CN101035509B - 用于治疗用途的有机凝胶制剂 - Google Patents
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Abstract
本发明提供一种适用于局部递送美容剂和/或药物物质进入皮肤的组合物,所述组合物包含至少两种可生物相容的有机溶剂、极性脂质、表面活性剂、水、尿素及增稠剂,其中所述有机溶剂包括酯和二元和/或多元醇。本发明还公开了另外包含美容剂和/或药物物质的组合物以及其制备和应用。
Description
相关申请的交叉引用
本申请是我于2005年6月13日提交的题目为“用于治疗用途的有机凝胶制剂”的第11/150,254号美国申请的部分继续,该申请反过来又是我于2005年2月28日提交的题目为“用于治疗用途的有机凝胶制剂”的同时在审的(copending)第11/066,485号美国申请的部分继续,该申请反过来又是我于2004年10月8日提交的题目为“用于治疗用途的有机凝胶制剂”的同时在审的第10/960,516号美国申请的部分继续,它们公开的所有内容均并入此处作为参考。
技术领域
本发明公开涉及一种可用于将美容剂和/或药物活性物质局部递送进入皮肤和指甲中的组合物。该组合物能够使含有活性物质的制剂迅速通过皮肤吸收,透过指甲,而且同时具有令人愉悦的、不腻及不油的外观和感觉。
背景技术
皮肤是机体中最大的器官,发挥对生命必不可少的重要功能。皮肤能充当对各种病原体及有毒物质的入侵的屏障。皮肤由两层组成:第一层为表皮,在表皮下面为真皮。
然而,由于皮肤必须充当病原体及有毒物质进入以及生理性液体流出的屏障,因此它具有高度的不可渗透性。为了保持皮肤本身的完整性而同时维持机体精密的动态电解质平衡,皮肤必须是不可渗透的。皮肤必须提供一种封闭功能(containment function);它还必须行使其作为微生物、化学、放射及热屏障的功能。
皮肤的不可渗透性很大程度上归因于一种非常薄的层的性质,该薄层由皮肤中正常发育的改变和生理学改变而形成。当细胞在基底层(basallayer)形成后,它们开始向皮肤的表面迁移,直到最后脱落。在它们迁移期间,它们逐渐脱水并角质化。当它们到达表面且刚好在脱落之前时,它们形成了致密的、在代谢上无活性细胞组成的薄层,厚度约为10微米(10~15个细胞)。该层称为角质层(stratum corneum)或“角质化层(cornified layer)”。由于组成角质层的细胞高度角质化,因而形成了强有力的屏障。因此,通过非极性途径,即通过这些细胞的膜来渗透,仍是最为困难的。
当试图通过指甲,即手指或脚趾末端趾骨远端背面上的角质(horny)皮肤板状物(手指甲和脚趾甲)递送药物物质时,该问题则显得甚至更加困难。它们由称为甲床(matrix)的分化的上皮细胞发育而成的扁平上皮鳞状物构成。指甲的厚和硬的性质使得目前局部用制剂通过指甲到达指甲下区域是几乎不可能的。本发明公开的主题具有的优势在于能够使药物物质通过指甲递送至在此之前几乎不可能到达的疾病靶点。
相应地,在意图利用该给药途径并克服由皮肤和指甲自然形成的障碍时,现有技术已致力于使用经特殊选择的赋形剂和载体,于其中加入药物活性成分,从而该赋形剂或载体将有助于、或起码不会对所选活性物质的渗透产生不利影响。现有技术认为,选择不恰当的赋形剂可在很大程度上明显降低药物活性成分的经皮传递速率。
由于容易到达、施用的动力学、表面积大、可广泛暴露于循环及淋巴网络以及是非侵入性(non-invasive)治疗的原因,药物活性物质经皮传递在长期以来被认为是一种很有希望的构思。无论所希望的生物利用度是全身性的或仅限于真皮,是区域性的(regional)或是局部的(local),都是如此。
该传递形式的优点包括但不局限于:避免与非胃肠道治疗有关的风险;消除非胃肠道治疗的不便;避免口服治疗中固有的吸收及代谢速率的变化;通过容许递送生物学半衰期短的活性物质来增加药物给药的连续性;以及避免由于药物活性物质、防腐剂、压片剂(tableting agent)等暴露于胃肠道所造成的胃肠道刺激等。最重要的是,局部递送具有以相同的治疗方案全身或者局部地有效治疗在本质上属于局部(或表现出局部表现症状)疾病的可能性。因此,人们极力寻求可有效递送药物物质的组合物。
虽然已有多种组合物被建议用于某些药物活性物质的经皮传递,但仍有必要去增强美容剂及药物物质通过皮肤传递的能力,以用于皮肤疾病的局部治疗。特别地,组合物应当易于以一定的量局部施用,使活性物质迅速渗透进入皮肤,到达活性物质所需要到达的部位,且组合物应当具有令人愉悦的气味及外观,而且不需要清洗而除去所述活性物质。
这些所希望的特征的组合很难实现。
发明内容
本发明公开涉及一种用于局部递送美容剂或药物物质或两者的组合物。该组合物包含至少两种可生物相容的有机溶剂、极性脂质、至少一种表面活性剂、水、尿素(urea)及增稠剂。所述有机溶剂包含酯以及二元和/或多元醇。所述组合物包含约2~约30重量%的酯和约0.5~约20重量%的二元和/或多元醇。
本发明公开也涉及一种将活性物质传递进入和通过人或动物的表皮或指甲组织的方法,其包括将含有美容剂和/或药物学活性物质以及上述公开的组合物的组合物局部施用于人或动物的皮肤或指甲。
本发明公开另一个方面涉及一种包含上述公开的递送组合物以及美容剂和/或药物学活性物质的组合物。典型地,含活性物质的组合物的pH为约5.5~约7.5。
本发明另一个方面涉及一种制备适用于经皮递送美容剂和/或药物学活性物质的组合物的方法,其包括:
a.使极性脂质至少溶解在两种可生物相容的有机溶剂中,所述有机溶剂包含至少一种酯及至少一种二元或多元醇;
b.向步骤(a)的组合物中加入一种或多种表面活性剂;
c.使美容剂和/或药物学活性物质溶解在步骤(b)的溶剂-极性脂质、表面活性剂混合物中;
d.向水中加入尿素及至少一种增稠剂;
e.合并c与d中的组合物,并根据需要调节pH至约5.5~约7.5。
本发明公开另外涉及一种通过上述公开的方法制备的组合物。
根据以下的详细描述,本领域技术人员将很容易明白本发明公开的其他目的和优点,其中仅通过举例说明所认为实施本发明公开的最佳方式而展示和描述了优选的实施方案。应当了解,本发明公开能够存在其他及不同的实施方案,而且能够在各种明显的方面对其若干细节进行修改而不偏离本发明公开。相应地,说明书在本质上应被认为是描述性的,而不具有限制性。
具体实施方式
在这里使用的“局部给药”系指直接涂抹或铺展在表皮或指甲组织上,尤其在外皮、指甲或膜上,包括口腔、直肠或阴道腔粘膜的皮肤或膜。
在这里使用的“安全和有效量”系指足够量的组合物,在该剂量下的组合物能够以伴随所有医学治疗的合理的受益/风险比例提供所需局部治疗活性和性能。在合理的医学判断范围内,所使用活性物质的量将随以下情况进行调整:所治疗的特定疾病、疾病的严重性、治疗的持续时间、所应用的具体活性成分及其浓度、患者的情况、同时给予的治疗、以及在患者或主治医师特定知识及专门知识理解之内的类似因素。
在这里使用的“毒理学或药理学可接受的”系指,在合理的受益/风险比下,该术语所描述的药物活性成分、以及其他可相容的药品、药物或惰性成分适用于与人及较低等动物的组织接触而不会引起过度的毒性、刺激性、过敏性反应等。
在这里使用的术语“包含”系指各种各样的其他可相容的美容剂、药品及药物、以及惰性成分、封闭剂(occlusive agents)和美容赋形剂均可以在本发明的组合物和方法中联合应用,只要使用了关键的二元渗透促进赋形剂及美容剂或药物活性成分。因此,术语“包含”涵盖和包括了表征了以于此公开的方式应用基本成分的限制性更高的术语“由……组成”及“基本上由……组成”。
在这里使用的“患病部位”系指病理学、不适、感染、炎症或损伤的局部区域,以及将其直接包围的区域。
在这里使用的“施用部位”系指适用于通过机械缓释设备或涂抹器施用的部位,例如,耳后、手臂上、背部、足顶等等。
在这里使用的“渗透促进”系指在相同化学势下,当与其他组合物相比较时,本发明的二元渗透促进载体为所包含的活性物质提供了显著的经表皮、经指甲或经皮递送。相同的化学势这方面很重要,因为美容剂或药物在不同赋形剂中的溶解度的变化将势必影响它们透过皮肤或通过指甲的转运。因此,例如,如果药物在赋形剂A中可溶解的程度为24%,而在赋形剂B中可溶解的程度是4%,如果组合物在相同浓度百分比下而不是在相同化学势能下进行比较时,则溶解度较低的载体将表现出与溶解度较高赋形剂令人误解地相差6倍。为了评估渗透促进作用,确保化学势相同的最简单方法是采用药理学活性成分在各种赋形剂中的饱和溶液,或者具有相同饱和百分比的溶液。
在这里所使用的“基本上不含”系指本发明的渗透促进组合物包含少于约10%,优选地少于约3.5%,更优选地少于约1%,以及最优选地少于约0.5%的该术语所描述的任何特定化合物或化合物组中的成员。
除另有说明外,所有在这里使用的百分比和比例均基于组合物的总重量计算。
术语“活性成分”,“药物活性成分”,“药理活性成分”,“药物物质”,“药理物质”,“药物学或药理学活性物质”,“化学物质”以及“治疗剂”在这里使用时可相互替换。
本发明公开的组合物包含于二元赋形剂或载体中的能够产生或具有局部活性美容剂和/或药物学活性物质。载体或赋形剂包含极性脂质如卵磷脂或磷脂酰胆碱、一种选自于酯而另一种选自于液态二元及多元醇的两种可生物相容的有机溶剂、防腐剂、水、增稠剂和尿素,pH在约5.5~约7.5之间,优选地在约6.0~约7.0之间。本发明公开的组合物可另外包含了其他可以降低皮肤刺激性或改善它们美容外观或可接受性的任选的组分,例如色素、芳香剂、香水等。
所使用的典型极性脂质是卵磷脂和磷脂酰胆碱。优选地,卵磷脂或磷脂酰胆碱具有较高的质量,为药用级别。适当的卵磷脂及磷脂酰胆碱可作为大豆卵磷脂或大豆磷脂酰胆碱而购得。优选地,在本发明组合物中使用大豆卵磷脂。
可生物相容的有机酯溶剂可以是任何可以溶解极性脂质、美容剂或药物学活性化合物及尿素、且作为增溶赋形剂有助于转运美容剂或药物学活性化合物透过哺乳动物的皮肤的无毒的酯。
