JP2013523603A - 活性成分としてl−カルニチンまたはプロピオニルl−カルニチンを含む慢性静脈不全の予防または治療のための併用組成物 - Google Patents
活性成分としてl−カルニチンまたはプロピオニルl−カルニチンを含む慢性静脈不全の予防または治療のための併用組成物 Download PDFInfo
- Publication number
- JP2013523603A JP2013523603A JP2012551703A JP2012551703A JP2013523603A JP 2013523603 A JP2013523603 A JP 2013523603A JP 2012551703 A JP2012551703 A JP 2012551703A JP 2012551703 A JP2012551703 A JP 2012551703A JP 2013523603 A JP2013523603 A JP 2013523603A
- Authority
- JP
- Japan
- Prior art keywords
- carnitine
- venous
- propionyl
- preferred dose
- combination composition
- 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.)
- Granted
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 34
- PHIQHXFUZVPYII-ZCFIWIBFSA-N (R)-carnitine Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O PHIQHXFUZVPYII-ZCFIWIBFSA-N 0.000 title claims abstract description 21
- UFAHZIUFPNSHSL-MRVPVSSYSA-N O-propanoyl-L-carnitine Chemical compound CCC(=O)O[C@H](CC([O-])=O)C[N+](C)(C)C UFAHZIUFPNSHSL-MRVPVSSYSA-N 0.000 title claims abstract description 18
- 239000004480 active ingredient Substances 0.000 title claims abstract description 12
- 201000002282 venous insufficiency Diseases 0.000 title claims description 32
- 201000002816 chronic venous insufficiency Diseases 0.000 title claims description 31
- VUYDGVRIQRPHFX-UHFFFAOYSA-N hesperidin Natural products COc1cc(ccc1O)C2CC(=O)c3c(O)cc(OC4OC(COC5OC(O)C(O)C(O)C5O)C(O)C(O)C4O)cc3O2 VUYDGVRIQRPHFX-UHFFFAOYSA-N 0.000 claims abstract description 35
- QUQPHWDTPGMPEX-QJBIFVCTSA-N hesperidin Chemical compound C1=C(O)C(OC)=CC=C1[C@H]1OC2=CC(O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@@H](CO[C@H]4[C@@H]([C@H](O)[C@@H](O)[C@H](C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-QJBIFVCTSA-N 0.000 claims abstract description 21
- 239000001100 (2S)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one Substances 0.000 claims abstract description 20
- QUQPHWDTPGMPEX-UHFFFAOYSA-N Hesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(COC4C(C(O)C(O)C(C)O4)O)O3)O)=CC(O)=C2C(=O)C1 QUQPHWDTPGMPEX-UHFFFAOYSA-N 0.000 claims abstract description 20
- QUQPHWDTPGMPEX-UTWYECKDSA-N aurantiamarin Natural products COc1ccc(cc1O)[C@H]1CC(=O)c2c(O)cc(O[C@@H]3O[C@H](CO[C@@H]4O[C@@H](C)[C@H](O)[C@@H](O)[C@H]4O)[C@@H](O)[C@H](O)[C@H]3O)cc2O1 QUQPHWDTPGMPEX-UTWYECKDSA-N 0.000 claims abstract description 20
- APSNPMVGBGZYAJ-GLOOOPAXSA-N clematine Natural products COc1cc(ccc1O)[C@@H]2CC(=O)c3c(O)cc(O[C@@H]4O[C@H](CO[C@H]5O[C@@H](C)[C@H](O)[C@@H](O)[C@H]5O)[C@@H](O)[C@H](O)[C@H]4O)cc3O2 APSNPMVGBGZYAJ-GLOOOPAXSA-N 0.000 claims abstract description 20
- 229940025878 hesperidin Drugs 0.000 claims abstract description 20
- ARGKVCXINMKCAZ-UHFFFAOYSA-N neohesperidine Natural products C1=C(O)C(OC)=CC=C1C1OC2=CC(OC3C(C(O)C(O)C(CO)O3)OC3C(C(O)C(O)C(C)O3)O)=CC(O)=C2C(=O)C1 ARGKVCXINMKCAZ-UHFFFAOYSA-N 0.000 claims abstract description 20
- GZSOSUNBTXMUFQ-YFAPSIMESA-N diosmin Chemical compound C1=C(O)C(OC)=CC=C1C(OC1=C2)=CC(=O)C1=C(O)C=C2O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO[C@H]2[C@@H]([C@H](O)[C@@H](O)[C@H](C)O2)O)O1 GZSOSUNBTXMUFQ-YFAPSIMESA-N 0.000 claims abstract description 17
- 229960004352 diosmin Drugs 0.000 claims abstract description 16
