JP5577100B2 - 高血圧症治療におけるリボフラビンの使用 - Google Patents
高血圧症治療におけるリボフラビンの使用 Download PDFInfo
- Publication number
- JP5577100B2 JP5577100B2 JP2009550246A JP2009550246A JP5577100B2 JP 5577100 B2 JP5577100 B2 JP 5577100B2 JP 2009550246 A JP2009550246 A JP 2009550246A JP 2009550246 A JP2009550246 A JP 2009550246A JP 5577100 B2 JP5577100 B2 JP 5577100B2
- Authority
- JP
- Japan
- Prior art keywords
- riboflavin
- blood pressure
- genotype
- mthfr
- pharmaceutical product
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 title claims description 73
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 title claims description 36
- 229960002477 riboflavin Drugs 0.000 title claims description 36
- 239000002151 riboflavin Substances 0.000 title claims description 36
- 235000019192 riboflavin Nutrition 0.000 title claims description 36
- 206010020772 Hypertension Diseases 0.000 title description 7
- 101000587058 Homo sapiens Methylenetetrahydrofolate reductase Proteins 0.000 claims description 27
- 102100029684 Methylenetetrahydrofolate reductase Human genes 0.000 claims description 27
- 230000036772 blood pressure Effects 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 15
- 239000002220 antihypertensive agent Substances 0.000 claims description 13
- 229940030600 antihypertensive agent Drugs 0.000 claims description 9
- 239000002876 beta blocker Substances 0.000 claims description 7
- 229940097320 beta blocking agent Drugs 0.000 claims description 7
- 239000002160 alpha blocker Substances 0.000 claims description 6
- 238000007911 parenteral administration Methods 0.000 claims description 5
- 239000005541 ACE inhibitor Substances 0.000 claims description 4
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 claims description 4
- 229940124308 alpha-adrenoreceptor antagonist Drugs 0.000 claims description 4
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 claims description 4
- 239000002934 diuretic Substances 0.000 claims description 4
- 229960002003 hydrochlorothiazide Drugs 0.000 claims description 4
- RMMXLENWKUUMAY-UHFFFAOYSA-N telmisartan Chemical compound CCCC1=NC2=C(C)C=C(C=3N(C4=CC=CC=C4N=3)C)C=C2N1CC(C=C1)=CC=C1C1=CC=CC=C1C(O)=O RMMXLENWKUUMAY-UHFFFAOYSA-N 0.000 claims description 4
- 239000002083 C09CA01 - Losartan Substances 0.000 claims description 3
- 239000005557 antagonist Substances 0.000 claims description 3
- 229940030606 diuretics Drugs 0.000 claims description 3
- 229960004773 losartan Drugs 0.000 claims description 3
- 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 claims description 3
- YKFCISHFRZHKHY-NGQGLHOPSA-N (2s)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid;trihydrate Chemical group 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 claims description 2
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical group CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 claims description 2
- KOHIRBRYDXPAMZ-YHBROIRLSA-N (S,R,R,R)-nebivolol Chemical compound C1CC2=CC(F)=CC=C2O[C@H]1[C@H](O)CNC[C@@H](O)[C@H]1OC2=CC=C(F)C=C2CC1 KOHIRBRYDXPAMZ-YHBROIRLSA-N 0.000 claims description 2
- RZPZLFIUFMNCLY-WLHGVMLRSA-N (e)-but-2-enedioic acid;1-(propan-2-ylamino)-3-[4-(2-propan-2-yloxyethoxymethyl)phenoxy]propan-2-ol Chemical compound OC(=O)\C=C\C(O)=O.CC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C1 RZPZLFIUFMNCLY-WLHGVMLRSA-N 0.000 claims description 2
- SGTNSNPWRIOYBX-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-{[2-(3,4-dimethoxyphenyl)ethyl](methyl)amino}-2-(propan-2-yl)pentanenitrile Chemical compound C1=C(OC)C(OC)=CC=C1CCN(C)CCCC(C#N)(C(C)C)C1=CC=C(OC)C(OC)=C1 SGTNSNPWRIOYBX-UHFFFAOYSA-N 0.000 claims description 2
- SGUAFYQXFOLMHL-UHFFFAOYSA-N 2-hydroxy-5-{1-hydroxy-2-[(4-phenylbutan-2-yl)amino]ethyl}benzamide Chemical compound C=1C=C(O)C(C(N)=O)=CC=1C(O)CNC(C)CCC1=CC=CC=C1 SGUAFYQXFOLMHL-UHFFFAOYSA-N 0.000 claims description 2
- XPCFTKFZXHTYIP-PMACEKPBSA-N Benazepril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N(CC(O)=O)C2=CC=CC=C2CC1)=O)CC1=CC=CC=C1 XPCFTKFZXHTYIP-PMACEKPBSA-N 0.000 claims description 2
- 239000004072 C09CA03 - Valsartan Substances 0.000 claims description 2
