CN1159754A - 改进的含有布洛芬和可待因的药物配方 - Google Patents
改进的含有布洛芬和可待因的药物配方 Download PDFInfo
- Publication number
- CN1159754A CN1159754A CN95195426A CN95195426A CN1159754A CN 1159754 A CN1159754 A CN 1159754A CN 95195426 A CN95195426 A CN 95195426A CN 95195426 A CN95195426 A CN 95195426A CN 1159754 A CN1159754 A CN 1159754A
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- Prior art keywords
- prescription
- codeine
- ibuprofen
- arbitrary
- aforementioned arbitrary
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 title claims abstract description 39
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- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims abstract description 12
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- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- 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
- A61K31/485—Morphinan derivatives, e.g. morphine, codeine
-
- 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
- A61K9/20—Pills, tablets, discs, rods
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Emergency Medicine (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
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Abstract
本发明涉及布洛芬和可待因(或其任一的药学可接受的盐)的配方,其中包括一种载体,该载体包含崩解剂、稀释剂和润滑剂,此润滑剂基本上不含硬脂酸和硬脂酸盐离子,并选自氢化植物油。优选地配方是有效治疗疼痛及炎症的直接压缩片剂。
Description
本发明涉及改进的含有布洛芬和可待因(作为活性成分)的药物配方、制备这些配方的方法及其在治疗中的用途。
布洛芬,其化学名称为2-(4-异丁基-苯基)丙酸,是一种已知的非甾族抗炎药物(或NSAD)。它具有抗炎、退热和镇痛作用,并以该酸本身的形式或其适用于药物的盐的形式,例如钠盐,应用于治疗和预防疼痛和炎症,如类风湿性关节炎、头痛、神经痛、痛经、减少血小板粘连,牙痛及类似病情。
可待因,其化学名称为7,8二脱氢-4,5-环氧-3-甲氧基-17-甲基-吗啡喃-6-醇,是已知的一种麻醉止痛剂,通常以其适用于药物的盐的形式,如乙酸盐、氢溴化物、氢氯化物、水杨酸盐、硫酸盐或优选磷酸盐,通常以水合或部分水合的形式,如半水合形式,用在治疗或预防疼痛,尤其是严重的疼痛上。
布洛芬和可待因的组合被建议作为一种具有特效的麻醉剂。例如Cooper等人,在(1980)249,27(2),临床药物和治疗中报道了将化合物用于牙阻生手术后有中等到严重疼痛的患者身上后,具有好的效果。欧洲专利说明书388125公开了该组合在治疗急性疼痛如头痛及牙痛上的用途。
欧洲专利说明书535 841公开了该组合用于治疗慢性疾病的疼痛,如骨关节炎、类风湿性关节炎、类风湿性脊椎炎、浆膜关节病、滑囊炎、肩周炎、腱炎、腱鞘炎和癌症。
但在一段时期大家公认,含有布洛芬和可待因的组合的配方的贮藏性能是不能令人满意的,如常用的剂型给药方式即片剂给药方式中尤其如此。经过一段时间和温度升高后,可发现传统的布洛芬加可待因配方退色,并开始因裂化和膨胀而分解。因此,要提出的问题是如何生产出“白色”片剂(如其中的组分是有很好的颜色稳定性,并不因时间或温度而退色或变黄)并同时不因储存而分解。为配方的目的,这些组分也应具有良好的可直接压缩性。