- GZSOSUNBTXMUFQ-NJGQXECBSA-N 5,7,3'-Trihydroxy-4'-methoxyflavone 7-O-rutinoside Natural products O(C[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](Oc2cc(O)c3C(=O)C=C(c4cc(O)c(OC)cc4)Oc3c2)O1)[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@H](C)O1 GZSOSUNBTXMUFQ-NJGQXECBSA-N 0.000 claims abstract description 15
- IGBKNLGEMMEWKD-UHFFFAOYSA-N diosmin Natural products COc1ccc(cc1)C2=C(O)C(=O)c3c(O)cc(OC4OC(COC5OC(C)C(O)C(O)C5O)C(O)C(O)C4O)cc3O2 IGBKNLGEMMEWKD-UHFFFAOYSA-N 0.000 claims abstract description 15
- 208000037998 chronic venous disease Diseases 0.000 claims abstract description 11
- -1 troxertin Chemical compound 0.000 claims abstract description 8
- 230000002265 prevention Effects 0.000 claims abstract description 7
- 210000003462 vein Anatomy 0.000 claims description 33
- 150000003839 salts Chemical class 0.000 claims description 11
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 8
- 206010047249 Venous thrombosis Diseases 0.000 claims description 8
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 8
- 208000037997 venous disease Diseases 0.000 claims description 8
- 206010030113 Oedema Diseases 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
- 208000014617 hemorrhoid Diseases 0.000 claims description 6
- 208000010729 leg swelling Diseases 0.000 claims description 6
- 208000025865 Ulcer Diseases 0.000 claims description 5
- 230000004054 inflammatory process Effects 0.000 claims description 5
- 208000001297 phlebitis Diseases 0.000 claims description 5
- 230000008961 swelling Effects 0.000 claims description 5
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 4
- 206010020772 Hypertension Diseases 0.000 claims description 4
- 206010061218 Inflammation Diseases 0.000 claims description 4
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 4
- 208000010378 Pulmonary Embolism Diseases 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 210000000436 anus Anatomy 0.000 claims description 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 4
- 231100000397 ulcer Toxicity 0.000 claims description 4
- 206010023232 Joint swelling Diseases 0.000 claims description 3
- 229910019142 PO4 Inorganic materials 0.000 claims description 3
- 239000003146 anticoagulant agent Substances 0.000 claims description 3
- 239000003963 antioxidant agent Substances 0.000 claims description 3
- 229940009098 aspartate Drugs 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 230000035699 permeability Effects 0.000 claims description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
- 210000000664 rectum Anatomy 0.000 claims description 3
- 201000005060 thrombophlebitis Diseases 0.000 claims description 3
- 210000003905 vulva Anatomy 0.000 claims description 3
- NDVRKEKNSBMTAX-BTVCFUMJSA-N (2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanal;phosphoric acid Chemical compound OP(O)(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O NDVRKEKNSBMTAX-BTVCFUMJSA-N 0.000 claims description 2
- QWJSAWXRUVVRLH-LREBCSMRSA-M 2-hydroxyethyl(trimethyl)azanium;(2r,3r)-2,3,4-trihydroxy-4-oxobutanoate Chemical compound C[N+](C)(C)CCO.OC(=O)[C@H](O)[C@@H](O)C([O-])=O QWJSAWXRUVVRLH-LREBCSMRSA-M 0.000 claims description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 2
