CN101869570A - 应用于粘膜的含环索奈德药用组合物 - Google Patents
应用于粘膜的含环索奈德药用组合物 Download PDFInfo
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- CN101869570A CN101869570A CN201010223433A CN201010223433A CN101869570A CN 101869570 A CN101869570 A CN 101869570A CN 201010223433 A CN201010223433 A CN 201010223433A CN 201010223433 A CN201010223433 A CN 201010223433A CN 101869570 A CN101869570 A CN 101869570A
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0043—Nose
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
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- Animal Behavior & Ethology (AREA)
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- Molecular Biology (AREA)
- Biochemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
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- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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- Steroid Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
本发明提供一种应用于粘膜的药用组合物，所述组合物可用于药物治疗，它包含纤维素和环索奈德，其渗透压是150mOsm或更小。由于有效且高的环索奈德保持力和渗入粘膜下层或粘膜中的血液的渗透力，对于应用于粘膜而言所述组合物优于常规药用组合物。
Description
本申请是分案申请，其母案是申请日为2010年10月20日、申请号为00814405.2、发明名称为“应用于粘膜的含环索奈德药用组合物”的申请。
技术领域
本发明涉及一种应用于粘膜的药用组合物，所述组合物可用于药物治疗，它包含水不溶性和/或低水溶性物质、环索奈德和水介质，它的渗透压小于290mOsm。更具体地说，本发明涉及一种应用于粘膜的药用组合物，所述组合物包含水不溶性和/或低水溶性物质、环索奈德和水介质，它的渗透压小于290mOsm，由于环索奈德的保持力和渗入粘膜下层和粘膜中的血液的高环索奈德渗透力，对于应用于粘膜而言所述组合物优于常规药用组合物。
技术背景
作为药物治疗的一种方法，应用于粘膜被认为是有用的药疗法，这是因为：(1)对于局部区域例如鼻粘膜、口腔粘膜和阴道粘膜的疾病，它允许直接应用于的受侵袭部位，(2)它对于系统性疾病的直接作用可以预料为与对鼻粘膜进行鼻喷雾和用于直肠粘膜的栓剂的情况一样，和(3)与注射比较，其应用容易，代表为靶向肠粘膜的口服药物等等。例如，应用于粘膜的药用制剂已有市售，原因是：(1)就鼻喷雾剂而言，用于治疗过敏性鼻炎，和(2)就栓剂而言，用于减轻疼痛。
作为用于局部粘膜疾病的药用制剂，Saunders等(WO 92-14473例如提供一种包含Tipredane作为主要药物的悬浮剂，作为用于治疗过敏性鼻炎的药用制剂。Helzner等(WO 97-01337)也提供一种包含抗组胺药和类固醇以及含水的药用制剂，作为用于治疗过敏性鼻炎的药用制剂。
作为用于系统性疾病的药用制剂，已经提供几种增强透过粘膜吸收药物的方法。Nagata等(日本未经审查的专利公布(Kokai)号63(1988)-303931)，例如，提供一种将一种渗透压比率为1(渗透压为290mOsm)或更低的液态生长激素释放因子应用于鼻腔的方法，作为使所述生长因子能够通过鼻粘膜快速而有效地吸收进入血液循环的方法。此外，Ohwaki等(日本未经审查的专利公布(Kokai)号60(1985)-123426)提供一种将一种渗透压比率为1-5(渗透压为290-1450mOsm)而pH为2-5的促胰液素应用于鼻腔的方法，作为使促胰液素能够通过鼻腔快速而有效地吸收进入血液循环的方法。此外，Awatsu等(Pharm.Red.Vol.10，No.9，1372-1377，1993)提供一种将加入聚氧化乙烯9-十二烷基醚作为吸收增强剂的药用溶液应用于鼻粘膜的方法，作为使粒细胞集落刺激因子能够透过鼻粘膜有效吸收进入血液循环的方法。
环索奈德是一种新产生的亲脂性类皮质激素。由于它的生物活性，期望有用于局部疾病或系统性疾病的含环索奈德的市售药用制剂。
