JP2000513020A - イヌにおける疼痛および炎症治療用ｃｏｘ−２選択性カルプロフェン - Google Patents

イヌにおける疼痛および炎症治療用ｃｏｘ−２選択性カルプロフェン

Info

Publication number: JP2000513020A
Authority: JP; Japan
Prior art keywords: cox; inhibitor; carprofen; inflammation; activity
Prior art date: 1997-05-05
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

Application number

JP10547869A

Other languages

English (en)

Japanese (ja)

Inventor

ランディ，クリスティン，マリイ

リケッツ，アンソニー，ポール

Original Assignee

ファイザーインク．

Priority date (The priority date 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 date listed.)

1997-05-05

Filing date

1998-05-01

Publication date

2000-10-03

1998-05-01 Application filed by ファイザーインク． filed Critical ファイザーインク．

2000-10-03 Publication of JP2000513020A publication Critical patent/JP2000513020A/ja

Status Pending legal-status Critical Current

Links

102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 title claims abstract description 205
241000282472 Canis lupus familiaris Species 0.000 title claims abstract description 196
230000004054 inflammatory process Effects 0.000 title claims abstract description 116
206010061218 Inflammation Diseases 0.000 title claims abstract description 115
229960003184 carprofen Drugs 0.000 title claims description 196
208000002193 Pain Diseases 0.000 title claims description 67
238000011282 treatment Methods 0.000 title claims description 50
108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 title 1
IVUMCTKHWDRRMH-UHFFFAOYSA-N carprofen Chemical compound C1=CC(Cl)=C[C]2C3=CC=C(C(C(O)=O)C)C=C3N=C21 IVUMCTKHWDRRMH-UHFFFAOYSA-N 0.000 title 1
PUXBGTOOZJQSKH-UHFFFAOYSA-N carprofen Chemical compound C1=C(Cl)C=C2C3=CC=C(C(C(O)=O)C)C=C3NC2=C1 PUXBGTOOZJQSKH-UHFFFAOYSA-N 0.000 claims abstract description 213
108010037462 Cyclooxygenase 2 Proteins 0.000 claims abstract description 211
239000003112 inhibitor Substances 0.000 claims abstract description 164
230000005764 inhibitory process Effects 0.000 claims abstract description 136
150000001875 compounds Chemical class 0.000 claims abstract description 123
230000000694 effects Effects 0.000 claims abstract description 109
230000003110 anti-inflammatory effect Effects 0.000 claims abstract description 86
230000002401 inhibitory effect Effects 0.000 claims abstract description 51
-1 heteroaryl acetic acids Chemical class 0.000 claims abstract description 36
210000004369 blood Anatomy 0.000 claims abstract description 34
239000008280 blood Substances 0.000 claims abstract description 34
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 31
201000010099 disease Diseases 0.000 claims abstract description 30
108010037464 Cyclooxygenase 1 Proteins 0.000 claims abstract description 23
102100038277 Prostaglandin G/H synthase 1 Human genes 0.000 claims abstract description 23
239000000470 constituent Substances 0.000 claims abstract description 12
230000001939 inductive effect Effects 0.000 claims abstract description 3
239000002552 dosage form Substances 0.000 claims description 105
239000000203 mixture Substances 0.000 claims description 105
239000003814 drug Substances 0.000 claims description 104
229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims description 86
229940079593 drug Drugs 0.000 claims description 75
238000013270 controlled release Methods 0.000 claims description 69
238000000034 method Methods 0.000 claims description 60
239000008194 pharmaceutical composition Substances 0.000 claims description 55
239000007787 solid Substances 0.000 claims description 44
239000007788 liquid Substances 0.000 claims description 41
239000004480 active ingredient Substances 0.000 claims description 37
241000894007 species Species 0.000 claims description 31
239000000839 emulsion Substances 0.000 claims description 29
238000001802 infusion Methods 0.000 claims description 26
238000002347 injection Methods 0.000 claims description 26
239000007924 injection Substances 0.000 claims description 26
239000007943 implant Substances 0.000 claims description 24
150000003839 salts Chemical group 0.000 claims description 23
229940111134 coxibs Drugs 0.000 claims description 21
239000000243 solution Substances 0.000 claims description 21
238000009472 formulation Methods 0.000 claims description 20
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
239000003255 cyclooxygenase 2 inhibitor Substances 0.000 claims description 19
239000003826 tablet Substances 0.000 claims description 19
239000002464 receptor antagonist Substances 0.000 claims description 18
229940044551 receptor antagonist Drugs 0.000 claims description 18
239000000725 suspension Substances 0.000 claims description 17
241000282465 Canis Species 0.000 claims description 16
239000002775 capsule Substances 0.000 claims description 16
230000009885 systemic effect Effects 0.000 claims description 15
230000001225 therapeutic effect Effects 0.000 claims description 15
239000007935 oral tablet Substances 0.000 claims description 14
229940124597 therapeutic agent Drugs 0.000 claims description 14
125000001309 chloro group Chemical group Cl* 0.000 claims description 13
239000003795 chemical substances by application Substances 0.000 claims description 12
238000007910 systemic administration Methods 0.000 claims description 12
125000003282 alkyl amino group Chemical group 0.000 claims description 11
125000001153 fluoro group Chemical group F* 0.000 claims description 11
150000002617 leukotrienes Chemical class 0.000 claims description 11
239000006186 oral dosage form Substances 0.000 claims description 11
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
239000002207 metabolite Substances 0.000 claims description 10
238000013268 sustained release Methods 0.000 claims description 10
IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 claims description 8
239000005541 ACE inhibitor Substances 0.000 claims description 8
229940002612 prodrug Drugs 0.000 claims description 8
239000000651 prodrug Substances 0.000 claims description 8
210000002784 stomach Anatomy 0.000 claims description 8
238000012384 transportation and delivery Methods 0.000 claims description 8
238000010521 absorption reaction Methods 0.000 claims description 7
238000011161 development Methods 0.000 claims description 7
239000003995 emulsifying agent Substances 0.000 claims description 7
239000000375 suspending agent Substances 0.000 claims description 7
239000000674 adrenergic antagonist Substances 0.000 claims description 6
229910052736 halogen Inorganic materials 0.000 claims description 6
150000002367 halogens Chemical class 0.000 claims description 6
238000007918 intramuscular administration Methods 0.000 claims description 6
238000007913 intrathecal administration Methods 0.000 claims description 6
238000001990 intravenous administration Methods 0.000 claims description 6
239000008297 liquid dosage form Substances 0.000 claims description 6
210000004072 lung Anatomy 0.000 claims description 6
239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims description 6
230000002265 prevention Effects 0.000 claims description 6
239000007909 solid dosage form Substances 0.000 claims description 6
239000012730 sustained-release form Substances 0.000 claims description 6
239000000730 antalgic agent Substances 0.000 claims description 5
238000001361 intraarterial administration Methods 0.000 claims description 5
239000007937 lozenge Substances 0.000 claims description 5
230000002441 reversible effect Effects 0.000 claims description 5
238000007920 subcutaneous administration Methods 0.000 claims description 5
239000000829 suppository Substances 0.000 claims description 5
208000011580 syndromic disease Diseases 0.000 claims description 5
LJRDOKAZOAKLDU-UDXJMMFXSA-N (2s,3s,4r,5r,6r)-5-amino-2-(aminomethyl)-6-[(2r,3s,4r,5s)-5-[(1r,2r,3s,5r,6s)-3,5-diamino-2-[(2s,3r,4r,5s,6r)-3-amino-4,5-dihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy-6-hydroxycyclohexyl]oxy-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl]oxyoxane-3,4-diol;sulfuric ac Chemical compound OS(O)(=O)=O.N[C@@H]1[C@@H](O)[C@H](O)[C@H](CN)O[C@@H]1O[C@H]1[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](N)C[C@@H](N)[C@@H]2O)O[C@@H]2[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)N)O[C@@H]1CO LJRDOKAZOAKLDU-UDXJMMFXSA-N 0.000 claims description 4
208000000044 Amnesia Diseases 0.000 claims description 4
206010002383 Angina Pectoris Diseases 0.000 claims description 4
101150071146 COX2 gene Proteins 0.000 claims description 4
206010007559 Cardiac failure congestive Diseases 0.000 claims description 4
206010019280 Heart failures Diseases 0.000 claims description 4
208000035150 Hypercholesterolemia Diseases 0.000 claims description 4
206010020772 Hypertension Diseases 0.000 claims description 4
208000026139 Memory disease Diseases 0.000 claims description 4
LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 claims description 4
TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 claims description 4
JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 4
229940122803 Vinca alkaloid Drugs 0.000 claims description 4
OFCNXPDARWKPPY-UHFFFAOYSA-N allopurinol Chemical compound OC1=NC=NC2=C1C=NN2 OFCNXPDARWKPPY-UHFFFAOYSA-N 0.000 claims description 4
229960003459 allopurinol Drugs 0.000 claims description 4
102000004305 alpha Adrenergic Receptors Human genes 0.000 claims description 4
108090000861 alpha Adrenergic Receptors Proteins 0.000 claims description 4
229940035676 analgesics Drugs 0.000 claims description 4
230000002927 anti-mitotic effect Effects 0.000 claims description 4
229940121375 antifungal agent Drugs 0.000 claims description 4
229960002708 antigout preparations Drugs 0.000 claims description 4
239000002220 antihypertensive agent Substances 0.000 claims description 4
239000002246 antineoplastic agent Substances 0.000 claims description 4
239000003904 antiprotozoal agent Substances 0.000 claims description 4
229960002529 benzbromarone Drugs 0.000 claims description 4
WHQCHUCQKNIQEC-UHFFFAOYSA-N benzbromarone Chemical compound CCC=1OC2=CC=CC=C2C=1C(=O)C1=CC(Br)=C(O)C(Br)=C1 WHQCHUCQKNIQEC-UHFFFAOYSA-N 0.000 claims description 4
102000012740 beta Adrenergic Receptors Human genes 0.000 claims description 4
108010079452 beta Adrenergic Receptors Proteins 0.000 claims description 4
239000007894 caplet Substances 0.000 claims description 4
239000002327 cardiovascular agent Substances 0.000 claims description 4
229940125692 cardiovascular agent Drugs 0.000 claims description 4
230000001055 chewing effect Effects 0.000 claims description 4
230000001149 cognitive effect Effects 0.000 claims description 4
229960001338 colchicine Drugs 0.000 claims description 4
238000009826 distribution Methods 0.000 claims description 4
239000002934 diuretic Substances 0.000 claims description 4
239000002792 enkephalinase inhibitor Substances 0.000 claims description 4
210000000416 exudates and transudate Anatomy 0.000 claims description 4
230000037406 food intake Effects 0.000 claims description 4
230000002178 gastroprotective effect Effects 0.000 claims description 4
239000003862 glucocorticoid Substances 0.000 claims description 4
PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 claims description 4
239000010931 gold Substances 0.000 claims description 4
229910052737 gold Inorganic materials 0.000 claims description 4
239000003324 growth hormone secretagogue Substances 0.000 claims description 4
229960003444 immunosuppressant agent Drugs 0.000 claims description 4
239000003018 immunosuppressive agent Substances 0.000 claims description 4
230000006984 memory degeneration Effects 0.000 claims description 4
208000023060 memory loss Diseases 0.000 claims description 4
208000010125 myocardial infarction Diseases 0.000 claims description 4
229960001639 penicillamine Drugs 0.000 claims description 4
239000002089 prostaglandin antagonist Substances 0.000 claims description 4
239000002461 renin inhibitor Substances 0.000 claims description 4
229940086526 renin-inhibitors Drugs 0.000 claims description 4
229940037128 systemic glucocorticoids Drugs 0.000 claims description 4
229940116269 uric acid Drugs 0.000 claims description 4
229940124549 vasodilator Drugs 0.000 claims description 4
239000003071 vasodilator agent Substances 0.000 claims description 4
229960003048 vinblastine Drugs 0.000 claims description 4
JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 4
OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 4
229960004528 vincristine Drugs 0.000 claims description 4
OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 4
239000003064 xanthine oxidase inhibitor Substances 0.000 claims description 4
102000005862 Angiotensin II Human genes 0.000 claims description 3
101800000733 Angiotensin-2 Proteins 0.000 claims description 3
201000001320 Atherosclerosis Diseases 0.000 claims description 3
241000894006 Bacteria Species 0.000 claims description 3
101100114534 Caenorhabditis elegans ctc-2 gene Proteins 0.000 claims description 3
229940127291 Calcium channel antagonist Drugs 0.000 claims description 3
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 description 3
108010036949 Cyclosporine Proteins 0.000 claims description 3
241000233866 Fungi Species 0.000 claims description 3
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 description 3
101150000187 PTGS2 gene Proteins 0.000 claims description 3
108700023400 Platelet-activating factor receptors Proteins 0.000 claims description 3
239000000150 Sympathomimetic Substances 0.000 claims description 3
241000700605 Viruses Species 0.000 claims description 3
229940123769 Xanthine oxidase inhibitor Drugs 0.000 claims description 3
239000002333 angiotensin II receptor antagonist Substances 0.000 claims description 3
229950006323 angiotensin ii Drugs 0.000 claims description 3
230000000840 anti-viral effect Effects 0.000 claims description 3
229940030600 antihypertensive agent Drugs 0.000 claims description 3
LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 claims description 3
229960002170 azathioprine Drugs 0.000 claims description 3
239000000480 calcium channel blocker Substances 0.000 claims description 3
229960001265 ciclosporin Drugs 0.000 claims description 3
239000012141 concentrate Substances 0.000 claims description 3
229930182912 cyclosporin Natural products 0.000 claims description 3
229940030606 diuretics Drugs 0.000 claims description 3
239000000284 extract Substances 0.000 claims description 3
239000003193 general anesthetic agent Substances 0.000 claims description 3
229940005494 general anesthetics Drugs 0.000 claims description 3
239000003589 local anesthetic agent Substances 0.000 claims description 3
229960005015 local anesthetics Drugs 0.000 claims description 3
229960000485 methotrexate Drugs 0.000 claims description 3
239000011859 microparticle Substances 0.000 claims description 3
208000031225 myocardial ischemia Diseases 0.000 claims description 3
102000030769 platelet activating factor receptor Human genes 0.000 claims description 3
DBABZHXKTCFAPX-UHFFFAOYSA-N probenecid Chemical compound CCCN(CCC)S(=O)(=O)C1=CC=C(C(O)=O)C=C1 DBABZHXKTCFAPX-UHFFFAOYSA-N 0.000 claims description 3
229960003081 probenecid Drugs 0.000 claims description 3
229960003329 sulfinpyrazone Drugs 0.000 claims description 3
MBGGBVCUIVRRBF-UHFFFAOYSA-N sulfinpyrazone Chemical compound O=C1N(C=2C=CC=CC=2)N(C=2C=CC=CC=2)C(=O)C1CCS(=O)C1=CC=CC=C1 MBGGBVCUIVRRBF-UHFFFAOYSA-N 0.000 claims description 3
230000001975 sympathomimetic effect Effects 0.000 claims description 3
239000003242 anti bacterial agent Substances 0.000 claims description 2
230000000843 anti-fungal effect Effects 0.000 claims description 2
230000000842 anti-protozoal effect Effects 0.000 claims description 2
229940088710 antibiotic agent Drugs 0.000 claims description 2
230000003115 biocidal effect Effects 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
239000008187 granular material Substances 0.000 claims description 2
229940041667 oral paste Drugs 0.000 claims description 2
229940100692 oral suspension Drugs 0.000 claims description 2
238000003860 storage Methods 0.000 claims description 2
238000012385 systemic delivery Methods 0.000 claims description 2
125000006526 (C1-C2) alkyl group Chemical group 0.000 claims 12
239000000867 Lipoxygenase Inhibitor Substances 0.000 claims 4
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 3
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 3
102100033367 Appetite-regulating hormone Human genes 0.000 claims 2
101710111255 Appetite-regulating hormone Proteins 0.000 claims 2
229940121710 HMGCoA reductase inhibitor Drugs 0.000 claims 2
CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C([O-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 claims 2
239000000384 adrenergic alpha-2 receptor agonist Substances 0.000 claims 2
229940126317 angiotensin II receptor antagonist Drugs 0.000 claims 2
229940041181 antineoplastic drug Drugs 0.000 claims 2
XXSMGPRMXLTPCZ-UHFFFAOYSA-N hydroxychloroquine Chemical compound ClC1=CC=C2C(NC(C)CCCN(CCO)CC)=CC=NC2=C1 XXSMGPRMXLTPCZ-UHFFFAOYSA-N 0.000 claims 2
229960004171 hydroxychloroquine Drugs 0.000 claims 2
239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 claims 2
230000001861 immunosuppressant effect Effects 0.000 claims 2
229940096701 plain lipid modifying drug hmg coa reductase inhibitors Drugs 0.000 claims 2
239000000612 proton pump inhibitor Substances 0.000 claims 2
229940126409 proton pump inhibitor Drugs 0.000 claims 2
IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 claims 2
DSNBHJFQCNUKMA-SCKDECHMSA-N thromboxane A2 Chemical compound OC(=O)CCC\C=C/C[C@@H]1[C@@H](/C=C/[C@@H](O)CCCCC)O[C@@H]2O[C@H]1C2 DSNBHJFQCNUKMA-SCKDECHMSA-N 0.000 claims 2
230000002924 anti-infective effect Effects 0.000 claims 1
239000007950 delayed release tablet Substances 0.000 claims 1
239000002702 enteric coating Substances 0.000 claims 1
238000009505 enteric coating Methods 0.000 claims 1
229940059096 powder for oral suspension Drugs 0.000 claims 1
239000002253 acid Substances 0.000 abstract description 31
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 abstract description 30
239000000126 substance Substances 0.000 abstract description 16
SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 abstract description 12
RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical class NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 abstract description 11
150000007513 acids Chemical class 0.000 abstract description 8
PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 abstract description 6
RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 abstract description 6
PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical class NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 abstract description 5
235000011054 acetic acid Nutrition 0.000 abstract description 4
PDODBKYPSUYQGT-UHFFFAOYSA-N acetic acid;1h-indene Chemical class CC(O)=O.C1=CC=C2CC=CC2=C1 PDODBKYPSUYQGT-UHFFFAOYSA-N 0.000 abstract description 4
235000019260 propionic acid Nutrition 0.000 abstract description 4
229940058287 salicylic acid derivative anticestodals Drugs 0.000 abstract description 3
150000003872 salicylic acid derivatives Chemical class 0.000 abstract description 3
108010044467 Isoenzymes Proteins 0.000 description 49
210000002381 plasma Anatomy 0.000 description 42
230000036470 plasma concentration Effects 0.000 description 25
238000012360 testing method Methods 0.000 description 24
239000012071 phase Substances 0.000 description 23
150000003180 prostaglandins Chemical class 0.000 description 23
210000001519 tissue Anatomy 0.000 description 23
102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 21
108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 21
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
239000012729 immediate-release (IR) formulation Substances 0.000 description 20
YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 18
230000002496 gastric effect Effects 0.000 description 18
102000004190 Enzymes Human genes 0.000 description 17
108090000790 Enzymes Proteins 0.000 description 17
125000000217 alkyl group Chemical group 0.000 description 17
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
230000009471 action Effects 0.000 description 14
229940124599 anti-inflammatory drug Drugs 0.000 description 14
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
238000004519 manufacturing process Methods 0.000 description 13
150000001732 carboxylic acid derivatives Chemical group 0.000 description 12
238000006243 chemical reaction Methods 0.000 description 12
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
238000000338 in vitro Methods 0.000 description 12
CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 12
238000005259 measurement Methods 0.000 description 12
201000008482 osteoarthritis Diseases 0.000 description 12
241000282414 Homo sapiens Species 0.000 description 11
229940124639 Selective inhibitor Drugs 0.000 description 11
230000002411 adverse Effects 0.000 description 11
239000000463 material Substances 0.000 description 11
230000015572 biosynthetic process Effects 0.000 description 10
230000037396 body weight Effects 0.000 description 10
210000004027 cell Anatomy 0.000 description 10
230000003111 delayed effect Effects 0.000 description 10
210000001035 gastrointestinal tract Anatomy 0.000 description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
229940094443 oxytocics prostaglandins Drugs 0.000 description 10
206010067484 Adverse reaction Diseases 0.000 description 9
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
241000282412 Homo Species 0.000 description 9
HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 9
241001465754 Metazoa Species 0.000 description 9
230000006838 adverse reaction Effects 0.000 description 9
229940114079 arachidonic acid Drugs 0.000 description 9
235000021342 arachidonic acid Nutrition 0.000 description 9
239000002585 base Substances 0.000 description 9
239000002158 endotoxin Substances 0.000 description 9
210000003491 skin Anatomy 0.000 description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Natural products CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
