐。这些成分通常组合形成包含酸及其共轭碱的缓冲溶液,使得添加酸和碱仅引起pH值发生相对较小的变化。在一个或多个实施方案中,润湿溶液的pH如上所述。缓冲液可另外包括2-(N-吗啉基)乙磺酸(MES)、氢氧化钠、2,2-双(羟基甲基)-2,2',"-次氮基三乙醇、N-三(羟甲基)甲基-2-氨基乙磺酸、柠檬酸、柠檬酸钠、碳酸钠、碳酸氢钠、乙酸、乙酸钠、乙二胺四乙酸等以及它们的组合。优选地,溶液为硼酸盐缓冲盐水溶液或磷酸盐缓冲盐水溶液或去离子水。尤其优选的溶液包含约500ppm至约18,500ppm的硼酸钠,最尤其优选约1000ppm的硼酸钠。
如果掺入到润湿溶液中的任何成分发生氧化降解,则可添加试剂使包含此类成分的润湿溶液稳定。此类“氧化稳定剂”包括但不限于螯合剂(诸如EDTA、Dequest、Desferal、二氧化硅)、甲壳质衍生物(诸如脱乙酰壳多糖、纤维素及其衍生物和N,N,N',N',N",N"-六(2-吡啶基)-1,3,5-三(氨甲基)苯)以及某些大环配体(诸如冠醚、包含结和链的配体)。参见,David A.Leigh等人,Angew.Chem Int.编辑,2001年,第40卷,第8期,第1538-1542页,以及Jean-Claude Chambron等人,Pure&Appl.Chem.,1990年,第62卷,第6期,1027页至1034页。氧化稳定剂可包括抑制氧化的其他化合物,诸如选自由以下项组成的组:2,2',2',6,6',6"-六(1,1-二甲基乙基)4,4',4"-[(2,4,6-三甲基-1,3,5-苯三基)-三亚甲基]-三苯酚(Irganox 1330)、1,3,5-三[3,5-二(1,1-二甲基乙基)4-羟基苄基]-1H,3H,5H-1,3,5-三嗪-2,4,6-三酮、季戊四醇四[3-[3,5-二(1,1-二甲基乙基)-4-羟基苯基]-丙酸酯]、十八烷基-3-[3,5-二(1,1-二甲基乙基)-4-羟基苯基]-丙酸酯、三[2,4-二(1,1-二甲基乙基)-苯基]-亚磷酸酯、2,2'-二(十八烷氧基)-5,5'-螺环二(1,3,2-二氧磷环戊烷)、二(十八烷基)二硫化物、二(十二烷基)-3,3'-硫代双丙酸酯、二(十八烷基)-3,3'-硫代双丙酸酯、丁基羟基甲苯、乙烯双[3,3-二[3-(1,1-二甲基乙基)-4-羟基苯基]丁酸酯]以及它们的混合物。优选的氧化稳定剂是二亚乙基三胺五乙酸(“DTPA”),或DTPA的盐诸如CaNa3DTPA、ZnNa3DTPA和Ca2DTPA。参见2006年3月17日提交的名称为“Methods for Stabilizing OxidativelyUnstable Pharmaceutical Compositions”的美国专利申请60/783,557及其对应的非临时性提交申请,这些专利申请的全部内容均以引用方式并入本文。在一个或多个实施方案中,氧化稳定剂在溶液中的浓度为约2.5微摩尔/升至约5000微摩尔/升,任选地约20微摩尔/升至约1000微摩尔/升,任选地约100微摩尔/升至约1000微摩尔/升,或任选地约100微摩尔/升至约500微摩尔/升。
在一个或多个实施方案中,眼科组合物被配制为以任何施用频率施用,包括每周一次、每五天一次、每三天一次、每两天一次、每天两次、每天三次、每天四次、每天五次、每天六次、每天八次、每小时或更高的频率。根据用户的治疗需要,也在可变的持续时间维持这种给药频率。具体治疗方案的持续时间可在单次给药到持续数月或数年的方案之间变化。本领域普通技术人员将会熟知确定具体指示的治疗方案。
药物用途
非极性冰岛苔提取物可用于皮肤上的肠道疼痛和/或瘙痒。在此类实施方案中,组合物经肠施用。可治疗的相关肠道病症包括但不限于与消化健康(例如,肠易激综合征等)、肌肉骨格系统(例如,骨关节炎、其他肌肉疼痛等)相关的病症。
为了制备用于本发明的非局部施用途径的组合物(在本文中称为“药物用途”),根据常规药物混配技术,可将非极性冰岛苔提取物与药学上可接受的载体紧密混合,该药学上可接受的载体可以采取多种形式,这取决于施用所需的制剂形式(例如,口服或肠胃外)。合适的药学上可接受的载体是本领域所熟知的。有关这些药学上可接受的载体中的一些的描述可在American Pharmaceutical Association和Pharmaceutical Society of GreatBritain出版的The Handbook of Pharmaceutical Excipients中找到。
