CN105358134A - 多层状乳化物结构的经皮药物传递系统 - Google Patents
多层状乳化物结构的经皮药物传递系统 Download PDFInfo
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- CN105358134A CN105358134A CN201480038486.6A CN201480038486A CN105358134A CN 105358134 A CN105358134 A CN 105358134A CN 201480038486 A CN201480038486 A CN 201480038486A CN 105358134 A CN105358134 A CN 105358134A
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- transdermal drug
- transmission system
- ceramide
- drug transmission
- skin
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- 125000001419 myristoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
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- CUNWUEBNSZSNRX-RKGWDQTMSA-N (2r,3r,4r,5s)-hexane-1,2,3,4,5,6-hexol;(z)-octadec-9-enoic acid Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O CUNWUEBNSZSNRX-RKGWDQTMSA-N 0.000 claims description 2
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- XDOFQFKRPWOURC-UHFFFAOYSA-N 16-methylheptadecanoic acid Chemical compound CC(C)CCCCCCCCCCCCCCC(O)=O XDOFQFKRPWOURC-UHFFFAOYSA-N 0.000 claims description 2
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Abstract
本发明涉及一种用于经皮吸收的传递系统,其为多层状乳化物结构的经皮药物传递系统,所述多层状乳化物结构的经皮药物传递系统包含:含有长链酰胺、固醇类、脂肪酸及脂肪醇的脂质;乳化剂;油;以及至少一种以上的经皮给药用药物。根据本发明的多层状结构的经皮药物传递系统具有可在人体的角质细胞间脂质中见到的由层状结构重复而成的薄片结构,从而不仅具有优异的皮肤屏障效果,而且药物通过皮肤脂质而被有效分配,从而能够实现优异的药物传递效果。
Description
技术领域
本发明涉及一种经皮给药用药物传递系统,所述经皮给药用药物传递系统利用具有能够提高皮肤角质层内有效成分分配的特性的组合物。
背景技术
皮肤的表皮层由角质层、透明层、颗粒层、棘层及基底层组成,其中,角质层存在于皮肤的最外壳层,起到防止水分流失,以及使人体免受外部环境有害污染物的伤害的第一道防御作用,是人体最重要的部分之一。
上述的角质层主要由角质细胞和角质细胞间脂质组成。其中,角质细胞作为从表皮的基底层中分化而生成的细胞,由被称为角蛋白的蛋白质组成,并且这些角质细胞之间填充有角质细胞间脂质,并且角质细胞间脂质主要由神经酰胺、胆固醇及脂肪酸等组成。已知角质细胞间脂质在正常状态的皮肤中,以多层状的薄片结构存在,是皮肤所显示出的非常低的物质渗透率的物理性根基。这种低的渗透率是皮肤表皮渗透屏障(epidermalpermeabilitybarrier)功能的重要因素,除此之外,皮肤屏障功能还起到保湿皮肤,以及保护物理性、化学性、微生物学性的作用。
对于这些角质层的结构特征和根据其的组成成分的作用,尤其是对于显示出多层状结构的角质细胞间脂质的作用的理论,美国加利福尼亚旧金山州立大学皮肤科学教室的PeterM.Elias在1970年代通过“砖和灰浆(BrickandMortar)模型”被最初公开。之后通过后续的研究证明了这种模型的有效性(TheCharacterizationofMolecularOrganizationofmultilamellarEmulsionsContainingPseudoceramideandTypeIIISyntheticCeramide.JInvestDermatol.2003Oct;121(4):794-801.)。
药物传递系统是通过最小化药物的副作用,并且最大化功效及效果来使所需量的药物能够有效传递的医药技术。药物通过口服、注射、经皮、粘膜及移植等多种途径来传递,其中,经皮药物传递能够容易调节药物的药物传递量,并且没有全身作用,能够避免肠道吸收时所产生的药物变性,从而能够提高药物的生物利用度(bioavailability)。
如上所述,角质细胞间脂质的多层状结构将成为皮肤具有的非常低的渗透性的物理性根基。然而,对于经皮药物传递系统(transdermaldrugdeliverysystem)或外用剂(topicalformulation)来说,这种低渗透性对开发有效的制剂方面一直是最大障碍。目前为止,开发的经皮药物传递系统或外用剂是主要用于克服这种问题的方法,一直使用的方法为通过物理性或化学性方法来使角质细胞间脂质的多层状结构变形或破坏等的方法。
在经皮药物传递系统中,通过角质层的药物传递途径为:1)从基材中释放(dissolution)药物,2)释放出的药物被分配到角质层,尤其被分配到角质细胞间脂质(partitioning)后,3)药物通过角质细胞间脂质扩散(diffusion),并通过角质层,4)在角质层和颗粒层的交界部位产生药物的分配,同时药物移动到颗粒层,5)再次经过扩散到颗粒层、棘层及基底层的一系列过程。这种过程可以说明为药物从基材中被释放后“分配-扩散”的过程重复进行。根据药物在基材和角质层之间具有何种分配系数,更详细地,根据药物在基材和角质细胞间脂质间具有何种的分配系数,药物在角质层内的分配会有不同。
本发明人通过先前的研究,曾开发出具有与角质细胞间脂质类似的多层状结构的组合物,并且确认了这种组合物对加强及恢复皮肤的屏障功能有帮助。本发明人最终发现由于这种组合物具有与角质细胞间脂质类似的结构,因此,将该组合物作为基材使用的外用制剂能够有效促进前述的经皮药物传递过程的第一次分配过程(基材-角质层间的药物分配),使得角质层内的药物分配得到提高,并具有角质层内的药物含量增加的特征,从而完成了本发明。
