CN101518537A - 炎症性呼吸道疾病的预防/治疗剂 - Google Patents
炎症性呼吸道疾病的预防/治疗剂 Download PDFInfo
- Publication number
- CN101518537A CN101518537A CNA2009100064252A CN200910006425A CN101518537A CN 101518537 A CN101518537 A CN 101518537A CN A2009100064252 A CNA2009100064252 A CN A2009100064252A CN 200910006425 A CN200910006425 A CN 200910006425A CN 101518537 A CN101518537 A CN 101518537A
- Authority
- CN
- China
- Prior art keywords
- respiratory tract
- prevents
- tract disease
- agent
- struvite
- 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
- 208000023504 respiratory system disease Diseases 0.000 title abstract description 4
- 230000002757 inflammatory effect Effects 0.000 title abstract 3
- 230000003449 preventive effect Effects 0.000 title abstract 3
- 150000003431 steroids Chemical class 0.000 claims abstract description 23
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 8
- 125000005843 halogen group Chemical group 0.000 claims abstract description 8
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 6
- 125000003118 aryl group Chemical group 0.000 claims abstract description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 27
- 208000006673 asthma Diseases 0.000 claims description 23
- 208000018569 Respiratory Tract disease Diseases 0.000 claims description 21
- CKMXBZGNNVIXHC-UHFFFAOYSA-L ammonium magnesium phosphate hexahydrate Chemical compound [NH4+].O.O.O.O.O.O.[Mg+2].[O-]P([O-])([O-])=O CKMXBZGNNVIXHC-UHFFFAOYSA-L 0.000 claims description 21
- 229910052567 struvite Inorganic materials 0.000 claims description 21
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 10
- 206010020751 Hypersensitivity Diseases 0.000 claims description 6
- 208000026935 allergic disease Diseases 0.000 claims description 6
- 230000007815 allergy Effects 0.000 claims description 6
- 208000030603 inherited susceptibility to asthma Diseases 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 210000003800 pharynx Anatomy 0.000 claims description 2
- 201000009890 sinusitis Diseases 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 abstract description 20
- 239000003814 drug Substances 0.000 abstract description 16
- 230000009885 systemic effect Effects 0.000 abstract description 7
- 239000004480 active ingredient Substances 0.000 abstract 1
- 208000037883 airway inflammation Diseases 0.000 abstract 1
- 229910052739 hydrogen Inorganic materials 0.000 abstract 1
- 239000001257 hydrogen Substances 0.000 abstract 1
- -1 and find Chemical class 0.000 description 22
- 241000700199 Cavia porcellus Species 0.000 description 13
- 210000002345 respiratory system Anatomy 0.000 description 12
- 239000000203 mixture Substances 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- 229940125782 compound 2 Drugs 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 241001465754 Metazoa Species 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 201000009961 allergic asthma Diseases 0.000 description 6
- 230000003110 anti-inflammatory effect Effects 0.000 description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 6
