CN101208091A - 促进口腔吸收的麻醉药的固体药制剂 - Google Patents
促进口腔吸收的麻醉药的固体药制剂 Download PDFInfo
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- CN101208091A CN101208091A CNA2006800232888A CN200680023288A CN101208091A CN 101208091 A CN101208091 A CN 101208091A CN A2006800232888 A CNA2006800232888 A CN A2006800232888A CN 200680023288 A CN200680023288 A CN 200680023288A CN 101208091 A CN101208091 A CN 101208091A
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Classifications
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- A61K9/00—Medicinal preparations characterised by special physical form
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- 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
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- 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
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
公开了一种适于口腔溶解的药片形式的药物化合物，所述的化合物含有i)一种麻醉活性成分的有效量，及ii)一种pK大于或等于8的药物可接受的胺，其中胺与活性成分的摩尔比至少为5∶1。
Description
本发明涉及促进口腔吸收的麻醉药的固体制剂
本发明制剂的特征是一种药物可接受的可溶解的口服的有机化合物，它具有pK约大于或等于8的伯胺、仲胺或叔胺基。药片优选的体内崩解时间约为5-25分钟。
背景技术
口服制剂在药物控制方面越来越普遍。它们在现实中显示了比其它固体药物形式更好的几点优势；尤其是，口服制剂不需要摄入水即可溶解在口腔中，并且药物接触口腔黏膜后可以溶解被口腔吸附。由于药物跨过黏膜的皮肤屏蔽，渗透入血液中的差异性，结果使得口服控制剂令人遗憾地有时不能经常快速地发挥药效，
发明内容
令人惊讶地发现在口服制剂中加入无毒的或药物可按受的胺，药物的穿透性将会显著提高，且较入没有如上所述地加入胺，能更快地达到更高的活性成分的血液浓度。
本发明所述的能提高生物药效率、pK约大于或等于8的胺基属于如下种类：
-基础胺基酸，如精氨酸，赖氨酸，组氨酸及鸟氨酸；
-叔胺，如三乙醇胺及氨基丁三醇；
-氨基磺酸，如牛磺酸；
-葵酰胺基体(mercapramines)，如半胱胺；
-季胺盐，如三甲铵乙内酯；
-杂环胺，如吡咯烷；以及
-胍。
精氨酸是一种较优选的无毒胺。本发明的制剂可以包括两种或两种以上所述胺的混合物。较优选的胺是非聚乙烯吡咯烷酮。
活性成分较好的是如本发明所述的固体剂形：
阿芬太尼、普罗啡、布托啡诺、可待因、苯乙哌啶、芬太奴、海洛因、氢可酮、氢吗啡酮、氧吗啡酮、左吗南、烯丙左吗喃、苯丁哌胺、度冷丁、吗啡、纳布啡、纳美芬、纳洛芬、纳洛酮、环丙甲羟二羟吗啡酮、瑞芬太尼、舒芬太尼及其衍生物、盐及其类似物。较优选芬太奴。本发明还包括活性成分的药物可接受形式的使用，如盐，氢氧化物等，如柠檬酸芬太奴。
胺与活性成分较优选的数量比(活性成分：胺的摩尔比)约为5∶1-1000∶1，更优选10∶1-500∶1，最优选20∶1-250∶1
体内崩解时间优选地约为2-50分钟，更优选5-25分钟。
本制剂还含有额外的形成口服控制药片的典型成分，如一种或多种稀释药、止泻药、滑润剂、助流剂、崩解剂、着色剂、调味剂等。该药片可由传统技术制成，包括湿、干或流化床成粒法，或直接浓缩法。该药片优选非冻干。
下述是本发明非限制性举例的实施例：
例#1
例#1A
含胺(精氨酸)的口服分散片的制备
含200mcg芬太奴的口服分散片按如下步骤获得：
A)将1.05g柠檬酸芬太奴和50g PEG 6000溶解在90g纯水中。
B)335.62g山梨糖醇、516.67g甘露醇、26.67g天冬氨酰苯丙氨酸甲酯和10g柠檬酸颗粒加入含有PEG和柠檬酸芬太奴的水中。
C)最后成粒并干燥，并加入43.33g精氨酸自由基和16.67g硬脂酸镁。
D)产品被混合均匀并压缩成环形药片，每片药的直径为10mm、重量为300mg、硬度约为70牛。
例#1B
非胺口服分散片的制备
含有400mcg芬太奴的口服分散片按如下步骤：
E)将2.1g柠檬酸芬太奴和50g PEG 6000溶解在90g纯水中。
F)455.62g山梨糖醇、455.62g甘露醇、26.67g天冬氨酰苯丙氨酸甲酯和10g柠檬酸颗粒加入含有PEG和柠檬酸芬太奴的水中。
G)产品被混合均匀并压缩成环形药片，每片药的直径为10mm、重量为300mg、硬度约为30牛。
例#2
通过对6个健康的禁食志愿者测试如例#1A中所制备的含有200mcg芬太奴的口服制剂，进行药物动力学研究。获得的结果与通过对6个禁食健康志愿者测试如例#1B中所制备的含有400mcg芬太奴的口服制剂，进行药物动力学研究的结果相比较。
结果如表1所示：
| 单元剂量的芬太奴浓度 | 体内崩解时间 | 最大时间 | 最大浓度 | AUC | |
| 例#1A | 200mcg | 15分钟 | 48分钟 | 496pg/ml | 2430h*(pg/ml) |