发明内容
要解决的技术问题
本发明的目的在于,提供一种经皮药物传递系统,所述经皮药物传递系统通过将由与人体的角质细胞间脂质类似的多层状结构形成的组合物作为基材使用,从而促进有效成分被分配到角质层,更详细地,被分配到角质细胞间脂质层。此外,另一目的在于,提供一种能够实现有效成分含量在角质层内得到增加,以及能够实现有效成分持续传递的优异的经皮药物传递系统。
技术方案
本发明涉及一种用于经皮吸收的传递系统,其为多层状乳化物(MultiLamellarEmulsion)结构的经皮药物传递系统,所述多层状乳化物结构的经皮药物传递系统包含:含有长链酰胺、固醇类、脂肪酸及脂肪醇的脂质;乳化剂;油;以及至少一种以上的经皮给药用药物。
本发明的所述多层状乳化结构不受限制,但是在X射线小角衍射(smallangleX-Raydiffraction)分析中,可以同时具有9.0至11.0nm及5.2至7.2nm的重复周期。从所述衍射测定结果中可以确认,这种多层状结构具有与角质细胞间的脂质类似的结构,并且,通过本发明的一实施例制得的具有所述多层状乳化结构的乳化物适合作为有效的药物传递系统,所述药物传递系统不仅可以实现适用于皮肤疾病的其它经皮传递药物的有效性,而且,同时可以实现多层状乳化物自身具有的皮肤有效效果。
所述药物优选被分配到皮肤的角质层内。此外,所述脂质和乳化剂的含量为总组合物的5~30重量%,经皮给药用药物为总组合物的0.001~25重量%,所述脂质成分中,长链酰胺和固醇合计为0.1~10重量%。
作为优选方式,所述多层状乳化物结构在10至30℃的温度下具有由长重复周期(longperiodicityphase:LPP)和短重复周期(shortperiodicityphase:SPP)形成的层状结构,更优选地,所述长重复周期为10至30nm,短重复周期为3至6nm。所述两个以上的长重复周期和短重复周期是用于说明皮肤角质细胞间脂质的分子排列中最具代表性特征的层状(lamellar)结构的结构性特征。这种两个以上的重复周期在多层状乳化剂型中的出现是为了显示出多层状乳化剂型和角质细胞间脂质的结构类似性。这种特征显示出本发明的剂型所具有的能够将药物有效分配到角质层内的结构性特征。这种结构特性因与皮肤角质层的薄片结构具有非常类似的结构而具有优异的皮肤屏障功能,并且对皮肤保护显示出非常卓越的效果,因此尤其对药物的稳定传递及保存有效。当不具有所述重复周期,或者长重复周期或短重复周期超出所述范围时,经皮给药用有效成分的药物分配效果及释放率会降低。
作为另一种优选方式,所述多层状乳化物结构通过示差扫描热量计(DSC,DifferentialScanningCalorimeter)进行分析的结果为,具有一个以上的液晶中间相,并且液晶中间相中显示的吸热焓(endothermicenthalpy)为20J/g以下。
所述液晶中间相提高由多层结构乳化物自身带来的皮肤有效效果,从而不仅能够提高药物传递,而且还能够提高皮肤屏障恢复功能,从而有效。这种结构不仅能够使皮肤自身的功能恢复,而且注入对炎症皮肤病非常有效的作为局部消炎剂类固醇时,能够使其在短时间内不能以高的浓度渗透,能够使其持续地维持一定的浓度,从而能够提高治疗效率的同时,减少副作用。
此外,作为优选方式,所述多层状乳化物结构在偏振显微镜(交叉偏振显微镜(cross-polarizedmicroscope))下具有马耳他十字(maltesecross)形状的光学各向异性(opticalanisotropy)。并且,剂型优选为乳液、霜、洗剂或膏,但并不限定于此。
多层状乳液(multi-lamellaremul-sion,MLE)剂型是指制备成中心具有油核,并且油核周围由多层的薄片液晶结构包围的形态的乳化物。本发明人发现了MLE剂型所具有的多层薄片液晶结构由于油层被稳定化,因此能够有效使用在对光或氧气的抵御力差的有效物质(Activeingredient)的稳定保存中,并发现作为用于药物持续传递的药物传递系统有效,从而完成了本发明。
本发明中,“经皮”是指通过皮肤或粘膜组织的药物传递。因此,除非对术语“经皮”及“经粘膜”具体明示,否则两者相互互换使用。此外,对于“皮肤”、“真皮”、“上皮”、“粘膜”及类似术语也一样,除非对其具体明示,否则相互互换使用。
作为本发明中使用的长链酰胺的代表性例子,可以列举如在皮肤中发现的神经酰胺,也可以从天然神经酰胺、合成神经酰胺或假神经酰胺中任意使用。天然神经酰胺作为存在于自然中的神经酰胺,包括神经酰胺1、神经酰胺2、神经酰胺3、神经酰胺4、神经酰胺5、神经酰胺6、神经酰胺7及神经酰胺8等,并且所述假(Pseudo)神经酰胺包括神经酰胺104及神经酰胺102等。来源于植物的天然神经酰胺类有神经酰胺(ceramide)、脑苷脂(cerebroside)、单糖基神经酰胺(monoglycosylceramide)、寡糖基神经酰胺(oligoglycosylceramide)及植物神经酰胺(phytoceramide)等。合成神经酰胺的一例,可以列举神经酰胺III(C36H73NO4)。神经酰胺已知为对保湿和皮肤保护非常重要的原料,合成为与人体的神经酰胺相同的结构或变形合成为类似形态而使用。本发明中可以使用肉豆蔻酰基氧代硬脂酰胺乙醇胺(MyristoyloxostearamideMEA)、肉豆蔻酰基氧代花生酰胺乙醇胺(MyristoyloxoarachamideMEA)、棕榈酰基氧代硬脂酰胺乙醇胺(PalmitoyloxostearamideMEA)、棕榈酰基氧代花生酰胺乙醇胺(PalmitoyloxoarachamideMEA)或以这四种成分的混合物而商业化的PC-9S(韩国,株式会社新药(NeoPharm)制造)、二羟基异丙基棕榈油酰基棕榈油酰胺(Dihydroxyisopropylpalmoylpalmamide)等的神经酰胺类似物或与神经酰胺-3的等合成神经酰胺具有相同结构的物质,这些可以适当混合而使用。含量优选为总多层状乳化物的0.01~5重量%。
本发明中使用的固醇类由稠环(fusedring)的板状结构形成,从而起到稳定维持多层状乳化物的作用。本发明中使用的固醇为选自胆固醇、胆固醇硫酸酯(Cholesterylsulfate)、胆固醇乙酸酯(Cholesterylacetate)、胆固醇硬脂酸酯(Cholesterylstearate)、胆固醇异硬脂酸酯(Cholesterylisostearate)、胆固醇羟基硬脂酸酯(Cholesterylhydroxystearate)及植物甾醇(Phytosterol)中的至少一种以上的化合物,但并不限定于此。胆固醇和来源于植物的植物甾醇可以单独或混合使用。含量优选为总多层状乳化物的0.01~10重量%。