- 229910052794 bromium Inorganic materials 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 229940125904 compound 1 Drugs 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 206010061218 Inflammation Diseases 0.000 description 5
- 108010058846 Ovalbumin Proteins 0.000 description 5
- 206010039085 Rhinitis allergic Diseases 0.000 description 5
- 206010070834 Sensitisation Diseases 0.000 description 5
- 201000010105 allergic rhinitis Diseases 0.000 description 5
- 229910052731 fluorine Inorganic materials 0.000 description 5
- 239000011737 fluorine Substances 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 210000003928 nasal cavity Anatomy 0.000 description 5
- 229940092253 ovalbumin Drugs 0.000 description 5
- 230000008313 sensitization Effects 0.000 description 5
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 210000001533 respiratory mucosa Anatomy 0.000 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 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 238000007912 intraperitoneal administration Methods 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 210000003437 trachea Anatomy 0.000 description 3
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- 206010057260 Lower respiratory tract inflammation Diseases 0.000 description 2
- 208000003251 Pruritus Diseases 0.000 description 2
- 206010057190 Respiratory tract infections Diseases 0.000 description 2
- 206010048908 Seasonal allergy Diseases 0.000 description 2
- 206010046306 Upper respiratory tract infection Diseases 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 2
- 230000003266 anti-allergic effect Effects 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 230000001684 chronic effect Effects 0.000 description 2
- 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
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 230000003203 everyday effect Effects 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 210000004698 lymphocyte Anatomy 0.000 description 2
- 150000002905 orthoesters Chemical class 0.000 description 2
- YCOZIPAWZNQLMR-UHFFFAOYSA-N pentadecane Chemical compound CCCCCCCCCCCCCCC YCOZIPAWZNQLMR-UHFFFAOYSA-N 0.000 description 2
- 230000000241 respiratory effect Effects 0.000 description 2
- 230000029058 respiratory gaseous exchange Effects 0.000 description 2
- 206010039083 rhinitis Diseases 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 125000000547 substituted alkyl group Chemical group 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- IIYFAKIEWZDVMP-UHFFFAOYSA-N tridecane Chemical compound CCCCCCCCCCCCC IIYFAKIEWZDVMP-UHFFFAOYSA-N 0.000 description 2
- UJHSIDUUJPTLDY-UHFFFAOYSA-N (2-nitrophenyl)-phenylmethanone Chemical compound [O-][N+](=O)C1=CC=CC=C1C(=O)C1=CC=CC=C1 UJHSIDUUJPTLDY-UHFFFAOYSA-N 0.000 description 1
- ZYMCBJWUWHHVRX-UHFFFAOYSA-N (4-nitrophenyl)-phenylmethanone Chemical compound C1=CC([N+](=O)[O-])=CC=C1C(=O)C1=CC=CC=C1 ZYMCBJWUWHHVRX-UHFFFAOYSA-N 0.000 description 1
