CN1747734A - 潘生丁或单哌潘生丁在治疗和预防mmp-9-依赖性疾病中的用途 - Google Patents
潘生丁或单哌潘生丁在治疗和预防mmp-9-依赖性疾病中的用途 Download PDFInfo
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- CN1747734A CN1747734A CNA2004800037161A CN200480003716A CN1747734A CN 1747734 A CN1747734 A CN 1747734A CN A2004800037161 A CNA2004800037161 A CN A2004800037161A CN 200480003716 A CN200480003716 A CN 200480003716A CN 1747734 A CN1747734 A CN 1747734A
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- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
公开了一种人或非人动物体的治疗方法,用于治疗或预防MMP-9-依赖性疾病,例如血管综合症、损伤或疾病、动脉粥样硬化性损伤、关节炎病症、炎性反应、自身免疫反应或增殖性疾病,其方法包括给予需要这种治疗的人或非人动物体有效量的药物组合物,所述的药物组合物含有潘生丁、单哌潘生丁或其药学上可接受的盐,以及潘生丁或单哌潘生丁在制备相应的药物组合物中的用途。
Description
发明领域
本发明涉及一种使用潘生丁或单哌潘生丁(mopidamole)作为有效成分治疗和预防MMP-9-依赖性疾病的方法,以及潘生丁或单哌潘生丁在制备相应的药物组合物中的用途。
发明背景
潘生丁{2,6-双(二乙醇氨基)-4,8-二哌啶基-嘧啶并[5,4-d]嘧啶}、非常相关的取代嘧啶并-嘧啶以及它们的制备例如已经在美国专利3,031,450中公开。其它相关的取代嘧啶并-嘧啶以及它们的制备例如已经描述在GB1,051,218中,尤其是化合物单哌潘生丁{2,6-双-(二乙醇氨基)-4-哌啶基嘧啶并[5,4-d]嘧啶}。潘生丁在60年代初作为冠状动脉血管扩张剂被引入。由于抑制腺苷摄取,还公知它具有血小板凝集抑制剂性质。后来,在兔子模型的脑动脉循环研究中,潘生丁显示出能够减少血栓形成。这些研究导致潘生丁作为抗血栓药物使用;很快成为如应用在预防中风、维持冠状动脉旁路的开放及瓣膜换置术中的治疗选择,以及用于冠状动脉血管成形术之前的治疗上。
此外,European Stroke Prevention Study 2(ESPS-2;J Neurol Sci.1996;143:1-13;Neurology 1998;51:17-19)证实:在减少中风风险方面,单独通过潘生丁治疗与低剂量的阿斯匹林效果一样,而用潘生丁和阿斯匹林进行的联合治疗的效果要大于单独用阿斯匹林进行治疗效果的两倍。
潘生丁似乎通过多种机理来抑制血栓形成。早期研究表明,它抑制腺苷的摄取,其被发现是一种有效的内源性抗凝血化合物。潘生丁还显示出抑制环状AMP磷酸二酯酶,由此增加胞内c-AMP。
在动物研究中,潘生丁已被证明是抗动脉粥样硬化药。该发现表明脂肪纹减少同时内膜变厚减少。在过去,这个被错误地认为是潘生丁的抗血小板作用。来自搅动或凝集血小板的血小板衍生的生长因子(PDGF)的释放很长时间被认为是平滑肌细胞增生、内膜变厚以及狭窄形成的唯一原因。然而,现代血管内介入性技术如气囊血管成形术或金属斯坦特固定模(stent)的放置仅在约一个月的时间内存在于原血管形成表面,即,血小板凝集以及随后释放PDGF仅在有限的时间内是有意义的。然而,再狭窄的增殖和形成却是在长得多的一段时间内形成的。这表明其它因素必定对内膜变厚、血小板和再狭窄形成过程起显著作用。
通过反应血管复杂生理学的实验室模型,显示出脉管系统不是被动导管,在血管受伤后经复杂的检测和平衡系统与血液产生深奥的交互作用以保护其完整性。因此,内皮产生前列环素,一种有效的凝集抑制剂。正常内皮不是血栓形成的并且预防血小板附着。各种刺激物促使内皮细胞舒血管因子(EDRF)释放,其抑制血小板附着和凝集。同时,将硝基化合物给药后cGMP的胞内增加被证明是造成平滑肌细胞松弛的原因。因此,通过两种不同的机理,所述内皮可以抑制血栓形成,一种是由前列环素和c-AMP介导,另一种由EDRF和c-GMP介导。除节约腺苷作用外,潘生丁还可以增强血管壁的这些抗凝血机理。潘生丁通过增加胞内cAMP水平刺激前列环素产生,并且通过增加cGMP提高强抗凝血氧化氮系统。
