KR20160079109A - 새로운 조성물 - Google Patents
새로운 조성물 Download PDFInfo
- Publication number
- KR20160079109A KR20160079109A KR1020167014998A KR20167014998A KR20160079109A KR 20160079109 A KR20160079109 A KR 20160079109A KR 1020167014998 A KR1020167014998 A KR 1020167014998A KR 20167014998 A KR20167014998 A KR 20167014998A KR 20160079109 A KR20160079109 A KR 20160079109A
- Authority
- KR
- South Korea
- Prior art keywords
- tris
- salts
- salt
- alkyl
- hydroxymethyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 239000000203 mixture Substances 0.000 title claims description 289
- 238000009472 formulation Methods 0.000 title 1
- WSHXPHFIHYXZKC-UHFFFAOYSA-N [2-[[3,5-bis(trifluoromethyl)phenyl]carbamoyl]-4-chlorophenyl] dihydrogen phosphate Chemical compound OP(O)(=O)OC1=CC=C(Cl)C=C1C(=O)NC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 WSHXPHFIHYXZKC-UHFFFAOYSA-N 0.000 claims abstract description 112
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- 150000003839 salts Chemical class 0.000 claims description 358
- 125000000217 alkyl group Chemical group 0.000 claims description 307
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 281
- 238000000034 method Methods 0.000 claims description 246
- -1 metal tartrate salts Chemical class 0.000 claims description 235
- 239000002585 base Substances 0.000 claims description 205
- 125000002947 alkylene group Chemical group 0.000 claims description 197
- PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 claims description 178
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 159
- 150000001875 compounds Chemical class 0.000 claims description 136
- 239000003513 alkali Substances 0.000 claims description 132
- 239000011734 sodium Substances 0.000 claims description 132
- 239000007983 Tris buffer Substances 0.000 claims description 128
- 229910052751 metal Inorganic materials 0.000 claims description 127
- 239000002184 metal Substances 0.000 claims description 127
- 239000012266 salt solution Substances 0.000 claims description 118
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 114
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims description 108
- 229960003194 meglumine Drugs 0.000 claims description 106
- 150000001412 amines Chemical class 0.000 claims description 97
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 87
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 86
- 239000008174 sterile solution Substances 0.000 claims description 86
- 239000001509 sodium citrate Substances 0.000 claims description 85
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 85
- 150000003013 phosphoric acid derivatives Chemical class 0.000 claims description 83
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims description 74
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 69
- 150000001860 citric acid derivatives Chemical class 0.000 claims description 65
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 63
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 63
- 239000008194 pharmaceutical composition Substances 0.000 claims description 58
- 239000000243 solution Substances 0.000 claims description 58
- 159000000021 acetate salts Chemical class 0.000 claims description 53
- 239000004475 Arginine Substances 0.000 claims description 47
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 47
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 45
- 239000011780 sodium chloride Substances 0.000 claims description 44
- 239000001488 sodium phosphate Substances 0.000 claims description 44
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 44
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 44
- 239000007864 aqueous solution Substances 0.000 claims description 43
- 229910001463 metal phosphate Inorganic materials 0.000 claims description 43
- 150000001413 amino acids Chemical class 0.000 claims description 40
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims description 35
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 33
- 150000001642 boronic acid derivatives Chemical class 0.000 claims description 31
- 239000008354 sodium chloride injection Substances 0.000 claims description 31
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 claims description 30
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 29
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 28
- 238000001802 infusion Methods 0.000 claims description 28
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 27
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 27
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 claims description 26
- 239000002253 acid Substances 0.000 claims description 25
- 150000003892 tartrate salts Chemical class 0.000 claims description 24
- 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 claims description 23
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 22
- 150000001768 cations Chemical class 0.000 claims description 20
- 238000002156 mixing Methods 0.000 claims description 20
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 20
- 230000008569 process Effects 0.000 claims description 20
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 20
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 19
- 229940001447 lactate Drugs 0.000 claims description 19
- 150000003893 lactate salts Chemical class 0.000 claims description 16
