JP2007502327A - 椎間板変性症の治療法 - Google Patents
椎間板変性症の治療法 Download PDFInfo
- Publication number
- JP2007502327A JP2007502327A JP2006533113A JP2006533113A JP2007502327A JP 2007502327 A JP2007502327 A JP 2007502327A JP 2006533113 A JP2006533113 A JP 2006533113A JP 2006533113 A JP2006533113 A JP 2006533113A JP 2007502327 A JP2007502327 A JP 2007502327A
- Authority
- JP
- Japan
- Prior art keywords
- antagonist
- formulation
- disc
- tnf
- highly specific
- 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.)
- Pending
Links
- 206010061246 Intervertebral disc degeneration Diseases 0.000 title claims abstract description 43
- 238000011282 treatment Methods 0.000 title claims abstract description 41
- 238000000034 method Methods 0.000 claims abstract description 313
- 239000005557 antagonist Substances 0.000 claims abstract description 217
- 239000003814 drug Substances 0.000 claims abstract description 85
- 102000004127 Cytokines Human genes 0.000 claims abstract description 57
- 108090000695 Cytokines Proteins 0.000 claims abstract description 57
- 239000003112 inhibitor Substances 0.000 claims abstract description 46
- 230000003412 degenerative effect Effects 0.000 claims abstract description 40
- 238000013268 sustained release Methods 0.000 claims abstract description 34
- 239000012730 sustained-release form Substances 0.000 claims abstract description 34
- 208000018180 degenerative disc disease Diseases 0.000 claims abstract description 24
- 208000021600 intervertebral disc degenerative disease Diseases 0.000 claims abstract description 24
- 208000002193 Pain Diseases 0.000 claims abstract description 21
- 230000007850 degeneration Effects 0.000 claims abstract description 11
- 239000000203 mixture Substances 0.000 claims description 133
- 238000009472 formulation Methods 0.000 claims description 117
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 72
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 claims description 72
- 150000001875 compounds Chemical class 0.000 claims description 64
- MZOFCQQQCNRIBI-VMXHOPILSA-N (3s)-4-[[(2s)-1-[[(2s)-1-[[(1s)-1-carboxy-2-hydroxyethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-3-[[2-[[(2s)-2,6-diaminohexanoyl]amino]acetyl]amino]-4-oxobutanoic acid Chemical compound OC[C@@H](C(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@@H](N)CCCCN MZOFCQQQCNRIBI-VMXHOPILSA-N 0.000 claims description 62
- 102000002274 Matrix Metalloproteinases Human genes 0.000 claims description 57
- 108010000684 Matrix Metalloproteinases Proteins 0.000 claims description 57
- 229940124597 therapeutic agent Drugs 0.000 claims description 55
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 claims description 51
- 108010068338 p38 Mitogen-Activated Protein Kinases Proteins 0.000 claims description 51
- 102000016736 Cyclin Human genes 0.000 claims description 48
- 108050006400 Cyclin Proteins 0.000 claims description 48
- 108090000623 proteins and genes Proteins 0.000 claims description 40
- 102000004169 proteins and genes Human genes 0.000 claims description 38
- 230000000770 proinflammatory effect Effects 0.000 claims description 37
- 102000015696 Interleukins Human genes 0.000 claims description 33
- 108010063738 Interleukins Proteins 0.000 claims description 33
- 239000003102 growth factor Substances 0.000 claims description 31
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 claims description 30
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 claims description 30
- 210000002744 extracellular matrix Anatomy 0.000 claims description 30
- 230000002459 sustained effect Effects 0.000 claims description 30
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 22
- 229940043355 kinase inhibitor Drugs 0.000 claims description 22
- 239000003757 phosphotransferase inhibitor Substances 0.000 claims description 22
- 239000000017 hydrogel Substances 0.000 claims description 21
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 21
- 102100039364 Metalloproteinase inhibitor 1 Human genes 0.000 claims description 19
- 230000001225 therapeutic effect Effects 0.000 claims description 19
- 210000001519 tissue Anatomy 0.000 claims description 19
- 229920000642 polymer Polymers 0.000 claims description 18
- 230000015556 catabolic process Effects 0.000 claims description 17
- 238000006731 degradation reaction Methods 0.000 claims description 17
- 102000004190 Enzymes Human genes 0.000 claims description 16
- 108090000790 Enzymes Proteins 0.000 claims description 16
- 102000004889 Interleukin-6 Human genes 0.000 claims description 16
- 108090001005 Interleukin-6 Proteins 0.000 claims description 16
- 229940088598 enzyme Drugs 0.000 claims description 16
- 229960000598 infliximab Drugs 0.000 claims description 16
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 claims description 16
- ZKRFOXLVOKTUTA-KQYNXXCUSA-N 9-(5-phosphoribofuranosyl)-6-mercaptopurine Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(NC=NC2=S)=C2N=C1 ZKRFOXLVOKTUTA-KQYNXXCUSA-N 0.000 claims description 15
- 101000669513 Homo sapiens Metalloproteinase inhibitor 1 Proteins 0.000 claims description 15
- 239000003966 growth inhibitor Substances 0.000 claims description 15
- 239000000430 cytokine receptor antagonist Substances 0.000 claims description 14
- 102000004890 Interleukin-8 Human genes 0.000 claims description 13
- 108090001007 Interleukin-8 Proteins 0.000 claims description 13
- 102000005741 Metalloproteases Human genes 0.000 claims description 13
- 108010006035 Metalloproteases Proteins 0.000 claims description 13
- 102000004887 Transforming Growth Factor beta Human genes 0.000 claims description 13
- 108090001012 Transforming Growth Factor beta Proteins 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 13
- 239000011159 matrix material Substances 0.000 claims description 13
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical group C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 claims description 13
- 102100031939 Erythropoietin Human genes 0.000 claims description 12
- 239000012528 membrane Substances 0.000 claims description 12
- 229920002683 Glycosaminoglycan Polymers 0.000 claims description 11
- 102000008299 Nitric Oxide Synthase Human genes 0.000 claims description 11
- 108010021487 Nitric Oxide Synthase Proteins 0.000 claims description 11
- 239000003963 antioxidant agent Substances 0.000 claims description 11
- 230000002068 genetic effect Effects 0.000 claims description 11
- 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 claims description 11
- 229960002930 sirolimus Drugs 0.000 claims description 11
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound 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 claims description 11
