JP2010510981A - 腸送達系のためのフェナントレンキノンベース化合物を含有する医薬組成物 - Google Patents
腸送達系のためのフェナントレンキノンベース化合物を含有する医薬組成物 Download PDFInfo
- Publication number
- JP2010510981A JP2010510981A JP2009538338A JP2009538338A JP2010510981A JP 2010510981 A JP2010510981 A JP 2010510981A JP 2009538338 A JP2009538338 A JP 2009538338A JP 2009538338 A JP2009538338 A JP 2009538338A JP 2010510981 A JP2010510981 A JP 2010510981A
- Authority
- JP
- Japan
- Prior art keywords
- composition
- active ingredient
- formulation
- composition according
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 83
- 230000000968 intestinal effect Effects 0.000 title claims abstract description 45
- YYVYAPXYZVYDHN-UHFFFAOYSA-N 9,10-phenanthroquinone Chemical compound C1=CC=C2C(=O)C(=O)C3=CC=CC=C3C2=C1 YYVYAPXYZVYDHN-UHFFFAOYSA-N 0.000 title claims abstract description 31
- 239000008194 pharmaceutical composition Substances 0.000 title description 13
- 239000000203 mixture Substances 0.000 claims abstract description 131
- 238000009472 formulation Methods 0.000 claims abstract description 77
- 239000004480 active ingredient Substances 0.000 claims abstract description 75
- 229940079593 drug Drugs 0.000 claims abstract description 40
- 239000003814 drug Substances 0.000 claims abstract description 40
- 150000003839 salts Chemical class 0.000 claims abstract description 20
- 239000000651 prodrug Substances 0.000 claims abstract description 14
- 229940002612 prodrug Drugs 0.000 claims abstract description 14
- 239000012453 solvate Substances 0.000 claims abstract description 7
- 229920000642 polymer Polymers 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 30
- 239000002904 solvent Substances 0.000 claims description 29
- 239000002245 particle Substances 0.000 claims description 23
- 125000000217 alkyl group Chemical group 0.000 claims description 19
- -1 dextran ester Chemical class 0.000 claims description 16
- 238000002360 preparation method Methods 0.000 claims description 16
- 238000001694 spray drying Methods 0.000 claims description 16
- 229920003169 water-soluble polymer Polymers 0.000 claims description 15
- 238000000227 grinding Methods 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 239000000463 material Substances 0.000 claims description 14
- 125000001424 substituent group Chemical group 0.000 claims description 14
- 239000010419 fine particle Substances 0.000 claims description 11
- 230000008569 process Effects 0.000 claims description 11
- 239000004094 surface-active agent Substances 0.000 claims description 11
- 125000003118 aryl group Chemical group 0.000 claims description 10
- 230000001225 therapeutic effect Effects 0.000 claims description 10
- 108090000790 Enzymes Proteins 0.000 claims description 9
- 102000004190 Enzymes Human genes 0.000 claims description 9
- 238000007792 addition Methods 0.000 claims description 9
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- 239000001856 Ethyl cellulose Substances 0.000 claims description 8
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 8
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 claims description 8
- 229920002988 biodegradable polymer Polymers 0.000 claims description 8
- 239000004621 biodegradable polymer Substances 0.000 claims description 8
- 238000000576 coating method Methods 0.000 claims description 8
- 229920001249 ethyl cellulose Polymers 0.000 claims description 8
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 8
- 210000000936 intestine Anatomy 0.000 claims description 8
- 235000019333 sodium laurylsulphate Nutrition 0.000 claims description 8
- 230000008685 targeting Effects 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 7
- 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 claims description 7
- 230000001580 bacterial effect Effects 0.000 claims description 7
- 230000015572 biosynthetic process Effects 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 125000004122 cyclic group Chemical group 0.000 claims description 7
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 239000008187 granular material Substances 0.000 claims description 7
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 7
- 239000000017 hydrogel Substances 0.000 claims description 7
- 150000002431 hydrogen Chemical class 0.000 claims description 7
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims description 6
- 239000011248 coating agent Substances 0.000 claims description 6
- 239000013078 crystal Substances 0.000 claims description 6
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 6
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 6
- 239000011159 matrix material Substances 0.000 claims description 6
- 238000010298 pulverizing process Methods 0.000 claims description 6
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 5
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 claims description 5
- 150000001336 alkenes Chemical class 0.000 claims description 5
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 5
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 5
- 230000003111 delayed effect Effects 0.000 claims description 5
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 claims description 5
- 239000003230 hygroscopic agent Substances 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
- 229920002818 (Hydroxyethyl)methacrylate Polymers 0.000 claims description 4
- 239000000654 additive Substances 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 239000002216 antistatic agent Substances 0.000 claims description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 4
- 229920001577 copolymer Polymers 0.000 claims description 4
- 150000004676 glycans Chemical class 0.000 claims description 4
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 claims description 4
- 230000004065 mitochondrial dysfunction Effects 0.000 claims description 4
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 239000004014 plasticizer Substances 0.000 claims description 4
- 229920001282 polysaccharide Polymers 0.000 claims description 4
- 239000005017 polysaccharide Substances 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 claims description 4
- 235000012239 silicon dioxide Nutrition 0.000 claims description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 3
- 230000000996 additive effect Effects 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 3
- 229910052736 halogen Inorganic materials 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
- 208000030159 metabolic disease Diseases 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 229920001277 pectin Polymers 0.000 claims description 3
- 239000001814 pectin Substances 0.000 claims description 3
- 235000010987 pectin Nutrition 0.000 claims description 3
- 229920001983 poloxamer Polymers 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- XTFIVUDBNACUBN-UHFFFAOYSA-N 1,3,5-trinitro-1,3,5-triazinane Chemical compound [O-][N+](=O)N1CN([N+]([O-])=O)CN([N+]([O-])=O)C1 XTFIVUDBNACUBN-UHFFFAOYSA-N 0.000 claims description 2
- 239000000263 2,3-dihydroxypropyl (Z)-octadec-9-enoate Substances 0.000 claims description 2
- BHIZVZJETFVJMJ-UHFFFAOYSA-N 2-hydroxypropyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCC(C)O BHIZVZJETFVJMJ-UHFFFAOYSA-N 0.000 claims description 2