潘生丁还具有抗氧化性质(Free Radic.Biol.Med.1995;18:239-247),其可促进抗凝血作用。当低密度脂蛋白被氧化时,它可以被巨噬细胞上的清道夫受体(scavenger receptor)识别,其被认为是动脉粥样硬化形成的必要步骤(Ann.Rev.Med.1992;43:219-25)。
现已发现,由潘生丁抑制自由基形成在实验性肝纤维化中可以抑制纤维蛋白生成(Hepatology 1996;24:855-864)以及在患氨基核苷肾病的实验动物中可以抑制氧自由基和蛋白尿(Eur.J.Clin.Invest.1998;28:877-883;RenalPhysiol.1984;7:218-226)。在人非肿瘤性肺组织中也观察到对脂质过氧化的抑制(Gen.Pharmacol.1996;27:855-859)。
单哌潘生丁已知具有抗抗凝血以及其它抗转移性质。
WO 01/30353公开了潘生丁可以治疗纤维蛋白依赖性微循环障碍,例如由代谢病、炎性反应或自身免疫疾病所引起的微循环障碍,而且还有外周性微循环障碍或与增加细胞分裂有关的微循环障碍。
此外,WO 02/085331公开了由于自由基清除剂的作用,潘生丁可以治疗NO-依赖性微循环障碍。
WO 02/34248公开了一种通过共同给予一种增加cGMP合成的药物以及一种抑制血管壁细胞或血细胞中cGMP降解的药物,例如通过共同给予抑制素和潘生丁,来增加用血液的组织灌注的方法。
基质金属蛋白酶(MMPs)是蛋白水解酶的一个家族,其降解基底膜的细胞外基质或组分并且参与各种生理和病理过程。MMP-9,也称为明胶酶B,是裂解IV胶原蛋白的主要基质金属蛋白酶。MMP-9还具有显著的弹性蛋白分解(elastinolytic)作用,裂解聚集蛋白聚糖,一种软骨蛋白聚糖,以及裂解连接蛋白,一种在蛋白聚糖凝集体中稳定聚集蛋白聚糖和透明质酸盐间相互作用的糖蛋白。MMP-9在滋养层细胞、破骨细胞、嗜中性白细胞和巨噬细胞中是组成型表达。然而,暴露于炎性刺激物中的各种细胞包括单核细胞可以诱发异常表达(参见实施例1)。通过局部降解细胞外基质组分,MMP-9可以提高白细胞从血管腔隙中迁移到动脉粥样硬化组织中或生成趋化性肽。MMP-9的异常表达被认为是促使动脉瘤形成的弹性板进行性恶化特征的原因,并且MMP-9活性的抵消抑制了主动脉瘤的发展。
发明概述
现已令人吃惊地发现,潘生丁和单哌潘生丁减少了MMP-9基因表达,由此提供了一种治疗和/或预防MMP-9-依赖性疾病的方法。
潘生丁和单哌潘生丁下调MMP-9合成由此促使稳定细胞膜的发现提供了一种与其它抗血栓形成药进行联合治疗的基本原理,所述的其它抗血栓形成药例如是血小板凝集抑制剂,如乙酰水杨酸(ASA)、氯砒格雷或噻氯匹啶或其药学上可接受的盐,纤维蛋白原受体拮抗剂(阿昔单抗、RDGS-肽、合成静脉注射或口服纤维蛋白原拮抗剂,例如夫雷非班、来达非班或其药学上可接受的盐),肝素及类肝素或抗凝血酶,或者使用其它心血管疗法进行联合治疗,例如用ACE抑制剂、血管紧张素II拮抗剂、Ca-拮抗剂或降脂药如抑制素进行治疗。现已报道,抑制素(与它们的降脂活性无关)降低了MMP-9的表达,提供了一种使用潘生丁与一种抑制素进行优选联合治疗MMP-9依赖性疾病的基本原理。(J.Vasc.Surg.2002,36(1),:158-63)。
ASA通过对血小板直接作用来抑制凝集,更详细地说,通过不可逆乙酰化血小板环氧合酶,由此抑制血栓烷的产生,其是强血栓形成的。然而,在高剂量的情况下,阿斯匹林跨越进入内皮细胞(N.Eng.J.Med.1984;311:1206-1211),在那里它中断前列环素的产生,一种有效的血小板凝集天然抑制剂和″arachidonic cascade″的副产物(N.Engl.J.Med.1979;300:1142-1147)。这些观察结果导致形成这样一种观念,即使用ASA进行低剂量抗血小板治疗以使血栓烷抑制达到最大化同时使前列环素损失达到最小(Lancet 1981;1:969-971)。低剂量ASA与本发明的潘生丁联合的观念同样是优选的。
一方面,本发明提供一种对人或非人动物体优选哺乳动物体的治疗方法,用于治疗和/或预防MMP-9-依赖性疾病或医学病症,伴随或其特征在于血浆中MMP-9的普遍升高或炎性部位处MMP-9的局部升高,所述方法包括给药所述动物体有效量的药物组合物,该药物组合物包含选自潘生丁、单哌潘生丁及其药学上可接受的盐的活性成分,任选与一种或多种其它抗血栓形成药、ACE抑制剂、血管紧张素II拮抗剂、Ca-拮抗剂或降脂药联合。
