CN108904489A - 5,7-甲氧基3,4’羟基黄酮的抗呼吸道炎症性疾病的用途 - Google Patents
5,7-甲氧基3,4’羟基黄酮的抗呼吸道炎症性疾病的用途 Download PDFInfo
- Publication number
- CN108904489A CN108904489A CN201810631852.9A CN201810631852A CN108904489A CN 108904489 A CN108904489 A CN 108904489A CN 201810631852 A CN201810631852 A CN 201810631852A CN 108904489 A CN108904489 A CN 108904489A
- Authority
- CN
- China
- Prior art keywords
- flavonol
- methoxyl group
- parts
- diseases associated
- respiratory diseases
- 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.)
- Pending
Links
- HVQAJTFOCKOKIN-UHFFFAOYSA-N flavonol Natural products O1C2=CC=CC=C2C(=O)C(O)=C1C1=CC=CC=C1 HVQAJTFOCKOKIN-UHFFFAOYSA-N 0.000 title claims abstract description 61
- 235000011957 flavonols Nutrition 0.000 title claims abstract description 61
- 150000007946 flavonol Chemical class 0.000 title claims abstract description 56
- 206010061218 Inflammation Diseases 0.000 title claims abstract description 27
- 230000004054 inflammatory process Effects 0.000 title claims abstract description 27
- 208000023504 respiratory system disease Diseases 0.000 title claims abstract description 15
- 239000003814 drug Substances 0.000 claims abstract description 31
- 229940079593 drug Drugs 0.000 claims abstract description 24
- 238000002347 injection Methods 0.000 claims abstract description 15
- 239000007924 injection Substances 0.000 claims abstract description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 13
- 208000006673 asthma Diseases 0.000 claims abstract description 12
- 239000003795 chemical substances by application Substances 0.000 claims abstract description 9
- 230000000241 respiratory effect Effects 0.000 claims abstract description 9
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims abstract description 7
- 208000004852 Lung Injury Diseases 0.000 claims abstract description 6
- 208000005069 pulmonary fibrosis Diseases 0.000 claims abstract description 6
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims abstract description 5
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims abstract description 5
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 claims abstract description 5
- 206010006451 bronchitis Diseases 0.000 claims abstract description 4
- OBRNDARFFFHCGE-QDSVTUBZSA-N arformoterol fumarate Chemical compound OC(=O)\C=C\C(O)=O.C1=CC(OC)=CC=C1C[C@@H](C)NC[C@H](O)C1=CC=C(O)C(NC=O)=C1.C1=CC(OC)=CC=C1C[C@@H](C)NC[C@H](O)C1=CC=C(O)C(NC=O)=C1 OBRNDARFFFHCGE-QDSVTUBZSA-N 0.000 claims description 12
- 239000000443 aerosol Substances 0.000 claims description 9
- 239000000843 powder Substances 0.000 claims description 9
- 239000002775 capsule Substances 0.000 claims description 8
- 239000008187 granular material Substances 0.000 claims description 8
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 6
- 239000002552 dosage form Substances 0.000 claims description 6
- 229960000193 formoterol fumarate Drugs 0.000 claims description 6
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 6
- 150000002216 flavonol derivatives Chemical class 0.000 claims description 5
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 5
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 5
- 229920001353 Dextrin Polymers 0.000 claims description 4
- 239000004375 Dextrin Substances 0.000 claims description 4
- 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 4
- 229930006000 Sucrose Natural products 0.000 claims description 4
- 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 4
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 claims description 4
- 239000011230 binding agent Substances 0.000 claims description 4
- 235000019425 dextrin Nutrition 0.000 claims description 4
- 239000002270 dispersing agent Substances 0.000 claims description 4
- 239000000945 filler Substances 0.000 claims description 4
- 239000008101 lactose Substances 0.000 claims description 4
- 239000000314 lubricant Substances 0.000 claims description 4
- 229960004793 sucrose Drugs 0.000 claims description 4
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 3
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 3
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 2
- 229940041682 inhalant solution Drugs 0.000 claims description 2
- 229960000935 dehydrated alcohol Drugs 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 229940124531 pharmaceutical excipient Drugs 0.000 claims 1