- 125000006732 (C1-C15) alkyl group Chemical group 0.000 description 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 1
- ZPQOPVIELGIULI-UHFFFAOYSA-N 1,3-dichlorobenzene Chemical compound ClC1=CC=CC(Cl)=C1 ZPQOPVIELGIULI-UHFFFAOYSA-N 0.000 description 1
- HNEGJTWNOOWEMH-UHFFFAOYSA-N 1-fluoropropane Chemical group [CH2]CCF HNEGJTWNOOWEMH-UHFFFAOYSA-N 0.000 description 1
- ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 description 1
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 1
- HNNQYHFROJDYHQ-UHFFFAOYSA-N 3-(4-ethylcyclohexyl)propanoic acid 3-(3-ethylcyclopentyl)propanoic acid Chemical class CCC1CCC(CCC(O)=O)C1.CCC1CCC(CCC(O)=O)CC1 HNNQYHFROJDYHQ-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- 125000004860 4-ethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 206010003645 Atopy Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 239000004606 Fillers/Extenders Substances 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- 208000035756 Infantile asthma Diseases 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 206010062575 Muscle contracture Diseases 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 206010039094 Rhinitis perennial Diseases 0.000 description 1
- PZSXCNWLLFEOPM-UHFFFAOYSA-N [F].C(CC)(=O)O Chemical compound [F].C(CC)(=O)O PZSXCNWLLFEOPM-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 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 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 230000000181 anti-adherent effect Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 230000001741 anti-phlogistic effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 208000030303 breathing problems Diseases 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 208000037893 chronic inflammatory disorder Diseases 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 208000006111 contracture Diseases 0.000 description 1
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 1
- YMGUBTXCNDTFJI-UHFFFAOYSA-N cyclopropanecarboxylic acid Chemical compound OC(=O)C1CC1 YMGUBTXCNDTFJI-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 230000000762 glandular Effects 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000003630 histaminocyte Anatomy 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000000527 lymphocytic effect Effects 0.000 description 1
- YECBIJXISLIIDS-UHFFFAOYSA-N mepyramine Chemical compound C1=CC(OC)=CC=C1CN(CCN(C)C)C1=CC=CC=N1 YECBIJXISLIIDS-UHFFFAOYSA-N 0.000 description 1
- 229960000582 mepyramine Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- FJLBFSROUSIWMA-UHFFFAOYSA-N metyrapone Chemical compound C=1C=CN=CC=1C(C)(C)C(=O)C1=CC=CN=C1 FJLBFSROUSIWMA-UHFFFAOYSA-N 0.000 description 1
- 229960004465 metyrapone Drugs 0.000 description 1
- 210000003097 mucus Anatomy 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 210000002850 nasal mucosa Anatomy 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000000414 obstructive effect Effects 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 208000022719 perennial allergic rhinitis Diseases 0.000 description 1