然而，当将包含环索奈德的组成与常规制剂相同的药用制剂给予粘膜时，可能出现液滴，或者由于粘液纤毛的清除功能等原因，在充分转运或渗透至粘膜组织之前，所述药用制剂被快速排出到粘膜组织之外。因为所述吸收增强剂具有刺激鼻粘膜的问题，所以仍有待实现采用吸收增强剂的方法。
因此非常需要开发一种应用于粘膜的包含环索奈德的药用制剂，在应用于粘膜之后，所述药用制剂允许透过粘膜转运足量的环索奈德到粘膜下层或血液中。
发明公开
本发明的目的是提供一种应用于粘膜的药用组合物，当应用于粘膜时，该组合物具有透过粘膜渗透至粘膜下层或血液的有效且高的环索奈德渗透力。
经过深入的研究达到上述第一目的之后，本发明人已经发现，通过配制含水不溶性和/或低水溶性的物质且渗透压小于290mOsm的环索奈德，有可能提供一种应用于粘膜的包含环索奈德的药用制剂，所述药用制剂由于透过粘膜渗透至粘膜下层或血液的有效且高的渗透性而优于常规液体组合物，并因此获得了本发明。
在Osada或Ohwaki的专利中公开并且已经在Awazu等的论文(Pharm.Res.Vol.10，No.9，1372-1377，1993)中报道了通过控制药用制剂的渗透压增强透过粘膜的药物吸收。然而，这些现象只是在不含水不溶性和/或低水溶性物质的水溶液制剂中观察到，因此实质上与本发明的所述含环索奈德药用制剂不同，在本发明的所述制剂中包含水不溶性和/或低水溶性物质是必不可少的。另外，在Osada的专利中已经表明，当所述制剂的渗透压比率为1(渗透压为290mOsm)或更低时，生长激素释放因子透过大鼠鼻粘膜的吸收较高；在Ohwaki的专利中，当促胰液素的渗透压比为1(渗透压为290mOsm)或者更高时，吸收较高；在Awazu的专利中，当所述制剂渗透压为285mOsm时，与174mOsm相比，粒细胞集落刺激因子的吸收较高。所以人们不能预期减小渗透压增强了环索奈德吸收的事实。
Saunder的专利申请(WO 92-14473)和上述Helzner的专利申请(WO 97-01337)描述了包含水不溶性和/或低水溶性物质的药用制剂。然而，Saunder的专利申请(WO 92-14473)在其权利要求中没有概括地描述药用制剂的渗透压，，在说明书中仅仅描述了优选等渗性；而Helzner的专利申请没有概括地描述了药用制剂的渗透压，在其权利要求中，仅仅具体描述优选添加等渗剂。因此，从这些专利中，人们不能预期在低渗透压下环索奈德吸收的显著增强。
因此令人惊奇地是，当水不溶性或低水溶性物质同时存在时，在较低渗透压下对透过粘膜的环索奈德吸收的增强作用是显著的。
因此，本发明提供一种应用于粘膜的含水制药用组合物，所述组合物包含一种或多种水不溶性物质和/或低水溶性物质以及环索奈德，其渗透压小于290mOsm。所述组合物是应用于粘膜的药用组合物，由于在粘膜处渗透到粘膜下层或血液中的显著有效和高的环索奈德渗透性，它优于应用于粘膜的常规药用组合物。
实施本发明的实施方案
在本发明中，所述水不溶性或低水溶性物质可以是任何物质，优选例子包括纤维素，更优选结晶纤维素。
在本发明的第一方面，以固体颗粒存在于水介质中的所述水不溶性和/或低水溶性物质的浓度，优选相当于所述制剂总量的0.3％w/w，更优选1％-10％w/w。
在本发明的任一方面，优选以固体颗粒存在于水介质中的所述水不溶性和/或低水溶性物质均匀分散于所述水介质中。
在本发明的任一方面，优选还将一种水溶性聚合物加入到所述组合物中。具体而言，可以提及藻酸、丙二醇、果胶、低甲氧基果胶、瓜尔豆胶、阿拉伯树胶、角叉藻聚糖、甲基纤维素、羧甲基纤维素钠、黄原胶、羟丙基纤维素、羟丙基甲基纤维素以及此类物质，优选提及羧甲基纤维素钠、黄原胶和羟丙基纤维素。另外，作为水溶性聚合物和水不溶性和/或低水溶性物质的优选组合，可以提及羧甲基纤维素钠和结晶纤维素的混合物一结晶纤维素羧甲纤维素钠。当添加时，优选这些水溶性聚合物的浓度相当于所述水不溶性和/或低水溶性物质的1％-30％w/w。
在本发明的第一方面中，所述药用制剂的渗透压小于290mOsm是一个必要条件，而且优选渗透压为150mOsm或更低，更优选60mOsm或更低，更优选30mOsm或更低，最优选10mOsm或更低。
在本发明中，不用特别要求添加控制渗透压的物质(渗透压控制剂)，但添加时可以使用任何物质。具体的例子包括盐例如氯化钠、和水溶性糖例如葡萄糖，其中优选盐，例如氯化钠。
在本发明中，可以添加一种已知的表面活性剂，具体例子包括聚山梨酯80、甘油单硬脂酸酯、硬脂酸-聚烃氧基酯、lauromacrogol、失水山梨糖醇油酸酯、蔗糖脂肪酸酯。
用于本发明的环索奈德的量是治疗有效量，并且可以根据疾病的类型和程度、患者的年龄和体重等等而确定。所述量通常是一般用于注射的每种药物量的1-20倍，更优选1-10倍。
优选本发明的环索奈德浓度相当于所述药用制剂总量的0.01％-1％w/w，最优选0.05％-0.5％w/w。
为了改善本发明的所述组合物的物理性质、外观或气味，根据需要可以添加一种已知的消毒防腐药、一种pH控制剂、一种防腐剂、一种缓冲液、一种着色剂、一种气味矫味剂以及诸如此类。例如可以提及苯扎氯铵作为消毒防腐药，盐酸作为pH控制剂，抗坏血酸作为防腐剂，柠檬酸及其盐作为缓冲剂，红色2号(Red No.2)作为着色剂，薄荷醇作为气味矫味剂。
本发明所应用的粘膜可以是任何粘膜。具体的例子包括肠粘膜、胃粘膜、鼻粘膜、气管/支气管/肺粘膜、口腔粘膜、直肠粘膜、阴道粘膜以及诸如此类，最优选鼻粘膜。
