CN104168892A - 用于口腔施用的含有孟鲁司特或其可药用盐的膜 - Google Patents
用于口腔施用的含有孟鲁司特或其可药用盐的膜 Download PDFInfo
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- CN104168892A CN104168892A CN201280070651.7A CN201280070651A CN104168892A CN 104168892 A CN104168892 A CN 104168892A CN 201280070651 A CN201280070651 A CN 201280070651A CN 104168892 A CN104168892 A CN 104168892A
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- 229960005127 montelukast Drugs 0.000 title claims abstract description 40
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- BECPQYXYKAMYBN-UHFFFAOYSA-N casein, tech. Chemical compound NCCCCC(C(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(CC(C)C)N=C(O)C(CCC(O)=O)N=C(O)C(CC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(C(C)O)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=N)N=C(O)C(CCC(O)=O)N=C(O)C(CCC(O)=O)N=C(O)C(COP(O)(O)=O)N=C(O)C(CCC(O)=N)N=C(O)C(N)CC1=CC=CC=C1 BECPQYXYKAMYBN-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4704—2-Quinolinones, e.g. carbostyril
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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
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- A61P11/00—Drugs for disorders of the respiratory system
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- A—HUMAN NECESSITIES
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- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/18—Halogen atoms or nitro radicals
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
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- General Health & Medical Sciences (AREA)
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- General Chemical & Material Sciences (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Otolaryngology (AREA)
- Zoology (AREA)
- Nutrition Science (AREA)
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明提供了口腔分散膜(ODF),其包含孟鲁司特或其可药用盐,优选孟鲁司特钠。另外,本发明提供了用于制备孟鲁司特口腔分散膜的方法,所述口腔分散膜显示出显著的物理性质而不劣化孟鲁司特的稳定性。