本发明中使用的脂肪酸可以使用选自碳原子数为14~22的任一种以上的脂肪酸。虽然在本发明中没有对其限制,但是适合使用棕榈酸(Palmiticacid)、硬脂酸(Stearicacid)及花生酸(Arachidicacid)等。含量优选为总多层状乳化物的0.1~20重量%。
本发明中使用的脂肪醇可以使用选自碳原子数为14~22的任一种以上的脂肪醇。虽然在本发明中没有对其限制,但是适合使用鲸蜡醇(Cetylalcohol)、硬脂醇(Stearylalcohol)、鲸蜡硬脂醇(Cetearylalcohol)及山嵛醇(Behenylalcohol)等。脂肪酸和脂肪醇也可以分别单独使用或混合使用。含量优选为总多层状乳化物的0.1~20重量%。
作为本发明中使用的乳化剂,只要是适合于形成多层状乳化物结构的乳化剂,则不受特别限制,但是可以使用聚甘油-10双棕榈酸酯(Polyglyceryl-10dipalmitate)、聚甘油-10二硬脂酸酯(Polyglyceryl-10distearate)、聚甘油-10硬脂酸酯(Polyglyceryl-10stearate)及聚甘油-10油酸酯(Polyglyceryl-10oleate)等的聚甘油(polyglycerin)类;山梨醇棕榈酸酯(Sorbitanpalmitate)、山梨醇硬脂酸酯(Sorbitanstearate)、山梨醇异硬脂酸酯(Sorbitanisostearate)、山梨醇倍半硬脂酸酯(Sorbitansesquistearate)、山梨醇油酸酯(Sorbitanoleate)、山梨醇倍半油酸酯(Sorbitansesquioleate)、山梨醇橄榄油酸酯(Sorbitanolivate)、蔗糖椰油酸酯(Sucrosecocoate)等的糖酯(Sugarester)类;甘油硬脂酸酯(Glycerylstearate)、甘油油酸酯(Glyceryloleate)等的甘油酯(Glycerylester)类;氢化卵磷脂(Hydrogenatedlecithin)、氢化棕榈甘油酯(Hydrogenatedpalmglyceride)等的氢化类。含量优选为总多层状乳化物的1~15重量%。
本发明中使用的油可以使用饱和烃类油或不饱和烃类油中的任一种,而且还可以使用它们的混合物,并且在本发明中不存在使用受到限制的油。所述饱和烃类油可以列举如矿物油及合成油等,例如有液体石蜡、角鲨烷、凡士林、固体石蜡及其它分枝型烃类油等。不饱和烃类油可以列举如动物性油、植物性油等的普通天然油等,这些均可以在本发明中使用。本发明中可以只使用一种油,但是更优选混合各种油而使用。其原因在于,当只利用一种油来制备多层状乳化物时,在通常情况下,饱和烃类虽然不能够充分地形成多层状乳化物,但是对于亲油性皮肤有效物质的稳定化方面有利,而不饱和烃类油中的甘油三酯形态的普通天然油虽然能够很好地形成多层状乳化物,但是在亲油性皮肤有效物质的稳定化中比饱和烃类油表现出较差的结果。
因此,能够形成良好的多层状乳化物的原因可以归结为通过混合各种油类来制备多层状乳化物。同时对亲油性皮肤有效物质的稳定化也有利。另外,混合所述各种油类对于制备包含类固醇成分的多层状乳化物也是有利的。含量优选为总多层状乳化物的1~30重量%。
作为用于稳定维持乳化物的脂质和乳化剂成分的混合量优选为总组成的5重量%~30重量%。当含量低时,难以得到由液晶形成带来的乳化物的稳定化,当含量过多时,会对其它成分的使用产生制约,从而难以制备出具有多种使用感的处方。此外,脂质成分中的长链酰胺和固醇合计优选为0.1重量%~10重量%。当含量低时,会导致所形成的液晶状不良或使稳定性降低,当含量过多时,会因根据温度变化的析出而导致稳定性降低。此外,通过大量研究所得出的结果为,长链酰胺/固醇成分的比例以重量比计优选为0.1~10。
本发明的制药有效成分或活性物质(亦称“药物”)是指,在通过皮肤进行给药时,可以带来局部或全身性效果的药物,其不受特别限制,可以列举如包含所有的类固醇类(例如,氢化可的松、强的松、去炎松)及非类固醇类(例如,萘普生、吡罗昔康)的消炎性药物;细菌发育阻止剂(例如,氯己定、己基间苯二酚);抗菌剂(例如,诸如青霉素V的青霉素、诸如头孢氨苄等的头孢菌素、红霉素、四环素、庆大霉素、磺胺噻唑、诸如呋喃咀啶及诺氟沙星的喹啉、氟甲喹及左氧氟沙星);抗原虫剂(例如,甲硝唑);抗真菌剂(例如,制霉菌素);心血管扩张剂;钙通道阻滞剂(例如,硝苯地平、地尔硫卓);支气管扩张剂(例如,茶碱、吡丁醇、沙美特罗、异丙肾上腺素);诸如胶原分解酶抑制剂、蛋白分解酶抑制剂、弹性蛋白酶抑制剂、脂肪氧化酶抑制剂(例如,A64077)及血管紧张素转换酶抑制剂(例如,卡托普利、赖诺普利)等的酶抑制剂;其它抗高血压剂(例如,普萘洛尔);白三烯拮抗剂(例如,ICI204,219);诸如H2拮抗剂的抗溃疡剂;类固醇类激素(例如,黄体酮、睾酮、雌二醇);抗病毒剂和/或免疫调节剂(例如,1-异丁基-1H-咪唑并[4,5-c]喹啉-4-胺、1-(2-羟基-2-甲基丙基)-1H-咪唑并[4,5-c]喹啉-4-胺及阿昔洛韦);局部麻醉剂(例如,苯佐卡因、丙泊酚);强心剂(例如,洋地黄、地高辛);咳嗽药(例如,可待因、右美沙芬);抗组胺剂(例如,苯海拉明、氯苯那敏、特非那定);麻醉性镇痛剂(例如,吗啡、丁丙诺啡);肽激素(例如,人体或动物生长激素、黄体生成素释放激素(LHRH));诸如心房肽的心脏药;蛋白性生成物(例如,胰岛素);酶(例如,抗牙菌斑酶、溶菌酶、葡聚糖酶);晕药;抗惊厥药(例如,乙胺嗪);免疫抑制剂(例如,环孢菌素);精神治疗药(例如,地西泮);镇静剂(例如,苯巴比妥);抗凝固剂(例如,肝素);镇痛剂(例如,对乙酰氨基酚);偏头痛药(例如,麦角胺、褪黑激素、舒马普坦);抗心律失常药(例如,氟卡尼);止吐药(例如,甲氧氯普胺、昂丹司琼);抗癌剂(例如,甲氨蝶呤);诸如抗焦虑剂的神经药;止血剂;抗肥胖药等,而且还可以列举如它们在制药学上可接受的盐及酯。构成在制药学上有效量的药物的量可以由本领域技术人员通过考虑特定的药物、特定的载体及所需的治疗效果而容易被确定。本发明的多层状结构的乳化物中的药物含量约为0.001%至约25重量%,优选约为0.001%至约20重量%,以及最优选约为0.01%至约10重量%的范围。