- 108090000723 Insulin-Like Growth Factor I Proteins 0.000 claims description 10
- 230000015572 biosynthetic process Effects 0.000 claims description 9
- 239000013612 plasmid Substances 0.000 claims description 9
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 9
- -1 pyrazole ketone Chemical class 0.000 claims description 9
- 238000003786 synthesis reaction Methods 0.000 claims description 9
- 102000004218 Insulin-Like Growth Factor I Human genes 0.000 claims description 8
- 150000002460 imidazoles Chemical class 0.000 claims description 8
- 102000005962 receptors Human genes 0.000 claims description 8
- 108020003175 receptors Proteins 0.000 claims description 8
- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 claims description 7
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 claims description 7
- 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 claims description 7
- 230000003078 antioxidant effect Effects 0.000 claims description 7
- 238000006065 biodegradation reaction Methods 0.000 claims description 7
- 229940043378 cyclin-dependent kinase inhibitor Drugs 0.000 claims description 7
- 238000009792 diffusion process Methods 0.000 claims description 7
- 229960003722 doxycycline Drugs 0.000 claims description 7
- 229940047122 interleukins Drugs 0.000 claims description 7
- 229940088872 Apoptosis inhibitor Drugs 0.000 claims description 6
- 108010008165 Etanercept Proteins 0.000 claims description 6
- 108010002350 Interleukin-2 Proteins 0.000 claims description 6
- ONYFNWIHJBLQKE-ZETCQYMHSA-N N(6)-acetimidoyl-L-lysine Chemical compound CC(=N)NCCCC[C@H](N)C(O)=O ONYFNWIHJBLQKE-ZETCQYMHSA-N 0.000 claims description 6
- 239000004098 Tetracycline Substances 0.000 claims description 6
- 239000000158 apoptosis inhibitor Substances 0.000 claims description 6
- XEYBRNLFEZDVAW-ARSRFYASSA-N dinoprostone Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1C\C=C/CCCC(O)=O XEYBRNLFEZDVAW-ARSRFYASSA-N 0.000 claims description 6
- 229960002986 dinoprostone Drugs 0.000 claims description 6
- 229940100601 interleukin-6 Drugs 0.000 claims description 6
- XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 claims description 6
- 230000008439 repair process Effects 0.000 claims description 6
- 229960002180 tetracycline Drugs 0.000 claims description 6
- 229930101283 tetracycline Natural products 0.000 claims description 6
- 235000019364 tetracycline Nutrition 0.000 claims description 6
- 150000003522 tetracyclines Chemical class 0.000 claims description 6
- 102000048143 Insulin-Like Growth Factor II Human genes 0.000 claims description 5
- 108090001117 Insulin-Like Growth Factor II Proteins 0.000 claims description 5
- 239000002875 cyclin dependent kinase inhibitor Substances 0.000 claims description 5
- 239000004005 microsphere Substances 0.000 claims description 5
- VKUYLANQOAKALN-UHFFFAOYSA-N 2-[benzyl-(4-methoxyphenyl)sulfonylamino]-n-hydroxy-4-methylpentanamide Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N(C(CC(C)C)C(=O)NO)CC1=CC=CC=C1 VKUYLANQOAKALN-UHFFFAOYSA-N 0.000 claims description 4
- 102100026802 72 kDa type IV collagenase Human genes 0.000 claims description 4
- 101710151806 72 kDa type IV collagenase Proteins 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 4
- 102000013462 Interleukin-12 Human genes 0.000 claims description 4
- 108010065805 Interleukin-12 Proteins 0.000 claims description 4
- 102100026262 Metalloproteinase inhibitor 2 Human genes 0.000 claims description 4
- NTNWOCRCBQPEKQ-YFKPBYRVSA-N N(omega)-methyl-L-arginine Chemical compound CN=C(N)NCCC[C@H](N)C(O)=O NTNWOCRCBQPEKQ-YFKPBYRVSA-N 0.000 claims description 4
- 102100030411 Neutrophil collagenase Human genes 0.000 claims description 4
- 101710118230 Neutrophil collagenase Proteins 0.000 claims description 4
- 102100030416 Stromelysin-1 Human genes 0.000 claims description 4
- 101710108790 Stromelysin-1 Proteins 0.000 claims description 4
- 108010031374 Tissue Inhibitor of Metalloproteinase-1 Proteins 0.000 claims description 4
- 108010031372 Tissue Inhibitor of Metalloproteinase-2 Proteins 0.000 claims description 4
- 230000002424 anti-apoptotic effect Effects 0.000 claims description 4
- 108020001507 fusion proteins Proteins 0.000 claims description 4
- 102000037865 fusion proteins Human genes 0.000 claims description 4
- 230000004054 inflammatory process Effects 0.000 claims description 4
- 229940096397 interleukin-8 Drugs 0.000 claims description 4
- XKTZWUACRZHVAN-VADRZIEHSA-N interleukin-8 Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@@H](NC(C)=O)CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCSC)C(=O)N1[C@H](CCC1)C(=O)N1[C@H](CCC1)C(=O)N[C@@H](C)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC(O)=CC=1)C(=O)N[C@H](CO)C(=O)N1[C@H](CCC1)C(N)=O)C1=CC=CC=C1 XKTZWUACRZHVAN-VADRZIEHSA-N 0.000 claims description 4
- FFTVPQUHLQBXQZ-KVUCHLLUSA-N (4s,4as,5ar,12ar)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O FFTVPQUHLQBXQZ-KVUCHLLUSA-N 0.000 claims description 3
- 229940123169 Caspase inhibitor Drugs 0.000 claims description 3
- 108060005980 Collagenase Proteins 0.000 claims description 3
- 102000029816 Collagenase Human genes 0.000 claims description 3
- 102000013382 Gelatinases Human genes 0.000 claims description 3
- 108010026132 Gelatinases Proteins 0.000 claims description 3
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims description 3
- 102100039879 Interleukin-19 Human genes 0.000 claims description 3
- 108050009288 Interleukin-19 Proteins 0.000 claims description 3
- 102000000422 Matrix Metalloproteinase 3 Human genes 0.000 claims description 3
- 102000019197 Superoxide Dismutase Human genes 0.000 claims description 3
- 108010012715 Superoxide dismutase Proteins 0.000 claims description 3
- 125000004122 cyclic group Chemical group 0.000 claims description 3
- 229960000403 etanercept Drugs 0.000 claims description 3
- 229960004023 minocycline Drugs 0.000 claims description 3
- 230000004044 response Effects 0.000 claims description 3
- 108091007196 stromelysin Proteins 0.000 claims description 3
- OFCWIPGKPUJTDP-CFVMTHIKSA-N (2s,3r)-n-hydroxy-2-methyl-n'-[(1s)-2-(methylamino)-2-oxo-1-phenylethyl]-3-(2-methylpropyl)butanediamide Chemical class ONC(=O)[C@@H](C)[C@@H](CC(C)C)C(=O)N[C@H](C(=O)NC)C1=CC=CC=C1 OFCWIPGKPUJTDP-CFVMTHIKSA-N 0.000 claims description 2
- NWXMGUDVXFXRIG-WESIUVDSSA-N (4s,4as,5as,6s,12ar)-4-(dimethylamino)-1,6,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4,4a,5,5a-tetrahydrotetracene-2-carboxamide Chemical compound C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]4(O)C(=O)C3=C(O)C2=C1O NWXMGUDVXFXRIG-WESIUVDSSA-N 0.000 claims description 2
