CN1159950A - 控制活性成分释放的生物粘合药物组合物 - Google Patents

控制活性成分释放的生物粘合药物组合物 Download PDF

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CN1159950A
CN1159950A CN96123198A CN96123198A CN1159950A CN 1159950 A CN1159950 A CN 1159950A CN 96123198 A CN96123198 A CN 96123198A CN 96123198 A CN96123198 A CN 96123198A CN 1159950 A CN1159950 A CN 1159950A
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polyvinylpyrrolidone
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I·劳尔特
G·皮乔恩
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Abstract

本发明涉及一种新的生物粘合药物组合物，它可延长活性成分在颊腔或经粘膜途径的释放。

Description

控制活性成分释放的生物粘合药物组合物
本发明涉及新的生物粘合药物组合物，它可控制活性成分在颊腔局部释放或者经颊(轭或龈)、经舌、鼻、***或直肠粘膜***释放。本发明的药物组合物确保活性成分在不同程度上快速释放，可长时间粘合于颊(轭或龈粘膜)、舌、鼻、***或直肠粘膜。
从代谢角度考虑，透粘膜途径施用是有益的，它可避免活性成分通过肝脏首过效应生产的明显代谢，因此在临床上可降低施用剂量，提高治疗效果。活性成分不易遭受胃肠道中的各种酶或化学降解，也不会带来与功能性和胃肠道生理有关的副作用。
活性成分经粘膜施用的可行性取决于各种因素。具体地说，在长时间接触后，组合物对组织不会生产任何不良影响，不会引起刺激、过敏或致敏；活性成分必须能以足以产生治疗所需的血浆浓度的扩散速率通过相当小的组织表面。
生物粘合形式表现出与生物组织，如颊腔粘膜粘合并且维持较长时间的特性。文献记载了生物粘合现象，该现象通过药剂的一种或多种化合物与存在于生物组织表面的功能性化学基团相连确立。据述，与生物粘合机制有关的相互作用是物理、机械或化学性的。
本发明请求保护的药物组合物，除新颍性外，它还具有很强的粘合作用并能控制和再现活性成分的释放。
本发明的生物粘合药物组合物特征在于使用：-由一种或多种乙烯基乙酸酯/聚乙烯吡咯烷酮共聚物组成的聚合物(A)。该赋形剂在商业上被用作片剂粘合剂和崩解剂，令人意外的是它可使透粘膜施用的膜或贴剂具有良好的粘合特性，-一种或多种活性成分，-任选的化合物(B)，它包括一种或多种化合物，如纤维素及其衍生物，例如乙基纤维素、羟丙基纤维素、羟丙甲基纤维素等，各种原生淀粉及其衍生物，***胶，黄蓍胶，瓜耳胶，苍耳胶，胶豆树胶或角叉酸盐(carrageenates)，-和用作增塑剂、调味剂或甜味剂的赋形剂。
化合物(A)由一种或多种下式的乙烯基乙酸酯/聚乙烯吡咯烷酮共聚物组成：
Figure A9612319800051
目前市售的这类共聚物的具体例子是Kollidon VA64(BASF)及共聚物E-335，E-535，E-735，I-235，I-335，I-535，I-735和S-630(ISP)。
本发明药剂中的化合物(B)可延长活性成分的释放。化合物(A)可形成生物粘合和控释。化合物(A)的比率是5-85％(重量)。选择乙烯基乙酸酯/聚乙烯吡咯烷酮共聚物的类型可改变加溶速率：聚乙烯吡咯烷酮的比率越高，加溶越快。如果含有化合物(B)，则其比率是5-85％(重量)。根据所用比率可调节控释。
另外，乙烯基乙酸酯/聚乙烯吡咯烷酮共聚物价格低廉，这反映在低价药物组合物的生产中。
更具体地说，如本发明权利要求的药物组合物以由优选厚度为0.2-3.0mm的膜组成的生物粘合基质层系形式提供。
与生物粘合片相比，该类层系特别有益：由于层系厚度薄使得患者易于接受；再者，加速了低溶解性活性成分的释放。