在本发明中,作为有效成分药物,优选为类固醇,并且可使用的类固醇为孕激素,例如,包括烯丙雌醇(allylestrenol)、阿那孕酮(anagestone)、醋酸克罗马孕酮(chlomardinoneacetate)、醋酸地马孕酮(delmadinoneacetate)、地美孕酮(demegestone)、去氧孕烯(desogestrel)、3-酮去氧孕烯(ketodesogestrel)、地美炔酮(dimethisterone)、屈螺酮(drospirenone)、地屈孕酮(dydrogesterone)、炔孕酮(ethisterone)、炔诺醇(ethynodiol)、醋酸氟孕酮(flurogestoneacetate)、孕二烯酮(gestodene)、己酸孕诺酮(gestonoronecaproate)、17-羟基-16-亚甲基-δ-孕酮、17α羟基孕酮、羟基孕酮、羟基孕酮醋酸酯、羟基孕酮己酸酯、左炔诺孕酮(levonorgestrel)、利奈孕酮(lynestrenol)、美罗孕酮(medrogestone)、甲羟孕酮(medroxyprogesterone)、甲羟孕酮醋酸酯、醋酸甲地孕酮(megestrolacetate)、美仑孕酮(melengestrol)、炔诺酮(norethindrone)、醋酸炔诺酮(norethindroneacetate)、异炔诺酮(norethynodrel)、乙烯异诺酮(norgesterone)、诺孕酯(norgestimate)、甲基炔诺酮(norgestrel)、诺孕烯酮(norgestrienone)、诺塞甾酮(norethisterone)、异炔诺酮(norethynodrel)、诺乙烯酮(norvinisterone)、喷他孕酮(pentagestrone)、黄体酮(progesterone)、普美孕酮(promegestone)及群孕酮(trengestone)。
作为类固醇的另一例,包括苯雌酚(benzestrol)、溴帕雌烯(broparoestrol)、氯烯雌酚(chlorotrianisene)、双烯雌酚(dienestrol)、己烯雌酚(diethylstilboestrol)、己烯雌酚二丙酸酯(diethylstilboestroldipropionate)、甲基己烯雌酚(dimestrol)、磷雌酚(fosfestrol)、己烷雌酚(hexoestrol)、美沙雌酸(methallenestril)及美雌酚(methestrol)等非类固醇类雌性激素及双醋羟雌酮(colpormon)、共轭雌激素(conjugatedestrogenichormone)、马萘雌酮(equilenin)、马烯雌酮(equilin)、雌二醇及其酯(例如,苯甲酸雌二醇、戊酸酯、环戊丙酸盐癸酸酯及醋酸盐)、雌三醇(estriol)、雌酮(estrone)、乙炔雌二醇(ethinylestradiol)、苯甲酸雌二醇(estradiolbenzoate)、炔雌醇甲醚(mestranol)、甲氧基降孕三烯炔二醇(moxestrol)、双甲雌三烯二醇(mytatrienediol)、奎雌醇(quinestradiol)、炔雌醚(quinestrol)等的诸如类固醇类雌激素的雌激素。作为类固醇的又一例,包括倍他米松(betamethasone)、醋酸倍他米松、可的松(cortisone)、氢化可的松(hydrocortisone)、醋酸氢化可的松、皮质酮(corticosterone)、醋酸氟轻松(fluocinoloneacetonide)、氢化波尼松(prednisolone)、强的松(prednisone)及去炎松(triamcinolone)等皮质类固醇及醛固酮、雄甾酮、睾酮及甲基睾酮等雄性激素及同化剂。
作为另一例,列举有勃地酮(boldenone)、氯索睾酮(cloxotestosterone)、氟甲睾酮(fluoxymesterone)、美雄诺龙(mestanolone)、美睾酮诺伦(mesteronolone)、17-甲基睾酮、17α-甲基睾酮3-环戊基烯醇醚、诺乙雄龙(norethandrolone)、甲基诺龙(normethandrone)、氧甲氢龙(oxandrolone)、羟甲睾酮(oxymesterone)、羟甲烯龙(oxymetholone)、普拉睾酮(prasterone)、雄诺龙(stanolone)、吡唑甲氢龙(stanolozol)、睾酮(testosterone)、硫甲睾酮(tiomesterone)等雄性激素,并且还有21-乙酰氧孕烯醇酮(21-acetoxypregnenolone)、阿氯米松(alclometasone)、阿尔孕酮(algestone)、安西奈德(amcinonide)、倍氯米松(beclomethasone)、倍他米松(bethamethasone)、布地奈德(budesonide)、氯泼尼松(chloroprednisone)、氯倍他索(clobetasol)、氯倍他松(clobetasone)、氯可托龙(clocortolone)、氯泼尼醇(cloprednol)、皮质酮(corticosterone)、可的松(cortisone)、可的伐唑(cortivazol)、地夫可特(deflazacort)、地索奈德(desonide)、去羟米松(desoximetasone)、地塞米松(dexamethasone)、双氟拉松(diflorasone)、二氟可龙(diflucortolone)、二氟泼尼酯(difluprednate)、甘草次酸(enoxolone)、氟扎可特(fluazacort)、氟二氯松(flucloronide)、氟米松(flumethasone)、氟尼缩松(flunisolide)、肤轻松醋酸酯(fluocinoloneacetonide)、氟轻松醋酸酯(fluocinonide)、氟考丁酯(fluocortinbutyl)、氟可龙(fluocortolone)、氟米龙(fluorometholone)、醋酸氟培龙(fluperoloneacetate)、醋酸氟泼尼定醋酸酯(fluprednineneacetate)、氟泼尼龙(fluprednisolone)、氟氢缩松(flurandrenolide)、氟替卡松丙酸酯(fluticasonepropionate)、福莫可他(formocortal)、哈西奈德(halcinonide)、卤倍他索丙酸酯(halobetasolpropionate)、卤米松(halometasone)、酸酸卤泼尼松(halopredoneacetate)、氢可他酯(hydrocortamate)、氢化可的松(hydrocortisone)、氯替泼诺(loteprednoletabonate)、马泼尼酮(mazipredone)、甲羟松(medrysone)、甲泼尼松(meprednisone)、甲基强的松龙(methylprednisolone)、糠酸莫米松(mometasonefuroate)、帕拉米松(paramethasone)、泼尼卡酯(prednicarbate)、泼尼松龙(prednisolone)、25-二乙氨基乙酸泼尼松龙、泼尼松龙磷酸钠、强的松(prednisone)、泼尼松龙戊酸酯(prednival)、泼尼立定(prednylidene)、利美索龙(rimexolone)、替可的松(tixocortol)、去炎松(triamcinolone)、曲安奈德(triamcinoloneacetonide)、苯曲安缩松(triamcinolonebenetonide)、己曲安奈德(triamcinolonehexacetonide)等的糖皮质激素,其它类固醇有甲基炔诺酮(norgestrel)、左炔诺孕酮(levonorgestrel)、诺孕曲明(norelgestromin)及它们的衍生物。