- 238000002474 experimental method Methods 0.000 abstract description 7
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 5
- 239000003963 antioxidant agent Substances 0.000 abstract description 3
- 230000003078 antioxidant effect Effects 0.000 abstract description 3
- 235000006708 antioxidants Nutrition 0.000 abstract description 3
- 230000000857 drug effect Effects 0.000 abstract description 2
- 230000009257 reactivity Effects 0.000 abstract description 2
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 abstract 1
- 241000700159 Rattus Species 0.000 description 30
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 28
- 238000012360 testing method Methods 0.000 description 24
- 238000000034 method Methods 0.000 description 17
- 230000000694 effects Effects 0.000 description 16
- 210000004493 neutrocyte Anatomy 0.000 description 15
- 229960001340 histamine Drugs 0.000 description 14
- 210000003630 histaminocyte Anatomy 0.000 description 13
- KJFMBFZCATUALV-UHFFFAOYSA-N phenolphthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2C(=O)O1 KJFMBFZCATUALV-UHFFFAOYSA-N 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 210000000683 abdominal cavity Anatomy 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 210000000265 leukocyte Anatomy 0.000 description 10
- 239000006228 supernatant Substances 0.000 description 10
- 239000000427 antigen Substances 0.000 description 9
- 102000036639 antigens Human genes 0.000 description 9
- 108091007433 antigens Proteins 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 108010058846 Ovalbumin Proteins 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- 229940092253 ovalbumin Drugs 0.000 description 8
- 239000002504 physiological saline solution Substances 0.000 description 8
- 230000008859 change Effects 0.000 description 7
- RQTOOFIXOKYGAN-UHFFFAOYSA-N nedocromil Chemical compound CCN1C(C(O)=O)=CC(=O)C2=C1C(CCC)=C1OC(C(O)=O)=CC(=O)C1=C2 RQTOOFIXOKYGAN-UHFFFAOYSA-N 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 102000019197 Superoxide Dismutase Human genes 0.000 description 6
- 108010012715 Superoxide dismutase Proteins 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 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 description 5
- 206010070834 Sensitisation Diseases 0.000 description 5
- 210000001367 artery Anatomy 0.000 description 5
- 239000011521 glass Substances 0.000 description 5
- 230000002757 inflammatory effect Effects 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 229960004398 nedocromil Drugs 0.000 description 5
- 230000002829 reductive effect Effects 0.000 description 5
- 230000036387 respiratory rate Effects 0.000 description 5
- 230000008313 sensitization Effects 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 4
- 102000053187 Glucuronidase Human genes 0.000 description 4
- 108010060309 Glucuronidase Proteins 0.000 description 4
- 241001465754 Metazoa Species 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- PRQROPMIIGLWRP-UHFFFAOYSA-N N-formyl-methionyl-leucyl-phenylalanin Chemical compound CSCCC(NC=O)C(=O)NC(CC(C)C)C(=O)NC(C(O)=O)CC1=CC=CC=C1 PRQROPMIIGLWRP-UHFFFAOYSA-N 0.000 description 4
- 229940124599 anti-inflammatory drug Drugs 0.000 description 4
- 238000000889 atomisation Methods 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 239000005482 chemotactic factor Substances 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 231100000673 dose–response relationship Toxicity 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 210000003200 peritoneal cavity Anatomy 0.000 description 4
- 230000001376 precipitating effect Effects 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 210000003462 vein Anatomy 0.000 description 4
- 241000700199 Cavia porcellus Species 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- GBOGMAARMMDZGR-UHFFFAOYSA-N UNPD149280 Natural products N1C(=O)C23OC(=O)C=CC(O)CCCC(C)CC=CC3C(O)C(=C)C(C)C2C1CC1=CC=CC=C1 GBOGMAARMMDZGR-UHFFFAOYSA-N 0.000 description 3
- 238000010521 absorption reaction Methods 0.000 description 3
- 239000008351 acetate buffer Substances 0.000 description 3
- 210000003567 ascitic fluid Anatomy 0.000 description 3
- IMZMKUWMOSJXDT-UHFFFAOYSA-N cromoglycic acid Chemical compound O1C(C(O)=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C(O)=O)O2 IMZMKUWMOSJXDT-UHFFFAOYSA-N 0.000 description 3
