JP2021500318A - チャネル病を引き起こす薬物に対するdmpc、dmpg、dmpc/dmpg、lysopg及びlysopcの防御効果 - Google Patents
チャネル病を引き起こす薬物に対するdmpc、dmpg、dmpc/dmpg、lysopg及びlysopcの防御効果 Download PDFInfo
- Publication number
- JP2021500318A JP2021500318A JP2020519676A JP2020519676A JP2021500318A JP 2021500318 A JP2021500318 A JP 2021500318A JP 2020519676 A JP2020519676 A JP 2020519676A JP 2020519676 A JP2020519676 A JP 2020519676A JP 2021500318 A JP2021500318 A JP 2021500318A
- Authority
- JP
- Japan
- Prior art keywords
- lysophosphatidylcholine
- cardiac
- dmpc
- dmpg
- channel
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000003814 drug Substances 0.000 title claims abstract description 74
- 229940079593 drug Drugs 0.000 title claims abstract description 70
- 201000010099 disease Diseases 0.000 title claims abstract description 38
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title claims abstract description 38
- GZDFHIJNHHMENY-UHFFFAOYSA-N Dimethyl dicarbonate Chemical compound COC(=O)OC(=O)OC GZDFHIJNHHMENY-UHFFFAOYSA-N 0.000 title claims description 66
- BPHQZTVXXXJVHI-UHFFFAOYSA-N dimyristoyl phosphatidylglycerol Chemical compound CCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCCCCCCCC BPHQZTVXXXJVHI-UHFFFAOYSA-N 0.000 title claims description 64
- 230000001681 protective effect Effects 0.000 title description 4
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 70
- 239000000203 mixture Substances 0.000 claims abstract description 65
- 230000000747 cardiac effect Effects 0.000 claims abstract description 45
- 238000000034 method Methods 0.000 claims abstract description 45
- 239000012190 activator Substances 0.000 claims abstract description 23
- ATBOMIWRCZXYSZ-XZBBILGWSA-N [1-[2,3-dihydroxypropoxy(hydroxy)phosphoryl]oxy-3-hexadecanoyloxypropan-2-yl] (9e,12e)-octadeca-9,12-dienoate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(COP(O)(=O)OCC(O)CO)OC(=O)CCCCCCC\C=C\C\C=C\CCCCC ATBOMIWRCZXYSZ-XZBBILGWSA-N 0.000 claims abstract description 17
- 239000013543 active substance Substances 0.000 claims abstract description 12
- AWUCVROLDVIAJX-UHFFFAOYSA-N alpha-glycerophosphate Natural products OCC(O)COP(O)(O)=O AWUCVROLDVIAJX-UHFFFAOYSA-N 0.000 claims abstract description 12
- 241001465754 Metazoa Species 0.000 claims abstract description 11
- -1 erogel Polymers 0.000 claims description 124
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 40
- 230000005764 inhibitory process Effects 0.000 claims description 37
- 230000000694 effects Effects 0.000 claims description 36
- 239000002502 liposome Substances 0.000 claims description 36
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 claims description 18
- 150000004665 fatty acids Chemical class 0.000 claims description 18
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 claims description 18
- 229960001252 methamphetamine Drugs 0.000 claims description 18
- 229960002748 norepinephrine Drugs 0.000 claims description 18
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 claims description 18
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 16
- 229930195729 fatty acid Natural products 0.000 claims description 16
- 239000000194 fatty acid Substances 0.000 claims description 16
- 150000002632 lipids Chemical class 0.000 claims description 15
- 229960004940 sulpiride Drugs 0.000 claims description 15
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 claims description 14
- 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 14
- 208000018452 Torsade de pointes Diseases 0.000 claims description 14
- 208000002363 Torsades de Pointes Diseases 0.000 claims description 14
- NDAUXUAQIAJITI-UHFFFAOYSA-N albuterol Chemical compound CC(C)(C)NCC(O)C1=CC=C(O)C(CO)=C1 NDAUXUAQIAJITI-UHFFFAOYSA-N 0.000 claims description 14
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 14
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 claims description 14
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims description 14
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 claims description 14
- 229960002052 salbutamol Drugs 0.000 claims description 14
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 claims description 12
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 claims description 12
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 claims description 12
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 claims description 12
- LOUPRKONTZGTKE-LHHVKLHASA-N quinidine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@H]2[C@@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-LHHVKLHASA-N 0.000 claims description 12
- RYCNUMLMNKHWPZ-SNVBAGLBSA-N 1-acetyl-sn-glycero-3-phosphocholine Chemical compound CC(=O)OC[C@@H](O)COP([O-])(=O)OCC[N+](C)(C)C RYCNUMLMNKHWPZ-SNVBAGLBSA-N 0.000 claims description 11
- ZBBHBTPTTSWHBA-UHFFFAOYSA-N Nicardipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OCCN(C)CC=2C=CC=CC=2)C1C1=CC=CC([N+]([O-])=O)=C1 ZBBHBTPTTSWHBA-UHFFFAOYSA-N 0.000 claims description 11
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 claims description 11
- 229920002678 cellulose Polymers 0.000 claims description 10
- 230000008859 change Effects 0.000 claims description 10
- 235000003599 food sweetener Nutrition 0.000 claims description 10
- 239000003765 sweetening agent Substances 0.000 claims description 10
- VXUOFDJKYGDUJI-OAQYLSRUSA-N 1-myristoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCC(=O)OC[C@@H](O)COP([O-])(=O)OCC[N+](C)(C)C VXUOFDJKYGDUJI-OAQYLSRUSA-N 0.000 claims description 9
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 9
- 102000008186 Collagen Human genes 0.000 claims description 9
- 108010035532 Collagen Proteins 0.000 claims description 9
- 108010010803 Gelatin Proteins 0.000 claims description 9
- 102000004310 Ion Channels Human genes 0.000 claims description 9
- 239000002146 L01XE16 - Crizotinib Substances 0.000 claims description 9
- GXDALQBWZGODGZ-UHFFFAOYSA-N astemizole Chemical compound C1=CC(OC)=CC=C1CCN1CCC(NC=2N(C3=CC=CC=C3N=2)CC=2C=CC(F)=CC=2)CC1 GXDALQBWZGODGZ-UHFFFAOYSA-N 0.000 claims description 9
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 9
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 9
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 9
- 239000001913 cellulose Substances 0.000 claims description 9
- 229920001436 collagen Polymers 0.000 claims description 9
- 229960005061 crizotinib Drugs 0.000 claims description 9
- KTEIFNKAUNYNJU-GFCCVEGCSA-N crizotinib Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NC=1)N)=CC=1C(=C1)C=NN1C1CCNCC1 KTEIFNKAUNYNJU-GFCCVEGCSA-N 0.000 claims description 9
- 230000003111 delayed effect Effects 0.000 claims description 9
- RMEDXOLNCUSCGS-UHFFFAOYSA-N droperidol Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CC=C(N2C(NC3=CC=CC=C32)=O)CC1 RMEDXOLNCUSCGS-UHFFFAOYSA-N 0.000 claims description 9
- 229960000394 droperidol Drugs 0.000 claims description 9
- 239000000796 flavoring agent Substances 0.000 claims description 9
- 235000019634 flavors Nutrition 0.000 claims description 9
- 229920000159 gelatin Polymers 0.000 claims description 9
- 239000008273 gelatin Substances 0.000 claims description 9
- 235000019322 gelatine Nutrition 0.000 claims description 9
- 235000011852 gelatine desserts Nutrition 0.000 claims description 9
- 239000000049 pigment Substances 0.000 claims description 9
- 229920001285 xanthan gum Polymers 0.000 claims description 9
- BGRJTUBHPOOWDU-NSHDSACASA-N (S)-(-)-sulpiride Chemical compound CCN1CCC[C@H]1CNC(=O)C1=CC(S(N)(=O)=O)=CC=C1OC BGRJTUBHPOOWDU-NSHDSACASA-N 0.000 claims description 8
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims description 8
- 229920000180 alkyd Polymers 0.000 claims description 8
- 239000002826 coolant Substances 0.000 claims description 8
- 150000004676 glycans Chemical class 0.000 claims description 8
- 239000011159 matrix material Substances 0.000 claims description 8
- 229920002401 polyacrylamide Polymers 0.000 claims description 8
- 229920001282 polysaccharide Polymers 0.000 claims description 8
- 239000005017 polysaccharide Substances 0.000 claims description 8
- GZKLJWGUPQBVJQ-UHFFFAOYSA-N sertindole Chemical compound C1=CC(F)=CC=C1N1C2=CC=C(Cl)C=C2C(C2CCN(CCN3C(NCC3)=O)CC2)=C1 GZKLJWGUPQBVJQ-UHFFFAOYSA-N 0.000 claims description 8
- ZBMZVLHSJCTVON-UHFFFAOYSA-N sotalol Chemical compound CC(C)NCC(O)C1=CC=C(NS(C)(=O)=O)C=C1 ZBMZVLHSJCTVON-UHFFFAOYSA-N 0.000 claims description 8
- 229960002370 sotalol Drugs 0.000 claims description 8
- AHOUBRCZNHFOSL-YOEHRIQHSA-N (+)-Casbol Chemical compound C1=CC(F)=CC=C1[C@H]1[C@H](COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-YOEHRIQHSA-N 0.000 claims description 7
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 claims description 7
- XMAYWYJOQHXEEK-OZXSUGGESA-N (2R,4S)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@@H]1O[C@@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-OZXSUGGESA-N 0.000 claims description 7