- 210000001539 phagocyte Anatomy 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- RSJKGSCJYJTIGS-UHFFFAOYSA-N undecane Chemical compound CCCCCCCCCCC RSJKGSCJYJTIGS-UHFFFAOYSA-N 0.000 description 1
- 230000008728 vascular permeability Effects 0.000 description 1
- 230000000283 vasomotion Effects 0.000 description 1
- 208000001319 vasomotor rhinitis Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002351 wastewater Substances 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J5/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane and substituted in position 21 by only one singly bound oxygen atom, i.e. only one oxygen bound to position 21 by a single bond
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- 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
-
- 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
- A61P11/04—Drugs for disorders of the respiratory system for throat disorders
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/16—Otologicals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J7/00—Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of two carbon atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Otolaryngology (AREA)
- Rheumatology (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Steroid Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
一种炎症性呼吸道疾病预防和/或治疗剂,其含有右式(1)所示的甾族衍生物作为活性组分,(其中R表示氢原子、卤原子、羟基或-OCOR1(其中R1表示可以被卤原子或环烷基取代的直链或支链烷基、环烷基或芳基))。这些化合物能够持续抑制呼吸道炎症和呼吸道反应过度,并且,当直接用于对呼吸道给药时,其部位选择性高,且几乎不具有全身性作用。基于这些特性,作为可以长期服用的高度安全的炎症性呼吸道疾病预防和/或治疗剂,这些化合物在临床医学中非常有用。
Description
本申请是专利申请号为0182104.2的发明专利申请的分案申请。
技术领域
本发明涉及用于诸如支气管性气喘和鼻过敏症的炎症性呼吸道疾病的预防和/或治疗剂。
背景技术
根据最近研究,包括支气管性气喘和鼻过敏症(例如,变应性鼻炎和血管舒缩性鼻炎)的呼吸道疾病应被认为是炎症性疾病,该炎症性疾病的特点在于呼吸道粘膜的慢性炎症(诸如肥大细胞、噬酸细胞和淋巴细胞的多种噬细胞参与该炎性过程)和由炎症引发的呼吸道过敏亢进。因此,呼吸道疾病的治疗剂逐渐由那些含支气管扩张剂、抗***反应剂或抗组胺剂的药剂转变为那些含抗炎剂的药剂,所述治疗剂降低了呼吸道粘膜上皮中存在的噬碱细胞和噬酸细胞以及淋巴细胞,并抑制淋巴细胞释放细胞素、噬碱细胞释放介质、抑制腺细胞的分泌和血管渗透性等。在所述抗炎剂中,人们考虑将能发挥巨大治疗效果且副作用较小的甾族化合物用于局部治疗,因此,现已开发了一些可通过吸入法对呼吸道给药的甾类药物。
但是,当使用通常被认为发挥局部抗炎活性的甾类化合物对呼吸道给药时,未必总能产生理想的部位选择性。目前仍采用的甾类化合物的部位选择性并不理想,而且不能完全确保这些药物的安全性(例如,由于长期给药带来了巨大副作用)。
因此,需要开发一种可用作炎症性呼吸道疾病治疗剂的甾族化合物,该化合物能发挥优良抗炎效果,当该化合物经吸入法直接对鼻腔或呼吸道给药时,其部位选择性高,并且,由于其生物利用率低,因而不具有全身性作用。
发明概述
本发明的目的是提供一种用于炎症性呼吸道疾病的预防和/或治疗剂,该预防和/或治疗剂能发挥优良的抗***反应和抗炎作用,对呼吸道部位选择性高,并且,全身性副作用低。
在上述情况下,本发明人针对目前的甾类化合物进行了广泛研究,并发现,下式(1)所示的甾族衍生物具有优良的抗***反应和抗炎作用,而且,当直接用于对呼吸道给药时,其部位选择性高,并能预防和/或治疗炎症性呼吸道疾病,同时基本上不具有全身性副作用。基于上述发现完成了本发明。
因此,本发明提供了一种炎症性呼吸道疾病的预防和/或治疗剂,其含有下式(1)所示的甾族衍生物作为活性组分,
(其中R表示氢原子、卤原子、羟基或-OCOR1(其中R1表示可以被卤原子或环烷基取代的直链或支链烷基、环烷基或芳基))。
本发明还提供了甾族衍生物用于制备炎症性呼吸道疾病预防和/或治疗剂的用途。
本发明还提供了治疗炎症性呼吸道疾病的方法,其特征在于使用甾族衍生物经口吸入给药或对鼻腔给药。
附图简述
图1表示:施用化合物2后,迟发期气道阻力曲线下的面积。
图2表示:施用化合物2后,迟发期鼻腔阻力曲线下的面积。
图3表示:施用化合物1后,噬酸细胞的数目。
图4(A)和4(B)表示:施用化合物2后,噬酸细胞的数目。
(A):在激发前24小时,施用化合物2(2%、4%或8%)。
(B):在激发前12、24和48小时,施用化合物2(8%)。
本发明最佳实施方案
在本发明用于炎症性呼吸道疾病的预防和/或治疗剂中,式(1)中R表示的卤原子优选为氟、氯、溴或碘。其中,特别优选氯和溴。
R1表示的直链或支链烷基优选为C1-C23烷基。其中,特别优选C1-C15烷基。可以取代烷基的卤原子优选为氟、氯、溴或碘,特别优选氯或溴。可以取代烷基的环烷基优选为C3-C6环烷基。