- GBOGMAARMMDZGR-JREHFAHYSA-N cytochalasin B Natural products C[C@H]1CCC[C@@H](O)C=CC(=O)O[C@@]23[C@H](C=CC1)[C@H](O)C(=C)[C@@H](C)[C@@H]2[C@H](Cc4ccccc4)NC3=O GBOGMAARMMDZGR-JREHFAHYSA-N 0.000 description 3
- GBOGMAARMMDZGR-TYHYBEHESA-N cytochalasin B Chemical compound C([C@H]1[C@@H]2[C@@H](C([C@@H](O)[C@@H]3/C=C/C[C@H](C)CCC[C@@H](O)/C=C/C(=O)O[C@@]23C(=O)N1)=C)C)C1=CC=CC=C1 GBOGMAARMMDZGR-TYHYBEHESA-N 0.000 description 3
- 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 3
- 230000007613 environmental effect Effects 0.000 description 3
- 229930003944 flavone Natural products 0.000 description 3
- 235000011949 flavones Nutrition 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 210000004969 inflammatory cell Anatomy 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 229920000609 methyl cellulose Polymers 0.000 description 3
- 239000001923 methylcellulose Substances 0.000 description 3
- 239000013641 positive control Substances 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- 206010067484 Adverse reaction Diseases 0.000 description 2
- 208000000059 Dyspnea Diseases 0.000 description 2
- 206010013975 Dyspnoeas Diseases 0.000 description 2
- 239000012981 Hank's balanced salt solution Substances 0.000 description 2
- 101000818522 Homo sapiens fMet-Leu-Phe receptor Proteins 0.000 description 2
- GAMYVSCDDLXAQW-AOIWZFSPSA-N Thermopsosid Natural products O(C)c1c(O)ccc(C=2Oc3c(c(O)cc(O[C@H]4[C@H](O)[C@@H](O)[C@H](O)[C@H](CO)O4)c3)C(=O)C=2)c1 GAMYVSCDDLXAQW-AOIWZFSPSA-N 0.000 description 2
- 206010047924 Wheezing Diseases 0.000 description 2
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
- 229960004373 acetylcholine Drugs 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000002671 adjuvant Substances 0.000 description 2
- 230000006838 adverse reaction Effects 0.000 description 2
- 230000000172 allergic effect Effects 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 208000010668 atopic eczema Diseases 0.000 description 2
- 238000011088 calibration curve Methods 0.000 description 2
- 239000000679 carrageenan Substances 0.000 description 2
- 235000010418 carrageenan Nutrition 0.000 description 2
- 229920001525 carrageenan Polymers 0.000 description 2
- 229940113118 carrageenan Drugs 0.000 description 2
- 210000000038 chest Anatomy 0.000 description 2
- 229920002055 compound 48/80 Polymers 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 230000036461 convulsion Effects 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 239000003405 delayed action preparation Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 239000006196 drop Substances 0.000 description 2
- 238000004043 dyeing Methods 0.000 description 2
- 210000003979 eosinophil Anatomy 0.000 description 2
- 210000002919 epithelial cell Anatomy 0.000 description 2
- 239000003889 eye drop Substances 0.000 description 2
- 229940012356 eye drops Drugs 0.000 description 2
- 102100021145 fMet-Leu-Phe receptor Human genes 0.000 description 2
- -1 flavone compound Chemical class 0.000 description 2
- 239000004459 forage Substances 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000003862 glucocorticoid Substances 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000002555 ionophore Substances 0.000 description 2
- 230000000236 ionophoric effect Effects 0.000 description 2
- 231100000518 lethal Toxicity 0.000 description 2
- 230000001665 lethal effect Effects 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000007923 nasal drop Substances 0.000 description 2
- 210000000440 neutrophil Anatomy 0.000 description 2
- 230000010412 perfusion Effects 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 230000002685 pulmonary effect Effects 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 210000002345 respiratory system Anatomy 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000007901 soft capsule Substances 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- VHBFFQKBGNRLFZ-UHFFFAOYSA-N vitamin p Natural products O1C2=CC=CC=C2C(=O)C=C1C1=CC=CC=C1 VHBFFQKBGNRLFZ-UHFFFAOYSA-N 0.000 description 2
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 2
- YJLIKUSWRSEPSM-WGQQHEPDSA-N (2r,3r,4s,5r)-2-[6-amino-8-[(4-phenylphenyl)methylamino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1CNC1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O YJLIKUSWRSEPSM-WGQQHEPDSA-N 0.000 description 1