- HJTAZXHBEBIQQX-UHFFFAOYSA-N 1,5-bis(chloromethyl)naphthalene Chemical compound C1=CC=C2C(CCl)=CC=CC2=C1CCl HJTAZXHBEBIQQX-UHFFFAOYSA-N 0.000 claims description 7
- VHVPQPYKVGDNFY-DFMJLFEVSA-N 2-[(2r)-butan-2-yl]-4-[4-[4-[4-[[(2r,4s)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-1,2,4-triazol-3-one Chemical compound O=C1N([C@H](C)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@@H]3O[C@](CN4N=CN=C4)(OC3)C=3C(=CC(Cl)=CC=3)Cl)=CC=2)C=C1 VHVPQPYKVGDNFY-DFMJLFEVSA-N 0.000 claims description 7
- AXRYRYVKAWYZBR-UHFFFAOYSA-N Atazanavir Natural products C=1C=C(C=2N=CC=CC=2)C=CC=1CN(NC(=O)C(NC(=O)OC)C(C)(C)C)CC(O)C(NC(=O)C(NC(=O)OC)C(C)(C)C)CC1=CC=CC=C1 AXRYRYVKAWYZBR-UHFFFAOYSA-N 0.000 claims description 7
- 108010019625 Atazanavir Sulfate Proteins 0.000 claims description 7
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 claims description 7
- DJBNUMBKLMJRSA-UHFFFAOYSA-N Flecainide Chemical compound FC(F)(F)COC1=CC=C(OCC(F)(F)F)C(C(=O)NCC2NCCCC2)=C1 DJBNUMBKLMJRSA-UHFFFAOYSA-N 0.000 claims description 7
- PWWVAXIEGOYWEE-UHFFFAOYSA-N Isophenergan Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 PWWVAXIEGOYWEE-UHFFFAOYSA-N 0.000 claims description 7
- 239000005511 L01XE05 - Sorafenib Substances 0.000 claims description 7
- 239000002136 L01XE07 - Lapatinib Substances 0.000 claims description 7
- GSDSWSVVBLHKDQ-JTQLQIEISA-N Levofloxacin Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-JTQLQIEISA-N 0.000 claims description 7
- UWWDHYUMIORJTA-HSQYWUDLSA-N Moexipril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC(OC)=C(OC)C=C2C1)C(O)=O)CC1=CC=CC=C1 UWWDHYUMIORJTA-HSQYWUDLSA-N 0.000 claims description 7
- KLBQZWRITKRQQV-UHFFFAOYSA-N Thioridazine Chemical compound C12=CC(SC)=CC=C2SC2=CC=CC=C2N1CCC1CCCCN1C KLBQZWRITKRQQV-UHFFFAOYSA-N 0.000 claims description 7
- QWGDMFLQWFTERH-UHFFFAOYSA-N amoxapine Chemical compound C12=CC(Cl)=CC=C2OC2=CC=CC=C2N=C1N1CCNCC1 QWGDMFLQWFTERH-UHFFFAOYSA-N 0.000 claims description 7
- 229960002519 amoxapine Drugs 0.000 claims description 7
- 229940025084 amphetamine Drugs 0.000 claims description 7
- 229960001694 anagrelide Drugs 0.000 claims description 7
- OTBXOEAOVRKTNQ-UHFFFAOYSA-N anagrelide Chemical compound N1=C2NC(=O)CN2CC2=C(Cl)C(Cl)=CC=C21 OTBXOEAOVRKTNQ-UHFFFAOYSA-N 0.000 claims description 7
- 229960004046 apomorphine Drugs 0.000 claims description 7
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 claims description 7
- GOLCXWYRSKYTSP-UHFFFAOYSA-N arsenic trioxide Inorganic materials O1[As]2O[As]1O2 GOLCXWYRSKYTSP-UHFFFAOYSA-N 0.000 claims description 7
- 229960003277 atazanavir Drugs 0.000 claims description 7
- AXRYRYVKAWYZBR-GASGPIRDSA-N atazanavir Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)[C@@H](O)CN(CC=1C=CC(=CC=1)C=1N=CC=CC=1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)C1=CC=CC=C1 AXRYRYVKAWYZBR-GASGPIRDSA-N 0.000 claims description 7
- ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 claims description 7
- 229960001076 chlorpromazine Drugs 0.000 claims description 7
- 229960004170 clozapine Drugs 0.000 claims description 7
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 claims description 7
- 229960003920 cocaine Drugs 0.000 claims description 7
- 229960000520 diphenhydramine Drugs 0.000 claims description 7
- 229960001066 disopyramide Drugs 0.000 claims description 7
- UVTNFZQICZKOEM-UHFFFAOYSA-N disopyramide Chemical compound C=1C=CC=NC=1C(C(N)=O)(CCN(C(C)C)C(C)C)C1=CC=CC=C1 UVTNFZQICZKOEM-UHFFFAOYSA-N 0.000 claims description 7
- DLNKOYKMWOXYQA-UHFFFAOYSA-N dl-pseudophenylpropanolamine Natural products CC(N)C(O)C1=CC=CC=C1 DLNKOYKMWOXYQA-UHFFFAOYSA-N 0.000 claims description 7
- IXTMWRCNAAVVAI-UHFFFAOYSA-N dofetilide Chemical compound C=1C=C(NS(C)(=O)=O)C=CC=1CCN(C)CCOC1=CC=C(NS(C)(=O)=O)C=C1 IXTMWRCNAAVVAI-UHFFFAOYSA-N 0.000 claims description 7
- 229960002994 dofetilide Drugs 0.000 claims description 7
- 229960003638 dopamine Drugs 0.000 claims description 7
- 229960005426 doxepin Drugs 0.000 claims description 7
- ODQWQRRAPPTVAG-GZTJUZNOSA-N doxepin Chemical compound C1OC2=CC=CC=C2C(=C/CCN(C)C)/C2=CC=CC=C21 ODQWQRRAPPTVAG-GZTJUZNOSA-N 0.000 claims description 7
- 229960002179 ephedrine Drugs 0.000 claims description 7
- KKGQTZUTZRNORY-UHFFFAOYSA-N fingolimod Chemical compound CCCCCCCCC1=CC=C(CCC(N)(CO)CO)C=C1 KKGQTZUTZRNORY-UHFFFAOYSA-N 0.000 claims description 7
- 229960000556 fingolimod Drugs 0.000 claims description 7
- 229960000449 flecainide Drugs 0.000 claims description 7
- RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 claims description 7
- 229960004884 fluconazole Drugs 0.000 claims description 7
- 229960002848 formoterol Drugs 0.000 claims description 7
- BPZSYCZIITTYBL-UHFFFAOYSA-N formoterol Chemical compound C1=CC(OC)=CC=C1CC(C)NCC(O)C1=CC=C(O)C(NC=O)=C1 BPZSYCZIITTYBL-UHFFFAOYSA-N 0.000 claims description 7
- 229960003980 galantamine Drugs 0.000 claims description 7
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 claims description 7
- ZRCVYEYHRGVLOC-HYARGMPZSA-N gemifloxacin Chemical compound C1C(CN)C(=N/OC)/CN1C(C(=C1)F)=NC2=C1C(=O)C(C(O)=O)=CN2C1CC1 ZRCVYEYHRGVLOC-HYARGMPZSA-N 0.000 claims description 7
- 229960003170 gemifloxacin Drugs 0.000 claims description 7
- 229960002003 hydrochlorothiazide Drugs 0.000 claims description 7
- NDDAHWYSQHTHNT-UHFFFAOYSA-N indapamide Chemical compound CC1CC2=CC=CC=C2N1NC(=O)C1=CC=C(Cl)C(S(N)(=O)=O)=C1 NDDAHWYSQHTHNT-UHFFFAOYSA-N 0.000 claims description 7
- 229960004569 indapamide Drugs 0.000 claims description 7
- 229940039009 isoproterenol Drugs 0.000 claims description 7
- 229960004130 itraconazole Drugs 0.000 claims description 7
- 229960004125 ketoconazole Drugs 0.000 claims description 7
- 229960004891 lapatinib Drugs 0.000 claims description 7
- BCFGMOOMADDAQU-UHFFFAOYSA-N lapatinib Chemical compound O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 BCFGMOOMADDAQU-UHFFFAOYSA-N 0.000 claims description 7
- 229960003376 levofloxacin Drugs 0.000 claims description 7
- 239000004005 microsphere Substances 0.000 claims description 7
- VKHAHZOOUSRJNA-GCNJZUOMSA-N mifepristone Chemical compound C1([C@@H]2C3=C4CCC(=O)C=C4CC[C@H]3[C@@H]3CC[C@@]([C@]3(C2)C)(O)C#CC)=CC=C(N(C)C)C=C1 VKHAHZOOUSRJNA-GCNJZUOMSA-N 0.000 claims description 7
- PBAPPPCECJKMCM-IBGZPJMESA-N mirabegron Chemical compound S1C(N)=NC(CC(=O)NC=2C=CC(CCNC[C@H](O)C=3C=CC=CC=3)=CC=2)=C1 PBAPPPCECJKMCM-IBGZPJMESA-N 0.000 claims description 7
- 229960001551 mirabegron Drugs 0.000 claims description 7
- 229960005170 moexipril Drugs 0.000 claims description 7
- FABPRXSRWADJSP-MEDUHNTESA-N moxifloxacin Chemical compound COC1=C(N2C[C@H]3NCCC[C@H]3C2)C(F)=CC(C(C(C(O)=O)=C2)=O)=C1N2C1CC1 FABPRXSRWADJSP-MEDUHNTESA-N 0.000 claims description 7
- VMZMNAABQBOLAK-DBILLSOUSA-N pasireotide Chemical compound C([C@H]1C(=O)N2C[C@@H](C[C@H]2C(=O)N[C@H](C(=O)N[C@H](CC=2C3=CC=CC=C3NC=2)C(=O)N[C@H](C(N[C@@H](CC=2C=CC(OCC=3C=CC=CC=3)=CC=2)C(=O)N1)=O)CCCCN)C=1C=CC=CC=1)OC(=O)NCCN)C1=CC=CC=C1 VMZMNAABQBOLAK-DBILLSOUSA-N 0.000 claims description 7
- 229960005415 pasireotide Drugs 0.000 claims description 7
- 108700017947 pasireotide Proteins 0.000 claims description 7
- XDRYMKDFEDOLFX-UHFFFAOYSA-N pentamidine Chemical compound C1=CC(C(=N)N)=CC=C1OCCCCCOC1=CC=C(C(N)=N)C=C1 XDRYMKDFEDOLFX-UHFFFAOYSA-N 0.000 claims description 7
- 229960004448 pentamidine Drugs 0.000 claims description 7
- DLNKOYKMWOXYQA-APPZFPTMSA-N phenylpropanolamine Chemical compound C[C@@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-APPZFPTMSA-N 0.000 claims description 7
- 229960000395 phenylpropanolamine Drugs 0.000 claims description 7
- YVUQSNJEYSNKRX-UHFFFAOYSA-N pimozide Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCN1CCC(N2C(NC3=CC=CC=C32)=O)CC1 YVUQSNJEYSNKRX-UHFFFAOYSA-N 0.000 claims description 7
- 229960003634 pimozide Drugs 0.000 claims description 7
- 229960001589 posaconazole Drugs 0.000 claims description 7
- RAGOYPUPXAKGKH-XAKZXMRKSA-N posaconazole Chemical compound O=C1N([C@H]([C@H](C)O)CC)N=CN1C1=CC=C(N2CCN(CC2)C=2C=CC(OC[C@H]3C[C@@](CN4N=CN=C4)(OC3)C=3C(=CC(F)=CC=3)F)=CC=2)C=C1 RAGOYPUPXAKGKH-XAKZXMRKSA-N 0.000 claims description 7
- FYPMFJGVHOHGLL-UHFFFAOYSA-N probucol Chemical compound C=1C(C(C)(C)C)=C(O)C(C(C)(C)C)=CC=1SC(C)(C)SC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 FYPMFJGVHOHGLL-UHFFFAOYSA-N 0.000 claims description 7
- 229960003912 probucol Drugs 0.000 claims description 7
- REQCZEXYDRLIBE-UHFFFAOYSA-N procainamide Chemical compound CCN(CC)CCNC(=O)C1=CC=C(N)C=C1 REQCZEXYDRLIBE-UHFFFAOYSA-N 0.000 claims description 7
- 229960000244 procainamide Drugs 0.000 claims description 7
- 229960003910 promethazine Drugs 0.000 claims description 7
- KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 claims description 7
- 229960003908 pseudoephedrine Drugs 0.000 claims description 7
- 229960002073 sertraline Drugs 0.000 claims description 7
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 claims description 7