R1表示的优选直链烷基的实例包括甲基、乙基、正丙基、正丁基、正壬基、正十一烷基、正十三烷基和正十五烷基。优选支链烷基的实例包括异丙基、异丁基、仲丁基、叔丁基、异戊基、新戊基、叔戊基和异己基。优选的卤代烷基的实例包括3-氯丙基、3-溴丙基、3-氟丙基、4-氯丁基、4-溴丁基、4-氟丁基、5-氯戊基、5-溴戊基、5-氟戊基、6-氯己基、6-溴己基和6-氟己基。优选的环烷基烷基的实例包括2-环己基乙基、2-环丙基乙基、2-环戊基乙基、3-环丙基丙基、3-环戊基丙基、3-环己基丙基、4-环丙基丁基、4-环戊基丁基、4-环己基丁基、5-环丙基戊基、5-环戊基戊基、5-环己基戊基和6-环戊基己基。优选的环烷基的实例包括环丙基、环丁基、环戊基和环己基。优选的芳基实例包括苯基、萘基、2-甲基苯基、4-甲基苯基、2-乙基苯基、4-乙基苯基、2-甲氧基苯基、4-甲氧基苯基、2-乙氧基苯基、4-乙氧基苯基、2-氨基苯基、4-氨基苯基、4-二甲基氨基苯基、2-羟基苯基、4-羟基苯基、2-硝基苯基、4-硝基苯基、2-氯苯基、4-氯苯基、2-溴苯基、4-溴苯基、2-氟苯基、4-氟苯基、2,6-二氯苯基、2,6-二溴苯基和联苯基。
考虑到效力,特别优选其中R为羟基或-OCOR1(R1是环己基)的甾族衍生物。
式(1)所示的甾族衍生物是已知化合物,其具有优良的抗炎作用,可用于治疗慢性类风湿病或类似疾病。采用任何已知方法(日本公告专利7-116215),可制得任一甾族衍生物。
已知上述甾族衍生物的经皮吸收率和部位选择性高,因而可以作为外用甾族化合物。但是,至于该衍生物是否可以直接施用于呼吸道粘膜,一直是未知的。实际上,在完成本发明之前,从未料到上述甾族化合物具有优良特性,即,当上述衍生物施用于呼吸道时,其表现出高部位选择性并且基本上不产生全身性作用。
本发明治疗剂的目标炎症性呼吸道疾病包括上呼吸道炎症性疾病和下呼吸道炎症性疾病以及咽***反应、慢性阻塞性肺部疾病、间质肺炎和类似疾病。上呼吸道炎症性疾病的实例包括诸如变应性鼻炎或血管舒缩性(特发)鼻炎的鼻过敏症和窦炎,下呼吸道炎症性疾病的实例包括支气管炎、支气管性气喘和婴儿哮喘。
尤其是,在本发明中,术语“变应性鼻炎”是指鼻粘膜的任何变应性反应,包括花粉病(季节性变应性鼻炎)和常年性变应性鼻炎,其特征在于喷嚏、粘液、阻塞、发痒、眼痒、充血或流泪。
根据呼吸道的病理学反应,支气管性气喘按时间顺序分为速发哮喘反应、迟发哮喘反应或后迟发哮喘反应(变应性哮喘)。本发明的预防和/或治疗剂可用于上述任何哮喘反应,并且对迟发哮喘反应尤为有效,迟发哮喘反应是在暴露于抗原数小时后发作,并且,其在呼吸道中的主要病理学症状为炎性反应。
本发明用于炎症性呼吸道疾病的预防和/或治疗剂直接对呼吸道粘膜给药,例如,给药于鼻腔或经口吸入给药。
施用于鼻腔的本发明预防和/或治疗剂的药物制剂可以以液体或粉末组合物的形式制备,并可以使用加压剂量喷雾器、干粉喷雾器、滴注器或类似器械给药。
经口吸入的本发明预防和/或治疗剂的药物制剂可以以液体或粉末组合物的形式制备,并可以使用加压剂量吸入器、干粉吸入器、喷射式喷雾器(jet-nebulizer)、超声波喷雾器或类似器械给药。
上述含有预防和/或治疗剂的液体或粉末组合物的制备如下:根据需要,将化合物(1)(活性组分)与赋予液体或粉末组合物形状的赋形剂(如溶剂、基质、稀释剂、填料或膨胀剂)、有助于保持液体或粉末组合物形状的辅剂(如辅溶剂、增溶剂、缓冲剂、等渗剂、乳化剂、表面活性剂、稳定剂、悬浮剂、分散剂、增稠剂、润滑剂、粘合剂、抗粘合剂或喷雾剂)和改善组合物使用性能的添加剂(如防腐剂、杀菌剂、抗菌剂、甜味剂、调味剂、芳香物、着色剂和抗氧剂)混合。用常规方法加工该混合物,制得鼻内给药或经口吸入给药的药物制剂。
本发明活性组分预防和/或治疗的有效剂量根据给药途径以及患者的年龄、性别和疾病严重程度而定。活性组分的日剂量一般为大约50-2000μg,优选为大约100-800μg。通常每天服用该剂量一次或以分开的方式服用数次。因此,优选使配制的药物适宜上述规则。
正如下文实施例所述,按上文制得的本发明的炎症性呼吸道疾病预防和/或治疗剂对气道阻力和鼻腔阻力增加具有显著抑制作用,并且基本上没有全身性作用。具体地讲,在天竺鼠和大鼠变应性哮喘(呼吸道挛缩)模型中,这些药剂经吸入给药,此外,在天竺鼠变应性鼻炎模型中,这些药剂经吸入给药或经鼻滴入。因此,由于本发明的炎症性呼吸道疾病预防和/或治疗剂基本上不具有副作用并且非常安全,所以可以临床应用。
实施例
制备实施例
根据日本公告专利7-116215中描述的方法,合成9-氟-11β,17,21-三羟基-16α-甲基-1,4-孕二烯-3,20-二酮17-环丙烷甲酸酯(化合物1)和9-氟-11β,17,21-三羟基-16α-甲基-1,4-孕二烯-3,20-二酮21-环己烷甲酸酯17-环丙烷甲酸酯(化合物2)。
具体地讲,在酸存在下,将***与原环丙烷甲酸三烷基酯反应,得到分子内原酸酯。随后,将原酸酯进行酸解,得到化合物1。接着,化合物1与环己烷甲酸的反应性衍生物反应,得到化合物2。
实施例1:对天竺鼠变应性哮喘模型的作用
使雄性天竺鼠(每组8只动物)每天吸入服用1%卵清蛋白溶液10分钟,持续8天。在最后致敏一周后,使每只天竺鼠吸入服用2%卵清蛋白溶液5分钟(激发)。在激发前24小时和1小时,对天竺鼠静脉内给药美替拉酮(10mg/kg),并且,在激发前30分钟,腹膜内给药吡拉明(10mg/kg)。使用呼吸机能综合分析***(Pulmos-I,M.I.P.S.),测定天竺鼠气道阻力(sRaw)。测定激发后4-8小时sRaw增加速率曲线下的面积,得到的数值用作迟发性哮喘反应指数。在激发前24小时和1小时,使天竺鼠吸入服用悬浮于0.2%HCO-60生理盐水中的本发明化合物2或丙酸氟提卡松(FP)30分钟。结果如图1所示。
由图1可以明显地看出,与FP相比较,本发明预防和/或治疗剂对迟发哮喘反应(LAR,一种天竺鼠变应性哮喘反应)具有增强的抑制作用。
实施例:对天竺鼠变应性鼻炎模型的作用
将20μg/mL卵清蛋白溶液与等量的20mg/mL氢氧化铝凝胶溶液混合,按每只动物1mL的量,用混合物对雄性天竺鼠(每组9只动物)进行腹膜内给药。给药一周后,重复相同操作。在最后致敏一周后,再次重复诱发鼻炎一周。在第5次诱发前2天、1天和1小时(总计3次),以20μL的体积(每只动物共40μL),将悬浮于0.2%HCO-60生理盐水中的本发明化合物2施用于天竺鼠各侧鼻腔。使用呼吸机能综合分析***(Pulmos-I,M.I.P.S.),测定鼻腔阻力(sRaw)。测定激发后3-7小时sRaw增加速率曲线下的面积,得到的数值用作迟发性哮喘反应指数。结果如图2所示。
由图2可以明显地看出,本发明的预防和/或治疗剂对迟发哮喘反应(LAR,一种天竺鼠变应性哮喘反应)具有抑制作用。
实施例3:对大鼠变应性哮喘模型的作用
为了致敏,按每只动物1mL的量,用20μg/mL卵清蛋白溶液与5mg/mL氢氧化铝凝胶溶液的等体积混合物对大鼠(每组7只动物)进行腹膜内给药。给药后1天和2天,重复相同操作,以再次致敏。致敏后第13天,使每只大鼠吸入服用抗原(2%卵清蛋白溶液)25分钟(激发)。激发后24小时,用生理盐水洗涤呼吸道,计数洗涤盐水中浮动的炎性细胞(噬酸细胞)数目,并用作哮喘反应指数。