该药物剂型可以是圆形、长方形或椭圆形状的，具有的表面积优选是0.1-5.0cm2。
值得一提的是使用的增塑剂是甘油，丙三醇，Transcutol，PEG400，丙二醇等。
药物剂型还可含有甜味剂，如糖精酸钠和调味赋形剂。
制备过程中，将化合物(A)、化合物(B)、一种或多种活性成分、作为增塑剂的赋形剂和其它赋形剂(如调味剂)的混合物涂布或由任何其它方法分配到生物降解性或非生物降解性保护膜或基底(玻璃、不锈钢等)上。使该层合物在30-70℃的温度下干燥10分钟至2小时。
对上面涂布药剂的保护膜的粘合或生物粘合特性可加以选择。
一种具体的药物制剂可按下述方式制备：如下图所示，覆盖颊贴剂基质部分的保护膜围绕基质部分形成一粘合性顶面：
带粘合性顶面的药物组合物具有防止活性成分脱离剂型两侧的优点，在贴于颊粘膜时，例如可提高透粘膜途径的吸收百分比。
如本发明权利要求的药物组合物，其特征在于它在颊、舌、鼻、直肠或***粘膜可维持粘附10分钟至24小时。
值得一提的是，应用于本发明药物组合物的活性成分的非限制性实例是：抗感染剂，如青霉素类、头孢菌素类、cyclines、β-内酰胺酶抑制剂、氨基糖甙类(aminosides)、喹诺酮类、硝基咪唑类、磺酰胺类或抗菌剂，抗组胺剂，抗变应剂，麻醉剂，甾类或非甾类抗炎剂，局部或***作用的镇痛剂，解痉剂，抗癌剂，利尿剂，β-阻断剂，抗高血压剂，抗心绞痛药，抗心律失常药，血管扩张剂，减慢心率药，钙抑制剂，镇静剂，强心剂，抗真菌剂，抗溃疡药，血管紧张剂，血管保护剂(vasoprotectants)，抗局部缺血药，止吐剂，解痉挛剂，抗凝血药，抗血栓形成剂，免疫抑制剂，免疫调节剂，抗病毒剂，抗糖尿病药，抗低血脂药，减肥药，抗惊厥药，催眠药，抗巴金森氏症药物，止偏头痛药，精神抑制剂，抗焦虑药，抗抑郁药，精神***，增强记忆的药物，支气管扩张剂，镇咳药，骨质疏松治疗剂，肽类激素，类固醇，酶，酶抑制剂或者褪黑激素能激动剂或拮抗剂。
下列实施例将说明本发明，但并不以任何方式限制本发明。实施例1：
将0.15g二氢麦角胺一甲磺酸盐和5g乙烯基乙酸酯/聚乙烯吡咯烷酮共聚物(PVP/VA E-735型，法国ISP)(干重)溶于10毫升50/50乙醇/0.1N盐酸溶液中。E-735型聚乙烯吡咯烷酮/乙烯基乙酸酯共聚物组成如下：70％聚乙烯吡咯烷酮和30％乙烯基乙酸酯。当该混合物呈均相时，加入0.5g丙二醇。搅拌30分钟直至获得十分均匀的混合物。
将所得混合物涂布到乙烯/乙烯基乙酸酯保护膜上。使该膜在室温干燥2小时。使用空心冲压机冲出直径1厘米的园片。该圆片厚度约为0.2毫米。实施例2
将0.88g二氢麦角胺一甲磺酸盐和5g乙烯基乙酸酯/聚乙烯吡咯烷酮共聚物(PVP/VA E-735型，法国ISP)溶于10毫升50/50乙醇/0.1N盐酸溶液中。E-735型聚乙烯吡咯烷酮/乙烯基乙酸酯共聚物组成如下：70％聚乙烯吡咯烷酮和30％乙烯基乙酸酯。当该混合物呈均相时，加入0.5g丙二醇。搅拌30分钟直至获得十分均匀的混合物。
将所得混合物涂布到乙烯/乙烯基乙酸酯保护膜上。使该膜在室温干燥2小时。使用空心冲压机冲出直径1厘米的圆片。实施例3
将0.7g二氢麦角胺甲磺酸盐和4.5g乙烯基乙酸酯/聚乙烯吡咯烷酮共聚物溶于4毫升乙醇溶液。该由BASF生产的VA 64型聚乙烯吡咯烷酮/乙烯基乙酸酯共聚物组成如下：60％聚乙烯吡咯烷酮和40％乙烯基乙酸酯。当该混合物呈均相时，加入0.15g糖精酸钠。往该均相混合物中加入1.00g聚乙二醇400，然后再加入0.4g液体混合调味剂。
将所得混合物涂布到乙烯/乙烯基乙酸酯保护膜上。使该膜在室温干燥2小时。使用空心冲压机冲出直径1厘米的圆片。实施例4
将1.0克amineptine盐酸化物和7.46g乙烯基乙酸酯/聚乙烯吡咯烷酮共聚物溶于含有防腐剂的8.75毫升乙醇溶液。该由BASF生产的VA 64型聚乙烯吡咯烷酮/乙烯基乙酸酯共聚物组成如下：60％聚乙烯吡咯烷酮和40％乙烯基乙酸酯。当该混合物呈均相时，加入含有0.24g糖精酸钠的6.25毫升水溶液。往所得均相混合物中加入1.5g聚乙二醇400，然后再加入0.55g液体混合调味剂。
将所得混合物涂布到乙烯/乙烯基乙酸酯保护膜上。使该膜在室温干燥2小时。使用空心冲压机冲出直径1厘米的圆片。实施例5