- RZRNAYUHWVFMIP-GDCKJWNLSA-N 3-oleoyl-sn-glycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-GDCKJWNLSA-N 0.000 claims description 2
- 239000004382 Amylase Substances 0.000 claims description 2
- 102000013142 Amylases Human genes 0.000 claims description 2
- 108010065511 Amylases Proteins 0.000 claims description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 2
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 claims description 2
- 229920003134 Eudragit® polymer Polymers 0.000 claims description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 2
- 229920001479 Hydroxyethyl methyl cellulose Polymers 0.000 claims description 2
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 claims description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 2
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 2
- 239000004743 Polypropylene Substances 0.000 claims description 2
- 229920001214 Polysorbate 60 Polymers 0.000 claims description 2
- SXQXMCWCWVCFPC-UHFFFAOYSA-N aluminum;potassium;dioxido(oxo)silane Chemical compound [Al+3].[K+].[O-][Si]([O-])=O.[O-][Si]([O-])=O SXQXMCWCWVCFPC-UHFFFAOYSA-N 0.000 claims description 2
- 235000019418 amylase Nutrition 0.000 claims description 2
- 239000003945 anionic surfactant Substances 0.000 claims description 2
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 2
- 229960001950 benzethonium chloride Drugs 0.000 claims description 2
- 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 claims description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 2
- 239000000404 calcium aluminium silicate Substances 0.000 claims description 2
- 235000012215 calcium aluminium silicate Nutrition 0.000 claims description 2
- WNCYAPRTYDMSFP-UHFFFAOYSA-N calcium aluminosilicate Chemical compound [Al+3].[Al+3].[Ca+2].[O-][Si]([O-])=O.[O-][Si]([O-])=O.[O-][Si]([O-])=O.[O-][Si]([O-])=O WNCYAPRTYDMSFP-UHFFFAOYSA-N 0.000 claims description 2
- 229940078583 calcium aluminosilicate Drugs 0.000 claims description 2
- 239000000378 calcium silicate Substances 0.000 claims description 2
- 229910052918 calcium silicate Inorganic materials 0.000 claims description 2
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 2
- 229940105329 carboxymethylcellulose Drugs 0.000 claims description 2
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 claims description 2
- 239000003093 cationic surfactant Substances 0.000 claims description 2
- 229960002798 cetrimide Drugs 0.000 claims description 2
- 239000008119 colloidal silica Substances 0.000 claims description 2
- 229960000913 crospovidone Drugs 0.000 claims description 2
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 2
- 239000000194 fatty acid Substances 0.000 claims description 2
- 229930195729 fatty acid Natural products 0.000 claims description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 2
- 229920003063 hydroxymethyl cellulose Polymers 0.000 claims description 2
- 229940031574 hydroxymethyl cellulose Drugs 0.000 claims description 2
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- RZRNAYUHWVFMIP-UHFFFAOYSA-N monoelaidin Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-UHFFFAOYSA-N 0.000 claims description 2
- 125000002811 oleoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])/C([H])=C([H])\C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 229960000502 poloxamer Drugs 0.000 claims description 2
- 229920002503 polyoxyethylene-polyoxypropylene Polymers 0.000 claims description 2
- 229920001155 polypropylene Polymers 0.000 claims description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 2
- 229940026235 propylene glycol monolaurate Drugs 0.000 claims description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 2
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 claims description 2
- 229940079832 sodium starch glycolate Drugs 0.000 claims description 2
- 239000008109 sodium starch glycolate Substances 0.000 claims description 2
- 229920003109 sodium starch glycolate Polymers 0.000 claims description 2
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims 3
- 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 claims 2
- 229920002307 Dextran Polymers 0.000 claims 1
- 239000002563 ionic surfactant Substances 0.000 claims 1
- 229960003511 macrogol Drugs 0.000 claims 1
- 239000008203 oral pharmaceutical composition Substances 0.000 abstract description 12
- 238000001727 in vivo Methods 0.000 abstract description 8
- 230000014759 maintenance of location Effects 0.000 abstract description 3
- GVKKJJOMQCNPGB-JTQLQIEISA-N Cryptotanshinone Chemical compound O=C1C(=O)C2=C3CCCC(C)(C)C3=CC=C2C2=C1[C@@H](C)CO2 GVKKJJOMQCNPGB-JTQLQIEISA-N 0.000 description 11
- GVKKJJOMQCNPGB-UHFFFAOYSA-N Cryptotanshinone Natural products O=C1C(=O)C2=C3CCCC(C)(C)C3=CC=C2C2=C1C(C)CO2 GVKKJJOMQCNPGB-UHFFFAOYSA-N 0.000 description 10
- 210000000813 small intestine Anatomy 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 9
- 229930192627 Naphthoquinone Natural products 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 150000002791 naphthoquinones Chemical class 0.000 description 9
- 230000002776 aggregation Effects 0.000 description 8
- 238000004090 dissolution Methods 0.000 description 8
- 238000007363 ring formation reaction Methods 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 241001465754 Metazoa Species 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 210000002784 stomach Anatomy 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 238000005054 agglomeration Methods 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 210000001035 gastrointestinal tract Anatomy 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 4
- 208000008589 Obesity Diseases 0.000 description 4
- 239000011149 active material Substances 0.000 description 4
- QZPQTZZNNJUOLS-UHFFFAOYSA-N beta-lapachone Chemical compound C12=CC=CC=C2C(=O)C(=O)C2=C1OC(C)(C)CC2 QZPQTZZNNJUOLS-UHFFFAOYSA-N 0.000 description 4
- 235000020824 obesity Nutrition 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 0 CC(C)C(C*)[C@]1*C*C1 Chemical compound CC(C)C(C*)[C@]1*C*C1 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 102100022365 NAD(P)H dehydrogenase [quinone] 1 Human genes 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 238000004220 aggregation Methods 0.000 description 3
- 150000001345 alkine derivatives Chemical group 0.000 description 3
- 108010066657 azoreductase Proteins 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 210000001072 colon Anatomy 0.000 description 3
- 238000004132 cross linking Methods 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 238000012377 drug delivery Methods 0.000 description 3
- 230000002496 gastric effect Effects 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 238000010902 jet-milling Methods 0.000 description 3
- 230000008961 swelling Effects 0.000 description 3
- MGADZUXDNSDTHW-UHFFFAOYSA-N 2H-pyran Chemical compound C1OC=CC=C1 MGADZUXDNSDTHW-UHFFFAOYSA-N 0.000 description 2
- 206010060954 Abdominal Hernia Diseases 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 241000894006 Bacteria Species 0.000 description 2
