CN1443067A - 含有环氧化酶-2抑制剂的止痛和抗炎药物 - Google Patents
含有环氧化酶-2抑制剂的止痛和抗炎药物 Download PDFInfo
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- CN1443067A CN1443067A CN01813180A CN01813180A CN1443067A CN 1443067 A CN1443067 A CN 1443067A CN 01813180 A CN01813180 A CN 01813180A CN 01813180 A CN01813180 A CN 01813180A CN 1443067 A CN1443067 A CN 1443067A
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Abstract
本发明涉及一种镇痛组合物,它基本上包括环氧化酶-2抑制剂和选自非甾体类抗炎药,醋氨酚及其混合物。本发明还涉及通过将这种组合物施用给病人以产生镇痛效果的方法。
Description
发明领域
本发明涉及用于减轻疼痛和/或炎症的组合物,它见效快并且作用持久。更具体说,本发明涉及一种组合物,它基本上由环氧化酶-2抑制剂(又称作环氧化酶II,COX-2或COXII抑制剂)和选自下组的第二种镇痛药组合物:NSAIDS(非甾族,抗炎药物),醋氨酚和它们的混合物形成的组合物。本发明还涉及通过施用这种组合物以减轻疼痛和炎症的方法。
发明背景
已经发现通过抑制前列腺素G/H合成酶,也被称作环氧化酶来发挥抗炎、镇痛和退热活性(另外还抑制激素诱导的子宫收缩和某些种类癌症的生长)的化合物。最初,仅知道一种形式的环氧化酶,这对应于环氧化酶-1或组成酶,如最初在牛精囊内发现的一样。这种酶已经从包括绵羊、小鼠和人的各种来源中被复制、排序和表征。还已经发现前列腺素既具有生理活性也在一些病理过程中起作用。环氧化酶-1影响内源性前列腺素的基础释放,并对它们的生理功能如维持胃肠整体性和肾血流起重要作用。非甾体类抗炎药(NSAIDS)已经被发现可抑制环氧化酶-1酶,从而发挥抗炎、镇痛和退热特性。
NSAIDS发挥极佳的抗炎、镇痛和退热特性并具有见效快的其他优点外,还有胃肠毒性,和/或肾脏副作用。
最近,对于环氧化酶的第二种诱导型基因,又称为环氧化酶-2的基因已经在小鸡、海洋生物和人源中复制、排序和表征。这种被称为环氧化酶-2的基因可用很多药剂包括分裂素、内毒素、激素、细胞因子和生长因子很迅速并容易地诱导。与环氧化酶-1相反,环氧化酶-2主要对前列腺素的病理作用负责,其中通常响应诸如抗炎药、激素、生长因子和细胞因子而迅速发生酶的诱导。因此,环氧化酶-2的选择性抑制剂具有与通过使用NSAIDS对环氧化酶-1的抑制所获得的相似的抗炎、镇痛和退热特性。
已知许多环氧化酶-2抑制剂。例如在美国专利号5,393,790;5,409,944;5,418,254;5,420,343;5,436,265;5,474,995;5,476,944;5,486,534;5,510,368;5,521,213;5,536,752;5,547,975;5,550,142;5,552,422;5,565,482;5,576,339;5,580,985;5,585,504;5,593,994和5,596,008中公开的那些。
在环氧化酶-2抑制剂具有类似于NSAIDS的抗炎、镇痛和退热活性时,环氧化酶-2抑制基还显示具有减小在施用NSAIDS时可能发生的诱导某些基于机理的副作用的趋势。具体地说,环氧化酶-2抑制剂显示具有降低的胃肠毒性和肾脏副作用,对出血时间影响的降低和可能减小的诱导阿斯匹林敏感的哮喘患者的哮喘发作。
然而,当环氧化酶-2抑制剂具有涉及副作用减小的潜在优势时,相对于环氧化酶-1抑制剂,例如NSAIDS或醋氨酚它的作用发挥的相对较慢。因此,使用它作为镇痛的病人会感觉到它在提供所需的镇痛作用时见效时间不是太令人满意。
