JP2005533003A5

JP2005533003A5 -

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Publication number: JP2005533003A5
Authority: JP; Japan
Prior art keywords: copper; patient; use according; diabetes; diabetic
Prior art date: 2003-03-10
Legal status : Granted

Application number

JP2003575954A

Other languages

English (en)

Japanese (ja)

Other versions

JP2005533003A (ja

JP4860906B2 (ja

Filing date

2003-03-10

Publication date

2006-10-19

2003-03-10 Application filed filed Critical

2003-03-10 Priority claimed from PCT/NZ2003/000042 external-priority patent/WO2003077901A1/en

2005-11-04 Publication of JP2005533003A publication Critical patent/JP2005533003A/ja

2006-10-19 Publication of JP2005533003A5 publication Critical patent/JP2005533003A5/ja

2012-01-25 Application granted granted Critical

2012-01-25 Publication of JP4860906B2 publication Critical patent/JP4860906B2/ja

2023-03-10 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

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239000010949 copper Substances 0.000 claims description 514
229910052802 copper Inorganic materials 0.000 claims description 503
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 494
206010012601 diabetes mellitus Diseases 0.000 claims description 280
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 131
239000002738 chelating agent Substances 0.000 claims description 125
210000001519 tissue Anatomy 0.000 claims description 89
239000003814 drug Substances 0.000 claims description 88
239000003795 chemical substances by application Substances 0.000 claims description 85
229940079593 drug Drugs 0.000 claims description 79
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 73
VILCJCGEZXAXTO-UHFFFAOYSA-N 2,2,2-tetramine Chemical group NCCNCCNCCN VILCJCGEZXAXTO-UHFFFAOYSA-N 0.000 claims description 70
201000010099 disease Diseases 0.000 claims description 67
208000035475 disorder Diseases 0.000 claims description 62
210000000130 stem cell Anatomy 0.000 claims description 56
208000031229 Cardiomyopathies Diseases 0.000 claims description 54
238000012544 monitoring process Methods 0.000 claims description 53
230000002792 vascular Effects 0.000 claims description 53
229960001124 trientine Drugs 0.000 claims description 51
210000001367 artery Anatomy 0.000 claims description 50
230000017423 tissue regeneration Effects 0.000 claims description 49
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 45
239000011701 zinc Substances 0.000 claims description 45
150000003751 zinc Chemical class 0.000 claims description 44
229910052725 zinc Inorganic materials 0.000 claims description 44
VVNCNSJFMMFHPL-VKHMYHEASA-N D-penicillamine Chemical compound CC(C)(S)[C@@H](N)C(O)=O VVNCNSJFMMFHPL-VKHMYHEASA-N 0.000 claims description 43
208000029078 coronary artery disease Diseases 0.000 claims description 43
229960001639 penicillamine Drugs 0.000 claims description 43
238000011282 treatment Methods 0.000 claims description 43
210000002216 heart Anatomy 0.000 claims description 40
229910052742 iron Inorganic materials 0.000 claims description 39
206010048858 Ischaemic cardiomyopathy Diseases 0.000 claims description 37
206010019280 Heart failures Diseases 0.000 claims description 32
210000004204 blood vessel Anatomy 0.000 claims description 29
201000001320 Atherosclerosis Diseases 0.000 claims description 28
206010020772 Hypertension Diseases 0.000 claims description 28
210000004351 coronary vessel Anatomy 0.000 claims description 28
230000004153 glucose metabolism Effects 0.000 claims description 28
230000036755 cellular response Effects 0.000 claims description 27
230000002159 abnormal effect Effects 0.000 claims description 26