另一方面,本发明提供了选自潘生丁、单哌潘生丁及其药学上可接受的盐的活性成分,任选地与一种或多种其它抗血栓形成药、ACE抑制剂、血管紧张素II拮抗剂、Ca-拮抗剂或降脂剂联合,在制备用于治疗人或非人动物体优选哺乳动物体的药物组合物中的用途,该药物组合物用于治疗和/或预防MMP-9-依赖性疾病或伴随或其特征在于MMP-9血浆浓度增加的医学病症。
发明详述
本发明提供一种新的治疗和/或预防MMP-9-依赖性疾病或伴随或其特征在于MMP-9血浆浓度增加的医学病症的方法,所述方法包括给药所述动物体有效量的药物组合物,该药物组合物包含选自潘生丁、单哌潘生丁及其药学上可接受的盐的活性成分,任选地与一种或多种其它抗血栓形成药、ACE抑制剂、血管紧张素II拮抗剂、Ca-拮抗剂或降脂药联合。
MMP-9-依赖性疾病是指这样的疾病或医学病症,其伴随或其特征在于MMP-9血浆水平增加,或这样的病症其中升高的MMP-9血浆水平涉及或导致所述疾病的发病或发展。例如,在这样的疾病中其中连续炎性反应促使或导致血管综合症、损伤或疾病,动脉粥样硬化性损伤或关节炎病症的发展。在所述的科学文献中,据报道升高的MMP-9血浆水平与一些疾病有关。
最近,发现血管壁中的弹性纤维可以控制平滑肌细胞(SMC)增殖。在低浓度弹性纤维或通过介入破坏的情况下,通过弹性纤维控制SMC增殖的作用消失了。在MMP-9血浆水平升高的情况下,必然假定结构蛋白被导致再狭窄的金属蛋白酶消化了。
应该理解,术语″MMP-9-依赖性疾病″以非限制的方式包含
(a)血管综合症、损伤或疾病,
例如动脉瘤的发生(Circ.Res.2001,89(6),509-16),主动脉瘤的发生(J.Vasc.Interv.Radiol.2000 11(10):1345-52;J.Clin.Invest.2002,110(5):625-32;Prevention:J.Clin.Invest.2000,105(11):1641-9),心肌梗塞后左心室扩大(J.Clin.Invest.2000,106(1):55-62),血小板破裂形成并随后造成血管血栓栓塞性堵塞例如心肌梗塞或中风,或者以动脉瘤大量出血的形式出现,其丧失或减弱它的结构成分然后破裂,气囊血管成形术或植入器件特别是植入斯坦特固定模、瓣膜、过滤器、静脉内或动脉内导管后的狭窄或再狭窄,
(b)动脉粥样硬化性损伤,
例如早期冠状动脉粥样硬化(Clin.Chem.Lab.2001,39(5):380-4;Arterioscler.Thromb.Vasc.Biol.2001,21(9):1446-50),动脉粥样硬化斑块的稳定(Yonsei Med J 2000,41(1):82-8),特别是其被理解为带薄盖(cap)的斑块或暴露于已知容易破裂的高水平切应力下的斑块(易损坏斑块),
(c)关节炎病症,
例如牛皮癣性关节炎、类风湿性关节炎、骨关节炎、颞颌关节炎(Clin.Exp.Rheumatol.2001,19(6):760;Arthritis Rheum.2001,44(9):2024-8,J.Orofac.Pain 2000,14(1):20-30;J.Rheumatol.2001,28(3):485-89)、莱姆关节炎(Arthritis Rheum.2001,44(6):1401-10),
(d)引起血管综合症、损伤或疾病的连续性炎性反应、动脉粥样硬化性损伤或关节炎病症,
(e)急性炎性反应,
例如脓毒症、肺炎、血栓形成以及急性肺损伤,
(f)自身免疫反应,
例如红斑狼疮(Clin.Exp.Immunol.2002,127(2):393-8),类风湿性滑膜炎(Rheumatology 2002,41(1):78-87),
(g)增殖性疾病,
例如癌症,如膝盖周围的IIB期骨肉瘤(J.Bone Joint.Surg.Br.2002,84(5):706-11),囊性肾癌(J.Urol.2002,168(1):19-22),前列腺癌(Acta.Oncol.2002,41(3):289-96),膀胱癌(J.Med.Invest.2001,48(1-2):31-43),非霍奇金淋巴瘤(Blood 1991,77(11):2475-81),白血病(Br.J.Haematol.2002,117(4):835-41),伴随肝转移的胰腺癌,伴随肝转移的结肠癌(J.Surg.Oncol.2002,80(2):105-10,colorectal cancer(Br.J.Cancer 2002,86(12):1876-83),肝细胞癌(World J.Gastroenterol.2002,8(3):385-92),头和颈鳞状细胞癌(Cancer 2002,94(5):1483-91),卵巢癌(Int.J.Oncol.2000,17(4):673-81),包括肿瘤侵入、转移和血管生成(Clin.Cancer Res.20006(12):4823-30;Pathol.Oncol.Res.2001,7(1):14-23),