这里要求保护的组合物具有比环氧化酶-2抑制剂单独使用时更快的镇痛作用时间。所要求保护的化合物还进一步减少了环氧化酶-1抑制剂给药的剂量,从而降低了潜在的胃肠道毒性的风险。这种组合物还进一步提供了长效作用,诸如“一天一次剂量”,同时还保持了使用环氧化酶-1抑制剂时镇痛作用快的优点。本发明还一个优点在于,所保护的组合物的组合对于环氧化酶-1抑制剂(并因此被称为要求保护的组合物)的发作时间比单独使用的任一成分的发作时间减短的协同作用,换句话说,环氧化酶-2抑制剂的存在出人意料缩短了环氧化酶-1抑制剂成分(例如NSAID)的见效时间。
发明概述
根据本发明,提供一种用于减轻疼痛和/或炎症的组合物,它主要含有(a)至少一种环氧化酶-2抑制剂和(b)至少一种选自以下的化合物:NSAIDs、醋氨酚和它们的混合物。
另外,本发明还提供一种减轻疼痛和/或炎症的方法,它包括给有疼痛症状的哺乳类施用以下组合物,该组合物包括(a)至少一种环氧化酶-2抑制剂和(b)至少一种选自以下的化合物:NSAIDs、醋氨酚和它们的混合物。
优选实施方式的详细描述
因此,本发明要求的方法和治疗用的组合物可用于治疗各种疼痛。这里所用的术语“疼痛减轻”意思是指“抑制疼痛”和“阻止疼痛”,即当施用本发明时对于存在的疼痛表现出抑制或阻止,否则在出现引起疼痛的事件时立即就会发生疼痛。迄今为止任何用于减轻疼痛的环氧化酶-2抑制剂皆可用于本发明。
本发明方法和组合物中所用的环氧化酶-1抑制剂和/或环氧化酶-2抑制剂的所谓“引起痛觉却失的量”是指当施用这一量时引起明显的痛觉却失效果。
可用于本发明实践中的特定环氧化酶-2抑制剂是指那些具有至少12小时作用时间的化合物。这些包括瑟来考昔勃(celecoxib)、罗非考昔勃(rofecoxib)、美洛昔康和尼美舒利。特别优选的是瑟来考昔勃和罗非考昔勃。
瑟来考昔勃是4-[5-(4-甲基苯基)-3-(三氟甲基)-1H-吡唑-1-基]苯磺酰胺,目前由G.D.Searle & Co.生产。商标名为Celebrex。罗非考昔勃是4-[4-(甲磺酰基)苯基]-3-苯基-2(5H)呋喃,目前由Merck & Co.Inc.生产。商标名为Vioxx。美洛昔康是4-羟基-2-甲基-N-(5-甲基-2-噻唑基)-2-H-1,2-苯并噻嗪-3-甲酰胺-1,1-二氧化物。在美国专利U.S.4233299中描述了它的生产,该文献全文并入此作为参考。它在美国以商标名Mobic被批准上市。尼美舒利是N-(44-硝基-2-苯氧基苯基)甲磺酰胺。美国专利U.S.3,840,597中描述了它的生产。其全文收编于此作为参考。
关于环氧化酶-1抑制剂成分,所用的减轻疼痛的NSAIDs、醋氨酚或它们的混合物中的任意一种都可以使用。用于本发明方法和组合物中的NSAIDs可以选自下列种类:
(1) 丙酸衍生物;
(2) 醋酸衍生物;
(3) 灭酸衍生物;
(4) 联苯羧酸衍生物;和
(5) 昔康类(oxicams)。
用于这里的丙酸衍生物包括但不限于:布洛芬、甲氧萘丙酸、氟比洛尔、非诺洛芬、芬布芬、酮洛芬、吡洛芬、卡洛芬、噁丙秦、普拉洛芬、咪洛芬、硫噁洛芬、舒洛芬、阿明洛芬、噻洛芬酸、氟洛芬和布氯酸。这里定义的丙酸衍生物是具有游离-CH(CH3)COOH或-CH2CH2COOH基团(任选地可以是可药用盐形式,例如-CH(CH3)COONa+或-CH2CH2COONa+)的衍生物,典型的是直接或经一个羰基官能团连接到环系上,优选是连接到芳香环系上的衍生物。具有类似的镇痛和抗炎特性的结构相关的丙酸衍生物也包括在这一组中。丙酸组中当前优选的成员包括:布洛芬、甲氧萘丙酸、氟比洛尔、非诺洛芬、酮洛芬和芬布芬。包括在丙酸衍生物的描述中的是如U.S.4,851,444中描述的诸如S+布洛芬的分离的异构体形式,其全文收编于此用于参考。还包括在本发明范围中的是其可药用盐,例如,萘普生钠。
本发明所用的醋酸衍生物包括但不限于:消炎痛、托美丁、二氯芬酸、芬氯酸、阿氯芬酸、布芬酸、伊索克酸、呋罗芬酸、硫平酸、齐多美辛、acetmitacin、芬替酸、环氯茚酸和oxipinac。这里定义的醋酸衍生物是具有游离的-CH2COOH基团(任选的可以是其可药用盐形式,例如-CH2COONa+),典型的是直接连接到环系上,优选是芳香环或杂芳环系上的衍生物。具有类似镇痛和抗炎特性的结构与醋酸相关的衍生物也包括在该组中。