-1 Desferoxamine Chemical compound 0.000 claims description 25
MDAXKAUIABOHTD-UHFFFAOYSA-N 1,4,8,11-tetraazacyclotetradecane Chemical compound C1CNCCNCCCNCCNC1 MDAXKAUIABOHTD-UHFFFAOYSA-N 0.000 claims description 21
210000000709 aorta Anatomy 0.000 claims description 21
210000001715 carotid artery Anatomy 0.000 claims description 21
210000001105 femoral artery Anatomy 0.000 claims description 21
230000000451 tissue damage Effects 0.000 claims description 21
231100000827 tissue damage Toxicity 0.000 claims description 21
210000003090 iliac artery Anatomy 0.000 claims description 20
230000003902 lesion Effects 0.000 claims description 20
210000003137 popliteal artery Anatomy 0.000 claims description 20
210000002254 renal artery Anatomy 0.000 claims description 20
230000000747 cardiac effect Effects 0.000 claims description 19
210000003734 kidney Anatomy 0.000 claims description 18
210000004165 myocardium Anatomy 0.000 claims description 18
210000005036 nerve Anatomy 0.000 claims description 18
229910052751 metal Inorganic materials 0.000 claims description 17
239000002184 metal Substances 0.000 claims description 17
UWMHHZFHBCYGCV-UHFFFAOYSA-N 2,3,2-tetramine Chemical compound NCCNCCCNCCN UWMHHZFHBCYGCV-UHFFFAOYSA-N 0.000 claims description 16
208000002972 Hepatolenticular Degeneration Diseases 0.000 claims description 16
208000018839 Wilson disease Diseases 0.000 claims description 16
MNNBCKASUFBXCO-YFKPBYRVSA-N N-acetyl-D-penicillamine Chemical compound CC(=O)N[C@@H](C(O)=O)C(C)(C)S MNNBCKASUFBXCO-YFKPBYRVSA-N 0.000 claims description 15
SSRIAMRLMUFTNV-UHFFFAOYSA-N 2,6-pyridinedicarbothioic acid Chemical compound SC(=O)C1=CC=CC(C(S)=O)=N1 SSRIAMRLMUFTNV-UHFFFAOYSA-N 0.000 claims description 14
KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 14
239000002253 acid Substances 0.000 claims description 14
230000007423 decrease Effects 0.000 claims description 14
IYRGXJIJGHOCFS-UHFFFAOYSA-N neocuproine Chemical compound C1=C(C)N=C2C3=NC(C)=CC=C3C=CC2=C1 IYRGXJIJGHOCFS-UHFFFAOYSA-N 0.000 claims description 14
FGGPAWQCCGEWTJ-UHFFFAOYSA-M sodium;2,3-bis(sulfanyl)propane-1-sulfonate Chemical compound [Na+].[O-]S(=O)(=O)CC(S)CS FGGPAWQCCGEWTJ-UHFFFAOYSA-M 0.000 claims description 14
150000002739 metals Chemical class 0.000 claims description 13
230000002829 reductive effect Effects 0.000 claims description 13
150000003839 salts Chemical class 0.000 claims description 13
210000001508 eye Anatomy 0.000 claims description 12
230000002107 myocardial effect Effects 0.000 claims description 12
YQUVCSBJEUQKSH-UHFFFAOYSA-N 3,4-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C(O)=C1 YQUVCSBJEUQKSH-UHFFFAOYSA-N 0.000 claims description 10
230000001434 glomerular Effects 0.000 claims description 10
230000002207 retinal effect Effects 0.000 claims description 10
208000004476 Acute Coronary Syndrome Diseases 0.000 claims description 9
201000010053 Alcoholic Cardiomyopathy Diseases 0.000 claims description 9
206010007637 Cardiomyopathy alcoholic Diseases 0.000 claims description 9
206010070909 Metabolic cardiomyopathy Diseases 0.000 claims description 9
208000009525 Myocarditis Diseases 0.000 claims description 9
ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims description 9
239000004246 zinc acetate Substances 0.000 claims description 9
102000012437 Copper-Transporting ATPases Human genes 0.000 claims description 8
210000003169 central nervous system Anatomy 0.000 claims description 8
OKHMDSCYUWAQPT-UHFFFAOYSA-N n'-[2-(2-aminoethylamino)ethyl]ethane-1,2-diamine;tetrahydrochloride Chemical compound Cl.Cl.Cl.Cl.NCCNCCNCCN OKHMDSCYUWAQPT-UHFFFAOYSA-N 0.000 claims description 8
