WO2017073729A1 - 糖尿病治療用組成物 - Google Patents
糖尿病治療用組成物 Download PDFInfo
- Publication number
- WO2017073729A1 WO2017073729A1 PCT/JP2016/082066 JP2016082066W WO2017073729A1 WO 2017073729 A1 WO2017073729 A1 WO 2017073729A1 JP 2016082066 W JP2016082066 W JP 2016082066W WO 2017073729 A1 WO2017073729 A1 WO 2017073729A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- composition
- diabetes
- acid
- treating diabetes
- chain amino
- Prior art date
Links
- 206010012601 diabetes mellitus Diseases 0.000 title claims abstract description 136
- 239000000203 mixture Substances 0.000 title claims abstract description 92
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims abstract description 128
- 210000004369 blood Anatomy 0.000 claims abstract description 60
- 239000008280 blood Substances 0.000 claims abstract description 60
- XZWYZXLIPXDOLR-UHFFFAOYSA-N metformin Chemical compound CN(C)C(=N)NC(N)=N XZWYZXLIPXDOLR-UHFFFAOYSA-N 0.000 claims abstract description 58
- 235000014655 lactic acid Nutrition 0.000 claims abstract description 54
- 239000004310 lactic acid Substances 0.000 claims abstract description 54
- 150000003839 salts Chemical class 0.000 claims abstract description 40
- 150000004283 biguanides Chemical class 0.000 claims abstract description 33
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims abstract description 32
- 239000008103 glucose Substances 0.000 claims abstract description 32
- 208000006443 lactic acidosis Diseases 0.000 claims abstract description 19
- 239000004480 active ingredient Substances 0.000 claims abstract description 12
- OCUSNPIJIZCRSZ-ZTZWCFDHSA-N (2s)-2-amino-3-methylbutanoic acid;(2s)-2-amino-4-methylpentanoic acid;(2s,3s)-2-amino-3-methylpentanoic acid Chemical compound CC(C)[C@H](N)C(O)=O.CC[C@H](C)[C@H](N)C(O)=O.CC(C)C[C@H](N)C(O)=O OCUSNPIJIZCRSZ-ZTZWCFDHSA-N 0.000 claims abstract description 7
- 150000005693 branched-chain amino acids Chemical class 0.000 claims description 63
- 238000002360 preparation method Methods 0.000 claims description 41
- 239000003814 drug Substances 0.000 claims description 35
- 229940090124 dipeptidyl peptidase 4 (dpp-4) inhibitors for blood glucose lowering Drugs 0.000 claims description 28
- 238000011282 treatment Methods 0.000 claims description 26
- 102100025012 Dipeptidyl peptidase 4 Human genes 0.000 claims description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 19
- 101000908391 Homo sapiens Dipeptidyl peptidase 4 Proteins 0.000 claims description 19
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 18
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 claims description 14
- 239000003795 chemical substances by application Substances 0.000 claims description 14
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 claims description 13
- 229960000310 isoleucine Drugs 0.000 claims description 13
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 claims description 12
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 claims description 12
- 230000009471 action Effects 0.000 claims description 11
- 238000001802 infusion Methods 0.000 claims description 11
- 201000010099 disease Diseases 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- 230000008085 renal dysfunction Effects 0.000 claims description 10
- 229940124597 therapeutic agent Drugs 0.000 claims description 10
- 102000004877 Insulin Human genes 0.000 claims description 9
- 108090001061 Insulin Proteins 0.000 claims description 9
- 239000003472 antidiabetic agent Substances 0.000 claims description 9
- 229960004111 buformin Drugs 0.000 claims description 9
- XSEUMFJMFFMCIU-UHFFFAOYSA-N buformin Chemical compound CCCC\N=C(/N)N=C(N)N XSEUMFJMFFMCIU-UHFFFAOYSA-N 0.000 claims description 9
- 229940125396 insulin Drugs 0.000 claims description 9
- 230000001225 therapeutic effect Effects 0.000 claims description 9
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 8
- 229960003243 phenformin Drugs 0.000 claims description 8
- ICFJFFQQTFMIBG-UHFFFAOYSA-N phenformin Chemical compound NC(=N)NC(=N)NCCC1=CC=CC=C1 ICFJFFQQTFMIBG-UHFFFAOYSA-N 0.000 claims description 8
- 230000002265 prevention Effects 0.000 claims description 8
- 229940123208 Biguanide Drugs 0.000 claims description 7
- 208000019423 liver disease Diseases 0.000 claims description 7
- DTHNMHAUYICORS-KTKZVXAJSA-N Glucagon-like peptide 1 Chemical class C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1N=CNC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 DTHNMHAUYICORS-KTKZVXAJSA-N 0.000 claims description 6
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 6
- 208000024891 symptom Diseases 0.000 claims description 6
- 239000004474 valine Substances 0.000 claims description 6
- 229940077274 Alpha glucosidase inhibitor Drugs 0.000 claims description 5
- XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 claims description 5
- 229940100389 Sulfonylurea Drugs 0.000 claims description 5
- 239000003888 alpha glucosidase inhibitor Substances 0.000 claims description 5
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 claims description 5
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 4
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 4
- 206010021143 Hypoxia Diseases 0.000 claims description 4
- 229940122199 Insulin secretagogue Drugs 0.000 claims description 4
- 239000003288 aldose reductase inhibitor Substances 0.000 claims description 4
- 229940126904 hypoglycaemic agent Drugs 0.000 claims description 4
- 208000018875 hypoxemia Diseases 0.000 claims description 4
- 230000005976 liver dysfunction Effects 0.000 claims description 4
- 230000001404 mediated effect Effects 0.000 claims description 4
- 229960004329 metformin hydrochloride Drugs 0.000 claims description 4
- OETHQSJEHLVLGH-UHFFFAOYSA-N metformin hydrochloride Chemical compound Cl.CN(C)C(=N)N=C(N)N OETHQSJEHLVLGH-UHFFFAOYSA-N 0.000 claims description 4
- 230000003449 preventive effect Effects 0.000 claims description 4
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 4
- 229940124213 Dipeptidyl peptidase 4 (DPP IV) inhibitor Drugs 0.000 claims description 3
- 239000003603 dipeptidyl peptidase IV inhibitor Substances 0.000 claims description 3
- 230000001771 impaired effect Effects 0.000 claims description 3
- 230000009325 pulmonary function Effects 0.000 claims description 2
- 229940126158 β3 adrenergic receptor agonist Drugs 0.000 claims description 2
- 229940118148 Aldose reductase inhibitor Drugs 0.000 claims 1
- 229940126033 PPAR agonist Drugs 0.000 claims 1
- MNQZXJOMYWMBOU-UHFFFAOYSA-N glyceraldehyde Chemical compound OCC(O)C=O MNQZXJOMYWMBOU-UHFFFAOYSA-N 0.000 claims 1
- 239000002307 peroxisome proliferator activated receptor agonist Substances 0.000 claims 1
- 229940121377 sodium-glucose co-transporter inhibitor Drugs 0.000 claims 1
- 229960003105 metformin Drugs 0.000 abstract description 54
- 230000000694 effects Effects 0.000 abstract description 18
- 230000003247 decreasing effect Effects 0.000 abstract description 11
- 229940024606 amino acid Drugs 0.000 abstract description 9
- 150000001413 amino acids Chemical class 0.000 abstract description 9
- 230000002218 hypoglycaemic effect Effects 0.000 abstract description 5
- 229960000448 lactic acid Drugs 0.000 description 61
- 235000002639 sodium chloride Nutrition 0.000 description 38
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 31
- -1 TA-6666 Chemical compound 0.000 description 18
- 229920002472 Starch Polymers 0.000 description 17
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 17
- 229940079593 drug Drugs 0.000 description 17
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- 150000001875 compounds Chemical class 0.000 description 14
- 239000008107 starch Substances 0.000 description 14
- 235000000346 sugar Nutrition 0.000 description 14
- 239000000556 agonist Substances 0.000 description 13
- 235000019698 starch Nutrition 0.000 description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 12
- 239000003826 tablet Substances 0.000 description 12
- 229960003136 leucine Drugs 0.000 description 11
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 10
- 235000010980 cellulose Nutrition 0.000 description 10
- 229920002678 cellulose Polymers 0.000 description 10
- 235000019441 ethanol Nutrition 0.000 description 10
- 108090000765 processed proteins & peptides Proteins 0.000 description 10
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 9
- 239000001913 cellulose Substances 0.000 description 9
- 239000013078 crystal Substances 0.000 description 9
- 239000008101 lactose Substances 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 238000000034 method Methods 0.000 description 8
- 239000002547 new drug Substances 0.000 description 8
- 210000000496 pancreas Anatomy 0.000 description 8
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 7
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 230000010030 glucose lowering effect Effects 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 235000015424 sodium Nutrition 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 6
- 229930006000 Sucrose Natural products 0.000 description 6
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 6
- WNLRTRBMVRJNCN-UHFFFAOYSA-N adipic acid Chemical compound OC(=O)CCCCC(O)=O WNLRTRBMVRJNCN-UHFFFAOYSA-N 0.000 description 6
- 235000001014 amino acid Nutrition 0.000 description 6
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 6
- 235000011187 glycerol Nutrition 0.000 description 6
- 229940001447 lactate Drugs 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000005720 sucrose Substances 0.000 description 6
- 238000002560 therapeutic procedure Methods 0.000 description 6
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 6
- 229960004295 valine Drugs 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 229920001817 Agar Polymers 0.000 description 5
- 108010088751 Albumins Proteins 0.000 description 5
- 102000009027 Albumins Human genes 0.000 description 5
- 108010010803 Gelatin Proteins 0.000 description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 5
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 235000021355 Stearic acid Nutrition 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 239000008272 agar Substances 0.000 description 5
- 235000010419 agar Nutrition 0.000 description 5
- 230000032683 aging Effects 0.000 description 5
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 5
- 229910000019 calcium carbonate Inorganic materials 0.000 description 5
- 235000010216 calcium carbonate Nutrition 0.000 description 5
- 229960004106 citric acid Drugs 0.000 description 5
- 235000015165 citric acid Nutrition 0.000 description 5
- 239000008273 gelatin Substances 0.000 description 5
- 229920000159 gelatin Polymers 0.000 description 5
- 229940014259 gelatin Drugs 0.000 description 5
- 235000019322 gelatine Nutrition 0.000 description 5
- 235000011852 gelatine desserts Nutrition 0.000 description 5
- 238000001727 in vivo Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 210000004185 liver Anatomy 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 229920000609 methyl cellulose Polymers 0.000 description 5
- 239000001923 methylcellulose Substances 0.000 description 5
- 235000010981 methylcellulose Nutrition 0.000 description 5
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 5
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 5
- 235000011007 phosphoric acid Nutrition 0.000 description 5
- 239000003755 preservative agent Substances 0.000 description 5
- 102000004196 processed proteins & peptides Human genes 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 235000012239 silicon dioxide Nutrition 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 229960002920 sorbitol Drugs 0.000 description 5
- 239000008117 stearic acid Substances 0.000 description 5
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 4
- 244000215068 Acacia senegal Species 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
- 241000416162 Astragalus gummifer Species 0.000 description 4
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 4
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- 102400000322 Glucagon-like peptide 1 Human genes 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 229920000084 Gum arabic Polymers 0.000 description 4
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- 102000023984 PPAR alpha Human genes 0.000 description 4
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 4
- 229920001615 Tragacanth Polymers 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 235000010489 acacia gum Nutrition 0.000 description 4
- 239000000205 acacia gum Substances 0.000 description 4
- 235000011054 acetic acid Nutrition 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 208000007502 anemia Diseases 0.000 description 4
- 229940125708 antidiabetic agent Drugs 0.000 description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- 239000011230 binding agent Substances 0.000 description 4
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 4
- 239000004327 boric acid Substances 0.000 description 4
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 4
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 4
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 239000003112 inhibitor Substances 0.000 description 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 4
- 239000011976 maleic acid Substances 0.000 description 4
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 4
- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- HYAFETHFCAUJAY-UHFFFAOYSA-N pioglitazone Chemical compound N1=CC(CC)=CC=C1CCOC(C=C1)=CC=C1CC1C(=O)NC(=O)S1 HYAFETHFCAUJAY-UHFFFAOYSA-N 0.000 description 4
- 229920001223 polyethylene glycol Polymers 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 230000002335 preservative effect Effects 0.000 description 4
- 230000001737 promoting effect Effects 0.000 description 4
- 230000000069 prophylactic effect Effects 0.000 description 4
- 239000008159 sesame oil Substances 0.000 description 4
- 235000011803 sesame oil Nutrition 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 4
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 4
- 235000002906 tartaric acid Nutrition 0.000 description 4
- 239000011975 tartaric acid Substances 0.000 description 4
- MGSRCZKZVOBKFT-UHFFFAOYSA-N thymol Chemical compound CC(C)C1=CC=C(C)C=C1O MGSRCZKZVOBKFT-UHFFFAOYSA-N 0.000 description 4
- 235000010487 tragacanth Nutrition 0.000 description 4
- 239000000196 tragacanth Substances 0.000 description 4
- 229940116362 tragacanth Drugs 0.000 description 4
- LMJSLTNSBFUCMU-UHFFFAOYSA-N trichlormethiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NC(C(Cl)Cl)NS2(=O)=O LMJSLTNSBFUCMU-UHFFFAOYSA-N 0.000 description 4
- GQPYTJVDPQTBQC-KLQYNRQASA-N (3r)-3-amino-1-[3-(trifluoromethyl)-6,8-dihydro-5h-[1,2,4]triazolo[4,3-a]pyrazin-7-yl]-4-(2,4,5-trifluorophenyl)butan-1-one;phosphoric acid;hydrate Chemical compound O.OP(O)(O)=O.C([C@H](CC(=O)N1CC=2N(C(=NN=2)C(F)(F)F)CC1)N)C1=CC(F)=C(F)C=C1F GQPYTJVDPQTBQC-KLQYNRQASA-N 0.000 description 3