本发明所用的灭酸衍生物包括但不限于:甲芬那酸、甲氯芬那酸、氟芬那酸、尼氟灭酸和托芬那酸。具有类似镇痛和抗炎特性的结构与灭酸衍生物相关的也包括在该组中。这里定义的灭酸衍生物可包括-COOH侧基或其可药用盐,例如以-COON+基的形式。
这里所用的联苯羧酸衍射物包括但不限于:氟苯柳和二氟苯水杨酸。具有类似镇痛和抗炎特性的结构与联苯羧酸衍生物相关的衍生物也包括在该组中。这里定义的灭酸衍生物可包括-COOH侧基或其可药用盐,例如以-COONa +基的形式。
这里所用的昔康类包括但不限于:吡罗昔康、舒多昔康、替诺昔康和伊索昔康。具有类似镇痛和抗炎特性的结构与昔康衍生物相关的衍生物也包括在该组中。
醋氨酚是4’-羟基乙酰苯胺。在市场上广泛使用,包括McNeil生产的商标名为Tylenol的药剂。
特别优选的是布洛芬、S+布洛芬、酮洛芬、甲氧萘丙酸和醋氨酚。
关于剂量水平,环氧化酶-2抑制剂存在的量必须是痛觉却失诱导量和/或疼痛减轻量。在优选的环氧化酶-2抑制剂中,瑟来考昔勃在权利要求所要求保护的化合物中存在的量在约25到约200毫克范围,优选其存在的量在约100到约200毫克范围。罗非考昔勃在权利要求所要求保护的化合物中存在的量在约12.5到约50毫克范围,优选其存在的量在约25到约50毫克范围。尼美舒利在权利要求所要求保护的化合物中存在的量在约50到约300毫克范围,优选其存在的量在约100到约200毫克范围,最优选其存在的量在约200毫克左右。美洛昔康在权利要求所要求保护的化合物中存在的量在约3到约15毫克范围,优选其存在的量在约10到约15毫克范围,最优选其存在的量为15毫克左右。
关于所要求保护的组合物中存在的环氧化酶-1抑制剂的剂量水平,它也必须是痛觉却失诱导量和/或疼痛减轻量。在用于本发明实践中的环氧化酶-1抑制剂中,包括被提到的优选的那些中,布洛芬在权利要求所要求保护的化合物中存在的量在约50到约400毫克范围,优选其存在的量在约200到约400毫克范围,最优选其存在的量为400毫克左右。酮洛芬在权利要求所要求保护的化合物中存在的量在约6.5到约25毫克范围,优选其存在的量在约12.5到约25毫克范围,最优选其存在的量为25毫克左右。氟比洛尔在权利要求所要求保护的化合物中存在的量在约12.5到约50毫克范围,优选其存在的量在约25到约50毫克范围,最优选其存在的量在约50毫克左右。非诺洛芬在权利要求所要求保护的化合物中存在的量在约50到约100毫克范围,优选其存在的量在约100到约200毫克范围,最优选其存在的量为200毫克左右。依托度酸在权利要求所要求保护的化合物中存在的量在约100到约400毫克范围,优选其存在的量在约200到约400毫克范围,最优选其存在的量为400毫克左右。甲氧萘丙酸钠在权利要求所要求保护的化合物中存在的量在约110到约440毫克范围,优选其存在的量在约200到约440毫克范围,最优选其存在的量为220毫克左右。噁丙秦在权利要求所要求保护的化合物中存在的量在约100到约1200毫克范围,优选其存在的量在约300到约900毫克范围,最优选其存在的量为600毫克左右。吡罗昔康在权利要求所要求保护的化合物中存在的量在约2.5到约40毫克范围,优选其存在的量在约10到约40毫克范围,最优选其存在的量为20毫克左右。二氯芬酸在权利要求所要求保护的化合物中存在的量在约12.5到约75毫克范围,优选其存在的量在约25到约75毫克范围,最优选其存在的量为50毫克左右。
如果组合物中使用醋氨酚作为环氧化酶-1抑制剂,则它在要求保护的组合物中存在的量在约200到约1000范围,优选它存在的量在约500到约1000毫克范围,最优选它存在的量约为1000毫克。
当环氧化酶-2抑制剂和环氧化酶-1抑制剂不需要在单一片剂或其它剂型中施用时,它们必须同时给病人施用各有效量。当在本发明的范围内以分别施用要求保护的组合物的成分时,为了方便起见,优选它们作为单一治疗组合物共同施用。考虑了所有施用方式,例如,口服、直肠内、鼻内、舌下、局部,或静脉内、肌肉内、胸骨内或皮下注射。制剂可以是任何适宜的、方便施用的分散剂量单位,并可以用制药领域中任何已知的方法制备。
要求保护的组合物按照已知的和实践中确立的方法用一种或多种可药用成分配制。因此,该组合物可以配制成液体、粉剂、悬浮液或酏剂。用于口服的制剂可以是片剂、液体凝胶(R.P.Scherer的Tm)或硬胶囊,其中药物活性成分与惰性固体稀释剂,例如碳酸钙、磷酸钙或高岭土混合,或者是软明胶胶囊,其中药物活性成分与水或易混合的溶剂,例如丙二醇、PEG’s和乙醇,或油性介质,例如花生油、液体石蜡或橄榄油混合。