本发明的所述组合物可以配制为适用于作为药用制剂给予的剂型。它可以包含一种间接剂型，比如用于给予胃粘膜和肠粘膜的口服制剂。在这种情况下，例如可以将本发明的所述组合物充填到胃溶胶囊或肠溶胶囊中，将所述组合物暴露在所需粘膜部位上。作为另一种剂型，当给予直肠粘膜时，可以将本发明的所述组合物以单位剂型充填于胶囊中，作为栓剂给予。当给予口腔粘膜、鼻粘膜或阴道粘膜时，本发明的所述组合物可以充填到喷雾型容器中，将固定量的所述组合物喷射到口腔、鼻子或阴道中。当给予气管/支气管/肺粘膜时，本发明的所述组合物可以充填到吸入型容器中，所述组合物可以允许被吸入到气管、支气管或肺中。
实施例
将参考以下实施例解释本发明。
从Byk Gulden Lomberg Chemische Fabrik GmbH获得环索奈德，结晶纤维素羧甲纤维素钠-AvicelTM RC-591NF由Asahi ChemicalIndustry，Co.，Ltd生产。苯扎氯铵得自Nakalai Tesque，葡萄糖得自WakoPure Chemicals。
实施例1
制备一种应用于粘膜的包含以下表1中所描述组分的含环索奈德的1号组合物。对于这种药用制剂，采用Advance Instruments，Inc.的3MO型微量渗透压计(Micro-Osmometer Model 3MO)测量渗透压。结果在表1中显示。
采用市售的悬浮装置，将应用于鼻粘膜的100μl所述1号组合物喷到兔(日本白(Japanese White)、雄性、体重3kg)的单侧鼻腔中。在给药后5、15和30分钟，收集从鼻腔流至食道的粘液，通过HPLC测定它们的环索奈德浓度。
然后，在给药后30分钟，用乙醇清洗鼻腔中的残留环索奈德，通过HPLC测定洗液的环索奈德浓度。
根据流出的粘液量和它们的环索奈德浓度，计算从鼻腔流至食道的环索奈德的清除量。然后根据所给予的环索奈德量和所收集的环索奈德量，计算环索奈德残留量。5只兔子的平均值在表1中显示。
表1
比较实施例1
制备一种应用于粘膜的包含以下表2中所描述组分的含环索奈德的2号组合物。对于这种药用制剂，采用Advance Instruments，Inc.的3MO型微量渗透压计测量渗透压。结果在表2中显示。
采用市售的悬浮装置，将应用于鼻粘膜的100μl所述2号组合物喷到兔(日本白(Japanese White)、雄性、体重3kg)的单侧鼻腔中。在给药后5、15和30分钟，收集从鼻腔流至食道的粘液，通过HPLC测定它们的环索奈德浓度。
然后，在给药后30分钟，用乙醇清洗鼻腔中的残留环索奈德，通过HPLC测定洗液的环索奈德浓度。
根据流出的粘液量和它们的环索奈德浓度，计算从鼻腔流至食道的的环索奈德的清除量。然后根据所给予的环索奈德量和所收集的环索奈德量，计算环索奈德残留量。5只兔子的平均值在表2中显示。
表2
随着渗透压的提高，应用于粘膜的含环索奈德组合物的清除量急剧增加。在给予2号组合物(330mOsm)后30分钟，所述环索奈德的清除量是1号组合物(5mOsm)的2.5倍，而1号组合物(5mOsm)的残留环索奈德量是2号组合物(330mOsm)的2倍。这些结果表明，通过将渗透压从330mOsm降至5mOsm，环索奈德的保持力提高了。
提高的环索奈德保持力在粘膜上留下大量的残留环索奈德，而且在粘膜周围形成环索奈德的浓度梯度。因此环索奈德渗透到粘膜下层以及粘膜中的血液中的渗透力提高了，并保持这种状态。
工业适用性
因此，本发明提供一种应用于粘膜的药用组合物，当应用于粘膜时，所述组合物具有透过粘膜渗透到粘膜下层或血液中的有效和高的环索奈德渗透力。
通过采用本发明的所述组合物应用于粘膜，甚至以比常规方法小的剂量或低的给药频率，可以获得同采用与常规组合物一样的组合物所获得的效果比较效果相同或效果更好。这样可以导致副作用减弱。
因此，本发明在应用于粘膜的环索奈德治疗的治疗效果和经济效益方面非常有用。
Claims (16)
1.一种应用于粘膜的含水制药用组合物，所述组合物包含纤维素和环索奈德，其渗透压是150mOsm或更小。
2.权利要求1的应用于粘膜的所述药用组合物，其中所述纤维素是结晶纤维素。
3.权利要求2的应用于粘膜的所述药用组合物，其中所述纤维素是结晶纤维素羧甲纤维素钠。
4.权利要求1的应用于粘膜的所述药用组合物，其中所述渗透压是60mOsm或更小。
5.权利要求4的应用于粘膜的所述药用组合物，其中所述渗透压是30mOsm或更小。
6.权利要求5的应用于粘膜的所述药用组合物，其中所述渗透压是10mOsm或更小。
7.权利要求1-6中任一项的应用于粘膜的所述药用组合物，所述组合物还包含一种选自氯化钠和葡萄糖的渗透压控制剂。
8.权利要求1-6中任一项的应用于粘膜的所述药用组合物，所述组合物还包含一种水溶性聚合物物质，所述水溶性聚合物是选自以下的一种或多种物质：藻酸、丙二醇、果胶、低甲氧基果胶、瓜尔豆胶、阿拉伯树胶、角叉藻聚糖、甲基纤维素、羧甲基纤维素钠、黄原胶、羟丙基纤维素和羟丙基甲基纤维素。
9.权利要求8的应用于粘膜的所述药用组合物，其中所述水溶性聚合物是羟丙基甲基纤维素。
10.权利要求1-6中任一项的应用于粘膜的所述药用组合物，所述组合物还包含pH控制剂。
11.权利要求10的应用于粘膜的所述药用组合物，其中所述pH控制剂是盐酸。
12.权利要求1-6中任一项的应用于粘膜的所述药用组合物，所述组合物还包含防腐剂。