230000002757 inflammatory effect Effects 0.000 description 8
229920006008 lipopolysaccharide Polymers 0.000 description 8
230000002829 reductive effect Effects 0.000 description 8
102100036201 Oxygen-dependent coproporphyrinogen-III oxidase, mitochondrial Human genes 0.000 description 7
241000700159 Rattus Species 0.000 description 7
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 7
230000007246 mechanism Effects 0.000 description 7
230000003389 potentiating effect Effects 0.000 description 7
239000000047 product Substances 0.000 description 7
239000000758 substrate Substances 0.000 description 7
208000024891 symptom Diseases 0.000 description 7
238000011200 topical administration Methods 0.000 description 7
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
208000032843 Hemorrhage Diseases 0.000 description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
125000003545 alkoxy group Chemical group 0.000 description 6
230000000202 analgesic effect Effects 0.000 description 6
239000002260 anti-inflammatory agent Substances 0.000 description 6
230000004071 biological effect Effects 0.000 description 6
230000000740 bleeding effect Effects 0.000 description 6
238000011260 co-administration Methods 0.000 description 6
238000001727 in vivo Methods 0.000 description 6
229960000905 indomethacin Drugs 0.000 description 6
238000003786 synthesis reaction Methods 0.000 description 6
PUXBGTOOZJQSKH-QMMMGPOBSA-N (S)-carprofen Chemical compound C1=C(Cl)C=C2C3=CC=C([C@@H](C(O)=O)C)C=C3NC2=C1 PUXBGTOOZJQSKH-QMMMGPOBSA-N 0.000 description 5
102000000589 Interleukin-1 Human genes 0.000 description 5
108010002352 Interleukin-1 Proteins 0.000 description 5
208000025865 Ulcer Diseases 0.000 description 5
238000004364 calculation method Methods 0.000 description 5
229910052799 carbon Inorganic materials 0.000 description 5
239000000679 carrageenan Substances 0.000 description 5
235000010418 carrageenan Nutrition 0.000 description 5
229920001525 carrageenan Polymers 0.000 description 5
229940113118 carrageenan Drugs 0.000 description 5
230000002354 daily effect Effects 0.000 description 5
XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 5
239000003651 drinking water Substances 0.000 description 5
235000020188 drinking water Nutrition 0.000 description 5
238000011156 evaluation Methods 0.000 description 5
230000010534 mechanism of action Effects 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 5
239000008363 phosphate buffer Substances 0.000 description 5
238000002360 preparation method Methods 0.000 description 5
RZWIIPASKMUIAC-VQTJNVASSA-N thromboxane Chemical compound CCCCCCCC[C@H]1OCCC[C@@H]1CCCCCCC RZWIIPASKMUIAC-VQTJNVASSA-N 0.000 description 5
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 5
231100000397 ulcer Toxicity 0.000 description 5
UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 5
HSJIVJPREZQHFK-UHFFFAOYSA-N 2-(9h-carbazol-2-yl)propanoic acid Chemical compound C1=CC=C2C3=CC=C(C(C(O)=O)C)C=C3NC2=C1 HSJIVJPREZQHFK-UHFFFAOYSA-N 0.000 description 4
KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical group NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
108091006146 Channels Proteins 0.000 description 4
101001098352 Homo sapiens OX-2 membrane glycoprotein Proteins 0.000 description 4
102000003820 Lipoxygenases Human genes 0.000 description 4
108090000128 Lipoxygenases Proteins 0.000 description 4
102100037589 OX-2 membrane glycoprotein Human genes 0.000 description 4
208000004550 Postoperative Pain Diseases 0.000 description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
238000013459 approach Methods 0.000 description 4
238000010790 dilution Methods 0.000 description 4
239000012895 dilution Substances 0.000 description 4
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 description 4
210000002615 epidermis Anatomy 0.000 description 4
230000006870 function Effects 0.000 description 4
230000009931 harmful effect Effects 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
238000011835 investigation Methods 0.000 description 4
210000001503 joint Anatomy 0.000 description 4
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
210000004877 mucosa Anatomy 0.000 description 4
229940096978 oral tablet Drugs 0.000 description 4
108090000623 proteins and genes Proteins 0.000 description 4
102000004169 proteins and genes Human genes 0.000 description 4
239000002904 solvent Substances 0.000 description 4
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 4
ZIIUUSVHCHPIQD-UHFFFAOYSA-N 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide Chemical compound CC1=CC(C)=CC(C)=C1S(=O)(=O)NC1=CC=CC(C(F)(F)F)=C1 ZIIUUSVHCHPIQD-UHFFFAOYSA-N 0.000 description 3
HIYAVKIYRIFSCZ-CYEMHPAKSA-N 5-(methylamino)-2-[[(2S,3R,5R,6S,8R,9R)-3,5,9-trimethyl-2-[(2S)-1-oxo-1-(1H-pyrrol-2-yl)propan-2-yl]-1,7-dioxaspiro[5.5]undecan-8-yl]methyl]-1,3-benzoxazole-4-carboxylic acid Chemical compound O=C([C@@H](C)[C@H]1O[C@@]2([C@@H](C[C@H]1C)C)O[C@@H]([C@@H](CC2)C)CC=1OC2=CC=C(C(=C2N=1)C(O)=O)NC)C1=CC=CN1 HIYAVKIYRIFSCZ-CYEMHPAKSA-N 0.000 description 3
239000004475 Arginine Substances 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
208000017667 Chronic Disease Diseases 0.000 description 3
208000000094 Chronic Pain Diseases 0.000 description 3
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 3
108010061435 Enalapril Proteins 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
235000005135 Micromeria juliana Nutrition 0.000 description 3
206010028980 Neoplasm Diseases 0.000 description 3
102000015439 Phospholipases Human genes 0.000 description 3
108010064785 Phospholipases Proteins 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
206010037660 Pyrexia Diseases 0.000 description 3
241000246354 Satureja Species 0.000 description 3
235000007315 Satureja hortensis Nutrition 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
239000005557 antagonist Substances 0.000 description 3
ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 3
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
208000034158 bleeding Diseases 0.000 description 3
230000036760 body temperature Effects 0.000 description 3
239000000872 buffer Substances 0.000 description 3
239000003710 calcium ionophore Substances 0.000 description 3
HIYAVKIYRIFSCZ-UHFFFAOYSA-N calcium ionophore A23187 Natural products N=1C2=C(C(O)=O)C(NC)=CC=C2OC=1CC(C(CC1)C)OC1(C(CC1C)C)OC1C(C)C(=O)C1=CC=CN1 HIYAVKIYRIFSCZ-UHFFFAOYSA-N 0.000 description 3
230000008859 change Effects 0.000 description 3
208000037976 chronic inflammation Diseases 0.000 description 3
229940000425 combination drug Drugs 0.000 description 3
230000006378 damage Effects 0.000 description 3
208000037765 diseases and disorders Diseases 0.000 description 3
150000002066 eicosanoids Chemical class 0.000 description 3
GBXSMTUPTTWBMN-XIRDDKMYSA-N enalapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 GBXSMTUPTTWBMN-XIRDDKMYSA-N 0.000 description 3
229960000873 enalapril Drugs 0.000 description 3
210000002889 endothelial cell Anatomy 0.000 description 3
238000005516 engineering process Methods 0.000 description 3
CJAONIOAQZUHPN-KKLWWLSJSA-N ethyl 12-[[2-[(2r,3r)-3-[2-[(12-ethoxy-12-oxododecyl)-methylamino]-2-oxoethoxy]butan-2-yl]oxyacetyl]-methylamino]dodecanoate Chemical compound CCOC(=O)CCCCCCCCCCCN(C)C(=O)CO[C@H](C)[C@@H](C)OCC(=O)N(C)CCCCCCCCCCCC(=O)OCC CJAONIOAQZUHPN-KKLWWLSJSA-N 0.000 description 3
238000001914 filtration Methods 0.000 description 3
229960002390 flurbiprofen Drugs 0.000 description 3
SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 3
235000013305 food Nutrition 0.000 description 3
125000001072 heteroaryl group Chemical group 0.000 description 3
230000001976 improved effect Effects 0.000 description 3
230000001965 increasing effect Effects 0.000 description 3
208000027866 inflammatory disease Diseases 0.000 description 3
239000004615 ingredient Substances 0.000 description 3
230000003993 interaction Effects 0.000 description 3
230000007794 irritation Effects 0.000 description 3
DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 description 3
229960000991 ketoprofen Drugs 0.000 description 3
230000001404 mediated effect Effects 0.000 description 3
239000002609 medium Substances 0.000 description 3
CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 3
210000000440 neutrophil Anatomy 0.000 description 3
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 3
229910052757 nitrogen Inorganic materials 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
230000000144 pharmacologic effect Effects 0.000 description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
230000001681 protective effect Effects 0.000 description 3
238000001953 recrystallisation Methods 0.000 description 3
238000011160 research Methods 0.000 description 3
230000004044 response Effects 0.000 description 3
210000002966 serum Anatomy 0.000 description 3
230000000638 stimulation Effects 0.000 description 3
229940124530 sulfonamide Drugs 0.000 description 3
125000000565 sulfonamide group Chemical group 0.000 description 3
239000007916 tablet composition Substances 0.000 description 3
231100001274 therapeutic index Toxicity 0.000 description 3
230000000699 topical effect Effects 0.000 description 3
RQEUFEKYXDPUSK-SSDOTTSWSA-N (1R)-1-phenylethanamine Chemical compound C[C@@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-SSDOTTSWSA-N 0.000 description 2
YKFCISHFRZHKHY-NGQGLHOPSA-N (2s)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid;trihydrate Chemical compound O.O.O.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1.OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1 YKFCISHFRZHKHY-NGQGLHOPSA-N 0.000 description 2
HZNVUJQVZSTENZ-UHFFFAOYSA-N 2,3-dichloro-5,6-dicyano-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(C#N)=C(C#N)C1=O HZNVUJQVZSTENZ-UHFFFAOYSA-N 0.000 description 2
UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
108091003079 Bovine Serum Albumin Proteins 0.000 description 2
239000002083 C09CA01 - Losartan Substances 0.000 description 2
241000252233 Cyprinus carpio Species 0.000 description 2
206010011732 Cyst Diseases 0.000 description 2
239000012981 Hank's balanced salt solution Substances 0.000 description 2
RPTUSVTUFVMDQK-UHFFFAOYSA-N Hidralazin Chemical compound C1=CC=C2C(NN)=NN=CC2=C1 RPTUSVTUFVMDQK-UHFFFAOYSA-N 0.000 description 2
NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
101000605127 Homo sapiens Prostaglandin G/H synthase 2 Proteins 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
206010027727 Mitral valve incompetence Diseases 0.000 description 2
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 2
241000699666 Mus <mouse, genus> Species 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
BLXXJMDCKKHMKV-UHFFFAOYSA-N Nabumetone Chemical compound C1=C(CCC(C)=O)C=CC2=CC(OC)=CC=C21 BLXXJMDCKKHMKV-UHFFFAOYSA-N 0.000 description 2
STJFYCWYHROASW-UHFFFAOYSA-N O-methyl-glaucamine Natural products CN1CCC2=CC(OC)=C(OC)C=C2C2OC(OC)C3=C4OCOC4=CC=C3C12 STJFYCWYHROASW-UHFFFAOYSA-N 0.000 description 2
206010030113 Oedema Diseases 0.000 description 2
