DE69715611T2 - Verwendung eines rapamycinderivates zur behandlung von gefäss erkrankungen und xenotransplantationen - Google Patents
Verwendung eines rapamycinderivates zur behandlung von gefäss erkrankungen und xenotransplantationenInfo
- Publication number
- DE69715611T2 DE69715611T2 DE69715611T DE69715611T DE69715611T2 DE 69715611 T2 DE69715611 T2 DE 69715611T2 DE 69715611 T DE69715611 T DE 69715611T DE 69715611 T DE69715611 T DE 69715611T DE 69715611 T2 DE69715611 T2 DE 69715611T2
- Authority
- DE
- Germany
- Prior art keywords
- compound
- pharmaceutical composition
- monoclonal antibodies
- rejection
- hydroxy
- 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.)
- Revoked
Links
- 208000019553 vascular disease Diseases 0.000 title claims description 6
- 230000035755 proliferation Effects 0.000 claims abstract description 6
- 208000037803 restenosis Diseases 0.000 claims abstract description 6
- 230000008719 thickening Effects 0.000 claims abstract description 6
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 claims abstract description 5
- 229930105110 Cyclosporin A Natural products 0.000 claims abstract description 5
- 108010036949 Cyclosporine Proteins 0.000 claims abstract description 5
- 206010053648 Vascular occlusion Diseases 0.000 claims abstract description 5
- 229960001265 ciclosporin Drugs 0.000 claims abstract description 5
- 208000021331 vascular occlusion disease Diseases 0.000 claims abstract description 5
- 239000003446 ligand Substances 0.000 claims abstract description 4
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 claims abstract description 3
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 claims abstract description 3
- 208000024248 Vascular System injury Diseases 0.000 claims abstract description 3
- 208000012339 Vascular injury Diseases 0.000 claims abstract description 3
- 210000000265 leukocyte Anatomy 0.000 claims abstract description 3
- 229960000485 methotrexate Drugs 0.000 claims abstract description 3
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 claims abstract description 3
- 229960004866 mycophenolate mofetil Drugs 0.000 claims abstract description 3
- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 claims abstract description 3
- 229960000951 mycophenolic acid Drugs 0.000 claims abstract description 3
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 claims abstract description 3
- 229960002170 azathioprine Drugs 0.000 claims abstract 2
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 claims abstract 2
- 230000001684 chronic effect Effects 0.000 claims description 18
- 210000000056 organ Anatomy 0.000 claims description 15
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 230000002265 prevention Effects 0.000 claims description 5
- 101001057504 Homo sapiens Interferon-stimulated gene 20 kDa protein Proteins 0.000 claims description 3
- 101001055144 Homo sapiens Interleukin-2 receptor subunit alpha Proteins 0.000 claims description 3
- 101001063392 Homo sapiens Lymphocyte function-associated antigen 3 Proteins 0.000 claims description 3
- 101000738771 Homo sapiens Receptor-type tyrosine-protein phosphatase C Proteins 0.000 claims description 3
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 claims description 3
- 102100026878 Interleukin-2 receptor subunit alpha Human genes 0.000 claims description 3
- 102100030984 Lymphocyte function-associated antigen 3 Human genes 0.000 claims description 3
- 102100037422 Receptor-type tyrosine-protein phosphatase C Human genes 0.000 claims description 3
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 claims description 3
- 230000001154 acute effect Effects 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- IDINUJSAMVOPCM-UHFFFAOYSA-N 15-Deoxyspergualin Natural products NCCCNCCCCNC(=O)C(O)NC(=O)CCCCCCN=C(N)N IDINUJSAMVOPCM-UHFFFAOYSA-N 0.000 claims description 2
- BLUYEPLOXLPVCJ-INIZCTEOSA-N n-[(1s)-2-[4-(3-aminopropylamino)butylamino]-1-hydroxyethyl]-7-(diaminomethylideneamino)heptanamide Chemical compound NCCCNCCCCNC[C@H](O)NC(=O)CCCCCCNC(N)=N BLUYEPLOXLPVCJ-INIZCTEOSA-N 0.000 claims description 2