典型地,所述酯是脂肪酸单酯,其结构可以通过使一元醇的烷基基团置换脂肪酸的活性氢来获得,其中脂肪酸含有4~22个碳原子,更典型地含有8~18个碳原子,在一个特定例子中含有12个碳原子。所述脂肪酸可以是饱和或不饱和脂肪酸,更典型地是饱和脂肪酸。典型地,所述一元醇含有2~8个碳原子,更典型地含有2~5个碳原子,在一个特定例子中含有3个碳原子。
根据本发明的目的,可接受的酯包括但不局限于异丙酯。优选地,所述酯为肉豆蔻酸异丙酯或棕榈酸异丙酯,尤其优选肉豆蔻酸异丙酯。
所述可生物相容的有机二元及多元醇溶剂可以是任何可以溶解所述极性脂质和活性化合物、且作为增溶赋形剂有助于携带活性化合物通过哺乳动物的皮肤的无毒的二元或多元醇。根据本发明目的,可接受的二元和多元醇包括但不局限于二元和三元烷醇(di-and tri-alcohol alkanes)。典型地,所述醇含有3~8个碳原子,更典型含有3~5个碳原子,并且是饱和醇。优选地,所述多元醇是丙二醇或甘油,尤其优选丙二醇。
本发明公开组合物典型地包含约2~30重量%、更典型地4~10重量%的所述酯,以及约0.5~约20重量%、更典型地1~约20重量%、甚至更典型地1~约10重量%的所述醇。许多组合物包含约2~约20重量%、或者2~约10重量%的所述醇。根据本发明公开的组合物具有更低的皮肤刺激性。
在制备本发明公开的组合物的过程中,通常以约5∶1∶1~约1∶5∶5的质量比将极性脂质溶解在有机酯溶剂和二元或多元醇溶剂中。优选地,极性脂质和有机酯溶剂和多元醇溶剂在相同质量比下进行混合。因此,在本发明一个实施方案中,将大豆卵磷脂、肉豆蔻酸异丙酯及丙二醇在相同质量比下混合,直到卵磷脂均匀分布为止。这被称为溶剂-极性脂质混合物。
根据美容剂或药物学活性化合物的性质以及最终制剂所希望的特性,可在制剂中加入浓度在最终组合物质量的约1~20%之间的表面活性剂。已经发现,在包括聚阳离子型活性物质的制剂中,根据本发明公开,优选非离子或阳离子表面活性剂。另一方面,就其他活性成分而言,阴离子、阳离子或非离子型表面活性剂均相当可以接受。优选地,所述表面活性剂是能够与体内给药相容而不会引起不应有的副作用的表面活性剂。一种优选的表面活性剂是多库酯钠及其水溶性更佳的苯甲酸多库酯钠(docusate sodium benzoate)。其他适当的离子或非离子型表面活性剂比如聚山梨酯80、吐温80、多库酯钙、十四烷基三甲基溴化铵、五甘醇单十二烷基醚(pentaoxyethylene glycol monododecyl ether)或月桂醇醚硫酸三乙醇胺(triethanolamine laureth sulfate)。一旦表面活性剂完全分散于溶剂-极性脂质混合物后,即可加入美容剂或药物学活性化合物并使之溶解。
当然,美容剂或药物物质的剂量应根据已知的因素进行调整,如特定物质的美容剂或药物物质特征;年龄;接受者的健康状况及体重;症状的性质及程度;并存的治疗的类型;治疗频率;以及所希望的效果。可以预期,活性成分的每日剂量为每公斤(kg)体重约0.001~1000毫克(mg),更典型的剂量为0.1~约30mg/kg。
典型地,活性物质存在的量占递送系统及活性物质总量的约0.001~约30重量%,更典型地占约0.001~约20重量%,甚至更典型地占约0.5~12重量%。对于固体活性成分,容易的实现方法包括:向加热的表面活性剂-溶剂-极性脂质混合物等分试样中其量等于基于所述表面活性剂-溶剂-极性脂质质量的约0.01~30%的活性化合物,并混和至完全溶解。因此例如,将约1~20克的粉末状硝苯地平加入约100克的加热的大豆卵磷脂∶肉豆蔻酸异丙酯∶丙二醇为1∶0.5∶0.5的混合物中,并搅拌使之溶解。
一些示例性的活性物质包括:血管舒张剂,如硝基甘油和硝苯地平;抗微生物或抗真菌剂,如环吡酮、伊曲康唑、甲硝唑、咪康唑和烯丙胺如萘替芬和特比萘芬及其盐;细胞生长或增殖抑制剂如2-脱氧-D-葡萄糖;多胺转运抑制剂;多胺合成抑制剂;抗酶诱导剂;皮肤脱钙剂(decalcifying skin agent)如乳酸;抗炎剂如布洛芬和酮洛芬;局部麻醉剂如利多卡因;甾体抗炎化合物如可的松;肽、蛋白或激素,如血小板因子4;P物质拮抗剂(substance P antagonist)如辣椒素;肌肉松弛药如环苯扎林;抗炎止痛剂如双氯芬酸钠以及磷酸二酯酶抑制剂如sudenifil。
如果使用易挥发的活性物质或类蛋白活性物质,则通常不希望将活性物质加到相对较热的表面活性剂-溶剂-极性脂质混合物溶液中,因为这可能会使活性物质在最终制剂中的量减少。
通过具体实例表明,就活性物质硝酸甘油而言,所述活性物质可以以10%浓度的丙二醇溶液的形式应用,该溶液可以直接加到极性脂质-溶剂-表面活性剂混合物中。
用于治疗包括Raynaud′s病、糖尿病性感觉异常(diabetic paresthesia)及夜间小腿痉挛(night leg cramp)的外周动脉疾病的血管扩张剂的量典型地为组合物的约0.2~约1.8%。
用于治疗包括甲癣、脚癣、红斑痤疮及阴道霉菌病的皮肤及指甲的感染性疾病(infectious disease)的抗微生物剂或抗真菌剂的量典型地是约0.5~约12重量%。
用于治疗光线性角化病的细胞生长或增殖抑制剂的量为约0.001~约10重量%。
典型地,多胺转运抑制剂的量为约0.001~约5重量%。用于治疗自身免疫性疾病包括皮肤红斑狼疮、风疹、银屑癣及异位性皮肤病的多胺合成抑制剂的量典型地为约0.001~约5重量%。
用于治疗干性皮肤病包括干燥病、硬皮病及鱼鳞癣的皮肤脱钙剂如乳酸的量典型地为约0.5~约10重量%。
另外应当了解,为了同时治疗多于一种的疾病,可以使用两种或更多种的活性物质。例如,可使用两种或更多种活性物质来同时治疗炎症、自身免疫性疾病、感染性疾病和/或干性皮肤病。
在加入美容剂或药物学活性化合物后,可向表面活性剂-溶剂-极性脂质混合物中加入一定量的优选为增稠的水溶液形式的尿素。典型地,加入的尿素使得其浓度为最终组合物质量的约1~约15质量%,更典型地为约5~约10质量%。
所述增稠剂选自于常见的《国家处方集》(National Formulary)增稠剂,包括但不局限于具有适当聚合物重量的聚乙二醇、聚乙烯吡咯烷酮、卡波姆及甲基纤维素。增稠剂的量典型地为约0.05~约5重量%。
因此,在一个具体实例中,将约5克含有0.7%的卡波姆934的10%尿素水溶液加入到约100克的溶有药物学活性化合物的表面活性剂-溶剂-极性脂质混合物中。在一些情况下,所述药物学活性物质如果在加入尿素水溶液之后再加入则更易于溶解,而在另一些情况下则在加入尿素水溶液之前加入更易于溶解。无论如何,一旦本领域技术人员了解了本发明公开,他们就很容易根据待制备的特定制剂以及要溶解的特定美容剂或药物学活性化合物的溶解度特征来作出选择。如果活性物质是蛋白,则由于已知尿素的离液序列高特性(chaotropic properties)可使一些蛋白质变性,因此对于暴露于在本制剂中所使用的特定尿素浓度的蛋白质,有必要对其生物学活性的保留进行测试。本领域普通技术人员即可很容易地进行这种测定。
典型地,在配制上述含有美容剂或药物学活性物质的组合物时,将pH调节至约5.5~约7.5,更典型地调节至约6.0~7.0。例如,当组合物在最初倾向于呈酸性时,可通过加入碱如氢氧化钠水溶液及三乙醇胺实现pH的调节。不过,如果药物学活性物质倾向于产生碱性非常高的溶液,则可能需要加入酸来降低pH。这可以通过加入酸如柠檬酸或生物学缓冲液如碳酸钠或磷酸钾来实现。当组合物pH范围在约5.5~7.5之间时,制剂变稠并形成可用于局部给药的细滑的粘性凝胶。
在本发明公开的一个实施方案中,将组合物与血管舒张剂如硝酸甘油一同配制。这种制剂可迅速通过皮肤吸收,提供局部血管舒张作用,增加血流量,以及恢复血流量低的四肢的正常温度。在本发明的另一个实施方案中,将组合物与抗感染剂一同配制。所述制剂可迅速通过皮肤吸收,或以稍微慢些的速率透过指甲,以提供局部传递以杀死入侵的微生物如真菌或细菌。
一旦了解了本发明,本领域技术人员将能够通过常规实验以及采用本组合物所列举的元素制备出基本上包含任何活性成分或其组合的可广泛用于各种典型用途的特定凝胶。此外,应当了解,组合物可以包含助剂(auxiliary agent),包括那些常规地为本领域所知和/或使用的辅助剂,比如但不局限于防腐剂及芳香剂。
为了简化制备过程,可方便地制备出在这里称为“MQX-GEL”的第一种凝胶组合物,它可以用来加入供局部给药用的最终组合物制剂中的其他组分。有几种可能的MQX-GEL制剂。例如,一种制备MQX-GEL的方法包括:将卵磷脂有机凝胶(L.O.),为卵磷脂、肉豆蔻酸异丙酯和丙二醇1∶1∶1(m/m/m)的混合物,与LID油(L.O.和多库酯钠1∶1[m/m]的混合物)混合,将其他的表面活性剂和/或多库酯钠粉末溶解在该混合物中,然后加入增稠的尿素水溶液。
在一个MQX-GEL制剂的实施方案中,最终浓度为:L.O.=30%;多库酯钠=9%;尿素=5%;增稠剂=1%;以及水=55%。很容易改变这些比例,使得各种组分的最终量如下:L.O.=15~50%;多库酯钠和/或另一种表面活性剂=3~15%;尿素=1~15%;增稠剂=0.5~5%;以及水=40~65%。然后向MQX-GEL中加入增溶了的活性成分。可用于增溶活性成分的赋形剂包括:L.O.、丙二醇、肉豆蔻酸异丙酯、薄荷油、甘油和/或聚乙二醇。小心混合各种组分后即得均质混合物。
一旦上述制剂被制备后,那么制剂的使用就是一件简单的事情了,将制剂施用在希望发生药物学活性物质的经皮递送的患病部位即可。因此,就Raynaud′s现象而言,将含硝酸甘油的制剂擦抹在患病部位如手指上。当症状复发时,或者当在临近症状可能出现前用作预防治疗时,反复进行治疗。在根据本发明制备的制剂的应用中,Raynaud′s病患者的手指中的血流量在施用后5分钟内恢复正常。
在本发明的另一个方面中,配制抗真菌抗微生物化合物以用于向真菌感染的脚趾甲传递。在9个月的治疗中,遍布整个国家的医生及患者均证实真菌感染的几乎完全降低。将该结果与采用当前市售的含相同活性成分的局部制剂所得的结果进行比较,发现在相同时期内,市售制剂仅提供有限的真菌感染减少。