- VFHUJFBEFDVZPJ-UHFFFAOYSA-N 1h-indole-2-carboxamide Chemical compound C1=CC=C2NC(C(=O)N)=CC2=C1 VFHUJFBEFDVZPJ-UHFFFAOYSA-N 0.000 claims description 2
- JPOJBQLUJAIHHL-UHFFFAOYSA-N 1h-pyrimido[4,5-d]pyrimidin-2-one Chemical compound N1=CN=C2NC(=O)N=CC2=C1 JPOJBQLUJAIHHL-UHFFFAOYSA-N 0.000 claims description 2
- 102000003951 Erythropoietin Human genes 0.000 claims description 2
- 108090000394 Erythropoietin Proteins 0.000 claims description 2
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 2
- GLYCPKCGMJSGOV-UHFFFAOYSA-N N-pyridin-2-ylquinazolin-2-amine Chemical compound N=1C=C2C=CC=CC2=NC=1NC1=CC=CC=N1 GLYCPKCGMJSGOV-UHFFFAOYSA-N 0.000 claims description 2
- RWCCWEUUXYIKHB-UHFFFAOYSA-N benzophenone Chemical compound C=1C=CC=CC=1C(=O)C1=CC=CC=C1 RWCCWEUUXYIKHB-UHFFFAOYSA-N 0.000 claims description 2
- 239000012965 benzophenone Substances 0.000 claims description 2
- 229940105423 erythropoietin Drugs 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- JWVCLYRUEFBMGU-UHFFFAOYSA-N quinazoline Chemical compound N1=CN=CC2=CC=CC=C21 JWVCLYRUEFBMGU-UHFFFAOYSA-N 0.000 claims description 2
- 101710096328 Phospholipase A2 Proteins 0.000 claims 1
- 102100026918 Phospholipase A2 Human genes 0.000 claims 1
- 230000017423 tissue regeneration Effects 0.000 claims 1
- 229940079593 drug Drugs 0.000 abstract description 28
- 230000000694 effects Effects 0.000 abstract description 22
- 238000007910 systemic administration Methods 0.000 abstract description 5
- 230000002829 reductive effect Effects 0.000 abstract description 2
- 201000010099 disease Diseases 0.000 abstract 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 1
- 101000611183 Homo sapiens Tumor necrosis factor Proteins 0.000 description 40
- 102100040247 Tumor necrosis factor Human genes 0.000 description 38
- 238000002347 injection Methods 0.000 description 29
- 239000007924 injection Substances 0.000 description 29
- 210000004027 cell Anatomy 0.000 description 24
- 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 23
- 102000003298 tumor necrosis factor receptor Human genes 0.000 description 23
- 239000000126 substance Substances 0.000 description 18
- 229920002674 hyaluronan Polymers 0.000 description 14
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 12
- 210000001612 chondrocyte Anatomy 0.000 description 12
- 229960003160 hyaluronic acid Drugs 0.000 description 12
- 239000002502 liposome Substances 0.000 description 12
- 238000004519 manufacturing process Methods 0.000 description 12
- 102000000589 Interleukin-1 Human genes 0.000 description 11
- 108010002352 Interleukin-1 Proteins 0.000 description 11
- 230000008569 process Effects 0.000 description 11
- 229920001577 copolymer Polymers 0.000 description 9
- 238000002405 diagnostic procedure Methods 0.000 description 9
- 102000016611 Proteoglycans Human genes 0.000 description 8
- 108010067787 Proteoglycans Proteins 0.000 description 8
- 235000006708 antioxidants Nutrition 0.000 description 8
- 239000012634 fragment Substances 0.000 description 8
- 230000004927 fusion Effects 0.000 description 8
- 229940116176 remicade Drugs 0.000 description 8
- 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 8
- 150000002632 lipids Chemical class 0.000 description 7
- 108010007726 Bone Morphogenetic Proteins Proteins 0.000 description 6
- 102000007350 Bone Morphogenetic Proteins Human genes 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 6
- 230000009471 action Effects 0.000 description 6
- 229940112869 bone morphogenetic protein Drugs 0.000 description 6
- 239000000463 material Substances 0.000 description 6
- 102100020873 Interleukin-2 Human genes 0.000 description 5
- 102000035195 Peptidases Human genes 0.000 description 5
- 108091005804 Peptidases Proteins 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 238000007792 addition Methods 0.000 description 5
- 239000000427 antigen Substances 0.000 description 5
- 108091007433 antigens Proteins 0.000 description 5
- 102000036639 antigens Human genes 0.000 description 5
- 230000005847 immunogenicity Effects 0.000 description 5
- 230000002401 inhibitory effect Effects 0.000 description 5
- 210000000278 spinal cord Anatomy 0.000 description 5
- 239000002451 tumor necrosis factor inhibitor Substances 0.000 description 5
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 4
- 102100037850 Interferon gamma Human genes 0.000 description 4
- 108010074328 Interferon-gamma Proteins 0.000 description 4
- 208000003618 Intervertebral Disc Displacement Diseases 0.000 description 4
- 239000000232 Lipid Bilayer Substances 0.000 description 4
- 102100033732 Tumor necrosis factor receptor superfamily member 1A Human genes 0.000 description 4
- 150000001413 amino acids Chemical group 0.000 description 4
- 230000001195 anabolic effect Effects 0.000 description 4
- 210000003484 anatomy Anatomy 0.000 description 4
- 210000000845 cartilage Anatomy 0.000 description 4
- 150000004676 glycans Chemical class 0.000 description 4
- 210000004408 hybridoma Anatomy 0.000 description 4
- 230000028709 inflammatory response Effects 0.000 description 4
- 210000002540 macrophage Anatomy 0.000 description 4
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 4
- 230000037361 pathway Effects 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 210000003491 skin Anatomy 0.000 description 4
- 208000008035 Back Pain Diseases 0.000 description 3
- 102000014914 Carrier Proteins Human genes 0.000 description 3
- 108020004705 Codon Proteins 0.000 description 3
- 102100024785 Fibroblast growth factor 2 Human genes 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 description 3
- 101710144554 Interleukin-1 receptor antagonist protein Proteins 0.000 description 3
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 3
- 239000012826 P38 inhibitor Substances 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 208000008765 Sciatica Diseases 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 102100031988 Tumor necrosis factor ligand superfamily member 6 Human genes 0.000 description 3
- 108050002568 Tumor necrosis factor ligand superfamily member 6 Proteins 0.000 description 3
- 239000002260 anti-inflammatory agent Substances 0.000 description 3
- 230000006907 apoptotic process Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 108091008324 binding proteins Proteins 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000004069 differentiation Effects 0.000 description 3
- 238000002651 drug therapy Methods 0.000 description 3
- 229940073621 enbrel Drugs 0.000 description 3
- 239000002532 enzyme inhibitor Substances 0.000 description 3
- 230000012010 growth Effects 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 239000003407 interleukin 1 receptor blocking agent Substances 0.000 description 3