配制药物组合物的方法描述于多个出版物,诸如Pharmaceutical Dosage Forms:Tablets,Second Edition,Revised and Expanded,第1-3卷,由Lieberman等人编辑;Pharmaceutical Dosage Forms:Parenteral Medications,第1-2卷,由Avis等人编辑;和Pharmaceutical Dosage Forms:Disperse Systems,第1-2卷,由Lieberman等人编辑;以上出版物由Marcel Dekker,Inc.出版。
优选地,药物组合物为单位剂型,诸如片剂、丸剂、胶囊、囊片、胶囊锭、锭剂、颗粒、粉末、无菌肠胃外溶液或悬浮液、计量气雾剂或液体喷雾剂、滴剂、安瓿、自动注射器装置或栓剂,用于通过口服、鼻内、舌下、透皮、肠胃外、直肠、阴道、吸入或吹入方式施用。另选地,组合物可以适于每周一次或每月一次施用的形式存在,或者可适于提供用于肌内注射的制剂。
在制备具有用于口服施用的固体剂型的药物组合物中,诸如片剂、丸剂、胶囊、囊片、胶囊锭、锭剂、颗粒或粉末(各自包括立即释放、定时释放和持续释放制剂),药学上合适的载体和添加剂包括但不限于稀释剂、制粒剂、润滑剂、粘剂、助流剂、崩解剂等。如果需要,片剂可通过标准技术包糖衣、包明胶衣、包膜衣或包肠溶衣。
为制备固体剂型,将主要活性成分与药学上可接受的载体(诸如常规的制片成分诸如稀释剂、粘结剂、粘合剂、崩解剂、润滑剂、抗粘剂和助流剂)混合。可向可咀嚼的固体剂型中加入甜味剂和香味剂以改善该口服剂型的适口性。此外,可向固体剂型添加或涂布着色剂和涂布剂以便易于识别药物或出于美学目的。这些药学上可接受的载体与药物活性物质配制在一起,以提供具有治疗释药特征的药物活性物质的精确、适宜剂量。
在制备具有用于口服、局部和肠胃外施用的液体剂型的药物组合物时,可以采用任何常用的药物介质或赋形剂。因此,对于液体单位剂型,诸如悬浮液(即,胶体、乳液和分散体)和溶液,可以采用药学上合适的载体和添加剂,包括但不限于药学上可接受的润湿剂、分散剂、絮凝剂、增稠剂、pH控制剂(即,缓冲剂)、渗透剂、着色剂、调味剂、芳香剂、防腐剂(即,控制微生物生长等)和液体媒介物。并非每种液体剂型都需要上述所有组分。可掺入本发明新型组合物用于口服或注射施用的液体制剂包括但不限于水溶液剂、适当矫味的糖浆剂、水性或油性混悬剂和用食用油(诸如棉籽油、芝蔴油、椰子油或花生油)矫味的乳剂,以及酏剂和类似药用媒介物。
虽然前述说明书表示本发明的示例性实施方案,但应当理解,在不脱离本发明的实质和范围的情况下,可对本发明做各种添加、修改和替换。具体地,本领域的技术人员应该清楚的是,不脱离本发明的实质或本质特征,本发明可以以其他具体形式、结构、布置、比例,以及用其他要素、材料和部件来实施。本领域的技术人员应当理解,本发明可与在本发明的实践中使用的结构、布置、比例、材料和部件等的许多修改使用,这些修改尤其能够适用于具体环境和操作要求,而不脱离本发明的原理。因此,当前公开的实施方案在各方面被认为是例示性的而非限制性的,本发明的范围由所附权利要求书指出,且不受前述描述的限制。应当理解在权利要求中,术语“包括/包括的”不排除其他要素或步骤。此外,单数形式的引用不排除复数。术语“一个”、“一种”“第一”、“第二”等不排除复数。
除非另外指明,否则所有百分比、份数和比率均基于本发明组合物的总重量计。除非另外指明,否则所有与所列成分相关的此类重量均基于所述特定成分的水平,因此不包括可能包含在可商购获得的材料中的载体或副产物。
实施例
实施例1:极性与非极性提取物
对比冰岛苔的两种提取物对TRPA1受体的拮抗活性。两种提取物均以10mg/mL的DMSO供应,并包含在Phytotitre天然产物提取物库中,可从Caithness生物技术有限公司获得。一种提取物是极性提取物(水性溶液)(对比),而另一种是非极性提取物(二氯甲烷作为溶剂)(本发明)。
对TRPA1受体的预筛选:
使用来自PerkinElmer的人TRPA1离子通道细胞系对提取物进行筛选。在CMV启动子的控制下,将含有人瞬时受体电位阳离子通道亚家族A成员1(TRPA1)离子通道编码序列的表达载体,转染到稳定表达线粒体靶向的HEK-293细胞中。
实验方案:
在第0天,将80.000个细胞/孔接种在100μL的培养基(MEM:Cell Eagle培养基+10%胎牛血清+抗生素G418)中,然后在37℃温育过夜。
在第1天,移除培养基,在每个孔中加入100μL腔肠素,并将细胞在25℃温育4小时。然后,分别加入25μl 0.001%或0.005%的冰岛苔提取物。将50μM的钌红(Sigma Aldrich)用作阳性对照,由于它是众所周知的TRPA1受体的拮抗剂。将拮抗剂在室温下温育10分钟。将板转移至FlexStation 3微板读数器(Molecular devices LLC,San José,美国),其中第二板含有10μM的TRPA1受体的拮抗剂:AITC(异硫氰酸烯丙酯,来自Sigma Aldrich)。FlexStation将AITC自动转移至每个孔中,并实时读取钙流。