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 claims description 2
- 229940127219 anticoagulant drug Drugs 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 229960004106 citric acid Drugs 0.000 claims description 2
- 239000005515 coenzyme Substances 0.000 claims description 2
- 235000015872 dietary supplement Nutrition 0.000 claims description 2
- 239000001530 fumaric acid Substances 0.000 claims description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 2
- 229960005336 magnesium citrate Drugs 0.000 claims description 2
- 239000004337 magnesium citrate Substances 0.000 claims description 2
- 235000002538 magnesium citrate Nutrition 0.000 claims description 2
- QUIOHQITLKCGNW-TYYBGVCCSA-L magnesium;(e)-but-2-enedioate Chemical compound [Mg+2].[O-]C(=O)\C=C\C([O-])=O QUIOHQITLKCGNW-TYYBGVCCSA-L 0.000 claims description 2
- YZURQOBSFRVSEB-UHFFFAOYSA-L magnesium;2-aminoethanesulfonate Chemical compound [Mg+2].NCCS([O-])(=O)=O.NCCS([O-])(=O)=O YZURQOBSFRVSEB-UHFFFAOYSA-L 0.000 claims description 2
- 239000011976 maleic acid Substances 0.000 claims description 2
- 239000011707 mineral Substances 0.000 claims description 2
- PXQPEWDEAKTCGB-UHFFFAOYSA-N orotic acid Chemical compound OC(=O)C1=CC(=O)NC(=O)N1 PXQPEWDEAKTCGB-UHFFFAOYSA-N 0.000 claims description 2
- 235000006408 oxalic acid Nutrition 0.000 claims description 2
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 239000011975 tartaric acid Substances 0.000 claims description 2
- 235000002906 tartaric acid Nutrition 0.000 claims description 2
- 229940095064 tartrate Drugs 0.000 claims description 2
- 229940066528 trichloroacetate Drugs 0.000 claims description 2
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 claims description 2
- PLSARIKBYIPYPF-UHFFFAOYSA-H trimagnesium dicitrate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O PLSARIKBYIPYPF-UHFFFAOYSA-H 0.000 claims description 2
- 229940088594 vitamin Drugs 0.000 claims description 2
- 239000011782 vitamin Substances 0.000 claims description 2
- 235000013343 vitamin Nutrition 0.000 claims description 2
- 229930003231 vitamin Natural products 0.000 claims description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-M 2-aminoethanesulfonate Chemical compound NCCS([O-])(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-M 0.000 claims 1
- 206010002329 Aneurysm Diseases 0.000 claims 1
- 206010042674 Swelling Diseases 0.000 claims 1
- 238000001990 intravenous administration Methods 0.000 claims 1
- 229940095060 magnesium tartrate Drugs 0.000 claims 1
- MUZDLCBWNVUYIR-ZVGUSBNCSA-L magnesium;(2r,3r)-2,3-dihydroxybutanedioate Chemical compound [Mg+2].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O MUZDLCBWNVUYIR-ZVGUSBNCSA-L 0.000 claims 1
- 230000000699 topical effect Effects 0.000 claims 1
- 210000004369 blood Anatomy 0.000 description 15
- 239000008280 blood Substances 0.000 description 15
- 150000001875 compounds Chemical class 0.000 description 13
- 241000700159 Rattus Species 0.000 description 12
- 206010046996 Varicose vein Diseases 0.000 description 9
- 208000027185 varicose disease Diseases 0.000 description 9
- 229930003935 flavonoid Natural products 0.000 description 6
- 150000002215 flavonoids Chemical class 0.000 description 6
- 235000017173 flavonoids Nutrition 0.000 description 6
