TWI636053B - 經[1,2,4]三唑[1,5-a]吡啶基取代之吲哚化合物 - Google Patents

Info

Publication number

TWI636053B

TWI636053B TW106121570A TW106121570A TWI636053B TW I636053 B TWI636053 B TW I636053B TW 106121570 A TW106121570 A TW 106121570A TW 106121570 A TW106121570 A TW 106121570A TW I636053 B TWI636053 B TW I636053B

Authority

TW

Taiwan

Prior art keywords

alkyl

triazole

isopropyl

hexahydropyridin

methyl

Prior art date

2016-06-29

Links

• Espacenet
• Global Dossier
• Discuss

• -1 Anthracene compound Chemical group 0.000 title claims description 1581
• MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Natural products C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 303
• 150000003839 salts Chemical class 0.000 claims abstract description 85
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 26
• 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 17
• 238000011282 treatment Methods 0.000 claims abstract description 15
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 202
• 125000000217 alkyl group Chemical group 0.000 claims description 129
• 125000003709 fluoroalkyl group Chemical group 0.000 claims description 101
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 87
• 125000004966 cyanoalkyl group Chemical group 0.000 claims description 65
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 53
• 125000002757 morpholinyl group Chemical group 0.000 claims description 53
• 229910052757 nitrogen Inorganic materials 0.000 claims description 52
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 48
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 46
• 125000003566 oxetanyl group Chemical group 0.000 claims description 39
• 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 39
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 36
• 229910052801 chlorine Inorganic materials 0.000 claims description 34
• 125000001425 triazolyl group Chemical group 0.000 claims description 34
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 30
• 125000002393 azetidinyl group Chemical group 0.000 claims description 29
• 229910052739 hydrogen Inorganic materials 0.000 claims description 29
• 229910052731 fluorine Inorganic materials 0.000 claims description 28
• 125000000335 thiazolyl group Chemical group 0.000 claims description 28
• 125000002883 imidazolyl group Chemical group 0.000 claims description 27
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 26
• 125000004076 pyridyl group Chemical group 0.000 claims description 24
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 22
• 229910052799 carbon Inorganic materials 0.000 claims description 20
• 125000002971 oxazolyl group Chemical group 0.000 claims description 20
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 20
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 19
• 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 18
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 18
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 18
• 125000001113 thiadiazolyl group Chemical group 0.000 claims description 18
• 125000001424 substituent group Chemical group 0.000 claims description 17
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 17
• 201000006417 multiple sclerosis Diseases 0.000 claims description 16
• 125000002541 furyl group Chemical group 0.000 claims description 14
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 14
• 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims description 13
• 125000004428 fluoroalkoxy group Chemical group 0.000 claims description 13
• IWELDVXSEVIIGI-UHFFFAOYSA-N piperazin-2-one Chemical compound O=C1CNCCN1 IWELDVXSEVIIGI-UHFFFAOYSA-N 0.000 claims description 13
• 125000004965 chloroalkyl group Chemical group 0.000 claims description 12
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 12
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 12
• 239000003937 drug carrier Substances 0.000 claims description 12
• 125000004432 carbon atom Chemical group C* 0.000 claims description 11
• 125000001041 indolyl group Chemical group 0.000 claims description 11
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 10
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 10
• 201000000596 systemic lupus erythematosus Diseases 0.000 claims description 9
• 125000004799 bromophenyl group Chemical group 0.000 claims description 7
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 7
• 238000004519 manufacturing process Methods 0.000 claims description 7
• 125000001715 oxadiazolyl group Chemical group 0.000 claims description 7
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 7
• 206010039073 rheumatoid arthritis Diseases 0.000 claims description 7
• 125000001544 thienyl group Chemical group 0.000 claims description 7
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
• 208000037976 chronic inflammation Diseases 0.000 claims description 5
• 208000037893 chronic inflammatory disorder Diseases 0.000 claims description 5
• 239000001257 hydrogen Substances 0.000 claims description 5
• FFSJPOPLSWBGQY-UHFFFAOYSA-N triazol-4-one Chemical group O=C1C=NN=N1 FFSJPOPLSWBGQY-UHFFFAOYSA-N 0.000 claims description 5
• 108010060825 Toll-Like Receptor 7 Proteins 0.000 claims description 4
• 108010060752 Toll-Like Receptor 8 Proteins 0.000 claims description 4
• 102000008235 Toll-Like Receptor 9 Human genes 0.000 claims description 4
• 108010060818 Toll-Like Receptor 9 Proteins 0.000 claims description 4
• 125000000532 dioxanyl group Chemical group 0.000 claims description 4
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
• 125000006431 methyl cyclopropyl group Chemical group 0.000 claims description 4
• 238000006467 substitution reaction Methods 0.000 claims description 4
• HUTNOYOBQPAKIA-UHFFFAOYSA-N 1h-pyrazin-2-one Chemical compound OC1=CN=CC=N1 HUTNOYOBQPAKIA-UHFFFAOYSA-N 0.000 claims description 3
• 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 3
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
• 125000005053 dihydropyrimidinyl group Chemical group N1(CN=CC=C1)* 0.000 claims description 3
• 125000002632 imidazolidinyl group Chemical group 0.000 claims description 3
• VSEAAEQOQBMPQF-UHFFFAOYSA-N morpholin-3-one Chemical compound O=C1COCCN1 VSEAAEQOQBMPQF-UHFFFAOYSA-N 0.000 claims description 3
• 125000001624 naphthyl group Chemical group 0.000 claims description 3
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
• 125000000160 oxazolidinyl group Chemical group 0.000 claims description 3
• XUWHAWMETYGRKB-UHFFFAOYSA-N piperidin-2-one Chemical compound O=C1CCCCN1 XUWHAWMETYGRKB-UHFFFAOYSA-N 0.000 claims description 3
• 208000011580 syndromic disease Diseases 0.000 claims description 3
• 208000021386 Sjogren Syndrome Diseases 0.000 claims description 2
• 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
• LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical compound O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 claims description 2
• 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 2
• 102000008236 Toll-Like Receptor 7 Human genes 0.000 claims 2
• 102000008208 Toll-Like Receptor 8 Human genes 0.000 claims 2
• 125000003386 piperidinyl group Chemical group 0.000 claims 2
• HPJALMWOZYIZGE-UHFFFAOYSA-N 2-oxa-6-azaspiro[3.3]heptane Chemical group C1NCC11COC1 HPJALMWOZYIZGE-UHFFFAOYSA-N 0.000 claims 1
• SOHAVULMGIITDH-UHFFFAOYSA-N Oxaline Natural products O=C1NC23N(OC)C4=CC=CC=C4C3(C(C)(C)C=C)C=C(OC)C(=O)N2C1=CC1=CN=CN1 SOHAVULMGIITDH-UHFFFAOYSA-N 0.000 claims 1
• 150000001335 aliphatic alkanes Chemical group 0.000 claims 1
• 125000001475 halogen functional group Chemical group 0.000 claims 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
• 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 claims 1
• 238000000034 method Methods 0.000 abstract description 64
• 239000003112 inhibitor Substances 0.000 abstract description 6
• 102000002689 Toll-like receptor Human genes 0.000 abstract description 5
• 108020000411 Toll-like receptor Proteins 0.000 abstract description 5
• 230000011664 signaling Effects 0.000 abstract description 3
• 206010061218 Inflammation Diseases 0.000 abstract description 2
• 230000004054 inflammatory process Effects 0.000 abstract description 2
• LENLQGBLVGGAMF-UHFFFAOYSA-N tributyl([1,2,4]triazolo[1,5-a]pyridin-6-yl)stannane Chemical compound C1=C([Sn](CCCC)(CCCC)CCCC)C=CC2=NC=NN21 LENLQGBLVGGAMF-UHFFFAOYSA-N 0.000 description 548
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 456
• 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 description 418
• IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 194
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 153
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 107
• 235000002639 sodium chloride Nutrition 0.000 description 72
• 239000000203 mixture Substances 0.000 description 63
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 61
• 239000012071 phase Substances 0.000 description 52
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 46
• 239000011541 reaction mixture Substances 0.000 description 46
• 239000000243 solution Substances 0.000 description 43
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 41
• 235000019439 ethyl acetate Nutrition 0.000 description 41
• 125000004093 cyano group Chemical group *C#N 0.000 description 40
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 38
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 36
• 201000010099 disease Diseases 0.000 description 36
• 229910052796 boron Inorganic materials 0.000 description 33
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 33
• 239000000543 intermediate Substances 0.000 description 31
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 31
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
• 238000006243 chemical reaction Methods 0.000 description 26
• 239000000460 chlorine Substances 0.000 description 26
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 26
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
• DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 25
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 24
• 102100039390 Toll-like receptor 7 Human genes 0.000 description 22
• 239000000725 suspension Substances 0.000 description 21
• 101000669402 Homo sapiens Toll-like receptor 7 Proteins 0.000 description 20
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 20
• 239000007787 solid Substances 0.000 description 20
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
• 239000010410 layer Substances 0.000 description 19
• UFUASNAHBMBJIX-UHFFFAOYSA-N propan-1-one Chemical compound CC[C]=O UFUASNAHBMBJIX-UHFFFAOYSA-N 0.000 description 19
• 239000002904 solvent Substances 0.000 description 19
• 125000004778 2,2-difluoroethyl group Chemical group [H]C([H])(*)C([H])(F)F 0.000 description 18
• KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 17
