RU2691951C2 - Новые составы - Google Patents
Новые составы Download PDFInfo
- Publication number
- RU2691951C2 RU2691951C2 RU2016121850A RU2016121850A RU2691951C2 RU 2691951 C2 RU2691951 C2 RU 2691951C2 RU 2016121850 A RU2016121850 A RU 2016121850A RU 2016121850 A RU2016121850 A RU 2016121850A RU 2691951 C2 RU2691951 C2 RU 2691951C2
- Authority
- RU
- Russia
- Prior art keywords
- salt
- tris
- pharmaceutical composition
- hydroxymethyl
- pharmaceutically acceptable
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 20
- 239000000203 mixture Substances 0.000 claims abstract description 275
- 238000000034 method Methods 0.000 claims abstract description 174
- 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 123
- 238000002347 injection Methods 0.000 claims abstract description 64
- 239000007924 injection Substances 0.000 claims abstract description 64
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 57
- 239000007864 aqueous solution Substances 0.000 claims abstract description 52
- 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 abstract description 47
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 21
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- 201000010099 disease Diseases 0.000 claims abstract description 17
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- 239000007787 solid Substances 0.000 claims abstract description 15
- 230000001404 mediated effect Effects 0.000 claims abstract description 9
- 239000003341 Bronsted base Substances 0.000 claims abstract 9
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- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 296
- 239000002585 base Substances 0.000 claims description 226
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 212
- -1 alkoxide salt Chemical class 0.000 claims description 212
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- 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 115
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- 239000001488 sodium phosphate Substances 0.000 claims description 61
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- 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 48
- 239000004475 Arginine Substances 0.000 claims description 47
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- 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 28
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- 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
- 229930195725 Mannitol 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
- 229930006000 Sucrose Natural products 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
- 239000000594 mannitol Substances 0.000 claims description 26
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- 239000005720 sucrose Substances 0.000 claims description 26
- 239000008103 glucose Substances 0.000 claims description 25
- 239000000243 solution Substances 0.000 claims description 25
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 22
- 239000008121 dextrose Substances 0.000 claims description 22
- 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 21
- 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 21
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims description 21
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- 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
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- 210000004556 brain Anatomy 0.000 claims description 20
- 229960001484 edetic acid Drugs 0.000 claims description 20
- 230000007954 hypoxia Effects 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
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical class CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 17
- 150000001642 boronic acid derivatives Chemical class 0.000 claims description 17
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 17
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 208000005735 Water intoxication Diseases 0.000 claims description 14
- 229910000000 metal hydroxide Inorganic materials 0.000 claims description 14
- 208000006011 Stroke Diseases 0.000 claims description 13
- 150000004703 alkoxides Chemical class 0.000 claims description 13
- 150000004692 metal hydroxides Chemical class 0.000 claims description 13
- 206010030113 Oedema Diseases 0.000 claims description 12
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
- 206010019280 Heart failures Diseases 0.000 claims description 11
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- 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
- 208000030886 Traumatic Brain injury Diseases 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 10
- 229920001223 polyethylene glycol Polymers 0.000 claims description 10
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 10
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- 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
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 10
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- 235000013855 polyvinylpyrrolidone Nutrition 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
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- 208000034388 Mountain sickness acute 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
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- 208000007903 liver failure Diseases 0.000 claims description 8
- 231100000835 liver failure Toxicity 0.000 claims description 8
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims description 8
- 208000005333 pulmonary edema Diseases 0.000 claims description 8
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 claims description 7
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 claims description 7
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- 238000004090 dissolution Methods 0.000 claims description 6
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- 210000004165 myocardium Anatomy 0.000 claims description 4
- 238000010255 intramuscular injection Methods 0.000 claims description 3
- 239000007927 intramuscular injection Substances 0.000 claims description 3
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- 230000005486 microgravity Effects 0.000 claims description 3
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- 229910000288 alkali metal carbonate Inorganic materials 0.000 claims 6
- 150000008041 alkali metal carbonates Chemical class 0.000 claims 6
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims 1
- 208000009447 Cardiac Edema Diseases 0.000 claims 1
- 208000018652 Closed Head injury Diseases 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 230000010412 perfusion Effects 0.000 claims 1
- PVGBHEUCHKGFQP-UHFFFAOYSA-N sodium;n-[5-amino-2-(4-aminophenyl)sulfonylphenyl]sulfonylacetamide Chemical compound [Na+].CC(=O)NS(=O)(=O)C1=CC(N)=CC=C1S(=O)(=O)C1=CC=C(N)C=C1 PVGBHEUCHKGFQP-UHFFFAOYSA-N 0.000 claims 1
- 239000000126 substance Substances 0.000 abstract description 4
- 230000000694 effects Effects 0.000 abstract 1
- PIEPQKCYPFFYMG-UHFFFAOYSA-N tris acetate Chemical compound CC(O)=O.OCC(N)(CO)CO PIEPQKCYPFFYMG-UHFFFAOYSA-N 0.000 description 217
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- 125000003161 (C1-C6) alkylene group Chemical group 0.000 description 92
- 239000007983 Tris buffer Substances 0.000 description 88
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- 229910052784 alkaline earth metal Inorganic materials 0.000 description 84
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 81
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- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical class [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 20
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- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 14
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- AXCZMVOFGPJBDE-UHFFFAOYSA-L calcium dihydroxide Chemical compound [OH-].[OH-].[Ca+2] AXCZMVOFGPJBDE-UHFFFAOYSA-L 0.000 description 12
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- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 12
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| BR112014027983B1 (pt) | 2012-05-08 | 2022-05-24 | Aeromics, Inc | Uso de inibidores de aquaporina seletivos |
| RU2691951C2 (ru) | 2013-11-06 | 2019-06-19 | Аэромикс, Инк. | Новые составы |
| AU2017261828B2 (en) * | 2016-05-13 | 2023-04-13 | Aeromics, Inc. | Crystals |
| 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 |
| MX2023001493A (es) * | 2020-08-05 | 2023-06-23 | Jiangsu Simcere Pharm Co Ltd | Composicion farmaceutica de un inhibidor de la acuaporina y metodo para la preparacion de la misma. |
| 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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