CN1769286A - 一种治疗鼻腔分泌过度和慢阻肺的化合物以及药物组合物 - Google Patents
一种治疗鼻腔分泌过度和慢阻肺的化合物以及药物组合物 Download PDFInfo
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- CN1769286A CN1769286A CNA2005101092923A CN200510109292A CN1769286A CN 1769286 A CN1769286 A CN 1769286A CN A2005101092923 A CNA2005101092923 A CN A2005101092923A CN 200510109292 A CN200510109292 A CN 200510109292A CN 1769286 A CN1769286 A CN 1769286A
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- LMUJEWVKOCYOQL-UHFFFAOYSA-M 1-cyclopentyl-2-[(1-methyl-1-azoniabicyclo[2.2.2]octan-3-yl)oxy]-1-phenylethanol bromide Chemical compound [Br-].C1C[N+](C)(C2)CCC1C2OCC(O)(C=1C=CC=CC=1)C1CCCC1 LMUJEWVKOCYOQL-UHFFFAOYSA-M 0.000 description 1
- YAHCEHSKYMREOS-UHFFFAOYSA-N 1-cyclopentyloxyethylbenzene Chemical compound C=1C=CC=CC=1C(C)OC1CCCC1 YAHCEHSKYMREOS-UHFFFAOYSA-N 0.000 description 1
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 1
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- UAIUNKRWKOVEES-UHFFFAOYSA-N 3,3',5,5'-tetramethylbenzidine Chemical compound CC1=C(N)C(C)=CC(C=2C=C(C)C(N)=C(C)C=2)=C1 UAIUNKRWKOVEES-UHFFFAOYSA-N 0.000 description 1
- IVLICPVPXWEGCA-UHFFFAOYSA-N 3-quinuclidinol Chemical compound C1C[C@@H]2C(O)C[N@]1CC2 IVLICPVPXWEGCA-UHFFFAOYSA-N 0.000 description 1
- LSLYOANBFKQKPT-DIFFPNOSSA-N 5-[(1r)-1-hydroxy-2-[[(2r)-1-(4-hydroxyphenyl)propan-2-yl]amino]ethyl]benzene-1,3-diol Chemical compound C([C@@H](C)NC[C@H](O)C=1C=C(O)C=C(O)C=1)C1=CC=C(O)C=C1 LSLYOANBFKQKPT-DIFFPNOSSA-N 0.000 description 1
- 240000003291 Armoracia rusticana Species 0.000 description 1
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- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- 208000003322 Coinfection Diseases 0.000 description 1
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 1
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- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical class C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 1
- 240000005578 Rivina humilis Species 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
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- 238000004458 analytical method Methods 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 229950000210 beclometasone dipropionate Drugs 0.000 description 1
- 229940082436 benzalkonium chloride 3 mg Drugs 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 201000009267 bronchiectasis Diseases 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- NEHMKBQYUWJMIP-NJFSPNSNSA-N chloro(114C)methane Chemical compound [14CH3]Cl NEHMKBQYUWJMIP-NJFSPNSNSA-N 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229960004544 cortisone Drugs 0.000 description 1
- VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
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- 238000004043 dyeing Methods 0.000 description 1
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- 229960004756 ethanol Drugs 0.000 description 1
- 229960001022 fenoterol Drugs 0.000 description 1
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- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 150000002462 imidazolines Chemical class 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
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- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 210000000627 locus coeruleus Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
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- 238000004519 manufacturing process Methods 0.000 description 1
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- 230000007935 neutral effect Effects 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
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- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
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- 210000003462 vein Anatomy 0.000 description 1
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Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0043—Nose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/008—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Organic Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pulmonology (AREA)
- Otolaryngology (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
化合物V | 12mg |
苯扎氯铵 | 3mg |
H2O | 10ml |
化合物II | 2.5mg |
非诺特罗 | 10mg |
苯扎氯铵 | 5mg |
H2O | 10ml |
化合物I | 3.33mg |
苯扎氯铵 | 5.00mg |
1N HCl(pH 4-6) | 0.018mg |
纯H2O | 2.0ml |
化合物I | 0.02g | |
表面活性剂(豆磷脂或吐温) | 0.03-0.3g | |
抛射剂 | 1-氟-3氯甲烷2-氟-2氯甲烷4-氟-2氯乙烷 | 20g20g30g |
化合物IV | 0.28g |
丙二醇 | 42g |
无水乙醇 | 210g |
2-氟-2氯甲烷4-氟-2氯乙烷 | 231g971g |
化合物V | 0.28g |
丙二醇 | 35g |
无水乙醇 | 382g |
2-氟-2氯甲烷和4-氟-2氯乙烷) | 540g443g |
化合物III | 0.05 g |
乳糖 | 98.95g |
苯甲酸钠 | 1.0g |
化合物V | 0.05g |
葡聚糖 | 99.45g |
硬脂酸镁 | 0.5g |
组别 | 动物数(只) | 剂量 | 血清OVA特异性IgE水平(OD值) |
模型组阴性对照组盐酸左卡巴斯汀伯克纳组实施例二之1实施例二之2实施例二之3 | 10101010101010 | 等容溶媒等容溶媒每个鼻孔一喷每个鼻孔一喷每个鼻孔二滴每个鼻孔二滴每个鼻孔一喷 | 0.241±0.028▲▲0.0830±0.038**0.0819±0.031**0.1008±0.041**0.996±0.029**0.0876±0.058**0.0967±0.069** |
组别 | 动物数(只) | 剂量 | 鼻分泌物中OVA特异性IgE水平(OD值) |
模型组阴性对照组盐酸左卡巴斯汀伯克纳组实施例二之1实施例二之2实施例二之3 | 10101010101010 | 等容溶媒等容溶媒每个鼻孔一喷每个鼻孔一喷每个鼻孔二滴每个鼻孔二滴每个鼻孔一喷 | 0.311±0.019▲▲0.175±0.028**0.208±0.035**▲0.209±0.022**▲▲0.197±0.040**0.209±0.047**▲▲0.201±0.027*▲▲ |
组别 | 剂量 | 皮点色斑吸光度值(OD值) |
模型组阴性对照组盐酸左卡巴斯汀伯克纳组 | 等容溶媒等容溶媒每个鼻孔一喷每个鼻孔一喷 | 0.602±0.0895▲▲0.159±0.0312**0.181±0.0376**0.191±0.0788** |
实施例二之1实施例二之2实施例二之3 | 每个鼻孔二滴每个鼻孔二滴每个鼻孔一喷 | 0.169±0.0289**0.178±0.0651**0.172±0.0395** |
组别 | 动物数(只) | 剂量 | 大鼠行为学打分(分) |
模型组阴性对照组盐酸左卡巴斯汀伯克纳组实施例二之1实施例二之2实施例二之3 | 101010101010 | 等容溶媒等容溶媒每个鼻孔一喷每个鼻孔一喷每个鼻孔二滴每个鼻孔二滴每个鼻孔一喷 | 4.7±1.109▲▲0.73±0.505**1.9±0.883**▲▲1.65±0.875**▲1.98±1.621**▲2.01±1.096**▲1.96±1.425**▲ |
组别 | 动物数(只) | 剂量 | 大鼠单侧鼻分泌物重量(mg) |
模型组阴性对照组盐酸左卡巴斯汀伯克纳组实施例二之1实施例二之2实施例二之3 | 10101010101010 | 等容溶媒等容溶媒每个鼻孔一喷每个鼻孔一喷每个鼻孔二滴每个鼻孔二滴每个鼻孔一喷 | 49.86±25.37▲▲19.58±6.250**19.27±5.133**28.99±5.677*▲▲22.06±6.407**28.73±9.367*▲▲28.01±8.567▲▲ |
组别 | 动物数(只) | 剂量 | 大鼠鼻粘膜病理学打分(分) |
模型组阴性对照组盐酸左卡巴斯汀伯克纳组实施例二之1实施例二之2实施例二之3 | 10101010101010 | 等容溶媒等容溶媒每个鼻孔一喷每个鼻孔一喷每个鼻孔二滴每个鼻孔二滴每个鼻孔一喷 | 4.61±1.502▲▲0.61±0.709**0.69±0.724**1.17±0.776**0.68±0.845**0.70±0.857**0.62±0.998** |
组别 | n | 剂量μg·只-1 | 潜伏期(s) |
空白对照组阳性对照组实施例二之4实施例二之5实施例二之6实施例二之7实施例二之8 | 10101010101010 | -202020202020 | 117.82±25.33228.15±32.42226.32±27.87219.53±29.79235.67±30.26226.42±31.29228.38±25.68 |
Claims (10)
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CN2005101092923A CN1769286B (zh) | 2005-10-20 | 2005-10-20 | 一种治疗鼻腔分泌过度和慢阻肺的化合物以及药物组合物 |
PCT/CN2006/002638 WO2007045151A1 (fr) | 2005-10-20 | 2006-10-09 | Composes et compositions pharmaceutiques les comprenant pour le traitement de l'hypersecretion de la cavite nasale et de la bronchopneumopathie chronique obstructive |
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CN101856327B (zh) * | 2009-04-08 | 2012-02-22 | 北京银谷世纪药业有限公司 | 一种苯环喹溴铵定量吸入气雾剂及制备方法 |
CN111377920A (zh) * | 2018-12-27 | 2020-07-07 | 银谷制药有限责任公司 | 一种含有季铵基团的奎宁类化合物的精制方法 |
CN115487180A (zh) * | 2022-09-01 | 2022-12-20 | 江苏联环药业股份有限公司 | 一种用于治疗变应性鼻炎的药物组合物 |
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CN1219513C (zh) * | 2002-08-16 | 2005-09-21 | 成都力思特制药股份有限公司 | 盐酸戊乙奎醚在制药中的应用 |
CN1257903C (zh) * | 2003-03-21 | 2006-05-31 | 嘉事堂药业股份有限公司 | 一种含有季铵基团的奎宁类化合物及其制法和药物用途 |
US7521559B2 (en) * | 2004-09-15 | 2009-04-21 | Shuqiang Zhao | Quinuclidine compounds having quaternary ammonium group, its preparation method and use as blocking agents of acetylcholine |
CN1709891A (zh) * | 2005-06-16 | 2005-12-21 | 成都力思特制药股份有限公司 | 一种药物化合物及其组合物和在制药中的应用 |
CN1813768A (zh) * | 2005-11-18 | 2006-08-09 | 成都力思特制药股份有限公司 | 治疗呼吸系统疾病的药用组合物及其在制药中的应用 |
-
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN101856327B (zh) * | 2009-04-08 | 2012-02-22 | 北京银谷世纪药业有限公司 | 一种苯环喹溴铵定量吸入气雾剂及制备方法 |
CN111377920A (zh) * | 2018-12-27 | 2020-07-07 | 银谷制药有限责任公司 | 一种含有季铵基团的奎宁类化合物的精制方法 |
CN111377920B (zh) * | 2018-12-27 | 2021-10-26 | 银谷制药有限责任公司 | 一种含有季铵基团的奎宁类化合物的精制方法 |
CN115487180A (zh) * | 2022-09-01 | 2022-12-20 | 江苏联环药业股份有限公司 | 一种用于治疗变应性鼻炎的药物组合物 |
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