- 208000024172 Cardiovascular disease Diseases 0.000 description 2
- 206010011891 Deafness neurosensory Diseases 0.000 description 2
- 208000002249 Diabetes Complications Diseases 0.000 description 2
- 108090000371 Esterases Proteins 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 108010031186 Glycoside Hydrolases Proteins 0.000 description 2
- 102000005744 Glycoside Hydrolases Human genes 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 208000031226 Hyperlipidaemia Diseases 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- 208000001647 Renal Insufficiency Diseases 0.000 description 2
- 208000009966 Sensorineural Hearing Loss Diseases 0.000 description 2
- 208000006011 Stroke Diseases 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 238000002441 X-ray diffraction Methods 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 125000000751 azo group Chemical group [*]N=N[*] 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 238000009395 breeding Methods 0.000 description 2
- 230000001488 breeding effect Effects 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 238000000975 co-precipitation Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 238000007334 copolymerization reaction Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000009501 film coating Methods 0.000 description 2
- 239000007888 film coating Substances 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 235000012631 food intake Nutrition 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 210000003405 ileum Anatomy 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 201000006370 kidney failure Diseases 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 210000002429 large intestine Anatomy 0.000 description 2
- 208000019423 liver disease Diseases 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 208000010125 myocardial infarction Diseases 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- NKGGYWQZHFAHRK-UHFFFAOYSA-N phenanthrene-3,4-dione Chemical compound C1=CC=CC2=C(C(C(=O)C=C3)=O)C3=CC=C21 NKGGYWQZHFAHRK-UHFFFAOYSA-N 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 230000000704 physical effect Effects 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 108090000765 processed proteins & peptides Proteins 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 231100000879 sensorineural hearing loss Toxicity 0.000 description 2
- 208000023573 sensorineural hearing loss disease Diseases 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000007962 solid dispersion Substances 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 239000007921 spray Substances 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- 229940124530 sulfonamide Drugs 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000001308 synthesis method Methods 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
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 208000001072 type 2 diabetes mellitus Diseases 0.000 description 2
- 230000004580 weight loss Effects 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- IGCJKJTYHIDZJN-UHFFFAOYSA-N (4-phenyldiazenylphenyl) 2-methylprop-2-enoate Chemical compound C1=CC(OC(=O)C(=C)C)=CC=C1N=NC1=CC=CC=C1 IGCJKJTYHIDZJN-UHFFFAOYSA-N 0.000 description 1
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 description 1
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 description 1
- SDRZFSPCVYEJTP-UHFFFAOYSA-N 1-ethenylcyclohexene Chemical compound C=CC1=CCCCC1 SDRZFSPCVYEJTP-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- RLYOPPJABLAKCZ-UHFFFAOYSA-N 2-butoxycarbonylbenzenecarboperoxoic acid Chemical compound CCCCOC(=O)C1=CC=CC=C1C(=O)OO RLYOPPJABLAKCZ-UHFFFAOYSA-N 0.000 description 1
- GHHURQMJLARIDK-UHFFFAOYSA-N 2-hydroxypropyl octanoate Chemical compound CCCCCCCC(=O)OCC(C)O GHHURQMJLARIDK-UHFFFAOYSA-N 0.000 description 1
- BMYZFVWZCNCJFG-UHFFFAOYSA-N 2-prop-2-enoxycyclohexa-2,5-diene-1,4-dione Chemical compound C=CCOC1=CC(=O)C=CC1=O BMYZFVWZCNCJFG-UHFFFAOYSA-N 0.000 description 1
- RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-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
- GEPDWFWEEIMFMO-UHFFFAOYSA-N 5,6,7,8-tetrahydrophenanthrene-3,4-dione Chemical compound C1CCCC2=C(C(C(=O)C=C3)=O)C3=CC=C21 GEPDWFWEEIMFMO-UHFFFAOYSA-N 0.000 description 1
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
- KTFUTPSBLYIILV-UHFFFAOYSA-N 6,6-dichlorohexan-1-amine Chemical compound NCCCCCC(Cl)Cl KTFUTPSBLYIILV-UHFFFAOYSA-N 0.000 description 1
- 208000023434 Alpers-Huttenlocher syndrome Diseases 0.000 description 1
- 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 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010003210 Arteriosclerosis Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 241000606125 Bacteroides Species 0.000 description 1
- 241000606124 Bacteroides fragilis Species 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 241000186000 Bifidobacterium Species 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- PXWXCTRHXICRQN-UHFFFAOYSA-N CC(C)(CC1)OC(c(cc(C)c2ccccc22)c2C2=O)=C1C2=O Chemical compound CC(C)(CC1)OC(c(cc(C)c2ccccc22)c2C2=O)=C1C2=O PXWXCTRHXICRQN-UHFFFAOYSA-N 0.000 description 1
- PKGILFSXNBELKV-UHFFFAOYSA-N CC(C1(C)C)OC(c(ccc2c3CCCC2(C)C)c3C2=O)=C1C2=O Chemical compound CC(C1(C)C)OC(c(ccc2c3CCCC2(C)C)c3C2=O)=C1C2=O PKGILFSXNBELKV-UHFFFAOYSA-N 0.000 description 1
- SQOACJSGXKJRSB-UHFFFAOYSA-N CC(C1(C)C)OC(c(ccc2c3CCCC2)c3C2=O)=C1C2=O Chemical compound CC(C1(C)C)OC(c(ccc2c3CCCC2)c3C2=O)=C1C2=O SQOACJSGXKJRSB-UHFFFAOYSA-N 0.000 description 1
- KBBAMOSMOYPKJV-UHFFFAOYSA-N CC(C1(C)C)OC(c(ccc2c3cccc2)c3C2=O)=C1C2=O Chemical compound CC(C1(C)C)OC(c(ccc2c3cccc2)c3C2=O)=C1C2=O KBBAMOSMOYPKJV-UHFFFAOYSA-N 0.000 description 1
- UZZHDMZJEORTJE-UHFFFAOYSA-N CC(C1(C)C)OC(c(ccc2ccc(C(C)(C)C)cc22)c2C2=O)=C1C2=O Chemical compound CC(C1(C)C)OC(c(ccc2ccc(C(C)(C)C)cc22)c2C2=O)=C1C2=O UZZHDMZJEORTJE-UHFFFAOYSA-N 0.000 description 1
- FDXAYHRVBCDXOT-UHFFFAOYSA-N CC(C1)OC(C2C(C3=O)=C(C=C(C=C4/[O]=C(\C5=C(c6c7c8cc(C)cc(/[O]=C(\C9=C(c%10c%11c(cc(cc%12)Cl)c%12cc%10)OC(C)C9)/C%11=O)c8cc6)OC(C)C5)/C7=O)O)C4=CC2)=C1C3=O Chemical compound CC(C1)OC(C2C(C3=O)=C(C=C(C=C4/[O]=C(\C5=C(c6c7c8cc(C)cc(/[O]=C(\C9=C(c%10c%11c(cc(cc%12)Cl)c%12cc%10)OC(C)C9)/C%11=O)c8cc6)OC(C)C5)/C7=O)O)C4=CC2)=C1C3=O FDXAYHRVBCDXOT-UHFFFAOYSA-N 0.000 description 1
- GCTCKPSAZXDVRR-UHFFFAOYSA-N CC(C1)OC(c(cc(C)c2c3cccc2)c3C2=O)=C1C2=O Chemical compound CC(C1)OC(c(cc(C)c2c3cccc2)c3C2=O)=C1C2=O GCTCKPSAZXDVRR-UHFFFAOYSA-N 0.000 description 1
- YPQGELVBHXVWAZ-UHFFFAOYSA-N CC(C1)OC(c(ccc2c3CCCC2)c3C2=O)=C1C2=O Chemical compound CC(C1)OC(c(ccc2c3CCCC2)c3C2=O)=C1C2=O YPQGELVBHXVWAZ-UHFFFAOYSA-N 0.000 description 1
- CVOWOHRIFYUPTM-UHFFFAOYSA-N CC(C1)OC(c(ccc2c3cc(C(C)(C)C)cc2)c3C2=O)=C1C2=O Chemical compound CC(C1)OC(c(ccc2c3cc(C(C)(C)C)cc2)c3C2=O)=C1C2=O CVOWOHRIFYUPTM-UHFFFAOYSA-N 0.000 description 1
- CAHVBEASHABWEV-UHFFFAOYSA-N CC(C1)OC(c2ccc(C(C)(C)CCC3)c3c2C2=O)=C1C2=O Chemical compound CC(C1)OC(c2ccc(C(C)(C)CCC3)c3c2C2=O)=C1C2=O CAHVBEASHABWEV-UHFFFAOYSA-N 0.000 description 1
- HYXITZLLTYIPOF-UHFFFAOYSA-N CC1(C)c2ccc(-c([o]cc3C)c3C(C3=O)=O)c3c2CCC1 Chemical compound CC1(C)c2ccc(-c([o]cc3C)c3C(C3=O)=O)c3c2CCC1 HYXITZLLTYIPOF-UHFFFAOYSA-N 0.000 description 1