210000001428 peripheral nervous system Anatomy 0.000 claims description 8
CXVCSRUYMINUSF-UHFFFAOYSA-N tetrathiomolybdate(2-) Chemical compound [S-][Mo]([S-])(=S)=S CXVCSRUYMINUSF-UHFFFAOYSA-N 0.000 claims description 8
AGMNQPKGRCRYQP-UHFFFAOYSA-N 2-[2-[2-[bis(carboxymethyl)amino]ethylamino]ethyl-(carboxymethyl)amino]acetic acid Chemical compound OC(=O)CN(CC(O)=O)CCNCCN(CC(O)=O)CC(O)=O AGMNQPKGRCRYQP-UHFFFAOYSA-N 0.000 claims description 7
WYMDDFRYORANCC-UHFFFAOYSA-N 2-[[3-[bis(carboxymethyl)amino]-2-hydroxypropyl]-(carboxymethyl)amino]acetic acid Chemical compound OC(=O)CN(CC(O)=O)CC(O)CN(CC(O)=O)CC(O)=O WYMDDFRYORANCC-UHFFFAOYSA-N 0.000 claims description 7
206010003210 Arteriosclerosis Diseases 0.000 claims description 7
DSRJIHMZAQEUJV-UHFFFAOYSA-N Cuprizon Chemical compound C1CCCCC1=NNC(=O)C(=O)NN=C1CCCCC1 DSRJIHMZAQEUJV-UHFFFAOYSA-N 0.000 claims description 7
YJPIGAIKUZMOQA-UHFFFAOYSA-N Melatonin Natural products COC1=CC=C2N(C(C)=O)C=C(CCN)C2=C1 YJPIGAIKUZMOQA-UHFFFAOYSA-N 0.000 claims description 7
QPCDCPDFJACHGM-UHFFFAOYSA-N N,N-bis{2-[bis(carboxymethyl)amino]ethyl}glycine Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(=O)O)CCN(CC(O)=O)CC(O)=O QPCDCPDFJACHGM-UHFFFAOYSA-N 0.000 claims description 7
VSWDORGPIHIGNW-UHFFFAOYSA-N Pyrrolidine dithiocarbamic acid Chemical compound SC(=S)N1CCCC1 VSWDORGPIHIGNW-UHFFFAOYSA-N 0.000 claims description 7
QNVSXXGDAPORNA-UHFFFAOYSA-N Resveratrol Natural products OC1=CC=CC(C=CC=2C=C(O)C(O)=CC=2)=C1 QNVSXXGDAPORNA-UHFFFAOYSA-N 0.000 claims description 7
LUKBXSAWLPMMSZ-OWOJBTEDSA-N Trans-resveratrol Chemical compound C1=CC(O)=CC=C1\C=C\C1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-OWOJBTEDSA-N 0.000 claims description 7
UHWVSEOVJBQKBE-UHFFFAOYSA-N Trimetazidine Chemical compound COC1=C(OC)C(OC)=CC=C1CN1CCNCC1 UHWVSEOVJBQKBE-UHFFFAOYSA-N 0.000 claims description 7
DGEZNRSVGBDHLK-UHFFFAOYSA-N [1,10]phenanthroline Chemical compound C1=CN=C2C3=NC=CC=C3C=CC2=C1 DGEZNRSVGBDHLK-UHFFFAOYSA-N 0.000 claims description 7
GIEAQDPIWWODTH-UHFFFAOYSA-N [Na].[Na].[Na].[Ca] Chemical compound [Na].[Na].[Na].[Ca] GIEAQDPIWWODTH-UHFFFAOYSA-N 0.000 claims description 7
229940116901 diethyldithiocarbamate Drugs 0.000 claims description 7
WQABCVAJNWAXTE-UHFFFAOYSA-N dimercaprol Chemical compound OCC(S)CS WQABCVAJNWAXTE-UHFFFAOYSA-N 0.000 claims description 7
AUZONCFQVSMFAP-UHFFFAOYSA-N disulfiram Chemical compound CCN(CC)C(=S)SSC(=S)N(CC)CC AUZONCFQVSMFAP-UHFFFAOYSA-N 0.000 claims description 7
230000001976 improved effect Effects 0.000 claims description 7
DRLFMBDRBRZALE-UHFFFAOYSA-N melatonin Chemical compound COC1=CC=C2NC=C(CCNC(C)=O)C2=C1 DRLFMBDRBRZALE-UHFFFAOYSA-N 0.000 claims description 7
229960003987 melatonin Drugs 0.000 claims description 7
PMRYVIKBURPHAH-UHFFFAOYSA-N methimazole Chemical compound CN1C=CNC1=S PMRYVIKBURPHAH-UHFFFAOYSA-N 0.000 claims description 7
WDLWFIMADVGTED-UHFFFAOYSA-N n'-[2-(2-aminoethylamino)ethyl]propane-1,3-diamine;tetrahydrochloride Chemical compound Cl.Cl.Cl.Cl.NCCCNCCNCCN WDLWFIMADVGTED-UHFFFAOYSA-N 0.000 claims description 7
VGICAQBLDJAGSJ-UHFFFAOYSA-N n'-[2-[2-(2-aminoethylamino)ethylamino]ethyl]ethane-1,2-diamine;pentahydrochloride Chemical compound Cl.Cl.Cl.Cl.Cl.NCCNCCNCCNCCN VGICAQBLDJAGSJ-UHFFFAOYSA-N 0.000 claims description 7
229960003330 pentetic acid Drugs 0.000 claims description 7
LUKBXSAWLPMMSZ-UHFFFAOYSA-N resveratrol Chemical compound C1=CC(O)=CC=C1C=CC1=CC(O)=CC(O)=C1 LUKBXSAWLPMMSZ-UHFFFAOYSA-N 0.000 claims description 7
ACTRVOBWPAIOHC-XIXRPRMCSA-N succimer Chemical compound OC(=O)[C@@H](S)[C@@H](S)C(O)=O ACTRVOBWPAIOHC-XIXRPRMCSA-N 0.000 claims description 7