Description
技术领域
本发明涉及用于口腔施用的膜制剂,含有孟鲁司特或其可药用盐,优选孟鲁司特钠。根据本发明的用于口腔施用的膜制剂在施用后在口腔中可易于崩解,因此易于施用而不用水。
背景技术
孟鲁司特是用于治疗哮喘、过敏性鼻炎等的白三烯受体拮抗剂(LTRA,leukotriene receptor antagonist)。
市售的口服制剂是以不用水难以服用的片剂、胶囊和颗粒的形式。
相反,通过将它们溶解在口腔中容易地施用的膜制剂,可容易地仅用口腔中的唾液崩解。因此,膜制剂适用于吞咽片剂等不舒服的儿童、老年人和长时间卧床不起的患者。另外,考虑到因为膜制剂的厚度便于在钱包或笔记本中携带,膜制剂是方便的。
然而,已知孟鲁司特对湿气、热和光相对不稳定。因此,在制备含有孟鲁司特的膜制剂中,必需确保膜制备期间以及膜制备后的贮存期间的稳定性。
发明详述
技术问题
因此,本发明的一个目的是提供用于口腔施用的膜制剂,其包含孟鲁司特或其可药用盐作为活性成分,其可容易地服用并且具有改进的稳定性。本发明的另一个目的是提供用于制备这样的膜制剂的方法。
技术方案
为了完成本发明的目的,本发明的一个方面提供了用于口腔施用的膜制剂,其包含孟鲁司特或其可药用盐,优选孟鲁司特钠。本发明的用于口腔施用的膜通过在口腔中溶解或精细分散来施用。这样的膜可以主要通过将它放置在舌头上用于溶解或通过将它贴附在上颚、舌下或颊区域上来施用。
在本发明中,孟鲁司特的可药用盐可以是具有锂、钠、钾、钙、铵、镁、二环己基胺、金刚胺、环丙基胺或其它有机胺的盐,但不限于此。
在本发明中,所述膜可以称为口腔分散膜(ODF,Oral DispersibleFilm)、条或者口腔溶解膜,并且它可以通过将其在口腔中溶解或精细分散来服用。这样的膜可以主要通过将它放置在舌头上用于溶解或通过将它贴附在上颚、舌下或颊区域上来施用。根据本发明的膜制剂具有可以不用水而施用的益处。
根据本发明的用于口腔施用的优选膜含有1mg至15mg的孟鲁司特并且每一片具有20mg至200mg的重量。另外,膜包含基于膜的总重量为5wt%至20wt%的量的增塑剂并且具有500μm或更小的厚度。优选地,这样的膜可以包含风味剂、着色剂和甜味剂的至少一种,并且其各自的量可以基于膜的总重量在10wt%以内。另外,如果需要,还可包含增粘剂、稳定剂、pH调节剂、崩解剂、抗微生物剂、唾液刺激剂、酸化剂和乳化剂。除了以上添加剂之外的大部分重量由形成所述膜的材料占据。
这样的成膜剂可以为选自以下的至少一种:淀粉、水溶性淀粉、改性淀粉、纤维素(例如羟丙基纤维素、羟丙基甲基纤维素、羧甲基纤维素、羟乙基纤维素)、聚乙烯吡咯烷酮、聚乙烯醇、支链淀粉、明胶、藻酸、瓜尔胶、黄原胶、聚乙二醇、金合欢胶、阿拉伯胶、聚丙烯酸、直链淀粉、果胶、糊精、壳多糖、脱乙酰壳多糖、明胶、谷蛋白、酪蛋白、角叉菜胶和刺槐豆胶。
增塑剂可以为选自甘油、丙二醇、聚乙二醇和甘油三乙酸酯的至少一种。
风味剂可以为人工食用香料、天然食用香料或其混合物,并且可以包含具有柠檬、薄荷、樱桃、苹果、葡萄、蓝莓、橙、桃、菠萝、葡萄柚、人参的风味的各种材料。
着色剂可以为人工着色剂、天然着色剂或其混合物。
酸化剂可以为柠檬酸、苹果酸、乳酸、乙酸、酒石酸、富马酸或其混合物。
根据本发明的用于口腔施用的膜可以通过以下来制备:将以上提到的组分溶解或分散在水、醇(例如具有1至4个碳原子的低级醇)、丙酮或其混合物中以获得溶液或液体组合物,并且将得到的溶液或液体组合物铺展为最大厚度1000μm或更少,随后干燥。在根据本发明的用于口腔施用的膜的制备中,除了以上提到的溶剂,还有丙酮、庚烷、丁醇、丙醇、戊醇、以及乙酸乙酯,但本发明不限于此。例如,如果必要可以使用ICH指导原则对于残余溶剂的类别3中所列的溶剂。
在本发明中,将通过混合这些组分获得的溶液铺展为最大厚度1000μm或更少,然后用热干燥以制备膜。将制备的膜切割成期望的大小和重量并且用能够阻挡湿气和光的材料(优选铝袋膜)包装,由此获得成品。
本发明还提供了用于制备用于口腔施用的含有孟鲁司特的膜的方法,其包括(S1)制备其中溶解或分散孟鲁司特或其可药用盐、成膜剂和增塑剂的液体组合物,(S2)将所述液体组合物铺展,以及(S3)将通过铺展形成的所得膜干燥直到LOD值达到1wt%至8wt%(优选2wt%至7wt%,更优选3wt%至6wt%),以获得具有改进的稳定性的膜。
在本发明中,可以通过使用MX-50湿气分析仪(AND Co.)测量LOD值,例如通过在标准模式(其用LO ACCURACY设定)中在105℃干燥约1g的膜并且测量相对于干燥前膜的重量所降低的含量(wt%)。