- LLPSORWIKSDGAO-UHFFFAOYSA-N CC1C(C(C(c2c(CCCC3(C)C)c3ccc22)=O)=O)=C2OC1(C)C Chemical compound CC1C(C(C(c2c(CCCC3(C)C)c3ccc22)=O)=O)=C2OC1(C)C LLPSORWIKSDGAO-UHFFFAOYSA-N 0.000 description 1
- HARGZZNYNSYSGJ-UHFFFAOYSA-N CC1C(C(C(c2c3ccc4c(C)cccc24)=O)=O)=C3OC1 Chemical compound CC1C(C(C(c2c3ccc4c(C)cccc24)=O)=O)=C3OC1 HARGZZNYNSYSGJ-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- AIGAZQPHXLWMOJ-UHFFFAOYSA-N Cc1c[o]c(-c(ccc2c(C)cccc22)c2C2=O)c1C2=O Chemical compound Cc1c[o]c(-c(ccc2c(C)cccc22)c2C2=O)c1C2=O AIGAZQPHXLWMOJ-UHFFFAOYSA-N 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 229920001287 Chondroitin sulfate Polymers 0.000 description 1
- 238000005821 Claisen rearrangement reaction Methods 0.000 description 1
- 206010009944 Colon cancer Diseases 0.000 description 1
- 206010010774 Constipation Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 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 1
- 208000019505 Deglutition disease Diseases 0.000 description 1
- 206010012289 Dementia Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010012655 Diabetic complications Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 238000005698 Diels-Alder reaction Methods 0.000 description 1
- 208000004986 Diffuse Cerebral Sclerosis of Schilder Diseases 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 206010061818 Disease progression Diseases 0.000 description 1
- 208000005189 Embolism Diseases 0.000 description 1
- 208000017701 Endocrine disease Diseases 0.000 description 1
- 241000305071 Enterobacterales Species 0.000 description 1
- 241000186398 Eubacterium limosum Species 0.000 description 1
- 229920003141 Eudragit® S 100 Polymers 0.000 description 1
- 208000004930 Fatty Liver Diseases 0.000 description 1
- 208000024412 Friedreich ataxia Diseases 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 206010019663 Hepatic failure Diseases 0.000 description 1
- 206010019708 Hepatic steatosis Diseases 0.000 description 1
- 206010019842 Hepatomegaly Diseases 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- 208000000038 Hypoparathyroidism Diseases 0.000 description 1
- 206010021118 Hypotonia Diseases 0.000 description 1
- 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 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- 208000015710 Iron-Deficiency Anemia Diseases 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 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 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 208000035177 MELAS Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 208000007379 Muscle Hypotonia Diseases 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- 208000029578 Muscle disease Diseases 0.000 description 1
- 208000000112 Myalgia Diseases 0.000 description 1
- 206010028629 Myoglobinuria Diseases 0.000 description 1
- 241000872931 Myoporum sandwicense Species 0.000 description 1
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 206010030216 Oesophagitis Diseases 0.000 description 1
- 206010061323 Optic neuropathy Diseases 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 206010060862 Prostate cancer Diseases 0.000 description 1
- 208000000236 Prostatic Neoplasms Diseases 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 208000010378 Pulmonary Embolism Diseases 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 206010037779 Radiculopathy Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 208000026980 Renal tubular disease Diseases 0.000 description 1
- 208000017442 Retinal disease Diseases 0.000 description 1
- 208000007014 Retinitis pigmentosa Diseases 0.000 description 1
- 206010038923 Retinopathy Diseases 0.000 description 1
- 201000007981 Reye syndrome Diseases 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- 206010042434 Sudden death Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 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 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 208000001435 Thromboembolism Diseases 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- 208000002495 Uterine Neoplasms Diseases 0.000 description 1
- 208000000558 Varicose Ulcer Diseases 0.000 description 1
- 208000035091 Ventral Hernia Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 125000001931 aliphatic group Chemical group 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
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 208000011775 arteriosclerosis disease Diseases 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 125000005110 aryl thio group Chemical group 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- YYRMJZQKEFZXMX-UHFFFAOYSA-L calcium bis(dihydrogenphosphate) Chemical compound [Ca+2].OP(O)([O-])=O.OP(O)([O-])=O YYRMJZQKEFZXMX-UHFFFAOYSA-L 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940045110 chitosan Drugs 0.000 description 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
- 229960001231 choline Drugs 0.000 description 1
- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 230000015271 coagulation Effects 0.000 description 1
- 238000005345 coagulation Methods 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 description 1
- 230000005750 disease progression Effects 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 238000009506 drug dissolution testing Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 201000002491 encephalomyelitis Diseases 0.000 description 1
- 208000030172 endocrine system disease Diseases 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 208000006881 esophagitis Diseases 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- LDLDYFCCDKENPD-UHFFFAOYSA-N ethenylcyclohexane Chemical class C=CC1CCCCC1 LDLDYFCCDKENPD-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 208000010706 fatty liver disease Diseases 0.000 description 1
- 235000021191 food habits Nutrition 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 208000020694 gallbladder disease Diseases 0.000 description 1
- 125000005456 glyceride group Chemical group 0.000 description 1
- 229940049654 glyceryl behenate Drugs 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 208000019622 heart disease Diseases 0.000 description 1
- 230000010224 hepatic metabolism Effects 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 206010020871 hypertrophic cardiomyopathy Diseases 0.000 description 1
- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 210000003000 inclusion body Anatomy 0.000 description 1
- 230000001939 inductive effect Effects 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
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 208000020658 intracerebral hemorrhage Diseases 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 208000023589 ischemic disease Diseases 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- 210000001630 jejunum Anatomy 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 230000005976 liver dysfunction Effects 0.000 description 1
- 208000007903 liver failure Diseases 0.000 description 1
- 231100000835 liver failure Toxicity 0.000 description 1
- 210000001365 lymphatic vessel Anatomy 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 201000011540 mitochondrial DNA depletion syndrome 4a Diseases 0.000 description 1