(h)或,其它适应症,
溶解血栓/溶解纤维蛋白的疗法所引起的大量出血的风险,包括颅内出血,例如在用组织纤溶酶原激活物(如rt-PA或TNK-PA)、链激酶、葡萄球菌激酶、尿激酶或其衍生物进行的溶解纤维蛋白的疗法中,因此通过本发明的方法减少了这种风险。
本发明的预防方法尤其适用于(a)、(b)、(c)、(d)和(h)组的适应症。
根据本发明的治疗和/或预防方法,潘生丁或单哌潘生丁的血浆浓度维持在约0.2-5μmol/L,优选约0.4-5μmol/L,尤其是约0.5-2μmol/L或者特别是约0.8-1.5μmol/L是有利的。这可以使用任何市售潘生丁口服延迟型、即时型或肠胃外制剂获得,延迟型制剂是优选的,例如可以以商品名潘生丁购得,或者与低剂量ASA联合治疗,使用以商品名Asasantin或Aggrenox购得的那些制剂。潘生丁延迟型制剂也公开在EP-A-0032562中,即时型制剂公开在EP-A-0068191中,ASA与潘生丁的联合用药公开在EP-A-0257344中,这些文献引入本说明书中作为参考。单哌潘生丁也有口服延迟型、即时型或肠胃外制剂可以使用,例如在GB 1,051,218或EP-A-0,108,898中公开的那些,其在此引入本说明书中作为参考,延迟型制剂是优选的。
潘生丁或单哌潘生丁可以经口给药,日剂量为25-1000mg,优选50-900mg,更优选100-480mg,最优选150-400mg。对于长期治疗,以重复剂量给药是有利的,如每日给药三次或四次,每次剂量为50-500mg,优选50-100mg的潘生丁或单哌潘生丁延迟型或任何其它即时释放型制剂。对于肠胃外给药,在24小时内以缓慢的静脉输注(不快于0.2mg/min)形式,以0.5-5mg/kg体重的剂量,优选1-3.5mg/kg体重的剂量给予潘生丁或单哌潘生丁。
如上文所提及的,潘生丁、单哌潘生丁或其药学上可接受的盐可以以单一制剂的形式单独使用,或者与其它治疗MMP-9-依赖性疾病的抗血栓形成药、ACE抑制剂、血管紧张素II拮抗剂、Ca-拮抗剂或降脂药联合使用。
此外,本发明的治疗和/或预防方法可以与本领域已知的用于上述疾病的治疗或预防的任何基本方法联合使用。
在动脉粥样硬化疾病中,这种治疗或预防的基本方法可以包括以本领域已知的剂量给予降脂药例如HMG-Co-A还原酶抑制剂或抑制素。
在关节炎病症或炎性反应中,这种治疗或预防的基本方法可以包括以本领域已知的剂量给予非甾体抗炎药(NSAID)。用于联合治疗的合适的NSAID是指包括所有的COX(环氧合酶)抑制剂,例如非选择性COX-抑制剂例如乙酰水杨酸、美沙拉秦、布洛芬、萘普生、氟比洛芬、非诺洛芬、芬布芬、酮洛芬、吲哚洛芬、吡洛芬、卡洛芬、奥沙普嗪、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、吲哚美辛、舒林酸、托美汀、佐美酸、萘丁美酮、双氯芬酸、芬氯酸、阿氯芬酸、溴芬酸、异丁苯乙酸、醋氯芬酸、阿西美辛、芬替酸、环氯茚酸、依托度酸、oxpinac、甲芬那酸、甲氯芬那酸、氟芬那酸、尼氟灭酸(nifluminic acid)、托灭酸、二氟尼酸、氟苯沙酸、吡罗昔康、替诺昔康、氯诺昔康和尼美舒利和所述的药学上可接受的盐其,以及选择性的COX2-抑制剂例如美洛昔康、塞来考昔和罗非考昔及其药学上可接受的盐。
在与本领域已知的任何治疗或预防的基本方法联合使用的情况中,每一活性成分可以根据它的常见剂量范围或以低于它的常见剂量范围的剂量给药。联合的NSAID或免疫抑制剂的剂量合适地为通常推荐的最低剂量的1/50至通常推荐剂量的1/1,优选1/20-1/2,更优选1/10-1/5。所述的联合药物的通常推荐剂量应该理解为例如在Rote Liste 2002,Editio Cantor VerlagAulendorf,Germany或在Physician′s Desk Reference中公开的剂量。
在自身免疫反应中,这种治疗或预防的基本方法可以包括给予本领域已知剂量的免疫抑制剂例如环孢菌素A及其衍生物、霉酚酸酯、FK 506、OKT-3、ATG、15-脱氧司加林(desoxyspergualin)、咪唑立宾、迷索前列醇、瑞帕霉素、reflunomide、硫唑嘌呤或NF-κB-抑制剂。
在增殖性疾病的情况中,这种治疗或预防的基本方法可以包括给予抗肿瘤治疗药物、拓扑异构酶抑制剂(例如依托泊苷)、有丝分裂抑制剂(例如长春碱)、与核酸相互作用的化合物(例如顺-铂、环磷酰胺、阿霉素)、激素拮抗药(例如他莫昔芬)、代谢过程抑制剂(例如5-FU等)、细胞因子(例如干扰素)或抗体等等。