根据本发明,可以调整含有孟鲁司特膜制剂的湿气百分比以控制孟鲁司特的稳定性和膜的数种性质(如果LOD值为1%以下,则膜可能很容易破裂,而如果LOD值超过8%,则膜变得发黏,使得它难以操作)。
更优选地,在本发明的含有孟鲁司特的膜的制备中,在LED灯、钠灯或用于阻挡变色的荧光灯(阻挡紫外线的荧光灯),优选LED灯或钠灯的条件下,进行制备液体组合物作为用于生产膜的溶液、干燥、将干燥的膜切割成期望的大小(重量)和将成品膜包装的步骤。
阻挡紫外线荧光灯阻挡了从普通荧光灯发射的紫外线射线,其原理上与将阻挡紫外线膜在进行紫外光照射的方向上贴附到普通荧光灯的方法相同。因此,这样的制备步骤可在将阻挡紫外线膜在进行紫外光照射的方向上贴附到普通荧光灯的条件下进行,其落入本发明的范围内。
不寻常的是,甚至在相同的照度(lux)条件下这样的照亮也允许维持孟鲁司特的稳定性。
更优选地,在本发明的含有孟鲁司特的膜的制备中,控制用于膜的暴露部分的照度水平以将照度值维持在约300或更少,并且将膜对光的暴露时间控制在2小时以内。
优选地,本发明基于这样的出人意料的发现,使用孟鲁司特钠作为活性成分,预糊化淀粉和/或羟丙基纤维素作为成膜剂,以及甘油作为增塑剂的用于口腔施用的膜与使用其他组分的孟鲁司特口腔膜相比具有优良的稳定性和良好的膜性能。更优选地,用于口腔的这种膜可以包含三氯半乳蔗糖作为甜味剂,另外还包含柠檬酸。
液体组合物(其含有水并且用作用于制备根据本发明的ODF的储备溶液)可维持孟鲁司特(活性成分)的稳定性两周或更长的时间而没有任何改变。此外,用于口腔的含有孟鲁司特的膜(其包装在铝袋中)在40℃和75%RH的条件下在6个月的贮存期间是稳定的。
本文所用的术语“稳定的”意指MOK-3-亚砜产生的量为1.7wt%或更少并且杂质的总含量不超过2.5wt%。
具有以上制剂的含有孟鲁司特钠的膜制剂可在其生产期间维持药的稳定性,考虑到大量生产是容易的,具有良好的感官特性(sensoryproperties)并且确保作为药物的长期稳定性。
有利的效果
本发明提供了口腔分散膜(ODF)制剂,其包含孟鲁司特或其可药用盐,优选孟鲁司特钠。本发明还提供了用于制备这样的制剂而不劣化孟鲁司特的稳定性的方法。
用于本发明的方式
下文中,为了更好的理解将详细描述本发明的多个优选实施例。然而,本发明的实施例可以以多种方式改变,并且其不应当被解释为限制本发明的范围。本发明的实施例仅为了使本领域的普通技术人员更好理解本发明。
<实施例1>
根据以下配方制备含有孟鲁司特钠的膜制剂。将所有的材料溶解在溶剂(水)中并均匀地混合,随后在80℃烘箱干燥直到LOD(干燥失重,120℃,10分钟)值达到1wt%至3wt%以获得膜。将所得膜切割成合适的大小以使得其重量变成约40.5mg并且含有约5.2mg的孟鲁司特钠。所得膜的厚度在50μm至150μm的范围内。
表1
成分 | 量(g) |
孟鲁司特钠 | 5.2 |
预糊化淀粉 | 8.8 |
羟丙基纤维素 | 21 |
甘油 | 4 |
三氯半乳蔗糖 | 1 |
柠檬酸 | 0.5 |
水 | 120 |
<实施例2>
除了进行干燥步骤以使得LOD值达到4wt%至6wt%以外,重复实施例1的步骤以获得膜。
<实验例1>
将实施例1和2中制备的膜在相同的条件下贮存并且比较孟鲁司特的杂质产生的程度。具体地,实施例1和2的样品各自包装在铝袋中并且贮存在保持温度为40℃并且相对湿度为75%的室中。6个月后,分析贮存样品所产生的杂质,并且其结果在表2中示出。实施例1的样品含有约2wt%的湿气百分比,并且实施例2的样品具有约5wt%的湿气百分比。在以下条件下通过UPLC进行杂质的分析:
-柱:2.1mm×100mm,WatersHSS C18 1.8μm
-注射量:2μl
-检测器:紫外吸收比色计(波长258nm)
-柱温度:40℃
-样品温度:5℃
流动相A:0.1%的在水中的柠檬酸,流动相B:100%乙腈
自开始至13分钟: 流动相A∶流动相B=35∶65
13分钟至13.1分钟: 流动相A∶流动相B=0∶100
13.1分钟至15分钟: 流动相A∶流动相B=35∶65
-稀释剂:100%甲醇
表2
<实施例3>
除了进行干燥以使得LOD值达到1wt%或更少以外,重复实施例1的步骤以获得膜。
<实施例4>
除了进行干燥以使得LOD值超过8wt%以外,重复实施例1的步骤以获得膜。
<实验例2>
将在实施例1至4中制备的膜缠绕在直径为约10mm的棒上,用非常弱的力拉伸。在这个过程中,将实施例1、2和4的膜弯曲而没有任何问题,而实施例3的膜在弯曲角度变成90°之前破裂。
<实验例3>