同样问题虽然在欧洲专利说明书159 852中也提出了,但它是从在制备片剂的湿成粒处理过程中避免活性组分的紧密物理接触这一观点出发的。提出的解决方法是使用另一种改进的处理过程,即:将其中一种活性组分与粘合剂和填料掺合;将这些制出的混合物在有溶剂的情况下湿法成粒;干燥已成粒的混合物;过滤成粒的混合物;并将此混合物与一种或多种其它药理学活性组分掺合。但这样一种多步骤处理过程的缺点是不言而喻的。
欧洲专利说明书220 805公开了解决此问题的一种改进方法,尤其是在与布洛芬加可待因片剂相关的低抗碎强度和长的崩解倍数的难题上。其中提出的解决方案是制得一种多相片剂:其中,例如可待因,可与如布洛芬、硬脂酸和硬脂酸盐脱离,并且,例如布洛芬可一样与可待因、硬脂酸和硬脂酸盐脱离。并且进一步,其中可待因相和布洛芬相至少包含一种自身润滑的压缩辅助剂(如微晶纤维素或者一种不流动、直接可压缩淀粉)。但是,即便这样此改进方法因其多相组分而显示出自身的问题。前面提及的欧洲专利说明书535 841号公开了双层片剂。
可是,布洛芬加可待因的单相配方的公开,指出为提供一种满意的配方,硬脂酸和/或硬脂酸盐是必需的。例如欧洲专利说明书68 838尽管只公开了氟比洛芬与包含硬脂酸镁的麻醉止痛剂,但并不特指布洛芬/可待因。前述的欧洲专利说明书388 125只公开了在配方中含有硬脂酸的布洛芬加可待因片剂。欧洲专利说明书274 845也提出了同样的问题,其公开的解决方法是在包括布洛芬加可待因的固体组分中给合羧基甲基片纤维素的不溶性盐。但是,即使用这种方法也指出要包含硬脂酸或硬脂酸镁作为润滑剂,尤其是硬脂酸。
那么,似乎采用一种多相配方是避免在配方中使用硬脂酸/硬脂酸盐的唯一方法,但相信这会引起或加重储存问题。但我们惊奇地发现一种配方,可以不使用硬脂酸或硬脂酸盐制备,并且这一配方是单相的,具有直接压缩性,并且通过采用氢化植物油作润滑剂的方法,克服了现有技术与布洛芬加可待因组合相关的稳定性和贮存问题。
因此,本发明提供了一种含布洛芬和可待因(或一种它们各自的适用于药物的盐)与一种适用于药物的载体所组合的药物配方,其中所述载体包含润滑剂、分解剂、及稀释剂,其特征在于,所述润滑剂基本上不含硬脂酸和硬脂酸盐离子,并且是从氢化植物油中挑选的。
优选地,润滑剂中,和,更优选地,整个配方中也基本上不含金属离子,如镁或其它微量杂质如铝及铁离子。“基本不含”在本文中是指所述金属离子可存在于ppm级的范围内(但优选少于10ppm),但优选不在百分之几或百分比的范围。
一种优选的氢化植物油选自氢化豆油和氢化蓖麻油及其混合物如甘油脂。油脂优选的例子是C16-C20甘油脂和三(12-羟基)硬脂酸甘油酯。一种这样的优选油脂是英国Hull Hul 0QA的Karlshamns出售的以“sterotex K”命名的,同样适用的还有Castorwax,Castorwax M70,Castorwax MP80、Genwachs G、Cerit CH,Opalwax,Ceroxin及Cutina。
尤其令人惊奇的是,根据本发明的配方,崩解剂例如交联的聚乙烯基吡咯烷酮(PVP),交联羧甲基纤维素纳和淀粉甘醇酸钠可以在该配方中满意地使用。尤其是,交联羧甲基纤维素钠和特别是淀粉甘醇酸钠或它们的混合物用在该配方中是优选的崩解剂。令我们惊奇的部分原因是前述欧洲专利说明书274 845指出“包含列出的有效水平的崩解剂”的配方“储存在50℃,定期观测其退色和膨胀或分解情况。只有含羧甲基纤维素的组分给出满意的结果,并且所有其它配方在12周内或多或少退色、膨胀或崩解,因而未能显示满意的储存性能。”相反,我们发现,当将氢化植物油作为滑润剂时,在使用所列出的崩解剂的情况下,在片剂一定时间和温度下(例如40℃时储存三个月),在保持“白色”及稳定性方面获得了满意效果。
本发明进一步提供了一种前面已经详细说明了的配方,其中优选崩解剂是交联羧甲基纤维素钠;淀粉甘醇酸盐,如淀粉甘醇酸钠(可以由Tunnel Avebe淀粉公司获得);以及聚乙烯基吡咯烷酮(PVP),如交联的PVP;以及它们的混合物。更优选地,淀粉甘醇酸钠和/或在每660mg配方中至多达到20mg的交联羧甲基纤维素钠作为崩解剂。
优选地,本配方进一步包含可随时压缩的润滑剂,例如一种从乳糖和纤维素或它们的混合物中挑选的润滑剂;优选为β-单水乳糖和/或纤维素;更优选为72-76%的单水乳糖加23%-27%的纤维素(基本比例3∶1);以乳糖和纤维素的重量计算,可任选含有3-5%的,如可从德国Meggle公司得到的Cellactose(注册商标),如Cellactose 80;可任选为微晶纤维素,如微晶纤维素PH 102(可以由F.M.C获得的Avicel)和/或羧甲基纤维素。Cellactose是特别优选的润滑剂。