在降低由溶解血栓/溶解纤维蛋白的疗法所引起的大量出血的风险的情况中,本发明的治疗和/或预防方法可以与给药WO 02/49665中公开的活化的凝血因子VII(VIIa)或其功能衍生物相联合。
潘生丁或单哌潘生丁可以与低剂量ASA联合经口给药,日剂量为10-30mg的ASA以及50-1200mg的潘生丁或单哌潘生丁,优选100-1200mg,更优选160-960mg,最优选160-480mg的潘生丁或单哌潘生丁,例如以1∶5至1∶12的重量比,最优选1∶8的重量比,例如典型地25mg的ASA以及200mg的潘生丁或单哌潘生丁,每日给药两次。
其它抗血栓形成化合物可以以临床所述剂量的0.1-10倍,优选0.3-5.0倍,最优选0.3-2.0倍(例如2002;夫雷非班、来达非班:EP-A-0483667),连同日剂量为25-900mg,优选50-480mg,最优选75-400mg的潘生丁或单哌潘生丁一起给予。
对于联合治疗,使用潘生丁或单哌潘生丁连同ACE抑制剂一起,本领域已知的任何ACE抑制剂都是合适的,例如贝那普利、卡托普利、西罗普利、依那普利、福森普利、咪达普利、赖诺普利、莫昔普利、喹那普利、雷米普利、群多普利或培哚普利,使用本领域已知的剂量,例如在Rote Liste2002,Editio Cantor Verlag Aulendorf中所述的。
对于联合治疗,使用潘生丁或单哌潘生丁连同血管紧张素II拮抗剂一起,本领域已知的任何血管紧张素II拮抗剂都是合适的,例如沙坦化合物(sartans)例如坎地沙坦、依普沙坦、依贝沙坦、氯沙坦、替米沙坦、缬沙坦、奥美沙坦或他索沙坦,使用本领域已知的剂量,例如在Rote Liste 2002,Editio Cantor Verlag Aulendorf中所述的。
对于联合治疗,使用潘生丁或单哌潘生丁连同Ca-拮抗剂一起,本领域已知的任何Ca-拮抗剂都是合适的,例如尼非地平、尼群地平、尼索地平、尼伐地平、伊拉地平、非洛地平或拉西地平,使用本领域已知的剂量,例如在Rote Liste 2002,Editio Cantor Verlag Aulendorf中所述的。
对于联合治疗,使用潘生丁或单哌潘生丁连同抑制素一起,本领域已知的任何抑制素都是合适的,例如洛伐他汀、辛伐他汀、帕伐他汀、氟伐地汀、阿伐他汀或西立伐他汀,使用本领域已知的剂量,例如在Rote Liste2002,Editio Cantor Verlag Aulendorf中所述的。
关于上文所述的本发明的所有方面,优选潘生丁及其盐。
为了研究潘生丁抑制MMP-9基因表达,进行如下实验:
实施例1:
由Aggrenox(AGG)的潘生丁组分抑制血小板-单核细胞凝集体中的MMP-9基因表达
Aggrenox(AGG)是一种缓释潘生丁(DIP)和阿斯匹林(ASA)的固定剂量的组合。AGG被推荐用于防止继发性中风和暂时性缺血性发作。在稳定型心绞痛或雷诺氏病的患者中,它还增加组织灌注。确定它是否AGG阻断了由血小板-单核细胞凝集体产生的炎性基因的合成。
将人血小板和单核细胞用潘生丁(DIP)(5μg/ml)、ASA(625ng/mL)、或DIP/ASA混合物(AGG);5μg/ml∶625ng/ml,8∶1比值的DIP/ASA)预先处理。所述细胞附着于I型胶原蛋白上。测定基质金属蛋白酶-9(MMP-9)的合成。血小板与单核细胞以及粘附于胶原蛋白上的共培养明显导致MMP-9合成显著增加。AGG和DIP减少了MMP-9表达(与未经AGG、DIP和ASA处理的细胞相比,MMP-9合成分别较少了53%,61%和17%;结果表示在图1中)。AGG对基因表达的抑制作用是由于这种药物的DIP组分。
附图说明:
图1:Aggrenox的潘生丁组分通过粘附于血小板(plts)和胶原蛋白上的单核细胞(monos)减弱了MMP-9的合成。将血小板和单核细胞单独放置,或用阿斯匹林(ASA:625ng/ml)、潘生丁(DIP:5μg/ml)或aggrenox(AGG:8∶1 DIP/ASA比值)预先处理15分钟。接着,将细胞附着于1型胶原蛋白上18小时,测定MMP-9表达。实验表示9个独立实验的平均值±SEM。
Claims (24)
1.一种用于治疗或预防人或非人动物体的MMP-9依赖性疾病或医学病症的治疗方法,所述方法包括给药所述动物体有效量的药物组合物,该药物组合物包含选自潘生丁、单哌潘生丁及其药学上可接受的盐的活性成分,任选地与一种或多种其它抗血栓形成药,或任选地与ACE抑制剂、血管紧张素II拮抗剂、Ca-拮抗剂或降脂药联合。