- DFEYYRMXOJXZRJ-UHFFFAOYSA-N sevoflurane Chemical compound FCOC(C(F)(F)F)C(F)(F)F DFEYYRMXOJXZRJ-UHFFFAOYSA-N 0.000 claims description 7
- 229960002078 sevoflurane Drugs 0.000 claims description 7
- 150000004666 short chain fatty acids Chemical class 0.000 claims description 7
- 229960004425 sibutramine Drugs 0.000 claims description 7
- UNAANXDKBXWMLN-UHFFFAOYSA-N sibutramine Chemical compound C=1C=C(Cl)C=CC=1C1(C(N(C)C)CC(C)C)CCC1 UNAANXDKBXWMLN-UHFFFAOYSA-N 0.000 claims description 7
- 229960003787 sorafenib Drugs 0.000 claims description 7
- DZZWHBIBMUVIIW-DTORHVGOSA-N sparfloxacin Chemical compound C1[C@@H](C)N[C@@H](C)CN1C1=C(F)C(N)=C2C(=O)C(C(O)=O)=CN(C3CC3)C2=C1F DZZWHBIBMUVIIW-DTORHVGOSA-N 0.000 claims description 7
- 229960004954 sparfloxacin Drugs 0.000 claims description 7
- 229960002784 thioridazine Drugs 0.000 claims description 7
- XFYDIVBRZNQMJC-UHFFFAOYSA-N tizanidine Chemical compound ClC=1C=CC2=NSN=C2C=1NC1=NCCN1 XFYDIVBRZNQMJC-UHFFFAOYSA-N 0.000 claims description 7
- 229960000488 tizanidine Drugs 0.000 claims description 7
- 229960003991 trazodone Drugs 0.000 claims description 7
- PHLBKPHSAVXXEF-UHFFFAOYSA-N trazodone Chemical compound ClC1=CC=CC(N2CCN(CCCN3C(N4C=CC=CC4=N3)=O)CC2)=C1 PHLBKPHSAVXXEF-UHFFFAOYSA-N 0.000 claims description 7
- HFFLGKNGCAIQMO-UHFFFAOYSA-N trichloroacetaldehyde Chemical compound ClC(Cl)(Cl)C=O HFFLGKNGCAIQMO-UHFFFAOYSA-N 0.000 claims description 7
- ZSCDBOWYZJWBIY-UHFFFAOYSA-N trimipramine Chemical compound C1CC2=CC=CC=C2N(CC(CN(C)C)C)C2=CC=CC=C21 ZSCDBOWYZJWBIY-UHFFFAOYSA-N 0.000 claims description 7
- 229960002431 trimipramine Drugs 0.000 claims description 7
- BWKILASWCLJPBO-UHFFFAOYSA-N (3-dodecanoyloxy-2-hydroxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCC(=O)OCC(O)COP([O-])(=O)OCC[N+](C)(C)C BWKILASWCLJPBO-UHFFFAOYSA-N 0.000 claims description 6
- AKYHKWQPZHDOBW-UHFFFAOYSA-N (5-ethenyl-1-azabicyclo[2.2.2]octan-7-yl)-(6-methoxyquinolin-4-yl)methanol Chemical compound OS(O)(=O)=O.C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 AKYHKWQPZHDOBW-UHFFFAOYSA-N 0.000 claims description 6
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 claims description 6
- 229930182837 (R)-adrenaline Natural products 0.000 claims description 6
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 claims description 6
- ASWBNKHCZGQVJV-HSZRJFAPSA-O 1-O-palmitoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](O)COP(O)(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-HSZRJFAPSA-O 0.000 claims description 6
- IQGPMZRCLCCXAG-RUZDIDTESA-N 2-stearoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@H](CO)COP([O-])(=O)OCC[N+](C)(C)C IQGPMZRCLCCXAG-RUZDIDTESA-N 0.000 claims description 6
- ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 claims description 6
- 239000001576 FEMA 2977 Substances 0.000 claims description 6
- 239000002067 L01XE06 - Dasatinib Substances 0.000 claims description 6
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 6
- GIIZNNXWQWCKIB-UHFFFAOYSA-N Serevent Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1 GIIZNNXWQWCKIB-UHFFFAOYSA-N 0.000 claims description 6
- 229960002594 arsenic trioxide Drugs 0.000 claims description 6
- 229960002448 dasatinib Drugs 0.000 claims description 6
- 229960005139 epinephrine Drugs 0.000 claims description 6
- 229960002464 fluoxetine Drugs 0.000 claims description 6
- 229960003878 haloperidol Drugs 0.000 claims description 6
- 229910052744 lithium Inorganic materials 0.000 claims description 6
- LMOINURANNBYCM-UHFFFAOYSA-N metaproterenol Chemical compound CC(C)NCC(O)C1=CC(O)=CC(O)=C1 LMOINURANNBYCM-UHFFFAOYSA-N 0.000 claims description 6
- 229960002657 orciprenaline Drugs 0.000 claims description 6
- 229960004431 quetiapine Drugs 0.000 claims description 6
- URKOMYMAXPYINW-UHFFFAOYSA-N quetiapine Chemical compound C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 URKOMYMAXPYINW-UHFFFAOYSA-N 0.000 claims description 6
- 229960001404 quinidine Drugs 0.000 claims description 6
- 229960003110 quinine sulfate Drugs 0.000 claims description 6
- 229960004017 salmeterol Drugs 0.000 claims description 6
- 229960001852 saquinavir Drugs 0.000 claims description 6
- QWAXKHKRTORLEM-UGJKXSETSA-N saquinavir Chemical compound C([C@@H]([C@H](O)CN1C[C@H]2CCCC[C@H]2C[C@H]1C(=O)NC(C)(C)C)NC(=O)[C@H](CC(N)=O)NC(=O)C=1N=C2C=CC=CC2=CC=1)C1=CC=CC=C1 QWAXKHKRTORLEM-UGJKXSETSA-N 0.000 claims description 6
- 235000021391 short chain fatty acids Nutrition 0.000 claims description 6
- 206010047302 ventricular tachycardia Diseases 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 150000001413 amino acids Chemical class 0.000 claims description 5
- 150000003904 phospholipids Chemical class 0.000 claims description 5
- 208000014321 polymorphic ventricular tachycardia Diseases 0.000 claims description 5
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 claims description 5
- 229960001534 risperidone Drugs 0.000 claims description 5
- XWTYSIMOBUGWOL-UHFFFAOYSA-N (+-)-Terbutaline Chemical compound CC(C)(C)NCC(O)C1=CC(O)=CC(O)=C1 XWTYSIMOBUGWOL-UHFFFAOYSA-N 0.000 claims description 4
- 206010067484 Adverse reaction Diseases 0.000 claims description 4
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 claims description 4
- 239000003798 L01XE11 - Pazopanib Substances 0.000 claims description 4
- 230000006838 adverse reaction Effects 0.000 claims description 4
- 239000004964 aerogel Substances 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 229960002430 atomoxetine Drugs 0.000 claims description 4
- VHGCDTVCOLNTBX-QGZVFWFLSA-N atomoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=CC=C1C VHGCDTVCOLNTBX-QGZVFWFLSA-N 0.000 claims description 4
- 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 claims description 4
- 229960003276 erythromycin Drugs 0.000 claims description 4
- 229960005017 olanzapine Drugs 0.000 claims description 4
- KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 claims description 4
- SSZBUIDZHHWXNJ-UHFFFAOYSA-N palmityl stearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCCCCCC SSZBUIDZHHWXNJ-UHFFFAOYSA-N 0.000 claims description 4
- 229960000639 pazopanib Drugs 0.000 claims description 4
- CUIHSIWYWATEQL-UHFFFAOYSA-N pazopanib Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CUIHSIWYWATEQL-UHFFFAOYSA-N 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- 229960000195 terbutaline Drugs 0.000 claims description 4
- 150000004669 very long chain fatty acids Chemical class 0.000 claims description 4
- 239000000230 xanthan gum Substances 0.000 claims description 4
- 229940082509 xanthan gum Drugs 0.000 claims description 4
- 235000010493 xanthan gum Nutrition 0.000 claims description 4
- 206010020751 Hypersensitivity Diseases 0.000 claims description 3
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 229910019142 PO4 Inorganic materials 0.000 claims description 3
- 150000001336 alkenes Chemical class 0.000 claims description 3
- 150000001345 alkine derivatives Chemical class 0.000 claims description 3
- 230000007815 allergy Effects 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
- ASWBNKHCZGQVJV-UHFFFAOYSA-N (3-hexadecanoyloxy-2-hydroxypropyl) 2-(trimethylazaniumyl)ethyl phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OCC(O)COP([O-])(=O)OCC[N+](C)(C)C ASWBNKHCZGQVJV-UHFFFAOYSA-N 0.000 claims description 2
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 claims description 2
- FJLUATLTXUNBOT-UHFFFAOYSA-N 1-Hexadecylamine Chemical compound CCCCCCCCCCCCCCCCN FJLUATLTXUNBOT-UHFFFAOYSA-N 0.000 claims description 2
- HIQIXEFWDLTDED-UHFFFAOYSA-N 4-hydroxy-1-piperidin-4-ylpyrrolidin-2-one Chemical compound O=C1CC(O)CN1C1CCNCC1 HIQIXEFWDLTDED-UHFFFAOYSA-N 0.000 claims description 2
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 claims description 2
- 241000282412 Homo Species 0.000 claims description 2
- LWUDAUVROWYJGV-RGMNGODLSA-N N[C@@H](CCCCN)CO.OCC(O)CO Chemical compound N[C@@H](CCCCN)CO.OCC(O)CO LWUDAUVROWYJGV-RGMNGODLSA-N 0.000 claims description 2
- REYJJPSVUYRZGE-UHFFFAOYSA-N Octadecylamine Chemical compound CCCCCCCCCCCCCCCCCCN REYJJPSVUYRZGE-UHFFFAOYSA-N 0.000 claims description 2
- CWRILEGKIAOYKP-SSDOTTSWSA-M [(2r)-3-acetyloxy-2-hydroxypropyl] 2-aminoethyl phosphate Chemical compound CC(=O)OC[C@@H](O)COP([O-])(=O)OCCN CWRILEGKIAOYKP-SSDOTTSWSA-M 0.000 claims description 2
- VUBTYKDZOQNADH-UHFFFAOYSA-N acetyl hexadecanoate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)=O VUBTYKDZOQNADH-UHFFFAOYSA-N 0.000 claims description 2
- 208000026935 allergic disease Diseases 0.000 claims description 2
- 235000012000 cholesterol Nutrition 0.000 claims description 2
- 150000001840 cholesterol esters Chemical class 0.000 claims description 2
- 150000001982 diacylglycerols Chemical class 0.000 claims description 2