本发明公开的有机凝胶组合物的另一种适应症是治疗指甲银屑病(nail psoriasis)。对于这种适应症,可使用的活性成分包括一种或多种适用于治疗银屑病的化合物,根据化合物的类型,其量典型地在约0.0005%~约10%之间,比如皮质甾体(丙酸氯倍他索约0.005~约0.05%,倍他米松二丙酸盐约0.005~约0.05%,醋酸双氟拉松为约0.005~约0.05%,哈西奈德约0.01~约0.1%,去羟米松约0.005~约0.5%,曲安奈德约0.01~约0.5%),抗增殖性癌剂(antiproliferative cancer agent)(氟尿嘧啶、甲氨蝶呤、多胺合成和转运抑制剂、抗酶诱导剂、每种约0.05~约5.0%),类维生素A(retinoids)(他扎罗汀、acetretin),维生素D类似物(卡泊三烯);这些化合物的组合以及与抗真菌剂(例如咪康唑、环吡酮、特比萘芬,每种约0.5~约10%)的组合。
在本发明的另一方面中,例如通过包含杆菌肽或另一种适当的抗生素而制备含有抗菌剂的组合物。这使得抗菌剂可渗透到由于穿刺伤口导致的感染部位。
通常,本发明组合物是在含约0.001%~30重量%的活性化合物的浓度下提供的。此外,含有多种活性成分的组合物也涵盖在本发明公布的范围之内,且其可以被给药至在一个局部位点需要超过一种活性物质治疗的患者。因此,例如含有血管舒张剂及抗真菌剂的组合物,可同时缓解真菌感染并通过恢复患病部位的血流量和养分供给而有助于长期的缓解。
只要活性成分引起的局部反应或毒性尚未成为问题时,则可预期本发明公开的组合物可根据需要的频率局部施用。因此,例如,与给予容易代谢的无毒化合物如酮洛芬相比,当给予抗肿瘤化合物时可能需要更加严格监控的施用方案。就给药酮洛芬而言,可以允许需要这种治疗的人们根据所需的频率局部施用以减轻局部疼痛或炎症。
尽管上文说明中概括描述了如何制备和使用本发明公开的组合物和制剂,我们仍提供以下实施例以更具体地指出如何实施本发明。然而,应当明确了解的是,本文所附权利要求书所定义的本发明公开的范围并不局限在以下实施例的具体细节中。另外,应当了解的是,在所描述及要求保护的具体组合物中,活性成分及其他成分的百分比可以在至少相差10%的量的范围内而仍实现与所具体公开的组合物的相同的目的。
为了进一步举例说明本发明所公开的内容,提供以下非限制性的实施例。
实施例
实施例1-MQX-GEL的制备
*LID油是卵磷脂有机凝胶:多库酯钠按质量计1∶1的混合物。
**L.O.是卵磷脂、肉豆蔻酸异丙酯及丙二醇的1∶1∶1的混合物。
1.向L.O.中加入LID并加热。
2.加入多库酯钠粉末,搅拌至获得细滑的混合物。
3.使增稠剂和尿素完全溶解在水中,加热,然后在搅拌下加到步骤2的混合物中。
4.将pH调节至6.5~6.9之间。
MQX-GEL可以很容易根据如下步骤制备出来:
加热L.O.,在搅拌下将苯甲酸多库酯钠粉末加入加热的L.O.中,直至获得细滑溶液。将水加热,使增稠剂和尿素溶解在水中,然后使增稠的尿素溶液与含L.O.溶液的多库酯钠充分混合。得到均匀(consistent)、透明、琥珀色的凝胶,pH约为6.0。
制备MQX-GEL的另一种方法如下:
使LID和L.O.充分混合,制备加热的增稠剂和尿素的水溶液,将该溶液加到LID-L.O.溶液中。得到均匀、透明、琥珀色的凝胶,pH为约6.0。
实施例2-1.2%硝酸甘油凝胶的制备
1.将多库酯钠加入L.O.中并搅拌以获得澄清溶液。
2.将硝酸甘油(含10%活性物质的丙二醇)加入步骤1所得的溶液中。
3.将尿素加入蒸馏水中,加热并搅拌以获得均匀溶液。
4.将卡波姆934和甲基纤维素加入步骤3所得的尿素水溶液中并增稠该溶液。
5.将步骤2所得的含活性成分的卵磷脂有机凝胶与步骤4所得的增稠的尿素水溶液合并,以形成一种均匀的混合物。
6.用稀NaOH水溶液调节pH至6.5,以形成极佳的稠的凝胶。
实施例3-0.5%硝酸甘油凝胶的制备
采用与实施例2中描述的相同的方法混合各组分。
MQX-GEL也可以采用卵磷脂有机凝胶中三种组分的其他比例来制备。在以下实施例中,卵磷脂有机凝胶(L.O.#2)的比例,是卵磷脂、肉豆蔻酸异丙酯和丙二醇1∶0.9∶0.1(m/m/m)的混合物,与LID油(L.O.#2与多库酯钠1∶1[m/m]的混合物),将另外的表面活性剂和/或多库酯钠粉末溶液该混合物中,然后加入增稠的尿素水溶液。
在MQX-GEL制剂的该实施方案中,最终浓度为:L.O.#2=25%;多库酯钠=10%;尿素=10%;增稠剂=1%;以及水=54%。这些比例也可容易地加以改变,使得每种成分的最终量如下:L.O.#2=15~50%;多库酯钠和/或另一种表面活性剂=3~15%;尿素=1~15%;增稠剂=0.5~5%;以及水=40~65%。然后可以将增溶的活性成分加到MQX-GEL中。可用于增溶活性成分的赋形剂包括:L.O.#2、丙二醇、肉豆蔻酸异丙酯、薄荷油、甘油和/或聚乙二醇。然后小心混和各种成分制得均匀的混合物。
实施例4-另一种1.2%硝酸甘油凝胶的制备
采用与实施例2中所用的相同的方法混合各组分。
实施例5-0.5%硝酸甘油凝胶的制备
该实施例中采用与前述实施例中相同的制备方法。
实施例6-8.0%环吡酮凝胶的制备
1.将多库酯钠加入L.O.#2中并搅拌以获得澄清溶液。
2.将环吡酮加至步骤1的溶液中。
3.将尿素加到蒸馏水中,加热并搅拌以获得均匀的溶液。
4.将卡波姆934和甲基纤维素加至步骤3的尿素水溶液中,并使之增稠。
5.将步骤2所得的含活性物质的卵磷脂有机凝胶与步骤4所得的增稠的尿素水溶液结合,以形成均匀的混合物。
6.用稀的NaOH水溶液调节pH至6.5,以形成极佳的稠的凝胶。
实施例7-15.0%乳酸凝胶的制备
采用与实施例6中相同的制备方法。
实施例8-8%环吡酮,1%硝酸甘油凝胶的制备
1.将多库酯钠加入L.O.#2中并搅拌以获得澄清溶液。
2.将环吡酮和10%硝酸甘油的丙二醇溶液加到步骤1溶液中。
3.向蒸馏水中加入尿素,加热并搅拌以获得均匀的溶液。
4.将卡波姆934和甲基纤维素加到步骤3的尿素水溶液中,并使之增稠。
5.将步骤2所得的含有活性物质的卵磷脂有机凝胶与步骤4所得的增稠的尿素水溶液结合,以形成均匀的混合物。
6.用稀的NaOH水溶液调节pH至6.5,以形成极佳的稠的凝胶。
实施例9-10%布洛芬,0.5%硝酸甘油凝胶的制备
1.向L.O.#2中加入多库酯钠和布洛芬,搅拌以获得澄清溶液。
2.将10%硝酸甘油的丙二醇溶液加到步骤1溶液中。
3.向蒸馏水中加入尿素,加热并搅拌以获得均匀的溶液。
4.将卡波姆934和甲基纤维素加到步骤3的尿素水溶液中,并使之增稠。
5.将步骤2所得的含有活性物质的卵磷脂有机凝胶与步骤4所得的增稠的尿素水溶液结合,以形成均匀的混合物。
6.用稀的NaOH水溶液调节pH至6.5,以形成极佳的稠的凝胶。
实施例10-5.0%2-脱氧-D-葡萄糖凝胶的制备
1.向L.O.#2中加入多库酯钠,并搅拌以得到澄清的溶液。
2.将2-脱氧-D-葡萄糖加到步骤1的溶液中。
3.向蒸馏水中加入尿素,加热并搅拌以得到均匀的溶液。
4.加入卡波姆934和甲基纤维素,以增稠步骤3的尿素水溶液。
5.将步骤2所得的含有活性物质的卵磷脂有机凝胶与步骤4所得的增稠的尿素水溶液结合,以形成均匀的混合物。
6.用稀的NaOH水溶液调节pH至6.5,以形成极佳的稠的凝胶。
可依照实施例6的方法制备的可用于治疗甲癣的其他制剂列出如下:
实施例11-2%咪康唑凝胶制剂
根据实施例6的方法制备包含2%硝酸咪康唑、48.5%蒸馏水、10%尿素、0.45%卡波普、8.8%肉豆蔻酸异丙酯、9.8%卵磷脂、19.1%多库酯钠、0.4%聚山梨酯80、1.0%丙二醇、0.8%三乙醇胺及0.12%1.0NNaOH的制剂。
实施例12-2%萘替芬凝胶制剂
根据实施例6的方法制备包含2%盐酸萘替芬、48.5%蒸馏水、10%尿素、0.45%卡波普、8.8%肉豆蔻酸异丙酯、9.8%卵磷脂、19.1%多库酯钠、0.4%聚山梨酯80、1.0%丙二醇、0.8%三乙醇胺及0.12%1.0NNaOH的制剂。
实施例13-5%特比萘芬凝胶制剂
根据实施例6的方法制备包含5%盐酸特比萘芬、45.5%蒸馏水、9.75%尿素、0.7%卡波普、8.8%肉豆蔻酸异丙酯、9.8%卵磷脂、19.1%多库酯钠、0.4%聚山梨酯80、1.0%丙二醇、0.8%三乙醇胺及0.12%1.0NNaOH的制剂。
实施例14-2%环吡酮凝胶制剂
根据实施例6的方法制备包含2%环吡酮胺、48.5%蒸馏水、10%尿素、0.45%卡波普、8.8%肉豆蔻酸异丙酯、9.8%卵磷脂、19.1%多库酯钠、0.4%聚山梨酯80、1.0%丙二醇、0.8%三乙醇胺及0.12%1.0N NaOH的制剂。
实施例15-含4%环吡酮凝胶的制剂
根据实施例6的方法制备包含4%环吡酮胺、46.5%蒸馏水、10%尿素、0.45%卡波普、8.8%肉豆蔻酸异丙酯、9.8%卵磷脂、19.1%多库酯钠、0.4%聚山梨酯80、1.0%丙二醇、0.8%三乙醇胺及0.12%1.0N NaOH的制剂。
实施例16-用于治疗指甲银屑病的0.001%双丙酸倍他米松和2.5%甲氨蝶呤制剂
根据实施例11的方法制备制剂,其中的2%咪康唑用0.001%双丙酸倍他米松及2.5%甲氨蝶呤来代替。
实施例17-用于治疗指甲银屑病的0.001%双丙酸倍他米松、2.5%甲氨蝶呤和2%咪康唑制剂
根据实施例11的方法制备制剂,其中的2%咪康唑用0.001%双丙酸倍他米松、2.5%甲氨蝶呤和2%咪康唑来代替。
在前面的描述中阐明并描述了本发明的公开。此外,本发明公开只展示和描述了所述公开的优选的实施方案,但是,如前所述,应当了解的是,能够根据前述教导和/或相关领域的技术或知识而在此处所表述的构思的范围之内进行改变或修改。上文所描述的实施方案进一步用于解释实施本发明的已知的最佳模式,并使其他本领域技术人员能够以所述或其他实施方案的形式、并可根据在这里所公开的特定应用或用途所需加以种种修改来利用本发明公开。相应地,并非用所述说明将本发明限制于这里所公开的形式。同时,所附的权利要求应被解释为包括了可替代的实施方案。
所有在本说明书中引用的出版物、专利及专利申请均并入此处作为参考,并且在所有情况下均如同分别明确地指出将各单独的出版物、专利或专利申请并入此处作为参考。如果出现不一致情况,以本发明公开为准。