- IYVFNTXFRYQLRP-VVSTWUKXSA-N 2-[3,4-bis(2-hydroxyethoxy)phenyl]-5-hydroxy-7-(2-hydroxyethoxy)-3-{[(2s,3r,4s,5s,6r)-3,4,5-trihydroxy-6-({[(2r,3r,4r,5r,6s)-3,4,5-trihydroxy-6-methyloxan-2-yl]oxy}methyl)oxan-2-yl]oxy}-4h-chromen-4-one Chemical compound O[C@@H]1[C@H](O)[C@@H](O)[C@H](C)O[C@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@H](OC=2C(C3=C(O)C=C(OCCO)C=C3OC=2C=2C=C(OCCO)C(OCCO)=CC=2)=O)O1 IYVFNTXFRYQLRP-VVSTWUKXSA-N 0.000 description 5
- 206010051055 Deep vein thrombosis Diseases 0.000 description 5
- 210000000709 aorta Anatomy 0.000 description 5
- HGUFODBRKLSHSI-UHFFFAOYSA-N 2,3,7,8-tetrachloro-dibenzo-p-dioxin Chemical compound O1C2=CC(Cl)=C(Cl)C=C2OC2=C1C=C(Cl)C(Cl)=C2 HGUFODBRKLSHSI-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229940081779 hesperidin 100 mg Drugs 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 210000003205 muscle Anatomy 0.000 description 4
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 4
- 229960001802 phenylephrine Drugs 0.000 description 4
- 238000001356 surgical procedure Methods 0.000 description 4
- 241000282412 Homo Species 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 230000003078 antioxidant effect Effects 0.000 description 3
- 230000036772 blood pressure Effects 0.000 description 3
- 230000008602 contraction Effects 0.000 description 3
- 230000000149 penetrating effect Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000002040 relaxant effect Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 3
- 210000001519 tissue Anatomy 0.000 description 3
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 102000007330 LDL Lipoproteins Human genes 0.000 description 2
- 108010007622 LDL Lipoproteins Proteins 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 208000007536 Thrombosis Diseases 0.000 description 2
- 208000000558 Varicose Ulcer Diseases 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- 230000004087 circulation Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 230000035935 pregnancy Effects 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 230000002195 synergetic effect Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 210000002073 venous valve Anatomy 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- PEMHSDTZMPDEMX-KIZASDAWSA-N (3R)-3-hydroxy-4-(trimethylazaniumyl)butanoate (E)-4-oxo-4-propanoyloxybut-2-enoic acid Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O.CCC(=O)OC(=O)\C=C\C(O)=O PEMHSDTZMPDEMX-KIZASDAWSA-N 0.000 description 1
- HHFNEMIBTZVXAA-FYZOBXCZSA-N 2,3-dihydroxy-4-oxo-4-propanoyloxybutanoic acid (3R)-3-hydroxy-4-(trimethylazaniumyl)butanoate Chemical compound C[N+](C)(C)C[C@H](O)CC([O-])=O.CCC(=O)OC(=O)C(O)C(O)C(O)=O HHFNEMIBTZVXAA-FYZOBXCZSA-N 0.000 description 1
- RZALONVQKUWRRY-FYZOBXCZSA-N 2,3-dihydroxybutanedioic acid;(3r)-3-hydroxy-4-(trimethylazaniumyl)butanoate Chemical compound OC(=O)C(O)C(O)C(O)=O.C[N+](C)(C)C[C@H](O)CC([O-])=O RZALONVQKUWRRY-FYZOBXCZSA-N 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 206010054044 Diabetic microangiopathy Diseases 0.000 description 1
- 208000010201 Exanthema Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 208000035150 Hypercholesterolemia Diseases 0.000 description 1