- 229960004194 lidocaine Drugs 0.000 description 3
- 210000003041 ligament Anatomy 0.000 description 3
- 239000007791 liquid phase Substances 0.000 description 3
- 239000003589 local anesthetic agent Substances 0.000 description 3
- 239000002829 mitogen activated protein kinase inhibitor Substances 0.000 description 3
- 210000003205 muscle Anatomy 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 229920001282 polysaccharide Polymers 0.000 description 3
- 239000005017 polysaccharide Substances 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 210000004003 subcutaneous fat Anatomy 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- 239000002452 tumor necrosis factor alpha inhibitor Substances 0.000 description 3
- 239000002699 waste material Substances 0.000 description 3
- WCDDVEOXEIYWFB-VXORFPGASA-N (2s,3s,4r,5r,6r)-3-[(2s,3r,5s,6r)-3-acetamido-5-hydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-4,5,6-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@@H]1C[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O)[C@H](O)[C@H]1O WCDDVEOXEIYWFB-VXORFPGASA-N 0.000 description 2
- KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 description 2
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 2
- 102100022089 Acyl-[acyl-carrier-protein] hydrolase Human genes 0.000 description 2
- 101150078577 Adora2b gene Proteins 0.000 description 2
- 102100036601 Aggrecan core protein Human genes 0.000 description 2
- 108010067219 Aggrecans Proteins 0.000 description 2
- 102100030988 Angiotensin-converting enzyme Human genes 0.000 description 2
- 101000964894 Bos taurus 14-3-3 protein zeta/delta Proteins 0.000 description 2
- 108010071942 Colony-Stimulating Factors Proteins 0.000 description 2
- 102000007644 Colony-Stimulating Factors Human genes 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 2
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 2
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 2
- 102000003971 Fibroblast Growth Factor 1 Human genes 0.000 description 2
- 206010016654 Fibrosis Diseases 0.000 description 2
- 206010019909 Hernia Diseases 0.000 description 2
- 101000824278 Homo sapiens Acyl-[acyl-carrier-protein] hydrolase Proteins 0.000 description 2
- 101000611023 Homo sapiens Tumor necrosis factor receptor superfamily member 6 Proteins 0.000 description 2
- 108060003951 Immunoglobulin Proteins 0.000 description 2
- 102000019223 Interleukin-1 receptor Human genes 0.000 description 2
- 108050006617 Interleukin-1 receptor Proteins 0.000 description 2
- 229940124761 MMP inhibitor Drugs 0.000 description 2
- 102100026632 Mimecan Human genes 0.000 description 2
- OVRNDRQMDRJTHS-UHFFFAOYSA-N N-acelyl-D-glucosamine Chemical class CC(=O)NC1C(O)OC(CO)C(O)C1O OVRNDRQMDRJTHS-UHFFFAOYSA-N 0.000 description 2
- OVRNDRQMDRJTHS-FMDGEEDCSA-N N-acetyl-beta-D-glucosamine Chemical class CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O OVRNDRQMDRJTHS-FMDGEEDCSA-N 0.000 description 2
- MBLBDJOUHNCFQT-LXGUWJNJSA-N N-acetylglucosamine Chemical class CC(=O)N[C@@H](C=O)[C@@H](O)[C@H](O)[C@H](O)CO MBLBDJOUHNCFQT-LXGUWJNJSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 208000025966 Neurological disease Diseases 0.000 description 2
- 101800002327 Osteoinductive factor Proteins 0.000 description 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 229920002845 Poly(methacrylic acid) Polymers 0.000 description 2
- 229920002125 Sokalan® Polymers 0.000 description 2
- 102000013275 Somatomedins Human genes 0.000 description 2
- 102000009618 Transforming Growth Factors Human genes 0.000 description 2
- 108010009583 Transforming Growth Factors Proteins 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- SHGAZHPCJJPHSC-YCNIQYBTSA-N all-trans-retinoic acid Chemical compound OC(=O)\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 230000001772 anti-angiogenic effect Effects 0.000 description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 description 2
- 230000001028 anti-proliverative effect Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 229960003115 certolizumab pegol Drugs 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 150000002016 disaccharides Chemical group 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000004761 fibrosis Effects 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 102000057041 human TNF Human genes 0.000 description 2
- KIUKXJAPPMFGSW-MNSSHETKSA-N hyaluronan Chemical group CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)C1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H](C(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-MNSSHETKSA-N 0.000 description 2
- 229940014041 hyaluronate Drugs 0.000 description 2
- 230000028993 immune response Effects 0.000 description 2
- 102000018358 immunoglobulin Human genes 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 210000000265 leukocyte Anatomy 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
- 239000003226 mitogen Substances 0.000 description 2
- 229950006780 n-acetylglucosamine Drugs 0.000 description 2
- 210000005036 nerve Anatomy 0.000 description 2
- 230000007383 nerve stimulation Effects 0.000 description 2
- 210000000929 nociceptor Anatomy 0.000 description 2
- 108091008700 nociceptors Proteins 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 235000015097 nutrients Nutrition 0.000 description 2
- 230000002018 overexpression Effects 0.000 description 2
- 230000000737 periodic effect Effects 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 150000003904 phospholipids Chemical class 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 229920002627 poly(phosphazenes) Polymers 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 230000008092 positive effect Effects 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 150000003180 prostaglandins Chemical class 0.000 description 2
- 238000001243 protein synthesis Methods 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 229930002330 retinoic acid Natural products 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000010254 subcutaneous injection Methods 0.000 description 2
- 239000007929 subcutaneous injection Substances 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 230000008467 tissue growth Effects 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 231100000816 toxic dose Toxicity 0.000 description 2
- 230000014616 translation Effects 0.000 description 2
- 229960001727 tretinoin Drugs 0.000 description 2
- 230000006433 tumor necrosis factor production Effects 0.000 description 2
- 239000002691 unilamellar liposome Substances 0.000 description 2
- 239000013603 viral vector Substances 0.000 description 2