Claims (37)
1.一种适用于递送至少一种美容剂或药物物质或两者通过哺乳动物皮肤或指甲的组合物,其包含两种可生物相容的有机溶剂、一种极性脂质、至少一种或多种选自于多库酯钠、苯甲酸多库酯钠以及多库酯钙的表面活性剂、40-65重量%水、尿素及增稠剂;其中所述有机溶剂包含酯和二元醇和/或多元醇;并且其中所述组合物包含2至~30%的所述酯和0.5~20%的所述二元醇和/或多元醇,并且其中所述酯为含有4~22个碳原子的脂肪酸的异丙酯。
2.如权利要求1的组合物,其中所述酯是肉豆蔻酸异丙酯或棕榈酸异丙酯中的至少一种。
3.如权利要求1的组合物,其中所述酯是肉豆蔻酸异丙酯。
4.如权利要求1的组合物,其中所述二元或多元醇是含有3~8个碳原子的烷醇。
5.如权利要求1~3中任一项的组合物,其中所述醇是丙二醇或甘油中的至少一种。
6.如权利要求1~3中任一项的组合物,其中所述醇是丙二醇。
7.如权利要求1的组合物,其中所述极性脂质是卵磷脂或磷脂酰胆碱中的至少一种。
8.如权利要求1的组合物,其中所述增稠剂选自于聚乙二醇、甲基纤维素及卡波姆。
9.如权利要求1的组合物,其中所述极性脂质的量为10~30重量%;所述表面活性剂的量为0.5~15重量%,尿素的量为1~15重量%,以及所述增稠剂的量为0.05~5重量%。
10.如权利要求1的组合物,其中所述醇是丙二醇,所述增稠剂选自于聚乙二醇、甲基纤维素及卡波姆,所述极性脂质是卵磷脂或磷脂酰胆碱中的至少一种,所述极性脂质的量为10~30重量%,所述表面活性剂的量为0.5~15重量%,尿素的量为1~15重量%,以及所述增稠剂的量为0.05~5重量%。
11.如权利要求1的组合物,其另外包含至少一种美容剂或药物物质或两者。
12.如权利要求11的组合物,其中所述美容剂或药物物质或两者的量为0.001~30重量%。
13.如权利要求11的组合物,其具有5.5~7.5的pH。
14.如权利要求13的组合物,其中所述pH是6~7。
15.如权利要求1的组合物,其另外包含至少0.2~1.8%的血管舒张剂。
16.如权利要求15的组合物,其中所述血管舒张剂是硝酸甘油。
17.如权利要求1的组合物,其另外包含1~12%的抗微生物剂。
18.如权利要求17的组合物,其中所述抗微生物剂选自于环吡酮、咪康唑、伊曲康唑、甲硝唑、烯丙胺以及它们的混合物及药物学可接受的盐。
19.如权利要求17的组合物,其中所述抗微生物剂选自于环吡酮、咪康唑、特比萘芬、萘替芬以及它们的混合物及盐。
20.如权利要求1的组合物,其另外包含0.001~10.0%的细胞生长或增殖抑制剂。
21.如权利要求19的组合物,其中所述的抑制剂是2-脱氧-D-葡萄糖。
22.如权利要求1的组合物,其另外包含0.001~5.0%的多胺转运抑制剂或0.005~5.0%的多胺合成抑制剂。
23.如权利要求1的组合物,其另外包含0.001~5.0%的抗酶诱导剂。
24.如权利要求1的组合物,其另外包含0.5~10%的皮肤脱钙剂。
25.如权利要求24的组合物,其中所述皮肤脱钙剂是乳酸。
26.如权利要求1的组合物,其另外包含有效量的一种或多种银屑病治疗剂。
27.如权利要求26的组合物,其中所述银屑病治疗剂包括倍他米松二丙酸盐或甲氨喋呤或两者。
28.如权利要求26的组合物,其另外包含咪康唑。
29.如权利要求1的组合物,其另外包含至少两种活性成分。
30.如权利要求11的组合物在制备用于递送活性物质进入及通过人或动物表皮组织的药物中的应用。
31.如权利要求18的组合物在制备用于治疗甲癣的药物中的应用。
32.如权利要求19的组合物在制备用于治疗甲癣的药物中的应用。
33.一种制备如权利要求1的组合物的方法,其包括:
a.使极性脂质至少溶解在两种可生物相容的有机溶剂中,所述溶剂包含至少一种酯和至少一种二元或多元醇,其中所述酯为含有4~22个碳原子的脂肪酸的异丙酯;
b.向步骤(a)的组合物中加入一种或多种表面活性剂,其中所述表面活性剂选自于多库酯钠、苯甲酸多库酯钠以及多库酯钙;
c.使药物学活性化合物溶解在步骤(b)的溶剂-极性脂质、表面活性剂混合物中;
d.向水中加入尿素及增稠剂;以及
e.合并c和d中的组合物,并根据需要调节pH至5.5~7.5。
34.一种制备如权利要求1的组合物的方法,其包括:
a.使极性脂质至少溶解在两种可生物相容的有机溶剂中,所述溶剂包含至少一种酯和至少一种二元或多元醇,其中所述酯为含有4~22个碳原子的脂肪酸的异丙酯;
b.向步骤(a)的组合物中加入一种或多种表面活性剂,其中所述表面活性剂选自于多库酯钠、苯甲酸多库酯钠以及多库酯钙;
c.向水中加入尿素和增稠剂;
d.使药物学活性化合物溶解在增稠的尿素水溶液中;以及
e.合并(b)和(d)中的组合物,并根据需要调节pH至5.5~7.5。
35.如权利要求26的组合物在制备用于治疗指甲银屑病的药物中的应用。
36.如权利要求28的组合物在制备用于治疗指甲银屑病的药物中的应用。
37.另外含有有效量的抗菌剂的如权利要求1的组合物在制备用于治疗患者感染的药物中的应用。
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US10/960,516 US7740875B2 (en) | 2004-10-08 | 2004-10-08 | Organo-gel formulations for therapeutic applications |
US11/066,485 | 2005-02-28 | ||
US11/066,485 US20060078579A1 (en) | 2004-10-08 | 2005-02-28 | Organo-gel formulations for therapeutic applications |
US11/150,254 US20060078580A1 (en) | 2004-10-08 | 2005-06-13 | Organo-gel formulations for therapeutic applications |
US11/150,254 | 2005-06-13 | ||
PCT/US2005/036064 WO2006042059A1 (en) | 2004-10-08 | 2005-10-11 | Organo-gel formulations for therapeutic applications |
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Families Citing this family (41)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7740875B2 (en) * | 2004-10-08 | 2010-06-22 | Mediquest Therapeutics, Inc. | Organo-gel formulations for therapeutic applications |
US20060078580A1 (en) * | 2004-10-08 | 2006-04-13 | Mediquest Therapeutics, Inc. | Organo-gel formulations for therapeutic applications |
EP2526928B1 (en) | 2007-02-05 | 2018-12-26 | Biophile Corporation, Ltd | Increased effectiveness of allylamine drug compounds |
US20090191138A1 (en) * | 2008-01-30 | 2009-07-30 | Mediquest Therapeutics, Inc. | Novel topical formulations for improving the appearance of nails |
US20100016446A1 (en) * | 2008-07-21 | 2010-01-21 | Sylvia Gonda | Stable water-based topical pharmaceutical creams and methods of making and using same |
WO2010047831A1 (en) * | 2008-10-23 | 2010-04-29 | Nycomed Us Inc. | Stable metronidazole gel formulations |
EP2355803A4 (en) * | 2008-11-14 | 2012-04-25 | Archer Daniels Midland Co | COMPOSITIONS AND METHODS FOR ORGANOGEL PRODUCTION |
KR101656121B1 (ko) | 2010-03-17 | 2016-09-08 | 노바리크 게엠베하 | 안압 증가를 치료하기 위한 약학 조성물 |
JP5901617B2 (ja) | 2010-05-14 | 2016-04-13 | アーチャー−ダニエルズ−ミッドランド カンパニー | オルガノゲルを含む食品組成物 |
EP2444063A1 (en) | 2010-10-20 | 2012-04-25 | Novaliq GmbH | Liquid pharmaceutical compositions for the delivery of active ingredients |
EP2462921A1 (en) | 2010-11-11 | 2012-06-13 | Novaliq GmbH | Liquid pharmaceutical compositions for the treatment of a posterior eye disease |