13.权利要求2的应用于粘膜的所述药用组合物，其中所述结晶纤维素以固体颗粒存在于水介质中。
14.权利要求2的应用于粘膜的所述药用组合物，其中所述结晶纤维素以固体颗粒分散于水介质中。
15.权利要求1-6中任一项的应用于粘膜的所述药用组合物，所述组合物还包含表面活性剂。
16.权利要求1-6中任一项的应用于粘膜的所述药用组合物，其中所述粘膜是鼻粘膜。
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| HU (1) | HU228893B1 (zh) |
| IL (2) | IL148691A0 (zh) |
| ME (1) | ME00567B (zh) |
| MX (1) | MXPA02003974A (zh) |
| MY (1) | MY136987A (zh) |
| NO (1) | NO327444B1 (zh) |
| NZ (1) | NZ518298A (zh) |
| PE (1) | PE20010712A1 (zh) |
| PL (1) | PL199702B1 (zh) |
| PT (1) | PT1225902E (zh) |
| RS (1) | RS50310B (zh) |
| SI (1) | SI1225902T1 (zh) |
| SK (1) | SK286196B6 (zh) |
| TR (1) | TR200200841T2 (zh) |
| TW (1) | TWI225788B (zh) |
| WO (1) | WO2001028562A1 (zh) |
| ZA (1) | ZA200203077B (zh) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR026072A1 (es) * | 1999-10-20 | 2002-12-26 | Nycomed Gmbh | Composicion farmaceutica que contiene ciclesonida para aplicacion a la mucosa |
| AR026073A1 (es) | 1999-10-20 | 2002-12-26 | Nycomed Gmbh | Composicion farmaceutica acuosa que contiene ciclesonida |
| BRPI0312377A8 (pt) | 2002-07-02 | 2015-12-15 | Altana Pharma Ag | Suspensão aquosa estéril contendo ciclesonida |
| US7221586B2 (en) | 2002-07-08 | 2007-05-22 | Micron Technology, Inc. | Memory utilizing oxide nanolaminates |
| RU2343160C2 (ru) * | 2002-07-26 | 2009-01-10 | Фмк Корпорейшн | Получение микрокристаллической целлюлозы |
| PL373433A1 (en) * | 2002-08-30 | 2005-08-22 | Altana Pharma Ag | The use of the combination of ciclesonide and antihistamines for the treatment of allergic rhinitis |
| ATE405275T1 (de) * | 2002-12-12 | 2008-09-15 | Nycomed Gmbh | Kombinationsarzneimittel aus r,r-formoterol und ciclesonide |
| MY143936A (en) | 2003-03-27 | 2011-07-29 | Nycomed Gmbh | Process for preparing crystalline ciclesonide with defined particle size |
| CA2538419C (en) * | 2003-09-16 | 2012-07-03 | Altana Pharma Ag | Use of ciclesonide for the treatment of respiratory diseases |
| PE20050941A1 (es) * | 2003-12-16 | 2005-11-08 | Nycomed Gmbh | Suspensiones acuosas de ciclesonida para nebulizacion |
| WO2005102354A1 (en) * | 2004-04-20 | 2005-11-03 | Altana Pharma Ag | Use of ciclesonide for the treatment of respiratory diseases in a smoking patient |
