CN1674916A - 环缩松与抗组胺药的组合用于治疗变应性鼻炎的用途 - Google Patents
环缩松与抗组胺药的组合用于治疗变应性鼻炎的用途 Download PDFInfo
- Publication number
- CN1674916A CN1674916A CNA038198606A CN03819860A CN1674916A CN 1674916 A CN1674916 A CN 1674916A CN A038198606 A CNA038198606 A CN A038198606A CN 03819860 A CN03819860 A CN 03819860A CN 1674916 A CN1674916 A CN 1674916A
- Authority
- CN
- China
- Prior art keywords
- inn
- pharmaceutical composition
- methyl
- acid
- shrinkage porosite
- 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
- 239000000739 antihistaminic agent Substances 0.000 title claims abstract description 44
- 238000011282 treatment Methods 0.000 title claims description 31
- 206010039085 Rhinitis allergic Diseases 0.000 title claims description 24
- 201000010105 allergic rhinitis Diseases 0.000 title claims description 24
- LUKZNWIVRBCLON-GXOBDPJESA-N Ciclesonide Chemical compound C1([C@H]2O[C@@]3([C@H](O2)C[C@@H]2[C@@]3(C[C@H](O)[C@@H]3[C@@]4(C)C=CC(=O)C=C4CC[C@H]32)C)C(=O)COC(=O)C(C)C)CCCCC1 LUKZNWIVRBCLON-GXOBDPJESA-N 0.000 title abstract description 4
- 229960003728 ciclesonide Drugs 0.000 title abstract description 4
- 229940125715 antihistaminic agent Drugs 0.000 title abstract description 3
- 230000001387 anti-histamine Effects 0.000 claims description 41
- 239000008194 pharmaceutical composition Substances 0.000 claims description 37
- 239000000203 mixture Substances 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
- 210000004877 mucosa Anatomy 0.000 claims description 19
- 230000003204 osmotic effect Effects 0.000 claims description 15
- 239000012453 solvate Substances 0.000 claims description 15
- -1 4-chlorphenyl Chemical group 0.000 claims description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims description 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 13
- 239000000463 material Substances 0.000 claims description 13
- 241001597008 Nomeidae Species 0.000 claims description 12
- 230000000926 neurological effect Effects 0.000 claims description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
- 206010010744 Conjunctivitis allergic Diseases 0.000 claims description 10
- 208000002205 allergic conjunctivitis Diseases 0.000 claims description 10
- 208000024998 atopic conjunctivitis Diseases 0.000 claims description 10
- 229960001120 levocabastine Drugs 0.000 claims description 9
- ZCGOMHNNNFPNMX-KYTRFIICSA-N levocabastine Chemical compound C1([C@@]2(C(O)=O)CCN(C[C@H]2C)[C@@H]2CC[C@@](CC2)(C#N)C=2C=CC(F)=CC=2)=CC=CC=C1 ZCGOMHNNNFPNMX-KYTRFIICSA-N 0.000 claims description 8
- 229960003088 loratadine Drugs 0.000 claims description 8
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 7
- 210000002850 nasal mucosa Anatomy 0.000 claims description 7
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 6
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 claims description 6
- 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 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 6
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 6
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 6
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 6
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 229910052760 oxygen Inorganic materials 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 6
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- SFOVDSLXFUGAIV-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]-n-piperidin-4-ylbenzimidazol-2-amine Chemical compound C1=CC(F)=CC=C1CN1C2=CC=CC=C2N=C1NC1CCNCC1 SFOVDSLXFUGAIV-UHFFFAOYSA-N 0.000 claims description 4
- JAUOIFJMECXRGI-UHFFFAOYSA-N Neoclaritin Chemical compound C=1C(Cl)=CC=C2C=1CCC1=CC=CN=C1C2=C1CCNCC1 JAUOIFJMECXRGI-UHFFFAOYSA-N 0.000 claims description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
- 239000012736 aqueous medium Substances 0.000 claims description 4
- 235000010980 cellulose Nutrition 0.000 claims description 4
- 229920002678 cellulose Polymers 0.000 claims description 4
- 239000001913 cellulose Substances 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 239000002198 insoluble material Substances 0.000 claims description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
- HIANJWSAHKJQTH-UHFFFAOYSA-N pemirolast Chemical compound CC1=CC=CN(C2=O)C1=NC=C2C=1N=NNN=1 HIANJWSAHKJQTH-UHFFFAOYSA-N 0.000 claims description 4