结果:
结果示于图1A-图1B中。如图1A所示,极性提取物在0.001%的浓度下表现出20%的抑制,在0.005%的浓度下表现出-6%的抑制。相反,如图1B所示,非极性提取物在浓度为0.005%时表现出与阳性对照相同的抑制百分比,在浓度为0.001%时表现出36%的抑制百分比。上述数据显示,与极性提取物对比,非极性提取物的TRPA1活性大得多。由于没有文献提示非极性冰岛苔提取物与极性提取物之间的差异,因此这些结果是令人惊奇的。
实施例2:非极性冰岛苔提取物对CHO(中国仓鼠卵巢细胞系)的细胞毒性
非极性冰岛苔提取物对CHO细胞的细胞毒性以2种浓度(0.005%和0.001%)一次重复评估24小时。细胞毒性测试在温育24小时后,通过将0.2mL MTT溶液(甲基噻唑基二苯基-四唑鎓溴化物,Sigma Aldrich,编号M2128)以0.5mg/mL分配到每孔培养基中来进行细胞毒性测试。然后,将细胞在37℃下温育3小时,并加入异丙醇(200μl)。将板摇动30分钟,在570nm处读数。如果与未处理的对照相比低于80%的细胞生存力,则认为值指示细胞毒性。
测试结果示于图2中。可以看出,非极性冰岛苔提取物在0.001%时没有细胞毒性。
实施例3:非极性冰岛苔提取物TrkA拮抗活性
使用eXpress受体酪氨酸激酶(RTK)功能测定试剂盒(Discoverx)来测试非极性冰岛苔提取物对TrkA受体的拮抗活性,该试剂盒提供用于监测受体酪氨酸激酶活化的基于细胞的功能测定。
在第0天,将细胞以30.000个细胞/孔接种于80μL细胞接种剂n°16(参见eXpress试剂盒,Discoverx)中,并温育(37℃)过夜。然后用20μL浓缩5倍的非极性冰岛苔提取物处理细胞,以获得孔中所需的最终浓度(孔中的最终容积=100μL)或用阳性对照处理。阳性对照是已知的TrKA受体的拮抗剂GW441756(Enzolife科学,编号:BML-EI364-0010)(Montagnoli C,Pistilli A,Stabile A M等人GW441756(NGF受体酪氨酸激酶a(TRKA)的新型抑制剂)在人肉瘤中的抗增殖作用。意大利解剖学与胚胎学杂志,2010,115(1/2):117)。将样品在37℃下温育1小时。
加入20μl浓度为4nM的NGF(神经生长因子),众所周知的TrKA受体拮抗剂,并在室温下温育180分钟。然后,根据制造商的说明书,加入50μL的试剂:1mL底物试剂1、5mL底物试剂2和19mL细胞测定缓冲剂的混合物,并在室温下温育1小时。然后在微板读数器(Perkin Elmer,Waltham,USA)上在540nm处读取化学发光信号。
结果示于图3中。从图中可以看出,非极性冰岛苔提取物显示出剂量依赖性TrKA拮抗活性。测定IC50(半数最大抑制浓度),非极性冰岛苔提取物为0.0005284%,GW441756为2.230×10-5%。由于不可能预测哪些化合物表现出这种效果,因此这些结果是令人惊奇的。
实施例4:通过PC12神经突生长晕功能模型验证非极性冰岛苔提取物TrKA拮抗活
性
根据以下方法,使用PC12神经突生长晕功能模型测试非极性冰岛苔提取物对TrkA受体的拮抗活性:
第0天:用胶原包被12孔板。
以20μg/ml重构来自大鼠尾巴(Sigma Aldrich,编号:122-20)的用以增强细胞附着和增殖的胶原溶液。每孔分配1ml,并在室温下温育3小时。除去溶液后,将板在室温下干燥过夜。
第1天:接种PC12细胞并用TrKA拮抗剂处理
每孔加入1ml PC12细胞(源自于大鼠肾上腺髓质嗜铬细胞瘤的细胞系,以50.000个细胞/ml接种在具有10%FCS(胎牛血清)的DMEM F12(Dulbecco改良的Eagle培养基:营养混合物F-12)中)。在37℃下温育细胞24小时。然后,在不冲洗的情况下更换培养基,并用含有DMEM-F12,25ng/ml NGF的基础培养基替换,以诱导神经突生长晕、胰岛素5μg/ml、氢化可的松(10ng/ml)和以1/10稀释(赛默飞世尔,编号:17504044)的B27 50X(神经元细胞培养的补充物)。将该基础培养基作为对照条件。然后,向该培养基中加入不同的处理:
··浓度为0.00006%的GW441756(相当于2μM)
··浓度为0.0005%的非极性冰岛苔提取物
··浓度为0.0001%的非极性冰岛苔提取物