将1.0克吡贝地尔(piribedil)一甲磺酸盐和7.31g乙烯基乙酸酯/聚乙烯吡咯烷酮共聚物溶于含有防腐剂的8.75毫升乙醇溶液。该由BASF生产的VA 64型聚乙烯吡咯烷酮/乙烯基乙酸酯共聚物组成如下：60％聚乙烯吡咯烷酮和40％乙烯基乙酸酯。当该混合物呈均相时，加入含有0.24g糖精酸钠的6.25毫升水溶液。往所得混合物中加入1.5g聚乙二醇400，然后再加入0.55g液体混合调味剂。
将所得混合物涂布到乙烯/乙烯基乙酸酯保护膜上。使该膜在室温干燥2小时。使用空心冲压机冲出直径1厘米的圆片。实施例6
将0.25g褪黑激素和7.46g乙烯基乙酸酯/聚乙烯吡咯烷酮共聚物溶于含有防腐剂的8.75毫升乙醇溶液。该由BASF生产的VA 64型聚乙烯吡咯烷酮/乙烯基乙酸酯共聚物组成如下：60％聚乙烯吡咯烷酮和40％乙烯基乙酸酯。当该混合物呈均相时，加入含有0.24g糖精酸钠的6.25毫升水溶液。往所得均相混合物中加入1.5g聚乙二醇400，然后再加入0.55g液体混合调味剂。
将所得混合物涂布到乙烯/乙烯基乙酸酯保护膜上。使该膜在室温干燥2小时。使用空心冲压机冲出直径1厘米的圆片。实施例7
将1.0g镰孢霉素和6.7g乙烯基乙酸酯/聚乙烯吡咯烷酮共聚物溶于含有防腐剂的8.75毫升乙醇溶液。该由BASF生产的VA 64型聚乙烯吡咯烷酮/乙烯基乙酸酯共聚物组成如下：60％聚乙烯吡咯烷酮和40％乙烯基乙酸酯。当该混合物呈均相时，加入含有0.24g糖精酸钠的1毫升水溶液。往所得混合物中加入1.5g聚乙二醇400，然后再加入0.55g液体混合调味剂。将所得混合物涂布到乙烯/乙烯基乙酸酯保护膜上。使该膜在室温干燥2小时。使用空心冲压机冲出直径1厘米的圆片。实施例8
将1.0g镰孢霉素和6.7g乙烯基乙酸酯/聚乙烯吡咯烷酮共聚物溶于含有防腐剂的8.75毫升乙醇溶液。该由BASF生产的VA 64型聚乙烯吡咯烷酮/乙烯基乙酸酯共聚物组成如下：60％聚乙烯吡咯烷酮和40％乙烯基乙酸酯。当该混合物呈均相时，加入含有0.24g糖精酸钠的1毫升水溶液。往所得混合物中加入1.50g聚乙二醇400，然后再加入0.47g芳香成分。将所得混合物涂布到乙烯/乙烯基乙酸酯保护膜上。使该膜在室温干燥2小时。使用空心冲压机冲出直径1厘米的圆片。实施例9-
将1.0g镰孢霉素和1.0g利多卡因盐酸化物与6g乙烯基乙酸酯/聚乙烯吡咯烷酮共聚物溶于含有防腐剂的8.75毫升乙醇溶液。该由BASF生产的VA 64型聚乙烯吡咯烷酮/乙烯基乙酸酯共聚物组成如下：60％聚乙烯吡咯烷酮和40％乙烯基乙酸酯。当该混合物呈均相时，加入含有0.23g糖精酸钠的1毫升水溶液。往所得混合物中加入1.30g聚乙二醇400，然后再加入0.47g芳香成分。将所得混合物涂布到乙烯/乙烯基乙酸酯保护膜上。使该膜在室温干燥2小时。使用空心冲压机冲出直径1厘米的圆片。实施例10
将1.0g镰孢霉素和0.4g利多卡因盐酸化物与6.6g乙烯基乙酸酯/聚乙烯吡咯烷酮共聚物溶于含有防腐剂的8.75毫升乙醇溶液。该由BASF生产的VA64型聚乙烯吡咯烷酮/乙烯基乙酸酯共聚物组成如下：60％聚乙烯吡咯烷酮和40％乙烯基乙酸酯。当该混合物呈均相时，加入含有0.23g糖精酸钠的1毫升水溶液。往所得混合物中加入1.30g聚乙二醇400，然后再加入0.47g芳香成分。将所得混合物涂布到乙烯/乙烯基乙酸酯保护膜上。使该膜在室温干燥2小时。使用空心冲压机冲出直径1厘米的圆片。实施例11
将0.05克倍他米松17-戊酸盐与7.66g乙烯基乙酸酯/聚乙烯吡咯烷酮共聚物溶于含有防腐剂的8.75毫升乙醇溶液。该由BASF生产的VA 64型聚乙烯吡咯烷酮/乙烯基乙酸酯共聚物组成如下：60％聚乙烯吡咯烷酮和40％乙烯基乙酸酯。当该混合物呈均相时，加入含有0.24g糖精酸钠的6.25毫升水溶液。往所得混合物中加入1.50g聚乙二醇400，然后再加入0.55g液体混合调味剂。将所得混合物涂布到乙烯/乙烯基乙酸酯保护膜上。使该膜在室温干燥2小时。使用空心冲压机冲出直径1厘米的圆片。实施例12
