首页> 外国专利> PHARMACEUTICAL COMPOSITION COMPRISING A COMPOUND HAVING ANTI-XA ACTIVITY AND A PLATELET AGGREGATION ANTAGONISTS COMPOUND, USE THEREOF, A KIT COMPRISING SAID COMPOUNDS, METHOD OF TREATING OR PREVENTING DISEASES ASSOCIATED WITH THROMBOSIS RELATED DISORDER

PHARMACEUTICAL COMPOSITION COMPRISING A COMPOUND HAVING ANTI-XA ACTIVITY AND A PLATELET AGGREGATION ANTAGONISTS COMPOUND, USE THEREOF, A KIT COMPRISING SAID COMPOUNDS, METHOD OF TREATING OR PREVENTING DISEASES ASSOCIATED WITH THROMBOSIS RELATED DISORDER

机译:包含具有抗XA活性的化合物和血小板聚集拮抗剂的药物组合物,使用其中的一种组合物,所述化合物,治疗或预防与血栓相关疾病相关的疾病的方法

摘要

1. A pharmaceutical composition comprising a pharnlaceutically acceptable carrier and pharmaceutically effective amounts of a compound having anti-Xa activity and a platelet aggregation antagonist compound. 2. The pharmaceutical composition according to claim 1 wherein the compound having anti-Xa activity is a low molecular weight heparin. 3. The pharmaceutical composition according to claim 1 wherein the low molecular weight heparin is selected from the group consisting of enoxaparin, nardroparin, dalteparin, certroparin, parnaparin, reviparin, ardeparin/RD heparin/ RDH or tinzaparin. 4. The pharmaceutical composition according to claim 1 wherein the low molecular weight heparin is enoxaparin. 5. The pharmaceutical composition according to claim 1 wherein the compound having anti-Xa activity is a heparinoid compound. 6. The pharmaceutical composition according to claim 1 wherein the heparinoid compound is danaparoid. 7. The pharmaceutical composition according to claim 1 wherein the platelet aggregation antagonist compound is abciximab, N-[N- [N-(4-(piperidin-4-yl)butanoyl)-N-ethylglycyl] aspartyl]-L--cyclohexyl alanine, N-[N-[N-(4-(piperidin-4-yl)butanoyl)-N-ethylglycyl] aspartyl]-L--cyclohexyl alanine amide or N-(n-butylsulfonyl)-4-(piperidin-4-ylbutyloxy)-L-phenylalanine. 8. The pharmaceutical composition according to claim 7 wherein the platelet aggregation antagonist compound antagonist is abciximab. 9. The pharmaceutical composition according to claim 7 wherein the platelet aggregation antagonist compound is N-[N-[N-(4-(piperidin-4-yl)butanoyl)-N-ethylglycyl] aspartyl]-L--cyclohexyl alanine. 10. The pharmaceutical composition according to claim 7 wherein the platelet aggregation antagonist compound is N-[N-[N-(4-(piperidin-4-yl)butanoyl)-N-ethylglycyl] aspartyl]-L--cyclohexyl alanine amide. 11. The pharmaceutical composition according to claim 7 wherein the platelet aggregation antagonist compound is N-(n-butylsulfonyl)-4-(piperidin-4-ylbutyloxy)-L-phenylalanine. 12. A method of treating or preventing a physiological condition associated with a thrombosis related ischemic disorder in a patient comprising administering to said patient pharmaceutically effective amounts of a compound having anti-Xa activity and a platelet aggregation antagonist compound. 13. The method of claim 12 wherein the physiological condition is selected from stroke, atherosclerosis, angiogenesis, thrombosis, a thromboembolic condition, disseminated intravascular coagulation, peripheral arterial occlusive disease, hemodialysis, an extra-corporeal circulation requirement associated with a surgical procedure, tissue damage caused by phospholipases A2, an acute coronary syndrome, or a thromboembolic syndrome associated with cancer, sepsis or obstetrical complications. 14. The method of claim 13 wherein the physiological condition is the acute coronary syndrome. 15. The method of claim 14 wherein the acute coronary syndrome is unstable angina or myocardial infarction. 16. The method of claim 12 wherein the treating or preventing occurs in the course of coronary artery bypass surgery or percutaneous transluminal coronary angioplasty. 17. The method of claim 12 wherein the treating or preventing occurs in the course of percutaneous transluminal coronary angioplasty. 