JP6535338B2 - 新規製剤 - Google Patents
新規製剤 Download PDFInfo
- Publication number
- JP6535338B2 JP6535338B2 JP2016552486A JP2016552486A JP6535338B2 JP 6535338 B2 JP6535338 B2 JP 6535338B2 JP 2016552486 A JP2016552486 A JP 2016552486A JP 2016552486 A JP2016552486 A JP 2016552486A JP 6535338 B2 JP6535338 B2 JP 6535338B2
- Authority
- JP
- Japan
- Prior art keywords
- equivalents
- tris
- salt
- hydroxymethyl
- alkyl
- 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.)
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- 239000000203 mixture Substances 0.000 title claims description 215
- 238000009472 formulation Methods 0.000 title description 5
- 150000003839 salts Chemical class 0.000 claims description 454
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 277
- -1 alkoxide salt Chemical class 0.000 claims description 208
- 125000000217 alkyl group Chemical group 0.000 claims description 185
- 239000002585 base Substances 0.000 claims description 183
- 238000000034 method Methods 0.000 claims description 165
- 239000008174 sterile solution Substances 0.000 claims description 120
- 239000011734 sodium Substances 0.000 claims description 117
- 229910052751 metal Inorganic materials 0.000 claims description 115
- 239000002184 metal Substances 0.000 claims description 115
- 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 112
- 229960003194 meglumine Drugs 0.000 claims description 111
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 106
- 239000002253 acid Substances 0.000 claims description 98
- 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 claims description 93
- 150000001412 amines Chemical class 0.000 claims description 89
- 239000001509 sodium citrate Substances 0.000 claims description 88
- 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 88
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 73
- 239000001488 sodium phosphate Substances 0.000 claims description 59
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 59
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 58
- 239000011780 sodium chloride Substances 0.000 claims description 53
- 229920002307 Dextran Polymers 0.000 claims description 52
- 239000004475 Arginine Substances 0.000 claims description 48
- 239000007864 aqueous solution Substances 0.000 claims description 48
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 48
- 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 39
- 239000008194 pharmaceutical composition Substances 0.000 claims description 37
- 238000002156 mixing Methods 0.000 claims description 34
- 229910001463 metal phosphate Inorganic materials 0.000 claims description 32
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 32
- 239000008227 sterile water for injection Substances 0.000 claims description 31
- 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 claims description 26
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 26
- 229930195725 Mannitol Natural products 0.000 claims description 26
- 229930006000 Sucrose Natural products 0.000 claims description 26
- 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 claims description 26
- 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 26
- 239000008103 glucose Substances 0.000 claims description 26
- 239000000594 mannitol Substances 0.000 claims description 26
- 235000010355 mannitol Nutrition 0.000 claims description 26
- 239000005720 sucrose Substances 0.000 claims description 26
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 26
- 239000007924 injection Substances 0.000 claims description 25
- 238000002347 injection Methods 0.000 claims description 25
- 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 claims description 22
- 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 claims description 22
- 208000006752 brain edema Diseases 0.000 claims description 22
- 239000008101 lactose Substances 0.000 claims description 22
- 150000004649 carbonic acid derivatives Chemical class 0.000 claims description 21
- 150000001860 citric acid derivatives Chemical class 0.000 claims description 21
- 206010048962 Brain oedema Diseases 0.000 claims description 20
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 20
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims description 18
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims description 18
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims description 18
- 150000001642 boronic acid derivatives Chemical class 0.000 claims description 17
- 208000031225 myocardial ischemia Diseases 0.000 claims description 17
- 206010021143 Hypoxia Diseases 0.000 claims description 16
- 230000007954 hypoxia Effects 0.000 claims description 16
- 229910019142 PO4 Inorganic materials 0.000 claims description 15
- 235000021317 phosphate Nutrition 0.000 claims description 15
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 14
- 239000008121 dextrose Substances 0.000 claims description 13
- 206010019280 Heart failures Diseases 0.000 claims description 12
- 206010030113 Oedema Diseases 0.000 claims description 11
- 208000006011 Stroke Diseases 0.000 claims description 11
- 206010015037 epilepsy Diseases 0.000 claims description 11
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 10
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 10
- 239000004471 Glycine Substances 0.000 claims description 10
- 206010021036 Hyponatraemia Diseases 0.000 claims description 10