CN103596554A (zh) | 2011-05-25 | 2014-02-19 | 诺瓦利克有限责任公司 | 基于半氟化烷烃类的外用药物组合物 |
KR101773648B1 (ko) * | 2011-05-25 | 2017-08-31 | 노바리크 게엠베하 | 조갑에 투여를 위한 제약학적 조성물 |
PL2806886T3 (pl) | 2012-01-23 | 2017-08-31 | Novaliq Gmbh | Stabilizowane kompozycje białkowe oparte na semifluorowanych alkanach |
EP3488847B1 (en) | 2012-09-12 | 2023-11-08 | Novaliq GmbH | Semifluorinated alkane compositions |
CN106511322B (zh) | 2012-09-12 | 2021-09-17 | 诺瓦利克有限责任公司 | 包含半氟化烷烃的混合物的组合物 |
US9433680B2 (en) | 2013-01-31 | 2016-09-06 | Merz Pharmaceuticals, Llc | Topical compositions and methods for making and using same |
US9452173B2 (en) | 2013-01-31 | 2016-09-27 | Merz Pharmaceuticals, Llc | Topical compositions and methods for making and using same |
US9446131B2 (en) | 2013-01-31 | 2016-09-20 | Merz Pharmaceuticals, Llc | Topical compositions and methods for making and using same |
US8778365B1 (en) | 2013-01-31 | 2014-07-15 | Merz Pharmaceuticals, Llc | Topical compositions and methods for making and using same |
BR112015024203A2 (pt) | 2013-03-22 | 2017-07-18 | Chemyunion Quim Ltda | processos de estruturação das composições cosméticas |
RU2715103C2 (ru) * | 2013-05-03 | 2020-02-27 | Липидор Аб | Местная композиция и носитель для введения фармацевтически или косметически активных ингредиентов |
MX370207B (es) | 2013-07-23 | 2019-12-05 | Novaliq Gmbh | Composiciones estabilizadas de anticuerpos. |
KR20170023776A (ko) | 2014-02-26 | 2017-03-06 | 루마 세러퓨틱스 인코포레이티드 | 자외선 광선 치료 장치들 및 방법들 |
WO2016011104A1 (en) * | 2014-07-18 | 2016-01-21 | Gensco Laboratories, Llc | Homeopathic topical gel for transdermal delivery of colchicine formulations and method of use |
PL3355990T3 (pl) | 2015-09-30 | 2019-11-29 | Novaliq Gmbh | Semifluorowane związki oraz ich kompozycje |
JP6642935B2 (ja) | 2015-09-30 | 2020-02-12 | ノバリック ゲーエムベーハー | 眼投与用の半フッ素化化合物 |
EP3413852A4 (en) | 2016-02-09 | 2019-07-31 | Luma Therapeutics, Inc. | METHOD, COMPOSITIONS AND DEVICES FOR TREATING PSORIASIS BY PHOTOTHERAPY |
JP2019520357A (ja) | 2016-06-23 | 2019-07-18 | ノバリック ゲーエムベーハー | 局所投与方法 |
AU2017329772B2 (en) | 2016-09-22 | 2023-02-02 | Novaliq Gmbh | Pharmaceutical compositions for use in the therapy of blepharitis |
ES2965677T3 (es) | 2016-09-23 | 2024-04-16 | Novaliq Gmbh | Composiciones oftálmicas que comprenden ciclosporina |
WO2018193093A1 (en) | 2017-04-21 | 2018-10-25 | Novaliq Gmbh | Iodine compositions |
WO2018206656A1 (en) | 2017-05-12 | 2018-11-15 | Novaliq Gmbh | Pharmaceutical compositions comprosing semifluorinated alkanes for the treatment of contact lense-related conditions |
KR20200059272A (ko) | 2017-09-27 | 2020-05-28 | 노바리크 게엠베하 | 안구 질환의 치료에서의 사용을 위한 라타노프로스트를 포함하는 안과적 조성물 |
WO2019068763A1 (en) | 2017-10-04 | 2019-04-11 | Novaliq Gmbh | OPHTHALMIC COMPOSITIONS COMPRISING F6H8 |
CA3091308A1 (en) | 2018-03-02 | 2019-09-06 | Novaliq Gmbh | Pharmaceutical compositions comprising nebivolol |
CN109085261A (zh) * | 2018-07-24 | 2018-12-25 | 株洲千金药业股份有限公司 | 一种检测甲硝唑凝胶皮肤透过性的方法 |
PL3856128T3 (pl) | 2018-09-27 | 2023-10-16 | Dermaliq Therapeutics, Inc. | Formulacja filtra przeciwsłonecznego do stosowania miejscowego |
CA3112031A1 (en) | 2018-10-12 | 2020-04-16 | Novaliq Gmbh | Ophthalmic composition for treatment of dry eye disease |
KR102072946B1 (ko) | 2019-08-06 | 2020-02-03 | 주식회사 씨엔엘바이오텍 | 조갑진균증 예방 또는 치료용 조성물 |
US11384182B2 (en) | 2019-12-11 | 2022-07-12 | City University Of Hong Kong | Supramolecular polymer composition and method of preparation thereof |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6316428B1 (en) * | 1995-03-10 | 2001-11-13 | Wilson Trafton Crandall | Topical moisturizing composition and method |
Family Cites Families (92)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3883545A (en) | 1968-08-31 | 1975-05-13 | Hoechst Ag | Certain 1-hydroxy-2-pyridones |
US4021573A (en) | 1974-04-22 | 1977-05-03 | The Regents Of The University Of California | Psoriasis treatment with retinoic acid analogs |
US3957971A (en) | 1974-07-29 | 1976-05-18 | Lever Brothers Company | Moisturizing units and moisturizing compositions containing the same |
US4036970A (en) | 1975-07-28 | 1977-07-19 | Syntex (U.S.A.) Inc. | Imidazol-1-yl propane derivatives |
DE19975055I1 (de) | 1979-08-22 | 2000-01-27 | Novartis Ag | Propenylamine Verfahren zu ihrer Herstellung sie enthaltende pharmazeutische Zusammensetzungen und ihre Verwending als Arzneimittel |