MITFXPHMIHQXPI-UHFFFAOYSA-N Oraflex Chemical compound N=1C2=CC(C(C(O)=O)C)=CC=C2OC=1C1=CC=C(Cl)C=C1 MITFXPHMIHQXPI-UHFFFAOYSA-N 0.000 description 2
102000004020 Oxygenases Human genes 0.000 description 2
108090000417 Oxygenases Proteins 0.000 description 2
229910019142 PO4 Inorganic materials 0.000 description 2
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
239000004743 Polypropylene Substances 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
206010037742 Rabies Diseases 0.000 description 2
229940123934 Reductase inhibitor Drugs 0.000 description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical group OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 2
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 2
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 2
230000001154 acute effect Effects 0.000 description 2
208000005298 acute pain Diseases 0.000 description 2
239000002671 adjuvant Substances 0.000 description 2
239000000048 adrenergic agonist Substances 0.000 description 2
125000002877 alkyl aryl group Chemical group 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
230000003466 anti-cipated effect Effects 0.000 description 2
230000001754 anti-pyretic effect Effects 0.000 description 2
239000003080 antimitotic agent Substances 0.000 description 2
239000012736 aqueous medium Substances 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
230000009286 beneficial effect Effects 0.000 description 2
230000008901 benefit Effects 0.000 description 2
239000011575 calcium Substances 0.000 description 2
239000007963 capsule composition Substances 0.000 description 2
150000007942 carboxylates Chemical class 0.000 description 2
125000002843 carboxylic acid group Chemical group 0.000 description 2
229940083181 centrally acting adntiadrenergic agent methyldopa Drugs 0.000 description 2
238000005119 centrifugation Methods 0.000 description 2
230000001684 chronic effect Effects 0.000 description 2
230000006020 chronic inflammation Effects 0.000 description 2
JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
208000031513 cyst Diseases 0.000 description 2
235000005911 diet Nutrition 0.000 description 2
230000037213 diet Effects 0.000 description 2
239000006185 dispersion Substances 0.000 description 2
239000000890 drug combination Substances 0.000 description 2
238000001035 drying Methods 0.000 description 2
239000002662 enteric coated tablet Substances 0.000 description 2
230000005284 excitation Effects 0.000 description 2
230000029142 excretion Effects 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
238000000605 extraction Methods 0.000 description 2
239000004744 fabric Substances 0.000 description 2
239000012530 fluid Substances 0.000 description 2
238000001917 fluorescence detection Methods 0.000 description 2
239000000499 gel Substances 0.000 description 2
239000003102 growth factor Substances 0.000 description 2
230000036541 health Effects 0.000 description 2
125000000487 histidyl group Chemical group [H]N([H])C(C(=O)O*)C([H])([H])C1=C([H])N([H])C([H])=N1 0.000 description 2
230000002209 hydrophobic effect Effects 0.000 description 2
VKOBVWXKNCXXDE-UHFFFAOYSA-N icosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCC(O)=O VKOBVWXKNCXXDE-UHFFFAOYSA-N 0.000 description 2
230000036039 immunity Effects 0.000 description 2
238000011534 incubation Methods 0.000 description 2
210000000936 intestine Anatomy 0.000 description 2
208000028867 ischemia Diseases 0.000 description 2
229960000310 isoleucine Drugs 0.000 description 2
AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
OZWKMVRBQXNZKK-UHFFFAOYSA-N ketorolac Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 OZWKMVRBQXNZKK-UHFFFAOYSA-N 0.000 description 2
229960004752 ketorolac Drugs 0.000 description 2
210000003734 kidney Anatomy 0.000 description 2
210000000265 leukocyte Anatomy 0.000 description 2
KJJZZJSZUJXYEA-UHFFFAOYSA-N losartan Chemical compound CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C=2[N]N=NN=2)C=C1 KJJZZJSZUJXYEA-UHFFFAOYSA-N 0.000 description 2
229960004773 losartan Drugs 0.000 description 2
229960004844 lovastatin Drugs 0.000 description 2
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 2
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 2
210000002540 macrophage Anatomy 0.000 description 2
235000019359 magnesium stearate Nutrition 0.000 description 2
231100000682 maximum tolerated dose Toxicity 0.000 description 2
238000000691 measurement method Methods 0.000 description 2
210000004379 membrane Anatomy 0.000 description 2
239000012528 membrane Substances 0.000 description 2
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
230000005012 migration Effects 0.000 description 2
238000013508 migration Methods 0.000 description 2
229960004270 nabumetone Drugs 0.000 description 2
239000002674 ointment Substances 0.000 description 2
239000000014 opioid analgesic Substances 0.000 description 2
229940005483 opioid analgesics Drugs 0.000 description 2
230000003287 optical effect Effects 0.000 description 2
210000004789 organ system Anatomy 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
239000012074 organic phase Substances 0.000 description 2
239000002245 particle Substances 0.000 description 2
206010034674 peritonitis Diseases 0.000 description 2
235000021317 phosphate Nutrition 0.000 description 2
150000003013 phosphoric acid derivatives Chemical class 0.000 description 2
229920001155 polypropylene Polymers 0.000 description 2
230000002980 postoperative effect Effects 0.000 description 2
239000000843 powder Substances 0.000 description 2
IENZQIKPVFGBNW-UHFFFAOYSA-N prazosin Chemical compound N=1C(N)=C2C=C(OC)C(OC)=CC2=NC=1N(CC1)CCN1C(=O)C1=CC=CO1 IENZQIKPVFGBNW-UHFFFAOYSA-N 0.000 description 2
229960001289 prazosin Drugs 0.000 description 2
AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
JWHOQZUREKYPBY-UHFFFAOYSA-N rubonic acid Natural products CC1(C)CCC2(CCC3(C)C(=CCC4C5(C)CCC(=O)C(C)(C)C5CC(=O)C34C)C2C1)C(=O)O JWHOQZUREKYPBY-UHFFFAOYSA-N 0.000 description 2
QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
239000011734 sodium Substances 0.000 description 2
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 2
238000010561 standard procedure Methods 0.000 description 2
230000000707 stereoselective effect Effects 0.000 description 2
238000006467 substitution reaction Methods 0.000 description 2
150000003456 sulfonamides Chemical group 0.000 description 2
229910052717 sulfur Inorganic materials 0.000 description 2
239000011593 sulfur Substances 0.000 description 2
238000001356 surgical procedure Methods 0.000 description 2
230000002459 sustained effect Effects 0.000 description 2
210000001179 synovial fluid Anatomy 0.000 description 2
230000001839 systemic circulation Effects 0.000 description 2
230000000451 tissue damage Effects 0.000 description 2
231100000827 tissue damage Toxicity 0.000 description 2
230000008791 toxic response Effects 0.000 description 2
238000012546 transfer Methods 0.000 description 2
239000004474 valine Substances 0.000 description 2
210000003462 vein Anatomy 0.000 description 2
QGVLYPPODPLXMB-UBTYZVCOSA-N (1aR,1bS,4aR,7aS,7bS,8R,9R,9aS)-4a,7b,9,9a-tetrahydroxy-3-(hydroxymethyl)-1,1,6,8-tetramethyl-1,1a,1b,4,4a,7a,7b,8,9,9a-decahydro-5H-cyclopropa[3,4]benzo[1,2-e]azulen-5-one Chemical compound C1=C(CO)C[C@]2(O)C(=O)C(C)=C[C@H]2[C@@]2(O)[C@H](C)[C@@H](O)[C@@]3(O)C(C)(C)[C@H]3[C@@H]21 QGVLYPPODPLXMB-UBTYZVCOSA-N 0.000 description 1
RJMIEHBSYVWVIN-LLVKDONJSA-N (2r)-2-[4-(3-oxo-1h-isoindol-2-yl)phenyl]propanoic acid Chemical compound C1=CC([C@H](C(O)=O)C)=CC=C1N1C(=O)C2=CC=CC=C2C1 RJMIEHBSYVWVIN-LLVKDONJSA-N 0.000 description 1
RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 description 1
MDKGKXOCJGEUJW-VIFPVBQESA-N (2s)-2-[4-(thiophene-2-carbonyl)phenyl]propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C(=O)C1=CC=CS1 MDKGKXOCJGEUJW-VIFPVBQESA-N 0.000 description 1
CUKWUWBLQQDQAC-VEQWQPCFSA-N (3s)-3-amino-4-[[(2s)-1-[[(2s)-1-[[(2s)-1-[[(2s,3s)-1-[[(2s)-1-[(2s)-2-[[(1s)-1-carboxyethyl]carbamoyl]pyrrolidin-1-yl]-3-(1h-imidazol-5-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-methyl-1-ox Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 CUKWUWBLQQDQAC-VEQWQPCFSA-N 0.000 description 1
GYPCWHHQAVLMKO-XXKQIVDLSA-N (7s,9s)-7-[(2r,4s,5s,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-[(e)-n-[(1-hydroxy-2,2,6,6-tetramethylpiperidin-4-ylidene)amino]-c-methylcarbonimidoyl]-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;hydrochloride Chemical group Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(\C)=N\N=C1CC(C)(C)N(O)C(C)(C)C1)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 GYPCWHHQAVLMKO-XXKQIVDLSA-N 0.000 description 1
XKLNOVWDVMWTOB-UHFFFAOYSA-N 2,3,4,9-tetrahydro-1h-carbazole Chemical compound N1C2=CC=CC=C2C2=C1CCCC2 XKLNOVWDVMWTOB-UHFFFAOYSA-N 0.000 description 1
JALUUBQFLPUJMY-UHFFFAOYSA-N 2-(4-phenylphenyl)propanoic acid Chemical compound C1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 JALUUBQFLPUJMY-UHFFFAOYSA-N 0.000 description 1
XEDSZIKWEGZUTC-UHFFFAOYSA-N 2-(9h-carbazol-2-yl)acetic acid Chemical compound C1=CC=C2C3=CC=C(CC(=O)O)C=C3NC2=C1 XEDSZIKWEGZUTC-UHFFFAOYSA-N 0.000 description 1
LRXFKKPEBXIPMW-UHFFFAOYSA-N 2-(9h-fluoren-2-yl)propanoic acid Chemical compound C1=CC=C2C3=CC=C(C(C(O)=O)C)C=C3CC2=C1 LRXFKKPEBXIPMW-UHFFFAOYSA-N 0.000 description 1
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
VRGCYEIGVVTZCC-UHFFFAOYSA-N 3,4,5,6-tetrachlorocyclohexa-3,5-diene-1,2-dione Chemical compound ClC1=C(Cl)C(=O)C(=O)C(Cl)=C1Cl VRGCYEIGVVTZCC-UHFFFAOYSA-N 0.000 description 1
102000008873 Angiotensin II receptor Human genes 0.000 description 1
108050000824 Angiotensin II receptor Proteins 0.000 description 1
108010064733 Angiotensins Proteins 0.000 description 1
102000015427 Angiotensins Human genes 0.000 description 1
YZXBAPSDXZZRGB-DOFZRALJSA-M Arachidonate Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC([O-])=O YZXBAPSDXZZRGB-DOFZRALJSA-M 0.000 description 1
102000011730 Arachidonate 12-Lipoxygenase Human genes 0.000 description 1
108010076676 Arachidonate 12-lipoxygenase Proteins 0.000 description 1
102000001381 Arachidonate 5-Lipoxygenase Human genes 0.000 description 1
108010093579 Arachidonate 5-lipoxygenase Proteins 0.000 description 1
BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 description 1
208000035143 Bacterial infection Diseases 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
108010017384 Blood Proteins Proteins 0.000 description 1
102000004506 Blood Proteins Human genes 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
101800004538 Bradykinin Proteins 0.000 description 1
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
102000016289 Cell Adhesion Molecules Human genes 0.000 description 1
108010067225 Cell Adhesion Molecules Proteins 0.000 description 1
241001232566 Chamaeleo sp. Species 0.000 description 1
VYZAMTAEIAYCRO-UHFFFAOYSA-N Chromium Chemical compound [Cr] VYZAMTAEIAYCRO-UHFFFAOYSA-N 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
229920002261 Corn starch Polymers 0.000 description 1