| 例#1B | 400mcg | 5分钟 | 35分钟 | 491pg/ml | 3331h*(pg/ml) |
尽管例1A(200mcg)所述的被控制在药片中的芬太奴剂量为例1B(400mcg)中的50％，但是它们的药物动力学参数却是相似的，证明芬太奴能显著提高本发明的制剂的生物药效率。
通过对6个健康的禁食志愿者测试如例#1A中所制备的含有200mcg芬太奴的口服制剂，进行药物动力学研究。获得的结果与通过对6个健康的禁食志愿者测试市售的(Actiq、Cephalon公司生产、盐湖城、UT 84116美国)含有200mcg芬太奴的口服制剂，进行药物动力学研究的结果相比较。
结果如表2所示：
| 单元剂量的芬太奴浓度 | 体内崩解时间 | 最大时间 | 最大浓度 | AUC | |
| 例#1A | 200mcg | 15分钟 | 48分钟 | 496pg/ml | 2430h*(pg/mi) |
| Actiq | 200mcg | 15分钟 | 3.25分钟 | 237pg/ml | 1607h*(pg/ml) |
尽管例1A(200mcg)所述的被控制在药片中的芬太奴剂量与Actiq(200mcg)中的相同，但是药物动力学参数却更高，证明芬太奴能显著提高本发明的制剂的生物药效率。
Claims (14)
1.一种适于口腔溶解的药片形式的药物化合物，所述的化合物含有：
i)一种麻醉活性成分的有效量，及
ii)一种pK大于或等于8的药物可接受的胺，
其特征在于胺与活性成分的摩尔比至少为5∶1。
2.如权利要求1所述的化合物，其特征在于胺选自基础胺基酸、叔胺、氨基磺酸、葵酰胺基体、季胺盐、杂环胺和胍及它们的混合物。
3.如权利要求2所述的化合物，其特征在于胺选自精氨酸、赖氨酸、组氨酸、三乙醇胺、氨基丁三醇、牛磺酸、半胱胺甜菜碱、胍和吡咯烷及其混合物。
4.如权利要求3所述的化合物，其特征在于胺包括精氨酸。
5.如权利要求1所述的化合物，其特征在于麻醉活性成分选自阿芬太尼、普罗啡、布托啡诺、可待因、苯乙哌啶、芬太奴、海洛因、氢可酮、氢吗啡酮、氧吗啡酮、左吗南、烯丙左吗喃、苯丁哌胺、度冷丁、吗啡、纳布啡、纳美芬、纳洛芬、纳洛酮、环丙甲羟二羟吗啡酮、瑞芬太尼、舒芬太尼及其药物可接受的盐、氢氧化物或它们的混合物。
6.如权利要求5所述的化合物，其特征在于活性成分是芬太奴或其药物可接受的盐。
7.如权利要求1所述的化合物，其特征在于胺与活性成分的摩尔比为5∶1-1000∶1。
8.如权利要求7所述的化合物，其特征在于胺与活性成分的摩尔比为10∶1-500∶1。
9.如权利要求8所述的化合物，其特征在于胺与活性成分的摩尔比为20∶1-250∶1。
10.如权利要求5所述的化合物，其特征在于该药片的体内崩解时间为2-50分钟。
11.如权利要求10所述的化合物，其特征在于该药片的体内崩解时间为5-25分钟。
12.一种适于口腔溶解的药片形式的药物化合物，所述的化合物含有：
i)一种含有芬太奴或其药物可接受的盐的活性成分的有效量，及
ii)精氨酸，
其特征在于精氨酸与活性成分的摩尔比至少为5∶1。
13.一种通过口腔黏膜麻醉控制哺乳动物的方法，所述的方法包括用适于口腔溶解的药片形式的药物化合物对所述的哺乳动物进行口服给药，所述的化合物含有：
i)一种麻醉成分的有效量，及
ii)一种pK大于或等于8的药物可接受的胺，
其特征在于胺与活性成分的摩尔比至少为5∶1。
14.如权利要求13所述的方法，其特征在于活性成分包括芬太奴或其药物可接受的盐，而胺包括精氨酸。
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Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8852638B2 (en) | 2005-09-30 | 2014-10-07 | Durect Corporation | Sustained release small molecule drug formulation |
| US8497258B2 (en) | 2005-11-12 | 2013-07-30 | The Regents Of The University Of California | Viscous budesonide for the treatment of inflammatory diseases of the gastrointestinal tract |
| US8252328B2 (en) * | 2006-01-06 | 2012-08-28 | Acelrx Pharmaceuticals, Inc. | Bioadhesive drug formulations for oral transmucosal delivery |
| US8202535B2 (en) * | 2006-01-06 | 2012-06-19 | Acelrx Pharmaceuticals, Inc. | Small-volume oral transmucosal dosage forms |
| US9066847B2 (en) * | 2007-01-05 | 2015-06-30 | Aceirx Pharmaceuticals, Inc. | Storage and dispensing devices for administration of oral transmucosal dosage forms |
| US8357114B2 (en) | 2006-01-06 | 2013-01-22 | Acelrx Pharmaceuticals, Inc. | Drug dispensing device with flexible push rod |
| US8865743B2 (en) | 2006-01-06 | 2014-10-21 | Acelrx Pharmaceuticals, Inc. | Small volume oral transmucosal dosage forms containing sufentanil for treatment of pain |