• 238000009472 formulation Methods 0.000 description 17
• 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 description 17
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 16
• 239000012044 organic layer Substances 0.000 description 16
• FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 16
• 239000012453 solvate Substances 0.000 description 16
• JRLTTZUODKEYDH-UHFFFAOYSA-N 8-methylquinoline Chemical group C1=CN=C2C(C)=CC=CC2=C1 JRLTTZUODKEYDH-UHFFFAOYSA-N 0.000 description 15
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 15
• 239000000047 product Substances 0.000 description 15
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 15
• MWZDIEIXRBWPLG-UHFFFAOYSA-N 1-methyl-1,2,4-triazole Chemical compound CN1C=NC=N1 MWZDIEIXRBWPLG-UHFFFAOYSA-N 0.000 description 14
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 14
• ZCRZCMUDOWDGOB-UHFFFAOYSA-N ethanesulfonimidic acid Chemical compound CCS(N)(=O)=O ZCRZCMUDOWDGOB-UHFFFAOYSA-N 0.000 description 14
• WSFSSNUMVMOOMR-BJUDXGSMSA-N methanone Chemical compound O=[11CH2] WSFSSNUMVMOOMR-BJUDXGSMSA-N 0.000 description 14
• 239000003921 oil Substances 0.000 description 14
• 235000019198 oils Nutrition 0.000 description 14
• 102100033110 Toll-like receptor 8 Human genes 0.000 description 13
• 239000003814 drug Substances 0.000 description 13
• 239000000463 material Substances 0.000 description 13
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 13
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 12
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
• 239000012267 brine Substances 0.000 description 12
• HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 12
• 239000000651 prodrug Substances 0.000 description 12
• 229940002612 prodrug Drugs 0.000 description 12
• 102000005962 receptors Human genes 0.000 description 12
• 108020003175 receptors Proteins 0.000 description 12
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 11
• USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 11
• 101000800483 Homo sapiens Toll-like receptor 8 Proteins 0.000 description 11
• 241000124008 Mammalia Species 0.000 description 11
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 11
• NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 11
• 239000012141 concentrate Substances 0.000 description 11
• 235000008504 concentrate Nutrition 0.000 description 11
• 238000001514 detection method Methods 0.000 description 11
• 238000004128 high performance liquid chromatography Methods 0.000 description 11
• 125000000896 monocarboxylic acid group Chemical group 0.000 description 11
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
• 239000005695 Ammonium acetate Substances 0.000 description 10
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 10
• 235000019257 ammonium acetate Nutrition 0.000 description 10
• 229940043376 ammonium acetate Drugs 0.000 description 10
• 238000010898 silica gel chromatography Methods 0.000 description 10
• 125000005988 1,1-dioxo-thiomorpholinyl group Chemical group 0.000 description 9
• DNUTZBZXLPWRJG-UHFFFAOYSA-N 1-Piperidine carboxylic acid Chemical compound OC(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-N 0.000 description 9
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
• 238000005481 NMR spectroscopy Methods 0.000 description 9
• 229910004809 Na2 SO4 Inorganic materials 0.000 description 9
• DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
• 239000002671 adjuvant Substances 0.000 description 9
• 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 description 9
• 239000002245 particle Substances 0.000 description 9
• 239000000126 substance Substances 0.000 description 9
• 239000003039 volatile agent Substances 0.000 description 9
• DTBDAFLSBDGPEA-UHFFFAOYSA-N 3-Methylquinoline Natural products C1=CC=CC2=CC(C)=CN=C21 DTBDAFLSBDGPEA-UHFFFAOYSA-N 0.000 description 8
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
• 239000000872 buffer Substances 0.000 description 8
• PCDHSSHKDZYLLI-UHFFFAOYSA-N butan-1-one Chemical compound CCC[C]=O PCDHSSHKDZYLLI-UHFFFAOYSA-N 0.000 description 8
• 235000014113 dietary fatty acids Nutrition 0.000 description 8
• 239000003995 emulsifying agent Substances 0.000 description 8
• 239000000194 fatty acid Substances 0.000 description 8
• 229930195729 fatty acid Natural products 0.000 description 8
• 239000000796 flavoring agent Substances 0.000 description 8
• 235000013355 food flavoring agent Nutrition 0.000 description 8
• 239000007937 lozenge Substances 0.000 description 8
• JSPCTNUQYWIIOT-UHFFFAOYSA-N piperidine-1-carboxamide Chemical compound NC(=O)N1CCCCC1 JSPCTNUQYWIIOT-UHFFFAOYSA-N 0.000 description 8
• 238000002360 preparation method Methods 0.000 description 8
• 239000003755 preservative agent Substances 0.000 description 8
• GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 8
• 229940124597 therapeutic agent Drugs 0.000 description 8
• LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 8
• 239000003643 water by type Substances 0.000 description 8
• PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Substances BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 7
• 239000004480 active ingredient Substances 0.000 description 7
• 239000007864 aqueous solution Substances 0.000 description 7
• 239000003153 chemical reaction reagent Substances 0.000 description 7
• 239000012043 crude product Substances 0.000 description 7
• 150000004665 fatty acids Chemical class 0.000 description 7
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
• 239000000546 pharmaceutical excipient Substances 0.000 description 7
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
• 230000002829 reductive effect Effects 0.000 description 7
• 239000003981 vehicle Substances 0.000 description 7
• KZPYGQFFRCFCPP-UHFFFAOYSA-N 1,1'-bis(diphenylphosphino)ferrocene Chemical compound [Fe+2].C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=C[C-]1P(C=1C=CC=CC=1)C1=CC=CC=C1 KZPYGQFFRCFCPP-UHFFFAOYSA-N 0.000 description 6
• XGYCWCIGCYGQFU-UHFFFAOYSA-N 1,2-thiazolidine 1,1-dioxide Chemical compound O=S1(=O)CCCN1 XGYCWCIGCYGQFU-UHFFFAOYSA-N 0.000 description 6
• SZCSQMWKHQABGW-UHFFFAOYSA-N 1-methylpyrrolidine-3-carbaldehyde Chemical compound CN1CCC(C=O)C1 SZCSQMWKHQABGW-UHFFFAOYSA-N 0.000 description 6
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 6
• 229920000858 Cyclodextrin Polymers 0.000 description 6
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
• 239000004698 Polyethylene Substances 0.000 description 6
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
• VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 6
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
• 230000037396 body weight Effects 0.000 description 6
• 238000001816 cooling Methods 0.000 description 6
• 239000013058 crude material Substances 0.000 description 6
• AUQDITHEDVOTCU-UHFFFAOYSA-N cyclopropyl cyanide Chemical compound N#CC1CC1 AUQDITHEDVOTCU-UHFFFAOYSA-N 0.000 description 6
• 239000003085 diluting agent Substances 0.000 description 6
• 150000002148 esters Chemical class 0.000 description 6
• 235000019441 ethanol Nutrition 0.000 description 6
• 235000003599 food sweetener Nutrition 0.000 description 6
• 208000027866 inflammatory disease Diseases 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 6
• 230000036961 partial effect Effects 0.000 description 6
• 230000002062 proliferating effect Effects 0.000 description 6
• 229910052938 sodium sulfate Inorganic materials 0.000 description 6
• 235000011152 sodium sulphate Nutrition 0.000 description 6
• 239000007858 starting material Substances 0.000 description 6
• 239000003765 sweetening agent Substances 0.000 description 6
• 238000004704 ultra performance liquid chromatography Methods 0.000 description 6
• 239000000080 wetting agent Substances 0.000 description 6
• 125000006583 (C1-C3) haloalkyl group Chemical group 0.000 description 5
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 5
• WRXAOKJBSUKRKX-UHFFFAOYSA-N 4-(3-propan-2-yl-1H-indol-5-yl)piperidine-1-carboxylic acid Chemical compound CC(C)C1=CNC2=C1C=C(C=C2)C3CCN(CC3)C(=O)O WRXAOKJBSUKRKX-UHFFFAOYSA-N 0.000 description 5
• NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical group C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 5
• FBNRLQRIMLEPOY-UHFFFAOYSA-N 5-bromo-3-propan-2-yl-1h-indole Chemical compound C1=C(Br)C=C2C(C(C)C)=CNC2=C1 FBNRLQRIMLEPOY-UHFFFAOYSA-N 0.000 description 5
• PZKFSRWSQOQYNR-UHFFFAOYSA-N 5-methyl-1h-1,2,4-triazole Chemical compound CC1=NC=NN1 PZKFSRWSQOQYNR-UHFFFAOYSA-N 0.000 description 5
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
• JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 description 5
• BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 5
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
• 206010028980 Neoplasm Diseases 0.000 description 5
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 5
• 239000013543 active substance Substances 0.000 description 5
• 125000003545 alkoxy group Chemical group 0.000 description 5
• DQPBABKTKYNPMH-UHFFFAOYSA-N amino hydrogen sulfate Chemical compound NOS(O)(=O)=O DQPBABKTKYNPMH-UHFFFAOYSA-N 0.000 description 5
• 239000007900 aqueous suspension Substances 0.000 description 5
• 239000002775 capsule Substances 0.000 description 5
• 239000003795 chemical substances by application Substances 0.000 description 5
• 239000007859 condensation product Substances 0.000 description 5
• 208000035475 disorder Diseases 0.000 description 5
• 230000000694 effects Effects 0.000 description 5
• 239000000839 emulsion Substances 0.000 description 5
• 208000015181 infectious disease Diseases 0.000 description 5
• 230000002401 inhibitory effect Effects 0.000 description 5
• 238000002156 mixing Methods 0.000 description 5
• 231100000252 nontoxic Toxicity 0.000 description 5
• 230000003000 nontoxic effect Effects 0.000 description 5
• 239000000843 powder Substances 0.000 description 5
• HNJBEVLQSNELDL-UHFFFAOYSA-N pyrrolidin-2-one Chemical compound O=C1CCCN1 HNJBEVLQSNELDL-UHFFFAOYSA-N 0.000 description 5
• 239000003381 stabilizer Substances 0.000 description 5
• RQCNHUCCQJMSRG-UHFFFAOYSA-N tert-butyl piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1 RQCNHUCCQJMSRG-UHFFFAOYSA-N 0.000 description 5
• PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 4
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
• NDOVLWQBFFJETK-UHFFFAOYSA-N 1,4-thiazinane 1,1-dioxide Chemical compound O=S1(=O)CCNCC1 NDOVLWQBFFJETK-UHFFFAOYSA-N 0.000 description 4
• DOJZSEYEQKWUSI-UHFFFAOYSA-N 1-methylcyclopropane-1-carbaldehyde Chemical compound O=CC1(C)CC1 DOJZSEYEQKWUSI-UHFFFAOYSA-N 0.000 description 4
• GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
• KZMQZFPRPILIHO-UHFFFAOYSA-N 2-(methylamino)acetaldehyde Chemical compound CNCC=O KZMQZFPRPILIHO-UHFFFAOYSA-N 0.000 description 4