本领域常规用的其它成分也可加入配方(但不是硬脂酸或硬脂酸盐),如流动增强剂或加强润滑剂,例如硅胶,如可以由德国Wacker-ChemieGmbH/Degussa购得的胶体二氧化硅,优选每200mg布洛芬至多含大约3mg。其它成分包括(但不限于此)粘合剂和压缩辅助剂,如发酵的玉米淀粉、羟基丙基纤维素(可以由Shinetsu/Dow购得)、微晶纤维素、聚乙烯吡咯烷酮、凝胶和树胶;润滑剂或填充剂如乳糖、氯化钠、山梨醇、甘露醇、微晶纤维素、磷酸钙和硫酸钙;另外的滑润剂如聚乙二醇类(如,PEG 400及PEG6000)(但不包括前面提到的硬脂酸或其盐);表面活性剂或加湿剂,如十二烷基硫酸钠,优选每200mg布洛芬中含2mg,及可购得的Tween 80(商标);油脂;脂;蜡;及着色剂和香味剂。
优选的其它活性成分选自胶体二氧化硅、玉米淀粉、羟基丙基甲基纤维素、微晶纤维素、聚乙烯吡咯烷酮、乳糖、山梨醇、甘露糖醇、聚乙二醇、油脂、脂、蜡、及着色剂和香味剂。
其它活性组分也可存在,如咖啡咽或其它适用于结合布洛芬和可待因使用的活性物质,例如减充血剂、抗组胺药和止咳素,如假麻黄碱、苯海拉明及类似物质。
从前述可以理解,尽管有许多配方可采用,但固体剂量形式是优选的,并且最优选单相片剂。该片剂优选地包括根据本发明的片剂芯及其上的涂层,该涂层优选含有成膜聚合物的膜,如羟基丙基甲基纤维素;增塑剂如聚乙二醇类(如PEG 400),及可任意选择使用的着色分散剂。优选通过使用有色涂膜为片剂提供颜色,这比加压前将着色剂直接掺入芯颗粒更可取。优选地,涂膜占配方的1%(重量),如需要,片剂可使用标准食品级染料。另外可以为压制而成。
布洛芬和可待因可以,例如前面提及的药物可接受的盐的形式,以任意的治疗有效量存在。例如布洛芬50-2400mg范围,如300-1200mg,优选200-800mg。特别优选的单位剂量配方包含200mg、300mg或600mg的布洛芬,尤其是200mg。可待因10-300mg范围,优选10-100mg;例如,作为半水合磷酸盐,含12-22.5mg,如约13.5mg。
尤其优选的配方中,包含在约660mg,如663mg的片剂芯中含有布洛芬200mg加约13.57mg半水合磷酸可待因(相当于10mg可待因)。任选地,咖啡因含量至多达65mg,优选约30mg。
优选地,配方提供了使最大人用方案剂量为2单位剂量,每日为四次。
这里给出的成分的剂量及组分的重量都遵从通常的药理学的允许剂量,此允许剂量偏差通常为±5%。例如优选的布洛芬成可待因的剂量是标明数值的95%-105%。
本发明的配方可以使用本领域公知的任何方法制备,例如单相片剂可以用直接压缩方法制备,其中片剂芯的所有成分被过滤、混合、然后加压。直接压缩方法避免了预处理粉状成分的需要,如通过湿成粒后干燥。优选地,最后压缩成胶囊形状片剂或“小胶囊(caplets)”。
在更广义上,本发明因此提供了制备配方的一种方法,根据本发明它包括将布洛芬和可待因(或其任一者的盐)与氢化植物油进行组合。优选地,在成分中,以及处理过程中,水分含量保持最少;更优选地,水分含量少于配方的约5%(重量比)。
片剂一旦制成,例如根据本发明的“小胶囊(caplets)”就包装在合适的容器中,例如玻璃或塑料瓶,或者优选地,一种所谓“泡”(blister)包装,如一种包括用铝箔热封的聚氯乙烯“泡”。尤其提供一种所谓“患者包装”,即容器装在一个纸盒里,纸盒内再装有给示配方储存和使用的信息的患者说明页。
本领域技术人员应将理解,本发明进一步提供了根据本发明的配方在治疗中的用途,尤其是治疗或预防前述的任一疾病,特别是缓解中等或严重疼痛。本发明因此提供了治疗疾病的一种方法,这种方法包括给药需治疗的患者有效剂量的根据本发明的药物配方。本发明还进一步提供了布洛芬和可待因在制备根据本发明的药剂上的用途。
现在将在以下列实施例说明本发明,尽管有效实施本发明的其它方法对所属领域技术人员是显见的。实施例1-片剂
片剂芯 mg/片
布洛芬 200.00
半水合磷酸可待因 13.57
氢化植物油 5.00
Cellactose 足量至660mg
Aerosil 3.00
崩解剂* 55.00
*淀粉甘醇酸钠和/或交联羧甲基纤维素钠(Acidi-sol)。
使用直接压缩方法将这些成分一起过滤、混合和加压。实施例2-片剂
片剂芯 mg/片
布洛芬 200.00
半水合磷酸可待因 13.57
Cellactose 200.00
微晶纤维素 183.43
氢化植物油 5.00
Aerosil 3.00该片剂根据实施例1的方法制备。实施例3-涂膜片剂
片剂芯 mg/片
布洛芬 200.00
半水合磷酸可待因 13.57
微晶纤维素 182.93
氢化植物油 5.00
淀粉甘醇酸钠 55.00
Aerosil(胶体二氧化硅) 0.50
Cellactose 200.00
该片芯以实施例1的方法制备,然后用下列包含羟基丙基甲基纤维素,PEG 400及适当的颜色分散剂的涂膜剂涂膜。
涂膜剂A
羟基丙基甲基纤维素 6.2846
聚乙二醇400 1.2569
颜色分散剂(1) 2.4584=7.3319mg
(湿时)
涂膜剂B
羟基丙基甲基纤维素 6.0964
聚乙二醇400 1.2193
颜色分散剂(2) 2.6843=7.1126mg