2.权利要求1的方法,其特征在于MMP-9依赖性疾病选自:
(a)血管综合症、损伤或疾病,
例如动脉瘤、主动脉瘤的发生,心肌梗塞后左心室扩大,狭窄或再狭窄,
(b)动脉粥样硬化性损伤,
例如早期冠状动脉粥样硬化,动脉粥样硬化斑块的稳定,
(c)关节炎病症,
例如牛皮癣性关节炎、类风湿性关节炎、骨关节炎、颞颌关节炎、莱姆关节炎,
(d)引起血管综合症、损伤或疾病的连续性炎性反应、动脉粥样硬化性损伤或关节炎病症,
(e)急性炎性反应,
例如脓毒症、肺炎、血栓形成以及急性肺损伤,
(f)自身免疫反应,
例如红斑狼疮,
(g)增殖性疾病,
例如癌症,如膝盖周围的IIB期骨肉瘤、囊性肾癌、前列腺癌、膀胱癌、非霍奇金淋巴瘤、白血病、伴随肝转移的胰腺癌、伴随肝转移的结肠癌、结肠直肠癌、肝细胞癌、头和颈鳞状细胞癌、卵巢癌,包括肿瘤侵入、转移和血管生成,以及
(h)溶解血栓/溶解纤维蛋白的疗法所引起的大量出血的风险,包括颅内出血,例如在用组织纤溶酶原激活物(例如rt-PA或TNK-PA)、链激酶、葡萄球菌激酶、尿激酶或其衍生物进行的溶解纤维蛋白的疗法中。
3.权利要求1或2的方法,其中所述活性成分的血浆浓度维持在约0.2-5μmol/L。
4.权利要求1或2的方法,其中所述的活性成分以25-1000mg的日剂量经口给药或以0.5-5mg/kg体重的日剂量胃肠外给药。
5.权利要求1或2的方法,其中所述的活性成分以单一制剂的形式单独给药。
6.权利要求1或2的方法,其中所述的活性成分与至少一种其它的药物活性化合物联合给药,所述的其它药物活性化合物选自抗血栓形成药、ACE抑制剂、血管紧张素II拮抗剂、Ca-拮抗剂和降脂药。
7.权利要求2的方法,其中所述的MMP-9依赖性疾病是动脉粥样硬化疾病,并且所述的方法包括给予降脂药。
8.权利要求2的方法,其中所述的MMP-9依赖性疾病是关节炎病症或炎性反应,并且所述的方法包括给予非甾体抗炎药(NSAID)。
9.权利要求8的方法,其中所述的NSAID选自美洛昔康、塞来考昔、罗非考昔及其药学上可接受的盐。
10.权利要求2的方法,其中所述的MMP-9依赖性疾病是自身免疫反应,并且所述的方法包括给予免疫抑制剂。
11.权利要求2的方法,其中所述的MMP-9依赖性疾病是增殖性疾病,并且所述的方法包括给予抗肿瘤治疗药。
12.权利要求2的方法,其中所述的MMP-9依赖性疾病是溶解血栓/溶解纤维蛋白的疗法所引起的大量出血的风险,并且所述方法包括给予活化的凝血因子VII(VIIa)或其功能衍生物。
13.权利要求1或2的方法,其中所述的活性成分以50-600mg的日剂量与10-30mg的ASA联合经口给药。
14.选自潘生丁、单哌潘生丁及其药学上可接受的盐的活性成分,任选地与一种或多种其它抗血栓形成药联合,或任选地与ACE抑制剂、血管紧张素II拮抗剂、Ca-拮抗剂或降脂药联合,在制备用于治疗人或非人动物体的药物组合物中的用途,该药物组合物用于治疗或预防MMP-9依赖性疾病或医学病症。
15.权利要求14的用途,其中所述的MMP-9依赖性疾病选自:
(a)血管综合症、损伤或疾病,
例如动脉瘤、主动脉瘤的发生,心肌梗塞后左心室扩大,
(b)动脉粥样硬化性损伤,
例如早期冠状动脉粥样硬化,动脉粥样硬化斑块的稳定,
(c)关节炎病症,
例如牛皮癣性关节炎、类风湿性关节炎、骨关节炎、颞颌关节炎、莱姆关节炎,
(d)引起血管综合症、损伤或疾病的连续性炎性反应、动脉粥样硬化性损伤或关节炎病症,
(e)急性炎性反应,
例如脓毒症、肺炎、血栓形成以及急性肺损伤,
(f)自身免疫反应,
例如红斑狼疮,
(g)增殖性疾病,
例如癌症,如膝盖周围的IIB期骨肉瘤、囊性肾癌、前列腺癌、膀胱癌、非霍奇金淋巴瘤、白血病、伴随肝转移的胰腺癌、伴随肝转移的结肠癌、结肠直肠癌、肝细胞癌、头和颈鳞状细胞癌、卵巢癌,包括肿瘤侵入、转移和血管生成,以及
(h)溶解血栓/溶解纤维蛋白的疗法所引起的大量出血的风险,包括颅内出血,例如在用组织纤溶酶原激活物(例如rt-PA或TNK-PA)、链激酶、葡萄球菌激酶、尿激酶或其衍生物进行的溶解纤维蛋白的疗法中。
16.权利要求14或15的用途,其中所述的药物组合物是包含活性成分的单一制剂。
17.权利要求14或15的用途,其中所述的药物组合物包含所述的活性成分与至少一种其它的药物活性化合物联合,所述的其它药物活性化合物选自抗血栓形成药、ACE抑制剂、血管紧张素II拮抗剂、Ca-拮抗剂和降脂药。
18.权利要求15的用途,其中所述的MMP-9依赖性疾病是动脉粥样硬化疾病,并且所述的药物组合物包含降脂药。