• LZPWAYBEOJRFAX-UHFFFAOYSA-N 4,4,5,5-tetramethyl-1,3,2$l^{2}-dioxaborolane Chemical compound CC1(C)O[B]OC1(C)C LZPWAYBEOJRFAX-UHFFFAOYSA-N 0.000 description 4
• DPBWFNDFMCCGGJ-UHFFFAOYSA-N 4-Piperidine carboxamide Chemical compound NC(=O)C1CCNCC1 DPBWFNDFMCCGGJ-UHFFFAOYSA-N 0.000 description 4
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
• VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
• 206010009900 Colitis ulcerative Diseases 0.000 description 4
• 201000005569 Gout Diseases 0.000 description 4
• 208000034578 Multiple myelomas Diseases 0.000 description 4
• 208000002193 Pain Diseases 0.000 description 4
• 235000019483 Peanut oil Nutrition 0.000 description 4
• 206010035226 Plasma cell myeloma Diseases 0.000 description 4
• 239000002202 Polyethylene glycol Substances 0.000 description 4
• 201000004681 Psoriasis Diseases 0.000 description 4
• 206010063837 Reperfusion injury Diseases 0.000 description 4
• 208000006011 Stroke Diseases 0.000 description 4
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
• 201000006704 Ulcerative Colitis Diseases 0.000 description 4
• 125000005083 alkoxyalkoxy group Chemical group 0.000 description 4
• 239000003963 antioxidant agent Substances 0.000 description 4
• 235000006708 antioxidants Nutrition 0.000 description 4
• 230000008901 benefit Effects 0.000 description 4
• KVNRLNFWIYMESJ-UHFFFAOYSA-N butyronitrile Chemical compound CCCC#N KVNRLNFWIYMESJ-UHFFFAOYSA-N 0.000 description 4
• 150000001721 carbon Chemical group 0.000 description 4
• 229920002678 cellulose Polymers 0.000 description 4
• WMSPXQIQBQAWLL-UHFFFAOYSA-N cyclopropanesulfonamide Chemical compound NS(=O)(=O)C1CC1 WMSPXQIQBQAWLL-UHFFFAOYSA-N 0.000 description 4
• ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 4
• 239000002270 dispersing agent Substances 0.000 description 4
• 229940079593 drug Drugs 0.000 description 4
• 239000008187 granular material Substances 0.000 description 4
• 125000005843 halogen group Chemical group 0.000 description 4
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 4
• 125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 description 4
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 4
• BBNYLDSWVXSNOQ-UHFFFAOYSA-N oxolane-2-carbaldehyde Chemical compound O=CC1CCCO1 BBNYLDSWVXSNOQ-UHFFFAOYSA-N 0.000 description 4
• 230000036407 pain Effects 0.000 description 4
• PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 4
• 239000000312 peanut oil Substances 0.000 description 4
• 239000003208 petroleum Substances 0.000 description 4
• 229920003023 plastic Polymers 0.000 description 4
• 239000004033 plastic Substances 0.000 description 4
• 229920001223 polyethylene glycol Polymers 0.000 description 4
• 229910000160 potassium phosphate Inorganic materials 0.000 description 4
• 235000011009 potassium phosphates Nutrition 0.000 description 4
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
• 235000017557 sodium bicarbonate Nutrition 0.000 description 4
• 235000010265 sodium sulphite Nutrition 0.000 description 4
• VNFWTIYUKDMAOP-UHFFFAOYSA-N sphos Chemical group COC1=CC=CC(OC)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 VNFWTIYUKDMAOP-UHFFFAOYSA-N 0.000 description 4
• 230000001225 therapeutic effect Effects 0.000 description 4
• AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 4
• SMSJFCUXEVOWLT-UHFFFAOYSA-N (2-amino-4-methylpyridin-3-yl)methanol Chemical compound CC1=CC=NC(N)=C1CO SMSJFCUXEVOWLT-UHFFFAOYSA-N 0.000 description 3
• ONIFNICATWBCHW-UHFFFAOYSA-N 1,3-dimethyl-1,2,4-triazole Chemical compound CC=1N=CN(C)N=1 ONIFNICATWBCHW-UHFFFAOYSA-N 0.000 description 3
• BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 3
• IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 3
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 3
• OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 3
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 3
• FZIIBDOXPQOKBP-UHFFFAOYSA-N 2-methyloxetane Chemical compound CC1CCO1 FZIIBDOXPQOKBP-UHFFFAOYSA-N 0.000 description 3
• WWJXARCCHPSXNV-UHFFFAOYSA-N 4-(2-bromo-3-propan-2-yl-1H-indol-5-yl)piperidine-1-carboxylic acid Chemical compound CC(C)C1=C(NC2=C1C=C(C=C2)C3CCN(CC3)C(=O)O)Br WWJXARCCHPSXNV-UHFFFAOYSA-N 0.000 description 3
• VXWVFZFZYXOBTA-UHFFFAOYSA-N 5-bromo-1h-indole Chemical group BrC1=CC=C2NC=CC2=C1 VXWVFZFZYXOBTA-UHFFFAOYSA-N 0.000 description 3
• OQLZINXFSUDMHM-UHFFFAOYSA-N Acetamidine Chemical compound CC(N)=N OQLZINXFSUDMHM-UHFFFAOYSA-N 0.000 description 3
• 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 3
• 201000006474 Brain Ischemia Diseases 0.000 description 3
• 206010008120 Cerebral ischaemia Diseases 0.000 description 3
• XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 3
• 208000011231 Crohn disease Diseases 0.000 description 3
• IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 3
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
• 241000282412 Homo Species 0.000 description 3
• 206010020751 Hypersensitivity Diseases 0.000 description 3
• 208000022559 Inflammatory bowel disease Diseases 0.000 description 3
• 102000019223 Interleukin-1 receptor Human genes 0.000 description 3
• 108050006617 Interleukin-1 receptor Proteins 0.000 description 3
• 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 3
• 208000031671 Large B-Cell Diffuse Lymphoma Diseases 0.000 description 3
• 241000699670 Mus sp. Species 0.000 description 3
• ZSXGLVDWWRXATF-UHFFFAOYSA-N N,N-dimethylformamide dimethyl acetal Chemical compound COC(OC)N(C)C ZSXGLVDWWRXATF-UHFFFAOYSA-N 0.000 description 3
• LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Substances IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 3
• 229910019142 PO4 Inorganic materials 0.000 description 3
• 229910002666 PdCl2 Inorganic materials 0.000 description 3
• 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 3
• 206010037660 Pyrexia Diseases 0.000 description 3
• 206010040047 Sepsis Diseases 0.000 description 3
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
• QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 3
• 241000700605 Viruses Species 0.000 description 3
• 125000001931 aliphatic group Chemical group 0.000 description 3
• 208000026935 allergic disease Diseases 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 206010003246 arthritis Diseases 0.000 description 3
• WXNOJTUTEXAZLD-UHFFFAOYSA-L benzonitrile;dichloropalladium Chemical compound Cl[Pd]Cl.N#CC1=CC=CC=C1.N#CC1=CC=CC=C1 WXNOJTUTEXAZLD-UHFFFAOYSA-L 0.000 description 3
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
• 201000011510 cancer Diseases 0.000 description 3
• 239000000969 carrier Substances 0.000 description 3
• 235000010980 cellulose Nutrition 0.000 description 3
• 239000001913 cellulose Substances 0.000 description 3
• 206010008118 cerebral infarction Diseases 0.000 description 3
• 239000003086 colorant Substances 0.000 description 3
• 206010012818 diffuse large B-cell lymphoma Diseases 0.000 description 3
• 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 3
• 239000003925 fat Substances 0.000 description 3
• 235000019197 fats Nutrition 0.000 description 3
• 239000000706 filtrate Substances 0.000 description 3
• 125000001153 fluoro group Chemical group F* 0.000 description 3
• 239000007903 gelatin capsule Substances 0.000 description 3
• 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 3
• 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 3
• 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 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 description 3
• 210000000987 immune system Anatomy 0.000 description 3
• 230000028709 inflammatory response Effects 0.000 description 3
• 239000004615 ingredient Substances 0.000 description 3
• 239000008101 lactose Substances 0.000 description 3
• 235000010445 lecithin Nutrition 0.000 description 3
• 239000000787 lecithin Substances 0.000 description 3
• 229940067606 lecithin Drugs 0.000 description 3
• 229940057995 liquid paraffin Drugs 0.000 description 3
• 206010025135 lupus erythematosus Diseases 0.000 description 3
• 235000019359 magnesium stearate Nutrition 0.000 description 3
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
• 235000019341 magnesium sulphate Nutrition 0.000 description 3
• 239000002609 medium Substances 0.000 description 3
• 239000004530 micro-emulsion Substances 0.000 description 3
• 208000010125 myocardial infarction Diseases 0.000 description 3
• 230000004770 neurodegeneration Effects 0.000 description 3
• 208000015122 neurodegenerative disease Diseases 0.000 description 3
• 239000000346 nonvolatile oil Substances 0.000 description 3
• 239000004006 olive oil Substances 0.000 description 3
• 235000008390 olive oil Nutrition 0.000 description 3
• 210000000056 organ Anatomy 0.000 description 3
• CEEBYUQSOKERJL-UHFFFAOYSA-N oxane 1H-pyrrole Chemical compound O1CCCCC1.N1C=CC=C1 CEEBYUQSOKERJL-UHFFFAOYSA-N 0.000 description 3
• 125000004430 oxygen atom Chemical group O* 0.000 description 3
• 239000000123 paper Substances 0.000 description 3
• 239000001267 polyvinylpyrrolidone Substances 0.000 description 3
• 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 3
• 230000002335 preservative effect Effects 0.000 description 3
• 239000000377 silicon dioxide Substances 0.000 description 3
• QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 3
• 239000011780 sodium chloride Substances 0.000 description 3
• 238000003756 stirring Methods 0.000 description 3
• 239000000375 suspending agent Substances 0.000 description 3
• 238000003786 synthesis reaction Methods 0.000 description 3
• 239000003826 tablet Substances 0.000 description 3
• 210000001519 tissue Anatomy 0.000 description 3
• TWMVQSMNUYDEHY-UHFFFAOYSA-N (2-amino-5-bromo-4-methylpyridin-3-yl)methanol Chemical compound NC1=NC=C(C(=C1CO)C)Br TWMVQSMNUYDEHY-UHFFFAOYSA-N 0.000 description 2
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 description 2
• WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 2
• ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 2
• QUWHGSSMZMPEGW-UHFFFAOYSA-N 1-(trifluoromethyl)cyclopropane-1-carbaldehyde Chemical compound FC(F)(F)C1(C=O)CC1 QUWHGSSMZMPEGW-UHFFFAOYSA-N 0.000 description 2
• IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
• LKIYWJKEOOFVCV-UHFFFAOYSA-N 1-methylpiperidine-4-carbaldehyde Chemical compound CN1CCC(C=O)CC1 LKIYWJKEOOFVCV-UHFFFAOYSA-N 0.000 description 2
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• ALEMFNFOEILZAB-UHFFFAOYSA-N 1-pyrazin-2-ylcyclopropane-1-carbaldehyde Chemical compound O=CC1(CC1)C1=CN=CC=N1 ALEMFNFOEILZAB-UHFFFAOYSA-N 0.000 description 2
• IQBFNXYAKGOFOB-UHFFFAOYSA-N 2,2,3,3-tetramethylcyclopropane-1-carbaldehyde Chemical compound CC1(C)C(C=O)C1(C)C IQBFNXYAKGOFOB-UHFFFAOYSA-N 0.000 description 2
• 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 2
• ICSNLGPSRYBMBD-UHFFFAOYSA-N 2-aminopyridine Chemical compound NC1=CC=CC=N1 ICSNLGPSRYBMBD-UHFFFAOYSA-N 0.000 description 2