- ZGSPNIOCEDOHGS-UHFFFAOYSA-L disodium [3-[2,3-di(octadeca-9,12-dienoyloxy)propoxy-oxidophosphoryl]oxy-2-hydroxypropyl] 2,3-di(octadeca-9,12-dienoyloxy)propyl phosphate Chemical compound [Na+].[Na+].CCCCCC=CCC=CCCCCCCCC(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COP([O-])(=O)OCC(O)COP([O-])(=O)OCC(OC(=O)CCCCCCCC=CCC=CCCCCC)COC(=O)CCCCCCCC=CCC=CCCCCC ZGSPNIOCEDOHGS-UHFFFAOYSA-L 0.000 claims description 2
- JRBPAEWTRLWTQC-UHFFFAOYSA-N dodecylamine Chemical compound CCCCCCCCCCCCN JRBPAEWTRLWTQC-UHFFFAOYSA-N 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 150000008104 phosphatidylethanolamines Chemical class 0.000 claims description 2
- 150000003905 phosphatidylinositols Chemical class 0.000 claims description 2
- 229920000058 polyacrylate Polymers 0.000 claims description 2
- HOMYIYLRRDTKAA-IXWJMURKSA-N soya-cerebroside II Natural products CCCCCCCCCCCCCC[C@H](O)C(=O)N[C@H](CO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O)[C@@H](O)C=CCCC=CCCCCCCCCC HOMYIYLRRDTKAA-IXWJMURKSA-N 0.000 claims description 2
- GSDSWSVVBLHKDQ-UHFFFAOYSA-N 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 claims 3
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims 3
- 229920000591 gum Polymers 0.000 claims 3
- ACRHBAYQBXXRTO-OAQYLSRUSA-N ivabradine Chemical compound C1CC2=CC(OC)=C(OC)C=C2CC(=O)N1CCCN(C)C[C@H]1CC2=C1C=C(OC)C(OC)=C2 ACRHBAYQBXXRTO-OAQYLSRUSA-N 0.000 claims 3
- 229960003825 ivabradine Drugs 0.000 claims 3
- DNKCFBJMFIUNRS-UHFFFAOYSA-N mephentermine sulfate Chemical compound OS(O)(=O)=O.CNC(C)(C)CC1=CC=CC=C1.CNC(C)(C)CC1=CC=CC=C1 DNKCFBJMFIUNRS-UHFFFAOYSA-N 0.000 claims 3
- 229960001180 norfloxacin Drugs 0.000 claims 3
- OGJPXUAPXNRGGI-UHFFFAOYSA-N norfloxacin Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 OGJPXUAPXNRGGI-UHFFFAOYSA-N 0.000 claims 3
- 229960001699 ofloxacin Drugs 0.000 claims 3
- PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 claims 1
- DMKDRSIXSDKEFQ-KDXMTYKHSA-N Cephaline Natural products CCCCCCCCCCCCCCCCCOC(=O)C[C@@H](COP(=O)(O)CCN)C(=O)OCCCCCCCC=CCCCCCCCC DMKDRSIXSDKEFQ-KDXMTYKHSA-N 0.000 claims 1
- 125000001095 phosphatidyl group Chemical group 0.000 claims 1
- 239000013008 thixotropic agent Substances 0.000 abstract description 8
- 239000005536 L01XE08 - Nilotinib Substances 0.000 description 72
- 229960001346 nilotinib Drugs 0.000 description 72
- HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 description 71
- 108091006146 Channels Proteins 0.000 description 59
- 101001047090 Homo sapiens Potassium voltage-gated channel subfamily H member 2 Proteins 0.000 description 42
- 102100022807 Potassium voltage-gated channel subfamily H member 2 Human genes 0.000 description 38
- 210000004027 cell Anatomy 0.000 description 34
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 31
- 150000002500 ions Chemical class 0.000 description 16
- 238000012360 testing method Methods 0.000 description 16
- 239000007864 aqueous solution Substances 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- 102000004257 Potassium Channel Human genes 0.000 description 11
- 108020001213 potassium channel Proteins 0.000 description 11
- 239000000843 powder Substances 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- 102100021177 ATP-sensitive inward rectifier potassium channel 11 Human genes 0.000 description 9
- 101000614701 Homo sapiens ATP-sensitive inward rectifier potassium channel 11 Proteins 0.000 description 9
- 238000004088 simulation Methods 0.000 description 9
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 8
- 235000013361 beverage Nutrition 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 8
- 229960000632 dexamfetamine Drugs 0.000 description 8
- 238000002565 electrocardiography Methods 0.000 description 8
- 229960004801 imipramine Drugs 0.000 description 8
- BCGWQEUPMDMJNV-UHFFFAOYSA-N imipramine Chemical compound C1CC2=CC=CC=C2N(CCCN(C)C)C2=CC=CC=C21 BCGWQEUPMDMJNV-UHFFFAOYSA-N 0.000 description 8
- 230000003834 intracellular effect Effects 0.000 description 8
- 229910052700 potassium Inorganic materials 0.000 description 8
- 239000011591 potassium Substances 0.000 description 8
- 230000036982 action potential Effects 0.000 description 7
- 206010003119 arrhythmia Diseases 0.000 description 7
- 210000004413 cardiac myocyte Anatomy 0.000 description 7
- 235000010980 cellulose Nutrition 0.000 description 7
- 235000018417 cysteine Nutrition 0.000 description 7
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 7
- 229910001414 potassium ion Inorganic materials 0.000 description 7
- 230000001105 regulatory effect Effects 0.000 description 7
- 102100033063 G protein-activated inward rectifier potassium channel 1 Human genes 0.000 description 6
- 101000944266 Homo sapiens G protein-activated inward rectifier potassium channel 1 Proteins 0.000 description 6
- 108090000862 Ion Channels Proteins 0.000 description 6
- 239000000539 dimer Substances 0.000 description 6
- 230000001965 increasing effect Effects 0.000 description 6
- 239000012528 membrane Substances 0.000 description 6
- 230000002336 repolarization Effects 0.000 description 6
- 230000001953 sensory effect Effects 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- GJCOSYZMQJWQCA-UHFFFAOYSA-N 9H-xanthene Chemical compound C1=CC=C2CC3=CC=CC=C3OC2=C1 GJCOSYZMQJWQCA-UHFFFAOYSA-N 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 239000000654 additive Substances 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 210000004899 c-terminal region Anatomy 0.000 description 5
- 235000012754 curcumin Nutrition 0.000 description 5
- 239000004148 curcumin Substances 0.000 description 5
- 229940109262 curcumin Drugs 0.000 description 5
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 description 5
- 230000003993 interaction Effects 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 239000013641 positive control Substances 0.000 description 5
- 230000036962 time dependent Effects 0.000 description 5
- DBGIVFWFUFKIQN-UHFFFAOYSA-N (+-)-Fenfluramine Chemical compound CCNC(C)CC1=CC=CC(C(F)(F)F)=C1 DBGIVFWFUFKIQN-UHFFFAOYSA-N 0.000 description 4
- MKJIEFSOBYUXJB-HOCLYGCPSA-N (3S,11bS)-9,10-dimethoxy-3-isobutyl-1,3,4,6,7,11b-hexahydro-2H-pyrido[2,1-a]isoquinolin-2-one Chemical compound C1CN2C[C@H](CC(C)C)C(=O)C[C@H]2C2=C1C=C(OC)C(OC)=C2 MKJIEFSOBYUXJB-HOCLYGCPSA-N 0.000 description 4
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 4
- SPCKHVPPRJWQRZ-UHFFFAOYSA-N 2-benzhydryloxy-n,n-dimethylethanamine;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 SPCKHVPPRJWQRZ-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- XNOPRXBHLZRZKH-UHFFFAOYSA-N Oxytocin Natural products N1C(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CC(C)C)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(C(C)CC)NC(=O)C1CC1=CC=C(O)C=C1 XNOPRXBHLZRZKH-UHFFFAOYSA-N 0.000 description 4
- 101800000989 Oxytocin Proteins 0.000 description 4
- 102100031951 Oxytocin-neurophysin 1 Human genes 0.000 description 4
- NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Chemical compound ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 4
- ZQTNQVWKHCQYLQ-UHFFFAOYSA-N dronedarone Chemical compound C1=CC(OCCCN(CCCC)CCCC)=CC=C1C(=O)C1=C(CCCC)OC2=CC=C(NS(C)(=O)=O)C=C12 ZQTNQVWKHCQYLQ-UHFFFAOYSA-N 0.000 description 4
- 229960002084 dronedarone Drugs 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 229960001582 fenfluramine Drugs 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 4
- 230000037427 ion transport Effects 0.000 description 4
- 230000000670 limiting effect Effects 0.000 description 4
- 208000004731 long QT syndrome Diseases 0.000 description 4
- RONZAEMNMFQXRA-UHFFFAOYSA-N mirtazapine Chemical compound C1C2=CC=CN=C2N2CCN(C)CC2C2=CC=CC=C21 RONZAEMNMFQXRA-UHFFFAOYSA-N 0.000 description 4
- 229960001785 mirtazapine Drugs 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 229960001783 nicardipine Drugs 0.000 description 4
- XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 description 4
- 229960001723 oxytocin Drugs 0.000 description 4
- 230000010412 perfusion Effects 0.000 description 4
- 239000011148 porous material Substances 0.000 description 4
- 125000001453 quaternary ammonium group Chemical group 0.000 description 4
- 229960000311 ritonavir Drugs 0.000 description 4
- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 4
- 208000011580 syndromic disease Diseases 0.000 description 4
- 229960005333 tetrabenazine Drugs 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 description 3
- 239000004606 Fillers/Extenders Substances 0.000 description 3
- PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical compound C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- 230000006793 arrhythmia Effects 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 210000000170 cell membrane Anatomy 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000013461 design Methods 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000012634 fragment Substances 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 230000002779 inactivation Effects 0.000 description 3