- 108020003175 receptors Proteins 0.000 claims description 2
- 201000010099 disease Diseases 0.000 abstract description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 4
- 229960002930 sirolimus Drugs 0.000 abstract description 3
- 229960001967 tacrolimus Drugs 0.000 abstract description 2
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 abstract description 2
- 229940126062 Compound A Drugs 0.000 description 36
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 36
- 241001465754 Metazoa Species 0.000 description 20
- 238000002054 transplantation Methods 0.000 description 16
- 241000700159 Rattus Species 0.000 description 14
- 238000002474 experimental method Methods 0.000 description 10
- 238000000034 method Methods 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 230000006378 damage Effects 0.000 description 8
- 210000003734 kidney Anatomy 0.000 description 8
- 210000000709 aorta Anatomy 0.000 description 7
- 210000001715 carotid artery Anatomy 0.000 description 7
- 208000027418 Wounds and injury Diseases 0.000 description 6
- 230000001506 immunosuppresive effect Effects 0.000 description 6
- 208000014674 injury Diseases 0.000 description 6
- 230000010412 perfusion Effects 0.000 description 6
- 239000000902 placebo Substances 0.000 description 6
- 229940068196 placebo Drugs 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical class CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 210000002216 heart Anatomy 0.000 description 5
- 210000004185 liver Anatomy 0.000 description 5
- 238000002595 magnetic resonance imaging Methods 0.000 description 5
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 5
- 210000001541 thymus gland Anatomy 0.000 description 5
- 206010003210 Arteriosclerosis Diseases 0.000 description 4
- 238000002399 angioplasty Methods 0.000 description 4
- 208000011775 arteriosclerosis disease Diseases 0.000 description 4
- 230000002519 immonomodulatory effect Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 239000004530 micro-emulsion Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 210000000952 spleen Anatomy 0.000 description 4
- 238000002689 xenotransplantation Methods 0.000 description 4
- 241000699800 Cricetinae Species 0.000 description 3
- 208000034827 Neointima Diseases 0.000 description 3
- 206010052779 Transplant rejections Diseases 0.000 description 3
- 238000011888 autopsy Methods 0.000 description 3
- 210000004204 blood vessel Anatomy 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 210000004072 lung Anatomy 0.000 description 3
- 238000013508 migration Methods 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical class C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 3
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 2
- 208000032843 Hemorrhage Diseases 0.000 description 2
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 2
- 208000032594 Vascular Remodeling Diseases 0.000 description 2
- 210000001015 abdomen Anatomy 0.000 description 2
- 239000008186 active pharmaceutical agent Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 229930182912 cyclosporin Natural products 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 229940088679 drug related substance Drugs 0.000 description 2
- 210000003743 erythrocyte Anatomy 0.000 description 2
- 230000008105 immune reaction Effects 0.000 description 2
- 230000008595 infiltration Effects 0.000 description 2
- 238000001764 infiltration Methods 0.000 description 2
- 230000004941 influx Effects 0.000 description 2
- 230000002427 irreversible effect Effects 0.000 description 2
- 238000011694 lewis rat Methods 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 230000005012 migration Effects 0.000 description 2
- 210000005087 mononuclear cell Anatomy 0.000 description 2
- 230000008692 neointimal formation Effects 0.000 description 2
- 210000000496 pancreas Anatomy 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 2
- 210000001625 seminal vesicle Anatomy 0.000 description 2