将经处理的细胞培养5天,然后拍摄照片(每孔随机拍摄5张图片)。通过软件(模块NeuronJ)进行图像分析来定量PC12细胞的神经突生长晕。简而言之,测量每个神经突的长度,然后计算每个条件下的平均神经突长度。
该实验重复三次,并用ANOVA进行统计学分析。
三个实验中的每个结果示于图4-图6中。图4-图6中所示的值显示在TrKA受体被抑制的情况下,神经元长度较低。以像素表示,这是从取自培养板的图像(图片)中提取的。神经突长度越小,对生长的抑制越高。三个实验中的平均值示于图7-图8中。在图7中,结果以未处理对照的百分比表示,在图8中,结果以神经元长度(像素)表示。从结果可以看出,与阳性对照相比,当用非极性冰岛苔提取物处理PC12细胞时,特别是浓度为0.0005%时,观察到神经突生长晕显著减少。由于冰岛苔在非常低的浓度(在作为纯分子的阳性化合物和非极性冰岛苔提取物之间的10倍浓度)下显示出与阳性对照相似的TrKA拮抗剂活性,因此这些结果是令人惊奇的。
Claims (15)
1.一种组合物,所述组合物包含治疗有效剂量的非极性冰岛苔提取物,用于减轻有需要的患者的疼痛或瘙痒。
2.根据权利要求1所述的组合物,其中所述非极性提取物用选自由以下组成的组的一种或多种溶剂提取:C1-C8烷烃、C1-C8环烷烃、C1-C8烷基醚、石油醚、C1-C8酮、二氯甲烷、乙酸乙酯、二甲苯、甲苯、氯仿、植物油、矿物油以及它们的组合,优选地所述非极性提取物用二氯甲烷提取。
3.根据权利要求1或2所述的组合物,其中所述疼痛是TRPA1或TrKA受体介导的疼痛和/或瘙痒。
4.根据权利要求1至3中任一项所述的组合物,其中所述组合物经肠施用、被施涂于所述患者的皮肤表面,或施用于所述患者的眼睛。
5.根据权利要求1至3中任一项所述的组合物,其中所述疼痛或瘙痒与消化健康、眼部瘙痒、骨关节炎、变态反应或特应性皮炎相关。
6.根据前述权利要求中任一项所述的组合物,其中所述组合物还包含选自由以下组成的组的皮肤病学可接受的载体:表面活性剂、螯合剂、润肤剂、保湿剂、调理剂、防腐剂、遮光剂、芳香剂以及它们中的两种或更多种的组合。
7.根据前述权利要求中任一项所述的组合物,其中所述组合物以溶液、悬浮液、洗剂、乳膏、浆液、凝胶、棒、喷雾、软膏、液体洗液、皂条、洗发剂、护发素、糊剂、泡沫、粉末、摩丝、剃须膏、水凝胶或成膜产品的形式施用。
8.根据前述权利要求中任一项所述的组合物,其中所述非极性提取物以按总组合物的重量计约0.00001重量%至约2重量%的浓度,优选以按所述总组合物的重量计约0.001重量%至约0.005重量%的浓度存在于所述组合物中。
9.一种组合物,所述组合物包含治疗有效剂量的非极性冰岛苔提取物的组合物,用于减轻有需要的患者的疼痛或瘙痒,
其中所述非极性提取物以按总组合物的重量计约0.001重量%至约0.005重量%的浓度存在于所述组合物中;并且
所述非极性提取物用二氯甲烷提取。
10.根据权利要求9所述的组合物,其中所述疼痛是TRPA1或TrKA受体介导的疼痛和/或瘙痒。
11.根据权利要求9或10所述组合物,其中所述组合物被施涂于所述患者的皮肤表面,或施用于所述患者的眼睛。
12.根据权利要求9或10所述的组合物,其中所述组合物经肠施用于所述患者。
13.根据权利要求9或10所述的组合物,其中所述疼痛或瘙痒与消化健康、眼部瘙痒、骨关节炎、变态反应或特应性皮炎相关。
14.根据权利要求9至13中任一项所述的组合物,其中所述组合物还包含选自由以下组成的组的皮肤病学可接受的载体:表面活性剂、螯合剂、润肤剂、保湿剂、调理剂、防腐剂、遮光剂、芳香剂以及它们中的两种或更多种的组合。
15.根据权利要求9至14中任一项所述的组合物,其中所述组合物以溶液、悬浮液、洗剂、乳膏、浆液、凝胶、棒、喷雾、软膏、液体洗液、皂条、洗发剂、护发素、糊剂、泡沫、粉末、摩丝、剃须膏、水凝胶或成膜产品的形式施用。
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US435966A (en) | 1890-09-09 | Sash-holder | ||
US4150123A (en) * | 1977-11-21 | 1979-04-17 | Wladyslaw Szturma | Method for treating gastro intestinal ulcers with extract of herb cetraria |