229960002178 thiamazole Drugs 0.000 claims description 7
229960001177 trimetazidine Drugs 0.000 claims description 7
OBBKVQRWBGOVCF-UHFFFAOYSA-N 1,4,8,11-tetrazabicyclo[6.6.2]hexadecane Chemical compound C1CCNCCN2CCCNCCN1CC2 OBBKVQRWBGOVCF-UHFFFAOYSA-N 0.000 claims description 6
QCDFBFJGMNKBDO-UHFFFAOYSA-N Clioquinol Chemical compound C1=CN=C2C(O)=C(I)C=C(Cl)C2=C1 QCDFBFJGMNKBDO-UHFFFAOYSA-N 0.000 claims description 6
JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical compound [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 claims description 6
JVHROZDXPAUZFK-UHFFFAOYSA-N TETA Chemical compound OC(=O)CN1CCCN(CC(O)=O)CCN(CC(O)=O)CCCN(CC(O)=O)CC1 JVHROZDXPAUZFK-UHFFFAOYSA-N 0.000 claims description 6
229960005228 clioquinol Drugs 0.000 claims description 6
238000007911 parenteral administration Methods 0.000 claims description 6
ACTRVOBWPAIOHC-UHFFFAOYSA-N succimer Chemical compound OC(=O)C(S)C(S)C(O)=O ACTRVOBWPAIOHC-UHFFFAOYSA-N 0.000 claims description 6
FAGUFWYHJQFNRV-UHFFFAOYSA-N tetraethylenepentamine Chemical compound NCCNCCNCCNCCN FAGUFWYHJQFNRV-UHFFFAOYSA-N 0.000 claims description 6
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 6
230000002490 cerebral effect Effects 0.000 claims description 5
208000007848 Alcoholism Diseases 0.000 claims description 3
WYHIICXRPHEJKI-UHFFFAOYSA-N Trientine hydrochloride Chemical group Cl.Cl.NCCNCCNCCN WYHIICXRPHEJKI-UHFFFAOYSA-N 0.000 claims description 3
201000007930 alcohol dependence Diseases 0.000 claims description 3
ODBLHEXUDAPZAU-UHFFFAOYSA-N isocitric acid Chemical compound OC(=O)C(O)C(C(O)=O)CC(O)=O ODBLHEXUDAPZAU-UHFFFAOYSA-N 0.000 claims description 3
229960002408 trientine hydrochloride Drugs 0.000 claims description 3
239000011592 zinc chloride Substances 0.000 claims description 3
235000005074 zinc chloride Nutrition 0.000 claims description 3
NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 claims description 3
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WHMDKBIGKVEYHS-IYEMJOQQSA-L Zinc gluconate Chemical compound [Zn+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O WHMDKBIGKVEYHS-IYEMJOQQSA-L 0.000 claims description 2
239000011670 zinc gluconate Substances 0.000 claims description 2
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VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 4
210000000944 nerve tissue Anatomy 0.000 claims 2
210000005084 renal tissue Anatomy 0.000 claims 2
PKMTWMDBJHRDBM-ODZAUARKSA-N (z)-but-2-enedioic acid;zinc Chemical compound [Zn].OC(=O)\C=C/C(O)=O PKMTWMDBJHRDBM-ODZAUARKSA-N 0.000 claims 1
210000000653 nervous system Anatomy 0.000 claims 1
AGGKEGLBGGJEBZ-UHFFFAOYSA-N tetramethylenedisulfotetramine Chemical compound C1N(S2(=O)=O)CN3S(=O)(=O)N1CN2C3 AGGKEGLBGGJEBZ-UHFFFAOYSA-N 0.000 claims 1
WGIWBXUNRXCYRA-UHFFFAOYSA-H trizinc;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound [Zn+2].[Zn+2].[Zn+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O WGIWBXUNRXCYRA-UHFFFAOYSA-H 0.000 claims 1
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239000011746 zinc citrate Substances 0.000 claims 1
235000006076 zinc citrate Nutrition 0.000 claims 1
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GYBLQYIEAGSJPW-UHFFFAOYSA-L zinc;2-oxopentanedioate Chemical compound [Zn+2].[O-]C(=O)CCC(=O)C([O-])=O GYBLQYIEAGSJPW-UHFFFAOYSA-L 0.000 claims 1
AGFGXVAAIXIOFZ-UHFFFAOYSA-L zinc;butanedioate Chemical compound [Zn+2].[O-]C(=O)CCC([O-])=O AGFGXVAAIXIOFZ-UHFFFAOYSA-L 0.000 claims 1
238000000034 method Methods 0.000 description 242
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JP2003575954A 2002-03-08 2003-03-10 心疾患および／または関連心不全の予防および／または治療 Expired - Fee Related JP4860906B2 (ja)