- 230000004083 survival effect Effects 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 210000001550 testis Anatomy 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 201000010653 vesiculitis Diseases 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- ZMKGDQSIRSGUDJ-VSROPUKISA-N (3s,6s,9s,12r,15s,18s,21s,24s,30s,33s)-33-[(e,1r,2r)-1-hydroxy-2-methylhex-4-enyl]-1,4,7,10,12,15,19,25,28-nonamethyl-6,9,18,24-tetrakis(2-methylpropyl)-3,21-di(propan-2-yl)-30-propyl-1,4,7,10,13,16,19,22,25,28,31-undecazacyclotritriacontane-2,5,8,11,14,1 Chemical compound CCC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O ZMKGDQSIRSGUDJ-VSROPUKISA-N 0.000 description 1
- NALREUIWICQLPS-UHFFFAOYSA-N 7-imino-n,n-dimethylphenothiazin-3-amine;hydrochloride Chemical compound [Cl-].C1=C(N)C=C2SC3=CC(=[N+](C)C)C=CC3=NC2=C1 NALREUIWICQLPS-UHFFFAOYSA-N 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 102000000989 Complement System Proteins Human genes 0.000 description 1
- 108010069112 Complement System Proteins Proteins 0.000 description 1
- CMSMOCZEIVJLDB-UHFFFAOYSA-N Cyclophosphamide Chemical compound ClCCN(CCCl)P1(=O)NCCCO1 CMSMOCZEIVJLDB-UHFFFAOYSA-N 0.000 description 1
- 108010036941 Cyclosporins Proteins 0.000 description 1
- 102100039498 Cytotoxic T-lymphocyte protein 4 Human genes 0.000 description 1
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 description 1
- 206010015866 Extravasation Diseases 0.000 description 1
- 101000889276 Homo sapiens Cytotoxic T-lymphocyte protein 4 Proteins 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 241000699673 Mesocricetus auratus Species 0.000 description 1
- HZQDCMWJEBCWBR-UUOKFMHZSA-N Mizoribine Chemical compound OC1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 HZQDCMWJEBCWBR-UUOKFMHZSA-N 0.000 description 1
- ZMKGDQSIRSGUDJ-UHFFFAOYSA-N NVa2 cyclosporine Natural products CCCC1NC(=O)C(C(O)C(C)CC=CC)N(C)C(=O)C(C(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(CC(C)C)N(C)C(=O)C(C)NC(=O)C(C)NC(=O)C(CC(C)C)N(C)C(=O)C(C(C)C)NC(=O)C(CC(C)C)N(C)C(=O)CN(C)C1=O ZMKGDQSIRSGUDJ-UHFFFAOYSA-N 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 229920002690 Polyoxyl 40 HydrogenatedCastorOil Polymers 0.000 description 1
- 241000187391 Streptomyces hygroscopicus Species 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 108010006877 Tacrolimus Binding Protein 1A Proteins 0.000 description 1
- 108010027179 Tacrolimus Binding Proteins Proteins 0.000 description 1
- 102000018679 Tacrolimus Binding Proteins Human genes 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 206010060872 Transplant failure Diseases 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 238000011316 allogeneic transplantation Methods 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000003872 anastomosis Effects 0.000 description 1
- 210000002376 aorta thoracic Anatomy 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000000740 bleeding effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 229950010231 brequinar Drugs 0.000 description 1
- PHEZJEYUWHETKO-UHFFFAOYSA-N brequinar Chemical compound N1=C2C=CC(F)=CC2=C(C(O)=O)C(C)=C1C(C=C1)=CC=C1C1=CC=CC=C1F PHEZJEYUWHETKO-UHFFFAOYSA-N 0.000 description 1
- 239000007978 cacodylate buffer Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 210000001168 carotid artery common Anatomy 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 238000001218 confocal laser scanning microscopy Methods 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 229960004397 cyclophosphamide Drugs 0.000 description 1
- 108010019249 cyclosporin G Proteins 0.000 description 1
- 230000001461 cytolytic effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- OGGXGZAMXPVRFZ-UHFFFAOYSA-M dimethylarsinate Chemical compound C[As](C)([O-])=O OGGXGZAMXPVRFZ-UHFFFAOYSA-M 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000003511 endothelial effect Effects 0.000 description 1