| US8535714B2 (en) | 2006-01-06 | 2013-09-17 | Acelrx Pharmaceuticals, Inc. | Small volume oral transmucosal dosage forms containing sufentanil for treatment of pain |
| US8753308B2 (en) | 2006-01-06 | 2014-06-17 | Acelrx Pharmaceuticals, Inc. | Methods for administering small volume oral transmucosal dosage forms using a dispensing device |
| US9289583B2 (en) * | 2006-01-06 | 2016-03-22 | Acelrx Pharmaceuticals, Inc. | Methods for administering small volume oral transmucosal dosage forms using a dispensing device |
| US8252329B2 (en) | 2007-01-05 | 2012-08-28 | Acelrx Pharmaceuticals, Inc. | Bioadhesive drug formulations for oral transmucosal delivery |
| US20070260491A1 (en) * | 2006-05-08 | 2007-11-08 | Pamela Palmer | System for delivery and monitoring of administration of controlled substances |
| US20070299687A1 (en) * | 2006-06-23 | 2007-12-27 | Pamela Palmer | Inpatient system for patient-controlled delivery of oral transmucosal medications dosed as needed |
| MX337286B (es) | 2007-05-25 | 2016-02-22 | Indivior Uk Ltd | Formulaciones de transferencia sostenida de compuestos de risperidona. |
| US8945592B2 (en) | 2008-11-21 | 2015-02-03 | Acelrx Pharmaceuticals, Inc. | Sufentanil solid dosage forms comprising oxygen scavengers and methods of using the same |
| US20110097401A1 (en) * | 2009-06-12 | 2011-04-28 | Meritage Pharma, Inc. | Methods for treating gastrointestinal disorders |
| GB2481017B (en) | 2010-06-08 | 2015-01-07 | Rb Pharmaceuticals Ltd | Microparticle buprenorphine suspension |
| US9272044B2 (en) | 2010-06-08 | 2016-03-01 | Indivior Uk Limited | Injectable flowable composition buprenorphine |
| RU2476209C1 (ru) * | 2012-02-29 | 2013-02-27 | Станислав Анатольевич Кедик | Имплантируемое лекарственное средство на основе налтрексона для лечения пациентов, зависимых от алкоголя или опиатов |
| BR112014024382B1 (pt) | 2012-04-18 | 2022-08-09 | SpecGx LLC | Composições farmacêuticas de contenção de abuso de liberação imediata e seu processo de preparação |
| MX362838B (es) * | 2012-07-12 | 2019-02-19 | SpecGx LLC | Composiciones farmacéuticas de liberación prolongada para disuadir el abuso de opioides que comprenden un plastómero, un elastómero y un plastificante delicuescente. |
| GB201404139D0 (en) | 2014-03-10 | 2014-04-23 | Rb Pharmaceuticals Ltd | Sustained release buprenorphine solution formulations |
| MY187877A (en) | 2014-12-23 | 2021-10-26 | Acelrx Pharmaceuticals Inc | Systems, devices and methods for dispensing oral transmucosal dosage forms |