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 3
- WNWHHMBRJJOGFJ-UHFFFAOYSA-N 16-methylheptadecan-1-ol Chemical class CC(C)CCCCCCCCCCCCCCCO WNWHHMBRJJOGFJ-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 239000005995 Aluminium silicate Substances 0.000 description 3
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 3
- 229920002261 Corn starch Polymers 0.000 description 3
- 229920000858 Cyclodextrin Polymers 0.000 description 3
- 206010012289 Dementia Diseases 0.000 description 3
- 229920001353 Dextrin Polymers 0.000 description 3
- 239000004375 Dextrin Substances 0.000 description 3
- 206010012735 Diarrhoea Diseases 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 239000001116 FEMA 4028 Substances 0.000 description 3
- 101710198884 GATA-type zinc finger protein 1 Proteins 0.000 description 3
- 108010004460 Gastric Inhibitory Polypeptide Proteins 0.000 description 3
- 102100039994 Gastric inhibitory polypeptide Human genes 0.000 description 3
- 208000003623 Hypoalbuminemia Diseases 0.000 description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 102000002808 Pituitary adenylate cyclase-activating polypeptide Human genes 0.000 description 3
- 108010004684 Pituitary adenylate cyclase-activating polypeptide Proteins 0.000 description 3
- 239000002202 Polyethylene glycol Substances 0.000 description 3
- 208000001647 Renal Insufficiency Diseases 0.000 description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 3
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 230000004913 activation Effects 0.000 description 3
- 230000000996 additive effect Effects 0.000 description 3
- 235000011037 adipic acid Nutrition 0.000 description 3
- 239000001361 adipic acid Substances 0.000 description 3
- 229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 description 3
- 235000012211 aluminium silicate Nutrition 0.000 description 3
- 229960005261 aspartic acid Drugs 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 3
- 235000011175 beta-cyclodextrine Nutrition 0.000 description 3
- 229960004853 betadex Drugs 0.000 description 3
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 3
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 229960004926 chlorobutanol Drugs 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 230000034994 death Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 235000019425 dextrin Nutrition 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 3
- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 239000001341 hydroxy propyl starch Substances 0.000 description 3
- 235000013828 hydroxypropyl starch Nutrition 0.000 description 3
- 230000003914 insulin secretion Effects 0.000 description 3
- 235000015110 jellies Nutrition 0.000 description 3
- 239000008274 jelly Substances 0.000 description 3
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 3
- 201000006370 kidney failure Diseases 0.000 description 3
- 239000000314 lubricant Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 230000004060 metabolic process Effects 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 150000007524 organic acids Chemical class 0.000 description 3
- 229940056211 paraffin Drugs 0.000 description 3
- 239000012188 paraffin wax Substances 0.000 description 3
- 230000000291 postprandial effect Effects 0.000 description 3
- LWIHDJKSTIGBAC-UHFFFAOYSA-K potassium phosphate Substances [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 3
- 229920001592 potato starch Polymers 0.000 description 3
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 3
- 235000010413 sodium alginate Nutrition 0.000 description 3
- 239000000661 sodium alginate Substances 0.000 description 3
- 229940005550 sodium alginate Drugs 0.000 description 3
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 3
- 235000010234 sodium benzoate Nutrition 0.000 description 3
- 239000004299 sodium benzoate Substances 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 235000010265 sodium sulphite Nutrition 0.000 description 3
- 239000003381 stabilizer Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000000454 talc Substances 0.000 description 3
- 229910052623 talc Inorganic materials 0.000 description 3
- 229940033134 talc Drugs 0.000 description 3
- 235000012222 talc Nutrition 0.000 description 3
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 2
- CUNWUEBNSZSNRX-RKGWDQTMSA-N (2r,3r,4r,5s)-hexane-1,2,3,4,5,6-hexol;(z)-octadec-9-enoic acid Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O.CCCCCCCC\C=C/CCCCCCCC(O)=O CUNWUEBNSZSNRX-RKGWDQTMSA-N 0.000 description 2
- SPSPIUSUWPLVKD-UHFFFAOYSA-N 2,3-dibutyl-6-methylphenol Chemical compound CCCCC1=CC=C(C)C(O)=C1CCCC SPSPIUSUWPLVKD-UHFFFAOYSA-N 0.000 description 2
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- QTWJRLJHJPIABL-UHFFFAOYSA-N 2-methylphenol;3-methylphenol;4-methylphenol Chemical compound CC1=CC=C(O)C=C1.CC1=CC=CC(O)=C1.CC1=CC=CC=C1O QTWJRLJHJPIABL-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 description 2
- QNAYBMKLOCPYGJ-UHFFFAOYSA-N Alanine Chemical compound CC([NH3+])C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 2
- 239000005711 Benzoic acid Substances 0.000 description 2
- 208000002381 Brain Hypoxia Diseases 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- CKLJMWTZIZZHCS-UHFFFAOYSA-N D-OH-Asp Natural products OC(=O)C(N)CC(O)=O CKLJMWTZIZZHCS-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 2
- 108010016626 Dipeptides Proteins 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 description 2
- 206010018429 Glucose tolerance impaired Diseases 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 208000013016 Hypoglycemia Diseases 0.000 description 2
- 206010070511 Hypoxic-ischaemic encephalopathy Diseases 0.000 description 2
- 229940122355 Insulin sensitizer Drugs 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- CKLJMWTZIZZHCS-UWTATZPHSA-N L-Aspartic acid Natural products OC(=O)[C@H](N)CC(O)=O CKLJMWTZIZZHCS-UWTATZPHSA-N 0.000 description 2
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- 229920001543 Laminarin Polymers 0.000 description 2
- 229940127470 Lipase Inhibitors Drugs 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- ZPXSCAKFGYXMGA-UHFFFAOYSA-N Mazindol Chemical compound N12CCN=C2C2=CC=CC=C2C1(O)C1=CC=C(Cl)C=C1 ZPXSCAKFGYXMGA-UHFFFAOYSA-N 0.000 description 2
- QIAFMBKCNZACKA-UHFFFAOYSA-N N-benzoylglycine Chemical compound OC(=O)CNC(=O)C1=CC=CC=C1 QIAFMBKCNZACKA-UHFFFAOYSA-N 0.000 description 2
- FZERHIULMFGESH-UHFFFAOYSA-N N-phenylacetamide Chemical compound CC(=O)NC1=CC=CC=C1 FZERHIULMFGESH-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- 102100035593 POU domain, class 2, transcription factor 1 Human genes 0.000 description 2
- 101710084414 POU domain, class 2, transcription factor 1 Proteins 0.000 description 2
- 108010016731 PPAR gamma Proteins 0.000 description 2
- 102100038825 Peroxisome proliferator-activated receptor gamma Human genes 0.000 description 2
- 229920001214 Polysorbate 60 Polymers 0.000 description 2
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 2
- 229920001800 Shellac Polymers 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 239000004288 Sodium dehydroacetate Substances 0.000 description 2
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 description 2
- KKEYFWRCBNTPAC-UHFFFAOYSA-N Terephthalic acid Chemical compound OC(=O)C1=CC=C(C(O)=O)C=C1 KKEYFWRCBNTPAC-UHFFFAOYSA-N 0.000 description 2
- 244000299461 Theobroma cacao Species 0.000 description 2
- 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 2
- 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 0.000 description 2
- 239000005844 Thymol Substances 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 108010003205 Vasoactive Intestinal Peptide Proteins 0.000 description 2
- 102400000015 Vasoactive intestinal peptide Human genes 0.000 description 2
- DFPAKSUCGFBDDF-ZQBYOMGUSA-N [14c]-nicotinamide Chemical compound N[14C](=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-ZQBYOMGUSA-N 0.000 description 2
- 229940124532 absorption promoter Drugs 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 229960000250 adipic acid Drugs 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 2
- 239000002220 antihypertensive agent Substances 0.000 description 2
- 229940030600 antihypertensive agent Drugs 0.000 description 2
- 239000002830 appetite depressant Substances 0.000 description 2
- 239000003125 aqueous solvent Substances 0.000 description 2
- 235000010323 ascorbic acid Nutrition 0.000 description 2
- 239000011668 ascorbic acid Substances 0.000 description 2
- 229960005070 ascorbic acid Drugs 0.000 description 2
- 239000000440 bentonite Substances 0.000 description 2
- 229910000278 bentonite Inorganic materials 0.000 description 2
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 2
- 229960000686 benzalkonium chloride Drugs 0.000 description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 2
- 229940092714 benzenesulfonic acid Drugs 0.000 description 2
- 235000010233 benzoic acid Nutrition 0.000 description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 2
- 108010014502 beta-3 Adrenergic Receptors Proteins 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N beta-monoglyceryl stearate Natural products CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- 210000004204 blood vessel Anatomy 0.000 description 2
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 description 2
- 235000014121 butter Nutrition 0.000 description 2
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
- 235000001046 cacaotero Nutrition 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229960005069 calcium Drugs 0.000 description 2
- 235000013539 calcium stearate Nutrition 0.000 description 2
- 239000008116 calcium stearate Substances 0.000 description 2
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 239000004202 carbamide Substances 0.000 description 2
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- DDRJAANPRJIHGJ-UHFFFAOYSA-N creatinine Chemical compound CN1CC(=O)NC1=N DDRJAANPRJIHGJ-UHFFFAOYSA-N 0.000 description 2
- 229930003836 cresol Natural products 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 229910000397 disodium phosphate Inorganic materials 0.000 description 2
- 235000019800 disodium phosphate Nutrition 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 229940043264 dodecyl sulfate Drugs 0.000 description 2
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 239000001530 fumaric acid Substances 0.000 description 2
- 235000011087 fumaric acid Nutrition 0.000 description 2
- 235000001727 glucose Nutrition 0.000 description 2
- 229960002989 glutamic acid Drugs 0.000 description 2
- 229960002449 glycine Drugs 0.000 description 2
- 235000013905 glycine and its sodium salt Nutrition 0.000 description 2
- 238000001631 haemodialysis Methods 0.000 description 2
- 230000000322 hemodialysis Effects 0.000 description 2
- 201000001421 hyperglycemia Diseases 0.000 description 2
- DBTMGCOVALSLOR-VPNXCSTESA-N laminarin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)OC1O[C@@H]1[C@@H](O)C(O[C@H]2[C@@H]([C@@H](CO)OC(O)[C@@H]2O)O)O[C@H](CO)[C@H]1O DBTMGCOVALSLOR-VPNXCSTESA-N 0.000 description 2
- 201000011486 lichen planus Diseases 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 230000004199 lung function Effects 0.000 description 2
- 229960003511 macrogol Drugs 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- HCWCAKKEBCNQJP-UHFFFAOYSA-N magnesium orthosilicate Chemical compound [Mg+2].[Mg+2].[O-][Si]([O-])([O-])[O-] HCWCAKKEBCNQJP-UHFFFAOYSA-N 0.000 description 2
- 239000000391 magnesium silicate Substances 0.000 description 2
- 229910052919 magnesium silicate Inorganic materials 0.000 description 2
- 235000019792 magnesium silicate Nutrition 0.000 description 2
- NFFJLMKHRCXLJO-DKWTVANSSA-L magnesium;(2s)-2-aminobutanedioate Chemical compound [Mg+2].[O-]C(=O)[C@@H](N)CC([O-])=O NFFJLMKHRCXLJO-DKWTVANSSA-L 0.000 description 2
- 229960000299 mazindol Drugs 0.000 description 2
- 235000012054 meals Nutrition 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 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
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 2
- 235000019799 monosodium phosphate Nutrition 0.000 description 2
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000004006 olive oil Substances 0.000 description 2
- 235000008390 olive oil Nutrition 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000003538 oral antidiabetic agent Substances 0.000 description 2
- 238000007410 oral glucose tolerance test Methods 0.000 description 2
- 229940127209 oral hypoglycaemic agent Drugs 0.000 description 2
- 239000003002 pH adjusting agent Substances 0.000 description 2
- 235000019271 petrolatum Nutrition 0.000 description 2
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 2
- 229960004838 phosphoric acid Drugs 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 229960005095 pioglitazone Drugs 0.000 description 2
- UFTCZKMBJOPXDM-XXFCQBPRSA-N pituitary adenylate cyclase-activating polypeptide Chemical compound C([C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(N)=O)C1=CN=CN1 UFTCZKMBJOPXDM-XXFCQBPRSA-N 0.000 description 2
- 102000054765 polymorphisms of proteins Human genes 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 235000010241 potassium sorbate Nutrition 0.000 description 2
- 239000004302 potassium sorbate Substances 0.000 description 2
- 229940069338 potassium sorbate Drugs 0.000 description 2
- 235000013772 propylene glycol Nutrition 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
- 201000004240 prostatic hypertrophy Diseases 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229960004937 saxagliptin Drugs 0.000 description 2
- 108010033693 saxagliptin Proteins 0.000 description 2
- QGJUIPDUBHWZPV-SGTAVMJGSA-N saxagliptin Chemical compound C1C(C2)CC(C3)CC2(O)CC13[C@H](N)C(=O)N1[C@H](C#N)C[C@@H]2C[C@@H]21 QGJUIPDUBHWZPV-SGTAVMJGSA-N 0.000 description 2
- 235000013874 shellac Nutrition 0.000 description 2
- 239000004208 shellac Substances 0.000 description 2
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 2
- 229940113147 shellac Drugs 0.000 description 2
- 229960004425 sibutramine Drugs 0.000 description 2
- 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 description 2
- 150000004760 silicates Chemical class 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 235000011083 sodium citrates Nutrition 0.000 description 2
- 235000019259 sodium dehydroacetate Nutrition 0.000 description 2
- 229940079839 sodium dehydroacetate Drugs 0.000 description 2
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 2
- 239000001488 sodium phosphate Substances 0.000 description 2