FR2507477A1 (fr) | 1981-06-12 | 1982-12-17 | Roussel Uclaf | Nouveau procede de preparation d'un extrait de feuilles d'olea europea riche en oleuropeine, produits obtenus, application a titre de medicaments et compositions les renfermant |
US4691820A (en) | 1985-11-18 | 1987-09-08 | Vistakon, Inc. | Package for hydrophilic contact lens |
NZ250453A (en) | 1992-12-21 | 1996-12-20 | Johnson & Johnson Vision Prod | Ophthalmic lens package; planar surface with concave bowl for containing lens, sealing sheet covering bowl with lens therein |
US5823327A (en) | 1993-11-02 | 1998-10-20 | Johnson & Johnson Vision Products, Inc. | Packaging arrangement for contact lenses |
US5577367A (en) | 1994-06-10 | 1996-11-26 | Johnson & Johnson Vision Products, Inc. | Apparatus and method for sterilization and secondary packaging |
US5488815A (en) | 1994-06-10 | 1996-02-06 | Johnson & Johnson Vision Products, Inc. | Apparatus and method for sterilization and secondary packaging |
US5696686A (en) | 1994-06-10 | 1997-12-09 | Johnson & Johnson Vision Products, Inc. | Computer system for quality control correlations |
US5704468A (en) | 1995-09-29 | 1998-01-06 | Johnson & Johnson Vision Products, Inc. | Packaging arrangement for contact lenses |
IT1298283B1 (it) | 1998-02-19 | 1999-12-20 | B & T S R L | Uso dell'estratto delle foglie di olea europea come antiradicalico |
US6018931A (en) | 1998-09-08 | 2000-02-01 | Johnson & Johnson Vision Products, Inc. | Method and support for supporting packages only at their edges during steam sterilization |
US6050398A (en) | 1998-11-25 | 2000-04-18 | Novartis, Ag | Contact lens storage container |
USD435966S1 (en) | 1999-01-29 | 2001-01-09 | Johnson & Johnson Vision Care, Inc. | Contact lens container |
US7442391B2 (en) | 2002-01-25 | 2008-10-28 | Integrated Botanical Technologies, Llc | Bioactive botanical cosmetic compositions and processes for their production |
US20030165545A1 (en) | 2002-01-30 | 2003-09-04 | Allergan, Inc. | Ophthalmic compositions including oil-in-water emulsions, and methods for making and using same |