- 239000002947 C09CA04 - Irbesartan Substances 0.000 claims description 2
- 239000005537 C09CA07 - Telmisartan Substances 0.000 claims description 2
- 239000002051 C09CA08 - Olmesartan medoxomil Substances 0.000 claims description 2
- GHOSNRCGJFBJIB-UHFFFAOYSA-N Candesartan cilexetil Chemical compound C=12N(CC=3C=CC(=CC=3)C=3C(=CC=CC=3)C3=NNN=N3)C(OCC)=NC2=CC=CC=1C(=O)OC(C)OC(=O)OC1CCCCC1 GHOSNRCGJFBJIB-UHFFFAOYSA-N 0.000 claims description 2
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 claims description 2
- 108010061435 Enalapril Proteins 0.000 claims description 2
- 108010007859 Lisinopril Proteins 0.000 claims description 2
- UQGKUQLKSCSZGY-UHFFFAOYSA-N Olmesartan medoxomil Chemical compound C=1C=C(C=2C(=CC=CC=2)C2=NNN=N2)C=CC=1CN1C(CCC)=NC(C(C)(C)O)=C1C(=O)OCC=1OC(=O)OC=1C UQGKUQLKSCSZGY-UHFFFAOYSA-N 0.000 claims description 2
- UJEWTUDSLQGTOA-UHFFFAOYSA-N Piretanide Chemical compound C=1C=CC=CC=1OC=1C(S(=O)(=O)N)=CC(C(O)=O)=CC=1N1CCCC1 UJEWTUDSLQGTOA-UHFFFAOYSA-N 0.000 claims description 2
- VXFJYXUZANRPDJ-WTNASJBWSA-N Trandopril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@H]2CCCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 VXFJYXUZANRPDJ-WTNASJBWSA-N 0.000 claims description 2
- 229960000528 amlodipine Drugs 0.000 claims description 2
- HTIQEAQVCYTUBX-UHFFFAOYSA-N amlodipine Chemical compound CCOC(=O)C1=C(COCCN)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1Cl HTIQEAQVCYTUBX-UHFFFAOYSA-N 0.000 claims description 2
- 229960002274 atenolol Drugs 0.000 claims description 2
- 229960004530 benazepril Drugs 0.000 claims description 2
- 229960003515 bendroflumethiazide Drugs 0.000 claims description 2
- HDWIHXWEUNVBIY-UHFFFAOYSA-N bendroflumethiazidum Chemical compound C1=C(C(F)(F)F)C(S(=O)(=O)N)=CC(S(N2)(=O)=O)=C1NC2CC1=CC=CC=C1 HDWIHXWEUNVBIY-UHFFFAOYSA-N 0.000 claims description 2
- 229960005400 bisoprolol fumarate Drugs 0.000 claims description 2
- 229960004349 candesartan cilexetil Drugs 0.000 claims description 2
- 229960000830 captopril Drugs 0.000 claims description 2
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 claims description 2
- 229960004195 carvedilol Drugs 0.000 claims description 2
- NPAKNKYSJIDKMW-UHFFFAOYSA-N carvedilol Chemical group COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=NC3=CC=C[CH]C3=C12 NPAKNKYSJIDKMW-UHFFFAOYSA-N 0.000 claims description 2
- 229940083181 centrally acting adntiadrenergic agent methyldopa Drugs 0.000 claims description 2
- 229960005025 cilazapril Drugs 0.000 claims description 2
- HHHKFGXWKKUNCY-FHWLQOOXSA-N cilazapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H]1C(N2[C@@H](CCCN2CCC1)C(O)=O)=O)CC1=CC=CC=C1 HHHKFGXWKKUNCY-FHWLQOOXSA-N 0.000 claims description 2
- 229960002896 clonidine Drugs 0.000 claims description 2
- HSUGRBWQSSZJOP-RTWAWAEBSA-N diltiazem Chemical compound C1=CC(OC)=CC=C1[C@H]1[C@@H](OC(C)=O)C(=O)N(CCN(C)C)C2=CC=CC=C2S1 HSUGRBWQSSZJOP-RTWAWAEBSA-N 0.000 claims description 2
- 229960004166 diltiazem Drugs 0.000 claims description 2
- RUZYUOTYCVRMRZ-UHFFFAOYSA-N doxazosin Chemical compound C1OC2=CC=CC=C2OC1C(=O)N(CC1)CCN1C1=NC(N)=C(C=C(C(OC)=C2)OC)C2=N1 RUZYUOTYCVRMRZ-UHFFFAOYSA-N 0.000 claims description 2
- 229960001389 doxazosin Drugs 0.000 claims description 2
- 229960000309 enalapril maleate Drugs 0.000 claims description 2
- OYFJQPXVCSSHAI-QFPUQLAESA-N enalapril maleate Chemical compound OC(=O)\C=C/C(O)=O.C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(O)=O)CC1=CC=CC=C1 OYFJQPXVCSSHAI-QFPUQLAESA-N 0.000 claims description 2
- 229960002198 irbesartan Drugs 0.000 claims description 2
- YCPOHTHPUREGFM-UHFFFAOYSA-N irbesartan Chemical compound O=C1N(CC=2C=CC(=CC=2)C=2C(=CC=CC=2)C=2[N]N=NN=2)C(CCCC)=NC21CCCC2 YCPOHTHPUREGFM-UHFFFAOYSA-N 0.000 claims description 2
- 229960001632 labetalol Drugs 0.000 claims description 2
- 229960002394 lisinopril Drugs 0.000 claims description 2
- RLAWWYSOJDYHDC-BZSNNMDCSA-N lisinopril Chemical compound C([C@H](N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(O)=O)C(O)=O)CC1=CC=CC=C1 RLAWWYSOJDYHDC-BZSNNMDCSA-N 0.000 claims description 2
- 229960001300 metoprolol tartrate Drugs 0.000 claims description 2