- 229910000000 metal hydroxide Inorganic materials 0.000 claims description 16
- 239000008223 sterile water Substances 0.000 claims description 16
- 239000008227 sterile water for injection Substances 0.000 claims description 16
- 150000003890 succinate salts Chemical class 0.000 claims description 16
- CHILCFMQWMQVAL-UHFFFAOYSA-N N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide Chemical compound OC1=CC=C(Cl)C=C1C(=O)NC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 CHILCFMQWMQVAL-UHFFFAOYSA-N 0.000 claims description 15
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 15
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 claims description 15
- 239000000920 calcium hydroxide Substances 0.000 claims description 15
- 229910001861 calcium hydroxide Inorganic materials 0.000 claims description 15
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims description 15
- 239000000347 magnesium hydroxide Substances 0.000 claims description 15
- 229910001862 magnesium hydroxide Inorganic materials 0.000 claims description 15
- 235000011056 potassium acetate Nutrition 0.000 claims description 15
- 239000001508 potassium citrate Substances 0.000 claims description 15
- 229960002635 potassium citrate Drugs 0.000 claims description 15
- QEEAPRPFLLJWCF-UHFFFAOYSA-K potassium citrate (anhydrous) Chemical compound [K+].[K+].[K+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O QEEAPRPFLLJWCF-UHFFFAOYSA-K 0.000 claims description 15
- 235000011082 potassium citrates Nutrition 0.000 claims description 15
- 239000001632 sodium acetate Substances 0.000 claims description 15
- 235000017281 sodium acetate Nutrition 0.000 claims description 15
- 235000011114 ammonium hydroxide Nutrition 0.000 claims description 14
- 229910021538 borax Inorganic materials 0.000 claims description 14
- 150000005323 carbonate salts Chemical class 0.000 claims description 14
- 150000004679 hydroxides Chemical class 0.000 claims description 14
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 14
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 14
- 235000010339 sodium tetraborate Nutrition 0.000 claims description 14
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 claims description 14
- 239000008121 dextrose Substances 0.000 claims description 13
- 238000002347 injection Methods 0.000 claims description 13
- 239000007924 injection Substances 0.000 claims description 13
- 229910000160 potassium phosphate Inorganic materials 0.000 claims description 13
- 235000011009 potassium phosphates Nutrition 0.000 claims description 13
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 12
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 claims description 11
- 239000004472 Lysine Substances 0.000 claims description 11
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 11
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 claims description 11
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 claims description 11
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims description 11
- 229960002887 deanol Drugs 0.000 claims description 11
- 239000012972 dimethylethanolamine Substances 0.000 claims description 11
- 238000011068 loading method Methods 0.000 claims description 11
- 235000019371 penicillin G benzathine Nutrition 0.000 claims description 11
- 230000000844 anti-bacterial effect Effects 0.000 claims description 10
- 230000001580 bacterial effect Effects 0.000 claims description 10
- 239000008355 dextrose injection Substances 0.000 claims description 10
- KWIUHFFTVRNATP-UHFFFAOYSA-N glycine betaine Chemical compound C[N+](C)(C)CC([O-])=O KWIUHFFTVRNATP-UHFFFAOYSA-N 0.000 claims description 10
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 claims description 10
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 9
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 claims description 8
- RVDLHGSZWAELAU-UHFFFAOYSA-N 5-tert-butylthiophene-2-carbonyl chloride Chemical compound CC(C)(C)C1=CC=C(C(Cl)=O)S1 RVDLHGSZWAELAU-UHFFFAOYSA-N 0.000 claims description 8
- 239000000908 ammonium hydroxide Substances 0.000 claims description 8
- 150000004692 metal hydroxides Chemical class 0.000 claims description 8
- IZXGZAJMDLJLMF-UHFFFAOYSA-N methylaminomethanol Chemical compound CNCO IZXGZAJMDLJLMF-UHFFFAOYSA-N 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- QILUFVJSEAEPCY-QXPFVDMISA-N propan-2-yl (2Z)-7-methyl-2-[[3-(3-methyl-4-prop-2-enoxyphenyl)-1-phenylpyrazol-4-yl]methylidene]-5-(4-methylsulfanylphenyl)-3-oxo-5H-[1,3]thiazolo[3,2-a]pyrimidine-6-carboxylate Chemical compound CSc1ccc(cc1)C1C(C(=O)OC(C)C)=C(C)N=c2s\c(=C/c3cn(nc3-c3ccc(OCC=C)c(C)c3)-c3ccccc3)c(=O)n12 QILUFVJSEAEPCY-QXPFVDMISA-N 0.000 claims description 8
- HELHAJAZNSDZJO-OLXYHTOASA-L sodium L-tartrate Chemical compound [Na+].[Na+].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O HELHAJAZNSDZJO-OLXYHTOASA-L 0.000 claims description 8
- 239000001540 sodium lactate Substances 0.000 claims description 8
- 235000011088 sodium lactate Nutrition 0.000 claims description 8
- 229940005581 sodium lactate Drugs 0.000 claims description 8
- ZDQYSKICYIVCPN-UHFFFAOYSA-L sodium succinate (anhydrous) Chemical compound [Na+].[Na+].[O-]C(=O)CCC([O-])=O ZDQYSKICYIVCPN-UHFFFAOYSA-L 0.000 claims description 8
- 239000001433 sodium tartrate Substances 0.000 claims description 8