- 208000007177 Left Ventricular Hypertrophy Diseases 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000018262 Peripheral vascular disease Diseases 0.000 description 1
- 206010036618 Premenstrual syndrome Diseases 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- HNSUOMBUJRUZHJ-REVJHSINSA-N [(2r)-3-carboxy-2-hydroxypropyl]-trimethylazanium;(z)-4-hydroxy-4-oxobut-2-enoate Chemical compound OC(=O)\C=C/C(O)=O.C[N+](C)(C)C[C@H](O)CC([O-])=O HNSUOMBUJRUZHJ-REVJHSINSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 210000003423 ankle Anatomy 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000002253 anti-ischaemic effect Effects 0.000 description 1
- 230000002785 anti-thrombosis Effects 0.000 description 1
- 210000002376 aorta thoracic Anatomy 0.000 description 1
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical class CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 229960005261 aspartic acid Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 229960004203 carnitine Drugs 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 210000002808 connective tissue Anatomy 0.000 description 1
- 230000009989 contractile response Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 201000009101 diabetic angiopathy Diseases 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 201000005884 exanthem Diseases 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 210000002683 foot Anatomy 0.000 description 1
- 239000008246 gaseous mixture Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 239000000411 inducer Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 210000004880 lymph fluid Anatomy 0.000 description 1
- 230000001926 lymphatic effect Effects 0.000 description 1
- 210000004324 lymphatic system Anatomy 0.000 description 1
- QXWXJSBFILYJNN-UHFFFAOYSA-L magnesium 2-aminoethanesulfonate 2,3,4-trihydroxy-4-oxobutanoate Chemical compound [Mg+2].NCCS([O-])(=O)=O.OC(=O)C(O)C(O)C([O-])=O QXWXJSBFILYJNN-UHFFFAOYSA-L 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000004089 microcirculation Effects 0.000 description 1
- 210000005063 microvascular endothelium Anatomy 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000000820 nonprescription drug Substances 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 229940082147 oxerutins Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 206010037844 rash Diseases 0.000 description 1
- 230000008439 repair process Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000002271 resection Methods 0.000 description 1
- 235000005493 rutin Nutrition 0.000 description 1
- 238000007632 sclerotherapy Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 231100000046 skin rash Toxicity 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 235000000891 standard diet Nutrition 0.000 description 1
- 230000009469 supplementation Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 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 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 230000036269 ulceration Effects 0.000 description 1
- 230000004218 vascular function Effects 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 230000001196 vasorelaxation Effects 0.000 description 1
- 230000002883 vasorelaxation effect Effects 0.000 description 1