• IZHVBANLECCAGF-UHFFFAOYSA-N 2-hydroxy-3-(octadecanoyloxy)propyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)COC(=O)CCCCCCCCCCCCCCCCC IZHVBANLECCAGF-UHFFFAOYSA-N 0.000 description 2
• AJSUOFFQMSMEOJ-UHFFFAOYSA-N 2-morpholin-4-ylethyl piperidine-1-carboxylate Chemical compound O=C(OCCN1CCOCC1)N1CCCCC1 AJSUOFFQMSMEOJ-UHFFFAOYSA-N 0.000 description 2
• LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 2
• WUCNXNGEHMFXNQ-UHFFFAOYSA-N 2h-pyridine-1-carboximidamide Chemical compound NC(=N)N1CC=CC=C1 WUCNXNGEHMFXNQ-UHFFFAOYSA-N 0.000 description 2
• QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 2
• DUQGFIKXKISULR-UHFFFAOYSA-N 3-methyloxetane-3-carbaldehyde Chemical compound O=CC1(C)COC1 DUQGFIKXKISULR-UHFFFAOYSA-N 0.000 description 2
• IINWNNKUXOSZAI-UHFFFAOYSA-N 4-(2-hydroxyethyl)piperazine-1-carbaldehyde Chemical compound OCCN1CCN(C=O)CC1 IINWNNKUXOSZAI-UHFFFAOYSA-N 0.000 description 2
• NVPIPJCKFHBQCN-UHFFFAOYSA-N 4-(3-propan-2-yl-1H-indol-5-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid Chemical compound CC(C)c1c[nH]c2ccc(cc12)C1=CCN(CC1)C(O)=O NVPIPJCKFHBQCN-UHFFFAOYSA-N 0.000 description 2
• JQTMGOLZSBTZMS-UHFFFAOYSA-N 4-methylpiperazine-1-carbaldehyde Chemical compound CN1CCN(C=O)CC1 JQTMGOLZSBTZMS-UHFFFAOYSA-N 0.000 description 2
• UGRNAAOSAUZBIT-UHFFFAOYSA-N 4-propan-2-ylpiperazine-1-carbaldehyde Chemical compound CC(C)N1CCN(C=O)CC1 UGRNAAOSAUZBIT-UHFFFAOYSA-N 0.000 description 2
• PPKZVDHYJDJXLD-UHFFFAOYSA-N 4-propylpiperazine-1-carbaldehyde Chemical compound CCCN1CCN(C=O)CC1 PPKZVDHYJDJXLD-UHFFFAOYSA-N 0.000 description 2
• QBWQJPDLLSPPMO-UHFFFAOYSA-N 4-pyridin-4-ylpiperazine-1-carbaldehyde Chemical compound C1CN(C=O)CCN1C1=CC=NC=C1 QBWQJPDLLSPPMO-UHFFFAOYSA-N 0.000 description 2
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
• YWXPPKJKSSLZOD-UHFFFAOYSA-N 5-(methoxymethyl)-1h-1,2,4-triazole Chemical compound COCC=1N=CNN=1 YWXPPKJKSSLZOD-UHFFFAOYSA-N 0.000 description 2
• YAVKJNIMFGZBSY-UHFFFAOYSA-N 5-bromo-3,4-dimethylpyridin-2-amine Chemical compound CC1=C(C)C(N)=NC=C1Br YAVKJNIMFGZBSY-UHFFFAOYSA-N 0.000 description 2
• QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 2
• OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 2
• 208000030507 AIDS Diseases 0.000 description 2
• 244000215068 Acacia senegal Species 0.000 description 2
• 208000031261 Acute myeloid leukaemia Diseases 0.000 description 2
• 208000024827 Alzheimer disease Diseases 0.000 description 2
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 201000001320 Atherosclerosis Diseases 0.000 description 2
• 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 description 2
• 208000020084 Bone disease Diseases 0.000 description 2
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 2
• OTWNFWUIJUSZAW-UHFFFAOYSA-N CCCN1CCCC(C(=O)N(CC)CC)C1 Chemical compound CCCN1CCCC(C(=O)N(CC)CC)C1 OTWNFWUIJUSZAW-UHFFFAOYSA-N 0.000 description 2
• 206010006895 Cachexia Diseases 0.000 description 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 2
• 208000010833 Chronic myeloid leukaemia Diseases 0.000 description 2
• 206010048843 Cytomegalovirus chorioretinitis Diseases 0.000 description 2
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
• 206010016207 Familial Mediterranean fever Diseases 0.000 description 2
• 108010010803 Gelatin Proteins 0.000 description 2
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
• 206010018634 Gouty Arthritis Diseases 0.000 description 2
• 208000009329 Graft vs Host Disease Diseases 0.000 description 2
• 229920000084 Gum arabic Polymers 0.000 description 2
• 208000031886 HIV Infections Diseases 0.000 description 2
• 208000037357 HIV infectious disease Diseases 0.000 description 2
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
• 102000015696 Interleukins Human genes 0.000 description 2
• 108010063738 Interleukins Proteins 0.000 description 2
• 208000007766 Kaposi sarcoma Diseases 0.000 description 2
• 239000005909 Kieselgur Substances 0.000 description 2
• 208000005777 Lupus Nephritis Diseases 0.000 description 2
• 206010027480 Metastatic malignant melanoma Diseases 0.000 description 2
• 241001465754 Metazoa Species 0.000 description 2
• 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
• 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 description 2
• 208000033776 Myeloid Acute Leukemia Diseases 0.000 description 2
• 102000010168 Myeloid Differentiation Factor 88 Human genes 0.000 description 2
• 108010077432 Myeloid Differentiation Factor 88 Proteins 0.000 description 2
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
• AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 2
• 206010029113 Neovascularisation Diseases 0.000 description 2
• MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 2
• 239000005642 Oleic acid Substances 0.000 description 2
• ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 2
• 208000001132 Osteoporosis Diseases 0.000 description 2
• 208000018737 Parkinson disease Diseases 0.000 description 2
• 101150003085 Pdcl gene Proteins 0.000 description 2
• 201000011152 Pemphigus Diseases 0.000 description 2
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
• 229920003171 Poly (ethylene oxide) Polymers 0.000 description 2
• QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 2
• 108050003267 Prostaglandin G/H synthase 2 Proteins 0.000 description 2
• 206010040070 Septic Shock Diseases 0.000 description 2
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
• 229920002472 Starch Polymers 0.000 description 2
• 235000021355 Stearic acid Nutrition 0.000 description 2
• 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 2
• 229930006000 Sucrose Natural products 0.000 description 2
• 229920001615 Tragacanth Polymers 0.000 description 2
• 239000007983 Tris buffer Substances 0.000 description 2
• 108060008683 Tumor Necrosis Factor Receptor Proteins 0.000 description 2
• 208000033559 Waldenström macroglobulinemia Diseases 0.000 description 2
• 235000010489 acacia gum Nutrition 0.000 description 2
• 239000000205 acacia gum Substances 0.000 description 2
• DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
• OFLXLNCGODUUOT-UHFFFAOYSA-N acetohydrazide Chemical compound C\C(O)=N\N OFLXLNCGODUUOT-UHFFFAOYSA-N 0.000 description 2
• 239000002253 acid Substances 0.000 description 2
• 230000004913 activation Effects 0.000 description 2
• 239000000853 adhesive Substances 0.000 description 2
• 230000001070 adhesive effect Effects 0.000 description 2
• 235000010443 alginic acid Nutrition 0.000 description 2
• 229920000615 alginic acid Polymers 0.000 description 2
• 239000000783 alginic acid Substances 0.000 description 2
• 229960001126 alginic acid Drugs 0.000 description 2
• 150000004781 alginic acids Chemical class 0.000 description 2
• 230000029936 alkylation Effects 0.000 description 2
• 238000005804 alkylation reaction Methods 0.000 description 2
• 230000007815 allergy Effects 0.000 description 2
• 125000003368 amide group Chemical group 0.000 description 2
• 150000001412 amines Chemical class 0.000 description 2
• 230000002491 angiogenic effect Effects 0.000 description 2
• 208000006673 asthma Diseases 0.000 description 2
• 125000004429 atom Chemical group 0.000 description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
• 230000001363 autoimmune Effects 0.000 description 2
• 208000037979 autoimmune inflammatory disease Diseases 0.000 description 2
• PBIUUJCEMUAWJJ-UHFFFAOYSA-N azetidine-3-carbonitrile Chemical compound N#CC1CNC1 PBIUUJCEMUAWJJ-UHFFFAOYSA-N 0.000 description 2
• WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 2
• 229960004853 betadex Drugs 0.000 description 2
• 210000004204 blood vessel Anatomy 0.000 description 2
• 208000019664 bone resorption disease Diseases 0.000 description 2
• 125000006309 butyl amino group Chemical group 0.000 description 2
• NMJJFJNHVMGPGM-UHFFFAOYSA-N butyl formate Chemical compound CCCCOC=O NMJJFJNHVMGPGM-UHFFFAOYSA-N 0.000 description 2
• 229910000019 calcium carbonate Inorganic materials 0.000 description 2
• 239000001506 calcium phosphate Substances 0.000 description 2
• 229910000389 calcium phosphate Inorganic materials 0.000 description 2
• 235000011010 calcium phosphates Nutrition 0.000 description 2
• 239000011111 cardboard Substances 0.000 description 2
• 125000001309 chloro group Chemical group Cl* 0.000 description 2
• 229940061627 chloromethyl methyl ether Drugs 0.000 description 2
• 238000007796 conventional method Methods 0.000 description 2
• 239000006071 cream Substances 0.000 description 2
• GFBLFDSCAKHHGX-UHFFFAOYSA-N cyclobutanecarbonitrile Chemical compound N#CC1CCC1 GFBLFDSCAKHHGX-UHFFFAOYSA-N 0.000 description 2
• 125000006311 cyclobutyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
• 125000006312 cyclopentyl amino group Chemical group [H]N(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
• 208000001763 cytomegalovirus retinitis Diseases 0.000 description 2
• 230000001086 cytosolic effect Effects 0.000 description 2
• 238000011161 development Methods 0.000 description 2
• 125000000950 dibromo group Chemical group Br* 0.000 description 2
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
• 239000002552 dosage form Substances 0.000 description 2
• 230000002526 effect on cardiovascular system Effects 0.000 description 2
• 238000005516 engineering process Methods 0.000 description 2
• 125000004494 ethyl ester group Chemical group 0.000 description 2
• 235000019253 formic acid Nutrition 0.000 description 2
• 125000000524 functional group Chemical group 0.000 description 2
• 239000008273 gelatin Substances 0.000 description 2
• 229920000159 gelatin Polymers 0.000 description 2
• 235000019322 gelatine Nutrition 0.000 description 2
• 235000011852 gelatine desserts Nutrition 0.000 description 2
• 239000003292 glue Substances 0.000 description 2
• PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 2
• 229910052737 gold Inorganic materials 0.000 description 2
• 239000010931 gold Substances 0.000 description 2
• 208000024908 graft versus host disease Diseases 0.000 description 2
• 229960002706 gusperimus Drugs 0.000 description 2
• 125000001188 haloalkyl group Chemical group 0.000 description 2
• BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
• 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 2
• 150000004677 hydrates Chemical class 0.000 description 2
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
• 230000004968 inflammatory condition Effects 0.000 description 2
• 230000005764 inhibitory process Effects 0.000 description 2
• 238000002347 injection Methods 0.000 description 2
• 239000007924 injection Substances 0.000 description 2
• 208000014674 injury Diseases 0.000 description 2
• QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 2
• 239000003446 ligand Substances 0.000 description 2