- 229960004025 sodium salicylate Drugs 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- DSOWAKKSGYUMTF-GZOLSCHFSA-M sodium;(1e)-1-(6-methyl-2,4-dioxopyran-3-ylidene)ethanolate Chemical compound [Na+].C\C([O-])=C1/C(=O)OC(C)=CC1=O DSOWAKKSGYUMTF-GZOLSCHFSA-M 0.000 description 2
- 235000010199 sorbic acid Nutrition 0.000 description 2
- 239000004334 sorbic acid Substances 0.000 description 2
- 229940075582 sorbic acid Drugs 0.000 description 2
- 229960005078 sorbitan sesquioleate Drugs 0.000 description 2
- 210000002784 stomach Anatomy 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 description 2
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 2
- 229940126585 therapeutic drug Drugs 0.000 description 2
- 229960000790 thymol Drugs 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 2
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 2
- 229910000406 trisodium phosphate Inorganic materials 0.000 description 2
- 235000019801 trisodium phosphate Nutrition 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- SYOKIDBDQMKNDQ-XWTIBIIYSA-N vildagliptin Chemical compound C1C(O)(C2)CC(C3)CC1CC32NCC(=O)N1CCC[C@H]1C#N SYOKIDBDQMKNDQ-XWTIBIIYSA-N 0.000 description 2
- XUFXOAAUWZOOIT-SXARVLRPSA-N (2R,3R,4R,5S,6R)-5-[[(2R,3R,4R,5S,6R)-5-[[(2R,3R,4S,5S,6R)-3,4-dihydroxy-6-methyl-5-[[(1S,4R,5S,6S)-4,5,6-trihydroxy-3-(hydroxymethyl)-1-cyclohex-2-enyl]amino]-2-oxanyl]oxy]-3,4-dihydroxy-6-(hydroxymethyl)-2-oxanyl]oxy]-6-(hydroxymethyl)oxane-2,3,4-triol Chemical compound O([C@H]1O[C@H](CO)[C@H]([C@@H]([C@H]1O)O)O[C@H]1O[C@@H]([C@H]([C@H](O)[C@H]1O)N[C@@H]1[C@@H]([C@@H](O)[C@H](O)C(CO)=C1)O)C)[C@@H]1[C@@H](CO)O[C@@H](O)[C@H](O)[C@H]1O XUFXOAAUWZOOIT-SXARVLRPSA-N 0.000 description 1
- QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 description 1
- CSTRPYAGFNTOEQ-MGMRMFRLSA-N (2r)-2-[(1s)-1,2-dihydroxyethyl]-3,4-dihydroxy-2h-furan-5-one;octadecanoic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O.CCCCCCCCCCCCCCCCCC(O)=O CSTRPYAGFNTOEQ-MGMRMFRLSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- VZZUJVDCIBINIT-YDALLXLXSA-N (2s)-2-acetamido-3-(1h-indol-3-yl)propanoic acid;sodium Chemical compound [Na].C1=CC=C2C(C[C@H](NC(=O)C)C(O)=O)=CNC2=C1 VZZUJVDCIBINIT-YDALLXLXSA-N 0.000 description 1
- KWSUGULOZFMUDH-RITPCOANSA-N (2s,3r)-2-amino-3-methylhexanoic acid Chemical compound CCC[C@@H](C)[C@H](N)C(O)=O KWSUGULOZFMUDH-RITPCOANSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- TUSDEZXZIZRFGC-UHFFFAOYSA-N 1-O-galloyl-3,6-(R)-HHDP-beta-D-glucose Natural products OC1C(O2)COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC1C(O)C2OC(=O)C1=CC(O)=C(O)C(O)=C1 TUSDEZXZIZRFGC-UHFFFAOYSA-N 0.000 description 1
- BOVGTQGAOIONJV-BETUJISGSA-N 1-[(3ar,6as)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]-3-(4-methylphenyl)sulfonylurea Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1C[C@H]2CCC[C@H]2C1 BOVGTQGAOIONJV-BETUJISGSA-N 0.000 description 1
- IBDOVKSLMMFQPJ-IUPOGUASSA-N 1-[2-[(4ar,11r,11as)-11-methyl-9-(trifluoromethyl)-1,3,4,4a,5,6,11,11a-octahydropyrido[4,3-b]carbazol-2-yl]ethyl]cyclohexane-1-carboxylic acid;benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1.C([C@@H]1[C@H](C=2C3=CC(=CC=C3NC=2C[C@H]1CC1)C(F)(F)F)C)N1CCC1(C(O)=O)CCCCC1 IBDOVKSLMMFQPJ-IUPOGUASSA-N 0.000 description 1
- 102000008645 11-beta-Hydroxysteroid Dehydrogenase Type 1 Human genes 0.000 description 1
- 108010088011 11-beta-Hydroxysteroid Dehydrogenase Type 1 Proteins 0.000 description 1
- 102000004277 11-beta-hydroxysteroid dehydrogenases Human genes 0.000 description 1
- 108090000874 11-beta-hydroxysteroid dehydrogenases Proteins 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- LUACLLSCZRRTIH-UPHRSURJSA-N 2-[[4-[(z)-4-[4-[(3,5-dioxo-1,2,4-oxadiazolidin-2-yl)methyl]phenoxy]but-2-enoxy]phenyl]methyl]-1,2,4-oxadiazolidine-3,5-dione Chemical compound O1C(=O)NC(=O)N1CC(C=C1)=CC=C1OC\C=C/COC(C=C1)=CC=C1CN1C(=O)NC(=O)O1 LUACLLSCZRRTIH-UPHRSURJSA-N 0.000 description 1
- WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical compound O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 description 1
- LTDYEDCDJFHPFI-UHFFFAOYSA-N 2-aminoacetic acid;2-aminopropanoic acid Chemical compound NCC(O)=O.CC(N)C(O)=O LTDYEDCDJFHPFI-UHFFFAOYSA-N 0.000 description 1
- LRQKBLKVPFOOQJ-UHFFFAOYSA-N 2-aminohexanoic acid Chemical compound CCCCC(N)C(O)=O LRQKBLKVPFOOQJ-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- MIDXCONKKJTLDX-UHFFFAOYSA-N 3,5-dimethylcyclopentane-1,2-dione Chemical compound CC1CC(C)C(=O)C1=O MIDXCONKKJTLDX-UHFFFAOYSA-N 0.000 description 1
- UOQHWNPVNXSDDO-UHFFFAOYSA-N 3-bromoimidazo[1,2-a]pyridine-6-carbonitrile Chemical compound C1=CC(C#N)=CN2C(Br)=CN=C21 UOQHWNPVNXSDDO-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- OSCCDBFHNMXNME-DSDZBIDZSA-N 4-Hydroxy-L-isoleucine Chemical compound CC(O)[C@H](C)[C@H](N)C(O)=O OSCCDBFHNMXNME-DSDZBIDZSA-N 0.000 description 1
- LGSOKZOQANLOEU-UHFFFAOYSA-N 4-[2-(2,4-dioxo-1,3-thiazolidin-5-yl)ethoxy]benzonitrile Chemical compound S1C(=O)NC(=O)C1CCOC1=CC=C(C#N)C=C1 LGSOKZOQANLOEU-UHFFFAOYSA-N 0.000 description 1
- QBQLYIISSRXYKL-UHFFFAOYSA-N 4-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-1,2-oxazolidine-3,5-dione Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C=C1)=CC=C1CC1C(=O)NOC1=O QBQLYIISSRXYKL-UHFFFAOYSA-N 0.000 description 1
- IETKPTYAGKZLKY-UHFFFAOYSA-N 5-[[4-[(3-methyl-4-oxoquinazolin-2-yl)methoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound N=1C2=CC=CC=C2C(=O)N(C)C=1COC(C=C1)=CC=C1CC1SC(=O)NC1=O IETKPTYAGKZLKY-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- RSWGJHLUYNHPMX-UHFFFAOYSA-N Abietic-Saeure Natural products C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000009304 Acute Kidney Injury Diseases 0.000 description 1
- 102000002281 Adenylate kinase Human genes 0.000 description 1
- 108020000543 Adenylate kinase Proteins 0.000 description 1
- 108700023418 Amidases Proteins 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical class N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 208000037157 Azotemia Diseases 0.000 description 1
- 102100034159 Beta-3 adrenergic receptor Human genes 0.000 description 1
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
- 102100033868 Cannabinoid receptor 1 Human genes 0.000 description 1
- 101710187010 Cannabinoid receptor 1 Proteins 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 102000019034 Chemokines Human genes 0.000 description 1
- 108010012236 Chemokines Proteins 0.000 description 1
- RKWGIWYCVPQPMF-UHFFFAOYSA-N Chloropropamide Chemical compound CCCNC(=O)NS(=O)(=O)C1=CC=C(Cl)C=C1 RKWGIWYCVPQPMF-UHFFFAOYSA-N 0.000 description 1
- DTPLOCBWAFWYND-UHFFFAOYSA-N Cl.C=1C=CC=CC=1C(=O)C(=O)C1=CC=CC=C1 Chemical compound Cl.C=1C=CC=CC=1C(=O)C(=O)C1=CC=CC=C1 DTPLOCBWAFWYND-UHFFFAOYSA-N 0.000 description 1
- 241001454694 Clupeiformes Species 0.000 description 1
- 239000001879 Curdlan Substances 0.000 description 1
- 229920002558 Curdlan Polymers 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- URRAHSMDPCMOTH-LNLFQRSKSA-N Denagliptin Chemical compound C=1C=C(F)C=CC=1C([C@H](N)C(=O)N1[C@@H](C[C@H](F)C1)C#N)C1=CC=C(F)C=C1 URRAHSMDPCMOTH-LNLFQRSKSA-N 0.000 description 1
- 208000002249 Diabetes Complications Diseases 0.000 description 1
- 208000007342 Diabetic Nephropathies Diseases 0.000 description 1
- 206010012655 Diabetic complications Diseases 0.000 description 1
- 108010067722 Dipeptidyl Peptidase 4 Proteins 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical class OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 208000004232 Enteritis Diseases 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 229920003134 Eudragit® polymer Polymers 0.000 description 1
- 239000001263 FEMA 3042 Substances 0.000 description 1
- 208000004930 Fatty Liver Diseases 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 208000004262 Food Hypersensitivity Diseases 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 229920002148 Gellan gum Polymers 0.000 description 1
- 206010018364 Glomerulonephritis Diseases 0.000 description 1
- 108010088406 Glucagon-Like Peptides Proteins 0.000 description 1
- 101800000224 Glucagon-like peptide 1 Proteins 0.000 description 1
- FAEKWTJYAYMJKF-QHCPKHFHSA-N GlucoNorm Chemical compound C1=C(C(O)=O)C(OCC)=CC(CC(=O)N[C@@H](CC(C)C)C=2C(=CC=CC=2)N2CCCCC2)=C1 FAEKWTJYAYMJKF-QHCPKHFHSA-N 0.000 description 1
- 208000002705 Glucose Intolerance Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- DCXXMTOCNZCJGO-UHFFFAOYSA-N Glycerol trioctadecanoate Natural products CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 1
- HNSCCNJWTJUGNQ-UHFFFAOYSA-N Glyclopyramide Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)NC(=O)NN1CCCC1 HNSCCNJWTJUGNQ-UHFFFAOYSA-N 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- 101000684208 Homo sapiens Prolyl endopeptidase FAP Proteins 0.000 description 1
- 101100152799 Homo sapiens TFDP3 gene Proteins 0.000 description 1
- 229940123502 Hormone receptor antagonist Drugs 0.000 description 1
- 208000031226 Hyperlipidaemia Diseases 0.000 description 1
- ZEXLJFNSKAHNFH-SYKYGTKKSA-N L-Phenylalaninamide, L-tyrosyl-L-prolyl-L-tryptophyl- Chemical compound C([C@H](N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)C1=CC=C(O)C=C1 ZEXLJFNSKAHNFH-SYKYGTKKSA-N 0.000 description 1
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-N L-arginine Chemical compound OC(=O)[C@@H](N)CCCN=C(N)N ODKSFYDXXFIFQN-BYPYZUCNSA-N 0.000 description 1
- 229930064664 L-arginine Natural products 0.000 description 1
- 235000014852 L-arginine Nutrition 0.000 description 1
- 229930182844 L-isoleucine Natural products 0.000 description 1
- 239000004395 L-leucine Substances 0.000 description 1
- 235000019454 L-leucine Nutrition 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 229920000161 Locust bean gum Polymers 0.000 description 1
- 102000029828 Melanin-concentrating hormone receptor Human genes 0.000 description 1
- 108010047068 Melanin-concentrating hormone receptor Proteins 0.000 description 1
- 101710151321 Melanostatin Proteins 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- IBAQFPQHRJAVAV-ULAWRXDQSA-N Miglitol Chemical compound OCCN1C[C@H](O)[C@@H](O)[C@H](O)[C@H]1CO IBAQFPQHRJAVAV-ULAWRXDQSA-N 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- IRLWJILLXJGJTD-UHFFFAOYSA-N Muraglitazar Chemical compound C1=CC(OC)=CC=C1OC(=O)N(CC(O)=O)CC(C=C1)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 IRLWJILLXJGJTD-UHFFFAOYSA-N 0.000 description 1
- WXNXCEHXYPACJF-UHFFFAOYSA-N N-acetyl-leucine Chemical compound CC(C)CC(C(O)=O)NC(C)=O WXNXCEHXYPACJF-UHFFFAOYSA-N 0.000 description 1
- JDTWZSUNGHMMJM-UHFFFAOYSA-N N-acetylisoleucine Chemical compound CCC(C)C(C(O)=O)NC(C)=O JDTWZSUNGHMMJM-UHFFFAOYSA-N 0.000 description 1
- 206010058116 Nephrogenic anaemia Diseases 0.000 description 1
- 102400000064 Neuropeptide Y Human genes 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 229920002230 Pectic acid Polymers 0.000 description 1
- LRBQNJMCXXYXIU-PPKXGCFTSA-N Penta-digallate-beta-D-glucose Natural products OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-PPKXGCFTSA-N 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 206010035669 Pneumonia aspiration Diseases 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- HCBIBCJNVBAKAB-UHFFFAOYSA-N Procaine hydrochloride Chemical compound Cl.CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 HCBIBCJNVBAKAB-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- HDSBZMRLPLPFLQ-UHFFFAOYSA-N Propylene glycol alginate Chemical compound OC1C(O)C(OC)OC(C(O)=O)C1OC1C(O)C(O)C(C)C(C(=O)OCC(C)O)O1 HDSBZMRLPLPFLQ-UHFFFAOYSA-N 0.000 description 1
- 239000004373 Pullulan Substances 0.000 description 1
- 229920001218 Pullulan Polymers 0.000 description 1
- 208000033626 Renal failure acute Diseases 0.000 description 1
- 206010038470 Renal infarct Diseases 0.000 description 1
- 208000026980 Renal tubular disease Diseases 0.000 description 1
- 239000008156 Ringer's lactate solution Substances 0.000 description 1
- KHPCPRHQVVSZAH-HUOMCSJISA-N Rosin Natural products O(C/C=C/c1ccccc1)[C@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 KHPCPRHQVVSZAH-HUOMCSJISA-N 0.000 description 1
- WINXNKPZLFISPD-UHFFFAOYSA-M Saccharin sodium Chemical compound [Na+].C1=CC=C2C(=O)[N-]S(=O)(=O)C2=C1 WINXNKPZLFISPD-UHFFFAOYSA-M 0.000 description 1
- 108010022999 Serine Proteases Proteins 0.000 description 1
- 102000012479 Serine Proteases Human genes 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 102000000070 Sodium-Glucose Transport Proteins Human genes 0.000 description 1
- 108010080361 Sodium-Glucose Transport Proteins Proteins 0.000 description 1
- 208000013200 Stress disease Diseases 0.000 description 1
- 102400000096 Substance P Human genes 0.000 description 1
- 101800003906 Substance P Proteins 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- JLRGJRBPOGGCBT-UHFFFAOYSA-N Tolbutamide Chemical compound CCCCNC(=O)NS(=O)(=O)C1=CC=C(C)C=C1 JLRGJRBPOGGCBT-UHFFFAOYSA-N 0.000 description 1
- 102100038129 Transcription factor Dp family member 3 Human genes 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
- 208000003443 Unconsciousness Diseases 0.000 description 1
- LEHOTFFKMJEONL-UHFFFAOYSA-N Uric Acid Chemical compound N1C(=O)NC(=O)C2=C1NC(=O)N2 LEHOTFFKMJEONL-UHFFFAOYSA-N 0.000 description 1
- TVWHNULVHGKJHS-UHFFFAOYSA-N Uric acid Natural products N1C(=O)NC(=O)C2NC(=O)NC21 TVWHNULVHGKJHS-UHFFFAOYSA-N 0.000 description 1
- FZNCGRZWXLXZSZ-CIQUZCHMSA-N Voglibose Chemical compound OCC(CO)N[C@H]1C[C@](O)(CO)[C@@H](O)[C@H](O)[C@H]1O FZNCGRZWXLXZSZ-CIQUZCHMSA-N 0.000 description 1
- 206010052428 Wound Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- WJEIYVAPNMUNIU-UHFFFAOYSA-N [Na].OC(O)=O Chemical compound [Na].OC(O)=O WJEIYVAPNMUNIU-UHFFFAOYSA-N 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- KFHYZKCRXNRKRC-MRXNPFEDSA-N abt-239 Chemical compound C[C@@H]1CCCN1CCC1=CC2=CC(C=3C=CC(=CC=3)C#N)=CC=C2O1 KFHYZKCRXNRKRC-MRXNPFEDSA-N 0.000 description 1
- 229960002632 acarbose Drugs 0.000 description 1
- XUFXOAAUWZOOIT-UHFFFAOYSA-N acarviostatin I01 Natural products OC1C(O)C(NC2C(C(O)C(O)C(CO)=C2)O)C(C)OC1OC(C(C1O)O)C(CO)OC1OC1C(CO)OC(O)C(O)C1O XUFXOAAUWZOOIT-UHFFFAOYSA-N 0.000 description 1
- 229960001413 acetanilide Drugs 0.000 description 1
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 1
- 229960001466 acetohexamide Drugs 0.000 description 1
- VGZSUPCWNCWDAN-UHFFFAOYSA-N acetohexamide Chemical compound C1=CC(C(=O)C)=CC=C1S(=O)(=O)NC(=O)NC1CCCCC1 VGZSUPCWNCWDAN-UHFFFAOYSA-N 0.000 description 1
- 239000012190 activator Substances 0.000 description 1
- 201000011040 acute kidney failure Diseases 0.000 description 1
- 208000012998 acute renal failure Diseases 0.000 description 1
- 239000000048 adrenergic agonist Substances 0.000 description 1
- 229940126157 adrenergic receptor agonist Drugs 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 229940023476 agar Drugs 0.000 description 1
- 229960003767 alanine Drugs 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- ZSBOMTDTBDDKMP-OAHLLOKOSA-N alogliptin Chemical compound C=1C=CC=C(C#N)C=1CN1C(=O)N(C)C(=O)C=C1N1CCC[C@@H](N)C1 ZSBOMTDTBDDKMP-OAHLLOKOSA-N 0.000 description 1