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- FWLKKPKZQYVAFR-LVEZLNDCSA-N (e)-but-2-enedioic acid;1-(2-ethoxyethyl)-2-(4-methyl-1,4-diazepan-1-yl)benzimidazole Chemical compound OC(=O)\C=C\C(O)=O.OC(=O)\C=C\C(O)=O.N=1C2=CC=CC=C2N(CCOCC)C=1N1CCCN(C)CC1 FWLKKPKZQYVAFR-LVEZLNDCSA-N 0.000 claims description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 2
- ZKLPARSLTMPFCP-OAQYLSRUSA-N 2-[2-[4-[(R)-(4-chlorophenyl)-phenylmethyl]-1-piperazinyl]ethoxy]acetic acid Chemical compound C1CN(CCOCC(=O)O)CCN1[C@@H](C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-OAQYLSRUSA-N 0.000 claims description 2
- CWNCDQYLHMXURI-UHFFFAOYSA-N 3-[4-(8-fluoro-5h-[1]benzoxepino[4,3-b]pyridin-11-ylidene)piperidin-1-yl]propanoic acid;dihydrate Chemical compound O.O.C1CN(CCC(=O)O)CCC1=C1C2=NC=CC=C2COC2=CC(F)=CC=C21 CWNCDQYLHMXURI-UHFFFAOYSA-N 0.000 claims description 2
- ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 claims description 2
- 241000124008 Mammalia Species 0.000 claims description 2
- PVLJETXTTWAYEW-UHFFFAOYSA-N Mizolastine Chemical compound N=1C=CC(=O)NC=1N(C)C(CC1)CCN1C1=NC2=CC=CC=C2N1CC1=CC=C(F)C=C1 PVLJETXTTWAYEW-UHFFFAOYSA-N 0.000 claims description 2
- PHVGLTMQBUFIQQ-UHFFFAOYSA-N Nortryptiline Chemical compound C1CC2=CC=CC=C2C(=CCCNC)C2=CC=CC=C21 PHVGLTMQBUFIQQ-UHFFFAOYSA-N 0.000 claims description 2
- UFLGIAIHIAPJJC-UHFFFAOYSA-N Tripelennamine Chemical compound C=1C=CC=NC=1N(CCN(C)C)CC1=CC=CC=C1 UFLGIAIHIAPJJC-UHFFFAOYSA-N 0.000 claims description 2
- SEBMTIQKRHYNIT-UHFFFAOYSA-N azatadine Chemical compound C1CN(C)CCC1=C1C2=NC=CC=C2CCC2=CC=CC=C21 SEBMTIQKRHYNIT-UHFFFAOYSA-N 0.000 claims description 2
- YWGDOWXRIALTES-NRFANRHFSA-N bepotastine Chemical compound C1CN(CCCC(=O)O)CCC1O[C@H](C=1N=CC=CC=1)C1=CC=C(Cl)C=C1 YWGDOWXRIALTES-NRFANRHFSA-N 0.000 claims description 2
- 229960002071 bepotastine Drugs 0.000 claims description 2
- FFSAXUULYPJSKH-UHFFFAOYSA-N butyrophenone Chemical compound CCCC(=O)C1=CC=CC=C1 FFSAXUULYPJSKH-UHFFFAOYSA-N 0.000 claims description 2
- 229960001803 cetirizine Drugs 0.000 claims description 2
- 229960002881 clemastine Drugs 0.000 claims description 2
- YNNUSGIPVFPVBX-NHCUHLMSSA-N clemastine Chemical compound CN1CCC[C@@H]1CCO[C@@](C)(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 YNNUSGIPVFPVBX-NHCUHLMSSA-N 0.000 claims 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 claims description 2
- 229960001271 desloratadine Drugs 0.000 claims description 2
- SOYKEARSMXGVTM-HNNXBMFYSA-N dexchlorpheniramine Chemical compound C1([C@H](CCN(C)C)C=2N=CC=CC=2)=CC=C(Cl)C=C1 SOYKEARSMXGVTM-HNNXBMFYSA-N 0.000 claims description 2
- 229960001882 dexchlorpheniramine Drugs 0.000 claims description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 2
- 229960001971 ebastine Drugs 0.000 claims description 2
- MJJALKDDGIKVBE-UHFFFAOYSA-N ebastine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(=O)CCCN1CCC(OC(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 MJJALKDDGIKVBE-UHFFFAOYSA-N 0.000 claims description 2
- 229960000325 emedastine Drugs 0.000 claims description 2
- 229960003449 epinastine Drugs 0.000 claims description 2
- WHWZLSFABNNENI-UHFFFAOYSA-N epinastine Chemical compound C1C2=CC=CC=C2C2CN=C(N)N2C2=CC=CC=C21 WHWZLSFABNNENI-UHFFFAOYSA-N 0.000 claims description 2
- 229960003592 fexofenadine Drugs 0.000 claims description 2
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 2
- WBJINCZRORDGAQ-UHFFFAOYSA-N formic acid ethyl ester Natural products CCOC=O WBJINCZRORDGAQ-UHFFFAOYSA-N 0.000 claims description 2
- 229960001508 levocetirizine Drugs 0.000 claims description 2
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 2
- 229960001144 mizolastine Drugs 0.000 claims description 2
- DUWWHGPELOTTOE-UHFFFAOYSA-N n-(5-chloro-2,4-dimethoxyphenyl)-3-oxobutanamide Chemical compound COC1=CC(OC)=C(NC(=O)CC(C)=O)C=C1Cl DUWWHGPELOTTOE-UHFFFAOYSA-N 0.000 claims description 2
- 229960001158 nortriptyline Drugs 0.000 claims description 2
- 239000002245 particle Substances 0.000 claims description 2
- 229960004439 pemirolast Drugs 0.000 claims description 2
- QQVIHTHCMHWDBS-UHFFFAOYSA-N perisophthalic acid Natural products OC(=O)C1=CC=CC(C(O)=O)=C1 QQVIHTHCMHWDBS-UHFFFAOYSA-N 0.000 claims description 2
- 125000006187 phenyl benzyl group Chemical group 0.000 claims description 2
- IJAPPYDYQCXOEF-UHFFFAOYSA-N phthalazin-1(2H)-one Chemical compound C1=CC=C2C(=O)NN=CC2=C1 IJAPPYDYQCXOEF-UHFFFAOYSA-N 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 235000019260 propionic acid Nutrition 0.000 claims description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