• 239000000314 lubricant Substances 0.000 description 2
• CCERQOYLJJULMD-UHFFFAOYSA-M magnesium;carbanide;chloride Chemical compound [CH3-].[Mg+2].[Cl-] CCERQOYLJJULMD-UHFFFAOYSA-M 0.000 description 2
• 230000014759 maintenance of location Effects 0.000 description 2
• 208000030159 metabolic disease Diseases 0.000 description 2
• 208000021039 metastatic melanoma Diseases 0.000 description 2
• 150000004702 methyl esters Chemical class 0.000 description 2
• 239000008108 microcrystalline cellulose Substances 0.000 description 2
• 229940016286 microcrystalline cellulose Drugs 0.000 description 2
• 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
• 239000002480 mineral oil Substances 0.000 description 2
• 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
• UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 2
• 208000031225 myocardial ischemia Diseases 0.000 description 2
• IDINUJSAMVOPCM-INIZCTEOSA-N n-[(1s)-2-[4-(3-aminopropylamino)butylamino]-1-hydroxy-2-oxoethyl]-7-(diaminomethylideneamino)heptanamide Chemical compound NCCCNCCCCNC(=O)[C@H](O)NC(=O)CCCCCCN=C(N)N IDINUJSAMVOPCM-INIZCTEOSA-N 0.000 description 2
• PVXSHGDPBHNNKT-UHFFFAOYSA-N n-[3-(methoxymethyl)-4-methylpyridin-2-yl]-2,2-dimethylpropanamide Chemical compound COCC1=C(C)C=CN=C1NC(=O)C(C)(C)C PVXSHGDPBHNNKT-UHFFFAOYSA-N 0.000 description 2
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 229940042880 natural phospholipid Drugs 0.000 description 2
• 239000012299 nitrogen atmosphere Substances 0.000 description 2
• 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
• QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
• OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
• ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 2
• 201000008482 osteoarthritis Diseases 0.000 description 2
• FYCBRGMZDWYEHI-UHFFFAOYSA-N oxetane-3-carbaldehyde Chemical compound O=CC1COC1 FYCBRGMZDWYEHI-UHFFFAOYSA-N 0.000 description 2
• PXDVPPINZKNVNF-UHFFFAOYSA-N oxetane-3-carbonitrile Chemical compound N#CC1COC1 PXDVPPINZKNVNF-UHFFFAOYSA-N 0.000 description 2
• 239000001301 oxygen Substances 0.000 description 2
• 229910052760 oxygen Inorganic materials 0.000 description 2
• 238000004806 packaging method and process Methods 0.000 description 2
• MUJIDPITZJWBSW-UHFFFAOYSA-N palladium(2+) Chemical compound [Pd+2] MUJIDPITZJWBSW-UHFFFAOYSA-N 0.000 description 2
• 210000000496 pancreas Anatomy 0.000 description 2
• 244000045947 parasite Species 0.000 description 2
• 201000001976 pemphigus vulgaris Diseases 0.000 description 2
• AENADFGFGIIQCU-UHFFFAOYSA-N piperidin-3-yl piperidine-1-carboxylate Chemical compound C1CCCCN1C(=O)OC1CCCNC1 AENADFGFGIIQCU-UHFFFAOYSA-N 0.000 description 2
• KFAHXBGDNMUDSC-UHFFFAOYSA-N piperidin-4-yl piperidine-1-carboxylate Chemical compound C1CCCCN1C(=O)OC1CCNCC1 KFAHXBGDNMUDSC-UHFFFAOYSA-N 0.000 description 2
• 239000008389 polyethoxylated castor oil Substances 0.000 description 2
• 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
• 229920000053 polysorbate 80 Polymers 0.000 description 2
• 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
• 125000006239 protecting group Chemical group 0.000 description 2
• 230000002685 pulmonary effect Effects 0.000 description 2
• AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridine hydrochloride Substances [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 2
• ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 2
• 230000009467 reduction Effects 0.000 description 2
• 229920006395 saturated elastomer Polymers 0.000 description 2
• 239000008159 sesame oil Substances 0.000 description 2
• 235000011803 sesame oil Nutrition 0.000 description 2
• 230000019491 signal transduction Effects 0.000 description 2
• 239000000741 silica gel Substances 0.000 description 2
• 229910002027 silica gel Inorganic materials 0.000 description 2
• 229960002930 sirolimus Drugs 0.000 description 2
• 235000010413 sodium alginate Nutrition 0.000 description 2
• 239000000661 sodium alginate Substances 0.000 description 2
• 229940005550 sodium alginate Drugs 0.000 description 2
• 235000011069 sorbitan monooleate Nutrition 0.000 description 2
• 239000001593 sorbitan monooleate Substances 0.000 description 2
• 229940035049 sorbitan monooleate Drugs 0.000 description 2
• 239000008107 starch Substances 0.000 description 2
• 235000019698 starch Nutrition 0.000 description 2
• 239000008117 stearic acid Substances 0.000 description 2
• 239000005720 sucrose Substances 0.000 description 2
• 229960004793 sucrose Drugs 0.000 description 2
• HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 2
• 229940124530 sulfonamide Drugs 0.000 description 2
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
• 239000004094 surface-active agent Substances 0.000 description 2
• 208000024891 symptom Diseases 0.000 description 2
• QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 2
• 239000000454 talc Substances 0.000 description 2
• 229910052623 talc Inorganic materials 0.000 description 2
• 235000012222 talc Nutrition 0.000 description 2
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
• HLZKNKRTKFSKGZ-UHFFFAOYSA-N tetradecan-1-ol Chemical compound CCCCCCCCCCCCCCO HLZKNKRTKFSKGZ-UHFFFAOYSA-N 0.000 description 2
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
• 231100000419 toxicity Toxicity 0.000 description 2
• 230000001988 toxicity Effects 0.000 description 2
• 230000008736 traumatic injury Effects 0.000 description 2
• QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
• YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 2
• 102000003298 tumor necrosis factor receptor Human genes 0.000 description 2
• 235000015112 vegetable and seed oil Nutrition 0.000 description 2
• 239000008158 vegetable oil Substances 0.000 description 2
• 230000003612 virological effect Effects 0.000 description 2
• 239000001993 wax Substances 0.000 description 2
• CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 description 1
• LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
• GVJHHUAWPYXKBD-IEOSBIPESA-N (R)-alpha-Tocopherol Natural products OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 1
• SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
• VSIMNRRKKQUGMF-UHFFFAOYSA-N 1,1-dimethoxy-n-methylmethanamine Chemical compound CNC(OC)OC VSIMNRRKKQUGMF-UHFFFAOYSA-N 0.000 description 1
• IBXMKLPFLZYRQZ-UHFFFAOYSA-N 1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1C=CC(=O)C=CC1=CC=CC=C1 IBXMKLPFLZYRQZ-UHFFFAOYSA-N 0.000 description 1
• BRGDGUJGSXQUTN-UHFFFAOYSA-N 1-(2-amino-5-bromopyridin-3-yl)ethanol Chemical compound CC(O)C1=CC(Br)=CN=C1N BRGDGUJGSXQUTN-UHFFFAOYSA-N 0.000 description 1
• PZNPLUBHRSSFHT-RRHRGVEJSA-N 1-hexadecanoyl-2-octadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[C@@H](COP([O-])(=O)OCC[N+](C)(C)C)COC(=O)CCCCCCCCCCCCCCC PZNPLUBHRSSFHT-RRHRGVEJSA-N 0.000 description 1
• AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 1
• KXIXHISTUVHOCY-UHFFFAOYSA-N 1-propan-2-ylpiperidine Chemical compound CC(C)N1CCCCC1 KXIXHISTUVHOCY-UHFFFAOYSA-N 0.000 description 1
• GMKUFMYZJOPWSH-UHFFFAOYSA-N 2,2-dimethyl-n-(4-methylpyridin-2-yl)propanamide Chemical compound CC1=CC=NC(NC(=O)C(C)(C)C)=C1 GMKUFMYZJOPWSH-UHFFFAOYSA-N 0.000 description 1
• CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
• OGGAWTWALXPMSK-UHFFFAOYSA-N 2-(2-amino-5-bromopyridin-3-yl)propan-2-ol Chemical compound CC(C)(O)C1=CC(Br)=CN=C1N OGGAWTWALXPMSK-UHFFFAOYSA-N 0.000 description 1
• XIOPEJHJRPVVDJ-UHFFFAOYSA-N 2-(2-aminopyridin-3-yl)acetic acid Chemical compound NC1=NC=CC=C1CC(O)=O XIOPEJHJRPVVDJ-UHFFFAOYSA-N 0.000 description 1
• KDOAJEVCIZYWDI-UHFFFAOYSA-N 2-amino-5-bromopyridine-3-carbaldehyde Chemical compound NC1=NC=C(Br)C=C1C=O KDOAJEVCIZYWDI-UHFFFAOYSA-N 0.000 description 1
• ZPRQXVPYQGBZON-UHFFFAOYSA-N 2-bromo-1h-indole Chemical compound C1=CC=C2NC(Br)=CC2=C1 ZPRQXVPYQGBZON-UHFFFAOYSA-N 0.000 description 1
• 125000001731 2-cyanoethyl group Chemical group [H]C([H])(*)C([H])([H])C#N 0.000 description 1
• 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
• 125000005916 2-methylpentyl group Chemical group 0.000 description 1
• TWBPWBPGNQWFSJ-UHFFFAOYSA-N 2-phenylaniline Chemical group NC1=CC=CC=C1C1=CC=CC=C1 TWBPWBPGNQWFSJ-UHFFFAOYSA-N 0.000 description 1
• CHHLKRYDWZLPLS-UHFFFAOYSA-N 3-(methoxymethyl)-4-methylpyridin-2-amine Chemical compound COCC1=C(C)C=CN=C1N CHHLKRYDWZLPLS-UHFFFAOYSA-N 0.000 description 1
• OGXVXOTXEHKRIL-UHFFFAOYSA-N 3-methoxy-5-methyl-1h-1,2,4-triazole Chemical compound COC1=NNC(C)=N1 OGXVXOTXEHKRIL-UHFFFAOYSA-N 0.000 description 1
• UJQZTMFRMLEYQN-UHFFFAOYSA-N 3-methyloxane Chemical compound CC1CCCOC1 UJQZTMFRMLEYQN-UHFFFAOYSA-N 0.000 description 1
• 125000005917 3-methylpentyl group Chemical group 0.000 description 1
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
• NFBIWMFMHLPVLT-UHFFFAOYSA-N 5-bromo-3-methoxypyridin-2-amine Chemical compound COC1=CC(Br)=CN=C1N NFBIWMFMHLPVLT-UHFFFAOYSA-N 0.000 description 1
• KBLGGRWUEVCNPY-UHFFFAOYSA-N 5-bromo-3-methylpyridin-2-amine Chemical compound CC1=CC(Br)=CN=C1N KBLGGRWUEVCNPY-UHFFFAOYSA-N 0.000 description 1
• JDNCMHOKWINDKI-UHFFFAOYSA-N 5-bromo-4-methylpyridin-2-amine Chemical compound CC1=CC(N)=NC=C1Br JDNCMHOKWINDKI-UHFFFAOYSA-N 0.000 description 1
• NYMLZIFRPNYAHS-UHFFFAOYSA-N 5-phenyl-1h-1,2,4-triazole Chemical compound C1=NNC(C=2C=CC=CC=2)=N1 NYMLZIFRPNYAHS-UHFFFAOYSA-N 0.000 description 1
• 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 1
• 229920001450 Alpha-Cyclodextrin Polymers 0.000 description 1
• 239000005995 Aluminium silicate Substances 0.000 description 1
• 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
• 108010011485 Aspartame Proteins 0.000 description 1
• 241000416162 Astragalus gummifer Species 0.000 description 1
• 206010055128 Autoimmune neutropenia Diseases 0.000 description 1
• 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 description 1
• 230000003844 B-cell-activation Effects 0.000 description 1
• 208000004429 Bacillary Dysentery Diseases 0.000 description 1
• 241000894006 Bacteria Species 0.000 description 1
• 208000023328 Basedow disease Diseases 0.000 description 1
• BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
• 108010017384 Blood Proteins Proteins 0.000 description 1
• 102000004506 Blood Proteins Human genes 0.000 description 1
• 241000713704 Bovine immunodeficiency virus Species 0.000 description 1
• 239000004322 Butylated hydroxytoluene Substances 0.000 description 1
• NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
• 241000282465 Canis Species 0.000 description 1
• KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical compound NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
• 239000004215 Carbon black (E152) Substances 0.000 description 1
• 206010007572 Cardiac hypertrophy Diseases 0.000 description 1
• 208000006029 Cardiomegaly Diseases 0.000 description 1