| EP3856160A4 (en) | 2018-09-25 | 2022-07-06 | SpecGx LLC | ANTI-ABUSE IMMEDIATE RELEASE CAPSULES DOSAGE FORMS |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5785989A (en) | 1985-05-01 | 1998-07-28 | University Utah Research Foundation | Compositions and methods of manufacturing of oral dissolvable medicaments |
| US5464632C1 (en) | 1991-07-22 | 2001-02-20 | Prographarm Lab | Rapidly disintegratable multiparticular tablet |
| JP3069458B2 (ja) | 1992-01-29 | 2000-07-24 | 武田薬品工業株式会社 | 口腔内崩壊型錠剤およびその製造法 |
| US5576014A (en) | 1994-01-31 | 1996-11-19 | Yamanouchi Pharmaceutical Co., Ltd | Intrabuccally dissolving compressed moldings and production process thereof |
| US5888534A (en) | 1995-06-13 | 1999-03-30 | Pentech Pharmaceuticals, Inc. | Controlled release of drugs delivered by sublingual or buccal administration |
| US5624677A (en) | 1995-06-13 | 1997-04-29 | Pentech Pharmaceuticals, Inc. | Controlled release of drugs delivered by sublingual or buccal administration |
| GB9517062D0 (en) | 1995-08-18 | 1995-10-25 | Scherer Ltd R P | Pharmaceutical compositions |
| KR20000022239A (ko) * | 1996-07-11 | 2000-04-25 | 토마스 헤인 | 인돌 선택성 세로토닌 작용약을 함유한 내포 복합체 |
| JP3770666B2 (ja) * | 1996-09-20 | 2006-04-26 | 株式会社ティ・ティ・エス技術研究所 | 経粘膜吸収製剤用組成物 |
| EP0839526A3 (en) | 1996-10-31 | 1999-01-07 | Takeda Chemical Industries, Ltd. | Solid pharmaceutical preparation with fast buccal disintegration or dissolution |
| US6024981A (en) | 1997-04-16 | 2000-02-15 | Cima Labs Inc. | Rapidly dissolving robust dosage form |
| AU8977698A (en) | 1997-07-25 | 1999-02-16 | Elan Corporation, Plc | A process for the preparation of a granulate suitable to the preparation of rapidly disintegrable mouth-soluble tablets |
| US5869098A (en) | 1997-08-20 | 1999-02-09 | Fuisz Technologies Ltd. | Fast-dissolving comestible units formed under high-speed/high-pressure conditions |
| US20030082107A1 (en) * | 1997-10-01 | 2003-05-01 | Dugger Harry A. | Buccal, polar and non-polar spray or capsule containing drugs for treating an infectious disease or cancer |
| US6350470B1 (en) | 1998-04-29 | 2002-02-26 | Cima Labs Inc. | Effervescent drug delivery system for oral administration |
| US6200604B1 (en) * | 1998-03-27 | 2001-03-13 | Cima Labs Inc. | Sublingual buccal effervescent |
| US6974590B2 (en) | 1998-03-27 | 2005-12-13 | Cima Labs Inc. | Sublingual buccal effervescent |
| US6270790B1 (en) | 1998-08-18 | 2001-08-07 | Mxneil-Ppc, Inc. | Soft, convex shaped chewable tablets having reduced friability |
| US6680071B1 (en) | 1999-03-03 | 2004-01-20 | R. P. Scherer Technologies, Inc. | Opioid agonist in a fast dispersing dosage form |