对于口腔中局部施用的制剂,药物组合物可以配制成颊内或舌下含片、滴剂或按常规的方式配制。
对于将局部施用到表皮的本发明的组合物可以配制成霜剂、凝胶、膏剂、喷雾剂或洗液,或透皮贴剂。这种组合物可以例如用水性或油性基质,另加入适当的增稠剂、胶凝剂、乳化剂、稳定剂、分散剂、悬浮剂和/或着色剂来配制。
本发明的组合物可以配制成用于胃肠外施用的制剂,例如注射剂,通常用于静脉内、肌肉内或皮下注射;例如静脉推注或连续静脉滴注。用于注射的制剂可以为单位剂型,例如于安瓿或者于多剂量容器内,其中加入防腐剂。该组合物可以为诸如在油性或水性载体中的悬浮剂、溶液或乳液形式,可以含有配制剂例如悬浮剂、稳定剂和/或分散剂。或者,活性成分可以为粉末形式,在临用前用适当的载体,例如灭菌无热原的水配制。
本发明的组合物还可以配制成直肠内施用的诸如栓剂或储留灌肠剂例如,含有常规的栓剂基质例如可可油或其它甘油酯。
水性悬浮液可包括可药用赋形剂,诸如羧甲基纤维素钠、甲基纤维素、羟丙基甲基纤维素、藻酸钠、聚乙烯吡咯烷酮、黄蓍树胶、阿拉伯树胶这些悬浮剂;分散剂或加湿剂,如天然的磷脂,例如卵磷脂、烯基氧化物与脂肪酸的缩合产物、例如聚氧乙烯硬脂酸盐或环氧乙烷和长链脂肪醇的缩合产物,例如十七烷基乙烯氧基鲸蜡醇(ethylene-oxycetanol),或环氧乙烷与脂肪酸和己糖醇的部分脂的衍生物的缩合产物,例如聚氧乙烯脱水山梨糖醇,或环氧乙烷与从脂肪酸和己糖醇酐衍和衍生的部分酯的缩合产物,如聚氧乙烯脱水山梨糖醇含油酸基化合物。水性悬浮剂还可包括一种或多种防腐剂,例如乙基-或-正丙基-对-羟基苯甲酸脂,一种或多种着色剂,一种或多种矫味剂和一种或多种甜味剂、如蔗糖、糖精或环己氨磺酸钠或环己氨基磺酸钙。
下面的实施例用于说明要求保护的本发明的各种实施方式,而不是对本发明的限制。
实施例
实施例1
进行了一种醋酸诱导的痛苦实验(如在Porreca F.,H.I.MosbergJ.R.Omnaas,T.F.Burks和A.Cowan in Supraspinal and spinalpotency of selective opioid agonists in the mouse writhing test(Journal of Pharmacology and Experimental Therapeutics)240:890-894,1987))的改进实验。所述小鼠痛苦模型通常用于研究镇痛效力和与药物联合增强的协同作用中。
重量在25-30克的雄性Swiss小鼠从Ace实验室获得。它们被单独放于矩形观察箱内并让其适应至少一个小时。准备1%Tween80%水的安慰剂。
每组各8-10只小鼠分别经胃管口服待测试剂或安慰剂(以0.25ml/25g体重的量)。接受安慰剂的组作为对照组。在20,30,40或60分钟后,每只小鼠非肠道注射0.6%的醋酸溶液(0.25ml/g体重)。
再过5分钟后,在十分钟期限内计数呈现腹部疼痛症状的每只小鼠的数。然后用对照(安慰剂)组将10分钟内表现痛苦的小鼠的数目标准化成平均数。痛苦的百分抑制率表示为:
(对照组的平均痛苦小鼠数)-(小鼠的痛苦数)*100/(对照组的平均痛苦小鼠数)
结果
在30分钟内进行了一个预试验,以分别建立布洛芬(从SigmaChemical获得)和瑟来考昔勃(由G.D.Searle & Co.生产,于200毫克胶囊内,商品名Celebrex)的抗疼痛剂量-反应曲线。结果显示于下表1。获得了布洛芬的口服29.07mg/kg(17.57-40.58)的A50值(置信区间95%)。瑟来考昔勃的相应值>80mg/kg。
表1
化合物 剂 量(mg/kg) 抑制百分率%均数
+s.e.m.
布洛芬 20 38.7±11.2
40 59.4±9.58
80 74.0±4.68
Celebrex 20 7.5±3.38
40 21.7±4.17
80 28.3±8.34