• 206010007953 Central nervous system lymphoma Diseases 0.000 description 1
• 206010063094 Cerebral malaria Diseases 0.000 description 1
• 102000019034 Chemokines Human genes 0.000 description 1
• 108010012236 Chemokines Proteins 0.000 description 1
• 206010008909 Chronic Hepatitis Diseases 0.000 description 1
• 208000035473 Communicable disease Diseases 0.000 description 1
• 229920002261 Corn starch Polymers 0.000 description 1
• 229920002785 Croscarmellose sodium Polymers 0.000 description 1
• 108010037462 Cyclooxygenase 2 Proteins 0.000 description 1
• 102000004127 Cytokines Human genes 0.000 description 1
• 108090000695 Cytokines Proteins 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
• 108020004414 DNA Proteins 0.000 description 1
• 102000053602 DNA Human genes 0.000 description 1
• 206010012438 Dermatitis atopic Diseases 0.000 description 1
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 1
• 241000196324 Embryophyta Species 0.000 description 1
• 208000037487 Endotoxemia Diseases 0.000 description 1
• 241000713730 Equine infectious anemia virus Species 0.000 description 1
• 239000001856 Ethyl cellulose Substances 0.000 description 1
• 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 description 1
• 241000713800 Feline immunodeficiency virus Species 0.000 description 1
• 241000233866 Fungi Species 0.000 description 1
• 206010018364 Glomerulonephritis Diseases 0.000 description 1
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
• 239000004471 Glycine Substances 0.000 description 1
• 208000015023 Graves' disease Diseases 0.000 description 1
• 239000007821 HATU Substances 0.000 description 1
• 229910004373 HOAc Inorganic materials 0.000 description 1
• 208000030836 Hashimoto thyroiditis Diseases 0.000 description 1
• 206010019233 Headaches Diseases 0.000 description 1
• 208000035186 Hemolytic Autoimmune Anemia Diseases 0.000 description 1
• 208000005176 Hepatitis C Diseases 0.000 description 1
• 206010019755 Hepatitis chronic active Diseases 0.000 description 1
• 101000831496 Homo sapiens Toll-like receptor 3 Proteins 0.000 description 1
• 102000008100 Human Serum Albumin Human genes 0.000 description 1
• 108091006905 Human Serum Albumin Proteins 0.000 description 1
• 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
• 206010021143 Hypoxia Diseases 0.000 description 1
• XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
• 108091069196 IL-1 family Proteins 0.000 description 1
• 102000039996 IL-1 family Human genes 0.000 description 1
• HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 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
• 206010061598 Immunodeficiency Diseases 0.000 description 1
• 208000029462 Immunodeficiency disease Diseases 0.000 description 1
• 102000000589 Interleukin-1 Human genes 0.000 description 1
• 108010002352 Interleukin-1 Proteins 0.000 description 1
• 102000003814 Interleukin-10 Human genes 0.000 description 1
• 108090000174 Interleukin-10 Proteins 0.000 description 1
• 102000003810 Interleukin-18 Human genes 0.000 description 1
• 108090000171 Interleukin-18 Proteins 0.000 description 1
• 108090001005 Interleukin-6 Proteins 0.000 description 1
• 102000004889 Interleukin-6 Human genes 0.000 description 1
• 206010058031 Joint adhesion Diseases 0.000 description 1
• 208000003456 Juvenile Arthritis Diseases 0.000 description 1
• 206010059176 Juvenile idiopathic arthritis Diseases 0.000 description 1
• 239000004166 Lanolin Substances 0.000 description 1
• 240000007472 Leucaena leucocephala Species 0.000 description 1
• 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
• 229930195725 Mannitol Natural products 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
• QXKHYNVANLEOEG-UHFFFAOYSA-N Methoxsalen Chemical group C1=CC(=O)OC2=C1C=C1C=COC1=C2OC QXKHYNVANLEOEG-UHFFFAOYSA-N 0.000 description 1
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 1
• 208000000112 Myalgia Diseases 0.000 description 1
• WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
• 206010030113 Oedema Diseases 0.000 description 1
• 244000131316 Panax pseudoginseng Species 0.000 description 1
• 235000005035 Panax pseudoginseng ssp. pseudoginseng Nutrition 0.000 description 1
• 235000003140 Panax quinquefolius Nutrition 0.000 description 1
• 206010033645 Pancreatitis Diseases 0.000 description 1
• 229920001214 Polysorbate 60 Polymers 0.000 description 1
• 239000004372 Polyvinyl alcohol Substances 0.000 description 1
• ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 1
• NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 1
• 102000007327 Protamines Human genes 0.000 description 1
• 108010007568 Protamines Proteins 0.000 description 1
• 201000001263 Psoriatic Arthritis Diseases 0.000 description 1
• 208000036824 Psoriatic arthropathy Diseases 0.000 description 1
• 208000033464 Reiter syndrome Diseases 0.000 description 1
• 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
• 208000005074 Retroviridae Infections Diseases 0.000 description 1
• 206010039710 Scleroderma Diseases 0.000 description 1
• 229940124639 Selective inhibitor Drugs 0.000 description 1
• 208000019802 Sexually transmitted disease Diseases 0.000 description 1
• 241000607768 Shigella Species 0.000 description 1
• 206010040550 Shigella infections Diseases 0.000 description 1
• 201000010001 Silicosis Diseases 0.000 description 1
• 108020004682 Single-Stranded DNA Proteins 0.000 description 1
• DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
• NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 1
• 201000002661 Spondylitis Diseases 0.000 description 1
• 108090000190 Thrombin Proteins 0.000 description 1
• 208000007536 Thrombosis Diseases 0.000 description 1
• 206010043781 Thyroiditis chronic Diseases 0.000 description 1
• 102100024324 Toll-like receptor 3 Human genes 0.000 description 1
• 206010044248 Toxic shock syndrome Diseases 0.000 description 1
• 231100000650 Toxic shock syndrome Toxicity 0.000 description 1
• 206010048873 Traumatic arthritis Diseases 0.000 description 1
• YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
• 206010067584 Type 1 diabetes mellitus Diseases 0.000 description 1
• 208000036142 Viral infection Diseases 0.000 description 1
• WERKSKAQRVDLDW-ANOHMWSOSA-N [(2s,3r,4r,5r)-2,3,4,5,6-pentahydroxyhexyl] (z)-octadec-9-enoate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO WERKSKAQRVDLDW-ANOHMWSOSA-N 0.000 description 1
• MCGSCOLBFJQGHM-SCZZXKLOSA-N abacavir Chemical compound C=12N=CN([C@H]3C=C[C@@H](CO)C3)C2=NC(N)=NC=1NC1CC1 MCGSCOLBFJQGHM-SCZZXKLOSA-N 0.000 description 1
• 229960004748 abacavir Drugs 0.000 description 1
• 230000002159 abnormal effect Effects 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• SPEUIVXLLWOEMJ-UHFFFAOYSA-N acetaldehyde dimethyl acetal Natural products COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 1
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
• VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 1
• 230000001154 acute effect Effects 0.000 description 1
• 231100000354 acute hepatitis Toxicity 0.000 description 1
• 239000000654 additive Substances 0.000 description 1
• 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 1
• 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
• 150000001336 alkenes Chemical class 0.000 description 1
• 125000005907 alkyl ester group Chemical group 0.000 description 1
• 125000002947 alkylene group Chemical group 0.000 description 1
• 230000000172 allergic effect Effects 0.000 description 1
• 229940087168 alpha tocopherol Drugs 0.000 description 1
• HFHDHCJBZVLPGP-RWMJIURBSA-N alpha-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO HFHDHCJBZVLPGP-RWMJIURBSA-N 0.000 description 1
• 229940043377 alpha-cyclodextrin Drugs 0.000 description 1
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
• 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
• 235000012211 aluminium silicate Nutrition 0.000 description 1
• CEGOLXSVJUTHNZ-UHFFFAOYSA-K aluminium tristearate Chemical compound [Al+3].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CEGOLXSVJUTHNZ-UHFFFAOYSA-K 0.000 description 1
• 229940063655 aluminum stearate Drugs 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 230000036592 analgesia Effects 0.000 description 1
• 230000033115 angiogenesis Effects 0.000 description 1
• 229940124599 anti-inflammatory drug Drugs 0.000 description 1
• 230000001028 anti-proliverative effect Effects 0.000 description 1
• 239000003430 antimalarial agent Substances 0.000 description 1
• 239000003443 antiviral agent Substances 0.000 description 1
• 230000002917 arthritic effect Effects 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 229960005070 ascorbic acid Drugs 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 239000000605 aspartame Substances 0.000 description 1
• IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
• 235000010357 aspartame Nutrition 0.000 description 1
• 229960003438 aspartame Drugs 0.000 description 1
• 239000000305 astragalus gummifer gum Substances 0.000 description 1
• 239000012298 atmosphere Substances 0.000 description 1
• 201000008937 atopic dermatitis Diseases 0.000 description 1
• 201000005000 autoimmune gastritis Diseases 0.000 description 1
• 201000000448 autoimmune hemolytic anemia Diseases 0.000 description 1
• KVVMXWRFYAGASO-UHFFFAOYSA-N azetidine-1-carboxylic acid Chemical compound OC(=O)N1CCC1 KVVMXWRFYAGASO-UHFFFAOYSA-N 0.000 description 1
• 210000003719 b-lymphocyte Anatomy 0.000 description 1
• 210000000227 basophil cell of anterior lobe of hypophysis Anatomy 0.000 description 1
• 235000013871 bee wax Nutrition 0.000 description 1
• 239000012166 beeswax Substances 0.000 description 1
• SIKJAQJRHWYJAI-UHFFFAOYSA-N benzopyrrole Natural products C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 1
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000033228 biological regulation Effects 0.000 description 1
• 230000015572 biosynthetic process Effects 0.000 description 1
• 229920001400 block copolymer Polymers 0.000 description 1
• 238000009835 boiling Methods 0.000 description 1
• 229910000085 borane Inorganic materials 0.000 description 1
• 230000031709 bromination Effects 0.000 description 1
• 238000005893 bromination reaction Methods 0.000 description 1
• 229910052794 bromium Inorganic materials 0.000 description 1
• 230000005587 bubbling Effects 0.000 description 1
• 235000010354 butylated hydroxytoluene Nutrition 0.000 description 1
• 229940095259 butylated hydroxytoluene Drugs 0.000 description 1
• 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
• 159000000007 calcium salts Chemical class 0.000 description 1
• 229930194791 calphostin Natural products 0.000 description 1
• 239000001768 carboxy methyl cellulose Substances 0.000 description 1
• 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 1
• 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 1
• RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 description 1
• 229960000590 celecoxib Drugs 0.000 description 1
• 210000004027 cell Anatomy 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 229920006217 cellulose acetate butyrate Polymers 0.000 description 1
• 229960000541 cetyl alcohol Drugs 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• 238000005660 chlorination reaction Methods 0.000 description 1
• NMMPMZWIIQCZBA-UHFFFAOYSA-M chloropalladium(1+);dicyclohexyl-[2-[2,4,6-tri(propan-2-yl)phenyl]phenyl]phosphane;2-phenylethanamine Chemical compound [Pd+]Cl.NCCC1=CC=CC=[C-]1.CC(C)C1=CC(C(C)C)=CC(C(C)C)=C1C1=CC=CC=C1P(C1CCCCC1)C1CCCCC1 NMMPMZWIIQCZBA-UHFFFAOYSA-M 0.000 description 1
• 238000004587 chromatography analysis Methods 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 239000003240 coconut oil Substances 0.000 description 1
• 235000019864 coconut oil Nutrition 0.000 description 1
• 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
• 238000013270 controlled release Methods 0.000 description 1
• 239000002285 corn oil Substances 0.000 description 1
• 235000005687 corn oil Nutrition 0.000 description 1
• 239000008120 corn starch Substances 0.000 description 1
• 239000003246 corticosteroid Substances 0.000 description 1
• 229960001334 corticosteroids Drugs 0.000 description 1
• 239000006184 cosolvent Substances 0.000 description 1
• 235000012343 cottonseed oil Nutrition 0.000 description 1
• 239000002385 cottonseed oil Substances 0.000 description 1
• 229960005168 croscarmellose Drugs 0.000 description 1
• 229960000913 crospovidone Drugs 0.000 description 1
• 238000006880 cross-coupling reaction Methods 0.000 description 1
• 239000001767 crosslinked sodium carboxy methyl cellulose Substances 0.000 description 1
• 239000010779 crude oil Substances 0.000 description 1
• 239000013078 crystal Substances 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• 229940097362 cyclodextrins Drugs 0.000 description 1
• 125000006317 cyclopropyl amino group Chemical group 0.000 description 1
• 230000016396 cytokine production Effects 0.000 description 1
• 231100000433 cytotoxic Toxicity 0.000 description 1
• 230000001472 cytotoxic effect Effects 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
• 230000007123 defense Effects 0.000 description 1
• 230000007850 degeneration Effects 0.000 description 1
• 238000013461 design Methods 0.000 description 1
• 230000001066 destructive effect Effects 0.000 description 1
• 230000006866 deterioration Effects 0.000 description 1
• 229910052805 deuterium Inorganic materials 0.000 description 1
• 229960003957 dexamethasone Drugs 0.000 description 1
• UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 206010012601 diabetes mellitus Diseases 0.000 description 1
• 238000000502 dialysis Methods 0.000 description 1
• 125000003963 dichloro group Chemical group Cl* 0.000 description 1
• 239000002027 dichloromethane extract Substances 0.000 description 1
• 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
• FSBVERYRVPGNGG-UHFFFAOYSA-N dimagnesium dioxido-bis[[oxido(oxo)silyl]oxy]silane hydrate Chemical compound O.[Mg+2].[Mg+2].[O-][Si](=O)O[Si]([O-])([O-])O[Si]([O-])=O FSBVERYRVPGNGG-UHFFFAOYSA-N 0.000 description 1
• 238000006471 dimerization reaction Methods 0.000 description 1
• ZTJBELXDHFJJEU-UHFFFAOYSA-N dimethylboron Chemical compound C[B]C ZTJBELXDHFJJEU-UHFFFAOYSA-N 0.000 description 1
• UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
• 229910000396 dipotassium phosphate Inorganic materials 0.000 description 1
• 235000019797 dipotassium phosphate Nutrition 0.000 description 1
• 208000016097 disease of metabolism Diseases 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
• UZUODNWWWUQRIR-UHFFFAOYSA-L disodium;3-aminonaphthalene-1,5-disulfonate Chemical compound [Na+].[Na+].C1=CC=C(S([O-])(=O)=O)C2=CC(N)=CC(S([O-])(=O)=O)=C21 UZUODNWWWUQRIR-UHFFFAOYSA-L 0.000 description 1
• 239000006185 dispersion Substances 0.000 description 1
• CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
• 238000012377 drug delivery Methods 0.000 description 1
• 238000009510 drug design Methods 0.000 description 1
• 238000009509 drug development Methods 0.000 description 1
• 238000001035 drying Methods 0.000 description 1
• 239000003792 electrolyte Substances 0.000 description 1
• 239000003974 emollient agent Substances 0.000 description 1
• 230000001804 emulsifying effect Effects 0.000 description 1
• 239000008387 emulsifying waxe Substances 0.000 description 1
• 210000001163 endosome Anatomy 0.000 description 1
• 239000002158 endotoxin Substances 0.000 description 1
• 239000002702 enteric coating Substances 0.000 description 1
• 238000009505 enteric coating Methods 0.000 description 1
• OLAMWIPURJGSKE-UHFFFAOYSA-N et2o diethylether Chemical compound CCOCC.CCOCC OLAMWIPURJGSKE-UHFFFAOYSA-N 0.000 description 1
• LHWWETDBWVTKJO-UHFFFAOYSA-N et3n triethylamine Chemical compound CCN(CC)CC.CCN(CC)CC LHWWETDBWVTKJO-UHFFFAOYSA-N 0.000 description 1
• OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
• BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
• 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
• 235000019325 ethyl cellulose Nutrition 0.000 description 1
• 229920001249 ethyl cellulose Polymers 0.000 description 1
• SMVBADCAMQOTOV-UHFFFAOYSA-N ethyl cyclobutanecarboxylate Chemical compound CCOC(=O)C1CCC1 SMVBADCAMQOTOV-UHFFFAOYSA-N 0.000 description 1
• 229960001617 ethyl hydroxybenzoate Drugs 0.000 description 1
• 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
• 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
• NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
• OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
• 238000002474 experimental method Methods 0.000 description 1
• 238000000605 extraction Methods 0.000 description 1
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 239000011888 foil Substances 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 description 1
• 229940080345 gamma-cyclodextrin Drugs 0.000 description 1
• 239000007789 gas Substances 0.000 description 1
• 210000001035 gastrointestinal tract Anatomy 0.000 description 1
• 238000003209 gene knockout Methods 0.000 description 1
• 235000008434 ginseng Nutrition 0.000 description 1
• 239000003862 glucocorticoid Substances 0.000 description 1
• 125000005456 glyceride group Chemical group 0.000 description 1
• 235000011187 glycerol Nutrition 0.000 description 1
• 229940074045 glyceryl distearate Drugs 0.000 description 1
• 229940075507 glyceryl monostearate Drugs 0.000 description 1
• 229960002449 glycine Drugs 0.000 description 1
• 239000003979 granulating agent Substances 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 150000002367 halogens Chemical class 0.000 description 1
• 239000007902 hard capsule Substances 0.000 description 1
• 231100000869 headache Toxicity 0.000 description 1
• 208000019622 heart disease Diseases 0.000 description 1
• 201000011066 hemangioma Diseases 0.000 description 1
• 208000006454 hepatitis Diseases 0.000 description 1
• 208000005252 hepatitis A Diseases 0.000 description 1
• 208000002672 hepatitis B Diseases 0.000 description 1
• 125000005842 heteroatom Chemical group 0.000 description 1
• 229930195733 hydrocarbon Natural products 0.000 description 1
• 150000002431 hydrogen Chemical class 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• XXSMGPRMXLTPCZ-UHFFFAOYSA-N hydroxychloroquine Chemical compound ClC1=CC=C2C(NC(C)CCCN(CCO)CC)=CC=NC2=C1 XXSMGPRMXLTPCZ-UHFFFAOYSA-N 0.000 description 1
• 229960004171 hydroxychloroquine Drugs 0.000 description 1
• 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
• 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
• 229940071676 hydroxypropylcellulose Drugs 0.000 description 1
• 230000007954 hypoxia Effects 0.000 description 1
• 229960001680 ibuprofen Drugs 0.000 description 1
• 150000002466 imines Chemical class 0.000 description 1
• 230000007813 immunodeficiency Effects 0.000 description 1
• PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 1
• RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 1
• 239000003701 inert diluent Substances 0.000 description 1
• 230000002458 infectious effect Effects 0.000 description 1
• 230000008595 infiltration Effects 0.000 description 1
• 238000001764 infiltration Methods 0.000 description 1
• 206010022000 influenza Diseases 0.000 description 1
• 238000001802 infusion Methods 0.000 description 1
• 229940102223 injectable solution Drugs 0.000 description 1
• 229940102213 injectable suspension Drugs 0.000 description 1
• 108091005434 innate immune receptors Proteins 0.000 description 1
• 229940076144 interleukin-10 Drugs 0.000 description 1
• 210000000936 intestine Anatomy 0.000 description 1
• 230000003834 intracellular effect Effects 0.000 description 1
• 230000004068 intracellular signaling Effects 0.000 description 1
• 230000009545 invasion Effects 0.000 description 1
• 229910052740 iodine Inorganic materials 0.000 description 1
• 150000002500 ions Chemical class 0.000 description 1
• 208000002551 irritable bowel syndrome Diseases 0.000 description 1
• 230000007794 irritation Effects 0.000 description 1
• 208000012947 ischemia reperfusion injury Diseases 0.000 description 1
• 230000000302 ischemic effect Effects 0.000 description 1
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
• 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
• 238000002955 isolation Methods 0.000 description 1
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
• 201000002215 juvenile rheumatoid arthritis Diseases 0.000 description 1
• NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
• 208000011379 keloid formation Diseases 0.000 description 1
• 210000003734 kidney Anatomy 0.000 description 1
• 235000019388 lanolin Nutrition 0.000 description 1
• 229940039717 lanolin Drugs 0.000 description 1
• VHOGYURTWQBHIL-UHFFFAOYSA-N leflunomide Chemical compound O1N=CC(C(=O)NC=2C=CC(=CC=2)C(F)(F)F)=C1C VHOGYURTWQBHIL-UHFFFAOYSA-N 0.000 description 1
• 229960000681 leflunomide Drugs 0.000 description 1
• 208000021601 lentivirus infection Diseases 0.000 description 1
• 230000000670 limiting effect Effects 0.000 description 1
• 238000004811 liquid chromatography Methods 0.000 description 1
• 239000012280 lithium aluminium hydride Substances 0.000 description 1
• 244000144972 livestock Species 0.000 description 1
• 239000000395 magnesium oxide Substances 0.000 description 1
• CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
• 239000000391 magnesium silicate Substances 0.000 description 1
• 229940099273 magnesium trisilicate Drugs 0.000 description 1
• 229910000386 magnesium trisilicate Inorganic materials 0.000 description 1
• 235000019793 magnesium trisilicate Nutrition 0.000 description 1
• AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