18. The use of pharmaceutically effective amounts of a compound having anti-Xa activity and a platelet aggregation antagonist compound in the preparation of a medicament for treating or preventing a physiological condition associated with thrombosis related ischemic disorder. 19. The use according to claim 18, wherein the physiological condition is the acute coronary syndrome. 20. The use according to claim 19 wherein the acute coronary syndrome is unstable angina or myocardial infarction. 21. The use according to claim 18 wherein the treating or preventing occurs in the course of coronary artery bypass surgery or percutaneous transluminal coronary angioplasty. 22. The use according to claim 18 wherein the treating or preventing occurs in the course of percutaneous transluminal coronary angioplasty. 23. A kit for treating or preventing a physiological condition associated with thrombosis related ischemic disorder, said kit comprising a plurality of separate containers, wherein at least one of said containers contains a compound having anti-Xa activity and at least another of said containers contains a platelet aggregation antagonist compound, and said containers optionally contain a pharmaceutical carrier. 24. A kit according to claim 23 wherein of said containers at least one of said containers should contain the compound having anti-Xa activity without the presence of the platelet aggregation antagonist compound, and at least another of said containers should contain the platelet aggregation antagonist compound without the presence of the compound having anti-Xa activity. 25. A product containing a compound having anti-Xa activity and a platelet aggregation antagonist compound as a combined preparation for simultaneous, separate or sequential use for treating or preventing a physiological condition associated with thrombosis related ischemic disorder. 26. A use of a compound having anti-Xa activity and a platelet aggregation antagonist compound together in therapy for treating or preventing a physiological condition associated with thrombosis related ischemic disorder.
机译:1.一种药物组合物,其包含药学上可接受的载体和药学有效量的具有抗Xa活性的化合物和血小板聚集拮抗剂化合物。 2.根据权利要求1所述的药物组合物,其中所述具有抗Xa活性的化合物是低分子量肝素。 3.根据权利要求1所述的药物组合物,其中所述低分子量肝素选自依诺肝素,纳达帕林,达肝素,certroparin,parnaparin,reviparin,ardeparin / RD肝素/ RDH或替扎肝素。 4.根据权利要求1所述的药物组合物,其中所述低分子量肝素为依诺肝素。 5.根据权利要求1的药物组合物,其中具有抗Xa活性的化合物是类肝素化合物。 6.根据权利要求1所述的药物组合物,其中所述类肝素化合物是达那非。 7.根据权利要求1的药物组合物,其中所述血小板聚集拮抗剂化合物是阿昔单抗,N- [N- [N-(4-(哌啶丁-4-基)丁酰基)-N-乙基甘氨酰]天冬氨酰] -L-环己基丙氨酸,N- [N- [N-(4-(哌啶-4-基)丁酰基] -N-乙基甘氨酰]天冬氨酰] -L-环己基丙氨酸酰胺或N-(正丁基磺酰基)-4-(哌啶- 4-基丁氧基)-L-苯丙氨酸。 8.根据权利要求7的药物组合物,其中所述血小板聚集拮抗剂化合物拮抗剂是阿昔单抗。 9.根据权利要求7所述的药物组合物,其中所述血小板聚集拮抗剂化合物是N- [N- [N-(4-(哌啶丁-4-基)丁酰基)-N-乙基甘氨酰基]天冬氨酰] -L-环己基丙氨酸。 10.根据权利要求7的药物组合物,其中所述血小板聚集拮抗剂化合物是N- [N- [N-(4-(哌啶丁-4-基)丁酰基)-N-乙基甘氨酰基]天冬氨酰] -L-环己基丙氨酸酰胺。 11.根据权利要求7的药物组合物,其中所述血小板聚集拮抗剂化合物是N-(正丁基磺酰基)-4-(哌啶-4-基丁氧基)-L-苯丙氨酸。 12.一种在患者中治疗或预防与血栓形成相关的缺血性疾病有关的生理状况的方法,其包括向所述患者施用药学有效量的具有抗Xa活性的化合物和血小板聚集拮抗剂化合物。 13.根据权利要求12所述的方法,其中所述生理状况选自中风,动脉粥样硬化,血管生成,血栓形成,血栓栓塞状况,弥散性血管内凝血,外周动脉闭塞性疾病,血液透析,与外科手术相关的体外循环需求,组织由磷脂酶A2,急性冠脉综合征或与癌症,败血症或产科并发症相关的血栓栓塞综合征引起的损伤。 14.根据权利要求13所述的方法,其中所述生理状况是急性冠状动脉综合征。 15.如权利要求14所述的方法,其中所述急性冠状动脉综合征是不稳定型心绞痛或心肌梗塞。 16.根据权利要求12所述的方法,其中所述治疗或预防在冠状动脉搭桥手术或经皮腔内冠状动脉血管成形术的过程中发生。 17.根据权利要求12所述的方法,其中所述治疗或预防在经皮腔内冠状动脉血管成形术的过程中发生。 18.药学有效量的具有抗Xa活性的化合物和血小板聚集拮抗剂化合物在制备用于治疗或预防与血栓形成相关的缺血性疾病有关的生理状况的药物中的用途。 19.根据权利要求18所述的用途,其中所述生理状况是急性冠状动脉综合征。 20.根据权利要求19所述的用途,其中所述急性冠状动脉综合征是不稳定型心绞痛或心肌梗塞。 21.根据权利要求18所述的用途,其中所述治疗或预防发生在冠状动脉搭桥手术或经皮腔内冠状动脉血管成形术的过程中。 22.根据权利要求18所述的用途,其中所述治疗或预防在经皮腔内冠状动脉血管成形术的过程中发生。 23.一种用于治疗或预防与血栓形成相关的缺血性疾病有关的生理状况的试剂盒,所述试剂盒包括多个单独的容器,其中至少一个所述容器包含具有抗Xa活性的化合物,并且至少另一个所述容器包含血小板聚集拮抗剂化合物,并且所述容器任选地包含药物载体。 24.根据权利要求23的试剂盒,其中在所述容器中,至少一个所述容器应装有不具有血小板凝集拮抗剂化合物的具有抗Xa活性的化合物。,并且至少另一个所述容器应容纳血小板聚集拮抗剂化合物,而该化合物不存在具有抗Xa活性的化合物。 25.一种产品,其包含具有抗Xa活性的化合物和血小板凝集拮抗剂化合物作为组合制剂,用于同时,分别或相继用于治疗或预防与血栓形成相关的缺血性疾病有关的生理状况。 26.具有抗Xa活性的化合物和血小板聚集拮抗剂化合物一起在治疗中用于治疗或预防与血栓形成相关的缺血性疾病有关的生理状况的用途。

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