- 239000004094 surface-active agent Substances 0.000 claims description 2
- 229950008068 tecastemizole Drugs 0.000 claims description 2
- 229960000351 terfenadine Drugs 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- 229960003223 tripelennamine Drugs 0.000 claims description 2
- 239000000080 wetting agent Substances 0.000 claims description 2
- 229920003169 water-soluble polymer Polymers 0.000 claims 2
- 238000002360 preparation method Methods 0.000 description 15
- 210000001331 nose Anatomy 0.000 description 11
- 208000024891 symptom Diseases 0.000 description 11
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 10
- 230000000699 topical effect Effects 0.000 description 7
- 239000003814 drug Substances 0.000 description 6
- 239000003862 glucocorticoid Substances 0.000 description 6
- 150000003431 steroids Chemical class 0.000 description 6
- 239000013566 allergen Substances 0.000 description 5
- 229960001340 histamine Drugs 0.000 description 5
- 239000000825 pharmaceutical preparation Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- MKDHTPTXOKJEFU-UHFFFAOYSA-N [N].Cl Chemical compound [N].Cl MKDHTPTXOKJEFU-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 229920000642 polymer Polymers 0.000 description 4
- 239000007921 spray Substances 0.000 description 4
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
- 206010061218 Inflammation Diseases 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000000890 drug combination Substances 0.000 description 3
- 230000003203 everyday effect Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 229940031705 hydroxypropyl methylcellulose 2910 Drugs 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 3
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 206010010741 Conjunctivitis Diseases 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 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 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 208000003251 Pruritus Diseases 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- HUCJFAOMUPXHDK-UHFFFAOYSA-N Xylometazoline Chemical compound CC1=CC(C(C)(C)C)=CC(C)=C1CC1=NCCN1 HUCJFAOMUPXHDK-UHFFFAOYSA-N 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- PIZLBWGMERQCOC-UHFFFAOYSA-N dibenzyl carbonate Chemical compound C=1C=CC=CC=1COC(=O)OCC1=CC=CC=C1 PIZLBWGMERQCOC-UHFFFAOYSA-N 0.000 description 2
- POULHZVOKOAJMA-UHFFFAOYSA-N dodecanoic acid Chemical compound CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 229960001828 levocabastine hydrochloride Drugs 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 239000007922 nasal spray Substances 0.000 description 2
- 229940097496 nasal spray Drugs 0.000 description 2
- 239000001814 pectin Substances 0.000 description 2
- 235000010987 pectin Nutrition 0.000 description 2
- 229920001277 pectin Polymers 0.000 description 2
- 230000035790 physiological processes and functions Effects 0.000 description 2
- 238000005507 spraying Methods 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- ODIGIKRIUKFKHP-UHFFFAOYSA-N (n-propan-2-yloxycarbonylanilino) acetate Chemical compound CC(C)OC(=O)N(OC(C)=O)C1=CC=CC=C1 ODIGIKRIUKFKHP-UHFFFAOYSA-N 0.000 description 1
- SJJCQDRGABAVBB-UHFFFAOYSA-N 1-hydroxy-2-naphthoic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CC=C21 SJJCQDRGABAVBB-UHFFFAOYSA-N 0.000 description 1
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- YGTUPRIZNBMOFV-UHFFFAOYSA-N 2-(4-hydroxybenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(=O)C1=CC=C(O)C=C1 YGTUPRIZNBMOFV-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical compound O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 description 1
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- FHVDTGUDJYJELY-UHFFFAOYSA-N 6-{[2-carboxy-4,5-dihydroxy-6-(phosphanyloxy)oxan-3-yl]oxy}-4,5-dihydroxy-3-phosphanyloxane-2-carboxylic acid Chemical compound O1C(C(O)=O)C(P)C(O)C(O)C1OC1C(C(O)=O)OC(OP)C(O)C1O FHVDTGUDJYJELY-UHFFFAOYSA-N 0.000 description 1
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
- KUVIULQEHSCUHY-XYWKZLDCSA-N Beclometasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COC(=O)CC)(OC(=O)CC)[C@@]1(C)C[C@@H]2O KUVIULQEHSCUHY-XYWKZLDCSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 description 1