(湿时)实施例4-涂膜片剂
片剂芯 mg/片
布洛芬 200.00
半水合磷酸可待因 13.57
微晶纤维素 162.93
氢化植物油 5.00
淀粉甘醇酸钠 55.00
Aerosil 0.50
交联羧甲基纤维素钠 20.00
Cellactose 200.00
该片芯以实施例1的方法制备,然后用下列包含羟基丙基甲基纤维素。PEG 400及适当的颜色分散剂的涂膜剂涂膜。
涂膜剂A
羟基丙基甲基纤维素 6.2846
聚乙二醇400 1.2569
颜色分散剂(1) 2.4584=7.3319mg
(湿时)
涂膜剂B
羟基丙基甲基纤维素 6.0964
聚乙二醇400 1.2193
颜色分散剂(2) 2.6843=7.1126mg
(湿时)实施例5-涂膜片剂
片剂芯 mg/片
布洛芬 200.00
半水合磷酸可待因 13.57
氢化植物油 5.00
淀粉甘醇酸钠 55.00
Aerosil 0.50
交联羧甲基纤维素钠 20.00
Cellactose 362.93
该片剂根据实施例1的方法制备,而后用实施例涂膜剂4A和4B涂膜。实施例6-含咖啡因片剂
片剂芯 mg/片
布洛芬 200.00
半水合磷酸可待因 13.57
Cellactose 355.08
Sterotex K 5.00
淀粉甘醇酸钠 55.00
咖啡因 30.00
该片剂芯是根据实施例1的方法制备的。可采用根据实施例4A和4B的涂膜方法涂膜本片剂。实施例7-患者包装
根据实施例3-6制备的涂膜片剂包装在白色、不透光、200微米的聚氯乙烯泡内,并以20微米的铝箔热封。此含泡包装放入有患者信息说明页的硬纸盒中。
Claims (26)
1、一种药剂配方,包含布洛芬或其药学可接受的盐和可待因或其药学可接受的盐结合药学可接受的载体,其中所述的载体含润滑剂、崩解剂和稀释剂,其特征在于:所述的润滑剂基本上不含硬脂酸和硬脂酸盐离子,并选自氢化植物油。
2、根据权利要求1的配方,其中氢化植物油选自氢化豆油和氢化蓖麻油及它们的混合物。
3、根据权利要求1和2的配方,其中氢化植物油选自甘油酯及其混合物。
4、根据前述任一权利要求的配方,其中氢化植物油是选自C16-C20甘油酯和三(12-羟基)硬脂酸甘油酯。
5、根据前述任一权利要求的配方,其中氢化植物油选自以如下商标出售的氢化植物油中:Sterotex K,Castorwax,Castorwax MP70,Castorwax MP80,Cenwachs G,Cerit CH,Opalwax,Ceroxin and Cutina。
6、根据前述任一权利要求的配方,其中崩解剂选自交联的羧甲基纤维素盐、淀粉甘醇酸盐、聚乙烯吡咯烷酮及它们的混合物。
7、根据前述任一权利要求的配方,其中崩解剂选自交联的聚乙烯吡咯烷酮,交联羧甲基纤维素钠和淀粉甘醇酸钠及它们的混合物。
8、根据前述任一权利要求的配方,其中崩解剂是或包括淀粉甘醇酸钠。
9、根据前述任一权利要求的配方,其中稀释剂选自乳糖和纤维素及它们的混合物。
10、根据前述任一权利要求的配方,其中稀释剂选自Cellactose(注册商标),微晶纤维素和羧甲基纤维素及它们的混合物。
11、根据前述任一权利要求的配方,其中所述载体进一步包括二氧化硅胶体。
12、根据前述任一权利要求的配方,其中还进一步包括选自咖啡因、减充血剂、抗组胺药,止咳素和它们的混合物的另外的活性成分。
13、根据前述任一权利要求的配方,包括50-2400mg的布洛芬和10-300mg的可待因。
14、根据前述任一权利要求的配方,包括大约200mg的布洛芬和大约13.57mg的半水合磷酸可待因,并且,任选地包括大约30mg咖啡咽。
15、根据前述任一权利要求的配方,它为片剂形式。
16、根据权利要求1的配方,其特征还在于,(如说明书中定义)基本上不含金属离子。
17、制备根据前述任一权利要求的配方的方法,此方法包括将布洛芬和可待因(或它们任一的药学可接受的盐)与氢化植物油组合。
18、根据权利要求17的方法,其中所有成分一起过滤,混合,然后加压。
19、布洛芬和可待因在制备根据前述任一权利要求的药剂中的用途。
20、根据权利要求1至16的任一权利要求的配方在治疗中的用途。
21、一种治疗或预防疼痛和炎症的方法,包括给药待治病人有效量的权利要求1至16的任一药物配方。
22、权利要求20或21的治疗和预防疾病的用途或方法,所述疾病选自头痛、神经痛、痛经、血小板粘连、牙痛、骨关节炎、类风湿关节炎、类风湿性脊椎炎、浆膜关节病、滑囊炎、肩周炎、腱炎、腱鞘炎和癌症。
23、根据权利要求1至16的任一的配方,它与根据权利要求20至22的其应用说明相联系。
24、一种患者包装,包括装在为准备好的容器中的根据权利要求1至16的配方,以及一个有根据权利要求20至22的其应用说明的插入页。
25、根据权利要求24的患者包装,包括含以下内容的硬纸盒:
(a)以单位剂量形式装在泡包装内的根据权利要求1至16的任一配方;以及
(b)说明根据权利要求20至22的任一配方的应用的患者信息活页。