- 238000007891 venous angioplasty Methods 0.000 description 1
- 230000037303 wrinkles Effects 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/17—Amino acids, peptides or proteins
- A23L33/175—Amino acids
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
- A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2200/00—Function of food ingredients
- A23V2200/30—Foods, ingredients or supplements having a functional effect on health
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Nutrition Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Mycology (AREA)
- Dermatology (AREA)
- Engineering & Computer Science (AREA)
- Food Science & Technology (AREA)
- Polymers & Plastics (AREA)
- Physiology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
Abstract
【選択図】図なし
Description
活性成分としてL−カルニチンまたはその誘導体(例えば、プロピオニルL−カルニチン)もしくはその塩、トロキセルチン、ジオスミン、およびヘスペリジンを含む組成物は、慢性静脈不全(CVI)および慢性静脈疾患(CVD)またはそれらの合併症から選択される常務薬の疾患の予防および/または治療のための驚くべき相乗効果を賦与されることが、いまや発見された。
(a)10〜3000mgの用量のL−カルニチンまたはプロピオニルL−カルニチン(好ましい用量は、50mg〜400mgであり、最も好ましい用量は136mgである)、
(b)900mg〜50mgの用量のトロキセルチン(好ましい用量は400mg〜200mgであり、最も好ましい用量は300mgである)、
(c)900mg〜50mgの用量のジオスミン(好ましい用量は400mg〜200mgであり、最も好ましい用量は300mgである)、および
(d)10mg〜500mgの用量のヘスペリジン(好ましい用量は50mg〜200mgであり、最も好ましい用量は100mgである)。
ラットのハズ油誘発性痔核モデルにおける直腸肛門(recto−anus)の腫脹の低下
雄SDラット(6週齢、およそ140g)をHarlan Sprague Dawleyから購入し、1週間順化させておいた。ラットを、National Research Council of Laboratory Animal取り扱いおよび使用のガイドラインに従って、無病原体施設において維持した。各実験を7〜8週齢の同齢のラットを用いて実施した。ラットのハズ油誘発性痔核モデルを、Nishiki(Nishiki el al. (1988) Folia Pharmacology Japan 92:215−225、Nishiki et al. (1988) Folia Pharmacol. Japan 92:227−240)によって公表された方法に従って実施した。簡潔には、直径4mmの綿棒を0.16mLの誘発剤(脱イオン水:ピリジン:エチルエーテル:6%ハズ油/エチルエーテル(1:4:5:10))をラットの肛門に12秒間塗布した。ハズ油の終濃度は3%であった。水腫は、塗布7〜8時間後まで直線的に発達し、水腫の重症度は、24時間超の間持続した。24時間後、ラットを安楽死させた後、直腸肛門組織(およそ10mm超)を単離した。ラットの体重および直腸肛門重量を測定した。直腸肛門係数(RAC)を、式:直腸肛門の重量(mg)/体重(g)を用いて算出した。
試験した化合物の大動脈輪に及ぼす弛緩効果
本研究の目的は、自然発症性高血圧ラットから単離された大動脈を用いて、本発明の組成物の血管弛緩効果を研究することであった。
試験した化合物を臓器チャンバーにおける終濃度として表される濃度で用いた。
雄の自然発症性高血圧ラット(SHR)10〜12週齢、体重250〜300gを24±2℃、60±20%相対湿度、12時間の明暗周期で飼育した。ラットに標準食および水への自由なアクセスを与えた。すべての実験を欧州連合の動物の倫理的処置についての指針に従って実施した。ラットを頸椎脱離により屠殺し、大動脈を迅速に摘出した。
下行胸大動脈(descending thoracic aorta)を、以下(mM)を含む改変したクレブス‐ヘンゼライト液(PSS)の中に配置した:NaCl 118、KCl 4.75、NaHCO3 25、MgSO4 1.2、CaCl2 1.8、KH2PO4 1.2、およびグルコース11。
試験した化合物の弛緩効果を、該化合物をフェニレフリン(1マイクロモル濃度)によってあらかじめ収縮させた大動脈輪に添加することによって評価した。
結果を最初の収縮前レベルからのパーセンテージとして表す。
(組成物1)
酒石酸L−カルニチン 200mg
-カルニチン136mgと等価
トロキセルチンNEC(登録商標) 700mg
トロキセルチナ300mgを含む
ジオスミン 300mg
98%ヘスペリジン 100mg
ヘスペリジン98mgと等価。
(組成物2)
酒石酸プロピオニルL−カルニチン 250mg
プロピオニルL−カルニチン136mgと等価
トロキセルチンNEC(登録商標) 700mg
トロキセルチナ300mgを含む
ジオスミン 300mg
98%ヘスペリジン 100mg
ヘスペリジン98mgと等価。
(組成物3)
フマル酸L−カルニチン 200mg
L−カルニチン136mgと等価
トロキセルチンNEC(登録商標) 700mg
トロキセルチナ300mgを含む
ジオスミン 300mg
98%ヘスペリジン 100mg
ヘスペリジン98mgと等価
(組成物4)
フマル酸プロピオニルL−カルニチン 250mg
プロピオニルL−カルニチン136mgと等価
トロキセルチンNEC(登録商標)700mg
トロキセルチナ300mgを含む
ジオスミン 300mg
98%ヘスペリジン 100mg
ヘスペリジン98mgと等価。
Claims (14)
- 活性成分としてL−カルニチン、またはその誘導体もしくは塩、トロキセルチン、ジオスミン、ヘスペリジン、および任意に医薬として許容し得る1つ以上の賦形剤を含む、併用組成物。
- L−カルニチンの誘導体はプロピオニルL−カルニチンである、請求項1に記載の併用組成物。
- 10〜3000mgの用量のL−カルニチンまたはプロピオニルL−カルニチン(好ましい用量は、50mg〜400mgであり、最も好ましい用量は136mgである)、
900mg〜50mgの用量のトロキセルチン(好ましい用量は400mg〜200mgであり、最も好ましい用量は300mgである)、
900mg〜50mgの用量のジオスミン(好ましい用量は400mg〜200mgであり、最も好ましい用量は300mgである)、および