- 230000036251 extravasation Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 210000003714 granulocyte Anatomy 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 210000003709 heart valve Anatomy 0.000 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000003463 hyperproliferative effect Effects 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 229940124622 immune-modulator drug Drugs 0.000 description 1
- 229940088592 immunologic factor Drugs 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940124589 immunosuppressive drug Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 210000004153 islets of langerhan Anatomy 0.000 description 1
- 229960000681 leflunomide Drugs 0.000 description 1
- VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 1
- 210000005240 left ventricle Anatomy 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 229950000844 mizoribine Drugs 0.000 description 1
- 210000000107 myocyte Anatomy 0.000 description 1
- 238000013059 nephrectomy Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000002559 palpation Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 210000001147 pulmonary artery Anatomy 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 210000002254 renal artery Anatomy 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 210000005241 right ventricle Anatomy 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 125000002345 steroid group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 231100000041 toxicology testing Toxicity 0.000 description 1
- 231100000216 vascular lesion Toxicity 0.000 description 1
- 238000007631 vascular surgery Methods 0.000 description 1
- 210000001631 vena cava inferior Anatomy 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
- A61K31/4353—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 ortho- or peri-condensed with heterocyclic ring systems
- A61K31/436—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 ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Epidemiology (AREA)
- Immunology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Vascular Medicine (AREA)
- Transplantation (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Saccharide Compounds (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9606452.2A GB9606452D0 (en) | 1996-03-27 | 1996-03-27 | Organic compounds |
| PCT/EP1997/001548 WO1997035575A1 (en) | 1996-03-27 | 1997-03-26 | Use of rapamycin derivatives in vasculopathies and xenotransplantation |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69715611D1 DE69715611D1 (de) | 2002-10-24 |
| DE69715611T2 true DE69715611T2 (de) | 2003-05-22 |
Family
ID=10791127
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69715611T Revoked DE69715611T2 (de) | 1996-03-27 | 1997-03-26 | Verwendung eines rapamycinderivates zur behandlung von gefäss erkrankungen und xenotransplantationen |
Country Status (29)
| Country | Link |
|---|---|
| US (5) | US6384046B1 (enExample) |
| EP (3) | EP0893996B1 (enExample) |
| JP (2) | JP2000507226A (enExample) |
| KR (2) | KR100836971B1 (enExample) |
| CN (1) | CN1124135C (enExample) |
| AT (1) | ATE224194T1 (enExample) |
| AU (1) | AU716514B2 (enExample) |
| BR (1) | BR9708358A (enExample) |
| CA (1) | CA2247275C (enExample) |
| CY (1) | CY2404B1 (enExample) |
| CZ (1) | CZ292483B6 (enExample) |
| DE (1) | DE69715611T2 (enExample) |
| DK (2) | DK0893996T3 (enExample) |
| ES (2) | ES2421455T3 (enExample) |
| GB (1) | GB9606452D0 (enExample) |
| HU (1) | HU226422B1 (enExample) |
| ID (1) | ID17195A (enExample) |
| IL (1) | IL125812A (enExample) |
| MY (1) | MY117798A (enExample) |
| NO (1) | NO316667B1 (enExample) |
| NZ (1) | NZ331463A (enExample) |
| PL (1) | PL187732B1 (enExample) |
| PT (2) | PT893996E (enExample) |
| RU (1) | RU2214247C2 (enExample) |
| SI (1) | SI2008657T1 (enExample) |
| SK (1) | SK284343B6 (enExample) |
| TR (1) | TR199801919T2 (enExample) |
| WO (1) | WO1997035575A1 (enExample) |
| ZA (1) | ZA972719B (enExample) |
Families Citing this family (73)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9606452D0 (en) * | 1996-03-27 | 1996-06-05 | Sandoz Ltd | Organic compounds |