- 229960000619 nebivolol Drugs 0.000 claims description 2
- 229960001597 nifedipine Drugs 0.000 claims description 2
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical group COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 claims description 2
- 229960001199 olmesartan medoxomil Drugs 0.000 claims description 2
- 229960002582 perindopril Drugs 0.000 claims description 2
- IPVQLZZIHOAWMC-QXKUPLGCSA-N perindopril Chemical compound C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 IPVQLZZIHOAWMC-QXKUPLGCSA-N 0.000 claims description 2
- 229960001085 piretanide Drugs 0.000 claims 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 claims description 2
- 229960001289 prazosin Drugs 0.000 claims description 2
- 229960001455 quinapril Drugs 0.000 claims description 2
- JSDRRTOADPPCHY-HSQYWUDLSA-N quinapril Chemical group C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 JSDRRTOADPPCHY-HSQYWUDLSA-N 0.000 claims description 2
- 229960003401 ramipril Drugs 0.000 claims description 2
- HDACQVRGBOVJII-JBDAPHQKSA-N ramipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](C[C@@H]2CCC[C@@H]21)C(O)=O)CC1=CC=CC=C1 HDACQVRGBOVJII-JBDAPHQKSA-N 0.000 claims description 2
- 229960005187 telmisartan Drugs 0.000 claims description 2
- WUBVEMGCQRSBBT-UHFFFAOYSA-N tert-butyl 4-(trifluoromethylsulfonyloxy)-3,6-dihydro-2h-pyridine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(OS(=O)(=O)C(F)(F)F)=CC1 WUBVEMGCQRSBBT-UHFFFAOYSA-N 0.000 claims description 2
- 229960002051 trandolapril Drugs 0.000 claims description 2
- 229960004699 valsartan Drugs 0.000 claims description 2
- SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 claims description 2
- 229960001722 verapamil Drugs 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims 5
- 229940127557 pharmaceutical product Drugs 0.000 claims 5
- 229940123413 Angiotensin II antagonist Drugs 0.000 claims 2
- 239000002333 angiotensin II receptor antagonist Substances 0.000 claims 2
- 239000011575 calcium Substances 0.000 claims 2
- 235000012041 food component Nutrition 0.000 claims 2
- 230000002265 prevention Effects 0.000 claims 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims 1
- 230000001882 diuretic effect Effects 0.000 claims 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 19
- 230000035487 diastolic blood pressure Effects 0.000 description 17
- 230000035488 systolic blood pressure Effects 0.000 description 12
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- 210000002966 serum Anatomy 0.000 description 9
- OVBPIULPVIDEAO-LBPRGKRZSA-N folic acid Chemical compound C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-LBPRGKRZSA-N 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 210000003743 erythrocyte Anatomy 0.000 description 6
- 235000019152 folic acid Nutrition 0.000 description 6
- 239000011724 folic acid Substances 0.000 description 6
- 238000005259 measurement Methods 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 229940014144 folate Drugs 0.000 description 5
- 208000010125 myocardial infarction Diseases 0.000 description 5
- 239000000902 placebo Substances 0.000 description 5
- 229940068196 placebo Drugs 0.000 description 5
- 230000023856 response to vitamin B2 Effects 0.000 description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- 229940127088 antihypertensive drug Drugs 0.000 description 4
- 208000019622 heart disease Diseases 0.000 description 4
- 235000016709 nutrition Nutrition 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 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
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 102000001554 Hemoglobins Human genes 0.000 description 3
- 108010054147 Hemoglobins Proteins 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 230000035764 nutrition Effects 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- NGVDGCNFYWLIFO-UHFFFAOYSA-N pyridoxal 5'-phosphate Chemical compound CC1=NC=C(COP(O)(O)=O)C(C=O)=C1O NGVDGCNFYWLIFO-UHFFFAOYSA-N 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000007619 statistical method Methods 0.000 description 3