10mg〜500mgの用量のヘスペリジン(好ましい用量は50mg〜200mgであり、最も好ましい用量は100mgである)
を含む、請求項1または2に記載の併用組成物。 - 栄養補助食品としての、請求項1に記載の併用組成物。
- 薬剤としての、請求項1に記載の併用組成物。
- 補酵素、ミネラル物質、抗酸化物質、ビタミン、抗凝固薬、および静脈の疾患を治療するのに有用な薬剤をさらに含む、請求項1に記載の併用組成物。
- 静脈の疾患の予防または治療のための使用のための、請求項1または2に記載の併用組成物。
- 活性成分として、L−カルニチンまたはその誘導体もしくは塩、トロキセルチン、ジオスミン、およびヘスペリジンを含む併用組成物の、静脈の疾患の予防または治療のための薬剤を調製するための、使用。
- 前記L−カルニチンの誘導体は、プロピオニルL−カルニチンである、請求項8に記載の使用。
- 前記静脈の疾患は、慢性静脈不全、慢性静脈疾患、およびそれらの合併症からなる群から選択される、請求項8または9に記載の使用。
- 前記合併症は、直腸、肛門、および外陰における静脈の腫脹および炎症、静脈高血圧症、増大した浸透性、水腫、毛細管損傷、皮膚の変化、脚静脈性潰瘍、足関節部腫脹、太い脚、静脈瘤、脚部腫脹、潰瘍、静脈血栓症、静脈炎、血栓性静脈炎、肺塞栓、または痔核からなる群から選択される、請求項10に記載の使用。
- 前記L−カルニチンまたはプロピオニルL−カルニチンの塩は、塩化物、臭化物、オロト酸塩、アスパラギン酸塩、アスパラギン酸、クエン酸、クエン酸マグネシウム、リン酸塩、リン酸、フマル酸塩およびフマル酸、フマル酸マグネシウム、硫酸塩、マレイン酸塩およびマレイン酸、シュウ酸塩、シュウ酸、パモ酸塩、パモ酸、硫酸塩、硫酸、グルコースリン酸塩、酒石酸塩および酒石酸、グリセロリン酸塩、ムチン酸塩、酒石酸マグネシウム、2-アミノ-エタンスルホン酸塩、2-アミノ-エタンスルホン酸塩マグネシウム、メタンスルホン酸塩、酒石酸コリン、トリクロロ酢酸塩、またはトリフルオロ酢酸塩からなる群から選択される、請求項8または9に記載の使用。
- 経口、非経口、静脈内、局所、および/または経皮的投与のための、請求項8または9に記載の使用。
- 経口投与のための、請求項8または9に記載の使用。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US32253210P | 2010-04-09 | 2010-04-09 | |
US61/322,532 | 2010-04-09 | ||
PCT/IB2011/000200 WO2011095882A1 (en) | 2010-02-02 | 2011-02-07 | Combination composition, comprising as active ingredient l-carnitine or propionyl l-carnitine, for the prevention or treatment of chronic venous insufficiency |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2013523603A true JP2013523603A (ja) | 2013-06-17 |
JP2013523603A5 JP2013523603A5 (ja) | 2014-03-27 |
JP5923044B2 JP5923044B2 (ja) | 2016-05-24 |
Family
ID=48778619
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012551703A Active JP5923044B2 (ja) | 2010-04-09 | 2011-02-07 | 活性成分としてl−カルニチンまたはプロピオニルl−カルニチンを含む慢性静脈不全の予防または治療のための併用組成物 |
Country Status (2)
Country | Link |
---|---|
JP (1) | JP5923044B2 (ja) |
KR (1) | KR101758949B1 (ja) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101725461B1 (ko) * | 2015-12-29 | 2017-04-10 | 연세대학교 산학협력단 | 디오스민을 유효성분으로 포함하는 탈모 예방 또는 치료용, 또는 발모 또는 육모 촉진용 조성물 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5888312A (ja) * | 1981-11-06 | 1983-05-26 | シグマ―タウ・インダストリエ・ファルマシゥティシェ・リウニテ・ソシエタ・ペル・アチオーニ | カルニチンまたは低級アシルカルニチンからなる静脈疾患治療剤 |
WO2000028986A1 (en) * | 1998-11-13 | 2000-05-25 | Sigma-Tau Healthscience S.P.A. | Antioxidant composition comprising propionyl l-carnitine and a flavonoid against thrombosis and atherosclerosis |
WO2009031878A1 (es) * | 2007-09-07 | 2009-03-12 | Espinosa Abdala Leopoldo De Je | Composición farmacéutica que comprende la combinación de diversos agentes venotónicos y vasoprotectores para el tratamiento de la insuficiencia venosa crónica. |
-
2011
- 2011-02-07 KR KR1020127020878A patent/KR101758949B1/ko active IP Right Grant
- 2011-02-07 JP JP2012551703A patent/JP5923044B2/ja active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5888312A (ja) * | 1981-11-06 | 1983-05-26 | シグマ―タウ・インダストリエ・ファルマシゥティシェ・リウニテ・ソシエタ・ペル・アチオーニ | カルニチンまたは低級アシルカルニチンからなる静脈疾患治療剤 |
WO2000028986A1 (en) * | 1998-11-13 | 2000-05-25 | Sigma-Tau Healthscience S.P.A. | Antioxidant composition comprising propionyl l-carnitine and a flavonoid against thrombosis and atherosclerosis |
WO2009031878A1 (es) * | 2007-09-07 | 2009-03-12 | Espinosa Abdala Leopoldo De Je | Composición farmacéutica que comprende la combinación de diversos agentes venotónicos y vasoprotectores para el tratamiento de la insuficiencia venosa crónica. |