- 230000003442 weekly effect Effects 0.000 description 2
- GMVPRGQOIOIIMI-UHFFFAOYSA-N (8R,11R,12R,13E,15S)-11,15-Dihydroxy-9-oxo-13-prostenoic acid Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CCCCCCC(O)=O GMVPRGQOIOIIMI-UHFFFAOYSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 1
- KGIGUEBEKRSTEW-UHFFFAOYSA-N 2-vinylpyridine Chemical compound C=CC1=CC=CC=N1 KGIGUEBEKRSTEW-UHFFFAOYSA-N 0.000 description 1
- 108050001326 26S Proteasome regulatory subunit 6A Proteins 0.000 description 1
- 102100029510 26S proteasome regulatory subunit 6A Human genes 0.000 description 1
- QBACMJFLMUCPNA-UHFFFAOYSA-N 4-[5-(4-fluorophenyl)-3-piperidin-4-ylimidazol-4-yl]pyridine Chemical compound C1=CC(F)=CC=C1C1=C(C=2C=CN=CC=2)N(C2CCNCC2)C=N1 QBACMJFLMUCPNA-UHFFFAOYSA-N 0.000 description 1
- 102100027400 A disintegrin and metalloproteinase with thrombospondin motifs 4 Human genes 0.000 description 1
- 101710100373 A disintegrin and metalloproteinase with thrombospondin motifs 4 Proteins 0.000 description 1
- RSWGJHLUYNHPMX-UHFFFAOYSA-N Abietic-Saeure Natural products C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 description 1
- 102100033312 Alpha-2-macroglobulin Human genes 0.000 description 1
- 102100022987 Angiogenin Human genes 0.000 description 1
- 108090000669 Annexin A4 Proteins 0.000 description 1
- 102100034612 Annexin A4 Human genes 0.000 description 1
- 108020004491 Antisense DNA Proteins 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- 206010063836 Atrioventricular septal defect Diseases 0.000 description 1
- 101150061927 BMP2 gene Proteins 0.000 description 1
- 108010081589 Becaplermin Proteins 0.000 description 1
- 108010049931 Bone Morphogenetic Protein 2 Proteins 0.000 description 1
- 108010049951 Bone Morphogenetic Protein 3 Proteins 0.000 description 1
- 102100028728 Bone morphogenetic protein 1 Human genes 0.000 description 1
- 108090000654 Bone morphogenetic protein 1 Proteins 0.000 description 1
- 102100024506 Bone morphogenetic protein 2 Human genes 0.000 description 1
- 102100024504 Bone morphogenetic protein 3 Human genes 0.000 description 1
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 1
- 101150071146 COX2 gene Proteins 0.000 description 1
- 101100114534 Caenorhabditis elegans ctc-2 gene Proteins 0.000 description 1
- 108010076667 Caspases Proteins 0.000 description 1
- 102000011727 Caspases Human genes 0.000 description 1
- 102000004225 Cathepsin B Human genes 0.000 description 1
- 108090000712 Cathepsin B Proteins 0.000 description 1
- 102000004171 Cathepsin K Human genes 0.000 description 1
- 108090000625 Cathepsin K Proteins 0.000 description 1
- 102000004172 Cathepsin L Human genes 0.000 description 1
- 108090000624 Cathepsin L Proteins 0.000 description 1
- 102000005600 Cathepsins Human genes 0.000 description 1
- 108010084457 Cathepsins Proteins 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 108010025461 Cyclin-Dependent Kinase 9 Proteins 0.000 description 1
- 102100024457 Cyclin-dependent kinase 9 Human genes 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 102000002045 Endothelin Human genes 0.000 description 1
- 108050009340 Endothelin Proteins 0.000 description 1
- 241000289659 Erinaceidae Species 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 102000009123 Fibrin Human genes 0.000 description 1
- 108010073385 Fibrin Proteins 0.000 description 1
- BWGVNKXGVNDBDI-UHFFFAOYSA-N Fibrin monomer Chemical compound CNC(=O)CNC(=O)CN BWGVNKXGVNDBDI-UHFFFAOYSA-N 0.000 description 1
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 1
- 108090000381 Fibroblast growth factor 4 Proteins 0.000 description 1
- 102100028072 Fibroblast growth factor 4 Human genes 0.000 description 1
- 108090000385 Fibroblast growth factor 7 Proteins 0.000 description 1
- 102000003972 Fibroblast growth factor 7 Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- 229940123457 Free radical scavenger Drugs 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- ZWQVYZXPYSYPJD-RYUDHWBXSA-N Glu-Gly-Phe Chemical compound OC(=O)CC[C@H](N)C(=O)NCC(=O)N[C@H](C(O)=O)CC1=CC=CC=C1 ZWQVYZXPYSYPJD-RYUDHWBXSA-N 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000004269 Granulocyte Colony-Stimulating Factor Human genes 0.000 description 1
- 108010017080 Granulocyte Colony-Stimulating Factor Proteins 0.000 description 1
- 108010090254 Growth Differentiation Factor 5 Proteins 0.000 description 1
- 102100035379 Growth/differentiation factor 5 Human genes 0.000 description 1
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 1
- 102100021866 Hepatocyte growth factor Human genes 0.000 description 1
- 101000801228 Homo sapiens Tumor necrosis factor receptor superfamily member 1A Proteins 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- 206010050296 Intervertebral disc protrusion Diseases 0.000 description 1
- AEMOLEFTQBMNLQ-HNFCZKTMSA-N L-idopyranuronic acid Chemical compound OC1O[C@@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-HNFCZKTMSA-N 0.000 description 1
- 102100032352 Leukemia inhibitory factor Human genes 0.000 description 1
- 108090000581 Leukemia inhibitory factor Proteins 0.000 description 1
- 102000003960 Ligases Human genes 0.000 description 1
- 108090000364 Ligases Proteins 0.000 description 1
- 208000008930 Low Back Pain Diseases 0.000 description 1
- 102000007651 Macrophage Colony-Stimulating Factor Human genes 0.000 description 1
- 108010046938 Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- OVRNDRQMDRJTHS-CBQIKETKSA-N N-Acetyl-D-Galactosamine Chemical class CC(=O)N[C@H]1[C@@H](O)O[C@H](CO)[C@H](O)[C@@H]1O OVRNDRQMDRJTHS-CBQIKETKSA-N 0.000 description 1
- MBLBDJOUHNCFQT-UHFFFAOYSA-N N-acetyl-D-galactosamine Chemical class CC(=O)NC(C=O)C(O)C(O)C(O)CO MBLBDJOUHNCFQT-UHFFFAOYSA-N 0.000 description 1
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 241000906034 Orthops Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 101150000187 PTGS2 gene Proteins 0.000 description 1
- 241000051107 Paraechinus aethiopicus Species 0.000 description 1
- BYPFEZZEUUWMEJ-UHFFFAOYSA-N Pentoxifylline Chemical compound O=C1N(CCCCC(=O)C)C(=O)N(C)C2=C1N(C)C=N2 BYPFEZZEUUWMEJ-UHFFFAOYSA-N 0.000 description 1
- 108010015078 Pregnancy-Associated alpha 2-Macroglobulins Proteins 0.000 description 1
- 108010076504 Protein Sorting Signals Proteins 0.000 description 1
- 230000006819 RNA synthesis Effects 0.000 description 1
- 241000219061 Rheum Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- KHPCPRHQVVSZAH-HUOMCSJISA-N Rosin Natural products O(C/C=C/c1ccccc1)[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 KHPCPRHQVVSZAH-HUOMCSJISA-N 0.000 description 1