US5132459A (en) | 1979-08-22 | 1992-07-21 | Sandoz Ltd. | Propenylamines, processes for their production, pharmaceutical compositions containing them and their use as pharmaceuticals |
FR2502951B1 (fr) | 1981-04-06 | 1985-12-06 | Sandoz Sa | Compositions pharmaceutiques topiques sous forme d'une micro-emulsion |
DE3225706C2 (de) | 1982-07-09 | 1984-04-26 | A. Nattermann & Cie GmbH, 5000 Köln | Flüssige Wirkstofformulierungen in Form von Konzentraten für Mikroemulsionen |
EP0191269B1 (en) | 1984-11-22 | 1991-03-06 | Sandoz Ag | Novel homopropargylamines |
US5030625A (en) | 1984-11-22 | 1991-07-09 | Sandoz Ltd. | Anti-fungal homopropargylamine compounds |
US4895727A (en) | 1985-05-03 | 1990-01-23 | Chemex Pharmaceuticals, Inc. | Pharmaceutical vehicles for exhancing penetration and retention in the skin |
US4788061A (en) | 1985-07-05 | 1988-11-29 | Shore Ronald N | Extended occlusive treatment of skin disorders |
US4764381A (en) | 1985-12-06 | 1988-08-16 | Key Pharmaceuticals, Inc. | Percutaneous penetration enhancer of oleic acid and 2-ethyl-1, 3-hexanediol |
DE3544983A1 (de) | 1985-12-19 | 1987-06-25 | Hoechst Ag | Antimykotisch wirksamer nagellack |
US5525635A (en) | 1986-02-04 | 1996-06-11 | Moberg; Sven | Pharmaceutical compositions containing propylene glycol and/or polyethylene glycol and urea as active main components and use thereof |
US4751245A (en) | 1986-06-25 | 1988-06-14 | E. R. Squibb & Sons, Inc. | Antifungal derivatives of N-(6,6-dimethyl-2-hepten-4-ynyl)-1-naphthalenemethanamine and method of using same |
US4782059A (en) | 1986-09-29 | 1988-11-01 | Merck & Co., Inc. | Method of controlling mycotic infections and compositions therefor |
US5389677B1 (en) | 1986-12-23 | 1997-07-15 | Tristrata Inc | Method of treating wrinkles using glycalic acid |
US4940586A (en) | 1987-02-26 | 1990-07-10 | Alza Corporation | Skin permeation enhancer compositions using sucrose esters |
DE3720147A1 (de) | 1987-06-16 | 1988-12-29 | Hoechst Ag | Antimykotisch wirksamer nagellack sowie verfahren zu dessen herstellung |
CH681427A5 (zh) | 1987-07-01 | 1993-03-31 | Zambon Spa | |
US5051260A (en) | 1987-07-16 | 1991-09-24 | The Regents Of The University Of California | Method and composition for enhancing the cutaneous penetration of pharmacologically active agents |
US5045317A (en) | 1987-07-16 | 1991-09-03 | The Regents Of The University Of California | Enhancing the cutaneous penetration of pharmacologically active agents |
US4920112A (en) | 1988-04-18 | 1990-04-24 | Merck & Co., Inc. | Fungicidal compositions and method |
US5181914A (en) | 1988-08-22 | 1993-01-26 | Zook Gerald P | Medicating device for nails and adjacent tissue |
FR2646603B1 (fr) | 1989-05-03 | 1991-07-12 | Oreal | Composition nettoyante |
US5219877A (en) | 1989-09-25 | 1993-06-15 | Bristol-Myers Squibb Company | Lauryl alcohol as skin penetration enhancer for topical imidazole agents |
JP3116364B2 (ja) | 1989-10-02 | 2000-12-11 | 萬有製薬株式会社 | エンイン誘導体の製造法 |
US5356633A (en) | 1989-10-20 | 1994-10-18 | Liposome Technology, Inc. | Method of treatment of inflamed tissues |
US5741513A (en) | 1990-02-08 | 1998-04-21 | A. Natterman & Cie. Gmbh | Alcoholic aqueous gel-like phospholipid composition, its use and topical preparations containing it |
ES2060365T3 (es) | 1990-02-08 | 1994-11-16 | Nattermann A & Cie | Composicion acuosa de fosfolipidos en forma de gel que contiene alcohol, su utilizacion y preparaciones topicas que la contienen. |
GB9027433D0 (en) | 1990-12-18 | 1991-02-06 | Merrell Dow Pharma | Anti-herpes castanospermine esters |
FR2673537B1 (fr) | 1991-03-08 | 1993-06-11 | Oreal | Utilisation d'agents de penetration hydrophiles dans les compositions dermatologiques pour le traitement des onychomycoses, et compositions correspondantes. |
HU223343B1 (hu) | 1991-05-20 | 2004-06-28 | Novartis Ag. | Allil-amin-származékot tartalmazó gyógyászati készítmények és eljárás azok előállítására |
US6005001A (en) | 1991-05-20 | 1999-12-21 | Novartis Ag (Formerly Sandoz Ag) | Pharmaceutical composition |
US5985860A (en) | 1992-06-03 | 1999-11-16 | Toppo; Frank | System for transdermal delivery of pain relieving substances |
US5318960A (en) | 1992-06-03 | 1994-06-07 | Frank Toppo | System for transdermal delivery of pain relieving substances |