| JP2000281589A (ja) | 1999-03-26 | 2000-10-10 | T T S Gijutsu Kenkyusho:Kk | 経粘膜吸収助剤 |
| US6210699B1 (en) | 1999-04-01 | 2001-04-03 | Watson Pharmaceuticals, Inc. | Oral transmucosal delivery of drugs or any other ingredients via the inner buccal cavity |
| US6264981B1 (en) | 1999-10-27 | 2001-07-24 | Anesta Corporation | Oral transmucosal drug dosage using solid solution |
| US20030104041A1 (en) * | 1999-12-16 | 2003-06-05 | Tsung-Min Hsu | Transdermal and topical administration of drugs using basic permeation enhancers |
| US20020013331A1 (en) * | 2000-06-26 | 2002-01-31 | Williams Robert O. | Methods and compositions for treating pain of the mucous membrane |
| US6733781B2 (en) | 2000-12-06 | 2004-05-11 | Wyeth | Fast dissolving tablet |
| US20030215502A1 (en) * | 2002-03-20 | 2003-11-20 | Elan Pharma International Limited | Fast dissolving dosage forms having reduced friability |
| CA2479098A1 (en) * | 2002-03-20 | 2003-09-25 | Maree Therese Smith | Methods and compositions comprising nitric oxide donors and opioid analgesics |
| US20040253307A1 (en) * | 2003-02-04 | 2004-12-16 | Brian Hague | Sugar-free oral transmucosal solid dosage forms and uses thereof |
| US20040202698A1 (en) | 2003-04-02 | 2004-10-14 | The Procter & Gamble Company | Drug delivery systems comprising an encapsulated active ingredient |
| JP4739217B2 (ja) * | 2003-05-07 | 2011-08-03 | サムヤン コーポレイション | 速く溶ける錠剤を製造するための高可塑性顆粒 |
| ATE498395T1 (de) * | 2003-12-31 | 2011-03-15 | Cima Labs Inc | Allgemein lineare brauseform von fentanyl zur oralen anwendung und verfahren zur verabreichung |
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2006
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- 2006-07-21 RU RU2007149044/15A patent/RU2408373C2/ru active
- 2006-07-21 WO PCT/EP2006/007189 patent/WO2007009806A2/en active Application Filing
- 2006-07-21 JP JP2008521904A patent/JP5714797B2/ja active Active
- 2006-07-21 DK DK06776336.7T patent/DK1906961T3/en active
- 2006-07-21 ES ES06776336.7T patent/ES2569228T3/es active Active
-
2007
- 2007-11-15 IL IL187387A patent/IL187387A/en not_active IP Right Cessation
- 2007-11-30 ZA ZA200710406A patent/ZA200710406B/xx unknown
-
2008
- 2008-02-15 NO NO20080827A patent/NO20080827L/no not_active Application Discontinuation
- 2008-02-18 MA MA30659A patent/MA29744B1/fr unknown
-
2013
- 2013-09-04 US US14/017,642 patent/US10258693B2/en active Active
-
2016
- 2016-04-01 HR HRP20160327TT patent/HRP20160327T1/hr unknown
- 2016-04-26 CY CY20161100346T patent/CY1117470T1/el unknown
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