• 239000000594 mannitol Substances 0.000 description 1
• 235000010355 mannitol Nutrition 0.000 description 1
• 238000004949 mass spectrometry Methods 0.000 description 1
• 239000011159 matrix material Substances 0.000 description 1
• 230000001404 mediated effect Effects 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• 229960000485 methotrexate Drugs 0.000 description 1
• POWKBBOOIZBIRZ-UHFFFAOYSA-N methyl 2-amino-5-bromopyridine-3-carboxylate Chemical compound COC(=O)C1=CC(Br)=CN=C1N POWKBBOOIZBIRZ-UHFFFAOYSA-N 0.000 description 1
• 229920000609 methyl cellulose Polymers 0.000 description 1
• 235000010981 methylcellulose Nutrition 0.000 description 1
• 239000001923 methylcellulose Substances 0.000 description 1
• 229960002900 methylcellulose Drugs 0.000 description 1
• 244000005700 microbiome Species 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 230000003387 muscular Effects 0.000 description 1
• 206010028417 myasthenia gravis Diseases 0.000 description 1
• 229940043348 myristyl alcohol Drugs 0.000 description 1
• LLYKPZOWCPVRPD-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine;n,n-dimethylpyridin-4-amine Chemical compound CN(C)C1=CC=NC=C1.CN(C)C1=CC=CC=N1 LLYKPZOWCPVRPD-UHFFFAOYSA-N 0.000 description 1
• WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
• 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
• XHFGWHUWQXTGAT-UHFFFAOYSA-N n-methylpropan-2-amine Chemical compound CNC(C)C XHFGWHUWQXTGAT-UHFFFAOYSA-N 0.000 description 1
• 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 230000001613 neoplastic effect Effects 0.000 description 1
• 210000000653 nervous system Anatomy 0.000 description 1
• 230000002232 neuromuscular Effects 0.000 description 1
• 210000000440 neutrophil Anatomy 0.000 description 1
• 230000005937 nuclear translocation Effects 0.000 description 1
• 239000007764 o/w emulsion Substances 0.000 description 1
• 235000014593 oils and fats Nutrition 0.000 description 1
• 239000003883 ointment base Substances 0.000 description 1
• JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 229940046781 other immunosuppressants in atc Drugs 0.000 description 1
• 230000002018 overexpression Effects 0.000 description 1
• 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 description 1
• YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
• 239000012188 paraffin wax Substances 0.000 description 1
• 238000007911 parenteral administration Methods 0.000 description 1
• 244000052769 pathogen Species 0.000 description 1
• 230000001717 pathogenic effect Effects 0.000 description 1
• 230000037361 pathway Effects 0.000 description 1
• 102000007863 pattern recognition receptors Human genes 0.000 description 1
• 108010089193 pattern recognition receptors Proteins 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 102000013415 peroxidase activity proteins Human genes 0.000 description 1
• 108040007629 peroxidase activity proteins Proteins 0.000 description 1
• 239000000825 pharmaceutical preparation Substances 0.000 description 1
• 229940127557 pharmaceutical product Drugs 0.000 description 1
• WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
• 235000021317 phosphate Nutrition 0.000 description 1
• 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 229920000058 polyacrylate Polymers 0.000 description 1
• 229920000573 polyethylene Polymers 0.000 description 1
• 229940113116 polyethylene glycol 1000 Drugs 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
• 229920000136 polysorbate Polymers 0.000 description 1
• 229920002451 polyvinyl alcohol Polymers 0.000 description 1
• 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
• 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
• 239000004302 potassium sorbate Substances 0.000 description 1
• 235000010241 potassium sorbate Nutrition 0.000 description 1
• 229940069338 potassium sorbate Drugs 0.000 description 1
• XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
• 229960004618 prednisone Drugs 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 208000016800 primary central nervous system lymphoma Diseases 0.000 description 1
• 230000008569 process Effects 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 229940072288 prograf Drugs 0.000 description 1
• 230000000770 proinflammatory effect Effects 0.000 description 1
• WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical group CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 description 1
• 235000013772 propylene glycol Nutrition 0.000 description 1
• QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
• 150000003180 prostaglandins Chemical class 0.000 description 1
• 229940048914 protamine Drugs 0.000 description 1
• 108090000623 proteins and genes Proteins 0.000 description 1
• 102000004169 proteins and genes Human genes 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 description 1
• 229940099538 rapamune Drugs 0.000 description 1
• 208000002574 reactive arthritis Diseases 0.000 description 1
• 238000010992 reflux Methods 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 230000008844 regulatory mechanism Effects 0.000 description 1
• 230000004044 response Effects 0.000 description 1
• RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 description 1
• 229960000371 rofecoxib Drugs 0.000 description 1
• HJORMJIFDVBMOB-UHFFFAOYSA-N rolipram Chemical compound COC1=CC=C(C2CC(=O)NC2)C=C1OC1CCCC1 HJORMJIFDVBMOB-UHFFFAOYSA-N 0.000 description 1
• 229950005741 rolipram Drugs 0.000 description 1
• 201000005404 rubella Diseases 0.000 description 1
• CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
• 235000019204 saccharin Nutrition 0.000 description 1
• 229940081974 saccharin Drugs 0.000 description 1
• 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
• YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical class OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 1
• 201000003774 sarcomatosis Diseases 0.000 description 1
• 231100000241 scar Toxicity 0.000 description 1
• HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
• 239000008299 semisolid dosage form Substances 0.000 description 1
• 230000036303 septic shock Effects 0.000 description 1
• 201000005113 shigellosis Diseases 0.000 description 1
• 230000035939 shock Effects 0.000 description 1
• 239000010802 sludge Substances 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
• 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
• 229960002668 sodium chloride Drugs 0.000 description 1
• 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
• 239000001488 sodium phosphate Substances 0.000 description 1
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
• 235000019345 sodium thiosulphate Nutrition 0.000 description 1
• 239000007901 soft capsule Substances 0.000 description 1
• 239000007909 solid dosage form Substances 0.000 description 1
• 230000007928 solubilization Effects 0.000 description 1
• 238000005063 solubilization Methods 0.000 description 1
• 230000003381 solubilizing effect Effects 0.000 description 1
• 238000007614 solvation Methods 0.000 description 1
• 239000004334 sorbic acid Substances 0.000 description 1
• 235000010199 sorbic acid Nutrition 0.000 description 1
• 229940075582 sorbic acid Drugs 0.000 description 1
• 239000003549 soybean oil Substances 0.000 description 1
• 235000012424 soybean oil Nutrition 0.000 description 1
• 239000008347 soybean phospholipid Substances 0.000 description 1
• 230000002269 spontaneous effect Effects 0.000 description 1
• 208000010110 spontaneous platelet aggregation Diseases 0.000 description 1
• 230000000087 stabilizing effect Effects 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 230000001954 sterilising effect Effects 0.000 description 1
• 238000004659 sterilization and disinfection Methods 0.000 description 1
• 150000003431 steroids Chemical class 0.000 description 1
• 238000003860 storage Methods 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 150000003456 sulfonamides Chemical class 0.000 description 1
• 201000004595 synovitis Diseases 0.000 description 1
• 238000001308 synthesis method Methods 0.000 description 1
• 238000010189 synthetic method Methods 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 229940037128 systemic glucocorticoids Drugs 0.000 description 1
• 229960001967 tacrolimus Drugs 0.000 description 1
• LXIKEPCNDFVJKC-QXMHVHEDSA-N tenidap Chemical compound C12=CC(Cl)=CC=C2N(C(=O)N)C(=O)\C1=C(/O)C1=CC=CS1 LXIKEPCNDFVJKC-QXMHVHEDSA-N 0.000 description 1
• 229960003676 tenidap Drugs 0.000 description 1
• YRHLNCNBWPTVPJ-UHFFFAOYSA-N tert-butyl 4-(2-bromo-3-propan-2-yl-1H-indol-5-yl)piperidine-1-carboxylate Chemical compound BrC=1NC2=CC=C(C=C2C=1C(C)C)C1CCN(CC1)C(=O)OC(C)(C)C YRHLNCNBWPTVPJ-UHFFFAOYSA-N 0.000 description 1
• WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
• 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
• OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 description 1
• WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
• 231100001274 therapeutic index Toxicity 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 239000002562 thickening agent Substances 0.000 description 1
• 229960004072 thrombin Drugs 0.000 description 1
• 206010043554 thrombocytopenia Diseases 0.000 description 1
• 210000001685 thyroid gland Anatomy 0.000 description 1
• 230000009772 tissue formation Effects 0.000 description 1
• AOBORMOPSGHCAX-DGHZZKTQSA-N tocofersolan Chemical compound OCCOC(=O)CCC(=O)OC1=C(C)C(C)=C2O[C@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C AOBORMOPSGHCAX-DGHZZKTQSA-N 0.000 description 1
• 229960000984 tocofersolan Drugs 0.000 description 1
• 208000004371 toothache Diseases 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 238000000844 transformation Methods 0.000 description 1
• 229910052723 transition metal Inorganic materials 0.000 description 1
• 150000003624 transition metals Chemical class 0.000 description 1
• 125000005271 tributylamino group Chemical group 0.000 description 1
• ZBZJXHCVGLJWFG-UHFFFAOYSA-N trichloromethyl(.) Chemical compound Cl[C](Cl)Cl ZBZJXHCVGLJWFG-UHFFFAOYSA-N 0.000 description 1
• RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
• 229910052722 tritium Inorganic materials 0.000 description 1
• 201000008827 tuberculosis Diseases 0.000 description 1
• 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 description 1
• 239000002452 tumor necrosis factor alpha inhibitor Substances 0.000 description 1
• 208000001072 type 2 diabetes mellitus Diseases 0.000 description 1
• 230000010472 type I IFN response Effects 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 230000009385 viral infection Effects 0.000 description 1
• 238000009736 wetting Methods 0.000 description 1
• 150000003751 zinc Chemical class 0.000 description 1
• 239000002076 α-tocopherol Substances 0.000 description 1
• 235000004835 α-tocopherol Nutrition 0.000 description 1