240000004487 Cynoglossum officinale Species 0.000 description 1
235000004266 Cynoglossum officinale Nutrition 0.000 description 1
102000004127 Cytokines Human genes 0.000 description 1
108090000695 Cytokines Proteins 0.000 description 1
206010073767 Developmental hip dysplasia Diseases 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
206010061818 Disease progression Diseases 0.000 description 1
238000011891 EIA kit Methods 0.000 description 1
206010015150 Erythema Diseases 0.000 description 1
UOACKFBJUYNSLK-XRKIENNPSA-N Estradiol Cypionate Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H](C4=CC=C(O)C=C4CC3)CC[C@@]21C)C(=O)CCC1CCCC1 UOACKFBJUYNSLK-XRKIENNPSA-N 0.000 description 1
206010016654 Fibrosis Diseases 0.000 description 1
206010053717 Fibrous histiocytoma Diseases 0.000 description 1
208000012671 Gastrointestinal haemorrhages Diseases 0.000 description 1
206010018001 Gastrointestinal perforation Diseases 0.000 description 1
206010059024 Gastrointestinal toxicity Diseases 0.000 description 1
108010010803 Gelatin Proteins 0.000 description 1
108010017213 Granulocyte-Macrophage Colony-Stimulating Factor Proteins 0.000 description 1
102100039620 Granulocyte-macrophage colony-stimulating factor Human genes 0.000 description 1
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical group NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 1
QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 1
239000007995 HEPES buffer Substances 0.000 description 1
208000007446 Hip Dislocation Diseases 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
206010020751 Hypersensitivity Diseases 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
208000012659 Joint disease Diseases 0.000 description 1
102100035792 Kininogen-1 Human genes 0.000 description 1
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
206010023804 Large intestine perforation Diseases 0.000 description 1
241000406668 Loxodonta cyclotis Species 0.000 description 1
ZRVUJXDFFKFLMG-UHFFFAOYSA-N Meloxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=C(C)S1 ZRVUJXDFFKFLMG-UHFFFAOYSA-N 0.000 description 1
XADCESSVHJOZHK-UHFFFAOYSA-N Meperidine Chemical compound C=1C=CC=CC=1C1(C(=O)OCC)CCN(C)CC1 XADCESSVHJOZHK-UHFFFAOYSA-N 0.000 description 1
241001024304 Mino Species 0.000 description 1
101000605126 Mus musculus Prostaglandin G/H synthase 2 Proteins 0.000 description 1
ONXPDKGXOOORHB-BYPYZUCNSA-N N(5)-methyl-L-glutamine Chemical compound CNC(=O)CC[C@H](N)C(O)=O ONXPDKGXOOORHB-BYPYZUCNSA-N 0.000 description 1
CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
238000011887 Necropsy Methods 0.000 description 1
241000772415 Neovison vison Species 0.000 description 1
241001207999 Notaris Species 0.000 description 1
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
206010033307 Overweight Diseases 0.000 description 1
244000131316 Panax pseudoginseng Species 0.000 description 1
235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
235000003140 Panax quinquefolius Nutrition 0.000 description 1
108091005804 Peptidases Proteins 0.000 description 1
102000035195 Peptidases Human genes 0.000 description 1
239000004698 Polyethylene Substances 0.000 description 1
206010036877 Prolonged Pregnancy Diseases 0.000 description 1
102000008866 Prostaglandin E receptors Human genes 0.000 description 1
108010088540 Prostaglandin E receptors Proteins 0.000 description 1
239000004365 Protease Substances 0.000 description 1
208000003251 Pruritus Diseases 0.000 description 1
241000700157 Rattus norvegicus Species 0.000 description 1
208000001647 Renal Insufficiency Diseases 0.000 description 1
240000005578 Rivina humilis Species 0.000 description 1
102100038043 Roquin-1 Human genes 0.000 description 1
101710168637 Roquin-1 Proteins 0.000 description 1
206010070834 Sensitisation Diseases 0.000 description 1
206010040483 Sexual inhibition Diseases 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
229920002472 Starch Polymers 0.000 description 1
OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
241000906446 Theraps Species 0.000 description 1
229940022663 acetate Drugs 0.000 description 1
MMBFUKUTZUAQMJ-UHFFFAOYSA-N acetic acid;9h-carbazole Chemical class CC(O)=O.C1=CC=C2C3=CC=CC=C3NC2=C1 MMBFUKUTZUAQMJ-UHFFFAOYSA-N 0.000 description 1
229960001138 acetylsalicylic acid Drugs 0.000 description 1
230000009858 acid secretion Effects 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
208000038016 acute inflammation Diseases 0.000 description 1
230000006022 acute inflammation Effects 0.000 description 1
239000000654 additive Substances 0.000 description 1
230000004520 agglutination Effects 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
230000004075 alteration Effects 0.000 description 1
AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
229940024606 amino acid Drugs 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
230000003444 anaesthetic effect Effects 0.000 description 1
238000010171 animal model Methods 0.000 description 1
230000001760 anti-analgesic effect Effects 0.000 description 1
230000002456 anti-arthritic effect Effects 0.000 description 1
229940121363 anti-inflammatory agent Drugs 0.000 description 1
230000000118 anti-neoplastic effect Effects 0.000 description 1
239000000883 anti-obesity agent Substances 0.000 description 1
230000009830 antibody antigen interaction Effects 0.000 description 1
239000003429 antifungal agent Substances 0.000 description 1
239000002255 antigout agent Substances 0.000 description 1
229940127088 antihypertensive drug Drugs 0.000 description 1
239000004599 antimicrobial Substances 0.000 description 1
229940034982 antineoplastic agent Drugs 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
239000003096 antiparasitic agent Substances 0.000 description 1
239000003908 antipruritic agent Substances 0.000 description 1
239000003435 antirheumatic agent Substances 0.000 description 1
239000003443 antiviral agent Substances 0.000 description 1
210000002403 aortic endothelial cell Anatomy 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
229940114078 arachidonate Drugs 0.000 description 1
238000005899 aromatization reaction Methods 0.000 description 1
210000001367 artery Anatomy 0.000 description 1
206010003246 arthritis Diseases 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
238000003556 assay Methods 0.000 description 1
125000004429 atom Chemical group 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
229960005370 atorvastatin Drugs 0.000 description 1
230000003190 augmentative effect Effects 0.000 description 1
VJBCNMFKFZIXHC-UHFFFAOYSA-N azanium;2-(4-methyl-5-oxo-4-propan-2-yl-1h-imidazol-2-yl)quinoline-3-carboxylate Chemical compound N.N1C(=O)C(C(C)C)(C)N=C1C1=NC2=CC=CC=C2C=C1C(O)=O VJBCNMFKFZIXHC-UHFFFAOYSA-N 0.000 description 1
208000022362 bacterial infectious disease Diseases 0.000 description 1
229910001863 barium hydroxide Inorganic materials 0.000 description 1
230000006399 behavior Effects 0.000 description 1
229960005430 benoxaprofen Drugs 0.000 description 1
229940050390 benzoate Drugs 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
229960001541 benzthiazide Drugs 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
230000001588 bifunctional effect Effects 0.000 description 1
238000011325 biochemical measurement Methods 0.000 description 1
229920013641 bioerodible polymer Polymers 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
230000017531 blood circulation Effects 0.000 description 1
239000003918 blood extract Substances 0.000 description 1
230000036770 blood supply Effects 0.000 description 1
238000007664 blowing Methods 0.000 description 1
229940098773 bovine serum albumin Drugs 0.000 description 1
QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
125000004799 bromophenyl group Chemical group 0.000 description 1
239000001110 calcium chloride Substances 0.000 description 1
229910001628 calcium chloride Inorganic materials 0.000 description 1
AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 1
239000000920 calcium hydroxide Substances 0.000 description 1
229910001861 calcium hydroxide Inorganic materials 0.000 description 1
LHJQIRIGXXHNLA-UHFFFAOYSA-N calcium peroxide Chemical compound [Ca+2].[O-][O-] LHJQIRIGXXHNLA-UHFFFAOYSA-N 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
201000011510 cancer Diseases 0.000 description 1
230000004856 capillary permeability Effects 0.000 description 1
125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
150000001721 carbon Chemical group 0.000 description 1
239000012876 carrier material Substances 0.000 description 1
239000003054 catalyst Substances 0.000 description 1
239000006285 cell suspension Substances 0.000 description 1
230000001413 cellular effect Effects 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
230000004087 circulation Effects 0.000 description 1
229940001468 citrate Drugs 0.000 description 1
238000000576 coating method Methods 0.000 description 1
239000000084 colloidal system Substances 0.000 description 1
238000004040 coloring Methods 0.000 description 1
230000000052 comparative effect Effects 0.000 description 1
230000002860 competitive effect Effects 0.000 description 1
239000008120 corn starch Substances 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
230000001120 cytoprotective effect Effects 0.000 description 1
230000007850 degeneration Effects 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
210000004207 dermis Anatomy 0.000 description 1
230000009547 development abnormality Effects 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
238000009792 diffusion process Methods 0.000 description 1
230000029087 digestion Effects 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
229960002986 dinoprostone Drugs 0.000 description 1
230000006806 disease prevention Effects 0.000 description 1
230000005750 disease progression Effects 0.000 description 1
208000035475 disorder Diseases 0.000 description 1
230000001882 diuretic effect Effects 0.000 description 1
238000012377 drug delivery Methods 0.000 description 1
238000009510 drug design Methods 0.000 description 1
230000009977 dual effect Effects 0.000 description 1
230000002183 duodenal effect Effects 0.000 description 1
238000010410 dusting Methods 0.000 description 1
244000078703 ectoparasite Species 0.000 description 1
230000000001 effect on platelet aggregation Effects 0.000 description 1
230000008030 elimination Effects 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
244000079386 endoparasite Species 0.000 description 1
238000001839 endoscopy Methods 0.000 description 1
230000002255 enzymatic effect Effects 0.000 description 1
210000002745 epiphysis Anatomy 0.000 description 1
231100000321 erythema Toxicity 0.000 description 1
210000003238 esophagus Anatomy 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
230000005496 eutectics Effects 0.000 description 1
230000003203 everyday effect Effects 0.000 description 1
238000013265 extended release Methods 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
229960001419 fenoprofen Drugs 0.000 description 1