将两片所制备的各个膜堆叠。实施例1、2和3的膜片材立即分离,而实施例4的膜片材相互粘附,所以变得难以分离。
<实施例5和6>
除了将表3(实施例5)和4(实施例6)中所列的原料的各成分溶解在溶剂中以获得溶液以外,重复实施例1的步骤。
表3
成分 | 量(g) |
孟鲁司特钠 | 5.2 |
淀粉 | 10 |
羟丙基纤维素 | 21.43 |
甘油 | 4.8 |
三氯半乳蔗糖 | 0.77 |
柠檬香精 | 3 |
柠檬酸 | 0.8 |
水 | 20 |
乙醇 | 50 |
表4
成分 | 量(g) |
孟鲁司特钠 | 5.2 |
预糊化淀粉 | 10 |
羟丙基纤维素 | 21.7 |
甘油 | 4.7 |
丁磺氨钾 | 1.4 |
柠檬香精 | 3 |
水 | 70 |
<实验例4>
将在实施例5和6中获得的溶液放在光阻挡容器中,并将容器贮存在温度维持为40℃的室中1周。1周后,分析溶液的杂质。总杂质保持没有大的改变,由此确认甚至在储存溶液自身的情况下也确保溶液自身的稳定性。测量的结果在表5中示出。
表5
实施例5 | 实施例6 | |
起始 | 0.5% | 0.5% |
1周后 | 0.4% | 0.6% |
<实验例5>
将实施例1中制备的膜样品放在透明玻璃瓶中,并且用盖子覆盖瓶子以使得空气中的湿气不能渗透。然后,将瓶子倒置并在每个LED灯、钠灯和用于阻挡变色的荧光灯下贮存2小时。控制每个灯的亮度和距离以使得各自的条件设定为约1000-lx和约200-lx照度。结果,样品的总杂质的产生率在表6和7中示出。
表6
表7
如表6和7中所示,当样品暴露在普通荧光灯下1小时时,即使照度水平降低为200lx也产生约0.63%的杂质,而当样品在LED灯或用于阻挡变色的荧光灯下暴露1小时时,即使照度水平为1000lx也仅产生最大0.51%的杂质。
在杂质由光产生的药物的情况下,应当缩短对光的暴露时间从而抑制杂质的产生。然而,在数个步骤(例如模制或包装)期间药物不可避免地在某种程度上暴露。另外,为了使工作人员目视检查产品的缺陷,高的照度水平是有利的。在甚至于1000lx的条件下使用LED灯、钠灯和用于阻挡变色的荧光灯的情况下,杂质的产生在持续15分钟时未增加,并且甚至持续30分钟时也没有杂质产生的显著增加。然而,在使用普通荧光灯的情况下,仅在15分钟内杂质的产生就开始增加,并且持续30分钟时杂质的量增加50wt%或更高。
<实施例7>
根据以下配方制备含有孟鲁司特钠的膜制剂。将所有成分溶解在溶剂(水)中并且均匀地混合,随后在80℃烘箱干燥直到LOD(干燥失重,120℃,10分钟)值达到4wt%至5wt%以获得膜。将所得膜切割成合适的大小以使得其重量变成约103.88mg并且含有约10.4mg的孟鲁司特钠。所得膜的厚度在50μm至150μm的范围内。
表8
成分 | 量(g) |
孟鲁司特钠 | 4.45 |
羟丙基纤维素 | 30 |
甘油 | 10 |
水 | 50 |
<实验例6>
将在实施例1中制备的膜和SingulairTM 10mg片剂(比较例1,MerckSharp&Dohme Limited,UK)各自在相同条件下贮存并且比较孟鲁司特的杂质产生的程度。具体地,实施例1的口腔膜样品和Singulair片剂各自包装在铝袋中并且贮存在维持温度为50℃和相对湿度为75%的室中。6个月后,分析贮存的样品所产生的杂质,其结果在表9中示出。
表9
实施例7 | 比较例1 | |
6个月 | 1.52% | 1.59% |
从表9和以上多个实验结果可以看出,与使用其它聚合物的膜制剂相比,通过使用淀粉、改性淀粉、羟丙基纤维素或其混合物作为聚合物制备的用于口腔的孟鲁司特膜制剂在吸湿性质和杂质的产生方面表现出优良的稳定性。
Claims (8)
1.一种含有孟鲁司特的口腔分散膜,包含孟鲁司特或其可药用盐、成膜聚合物以及增塑剂,
其中所述膜的干燥失重为1wt%至8wt%。
2.根据权利要求1所述的含有孟鲁司特的口腔分散膜,其中所述聚合物为选自淀粉、改性淀粉和羟丙基纤维素中的至少一种。
3.根据权利要求1所述的含有孟鲁司特的口腔分散膜,其中所述增塑剂为选自甘油、丙二醇、聚乙二醇和甘油三乙酸酯中的至少一种。
4.一种用于制备含有孟鲁司特的口腔分散膜的方法,包括:
(S1)制备其中溶解或分散孟鲁司特或其可药用盐、成膜聚合物和增塑剂的液体组合物成膜,
(S2)将所述液体组合物铺展以形成膜,以及
(S3)将通过所述铺展形成的所述膜干燥直到干燥失重值达到1wt%至8wt%。
5.根据权利要求4所述的用于制备含有孟鲁司特的口腔分散膜的方法,其在LED灯、钠灯或阻挡紫外线的荧光灯下进行。