| US6239124B1 (en) | 1996-07-30 | 2001-05-29 | Novartis Ag | Pharmaceutical compositions for the treatment of transplant rejection or autoimmune or inflammatory conditions comprising cyclosporin A and 40-0-(2-hydroxyethyl)-rapamycin |
| US6890546B2 (en) | 1998-09-24 | 2005-05-10 | Abbott Laboratories | Medical devices containing rapamycin analogs |
| US20030129215A1 (en) * | 1998-09-24 | 2003-07-10 | T-Ram, Inc. | Medical devices containing rapamycin analogs |
| ATE474590T1 (de) * | 1999-05-10 | 2010-08-15 | Paolo Brenner | Kombination von immunsuppressiven substanzen zur behandlung oder vorbeugung von transplantat abstossungen |
| US6790228B2 (en) | 1999-12-23 | 2004-09-14 | Advanced Cardiovascular Systems, Inc. | Coating for implantable devices and a method of forming the same |
| US20070032853A1 (en) † | 2002-03-27 | 2007-02-08 | Hossainy Syed F | 40-O-(2-hydroxy)ethyl-rapamycin coated stent |
| US7807211B2 (en) | 1999-09-03 | 2010-10-05 | Advanced Cardiovascular Systems, Inc. | Thermal treatment of an implantable medical device |
| EP1263484B1 (en) | 2000-03-15 | 2007-05-16 | OrbusNeich Medical, Inc. | Coating which promotes endothelial cell adherence |
| US8088060B2 (en) | 2000-03-15 | 2012-01-03 | Orbusneich Medical, Inc. | Progenitor endothelial cell capturing with a drug eluting implantable medical device |
| US20030229393A1 (en) * | 2001-03-15 | 2003-12-11 | Kutryk Michael J. B. | Medical device with coating that promotes cell adherence and differentiation |
| US9522217B2 (en) | 2000-03-15 | 2016-12-20 | Orbusneich Medical, Inc. | Medical device with coating for capturing genetically-altered cells and methods for using same |
| US20070055367A1 (en) * | 2000-03-15 | 2007-03-08 | Orbus Medical Technologies, Inc. | Medical device with coating that promotes endothelial cell adherence and differentiation |
| US20040039441A1 (en) * | 2002-05-20 | 2004-02-26 | Rowland Stephen Maxwell | Drug eluting implantable medical device |
| US20070141107A1 (en) * | 2000-03-15 | 2007-06-21 | Orbusneich Medical, Inc. | Progenitor Endothelial Cell Capturing with a Drug Eluting Implantable Medical Device |
| US8460367B2 (en) * | 2000-03-15 | 2013-06-11 | Orbusneich Medical, Inc. | Progenitor endothelial cell capturing with a drug eluting implantable medical device |
| US20050002986A1 (en) * | 2000-05-12 | 2005-01-06 | Robert Falotico | Drug/drug delivery systems for the prevention and treatment of vascular disease |
| US8236048B2 (en) | 2000-05-12 | 2012-08-07 | Cordis Corporation | Drug/drug delivery systems for the prevention and treatment of vascular disease |
| US7300662B2 (en) | 2000-05-12 | 2007-11-27 | Cordis Corporation | Drug/drug delivery systems for the prevention and treatment of vascular disease |
| US6670355B2 (en) * | 2000-06-16 | 2003-12-30 | Wyeth | Method of treating cardiovascular disease |
| US20020013335A1 (en) * | 2000-06-16 | 2002-01-31 | American Home Products Corporation | Method of treating cardiovascular disease |
| EP1709974A3 (en) * | 2000-06-16 | 2006-12-06 | Wyeth | Method of treating cardiovascular disease using rapamycin |
| EP1322235B2 (en) | 2000-09-29 | 2010-08-11 | Cordis Corporation | Coated medical devices |
| EP3342411B1 (en) | 2001-02-19 | 2019-08-21 | Novartis Pharma AG | Rapamycin derivative for treating pancreas cancer |
| US8741378B1 (en) | 2001-06-27 | 2014-06-03 | Advanced Cardiovascular Systems, Inc. | Methods of coating an implantable device |
| US7682387B2 (en) * | 2002-04-24 | 2010-03-23 | Biosensors International Group, Ltd. | Drug-delivery endovascular stent and method for treating restenosis |
| US6939376B2 (en) * | 2001-11-05 | 2005-09-06 | Sun Biomedical, Ltd. | Drug-delivery endovascular stent and method for treating restenosis |
| AU2003206571A1 (en) * | 2002-02-22 | 2003-09-09 | Prophy Med Ab | Use of an inhibitor or antagonist against tissue factor |
| US20040024450A1 (en) * | 2002-04-24 | 2004-02-05 | Sun Biomedical, Ltd. | Drug-delivery endovascular stent and method for treating restenosis |
| US8109987B2 (en) | 2003-04-14 | 2012-02-07 | Tryton Medical, Inc. | Method of treating a lumenal bifurcation |