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 241000218645 Cedrus Species 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 1
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 102000003834 Histamine H1 Receptors Human genes 0.000 description 1
- 108090000110 Histamine H1 Receptors Proteins 0.000 description 1
- 229920002884 Laureth 4 Polymers 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- UQOFGTXDASPNLL-XHNCKOQMSA-N Muscarine Chemical compound C[C@@H]1O[C@H](C[N+](C)(C)C)C[C@H]1O UQOFGTXDASPNLL-XHNCKOQMSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- 206010028735 Nasal congestion Diseases 0.000 description 1
- 229940123424 Neuraminidase inhibitor Drugs 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 239000004218 Orcein Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 206010039094 Rhinitis perennial Diseases 0.000 description 1
- 208000036071 Rhinorrhea Diseases 0.000 description 1
- 206010039101 Rhinorrhoea Diseases 0.000 description 1
- 206010048908 Seasonal allergy Diseases 0.000 description 1
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000001785 acacia senegal l. willd gum Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 239000013572 airborne allergen Substances 0.000 description 1
- 229940072056 alginate Drugs 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 230000002009 allergenic effect Effects 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000002421 anti-septic effect Effects 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 229960004495 beclometasone Drugs 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229960004436 budesonide Drugs 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 210000000795 conjunctiva Anatomy 0.000 description 1
- 229960003957 dexamethasone Drugs 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
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000003172 expectorant agent Substances 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 229960000676 flunisolide Drugs 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229950006191 gluconic acid Drugs 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 239000000938 histamine H1 antagonist Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 230000001861 immunosuppressant effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 208000030603 inherited susceptibility to asthma Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- OEXHQOGQTVQTAT-JRNQLAHRSA-N ipratropium Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 OEXHQOGQTVQTAT-JRNQLAHRSA-N 0.000 description 1
- 229960001888 ipratropium Drugs 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 239000003199 leukotriene receptor blocking agent Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- YPZVAYHNBBHPTO-MXRBDKCISA-N loteprednol Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)OCCl)[C@@H]4[C@@H]3CCC2=C1 YPZVAYHNBBHPTO-MXRBDKCISA-N 0.000 description 1
- 229960001798 loteprednol Drugs 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 210000000350 mc(t) Anatomy 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 210000000214 mouth Anatomy 0.000 description 1
- 229940066491 mucolytics Drugs 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000013588 oral product Substances 0.000 description 1
- 235000019248 orcein Nutrition 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 208000022719 perennial allergic rhinitis Diseases 0.000 description 1
- RLLPVAHGXHCWKJ-UHFFFAOYSA-N permethrin Chemical compound CC1(C)C(C=C(Cl)Cl)C1C(=O)OCC1=CC=CC(OC=2C=CC=CC=2)=C1 RLLPVAHGXHCWKJ-UHFFFAOYSA-N 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 150000007519 polyprotic acids Chemical class 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- MIXMJCQRHVAJIO-TZHJZOAOSA-N qk4dys664x Chemical compound O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O MIXMJCQRHVAJIO-TZHJZOAOSA-N 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000002911 sialidase inhibitor Substances 0.000 description 1
- 201000009890 sinusitis Diseases 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 230000035943 smell Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229950004959 sorbitan oleate Drugs 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 229960000833 xylometazoline Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- 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