6.根据权利要求4所述的用于制备含有孟鲁司特的口腔分散膜的方法,其中所述聚合物为选自淀粉、改性淀粉和羟丙基纤维素中的至少一种。
7.根据权利要求4所述的用于制备含有孟鲁司特的口腔分散膜的方法,其中所述增塑剂为选自甘油、丙二醇、聚乙二醇和甘油三乙酸酯中的至少一种。
8.根据权利要求7所述的用于制备含有孟鲁司特的口腔分散膜的方法,其中所述增塑剂为甘油。
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CN104784157A (zh) * | 2015-04-04 | 2015-07-22 | 齐鲁制药有限公司 | 一种稳定的孟鲁司特口腔薄膜剂 |
CN105769825A (zh) * | 2014-12-24 | 2016-07-20 | 广州朗圣药业有限公司 | 一种孟鲁司特钠的口腔膜剂及其制备方法 |
CN105878215A (zh) * | 2014-12-31 | 2016-08-24 | 天津康鸿医药科技发展有限公司 | 一种稳定的孟鲁司特口腔速溶膜及其制备方法和用途 |
CN109843273A (zh) * | 2016-10-20 | 2019-06-04 | 因特根克斯公司 | 治疗与神经炎症相关的病症的装置和方法 |
US11672792B2 (en) | 2017-07-05 | 2023-06-13 | Enlitisa (Shanghai) Pharmaceutical Co., Ltd | Topical formulations comprising montelukast and combinations with mussel adhesive proteins |
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JP2017001989A (ja) * | 2015-06-11 | 2017-01-05 | ニプロ株式会社 | 医薬組成物の製造方法及び医薬組成物 |
DE102018101778A1 (de) * | 2018-01-26 | 2019-08-01 | Lts Lohmann Therapie-Systeme Ag | Mehrschichtiger Oraler Dünnfilm |
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Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105769825A (zh) * | 2014-12-24 | 2016-07-20 | 广州朗圣药业有限公司 | 一种孟鲁司特钠的口腔膜剂及其制备方法 |
CN105878215A (zh) * | 2014-12-31 | 2016-08-24 | 天津康鸿医药科技发展有限公司 | 一种稳定的孟鲁司特口腔速溶膜及其制备方法和用途 |
CN104784157A (zh) * | 2015-04-04 | 2015-07-22 | 齐鲁制药有限公司 | 一种稳定的孟鲁司特口腔薄膜剂 |
CN109843273A (zh) * | 2016-10-20 | 2019-06-04 | 因特根克斯公司 | 治疗与神经炎症相关的病症的装置和方法 |
US11672792B2 (en) | 2017-07-05 | 2023-06-13 | Enlitisa (Shanghai) Pharmaceutical Co., Ltd | Topical formulations comprising montelukast and combinations with mussel adhesive proteins |
Also Published As
Publication number | Publication date |
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WO2013100564A1 (ko) | 2013-07-04 |
JP2015503549A (ja) | 2015-02-02 |
CN104168892B (zh) | 2017-06-30 |
KR20130074766A (ko) | 2013-07-04 |
JP6200432B2 (ja) | 2017-09-20 |
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