| US7279174B2 (en) | 2003-05-08 | 2007-10-09 | Advanced Cardiovascular Systems, Inc. | Stent coatings comprising hydrophilic additives |
| US20050118344A1 (en) | 2003-12-01 | 2005-06-02 | Pacetti Stephen D. | Temperature controlled crimping |
| US7220755B2 (en) * | 2003-11-12 | 2007-05-22 | Biosensors International Group, Ltd. | 42-O-alkoxyalkyl rapamycin derivatives and compositions comprising same |
| US9114198B2 (en) | 2003-11-19 | 2015-08-25 | Advanced Cardiovascular Systems, Inc. | Biologically beneficial coatings for implantable devices containing fluorinated polymers and methods for fabricating the same |
| WO2005107817A2 (en) * | 2004-04-30 | 2005-11-17 | Orbus Medical Technologies, Inc. | Medical device with coating for capturing genetically-altered cells and methods of using same |
| US20110104186A1 (en) | 2004-06-24 | 2011-05-05 | Nicholas Valiante | Small molecule immunopotentiators and assays for their detection |
| US8709469B2 (en) | 2004-06-30 | 2014-04-29 | Abbott Cardiovascular Systems Inc. | Anti-proliferative and anti-inflammatory agent combination for treatment of vascular disorders with an implantable medical device |
| US7901451B2 (en) | 2004-09-24 | 2011-03-08 | Biosensors International Group, Ltd. | Drug-delivery endovascular stent and method for treating restenosis |
| EP1838288A4 (en) * | 2004-12-20 | 2010-08-04 | Ariad Pharma Inc | THERAPEUTIC MATERIALS AND METHODS |
| AU2006315512B2 (en) | 2005-11-14 | 2012-11-01 | Ariad Pharmaceuticals, Inc. | Administration of an mTOR inhibitor to treat patients with cancer |
| US20080317814A1 (en) * | 2005-11-17 | 2008-12-25 | Access Plus Co., Ltd. | Tube for Connecting Marteriovenous and Interposition for Medical Operation |
| US20070173923A1 (en) * | 2006-01-20 | 2007-07-26 | Savage Douglas R | Drug reservoir stent |
| EP2702993B1 (en) | 2006-09-13 | 2017-12-06 | Elixir Medical Corporation | Macrocyclic lactone compounds and methods for their use |
| US8067055B2 (en) * | 2006-10-20 | 2011-11-29 | Biosensors International Group, Ltd. | Drug-delivery endovascular stent and method of use |
| US20080097591A1 (en) | 2006-10-20 | 2008-04-24 | Biosensors International Group | Drug-delivery endovascular stent and method of use |
| US20080103584A1 (en) * | 2006-10-25 | 2008-05-01 | Biosensors International Group | Temporal Intraluminal Stent, Methods of Making and Using |
| KR100930167B1 (ko) * | 2007-09-19 | 2009-12-07 | 삼성전기주식회사 | 초광각 광학계 |
| US8661630B2 (en) | 2008-05-21 | 2014-03-04 | Abbott Cardiovascular Systems Inc. | Coating comprising an amorphous primer layer and a semi-crystalline reservoir layer |
| JP5693228B2 (ja) | 2007-11-14 | 2015-04-01 | バイオセンサーズ インターナショナル グループ、リミテッド | 自動被覆装置および方法 |
| EP2245165A4 (en) * | 2008-01-11 | 2011-06-01 | Massachusetts Eye & Ear Infirm | TRANSGENIC CONDITIONAL STOP DIMERICABLE CASPASE ANIMALS |
| CN102231969A (zh) * | 2008-10-03 | 2011-11-02 | 万能医药公司 | 大环内酯化合物及其使用方法 |
| US8366763B2 (en) | 2009-07-02 | 2013-02-05 | Tryton Medical, Inc. | Ostium support for treating vascular bifurcations |
| US8685433B2 (en) | 2010-03-31 | 2014-04-01 | Abbott Cardiovascular Systems Inc. | Absorbable coating for implantable device |
| UA104738C2 (ru) | 2011-05-18 | 2014-03-11 | Олег Миколайович Лазаренко | Композиция для повышения биосовместимости имплантатов и клеток для трансплантации с организмом реципиента и способ ее приготовления |
| CN102268015B (zh) * | 2011-08-30 | 2013-08-28 | 成都摩尔生物医药有限公司 | 一种依维莫司的合成方法 |
| US10682415B2 (en) | 2013-07-22 | 2020-06-16 | Wisconsin Alumni Research Foundation | Thermogel formulation for combination drug delivery |
| KR101723265B1 (ko) | 2013-08-16 | 2017-04-04 | 가톨릭대학교 산학협력단 | mTOR/STAT3 신호억제제 처리된 면역조절능을 갖는 간엽줄기세포 및 이를 포함하는 면역질환의 예방 또는 치료용 세포치료제 조성물 |
| JP6749239B2 (ja) | 2013-09-24 | 2020-09-02 | ガイナー ライフ サイエンシズ，インク． | 細胞インプラントのガス処理用システム |
| KR102256576B1 (ko) | 2013-10-08 | 2021-05-27 | 에이아이 테라퓨틱스, 인코포레이티드 | 림프관평활근종증의 치료를 위한 라파마이신 |
| US10307371B2 (en) | 2014-02-11 | 2019-06-04 | AI Therapeutics, Inc. | Rapamycin for the treatment of lymphangioleiomyomatosis |