- 235000019691 monocalcium phosphate Nutrition 0.000 description 1
- 229910000150 monocalcium phosphate Inorganic materials 0.000 description 1
- 125000002950 monocyclic group Chemical group 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 230000020763 muscle atrophy Effects 0.000 description 1
- 201000000585 muscular atrophy Diseases 0.000 description 1
- XFHJDMUEHUHAJW-UHFFFAOYSA-N n-tert-butylprop-2-enamide Chemical compound CC(C)(C)NC(=O)C=C XFHJDMUEHUHAJW-UHFFFAOYSA-N 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000004235 neutropenia Diseases 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 239000002736 nonionic surfactant Substances 0.000 description 1
- 238000013116 obese mouse model Methods 0.000 description 1
- 208000001749 optic atrophy Diseases 0.000 description 1
- 208000020911 optic nerve disease Diseases 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000007800 oxidant agent Substances 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
- 229960000292 pectin Drugs 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 230000002572 peristaltic effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229920000233 poly(alkylene oxides) Polymers 0.000 description 1
- 229920005575 poly(amic acid) Polymers 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229940104257 polyglyceryl-6-dioleate Drugs 0.000 description 1
- 229920000098 polyolefin Polymers 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 229920002689 polyvinyl acetate Polymers 0.000 description 1
- 239000011118 polyvinyl acetate Substances 0.000 description 1
- 229940100467 polyvinyl acetate phthalate Drugs 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 description 1
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- ZVJHJDDKYZXRJI-UHFFFAOYSA-N pyrroline Natural products C1CC=NC1 ZVJHJDDKYZXRJI-UHFFFAOYSA-N 0.000 description 1
- 206010061928 radiculitis Diseases 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000003303 reheating Methods 0.000 description 1
- 208000014318 renal tubule disease Diseases 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 201000002859 sleep apnea Diseases 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 239000002195 soluble material Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 229940032147 starch Drugs 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 231100000240 steatosis hepatitis Toxicity 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 125000003396 thiol group Chemical class [H]S* 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 125000005152 trihalomethanesulfonyl group Chemical group 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 125000004417 unsaturated alkyl group Chemical group 0.000 description 1
- 210000002438 upper gastrointestinal tract Anatomy 0.000 description 1
- 206010046766 uterine cancer Diseases 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000000733 zeta-potential measurement Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/10—Laxatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/18—Drugs for disorders of the alimentary tract or the digestive system for pancreatic disorders, e.g. pancreatic enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/12—Ophthalmic agents for cataracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- 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
-
- 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
- A61P3/04—Anorexiants; Antiobesity agents
-
- 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
- A61P3/06—Antihyperlipidemics
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/10—Antimycotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/06—Antianaemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/12—Antidiuretics, e.g. drugs for diabetes insipidus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Diabetes (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Cardiology (AREA)
- Oncology (AREA)
- Heart & Thoracic Surgery (AREA)
- Obesity (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Communicable Diseases (AREA)
- Reproductive Health (AREA)
- Psychiatry (AREA)
- Ophthalmology & Optometry (AREA)
- Urology & Nephrology (AREA)
- Gynecology & Obstetrics (AREA)
- Rheumatology (AREA)
- Psychology (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Immunology (AREA)
- Physiology (AREA)
Abstract
【選択図】なし
Description
上式中
R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12、R13、R14、R15およびR16は各々独立して水素、ハロゲン、ヒドロキシル、またはC1−C6アルキル、アルケンまたはアルコキシ、C4−C10シクロアルキル、ヘテロシクロアルキル、アリールまたはヘテロアリールであるか、そうでなければそれらの2つの置換基が合わされて環式構造を形成するかまたは二重結合を形成していてよく;
XはC(R)(R’)、N(R’’)、OおよびSからなる群から選択され、ここで、R、R’およびR’’が各々独立して水素またはC1−C6低級アルキルであり;
mまたはnが0である場合、mまたはnに隣接する炭素原子は、直接結合を介して環式構造を形成することを条件として、mおよびnがそれぞれ独立して0または1である、
経口医薬組成物を提供することによって達成可能である。
R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12、R13、R14、R15、R16、m、nおよびXは構造式1に定義されている通りである。
上式中、
R19およびR20は各々独立して水素或いは置換または未置換のC1〜C20直鎖アルキルまたはC1〜C20分岐アルキルであり、
R21は、以下の置換基i)〜viii):
i)水素;
ii)置換または未置換のC1〜C20直鎖アルキルまたはC1〜C20分岐アルキル;
iii)置換または未置換アミン;
iv)置換または未置換のC3〜C10シクロアルキルまたはC3〜C10ヘテロシクロアルキル;
v)置換または未置換のC4〜C10アリールまたはC4〜C10ヘテロアリール;
vi)R、R’およびR’’が各々独立して水素、または置換または未置換のC1〜C20直鎖アルキルまたはC1〜C20分岐アルキルであり、R14が水素、置換または未置換アミン、シクロアルキル、ヘテロシクロアルキル、アリールおよびヘテロアリールからなる群から選択されており、1が1〜5の中から選択されている、−(CRR’ −NR’’CO)l−R22;
vii)置換または未置換カルボキシル;
viii)−OSO3−Na+;
からなる群から選択されており;
kが0である場合、R19およびR20は存在せず、R21は直接カルボニル基に対し結合されていることを条件として、kは0〜20の中から選択されている。
本発明に従った医薬組成物においては、以下で示すように活性材料である構造式1の化合物が調製可能である。以下で記述されている調製プロセスは、単に一例にすぎず、その他のプロセスを利用することも可能である。従って、本発明の範囲は以下のプロセスに限定されない。
(a)構造式1のフェナントレンキノンベースの化合物を単独で、または界面活性剤および吸湿剤材料と組合せた形で添加し、構造式1のフェナントレンキノンベースの化合物をジェットミルで粉砕して活性成分微細粒子を調製する工程;
(b)水溶性重合体、可溶化剤および崩壊促進剤と併せて活性成分微細粒子を溶媒中に溶解させ、結果として得られた溶液を噴霧乾燥して処方物粒子を調製する工程;および
(c)pH感受性重合体および可塑化剤と併せて処方剤粒子を溶媒中に溶解させ、結果として得られた溶液を噴霧乾燥して、処方物粒子上に腸標的コーティングを実施する工程、
を含むプロセスによって調製され得る。
活性成分の微粉化は、ジェットミル(SJ−100、日新エンジニアリング(Nisshin)、日本)を用いて実施した。0.65Mpaの供給圧力および16〜20g/時の補給速度で作業を行なった。0.2gのラウリル硫酸ナトリウム(sodium lauryl sulfate)およびフェナントレンキノンベースの化合物としての10gのクリプトタンシノンを100mlの水に添加し、次に10時間粉砕した。微粉化した粒子を回収し、粒子サイズをゼータ電位測定によって判定した。平均粒径は1500nmであった。
そのままのクリプトタンシノンまたは実施例1で微粉化されたクリプトタンシノンをメタノールに添加した。次に、塩化ナトリウムといったような塩、白糖またはラクトースといったようなサッカリド、または微晶質セルロース、第一リン酸カルシウム、でんぷんまたはマンニトールといったビヒクル、ステアリン酸マグネシウムといったような潤滑剤、タルクまたはベヘン酸グリセリルといったような潤滑剤、そしてポロキサマーといった可溶化剤をそれに添加し、その後均一に分散させて、その後の噴霧乾燥のために用いられる噴霧乾燥溶液を調製した。
実施例2の噴霧乾燥した生成物に対して、活性成分との関係においてほぼ等量の水溶性重合体(ヒドロキシプロピルメチルセルロース)とクロスカルメロースナトリウムおよび軽質無水ケイ酸といったビヒクルとを添加し、崩壊干渉(interference of disintegration)をひき起こすことなく混合物を処方した。緩衝液(pH6.8)中で薬物溶解試験を実施した。全ての組成物は、6時間後に90%以上の薬物溶解を示した。
10匹の雄のSD(Sprague−Dawley)ラットを絶食させ、動物の体内の相対的生物学的利用能をさまざまな処方物について評価した。具体的には、クリプトタンシノンを粗粉砕して2重量%のラウリル硫酸ナトリウム(SLS)と併せて水溶液に添加した調製物(活性成分の粉砕に先立つ調製物)、クリプトタンシノンをジェットミルで微細粒子へと粉砕して2重量%のSLSと併せて水溶液に添加した調製物(活性成分の粉砕後の調製物)、実施例2の噴霧乾燥生成物と実験例1のビヒクルから成る処方物を水溶液に添加した調製物(噴霧乾燥調製物)およびクリプトタンシノンをジェットミルで微粉末に粉砕し、実験例1のビヒクルを用いて処方して水溶液に添加した調製物(固体分散調製物)について、相対的生物学的利用能の評価を行なった。
実験例1で調製した噴霧乾燥処方物を、pH感受性重合体としての約20重量%のオイドラギットS−100および可塑化剤としての約2重量%のPEG#6000を含有するエタノール溶液に添加し、次に混合物を噴霧乾燥して腸標的処方物を調製した。
実施例3で調製した腸標的処方物をそれぞれpH1.2とpH6.8に曝露した。6時間後に、腸標的処方物を除去し、洗浄し、活性成分の含有量をHPLCによって分析した。活性成分の有効量を、耐酸性の尺度として査定した。耐酸性は、90〜100%という非常にすぐれた結果を示し、かくして、腸標的処方物が胃内または小腸内で化学的に安定していることを示唆した。