- AJLFOPYRIVGYMJ-UHFFFAOYSA-N SJ000287055 Natural products C12C(OC(=O)C(C)CC)CCC=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 AJLFOPYRIVGYMJ-UHFFFAOYSA-N 0.000 description 1
- 229910000831 Steel Inorganic materials 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 1
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 1
- 102000046299 Transforming Growth Factor beta1 Human genes 0.000 description 1
- 101800002279 Transforming growth factor beta-1 Proteins 0.000 description 1
- 101710187743 Tumor necrosis factor receptor superfamily member 1A Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 108010003059 aggrecanase Proteins 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 230000000735 allogeneic effect Effects 0.000 description 1
- 229960000711 alprostadil Drugs 0.000 description 1
- BIIVYFLTOXDAOV-YVEFUNNKSA-N alvocidib Chemical compound O[C@@H]1CN(C)CC[C@@H]1C1=C(O)C=C(O)C2=C1OC(C=1C(=CC=CC=1)Cl)=CC2=O BIIVYFLTOXDAOV-YVEFUNNKSA-N 0.000 description 1
- 229950010817 alvocidib Drugs 0.000 description 1
- 229940005553 analgesics and anesthetics Drugs 0.000 description 1
- 239000002870 angiogenesis inducing agent Substances 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 108010072788 angiogenin Proteins 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003816 antisense DNA Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 239000003181 biological factor Substances 0.000 description 1
- 229920001222 biopolymer Polymers 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 210000002805 bone matrix Anatomy 0.000 description 1
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 1
- 229960000830 captopril Drugs 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229960000590 celecoxib Drugs 0.000 description 1
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000012292 cell migration Effects 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 229940106189 ceramide Drugs 0.000 description 1
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000006957 competitive inhibition Effects 0.000 description 1
- 239000003184 complementary RNA Substances 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 229960001334 corticosteroids Drugs 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000032798 delamination Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 238000004925 denaturation Methods 0.000 description 1
- 230000036425 denaturation Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960001259 diclofenac Drugs 0.000 description 1
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
- 235000015872 dietary supplement Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 229940125436 dual inhibitor Drugs 0.000 description 1
- 230000002884 effect on inflammation Effects 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 238000001211 electron capture detection Methods 0.000 description 1
- 238000001962 electrophoresis Methods 0.000 description 1
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 229940125532 enzyme inhibitor Drugs 0.000 description 1
- 230000003628 erosive effect Effects 0.000 description 1
- UYMKPFRHYYNDTL-UHFFFAOYSA-N ethenamine Chemical compound NC=C UYMKPFRHYYNDTL-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000016691 extracellular matrix constituent secretion Effects 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 238000001415 gene therapy Methods 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 229940048921 humira Drugs 0.000 description 1
- 229940099552 hyaluronan Drugs 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000004941 influx Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 150000002500 ions Chemical group 0.000 description 1
- 238000002032 lab-on-a-chip Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 description 1
- 229960004844 lovastatin Drugs 0.000 description 1
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000037353 metabolic pathway Effects 0.000 description 1
- 239000003475 metalloproteinase inhibitor Substances 0.000 description 1
- AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 description 1
- 229950009116 mevastatin Drugs 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 229940126619 mouse monoclonal antibody Drugs 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
- 229960000965 nimesulide Drugs 0.000 description 1
- HYWYRSMBCFDLJT-UHFFFAOYSA-N nimesulide Chemical compound CS(=O)(=O)NC1=CC=C([N+]([O-])=O)C=C1OC1=CC=CC=C1 HYWYRSMBCFDLJT-UHFFFAOYSA-N 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 229950010444 onercept Drugs 0.000 description 1
- 229920000620 organic polymer Polymers 0.000 description 1
- 230000000399 orthopedic effect Effects 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 229960001476 pentoxifylline Drugs 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 1
- 239000002644 phorbol ester Substances 0.000 description 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
- 108010000685 platelet-derived growth factor AB Proteins 0.000 description 1
- 229920002006 poly(N-vinylimidazole) polymer Polymers 0.000 description 1
- 150000004804 polysaccharides Polymers 0.000 description 1
- 229920002689 polyvinyl acetate Polymers 0.000 description 1
- 239000011118 polyvinyl acetate Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- GMVPRGQOIOIIMI-DWKJAMRDSA-N prostaglandin E1 Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)CC(=O)[C@@H]1CCCCCCC(O)=O GMVPRGQOIOIIMI-DWKJAMRDSA-N 0.000 description 1
- 229940076372 protein antagonist Drugs 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000005086 pumping Methods 0.000 description 1
- 239000003379 purinergic P1 receptor agonist Substances 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 108091006082 receptor inhibitors Proteins 0.000 description 1
- 108010003189 recombinant human tumor necrosis factor-binding protein-1 Proteins 0.000 description 1
- 238000010188 recombinant method Methods 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 229960000371 rofecoxib Drugs 0.000 description 1
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
- HJORMJIFDVBMOB-UHFFFAOYSA-N rolipram Chemical compound COC1=CC=C(C2CC(=O)NC2)C=C1OC1CCCC1 HJORMJIFDVBMOB-UHFFFAOYSA-N 0.000 description 1
- 229950005741 rolipram Drugs 0.000 description 1
- 229940043266 rosin Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- BTIHMVBBUGXLCJ-OAHLLOKOSA-N seliciclib Chemical compound C=12N=CN(C(C)C)C2=NC(N[C@@H](CO)CC)=NC=1NCC1=CC=CC=C1 BTIHMVBBUGXLCJ-OAHLLOKOSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 210000000273 spinal nerve root Anatomy 0.000 description 1
- 239000010959 steel Substances 0.000 description 1
- 210000000130 stem cell Anatomy 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000000542 sulfonic acid group Chemical group 0.000 description 1