| RU2016136348A (ru) | 2014-02-11 | 2018-03-16 | Лэм Терапьютикс, Инк. | Рапамицин для лечения лимфангиолейомиоматоза |
| PL3125875T3 (pl) | 2014-04-04 | 2023-11-20 | AI Therapeutics, Inc. | Nadający się do inhalacji preparat rapamycyny do leczenia stanów związanych z wiekiem |
| AU2015330905B2 (en) | 2014-10-07 | 2021-02-25 | AI Therapeutics, Inc. | An inhalable rapamycin formulation for the treatment of pulmonary hypertension |
| MA40910A (fr) | 2014-11-07 | 2017-09-12 | Civitas Therapeutics Inc | Poudres de rapamycine pour administration pulmonaire |
| WO2016130645A1 (en) | 2015-02-10 | 2016-08-18 | Lam Therapeutics, Inc. | Rapamycin for the treatment of lymphangioleiomyomatosis |
| WO2018031789A1 (en) | 2016-08-10 | 2018-02-15 | The Board Of Regents Of The University Of Texas System | Topical rapamycin therapy |
| WO2018050916A1 (en) | 2016-09-19 | 2018-03-22 | Biotronik Ag | Polymer-free drug eluting vascular stents |
| EP3541449B1 (en) | 2016-11-15 | 2021-11-10 | Giner Life Sciences, Inc. | Percutaneous gas diffusion device suitable for use with a subcutaneous implant |
| WO2018114992A1 (en) | 2016-12-22 | 2018-06-28 | Biotronik Ag | Drug releasing coatings for medical devices and methods of making same |
| US11642501B2 (en) | 2017-05-04 | 2023-05-09 | Giner, Inc. | Robust, implantable gas delivery device and methods, systems and devices including same |
| AR112834A1 (es) | 2017-09-26 | 2019-12-18 | Novartis Ag | Derivados de rapamicina |
| LT3898637T (lt) | 2018-12-18 | 2025-03-10 | Novartis Ag | Rapamicino dariniai |
| AU2020226527A1 (en) | 2019-02-20 | 2021-10-14 | AI Therapeutics, Inc. | Topical rapamycin formulations and their use in treating facial angiofibromas and other skin disorders |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5639724A (en) * | 1984-07-24 | 1997-06-17 | Sandoz Ltd. | Cyclosporin galenic forms |
| US5364612A (en) * | 1991-05-06 | 1994-11-15 | Immunomedics, Inc. | Detection of cardiovascular lesions |
| ZA924953B (en) * | 1991-07-25 | 1993-04-28 | Univ Louisville Res Found | Method of treating ocular inflammation |
| US5516781A (en) * | 1992-01-09 | 1996-05-14 | American Home Products Corporation | Method of treating restenosis with rapamycin |
| CA2086642C (en) * | 1992-01-09 | 2004-06-15 | Randall E. Morris | Method of treating hyperproliferative vascular disease |
| CA2094858C (en) * | 1992-04-28 | 2004-06-15 | Robert D. Mitchell | Method of treating hyperproliferative vascular disease |
| US5747034A (en) * | 1992-07-09 | 1998-05-05 | Chiron Corporation | Methods and materials for the induction of T cell anergy |
| US5283257A (en) * | 1992-07-10 | 1994-02-01 | The Board Of Trustees Of The Leland Stanford Junior University | Method of treating hyperproliferative vascular disease |
| GB9221220D0 (en) * | 1992-10-09 | 1992-11-25 | Sandoz Ag | Organic componds |
| NZ277498A (en) * | 1993-12-17 | 1998-03-25 | Novartis Ag | Rapamycin derivatives |
| US5362718A (en) * | 1994-04-18 | 1994-11-08 | American Home Products Corporation | Rapamycin hydroxyesters |
| US6265427B1 (en) * | 1995-06-07 | 2001-07-24 | The Proctor & Gamble Company | Pharmaceutical composition for the method of treating leukemia |
| KR100400620B1 (ko) * | 1995-06-09 | 2004-02-18 | 노파르티스 아게 | 라파마이신유도체 |
| GB9606452D0 (en) * | 1996-03-27 | 1996-06-05 | Sandoz Ltd | Organic compounds |
-
1996
- 1996-03-27 GB GBGB9606452.2A patent/GB9606452D0/en active Pending
-
1997
- 1997-03-25 MY MYPI97001258A patent/MY117798A/en unknown
- 1997-03-25 ID IDP970980A patent/ID17195A/id unknown
- 1997-03-26 ES ES08017336T patent/ES2421455T3/es not_active Expired - Lifetime
- 1997-03-26 IL IL12581297A patent/IL125812A/en not_active IP Right Cessation
- 1997-03-26 SK SK1327-98A patent/SK284343B6/sk not_active IP Right Cessation
- 1997-03-26 CA CA2247275A patent/CA2247275C/en not_active Expired - Lifetime
- 1997-03-26 TR TR1998/01919T patent/TR199801919T2/xx unknown
- 1997-03-26 WO PCT/EP1997/001548 patent/WO1997035575A1/en not_active Ceased