26、根据权利要求24或25的患者包装,其中的配方包括在约660mg片剂芯内含有约200mg的布洛芬和13.57mg的半水合磷酸可待因的涂膜片剂。
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9417041.2 | 1994-08-23 | ||
GB9417041A GB9417041D0 (en) | 1994-08-23 | 1994-08-23 | Improved formulations |
GB9419921.3 | 1994-10-04 | ||
GB9419921A GB9419921D0 (en) | 1994-10-04 | 1994-10-04 | Improved formulations |
Publications (2)
Publication Number | Publication Date |
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CN1159754A true CN1159754A (zh) | 1997-09-17 |
CN1083265C CN1083265C (zh) | 2002-04-24 |
Family
ID=26305507
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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CN95195426A Expired - Fee Related CN1083265C (zh) | 1994-08-23 | 1995-08-16 | 改进的含有布洛芬和可待因的药物配方 |
Country Status (24)
Country | Link |
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EP (1) | EP0777477B1 (zh) |
JP (1) | JP3874793B2 (zh) |
KR (1) | KR100397082B1 (zh) |
CN (1) | CN1083265C (zh) |
AT (1) | ATE227574T1 (zh) |
AU (1) | AU699224B2 (zh) |
BG (1) | BG63329B1 (zh) |
BR (1) | BR9508760A (zh) |
CA (1) | CA2156768A1 (zh) |
CZ (1) | CZ287558B6 (zh) |
DE (1) | DE69528838T2 (zh) |
DK (1) | DK0777477T3 (zh) |
ES (1) | ES2187566T3 (zh) |
HU (1) | HU227759B1 (zh) |
MX (1) | MX9701390A (zh) |
NO (1) | NO322200B1 (zh) |
NZ (1) | NZ291223A (zh) |
PL (1) | PL181215B1 (zh) |
PT (1) | PT777477E (zh) |
RU (1) | RU2140782C1 (zh) |
SK (1) | SK282183B6 (zh) |
TW (1) | TW493984B (zh) |
UA (1) | UA42781C2 (zh) |
WO (1) | WO1996005834A1 (zh) |
Cited By (1)
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CN105395508A (zh) * | 2015-12-14 | 2016-03-16 | 西南药业股份有限公司 | 一种洛芬待因复方制剂及其制备方法 |
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US6608073B1 (en) | 1998-10-14 | 2003-08-19 | New Millennium Pharmaceutical Research, Inc. | Intranasal codeine for the rapid suppression of cough and rapid relief of pain |
US6368618B1 (en) | 1999-07-01 | 2002-04-09 | The University Of Georgia Research Foundation, Inc. | Composition and method for enhanced transdermal absorption of nonsteroidal anti-inflammatory drugs |