Also Published As
Publication number | Publication date |
---|---|
KR20130103297A (ko) | 2013-09-23 |
KR101758949B1 (ko) | 2017-07-17 |
JP5923044B2 (ja) | 2016-05-24 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2011212153B2 (en) | Combination composition, comprising as active ingredient L-carnitine or propionyl L-carnitine, for the prevention or treatment of chronic venous insufficiency | |
Al-Qattan et al. | The antihypertensive effect of garlic (Allium sativum) in the rat two-kidney–one-clip Goldblatt model | |
WO2009031878A1 (es) | Composición farmacéutica que comprende la combinación de diversos agentes venotónicos y vasoprotectores para el tratamiento de la insuficiencia venosa crónica. | |
Sigurdsson | Intensive care management of acute pancreatitis | |
JPS5888312A (ja) | カルニチンまたは低級アシルカルニチンからなる静脈疾患治療剤 | |
KR20120089623A (ko) | 정맥내 투여용 이부프로펜을 이용한 환자의 치료 | |
JP5923044B2 (ja) | 活性成分としてl−カルニチンまたはプロピオニルl−カルニチンを含む慢性静脈不全の予防または治療のための併用組成物 | |
CN102048160A (zh) | 蛇葡萄素在制备保护血管内皮细胞的保健食品及药物中的应用 | |
CA2787470C (en) | Combination composition, comprising as active ingredients l-carnitine or propionyl l-carnitine, for the prevention or treatment of chronic venous insufficiency | |
JPS5998018A (ja) | 老化治療剤 | |
JPH01503780A (ja) | プロスタサイクリン誘導体含有の局所適用剤 | |
JP5837128B2 (ja) | カルボスチリルとカルニチンの組み合わせ医薬 | |
CN104001175B (zh) | 一种治疗慢性心力衰竭的药物组合物及其应用 | |
JP2011505408A (ja) | 3−(2,2,2−トリメチルヒドラジニウム)プロピオナートのフマル酸水素塩及びリン酸二水素塩を医療に用いる方法 | |
CN1682715A (zh) | 一种抗缺氧药物组合物 | |
WO2022182703A1 (en) | Compositions and methods for treating inflammatory bowel disease | |
JP6609322B2 (ja) | 4−フェニル酪酸誘導体 | |
TW202216145A (zh) | 伴隨代謝異常之疾病或症候群中的肌力低下症狀之改善劑或預防劑 | |
CN104434920B (zh) | 一种治疗心力衰竭的药物组合物及其应用 | |
CN106361746A (zh) | 一种治疗继发性高血压的药物复方制剂 | |
Morali et al. | What does “reduced central blood volume in cirrhosis” really mean? | |
US20120277264A1 (en) | Antithrombotic agent | |
CN106551932A (zh) | 一种耐受性好的降压药物复方制剂 | |
TW201200131A (en) | Use of dronedarone for the preparation of a medicament for the prevention of cardiovacular hospitalizations or death or cardiovascular events in patients with premanent atrial fibrillation | |
JP2000026303A (ja) | 胆汁アルコールを有効成分とする医薬組成物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20140120 |
|
A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140205 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20140205 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150127 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20150422 |
|
A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20150626 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20151027 |
|
A521 | Written amendment |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160226 |
|
A911 | Transfer of reconsideration by examiner before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20160304 |
|
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: 20160329 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20160415 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5923044 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313111 |
|
R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |