CN114502187A - 一种肽酰胺类组合物及其制备 - Google Patents
一种肽酰胺类组合物及其制备 Download PDFInfo
- Publication number
- CN114502187A CN114502187A CN202080058211.4A CN202080058211A CN114502187A CN 114502187 A CN114502187 A CN 114502187A CN 202080058211 A CN202080058211 A CN 202080058211A CN 114502187 A CN114502187 A CN 114502187A
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- Prior art keywords
- alkyl
- injection
- compound
- radical
- carbocyclyl
- Prior art date
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- 238000002360 preparation method Methods 0.000 title claims abstract description 104
- 239000000203 mixture Substances 0.000 title claims abstract description 72
- 108090000765 processed proteins & peptides Proteins 0.000 title abstract description 8
- 150000001408 amides Chemical class 0.000 title description 4
- -1 amide compound Chemical class 0.000 claims abstract description 139
- 150000001875 compounds Chemical class 0.000 claims abstract description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 159
- 239000000243 solution Substances 0.000 claims description 135
- 238000002347 injection Methods 0.000 claims description 129
- 239000007924 injection Substances 0.000 claims description 129
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 99
- 125000000623 heterocyclic group Chemical group 0.000 claims description 88
- 239000008215 water for injection Substances 0.000 claims description 77
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 58
- 238000001914 filtration Methods 0.000 claims description 46
- 230000001954 sterilising effect Effects 0.000 claims description 46
- 125000001424 substituent group Chemical group 0.000 claims description 38
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 37
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 37
- 125000000217 alkyl group Chemical group 0.000 claims description 37
- 229910052794 bromium Inorganic materials 0.000 claims description 37
- 239000011975 tartaric acid Substances 0.000 claims description 37
- 235000002906 tartaric acid Nutrition 0.000 claims description 37
- 229910052740 iodine Inorganic materials 0.000 claims description 36
- 239000000460 chlorine Substances 0.000 claims description 32
- 229910052801 chlorine Inorganic materials 0.000 claims description 31
- 229910052731 fluorine Inorganic materials 0.000 claims description 31
- 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 30
- 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 30
- 229910052717 sulfur Inorganic materials 0.000 claims description 30
- 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 29
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 28
- 239000013543 active substance Substances 0.000 claims description 28
- 229910001873 dinitrogen Inorganic materials 0.000 claims description 26
- 229910052760 oxygen Inorganic materials 0.000 claims description 25
- 125000005842 heteroatom Chemical group 0.000 claims description 24
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical group OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 23
- 229930195725 Mannitol Natural products 0.000 claims description 23
- 239000003963 antioxidant agent Substances 0.000 claims description 23
- 230000003078 antioxidant effect Effects 0.000 claims description 23
- 239000000594 mannitol Substances 0.000 claims description 23
- 235000010355 mannitol Nutrition 0.000 claims description 23
- 229910052757 nitrogen Inorganic materials 0.000 claims description 23
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 18
- 239000003381 stabilizer Substances 0.000 claims description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical group [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims description 16
- 208000002193 Pain Diseases 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- 238000005192 partition Methods 0.000 claims description 16
- 239000003242 anti bacterial agent Substances 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- 238000007710 freezing Methods 0.000 claims description 14
- 230000008014 freezing Effects 0.000 claims description 14
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- 239000000843 powder Substances 0.000 claims description 14
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 12
- 239000007853 buffer solution Substances 0.000 claims description 11
- 102000048260 kappa Opioid Receptors Human genes 0.000 claims description 11
- 108020001588 κ-opioid receptors Proteins 0.000 claims description 11
- 125000003342 alkenyl group Chemical group 0.000 claims description 10
- 125000000304 alkynyl group Chemical group 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 10
- 239000003002 pH adjusting agent Substances 0.000 claims description 10
- 239000000945 filler Substances 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 9
- 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 8
- 208000003251 Pruritus Diseases 0.000 claims description 8
- 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 8
- 239000008103 glucose Substances 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 238000000034 method Methods 0.000 claims description 6
- 208000004296 neuralgia Diseases 0.000 claims description 6
- 208000021722 neuropathic pain Diseases 0.000 claims description 6
- 206010011224 Cough Diseases 0.000 claims description 5
- 208000010412 Glaucoma Diseases 0.000 claims description 5
- 208000019025 Hypokalemia Diseases 0.000 claims description 5
- 206010021036 Hyponatraemia Diseases 0.000 claims description 5
- 206010061218 Inflammation Diseases 0.000 claims description 5
- 206010030113 Oedema Diseases 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 5
- 208000008384 ileus Diseases 0.000 claims description 5
- 230000004054 inflammatory process Effects 0.000 claims description 5
- 208000024896 potassium deficiency disease Diseases 0.000 claims description 5
- BHZOKUMUHVTPBX-UHFFFAOYSA-M sodium acetic acid acetate Chemical compound [Na+].CC(O)=O.CC([O-])=O BHZOKUMUHVTPBX-UHFFFAOYSA-M 0.000 claims description 5
- 125000005330 8 membered heterocyclic group Chemical group 0.000 claims description 4
- 208000001294 Nociceptive Pain Diseases 0.000 claims description 4
- 125000002837 carbocyclic group Chemical group 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 238000004108 freeze drying Methods 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- 208000009935 visceral pain Diseases 0.000 claims description 4
- 235000011054 acetic acid Nutrition 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 239000007974 sodium acetate buffer Substances 0.000 claims description 3
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 2
- 239000005711 Benzoic acid Substances 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims description 2
- 150000007513 acids Chemical class 0.000 claims description 2
- 235000010233 benzoic acid Nutrition 0.000 claims description 2
- UEAVLBXLOZNDHT-UHFFFAOYSA-K calcium;sodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxymethyl)amino]acetate Chemical compound [Na+].[Ca+2].OC(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEAVLBXLOZNDHT-UHFFFAOYSA-K 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- WSTFOXFZSUMNHY-UHFFFAOYSA-L disodium 2,3-dihydroxybutanedioate 2,3-dihydroxybutanedioic acid Chemical compound [Na+].[Na+].OC(C(O)C(O)=O)C(O)=O.OC(C(O)C(O)=O)C(O)=O.OC(C(O)C([O-])=O)C([O-])=O WSTFOXFZSUMNHY-UHFFFAOYSA-L 0.000 claims 1
- 235000011007 phosphoric acid Nutrition 0.000 claims 1
- ZEFCBWQRHWLUTC-UHFFFAOYSA-M sodium;2,3-dihydroxybutanedioic acid;2,3,4-trihydroxy-4-oxobutanoate Chemical compound [Na+].OC(=O)C(O)C(O)C(O)=O.OC(=O)C(O)C(O)C([O-])=O ZEFCBWQRHWLUTC-UHFFFAOYSA-M 0.000 claims 1
- 239000000463 material Substances 0.000 abstract description 4
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 171
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 78
- 238000003756 stirring Methods 0.000 description 72
- 239000000126 substance Substances 0.000 description 51
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- 238000005303 weighing Methods 0.000 description 43
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 39
- 150000003254 radicals Chemical class 0.000 description 38
- 238000010438 heat treatment Methods 0.000 description 36
- 239000007788 liquid Substances 0.000 description 33
- 239000001632 sodium acetate Substances 0.000 description 26
- 235000017281 sodium acetate Nutrition 0.000 description 26
- 125000003118 aryl group Chemical group 0.000 description 24
- 238000001816 cooling Methods 0.000 description 24
- 239000012535 impurity Substances 0.000 description 24
- 125000000753 cycloalkyl group Chemical group 0.000 description 18
- 125000001072 heteroaryl group Chemical group 0.000 description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 14
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- 238000007789 sealing Methods 0.000 description 14
- 125000003003 spiro group Chemical group 0.000 description 13
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- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 12
- 229940049954 penicillin Drugs 0.000 description 12
- 238000003825 pressing Methods 0.000 description 11
- 239000002994 raw material Substances 0.000 description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 9
- 150000001733 carboxylic acid esters Chemical class 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 8
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- 239000004067 bulking agent Substances 0.000 description 7
- 229940124274 edetate disodium Drugs 0.000 description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
- 238000011835 investigation Methods 0.000 description 7
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- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 150000001299 aldehydes Chemical class 0.000 description 6
- 125000001188 haloalkyl group Chemical group 0.000 description 6
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 6
- 125000002462 isocyano group Chemical group *[N+]#[C-] 0.000 description 6
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- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
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- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- Hematology (AREA)
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
Claims (24)
- PCT国内申请,权利要求书已公开。
Applications Claiming Priority (3)
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CN2019107517007 | 2019-08-23 | ||
CN201910751700 | 2019-08-23 | ||
PCT/CN2020/110760 WO2021036975A1 (zh) | 2019-08-23 | 2020-08-24 | 一种肽酰胺类组合物及其制备 |
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US (1) | US20220305074A1 (zh) |
EP (1) | EP4019033A4 (zh) |
JP (1) | JP7571123B2 (zh) |
KR (1) | KR20220069000A (zh) |
CN (1) | CN114502187B (zh) |
AU (1) | AU2020338767A1 (zh) |
BR (1) | BR112022003359A2 (zh) |
CA (1) | CA3152065A1 (zh) |
MX (1) | MX2022002187A (zh) |
TW (1) | TWI764248B (zh) |
WO (1) | WO2021036975A1 (zh) |
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US20240207353A1 (en) * | 2021-04-12 | 2024-06-27 | Xizang Haisco Pharmaceutical Co., Ltd. | Use of peptide amide compound in preparation of drug for treating pruritus |
Citations (6)
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CN1666741A (zh) * | 2004-03-10 | 2005-09-14 | 山东绿叶制药股份有限公司 | 稳定的纳洛酮冻干粉针剂及其制备工艺 |
CN1895251A (zh) * | 2005-07-13 | 2007-01-17 | 汕头大学医学院 | 稳定的盐酸纳美芬注射液及其制备方法 |
US7402564B1 (en) * | 2006-11-10 | 2008-07-22 | Cara Therapeutics, Inc. | Synthetic peptide amides |
WO2019015644A1 (zh) * | 2017-07-21 | 2019-01-24 | 四川海思科制药有限公司 | 肽酰胺类化合物及其制备方法和在医药上的用途 |
CN109280075A (zh) * | 2017-07-21 | 2019-01-29 | 四川海思科制药有限公司 | 肽酰胺类化合物及其制备方法和在医药上的用途 |
CN109280076A (zh) * | 2017-07-21 | 2019-01-29 | 四川海思科制药有限公司 | 肽酰胺类化合物及其制备方法和在医药上的用途 |
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2020
- 2020-08-21 TW TW109128673A patent/TWI764248B/zh active
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- 2020-08-24 WO PCT/CN2020/110760 patent/WO2021036975A1/zh unknown
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- 2020-08-24 US US17/637,189 patent/US20220305074A1/en active Pending
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- 2020-08-24 EP EP20855974.0A patent/EP4019033A4/en active Pending
- 2020-08-24 KR KR1020227009340A patent/KR20220069000A/ko unknown
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1666741A (zh) * | 2004-03-10 | 2005-09-14 | 山东绿叶制药股份有限公司 | 稳定的纳洛酮冻干粉针剂及其制备工艺 |
CN1895251A (zh) * | 2005-07-13 | 2007-01-17 | 汕头大学医学院 | 稳定的盐酸纳美芬注射液及其制备方法 |
US7402564B1 (en) * | 2006-11-10 | 2008-07-22 | Cara Therapeutics, Inc. | Synthetic peptide amides |
CN101627049A (zh) * | 2006-11-10 | 2010-01-13 | 卡拉治疗学股份有限公司 | 合成酞酰胺 |
WO2019015644A1 (zh) * | 2017-07-21 | 2019-01-24 | 四川海思科制药有限公司 | 肽酰胺类化合物及其制备方法和在医药上的用途 |
CN109280075A (zh) * | 2017-07-21 | 2019-01-29 | 四川海思科制药有限公司 | 肽酰胺类化合物及其制备方法和在医药上的用途 |
CN109280076A (zh) * | 2017-07-21 | 2019-01-29 | 四川海思科制药有限公司 | 肽酰胺类化合物及其制备方法和在医药上的用途 |
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KR20220069000A (ko) | 2022-05-26 |
EP4019033A4 (en) | 2022-12-14 |
JP7571123B2 (ja) | 2024-10-22 |
EP4019033A1 (en) | 2022-06-29 |
TW202114727A (zh) | 2021-04-16 |
JP2022552065A (ja) | 2022-12-15 |
WO2021036975A1 (zh) | 2021-03-04 |
CA3152065A1 (en) | 2021-03-04 |
US20220305074A1 (en) | 2022-09-29 |
TWI764248B (zh) | 2022-05-11 |
BR112022003359A2 (pt) | 2022-05-17 |
AU2020338767A1 (en) | 2022-03-31 |
CN114502187B (zh) | 2024-06-25 |
MX2022002187A (es) | 2022-03-11 |
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