JP2001253826A (ja) * | 2000-03-09 | 2001-09-18 | Maruzen Pharmaceut Co Ltd | 内服用剤 |
US7183410B2 (en) | 2001-08-02 | 2007-02-27 | Bidachem S.P.A. | Stable polymorph of flibanserin |
US10675280B2 (en) | 2001-10-20 | 2020-06-09 | Sprout Pharmaceuticals, Inc. | Treating sexual desire disorders with flibanserin |
UA78974C2 (en) | 2001-10-20 | 2007-05-10 | Boehringer Ingelheim Pharma | Use of flibanserin for treating disorders of sexual desire |
US20040253311A1 (en) * | 2002-12-18 | 2004-12-16 | Roger Berlin | Multi-layer tablet comprising non-steroidal anti-inflammatory drugs, decongestants and non-sedating antihist amines |
PL1912650T3 (pl) | 2005-08-03 | 2018-01-31 | Sprout Pharmaceuticals Inc | Zastosowanie flibanseryny w leczeniu otyłości |
WO2007048803A1 (en) | 2005-10-29 | 2007-05-03 | Boehringer Ingelheim International Gmbh | Benzimidazolone derivatives for the treatment of premenstrual and other female sexual disorders |
ZA200803566B (en) * | 2005-12-12 | 2009-10-28 | Adcock Ingram Ltd | Pharmaceutical compositions |
US20090312242A1 (en) | 2006-06-30 | 2009-12-17 | Ramiro Castro | Flibanserin for the treatment of urinary incontinence and related diseases |
US8034801B2 (en) | 2006-07-12 | 2011-10-11 | Aska Pharmaceutical Co., Ltd. | Analgesic agent |
AR062320A1 (es) | 2006-08-14 | 2008-10-29 | Boehringer Ingelheim Int | Formulaciones de flibanserina y metodo para fabricarlas |
CN104721168A (zh) | 2006-08-25 | 2015-06-24 | 贝林格尔·英格海姆国际有限公司 | 控制释放系统及其制造方法 |
WO2008044331A1 (fr) * | 2006-10-05 | 2008-04-17 | Kowa Company, Ltd. | Préparation solide comprenant de l'ibuprofène et de l'acide tranexamique |
UY31335A1 (es) | 2007-09-12 | 2009-04-30 | Tratamiento de sintomas vasomotores | |
ES2400006T3 (es) | 2008-04-23 | 2013-04-04 | Farmasierra Manufacturing, S.L. | Formulación farmacéutica mejorada a base de ibuprofeno y codeína |
ES2365961B1 (es) | 2010-03-30 | 2013-01-24 | Farmasierra Manufacturing S.L. | Formulación farmacéutica a base de ibuprofeno y codeína de estabilidad mejorada. |
KR101317809B1 (ko) * | 2011-06-07 | 2013-10-16 | 한미약품 주식회사 | 암세포의 성장을 억제하는 아마이드 유도체 및 비금속염 활택제를 포함하는 약학 조성물 |