- 229940024546 aluminum hydroxide gel Drugs 0.000 description 1
- SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 description 1
- 102000005922 amidase Human genes 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229920003144 amino alkyl methacrylate copolymer Polymers 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 229910021417 amorphous silicon Inorganic materials 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 235000019513 anchovy Nutrition 0.000 description 1
- 229960004543 anhydrous citric acid Drugs 0.000 description 1
- 229940040526 anhydrous sodium acetate Drugs 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 229940127003 anti-diabetic drug Drugs 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 201000009807 aspiration pneumonia Diseases 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 229940092782 bentonite Drugs 0.000 description 1
- 229960001950 benzethonium chloride Drugs 0.000 description 1
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 235000019445 benzyl alcohol Nutrition 0.000 description 1
- 229960004217 benzyl alcohol Drugs 0.000 description 1
- 102000016959 beta-3 Adrenergic Receptors Human genes 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 229960000516 bezafibrate Drugs 0.000 description 1
- IIBYAHWJQTYFKB-UHFFFAOYSA-N bezafibrate Chemical compound C1=CC(OC(C)(C)C(O)=O)=CC=C1CCNC(=O)C1=CC=C(Cl)C=C1 IIBYAHWJQTYFKB-UHFFFAOYSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 210000000601 blood cell Anatomy 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 229960002645 boric acid Drugs 0.000 description 1
- 235000008429 bread Nutrition 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- YYRMJZQKEFZXMX-UHFFFAOYSA-L calcium bis(dihydrogenphosphate) Chemical class [Ca+2].OP(O)([O-])=O.OP(O)([O-])=O YYRMJZQKEFZXMX-UHFFFAOYSA-L 0.000 description 1
- FNAQSUUGMSOBHW-UHFFFAOYSA-H calcium citrate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O FNAQSUUGMSOBHW-UHFFFAOYSA-H 0.000 description 1
- 239000001354 calcium citrate Substances 0.000 description 1
- 239000004227 calcium gluconate Substances 0.000 description 1
- 235000013927 calcium gluconate Nutrition 0.000 description 1
- 229960004494 calcium gluconate Drugs 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- NEEHYRZPVYRGPP-UHFFFAOYSA-L calcium;2,3,4,5,6-pentahydroxyhexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(O)C([O-])=O.OCC(O)C(O)C(O)C(O)C([O-])=O NEEHYRZPVYRGPP-UHFFFAOYSA-L 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 235000013736 caramel Nutrition 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229950008138 carmellose Drugs 0.000 description 1
- 239000004203 carnauba wax Substances 0.000 description 1
- 235000013869 carnauba wax Nutrition 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 229960001927 cetylpyridinium chloride Drugs 0.000 description 1
- YMKDRGPMQRFJGP-UHFFFAOYSA-M cetylpyridinium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 YMKDRGPMQRFJGP-UHFFFAOYSA-M 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- FAIMGWSOSCFGRU-IYBDPMFKSA-N chembl182150 Chemical compound N([C@H]1CC[C@H](CC1)NC=1N=C(C2=CC=CC=C2N=1)N(C)C)C(=O)C1=CC=C(F)C(F)=C1 FAIMGWSOSCFGRU-IYBDPMFKSA-N 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229960002242 chlorocresol Drugs 0.000 description 1
- 229960001761 chlorpropamide Drugs 0.000 description 1
- KXKPYJOVDUMHGS-OSRGNVMNSA-N chondroitin sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](OS(O)(=O)=O)[C@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](C(O)=O)O1 KXKPYJOVDUMHGS-OSRGNVMNSA-N 0.000 description 1
- 208000020832 chronic kidney disease Diseases 0.000 description 1
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 1
- 229960001214 clofibrate Drugs 0.000 description 1
- KNHUKKLJHYUCFP-UHFFFAOYSA-N clofibrate Chemical compound CCOC(=O)C(C)(C)OC1=CC=C(Cl)C=C1 KNHUKKLJHYUCFP-UHFFFAOYSA-N 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 229940000425 combination drug Drugs 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 239000002385 cottonseed oil Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 229940109239 creatinine Drugs 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 235000019316 curdlan Nutrition 0.000 description 1
- 229940078035 curdlan Drugs 0.000 description 1
- 229950010300 denagliptin Drugs 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 208000033679 diabetic kidney disease Diseases 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- PGZIKUPSQINGKT-UHFFFAOYSA-N dialuminum;dioxido(oxo)silane Chemical compound [Al+3].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O.[O-][Si]([O-])=O PGZIKUPSQINGKT-UHFFFAOYSA-N 0.000 description 1
- 238000000502 dialysis Methods 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
- 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
- 235000019797 dipotassium phosphate Nutrition 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- PXEDJBXQKAGXNJ-QTNFYWBSSA-L disodium L-glutamate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](N)CCC([O-])=O PXEDJBXQKAGXNJ-QTNFYWBSSA-L 0.000 description 1
- 239000002526 disodium citrate Substances 0.000 description 1
- 235000019262 disodium citrate Nutrition 0.000 description 1
- CEYULKASIQJZGP-UHFFFAOYSA-L disodium;2-(carboxymethyl)-2-hydroxybutanedioate Chemical compound [Na+].[Na+].[O-]C(=O)CC(O)(C(=O)O)CC([O-])=O CEYULKASIQJZGP-UHFFFAOYSA-L 0.000 description 1
- 229940124567 diuretic antihypertensive agent Drugs 0.000 description 1
- 229950010030 dl-alanine Drugs 0.000 description 1
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 229940048820 edetates Drugs 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 108010015205 endomorphin 1 Proteins 0.000 description 1
- 108010015198 endomorphin 2 Proteins 0.000 description 1
- XIJHWXXXIMEHKW-LJWNLINESA-N endomorphin-2 Chemical compound C([C@H](N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)C1=CC=C(O)C=C1 XIJHWXXXIMEHKW-LJWNLINESA-N 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 239000002662 enteric coated tablet Substances 0.000 description 1
- CHNUOJQWGUIOLD-NFZZJPOKSA-N epalrestat Chemical compound C=1C=CC=CC=1\C=C(/C)\C=C1/SC(=S)N(CC(O)=O)C1=O CHNUOJQWGUIOLD-NFZZJPOKSA-N 0.000 description 1
- 229950010170 epalrestat Drugs 0.000 description 1
- CHNUOJQWGUIOLD-UHFFFAOYSA-N epalrestate Natural products C=1C=CC=CC=1C=C(C)C=C1SC(=S)N(CC(O)=O)C1=O CHNUOJQWGUIOLD-UHFFFAOYSA-N 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- AKFNKZFJBFQFAA-DIOPXHOYSA-N ethyl 4-[[2-[(2s,4s)-2-cyano-4-fluoropyrrolidin-1-yl]-2-oxoethyl]amino]bicyclo[2.2.2]octane-1-carboxylate Chemical compound C1CC(C(=O)OCC)(CC2)CCC12NCC(=O)N1C[C@@H](F)C[C@H]1C#N AKFNKZFJBFQFAA-DIOPXHOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- FMMOOAYVCKXGMF-MURFETPASA-N ethyl linoleate Chemical compound CCCCC\C=C/C\C=C/CCCCCCCC(=O)OCC FMMOOAYVCKXGMF-MURFETPASA-N 0.000 description 1
- 229940031016 ethyl linoleate Drugs 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 238000009207 exercise therapy Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 206010016256 fatigue Diseases 0.000 description 1
- 208000010706 fatty liver disease Diseases 0.000 description 1
- 229960002297 fenofibrate Drugs 0.000 description 1
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 description 1
- WAAPEIZFCHNLKK-PELKAZGASA-N fidarestat Chemical compound C([C@@H](OC1=CC=C(F)C=C11)C(=O)N)[C@@]21NC(=O)NC2=O WAAPEIZFCHNLKK-PELKAZGASA-N 0.000 description 1
- 229950007256 fidarestat Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000007941 film coated tablet Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 235000020932 food allergy Nutrition 0.000 description 1
- 229960004279 formaldehyde Drugs 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- LRBQNJMCXXYXIU-QWKBTXIPSA-N gallotannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@H]2[C@@H]([C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-QWKBTXIPSA-N 0.000 description 1
- OSCCDBFHNMXNME-UHFFFAOYSA-N gamma-hydroxyisoleucine Natural products CC(O)C(C)C(N)C(O)=O OSCCDBFHNMXNME-UHFFFAOYSA-N 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 235000010492 gellan gum Nutrition 0.000 description 1
- 239000000216 gellan gum Substances 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 229960004580 glibenclamide Drugs 0.000 description 1
- 229960000346 gliclazide Drugs 0.000 description 1
- 229960004346 glimepiride Drugs 0.000 description 1
- WIGIZIANZCJQQY-RUCARUNLSA-N glimepiride Chemical compound O=C1C(CC)=C(C)CN1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)N[C@@H]2CC[C@@H](C)CC2)C=C1 WIGIZIANZCJQQY-RUCARUNLSA-N 0.000 description 1
- 239000000174 gluconic acid Substances 0.000 description 1
- 235000012208 gluconic acid Nutrition 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 1
- ZNNLBTZKUZBEKO-UHFFFAOYSA-N glyburide Chemical compound COC1=CC=C(Cl)C=C1C(=O)NCCC1=CC=C(S(=O)(=O)NC(=O)NC2CCCCC2)C=C1 ZNNLBTZKUZBEKO-UHFFFAOYSA-N 0.000 description 1
- 229950002888 glyclopyramide Drugs 0.000 description 1
- 208000037824 growth disorder Diseases 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000000415 inactivating effect Effects 0.000 description 1
- KHLVKKOJDHCJMG-QDBORUFSSA-L indigo carmine Chemical compound [Na+].[Na+].N/1C2=CC=C(S([O-])(=O)=O)C=C2C(=O)C\1=C1/NC2=CC=C(S(=O)(=O)[O-])C=C2C1=O KHLVKKOJDHCJMG-QDBORUFSSA-L 0.000 description 1
- 229960003988 indigo carmine Drugs 0.000 description 1
- 235000012738 indigotine Nutrition 0.000 description 1
- 239000004179 indigotine Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 208000000509 infertility Diseases 0.000 description 1
- 230000036512 infertility Effects 0.000 description 1
- 231100000535 infertility Toxicity 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 201000006334 interstitial nephritis Diseases 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 210000004731 jugular vein Anatomy 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 229940099563 lactobionic acid Drugs 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 229960004393 lidocaine hydrochloride Drugs 0.000 description 1
- YECIFGHRMFEPJK-UHFFFAOYSA-N lidocaine hydrochloride monohydrate Chemical compound O.[Cl-].CC[NH+](CC)CC(=O)NC1=C(C)C=CC=C1C YECIFGHRMFEPJK-UHFFFAOYSA-N 0.000 description 1
- FMMOOAYVCKXGMF-UHFFFAOYSA-N linoleic acid ethyl ester Natural products CCCCCC=CCC=CCCCCCCCC(=O)OCC FMMOOAYVCKXGMF-UHFFFAOYSA-N 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 235000010420 locust bean gum Nutrition 0.000 description 1
- 239000000711 locust bean gum Substances 0.000 description 1
- 229960005060 lorcaserin Drugs 0.000 description 1
- XTTZERNUQAFMOF-QMMMGPOBSA-N lorcaserin Chemical compound C[C@H]1CNCCC2=CC=C(Cl)C=C12 XTTZERNUQAFMOF-QMMMGPOBSA-N 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
- 239000001095 magnesium carbonate Substances 0.000 description 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 1
- 235000014380 magnesium carbonate Nutrition 0.000 description 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 1
- 239000000347 magnesium hydroxide Substances 0.000 description 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 1
- 235000012254 magnesium hydroxide Nutrition 0.000 description 1
- RXMQCXCANMAVIO-CEOVSRFSSA-L magnesium;(2s)-2-amino-4-hydroxy-4-oxobutanoate Chemical compound [H+].[H+].[Mg+2].[O-]C(=O)[C@@H](N)CC([O-])=O.[O-]C(=O)[C@@H](N)CC([O-])=O RXMQCXCANMAVIO-CEOVSRFSSA-L 0.000 description 1
- 229940098895 maleic acid Drugs 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 229940093462 metformin hydrochloride 250 mg Drugs 0.000 description 1
- 229920003145 methacrylic acid copolymer Polymers 0.000 description 1
- 229940102396 methyl bromide Drugs 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 229960002900 methylcellulose Drugs 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 229960001110 miglitol Drugs 0.000 description 1
- 229960003365 mitiglinide Drugs 0.000 description 1
- WPGGHFDDFPHPOB-BBWFWOEESA-N mitiglinide Chemical compound C([C@@H](CC(=O)N1C[C@@H]2CCCC[C@@H]2C1)C(=O)O)C1=CC=CC=C1 WPGGHFDDFPHPOB-BBWFWOEESA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 230000000407 monoamine reuptake Effects 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 235000016337 monopotassium tartrate Nutrition 0.000 description 1
- 229950001135 muraglitazar Drugs 0.000 description 1
- ACTNHJDHMQSOGL-UHFFFAOYSA-N n',n'-dibenzylethane-1,2-diamine Chemical compound C=1C=CC=CC=1CN(CCN)CC1=CC=CC=C1 ACTNHJDHMQSOGL-UHFFFAOYSA-N 0.000 description 1
- PSZYNBSKGUBXEH-UHFFFAOYSA-N naphthalene-1-sulfonic acid Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-N 0.000 description 1
- 229940037525 nasal preparations Drugs 0.000 description 1
- 229960000698 nateglinide Drugs 0.000 description 1
- OELFLUMRDSZNSF-BRWVUGGUSA-N nateglinide Chemical compound C1C[C@@H](C(C)C)CC[C@@H]1C(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 OELFLUMRDSZNSF-BRWVUGGUSA-N 0.000 description 1
- 230000001338 necrotic effect Effects 0.000 description 1
- 201000008383 nephritis Diseases 0.000 description 1
- 201000009925 nephrosclerosis Diseases 0.000 description 1
- PKWDZWYVIHVNKS-UHFFFAOYSA-N netoglitazone Chemical compound FC1=CC=CC=C1COC1=CC=C(C=C(CC2C(NC(=O)S2)=O)C=C2)C2=C1 PKWDZWYVIHVNKS-UHFFFAOYSA-N 0.000 description 1
- URPYMXQQVHTUDU-OFGSCBOVSA-N nucleopeptide y Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 URPYMXQQVHTUDU-OFGSCBOVSA-N 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- AHLBNYSZXLDEJQ-FWEHEUNISA-N orlistat Chemical compound CCCCCCCCCCC[C@H](OC(=O)[C@H](CC(C)C)NC=O)C[C@@H]1OC(=O)[C@H]1CCCCCC AHLBNYSZXLDEJQ-FWEHEUNISA-N 0.000 description 1
- 229960001243 orlistat Drugs 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- 230000004203 pancreatic function Effects 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 229940067107 phenylethyl alcohol Drugs 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 201000010065 polycystic ovary syndrome Diseases 0.000 description 1
- 239000010318 polygalacturonic acid Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229940068965 polysorbates Drugs 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 230000005195 poor health Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229960003975 potassium Drugs 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- KYKNRZGSIGMXFH-ZVGUSBNCSA-M potassium bitartrate Chemical compound [K+].OC(=O)[C@H](O)[C@@H](O)C([O-])=O KYKNRZGSIGMXFH-ZVGUSBNCSA-M 0.000 description 1
- 229940086065 potassium hydrogentartrate Drugs 0.000 description 1
- 229910000160 potassium phosphate Inorganic materials 0.000 description 1