(1)用乳糖(8%)稀释本发明化合物1。激发前24小时和12小时,按每只大鼠10mg的量,用粉状药物制剂对大鼠进行气管内给药,结果见图3。
(2)1)用乳糖(2%、4%和8%)稀释本发明化合物2。激发前24小时,按每只大鼠10mg的量,用各粉状药物制剂对大鼠进行气管内给药,结果见图4(A)。
2)激发前48、24和12小时,按每只大鼠10mg的量,用含8%本发明化合物2的粉状药物制剂对大鼠进行气管内给药,结果见图4(B)。
试验结果表明,当以粉剂形式给药时,本发明预防和/或治疗剂的抗哮喘作用持续24小时或更长时间。
实施例4:单次剂量毒性研究
给大鼠施用一次本发明化合物1或2,测定其至死剂量。结果见表1。结果证明,本发明化合物1和2的毒性低。
表1
动物种类(性别) | 给药途径 | 至死剂量(大体上) |
大鼠(雄性、雌性) | 口服 | 2000mg/kg或更高 |
大鼠(雄性、雌性) | 皮下 | 2000mg/kg或更高 |
实施例5:制剂实施例
(1)吸入剂
根据下列配制,采用常规方法制备吸入粉剂。
化合物1或2 0.8mg
乳糖 19.2mg
总计 20.0mg
(2)滴鼻剂
根据下列配制,采用常规方法制备滴鼻溶液。
化合物1或2 0.01%重量/重量
羧甲基纤维素钠 1.0%重量/重量
氯化钠 0.9%重量/重量
用净化水补差 总计100%
工业实用性
式(1)所示的本发明甾族衍生物能够持续抑制呼吸道炎症和呼吸道反应过度,并且,当直接用于对呼吸道给药时,其部位选择性高,且几乎不具有全身性作用。因此,作为可以长期服用的高度安全的炎症性呼吸道疾病预防和/或治疗剂,本发明甾族衍生物在临床医学中非常有用。
Claims (6)
2.根据权利要求1的炎症性呼吸道疾病预防和/或治疗剂,其中甾族衍生物为9-氟-11β,17,21-三羟基-16α-甲基-1,4-孕二烯-3,20-二酮17-环丙烷甲酸酯或9-氟-11β,17,21-三羟基-16α-甲基-1,4-孕二烯-3,20-二酮21-环己烷甲酸酯17-环丙烷甲酸酯。
3.根据权利要求1或2的炎症性呼吸道疾病预防和/或治疗剂,其中炎症性呼吸道疾病选自支气管性气喘、鼻过敏症、咽***反应和窦炎。
4.根据权利要求1-3中任一权利要求的炎症性呼吸道疾病预防和/或治疗剂,其为经口吸入或鼻内给药制剂。
5.权利要求1或2中描述的甾族衍生物用于制备炎症性呼吸道疾病预防和/或治疗剂的用途。
6.治疗炎症性呼吸道疾病的方法,其特征在于,经口吸入或鼻内施用权利要求1或2中描述的甾族衍生物。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2000390941 | 2000-12-22 | ||
JP2000390941 | 2000-12-22 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNA018210422A Division CN1481246A (zh) | 2000-12-22 | 2001-12-21 | 炎症性呼吸道疾病的预防/治疗剂 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN101518537A true CN101518537A (zh) | 2009-09-02 |
Family
ID=18857198
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNA018210422A Pending CN1481246A (zh) | 2000-12-22 | 2001-12-21 | 炎症性呼吸道疾病的预防/治疗剂 |
CNA2009100064252A Pending CN101518537A (zh) | 2000-12-22 | 2001-12-21 | 炎症性呼吸道疾病的预防/治疗剂 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CNA018210422A Pending CN1481246A (zh) | 2000-12-22 | 2001-12-21 | 炎症性呼吸道疾病的预防/治疗剂 |
Country Status (16)
Country | Link |
---|---|
US (1) | US7214672B2 (zh) |
EP (1) | EP1344526B1 (zh) |
JP (1) | JP3691487B2 (zh) |
KR (1) | KR100833157B1 (zh) |
CN (2) | CN1481246A (zh) |
AR (2) | AR031969A1 (zh) |
AT (1) | ATE396733T1 (zh) |
CA (1) | CA2438799C (zh) |
DE (1) | DE60134267D1 (zh) |
DK (1) | DK1344526T3 (zh) |
ES (1) | ES2305029T3 (zh) |
MX (1) | MXPA03005660A (zh) |
PE (1) | PE20020793A1 (zh) |
PT (1) | PT1344526E (zh) |
TW (1) | TWI290145B (zh) |
WO (1) | WO2002051422A1 (zh) |
Families Citing this family (15)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU7576001A (en) * | 2000-08-05 | 2002-02-18 | Glaxo Group Ltd | 6.alpha., 9.alpha.-difluoro-17.alpha.-`(2-furanylcarboxyl) oxy]-11.beta.-hydroxy-16.alpha.-methyl-3-oxo-androst-1,4,-diene-17-carbothioic acid s-fluoromethyl ester as an anti-inflammatory agent |
GB0019172D0 (en) * | 2000-08-05 | 2000-09-27 | Glaxo Group Ltd | Novel compounds |
US6759398B2 (en) * | 2000-08-05 | 2004-07-06 | Smithkline Beecham Corporation | Anti-inflammatory androstane derivative |
US6858596B2 (en) * | 2000-08-05 | 2005-02-22 | Smithkline Beecham Corporation | Formulation containing anti-inflammatory androstane derivative |