KR20140096571A (ko) | 2013-01-28 | 2014-08-06 | 한미약품 주식회사 | 1-(4-(4-(3,4-디클로로-2-플루오로페닐아미노)-7-메톡시퀴나졸린-6-일옥시)피페리딘-1-일)프로프-2-엔-1-온의 제조방법 |
PT3185855T (pt) | 2014-08-28 | 2022-12-13 | Sanofi Aventis Deutschland | Comprimido revestido por película para o tratamento da dor aguda |
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US4571400A (en) * | 1984-12-18 | 1986-02-18 | Belleview Pharmaceutical, Inc. | Dihydrocodeine/ibuprofen pharmaceutical compositions and method |
GB8905815D0 (en) * | 1989-03-14 | 1989-04-26 | Beecham Group Plc | Medicament |
GB9121204D0 (en) * | 1991-10-04 | 1991-11-20 | Euro Celtique Sa | Medicament |
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1995
- 1995-08-16 RU RU97104235A patent/RU2140782C1/ru active
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- 1995-08-16 JP JP50785696A patent/JP3874793B2/ja not_active Expired - Fee Related
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- 1995-08-16 WO PCT/GB1995/001947 patent/WO1996005834A1/en active IP Right Grant
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- 1995-08-16 SK SK236-97A patent/SK282183B6/sk not_active IP Right Cessation
- 1995-08-16 DK DK95928574T patent/DK0777477T3/da active
- 1995-08-16 AU AU32289/95A patent/AU699224B2/en not_active Ceased
- 1995-08-16 UA UA97020807A patent/UA42781C2/uk unknown
- 1995-08-16 KR KR1019970701128A patent/KR100397082B1/ko not_active IP Right Cessation
- 1995-08-16 PL PL95318807A patent/PL181215B1/pl not_active IP Right Cessation
- 1995-08-22 TW TW084108754A patent/TW493984B/zh not_active IP Right Cessation
- 1995-08-23 CA CA002156768A patent/CA2156768A1/en not_active Abandoned
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1997
- 1997-02-20 NO NO19970782A patent/NO322200B1/no not_active IP Right Cessation
- 1997-02-21 BG BG101252A patent/BG63329B1/bg unknown
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105395508A (zh) * | 2015-12-14 | 2016-03-16 | 西南药业股份有限公司 | 一种洛芬待因复方制剂及其制备方法 |
CN105395508B (zh) * | 2015-12-14 | 2018-06-29 | 西南药业股份有限公司 | 一种洛芬待因复方制剂及其制备方法 |
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