239000012091 fetal bovine serum Substances 0.000 description 1
230000004761 fibrosis Effects 0.000 description 1
239000012065 filter cake Substances 0.000 description 1
239000012467 final product Substances 0.000 description 1
239000010419 fine particle Substances 0.000 description 1
125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
230000009246 food effect Effects 0.000 description 1
235000021471 food effect Nutrition 0.000 description 1
210000001156 gastric mucosa Anatomy 0.000 description 1
208000030304 gastrointestinal bleeding Diseases 0.000 description 1
231100000414 gastrointestinal toxicity Toxicity 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
235000008434 ginseng Nutrition 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
208000035861 hematochezia Diseases 0.000 description 1
230000002440 hepatic effect Effects 0.000 description 1
229960001340 histamine Drugs 0.000 description 1
239000000938 histamine H1 antagonist Substances 0.000 description 1
HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
201000000284 histiocytoma Diseases 0.000 description 1
229940088597 hormone Drugs 0.000 description 1
239000005556 hormone Substances 0.000 description 1
239000003906 humectant Substances 0.000 description 1
229960002474 hydralazine Drugs 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
229960001680 ibuprofen Drugs 0.000 description 1
238000005286 illumination Methods 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
238000002649 immunization Methods 0.000 description 1
230000003053 immunization Effects 0.000 description 1
238000003119 immunoblot Methods 0.000 description 1
230000001771 impaired effect Effects 0.000 description 1
238000010874 in vitro model Methods 0.000 description 1
238000012623 in vivo measurement Methods 0.000 description 1
238000010348 incorporation Methods 0.000 description 1
229960004187 indoprofen Drugs 0.000 description 1
230000006698 induction Effects 0.000 description 1
239000012678 infectious agent Substances 0.000 description 1
230000008595 infiltration Effects 0.000 description 1
238000001764 infiltration Methods 0.000 description 1
208000014674 injury Diseases 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
238000003780 insertion Methods 0.000 description 1
230000037431 insertion Effects 0.000 description 1
230000002452 interceptive effect Effects 0.000 description 1
230000000968 intestinal effect Effects 0.000 description 1
238000007919 intrasynovial administration Methods 0.000 description 1
208000018937 joint inflammation Diseases 0.000 description 1
210000005067 joint tissue Anatomy 0.000 description 1
201000006370 kidney failure Diseases 0.000 description 1
230000003907 kidney function Effects 0.000 description 1
239000008101 lactose Substances 0.000 description 1
229910000464 lead oxide Inorganic materials 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
230000005923 long-lasting effect Effects 0.000 description 1
239000006210 lotion Substances 0.000 description 1
206010025135 lupus erythematosus Diseases 0.000 description 1
230000002132 lysosomal effect Effects 0.000 description 1
230000018984 mastication Effects 0.000 description 1
238000010077 mastication Methods 0.000 description 1
229960001929 meloxicam Drugs 0.000 description 1
239000000155 melt Substances 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
210000002418 meninge Anatomy 0.000 description 1
230000037353 metabolic pathway Effects 0.000 description 1
230000004060 metabolic process Effects 0.000 description 1
239000000693 micelle Substances 0.000 description 1
239000004530 micro-emulsion Substances 0.000 description 1
244000005700 microbiome Species 0.000 description 1
239000004005 microsphere Substances 0.000 description 1
239000011707 mineral Substances 0.000 description 1
235000010755 mineral Nutrition 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
238000012544 monitoring process Methods 0.000 description 1
210000005087 mononuclear cell Anatomy 0.000 description 1
210000004400 mucous membrane Anatomy 0.000 description 1
210000003097 mucus Anatomy 0.000 description 1
210000003205 muscle Anatomy 0.000 description 1
230000035772 mutation Effects 0.000 description 1
229960002009 naproxen Drugs 0.000 description 1
210000005036 nerve Anatomy 0.000 description 1
210000001640 nerve ending Anatomy 0.000 description 1
HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
229960001597 nifedipine Drugs 0.000 description 1
150000002823 nitrates Chemical class 0.000 description 1
210000000929 nociceptor Anatomy 0.000 description 1
230000035764 nutrition Effects 0.000 description 1
235000016709 nutrition Nutrition 0.000 description 1
239000003921 oil Substances 0.000 description 1
235000019198 oils Nutrition 0.000 description 1
229940049964 oleate Drugs 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
229940126701 oral medication Drugs 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
230000003204 osmotic effect Effects 0.000 description 1
YEXPOXQUZXUXJW-UHFFFAOYSA-N oxolead Chemical compound [Pb]=O YEXPOXQUZXUXJW-UHFFFAOYSA-N 0.000 description 1
229910052760 oxygen Inorganic materials 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
208000027753 pain disease Diseases 0.000 description 1
230000008058 pain sensation Effects 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
230000008506 pathogenesis Effects 0.000 description 1
210000004197 pelvis Anatomy 0.000 description 1
230000035515 penetration Effects 0.000 description 1
230000002085 persistent effect Effects 0.000 description 1
229960000482 pethidine Drugs 0.000 description 1
210000001539 phagocyte Anatomy 0.000 description 1
230000003285 pharmacodynamic effect Effects 0.000 description 1
HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
229940067157 phenylhydrazine Drugs 0.000 description 1
QGVLYPPODPLXMB-QXYKVGAMSA-N phorbol Natural products C[C@@H]1[C@@H](O)[C@]2(O)[C@H]([C@H]3C=C(CO)C[C@@]4(O)[C@H](C=C(C)C4=O)[C@@]13O)C2(C)C QGVLYPPODPLXMB-QXYKVGAMSA-N 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
PIDSZXPFGCURGN-UHFFFAOYSA-N pirprofen Chemical compound ClC1=CC(C(C(O)=O)C)=CC=C1N1CC=CC1 PIDSZXPFGCURGN-UHFFFAOYSA-N 0.000 description 1
229960000851 pirprofen Drugs 0.000 description 1
210000004623 platelet-rich plasma Anatomy 0.000 description 1
208000008423 pleurisy Diseases 0.000 description 1
229920001515 polyalkylene glycol Polymers 0.000 description 1
229920000573 polyethylene Polymers 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
235000020777 polyunsaturated fatty acids Nutrition 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000002243 precursor Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000008569 process Effects 0.000 description 1
230000035752 proliferative phase Effects 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
150000004672 propanoic acids Chemical class 0.000 description 1
229960003712 propranolol Drugs 0.000 description 1
XEYBRNLFEZDVAW-UHFFFAOYSA-N prostaglandin E2 Natural products CCCCCC(O)C=CC1C(O)CC(=O)C1CC=CCCCC(O)=O XEYBRNLFEZDVAW-UHFFFAOYSA-N 0.000 description 1
230000009993 protective function Effects 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical group O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
239000000700 radioactive tracer Substances 0.000 description 1
238000011552 rat model Methods 0.000 description 1
239000000376 reactant Substances 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
102000005962 receptors Human genes 0.000 description 1
108020003175 receptors Proteins 0.000 description 1
230000009467 reduction Effects 0.000 description 1
231100000628 reference dose Toxicity 0.000 description 1
229960001860 salicylate Drugs 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
210000001991 scapula Anatomy 0.000 description 1
238000007790 scraping Methods 0.000 description 1
230000028327 secretion Effects 0.000 description 1
230000001624 sedative effect Effects 0.000 description 1
238000010956 selective crystallization Methods 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
230000008313 sensitization Effects 0.000 description 1
230000001568 sexual effect Effects 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
RCOSUMRTSQULBK-UHFFFAOYSA-N sodium;propan-1-olate Chemical compound [Na+].CCC[O-] RCOSUMRTSQULBK-UHFFFAOYSA-N 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
210000000278 spinal cord Anatomy 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
230000007480 spreading Effects 0.000 description 1
238000003892 spreading Methods 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
229940086735 succinate Drugs 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
KJVQYDYPDFFJMP-UHFFFAOYSA-N sulfamethylthiazole Chemical group CC1=CSC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 KJVQYDYPDFFJMP-UHFFFAOYSA-N 0.000 description 1
150000003871 sulfonates Chemical class 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
229960004492 suprofen Drugs 0.000 description 1
230000008961 swelling Effects 0.000 description 1
230000002889 sympathetic effect Effects 0.000 description 1
229940064707 sympathomimetics Drugs 0.000 description 1
210000001258 synovial membrane Anatomy 0.000 description 1
238000010189 synthetic method Methods 0.000 description 1
239000000454 talc Substances 0.000 description 1
229910052623 talc Inorganic materials 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
230000008685 targeting Effects 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
235000012976 tarts Nutrition 0.000 description 1
UGNWTBMOAKPKBL-UHFFFAOYSA-N tetrachloro-1,4-benzoquinone Chemical compound ClC1=C(Cl)C(=O)C(Cl)=C(Cl)C1=O UGNWTBMOAKPKBL-UHFFFAOYSA-N 0.000 description 1
238000011285 therapeutic regimen Methods 0.000 description 1
239000003848 thrombocyte activating factor antagonist Substances 0.000 description 1
150000003595 thromboxanes Chemical class 0.000 description 1
229940098465 tincture Drugs 0.000 description 1
208000037816 tissue injury Diseases 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
230000001052 transient effect Effects 0.000 description 1
238000002054 transplantation Methods 0.000 description 1
230000008736 traumatic injury Effects 0.000 description 1
238000011269 treatment regimen Methods 0.000 description 1
210000003606 umbilical vein Anatomy 0.000 description 1
238000010200 validation analysis Methods 0.000 description 1
125000002987 valine group Chemical group [H]N([H])C([H])(C(*)=O)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
230000002792 vascular Effects 0.000 description 1
230000024883 vasodilation Effects 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
230000035899 viability Effects 0.000 description 1
239000000052 vinegar Substances 0.000 description 1
230000002747 voluntary effect Effects 0.000 description 1
238000001262 western blot Methods 0.000 description 1
239000008096 xylene Substances 0.000 description 1
229910052727 yttrium Inorganic materials 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- 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