- 229960001078 lithium Drugs 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 238000000329 molecular dynamics simulation Methods 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 229960004688 venlafaxine Drugs 0.000 description 3
- PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 description 3
- 229930003231 vitamin Natural products 0.000 description 3
- 239000011782 vitamin Substances 0.000 description 3
- 229940088594 vitamin Drugs 0.000 description 3
- 235000013343 vitamin Nutrition 0.000 description 3
- 102100033056 ATP-sensitive inward rectifier potassium channel 1 Human genes 0.000 description 2
- ACTIUHUUMQJHFO-UHFFFAOYSA-N Coenzym Q10 Natural products COC1=C(OC)C(=O)C(CC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UHFFFAOYSA-N 0.000 description 2
- 101000944272 Homo sapiens ATP-sensitive inward rectifier potassium channel 1 Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 206010049418 Sudden Cardiac Death Diseases 0.000 description 2
- 206010042434 Sudden death Diseases 0.000 description 2
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 2
- 229930003427 Vitamin E Natural products 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 235000020661 alpha-linolenic acid Nutrition 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 235000006708 antioxidants Nutrition 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- DCSUBABJRXZOMT-IRLDBZIGSA-N cisapride Chemical compound C([C@@H]([C@@H](CC1)NC(=O)C=2C(=CC(N)=C(Cl)C=2)OC)OC)N1CCCOC1=CC=C(F)C=C1 DCSUBABJRXZOMT-IRLDBZIGSA-N 0.000 description 2
- 229960005132 cisapride Drugs 0.000 description 2
- DCSUBABJRXZOMT-UHFFFAOYSA-N cisapride Natural products C1CC(NC(=O)C=2C(=CC(N)=C(Cl)C=2)OC)C(OC)CN1CCCOC1=CC=C(F)C=C1 DCSUBABJRXZOMT-UHFFFAOYSA-N 0.000 description 2
- 235000017471 coenzyme Q10 Nutrition 0.000 description 2
- 229940110767 coenzyme Q10 Drugs 0.000 description 2
- ACTIUHUUMQJHFO-UPTCCGCDSA-N coenzyme Q10 Chemical compound COC1=C(OC)C(=O)C(C\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CC\C=C(/C)CCC=C(C)C)=C(C)C1=O ACTIUHUUMQJHFO-UPTCCGCDSA-N 0.000 description 2
- 230000002860 competitive effect Effects 0.000 description 2
- 235000008504 concentrate Nutrition 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 150000001945 cysteines Chemical class 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 238000013400 design of experiment Methods 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- 238000009509 drug development Methods 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- VZCCETWTMQHEPK-QNEBEIHSSA-N gamma-linolenic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/CCCCC(O)=O VZCCETWTMQHEPK-QNEBEIHSSA-N 0.000 description 2
- 235000020664 gamma-linolenic acid Nutrition 0.000 description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 210000002837 heart atrium Anatomy 0.000 description 2
- 208000019622 heart disease Diseases 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- 229910021645 metal ion Inorganic materials 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 102000040430 polynucleotide Human genes 0.000 description 2
- 108091033319 polynucleotide Proteins 0.000 description 2
- 239000002157 polynucleotide Substances 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 238000000718 qrs complex Methods 0.000 description 2
- 230000008707 rearrangement Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000013577 regulation of ventricular cardiomyocyte membrane repolarization Effects 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 229960000351 terfenadine Drugs 0.000 description 2
- 235000019165 vitamin E Nutrition 0.000 description 2
- 229940046009 vitamin E Drugs 0.000 description 2
- 239000011709 vitamin E Substances 0.000 description 2
- DVSZKTAMJJTWFG-SKCDLICFSA-N (2e,4e,6e,8e,10e,12e)-docosa-2,4,6,8,10,12-hexaenoic acid Chemical compound CCCCCCCCC\C=C\C=C\C=C\C=C\C=C\C=C\C(O)=O DVSZKTAMJJTWFG-SKCDLICFSA-N 0.000 description 1
- XUBOMFCQGDBHNK-JTQLQIEISA-N (S)-gatifloxacin Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CCN[C@@H](C)C1 XUBOMFCQGDBHNK-JTQLQIEISA-N 0.000 description 1
- HKWJHKSHEWVOSS-OMDJCSNQSA-N 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4-bisphosphate) Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@@H](OC(=O)CCCCCCCCCCCCCCC)COP(O)(=O)O[C@H]1[C@H](O)[C@@H](O)[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H]1O HKWJHKSHEWVOSS-OMDJCSNQSA-N 0.000 description 1
- SNKAWJBJQDLSFF-NVKMUCNASA-N 1,2-dioleoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/CCCCCCCC SNKAWJBJQDLSFF-NVKMUCNASA-N 0.000 description 1
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 description 1
- OVSKIKFHRZPJSS-UHFFFAOYSA-N 2,4-D Chemical compound OC(=O)COC1=CC=C(Cl)C=C1Cl OVSKIKFHRZPJSS-UHFFFAOYSA-N 0.000 description 1
- CFWRDBDJAOHXSH-SECBINFHSA-N 2-azaniumylethyl [(2r)-2,3-diacetyloxypropyl] phosphate Chemical compound CC(=O)OC[C@@H](OC(C)=O)COP(O)(=O)OCCN CFWRDBDJAOHXSH-SECBINFHSA-N 0.000 description 1
- GZJLLYHBALOKEX-UHFFFAOYSA-N 6-Ketone, O18-Me-Ussuriedine Natural products CC=CCC=CCC=CCC=CCC=CCC=CCCCC(O)=O GZJLLYHBALOKEX-UHFFFAOYSA-N 0.000 description 1
- 229910002016 Aerosil® 200 Inorganic materials 0.000 description 1
- 206010001497 Agitation Diseases 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical group O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 206010049993 Cardiac death Diseases 0.000 description 1
- 208000032170 Congenital Abnormalities Diseases 0.000 description 1
- 206010010356 Congenital anomaly Diseases 0.000 description 1
- 241000195493 Cryptophyta Species 0.000 description 1
- 244000163122 Curcuma domestica Species 0.000 description 1
- 235000003392 Curcuma domestica Nutrition 0.000 description 1
- PAFZNILMFXTMIY-UHFFFAOYSA-N Cyclohexylamine Natural products NC1CCCCC1 PAFZNILMFXTMIY-UHFFFAOYSA-N 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 206010011906 Death Diseases 0.000 description 1
- 235000011201 Ginkgo Nutrition 0.000 description 1
- 235000008100 Ginkgo biloba Nutrition 0.000 description 1
- 244000194101 Ginkgo biloba Species 0.000 description 1
- 101000944277 Homo sapiens Inward rectifier potassium channel 2 Proteins 0.000 description 1
- 102100033114 Inward rectifier potassium channel 2 Human genes 0.000 description 1
- 108010009983 Inwardly Rectifying Potassium Channels Proteins 0.000 description 1
- 102000009855 Inwardly Rectifying Potassium Channels Human genes 0.000 description 1
- 101150051809 KCNH2 gene Proteins 0.000 description 1
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 1
- 125000002707 L-tryptophyl group Chemical group [H]C1=C([H])C([H])=C2C(C([C@](N([H])[H])(C(=O)[*])[H])([H])[H])=C([H])N([H])C2=C1[H] 0.000 description 1
- UPYKUZBSLRQECL-UKMVMLAPSA-N Lycopene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1C(=C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=C)CCCC2(C)C UPYKUZBSLRQECL-UKMVMLAPSA-N 0.000 description 1
- JEVVKJMRZMXFBT-XWDZUXABSA-N Lycophyll Natural products OC/C(=C/CC/C(=C\C=C\C(=C/C=C/C(=C\C=C\C=C(/C=C/C=C(\C=C\C=C(/CC/C=C(/CO)\C)\C)/C)\C)/C)\C)/C)/C JEVVKJMRZMXFBT-XWDZUXABSA-N 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- UQOFGTXDASPNLL-XHNCKOQMSA-N Muscarine Chemical compound C[C@@H]1O[C@H](C[N+](C)(C)C)C[C@H]1O UQOFGTXDASPNLL-XHNCKOQMSA-N 0.000 description 1
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- AHOUBRCZNHFOSL-UHFFFAOYSA-N Paroxetine hydrochloride Natural products C1=CC(F)=CC=C1C1C(COC=2C=C3OCOC3=CC=2)CNCC1 AHOUBRCZNHFOSL-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 241000187398 Streptomyces lividans Species 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 1
- 235000017537 Vaccinium myrtillus Nutrition 0.000 description 1
- 244000078534 Vaccinium myrtillus Species 0.000 description 1
- 206010047281 Ventricular arrhythmia Diseases 0.000 description 1
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 229930003316 Vitamin D Natural products 0.000 description 1
- QYSXJUFSXHHAJI-XFEUOLMDSA-N Vitamin D3 Natural products C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C/C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-XFEUOLMDSA-N 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 description 1
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 description 1
- DTOSIQBPPRVQHS-PDBXOOCHSA-N alpha-linolenic acid Chemical compound CC\C=C/C\C=C/C\C=C/CCCCCCCC(O)=O DTOSIQBPPRVQHS-PDBXOOCHSA-N 0.000 description 1
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 description 1
- 229960003805 amantadine Drugs 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 230000003288 anthiarrhythmic effect Effects 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 229960004754 astemizole Drugs 0.000 description 1
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 MQTOSJVFKKJCRP-BICOPXKESA-N 0.000 description 1
- 229960004099 azithromycin Drugs 0.000 description 1