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 10
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims description 10
- 208000019695 Migraine disease Diseases 0.000 claims description 10
- 239000002202 Polyethylene glycol Substances 0.000 claims description 10
- MUPFEKGTMRGPLJ-RMMQSMQOSA-N Raffinose Natural products O(C[C@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O[C@@]2(CO)[C@H](O)[C@@H](O)[C@@H](CO)O2)O1)[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 MUPFEKGTMRGPLJ-RMMQSMQOSA-N 0.000 claims description 10
- MUPFEKGTMRGPLJ-UHFFFAOYSA-N UNPD196149 Natural products OC1C(O)C(CO)OC1(CO)OC1C(O)C(O)C(O)C(COC2C(C(O)C(O)C(CO)O2)O)O1 MUPFEKGTMRGPLJ-UHFFFAOYSA-N 0.000 claims description 10
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims description 10
- 208000010125 myocardial infarction Diseases 0.000 claims description 10
- 229920001223 polyethylene glycol Polymers 0.000 claims description 10
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 10
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 10
- 229920001451 polypropylene glycol Polymers 0.000 claims description 10
- 229940068968 polysorbate 80 Drugs 0.000 claims description 10
- 229920000053 polysorbate 80 Polymers 0.000 claims description 10
- MUPFEKGTMRGPLJ-ZQSKZDJDSA-N raffinose 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[C@@H]2[C@@H]([C@@H](O)[C@@H](O)[C@@H](CO)O2)O)O1 MUPFEKGTMRGPLJ-ZQSKZDJDSA-N 0.000 claims description 10
- 239000000600 sorbitol Substances 0.000 claims description 10
- 238000011282 treatment Methods 0.000 claims description 10
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 9
- 208000005374 Poisoning Diseases 0.000 claims description 9
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 9
- 230000002107 myocardial effect Effects 0.000 claims description 9
- 231100000572 poisoning Toxicity 0.000 claims description 9
- 230000000607 poisoning effect Effects 0.000 claims description 9
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 9
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 9
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 9
- 239000007787 solid Substances 0.000 claims description 9
- 230000009529 traumatic brain injury Effects 0.000 claims description 9
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 claims description 8
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 claims description 8
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 claims description 8
- 208000001380 Diabetic Ketoacidosis Diseases 0.000 claims description 8
- 208000001640 Fibromyalgia Diseases 0.000 claims description 8
- 208000032612 Glial tumor Diseases 0.000 claims description 8
- 206010018338 Glioma Diseases 0.000 claims description 8
- 206010019663 Hepatic failure Diseases 0.000 claims description 8
- 206010025130 Lupus encephalitis Diseases 0.000 claims description 8
- 201000009906 Meningitis Diseases 0.000 claims description 8
- 206010033266 Ovarian Hyperstimulation Syndrome Diseases 0.000 claims description 8
- 206010037423 Pulmonary oedema Diseases 0.000 claims description 8
- 206010000269 abscess Diseases 0.000 claims description 8
- 208000002296 eclampsia Diseases 0.000 claims description 8
- 208000005017 glioblastoma Diseases 0.000 claims description 8
- 208000007386 hepatic encephalopathy Diseases 0.000 claims description 8
- 208000015181 infectious disease Diseases 0.000 claims description 8
- 208000007903 liver failure Diseases 0.000 claims description 8
- 231100000835 liver failure Toxicity 0.000 claims description 8
- 206010027599 migraine Diseases 0.000 claims description 8
- 201000006417 multiple sclerosis Diseases 0.000 claims description 8
- 239000010452 phosphate Substances 0.000 claims description 8
- 208000005333 pulmonary edema Diseases 0.000 claims description 8
- 206010033712 Papilloedema Diseases 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims description 7
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 7
- 208000032382 Ischaemic stroke Diseases 0.000 claims description 6
- 208000030159 metabolic disease Diseases 0.000 claims description 6
- 208000032253 retinal ischemia Diseases 0.000 claims description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 4
- 208000034388 Mountain sickness acute Diseases 0.000 claims description 4
- 239000008156 Ringer's lactate solution Substances 0.000 claims description 4
- 208000018315 acute mountain sickness Diseases 0.000 claims description 4
- ZEWYCNBZMPELPF-UHFFFAOYSA-J calcium;potassium;sodium;2-hydroxypropanoic acid;sodium;tetrachloride Chemical compound [Na].[Na+].[Cl-].[Cl-].[Cl-].[Cl-].[K+].[Ca+2].CC(O)C(O)=O ZEWYCNBZMPELPF-UHFFFAOYSA-J 0.000 claims description 4
- 238000004090 dissolution Methods 0.000 claims description 4
- NNHMQZBVJPQCAK-UHFFFAOYSA-N 5-chloro-2-hydroxybenzamide Chemical compound NC(=O)C1=CC(Cl)=CC=C1O NNHMQZBVJPQCAK-UHFFFAOYSA-N 0.000 claims description 3
- 208000010496 Heart Arrest Diseases 0.000 claims description 3
- 206010063036 Spinal cord oedema Diseases 0.000 claims description 3
- 238000010253 intravenous injection Methods 0.000 claims description 3
- 230000005486 microgravity Effects 0.000 claims description 3
- 206010019196 Head injury Diseases 0.000 claims description 2
- 201000010183 Papilledema Diseases 0.000 claims description 2
- 206010038886 Retinal oedema Diseases 0.000 claims description 2