将0.11克氯化十六烷基吡啶鎓与7.6g乙烯基乙酸酯/聚乙烯吡咯烷酮共聚物溶于含有防腐剂的8.75毫升乙醇溶液。该由BASF生产的VA 64型聚乙烯吡咯烷酮/乙烯基乙酸酯共聚物组成如下：60％聚乙烯吡咯烷酮和40％乙烯基乙酸酯。当该混合物呈均相时，加入含有0.24g糖精酸钠的6.25毫升水溶液。往所得混合物中加入1.50g聚乙二醇400，然后再加入0.55g液体混合调味剂。将所得混合物涂布到乙烯/乙烯基乙酸酯保护膜上。使该膜在室温干燥2小时。使用空心冲压机冲出直径1厘米的圆片。

Claims (9)

1)一种控制活性成分在颊腔或经粘膜释放的生物粘合药物组合物，其中生物粘合和控释由包含一种或多种乙烯基乙酸酯/聚乙烯吡咯烷酮共聚物的化合物(A)提供。
2)权利要求l的药物组合物，其中除化合物(A)外，它还含有一种或多种活性成分和一种或多种治疗学上可接受的赋形剂。
3)权利要求1的药物组合物，其中除化合物(A)外，它还含有一种或多种活性成分，一种或多种药学上可接受的赋形剂和包含一种或多种选自纤维素及其衍生物、淀粉及其衍生物、树胶、角豆树胶和角叉酸盐的化合物(B)。
4)如权利要求2或3的药物组合物，其中药学上可接受的赋形剂选自增塑剂、调味剂和甜味剂。
5)如权利要求1-3任一项的药物组合物，其中化合物(A)的量是组合物总重的5-85％。
6)权利要求3的药物组合物，其中化合物(B)的量是组合物总重的5-85％。
7)权利要求1的药物组合物，其中它呈基质层系形式。
8)如权利要求1-3任一项的药物组合物，其中所提供的生物粘合可长达24小时。
9)如权利要求2或3的药物组合物，其中所用的一种或多种活性成分选自抗感染剂，如青霉素类、头孢菌素类、cyclines、β-内酰胺酶抑制剂、氨基糖甙类、喹诺酮类、硝基咪唑类、磺酰胺类或抗菌剂，抗组胺剂，抗变应剂，麻醉剂，甾类或非甾类抗炎剂，局部或***作用的镇痛剂，解痉剂，抗癌药，利尿剂，β-阻断剂，抗高血压剂，抗心绞痛药，抗心律失常药，血管扩张剂，减慢心率药，钙抑制剂，镇静剂，强心剂，抗真菌剂，抗溃疡药，血管紧张剂，血管保护剂，抗局部缺血药，止吐剂，解痉挛剂，抗凝血药，抗血栓形成剂，免疫抑制剂，免疫调节剂，抗病毒剂，抗糖尿病药，抗低血脂药，减肥药，抗惊厥药，催眠药，抗巴金森氏症药物，止偏头痛药，精神抑制剂，抗焦虑药，抗抑郁药，精神***，增强记忆的药物，支气管扩张剂，镇咳药，骨质疏松治疗剂，肽类激素，类固醇，酶，酶抑制剂或者褪黑激素能激动剂或拮抗剂。
CN96123198A 1995-12-29 1996-12-27 控制活性成分释放的生物粘合药物组合物 Pending CN1159950A (zh)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101005824B (zh) * 2004-06-17 2012-05-30 高露洁-棕榄公司 口腔护理薄膜

Families Citing this family (63)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5800832A (en) * 1996-10-18 1998-09-01 Virotex Corporation Bioerodable film for delivery of pharmaceutical compounds to mucosal surfaces
DE19646392A1 (de) 1996-11-11 1998-05-14 Lohmann Therapie Syst Lts Zubereitung zur Anwendung in der Mundhöhle mit einer an der Schleimhaut haftklebenden, Pharmazeutika oder Kosmetika zur dosierten Abgabe enthaltenden Schicht
US20050048102A1 (en) * 1997-10-16 2005-03-03 Virotex Corporation Pharmaceutical carrier device suitable for delivery of pharmaceutical compounds to mucosal surfaces