実験例3の場合と同様に、腸標的処方物をpH1.2の酸性環境に曝露した後、人工的な環境内でpH6.8の値に酸性度を変更した。溶解した活性成分の残留量をHPLCで測定した。かくして得られた結果を下表3に示す。
活性成分含有量に関して400mg/kgの腸標的処方物を毎日一回ob/obマウスに投与し、動物の体重(BW)の変化を検査した。
Claims (38)
- 活性成分として、下記式(1):
R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12、R13、R14、R15およびR16が、各々独立して水素、ハロゲン、ヒドロキシル、またはC1−C6アルキル、アルケンまたはアルコキシ、C4−C10シクロアルキル、ヘテロシクロアルキル、アリールまたはヘテロアリールであるか、そうでなければ、それらの2つの置換基が合わされて環状構造を形成するかまたは二重結合を形成していてよく;
Xは、C(R)(R’)、N(R’’)、OおよびSからなる群から選択され(式中、R、R’およびR’’が各々独立して水素またはC1−C6低級アルキルである);
mおよびnは独立して0または1であり、ただし、mまたはnが0である場合、mまたはnに隣接する炭素原子は、直接結合を介して環状構造を形成する)
で表されるフェナントレンキノンベースの化合物、またはその薬学的に許容される塩、プロドラッグ、溶媒和物または異性体が、腸を標的とする処方物に調製されている経口医薬組成物。 - XがOであることを特徴とする請求項1に記載の組成物。
- 前記プロドラッグが、下記式(1a):
R1、R2、R3、R4、R5、R6、R7、R8、R9、R10、R11、R12、R13、R14、R15、R16、m、nおよびXは、前記式(1)に定義されている通りであり;
R17およびR18は、各々独立して−SO3−Na+または、以下の下記式(2):
R19およびR20は、各々独立して、水素、或いは置換または未置換のC1〜C20直鎖アルキルまたはC1〜C20分岐アルキルであり、
で表わされる置換基またはその塩であり、
R21は、下記置換基i)〜viii):
i)水素;
ii)置換または未置換のC1〜C20直鎖アルキルまたはC1〜C20分岐アルキル;
iii)置換または未置換アミン;
iv)置換または未置換のC3〜C10シクロアルキルまたはC3〜C10ヘテロシクロアルキル;
v)置換または未置換のC4〜C10アリールまたはC4〜C10ヘテロアリール;
vi)式−(CRR’ −NR’’CO)l−R22(式中、R、R’およびR’’は、各々独立して、水素、または置換または未置換のC1〜C20直鎖アルキルまたはC1〜C20分岐アルキルであり、R14は、水素、置換または未置換アミン、シクロアルキル、ヘテロシクロアルキル、アリールおよびヘテロアリールからなる群から選択され、lは、1〜5から選択される);で表わされる置換基
vii)置換または未置換カルボキシル;
viii)−OSO3−Na+;
からなる群から選択される)
kは、0〜20の中から選択され、ただし、kが0である場合、R19およびR20は存在せず、R21はカルボニル基に直接結合する)
で表わされる化合物であることを特徴とする請求項1に記載の組成物。 - 腸を標的とする処方が、pH感受性重合体の付加によって実施されることを特徴とする請求項1に記載の組成物。
- 前記pH感受性重合体が、メタクリル酸−アクリル酸エチル共重合体(オイドラギット(Eudragit):ロームファルマ社(Rohm Pharma GmbH)の登録商標)、ヒドロキシプロピルメチルセルロースフタレート(HPMCP)およびそれらの混合物からなる群から選択された1種以上であることを特徴とする請求項7に記載の組成物。
- 前記pH感受性重合体が、コーティングプロセスによって添加されることを特徴とする請求項7に記載の組成物。
- 腸を標的とする処方が、腸特異的細菌酵素によって分解可能である生分解性重合体の付加によって実施されることを特徴とする請求項1に記載の組成物。
- 前記重合体が、アゾ芳香族連結を含有することを特徴とする請求項10に記載の組成物。
- 前記アゾ芳香族連結を含有する前記重合体が、スチレンとヒドロキシエチルメタクリレート(HEMA)の共重合体であることを特徴とする請求項11に記載の組成物。
- 前記重合体が、天然多糖またはその置換誘導体であることを特徴とする請求項10に記載の組成物。
- 前記多糖またはその置換誘導体が、デキストランエステル、ペクチン、アミラーゼおよびエチルセルロースまたはその薬学的に許容可能な塩からなる群から選択された1種以上であることを特徴とする請求項13に記載の組成物。
- 腸を標的とする処方が、腸特異的細菌酵素により分解可能である生分解性マトリクスの付加によって実施されることを特徴とする請求項1に記載の組成物。
- 前記マトリクスが、N置換アクリルアミドをベースとする合成ヒドロゲルであることを特徴とする請求項15に記載の組成物。
- 腸を標的とする処方が、一定の遅延時間後に薬物が経時的に放出される構成(「時間特異的遅延放出型処方」)によって実施されることを特徴とする請求項1に記載の組成物。
- 前記時間特異的遅延放出型処方が、ヒドロゲルの付加によって実施されることを特徴とする請求項17に記載の組成物。
- 前記活性成分が、結晶構造を有することを特徴とする請求項1に記載の組成物。
- 前記活性成分が、結晶化度が50%以下である結晶構造を有することを特徴とする請求項1に記載の組成物。
- 前記活性成分が、非晶質構造を有することを特徴とする請求項20に記載の組成物。
- 前記活性成分が、細粒の形で含まれることを特徴とする請求項1に記載の組成物。
- 前記細粒が、5nm〜500μmの範囲内の粒径を有することを特徴とする請求項22に記載の組成物。
- 前記細粒が、前記活性成分の噴霧乾燥または機械的粉砕によって調製されることを特徴とする請求項22に記載の組成物。
- 前記機械的粉砕が、ジェット粉砕によって実施されることを特徴とする請求項24に記載の組成物。
- 界面活性剤、帯電防止剤および吸湿剤からなる群から選択された1種以上が、前記細粒の形成中に添加されることを特徴とする請求項22に記載の組成物。
- 前記界面活性剤が、ドキュセートナトリウムおよびラウリル硫酸ナトリウムというアニオン界面活性剤;塩化ベンザルコニウム、塩化ベンゼトニウムおよびセトリミドというカチオン界面活性剤;モノオレイン酸グリセリル、ポリオキシエチレンソルビタン脂肪酸エステルおよびソルビタンエステルという非イオン性界面活性剤;ポリエチレン−ポリプロピレン重合体およびポリオキシエチレン−ポリオキシプロピレン重合体(ポロキサマー(Poloxamer))およびGelucireTMシリーズ(ガットフォスコーポレーション(Gattofosse Corporation)、米国)という両親媒性重合体;モノカプリル酸プロピレングリコール;オレオイル・マクロゴール−6−グリセリド、リノレオイル・マクロゴール−6−グリセリド、カプリロカプロイル・マクロゴール−8−グリセリド、モノラウリン酸プロピレングリコールおよびポリグリセリル−6−ジオレエートからなる群から選択された1種以上であることを特徴とする請求項26に記載の組成物。
- 前記吸湿剤が、コロイダルシリカ、軽質無水ケイ酸、重質無水ケイ酸、塩化ナトリウム、ケイ酸カルシウム、アルミノケイ酸カリウムおよびアルミノケイ酸カルシウムからなる群から選択された1種以上であることを特徴とする請求項26に記載の組成物。
- 経口投与用の前記処方物の調製中に、水溶性重合体、可溶化剤および崩壊促進剤が添加されることを特徴とする請求項1に記載の組成物。
- 前記処方物が、細粒の形で前記添加剤と前記活性成分を溶媒中で混合し、次いで得られた混合物を噴霧乾燥させることによって作られることを特徴とする請求項29に記載の組成物。
- 前記水溶性重合体が、メチルセルロース、ヒドロキシメチルセルロース、ヒドロキシエチルセルロース、エチルセルロース、ヒドロキシエチルメチルセルロース、カルボキシメチルセルロース、ヒドロキシプロピルメチルセルロース、ヒドロキシプロピルメチルセルロースフタレート、ナトリウムカルボキシメチルセルロースおよびカルボキシメチルエチルセルロースからなる群から選択された1種以上であることを特徴とする請求項29に記載の組成物。
- 前記水溶性重合体が、ヒドロキシプロピルメチルセルロースであることを特徴とする請求項31に記載の組成物。
- 前記崩壊促進剤が、クロスカルメロースナトリウム、クロスポビドン、カルボキシメチルセルロースカルシウム、デンプングリコール酸ナトリウムおよび低置換度ヒドロキシプロピルセルロースからなる群から選択された1種以上であることを特徴とする請求項29に記載の組成物。
- 前記崩壊促進剤が、クロスカルメロースナトリウムであることを特徴とする請求項33に記載の組成物。
- 前記可溶化剤が、界面活性剤または両親媒性化合物であることを特徴とする請求項29に記載の組成物。
- 活性成分100重量部に基づいて、10〜1000重量部の水溶性重合体、1〜30重量部の崩壊促進剤および0.1〜20重量部の可溶化剤が添加されることを特徴とする請求項29に記載の組成物。
- (a)前記式(1)のフェナントレンキノンベースの化合物を単独で、または界面活性剤および吸湿剤材料と組み合わせた形で添加し、前記式(1)の前記フェナントレンキノンベースの化合物をジェットミルで粉砕して活性成分微細粒子を調製する工程;
(b)水溶性重合体、可溶化剤および崩壊促進剤と併せて前記活性成分微細粒子を溶媒中に溶解させ、得られた溶液を噴霧乾燥して処方物粒子を調製する工程;および
(c)pH感受性重合体および可塑化剤と併せて前記処方物粒子を溶媒中に溶解させ、得られた溶液を噴霧乾燥して、前記処方物粒子上に腸標的コーティングを実施する工程
を含むプロセスによって前記腸標的処方物が調製されることを特徴とする請求項1に記載の組成物。 - 前記活性成分が、代謝性疾患、変性疾患およびミトコンドリア機能障害関連疾患の治療および/または予防のための治療的効果をもたらすことを特徴とする請求項1に記載の組成物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR20060117685 | 2006-11-27 | ||
KR1020070102478A KR20080047969A (ko) | 2006-11-27 | 2007-10-11 | 페난스렌퀴논계 화합물 함유 장 표적용 약제 조성물 |
PCT/KR2007/006010 WO2008066296A1 (en) | 2006-11-27 | 2007-11-26 | Pharmaceutical composition containing phenanthrenequinone-based compound for intestine delivery system |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2010510981A true JP2010510981A (ja) | 2010-04-08 |
Family
ID=39468042
Family Applications (5)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2009538338A Pending JP2010510981A (ja) | 2006-11-27 | 2007-11-26 | 腸送達系のためのフェナントレンキノンベース化合物を含有する医薬組成物 |
JP2009538339A Pending JP2010510982A (ja) | 2006-11-27 | 2007-11-26 | 再狭窄の治療および予防のための医薬組成物 |
JP2009538341A Pending JP2010510984A (ja) | 2006-11-27 | 2007-11-26 | インポテンスが関与する疾患の治療および予防のための医薬組成物 |
JP2009538340A Pending JP2010510983A (ja) | 2006-11-27 | 2007-11-26 | 前立腺関連疾患の治療および予防のための化合物およびそれを含有する結腸送達系の医薬組成物 |
JP2009538337A Pending JP2010510980A (ja) | 2006-11-27 | 2007-11-26 | 腸送達系のためのナフトキノンベース化合物を含有する医薬組成物 |
Family Applications After (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2009538339A Pending JP2010510982A (ja) | 2006-11-27 | 2007-11-26 | 再狭窄の治療および予防のための医薬組成物 |
JP2009538341A Pending JP2010510984A (ja) | 2006-11-27 | 2007-11-26 | インポテンスが関与する疾患の治療および予防のための医薬組成物 |
JP2009538340A Pending JP2010510983A (ja) | 2006-11-27 | 2007-11-26 | 前立腺関連疾患の治療および予防のための化合物およびそれを含有する結腸送達系の医薬組成物 |
JP2009538337A Pending JP2010510980A (ja) | 2006-11-27 | 2007-11-26 | 腸送達系のためのナフトキノンベース化合物を含有する医薬組成物 |
Country Status (6)
Country | Link |
---|---|
US (6) | US20100239674A1 (ja) |
EP (5) | EP2099449A4 (ja) |
JP (5) | JP2010510981A (ja) |
KR (14) | KR20080047959A (ja) |
CN (3) | CN101600424A (ja) |
WO (1) | WO2008066294A1 (ja) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010510980A (ja) * | 2006-11-27 | 2010-04-08 | マゼンス インコーポレイテッド | 腸送達系のためのナフトキノンベース化合物を含有する医薬組成物 |
JP2011507948A (ja) * | 2007-12-31 | 2011-03-10 | マゼンス インコーポレイテッド | 心臓病の治療および予防用の医薬組成物 |
Families Citing this family (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR101468449B1 (ko) | 2007-04-26 | 2014-12-04 | 주식회사 케이티앤지생명과학 | 신규한 페난스렌퀴논계 화합물 및 이를 포함하는대사증후군 질환의 치료 또는 예방용 약제 조성물 |
CN101820873A (zh) * | 2007-10-11 | 2010-09-01 | 麦仁斯有限公司 | 包含萘醌基化合物的微粉化粒子的药物组合物 |
KR101405823B1 (ko) * | 2007-12-24 | 2014-06-12 | 주식회사 케이티앤지생명과학 | 녹내장의 치료 및 예방을 위한 약제 조성물 |
KR20090071829A (ko) * | 2007-12-28 | 2009-07-02 | 주식회사 머젠스 | 신장질환의 치료 및 예방을 위한 약제 조성물 |
KR101495223B1 (ko) * | 2009-12-28 | 2015-02-26 | 주식회사 케이티앤지생명과학 | 나프토퀴논계 화합물을 포함하는 난청의 치료 또는 예방을 위한 조성물 |
WO2012019029A2 (en) * | 2010-08-06 | 2012-02-09 | Edison Pharmaceuticals, Inc. | Treatment of mitochondrial diseases with naphthoquinones |
EP2632437A4 (en) * | 2010-10-29 | 2014-03-19 | Univ Western Health Sciences | TERNARY MIX FORMULATIONS |