为了研究联合服用化合物的效果,一组小鼠(n=8-10)接受29mg/kg布洛芬,之后立即服用基本上无活性剂量的瑟来考昔勃(20mg/kg)。第二组小鼠(n=8-10)接受29mg/kg布洛芬之后立即服用安慰剂。在服药后+20、+40或+60分钟后给动物腹膜内注射0.6%醋酸(0.25ml/25mg体重)以进行痛苦实验。获得的数据显示在表2。
表2
化合物 时间(分钟) 抑制百分率%均数
+s.e.m.
布洛芬+安慰剂 20 36.4±3.2
布洛芬+瑟来考昔勃 20 63.2±8.7
布洛芬+安慰剂 40 14.1±6.2
布洛芬+瑟来考昔勃 40 52.7±9.6
布洛芬+安慰剂 60 27.3±8.2
布洛芬+瑟来考昔勃 60 63.6±9.2
从表1和2的数据显然可以看出即使只有基本上无活性量的瑟来考昔勃存在,也能够通过见效快和作用持久两方面增强布洛芬的作用。
实施例2
根据一般片剂制备方法制备下列配方的片剂
配方I
成分 mg/片 %w/w
布洛芬 200 38.6
瑟来考昔勃 100 19.3
预凝胶化淀粉 75 14.5
微晶纤维素 60 11.6
含水乳糖 50 9.7
交联羟甲纤维素钠 20 3.9
二氧化硅胶体 5 1.0
十二烷基硫酸钠 3 0.6
硬脂酸 5 1.0
配方II
成分 mg/片 %w/w
酮洛芬 12.5 4.8
瑟来考昔勃 100 38.5
预凝胶化淀粉 40 15.4
微晶纤维素 50 19.3
含水乳糖 40 15.4
交联羟甲纤维素钠 10 3.9
二氧化硅胶体 2.5 1.0
十二烷基硫酸钠 2 0.8
硬脂酸 2.6 1.0
配方III
成分 mg/片 %w/w
布洛芬 200 52.2
refocoxib 25 3.3
预凝胶化淀粉 60 15.6
微晶纤维素 60 15.6
含水乳糖 25 6.5
交联羟甲纤维素钠 15 3.9
二氧化硅胶体 4 1.0
十二烷基硫酸钠 3 0.8
硬脂酸 4 1.0配方IV
成分 mg/片 %w/w
酮洛芬 12.5 6.0
refocoxib 25 6.0
预凝胶化淀粉 30 14.4
微晶纤维素 100 48
含水乳糖 40 19.2
交联羟甲纤维素钠 8 3.2
二氧化硅胶体 2 1.0
十二烷基硫酸钠 1.5 0.7
硬脂酸 2 1.0
Claims (70)
1.一种组合物,基本上由(a)至少一种环氧化酶-2抑制剂,和(b)至少一种选自NSAIDs、醋氨酚及其混合物的一种化合物组成。
2.权利要求1的组合物,其中所述环氧化酶-2抑制剂选自瑟来考昔勃、美洛昔康、尼美舒利和罗非考昔勃,及其混合物,并且成分(b)是NSAIDs。
3.权利要求2的组合物,其中NSAIDs选自布洛芬、酮洛芬、非诺洛芬、氟比洛尔、甲氧萘丙酸钠(paroxen sodium)、噁丙秦、吡罗昔康及其混合物。
4.权利要求1的组合物,其中所述环氧化酶-2抑制剂是瑟来考昔勃,并且成分(b)是布洛芬。
5.权利要求4的组合物,其中瑟来考昔勃存在的量约为25-200毫克范围,布洛芬存在的量约为50-800毫克范围。
6.权利要求4的组合物,其中瑟来考昔勃存在的量约为100-200毫克范围,布洛芬存在的量约为200-400毫克范围。
7.权利要求4的组合物,其中瑟来考昔勃存在的量约为200毫克,布洛芬存在的量约为400毫克。
8.权利要求1的组合物,其中环氧化酶-2抑制剂是罗非考昔勃,并且成分(b)是布洛芬。
9.权利要求8的组合物,其中罗非考昔勃存在的量约为12.5-50毫克范围,布洛芬存在的量约为50-800毫克范围。
10.权利要求8的组合物,其中罗非考昔勃存在的量约为25-50毫克范围,布洛芬存在的量约为200-400毫克范围。
11.权利要求8的组合物,其中罗非考昔勃存在的量约为50毫克,布洛芬存在的量约为400毫克。
12.权利要求1的组合物,其中环氧化酶-2抑制剂是美洛昔康,并且成分(b)是布洛芬。
13.权利要求12的组合物,其中美洛昔康存在的量约为3-15毫克范围,布洛芬存在的量约为50-800毫克范围。
14.权利要求12的组合物,其中美洛昔康存在的量约为10-15毫克范围,布洛芬存在的量约为200-400毫克范围。
15.权利要求12的组合物,其中美洛昔康存在的量约为15毫克,布洛芬存在的量约为400毫克。
16.权利要求1的组合物,其中环氧化酶-2抑制剂是尼美舒利,并且成分(b)是布洛芬。