- -1 tertatrol Chemical compound 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 229940105150 5-methyltetrahydrofolic acid Drugs 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 238000000540 analysis of variance Methods 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 238000005345 coagulation Methods 0.000 description 2
- 230000015271 coagulation Effects 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 239000003906 humectant Substances 0.000 description 2
- 229910052742 iron Inorganic materials 0.000 description 2
- ZNOVTXRBGFNYRX-ABLWVSNPSA-N levomefolic acid Chemical compound C1NC=2NC(N)=NC(=O)C=2N(C)C1CNC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 ZNOVTXRBGFNYRX-ABLWVSNPSA-N 0.000 description 2
- 150000002632 lipids Chemical class 0.000 description 2
- 230000002906 microbiologic effect Effects 0.000 description 2
- 239000006186 oral dosage form Substances 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- XDIYNQZUNSSENW-UUBOPVPUSA-N (2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O XDIYNQZUNSSENW-UUBOPVPUSA-N 0.000 description 1
- JIVPVXMEBJLZRO-CQSZACIVSA-N 2-chloro-5-[(1r)-1-hydroxy-3-oxo-2h-isoindol-1-yl]benzenesulfonamide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC([C@@]2(O)C3=CC=CC=C3C(=O)N2)=C1 JIVPVXMEBJLZRO-CQSZACIVSA-N 0.000 description 1
- 101710188260 5,10-methylenetetrahydrofolate reductase Proteins 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 102000005862 Angiotensin II Human genes 0.000 description 1
- 101800000733 Angiotensin-2 Proteins 0.000 description 1
- 108010063907 Glutathione Reductase Proteins 0.000 description 1
- 102100036442 Glutathione reductase, mitochondrial Human genes 0.000 description 1
- 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 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- OVBPIULPVIDEAO-UHFFFAOYSA-N N-Pteroyl-L-glutaminsaeure Natural products C=1N=C2NC(N)=NC(=O)C2=NC=1CNC1=CC=C(C(=O)NC(CCC(O)=O)C(O)=O)C=C1 OVBPIULPVIDEAO-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 108010039491 Ricin Proteins 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- 238000010162 Tukey test Methods 0.000 description 1
- 229930003270 Vitamin B Natural products 0.000 description 1
- 230000003187 abdominal effect Effects 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 229950006323 angiotensin ii Drugs 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000012742 biochemical analysis Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 238000009530 blood pressure measurement Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000000546 chi-square test Methods 0.000 description 1
- 229960001523 chlortalidone Drugs 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000010219 correlation analysis Methods 0.000 description 1
- 238000005138 cryopreservation Methods 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 230000003205 diastolic effect Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 235000018823 dietary intake Nutrition 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000001917 fluorescence detection Methods 0.000 description 1
- 229960000304 folic acid Drugs 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 238000003205 genotyping method Methods 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 229940060367 inert ingredients Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 239000006166 lysate Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 238000010197 meta-analysis Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 235000020925 non fasting Nutrition 0.000 description 1
- 238000010606 normalization Methods 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 238000007427 paired t-test Methods 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229960002508 pindolol Drugs 0.000 description 1
- PHUTUTUABXHXLW-UHFFFAOYSA-N pindolol Chemical compound CC(C)NCC(O)COC1=CC=CC2=NC=C[C]12 PHUTUTUABXHXLW-UHFFFAOYSA-N 0.000 description 1
- 210000004180 plasmocyte Anatomy 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000007115 recruitment Effects 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Images