- 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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic 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
- A61P27/02—Ophthalmic agents
- A61P27/14—Decongestants or antiallergics
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Pulmonology (AREA)
- Otolaryngology (AREA)
- Ophthalmology & Optometry (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
本发明涉及环缩松与抗组胺药的组合。
Description
发明的技术领域
本发明涉及一种用于药物治疗，特别是变应性鼻炎治疗的环缩松与抗组胺药的新组合。具体而言，所述新组合是以含水药物组合物的形式给予的，它含有环缩松和抗组胺药且具有小于290mOsm的渗透压。
背景技术
变应性鼻炎是一种常见病且患者数目稳定生长。该病是由周围空中传播的变应原引起的，其在鼻粘膜内引起变应性炎症且常伴有结膜炎。根据变应原的不同，变应性鼻炎可分成季节性变应性鼻炎(变应原像禾本科植物的花粉、雪松的花粉)和常年性变应性鼻炎(室内变应原像霉菌、来源于动物和房间尘螨的变应原)。变应性鼻炎对生活质量具有很大影响。患者会有鼻子发痒和流鼻涕、鼻子堵塞，头疼和疲劳的症状。变应性结膜炎常常与变应性鼻炎有关且需要共同-治疗。结膜炎的主要症状是眼睛感觉灼热和发痒且流泪。涉及该病的基本原理与变应性鼻炎的相同。
目前变应性鼻炎的治疗主要集中在缓解症状。口服以及小范围的局部抗组胺药是最广泛使用的疗法。口服抗组胺药仅仅缓解组胺造成的症状。变应原接触引起粘膜肥大细胞脱粒并释放出组胺。组胺导致发痒和打喷嚏以及鼻分泌增加。抗组胺药可阻断组胺与组胺-H1-受体结合以及组胺介导的症状。与这种显而易见的途径无关，变应原还可引起鼻粘膜的嗜酸细胞性炎症，其主要导致的症状为鼻子的过度反应性、鼻子堵塞和担心所谓的底部改变，这是指没有治疗过的变应性鼻炎可发展成鼻窦炎和支气管哮喘。
用糖皮质激素进行治疗是目前唯一的一种疗法，其针对潜在的变应性炎症。为了避免通常与糖皮质激素有关的全身副作用，例如，免疫抑制、蛋白合成减少、儿童生长减慢，用糖皮质激素进行局部治疗是给药的优选方式。
鼻用甾族化合物的缺点是起效慢且需要连续治疗。在观察到症状缓解前，要进行4-6天的连续治疗。因此，建议患者在花粉传播季节开始前，开始服用糖皮质激素。起效慢、需要连续治疗以及担心甾族化合物诱导副作用都对鼻内用甾族化合物的使用以及患者的顺应性具有不利的影响。
可用于治疗的其它药物仅仅用于缓解症状，例如鼻内用毒蕈碱拮抗剂(减少鼻分泌的异丙托品)、肾上腺受体激动剂(减少鼻充血的赛洛唑啉)。
WO97/01337描述了一种鼻用喷雾剂或滴鼻剂，其含有丙酸倍氯米松、氟尼缩松、去炎松、地塞米松或布地缩松和抗组胺药左卡巴司汀、氮司汀或氯雷他定以及无菌水。
WO97/46243涉及含有鼻内用甾族化合物以及抗组胺药的鼻用喷雾剂。
WO98/48839涉及局部应用的鼻用组合物，它含有治疗有效量的抗炎剂和治疗有效量的选自血管收缩剂、神经氨酸苷酶抑制剂、白三烯抑制剂、抗组胺药、抗变应剂、抗胆碱能剂、麻醉剂和粘液溶解剂的至少一种药剂。
WO01/22955涉及氯替泼诺，一种所谓温和的甾族化合物与抗组胺药的新组合。
WO03/049770公开了用H1拮抗剂/抗变应且安全的甾族化合物治疗鼻炎的组合物和方法。
US5164194涉及氮司汀的鼻用制剂。
发明详述
令人惊讶地是，现在人们已经发现环缩松与至少一种抗组胺药的联合给药可非常有效且安全地治疗与变应性鼻炎和/或变应性结膜炎有关的症状。具体而言，通过以低渗含水药物制剂的形式将环缩松与抗组胺药联合给药，可观察到起效快以及症状迅速缓解，而不必担心糖皮质激素样副作用。通过将本发明这种低渗含水药物组合物给予鼻粘膜，活性成分迅速进入鼻粘膜且具有非常长的停留时间。因此，剂量非常低的环缩松以及每天一次，最多每天两次的治疗是获得有效治疗所必需的。
一方面，本发明因此涉及用于治疗变应性鼻炎和/或变应性结膜炎的环缩松与至少一种抗组胺药的联合给药。本发明另一目的因此是一种用于治疗变应性鼻炎和/或变应性结膜炎的药物组合物，所述组合物含有作为活性成分的至少一种抗组胺药、其药学上可接受的盐和/或溶剂化物或生理功能性衍生物与环缩松、环缩松药学上可接受的盐、任选以任何比例和环缩松混合的环缩松差向异构体、环缩松的溶剂化物、环缩松的生理功能性衍生物或其溶剂化物的组合，以及药学上可接受的载体和/或一种或多种赋形剂。
应认识到所述组合中的化合物可同时给药，或存在于相同的药物制剂(在下文中也称作固定组合)中或存在于不同的药物制剂(在下文中也称作自由组合)中，或以任何顺序连续给药。如果是顺序给药，则给予第二种化合物时的延迟不应使组合的有益治疗作用损失。例如，两种药物可以口服制剂的形式分开提供，或一种是口服制品而另一种是吸入剂，或两者都以适用于粘膜的形式提供(鼻用)。给药可同时进行。或可以较近或较远的时间间隔给予它们，如早上给予其中一种药物而晚上给予第二种药物。
因此，本发明还提供一种用于预防或治疗哺乳动物，如人变应性鼻炎和/或变应性结膜炎的方法，包括给予治疗有效量的药物制剂，所述药物制剂含有至少一种抗组胺药或其药学上可接受的盐、溶剂化物、或生理功能性衍生物和环缩松或其药学上可接受的盐、溶剂化物、或生理功能性衍生物，以及药学上可接受的载体和/或一种或多种赋形剂。在优选方面，提供这样一种方法，其包括给予治疗有效量的组合，所述组合含有至少一种抗组胺药和环缩松，以及药学上可接受的载体和/或一种或多种赋形剂。
所述制剂包括适于口服、肠胃外包括皮下、真皮内、肌内、静脉内和关节内、鼻内、吸入(包括精细的颗粒粉尘，它们可利用各种类型的计量加压气溶胶、喷雾器、吹入器产生)、直肠和局部(包括皮肤、口腔、舌下和眼内给药)的那些，尽管最适宜的途径可能取决于，例如受体的状况和病症。在本发明的优选实施方案中，所述制剂适于局部给药。在优选实施方案中，在治疗变应性鼻炎的情况下，本发明的制剂是适用于粘膜的制剂。在治疗变应性结膜炎的情况下，优选制剂是适于结膜给药的制剂(用于结膜囊)。便利地，所述制剂可以单位剂量形式提供，且可通过制药领域熟知的任何方法制备。所有方法均包括使活性成分与载体缔合的步骤，其构成一种或多种补充的成分/赋形剂。通常，所述制剂是通过均匀且紧密地使活性成分与液态载体或精细分散的固态载体或两者缔合，然后如果需要，将产物制成所需制剂而制备的。
在优选实施方案中，本发明涉及应用于粘膜上治疗变应性鼻炎的含水药物组合物，它含有至少一种抗组胺药和环缩松的组合作为活性成分。具体而言，所述含水药物组合物是无菌的含水药物组合物。
本发明还涉及应用于粘膜上治疗变应性鼻炎的含水药物组合物，它含有作为活性成分的至少一种抗组胺药和环缩松，以及一种或多种水不溶性和/或水溶性低的物质，并具有低于290mOsm的渗透压。优选，所述渗透压为150mOsm或更低、更优选72mOsm或更低、更优选60mOsm或更低、更优选40mOsm或更低、更优选30mOsm或更低且更优选20mOsm(例如，10mOsm或更低)。
根据本发明，并不特别要求加入控制渗透压的物质(渗透压-控制剂)，但当加入它时，可使用任何物质。在本发明中，可加入用于控制渗透压的物质(渗透压控制剂)以控制渗透压，它们的具体例子包括盐如氯化钠和水溶性糖如葡萄糖，特别优选的例子是葡萄糖。
在优选实施方案中，所述药物组合物是在WO01/28562或WO01/28563中相对于环缩松描述的药物组合物。
因此，一方面本发明涉及一种应用于粘膜上治疗变应性鼻炎的含水药物组合物，它含有作为活性成分的至少一种抗组胺药与环缩松的组合，以及一种或多种水不溶性和/或水溶性低的物质，并具有低于290mOsm的渗透压。
所述水不溶性或水溶性低的物质可以是任何物质，且优选的例子包括纤维素，更优选结晶纤维素，且特别优选微晶纤维素。根据本发明，相对于组合物的总量，以固体颗粒形式存在于水介质中的水不溶性和/或水溶性低的物质的浓度优选0.3％w/w及以上，特别优选0.5％w/w-5％w/w。
此外，还可将含水聚合物加入到本发明的药物组合物中。这种聚合物的具体例子包括丙二醇、藻酸盐、果胶、低分子甲氧基果胶、瓜尔胶、阿拉伯胶、角叉菜胶、甲基纤维素、羧甲基纤维素钠、黄原胶、羟丙基甲基纤维素和羟丙基纤维素，而特别优选的例子包括羧甲基纤维素钠、聚乙二醇和羟丙基纤维素。羧甲基纤维素钠与微晶纤维素的混合物是可用于本发明中的这些水溶性物质和水不溶性物质组合的例子。此外，在加入这些聚合物的情况下，相对于水不溶性物质和/或水溶性低的物质，所述聚合物的浓度优选1％w/w-30％w/w。
在本发明的优选实施方案中，羟丙基甲基纤维素包含在本发明的药物组合物中。羟丙基甲基纤维素可以是任何等级的，具体的例子是羟丙基甲基纤维素2910。虽然所述羟丙基甲基纤维素可以任何浓度存在，但相对于组合物的总量，它的浓度优选0.001％w/w-30％w/w、特别优选0.01％w/w-5％w/w、更特别优选0.01％w/w-1％w/w、且最优选0.01％w/w-0.5％w/w。
表面活性剂和/或湿润剂，虽然在本发明中并不是必需的，但也可加入，它们的具体例子包括吐温80、甘油一硬脂酸酯、硬脂酸聚烃氧基酯、lauromacrogol、脱水山梨糖醇油酸酯和蔗糖脂肪酸酯。
用于本发明中的环缩松及局部抗组胺药的有效量可根据各自疾病的类型和程度，以及患者的年龄和体重等确定。优选每天1或2次，每次向每个鼻孔喷1-4下本发明的药物组合物。有利地，每喷一下，环缩松的剂量为10μg-400μg、优选20μg-200μg。每喷一下的抗组胺药的剂量取决于给药类型和给药途径。有利地，每喷一下的剂量为10μg-500μg、优选25μg-250μg。在氮司汀的情况下，所述剂量优选在US5164194描述的范围内。