17.权利要求16的组合物,其中尼美舒利存在的量约为50-300毫克范围,布洛芬存在的量约为50-800毫克范围。
18.权利要求16的组合物,其中尼美舒利存在的量约为100-200毫克范围,布洛芬存在的量约为200-400毫克范围。
19.权利要求1的组合物,其中环氧化酶-2抑制剂选自瑟来考昔勃、美洛昔康、尼美舒利和罗非考昔勃,及其混合物,并且成分(b)是醋氨酚。
20.权利要求19的组合物,其中瑟来考昔勃存在的量约为25-200毫克范围,醋氨酚存在的量约为200-1000毫克范围。
21.权利要求19的组合物,其中瑟来考昔勃存在的量约为100-200毫克范围,醋氨酚存在的量约为500-1000毫克范围。
22.权利要求19的组合物,其中瑟来考昔勃存在的量约为200毫克,醋氨酚存在的量约为500-1000毫克范围。
23.权利要求19的组合物,其中罗非考昔勃存在的量约为12.5-50毫克范围,醋氨酚存在的量约为200-1000毫克范围。
24.权利要求19的组合物,其中罗非考昔勃存在的量约为25-50毫克范围,醋氨酚存在的量约为500-1000毫克范围。
25.权利要求19的组合物,其中罗非考昔勃存在的量约为50毫克,醋氨酚存在的量约为1000毫克。
26.权利要求19的组合物,其中美洛昔康存在的量约为3-15毫克范围,醋氨酚存在的量约为200-1000毫克范围。
27.权利要求19的组合物,其中美洛昔康存在的量约为10-15毫克范围,醋氨酚存在的量约为500-1000毫克范围。
28.权利要求19的组合物,其中美洛昔康存在的量约为15毫克,醋氨酚存在的量约为1000毫克。
29.根据权利要求19的组合物,其中尼美舒利存在的量为50-300毫克,并且醋氨酚存在的量为200-1000毫克。
30.根据权利要求19的组合物,其中尼美舒利存在的量为100-200毫克,并且醋氨酚存在的量为500-1000毫克。
31.根据权利要求19的组合物,其中尼美舒利存在的量为200毫克,并且醋氨酚存在的量为1000毫克。
32.一种缓解疼痛和/或炎症的方法,包括给哺乳动物施用一种组合物,其基本上由(a)至少一种环氧化酶-2抑制剂,和(b)至少一种选自NSAIDs、醋氨酚及其混合物的一种化合物。
33.权利要求32的方法,其中所述环氧化酶-2抑制剂选自瑟来考昔勃、美洛昔康、尼美舒利和罗非考昔勃,及其混合物,并且成分(b)是NSAIDs。
34.权利要求33的方法,其中NSAIDs选自布洛芬、酮洛芬、非诺洛芬、氟比洛尔、甲氧萘丙酸钠、噁丙秦、吡罗昔康及其混合物。
35.权利要求33的方法,其中所述环氧化酶-2抑制剂是瑟来考昔勃,并且成分(b)是布洛芬。
36.权利要求33的方法,其中瑟来考昔勃存在的量约为25-200毫克范围,布洛芬存在的量约为50-800毫克范围。
37.权利要求33的方法,其中瑟来考昔勃存在的量约为100-200毫克范围,布洛芬存在的量约为200-400毫克范围。
38.权利要求35的方法,其中瑟来考昔勃存在的量约为200毫克范围,布洛芬存在的量约为400毫克范围。
39.权利要求33的方法,其中环氧化酶-2抑制剂是罗非考昔勃,并且成分(b)是布洛芬。
40.权利要求33的方法,其中罗非考昔勃存在的量约为12.5-50毫克范围,布洛芬存在的量约为50-800毫克范围。
41.权利要求33的方法,其中罗非考昔勃存在的量约为25-50毫克范围,布洛芬存在的量约为200-400毫克范围。
42.权利要求33的方法,其中罗非考昔勃存在的量约为50毫克范围,布洛芬存在的量约为400毫克范围。
43.权利要求33的方法,其中环氧化酶-2抑制剂是美洛昔康,并且成分(b)是布洛芬。
44.权利要求43的方法,其中美洛昔康存在的量约为3-15毫克范围,布洛芬存在的量约为50-800毫克范围。
45.权利要求43的方法,其中美洛昔康存在的量约为10-15毫克范围,布洛芬存在的量约为200-400毫克范围。
46.权利要求43的方法,其中美洛昔康存在的量约为15毫克,布洛芬存在的量约为400毫克。
47.权利要求33的方法,其中环氧化酶-2抑制剂是尼美舒利,并且成分(b)是布洛芬。
48.权利要求47的方法,其中尼美舒利存在的量约为50-300毫克范围,布洛芬存在的量约为50-800毫克范围。