19.权利要求15的用途,其中所述的MMP-9依赖性疾病是关节炎病症或炎性反应,并且所述的药物组合物包含非甾体抗炎药(NSAID)。
20.权利要求19的用途,其中所述的NSAID选自美洛昔康、塞来考昔、罗非考昔及其药学上可接受的盐。
21.权利要求15的用途,其中所述的MMP-9依赖性疾病是自身免疫反应,并且所述的药物组合物包含免疫抑制剂。
22.权利要求15的用途,其中所述的MMP-9依赖性疾病是增殖性疾病,并且所述的药物组合物包括抗肿瘤治疗药。
23.权利要求15的用途,其中所述的MMP-9依赖性疾病是溶解血栓/溶解纤维蛋白的疗法所引起的大量出血的风险,并且所述药物组合物包含活化的凝血因子VII(VIIa)或其功能衍生物。
24.权利要求14或15的用途,其中所述的药物组合物包含口服日剂量单位为50-600mg的活性成分以及口服日剂量单位为10-30mg的ASA联合。
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Family Cites Families (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3031450A (en) | 1959-04-30 | 1962-04-24 | Thomae Gmbh Dr K | Substituted pyrimido-[5, 4-d]-pyrimidines |
DE2735830A1 (de) * | 1977-08-09 | 1979-03-01 | Thomae Gmbh Dr K | Antithrombotische arzneimittelkombination und verfahren zu ihrer herstellung |
DE3000979A1 (de) * | 1980-01-12 | 1981-07-23 | Dr. Karl Thomae Gmbh, 7950 Biberach | Neue dipyridamol-retardformen und verfahren zu ihrer herstellung |
DE3124090A1 (de) * | 1981-06-19 | 1983-01-05 | Dr. Karl Thomae Gmbh, 7950 Biberach | Neue orale dipyridamolformen |
DE3237575A1 (de) * | 1982-10-09 | 1984-04-12 | Dr. Karl Thomae Gmbh, 7950 Biberach | Neue orale mopidamolformen |
ATE50497T1 (de) * | 1984-07-21 | 1990-03-15 | Hoechst Ag | Kombinationspraeparat aus pyrimido-pyrimidinen und o-acetylsalicylsaeure bzw. deren pharmakologisch vertraeglichen salzen und dessen verwendung. |
DE3627423A1 (de) * | 1986-08-13 | 1988-02-18 | Thomae Gmbh Dr K | Arzneimittel enthaltend dipyridamol oder mopidamol und o-acetylsalicylsaeure bzw. deren physiologisch vertraegliche salze, verfahren zu ihrer herstellung und ihre verwendung zur bekaempfung der thrombusbildung |
US5242921A (en) * | 1988-04-27 | 1993-09-07 | Yale University | Compositions and methods for treating cutaneous hyperproliferative disorders |
DE4035961A1 (de) * | 1990-11-02 | 1992-05-07 | Thomae Gmbh Dr K | Cyclische iminoderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
US5270047A (en) * | 1991-11-21 | 1993-12-14 | Kauffman Raymond F | Local delivery of dipyridamole for the treatment of proliferative diseases |