US5750141A (en) * | 1993-04-08 | 1998-05-12 | The University Of Queensland | Administration of vaso-active agent and therapeutic agent |
JP2545729B2 (ja) | 1993-05-11 | 1996-10-23 | 工業技術院長 | メトトレキセート誘導体とピラン共重合体の高分子結合体及びその製造方法 |
US5698589A (en) | 1993-06-01 | 1997-12-16 | International Medical Innovations, Inc. | Water-based topical cream containing nitroglycerin and method of preparation and use thereof |
DE4337945A1 (de) | 1993-11-06 | 1995-05-11 | Labtec Gmbh | Pflaster zur Behandlung von Nagelmykosen |
US5514698A (en) | 1994-03-21 | 1996-05-07 | Ortho Pharmaceutical Corporation | Antifungal vaginal cream composition |
US5925669A (en) | 1994-03-22 | 1999-07-20 | Molecular/Structural Bio Technologies, Inc. | Carrier compositions for anti-neoplastic drugs |
JP3081766B2 (ja) | 1994-05-06 | 2000-08-28 | 東興薬品工業株式会社 | 角質貯留型抗真菌外用組成物 |
ATE196082T1 (de) | 1994-05-27 | 2000-09-15 | Cellegy Pharma Inc | Stickstoffoxyd abgebendes präparat zur behandlung von analen erkrankungen |
US5696164A (en) | 1994-12-22 | 1997-12-09 | Johnson & Johnson Consumer Products, Inc. | Antifungal treatment of nails |
JPH11502509A (ja) | 1995-01-16 | 1999-03-02 | コモンウェルス サイエンティフィック アンド インダストリアル リサーチ オーガニゼーション | 治療用化合物 − 脂肪酸抱合体 |
US5639740A (en) | 1995-03-10 | 1997-06-17 | Crandall; Wilson Trafton | Topical moisturizing composition and method |
US5654337A (en) * | 1995-03-24 | 1997-08-05 | II William Scott Snyder | Topical formulation for local delivery of a pharmaceutically active agent |
GB9509631D0 (en) | 1995-05-12 | 1995-07-05 | Sandoz Ltd | Antifungal combination |
US5652256A (en) | 1995-06-06 | 1997-07-29 | Knowles; W. Roy | Topical composition for fungal treatment |
EP0866683A4 (en) | 1995-09-14 | 1999-01-07 | Sorenson Pharmaceutical Inc | MEANS AND METHOD FOR TREATING DISEASE NAILS |
NZ280065A (en) | 1995-09-20 | 1998-04-27 | Apotex Inc | Preparation of n-alkyl-n-(1-naphthylmethyl)alk-2-en-4-ynylamine derivatives |
US7094422B2 (en) | 1996-02-19 | 2006-08-22 | Acrux Dds Pty Ltd. | Topical delivery of antifungal agents |
US20040039030A1 (en) | 1996-09-27 | 2004-02-26 | Hoechst Akeengesellschaft | Use of 1-hydroxy-2-pyridones for the treatment of seborrheic dermatitis |
US5891472A (en) | 1996-11-19 | 1999-04-06 | Meri Charmyne Russell | Treatment of equine laminitis |
US5807957A (en) * | 1996-12-23 | 1998-09-15 | Macrochem Corporation | Cationic film-forming polymer compositions, and use thereof in topical agents delivery system and method of delivering agents to the skin |
US6372234B1 (en) | 1997-05-27 | 2002-04-16 | Sembiosys Genetics Inc. | Products for topical applications comprising oil bodies |
AU756136B2 (en) | 1997-06-23 | 2003-01-02 | Queen's University At Kingston | Microdose therapy |
JP4044728B2 (ja) | 1997-07-15 | 2008-02-06 | メディクエスト セラピューティックス インク | 治療および診断薬剤としての新規なポリアミンアナログ |
US5993790A (en) | 1997-08-04 | 1999-11-30 | Pedinol Pharmacal Inc. | Nail evulsion compositions and method for evulsing nails and treating nail and nail bed infections |
US5935577A (en) | 1998-01-23 | 1999-08-10 | Autoimmune Inc. | Treatment of autoimmune disease using tolerization in combination with methotrexate |
ATE269067T1 (de) | 1998-04-17 | 2004-07-15 | Bertek Pharm Inc | Topische formulierungen zur behandlung von nagel pilzerkrankungen |
US6231889B1 (en) | 1998-09-21 | 2001-05-15 | Chronorx, Llc | Unit dosage forms for the treatment of herpes simplex |
US6159977A (en) | 1998-11-16 | 2000-12-12 | Astan, Inc. | Therapeutic anti-fungal nail preparation |
US6248363B1 (en) | 1999-11-23 | 2001-06-19 | Lipocine, Inc. | Solid carriers for improved delivery of active ingredients in pharmaceutical compositions |
US6309663B1 (en) | 1999-08-17 | 2001-10-30 | Lipocine Inc. | Triglyceride-free compositions and methods for enhanced absorption of hydrophilic therapeutic agents |
US6720001B2 (en) | 1999-10-18 | 2004-04-13 | Lipocine, Inc. | Emulsion compositions for polyfunctional active ingredients |
US6558695B2 (en) * | 1999-12-16 | 2003-05-06 | Dermatrends, Inc. | Topical and transdermal administration of peptidyl drugs using hydroxide releasing agents as permeation enhancers |
US6632843B1 (en) | 2000-02-01 | 2003-10-14 | Mark Friedman | Treatment of bruxism |
DE10011081A1 (de) | 2000-03-09 | 2001-09-13 | Aventis Pharma Gmbh | Antiinfektive Wirkstoffkombinationen und ihre Verwendung zur topischen Behandlung von Pilzerkrankungen der Fuß- und Fingernägel |