49.权利要求47的方法,其中尼美舒利存在的量约为100-200毫克范围,布洛芬存在的量约为200-400毫克范围。
50.权利要求47的方法,其中尼美舒利存在的量约为200毫克,布洛芬存在的量约为400毫克。
51.权利要求33的方法,其中环氧化酶-2抑制剂选自瑟来考昔勃、美洛昔康、尼美舒利和罗非考昔勃,及其混合物,并且成分(b)是醋氨酚。
52.权利要求51的方法,其中瑟来考昔勃存在的量约为25-200毫克范围,醋氨酚存在的量约为200-1000毫克范围。
53.权利要求51的方法,其中瑟来考昔勃存在的量约为100-200毫克范围,醋氨酚存在的量约为500-1000毫克范围。
54.权利要求51的方法,其中瑟来考昔勃存在的量约为200毫克,醋氨酚存在的量约为1000毫克。
55.权利要求51的方法,其中罗非考昔勃存在的量约为12.5-50毫克范围,醋氨酚存在的量约为200-1000毫克范围。
56.权利要求51的方法,其中罗非考昔勃存在的量约为25-50毫克范围,醋氨酚存在的量约为500-1000毫克范围。
57.权利要求51的方法,其中罗非考昔勃存在的量约为50毫克,醋氨酚存在的量约为1000毫克。
58.权利要求52的方法,其中美洛昔康存在的量约为3-15毫克范围,醋氨酚存在的量约为200-1000毫克范围。
59.权利要求51的方法,其中美洛昔康存在的量约为10-15毫克范围,醋氨酚存在的量约为500-1000毫克范围。
60.权利要求51的方法,其中美洛昔康存在的量约为15毫克,醋氨酚存在的量约为1000毫克。
61.根据权利要求51的方法,其中尼美舒利存在的量为50-300毫克,并且醋氨酚存在的量为200-1000毫克。
62.根据权利要求51的方法,其中尼美舒利存在的量为100-200毫克,并且醋氨酚存在的量为500-1000毫克。
63.根据权利要求51的方法,其中尼美舒利存在的量为200毫克,并且醋氨酚存在的量为1000毫克。
64.一种用于增强选自下组的镇痛化合物的方法,包括在施用该化合物的同时还施用至少一种环氧化酶-2抑制剂,所述化合物选自:NSAIDs、醋氨酚及其混合物。
65.权利要求64的方法,其中所述环氧化酶-2抑制剂选自瑟来考昔勃、美洛昔康、尼美舒利和罗非考昔勃,及其混合物,并且成分(b)是NSAIDs。
66.权利要求65的方法,其中NSAIDs选自布洛芬、酮洛芬、非诺洛芬、氟比洛尔、甲氧萘丙酸钠、噁丙秦、吡罗昔康及其混合物。
67.权利要求65的方法,其中所述环氧化酶-2抑制剂是瑟来考昔勃,并且成分(b)是布洛芬。
68.权利要求65的方法,其中环氧化酶-2抑制剂是罗非考昔勃,并且成分(b)是布洛芬。
69.权利要求64的方法,其中环氧化酶-2抑制剂是瑟来考昔勃,并且成分(b)是醋氨酚。
70.权利要求64的方法,其中环氧化酶-2抑制剂是罗非考昔勃,并且成分(b)是醋氨酚。
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CN100418533C (zh) * | 2002-02-19 | 2008-09-17 | 阿德科克因格拉姆有限公司 | 环加氧酶-2抑制剂和阿片剂的药物组合体 |
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US20060281775A1 (en) | 2005-06-14 | 2006-12-14 | Applied Pharmacy Services, Inc. | Two-component pharmaceutical composition for the treatment of pain |
US8580855B2 (en) | 2006-10-20 | 2013-11-12 | Mcneil-Ppc, Inc. | Acetaminophen / ibuprofen combinations and method for their use |
TR200904862A1 (tr) * | 2009-05-29 | 2010-12-21 | Sanovel İlaç San. Ve Ti̇c. A.Ş. | Sukraloz formülasyonu ve üretim prosesi |