US6777399B2 (en) * | 2000-08-05 | 2004-08-17 | Smithkline Beecham Corporation | Anti-inflammatory androstane derivative compositions |
EP1383786B1 (en) * | 2001-04-30 | 2008-10-15 | Glaxo Group Limited | Anti-inflammatory 17.beta.-carbothioate ester derivatives of androstane with a cyclic ester group in position 17.alpha |
DE60227254D1 (de) * | 2001-06-12 | 2008-08-07 | Glaxo Group Ltd | Neue anti inflammatorische 17.alpha.-heterozyklische ester von 17.beta.-carbothioat androstan derivativen |
US20050175545A1 (en) * | 2002-02-04 | 2005-08-11 | Keith Biggadike | Formulation for inhalation comprising a glucocorticoid and a beta 2-adrenoreceptor agonist |
GB0202635D0 (en) * | 2002-02-05 | 2002-03-20 | Glaxo Wellcome Mfg Pte Ltd | Formulation containing novel anti-inflammatory androstane derivative |
JP3691459B2 (ja) * | 2002-06-14 | 2005-09-07 | 久光メディカル株式会社 | 粉末状吸入剤組成物 |
GB2389530B (en) | 2002-06-14 | 2007-01-10 | Cipla Ltd | Pharmaceutical compositions |
EP1645266A1 (en) * | 2004-10-08 | 2006-04-12 | Hisamitsu Medical Co., Ltd. | Aqueous suspension for nasal drops |
GB0507165D0 (en) * | 2005-04-08 | 2005-05-18 | Glaxo Group Ltd | Novel crystalline pharmaceutical product |
GB0615108D0 (en) * | 2006-07-28 | 2006-09-06 | Glaxo Group Ltd | Novel formulations |
EP2111861A1 (en) | 2008-04-21 | 2009-10-28 | Ranbaxy Laboratories Limited | Compositions of phosphodiesterase type IV inhibitors |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3639434A (en) * | 1967-02-02 | 1972-02-01 | Boots Pure Drug Co Ltd | 17-acyloxysteroids and their manufacture |
SE418294B (sv) * | 1974-03-27 | 1981-05-18 | Plurichemie Anstalt | Sett att framstella en 16alfa- eller 16beta-9alfa-klor eller -fluorsteroidester |
US4933168A (en) * | 1975-05-27 | 1990-06-12 | Syntex Pharmaceuticals International Limited | Stable, crystalline flunisolide |
IL66432A0 (en) * | 1981-08-04 | 1982-12-31 | Plurichemie Anstalt | Process for the preparation of steroidal esters |
JPH07116215B2 (ja) * | 1989-04-19 | 1995-12-13 | エスエス製薬株式会社 | 新規なステロイド化合物 |
PE44995A1 (es) | 1994-01-27 | 1995-12-18 | Schering Corp | Furoato de mometasona para el tratamiento de las enfermedades pulmonares y de las vias respiratorias |
-
2001
- 2001-12-21 WO PCT/JP2001/011264 patent/WO2002051422A1/ja active IP Right Grant
- 2001-12-21 CN CNA018210422A patent/CN1481246A/zh active Pending
- 2001-12-21 JP JP2002552566A patent/JP3691487B2/ja not_active Expired - Lifetime
- 2001-12-21 AT AT01271858T patent/ATE396733T1/de active
- 2001-12-21 DE DE60134267T patent/DE60134267D1/de not_active Expired - Lifetime
- 2001-12-21 KR KR1020037007282A patent/KR100833157B1/ko active Protection Beyond IP Right Term
- 2001-12-21 TW TW090131849A patent/TWI290145B/zh not_active IP Right Cessation
- 2001-12-21 MX MXPA03005660A patent/MXPA03005660A/es active IP Right Grant
- 2001-12-21 CA CA002438799A patent/CA2438799C/en not_active Expired - Lifetime
- 2001-12-21 PT PT01271858T patent/PT1344526E/pt unknown
- 2001-12-21 US US10/451,061 patent/US7214672B2/en not_active Expired - Lifetime
- 2001-12-21 CN CNA2009100064252A patent/CN101518537A/zh active Pending