- FXJYOZKDDSONLX-XADSOVDISA-N (2s,3s,4s,5r,6s)-3,4,5-trihydroxy-6-[4-[1-(4-hydroxyphenyl)-3-oxo-2-benzofuran-1-yl]phenoxy]oxane-2-carboxylic acid Chemical compound O1[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1OC1=CC=C(C2(C3=CC=CC=C3C(=O)O2)C=2C=CC(O)=CC=2)C=C1 FXJYOZKDDSONLX-XADSOVDISA-N 0.000 description 1
- MPDDTAJMJCESGV-CTUHWIOQSA-M (3r,5r)-7-[2-(4-fluorophenyl)-5-[methyl-[(1r)-1-phenylethyl]carbamoyl]-4-propan-2-ylpyrazol-3-yl]-3,5-dihydroxyheptanoate Chemical compound C1([C@@H](C)N(C)C(=O)C2=NN(C(CC[C@@H](O)C[C@@H](O)CC([O-])=O)=C2C(C)C)C=2C=CC(F)=CC=2)=CC=CC=C1 MPDDTAJMJCESGV-CTUHWIOQSA-M 0.000 description 1
- YFMFNYKEUDLDTL-UHFFFAOYSA-N 1,1,1,2,3,3,3-heptafluoropropane Chemical compound FC(F)(F)C(F)C(F)(F)F YFMFNYKEUDLDTL-UHFFFAOYSA-N 0.000 description 1
- TZCPCKNHXULUIY-RGULYWFUSA-N 1,2-distearoyl-sn-glycero-3-phosphoserine Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(=O)OC[C@H](N)C(O)=O)OC(=O)CCCCCCCCCCCCCCCCC TZCPCKNHXULUIY-RGULYWFUSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- KVYRCBOUKXJXDK-UHFFFAOYSA-N 3,4-dimethylphenazine-1,2-diamine hydrochloride Chemical compound Cl.C1=CC=CC2=NC3=C(C)C(C)=C(N)C(N)=C3N=C21 KVYRCBOUKXJXDK-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 101710145634 Antigen 1 Proteins 0.000 description 1
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- 206010006482 Bronchospasm Diseases 0.000 description 1
- COXVTLYNGOIATD-HVMBLDELSA-N CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O Chemical compound CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O COXVTLYNGOIATD-HVMBLDELSA-N 0.000 description 1
- ARZLNCVUULQBQG-HBEZZINHSA-N C[C@@H]1CCCC(=O)\C=C\C(=O)O[C@]23[C@@H](\C=C\C1)[C@H](O)C(=C(C)[C@H]2[C@H](Cc4ccccc4)NC3=O)C Chemical compound C[C@@H]1CCCC(=O)\C=C\C(=O)O[C@]23[C@@H](\C=C\C1)[C@H](O)C(=C(C)[C@H]2[C@H](Cc4ccccc4)NC3=O)C ARZLNCVUULQBQG-HBEZZINHSA-N 0.000 description 1
- 101100203566 Caenorhabditis elegans sod-3 gene Proteins 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- 102000018832 Cytochromes Human genes 0.000 description 1
- 108010052832 Cytochromes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010015719 Exsanguination Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 239000001828 Gelatine Substances 0.000 description 1
- 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 description 1
- ZWZWYGMENQVNFU-UHFFFAOYSA-N Glycerophosphorylserin Natural products OC(=O)C(N)COP(O)(=O)OCC(O)CO ZWZWYGMENQVNFU-UHFFFAOYSA-N 0.000 description 1
- 229920002527 Glycogen Polymers 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 239000007836 KH2PO4 Substances 0.000 description 1
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 1
- 101150031658 Nacc1 gene Proteins 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 208000002151 Pleural effusion Diseases 0.000 description 1
- 101100533820 Rattus norvegicus Sod3 gene Proteins 0.000 description 1
- 208000037656 Respiratory Sounds Diseases 0.000 description 1
- 206010038669 Respiratory arrest Diseases 0.000 description 1
- 206010038687 Respiratory distress Diseases 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 241000256856 Vespidae Species 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- GLLRIXZGBQOFLM-UHFFFAOYSA-N Xanthorin Natural products C1=C(C)C=C2C(=O)C3=C(O)C(OC)=CC(O)=C3C(=O)C2=C1O GLLRIXZGBQOFLM-UHFFFAOYSA-N 0.000 description 1
- 210000001015 abdomen Anatomy 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 238000000862 absorption spectrum Methods 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- ZEHGKSPCAMLJDC-UHFFFAOYSA-M acetylcholine bromide Chemical compound [Br-].CC(=O)OCC[N+](C)(C)C ZEHGKSPCAMLJDC-UHFFFAOYSA-M 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- 238000004220 aggregation Methods 0.000 description 1
- 201000009961 allergic asthma Diseases 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- AEMOLEFTQBMNLQ-QIUUJYRFSA-N beta-D-glucuronic acid Chemical compound O[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-QIUUJYRFSA-N 0.000 description 1
- 230000008033 biological extinction Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229940098773 bovine serum albumin Drugs 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 230000007885 bronchoconstriction Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000007881 chronic fibrosis Effects 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 229960003699 evans blue Drugs 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 239000003337 fertilizer Substances 0.000 description 1
- 150000002213 flavones Chemical class 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 238000011010 flushing procedure Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940096919 glycogen Drugs 0.000 description 1
- 229960001660 histamine phosphate Drugs 0.000 description 1
- ZHIBQGJKHVBLJJ-UHFFFAOYSA-N histamine phosphate Chemical compound OP(O)(O)=O.OP(O)(O)=O.NCCC1=CNC=N1 ZHIBQGJKHVBLJJ-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000011268 leukocyte chemotaxis Effects 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 210000000627 locus coeruleus Anatomy 0.000 description 1
- 230000004199 lung function Effects 0.000 description 1
- 238000013123 lung function test Methods 0.000 description 1
- 229940071648 metered dose inhaler Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 229940066827 pertussis vaccine Drugs 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 210000004224 pleura Anatomy 0.000 description 1
- 210000003281 pleural cavity Anatomy 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 238000009531 respiratory rate measurement Methods 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000007619 statistical method Methods 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 238000002627 tracheal intubation Methods 0.000 description 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 description 1
- 230000002618 waking effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- 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
-
- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
-
- 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
- A61P11/06—Antiasthmatics
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Otolaryngology (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
本发明提供5,7‑甲氧基3,4’羟基黄酮的抗呼吸道炎症性疾病的用途，涉及5,7‑甲氧基3,4’羟基黄酮在制备抗呼吸道炎症性疾病药物中的应用。本发明通过一系列实验证实,7‑甲氧基3,4’羟基黄酮具有明显的抗炎、抗氧化、抗气管收缩反应活性，且口服给药能吸收，显示较强的药效，有10％～25％的生物利用度，可制备成口服剂、注射剂和吸入剂。可替代糖皮质激素制剂，适用于各种呼吸道炎症性疾病如支气管哮喘、急性支气管炎、慢性阻塞性肺病、急/慢性肺损伤和呼吸窘迫症、肺纤维化。
Description
技术领域
本发明属于医药领域，具体涉及5,7-甲氧基3,4’羟基黄酮在制备抗呼吸道炎症性疾病药物中的应用。
背景技术
支气管哮喘、慢性阻塞性肺病发病率高,是常见的呼吸道炎症性疾病，其主要原因是由于大气污染和环境变化。环境变化引起的肺部病毒和细菌感染常诱发急性支气管炎、急/慢性肺损伤和呼吸窘迫症。而支气管哮喘、慢性阻塞性肺病、急/慢性肺损伤和呼吸窘迫症严重阶段均可产生难以治愈的肺纤维化。这些疾病的共同临床症状为气喘、呼吸困难、胸闷；影响患者生活质量，严重时危及生命。积极采取措施预防和治疗具有十分重要的作用。目前抗呼吸道炎症药物非常匮乏。糖皮质激素虽然有较好的抗炎作用，但其不良反应比较多。因此，迫切需要开发出药效强不良反应少的抗炎药物。
炎症细胞浸润气道释放炎症介质、细胞因子、趋化因子可导致肺上皮细胞损伤，进而使得上皮细胞进一步释放炎症介质、细胞因子、趋化因子，导致气道上皮水肿，支气管平滑肌收缩，周而复始造成慢性炎症和纤维化。而黄酮类化合物有直接的抗炎作用，能清除自由基，提高机体的免疫能力，缓解支气管收缩和肺纤维化。
5,7-甲氧基3,4’羟基黄酮是一种黄酮类化合物，但是其在天然产物的分布较少而且含量极微，未见有关5,7-甲氧基3,4’羟基黄酮的生物活性报道。
发明内容
本发明的目的是提供5,7-甲氧基3,4’羟基黄酮在制备抗呼吸道炎症性疾病药物中的应用，是5,7-甲氧基3,4’羟基黄酮的新的药物用途。5,7-甲氧基3,4’羟基黄酮结构式如式(I)所示：
所述5,7-甲氧基3,4’羟基黄酮的纯度大于98％。
所述呼吸道炎症性疾病为炎症导致的支气管哮喘、急性支气管炎、慢性阻塞性肺病、急/ 慢性肺损伤和呼吸窘迫症、肺纤维化等疾病。
所述药物为5,7-甲氧基3,4’羟基黄酮与药学上的辅料制成。按照常规方法制成的口服剂、注射剂和吸入剂，口服剂为片剂、胶囊剂、分散剂或颗粒剂；注射剂为注射液或注射液冻干粉针剂；吸入剂包括纳米干粉吸入剂、定量压力气雾吸入剂、吸入溶液。
本发明的药物剂型也不完全限于此，它可以制备成更多的剂型，如滴丸、胶囊剂、软胶囊剂、分散剂、缓控释制剂、注射剂等。
所述5,7-甲氧基3,4’羟基黄酮片剂中，包括有按重量份计的以下组分：纯度大于98％的5,7- 甲氧基3,4’羟基黄酮100份，填充剂260份，崩解剂20份，黏合剂12份，润滑剂8份。
所述5,7-甲氧基3,4’羟基黄酮分散片剂中，包括有按重量份计的以下组分：纯度大于98％的5,7-甲氧基3,4’羟基黄酮100份，微晶纤维素270份，交联羧甲基纤维素钠30份。
所述5,7-甲氧基3,4’羟基黄酮颗粒剂中，包括有按重量份计的以下组分：纯度大于98％的 5,7-甲氧基3,4’羟基黄酮100份，糊精100份，蔗糖粉200份。
所述5,7-甲氧基3,4’羟基黄酮干粉吸入剂中，包括有按重量份计的以下组分：纯度大于98％的5,7-甲氧基3,4’羟基黄酮15份，乳糖25份。
所述5,7-甲氧基3,4’羟基黄酮定量气雾吸入器中，包括有按重量份计的以下组分：纯度大于98％的5,7-甲氧基3,4’羟基黄酮1.5份，HFA227 60份，HFA134a 36份，无水乙醇2.5份。
本发明通过一系列的离体细胞和组织以及整体动物实验证实5,7-甲氧基3,4’羟基黄酮具有明显的抗炎、抗氧化、抗气管收缩反应活性。在实施例中显示，5,7-甲氧基3,4’羟基黄酮口服给药能吸收，显示较强的药效，而阳性对照药色甘酸二钠或奈多罗米钠口服无效或作用很弱。由于5,7-甲氧基3,4’羟基黄酮口服有10％～25％的生物利用度，因此可以制备成口服剂，而阳性对照药色甘酸二钠或奈多罗米钠因口服生物利用度小，目前临床上只有吸入制剂。实施例中所用阳性对照药色甘酸二钠和奈多罗米钠制成的局部用药制剂(气雾剂、滴鼻剂、滴眼液等)主要适应症为过敏性疾病如过敏性支气管哮喘、鼻炎、结膜炎，对呼吸道其他原因引起的炎症无作用，而5,7-甲氧基3,4’羟基黄酮除了过敏性炎症性疾病，对其他原因引起的炎症同样有效。此外，5,7-甲氧基3,4’羟基黄酮制成的各种制剂，可用于替代糖皮质激素的各种制剂，适用于各种呼吸道炎症性疾病如支气管哮喘、急性支气管炎、慢性阻塞性肺病、急/慢性肺损伤和呼吸窘迫症、肺纤维化。
具体实施方式
本发明通过实施例作进一步的说明。
实施例1 大鼠腹腔肥大细胞脱颗粒试验
方法：致敏大鼠：取SD种大鼠，每只脚掌皮下注射2.5mg/ml精制天花粉0.1ml(混悬于 4％AL(OH)3凝胶中，致敏14天后，由股动脉放血致死，腹腔内注入Hank氏液10ml，注射后轻柔腹部2-3分钟，打开腹腔。将腹腔内容物推向一侧，用滴管将腹腔液吸集于试管中，置冰浴中，500×g离心5min，去上清,沉淀用2ml Hank液轻轻摇匀，取悬液lml,Hank液lml，抗原(10 μg/ml)lml，受试药0.1ml，混匀后置37℃水浴5min，取出后用滴管吸取试管底部肥大细胞l～2 滴，滴于波片上，与l滴0.5％中性红混匀后，置显微镜高倍镜(40×10)下观察计数脱颗粒百分率。
结果：受试物5,7-甲氧基3,4’羟基黄酮(MHF)、对照药奈多罗米钠(NS)和对照药色甘酸二钠(DSCG)均呈剂量依赖抑制大鼠腹腔肥大细胞脱颗粒，MHF、NS和DSCG对大鼠腹腔肥大细胞脱颗粒抑制率50％的浓度(IC50)和95％可信限(95％Cl)分别为21.82 (12.55～37.93)μM，9.47(5.32～16.34)μM和180.43(103.59～314.30)μM。MHF的作用强于DSCG 约8倍，弱于NS约1倍。
实施例2 大鼠腹腔肥大细胞释放组胺试验：
方法：致敏大鼠方法同上，14～21天，收集腹腔肥大细胞(MC)。收集MC：将大鼠颈动脉放血致死，用缓冲液37℃(mM)Nac1 150，Kc1 0.7，Cacl 0.9，Na2HPO4 4.3，KH2PO4 3.5，Glucose 5.6，pH 7.2冲洗腹腔，15m1×2。收集腹腔冲洗液，置于冰浴的硅化试管中(以上实验步骤均在4℃下进行)。500×g离心5min，去上清。沉淀用适量缓冲液摇匀，即为大鼠腹腔MC悬液。
抗原诱导MC释放组胺：吸取致敏大鼠MC悬液0.4ml，加入磷脂酰丝氨酸10μg/ml，加入各种浓度受试药(37℃,温浴5min)，加入精制天花粉抗原10μg/ml，使最终体积为lml， 37℃温浴10min，加入2ml冰冷缓冲液终止反应，500×g离心5min，吸取上清液2ml，测定组胺含量，弃去剩余的上清液，沉淀用3ml缓冲液摇匀，100℃煮浴3min，500×g离5min，吸取2ml上清液，测定残余组胺含量。
Ionophore A23187与Compound 48/80诱导MC释放组胺：吸取正常大鼠腹腔MC悬液0.5ml，加入各种浓度受试药物37℃温浴5min，0.15μmol/L Ionophore A23187或者lμg/mlCompound 48/80(在Compound 48/80实验中，所有溶液均无Ca2+)，37℃温浴10min，其余实验步骤同上。
组胺测定：吸2ml待测液，加双蒸水2ml，25％三氯醋酸lml，混匀。1500×g离心5min，取上清液4ml，加Nacl 1.5g，正丁醇4ml，5N NaOH 0.5ml，剧烈振摇10min，静止10min。取3.6ml正丁醇层，加正庚烷2.0ml，0.2N Hcl 12.4ml，振摇2.0min，静置10min，取适量 Hcl层液体，加蒸馏水到4.0ml，加lN HaOH 0.8ml，混匀后，加l％OPT甲醇溶液(w/v)，反应4min，加入3N Hc1 0.4m1，混匀后。30min内用Hitachi-F-4000荧光分光光度计测定,发射波长450nm，激发狭缝5.0nm，发射狭缝10nm。
组胺净释放率％＝加药组或刺激对照组的组胺释放率％-缓冲液对照组的组胺释放率％。
结果：1)MHF和NS对抗原诱导大鼠腹腔肥大细胞释放组胺抑制率50％的浓度(IC50)和95％可信限(95％Cl)分别为17.91(7.62～32.08)μM和18.47(9.32～36.34)μM。MHF的作用强度与NS相似。2)MHF和NS对A23187诱导大鼠腹腔肥大细胞释放组胺抑制率50％的浓度(IC50)和95％可信限(95％Cl)分别为33.28(17.44～63.52)μM和47.36(22.00～87.89)μM。MHF的作用略强于NS。3)MHF和NS对Compound 48/80诱导大鼠腹腔肥大细胞释放组胺抑制率50％的浓度(IC50)和95％可信限(95％Cl)分别为48.81(29.61～80.43)μM和 119.83(76.17～188.54)μM。MHF的作用强于NS约1倍。
实施例3 大鼠腹腔中性粒细胞β-葡萄糖醛酸酶释放试验：
方法：大鼠腹腔中性粒细胞(NP)收集：乙醚麻醉大鼠，腹腔注射0.7％糖原生理盐水25ml。 4h后颈动脉放血处死大鼠，打开腹腔，小心吸取腹腔液(勿碰肠管)，和4℃ HBSS(mM，NaCl 138.0，KC1 5.4，CaC1 21.8 HEPES 20，Clucose 5.6，0.1％BSA，pH 7.4)等量稀释，250× g离心5min，弃去上清，沉淀加2ml冰水，2sec后加1.8％NaCl溶液2ml，离心，去上清，重悬于HBSS，离心去上清制得NP悬液。涂片后，Wright染色检查，NP纯度>95％，台盼蓝检查细胞活性>95％。fMLP诱导NP释放：NP悬液lml(5×106ml/NP)加入硅化玻璃试管内，然后加入cytochalasin B 3μg，0.1mmol·L-1M fMLP 10μl，轻轻摇匀，37℃水浴10min，冰浴终止反应。1000×g离心5min，取上清测定β-葡萄醛酸酶活力。自然释放管不加cytochalasin B，余同fMLP刺激管。受试药物管于fMLP加入前先37℃水浴10min。
β-葡萄糖醛酸酶测定：试管内加入0.2M醋酸缓冲液(pH 4.5)0.8ml，0.01M酚酞葡萄糖醛酸(用0.2M醋酸缓冲液配制)及样品0.1ml，空白对照管：0.2M醋酸缓冲液0.8ml，0.01M酚酞葡萄糖醛酸0.1ml，灭活样品0.1ml。轻摇后，37℃水浴16h后加0.1N NaOH 2.2ml。摇匀后取550nm比色。β-葡萄糖醛酸酶活力以5×106NP产生的酚酞μg表示(从酚酞标准曲线查得的值乘以10)。
酚酞标准曲线的制备：按下表加试剂，摇匀后比色，波长550nm。以酚酞μg数为横坐标， 550nm吸收值为纵坐标，据所测的光吸收值得直线回归方程画一直线。
表1.酚酞的标准曲线制备
结果：MHF和NS对中性粒细胞β-葡萄糖醛酸酶释放的抑制50％的浓度(IC50)和95％可信限(95％Cl)分别为64.41(45.16～91.16)μM和90.46(60.58～136.25)μM。MHF的作用略强于NS。
实施例4 大鼠腹腔中性粒细胞超氧阴离子生成试验：
方法：采用超氧化物歧化酶(SOD)抑制-细胞色素C还原法。还原型细胞色素C与氧化型细胞色素C吸收光谱有差异，大鼠腹腔中性粒细胞(NP)生成可将细胞色素C还原，SOD 清除而抑制细胞C还原，SOD抑制管作对照，生成管400-600波长扫描(UV-2000 双光束分光光度计)，可见419nm，419nm，550有吸收峰；550nm吸收值(A550)作为细胞色素C还原的参数。氧化型-还原型细胞色素C是550nm消光系数为2.1×104/nm·cm，生成量计算公式如下：
V：反应液总体积
管置冰浴，反应液总体积为2.58ml,含NP 107个,2mmol·L-1细胞色素25μl。SOD抑制管：含SOD 30μg，cytochalasin B 3μg，fMLP1.9mmol·L-1。fMLP刺激管：含cytochalasinB 3μg。以上各管轻轻摇匀37℃水浴10min，冰浴终止反应，1000g离心5min，上清液用双光束分光光度计比色，波长550nm，以SOD抑制管作对照比色(UV-2000双光束分光光度计)比色。
据测得A550nm通过公式计算得各管生成量。
结果：随着孵育NP的MHF和NS剂量增加，生成减少，表明MHF和NS抑制fMLP 刺激并呈浓度依赖关系。MHF和NS对中性粒细胞β-葡萄糖醛酸酶释放的抑制50％的浓度(IC50)和95％可信限(95％Cl)分别为34.41(15.16～61.16)μM和45.46(30.58～85.25)μM。 MHF的作用略强于NS。
实施例5 大鼠被动皮肤过敏试验(PCA):
方法：SD大鼠，体重140—160g，♂♀各半，共10只，每鼠用精制天花粉lmg和氢氧化铝凝胶200mg混匀后于四足掌皮下注射，然后腹腔注射百日咳菌苗l×109，14天，从颈动脉取血，分离得血清置冰箱备用。此抗血清比价为1:120。另取正常SD大鼠160只，♀♂各半，体重130-160g，用乙醚麻醉后，在大鼠背中线两侧将毛剪光，取上述抗血清1:40稀释，在两侧各皮内注射两点，每点0.1ml，72h后，iv 1％伊文思蓝生理盐水5ml/kg和0.2％精制天花粉5ml/kg。30min后处死大鼠，剪下蓝斑皮肤，剪碎后置试管内，加入丙酮－生理盐水 (7:3)混合溶液5ml，浸泡48h后，2000rpm/min离心，取上清液，OD 610nm测光密度。
结果：MHF呈剂量反应抑制大鼠PCA。MHF和NS口服给药(p.o)对大鼠PCA的抑制50％的剂量(ID50)和95％可信限(95％Cl)分别为136.86(75.69～236.51)mg/kg和155.54(89.63～288.89)mg/kg。MHF和NS静脉注射给药(i.v)的ID50(95％Cl)分别为18.15(10.36～38.21)mg/kg和20.63(12.31～32.54)mg/kg。MHF的作用略强于NS。
实施例6 致敏肠鼠抗原攻击支气管肺泡灌流液中炎症细胞试验：
方法：致敏动物：Hartley豚鼠，体重300-350g，♂♀各半，每鼠腿部im卵白蛋白完全弗氏佐剂0.5ml(含卵白蛋白10mg)，雌雄分笼，常规颗粒饲料喂养。4-6周后实验。抗原攻击：将致敏脉鼠置于一4L玻璃钟罩内，用超声波雾化器气雾0.5％卵白蛋白lmin，豚鼠在此钟罩内继续吸入lmin，共2min，将豚鼠放回鼠笼再养48h后供实验用。支气管肺泡灌流按文献方法[8]，戊巴比妥钠30mg/kg ip豚鼠，麻醉后切开颈部皮肤，分离出气管，切开气管，插入气管插管，用l％牛血清蛋白生理盐水溶液12ml，分两次从气管插管注入气道，每次来回冲洗3回，冲洗液收集于试管内，回收率约70-80％(8-10ml)。白细胞计数和分类计数：1％冰醋酸3:1稀释灌流液，用计数板在显微镜下计总数。将灌流液涂于玻片上，代干后用 Wright-Giemsa染色液染色，然后在油镜下分类计数。分组、给药剂量和时间：共分8组，l) 空白对照组(致敏脉鼠，用0.9％Nacl代替0.5％卵白蛋白气雾攻击，灌流方法同样)；2)生理盐水对照组，用0.9％Nacl超声雾化吸入2min，3)1mg/ml、2.5mg/ml、5mg/ml MHF超声雾化吸入2min，4)1mg/ml、2.5mg/ml、5mg/ml NS超声雾化吸入2min。
结果：与空白组比较，生理盐水组经0.5％卵白蛋白攻击后，白细胞总数，嗜酸性白细胞、嗜中性白细胞、单核细胞分类计数均有非常明显的增多，特别是嗜酸性白细胞和嗜中性白细胞数目增多最为明显，达20倍之多，表明致敏豚鼠抗原攻击产生过敏性哮喘之后，有一个非常明显的炎症反应过程。1mg/ml、2.5mg/ml、5mg/ml MHF呈剂量反应抑制这一过敏性炎症反应，炎症细胞在支气管肺泡的聚集明显减少，特别是对嗜酸性和嗜中性白细胞尤为明显。 MHF对嗜酸性白细胞ID50(95％可信限)＝1.41(1.05～1.95)mg/ml,NS＝3.05(1.91～4.72)mg/ml； MHF对白细胞总数(WBC)ID50(95％可信限)＝1.72(1.43～3.68)mg/ml,NS＝2.94(2.14～4.12) mg/ml。MHF的作用强于NS约1倍。
实施例7 大鼠胸腔炎试验：
方法：SD大鼠，体重200-250g，♂♀各半，分7组实验，每组6-8只，即生理盐水组，MHF和NS 25、50、100mg/kg各l组，于实验前5min和实验2h各给药1次。或EDM-90 和NS 50、100、200mg/kg，p.o给药2次，第1次于实验前30min，第2次于实验2h后。用胸膜腔穿刺法注入0.5％角叉菜胶0.1ml/只，5h后处理动物，打开胸膜腔，吸取和计量渗出液，并计数渗出液今白细胞，计算出白细胞总数量，统计处理结果，统计方法：Dunnett’s, 比较EDM-90和NS组间及它们与生理盐水组之间的显著性差异。
结果：MHF和NS iv或p.o给药均呈剂量依赖抑制角叉菜胶引起大鼠胸膜炎性渗出液，显著抑制白细胞趋化性，减少胸腔渗出液中的白细胞总数，MHF(i.v)对白细胞总数(WBC) ID50(95％可信限)＝68.83(49.78～95.16)mg/kg,NS＝25.41(20.27～31.86)mg/kg，NS作用强于 MHF 1倍多。MHF(p.o)对白细胞总数(WBC)ID50(95％可信限)＝170.88(122.84～237.72) mg/kg,NS＝319.88(231.21～440.14)mg/kg，MHF作用强于NS近1倍。
实施例8 组胺和乙酰胆碱诱发豚鼠哮喘试验：
方法：Hartley豚鼠，体重250-330g，♀♂各半，按体重均匀分9组，每组6-7只，即生理盐水l组，1mg/ml、2.5mg/ml、5mg/ml MHF各l组，1mg/ml和5mg/ml MHF NS各l组， 0.5mg/ml和1mg/ml异丙肾上腺素(ISO，对照药)各l组，均于实验前lmin超声雾化给药。将豚鼠置4L密闭玻璃钟罩内，用超声波雾化器以0.8ml/min雾化量向密闭钟罩内雾化受试药 lmin，然后以0.5ml/min的雾化量向密闭钟罩内雾化2％溴化乙酰胆碱和0.1％磷酸组胺(1:1 V/V)混合液10sec(雾粒直径l-5μ)，关机后观察豚鼠从气雾开始到产生抽搐跌倒(由气道痉挛窒息所致)即喘息潜伏期的长短。
结果：MHF呈剂量反应延长组胺和乙酰胆碱诱发的豚鼠喘息潜伏期，2.5mg/ml和5mg/ml MHF组与生理盐水组比较有显著性差异(P<0.05和0.01)。1mg/ml ISO组的豚鼠在240sec 内无一抽搐跌倒，而1mg/ml和5mg/ml MHF NS无作用。
实施例9 豚鼠哮喘模型肺功能测定:
方法：致敏动物：Hartley豚鼠，体重300-350g，♂♀各半，每鼠腿部im卵白蛋白完全弗氏佐剂0.5ml(含卵白蛋白10mg)，雌雄分笼，常规颗粒饲料喂养。4-6周后实验。肺功能测定方法[6-7]：将豚鼠装入1.5L容积，完全密闭的体积描记箱内，描记箱分前后两端，将脉鼠的颈部置前端，四肢躯体置后端，固定后两端互不相通，呈密闭状，尔后将测定潮气量和气道流速的导管通出箱外。潮气量(V)测定：随着豚鼠自主呼吸，胸廓起伏，密闭的体积描记相内气体压力发生周期性变化，经过压力换能器把压力变化转换成电讯号输入记录仪。定标：用注射器向体积描记内注入定量空气即可从记录仪上获得标准潮气量值，作定标曲线。气流速度(P)测定：用经改良的一玻质Feisch呼吸流速计，一端连接于描记器的前端，侧管连接于压力换能器，由于流速计远端用玻质毛细管填充形成的气流阻力，随着呼吸运动，侧管中的压力发生变化，经压力换能器转换成电讯号输入记录仪。定标：以不同流速的恒速气流通过转子流速仪和改良的Feisch流速计，换能器产生的电讯号输入记录仪即可获得标准气流速值，作定标曲线。呼吸频率测定：记数记录仪上每分钟的呼吸频率。抗原攻击：0.5％(W/V)卵白蛋白生理盐水溶液超声雾化吸入2min后，描记吸入后1、2、3、4、5、7.5、20、15min 的V和F以及呼吸频率的变化。
结果：生理盐水组有5/10豚鼠在抗原攻击后呈现呼吸骤停，潮气量(V)和气道流速(F) 以及呼吸频率消失或明显减少，另有3/10呈现不同程度的V和F及呼吸频率减少，有2/10 豚鼠表现为呼吸频率加快，但V和F仍减少；MHF呈剂量反应抑制抗原攻击引起的致敏清醒豚鼠肺机功能降低，5mg/ml MHF组与生理盐水组比较有显著性差异(P<0.05)，10mg/mlMHF组呈完全保护作用(P<0.001)，作用强度与对照药l0mg/ml NS组的相同。
本发明的有益效果为：通过实验证明，5,7-甲氧基3,4’羟基黄酮(MHF)具有显著的抗炎、抗氧化、抗支气管平滑肌收缩等作用，而且效果优于临床治疗用药奈多罗米钠(NS)的趋势，以其为活性成分制备的抗炎药物，用于防治炎症性损伤或治疗因外界环境污染或变化而引起的各种呼吸道炎症性疾病，也可用于预防或治疗因疾病等导致气喘和呼吸困难造成心、脑和呼吸系统等缺氧病理状态。
制剂实施例
以5,7-甲氧基3,4’羟基黄酮为活性成分，按药剂学上的常规工艺制备成各种剂型的抗炎药物。所用药剂来源如下：5,7-甲氧基3,4’羟基黄酮：(纯度大于98％)，5,7-甲氧基3,4’羟基黄酮由申请人合成制备；淀粉：填充剂，江苏华耀医药科技有限公司；微晶纤维素：MCC，崩解剂，西安泰华医药科技有限公司；甲基纤维素：黏合剂，西安泰华医药科技有限公司；硬脂酸镁：润滑剂，西安天正药用辅料有限公司；糊精：西安泰华医药科技有限公司；交联羧甲基纤维素钠：西安泰华医药科技有限公司；蔗糖粉：西安泰华医药科技有限公司；乳糖：西安泰华医药科技有限公司；HFA227，HFA134a：苏威氟化学有限公司。
实施例10 片剂
5,7-甲氧基3,4’羟基黄酮：(纯度大于98％) 100g，
淀粉(江苏华耀医药科技有限公司) 260g，
微晶纤维素(西安泰华医药科技有限公司) 20g，
甲基纤维素(西安泰华医药科技有限公司) 12g，
硬脂酸镁(西安天正药用辅料有限公司) 8g，
共计400.0g
按片剂常规方法制备，共制成1000片，每片含5,7-甲氧基3,4’羟基黄酮100mg。
实施例11 胶囊剂：
5,7-甲氧基3,4’羟基黄酮：(纯度大于98％) 100g，
淀粉(江苏华耀医药科技有限公司) 270g，
甲基纤维素(西安泰华医药科技有限公司) 10g，
硬脂酸镁(西安天正药用辅料有限公司) 20g，
共计400.0g
按胶囊剂常规方法制备，共制成1000粒，每粒含5,7-甲氧基3,4’羟基黄酮100mg。
实施例12 分散片剂：
5,7-甲氧基3,4’羟基黄酮：(纯度大于98％) 100g，
微晶纤维素(西安泰华医药科技有限公司) 270g，
交联羧甲基纤维素钠 30.0g，
共计400.0g
按分散片剂常规方法制备，共制成1000片，每片含5,7-甲氧基3,4’羟基黄酮100mg。
实施例13 颗粒剂：
5,7-甲氧基3,4’羟基黄酮：(纯度大于98％) 100g，
糊精 100g，
蔗糖粉 200g，
共计400.0g
按颗粒剂常规方法制备，共制成1000包，每包含5,7-甲氧基3,4’羟基黄酮100mg。
实施例14 干粉吸入剂：
5,7-甲氧基3,4’羟基黄酮 15g
乳糖 25g
按照干粉吸入剂制备工艺，分别将5,7-甲氧基3,4’羟基黄酮和乳糖微粉化，再分别过40目筛。将所得预混物三维混合(T2F)5min，转速72rpm；再经高速搅拌(G6)混合10min，转速 600rpm，既得干粉，再将干粉罐装于1000粒明胶胶囊中，每粒40mg(即每粒含5,7-甲氧基3,4’羟基黄酮15mg)。
实施例15 计量剂量吸入器的气雾剂(MDI)
本发明的药物剂型也不完全限于此，它可以制备成更多的剂型，如滴丸、胶囊剂、软胶囊剂、分散剂、缓控释制剂、注射剂、滴鼻剂、喷鼻剂、滴眼剂、各种气雾吸入剂等。
最后应说明的是：以上所述仅为本发明的优选实施例而已，并不用于限制本发明，尽管参照前述实施例对本发明进行了详细的说明，对于本领域的技术人员来说，其依然可以对前述各实施例所记载的技术方案进行修改，或者对其中部分技术特征进行等同替换。凡在本发明的精神和原则之内，所作的任何修改、等同替换、改进等，均应包含在本发明的保护范围之内。
Claims (10)
1.5,7-甲氧基3,4’羟基黄酮在制备抗呼吸道炎症性疾病药物中的应用，其特征在于，所述5,7-甲氧基3,4’羟基黄酮的纯度大于98％。
2.根据权利要求1所述的5,7-甲氧基3,4’羟基黄酮在制备抗呼吸道炎症性疾病药物中的应用，其特征在于，所述呼吸道炎症性疾病为支气管哮喘、急性支气管炎、慢性阻塞性肺病、急/慢性肺损伤和呼吸窘迫症、肺纤维化。
3.根据权利要求1所述的5,7-甲氧基3,4’羟基黄酮在制备抗呼吸道炎症性疾病药物中的应用，其特征在于，所述药物与5,7-甲氧基3,4’羟基黄酮与药学辅料制成。
4.根据权利要求1所述的5,7-甲氧基3,4’羟基黄酮在制备抗呼吸道炎症性疾病药物中的应用，其特征在于，所述药物剂型为口服剂、注射剂和吸入剂，口服剂为片剂、胶囊剂、分散剂或颗粒剂；注射剂为注射液或注射液冻干粉针剂；吸入剂包括纳米干粉吸入剂、定量压力气雾吸入剂、吸入溶液。
5.根据权利要求4所述的5,7-甲氧基3,4’羟基黄酮在制备抗呼吸道炎症性疾病药物中的应用，其特征在于，所述片剂中，按重量份计的组分为：纯度大于98％的5,7-甲氧基3,4’羟基黄酮100份，填充剂260份，崩解剂20份，黏合剂12份，润滑剂8份。
6.根据权利要求4所述的5,7-甲氧基3,4’羟基黄酮在制备抗呼吸道炎症性疾病药物中的应用，其特征在于，所述胶囊剂中，按重量份计的组分为：纯度大于98％的5,7-甲氧基3,4’羟基黄酮100份，填充剂270份，黏合剂10份，润滑剂20份。
7.根据权利要求4所述的5,7-甲氧基3,4’羟基黄酮在制备抗呼吸道炎症性疾病药物中的应用，其特征在于，所述分散剂中，按重量份计的组分为：纯度大于98％的5,7-甲氧基3,4’羟基黄酮100份，微晶纤维素270份，交联羧甲基纤维素钠30份。