环缩松(下文也称作活性成分)是化学名称为[11β，16α(R)]-16，17-[(环己基亚甲基)二(氧基)]-11-羟基-21-(2-甲基-1-氧代丙氧基)孕-1，4-二烯-3，20-二酮的化合物的INN。环缩松及其制备在DE 4129535中公开。此处所用的环缩松还包括环缩松药学上可接受的盐、以任何比例与环缩松混合的环缩松差向异构体(例如[11β，16α(S)]-16，17-[(环己基亚甲基)二(氧基)]-11-羟基-21-(2-甲基-1-氧代丙氧基)孕-1，4-二烯-3，20-二酮)、环缩松的溶剂化物、环缩松的生理功能性衍生物或其溶剂化物。术语“生理功能性衍生物”是指具有与环缩松相同生理功能的环缩松化学衍生物，例如，它可在肌体中转化成环缩松或是环缩松的活性代谢物。本发明提及的环缩松生理功能性衍生物是，例如，环缩松的21-羟基衍生物，化学名称为16α，17-(22R，S)-环己基亚甲二氧基-11β，21-二羟基孕-1，4-二烯-3，20-二酮、16α，17-(22S)-环己基亚甲二氧基-11β，21-二羟基孕-1，4-二烯-3，20-二酮，和特别是16α，17-(22R)-环己基亚甲二氧基-11β，21-二羟基孕-1，4-二烯-3，20-二酮。该化合物及其制备在WO9422899中公开。
优选环缩松以固体颗粒的形式分散于水介质中。
相对于组合物的总量，本发明环缩松的浓度优选0.01％w/w-1％w/w、且特别优选0.05w/w-0.5％w/w。
虽然用于本发明中的环缩松颗粒可以是任何大小，但优选它们在10nm-100μm、且特别优选在100nm-10μm的范围内。
本发明中提及的抗组胺药可以是适用于治疗变应性鼻炎和/或变应性结膜炎的任何抗组胺药。可提及的例子是(E)-6-[(E)-3-(1-吡咯烷基)-1-对甲苯基丙烯基]-2-吡啶丙烯酸[INN：阿伐司丁]、6，11-二氢-11-(1-甲基-4-亚哌啶基)-5H-苯并[5，6]环庚三烯并[1，2-b]吡啶[INN：氯雷他定]、4-[(4-氯苯基)甲基]-2-(六氢-1-甲基-1H-氮杂-4-基)-1(2H)酞嗪酮[INN：氮司汀]、(+)-(S)-4-[4-[1-(4-氯苯基)-1-(2-吡啶基)甲氧基]哌啶-1-基]-丁酸[INN：贝他斯汀]、(+/-)-[2-[4-(对-氯-α-苯基苄基)-1-哌嗪基]乙氧基]-乙酸[INN：西替利嗪]、(+)-2-{2-[(对-氯-α-甲基-α苯基苄基)氧基]乙基}-1-甲基吡咯烷[INN：氯马斯汀]、8-氯-6，11-二氢-11-(4-亚哌啶基)-5H-苯并[5，6]环庚三烯并[1，2-b]吡啶[INN：地氯雷他定]、[3-(4-氯苯基)-3-吡啶-2-基-丙基]-二甲胺[INN：右氯苯那敏]、4′-叔丁基-4-[4-(二苯基甲氧基)哌啶子基]丙基苯基酮[INN：艾巴停]、[2-[4-[双(对-氟苯基)甲基]-1-哌嗪基]乙氧基]乙酸[INN：依来瑞秦]、1-(2-乙氧基乙基)-2-(六氢-4-甲基-1H-1，4-二氮杂-1-基)-苯并咪唑[INN：依美司汀]、3-氨基-9，13b-二氢-1H-二苯并[c，f]咪唑并[1，5-a]氮杂[INN：依匹那丁]、(+/-)-对-[1-羟基-4-[4-(羟基二苯基甲基)哌啶子基]-丁基]-α-甲基氢化阿托酸[INN：甲美芳铵]、3-[4-(8-氟-5，11-二氢苯并[b]氧杂[4，3-b]吡啶-11-亚基)-哌啶-1-基]丙酸[检索代码：HSR-609]、(-)-(3S，4R)-1-[顺-4-氰基-4-(对-氟苯基)环己基]-3-甲基-4-苯基六氢异烟酸[INN：左卡巴司汀]、[2-[4-[(R)-对-氯-α-苯基苄基]-1-哌嗪基]乙氧基]-乙酸[INN：左西替利嗪]、4-(8-氯-5，6-二氢-11H-苯并[5，6]环庚三烯并[1，2-b]吡啶-11-亚基)-1-哌啶甲酸乙酯[INN：克敏能]、2-[N-[1-(4-氟苄基)-1H-苯并咪唑-2-基]-4-哌啶基]-N-甲基-氨基]嘧啶-4(3H)-酮[INN：咪唑斯汀]、1-(4-氟苄基)-2-(哌啶-4-基氨基)-1H-苯并咪唑[INN：去甲阿司咪唑]、3-(10，11-二氢-5H-二苯并[a，d]环庚烯-5-亚基)-N-甲基-1-丙胺[INN：去甲替林]、9-甲基-3-(1H-四唑-5-基)-4H-吡啶并[1，2-a]嘧啶-4-酮[INN：哌米拉特]、8-氯-11-[1-(5-甲基吡啶-3-基甲基)哌啶-4-亚基]-6，11-二氢-5H-苯并[5，6]环七[1，2-b]吡啶[INN：舒帕他定]、1-[2-[(对-氯-α-甲基-α-苯基苄基)氧]乙基]六氢-1H-氮杂[INN：赛达斯丁]、S-(7-羧基-4-己基-9-氧代呫吨-2-基)-S-甲基磺酰亚胺[INN：秀地洛克司]、1-(对叔丁基苯基)-4-[4′-(α-羟基二苯基甲基)-1′-哌啶基]-丁醇[INN：特非那定]、N-苄基-N，N′-二甲基-N-(2-吡啶基)-乙二胺[INN：曲吡那敏]和1-(4-氟苄基)-2-(哌啶-4-基氨基)-1H-苯并咪唑[INN：TECASTEMIZOLE]及其混合物。所述抗组胺药还可以药学上可接受的盐和/或溶剂化物的形式存在。根据化学结构的不同，抗组胺药可以不同的立体异构体形式存在。术语抗组胺药包括纯立体异构体(例如，纯差向异构体、非对映异构体或对映异构体)和以任何比例混合的它们的混合物。抗组胺药适宜的药学上可接受的盐特别是水溶性和水不溶性酸加成盐，所述酸是例如盐酸、氢溴酸、磷酸、硝酸、硫酸、乙酸、柠檬酸、D-葡萄糖酸、苯甲酸、2-(4-羟基苯甲酰基)-苯甲酸、丁酸、磺基水杨酸、马来酸、月桂酸、苹果酸、富马酸、琥珀酸、草酸、酒石酸、扑酸、硬脂酸、甲苯磺酸、甲磺酸或1-羟基-2-萘甲酸，所述酸可用于盐的制备-这取决于它是一元酸还是多元酸且取决于需要什么盐-相等的摩尔数量比还是与其不同的摩尔数量比。术语“生理功能性衍生物”是指具有与抗组胺药相同生理功能的抗组胺药化学衍生物，例如，它可在肌体中转化成抗组胺药或是抗组胺药的活性代谢物。在优选实施方案中，所述抗组胺药是具有长时间发挥作用的局部活性的抗组胺药。氯雷他定、氮司汀、左卡巴司汀及其药学上可接受的盐是特别优选的。氯雷他定是从例如US3326924了解的。氯雷他定的优选盐包括它的马来酸盐、硫酸盐、琥珀酸盐和乙酸盐。氮司汀是从US 3813384和US 5164194了解的。优选酸加成盐，如，卤化氢盐和有机酸盐。优选的盐包括盐酸盐、氢溴酸盐、扑酸盐、马来酸盐、柠檬酸盐和酒石酸盐。左卡巴司汀是从US4369184了解的。适宜的盐包括盐酸盐、氢溴酸盐、和硫酸盐、硝酸盐、乙酸盐和丙酸盐。
在水溶性抗组胺药，如盐酸氮司汀的情况下，所述抗组胺药将溶于本发明的药物组合物中。
相对于组合物的总量，局部抗组胺药的浓度优选0.01％w/w-0.5％w/w，且特别优选0.05w/w-0.2％wlw。
将水不溶性物质和/或水溶性低的物质分散在水介质中的任何方法都可用于生产本发明的含水药物组合物，其具体的例子是使用均相混合机的方法。
根据需要，可将已知的抗菌剂、pH控制剂、防腐剂、缓冲剂、着色剂、矫味剂等加入到本发明的组合物中，从而改善所述制剂的物理性质、稳定性、外观或气味等。
抗菌剂的例子包括苯扎氯铵，pH控制剂的例子包括盐酸和氢氧化钠，防腐剂的例子包括山梨酸钾，缓冲剂的例子包括磷酸及其盐，着色剂的例子包括2号红色染料，矫味剂的例子包括薄荷醇。
由于独特的盖仑制剂，环缩松迅速进入鼻粘膜并具有非常长的停留时间。因此，剂量非常低的环缩松以及每天一次，最多每天两次的治疗是获得有效治疗所必需的。低剂量的环缩松与局部抗组胺药(如氮司汀或左卡巴司汀)在低渗含水混悬液中的组合可十分有效且安全地治疗与变应性鼻炎有关的所有症状。该组合显而易见的优点是起效快且迅速缓解症状，而不必担心糖皮质激素样副作用。
在另一实施方案中，本发明涉及环缩松与氮司汀的组合，并将环缩松用于WO01/28562或WO01/28563中相对于环缩松描述的药物组合物中，将左卡巴司汀用于US5164194的药物制剂中。
当给予鼻粘膜时，可将本发明的制剂填充到塑料挤瓶或玻璃瓶中，它们是用计量雾化泵和鼻用适配器或用适宜的滴管填装的。当给予眼睛时，可将本发明的制剂填充到塑料挤平或玻璃瓶中，它们是使用适宜的滴管填装的。
实施例
含有下列组分的环缩松含水药物组合物是用均相混合机加工制备的。均相混合机的加工是在6000rpm下进行30分钟。
实施例1：环缩松与盐酸氮司汀的组合：
环缩松： 0.05％
盐酸氮司汀 0.14％
微晶纤维素和羧甲基纤维素钠 1.7％
羟丙基甲基纤维素2910 0.1％
通过鼻用涂药器输送的每100mg喷雾可输送50μg环缩松和140μg盐酸氮司汀。
实施例2：环缩松与盐酸左卡巴司汀
环缩松： 0.05％
盐酸左卡巴司汀 0.054％
微晶纤维素和羧甲基纤维素钠 1.7％
羟丙基甲基纤维素2910 0.1％
通过鼻用涂药器输送的每100mg喷雾可输送50μg环缩松及54μg盐酸左卡巴司汀(相当于50μg左卡巴司汀)。
Claims (18)
1.用于治疗变应性鼻炎和/或变应性结膜炎的药物组合物，所述组合物含有作为活性成分的至少一种抗组胺药、其立体异构体、药学上可接受的盐、溶剂化物、或生理功能性衍生物与环缩松、环缩松药学上可接受的盐、任选以任何比例和环缩松混合的环缩松差向异构体、环缩松的溶剂化物、环缩松的生理功能性衍生物或其溶剂化物的组合，以及药学上可接受的载体和/或一种或多种赋形剂。
2.根据权利要求1所述的应用于粘膜上治疗变应性鼻炎的药物组合物，所述组合物是含有活性成分以及一种或多种水不溶性和/或水溶性低的物质且具有低于290mOsm的渗透压的含水药物组合物。
3.根据权利要求2所述的应用于粘膜上的药物组合物，其中所述渗透压为150mOsm或更低。
4.根据权利要求2所述的应用于粘膜上的药物组合物，其中所述渗透压为60mOsm或更低。
5.根据权利要求2所述的应用于粘膜上的药物组合物，其中所述渗透压为40mOsm或更低。
6.根据权利要求2所述的应用于粘膜上的药物组合物，其中所述渗透压为20mOsm或更低。
7.根据权利要求2所述的应用于粘膜上的药物组合物，其中所述组合物还含有渗透压-控制剂。
8.根据权利要求2所述的应用于粘膜上的药物组合物，其中所述水不溶性和/或水溶性低的物质是纤维素。
9.根据权利要求8所述的应用于粘膜上的药物组合物，其中所述纤维素是微晶纤维素。
10.根据权利要求2所述的应用于粘膜上的药物组合物，其中所述一种或多种水不溶性和/或水溶性低的物质以固体颗粒存在于水介质中。