- 238000010009 beating Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 235000013734 beta-carotene Nutrition 0.000 description 1
- 239000011648 beta-carotene Substances 0.000 description 1
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 description 1
- 229960002747 betacarotene Drugs 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 230000003833 cell viability Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000007705 chemical test Methods 0.000 description 1
- 239000005515 coenzyme Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 235000003373 curcuma longa Nutrition 0.000 description 1
- 230000009089 cytolysis Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 230000002999 depolarising effect Effects 0.000 description 1
- 230000001687 destabilization Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000000378 dietary effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 235000020669 docosahexaenoic acid Nutrition 0.000 description 1
- KAUVQQXNCKESLC-UHFFFAOYSA-N docosahexaenoic acid (DHA) Natural products COC(=O)C(C)NOCC1=CC=CC=C1 KAUVQQXNCKESLC-UHFFFAOYSA-N 0.000 description 1
- 231100000673 dose–response relationship Toxicity 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 description 1
- 229960001596 famotidine Drugs 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000021323 fish oil Nutrition 0.000 description 1
- 238000005187 foaming Methods 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- VZCCETWTMQHEPK-UHFFFAOYSA-N gamma-Linolensaeure Natural products CCCCCC=CCC=CCC=CCCCCC(O)=O VZCCETWTMQHEPK-UHFFFAOYSA-N 0.000 description 1
- 229960002733 gamolenic acid Drugs 0.000 description 1
- 229960003923 gatifloxacin Drugs 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 230000009395 genetic defect Effects 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000007614 genetic variation Effects 0.000 description 1
- 125000003976 glyceryl group Chemical group [H]C([*])([H])C(O[H])([H])C(O[H])([H])[H] 0.000 description 1
- 229940087603 grape seed extract Drugs 0.000 description 1
- 235000002532 grape seed extract Nutrition 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000007407 health benefit Effects 0.000 description 1
- 235000008216 herbs Nutrition 0.000 description 1
- 235000019534 high fructose corn syrup Nutrition 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 210000003292 kidney cell Anatomy 0.000 description 1
- MYWUZJCMWCOHBA-SECBINFHSA-N levmetamfetamine Chemical compound CN[C@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-SECBINFHSA-N 0.000 description 1
- 229950007554 levmetamfetamine Drugs 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229960004488 linolenic acid Drugs 0.000 description 1
- KQQKGWQCNNTQJW-UHFFFAOYSA-N linolenic acid Natural products CC=CCCC=CCC=CCCCCCCCC(O)=O KQQKGWQCNNTQJW-UHFFFAOYSA-N 0.000 description 1
- 235000021388 linseed oil Nutrition 0.000 description 1
- 239000000944 linseed oil Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 150000004668 long chain fatty acids Chemical class 0.000 description 1
- 239000001656 lutein Substances 0.000 description 1
- 229960005375 lutein Drugs 0.000 description 1
- 235000012680 lutein Nutrition 0.000 description 1
- KBPHJBAIARWVSC-RGZFRNHPSA-N lutein Chemical compound C([C@H](O)CC=1C)C(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\[C@H]1C(C)=C[C@H](O)CC1(C)C KBPHJBAIARWVSC-RGZFRNHPSA-N 0.000 description 1
- ORAKUVXRZWMARG-WZLJTJAWSA-N lutein Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2C(=CC(O)CC2(C)C)C ORAKUVXRZWMARG-WZLJTJAWSA-N 0.000 description 1
- 235000012661 lycopene Nutrition 0.000 description 1
- 239000001751 lycopene Substances 0.000 description 1
- 229960004999 lycopene Drugs 0.000 description 1
- OAIJSZIZWZSQBC-GYZMGTAESA-N lycopene Chemical compound CC(C)=CCC\C(C)=C\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C=C(/C)CCC=C(C)C OAIJSZIZWZSQBC-GYZMGTAESA-N 0.000 description 1
- 230000002934 lysing effect Effects 0.000 description 1
- 210000003712 lysosome Anatomy 0.000 description 1
- 230000001868 lysosomic effect Effects 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 230000028161 membrane depolarization Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 210000000663 muscle cell Anatomy 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
- 210000000107 myocyte Anatomy 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 235000020660 omega-3 fatty acid Nutrition 0.000 description 1
- 229940012843 omega-3 fatty acid Drugs 0.000 description 1
- 239000006014 omega-3 oil Substances 0.000 description 1
- 235000020665 omega-6 fatty acid Nutrition 0.000 description 1
- 229940033080 omega-6 fatty acid Drugs 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 229960002296 paroxetine Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 229940106587 pine bark extract Drugs 0.000 description 1
- 235000020741 pine bark extract Nutrition 0.000 description 1
- 235000002378 plant sterols Nutrition 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 102000054765 polymorphisms of proteins Human genes 0.000 description 1
- 235000020777 polyunsaturated fatty acids Nutrition 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 238000012910 preclinical development Methods 0.000 description 1
- 238000000513 principal component analysis Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000034225 regulation of ventricular cardiomyocyte membrane depolarization Effects 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- IOVGROKTTNBUGK-SJCJKPOMSA-N ritodrine Chemical compound N([C@@H](C)[C@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJCJKPOMSA-N 0.000 description 1
- 229960001634 ritodrine Drugs 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000005476 size effect Effects 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 229960001967 tacrolimus Drugs 0.000 description 1
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 1
- CBXCPBUEXACCNR-UHFFFAOYSA-N tetraethylammonium Chemical compound CC[N+](CC)(CC)CC CBXCPBUEXACCNR-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000009974 thixotropic effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- ZCIHMQAPACOQHT-ZGMPDRQDSA-N trans-isorenieratene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/c1c(C)ccc(C)c1C)C=CC=C(/C)C=Cc2c(C)ccc(C)c2C ZCIHMQAPACOQHT-ZGMPDRQDSA-N 0.000 description 1
- KBPHJBAIARWVSC-XQIHNALSSA-N trans-lutein Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2C(=CC(O)CC2(C)C)C KBPHJBAIARWVSC-XQIHNALSSA-N 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 235000013976 turmeric Nutrition 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 239000013598 vector Substances 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
- 208000003663 ventricular fibrillation Diseases 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 235000019155 vitamin A Nutrition 0.000 description 1
- 239000011719 vitamin A Substances 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019166 vitamin D Nutrition 0.000 description 1
- 239000011710 vitamin D Substances 0.000 description 1
- 150000003710 vitamin D derivatives Chemical class 0.000 description 1
- 229940045997 vitamin a Drugs 0.000 description 1
- 229940046008 vitamin d Drugs 0.000 description 1
- FJHBOVDFOQMZRV-XQIHNALSSA-N xanthophyll Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC2C=C(C)C(O)CC2(C)C FJHBOVDFOQMZRV-XQIHNALSSA-N 0.000 description 1
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 description 1
Classifications
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Liposomes
-
- 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
- A61K31/12—Ketones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- 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
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
-
- 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
- A61K31/66—Phosphorus compounds
- A61K31/683—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols
- A61K31/685—Diesters of a phosphorus acid with two hydroxy compounds, e.g. phosphatidylinositols one of the hydroxy compounds having nitrogen atoms, e.g. phosphatidylserine, lecithin
-
- 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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
-
- 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
- A61P9/02—Non-specific cardiovascular stimulants, e.g. drugs for syncope, antihypotensives
-
- 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
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- A61P9/06—Antiarrhythmics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Cardiology (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Heart & Thoracic Surgery (AREA)
- Dispersion Chemistry (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
基本構造:
カリウムチャネルは、遅延整流性カリウム電流Kirの迅速な構成成分を伝導し、それは、心臓活動電位の再分極に不可欠である。遺伝的欠陥又は有害な薬物の影響のいずれかに起因したhERG電流の低減は、活動電位延長、表面ECG上でのQT間隔の長期化、並びに「トルサード・ド・ポアンツ」不整脈及び突然死に対するリスクの増加を特徴とする遺伝性又は後天性QT延期症候群を招き得る。非抗不整脈化合物のこの望ましくない副作用が、薬物の市場からの取り下げを促してきた。hERGチャネル阻害のメカニズムに関する研究は、hERG電流阻止の状態、電圧及び使用依存度を決定する分子要因への有意な洞察を提供する。hERGにおける高親和性薬物結合部位及び薬物分子とのその相互作用の特性を変更させる変異は、生命に関わる不整脈に関して高いリスクで、電流増加及び遺伝性短期QT症候群を引き起こす(Thomas D1, 2006)。
ヒトether−a−go−go遺伝子関連心臓四量体カリウムチャネルは、変異されると、患者を、163個を上回る薬物に対して感受性にさせることができ、それは、イオン伝導を阻害して、活動電位をダウンレギュレートし得る(Credible Meds)。カリウムチャネルの影響の結果として、活動電位の延長が起きる。イオンチャネル活性薬物は、QTc間隔を直接増加させて、トルサード・ド・ポアンツ及び突然心臓死のリスクを増加させ得る(表1)。薬物に対する心筋細胞のカリウムチャネル感受性の増悪はまた、糖尿病を含む代謝性罹患状態と関連付けられ得る(Veglio M, 2002)か、又は特発性起源であり得る。
1−DMPC
2−DMPG
3−DMPC/DMPG 90:9
4−14:0 LysoPC
5−14:0 LysoPG
6−DMPC+ニロチニブ(0.1μM)
7−DMPG+ニロチニブ(0.1μM)
8−DMPC/DMPG 90:9+ニロチニブ(0.1μM)
9−14:0 LysoPC+ニロチニブ(0.1μM)
10−14:0 LysoPG+ニロチニブ(0.1μM)
ベースライン条件で行われる記録1
濃度1の存在下で行われる記録1
ベースライン条件で行われる記録1
正の対照の存在下で行われる記録1
n=上記全プロトコールを適用することができたパッチした応答細胞の数。
1.評判の悪い薬物曝露の時間枠
2.封の不安定性
3.パッチした細胞により発生するテール電流なし
4.正の対照の有意な効果なし
5.研究の持続期間にわたるキャパシタンス過渡振幅における10%を超える可変性
1- DMPC (水溶液中)
2- DMPG (水溶液中)
3- DMPC/DMPG 90:9 (水溶液中)
4- 14:0 LysoPC (水溶液中)
5- 14:0 LysoPG(水溶液中)
6- DMPC + ニロチニブ (0.1 μM) (水溶液中)
7- DMPG + ニロチニブ (0.1 μM) (水溶液中)
8- DMPC/DMPG 90:9 + ニロチニブ (0.1 μM) (水溶液中)
9- 14:0 LysoPC + ニロチニブ (0.1 μM) (水溶液中)
10- 14:0 LysoPG + ニロチニブ (0.1 μM) (水溶液中)
11- ニロチニブ単独 (DMSO中)
米国特許公開第2010/0004549号明細書:System and Method of Serial Comparison for Detection of Long QT Syndrome (LQTS)。
米国特許公開第2008/0255464号明細書:System and Method for Diagnosing and Treating Long QT Syndrome。
米国特許公開第2007/0048284号明細書:Cardiac Arrhythmia Treatment Methods。
米国特許公開第2001/00120890号明細書:Ion Channel Modulating Activity I。
Claims (26)
- ヒト又は動物対象において活性剤又は薬物により引き起こされる心臓パターンにおける不規則性又は変化に起因する1又は2以上の心臓チャネル病又は状態を予防するための組成物であって、
前記活性剤又は薬物により引き起こされる心臓パターンにおける不規則性又は変化に起因する1又は2以上の心臓チャネル病又は状態を低減又は予防するのに有効な、経口投与用に適合されたある量のホスファチジルグリセロール、並びに1又は2以上の官能剤、チキソトロピー剤、又は官能剤及びチキソトロピー剤の両方
を含む組成物。 - ホスファチジルグリセロールが、リゾホスファチジルコリン、ラウロイル−リゾホスファチジルコリン、ミリストイル−リゾホスファチジルコリン、パルミトイル−リゾホスファチジルコリン、ステアロイル−リゾホスファチジルコリン、アラキドイル−リゾホスファチジルコリン、オレオイル−リゾホスファチジルコリン、リノレオイル−リゾホスファチジルコリン、リノレノイル−リゾホスファチジルコリン又はエルコイル−リゾホスファチジルコリンのうちの少なくとも1つを含む、請求項1に記載の組成物。
- 1又は2以上の官能剤が、1若しくは2以上の香味料、甘味料、冷却剤、色素、又はこれらの組合せ及び混合物を含む、請求項1に記載の組成物。
- 1又は2以上のチキソトロピー剤が、チキソトロピーマトリックスを形成し、多糖類、セルロース、カルボキシメチルセルロース、ガム、キサンタンガム、コラーゲン、ゼラチン、エーロゲル、ポリアクリルアミド、アルキド樹脂、又はシリカ−脂質の少なくとも1つから選択される、請求項1に記載の組成物。
- ホスファチジルグリセロールが空リポソームを形成し、10、20、25、30、40、50、60、75、80、90又は100nMの平均直径を有する、請求項1に記載の組成物。
- ホスファチジルグリセロールが、10、20、25、30、40、50、60、75、80、90又は100nMの平均直径を有するリポソームを形成する、1−ミリストイル−2−ヒドロキシ−sn−グリセロ−3−ホスホコリン(DMPC)、12−ミステロイル−2−ヒドロキシ−sn−グリセロ−3−[ホスホ−rac−(グリセロール)](DMPG)、又はDMPC/DMPGである、請求項1に記載の組成物。
- ホスファチジルグリセロールが、1−ミリストイル−2−ヒドロキシ−sn−グリセロ−3−ホスホコリン(DMPC)、12−ミステロイル−2−ヒドロキシ−sn−グリセロ−3−[ホスホ−rac−(グリセロール)](DMPG)、DMPC/DMPG、1−ミリストイル−2−ヒドロキシ−sn−グリセロ−3−ホスホ−(1’−rac−グリセロール)(LysoPG)、又は1−ミリストイル−2−ヒドロキシ−sn−グリセロ−3−ホスホコリン(LysoPC)のうちの少なくとも1つを含む、請求項1に記載の組成物。
- ホスファチジルグリセロールが、短鎖脂肪酸は最大5個の炭素、中鎖は6〜12個の炭素、長鎖は13〜21個の炭素、超長鎖脂肪酸は22個を超える炭素であり、偶数及び奇数鎖の両方の脂肪酸を含むとさらに規定される、請求項1に記載の組成物。
- ホスファチジルグリセロールが、飽和又は不飽和である3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、35、40、45、50、55又は56個以上の炭素を有する、請求項1に記載の組成物。
- 心臓パターンにおける不規則性若しくは変化に起因する心臓チャネル病若しくは状態が、心臓内の遅延整流性K+電流に関与するイオンチャネルの阻害、多形性心室性頻拍、QTc、LQT2、LQTSの延長、若しくはトルサード・ド・ポアンツである、又は、心臓、アレルギー若しくはがん関連疾患の治療に使用される活性剤若しくは薬物の投与により誘導されるIKrチャネル阻害の延長若しくはQT延長の治療若しくは予防に使用される、請求項1に記載の組成物。
- 薬物が、アルブテロール(サルブタモール)、アルフゾシン、アマンタジン、アミオダロン、アミスルプリド、アミトリプチリン、アモキサピン、アンフェタミン、アナグレリド、アポモルヒネ、アルフォルモテロール、アリピプラゾール、三酸化ヒ素、アステミゾール、アタザナビル、アトモキセチン、アジスロマイシン、ベダキリン、ベプリジル、ボルテゾミブ、ボスチニブ、抱水クロラール、クロロキン、クロルプロマジン、シプロフロキサシン、シサプリド、シタロプラム、クラリスロマイシン、クロミプラミン、クロザピン、コカイン、クリゾチニブ、ダブラフェニブ、ダサチニブ、デシプラミン、デクスメデトミジン、デクスメチルフェニデート、デキストロアンフェタミン(d−アンフェタミン)、ジヒドロアルテミシニン+ピペラキン、ジフェンヒドラミン、ジソピラミド、ドブタミン、ドフェチリド、ドラセトロン、ドンペリドン、ドーパミン、ドキセピン、ドロネダロン、ドロペリドール、エフェドリン、エピネフリン(アドレナリン)、エリブリン、エリスロマイシン、エスシタロプラム、ファモチジン、フェルバメート、フェンフルラミン、フィンゴリモド、フレカイニド、フルコナゾール、フルオキセチン、ホルモテロール、ホスカルネット、ホスフェニトイン、フロセミド(フルセミド)、ガランタミン、ガチフロキサシン、ゲミフロキサシン、ゲラニセトロン、ハロファントリン、ハロペリドール、ヒドロクロロチアジド、イブチリド、イロペリドン、イミプラミン(メリプラミン)、インダパミド、イソプロテレノール、イスラジピン、イトラコナゾール、イバブラジン、ケトコナゾール、ラパチニブ、レブアルブテロール(レブサルブタモール)、レボフロキサシン、レボメタジル、リスデキサンフェタミン、リチウム、メソリダジン、メタプロテレノール、メサドン、メタンフェタミン(Methamphetamine)(メタンフェタミン(methamfetamine))、メチルフェニデート、ミドドリン、ミフェプリストン、ミラベグロン、ミルタザピン、モエキシプリル/HCTZ、モキシフロキサシン、ネルフィナビル、ニカルジピン、ニロチニブ、ノルエピネフリン(ノルアドレナリン)、ノルフロキサシン、ノルトリプチリン、オフロキサシン、オランザピン、オンダンセトロン、オキシトシン、パリペリドン、パロキセチン、パシレオチド、パゾパニブ、ペンタミジン、パーフルトレン脂質ミクロスフェア、フェンテルミン、フェニレフリン、フェニルプロパノールアミン、ピモジド、ポサコナゾール、プロブコール、プロカインアミド、プロメタジン、プロトリプチリン、プソイドエフェドリン、クエチアピン、キニジン、硫酸キニーネ、ラノラジン、リルピビリン、リスペリドン、リトドリン、リトナビル、ロキシスロマイシン、サルメテロール、サキナビル、セルチンドール、セルトラリン、セボフルラン、シブトラミン、ソリフェナシン、ソラフェニブ、ソタロール、スパルフロキサシン、スルピリド、スニチニブ、タクロリムス、タモキシフェン、テラプレビル、テラバンシン、テリスロマイシン、テルブタリン、テルフェナジン、テトラベナジン、チオリダジン、チザニジン、トルテロジン、トレミフェン、トラゾドン、トリメトプリム−サルファ、トリミプラミン、バンデタニブ、バルデナフィル、ベムラフェニブ、ベンラファキシン、ボリコナゾール、ボリノスタット、又はジプラシドンから選択される、請求項1に記載の組成物。
- 心臓チャネル病、IKrチャネル阻害又はQT延長のうちの少なくとも1つを引き起こすヒトにおける活性剤又は薬物の投与から生じる1又は2以上の有害反応を引き起こす活性剤又は薬物で疾患を予防又は治療するための組成物であって、
基本構造:
IKrチャネル阻害又はQT延長のうちの少なくとも1つを引き起こす1又は2以上の活性剤又は薬物;並びに
1又は2以上の官能剤、チキソトロピー剤、又は官能剤及びチキソトロピー剤の両方
を含む組成物。 - 1又は2以上の官能剤が、1若しくは2以上の香味料、甘味料、冷却剤、色素、又はこれらの組合せ及び混合物を含む、請求項12に記載の組成物。
- 1又は2以上のチキソトロピー剤が、チキソトロピーマトリックスを形成し、多糖類、セルロース、カルボキシメチルセルロース、ガム、キサンタンガム、コラーゲン、ゼラチン、エーロゲル、ポリアクリルアミド、アルキド樹脂、又はシリカ−脂質の少なくとも1つから選択される、請求項12に記載の組成物。
- ホスファチジルグリセロールが空リポソームを形成し、10、20、25、30、40、50、60、75、80、90又は100nMの平均直径を有する、請求項12に記載の組成物。
- ホスファチジルグリセロールが、10、20、25、30、40、50、60、75、80、90又は100nMの平均直径を有するリポソームを形成する、1−ミリストイル−2−ヒドロキシ−sn−グリセロ−3−ホスホコリン(DMPC)、12−ミステロイル−2−ヒドロキシ−sn−グリセロ−3−[ホスホ−rac−(グリセロール)](DMPG)、又はDMPC/DMPGである、請求項12に記載の組成物。
- 心臓パターンにおける不規則性若しくは変化に起因する心臓チャネル病若しくは状態が、心臓内の遅延整流性K+電流に関与するイオンチャネルの阻害、多形性心室性頻拍、QTc、LQT2、LQTSの延長、若しくはトルサード・ド・ポアンツである、又は、組成物が、心臓、アレルギー、若しくはがん関連疾患の治療に使用される1若しくは2以上の薬物の投与により誘導されるIKrチャネル阻害の延長若しくはQT延長の治療若しくは予防に使用される、請求項12に記載の組成物。
- リポソームが、脂質又はリン脂質壁を含み、前記脂質又は前記リン脂質が、ホスファチジルコリン(レシチン)、リゾレシチン、リゾホスファチジルエタノール−アミン、ホスファチジルセリン、ホスファチジルイノシトール、スフィンゴミエリン、ホスファチジルエタノールアミン(セファリン)、カルジオリピン、ホスファチジン酸、セレブロシド、リン酸ジセチル、ホスファチジルコリン、及びジパルミトイル−ホスファチジルグリセロール、ステアリルアミン、ドデシルアミン、ヘキサデシル−アミン、パルミチン酸アセチル、リシノール酸グリセロール、ステアリン酸ヘキサデシル、ミリスチン酸イソプロピル、両性アクリルポリマー、脂肪酸、脂肪酸アミド、コレステロール、コレステロールエステル、ジアシルグリセロール、及びコハク酸ジアシルグリセロールからなる群から選択される、請求項12に記載の組成物。
- 薬物が、アルブテロール(サルブタモール)、アルフゾシン、アマンタジン、アミオダロン、アミスルプリド、アミトリプチリン、アモキサピン、アンフェタミン、アナグレリド、アポモルヒネ、アルフォルモテロール、アリピプラゾール、三酸化ヒ素、アステミゾール、アタザナビル、アトモキセチン、アジスロマイシン、ベダキリン、ベプリジル、ボルテゾミブ、ボスチニブ、抱水クロラール、クロロキン、クロルプロマジン、シプロフロキサシン、シサプリド、シタロプラム、クラリスロマイシン、クロミプラミン、クロザピン、コカイン、クリゾチニブ、ダブラフェニブ、ダサチニブ、デシプラミン、デクスメデトミジン、デクスメチルフェニデート、デキストロアンフェタミン(d−アンフェタミン)、ジヒドロアルテミシニン+ピペラキン、ジフェンヒドラミン、ジソピラミド、ドブタミン、ドフェチリド、ドラセトロン、ドンペリドン、ドーパミン、ドキセピン、ドロネダロン、ドロペリドール、エフェドリン、エピネフリン(アドレナリン)、エリブリン、エリスロマイシン、エスシタロプラム、ファモチジン、フェルバメート、フェンフルラミン、フィンゴリモド、フレカイニド、フルコナゾール、フルオキセチン、ホルモテロール、ホスカルネット、ホスフェニトイン、フロセミド(フルセミド)、ガランタミン、ガチフロキサシン、ゲミフロキサシン、ゲラニセトロン、ハロファントリン、ハロペリドール、ヒドロクロロチアジド、イブチリド、イロペリドン、イミプラミン(メリプラミン)、インダパミド、イソプロテレノール、イスラジピン、イトラコナゾール、イバブラジン、ケトコナゾール、ラパチニブ、レブアルブテロール(レブサルブタモール)、レボフロキサシン、レボメタジル、リスデキサンフェタミン、リチウム、メソリダジン、メタプロテレノール、メサドン、メタンフェタミン(Methamphetamine)(メタンフェタミン(methamfetamine))、メチルフェニデート、ミドドリン、ミフェプリストン、ミラベグロン、ミルタザピン、モエキシプリル/HCTZ、モキシフロキサシン、ネルフィナビル、ニカルジピン、ニロチニブ、ノルエピネフリン(ノルアドレナリン)、ノルフロキサシン、ノルトリプチリン、オフロキサシン、オランザピン、オンダンセトロン、オキシトシン、パリペリドン、パロキセチン、パシレオチド、パゾパニブ、ペンタミジン、パーフルトレン脂質ミクロスフェア、フェンテルミン、フェニレフリン、フェニルプロパノールアミン、ピモジド、ポサコナゾール、プロブコール、プロカインアミド、プロメタジン、プロトリプチリン、プソイドエフェドリン、クエチアピン、キニジン、硫酸キニーネ、ラノラジン、リルピビリン、リスペリドン、リトドリン、リトナビル、ロキシスロマイシン、サルメテロール、サキナビル、セルチンドール、セルトラリン、セボフルラン、シブトラミン、ソリフェナシン、ソラフェニブ、ソタロール、スパルフロキサシン、スルピリド、スニチニブ、タクロリムス、タモキシフェン、テラプレビル、テラバンシン、テリスロマイシン、テルブタリン、テルフェナジン、テトラベナジン、チオリダジン、チザニジン、トルテロジン、トレミフェン、トラゾドン、トリメトプリム−サルファ、トリミプラミン、バンデタニブ、バルデナフィル、ベムラフェニブ、ベンラファキシン、ボリコナゾール、ボリノスタット、又はジプラシドンから選択される、請求項12に記載の組成物。
- 活性剤又は薬物により引き起こされる、ヒト又は動物対象における1又は2以上の心臓チャネル病、心臓パターンにおける不規則性若しくは変化、IKrチャネル阻害又はQT延長を予防又は治療する方法であって、前記活性剤又は薬物がヒト又は動物対象における疾患を治療するのに使用され、
前記ヒト又は動物対象へ、前記活性剤又は薬物により引き起こされる1又は2以上の心臓チャネル病、心臓パターンにおける不規則性若しくは変化、IKrチャネル阻害、又はQT延長を低減又は予防するのに有効な、経口投与用に適合されたある量のリゾホスファチジルグリセロール;
前記疾患を治療するのに十分な有効量の前記活性剤又は薬物であって、経口供給されるリゾホスファチジルグリセロールが、前記少なくとも1つの心臓チャネル病、心臓パターンにおける不規則性若しくは変化、IKrチャネル阻害又はQT延長を低減又は排除する、活性剤又は薬物;並びに
1又は2以上の官能剤、チキソトロピー剤、又は官能剤及びチキソトロピー剤の両方
を投与するステップを含む、前記方法。 - ホスファチジルグリセロールが、リゾホスファチジルコリン、ラウロイル−リゾホスファチジルコリン、ミリストイル−リゾホスファチジルコリン、パルミトイル−リゾホスファチジルコリン、ステアロイル−リゾホスファチジルコリン、アラキドイル−リゾホスファチジルコリン、オレオイル−リゾホスファチジルコリン、リノレオイル−リゾホスファチジルコリン、リノレノイル−リゾホスファチジルコリン又はエルコイル−リゾホスファチジルコリンのうちの少なくとも1つを含む、請求項20に記載の方法。
- 1又は2以上の官能剤が、1若しくは2以上の香味料、甘味料、冷却剤、色素、又はこれらの組合せ及び混合物を含む、請求項20に記載の方法。
- 1又は2以上のチキソトロピー剤が、チキソトロピーマトリックスを形成し、多糖類、セルロース、カルボキシメチルセルロース、ガム、キサンタンガム、コラーゲン、ゼラチン、エーロゲル、ポリアクリルアミド、アルキド樹脂、又はシリカ−脂質の少なくとも1つから選択される、請求項20に記載の方法。
- ホスファチジルグリセロールが空リポソームを形成し、10、20、25、30、40、50、60、75、80、90又は100nMの平均直径を有する、請求項20に記載の方法。
- 心臓パターンにおける不規則性又は変化に起因する心臓チャネル病又は状態が、心臓内の遅延整流性K+電流に関与するイオンチャネルの阻害、多形性心室性頻拍、QTc、LQT2、LQTSの延長、又はトルサード・ド・ポアンツである、請求項20に記載の方法。