- 1997-03-26 SI SI9730801T patent/SI2008657T1/sl unknown
- 1997-03-26 DK DK97915441T patent/DK0893996T3/da active
- 1997-03-26 KR KR1020057005463A patent/KR100836971B1/ko not_active Expired - Lifetime
- 1997-03-26 EP EP97915441A patent/EP0893996B1/en not_active Revoked
- 1997-03-26 AT AT97915441T patent/ATE224194T1/de not_active IP Right Cessation
- 1997-03-26 AU AU22918/97A patent/AU716514B2/en not_active Expired
- 1997-03-26 EP EP08017336.2A patent/EP2008657B1/en not_active Expired - Lifetime
- 1997-03-26 EP EP01116262A patent/EP1149581A3/en not_active Withdrawn
- 1997-03-26 JP JP9532077A patent/JP2000507226A/ja not_active Withdrawn
- 1997-03-26 DE DE69715611T patent/DE69715611T2/de not_active Revoked
- 1997-03-26 KR KR1020077008212A patent/KR20070083654A/ko not_active Withdrawn
- 1997-03-26 NZ NZ331463A patent/NZ331463A/en not_active IP Right Cessation
- 1997-03-26 CN CN97193278A patent/CN1124135C/zh not_active Expired - Lifetime
- 1997-03-26 PT PT97915441T patent/PT893996E/pt unknown
- 1997-03-26 PT PT80173362T patent/PT2008657E/pt unknown
- 1997-03-26 RU RU98119312/14A patent/RU2214247C2/ru active
- 1997-03-26 CZ CZ19983070A patent/CZ292483B6/cs not_active IP Right Cessation
- 1997-03-26 ES ES97915441T patent/ES2184078T3/es not_active Expired - Lifetime
- 1997-03-26 PL PL97328659A patent/PL187732B1/pl unknown
- 1997-03-26 HU HU0001267A patent/HU226422B1/hu unknown
- 1997-03-26 BR BR9708358A patent/BR9708358A/pt not_active Application Discontinuation
- 1997-03-26 DK DK08017336.2T patent/DK2008657T3/da active
- 1997-03-27 ZA ZA972719A patent/ZA972719B/xx unknown
-
1998
- 1998-09-18 NO NO19984340A patent/NO316667B1/no not_active IP Right Cessation
-
2000
- 2000-11-14 US US09/712,359 patent/US6384046B1/en not_active Expired - Lifetime
-
2002
- 2002-03-07 US US10/092,639 patent/US20020127248A1/en not_active Abandoned
-
2004
- 2004-01-08 CY CY0400004A patent/CY2404B1/xx unknown
-
2008
- 2008-12-10 JP JP2008314494A patent/JP5124431B2/ja not_active Expired - Lifetime
-
2010
- 2010-03-01 US US12/715,007 patent/US20100152105A1/en not_active Abandoned
-
2012
- 2012-01-24 US US13/357,199 patent/US20120177690A1/en not_active Abandoned
-
2014
- 2014-03-05 US US14/197,368 patent/US20140187574A1/en not_active Abandoned
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE69715611T2 (de) | Verwendung eines rapamycinderivates zur behandlung von gefäss erkrankungen und xenotransplantationen | |
| DE69730727T2 (de) | Neue verwendung von 1,3-propanediol derivaten | |
| JP3287851B2 (ja) | ポルフィリンによる移植片生存の延長 | |
| JP2009102349A6 (ja) | 血管疾病および異種移植におけるラパマイシン誘導体の使用 | |
| Tajima et al. | Regeneration through nerve allografts in the cynomolgus monkey (Macaca fascicularis). | |
| EP0251134B1 (en) | Compositions for preventing graft rejection | |
| Veith et al. | Cyclosporin A in experimental lung transplantation | |
| DE60213766T2 (de) | Verwendung von beschleunigten lymphozyten zielansteuernden wirkstoffen zur herstellung eines medikaments für die behandlung der verzögertern transplantat-funktion | |
| DE69932728T2 (de) | 3-deazaadenosin zur vorbeugung der atherosklerose und mit transplantat assoziierten vaskulopathie | |
| DE69903964T2 (de) | Chemokin rezeptor antagonist und cyclosporin in kombinationstherapie | |
| JP6878418B2 (ja) | 移植片拒絶反応の処置方法 | |
| TW550074B (en) | Pharmaceutical composition for preventing or treating vasculopathies and chronic rejection | |
| KR100616020B1 (ko) | 맥관장애및이종이식술에서의라파마이신유도체의용도 | |
| EP1227808A2 (de) | Verwendung von treosulfan zur konditionierung von patienten vor knochenmarktransplantation oder blutstammzelltransplantation | |
| Hess et al. | Immunosuppression by succinylacetone. II. Prevention of graft-vs-host disease. | |
| Sinzinger et al. | The use of indium-111-labeled platelets in the management of renal transplant patients | |
| Sinzinger et al. | University of Vienna, Garnisongasse 13 A-1090 Vienna, Austria |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8363 | Opposition against the patent | ||
| 8331 | Complete revocation |