Landscapes

Health & Medical Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Veterinary Medicine (AREA)
Chemical & Material Sciences (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Chemical Kinetics & Catalysis (AREA)
Epidemiology (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Pain & Pain Management (AREA)
Rheumatology (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Indole Compounds (AREA)
Medicinal Preparation (AREA)

JP10547869A 1997-05-05 1998-05-01 イヌにおける疼痛および炎症治療用ｃｏｘ−２選択性カルプロフェン Pending JP2000513020A (ja)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US4563597P	1997-05-05	1997-05-05
US60/045,635		1997-05-05
PCT/IB1998/000662 WO1998050033A1 (en)	1997-05-05	1998-05-01	Cox-2 selective carprofen for treating pain and inflammation in dogs

Publications (1)

Publication Number	Publication Date
JP2000513020A true JP2000513020A (ja)	2000-10-03

Family

ID=21939053

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
JP10547869A Pending JP2000513020A (ja)	1997-05-05	1998-05-01	イヌにおける疼痛および炎症治療用ｃｏｘ−２選択性カルプロフェン

Country Status (32)

Country	Link
EP (1)	EP0988034A1 (is)
JP (1)	JP2000513020A (is)
KR (2)	KR20040004406A (is)
CN (1)	CN1255059A (is)
AP (1)	AP9801234A0 (is)
AR (2)	AR011726A1 (is)
AU (1)	AU6932198A (is)
BG (1)	BG103852A (is)
BR (1)	BR9808720A (is)
CA (1)	CA2288759A1 (is)
DZ (1)	DZ2479A1 (is)
EA (1)	EA003696B1 (is)
GT (1)	GT199800063A (is)
HR (1)	HRP980244A2 (is)
HU (1)	HUP0001286A3 (is)
ID (1)	ID21311A (is)
IL (1)	IL132570A0 (is)
IS (1)	IS5220A (is)
MA (1)	MA26491A1 (is)
NO (1)	NO995389L (is)
NZ (1)	NZ500183A (is)
OA (1)	OA11213A (is)
PA (1)	PA8450601A1 (is)
PE (1)	PE72599A1 (is)
PL (1)	PL337003A1 (is)
SK (1)	SK148199A3 (is)
TN (1)	TNSN98059A1 (is)
TW (1)	TW590773B (is)
UY (1)	UY24989A1 (is)
WO (1)	WO1998050033A1 (is)
YU (1)	YU55899A (is)
ZA (1)	ZA983722B (is)

Families Citing this family (28)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US6245797B1 (en)	1997-10-22	2001-06-12	Merck & Co., Inc.	Combination therapy for reducing the risks associated with cardio-and-cerebrovascular disease
US6506785B2 (en) *	1998-05-22	2003-01-14	Pfizer, Inc.	Treating or preventing the early stages of degeneration of articular cartilage or subchondral bone in mammals using carprofen and derivatives
AU2003204888B2 (en) *	1998-05-22	2005-07-28	Pfizer Products Inc.	Treating or Preventing the Early Stages of Degeneration of Articular Cartilage or Subchondral Bone in Mammals Using Carprofen and Derivatives
AU764872B2 (en) *	1998-10-23	2003-09-04	Merck Frosst Canada & Co.	Combination product comprising an E-type prostaglandin ligand and a cox-2 selective inhibitor and methods of use
ATE306263T1 (de) *	1999-03-10	2005-10-15	Searle Llc	Zusammensetzungen zur verabreichung eines cyclooxygenase-2-hemmers an tiere
AU1592901A (en) *	1999-11-11	2001-06-06	Eli Lilly And Company	Oncolytic combinations for the treatment of cancer
AU2001259974A1 (en) *	2000-05-15	2001-11-26	Merck Frosst Canada & Co	Combination therapy using cox-2 selective inhibitor and thromboxane inhibitor and compositions therefor
IL153303A0 (en)	2000-06-13	2003-07-06	Wyeth Corp	Analgesic and anti-inflammatory compositions conaining cox-2 inhibitors
DE10032132A1 (de) *	2000-07-01	2002-01-17	Lohmann Therapie Syst Lts	Dermales Therapeutisches System enthaltend nichtsteroidale Antiphlogistika mit selektiver COX-2-Hemmung
ATE420201T1 (de)	2000-08-07	2009-01-15	Univ Vanderbilt	Nachweis der cox-2 aktivität und von anandamid- metaboliten
AU2002354901A1 (en) *	2001-07-16	2003-03-03	Edward Hogestatt	Compounds with analgesic, antipyretic and/or anti-inflammatory activity
EP1745791B1 (en)	2003-05-07	2013-06-26	Osteologix A/S	Treating cartilage/bone conditions with water-soluble strontium salts
RU2319508C2 (ru) *	2003-07-31	2008-03-20	ФАРМАЦИЯ ЭНД АПДЖОН КОМПАНИ ЭлЭлСи	Диспергируемый препарат противовоспалительного агента
AU2006248645A1 (en) *	2005-05-20	2006-11-23	Pfizer Limited	Synergistic combinations of non-steroidal antiinflammatory drugs with alpha-delta-ligands
EP2079456B1 (en)	2007-04-04	2012-12-05	Sigmoid Pharma Limited	Pharmaceutical cyclosporin compositions
EP2586428B1 (en)	2007-04-26	2023-11-08	Sublimity Therapeutics Limited	Manufacture of multiple minicapsules
ES2649112T3 (es)	2009-05-18	2018-01-10	Sigmoid Pharma Limited	Composición que comprende gotas de aceite
CN107582526A (zh)	2009-08-12	2018-01-16	希格默伊德药业有限公司	包含聚合物基质和油相的免疫调节组合物
GB201020032D0 (en)	2010-11-25	2011-01-12	Sigmoid Pharma Ltd	Composition
GB201212010D0 (en)	2012-07-05	2012-08-22	Sigmoid Pharma Ltd	Formulations
GB201319791D0 (en)	2013-11-08	2013-12-25	Sigmoid Pharma Ltd	Formulations
JP6419857B2 (ja) *	2014-03-06	2018-11-07	アラタナセラピューティクス、インコーポレイテッド	グラピプラント組成物およびその使用方法
US12109218B2 (en)	2014-12-09	2024-10-08	Aratana Therapeutics, Inc.	Compositions of grapiprant and methods for using the same
EP3881829A1 (en)	2014-11-07	2021-09-22	Sublimity Therapeutics Limited	Compositions comprising cyclosporin
US20180264061A1 (en) *	2015-01-09	2018-09-20	Jaguar Animal Health	Methods of Treating Diarrhea in Companion Animals
EP4125874A4 (en) *	2020-03-25	2024-05-01	SRI International	LIPOXYGENASE INHIBITORS
US11116737B1 (en)	2020-04-10	2021-09-14	University Of Georgia Research Foundation, Inc.	Methods of using probenecid for treatment of coronavirus infections
KR102404883B1 (ko)	2020-11-30	2022-06-07	(주)이노보테라퓨틱스	벤즈브로마론을 포함하는 켈로이드 또는 비대흉터 예방 또는 치료용 약학 조성물