- 235000011009 potassium phosphates Nutrition 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 201000009104 prediabetes syndrome Diseases 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 229960001309 procaine hydrochloride Drugs 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000035755 proliferation Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 235000010409 propane-1,2-diol alginate Nutrition 0.000 description 1
- 239000000770 propane-1,2-diol alginate Substances 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 235000019833 protease Nutrition 0.000 description 1
- 235000019423 pullulan Nutrition 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 239000006215 rectal suppository Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229960002354 repaglinide Drugs 0.000 description 1
- 235000019192 riboflavin Nutrition 0.000 description 1
- 239000002151 riboflavin Substances 0.000 description 1
- 229960002477 riboflavin Drugs 0.000 description 1
- JZCPYUJPEARBJL-UHFFFAOYSA-N rimonabant Chemical compound CC=1C(C(=O)NN2CCCCC2)=NN(C=2C(=CC(Cl)=CC=2)Cl)C=1C1=CC=C(Cl)C=C1 JZCPYUJPEARBJL-UHFFFAOYSA-N 0.000 description 1
- 229960003015 rimonabant Drugs 0.000 description 1
- 229960004586 rosiglitazone Drugs 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- PYPPENBDXAWXJC-QNTKWALQSA-N sca-136 Chemical compound Cl.C1CNCC2=CC=CC3=C2N1C[C@@H]1CCC[C@@H]13 PYPPENBDXAWXJC-QNTKWALQSA-N 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 239000002485 serotonin 2C agonist Substances 0.000 description 1
- 235000020374 simple syrup Nutrition 0.000 description 1
- 229960004034 sitagliptin Drugs 0.000 description 1
- 229960004115 sitagliptin phosphate Drugs 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 210000001626 skin fibroblast Anatomy 0.000 description 1
- 229960003885 sodium benzoate Drugs 0.000 description 1
- 229940001593 sodium carbonate Drugs 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- BBMHARZCALWXSL-UHFFFAOYSA-M sodium dihydrogenphosphate monohydrate Chemical compound O.[Na+].OP(O)([O-])=O BBMHARZCALWXSL-UHFFFAOYSA-M 0.000 description 1
- 229940037001 sodium edetate Drugs 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000007480 spreading Effects 0.000 description 1
- 238000003892 spreading Methods 0.000 description 1
- 231100000240 steatosis hepatitis Toxicity 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007940 sugar coated tablet Substances 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- 235000010491 tara gum Nutrition 0.000 description 1
- 239000000213 tara gum Substances 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- RTZRUVMEWWPNRR-UHFFFAOYSA-N tert-butyl n-(3-iodo-1h-pyrrolo[2,3-b]pyridin-5-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CN=C2NC=C(I)C2=C1 RTZRUVMEWWPNRR-UHFFFAOYSA-N 0.000 description 1
- CXGTZJYQWSUFET-IBGZPJMESA-N tesaglitazar Chemical compound C1=CC(C[C@H](OCC)C(O)=O)=CC=C1OCCC1=CC=C(OS(C)(=O)=O)C=C1 CXGTZJYQWSUFET-IBGZPJMESA-N 0.000 description 1
- 229950004704 tesaglitazar Drugs 0.000 description 1
- 150000003548 thiazolidines Chemical class 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 229960002277 tolazamide Drugs 0.000 description 1
- OUDSBRTVNLOZBN-UHFFFAOYSA-N tolazamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1CCCCCC1 OUDSBRTVNLOZBN-UHFFFAOYSA-N 0.000 description 1
- 229960005371 tolbutamide Drugs 0.000 description 1
- 239000012929 tonicity agent Substances 0.000 description 1
- KHPCPRHQVVSZAH-UHFFFAOYSA-N trans-cinnamyl beta-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OCC=CC1=CC=CC=C1 KHPCPRHQVVSZAH-UHFFFAOYSA-N 0.000 description 1
- 235000013337 tricalcium citrate Nutrition 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 1
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
- 229960001641 troglitazone Drugs 0.000 description 1
- GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
- 229960004418 trolamine Drugs 0.000 description 1
- 208000009852 uremia Diseases 0.000 description 1
- 229940116269 uric acid Drugs 0.000 description 1
- 239000006216 vaginal suppository Substances 0.000 description 1
- 229960001254 vildagliptin Drugs 0.000 description 1
- 229960001729 voglibose Drugs 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000010497 wheat germ oil Substances 0.000 description 1
- 229940100445 wheat starch Drugs 0.000 description 1
- 239000003871 white petrolatum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- SXONDGSPUVNZLO-UHFFFAOYSA-N zenarestat Chemical compound O=C1N(CC(=O)O)C2=CC(Cl)=CC=C2C(=O)N1CC1=CC=C(Br)C=C1F SXONDGSPUVNZLO-UHFFFAOYSA-N 0.000 description 1
- 229950006343 zenarestat Drugs 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid or pantothenic acid
- A61K31/198—Alpha-amino acids, e.g. alanine or edetic acid [EDTA]
-
- 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
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/18—Growth factors; Growth regulators
- A61K38/1816—Erythropoietin [EPO]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/28—Insulins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
Definitions
- the present invention relates to a therapeutic agent for diabetes, and more particularly to a therapeutic agent for diabetes containing a biguanide derivative such as metformin and a branched chain amino acid such as valine, leucine and isoleucine as active ingredients.
- a biguanide derivative such as metformin
- a branched chain amino acid such as valine, leucine and isoleucine
- hypoglycemic agent has been taken as one of the treatments for diabetic patients.
- oral hypoglycemic agents such as insulin preparations, sulfonylurea agents, thiazolidine derivatives, alpha-glucosidase inhibitors, biguanide agents are mainly used (for example, Patent Document 1).
- biguanide derivatives are generally likely to cause lactic acidosis. Therefore, for example, existing biguanides such as metformin are diabetic patients with a history of lactic acidosis, diabetic patients with renal dysfunction, diabetic patients with liver dysfunction, cardiovascular disorders Lactic acidosis is induced in diabetics, diabetics with impaired lung function, diabetics prone to hypoxemia, diabetics with excessive alcohol intake, diabetics with gastrointestinal disorders, and diabetics with older age It is said that there is a risk of.
- biguanides such as metformin are diabetic patients with a history of lactic acidosis, diabetic patients with renal dysfunction, diabetic patients with liver dysfunction, cardiovascular disorders Lactic acidosis is induced in diabetics, diabetics with impaired lung function, diabetics prone to hypoxemia, diabetics with excessive alcohol intake, diabetics with gastrointestinal disorders, and diabetics with older age It is said that there is a risk of.
- the present invention has been made in view of the above problems, and provides a composition for treating diabetes that does not substantially increase blood lactic acid level and has an excellent hypoglycemic action and can suppress lactic acidosis. Objective.
- the present invention provides a composition for treating diabetes having an action of lowering blood glucose level without substantially increasing blood lactic acid level, wherein the composition comprises a branched chain amino acid or a branched chain amino acid. It comprises a derivative of a chain amino acid and a biguanide derivative or a salt of the biguanide derivative as active ingredients.
- metformin, phenformin or buformin may be contained as the biguanide derivative.
- another disease that is a subject of the present invention can be diabetes accompanied by renal dysfunction, and the present invention can be used for prevention and / or treatment of lactic acidosis.
- this invention can be made into the form of an infusion formulation, or the form of an oral formulation.
- composition of the present invention described above is also effective as a therapeutic, preventive and / or ameliorating agent for diseases and / or symptoms mediated by DPP4.
- 1) complementation and / or enhancement of the therapeutic and / or prophylactic effect of the composition, 2) Improving the kinetics / absorption of the composition, reducing the dose, And / or 3) may be administered as a pharmaceutical in combination with other drugs to reduce side effects due to the composition.
- branched chain amino acid BCAA
- biguanide derivative such as metformin or a salt of the biguanide derivative or a branched chain amino acid
- the antidiabetic agent is not particularly limited as long as it can be used for diabetic treatment.
- dipeptidyl peptidase IV inhibitor hereinafter abbreviated as “DPP4 inhibitor”
- DPP4 inhibitor dipeptidyl peptidase IV inhibitor
- Drugs biguanide preparations, ⁇ -glucosidase inhibitors, fast-acting insulin secretagogues, insulin preparations, PPAR agonists, ⁇ 3 adrenergic receptor agonists, aldose reductase inhibitors, GLP-1 analogs, SGLT inhibitors, etc. It is done.
- composition for treating diabetes it is possible to provide a therapeutic agent capable of lowering blood glucose level and suppressing lactic acidosis without substantially increasing blood lactic acid level. Become.
- composition of the present invention is effective as a therapeutic, preventive and / or ameliorating agent for diseases and / or symptoms mediated by DPP4, and can be used in combination with a general therapeutic agent for diabetes.
- DPP4 inhibitor As a new drug for diabetes in the past, and a combination drug of this DPP4 inhibitor and metformin has been used recently, and it cannot be controlled without using a biguanide derivative typified by metformin. It seems to indicate that awareness is spreading.
- BCAA Branched Chain Amino Acid: branched chain amino acid
- pancreas organ is regained its activity when rested.
- Metformin is thought to promote activation of the pancreas because it suppresses newborns such as in the liver, lowers blood sugar, and rests the pancreas without fatigue.
- Metformin has a remarkable blood glucose lowering effect when used in the early stages of diabetes.
- BCAA is added to metformin, blood glucose lowering is further enhanced, and administration to elderly people who have been carefully administered until now can be performed without any particular problems.
- composition for treating diabetes of the present invention comprising metformin and BCAA as active ingredients is expected to become a great gospel not only in Japan but also in countries and people around the world.
- composition for treating diabetes has an action of lowering blood glucose level without substantially increasing blood lactic acid level, and the composition comprises a branched chain amino acid or a branched chain amino acid derivative, and a biguanide.
- a derivative or a salt of the biguanide derivative is an active ingredient.
- the composition for treating diabetes of the present invention contains a branched chain amino acid or a branched chain amino acid derivative as one of active ingredients.
- branched chain amino acid derivatives include N-acetyl-DL-leucine, DL-norleucine, N-acetyl-DL-isoleucine, 4-hydroxy-L-isoleucine, ⁇ -methylnorleucine, and the like. These derivatives can be effectively used as free amino acids by the action of in vivo acylases and the like.
- the branched chain amino acid may contain leucine, isoleucine or valine, or both leucine and isoleucine, and further, leucine, isoleucine and valine.
- Leucine, isoleucine and valine are compounds represented by the following chemical structural formulas (1) to (3), respectively.
- the composition for treating diabetes may contain all of leucine, isoleucine and valine as branched chain amino acids.
- the composition for treating diabetes exhibits an antagonistic action on the albumin producing action of leucine, isoleucine and valine, particularly when used as a preparation.
- the effect of promoting the production of albumin in vivo can be effectively improved.
- composition for treating diabetes may contain only one of leucine, isoleucine or valine as a branched chain amino acid.
- leucine, isoleucine, or valine alone, the composition for treating diabetes can further reduce the load of protein in vivo and effectively reduce side effects, particularly when used as a preparation. be able to.
- the composition for treating diabetes for example, if it is important to be effective in administration to patients with liver disease, is intended to addi- tionally improve the above-described albumin production promoting effect, and contains both leucine and isoleucine. Good.
- the composition for treating diabetes is intended to effectively reduce side effects by reducing the above-mentioned protein load, and only leucine or isoleucine is used alone. It is good to contain. That is, the composition for treating diabetes can achieve a balance between effectiveness and safety according to the condition of a patient with liver disease.
- composition for treating diabetes of the present invention contains a biguanide derivative or a salt of the biguanide derivative as one of active ingredients.
- the salt of the biguanide derivative may be a pharmacologically acceptable salt, and examples thereof include a salt with an inorganic acid, a salt with an organic acid, and a salt with an acidic amino acid.
- examples of the salt with inorganic acid include salts with hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid and the like.
- Examples of the salt with the organic acid include formic acid, acetic acid, trifluoroacetic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzenesulfonic acid, p -Salts with toluenesulfonic acid and the like.
- examples of the salt with acidic amino acid include salts with aspartic acid and glutamic acid.
- buformin or phenformin which is a biguanide derivative, is a compound represented by the following chemical structural formula [I] or [II], respectively.
- Salts with organic acids quaternary ammonium salts with methyl bromide, methyl iodide, , Salts with halogen ions such as chlorine ions and iodine ions, salts with alkali metals such as lithium, sodium and potassium, salts with alkaline earth metals such as calcium and magnesium, metal salts with iron and zinc, ammonia Salt, triethylenediamine, 2-aminoethanol, 2,2-iminobis (ethanol), 1-deoxy-1- (methylamino) -2-D-sorbitol, 2-amino-2- (hydroxymethyl) -1 , 3-propanediol, procaine, salts with organic amines such as N, N-bis (phenylmethyl) -1,2-ethanediamine, and the like, and the hydrochloride is particularly preferable.
- Buformin or phenformin may take the form of hydrate or solvate.
- crystal polymorphism groups crystal polymorphic systems
- the crystal polymorphisms Forms and crystal polymorph groups are also within the scope of the present invention.
- the crystal polymorphism group crystal polymorphism system
- the crystal form changes depending on the conditions and state of production, crystallization and storage of these crystals (including the formulated state in this state). Means the individual crystal forms at each stage and the whole process.