US6485740B1 (en) | 2000-03-14 | 2002-11-26 | Yutoku Pharmaceutical Ind., Co., Ltd. | Transdermal methotrexate preparations |
IT1318425B1 (it) | 2000-03-24 | 2003-08-25 | D B P Dev Biotechnological Pro | Impiego del resveratrolo per il trattamento di eczema desquamativo,acne e psoriasi. |
US6281239B1 (en) | 2000-04-12 | 2001-08-28 | Bradley Pharmeaceuticals, Inc. | Method of treating onychomycosis |
CA2440389A1 (en) | 2001-03-09 | 2002-10-03 | Ortho-Mcneil Pharmaceutical, Inc. | Aminopyrrolidine sulfonamides as serine protease inhibitors |
GB0108082D0 (en) | 2001-03-30 | 2001-05-23 | Novartis Consumer Health Sa | Topical composition |
US6638981B2 (en) * | 2001-08-17 | 2003-10-28 | Epicept Corporation | Topical compositions and methods for treating pain |
US20030091540A1 (en) | 2001-10-16 | 2003-05-15 | Nawaz Ahmad | Compositions and methods for delivering antibacterial, antifungal and antiviral ointments to the oral, nasal or vaginal cavity |
AU2002364893A1 (en) | 2001-10-22 | 2003-06-17 | University Of Mississippi | Delivery of medicaments to the nail |
US6986896B2 (en) | 2002-03-20 | 2006-01-17 | Bradley Pharmaceuticals, Inc. | Method of treating fungal conditions of the skin |
US6673842B2 (en) | 2002-03-20 | 2004-01-06 | Bradley Pharmaceuticals, Inc. | Method of treating onychomycosis |
US6743417B2 (en) | 2002-04-22 | 2004-06-01 | Bradley Pharmaceuticals, Inc. | Method of treating onychomycosis with urea and an antioxidant |
US6846837B2 (en) | 2002-06-21 | 2005-01-25 | Howard I. Maibach | Topical administration of basic antifungal compositions to treat fungal infections of the nails |
CN1678277B (zh) | 2002-07-29 | 2010-05-05 | 艾克里麦德公司 | 治疗皮肤病的方法和组合物 |
US6914079B2 (en) * | 2002-09-23 | 2005-07-05 | Mediquest Therapeutics, Inc. | Polyamine analogs that activate antizyme frameshifting |
US7135194B2 (en) | 2002-09-27 | 2006-11-14 | Birnbaum Jay E | Subunguicide, and method for treating onychomycosis |
US7700076B2 (en) | 2002-10-25 | 2010-04-20 | Foamix, Ltd. | Penetrating pharmaceutical foam |
JP2006515883A (ja) * | 2003-01-10 | 2006-06-08 | スレッシュオールド ファーマシューティカルズ, インコーポレイテッド | 2−デオキシグルコースによる癌の処置 |
WO2005009342A2 (en) | 2003-07-16 | 2005-02-03 | Pharmacia Corporation | Method for the treatment or prevention of dermatological disorders with a cyclooxygenase-2 inhibitor alone and in combination with a dermatological treatment agent and compositions therewith |
US7740875B2 (en) | 2004-10-08 | 2010-06-22 | Mediquest Therapeutics, Inc. | Organo-gel formulations for therapeutic applications |
US20060078580A1 (en) | 2004-10-08 | 2006-04-13 | Mediquest Therapeutics, Inc. | Organo-gel formulations for therapeutic applications |
US20090191138A1 (en) * | 2008-01-30 | 2009-07-30 | Mediquest Therapeutics, Inc. | Novel topical formulations for improving the appearance of nails |
-
2004
- 2004-10-08 US US10/960,516 patent/US7740875B2/en active Active
-
2005
- 2005-02-28 US US11/066,485 patent/US20060078579A1/en not_active Abandoned
- 2005-10-11 RU RU2006146921/15A patent/RU2422132C2/ru active
- 2005-10-11 MX MX2007003995A patent/MX2007003995A/es active IP Right Grant
- 2005-10-11 ZA ZA200610377A patent/ZA200610377B/en unknown
- 2005-10-11 CN CN2005800342224A patent/CN101035509B/zh active Active
- 2005-10-11 SG SG200906727-3A patent/SG156624A1/en unknown
- 2005-10-11 NZ NZ551887A patent/NZ551887A/en unknown
- 2005-11-10 UA UAA200701001A patent/UA89500C2/uk unknown
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2007
- 2007-01-14 IL IL180691A patent/IL180691A/en active IP Right Grant
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6316428B1 (en) * | 1995-03-10 | 2001-11-13 | Wilson Trafton Crandall | Topical moisturizing composition and method |
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RU2006146921A (ru) | 2008-11-20 |
MX2007003995A (es) | 2008-03-04 |
RU2422132C2 (ru) | 2011-06-27 |
IL180691A0 (en) | 2007-06-03 |
US20060078579A1 (en) | 2006-04-13 |
US20060078577A1 (en) | 2006-04-13 |
SG156624A1 (en) | 2009-11-26 |
US7740875B2 (en) | 2010-06-22 |
CN101035509A (zh) | 2007-09-12 |
UA89500C2 (uk) | 2010-02-10 |
NZ551887A (en) | 2010-08-27 |
IL180691A (en) | 2011-09-27 |
ZA200610377B (en) | 2008-07-30 |
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