US6548490B1 (en) 1997-10-28 2003-04-15 Vivus, Inc. Transmucosal administration of phosphodiesterase inhibitors for the treatment of erectile dysfunction
US20050197283A1 (en) * 1998-10-04 2005-09-08 Vascular Biogenics Ltd. Compositions containing beta 2-glycoprotein I for the prevention and/or treatment of vascular disease
IL126447A (en) * 1998-10-04 2004-09-27 Vascular Biogenics Ltd An immune preparation that confers tolerance in oral administration and its use in the prevention and / or treatment of atherosclerosis
US6231957B1 (en) 1999-05-06 2001-05-15 Horst G. Zerbe Rapidly disintegrating flavor wafer for flavor enrichment
AU2001257129A1 (en) * 2000-04-21 2001-11-07 Advanced Research And Technology Institute, Inc. Novel pharmacotherapeutic process and composition for central nervous system disorders
AU2001260612B9 (en) * 2000-05-26 2005-06-09 Kanji Takada Nonoral preparation having three-layer structure
US20020013331A1 (en) 2000-06-26 2002-01-31 Williams Robert O. Methods and compositions for treating pain of the mucous membrane
US6756051B1 (en) 2000-11-15 2004-06-29 Li-Lan H. Chen Bioadhesive, closed-cell foam film, sustained release, delivery devices and methods of making and using same
US7803392B2 (en) * 2000-12-27 2010-09-28 University Of Kentucky Research Foundation pH-Sensitive mucoadhesive film-forming gels and wax-film composites suitable for topical and mucosal delivery of molecules
US6660292B2 (en) 2001-06-19 2003-12-09 Hf Flavoring Technology Llp Rapidly disintegrating flavored film for precooked foods
KR20040029415A (ko) * 2001-08-10 2004-04-06 히사미쯔 제약 주식회사 경피 흡수형 제제
US7425292B2 (en) * 2001-10-12 2008-09-16 Monosol Rx, Llc Thin film with non-self-aggregating uniform heterogeneity and drug delivery systems made therefrom
US11207805B2 (en) 2001-10-12 2021-12-28 Aquestive Therapeutics, Inc. Process for manufacturing a resulting pharmaceutical film