- 210000003169 central nervous system Anatomy 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 201000011195 retinal edema Diseases 0.000 claims description 2
- 239000003341 Bronsted base Substances 0.000 claims 15
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 claims 8
- 229910000288 alkali metal carbonate Inorganic materials 0.000 claims 2
- 150000008041 alkali metal carbonates Chemical class 0.000 claims 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims 2
- 208000009447 Cardiac Edema Diseases 0.000 claims 1
- 208000018652 Closed Head injury Diseases 0.000 claims 1
- 238000003801 milling Methods 0.000 claims 1
- 239000000178 monomer Substances 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 166
- 239000007983 Tris buffer Substances 0.000 description 153
- 239000002904 solvent Substances 0.000 description 99
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 96
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 description 87
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 87
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 78
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 76
- 150000001340 alkali metals Chemical class 0.000 description 76
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 58
- 229910052783 alkali metal Inorganic materials 0.000 description 56
- 239000012266 salt solution Substances 0.000 description 54
- 235000011008 sodium phosphates Nutrition 0.000 description 54
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 50
- 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 description 47
- 239000003513 alkali Substances 0.000 description 46
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 42
- 229940119744 dextran 40 Drugs 0.000 description 41
- 235000001014 amino acid Nutrition 0.000 description 36
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- 239000000945 filler Substances 0.000 description 32
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- 150000001242 acetic acid derivatives Chemical class 0.000 description 30
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 30
- 229940124597 therapeutic agent Drugs 0.000 description 29
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 27
- 229910000318 alkali metal phosphate Inorganic materials 0.000 description 26
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 26
- 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 description 25
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 24
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 24
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 21
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 21
- 229940001447 lactate Drugs 0.000 description 21
- 150000003892 tartrate salts Chemical class 0.000 description 21
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 20
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 20
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- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 18
- 239000000654 additive Substances 0.000 description 18
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 16
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 16
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 16
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 16
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 16
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 16
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 16
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 16
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 16
- 239000000243 solution Substances 0.000 description 16
- 102000012002 Aquaporin 4 Human genes 0.000 description 15
- 108010036280 Aquaporin 4 Proteins 0.000 description 15
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 14
- 229910000000 metal hydroxide Inorganic materials 0.000 description 14
- 229910000160 potassium phosphate Inorganic materials 0.000 description 14
- 235000011009 potassium phosphates Nutrition 0.000 description 14
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 13
- 229910000272 alkali metal oxide Inorganic materials 0.000 description 13
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 13
- 229910000316 alkaline earth metal phosphate Inorganic materials 0.000 description 13
- 150000004703 alkoxides Chemical class 0.000 description 13
- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 13
- 239000000920 calcium hydroxide Substances 0.000 description 13
- 229910001861 calcium hydroxide Inorganic materials 0.000 description 13
- 238000001802 infusion Methods 0.000 description 13
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 description 13
- 229910001862 magnesium hydroxide Inorganic materials 0.000 description 13
- 235000011056 potassium acetate Nutrition 0.000 description 13
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| WO2016196113A1 (en) | 2015-05-29 | 2016-12-08 | University Of Maryland, Baltimore | Methods of reducing or preventing intimal damage caused by mechanical stimulation of endothelial cells |
| BR112018006925A2 (pt) | 2015-10-07 | 2018-10-16 | Biogen Chesapeake Llc | métodos de tratamento de lesões ou patologias associadas com um edema do snc |
| CN115093443A (zh) | 2016-05-13 | 2022-09-23 | 埃罗米克斯公司 | 晶体 |
| CA3032294C (en) | 2016-07-29 | 2025-03-11 | Biogen Chesapeake Llc | MEDICAL TREATMENT METHODS WITH SUR1-TRPM4 CHANNEL INHIBITORS |
| 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 |
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