ES2652603T3 (es) | 2004-01-12 | 2018-02-05 | Isp Investments Llc | Composiciones bioactivas de plantas de Theacea y procedimientos para su producción y uso |
US7452547B2 (en) | 2004-03-31 | 2008-11-18 | Johnson&Johnson Consumer Co., Inc. | Product for treating the skin comprising a polyamine microcapsule wall and a skin lightening agent |
DE102004050591A1 (de) * | 2004-09-22 | 2006-04-06 | Maria Clementine Martin Klosterfrau Vertriebsgesellschaft Mbh | Schleimdrogenbasierte Lutschtablette gegen entzündliche Erkrankungen des Mund- und Rachenraums |
AU2007217003B2 (en) | 2006-02-21 | 2013-04-04 | Isp Investments Inc. | Parthenolide free bioactive ingredients from feverfew (Tanacetum parthenium) and processes for their production |
JP2007300862A (ja) * | 2006-05-11 | 2007-11-22 | Ivy Cosmetics Corp | コラーゲン産生用食品 |
US20090241242A1 (en) | 2008-03-31 | 2009-10-01 | Heidi Beatty | Facial mask |
US9480645B2 (en) | 2009-06-02 | 2016-11-01 | Abbott Medical Optics Inc. | Omega-3 oil containing ophthalmic emulsions |
US20100305046A1 (en) | 2009-06-02 | 2010-12-02 | Abbott Medical Optics Inc. | Stable cyclosporine containing ophthalmic emulsion for treating dry eyes |
RU2589837C2 (ru) | 2009-06-05 | 2016-07-10 | Аллерган, Инк. | Искусственные слезы и терапевтические применения |
CN105050610A (zh) * | 2013-04-02 | 2015-11-11 | 勃林格殷格翰国际有限公司 | 用于治疗咽喉痛、声嘶及相关的干咳以及治疗口腔和咽的炎性疾病的锭剂 |
EP2829303A1 (en) * | 2013-07-22 | 2015-01-28 | Johnson & Johnson Consumer Companies Inc. | Compositions comprising extract of malva neglecta and method of treating a skin condition with malva neglecta |
KR20150145947A (ko) * | 2014-06-20 | 2015-12-31 | 주식회사 더마랩 | 캣츠클로, 아이슬란드 이끼 및 아사이베리 혼합 추출물을 유효성분으로 하는 자외선 차단용 화장료 조성물 |
WO2018112666A1 (en) * | 2016-12-23 | 2018-06-28 | Klox Technologies Inc. | Biophotonic compositions comprising lichen extract and their use to treat skin disorders |
KR101798505B1 (ko) * | 2017-02-22 | 2017-11-17 | 코웨이 주식회사 | 피부 유익 미생물상 증진용 화장료 조성물 |
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