类固醇作为局部消炎剂,非常有效地作用于炎症性皮肤疾病(皮炎、湿疹),并且以少量也显示出卓越的效果,并且比较容易使用,而且不会引起疼痛,且无味,从而一直以来被广泛地使用于炎症性皮肤病中。然而,引起大部分皮肤疾病的首要因素或恶化因素为皮肤屏障功能的损伤的情况下,类固醇不能从根本上治疗这种疾病,当长时间使用类固醇时,反而会使赋予皮肤屏障功能的皮肤细胞间脂质的生成减少,从而导致皮肤屏障功能变弱,而且胶原蛋白及弹性蛋白的合成也会减少,从而会引起痤疮、多毛症、萎缩纹、毛囊炎、接触性皮肤炎及二次感染等的副作用。基于上述理由,欲开发一种通过使皮肤屏障功能恢复的同时,不会使类固醇在短时间内以高的浓度渗透到皮肤内,并且能够使其持续地维持适当的浓度而被吸收,从而能够提高治疗效率且减少副作用的剂型。并且确认了本发明的多层结构的药物传递系统能够恢复皮肤屏障功能并带来突出的病症改善效果,同时还显示出低的副作用。
此外,本发明的另一优选药物为非类固醇(NSAID)消炎镇痛剂。非类固醇消炎镇痛剂使用选自包括酮洛芬(ketoprofen)、氟比洛芬(flurbiprofen)、非诺洛芬(fenoprofen)、布洛芬(ibuprofen)的苯丙酸衍生物系列的非甾体抗炎药类;包括吡罗昔康(piroxicam)、替诺昔康(tenoxicam)、美洛昔康(meloxicam)的昔康衍生物系列的非甾体抗炎药类;双氯芬酸(diclofenac);以及吲哚美辛(indomethacin)中的一种以上。非类固醇性药物的药效卓越,并且半衰期长,从而优选作为经皮用给药药物使用。尤其是本发明的剂型在促进药物分配到皮肤角质层,以维持一定的药效方面具有卓越的效果。
此外,本发明的又一优选药物可以为阿莫罗芬、异康唑、克霉唑、益康唑、咪康唑、制霉菌素、特比萘芬、联苯苄唑、两性霉素、灰黄霉素、酮康唑、氟康唑及氟胞嘧啶、水杨酸、非扎硫酮 氯苯异噻唑酮托萘酯(tolnaftate)、三乙酸甘油酯、锌、羟基吡啶硫酮(pyrithione)及吡啶硫酮钠中的一种以上的抗真菌剂。
除了含有制药活性物质以外,还可以进一步含有其它添加剂或赋形剂。这种添加剂包括在经皮药物传递系统中可作为皮肤渗透提高剂(即,增加药物通过皮肤或渗透到皮肤内的速度的物质)或可溶化剂(即,使药物有效可溶化的物质)使用的制药学上可接受的物质。从使有效药物有效地渗透到皮肤方面考虑,适合作为皮肤渗透提高剂使用的物质优选为选自亚油酸、油酸、棕榈酸、硬脂酸、癸酸及肉豆蔻酸等的脂肪酸;丙二醇、聚乙二醇、二丙二醇、二乙二醇及丙三醇等多元醇;吐温80(Tween80)、酸甘油酯(labrasol)、氢化蓖麻油等表面活性剂;油醇及硬脂醇等的脂肪酸醇;肉豆蔻酸异丙酯、丙二醇辛酸酯、丙二醇月桂酸酯及聚乙二醇月桂酸酯等脂肪酸酯;聚氧乙烯二十二烷基醚、聚氧乙烯己基癸基醚及聚氧乙烯癸基十四烷基醚等非离子表面活性剂中的一种以上。作为其它添加剂,例如包括增粘剂、增塑剂及抗氧化剂。
此外,本发明涉及一种包含具有多层状乳化结构的乳化物的外用药物组合物。所述药物组合物的剂型虽然不受限制,但是作为一例,可以使用如硬膏剂(PLASTERS)、洗剂(LOTIONS)、搽剂(LINIMENTS)、液剂(LIQUIDSANDSOLUTIONS)、气溶胶剂(AEROSOLS)、浸膏剂(EXTRACTS)、软膏剂(OINTMENTS)、流浸膏剂(FLUIDEXTRACTS)、乳剂(EMULSIONS)、悬浮剂(SUSPENSIONS)、胶囊剂(CAPSULES)、霜剂(CREAMS)、软质或硬质的明胶胶囊、贴剂及缓释剂。另外,所述药物组合物可以包含药理学上可接受的基材;传递剂;赋形剂;包括淀粉、黄蓍胶、明胶、糖蜜、聚乙烯醇、聚乙烯醚、聚乙烯吡咯烷酮、羟丙基纤维素、甲基纤维素、乙基纤维素及羧甲基纤维素的粘合剂;包括琼脂、淀粉、明胶粉、羧甲基纤维素钠、羧甲基纤维素钙、结晶纤维素、碳酸钙、碳酸氢钠及藻酸钠的研磨剂;包括硬脂酸镁、滑石及氢化植物油的润滑剂;以及着色剂等。所述传递剂及赋形剂有乳糖、葡萄糖、蔗糖、甘露醇、马铃薯淀粉、玉米淀粉、碳酸钙、磷酸钙及纤维素等。除了上述添加剂以外,还可以进一步添加稳定剂、助溶剂、经皮吸收促进剂等的助剂、芳香剂、防腐剂等的添加剂。
另外,对于很多患者来说,本发明的皮肤外用剂组合物的标准药物传递量会根据患者的个别特性而有所变化,实质上熟练的临床医生可以为患者确定本发明的皮肤外用剂组合物的理想的药物传递量及药物传递计划,例如,从特定需要及患者的总体条件的观点出发,可以确定最适合的治疗方案。对于确定合适的本发明的皮肤外用剂组合物的药物传递量,可以参考很多参考文献。此外,本发明的皮肤外用剂的合适的药物传递量通常可以在试管内或动物模型中确定。例如,对试管内的靶细胞添加各种浓度的本发明的皮肤外用剂组合物,从而确定适合的药物传递量。
如在皮肤角质层中所示,上述多层状乳化物结构的经皮药物系统显示出长重复周期(LPP)和短重复周期(SPP)而与皮肤角质层的层状结构的类似性非常高,因此作为至少一种以上的用于经皮吸收药物的传递系统使用时,药物会有效分配到皮肤中,尤其分配到角质层内,而且对于损伤的皮肤来说,皮肤屏障的恢复效果非常快,并且对皮肤的功能复原也非常有效,从而证明了能够成为用于经皮传递的有效的药物传递系统。
有益效果
根据本发明的多层状乳化物结构的经皮药物传递系统具有可在人体的角质细胞间脂质中见到的由层状结构重复而成的薄片结构,从而与角质细胞间脂质的相容性非常高,因此促进有效成分从基材中分配到角质细胞间脂质。通过这些,能够提高角质层内药物的含量,并且增加角质层的药物存储功能,以使药物可以持续传递,从而能够得到优异的药物传递效果。
附图说明
图1为示出作为有效药物的氢化可的松的经皮渗透率的图表。
图2为测定作为有效药物的氢化可的松的皮肤内沉积量并示出的图表。
图3为用X射线小角衍射分析本发明的多层状乳化物的结果。
图4为用示差扫描热量计分析本发明的多层状乳化物的结果。
图5为用偏振显微镜(交叉偏振显微镜(cross-polarizedmicroscope))分析本发明的多层状乳化物的结果。
具体实施方式
下面,通过实施例对本发明进行更加详细的说明。然而,这些实施例仅是为了例示本发明,本发明的范围并不限定于这些实施例。
[实施例1、2]
本发明的用于经皮药物传递的剂型的制备