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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/525—Isoalloxazines, e.g. riboflavins, vitamin B2
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0703514.0A GB0703514D0 (en) | 2007-02-23 | 2007-02-23 | Use of riboflavin |
| GB0703514.0 | 2007-02-23 | ||
| PCT/EP2008/001437 WO2008101724A1 (en) | 2007-02-23 | 2008-02-22 | Use of riboflavin in the treatment of hypertension |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2010519235A JP2010519235A (ja) | 2010-06-03 |
| JP2010519235A5 JP2010519235A5 (enExample) | 2011-03-31 |
| JP5577100B2 true JP5577100B2 (ja) | 2014-08-20 |
Family
ID=37945596
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009550246A Expired - Fee Related JP5577100B2 (ja) | 2007-02-23 | 2008-02-22 | 高血圧症治療におけるリボフラビンの使用 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20100324019A1 (enExample) |
| EP (1) | EP2139488B1 (enExample) |
| JP (1) | JP5577100B2 (enExample) |
| CN (1) | CN101678030B (enExample) |
| CA (1) | CA2679217C (enExample) |
| EA (1) | EA019281B1 (enExample) |
| ES (1) | ES2393144T3 (enExample) |
| GB (1) | GB0703514D0 (enExample) |
| MX (1) | MX2009009020A (enExample) |
| WO (1) | WO2008101724A1 (enExample) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104737023B (zh) * | 2012-08-16 | 2017-07-28 | 重症监护诊断股份有限公司 | 预测患高血压风险的方法 |
| CN103721259A (zh) * | 2014-01-07 | 2014-04-16 | 深圳奥萨医药有限公司 | 血管紧张素ⅱ受体阻断剂/噻嗪类利尿剂/5-甲基四氢叶酸药物组合物 |
| CN109295216A (zh) * | 2018-11-06 | 2019-02-01 | 宁波艾捷康宁生物科技有限公司 | 预测高血压个体化药物药效的snp位点和检测试剂盒 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4264601A (en) * | 1979-06-12 | 1981-04-28 | The Board Of Regents Of The University Of Oklahoma | Antihypertensive agents and their use in treatment of hypertension |
| DE3682208D1 (de) * | 1986-12-18 | 1991-11-28 | Kurt Heinz Bauer | Gegenueber lichteinfluss stabilisiertes nifedipin-konzentrat und verfahren zu seiner herstellung. |
| US6485959B1 (en) * | 1998-10-07 | 2002-11-26 | Cedars Sinai Medical Center | Cell preconditioning and cryopresevation medium |
| CN1136895C (zh) * | 2001-05-24 | 2004-02-04 | 魏振鸣 | 一种治疗冠心病的药物 |
| WO2006085128A1 (en) * | 2005-02-09 | 2006-08-17 | Wockhardt Limited | Cardiovascular therapeutic combinations |
| US7838526B2 (en) * | 2005-08-05 | 2010-11-23 | Esther Baldinger | Method of treating neurological disorders |
-
2007
- 2007-02-23 GB GBGB0703514.0A patent/GB0703514D0/en not_active Ceased
-
2008
- 2008-02-22 EA EA200901145A patent/EA019281B1/ru not_active IP Right Cessation
- 2008-02-22 EP EP08715988A patent/EP2139488B1/en not_active Not-in-force
- 2008-02-22 WO PCT/EP2008/001437 patent/WO2008101724A1/en not_active Ceased
- 2008-02-22 MX MX2009009020A patent/MX2009009020A/es active IP Right Grant
- 2008-02-22 CA CA2679217A patent/CA2679217C/en active Active
- 2008-02-22 CN CN2008800135209A patent/CN101678030B/zh not_active Expired - Fee Related
- 2008-02-22 JP JP2009550246A patent/JP5577100B2/ja not_active Expired - Fee Related
- 2008-02-22 US US12/528,105 patent/US20100324019A1/en not_active Abandoned
- 2008-02-22 ES ES08715988T patent/ES2393144T3/es active Active
Also Published As
| Publication number | Publication date |
|---|---|
| US20100324019A1 (en) | 2010-12-23 |
| CA2679217A1 (en) | 2008-08-28 |
| EP2139488A1 (en) | 2010-01-06 |
| EA019281B1 (ru) | 2014-02-28 |
| GB0703514D0 (en) | 2007-04-04 |
| CN101678030B (zh) | 2013-06-05 |
| EP2139488B1 (en) | 2012-08-15 |
| CN101678030A (zh) | 2010-03-24 |
| WO2008101724A1 (en) | 2008-08-28 |
| EA200901145A1 (ru) | 2010-02-26 |
| JP2010519235A (ja) | 2010-06-03 |
| WO2008101724A8 (en) | 2009-10-08 |
| MX2009009020A (es) | 2010-02-17 |
| CA2679217C (en) | 2016-05-17 |
| ES2393144T3 (es) | 2012-12-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Kivity et al. | Clinical characteristics and risk factors for low dose methotrexate toxicity: a cohort of 28 patients | |
| Rosmond et al. | Tsp509I polymorphism in exon 2 of the glucocorticoid receptor gene in relation to obesity and cortisol secretion: cohort study | |
| RU2663450C2 (ru) | Способы лечения рака поджелудочной железы с применением комбинированной терапии, включающей липосомный иринотекан | |