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3896145A (en) *	1972-07-24	1975-07-22	Hoffmann La Roche	Carbazoles
CA1319886C (en) *	1987-02-03	1993-07-06	Alberto Ferro	Mixed micelle solutions

1998
- 1998-03-02 DZ DZ980089A patent/DZ2479A1/xx active
- 1998-04-30 TW TW087106689A patent/TW590773B/zh not_active IP Right Cessation
- 1998-05-01 WO PCT/IB1998/000662 patent/WO1998050033A1/en not_active Ceased
- 1998-05-01 BR BR9808720-7A patent/BR9808720A/pt not_active IP Right Cessation
- 1998-05-01 CN CN98804845A patent/CN1255059A/zh active Pending
- 1998-05-01 HU HU0001286A patent/HUP0001286A3/hu unknown
- 1998-05-01 CA CA002288759A patent/CA2288759A1/en not_active Abandoned
- 1998-05-01 ID IDP980651A patent/ID21311A/id unknown
- 1998-05-01 SK SK1481-99A patent/SK148199A3/sk unknown
- 1998-05-01 JP JP10547869A patent/JP2000513020A/ja active Pending
- 1998-05-01 AU AU69321/98A patent/AU6932198A/en not_active Abandoned
- 1998-05-01 KR KR10-2003-7005258A patent/KR20040004406A/ko not_active Ceased
- 1998-05-01 PL PL98337003A patent/PL337003A1/xx unknown
- 1998-05-01 EA EA199900895A patent/EA003696B1/ru not_active IP Right Cessation
- 1998-05-01 KR KR1019997010252A patent/KR20010012300A/ko not_active Ceased
- 1998-05-01 EP EP98915041A patent/EP0988034A1/en not_active Withdrawn
- 1998-05-01 YU YU55899A patent/YU55899A/sh unknown
- 1998-05-01 IL IL13257098A patent/IL132570A0/xx unknown
- 1998-05-01 NZ NZ500183A patent/NZ500183A/en unknown
- 1998-05-04 MA MA25059A patent/MA26491A1/fr unknown
- 1998-05-04 AP APAP/P/1998/001234A patent/AP9801234A0/en unknown
- 1998-05-04 GT GT199800063A patent/GT199800063A/es unknown
- 1998-05-04 TN TNTNSN98059A patent/TNSN98059A1/fr unknown
- 1998-05-04 UY UY24989A patent/UY24989A1/es not_active Application Discontinuation
- 1998-05-04 ZA ZA9803722A patent/ZA983722B/xx unknown
- 1998-05-04 PE PE1998000335A patent/PE72599A1/es not_active Application Discontinuation
- 1998-05-05 AR ARP980102089A patent/AR011726A1/es unknown
- 1998-05-05 PA PA19988450601A patent/PA8450601A1/es unknown
- 1998-05-05 HR HR60/045,635A patent/HRP980244A2/hr not_active Application Discontinuation
1999
- 1999-10-19 IS IS5220A patent/IS5220A/is unknown
- 1999-11-02 OA OA9900242A patent/OA11213A/en unknown
- 1999-11-03 BG BG103852A patent/BG103852A/xx unknown
- 1999-11-04 NO NO995389A patent/NO995389L/no not_active Application Discontinuation
2003
- 2003-04-09 AR ARP030101251A patent/AR039628A2/es unknown

Also Published As

Publication number	Publication date
BG103852A (en)	2000-06-30
DZ2479A1 (fr)	2003-02-01
EA199900895A1 (ru)	2000-06-26
HUP0001286A2 (hu)	2000-11-28
EP0988034A1 (en)	2000-03-29
AP9801234A0 (en)	1999-11-04
PE72599A1 (es)	1999-08-12
HRP980244A2 (en)	1999-02-28
PL337003A1 (en)	2000-07-31
NO995389D0 (no)	1999-11-04
AR039628A2 (es)	2005-03-02
TNSN98059A1 (fr)	2005-03-15
ZA983722B (en)	1999-11-04
NZ500183A (en)	2002-04-26
NO995389L (no)	2000-01-04
BR9808720A (pt)	2000-07-11
AR011726A1 (es)	2000-08-30
CA2288759A1 (en)	1998-11-12
PA8450601A1 (es)	2000-05-24
MA26491A1 (fr)	2004-12-20
IS5220A (is)	1999-10-19
GT199800063A (es)	1999-10-26
WO1998050033A1 (en)	1998-11-12
IL132570A0 (en)	2001-03-19
YU55899A (sh)	2003-08-29
SK148199A3 (en)	2001-09-11
KR20010012300A (ko)	2001-02-15
EA003696B1 (ru)	2003-08-28
TW590773B (en)	2004-06-11
KR20040004406A (ko)	2004-01-13
CN1255059A (zh)	2000-05-31
OA11213A (en)	2003-07-14
UY24989A1 (es)	2001-10-25
AU6932198A (en)	1998-11-27
ID21311A (id)	1999-05-20
HUP0001286A3 (en)	2000-12-28

Publication	Publication Date	Title
JP2000513020A (ja)	2000-10-03	イヌにおける疼痛および炎症治療用ｃｏｘ−２選択性カルプロフェン
CA1165689A (en)	1984-04-17	Method of increasing oral absorption of polar bioactive agents
US9962378B2 (en)	2018-05-08	ROS1 inhibitor and its use
US6399647B2 (en)	2002-06-04	Amide derivatives for antiangiogenic and/or antitumorigenic use
US20020010203A1 (en)	2002-01-24	Methods of modulating c-kit tyrosine protein kinase function with indolinone compounds
JP2002528498A (ja)	2002-09-03	片頭痛の治療方法及び医薬組成物
JPH09505809A (ja)	1997-06-10	ヒドロキシカルバゾール化合物類による平滑筋移動および増殖の阻害
KR20210151816A (ko)	2021-12-14	칸나비노이드 산 에스테르 조성물 및 이의 용도
CN1444478A (zh)	2003-09-24	塞利克西组合物在快速缓解疼痛中的用途
Mazaleuskaya et al.	2020	Druggable prostanoid pathway
KR20180124976A (ko)	2018-11-21	신경교종을 포함하는 암을 치료하기 위해 에플로르니틴 및 이의 유도체 및 동족체를 사용하기 위한 조성물 및 방법
KR102517650B1 (ko)	2023-04-05	유방암의 치료를 위한 조합물 요법
US20100144749A1 (en)	2010-06-10	Treatment of cancers with acquired resistance to kit inhibitors
US20030212123A1 (en)	2003-11-13	COX-2 selective carprofen for treating pain and inflammation in dogs
JPS58185517A (ja)	1983-10-29	塩利尿作用を有する薬物
US20040097539A1 (en)	2004-05-20	Hsp inductor
KR101074374B1 (ko)	2011-10-17	소염진통 외용제
CN102271507A (zh)	2011-12-07	分泌型磷脂酶a2(spla2)抑制剂和烟酸药物组合物以及治疗心血管疾病和血脂异常的方法
AU773615B2 (en)	2004-05-27	COX-2 selective carprofen for treating pain and inflammation in dogs
WO2004024145A1 (en)	2004-03-25	Anti-cancer activity of carvedilol and its isomers
US20150065486A1 (en)	2015-03-05	Methods for treating polycystic kidney disease
CZ9903896A3 (cs)	2001-05-16	Léčivo, farmaceutický přípravek a souprava pro léčení nebo prevenci bolesti a zánětlivých procesů
NZ516914A (en)	2003-08-29	Compositions containing COX-2 selective carprofen and derivatives thereof for treating pain and inflammation in dogs
WO1988009675A1 (en)	1988-12-15	Inhibition of arachidonic acid metabolism
JP2000355551A (ja)	2000-12-26	医薬組成物