JP5828646B2 (ja) * | 2010-12-17 | 2015-12-09 | 東ソー・ファインケム株式会社 | ジエチル亜鉛の熱安定化の方法及びジエチル亜鉛組成物 |
EP2653474B1 (en) | 2010-12-17 | 2017-06-14 | Tosoh Finechem Corporation | Diethyl zinc composition, method for thermal stabilization and compound for thermal stabilization |
EP2540712A1 (de) * | 2011-06-30 | 2013-01-02 | Basf Se | Verfahren zu Herstellung cyclischer Enolether |
US9328083B2 (en) * | 2011-11-30 | 2016-05-03 | Hangzhou Bensheng Pharmaceutical Co., Ltd. | 2-aminated methylene or 2-esterified methylene tanshinone derivatives, and preparation method and application thereof |
JP6059734B2 (ja) * | 2011-11-30 | 2017-01-11 | ハンジョウ ベンシェン ファーマシューティカル シーオー., エルティーディー.Hangzhou Bensheng Pharmaceutical Co., Ltd. | 2−アルキル−又は2−アリール−置換タンシノン誘導体、その調製方法及び適用 |
US20150216820A1 (en) | 2012-09-07 | 2015-08-06 | Edison Pharmaceuticals, Inc. | Quinone derivatives for use in the modulation of redox status of individuals |
HUE051406T2 (hu) | 2012-11-14 | 2021-03-01 | Grace W R & Co | Biológiailag aktív anyagot és rendezetlen szervetlen oxidot tartalmazó kompozíciók |
DE102013003107A1 (de) | 2013-02-25 | 2014-09-11 | Thomas Rühl | Naphthofurandione mit einer 1-Bromalkylgruppe oder einer 1-Hydroxyalkylgruppe in 2-Position und einer Alkylgruppe in 3-Position zum Furanring-Sauerstoff und Verfahren zu deren Herstellung |
WO2014153349A1 (en) | 2013-03-18 | 2014-09-25 | R&R Regester Enterprises, Inc. | Water treatment and purification system and methods |
CN105992759B (zh) * | 2013-12-30 | 2020-10-30 | 永进药品工业株式会社 | 1,2-萘醌的衍生物及其制备方法 |
EP3091005B1 (en) * | 2013-12-30 | 2020-11-11 | HUEN Co., Ltd. | 1,2-naphthoquinone derivative and method for preparing same |
KR102005068B1 (ko) * | 2015-03-27 | 2019-07-30 | 주식회사 휴엔 | 1,2 나프토퀴논 유도체 및 이의 제조방법 |
US10182993B2 (en) | 2015-04-06 | 2019-01-22 | Patheon Softgels Inc. | Compositions for colonic delivery of drugs |
CN107771083A (zh) | 2015-04-23 | 2018-03-06 | 卡莱多生物科技有限公司 | 聚糖治疗剂和治疗方法 |
CN106478567B (zh) * | 2015-08-28 | 2019-02-15 | 中国科学院大连化学物理研究所 | 一种制备手性2-亚甲基-2,3-二氢萘并[2,1-b]呋喃类化合物的方法 |
US10829427B2 (en) | 2015-12-18 | 2020-11-10 | The Board Of Regents Of The University Of Texas System | Naphthoquinones, pro-drugs, and methods of use thereof |
US20210137964A1 (en) * | 2016-07-13 | 2021-05-13 | Kaleido Biosciences, Inc. | Glycan compositions and methods of use |
BR112019019098A2 (pt) | 2017-03-15 | 2020-04-22 | Cerecin Inc | composições farmacêuticas tendo altos carregamentos de fármaco de triglicerídeos de cadeia média, seu método de produção e seu uso |
US11278514B2 (en) * | 2018-01-18 | 2022-03-22 | Nadianbio Ltd. | Composition compromising dunnione as effective ingredient for prevention or alleviation of hair loss |
CN110709079B (zh) | 2018-04-09 | 2023-09-12 | 煊有限责任公司 | 包含1,2-萘醌衍生物化合物的实体癌或血液癌的预防或治疗用药物组合物 |
WO2020246807A2 (ko) * | 2019-06-04 | 2020-12-10 | 주식회사 엘마이토테라퓨틱스 | 나프토퀴논 화합물을 포함하는 암 치료용 약학적 조성물 |
CN111925347B (zh) * | 2020-07-17 | 2022-01-25 | 江西中医药大学 | 从灰枝紫菀中分离的二萜苷类化合物、制备及其保肝用途 |
CN112225713B (zh) * | 2020-11-16 | 2023-02-28 | 华东理工大学 | 一种5-羟基苯并呋喃类化合物的合成工艺 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2916152B2 (ja) * | 1987-10-12 | 1999-07-05 | バイオサミット リミテッド | 薬物放出速度調節型製剤 |
JP2001163769A (ja) * | 1999-03-25 | 2001-06-19 | Otsuka Pharmaceut Co Ltd | シロスタゾール製剤 |
WO2006048261A2 (en) * | 2004-11-02 | 2006-05-11 | Bayer Schering Pharma Aktiengesellschaft | Oral solid dosage forms containing a low dose of estradiol |
Family Cites Families (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4663308A (en) * | 1984-07-18 | 1987-05-05 | Medical College Of Ohio | Method of use of polymers containing cross-linked azo bonds for releasing therapeutic agents into the lower gastrointestinal tract |
US5200193A (en) * | 1987-04-22 | 1993-04-06 | Mcneilab, Inc. | Pharmaceutical sustained release matrix and process |
AU654483B2 (en) * | 1990-04-18 | 1994-11-10 | University Of Utah Research Foundation | Crosslinked hydrogels containing azobonds |
IL98087A (en) * | 1990-05-04 | 1996-11-14 | Perio Prod Ltd | Preparation for dispensing drugs in the colon |
JPH04230625A (ja) * | 1990-12-27 | 1992-08-19 | Standard Chem & Pharmaceut Corp Ltd | 噴霧乾燥したジクロフェナクナトリウムを含み腸溶性の被覆を有するマイクロカプセルからなる微分散した錠剤組成物の製造方法 |
US5145684A (en) * | 1991-01-25 | 1992-09-08 | Sterling Drug Inc. | Surface modified drug nanoparticles |
US5430021A (en) * | 1994-03-18 | 1995-07-04 | Pharmavene, Inc. | Hydrophobic drug delivery systems |
US6245807B1 (en) * | 1995-08-24 | 2001-06-12 | Dana-Farber Cancer Institute | Treatment of human prostate disease |
US5824700A (en) * | 1996-02-20 | 1998-10-20 | Wisconsin Alumni Research Foundation | Ortho-quinone derivatives novel synthesis therefor and their use in the inhibition of neoplastic cell growth |
EP0885891A4 (en) * | 1996-02-27 | 2001-02-21 | Sankyo Co | ISOXAZOLE DERIVATIVES |
US8883856B2 (en) * | 2000-02-28 | 2014-11-11 | John Jackson | Compositions and methods for the treatment of inflammatory diseases using topoisomerase inhibitors |
IL152116A0 (en) * | 2000-04-05 | 2003-05-29 | Vi Technologies Inc | Prion-binding ligands and methods of using same |
KR100521841B1 (ko) * | 2001-01-15 | 2005-10-17 | 재단법인서울대학교산학협력재단 | 새로운 오르토-나프토피라노퀴논 유도체 및 이를 포함하는항균 및 항진균제 |
CN1369276A (zh) * | 2001-02-12 | 2002-09-18 | 徐秀荣 | 有效减轻体重的组合物和方法 |
WO2003090710A1 (en) * | 2002-04-23 | 2003-11-06 | Case Western Reserve University | Lapachone delivery systems, compositions and uses related thereto |
DE10224352A1 (de) * | 2002-06-01 | 2003-12-11 | Mueller Schulte Detlef | Thermosensitive Polymerträger mit veränderbarer physikalischer Struktur für die biochemische Analytik, Diagnostik und Therapie |
CN1415303A (zh) * | 2002-10-24 | 2003-05-07 | 成都浦泓生物科技开发有限公司 | 丹七缓释制剂和制备方法及其在血管性痴呆中的医学应用 |
US20040191334A1 (en) * | 2003-03-24 | 2004-09-30 | Pang-Chui Shaw | Use of transhinone derivates as cholinesterase inhibitors in treating related diseases |
CN1631364A (zh) * | 2003-12-24 | 2005-06-29 | 昆明希捷医药研发有限公司 | 丹参酮ⅱa在制药中的应用 |
CN102579460B (zh) * | 2003-12-30 | 2015-04-29 | 麦仁斯有限公司 | 用增强代谢活性的丹参衍生物治疗肥胖和代谢综合症 |
CA2561266A1 (en) * | 2004-03-29 | 2005-10-20 | Inotek Pharmaceuticals Corporation | Pyridyl-substituted porphyrin compounds and methods of use thereof |
US7812051B2 (en) * | 2004-08-11 | 2010-10-12 | Arqule, Inc. | Pharmaceutical compositions of β-lapachone and β-lapachone analogs with improved tumor targeting potential |
US8614228B2 (en) * | 2004-08-11 | 2013-12-24 | Arqule, Inc. | Quinone prodrug compositions and methods of use |
CA2595564C (en) * | 2005-02-16 | 2015-03-31 | Md Bioalpha Co., Ltd. | Use of .beta.-lapachone and related naphthoquinones in the treatment of amp-activated protein kinase (ampk) mediated disorders |
CN100435783C (zh) * | 2005-08-12 | 2008-11-26 | 广州市医药工业研究所 | 含丹参脂溶性成分的口服组合物 |
KR100917657B1 (ko) * | 2006-02-15 | 2009-09-18 | 주식회사 머젠스 | 산화환원 효소에 의해 nad(p)/nad(p)h비율을 조절하는 방법 |
WO2008066295A1 (en) * | 2006-11-27 | 2008-06-05 | Mazence Inc. | Pharmaceutical composition containing naphthoquinone-based compound for intestine delivery system |
WO2008066300A1 (en) * | 2006-11-27 | 2008-06-05 | Mazence Inc. | Naphthoquinone-based pharmaceutical composition for treatment or prevention of diseases involving obesity, diabetes, metabolic syndrome, neuro-degenerative diseases and mitochondria dysfunction diseases |