按照如下述表1中所示的组成成分及组成比来混合长链酰胺和固醇、脂肪酸、脂肪醇,以及非离子表面活性剂、增粘剂及精制水,从而制备液晶乳化物。作为有效药物分别使用了类固醇或非类固醇消炎剂。作为长链酰胺使用了肉豆蔻酰基/棕榈酰基氧代硬脂酰胺/花生酰胺乙醇胺(Myristoyl/Palmitoyloxostearamide/arachamideMEA)(商品名为PC-9S,株式会社新药制)。
表1
原料名称 | 实施例1 | 实施例2 |
假神经酰胺(PC-9S) | 0.60 | 0.60 |
胆固醇 | 0.20 | 0.20 |
硬脂酸 | 1.50 | 1.50 |
鲸蜡醇 | 5.00 | 5.00 |
单硬脂酸甘油酯 | 1.50 | 1.50 |
聚氧乙烯单硬脂酸甘油酯15 | 2.50 | 0.50 |
聚氧乙烯单硬脂酸甘油酯10 | 1.00 | 1.00 |
聚山梨酯60 | ||
角鲨烷 | 1.00 | 1.00 |
橄榄油 | 2.00 | 2.00 |
硬质液体石蜡 | ||
1,3–丁二醇 | 10.00 | 10.00 |
肉豆蔻酸异丙酯 | ||
浓甘油 | ||
丁基羟基甲苯 | 0.02 | 0.02 |
尼泊金丙酯 | 0.05 | 0.05 |
尼泊金甲酯 | 0.10 | 0.10 |
苯甲醇 | ||
氯甲酚 | ||
卡波姆 | ||
氢氧化钠 | ||
三乙醇胺 | ||
磷酸氢钠水合物 | ||
精制水 | 适量 | 适量 |
氢化可的松 | 1.00 | |
酮洛芬 | 3.00 |
[比较例1、2]
为了与实施例进行比较的比较例使用了在市场上出售的含有相同的药理成分的现有的药物。各比较例的产品的名称和制备来源及制备号如下述表2中所示。
表2
[实施例3]
X射线小角衍射(SmallAngleX-RayDiffraction(SXRD))分
析
为了分析所述实施例1的剂型的多层状(Lamellar)结构,通过增加温度而得到了X射线小角衍射分析结果。对于X射线小角衍射分析,利用参考文献(JournalofControlledRelease115卷页数275??279.2006年)中所述的方法来进行。X射线衍射测定是利用光子工厂(PhotonFactory)(茨城县,日本)的BL15A站(BL15AStation)的单色同步加速器(monochromaticsynchrotron)设备来进行的。X射线的波长为0.1506nm,并且试料-检测期间距离约为150nm。X射线衍射的记录是利用成像板(imagingplate)(BAS-III型,富士胶片,日本)来进行的。其结果示于图3中,多层结构显示出了规律的长重复周期和短重复周期,并且在作为最初测定温度的20℃下检测出具有约10.2nm的长重复周期的峰(0.09714及0.203301)和6.2nm的短重复周期的峰(0.16388)。从所述衍射测定结果可以确认这种多层状结构具有与角质细胞间脂质类似的结构。
[实施例4]
示差扫描热量法(DifferentialScanningCalorimeter:DSC)分析
为了观察随温度变化而产生的相转变,用示差扫描热量法(DifferentialScanningCalorimeter)(DSCQ1000V9.9Build303)对所述实施例1的剂型进行了分析。其结果如图4中所示,在加热条件下显示出了一个液晶中间相(mesophase),并且吸热焓为7.484J/g。
[实施例5]
偏振显微镜(交叉偏振显微镜)分析
为了分析所述实施例1的剂型的光学特性,利用偏光显微镜(Optiphot-2,尼康公司制备)进行观察。其结果示于图5中,并且可以确认具有马耳他十字形状的光学各向异性。
[实验例1]
*经皮渗透率测定
对于根据所述实施例及比较例的剂型化而制得的实施例1(K17838爱多康(Atopalm))及比较例1(K17836氢化可的松制剂(Cortaid)),比较了剂型内氢化可的松物质的经皮渗透率。
收集通过以美容为目的而进行的切除术来确保的人体皮肤后,在4℃下保存,然后去除皮下脂肪层。对各皮肤标记分类号后,在-20℃下保存,之后在实验中使用。将保存的皮肤溶解至常温后,利用皮刀(Dermatome)设备来切割真皮部位,使得厚度约为500μm。对切割的皮肤进行24mm直径的钻取活组织检查(punchbiopsy),从而确保实验中使用的组织,并将各组织固定在弗朗茨细胞(Franzcell)上,从而进行了渗透实验。将药物涂覆在约1.77cm2的面积上,并将受体室(receptorchamber)用KRB缓冲液/诺乃清洁剂(Nonidet)填充,并进行了实验。进行实验时,将温度维持在32℃,并且,在3小时、5小时、6小时、21小时、22小时、23小时后,分别从受体室中收集300μl的溶液,并利用高效液相色谱/质谱(HPLC/MS)设备来分析透过皮肤的氢化可的松(hydrocortison)的量。
其结果示于图1的经皮渗透率测定结果中。如在图表中能够确认的那样,观察到了本发明的实施例1的剂型比比较例1(氢化可的松制剂(Cortaid))的经皮渗透率低。
[实验例2]
角质层及皮肤内药物含量测定
向皮肤涂覆根据上述实施例及比较例的剂型化而制得的实施例1(K17838爱多康)及比较例1(K17836氢化可的松制剂)后,经过一定时间后对角质层和表皮、真皮内的药物的浓度进行了比较。
收集通过以美容为目的而进行的切除术来确保的人体皮肤后,在4℃下保存,然后去除皮下脂肪层。对各皮肤标记分类号后,在-20℃下保存,之后在实验中使用。将保存的皮肤溶解至常温后,利用皮刀设备来切割真皮部位,使得厚度约为500μm。对切割的皮肤进行24mm直径的钻取活组织检查,从而确保实验中使用的组织,并将各组织固定在(萨尔布鲁克尔模型(Saarbrukermodel))上。涂覆试料后,在32℃下维持,6小时后去除皮肤表面的产品。为了分离角质层和表皮及真皮,使用了胶带剥离(tapestripping)方法和冰冻断层(Cryosection)方法。用胶带(tape)对皮肤角质层反复进行20次的粘贴并分离的操作,从而分离角质层,使得露出2.01cm2的宽度的皮肤角质层。另行保存最初的2个胶带,对之后的18个胶带进行氢化可的松(hydrocortisone)含量的测定。对去除角质层的组织再次进行冰冻断层操作,从而分离各层,然后共分为4个部分,并测定组织内氢化可的松(hydrocortisone)的含量。
将其结果示于图2的角质层内皮肤内药物含量测定结果中,并且如在图表中能够确认的那样,观察到了本发明的实施例1的剂型与比较例1(氢化可的松制剂)相比,角质层内药物的浓度最高约高出1.6倍,从而证明了角质层内的分配效果卓越。
[实验例3]
药物释放率测定
为了用包含所述实施例及比较例中制得的个别药物的剂型来测定剂型中的药物释放率,利用微孔滤膜(Duraporemembrane)(密理博(Millipore))进行测定。在弗朗茨细胞上设置微孔滤膜后,涂覆各药物,并对药物的释放进行测定6小时,从而确认了如表3中示出的结果。