11.根据权利要求2所述的应用于粘膜上的药物组合物，其中所述组合物还含有水溶性聚合物。
12.根据权利要求11所述的应用于粘膜上的药物组合物，其中存在的所述水不溶性物质与水溶性聚合物的组合是微晶纤维素与羧甲基纤维素钠的组合。
13.根据权利要求2所述的应用于粘膜上的药物组合物，其中所述组合物还含有表面活性剂和/或湿润剂。
14.根据权利要求2所述的应用于粘膜上的药物组合物，其中所述粘膜是鼻粘膜。
15.根据权利要求1-14所述的药物组合物，其中所述抗组胺药选自(E)-6-[(E)-3-(1-吡咯烷基)-1-对甲苯基丙烯基]-2-吡啶丙烯酸[INN：阿伐司丁]、6，11-二氢-11-(1-甲基-4-亚哌啶基)-5H-苯并[5，6]环庚三烯并[1，2-b]吡啶[INN：氯雷他定]、4-[(4-氯苯基)甲基]-2-(六氢-1-甲基-1H-氮杂-4-基)-1(2H)酞嗪酮[INN：氮司汀]、(+)-(S)-4-[4-[1-(4-氯苯基)-1-(2-吡啶基)甲氧基]哌啶-1-基]-丁酸[INN：贝他斯汀]、(+/-)-[2-[4-(对-氯-α-苯基苄基)-1-哌嗪基]乙氧基]-乙酸[INN：西替利嗪]、(+)-2-{2-[(对-氯-α-甲基-α苯基苄基)氧基]乙基}-1-甲基吡咯烷[INN：氯马斯汀]、8-氯-6，11-二氢-11-(4-亚哌啶基)-5H-苯并[5，6]环庚三烯并[1，2-b]吡啶[INN：地氯雷他定]、[3-(4-氯苯基)-3-吡啶-2-基-丙基]-二甲胺[INN：右氯苯那敏]、4′-叔丁基-4-[4-(二苯基甲氧基)哌啶子基]丙基苯基酮[INN：艾巴停]、[2-[4-[双(对-氟苯基)甲基]-1-哌嗪基]乙氧基]乙酸[INN：依来瑞秦]、1-(2-乙氧基乙基)-2-(六氢-4-甲基-1H-1，4-二氮杂-1-基)-苯并咪唑[INN：依美司汀]、3-氨基-9，13b-二氢-1H-二苯并[c，f]咪唑并[1，5-a]氮杂[INN：依匹那丁]、(+/-)-对-[1-羟基-4-[4-(羟基二苯基甲基)哌啶子基]-丁基]-α-甲基氢化阿托酸[INN：甲美芳铵]、3-[4-(8-氟-5，11-二氢苯并[b ]氧杂[4，3-b]吡啶-11-亚基)-哌啶-1-基]丙酸[检索代码：HSR-609]、(-)-(3S，4R)-1-[顺-4-氰基-4-(对-氟苯基)环己基]-3-甲基-4-苯基六氢异烟酸[INN：左卡巴司汀]、[2-[4-[(R)-对-氯-α-苯基苄基]-1-哌嗪基]乙氧基]-乙酸[INN：左西替利嗪]、4-(8-氯-5，6-二氢-11H-苯并[5，6]环庚三烯并[1，2-b]吡啶-11-亚基)-1-哌啶甲酸乙酯[INN：克敏能]、2-[N-[1-(4-氟苄基)-1H-苯并咪唑-2-基]-4-哌啶基]-N-甲基-氨基]嘧啶-4(3H)-酮[INN：咪唑斯汀]、1-(4-氟苄基)-2-(哌啶-4-基氨基)-1H-苯并咪唑[INN：去甲阿司咪唑]、3-(10，11-二氢-5H-二苯并[a，d]环庚烯-5-亚基)-N-甲基-1-丙胺[INN：去甲替林]、9-甲基-3-(1H-四唑-5-基)-4H-吡啶并[1，2-a]嘧啶-4-酮[INN：哌米拉特]、8-氯-11-[1-(5-甲基吡啶-3-基甲基)哌啶-4-亚基]-6，11-二氢-5H-苯并[5，6]环七[1，2-b]吡啶[INN：舒帕他定]、1-[2-[(对-氯-α-甲基-α-苯基苄基)氧]乙基]六氢-1H-氮杂[INN：赛达斯丁]、S-(7-羧基-4-己基-9-氧代呫吨-2-基)-S-甲基磺酰亚胺[INN：秀地洛克司]、1-(对叔丁基苯基)-4-[4′-(α-羟基二苯基甲基)-1′-哌啶基]-丁醇[INN：特非那定]、N-苄基-N，N′-二甲基-N-(2-吡啶基)-乙二胺[INN：曲吡那敏]和1-(4-氟苄基)-2-(哌啶-4-基氨基)-lH-苯并咪唑[INN：TECASTEMIZOLE]及其混合物、立体异构体、其药学上可接受的盐和/或溶剂化物。
16.根据权利要求1-14所述的药物组合物，其中所述抗组胺药是氮司汀、左卡巴司汀、其盐或溶剂化物。
17.环缩松与至少一种抗组胺药的组合用于制备治疗变应性鼻炎和/或变应性结膜炎的药物组合物的用途。
18.用于预防或治疗哺乳动物，如人变应性鼻炎和/或变应性结膜炎的方法，包括给予治疗有效量的药物组合物，所述药物组合物含有至少一种抗组胺药或其药学上可接受的盐、溶剂化物、或生理功能性衍生物和环缩松或其药学上可接受的盐、溶剂化物、或生理功能性衍生物，以及药学上可接受的载体和/或一种或多种赋形剂。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP02019406 | 2002-08-30 | ||
| EP02019406.4 | 2002-08-30 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1674916A true CN1674916A (zh) | 2005-09-28 |
Family
ID=31970274
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNA038198606A Pending CN1674916A (zh) | 2002-08-30 | 2003-08-29 | 环缩松与抗组胺药的组合用于治疗变应性鼻炎的用途 |
Country Status (21)
| Country | Link |
|---|---|
| US (2) | US7879832B2 (zh) |
| EP (2) | EP1545548B1 (zh) |
| JP (2) | JP4746318B2 (zh) |
| KR (1) | KR101067795B1 (zh) |
| CN (1) | CN1674916A (zh) |
| AT (1) | ATE472329T1 (zh) |
| AU (1) | AU2003273396B2 (zh) |
| BR (2) | BR0313611A (zh) |
| CA (1) | CA2495830C (zh) |
| DE (1) | DE60333205D1 (zh) |
| DK (1) | DK1545548T3 (zh) |
| ES (2) | ES2393864T3 (zh) |
| IL (1) | IL166483A (zh) |
| MX (1) | MXPA05001885A (zh) |
| NO (1) | NO335400B1 (zh) |
| NZ (1) | NZ538954A (zh) |
| PL (1) | PL373433A1 (zh) |
| PT (1) | PT1545548E (zh) |
| SI (1) | SI1545548T1 (zh) |
| WO (1) | WO2004019955A1 (zh) |
| ZA (1) | ZA200500719B (zh) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103269687A (zh) * | 2011-01-04 | 2013-08-28 | 伊斯塔制药公司 | 贝托斯汀组合物 |
| CN106692115A (zh) * | 2015-11-13 | 2017-05-24 | 天津金耀集团有限公司 | 一种环索奈德混悬鼻喷剂组合物 |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2389530B (en) | 2002-06-14 | 2007-01-10 | Cipla Ltd | Pharmaceutical compositions |
| DK1572217T3 (da) * | 2002-12-12 | 2008-12-15 | Nycomed Gmbh | Kombinationsmedikament af R,R-formoterol og ciclesonid |
| WO2004110460A1 (en) * | 2003-06-13 | 2004-12-23 | Altana Pharma Ag | Formoterol and ciclesonide combination |
| PE20050941A1 (es) | 2003-12-16 | 2005-11-08 | Nycomed Gmbh | Suspensiones acuosas de ciclesonida para nebulizacion |
| US20070020330A1 (en) | 2004-11-24 | 2007-01-25 | Medpointe Healthcare Inc. | Compositions comprising azelastine and methods of use thereof |
| US8758816B2 (en) | 2004-11-24 | 2014-06-24 | Meda Pharmaceuticals Inc. | Compositions comprising azelastine and methods of use thereof |
| NZ555501A (en) | 2004-11-24 | 2010-01-29 | Medpointe Healthcare Inc | Compositions comprising azelastine and methods of use thereof |
| WO2006097458A1 (en) * | 2005-03-15 | 2006-09-21 | Nycomed Gmbh | Novel combination |
| US20080015241A1 (en) * | 2006-07-13 | 2008-01-17 | Cornerstone Biopharma, Inc. | All day rhinitic condition treatment regimen |
| US20080311196A1 (en) * | 2006-07-13 | 2008-12-18 | White Donna F | All Day Rhinitic Condition Treatment Regimen |