- the composition for treating diabetes only needs to contain the branched chain amino acid or the derivative of the branched chain amino acid and a biguanide derivative or a salt of the biguanide derivative as active ingredients.
- active ingredients for example, excipients, binders, stabilizers, lubricants, flavoring agents, disintegrating agents, coating agents, coloring agents, buffering agents, aqueous solvents, oily solvents, isotonic agents, dispersing agents, What is necessary is just to formulate by mixing with a preservative, a solubilizer, a fluidizing agent, a soothing agent, a pH adjuster, a preservative, a base and the like.
- a physiologically acceptable carrier can also be used as an additive component of the composition for treating diabetes.
- binder examples include cellulose such as crystalline cellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose and methylcellulose and derivatives thereof, corn starch, potato starch, ⁇ -starch, dextrin, ⁇ -cyclodextrin, carboxymethyl starch sodium And starch such as hydroxypropyl starch and derivatives thereof, lactose, sucrose, glucose, sugars such as D-mannitol and sorbitol, agar, stearyl alcohol, gelatin, tragacanth, polyvinyl alcohol, polyvinylpyrrolidone and the like.
- cellulose such as crystalline cellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose and methylcellulose and derivatives thereof
- corn starch potato starch, ⁇ -starch, dextrin, ⁇ -cyclodextrin
- carboxymethyl starch sodium And starch such as hydroxypropyl starch and derivatives thereof, lactose, sucrose, glucose, sugars such as
- the stabilizer examples include paraoxybenzoates such as methylparaben and propylparaben, alcohols such as chlorobutanol, benzyl alcohol and phenylethyl alcohol, phenols such as phenol and cresol, sodium bisulfite and sulfite.
- paraoxybenzoates such as methylparaben and propylparaben
- alcohols such as chlorobutanol, benzyl alcohol and phenylethyl alcohol
- phenols such as phenol and cresol
- sodium bisulfite and sulfite sodium bisulfite and sulfite.
- lubricant examples include stearic acid, stearic acid such as calcium stearate and magnesium stearate, wax such as beeswax and carnauba wax, sulfate such as sodium sulfate, magnesium silicate and light anhydrous silicic acid, etc.
- Silicates lauryl sulfate such as sodium lauryl sulfate, gum arabic powder, cacao butter, carmellose calcium, carmellose sodium, caropeptide, hydrous silicon dioxide, hydrous amorphous silicon oxide, dry aluminum hydroxide gel, glycerin, light flow Paraffin, crystalline cellulose, hydrogenated oil, synthetic aluminum silicate, sesame oil, wheat starch, talc, macrogol, phosphoric acid and the like can be mentioned.
- lauryl sulfate such as sodium lauryl sulfate
- gum arabic powder cacao butter
- carmellose calcium carmellose sodium
- caropeptide hydrous silicon dioxide
- hydrous amorphous silicon oxide dry aluminum hydroxide gel
- glycerin light flow Paraffin
- crystalline cellulose hydrogenated oil
- synthetic aluminum silicate sesame oil
- wheat starch talc
- macrogol macrogol
- phosphoric acid and the like can be mentioned.
- examples of the flavoring agent include saccharides such as lactose, sucrose, glucose, and D-mannitol, ascorbic acid, L-aspartic acid, sodium L-aspartate, magnesium L-aspartate, aspartame, amateur, amateur extract, Examples include amateur powder, aminoethylsulfonic acid, aminoacetic acid, DL-alanine, sodium saccharin, DL-menthol, and l-menthol.
- disintegrant examples include cellulose such as crystalline cellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose and methylcellulose and derivatives thereof, carbonates such as calcium carbonate, sodium hydrogencarbonate and magnesium carbonate, corn starch, potato starch, ⁇ -Starches such as starch, dextrin, ⁇ -cyclodextrin, sodium carboxymethyl starch and hydroxypropyl starch, and derivatives thereof such as agar, gelatin, tragacanth, adipic acid, alginic acid, sodium alginate and the like.
- cellulose such as crystalline cellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose and methylcellulose and derivatives thereof
- carbonates such as calcium carbonate, sodium hydrogencarbonate and magnesium carbonate
- corn starch potato starch
- ⁇ -Starches such as starch, dextrin, ⁇ -cyclodextrin, sodium carboxymethyl starch and hydroxypropyl starch
- derivatives thereof such as agar,
- the coating agent examples include cellulose derivatives such as cellulose acetate, hydroxypropyl cellulose, cellulose acetate phthalate and hydroxypropyl methylcellulose, shellac, polyvinyl pyrrolidones, polyethylene glycol, macrogol, methacrylic acid copolymers, fluid Examples include paraffin and Eudragit.
- the colorant examples include indigo carmine, caramel, riboflavin and the like.
- the buffer examples include aminoacetic acid, L-arginine, benzoic acid, sodium benzoate, ammonium chloride, potassium chloride, sodium chloride, dry sodium sulfite, dry sodium carbonate, dilute hydrochloric acid, citric acid, calcium citrate, Sodium citrate, disodium citrate, calcium gluconate, L-glutamic acid, sodium L-glutamate, creatinine, chlorobutanol, crystalline sodium dihydrogen phosphate, disodium succinate, acetic acid, potassium acetate, sodium acetate, tartaric acid, carbonic acid Sodium hydrogen, sodium carbonate, triethanolamine, lactic acid, sodium lactate solution, glacial acetic acid, boric acid, maleic acid, anhydrous citric acid, anhydrous sodium citrate, anhydrous sodium acetate, anhydrous sodium carbonate, anhydrous sodium hydrogen phosphate , Anhydrous trisodium phosphate, anhydrous dihydrogen phosphate, DL-malic acid, phospho
- examples of the aqueous solvent include distilled water, physiological saline, Ringer's solution, and the like.
- examples of the oily solvent include vegetable oils such as olive oil, sesame oil, cottonseed oil and corn oil, and propylene glycol.
- examples of the tonicity agent include potassium chloride, sodium chloride, glycerin, sodium bromide, D-sorbitol, nicotinamide, glucose, boric acid and the like.
- examples of the dispersant include stearic acid such as zinc stearate and magnesium stearate and salts thereof, gum arabic, propylene glycol alginate, sorbitan sesquioleate, D-sorbitol, tragacanth, methylcellulose, aluminum monostearate Aminoalkyl methacrylate copolymer RS, lactose, concentrated glycerin, propylene glycol, macrogols, sodium lauryl sulfate and the like.
- preservative examples include alcohols such as chlorobutanol, phenethyl alcohol, propylene glycol and benzyl alcohol, paraoxybenzoic acid esters such as isobutyl paraoxybenzoate, ethyl paraoxybenzoate and methyl paraoxybenzoate, and benzil chloride.
- alcohols such as chlorobutanol, phenethyl alcohol, propylene glycol and benzyl alcohol
- paraoxybenzoic acid esters such as isobutyl paraoxybenzoate, ethyl paraoxybenzoate and methyl paraoxybenzoate
- benzil chloride Luconium, benzethonium chloride, dry sodium sulfite, dry sodium sulfate, cresol, chlorocresol, dibutylhydroxytoluene, potassium sorbate, sodium dehydroacetate, phenol, formalin, phosphoric acid, anchovy, thimerosal, thymol, sodium dehydro
- examples of the pH adjuster include hydrochloric acid, citric acid, succinic acid, acetic acid, boric acid, maleic acid, sodium hydroxide, and the like.
- examples of the preservative include benzoic acid, sodium benzoate, cetylpyridinium chloride, salicylic acid, sodium salicylate, sorbic acid, potassium sorbate, thymol, methyl paraoxybenzoate, and butyl paraoxybenzoate.
- the dosage form of the composition for treating diabetes of the present invention is not particularly limited, and examples thereof include granules, powders, tablets, capsules, syrups, emulsions, suspensions, etc.
- parenteral agents include Injections such as subcutaneous injections, intravenous injections, intramuscular injections and intraperitoneal injections, transdermal preparations such as ointments, creams and lotions, rectal suppositories and vaginal suppositories And nasal preparations.
- the above-mentioned various preparations can be produced by known methods usually used in the preparation process.
- the composition for treating diabetes according to the present invention lowers blood glucose level without substantially increasing blood lactic acid level as described above, it tends to cause lactic acidosis, particularly among diabetic patients.
- Such diabetic patients who are prone to lactic acidosis include, for example, diabetic patients with a history of lactic acidosis, diabetic patients with renal dysfunction, diabetic patients with liver dysfunction, diabetic patients with cardiovascular disorders, It means diabetic patients with impaired lung function, diabetic patients who are likely to have hypoxemia, diabetic patients who are excessive alcohol users, diabetic patients with gastrointestinal disorders, type 2 diabetes and diabetic patients who are elderly .
- the method for administering the composition for treating diabetes according to the present invention is not particularly limited.
- the pharmaceutical composition using the branched chain amino acid or the branched chain amino acid derivative, the biguanide derivative or the salt of the biguanide derivative, and the additive component described above. It can be administered orally or parenterally as a composition (formulation).
- the dosage of the composition for treating diabetes according to the present invention is appropriately determined according to the type of administration subject (warm-blooded animals including humans), severity of symptoms, age, administration method, doctor's diagnosis result, etc.
- the dose of biguanide derivative is preferably 0.1 to 2000 mg / kg per day for adults, and in the case of parenteral administration, It is preferably 0.1 to 1000 mg / kg per unit.
- said dosage is the value per unit weight (body weight 1kg) of administration object.
- the above dose may be administered once in 1 to 7 days, or may be divided into several doses, depending on the severity of symptoms, judgment of a doctor, and the like. Good.
- the composition for treating diabetes is suitably used in the form of a preparation.
- the form of the preparation is not particularly limited, and examples thereof include infusion preparations, oral preparations, transdermal preparations, suppositories, patches, ointments, haptics, lotions and the like.
- the composition for treating diabetes is preferably used in the form of an infusion preparation.
- the composition for diabetes treatment can be quickly and effectively administered through the blood vessels, and the most effective in promoting albumin production in vivo. High performance can be achieved.
- Examples of the above-mentioned infusion preparation include injections and drops.
- a diluent for example, water, ethyl alcohol, polyethylene glycol, propylene glycol, ethoxylated isostearyl alcohol, polyoxylated isostearyl alcohol, polyoxyethylene Sorbitan fatty acid esters and the like can be used, and a sufficient amount of sodium chloride, glucose or glycerin can be added to adjust the solution to be isotonic with body fluid.
- the said infusion preparation can be stored frozen and can also be preserve
- the above-mentioned infusion preparation preserved by freeze-drying can be used by dissolving again by adding distilled water for injection, sterilized water, etc. at the time of use.
- the composition for treating diabetes is also preferably used in the form of an oral preparation.
- the said composition for diabetes treatment can be administered easily and simply without invading the living body, and the albumin production promoting effect in the living body can be achieved. It can be fully demonstrated.
- Such carriers include lactose, sucrose, sodium chloride, glucose, urea, starch, calcium carbonate, kaolin, crystalline cellulose, silicic acid and other excipients; water, ethanol, propanol, simple syrup, glucose solution, starch solution, Binders such as gelatin solution, carboxymethylcellulose, shellac, methylcellulose, potassium phosphate, polyvinylpyrrolidone; dry starch, sodium alginate, agar powder, laminaran powder, sodium bicarbonate, calcium carbonate, polyoxyethylene sorbitan fatty acid esters, lauryl sulfate Disintegrating agents such as sodium, stearic acid monoglyceride, starch and lactose; disintegration inhibitors such as sucrose, stearin, cocoa butter and hydrogenated oil; absorption promoters such as quaternary ammonium base and sodium lauryl sulfate; Phosphorus, moisturizing agents such as starch; starch, lactose,
- various carriers known in the field of hypoalbuminemia improvement are used.
- the carrier include excipients such as glucose, lactose, starch, cacao butter, hydrogenated vegetable oil, kaolin and talc; binders such as gum arabic powder, tragacanth powder, gelatin and ethanol; laminaran and agar.
- the above oral preparation may further contain an additive.
- additives include surfactants, absorption promoters, fillers, extenders, moisturizers, preservatives, stabilizers, emulsifiers, solubilizers, salts that regulate osmotic pressure, and the like, and oral preparations Can be appropriately selected and used depending on the dosage unit form.
- the composition for treating diabetes according to the present invention is not limited to the above embodiment.
- a paste thickener, gelling agent
- a paste can be added as necessary to prepare a gel or jelly.
- the type of the paste is not particularly limited.
- the material include polysaccharides that can be usually used, and these can be used alone or in combination of two or more.
- the ratio of 5 mass parts or less is preferable with respect to 100 mass parts of compositions for diabetes treatment prepared in the gel form or the jelly form.
- compositions for treating diabetes are effective as a therapeutic, preventive and / or ameliorating agent for diseases and / or symptoms mediated by DPP4.
- 1) complementation and / or enhancement of the therapeutic and / or prophylactic effect of the composition, 2) Improving the kinetics / absorption of the composition, reducing the dose, And / or 3) may be administered as a pharmaceutical in combination with other drugs to reduce side effects due to the composition.
- the antidiabetic agent is not particularly limited as long as it can be used for diabetic treatment.
- dipeptidyl peptidase IV inhibitor hereinafter abbreviated as “DPP4 inhibitor”
- sulfonylurea Biguanides
- ⁇ -glucosidase inhibitors insulin secretagogues
- insulin sensitizers insulin preparations
- PPAR agonists PPAR ⁇ agonists, PPAR ⁇ agonists, PPAR ⁇ + ⁇ agonists, PPAR pan agonists, etc.
- ⁇ 3 adrenergic receptors Agonists, aldose reductase inhibitors, AMP kinase activators, type 1 11 ⁇ -hydroxysteroid dehydrogenase (11 ⁇ -HSD1) inhibitors, lipase inhibitors, appetite suppressants and the like.
- DPP4 inhibitors examples include LAF-237, sitagliptin phosphate (MK-431, ONO-5435), BMS-477118, P93-01, GSK829033, GSK815541, GSK825964, TS-021, T-6666, SYR -322, E-3024, NN-7201, PSN-9301 and the like.
- sulfonylurea drugs examples include acetohexamide, glibenclamide, gliclazide, glyclopyramide, chlorpropamide, tolazamide, tolbutamide, glimepiride and the like.
- Examples of biguanide drugs include buformin hydrochloride and metformin hydrochloride.
- Examples of the ⁇ -glucosidase inhibitor include acarbose, voglibose, miglitol and the like.
- Examples of the insulin secretagogue include nateglinide, repaglinide, mitiglinide and the like.
- Examples of the insulin sensitizer include ONO-5816, YM-440, JTT-501, NN-2344, and the like.
- PPAR agonists are PPAR agonists, for example, PPAR ⁇ agonists include bezafibrate, clofibrate, fenofibrate, gemfibrate, etc., PPAR ⁇ agonists such as pioglitazone, troglitazone, rosiglitazone, and PPAR ⁇ + ⁇ agonists Some muraglitazar, tesaglitazar, ONO-5129 and the like, and PSK bread agonists GSK677754, PLX204, MCC-555 and the like.
- Examples of the ⁇ 3 adrenergic receptor agonist include AJ9677, L750355, CP331648 and the like.