- 229960002167 sodium tartrate Drugs 0.000 claims description 8
- 235000011004 sodium tartrates Nutrition 0.000 claims description 8
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 claims description 8
- 150000003627 tricarboxylic acid derivatives Chemical class 0.000 claims description 8
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 7
- 238000010255 intramuscular injection Methods 0.000 claims description 7
- 125000001453 quaternary ammonium group Chemical group 0.000 claims description 7
- 229910052708 sodium Inorganic materials 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- 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 claims description 6
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 6
- 238000007918 intramuscular administration Methods 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- VVLAIYIMMFWRFW-UHFFFAOYSA-N 2-hydroxyethylazanium;acetate Chemical compound CC(O)=O.NCCO VVLAIYIMMFWRFW-UHFFFAOYSA-N 0.000 claims description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 5
- 241000894006 Bacteria Species 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 239000007927 intramuscular injection Substances 0.000 claims description 5
- 238000007913 intrathecal administration Methods 0.000 claims description 5
- 238000001990 intravenous administration Methods 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- 239000000725 suspension Substances 0.000 claims description 5
- 239000010953 base metal Substances 0.000 claims description 3
- 238000007920 subcutaneous administration Methods 0.000 claims description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims 30
- 229940043237 diethanolamine Drugs 0.000 claims 14
- 238000010253 intravenous injection Methods 0.000 claims 5
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims 3
- 239000012891 Ringer solution Substances 0.000 claims 3
- JZXVADSBLRIAIB-UHFFFAOYSA-N 2-pyrrolidin-2-ylethanol Chemical compound OCCC1CCCN1 JZXVADSBLRIAIB-UHFFFAOYSA-N 0.000 claims 2
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 claims 2
- ILJSQTXMGCGYMG-UHFFFAOYSA-N triacetic acid Chemical compound CC(=O)CC(=O)CC(O)=O ILJSQTXMGCGYMG-UHFFFAOYSA-N 0.000 claims 2
- HMBHAQMOBKLWRX-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxine-3-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)COC2=C1 HMBHAQMOBKLWRX-UHFFFAOYSA-N 0.000 claims 1
- SNMUYHVTHLCYQT-UHFFFAOYSA-N 3-chloro-2-hydroxybenzamide Chemical compound NC(=O)C1=CC=CC(Cl)=C1O SNMUYHVTHLCYQT-UHFFFAOYSA-N 0.000 claims 1
- 150000003973 alkyl amines Chemical class 0.000 claims 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims 1
- 229940075419 choline hydroxide Drugs 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 abstract description 13
- 239000002904 solvent Substances 0.000 description 64
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 63
- 235000011008 sodium phosphates Nutrition 0.000 description 36
- 229920002307 Dextran Polymers 0.000 description 34
- 235000001014 amino acid Nutrition 0.000 description 32
- 239000003814 drug Substances 0.000 description 30
- 229940119744 dextran 40 Drugs 0.000 description 29
- 229940124597 therapeutic agent Drugs 0.000 description 25
- 239000004606 Fillers/Extenders Substances 0.000 description 23
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 22
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 21
- 208000006752 brain edema Diseases 0.000 description 19
- 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 18
- 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 18
- 206010021143 Hypoxia Diseases 0.000 description 18
- 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 18
- 229930195725 Mannitol Natural products 0.000 description 18
- 229930006000 Sucrose Natural products 0.000 description 18
- 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 18
- 230000007954 hypoxia Effects 0.000 description 18
- 239000008101 lactose Substances 0.000 description 18
- 239000000594 mannitol Substances 0.000 description 18
- 235000010355 mannitol Nutrition 0.000 description 18
- 239000005720 sucrose Substances 0.000 description 18
- 239000008103 glucose Substances 0.000 description 17
- 206010048962 Brain oedema Diseases 0.000 description 16
- 102000012002 Aquaporin 4 Human genes 0.000 description 15
- 108010036280 Aquaporin 4 Proteins 0.000 description 15
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 14
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 14
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 14
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 14
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical class COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 14
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical class CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 14
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| JP2021023226A (ja) * | 2019-08-06 | 2021-02-22 | 学校法人慶應義塾 | アクアポリン活性調節剤候補のハイスループットスクリーニング方法 |
| CN110790787B (zh) * | 2019-11-12 | 2022-06-14 | 广东药科大学 | 一类水溶性前药、其制备方法及其作为药物的用途 |
| JP2023536509A (ja) * | 2020-08-05 | 2023-08-25 | ジャンスー・シムセレ・ファーマシューティカル・カンパニー・リミテッド | アクアポリン阻害剤の医薬組成物およびその製造方法 |
| CN117105810B (zh) * | 2023-10-23 | 2024-02-09 | 中国农业大学 | 一种具有广谱抗菌活性的化合物及其抗菌组合物 |
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