8.根据权利要求4所述的5,7-甲氧基3,4’羟基黄酮在制备抗呼吸道炎症性疾病药物中的应用，其特征在于，所述颗粒剂中，按重量份计的组分为：纯度大于98％的5,7-甲氧基3,4’羟基黄酮100份，糊精100份，蔗糖粉200份。
9.根据权利要求4所述的5,7-甲氧基3,4’羟基黄酮在制备抗呼吸道炎症性疾病药物中的应用，其特征在于，所述干粉吸入剂中，按重量份计的组分为：纯度大于98％的5,7-甲氧基3,4’羟基黄酮15份，乳糖25份。
10.根据权利要求4所述的5,7-甲氧基3,4’羟基黄酮在制备抗呼吸道炎症性疾病药物中的应用，其特征在于，所述定量气雾吸入剂中，按重量份计的组分为：纯度大于98％的5,7-甲氧基3,4’羟基黄酮1.5份，HFA227 60份，HFA134a 36份，无水乙醇2.5份。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810631852.9A CN108904489A (zh) | 2018-06-19 | 2018-06-19 | 5,7-甲氧基3,4’羟基黄酮的抗呼吸道炎症性疾病的用途 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810631852.9A CN108904489A (zh) | 2018-06-19 | 2018-06-19 | 5,7-甲氧基3,4’羟基黄酮的抗呼吸道炎症性疾病的用途 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108904489A true CN108904489A (zh) | 2018-11-30 |
Family
ID=64419403
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810631852.9A Pending CN108904489A (zh) | 2018-06-19 | 2018-06-19 | 5,7-甲氧基3,4’羟基黄酮的抗呼吸道炎症性疾病的用途 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108904489A (zh) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114432323A (zh) * | 2020-11-02 | 2022-05-06 | 苏州凯祥生物科技有限公司 | 黄酮类化合物在制备预防或治疗急性肺损伤和/或急性呼吸窘迫综合征的药物中的应用 |
| CN114432291A (zh) * | 2020-11-02 | 2022-05-06 | 苏州凯祥生物科技有限公司 | 异戊烯基黄酮类化合物在制备药物中的应用 |
| CN114432327A (zh) * | 2020-11-02 | 2022-05-06 | 苏州凯祥生物科技有限公司 | 黄酮碳苷类化合物在制备预防或治疗急性肺损伤和/或急性呼吸窘迫综合征的药物中的应用 |
| CN114432289A (zh) * | 2020-11-02 | 2022-05-06 | 苏州凯祥生物科技有限公司 | 杂环黄酮类化合物在制备预防或治疗急性肺损伤和/或急性呼吸窘迫综合征的药物中的应用 |
| CN114432290A (zh) * | 2020-11-02 | 2022-05-06 | 苏州凯祥生物科技有限公司 | 甲基黄酮类化合物在制备预防或治疗急性肺损伤和/或急性呼吸窘迫综合征药物中的应用 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090036518A1 (en) * | 2005-04-12 | 2009-02-05 | Taipei Medical University | Pharmaceutical composition containing flavonoids |
| CN106456597A (zh) * | 2014-05-09 | 2017-02-22 | 三得利控股株式会社 | 包含甲氧基黄酮的NOX抑制剤及NFκB抑制剤 |
-
2018
- 2018-06-19 CN CN201810631852.9A patent/CN108904489A/zh active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090036518A1 (en) * | 2005-04-12 | 2009-02-05 | Taipei Medical University | Pharmaceutical composition containing flavonoids |
| CN106456597A (zh) * | 2014-05-09 | 2017-02-22 | 三得利控股株式会社 | 包含甲氧基黄酮的NOX抑制剤及NFκB抑制剤 |
Non-Patent Citations (1)
| Title |
|---|
| 周芳等: "多甲氧基黄酮的化学成分及药理作用研究进展", 《中南药学》 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114432323A (zh) * | 2020-11-02 | 2022-05-06 | 苏州凯祥生物科技有限公司 | 黄酮类化合物在制备预防或治疗急性肺损伤和/或急性呼吸窘迫综合征的药物中的应用 |
| CN114432291A (zh) * | 2020-11-02 | 2022-05-06 | 苏州凯祥生物科技有限公司 | 异戊烯基黄酮类化合物在制备药物中的应用 |
| CN114432327A (zh) * | 2020-11-02 | 2022-05-06 | 苏州凯祥生物科技有限公司 | 黄酮碳苷类化合物在制备预防或治疗急性肺损伤和/或急性呼吸窘迫综合征的药物中的应用 |
| CN114432289A (zh) * | 2020-11-02 | 2022-05-06 | 苏州凯祥生物科技有限公司 | 杂环黄酮类化合物在制备预防或治疗急性肺损伤和/或急性呼吸窘迫综合征的药物中的应用 |
| CN114432290A (zh) * | 2020-11-02 | 2022-05-06 | 苏州凯祥生物科技有限公司 | 甲基黄酮类化合物在制备预防或治疗急性肺损伤和/或急性呼吸窘迫综合征药物中的应用 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108904489A (zh) | 5,7-甲氧基3,4’羟基黄酮的抗呼吸道炎症性疾病的用途 | |
| TW318141B (zh) | ||
| CN101229122B (zh) | 具有相转变性质的扎那米韦鼻用原位凝胶剂及其制备方法 | |
| CN107998110A (zh) | 白藜芦醇用于制备治疗或缓解慢性气道炎症性疾病用药物的用途 | |
| CN106667975A (zh) | 一种吸入用异丙托溴铵溶液的制备方法 | |
| Medicine | Expert consensus on nebulization therapy in pre-hospital and in-hospital emergency care | |
| WO2019119720A1 (zh) | 一种福多司坦雾化吸入用溶液制剂及其制备方法 | |
| JP2022521558A (ja) | ペラミビル溶液吸入剤およびその製造方法 | |
| CN104507918A (zh) | 用于治疗或预防肺炎病毒感染和相关疾病的组合物和方法 | |
| CN103989695A (zh) | 一种治疗支气管哮喘的药物组合物及其应用 | |
| Chen et al. | Ketorolac-induced bronchospasm in an aspirin-intolerant patient | |
| CN111991374A (zh) | 一种瑞德西韦吸入气雾剂及其制备方法 | |
| US11744841B2 (en) | Use of trezastilbenoside in manufacture of product for treating and/or preventing disease of respiratory system | |
| CN102558224A (zh) | 甲磷丙泊酚钠水合物及其制备方法和用途 | |
| CN108283629A (zh) | 吸入用罗氟司特混悬液及其制备方法 | |
| CN113599376A (zh) | 鸢尾甲黄素a在制备防治支气管哮喘疾病药物中的应用 | |
| CN114948914B (zh) | 一种盐酸莫西沙星雾化吸入用溶液剂及其制备方法 | |
| CN106806418A (zh) | 一种双黄连雾化吸入用溶液制剂及其制备方法 | |
| JPH09227373A (ja) | 抗インフルエンザウイルス剤 | |
| Aswar et al. | Inhalation Therapy for Lung Diseases: A Comprehensive Review of Pulmonary Drug Delivery Systems | |
| CN117224518B (zh) | 索法酮在制备用于预防/治疗过敏性哮喘的药物中的应用 | |
| CN111110634A (zh) | 一种磷酸氯喹吸入气雾剂及其制备方法 | |
| CN109793731A (zh) | 二甲基胺4-o-乙酰基线叶旋覆花内酯a及其盐在制备预防/治疗慢阻肺药物中的应用 | |
| RU2504395C1 (ru) | Способ профилактики бронхолегочной дисплазии у новорожденных с очень низкой и экстремально низкой массой тела при рождении | |
| CN107970237A (zh) | 艾瑞昔布在制备治疗肺纤维化药物中的应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20181130 |