- MDKGKXOCJGEUJW-UHFFFAOYSA-N suprofen Chemical compound C1=CC(C(C(O)=O)C)=CC=C1C(=O)C1=CC=CS1 MDKGKXOCJGEUJW-UHFFFAOYSA-N 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229960003676 tenidap Drugs 0.000 description 1
- LXIKEPCNDFVJKC-QXMHVHEDSA-N tenidap Chemical compound C12=CC(Cl)=CC=C2N(C(=O)N)C(=O)\C1=C(/O)C1=CC=CS1 LXIKEPCNDFVJKC-QXMHVHEDSA-N 0.000 description 1
- XYKWNRUXCOIMFZ-UHFFFAOYSA-N tepoxalin Chemical compound C1=CC(OC)=CC=C1N1C(C=2C=CC(Cl)=CC=2)=CC(CCC(=O)N(C)O)=N1 XYKWNRUXCOIMFZ-UHFFFAOYSA-N 0.000 description 1
- 229950009638 tepoxalin Drugs 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- 239000003634 thrombocyte concentrate Substances 0.000 description 1
- 229960001017 tolmetin Drugs 0.000 description 1
- UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- KHPCPRHQVVSZAH-UHFFFAOYSA-N trans-cinnamyl beta-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OCC=CC1=CC=CC=C1 KHPCPRHQVVSZAH-UHFFFAOYSA-N 0.000 description 1
- 108010072415 tumor necrosis factor precursor Proteins 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 150000002266 vitamin A derivatives Chemical class 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/43—Enzymes; Proenzymes; Derivatives thereof
- A61K38/46—Hydrolases (3)
- A61K38/48—Hydrolases (3) acting on peptide bonds (3.4)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/38—Materials or treatment for tissue regeneration for reconstruction of the spine, vertebrae or intervertebral discs
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth 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)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Physical Education & Sports Medicine (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Neurology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Gastroenterology & Hepatology (AREA)
- Neurosurgery (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US47009803P | 2003-05-13 | 2003-05-13 | |
| US10/456,948 US7344716B2 (en) | 2003-05-13 | 2003-06-06 | Transdiscal administration of specific inhibitors of pro-inflammatory cytokines |
| US10/610,355 US7429378B2 (en) | 2003-05-13 | 2003-06-30 | Transdiscal administration of high affinity anti-MMP inhibitors |
| US10/631,487 US20040229878A1 (en) | 2003-05-13 | 2003-07-31 | Transdiscal administration of specific inhibitors of P38 kinase |
| US10/640,412 US7553827B2 (en) | 2003-08-13 | 2003-08-13 | Transdiscal administration of cycline compounds |
| PCT/US2004/015285 WO2005000283A2 (en) | 2003-05-13 | 2004-05-13 | A method of treating degenerative disc disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007502327A true JP2007502327A (ja) | 2007-02-08 |
| JP2007502327A5 JP2007502327A5 (https=) | 2007-06-28 |
Family
ID=33556747
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2006533113A Pending JP2007502327A (ja) | 2003-05-13 | 2004-05-13 | 椎間板変性症の治療法 |
Country Status (8)
| Country | Link |
|---|---|
| EP (2) | EP1631266B1 (https=) |
| JP (1) | JP2007502327A (https=) |
| KR (1) | KR20060014048A (https=) |
| AU (1) | AU2004251042A1 (https=) |
| BR (1) | BRPI0410331A (https=) |
| CA (1) | CA2525928A1 (https=) |
| MX (1) | MXPA05012275A (https=) |
| WO (1) | WO2005000283A2 (https=) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2019513823A (ja) * | 2016-04-04 | 2019-05-30 | ゲーウー・ベンチャーズ・アーベー | 椎間板ヘルニアの治療のための方法及び組成物 |
Families Citing this family (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7744651B2 (en) | 2002-09-18 | 2010-06-29 | Warsaw Orthopedic, Inc | Compositions and methods for treating intervertebral discs with collagen-based materials |
| US20040054414A1 (en) | 2002-09-18 | 2004-03-18 | Trieu Hai H. | Collagen-based materials and methods for augmenting intervertebral discs |
| JP2006515765A (ja) | 2002-11-15 | 2006-06-08 | エスディージーアイ・ホールディングス・インコーポレーテッド | 滑膜性関節を治療するためのコラーゲンベース材料および方法 |
| US7429378B2 (en) | 2003-05-13 | 2008-09-30 | Depuy Spine, Inc. | Transdiscal administration of high affinity anti-MMP inhibitors |
| US7344716B2 (en) | 2003-05-13 | 2008-03-18 | Depuy Spine, Inc. | Transdiscal administration of specific inhibitors of pro-inflammatory cytokines |
| US7553827B2 (en) | 2003-08-13 | 2009-06-30 | Depuy Spine, Inc. | Transdiscal administration of cycline compounds |
| US8273347B2 (en) | 2003-05-13 | 2012-09-25 | Depuy Spine, Inc. | Autologous treatment of degenerated disc with cells |
| US8361467B2 (en) | 2003-07-30 | 2013-01-29 | Depuy Spine, Inc. | Trans-capsular administration of high specificity cytokine inhibitors into orthopedic joints |
| US20050100538A1 (en) * | 2003-07-31 | 2005-05-12 | Attawia Mohamed | Intradiscal injection of anti-oxidants |
| US8895540B2 (en) | 2003-11-26 | 2014-11-25 | DePuy Synthes Products, LLC | Local intraosseous administration of bone forming agents and anti-resorptive agents, and devices therefor |
| EP1931328A4 (en) * | 2005-08-16 | 2011-07-13 | Discogen Llc | METHOD FOR TREATING A GREENER SUBJECT WITH DEGENERATIVE DISCOPATHY USING AN INHIBITOR OF NITRIC OXIDE SYNTHASE |
| JP2009508970A (ja) | 2005-09-21 | 2009-03-05 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | 疼痛の局所造影および治療のためのシステム、組成物並びに方法 |
| EP1986657A4 (en) * | 2006-02-16 | 2011-07-20 | Discogen Llc | METHOD OF TREATING A SUBJECT SUFFERING FROM DEGENERATIVE DISCOPATHY BY A MATRIX METALLOPROTEASE INHIBITOR |
| US8399619B2 (en) | 2006-06-30 | 2013-03-19 | Warsaw Orthopedic, Inc. | Injectable collagen material |
| US8118779B2 (en) | 2006-06-30 | 2012-02-21 | Warsaw Orthopedic, Inc. | Collagen delivery device |
| US7928111B2 (en) * | 2007-06-08 | 2011-04-19 | Senomyx, Inc. | Compounds including substituted thienopyrimidinone derivatives as ligands for modulating chemosensory receptors |
| US8986696B2 (en) | 2007-12-21 | 2015-03-24 | Depuy Mitek, Inc. | Trans-capsular administration of p38 map kinase inhibitors into orthopedic joints |
| KR101577159B1 (ko) | 2008-07-31 | 2015-12-11 | 세노믹스, 인코포레이티드 | 단맛 향상제의 제조 방법 및 중간체 |
| CA3076662A1 (en) | 2017-09-25 | 2019-03-28 | Ecm Diagnostics, Inc. | Methods for treating degenerative disc disease and chronic lower back pain |
| WO2019152917A1 (en) * | 2018-02-02 | 2019-08-08 | Galen Therapeutics Llc | Apparatus and method for protecting neurons and reducing inflammation and scarring |
| JP7453210B2 (ja) | 2018-08-07 | 2024-03-19 | フィルメニッヒ インコーポレイテッド | ５－置換４－アミノ－１Ｈ－ベンゾ［ｃ］［１，２，６］チアジアジン２，２－ジオキシド並びにその配合物及び使用 |
| CN110613837A (zh) * | 2019-10-24 | 2019-12-27 | 内蒙古医科大学第二附属医院 | TGF-β在制备预防或治疗腰椎间盘突出药物中的应用 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20010006948A1 (en) * | 1998-11-25 | 2001-07-05 | James D. Kang | Gene transfer to intervertebral disc cells |