- 薬物が、アルブテロール(サルブタモール)、アルフゾシン、アマンタジン、アミオダロン、アミスルプリド、アミトリプチリン、アモキサピン、アンフェタミン、アナグレリド、アポモルヒネ、アルフォルモテロール、アリピプラゾール、三酸化ヒ素、アステミゾール、アタザナビル、アトモキセチン、アジスロマイシン、ベダキリン、ベプリジル、ボルテゾミブ、ボスチニブ、抱水クロラール、クロロキン、クロルプロマジン、シプロフロキサシン、シサプリド、シタロプラム、クラリスロマイシン、クロミプラミン、クロザピン、コカイン、クリゾチニブ、ダブラフェニブ、ダサチニブ、デシプラミン、デクスメデトミジン、デクスメチルフェニデート、デキストロアンフェタミン(d−アンフェタミン)、ジヒドロアルテミシニン+ピペラキン、ジフェンヒドラミン、ジソピラミド、ドブタミン、ドフェチリド、ドラセトロン、ドンペリドン、ドーパミン、ドキセピン、ドロネダロン、ドロペリドール、エフェドリン、エピネフリン(アドレナリン)、エリブリン、エリスロマイシン、エスシタロプラム、ファモチジン、フェルバメート、フェンフルラミン、フィンゴリモド、フレカイニド、フルコナゾール、フルオキセチン、ホルモテロール、ホスカルネット、ホスフェニトイン、フロセミド(フルセミド)、ガランタミン、ガチフロキサシン、ゲミフロキサシン、ゲラニセトロン、ハロファントリン、ハロペリドール、ヒドロクロロチアジド、イブチリド、イロペリドン、イミプラミン(メリプラミン)、インダパミド、イソプロテレノール、イスラジピン、イトラコナゾール、イバブラジン、ケトコナゾール、ラパチニブ、レブアルブテロール(レブサルブタモール)、レボフロキサシン、レボメタジル、リスデキサンフェタミン、リチウム、メソリダジン、メタプロテレノール、メサドン、メタンフェタミン(Methamphetamine)(メタンフェタミン(methamfetamine))、メチルフェニデート、ミドドリン、ミフェプリストン、ミラベグロン、ミルタザピン、モエキシプリル/HCTZ、モキシフロキサシン、ネルフィナビル、ニカルジピン、ニロチニブ、ノルエピネフリン(ノルアドレナリン)、ノルフロキサシン、ノルトリプチリン、オフロキサシン、オランザピン、オンダンセトロン、オキシトシン、パリペリドン、パロキセチン、パシレオチド、パゾパニブ、ペンタミジン、パーフルトレン脂質ミクロスフェア、フェンテルミン、フェニレフリン、フェニルプロパノールアミン、ピモジド、ポサコナゾール、プロブコール、プロカインアミド、プロメタジン、プロトリプチリン、プソイドエフェドリン、クエチアピン、キニジン、硫酸キニーネ、ラノラジン、リルピビリン、リスペリドン、リトドリン、リトナビル、ロキシスロマイシン、サルメテロール、サキナビル、セルチンドール、セルトラリン、セボフルラン、シブトラミン、ソリフェナシン、ソラフェニブ、ソタロール、スパルフロキサシン、スルピリド、スニチニブ、タクロリムス、タモキシフェン、テラプレビル、テラバンシン、テリスロマイシン、テルブタリン、テルフェナジン、テトラベナジン、チオリダジン、チザニジン、トルテロジン、トレミフェン、トラゾドン、トリメトプリム−サルファ、トリミプラミン、バンデタニブ、バルデナフィル、ベムラフェニブ、ベンラファキシン、ボリコナゾール、ボリノスタット、又はジプラシドンから選択される、請求項20に記載の方法。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US15/788,683 US10238602B2 (en) | 2011-06-03 | 2017-10-19 | Protective effect of DMPC, DMPG, DMPC/DMPG, LysoPG and LysoPC against drugs that cause channelopathies |
US15/788,683 | 2017-10-19 | ||
PCT/US2018/056721 WO2019079726A2 (en) | 2017-10-19 | 2018-10-19 | PROTECTIVE EFFECT OF DMPC, DMPG, DMPC / DMPG, LYSOPG AND LYSOPC AGAINST DRUGS CAUSING CANALOPATHIES |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2021500318A true JP2021500318A (ja) | 2021-01-07 |
Family
ID=66174240
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2020519676A Pending JP2021500318A (ja) | 2017-10-19 | 2018-10-19 | チャネル病を引き起こす薬物に対するdmpc、dmpg、dmpc/dmpg、lysopg及びlysopcの防御効果 |
Country Status (8)
Country | Link |
---|---|
EP (2) | EP3697386B1 (ja) |
JP (1) | JP2021500318A (ja) |
KR (1) | KR20200072479A (ja) |
AU (1) | AU2018351499A1 (ja) |
CA (1) | CA3076820A1 (ja) |
ES (1) | ES2960541T3 (ja) |
MX (2) | MX2020003435A (ja) |
WO (1) | WO2019079726A2 (ja) |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008093848A1 (ja) * | 2007-02-02 | 2008-08-07 | Sunstar Inc. | ホスファチジルコリンを含有する炎症マーカー低減組成物 |
JP2010275242A (ja) * | 2009-05-29 | 2010-12-09 | Okayama Univ | 経口投与用リポソーム製剤およびその製造方法 |
JP2012140395A (ja) * | 2011-01-05 | 2012-07-26 | Livon Laboratories | リポソームの製造方法、該方法によって製造されるリポソーム組成物、及び該リポソーム組成物の使用方法 |
US20120308643A1 (en) * | 2011-06-03 | 2012-12-06 | Signpath Pharma Inc. | Liposomal mitigation of drug-induced long qt syndrome and potassium delayed-rectifier current |
US20150343063A1 (en) * | 2014-06-03 | 2015-12-03 | Signpath Pharma Inc. | Protective effect of dmpc, dmpg, dmpc/dmpg, egpg, lysopg and lysopc against drugs that cause channelopathies |
JP2019531309A (ja) * | 2016-10-19 | 2019-10-31 | サインパス ファルマ, インク.Signpath Pharma, Inc. | チャネル病を引き起こす薬物に対するdmpc、dmpg、dmpc/dmpg、lysopg及びlysopcの防御効果 |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2296080C (en) | 1997-07-29 | 2005-02-01 | Alcon Laboratories, Inc. | Ophthalmic compositions containing galactomannan polymers and borate |
FR2781373B1 (fr) | 1998-07-07 | 2001-09-21 | Pf Medicament | Formulations thixotropes pour le remplissage de gelules |
US6818018B1 (en) | 1998-08-14 | 2004-11-16 | Incept Llc | In situ polymerizable hydrogels |
WO2002019966A2 (en) | 2000-09-06 | 2002-03-14 | Johns Hopkins University | Cardiac arrhythmia treatment methods |
US20050233970A1 (en) | 2004-03-23 | 2005-10-20 | Praecis Pharmaceuticals, Inc. | Methods for treating long QT syndrome |
US7593764B2 (en) | 2006-10-03 | 2009-09-22 | General Electric Company | System and method of serial comparison for detection of long QT syndrome (LQTS) |
US20080255464A1 (en) | 2007-04-10 | 2008-10-16 | Vincent G Michael | System and method for diagnosing and treating long qt syndrome |
US10449193B2 (en) * | 2011-06-03 | 2019-10-22 | Signpath Pharma Inc. | Protective effect of DMPC, DMPG, DMPC/DMPG, lysoPG and lysoPC against drugs that cause channelopathies |
DE112013004278T5 (de) | 2012-08-31 | 2015-05-21 | Signpath Pharma Inc. | Curcumin-Er, ein liposomales PLGA-Nanocurcumin mit verlängerter oder verzögerter Freisetzung zur Minimierung der QT-Verlängerung für eine Krebstherapie |
-
2018
- 2018-10-19 AU AU2018351499A patent/AU2018351499A1/en not_active Abandoned
- 2018-10-19 WO PCT/US2018/056721 patent/WO2019079726A2/en unknown
- 2018-10-19 KR KR1020207009994A patent/KR20200072479A/ko not_active Application Discontinuation
- 2018-10-19 MX MX2020003435A patent/MX2020003435A/es unknown
- 2018-10-19 CA CA3076820A patent/CA3076820A1/en not_active Abandoned
- 2018-10-19 JP JP2020519676A patent/JP2021500318A/ja active Pending
- 2018-10-19 EP EP18868801.4A patent/EP3697386B1/en active Active
- 2018-10-19 ES ES18868801T patent/ES2960541T3/es active Active
- 2018-10-19 EP EP23175714.7A patent/EP4234037A3/en active Pending
-
2020
- 2020-07-13 MX MX2023007136A patent/MX2023007136A/es unknown
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2008093848A1 (ja) * | 2007-02-02 | 2008-08-07 | Sunstar Inc. | ホスファチジルコリンを含有する炎症マーカー低減組成物 |
JP2010275242A (ja) * | 2009-05-29 | 2010-12-09 | Okayama Univ | 経口投与用リポソーム製剤およびその製造方法 |
JP2012140395A (ja) * | 2011-01-05 | 2012-07-26 | Livon Laboratories | リポソームの製造方法、該方法によって製造されるリポソーム組成物、及び該リポソーム組成物の使用方法 |
US20120308643A1 (en) * | 2011-06-03 | 2012-12-06 | Signpath Pharma Inc. | Liposomal mitigation of drug-induced long qt syndrome and potassium delayed-rectifier current |
US20150343063A1 (en) * | 2014-06-03 | 2015-12-03 | Signpath Pharma Inc. | Protective effect of dmpc, dmpg, dmpc/dmpg, egpg, lysopg and lysopc against drugs that cause channelopathies |
JP2019531309A (ja) * | 2016-10-19 | 2019-10-31 | サインパス ファルマ, インク.Signpath Pharma, Inc. | チャネル病を引き起こす薬物に対するdmpc、dmpg、dmpc/dmpg、lysopg及びlysopcの防御効果 |
Non-Patent Citations (2)
Title |
---|
ANTICANCER RESEARCH, vol. 34, JPN6020018828, 2014, pages 4733 - 4740, ISSN: 0004752062 * |
新・薬剤学総論, vol. 改訂第3版, JPN6020018830, 1987, pages 414 - 416, ISSN: 0004870309 * |
Also Published As
Publication number | Publication date |
---|---|
EP4234037A3 (en) | 2023-09-06 |
MX2023007136A (es) | 2023-06-27 |
KR20200072479A (ko) | 2020-06-22 |
MX2020003435A (es) | 2020-07-29 |
AU2018351499A1 (en) | 2020-04-09 |
EP3697386B1 (en) | 2023-07-26 |
EP4234037A2 (en) | 2023-08-30 |
ES2960541T3 (es) | 2024-03-05 |
CA3076820A1 (en) | 2019-04-25 |
EP3697386A2 (en) | 2020-08-26 |
EP3697386A4 (en) | 2021-07-28 |
WO2019079726A3 (en) | 2019-06-06 |
WO2019079726A2 (en) | 2019-04-25 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US10238602B2 (en) | Protective effect of DMPC, DMPG, DMPC/DMPG, LysoPG and LysoPC against drugs that cause channelopathies | |
AU2020286267B2 (en) | Protective effect of dmpc, dmpg, dmpc/dmpg, egpg, lysopg and lysopc against drugs that cause channelopathies | |
US10449193B2 (en) | Protective effect of DMPC, DMPG, DMPC/DMPG, lysoPG and lysoPC against drugs that cause channelopathies | |
Hirose et al. | Interactions among mu-and delta-opioid receptors, especially putative delta1-and delta2-opioid receptors, promote dopamine release in the nucleus accumbens | |
US8753674B2 (en) | Liposomal mitigation of drug-induced long QT syndrome and potassium delayed-rectifier current | |
ES2940564T3 (es) | Mitigación liposómica de la inhibición inducida por fármaco del canal IKr cardíaco | |
US20170119802A1 (en) | Liposomal mitigation of drug-induced inhibition of the cardiac ikr channel | |
CN110167562A (zh) | Dmpc、dmpg、dmpc/dmpg、lysopg和lysopc针对引起离子通道病的药物的保护作用 | |
AU2020267307A1 (en) | Protective effect of dmpc, dmpg, dmpc/dmpg, lysopg and lysopc against drugs that cause channelopathies | |
JP2021500318A (ja) | チャネル病を引き起こす薬物に対するdmpc、dmpg、dmpc/dmpg、lysopg及びlysopcの防御効果 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200630 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20200630 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210705 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20210927 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20211129 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20220418 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20220815 |
|
C60 | Trial request (containing other claim documents, opposition documents) |
Free format text: JAPANESE INTERMEDIATE CODE: C60 Effective date: 20220815 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20220822 |
|
C21 | Notice of transfer of a case for reconsideration by examiners before appeal proceedings |
Free format text: JAPANESE INTERMEDIATE CODE: C21 Effective date: 20220829 |
|
A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20220909 |
|
C211 | Notice of termination of reconsideration by examiners before appeal proceedings |
Free format text: JAPANESE INTERMEDIATE CODE: C211 Effective date: 20220921 |