US8900498B2 (en) 2001-10-12 2014-12-02 Monosol Rx, Llc Process for manufacturing a resulting multi-layer pharmaceutical film
US8603514B2 (en) 2002-04-11 2013-12-10 Monosol Rx, Llc Uniform films for rapid dissolve dosage form incorporating taste-masking compositions
US20110033542A1 (en) 2009-08-07 2011-02-10 Monosol Rx, Llc Sublingual and buccal film compositions
US8663687B2 (en) 2001-10-12 2014-03-04 Monosol Rx, Llc Film compositions for delivery of actives
US7357891B2 (en) 2001-10-12 2008-04-15 Monosol Rx, Llc Process for making an ingestible film
US8765167B2 (en) 2001-10-12 2014-07-01 Monosol Rx, Llc Uniform films for rapid-dissolve dosage form incorporating anti-tacking compositions
US20190328679A1 (en) 2001-10-12 2019-10-31 Aquestive Therapeutics, Inc. Uniform films for rapid-dissolve dosage form incorporating anti-tacking compositions
US20070281003A1 (en) 2001-10-12 2007-12-06 Fuisz Richard C Polymer-Based Films and Drug Delivery Systems Made Therefrom
US8900497B2 (en) 2001-10-12 2014-12-02 Monosol Rx, Llc Process for making a film having a substantially uniform distribution of components
US10285910B2 (en) 2001-10-12 2019-05-14 Aquestive Therapeutics, Inc. Sublingual and buccal film compositions
US20030194420A1 (en) * 2002-04-11 2003-10-16 Richard Holl Process for loading a drug delivery device
AU2003265446A1 (en) * 2002-08-13 2004-02-25 Medtronic, Inc. Active agent delivery system including a hydrophilic polymer, medical device, and method
AU2003260803A1 (en) * 2002-08-30 2004-03-19 Orchid Chemicals And Pharmaceuticals Ltd. Sustained release pharmaceutical composition
ES2209649B1 (es) * 2002-12-09 2005-03-16 Carlos Arana Molina (Titular Al 25%) Utilizacion de la melatonina para la higiene bucodental para uso humano y veterinario como producto activo.
US9254294B2 (en) 2003-02-24 2016-02-09 Pharmaceutical Productions Inc. Transmucosal hormone delivery system
US9358296B2 (en) 2003-02-24 2016-06-07 Pharmaceutical Productions Inc. Transmucosal drug delivery system
US9498454B2 (en) 2003-02-24 2016-11-22 Pharmaceutical Productions Inc. Transmucosal drug delivery system
US7306812B2 (en) 2003-05-09 2007-12-11 Cephalon, Inc. Dissolvable backing layer for use with a transmucosal delivery device
US7276246B2 (en) * 2003-05-09 2007-10-02 Cephalon, Inc. Dissolvable backing layer for use with a transmucosal delivery device
DE10328942A1 (de) * 2003-06-27 2005-01-27 Lts Lohmann Therapie-Systeme Ag Transmukosale Darreichungsformen mit verminderter Schleimhautirritation
FR2857594B1 (fr) * 2003-07-17 2005-09-16 Servier Lab Composition pharmaceutique pour l'administration par voie nasale de piribedil
DE10358749A1 (de) * 2003-12-12 2005-07-14 Lts Lohmann Therapie-Systeme Ag Darreichungsform zur Bekämpfung von primären Kopfschmerzen
US9044500B2 (en) 2004-08-02 2015-06-02 Glaxosmithkline Consumer Healthcare Gmbh & Co Kg Composition for xerostomia
EP1877446A1 (en) * 2005-03-02 2008-01-16 Polyrizon Ltd. Method for removal of toxins from mucosal membranes
FR2901701B1 (fr) * 2006-05-31 2010-10-29 Galderma Res & Dev Compostions comprenant au moins un derive de l'acide naphtoique et au moins un agent filmogene, leurs procedes de preparation, et leurs utilisations
EP2046359B1 (en) 2006-06-20 2020-05-27 Izun Pharmaceuticals Corporation Anti-inflammatory dissolvable film
KR101474809B1 (ko) * 2006-07-20 2014-12-19 이준 파마슈티컬스 코포레이션 필름 전달 린스
ES2577390T3 (es) 2006-07-21 2016-07-14 Biodelivery Sciences International, Inc. Dispositivos de administración transmucosa con mayor captación
AP2009004897A0 (en) 2006-11-13 2009-06-30 Basf Se Use of block copolymers based on vinyllactams and vinyl acetate as solubilizers
JP5209643B2 (ja) 2007-01-11 2013-06-12 ノボザイムス アクティーゼルスカブ 活性化合物を含む粒子
US20100119601A1 (en) 2007-04-11 2010-05-13 Pharmaceutical Productions Inc. Melatonin tablet and methods of preparation and use
US8974825B2 (en) * 2007-07-06 2015-03-10 Lupin Limited Pharmaceutical compositions for gastrointestinal drug delivery
EP2942053A1 (en) 2007-07-06 2015-11-11 Lupin Limited Pharmaceutical compositions for gastrointestinal drug delivery
US20120027855A1 (en) 2007-07-06 2012-02-02 Lupin Limited Pharmaceutical compositions for gastrointestinal drug delivery
US8475832B2 (en) * 2009-08-07 2013-07-02 Rb Pharmaceuticals Limited Sublingual and buccal film compositions
US10610528B2 (en) 2009-12-08 2020-04-07 Intelgenx Corp. Solid oral film dosage forms and methods for making same
US20110136815A1 (en) 2009-12-08 2011-06-09 Horst Zerbe Solid oral film dosage forms and methods for making same