| JP2002525331A (ja) * | 1998-09-25 | 2002-08-13 | エイプラス サイエンス インベスト アーベー | 神経根障害を処置するための所定薬剤の使用 |
| JP2002537356A (ja) * | 1999-02-24 | 2002-11-05 | トビニク、エドワード、エル． | 神経障害治療のための腫瘍壊死因子拮抗薬 |
Family Cites Families (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4870163A (en) | 1985-08-29 | 1989-09-26 | New York Blood Center, Inc. | Preparation of pure human tumor necrosis factor and hybridomas producing monoclonal antibodies to human tumor necrosis factor |
| DE3631229A1 (de) | 1986-09-13 | 1988-03-24 | Basf Ag | Monoklonale antikoerper gegen humanen tumornekrosefaktor (tnf) und deren verwendung |
| EP0288088B1 (en) | 1987-04-24 | 1994-03-09 | Teijin Limited | Detection of tumor necrosis factor; monoclonal antibody and kit |
| US5225538A (en) | 1989-02-23 | 1993-07-06 | Genentech, Inc. | Lymphocyte homing receptor/immunoglobulin fusion proteins |
| US5116964A (en) | 1989-02-23 | 1992-05-26 | Genentech, Inc. | Hybrid immunoglobulins |
| DE69027121T3 (de) | 1989-08-07 | 2001-08-30 | Peptech Ltd., Dee Why | Bindeligande für tumornekrosisfaktor |
| GB9022648D0 (en) | 1990-10-18 | 1990-11-28 | Charing Cross Sunley Research | Polypeptide and its use |
| US6277969B1 (en) | 1991-03-18 | 2001-08-21 | New York University | Anti-TNF antibodies and peptides of human tumor necrosis factor |
| US5270300A (en) | 1991-09-06 | 1993-12-14 | Robert Francis Shaw | Methods and compositions for the treatment and repair of defects or lesions in cartilage or bone |
| US5447851B1 (en) | 1992-04-02 | 1999-07-06 | Univ Texas System Board Of | Dna encoding a chimeric polypeptide comprising the extracellular domain of tnf receptor fused to igg vectors and host cells |
| ES2233768T3 (es) | 1996-02-02 | 2005-06-16 | Alza Corporation | Liberacion prolongada de un agente activo utilizando un sistema implantable. |
| US7115557B2 (en) | 1998-09-25 | 2006-10-03 | Sciaticon Ab | Use of certain drugs for treating nerve root injury |
| US6537549B2 (en) * | 1999-02-24 | 2003-03-25 | Edward L. Tobinick | Cytokine antagonists for the treatment of localized disorders |
| US6419944B2 (en) | 1999-02-24 | 2002-07-16 | Edward L. Tobinick | Cytokine antagonists for the treatment of localized disorders |
| US6982089B2 (en) | 1999-02-24 | 2006-01-03 | Tact Ip, Llc | Cytokine antagonists for neurological and neuropsychiatric disorders |
| US6428576B1 (en) * | 1999-04-16 | 2002-08-06 | Endospine, Ltd. | System for repairing inter-vertebral discs |
| US6352557B1 (en) | 1999-08-13 | 2002-03-05 | Bret A. Ferree | Treating degenerative disc disease through transplantion of extracellular nucleus pulposus matrix and autograft nucleus pulposus cells |
| US6541477B2 (en) | 1999-08-27 | 2003-04-01 | Scios, Inc. | Inhibitors of p38-a kinase |
| US20020032155A1 (en) * | 2000-06-30 | 2002-03-14 | Ferree Bret A. | Method of treating disc herniation and disc degeneration with concentrated growth and differentiation factors |
| US20020026244A1 (en) | 2000-08-30 | 2002-02-28 | Trieu Hai H. | Intervertebral disc nucleus implants and methods |
| DE60120494T2 (de) | 2000-12-22 | 2006-12-21 | Ortho-Mcneil Pharmaceutical, Inc. | Substituieten triazoldiamin derivaten und ihre verwendung als kinase inhibitoren |
| SE0102067D0 (sv) | 2001-06-11 | 2001-06-11 | A & Science Invest Ab | Prevention of neovascularization of intervertebral discs and/or of tissues with local inflammation |
| CA2451245A1 (en) | 2001-06-25 | 2003-01-03 | Depuy International Limited | Liposomal encapsulation of glycosaminoglycans for the treatment of arthritic joints |
-
2004
- 2004-05-13 BR BRPI0410331-9A patent/BRPI0410331A/pt not_active Application Discontinuation
- 2004-05-13 KR KR1020057021572A patent/KR20060014048A/ko not_active Withdrawn
- 2004-05-13 EP EP04776014A patent/EP1631266B1/en not_active Expired - Lifetime
- 2004-05-13 JP JP2006533113A patent/JP2007502327A/ja active Pending
- 2004-05-13 CA CA002525928A patent/CA2525928A1/en not_active Abandoned
- 2004-05-13 WO PCT/US2004/015285 patent/WO2005000283A2/en not_active Ceased
- 2004-05-13 MX MXPA05012275A patent/MXPA05012275A/es not_active Application Discontinuation
- 2004-05-13 AU AU2004251042A patent/AU2004251042A1/en not_active Abandoned
- 2004-05-13 EP EP20100183305 patent/EP2286804A1/en not_active Withdrawn
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002525331A (ja) * | 1998-09-25 | 2002-08-13 | エイプラス サイエンス インベスト アーベー | 神経根障害を処置するための所定薬剤の使用 |
| US20010006948A1 (en) * | 1998-11-25 | 2001-07-05 | James D. Kang | Gene transfer to intervertebral disc cells |
| JP2002537356A (ja) * | 1999-02-24 | 2002-11-05 | トビニク、エドワード、エル． | 神経障害治療のための腫瘍壊死因子拮抗薬 |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2019513823A (ja) * | 2016-04-04 | 2019-05-30 | ゲーウー・ベンチャーズ・アーベー | 椎間板ヘルニアの治療のための方法及び組成物 |
Also Published As
| Publication number | Publication date |
|---|---|
| MXPA05012275A (es) | 2006-02-10 |
| WO2005000283A2 (en) | 2005-01-06 |
| AU2004251042A1 (en) | 2005-01-06 |
| CA2525928A1 (en) | 2005-01-06 |
| KR20060014048A (ko) | 2006-02-14 |
| EP1631266A2 (en) | 2006-03-08 |
| EP2286804A1 (en) | 2011-02-23 |
| AU2004251042A2 (en) | 2005-01-06 |
| WO2005000283A3 (en) | 2005-08-11 |
| BRPI0410331A (pt) | 2006-05-30 |
| EP1631266B1 (en) | 2011-03-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8361467B2 (en) | Trans-capsular administration of high specificity cytokine inhibitors into orthopedic joints | |
| US8067397B2 (en) | Transdiscal administration of cycline compounds | |
| US8728523B2 (en) | Transdiscal administration of specific inhibitors of pro-inflammatory cytokines | |
| EP1631266B1 (en) | A method of treating degenerative disc disease | |
| US7429378B2 (en) | Transdiscal administration of high affinity anti-MMP inhibitors | |
| US20040229878A1 (en) | Transdiscal administration of specific inhibitors of P38 kinase | |
| AU2004294967B2 (en) | Local intraosseous administration of bone forming agents and anti-resorptive agents, and devices therefor | |
| US8986696B2 (en) | Trans-capsular administration of p38 map kinase inhibitors into orthopedic joints | |
| US20090162351A1 (en) | Transdiscal administration of inhibitors of p38 MAP kinase | |
| AU2007203631A1 (en) | Method and formulation of treating degenerative disc disease | |
| MXPA06006007A (en) | Local intraosseous administration of bone forming agents and anti-resorptive agents, and devices therefor |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20070425 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20070425 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20071203 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20080926 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20100518 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20101019 |