表3
测定结果,观察到比较例与实施例相比显示出了高的药物释放。
[实验例4]
通过人工膜的药物渗透测定
对包含所述实施例及比较例中制得的个别的药物的剂型,测定对具有与人体皮肤角质层类似结构的膜的斯特拉特(Strat)-M膜(密理博)的药物渗透。已知斯特拉特(Strat)-M膜为在合成滤膜上套上具有与人体角质层类似成分的脂质膜,从而显示出与人体角质层类似的渗透举动的膜。在弗朗茨细胞上设置斯特拉特-M膜,并以一定量涂覆各药物后,24小时后测定药物的渗透量,从而得到如表4的结果。
表4
对于通过斯特拉特-M的药物渗透结果为,与从表3中所示的药物释放相反,在实施例中显示出了高的药物释放。
[实验例5]
动物实验中的皮肤药物渗透率
如下述表5中所示,利用所述实施例1及比较例1的剂型,在小鼠及微型猪的皮肤上分别涂覆1g后,24小时后测定了渗透率。
表5
与利用人体皮肤的实验结果一样,测定出在比较例中显示出约高出3~4倍的皮肤渗透效果。
[实验例6]
动物实验中的皮肤内药物沉积量
如下述表6中所示,利用所述实施例1及比较例1的剂型,在小鼠及微型猪的皮肤上分别涂覆1g后,24小时后测定了皮肤内药物的含量。
表6
如上述实验结果所示,在利用微型猪的实验中,皮肤内药物的含量比比较例高。
如上述的实验结果中所示,对包含本发明的一实施例中使用的乳化物的经皮药物传递系统进行X射线衍射分析的结果为,检测出具有约10.2nm的长重复周期的峰(0.09714及0.203301)和具有6.2nm的短重复周期的峰(0.16388)。从由所述衍射测定结果中可以确认,这种多层状结构具有与角质细胞间脂质类似的结构,而且适合作为有效的药物传递系统,所述药物传递系统不仅可以实现适用于皮肤病的其它经皮传递的药物的有效性,而且,同时可以实现多层状乳化物自身具有的皮肤有效效果。
Claims (15)
1.一种用于经皮吸收的传递系统,其特征在于,其为多层状乳化物结构的经皮药物传递系统,所述多层状乳化物结构的经皮药物传递系统包含:含有长链酰胺、固醇类、脂肪酸及脂肪醇的脂质;乳化剂;油;以及至少一种以上的经皮给药用有效成分。
2.根据权利要求1所述的经皮药物传递系统,其特征在于,所述多层状乳化结构在X射线小角衍射(smallangleX-Raydiffraction)分析中,同时具有9.0至11.0nm及5.2至7.2nm的重复周期。
3.根据权利要求1所述的经皮药物传递系统,其特征在于,所述脂质和乳化剂的含量为总组合物的5~30重量%,经皮给药用有效成分为总组合物的0.001~25重量%,所述脂质成分中的长链酰胺和固醇合计为0.1~10重量%。
4.根据权利要求1所述的经皮药物传递系统,其特征在于,所述有效成分被分配到皮肤的角质层内。
5.根据权利要求1所述的经皮药物传递系统,其特征在于,所述多层状乳化物结构在10至30℃的温度下具有由长重复周期和短重复周期形成的层状结构。
6.根据权利要求5所述的经皮药物传递系统,其特征在于,所述长重复周期为10至30nm,短重复周期为3至6nm。
7.根据权利要求1所述的经皮药物传递系统,其特征在于,通过示差扫描热量计(DSC,DifferentialScanningCalorimeter)对所述多层状乳化物结构进行分析的结果为,具有一个以上的液晶中间相,并且吸热焓(endothermicenthalpy)为20J/g以下。
8.根据权利要求1所述的经皮药物传递系统,其特征在于,所述多层状乳化物结构在偏振显微镜(交叉偏振显微镜(cross-polarizedmicroscope))下具有马耳他十字(maltesecross)形状的光学各向异性(opticalanisotropy)。
9.根据权利要求1所述的经皮药物传递系统,其特征在于,所述经皮药物传递系统的剂型为乳液剂、霜剂、洗剂或膏剂。
10.根据权利要求1所述的经皮给药系统,其特征在于,所述长链酰胺为选自肉豆蔻酰基氧代硬脂酰胺乙醇胺(MyristoyloxostearamideMEA)、肉豆蔻酰基氧代花生酰胺乙醇胺(MyristoyloxoarachamideMEA)、棕榈酰基氧代硬脂酰胺乙醇胺(PalmitoyloxostearamideMEA)、棕榈酰基氧代花生酰胺乙醇胺(PalmitoyloxoarachamideMEA)、二羟基异丙基棕榈油酰基棕榈油酰胺(Dihydroxyisopropylpalmoylpalmamide)、神经酰胺-1(Ceramide-1)、神经酰胺-2、神经酰胺-3、神经酰胺-3B、神经酰胺-4、神经酰胺-5及神经酰胺-6中的至少一种以上的化合物。
11.根据权利要求1所述的经皮药物传递系统,其特征在于,所述固醇为选自胆固醇、胆固醇硫酸酯(Cholesterylsulfate)、胆固醇乙酸酯(Cholesterylacetate)、胆固醇硬脂酸酯(Cholesterylstearate)、胆固醇异硬脂酸酯(Cholesterylisostearate)、胆固醇羟基硬脂酸酯(Cholesterylhydroxystearate)及植物甾醇(Phytosterol)中的至少一种以上的化合物。
12.根据权利要求1所述的经皮药物传递系统,其特征在于,所述乳化剂为选自聚甘油-10双棕榈酸酯(Polyglyceryl-10dipalmitate)、聚甘油-10二硬脂酸酯(Polyglyceryl-10distearate)、聚甘油-10硬脂酸酯(Polyglyceryl-10stearate)及聚甘油-10油酸酯(Polyglyceryl-10oleate)的聚甘油(polyglycerin)类;山梨醇棕榈酸酯(Sorbitanpalmitate)、山梨醇硬脂酸酯(Sorbitanstearate)、山梨醇异硬脂酸酯(Sorbitanisostearate)、山梨醇倍半硬脂酸酯(Sorbitansesquistearate)、山梨醇油酸酯(Sorbitanoleate)、山梨醇倍半油酸酯(Sorbitansesquioleate)、山梨醇橄榄油酸酯(Sorbitanolivate)、蔗糖椰油酸酯(Sucrosecocoate)的糖酯(Sugarester)类;甘油硬脂酸酯(Glycerylstearate)、甘油油酸酯(Glyceryloleate)的甘油酯(Glycerylester)类;氢化卵磷脂(Hydrogenatedlecithin)、氢化棕榈甘油酯(Hydrogenatedpalmglyceride)的氢化类中的至少一种以上的化合物。
13.根据权利要求1所述的经皮药物传递系统,其特征在于,所述有效成分为氢化可的松类、可的松类、皮质酮类的类固醇类药物中的至少一种以上。