| Van Ahlen et al. | Safety and efficacy of vardenafil, a selective phosphodiesterase 5 inhibitor, in patients with erectile dysfunction and arterial hypertension treated with multiple antihypertensives | |
| Kahan | Two-year results of multicenter phase III trials on the effect of the addition of sirolimus to cyclosporine-based immunosuppressive regimens in renal transplantation | |
| Yu et al. | Frequency of potential azole drug–drug interactions and consequences of potential fluconazole drug interactions | |
| Hussaini et al. | Therapeutic drug monitoring of voriconazole and posaconazole | |
| Boogaerts et al. | Itraconazole versus amphotericin B plus nystatin in the prophylaxis of fungal infections in neutropenic cancer patients | |
| US20210338648A1 (en) | Methods and compositions for reducing serum uric acid | |
| JP5577100B2 (ja) | 高血圧症治療におけるリボフラビンの使用 | |
| Saad et al. | Effect of ciprofloxacin vs levofloxacin on QTc‐interval and dysglycemia in diabetic and non‐diabetic patients | |
| Vogt et al. | Individual titration for maximal blockade of the renin-angiotensin system in proteinuric patients: a feasible strategy? | |
| Puspitasari et al. | Analysis of potential drugs interaction on antihypertension drugs prescription in community health center of sukmajaya district in period of june-november 2015 | |
| Nakashima et al. | Nicergoline improves dysphagia by upregulating substance P in the elderly | |
| Weinberg et al. | Long-term safety of high-dose angiotensin receptor blocker therapy in hypertensive patients with chronic kidney disease | |
| Huang et al. | A multicentered, randomized, double-blind, parallel-controlled clinical trial on the homocysteine and blood pressure-lowering effects of amlodipine-folic acid versus amlodipine among H-type hypertensive patients intolerant to ACEI: principles and methods | |
| Papadakis et al. | Influence of the methylene tetrahydrofolate reductase (mthfr) gene polymorphisms on serum folate, cobalanin and homocysteine levels in healthy greek adults | |
| Sasaki et al. | Preface: evidence-based practice guideline for the treatment of chronic kidney disease | |
| Ahmed | Update on diagnosis and management of early stage diabetic kidney disease | |
| Robles et al. | Effectiveness and safety of eprosartan on pulse pressure for the treatment of hypertensive patients | |
| Benz et al. | Mycophenolate mofetil introduction stabilizes and subsequent cyclosporine A reduction slightly improves kidney function in pediatric renal transplant patients: a retrospective analysis | |
| Vacante et al. | Work productivity and activity impairment in breast cancer patients treated with capecitabine | |
| JAMES et al. | COMPARISON OF ANTI-PROTEINURIC EFFECTS OF AMLODIPINE AND CILNIDIPINE AS AN ADD-ON DRUG TO BASELINE MEDICATION IN HYPERTENSIVE CHRONIC KIDNEY DISEASE PATIENTS | |
| Wagg et al. | 880 ASSESSMENT OF FESOTERODINE TREATMENT IN OLDER PEOPLE WITH OVERACTIVE BLADDER: RESULTS OF SOFIA, A DOUBLE-BLIND, PLACEBO-CONTROLLED PAN EUROPEAN TRIAL | |
| Garcell et al. | Factors related with sputum smear conversion time among tuberculosis patients |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20110207 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20110207 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130108 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130405 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130412 |
|
| A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130507 |
|
| A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130514 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130610 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20140114 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140513 |
|
| A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20140520 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20140610 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20140707 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 5577100 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| LAPS | Cancellation because of no payment of annual fees |