- Examples of aldose reductase inhibitors include epalrestat, fidarestat, zenarestat and the like.
- Examples of lipase inhibitors include orlistat and the like.
- Appetite suppressants include cannabinoid receptor 1 antagonists (eg, rimonabant), melanin-concentrating hormone receptor antagonists (eg, GSK856464, ATC-0065, ATC-0175, AMG-076, etc.), monoamine reuptake inhibitors (Eg, mazindol, sibutramine, etc.), serotonin 2c receptor agonist (eg, APD-356, SCA-136, etc.), histamine 3 receptor antagonist (eg, ABT-239, ABT-837, GT-2331, NNC-0038) -0000-1220), mazindol, sibutramine and the like.
- cannabinoid receptor 1 antagonists eg, rimonabant
- melanin-concentrating hormone receptor antagonists eg, GSK856464, ATC-0065, ATC-0175, AMG-076, etc.
- monoamine reuptake inhibitors Eg, mazindol, sibutramine, etc.
- DPP4 is dipeptidyl peptidase IV, also called DPP-IV, DP4, DPPIV, CD26.
- This dipeptidyl peptidase IV is dipeptide Xaa-Pro or Xaa from a peptide chain having proline or alanine second from the N-terminus.
- a serine protease that produces Ala is widely distributed in mammalian tissues, particularly known to be present in the kidney, liver, intestinal epithelium, placenta and plasma, and is involved in the metabolism of various bioactive peptides.
- Glucagon-Like Peptide-1 also referred to as GLP-1 hereinafter, which is abbreviated as GLP-1
- GLP-1 glucagon-Like Peptide-1
- GLP-1 as a physiologically active peptide that promotes insulin secretion from the pancreas, a gastric inhibitory polypeptide (also called gastric-inhibitory-polypeptide or Glucose-dependent insulin-peptide; GIP), pituitary adenylate cyclase-activating polypeptide (Pituitary Adenylate Cyclase Activating Polypeptide; also referred to as PACAP), Vasoactive Intestinal Polypeptide (also referred to as VIP), and the like.
- GIP gastric inhibitory polypeptide
- PACAP pituitary adenylate Cyclase Activating Polypeptide
- VIP Vasoactive Intestinal Polypeptide
- DPP4 is also involved in the degradation of these physiologically active peptides
- a compound that inhibits DPP4 also suppresses the degradation of these physiologically active peptides, enhances the action, and enhances insulin secretion.
- it is expected to be useful for prevention and / or treatment of type 2 diabetes and the like, or prevention and / or improvement of postprandial hyperglycemia, glucose intolerance and the like.
- DPP4 is also involved in the metabolism of neuropeptides such as neuropeptide Y, endomorphin 1, endomorphin 2, and substance P. Therefore, a compound that inhibits DPP4 can also be expected as a therapeutic or analgesic for schizophrenia, depression, anxiety, epilepsy, and stress diseases by suppressing the degradation of these physiologically active peptides.
- DPP4 is known to be involved in metabolism of various cytokines and chemokines, activation of T cells that are immunocompetent cells, adhesion of cancer cells to endothelium, proliferation of blood cells, and the like.
- compounds that inhibit DPP4 are such as rheumatoid arthritis, autoimmune diseases such as type I diabetes, allergic diseases such as asthma and food allergies, cancer, cancer metastasis, HIV infection, anemia, thrombocytopenia, etc. Useful for treatment and / or prevention.
- metformin + BCAA therapy treatment based on administration of metformin hydrochloride and branched chain amino acids such as L-isoleucine, L-leucine, L-valine
- metalformin + BCAA therapy branched chain amino acids such as L-isoleucine, L-leucine, L-valine
- a general antidiabetic agent such as DPP4 is used in combination.
- HbA1c glycohemoglobin grasps the patient's blood glucose status according to the administered active ingredient and the amount of the ingredient, and at the same time, changes in the lactic acid level are observed, and the feelings by the doctor are recorded along with the change in the value. did.
- Metformin hydrochloride 250 mg was prescribed on June 15, 2015, and on July 29, 2015, it was Cr 1.67.
- BCAA2P was added on July 30, 2015. On August 17, 2015, the lactic acid level was 15.9. Since HbA1c decreased to 5.1 on September 5, 2015, metformin 250 mg was reduced to 125 mg.
- the HbA1c value decreased from 7.6 mg / dl to 5.9 mg / dl (about 20%), and the final value of lactic acid during the observation period was 5.1 ( ⁇ 16.0) and stable.
- metformin and BCAA of the present invention are expected to become a great gospel not only in Japan but also in countries and people around the world.
- Metformin has the side effect of increasing lactic acid levels, but there is data that seems to have the same side effect with new drugs. BCAA should be used in combination with the new drug.
- HbA1c6.4 and lactic acid level were 8.4, and on May 17, 2016, HbA1c5.6 had a lactic acid level of 14.7.
- Metformin was used from May 18, 2016. Thereafter, the lactic acid value was 13, 3 on August 24, 2016, and HbA1c was 5.4 on October 1, 2016. There was no influence of the new drug, and the same effect was recognized.
- lactic acid levels fluctuate greatly when repeated measurement, but may increase when the patient is in poor health (infection, anemia, fatigue, increased GOTGPT, increased BUN, etc.) It has been understood by observation for about two years. Therefore, if the lactic acid level increases in the course of diabetes treatment with metformin + BCAA, which is the composition for treating diabetes according to the present invention, it is necessary to search not only the amount of metformin but also other factors.
- the therapeutic agent for diabetes it is possible to provide a therapeutic agent having an action of lowering blood glucose level without substantially increasing blood lactic acid level and preventing the initiation of lactic acidosis. Is possible. Therefore, according to the present invention, it is possible to provide a therapeutic agent capable of preventing and treating hyperglycemia without increasing blood lactic acid level for diabetic patients who may cause lactic acidosis.
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Diabetes (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Emergency Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Gastroenterology & Hepatology (AREA)
- Zoology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Immunology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
そして、本発明は、輸液製剤の形態、又は経口製剤の形態とすることができる。
1)その組成物による治療及び/又は予防効果の補完及び/又は増強、
2)その組成物の動態・吸収改善、投与量の低減、
及び/又は
3)その組成物による副作用を軽減するために他の薬剤と組み合わせた医薬として投与してもよい。
以下、本発明の好適な実施形態について詳細に説明する。本発明に係る糖尿病治療用組成物は、血中乳酸値を実質的に上昇させずに血糖値を降下させる作用を有し、その組成物が、分岐鎖アミノ酸又は分岐鎖アミノ酸の誘導体と、ビグアニド誘導体又は該ビグアニド誘導体の塩とを有効成分とする。
ロイシン、イソロイシン又はバリンは、それぞれ、下記の化学構造式(1)~(3)で示される化合物である。
本発明の糖尿病治療用組成物の投与方法は特に制限されないが、例えば、前記分岐鎖アミノ酸又は分岐鎖アミノ酸の誘導体と、ビグアニド誘導体又は該ビグアニド誘導体の塩と、前述の添加成分とを用いて医薬組成物(製剤)とし、経口的又は非経口的に投与することができる。
当該糖尿病治療用組成物は、製剤の形態で好適に使用される。かかる製剤の形態としては、特に限定されず、例えば輸液製剤、経口製剤、経皮吸収型製剤、坐剤、貼付剤、軟膏剤、ハップ剤、ローション剤等の形態が挙げられる。
なお、上述した本発明の糖尿病治療用組成物は、DPP4が介在する疾患及び/又は症状の治療、予防及び/又は改善剤として有効であり、
1)その組成物による治療及び/又は予防効果の補完及び/又は増強、
2)その組成物の動態・吸収改善、投与量の低減、
及び/又は
3)その組成物による副作用を軽減するために他の薬剤と組み合わせた医薬として投与してもよい。例えば、分岐鎖アミノ酸(BCAA)と、メトホルミン等のビグアニド誘導体又は該ビグアニド誘導体又は分岐鎖アミノ酸の誘導体の塩と、さらに糖尿病治療薬とを組み合わせた医薬として投与することができる。
α-グルコシダーゼ阻害薬としては、例えば、アカルボース、ボグリボース、ミグリトール等が挙げられる。
インスリン分泌促進薬としては、例えば、ナテグリニド、レパグリニド、ミチグリニド等が挙げられる。 インスリン増感薬としては、例えば、ONO-5816、YM-440、JTT-501、NN-2344等が挙げられる。
アルドース還元酵素阻害薬としては、例えば、エパルレスタット、フィダレスタット、ゼナレスタット等が挙げられる。
リパーゼ阻害薬としては、例えばオルリスタット等が挙げられる。
性別 女性
年齢 99歳
処方期間 H27年6月13日 HbA1c…6.6mg/dl
H27年7月18日 HbA1c…5.6mg/dl 乳酸値…8.1
H27年7月29日 HbA1c…5.5mg/dl
H27年8月17日 乳酸値…15.9
H27年9月4日 乳酸値…12.1
H27年9月5日 HbA1c…5.1mg/dl
H27年11月5日 乳酸値…17.2
○医師による所感
高齢者で腎機能障害も合併していたが、ほぼ1ヶ月でHbA1c値が1.0(約15%)下が、血糖値が下がるにつれて食欲も出てきて、副作用も出ていない。観察期間終了時における乳酸値も正常値である8.1(<16.0)で安定している。
本処方例に患者は99歳の女性であり、平成27年6月13日から平成27年11月29日の約5ヶ月半にわたり治療にあたった。初診時HbA1c6.6であり、腎性貧血もあり、6月27日におけるHb5.5であり、Ht17.3であった。
17歳の頃からインシュリンを使用している糖尿病患者であるが、メトフォルミンとBCAA(Branched Chain Amino Acid:分岐鎖アミノ酸)を併用して治療した。
性別 女性
年齢 41歳
処方期間 H27年8月12日 乳酸5.9
H27年8月26日 乳酸4.7
H27年9月12日 乳酸3.6
○医師による所感
血糖値は下がらなかったものの、乳酸値は5.9から3.6へと下がった。
寝たきりになってから食事が摂れず、高カロリー輸液になり、その後徐々に血糖値が上がってきていた。メトホルミン(250mg)を1錠及び、低アルブミン血症のためBCAAを処方。
性別 女性
年齢 89歳
処方期間 H27年7月7日 HbA1c…6.2mg/dl
H27年8月5日 HbA1c…5.7mg/dl 乳酸値…10.8
○医師による所感
1ヶ月でHbA1c値が0.5mg/dl(約8%)下がっており、途中下がりすぎる傾向があるので、メトホルミンは125mg/日としている。境界型糖尿病を正常値まで持って行くのは比較的難しいと思われるが、乳酸値も高齢者でもあるにもかかわらず副作用なく正常域(<16.0)に達した。
低血糖からくる低酸素脳症が原因で寝たきりとなっている患者に、インシュリン治療と併せて、メトホルミン(250mg)×1~2錠を処方した。
性別 男性
年齢 68歳
処方期間 H25年10月29日 HbA1c…7.6mg/dl
H26年3月16日 HbA1c…5.9mg/dl(基準値6.2)
H27年6月6日 HbA1c…5.9mg/dl 乳酸値…5.1
○医師による所感
処方当初と比べてHbA1c値が7.6mg/dlから5.9mg/dl(約20%)まで下がっており、観察期間における乳酸の最終値が正常値である5.1(<16.0)で安定している。
性別 男性
年齢 49歳
処方期間 H26年3月13日 HbA1c…9.2mg/dl
H26年12月8日 HbA1c…11.1mgdl 乳酸値…16.3
H27年3月18日 HbA1c…8.6mg/dl
H27年4月1日 HbA1c…8.2mg/dl 乳酸値…9.3
H27年6月12日 HbA1c…7.4mg/dl 乳酸値…12.3
○医師による所感
インシュリン治療と併せて、BCAAとメトホルミン(250mg)×6錠により、平成27年に入ってからの2ヶ月間でHbA1c値が8.6mg/dlから7.4mg/dl(約14%)まで下がり、最高値11.1mg/dlからは約30%下がっている。乳酸値も正常値である12.3で安定している。
糖尿病治療に際し、メトホルミンとBCAAを処方。
性別 女性
年齢 74歳
処方期間 H26年3月27日 HbA1c…9.4mg/dl
H26年7月10日 HbA1c…6.1mg/dl
H27年3月28日 乳酸値…6.1
H27年6月6日 HbA1c…5.6mg/dl
○医師による所感
初期段階で平成26年3月~7月という短期間にHbA1c値が9.4mg/dlから6.1mg/dl(約35%)まで下がり、この期間を含む1年数ヶ月でHbA1c値が9.4mg/dlから5.6mg/dlまで約40%も落ちている。平成27年6月の時点で乳酸値も、正常値である9.6(<16.0)で安定している。
性別 男性
年齢 76歳
処方期間 H27年9月11日 HbA1c…7.0mg/dl
H27年10月4日 HbA1c…6.3mg/dl
H27年10月16日 乳酸値…14.2
○医師による所感
初期段階で平成27年9月~10月という短い期間にHbA1c値が7.0mg/dlから6.3mg/dl(約10%)まで下がり、平成27年10月の時点で乳酸値も14.2(<16.0)で安定している。
性別 男性
年齢 75歳(糖尿病、認知症)
処方期間 H27年10月14日 HbA1c…8.6mg/dl 乳酸値…18.6
H28年6月29日 HbA1c…7.9mg/dl
H28年7月4日 乳酸値…15.1
○医師による所感
当患者は、初診時(平成27年10月14日)の検査結果はHbA1c8.6 乳酸値18.6>16.0であり、投薬経口糖尿病薬(5種類そのうち1種類はメトホルミンで500mg使用)を投与し、さらに24時間持続性のインスリン(5単位)を使用した。
年齢 52歳
処方期間 H28年2月24日 HbA1c…9.1mg/dl
H28年6月25日 HbA1c…7.6mg/dl
○医師による所感
発明の糖尿病治療用組成物によるメトホルミン+BCAA療法の結果として、HbA1cの改善とともに脂肪肝(非アルコール性)によると思われる肝臓酵素(Liver enzyme)の改善例として付け加えておく。
性別 男性
年齢 73歳
処方期間 H27年6月11日 HbA1c…6.4mg/dl
H27年8月5日 乳酸値…9.5
H28年2月5日 HbA1c…5.5mg/dl
H28年7月5日 HbA1c…5.5mg/dl 乳酸値…15.1
○医師による所感