14.根据权利要求1所述的经皮经皮药物传递系统,其特征在于,所述有效成分为选自包括酮洛芬(ketoprofen)、氟比洛芬(flurbiprofen)、非诺洛芬(fenoprofen)、布洛芬(ibuprofen)的苯丙酸衍生物系列的非甾体抗炎药类;包括吡罗昔康(piroxicam)、替诺昔康(tenoxicam)、美洛昔康(meloxicam)的昔康衍生物系列的非甾体抗炎药类;双氯芬酸(diclofenac);以及吲哚美辛(indomethacin)中的至少一种以上的非类固醇性消炎镇痛剂。
15.一种外用药物组合物,其包含权利要求1至14中任一项所述的具有多层状乳化结构的乳化物。
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR19980034991A (ko) | 1996-11-11 | 1998-08-05 | 안용찬 | 비천연세라미드 관련화합물 및 이를 함유하는 피부외용제 |
KR19980034991U (ko) * | 1996-12-12 | 1998-09-15 | 김영귀 | 자동차의 카울 배플 |
KR100527346B1 (ko) * | 1999-02-03 | 2005-11-09 | (주)네오팜 | 유사 세라마이드를 함유한 다중 라멜라 에멀젼 형태의 화장료 |
AU2003233396B2 (en) * | 2002-03-13 | 2007-05-24 | Thomas Skold | Water-based delivery systems |
US20040087564A1 (en) * | 2002-10-31 | 2004-05-06 | Wright D. Craig | Delivery composition and method |
KR100638170B1 (ko) * | 2005-02-03 | 2006-10-26 | 한국콜마 주식회사 | 유용성 감초추출물을 안정화하고 경피흡수를 촉진하는제미니계 계면활성제를 함유한 유상부 액정 조성물 및이로부터 미백 화장료의 제조방법 |
KR100840905B1 (ko) * | 2006-06-09 | 2008-06-24 | (주)네오팜 | 헥사고날 젤 구조를 가지는 피부 외용제 |
EP2020221B1 (de) * | 2007-06-19 | 2012-02-29 | Neubourg Skin Care GmbH & Co. KG | DMS (Derma Membrane Structure) in Schaum-Cremes |
KR101198275B1 (ko) * | 2010-08-27 | 2012-11-07 | (주)네오팜 | 폴리글리세릴 지방산 에스테르를 함유하는 헥사고날 구조의 피부외용제조성물 |
-
2014
- 2014-07-01 US US14/902,102 patent/US9867776B2/en active Active
- 2014-07-01 CN CN201480038486.6A patent/CN105358134B/zh active Active
- 2014-07-01 WO PCT/KR2014/005856 patent/WO2015002435A1/ko active Application Filing
- 2014-07-01 JP JP2016523660A patent/JP2016523903A/ja active Pending
- 2014-07-01 KR KR1020140081636A patent/KR20150003685A/ko not_active Application Discontinuation
- 2014-07-01 EP EP14819797.3A patent/EP3017810B1/en active Active
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP1236462A1 (en) * | 2001-02-28 | 2002-09-04 | Neopharm Co., Ltd. | Multi-lamella based emulsion for stabilizing dermatologically useful ingredients and external preparation containing the same |
CN1372922A (zh) * | 2001-02-28 | 2002-10-09 | 株式会社新药 | 用于稳定皮肤病学上有效成分的多层乳液和应用它的外用制剂 |
WO2007112712A1 (de) * | 2006-03-31 | 2007-10-11 | Kuhs Gmbh | Topisch zu applizierende zusammensetzung |
CN101410085A (zh) * | 2006-03-31 | 2009-04-15 | 库斯有限公司 | 局部施用的组合物 |
CN102349860A (zh) * | 2006-03-31 | 2012-02-15 | 库斯有限公司 | 局部施用的组合物 |
Non-Patent Citations (2)
Title |
---|
HYUN JUNG KIM ET AL.: ""Pseudoceramide-Containing Physiological Lipid Mixture Reduces Adverse Effects of Topical Steroids"", 《ALLERGY,ASTHMA & IMMUNOLOGY RESEARCH》 * |
黄宗甄等: "《生物科学参考资料》", 31 May 1981, 科学出版社 * |
Also Published As
Publication number | Publication date |
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CN105358134B (zh) | 2019-05-31 |
US20160367475A1 (en) | 2016-12-22 |
JP2016523903A (ja) | 2016-08-12 |
EP3017810A4 (en) | 2017-02-22 |
KR20150003685A (ko) | 2015-01-09 |
EP3017810A1 (en) | 2016-05-11 |
WO2015002435A1 (ko) | 2015-01-08 |
US9867776B2 (en) | 2018-01-16 |
EP3017810B1 (en) | 2021-06-02 |
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