EP2579844B1 (en) 2010-06-10 2016-02-24 Midatech Ltd. Nanoparticle film delivery systems
EP2397125A1 (en) 2010-06-15 2011-12-21 Histocell, S.L. Antioxidant composition
US9149959B2 (en) 2010-10-22 2015-10-06 Monosol Rx, Llc Manufacturing of small film strips
CA2845634C (en) 2011-08-18 2021-07-13 Biodelivery Sciences International, Inc. Abuse-resistant mucoadhesive devices for delivery of buprenorphine
JP2013095687A (ja) * 2011-10-31 2013-05-20 Tsukioka Film Pharma Co Ltd 口腔内貼付薬
US9901539B2 (en) 2011-12-21 2018-02-27 Biodelivery Sciences International, Inc. Transmucosal drug delivery devices for use in chronic pain relief
US20160354509A1 (en) * 2014-02-10 2016-12-08 The Johns Hopkins University Devices for and methods of treatment of metabolic syndromes
EP3331499A4 (en) 2015-08-06 2019-04-10 The Johns Hopkins University COMPOSITION AND METHOD OF TREATING METABOLIC DISORDERS
US11273131B2 (en) 2016-05-05 2022-03-15 Aquestive Therapeutics, Inc. Pharmaceutical compositions with enhanced permeation
CN109310646A (zh) 2016-05-05 2019-02-05 阿奎斯蒂弗医疗股份有限公司 增强递送的肾上腺素组合物

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3045914A1 (de) * 1980-12-05 1982-07-22 Bayer Ag, 5090 Leverkusen Antimykotische mittel mit hoher wirkstoff-freisetzung in form von elastischen fluessig-pflastern
IL61721A (en) * 1980-12-16 1984-03-30 Blank Izhak Nitroglycerin preparations
JPH0729915B2 (ja) * 1986-02-01 1995-04-05 帝國製薬株式会社 シ−ト状口腔内貼付剤
JPH0794384B2 (ja) * 1986-09-01 1995-10-11 帝国製薬株式会社 徐放性口腔内用製剤
JPS63171564A (ja) * 1987-01-07 1988-07-15 積水化学工業株式会社 口腔粘膜貼付用構成体およびその製造方法
JPS63265983A (ja) * 1987-04-23 1988-11-02 Sekisui Chem Co Ltd 親水性粘着剤組成物
JPH01268630A (ja) * 1988-04-19 1989-10-26 Nitto Denko Corp 徐放性製剤
PH26730A (en) * 1988-12-30 1992-09-28 Ciba Geigy Ag Coated adhesive tablets
US5527545A (en) * 1989-09-18 1996-06-18 Recordati S.A. Chemical And Pharmaceutical Company Liquid-suspension controlled-release pharmaceutical composition
FR2710265B1 (fr) * 1993-09-22 1995-10-20 Adir Composition pharmaceutique bioadhésive pour la libération contrôlée de principes actifs.

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101005824B (zh) * 2004-06-17 2012-05-30 高露洁-棕榄公司 口腔护理薄膜

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DE69622980D1 (de) 2002-09-19
EP0781550B1 (fr) 2002-08-14
NZ314009A (en) 1998-02-26
DK0781550T3 (da) 2002-12-09
CA2193454C (fr) 2001-07-24
AU7549696A (en) 1997-07-03
EP0781550A1 (fr) 1997-07-02
US5900247A (en) 1999-05-04
ATE222098T1 (de) 2002-08-15
ZA9610864B (en) 1997-06-27
JPH09194395A (ja) 1997-07-29
FR2742989A1 (fr) 1997-07-04
CA2193454A1 (fr) 1997-06-30
AU725283B2 (en) 2000-10-12
DE69622980T2 (de) 2003-04-10
NO965475D0 (no) 1996-12-19
PT781550E (pt) 2002-11-29
ES2180722T3 (es) 2003-02-16
FR2742989B1 (fr) 1998-01-23

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