| EP1796679A1 (en) * | 2004-09-10 | 2007-06-20 | Altana Pharma AG | Ciclesonide and syk inhibitor combination and methods of use thereof |
| EP1645266A1 (en) * | 2004-10-08 | 2006-04-12 | Hisamitsu Medical Co., Ltd. | Aqueous suspension for nasal drops |
| EP2265250A2 (en) * | 2008-03-14 | 2010-12-29 | Cephalon, Inc. | Enhanced transmucosal composition and dosage form |
| WO2011135585A2 (en) | 2010-04-28 | 2011-11-03 | Cadila Healthcare Limited | Aqueous pharmaceutical solution of ciclesonide |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS63303931A (ja) * | 1987-06-05 | 1988-12-12 | Sumitomo Pharmaceut Co Ltd | 経鼻投与用成長ホルモン放出活性物質製剤 |
| GB9103824D0 (en) | 1991-02-23 | 1991-04-10 | Fisons Ag | Formulation |
| WO1997001337A1 (en) | 1995-06-29 | 1997-01-16 | Mcneil-Ppc, Inc. | The combination of topical nasal antihistamines and topical nasal steroids |
| US6120752A (en) * | 1997-05-21 | 2000-09-19 | 3M Innovative Properties Company | Medicinal aerosol products containing formulations of ciclesonide and related steroids |
| SE9704186D0 (sv) | 1997-11-14 | 1997-11-14 | Astra Ab | New composition of matter |
| EP1050299A4 (en) * | 1998-01-22 | 2007-05-02 | Santen Pharmaceutical Co Ltd | SUSPENSION COLLYRE OF FLUOROMETHOLONE |
| SE514128C2 (sv) * | 1998-03-17 | 2001-01-08 | Pharmalink Ab | Användning av en glukokortikoid för framställning av ett läkemedel för behandling av glomerulonefrit |
| TWI243687B (en) | 1998-04-21 | 2005-11-21 | Teijin Ltd | Pharmaceutical composition for application to mucosa |
| AR026072A1 (es) * | 1999-10-20 | 2002-12-26 | Nycomed Gmbh | Composicion farmaceutica que contiene ciclesonida para aplicacion a la mucosa |
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2000
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2002
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2003
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Also Published As
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| Publication | Publication Date | Title |
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| CN101869570B (zh) | 应用于粘膜的含环索奈德药用组合物 | |
| AU757772B2 (en) | Medicinal compositions for application to mucosa | |
| MXPA99011639A (en) | Medicinal compositions for application to mucosa |
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