一般的に糖尿病の治療は、運動療法も必要なものと思われている。血糖のコントロールに確かに身体を動かした方が血糖は下がる。
平成27年6月 HbA1c 6.4(メトホルミン250mg 乳酸値9.5)
平成28年7月 HbA1c 5.5(乳酸値15.1)
であり、本発明の糖尿病治療用組成物によれば、初診時から一年数ヶ月全く体動のない人の血糖コントロールも可能であることを示している。さらにIVHは直接血管の中にブドウ糖が入っていくが、血糖のコントロールが可能であることを示している。血糖のコントロールにはやはり糖尿病の軽いうちに本発明の糖尿病治療用組成物によるメトホルミン+BCAA療法を行うのがよいことを示している。
性別 男性
年齢 85歳
処方期間 H28年4月19日 HbA1c…6.4mg/dl 乳酸値…8.4
H28年5月17日 HbA1c…5.6mg/dl 乳酸値…14.7
H28年6月28日 HbA1c…5.1mg/dl 乳酸値…12.2
H28年7月20日 HbA1c…5.2mg/dl
H28年8月24日 乳酸値…13.3
H28年10月1日 HbA1c…5.4mg/dl 乳酸値…10.2
○医師による所感
糖尿病治療薬である新薬(DPP4阻害薬:ザファテック)を単独及び併用した場合のメトホルミン+BCAA療法における、当患者に関するHbA1cの推移を図1に示す。当患者について、新薬(DPP4阻害薬)のみでHbA1c5.6になっていたのに気づいたのはメトホルミン250mg+BCAAを使用する時点である。食後血糖値が平成28年5月9日に246mg/dlと血糖コントロールが悪かったので平成28年5月18日にメトホルミン+BCAAとの併用を開始した。平成28年6月28日、HbA1cが5.1に下がったため当該新薬の投与を中止し、メトホルミン+BCAA療法のみに変更した。平成28年7月20日HbA1cは5.2と0.1上昇した。入院当初は食欲があまりなかったが7月20日現在、食事は全量摂取している。血糖のコントロールも良くなっている(空腹時血糖、食後血糖など)。
入院時(平成28年4月19日)は、HbA1c6.4、乳酸値8.4であり、平成28年5月17日には、HbA1c5.6で乳酸値14.7であった。メトホルミンを使用したのは平成28年5月18日からである。その後、平成28年8月24日に乳酸値13,3であり、平成28年10月1日はHbA1cが5.4であり、新薬の影響は全くなく、同等の効果が認められる。
性別 女性
年齢 89歳
処方期間 H28年7月21日 HbA1c…6.9mg/dl
H28年8月3日 HbA1c…6.9mg/dl
H28年8月24日 乳酸値…8.4
H28年9月1日 HbA1c…6.9mg/dl
H28年10月1日 HbA1c…6.4mg/dl 乳酸値…9.1
○医師による所感
本処方例では、慎重投与の薬剤を併用した副作用を抑えた例と思われる。初診時(平成28年7月21日)には、HbA1c6.9、乳酸値17.9であった。この患者は糖尿病患者に慎重投与となっている利尿降圧剤フルイトランを多めの4mgを使用していたが、フルイトランは糖尿病を悪化させるため別の降圧剤に変更し少し様子を見た。
Claims (14)
- 血中乳酸値を実質的に上昇させずに血糖値を降下させる作用を有する糖尿病治療用組成物であって、該組成物が、
分岐鎖アミノ酸と、
ビグアニド誘導体又は該ビグアニド誘導体又は分岐鎖アミノ酸の誘導体の塩と
を有効成分とすることを特徴とする糖尿病治療用組成物。 - DPP4が介在する疾患及び/又は症状の治療、予防及び/又は改善剤である請求項1記載の糖尿病治療用組成物。
- 分岐鎖アミノ酸と、
ビグアニド誘導体又は該ビグアニド誘導体又は分岐鎖アミノ酸の誘導体の塩と、
糖尿病治療薬と
を組み合わせてなることを特徴とする糖尿病治療用組成物。 - 前記分岐鎖アミノ酸として、ロイシン、イソロイシン又はバリンのいずれかを含有することを特徴とする請求項1乃至3のいずれかに記載の糖尿病治療用組成物。
- 前記分岐鎖アミノ酸として、ロイシン及びイソロイシンを含有する請求項1乃至3のいずれかに記載の糖尿病治療用組成物。
- 前記分岐鎖アミノ酸として、ロイシン、イソロイシン及びバリンを含有することを特徴とする請求項1乃至3のいずれかに記載の糖尿病治療用組成物。
- 前記ビグアニド誘導体として、メトホルミン塩酸塩を含有することを特徴とする請求項1乃至3のいずれかに記載の糖尿病治療用組成物。
- 前記ビグアニド誘導体として、フェンホルミン又はブホルミンを含有することを特徴とする請求項1乃至3のいずれかに記載の糖尿病治療用組成物。
- 前記糖尿病治療薬が、ジペプチジルペプチダーゼIV阻害薬、スルホニル尿素系血糖低下薬、ビグアナイド系製剤、α-グルコシダーゼ阻害薬、速効型インスリン分泌促進薬、インスリン製剤、PPARアゴニスト、β3アドレナリン受容体作動薬、アルドース還元酵素阻害薬、GLP-1類縁体及びSGLT阻害薬からなる群より選択される1種以上であることを特徴とする請求項3に記載の糖尿病治療用組成物。
- 対象となる疾患が乳酸アシドーシスの既往を伴う糖尿病、腎機能障害を伴う糖尿病、肝機能障害を伴う糖尿病、心血管系の障害を伴う糖尿病、肺機能の障害を伴う糖尿病、低酸素血症を伴いやすい糖尿病、過度のアルコール摂取者における糖尿病、胃腸障害を伴う糖尿病、2型糖尿病及び高齢者の糖尿病からなる群より選ばれる少なくとも一つであることを特徴とする請求項1乃至3のいずれかに記載の糖尿病治療用組成物。
- 対象となる疾患が腎機能障害を伴う糖尿病であることを特徴とする請求項1乃至3のいずれかに記載の糖尿病治療用組成物。
- 乳酸アシドーシスの予防及び/又は治療用である請求項1乃至3のいずれかに記載の糖尿病治療用組成物。
- 輸液製剤の形態である請求項1乃至3のいずれかに記載の糖尿病治療用組成物。
- 経口製剤の形態である請求項1乃至3のいずれかに記載の糖尿病治療用組成物。
Priority Applications (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR1020187012578A KR102022682B1 (ko) | 2015-10-30 | 2016-10-28 | 당뇨병 치료용 조성물 |
JP2016571755A JP6250196B2 (ja) | 2015-10-30 | 2016-10-28 | 糖尿病治療用組成物 |
CN201680062505.8A CN108348495A (zh) | 2015-10-30 | 2016-10-28 | 糖尿病治疗用组合物 |
CA3001662A CA3001662C (en) | 2015-10-30 | 2016-10-28 | Composition for treating diabetes mellitus |
EP16859957.9A EP3369419A4 (en) | 2015-10-30 | 2016-10-28 | Composition for treating diabetes |
RU2018119948A RU2679602C1 (ru) | 2015-10-30 | 2016-10-28 | Состав для лечения сахарного диабета |
US15/939,289 US20180214396A1 (en) | 2015-10-30 | 2018-03-29 | Composition for treating diabetes mellitus |
US17/063,673 US11701336B2 (en) | 2015-10-30 | 2020-10-05 | Method of determining composition effective for treating diabetes |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2015214824 | 2015-10-30 | ||
JP2015-214824 | 2015-10-30 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US15/939,289 Continuation US20180214396A1 (en) | 2015-10-30 | 2018-03-29 | Composition for treating diabetes mellitus |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2017073729A1 true WO2017073729A1 (ja) | 2017-05-04 |
Family
ID=58631640
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP2016/082066 WO2017073729A1 (ja) | 2015-10-30 | 2016-10-28 | 糖尿病治療用組成物 |
Country Status (8)
Country | Link |
---|---|
US (1) | US20180214396A1 (ja) |
EP (1) | EP3369419A4 (ja) |
JP (1) | JP6250196B2 (ja) |
KR (1) | KR102022682B1 (ja) |
CN (1) | CN108348495A (ja) |
CA (1) | CA3001662C (ja) |
RU (1) | RU2679602C1 (ja) |
WO (1) | WO2017073729A1 (ja) |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2021142733A1 (en) * | 2020-01-16 | 2021-07-22 | Shanghai Benemae Pharmaceutical Corporation | Combinational therapy comprising glp-1 and/or glp-1 analogs, and insulin and/or insulin analogs |
CN116268425A (zh) * | 2023-04-04 | 2023-06-23 | 天津医科大学朱宪彝纪念医院(天津医科大学代谢病医院、天津代谢病防治中心) | 间歇性限制蛋白摄入促进二甲双胍降血糖效果方面的应用 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004002272A (ja) * | 2002-10-01 | 2004-01-08 | Chugai Pharmaceut Co Ltd | 2型糖尿病治療剤 |
WO2005049006A1 (ja) * | 2003-11-21 | 2005-06-02 | Ajinomoto Co., Inc. | 糖尿病治療剤 |
JP2007008814A (ja) * | 2001-04-16 | 2007-01-18 | Chugai Pharmaceut Co Ltd | 糖尿病治療剤 |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060020563A1 (en) * | 2004-07-26 | 2006-01-26 | Coleman Christopher R | Supervised neural network for encoding continuous curves |
JP5682990B2 (ja) * | 2005-08-04 | 2015-03-11 | 味の素株式会社 | 酸化型アルブミン低下剤 |
US7879089B2 (en) * | 2006-05-17 | 2011-02-01 | Alcon, Inc. | Correction of higher order aberrations in intraocular lenses |
WO2011051974A1 (en) * | 2009-10-29 | 2011-05-05 | Nutracryst Therapeutics Private Limited | Metformin and a-amino acids |
RU2631597C2 (ru) * | 2011-07-15 | 2017-09-25 | Нусерт Сайенсиз, Инк. | Композиции и способы модулирования метаболических путей |
US9198454B2 (en) * | 2012-03-08 | 2015-12-01 | Nusirt Sciences, Inc. | Compositions, methods, and kits for regulating energy metabolism |
WO2016049236A1 (en) * | 2014-09-24 | 2016-03-31 | Nusirt Sciences, Inc. | Compositions, methods and kits for treatment of diabetes and/or hyperlipidemia |
-
2016
- 2016-10-28 WO PCT/JP2016/082066 patent/WO2017073729A1/ja active Application Filing
- 2016-10-28 KR KR1020187012578A patent/KR102022682B1/ko active IP Right Grant
- 2016-10-28 JP JP2016571755A patent/JP6250196B2/ja active Active
- 2016-10-28 EP EP16859957.9A patent/EP3369419A4/en active Pending
- 2016-10-28 RU RU2018119948A patent/RU2679602C1/ru active
- 2016-10-28 CN CN201680062505.8A patent/CN108348495A/zh active Pending
- 2016-10-28 CA CA3001662A patent/CA3001662C/en active Active
-
2018
- 2018-03-29 US US15/939,289 patent/US20180214396A1/en not_active Abandoned
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2007008814A (ja) * | 2001-04-16 | 2007-01-18 | Chugai Pharmaceut Co Ltd | 糖尿病治療剤 |
JP2004002272A (ja) * | 2002-10-01 | 2004-01-08 | Chugai Pharmaceut Co Ltd | 2型糖尿病治療剤 |
WO2005049006A1 (ja) * | 2003-11-21 | 2005-06-02 | Ajinomoto Co., Inc. | 糖尿病治療剤 |
Non-Patent Citations (2)
Title |
---|
LIZHI FU ET AL.: "Interaction between metformin and leucine in reducing hyperlipidemia and hepatic lipid accumulation in diet-induced obese mice", METABOLISM, vol. 64, no. 11, 17 July 2015 (2015-07-17), pages 1426 - 1434, XP055379137 * |
See also references of EP3369419A4 * |
Also Published As
Publication number | Publication date |
---|---|
CN108348495A (zh) | 2018-07-31 |
EP3369419A4 (en) | 2018-10-31 |
JPWO2017073729A1 (ja) | 2017-10-26 |
JP6250196B2 (ja) | 2017-12-20 |
KR20180051659A (ko) | 2018-05-16 |
CA3001662A1 (en) | 2017-05-04 |
CA3001662C (en) | 2019-04-09 |
KR102022682B1 (ko) | 2019-09-18 |
RU2679602C1 (ru) | 2019-02-12 |
US20180214396A1 (en) | 2018-08-02 |
EP3369419A1 (en) | 2018-09-05 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP4643760B2 (ja) | Dpp−iv阻害薬と他の糖尿病治療薬との併用又は組み合せからなる医薬 | |
TWI823072B (zh) | 以2-〔(4-{6-〔(4-氰基-2-氟苄基)氧基〕吡啶-2-基}哌啶-1-基)甲基〕-1-〔(2s)-氧雜環丁烷-2-基甲基〕-1h-苯並咪唑-6-甲酸或其藥學上的鹽治療第2型糖尿病或肥胖症或體重過重 | |
CN103906514A (zh) | 用于治疗代谢障碍的组合物和方法 | |
TW201105336A (en) | Combined medicine of pyrazole derivative and biguanide drug | |
WO2005049006A1 (ja) | 糖尿病治療剤 | |
JP6250196B2 (ja) | 糖尿病治療用組成物 | |
EP1935424A1 (en) | Pharmaceutical compositions comprising combined antidiabetic substances for use in diabetes mellitus | |
EP1752146A1 (en) | Therapeutic agent for diabetes | |
WO2009128360A1 (ja) | 糖尿病治療剤 | |
TW201127387A (en) | Therapeutic or preventive agents for diabetes | |
US11701336B2 (en) | Method of determining composition effective for treating diabetes | |
WO2021036884A1 (zh) | 海兰地嗪或其药学上可接受的盐在糖尿病或糖尿病并发症药物中的应用 | |
WO2004009118A1 (ja) | 糖尿病の発症予防薬 | |
JP5376785B2 (ja) | 医薬組成物 | |
JP5366386B2 (ja) | 神経細胞賦活及び神経伸長促進用組成物 | |
EA028995B1 (ru) | Соль тезофензина и оптически активных ацетиламинокислот, их применение для лечения и/или профилактики нарушений, связанных с ожирением | |
WO2012057343A1 (ja) | Nad(p)hオキシダーゼ阻害剤、酸化ストレス疾患治療薬、酸化ストレス疾患治療方法及びスクリーニング方法 | |
WO2023228023A1 (en) | Treatment of type 2 diabetes or weight management control with 2-((4-((s)-2-(5-chloropyridin-2-yl)-2-methylbenzo[d][1,3]dioxol-4-yl)piperidin-1-yl)methyl)-1-(((s)-oxetan-2-yl)methyl)-1h-benzo[d]imidazole-6-carboxylic acid or a pharmaceutically salt thereof | |
JP4391122B2 (ja) | 糖尿病予防、治療剤 | |
WO2011141419A1 (en) | Association of the xanthine oxidase inhibitor febuxostat and metformin and use thereof | |
TW200408386A (en) | Medicine for renal failure containing oxaluric acid derivatives | |
WO2016075539A1 (ru) | Композиция для лечения нарушений, связанных с избыточным весом или ожирением | |
JP2015098464A (ja) | Dpp−4阻害剤の増強剤 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
ENP | Entry into the national phase |
Ref document number: 2016571755 Country of ref document: JP Kind code of ref document: A |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 16859957 Country of ref document: EP Kind code of ref document: A1 |
|
ENP | Entry into the national phase |
Ref document number: 3001662 Country of ref document: CA |
|
NENP | Non-entry into the national phase |
Ref country code: DE |
|
ENP | Entry into the national phase |
Ref document number: 20187012578 Country of ref document: KR Kind code of ref document: A |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2018119948 Country of ref document: RU Ref document number: 2016859957 Country of ref document: EP |