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US5474995A (en) * | 1993-06-24 | 1995-12-12 | Merck Frosst Canada, Inc. | Phenyl heterocycles as cox-2 inhibitors |
CA2276945C (en) * | 1993-11-30 | 2006-08-01 | G.D. Searle & Co. | Tricyclic-substituted pyrazolyl benzenesulfonamides and pharmaceutical compositions thereof |
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US6160020A (en) * | 1996-12-20 | 2000-12-12 | Mcneill-Ppc, Inc. | Alkali metal and alkaline-earth metal salts of acetaminophen |
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EP0868915A1 (en) | 1997-04-02 | 1998-10-07 | Panacea Biotec Limited | An anti-spasmodic and antiinflammatory composition containing a NSAID, pentifenone and fenpiverinium |
DZ2479A1 (fr) | 1997-05-05 | 2003-02-01 | Pfizer | Composés inhibiteurs sélectifs de cox-2 anti-inflammatoires et compositions pharmaceutiques les contenant. |
RS49982B (sr) * | 1997-09-17 | 2008-09-29 | Euro-Celtique S.A., | Sinergistička analgetička kombinacija analgetičkog opijata i inhibitora ciklooksigenaze-2 |
FR2770131A1 (fr) * | 1997-10-27 | 1999-04-30 | Union Pharma Scient Appl | Nouvelle association pharmaceutique a activite analgesique |
DE60007267T2 (de) | 1999-04-14 | 2004-09-16 | Pacific Corp. | 4,5-diaryl-3(2h)-furanon derivate als cyclooxygenase-2 inhibitoren |
US6524623B1 (en) * | 1999-11-12 | 2003-02-25 | Milton Hodosh | Therapeutic compositions and methods of use thereof |
DE60027464T2 (de) * | 1999-12-22 | 2006-08-31 | Pharmacia Corp. | Arzneizubereitungen mit zwei verschiedenen freisetzungsraten enthaltend einen cyclooxygenase-2 hemmer |
US6306842B1 (en) * | 2000-06-02 | 2001-10-23 | Medinox, Inc. | Protected forms of a combination of pharmacologically active agents and uses therefor |
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