KR20080047959A (ko) * | 2006-11-27 | 2008-05-30 | 주식회사 엠디바이오알파 | 비만, 당뇨, 대사성 질환, 퇴행성 질환 및 미토콘드리아이상 질환의 치료 또는 예방을 위한 나프토퀴논계 약제조성물 |
WO2008066301A1 (en) * | 2006-11-27 | 2008-06-05 | Mazence Inc. | Anticancer composition containing naphthoquinone-based compound for intestine delivery system |
CN101820873A (zh) * | 2007-10-11 | 2010-09-01 | 麦仁斯有限公司 | 包含萘醌基化合物的微粉化粒子的药物组合物 |
-
2007
- 2007-06-29 KR KR1020070065690A patent/KR20080047959A/ko unknown
- 2007-06-29 KR KR1020070065198A patent/KR20080047957A/ko not_active Application Discontinuation
- 2007-06-29 KR KR1020070065163A patent/KR20080047956A/ko unknown
- 2007-10-11 KR KR1020070102470A patent/KR20080047968A/ko unknown
- 2007-10-11 KR KR1020070102478A patent/KR20080047969A/ko unknown
- 2007-10-24 KR KR1020070107041A patent/KR20080047971A/ko unknown
- 2007-10-29 KR KR1020070108641A patent/KR20080047972A/ko unknown
- 2007-11-01 KR KR1020070111183A patent/KR20080047975A/ko unknown
- 2007-11-01 KR KR1020070110747A patent/KR20080047973A/ko unknown
- 2007-11-26 EP EP07834308A patent/EP2099449A4/en not_active Withdrawn
- 2007-11-26 CN CNA2007800437473A patent/CN101600424A/zh active Pending
- 2007-11-26 EP EP07834307A patent/EP2101757A4/en not_active Withdrawn
- 2007-11-26 US US12/515,088 patent/US20100239674A1/en not_active Abandoned
- 2007-11-26 JP JP2009538338A patent/JP2010510981A/ja active Pending
- 2007-11-26 KR KR1020097010424A patent/KR20090083393A/ko not_active Application Discontinuation
- 2007-11-26 KR KR1020097010375A patent/KR20090085067A/ko not_active Application Discontinuation
- 2007-11-26 KR KR1020097010386A patent/KR20090083391A/ko not_active Application Discontinuation
- 2007-11-26 JP JP2009538339A patent/JP2010510982A/ja active Pending
- 2007-11-26 JP JP2009538341A patent/JP2010510984A/ja active Pending
- 2007-11-26 US US12/515,013 patent/US20100234453A1/en not_active Abandoned
- 2007-11-26 CN CN200780044019A patent/CN101616666A/zh active Pending
- 2007-11-26 US US12/515,015 patent/US20100255054A1/en not_active Abandoned
- 2007-11-26 KR KR1020097010384A patent/KR20090083390A/ko not_active Application Discontinuation
- 2007-11-26 US US12/515,014 patent/US20100239685A1/en not_active Abandoned
- 2007-11-26 KR KR1020097010407A patent/KR20090083392A/ko not_active Application Discontinuation
- 2007-11-26 EP EP07834303A patent/EP2094261A4/en not_active Withdrawn
- 2007-11-26 WO PCT/KR2007/006006 patent/WO2008066294A1/en active Application Filing
- 2007-11-26 JP JP2009538340A patent/JP2010510983A/ja active Pending
- 2007-11-26 EP EP07834305A patent/EP2094262A4/en not_active Withdrawn
- 2007-11-26 EP EP07834306A patent/EP2099448A4/en not_active Withdrawn
- 2007-11-26 US US12/513,577 patent/US20100062065A1/en not_active Abandoned
- 2007-11-26 CN CNA2007800438565A patent/CN101610766A/zh active Pending
- 2007-11-26 JP JP2009538337A patent/JP2010510980A/ja active Pending
-
2012
- 2012-01-13 US US13/350,419 patent/US20120114714A1/en not_active Abandoned
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2916152B2 (ja) * | 1987-10-12 | 1999-07-05 | バイオサミット リミテッド | 薬物放出速度調節型製剤 |
JP2001163769A (ja) * | 1999-03-25 | 2001-06-19 | Otsuka Pharmaceut Co Ltd | シロスタゾール製剤 |
WO2006048261A2 (en) * | 2004-11-02 | 2006-05-11 | Bayer Schering Pharma Aktiengesellschaft | Oral solid dosage forms containing a low dose of estradiol |
Non-Patent Citations (10)
Title |
---|
JPN5009001611; CHAUMEIL J C: METHODS AND FINDINGS IN EXPERIMENTAL AND CLINICAL PHARMACOLOGY V20 N3, 199804, P211-215, PROUS * |
JPN6012068878; Planta Med 72, 20061120, p.1311-1317 * |
JPN6012068879; Clin Pharm J 39, 8, 2004, p.611-613 * |
JPN6012068880; J Biomed Eng 23, 3, 200606, p.592-596 * |
JPN6012068881; The Journal of Pharmacology and Experimental Therapeutics 317, 3, 200606, p.1285-1294 * |
JPN6012068882; J Pharm Pharmaceut Sci 6, 1, 2003, p.33-66 * |
JPN6012068883; Expert Opinion on Drug Delivery 3, 5, 200609, p.583-597 * |
JPN6012068884; Journal of Controlled Release 58, 1999, p.215-222 * |
JPN6012068885; Biomaterials 16, 1995, p.1313-1318 * |
JPN6012068886; Drug Delivery 11, 2004, p.129-148 * |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2010510980A (ja) * | 2006-11-27 | 2010-04-08 | マゼンス インコーポレイテッド | 腸送達系のためのナフトキノンベース化合物を含有する医薬組成物 |
JP2011507948A (ja) * | 2007-12-31 | 2011-03-10 | マゼンス インコーポレイテッド | 心臓病の治療および予防用の医薬組成物 |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2010510981A (ja) | 腸送達系のためのフェナントレンキノンベース化合物を含有する医薬組成物 | |
TWI706793B (zh) | 包含紫杉烷之非晶形固體分散體、包含其之錠劑及其等之製備方法 | |
WO2008136642A1 (en) | Naphthoquinone-based pharmaceutical composition for treatment or prevention of diseases involving obesity, diabetes, metabolic syndrome, neuro-degenerative diseases and mitochondria dysfunction diseases | |
US20160303102A1 (en) | Process for the production of drug formulations for oral administration | |
BRPI0414000B1 (pt) | composição farmacêutica sólida oral de liberação prolongada contendo tacrolimus na forma de uma dispersão sólida, forma de dosagem, e, uso da composição farmacêutica | |
JP2011500557A (ja) | ナフトキノン系化合物の微粒化粒子を含有する医薬組成物 | |
BR112017018533B1 (pt) | Composição que compreende uma dispersão sólida de ospemifeno e seu método de preparação | |
KR20100017109A (ko) | 지프라시돈 제제 | |
US20140154319A1 (en) | Pharmaceutical composition for the treatment and prevention of cardiac disease | |
WO2008066301A1 (en) | Anticancer composition containing naphthoquinone-based compound for intestine delivery system | |
KR102197465B1 (ko) | 디메틸푸마르산염을 함유한 장용성 정제 | |
US20090124680A1 (en) | Use of prodrug composition containing naphthoquinone-based compound for manufacture of medicament for treatment or prevention of diseases involving metabolic syndrome | |
WO2008066295A1 (en) | Pharmaceutical composition containing naphthoquinone-based compound for intestine delivery system | |
US20110311625A1 (en) | Solid dosage forms of fenofibrate | |
JP2010509400A (ja) | 経口処方組成物 | |
WO2008066298A1 (en) | Compound for treatment or prevention of prostate-related diseases and pharmaceutical composition of colon delivery system containing the same | |
JP2011507949A (ja) | 腎臓病を処置及び予防するための薬学的組成物 | |
WO2008066296A1 (en) | Pharmaceutical composition containing phenanthrenequinone-based compound for intestine delivery system | |
WO2008066300A1 (en) | Naphthoquinone-based pharmaceutical composition for treatment or prevention of diseases involving obesity, diabetes, metabolic syndrome, neuro-degenerative diseases and mitochondria dysfunction diseases | |
JP5365949B2 (ja) | 低用量ラモセトロン含有口腔内崩壊錠 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20101118 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130115 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130408 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130604 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130820 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130827 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20130918 |
|
A602 | Written permission of extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A602 Effective date: 20130926 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20140304 |