US7060708B2 (en) * | 1999-03-10 | 2006-06-13 | New River Pharmaceuticals Inc. | Active agent delivery systems and methods for protecting and administering active agents |
EP1093814A1 (en) * | 1999-10-22 | 2001-04-25 | Boehringer Ingelheim Pharma KG | Use of dipyridamole or mopidamol in the manufacture of a medicament for the treatment and prevention of fibrin-dependent microcirculation disorders |
US20020049162A1 (en) * | 2000-01-27 | 2002-04-25 | Rodgers Kathleen E. | Methods for inhibiting smooth muscle cell proliferation |
WO2002034248A2 (en) | 2000-10-20 | 2002-05-02 | Boehringer Ingelheim Pharmaceuticals, Inc. | METHOD FOR INCREASING TISSUE PERFUSION BY CO-ADMINISTRATION OF AN AGENT THAT INCREASES cGMP SYNTHESIS AND AN AGENT THAT INHIBITS cGMP DEGRADATION |
US20020187187A1 (en) * | 2001-04-21 | 2002-12-12 | Toshimitsu Ohki | Fast disintegrating meloxicam tablet |
EP1250921A1 (en) | 2001-04-21 | 2002-10-23 | BOEHRINGER INGELHEIM INTERNATIONAL GmbH | Fast disintegrating meloxicam tablet |
US7651695B2 (en) * | 2001-05-18 | 2010-01-26 | Advanced Cardiovascular Systems, Inc. | Medicated stents for the treatment of vascular disease |
-
2004
- 2004-02-06 WO PCT/EP2004/001091 patent/WO2004069254A2/en active Application Filing
- 2004-02-06 JP JP2006501752A patent/JP2006516593A/ja active Pending
- 2004-02-06 EP EP04708732A patent/EP1594503A2/en not_active Withdrawn
- 2004-02-06 CN CNA2004800037161A patent/CN1747734A/zh active Pending
- 2004-02-06 CA CA002515266A patent/CA2515266A1/en not_active Abandoned
-
2005
- 2005-07-25 US US11/188,315 patent/US20050282830A1/en not_active Abandoned
Also Published As
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EP1594503A2 (en) | 2005-11-16 |
JP2006516593A (ja) | 2006-07-06 |
WO2004069254A3 (en) | 2004-11-04 |
CA2515266A1 (en) | 2004-08-19 |
US20050282830A1 (en) | 2005-12-22 |
WO2004069254A2 (en) | 2004-08-19 |
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