- 2001-12-21 ES ES01271858T patent/ES2305029T3/es not_active Expired - Lifetime
- 2001-12-21 EP EP01271858A patent/EP1344526B1/en not_active Expired - Lifetime
- 2001-12-21 DK DK01271858T patent/DK1344526T3/da active
- 2001-12-26 AR ARP010106024A patent/AR031969A1/es not_active Application Discontinuation
- 2001-12-26 PE PE2001001303A patent/PE20020793A1/es not_active Application Discontinuation
-
2014
- 2014-09-23 AR ARP140103518A patent/AR097737A2/es unknown
Also Published As
Publication number | Publication date |
---|---|
DE60134267D1 (de) | 2008-07-10 |
ATE396733T1 (de) | 2008-06-15 |
US7214672B2 (en) | 2007-05-08 |
EP1344526B1 (en) | 2008-05-28 |
JP3691487B2 (ja) | 2005-09-07 |
US20040053904A1 (en) | 2004-03-18 |
CA2438799A1 (en) | 2002-07-04 |
DK1344526T3 (da) | 2008-09-15 |
MXPA03005660A (es) | 2004-12-03 |
PE20020793A1 (es) | 2002-09-06 |
KR100833157B1 (ko) | 2008-05-28 |
CA2438799C (en) | 2009-09-01 |
WO2002051422A1 (fr) | 2002-07-04 |
AR097737A2 (es) | 2016-04-13 |
EP1344526A1 (en) | 2003-09-17 |
EP1344526A4 (en) | 2005-03-16 |
JPWO2002051422A1 (ja) | 2004-04-22 |
TWI290145B (en) | 2007-11-21 |
CN1481246A (zh) | 2004-03-10 |
PT1344526E (pt) | 2008-06-18 |
KR20030064414A (ko) | 2003-07-31 |
ES2305029T3 (es) | 2008-11-01 |
AR031969A1 (es) | 2003-10-08 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN101518537A (zh) | 炎症性呼吸道疾病的预防/治疗剂 | |
EP0735877B1 (en) | 6-(2-imidazolinylamino)quinoxaline compounds useful as alpha-2 adrenoceptor agonists | |
JP2001505553A (ja) | ウリジン三リン酸および関連化合物で気管支炎を治療する方法 | |
AU738310B2 (en) | Use of an H+, K+-ATPase inhibitor in the treatment of nasal polyps | |
AU781133B2 (en) | Nitrosated and nitrosylated proton pump inhibitors, compositions and methods of use | |
US6380222B2 (en) | Use of an H+, K+-atpase inhibitor in the treatment of nasal polyps | |
JPH09511483A (ja) | α−2−アドレノセプター作動剤として有用な6−(2−イミダゾリニルアミノ)キノリン化合物 | |
WO2021047648A1 (en) | New peptides | |
WO2020143744A1 (en) | New formulations containing leukotriene receptor antagonists | |
CN101432002B (zh) | 治疗慢性阻塞性肺疾病的方法和组合物 | |
KR940703840A (ko) | 치환 벤즈이미다졸, 그의 제조 방법 및 용도(substituted benzimidazoles, process for their preparation as well as their use) | |
US6201027B1 (en) | Substituted β diketones and their use | |
JP6294773B2 (ja) | 口腔粘膜疾患の予防または治療用経口製剤 | |
CN109694376B (zh) | 新型β2受体激动剂化合物及其在治疗哮喘类疾病的用途 | |
AU2020396109A1 (en) | Peptides and their use in the treatment of inflammation | |
JPS5810577A (ja) | 2−セノイルメルカプトプロピオニルグリシンのエステル、その製造法およびそれを有効成分とする医薬組成物 | |
JPS62223123A (ja) | 去痰剤 | |
CN105801557A (zh) | 一种新化合物 | |
WO2008109936A1 (en) | Steroidal compounds |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1132449 Country of ref document: HK |
|
C12 | Rejection of a patent application after its publication | ||
RJ01 | Rejection of invention patent application after publication |
Application publication date: 20090902 |
|
REG | Reference to a national code |
Ref country code: HK Ref legal event code: WD Ref document number: 1132449 Country of ref document: HK |