| JP5661985B2 (ja) | 2006-12-27 | 2015-01-28 | 帝人ファーマ株式会社 | 無菌性水性懸濁製剤 |
| KR100878698B1 (ko) * | 2007-04-05 | 2009-01-13 | 한미약품 주식회사 | 결정형의 베포타스틴 금속염 수화물, 이의 제조방법 및이를 포함하는 약학 조성물 |
| EP2624836B1 (en) * | 2010-10-06 | 2015-09-23 | Bausch & Lomb Incorporated | Bepotastine compositions |
| CA2906008C (en) | 2013-03-13 | 2019-07-09 | Flatley Discovery Lab, Llc | Pyridazinone compounds and methods for the treatment of cystic fibrosis |
Family Cites Families (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL132137C (zh) | 1963-04-24 | |||
| US3813384A (en) | 1972-01-17 | 1974-05-28 | Asta Werke Ag Chem Fab | Basically substituted benzyl phthalazone derivatives,acid salts thereof and process for the production thereof |
| US4369184A (en) | 1980-01-24 | 1983-01-18 | Janssen Pharmaceutica N.V. | 1-(Cyclohexyl)-4-aryl-4-piperidinecarboxylic acid derivatives |
| JPS6150978A (ja) | 1984-08-16 | 1986-03-13 | Takeda Chem Ind Ltd | ピリジン誘導体およびその製造法 |
| ATE84968T1 (de) | 1987-11-13 | 1993-02-15 | Asta Medica Ag | Azelastin enthaltende arzneimittel zur anwendung in der nase und/oder am auge. |
| GR1001529B (el) | 1990-09-07 | 1994-03-31 | Elmuquimica Farm Sl | Μέ?οδος για την λήψη νέων 21-εστέρων της 16-17-ακετάλης της πρ να-1,4-διενο-3,20-διόνης. |
| EP0701565B1 (de) | 1993-04-02 | 1998-10-28 | Byk Gulden Lomberg Chemische Fabrik GmbH | Neue prednisolonderivate |
| EP0709099A3 (en) | 1994-09-28 | 1996-07-24 | Senju Pharma Co | Aqueous suspension for nasal administration containing cyclodextrin |
| DE19541689A1 (de) | 1994-11-14 | 1996-05-15 | Byk Gulden Lomberg Chem Fab | Kombinationsarzneimittel |
| AU6290396A (en) | 1995-06-29 | 1997-01-30 | Mcneil-Ppc, Inc. | The combination of topical nasal mast cell stabilizers and topical nasal steroids |
| WO1997001337A1 (en) * | 1995-06-29 | 1997-01-16 | Mcneil-Ppc, Inc. | The combination of topical nasal antihistamines and topical nasal steroids |
| EP0780127A1 (en) | 1995-12-19 | 1997-06-25 | The Procter & Gamble Company | A nasal spray containing a steroid and a antihistamine |
| JPH11511758A (ja) | 1996-06-04 | 1999-10-12 | ザ、プロクター、エンド、ギャンブル、カンパニー | 鼻腔用ステロイドと抗ヒスタミン剤を含む鼻腔内噴霧薬 |
| FR2754712B1 (fr) * | 1996-10-17 | 1999-09-03 | Merck Sharp Dohme Chibret Lab | Compositions ophtalmiques |
| US20020111495A1 (en) * | 1997-04-04 | 2002-08-15 | Pfizer Inc. | Nicotinamide acids, amides, and their mimetics active as inhibitors of PDE4 isozymes |
| IL131492A0 (en) | 1997-04-30 | 2001-01-28 | Warner Lambert Co | Topical nasal antiinflammatory compositions |
| EP0903151A1 (en) | 1997-09-22 | 1999-03-24 | ASTA Medica Aktiengesellschaft | Use of combinations comprising non-sedating antihistamines and alpha-adrenergic drugs for the topical treatment of rhinitis/conjunctivitis and cold, cold-like and/or flu symptoms |
| TWI243687B (en) | 1998-04-21 | 2005-11-21 | Teijin Ltd | Pharmaceutical composition for application to mucosa |
| US6297227B1 (en) | 1998-09-10 | 2001-10-02 | Schering Corporation | Methods and compositions for treating sinusitis, otitis media and other related disorders using antihistamines |
| US20020061281A1 (en) | 1999-07-06 | 2002-05-23 | Osbakken Robert S. | Aerosolized anti-infectives, anti-inflammatories, and decongestants for the treatment of sinusitis |
| DE19947234A1 (de) * | 1999-09-30 | 2001-04-05 | Asta Medica Ag | Neue Kombination von Loteprednol und Antihistaminika |
| AR026073A1 (es) | 1999-10-20 | 2002-12-26 | Nycomed Gmbh | Composicion farmaceutica acuosa que contiene ciclesonida |
| CA2356177A1 (en) | 1999-10-20 | 2001-04-26 | Kazuya Takanashi | Aqueous pharmaceutical compositions |
| AR026072A1 (es) | 1999-10-20 | 2002-12-26 | Nycomed Gmbh | Composicion farmaceutica que contiene ciclesonida para aplicacion a la mucosa |
| AU772406B2 (en) | 1999-11-18 | 2004-04-29 | Alcon Inc. | Use of H1 antagonist and a safe steroid to treat eye conditions |
| US20040097486A1 (en) | 1999-11-18 | 2004-05-20 | Yanni John M. | Use of an H1 antagonist and a safe steroid to treat eye conditions |
| US6653313B2 (en) * | 2000-08-10 | 2003-11-25 | Warner-Lambert Company Llc | 1,4-dihydropyridine compounds as bradykinin antagonists |
| US6706726B2 (en) * | 2000-10-14 | 2004-03-16 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Anticholinergics which may be used as medicaments as well as processes for preparing them |
| CN1599625A (zh) | 2001-12-05 | 2005-03-23 | 爱尔康公司 | H1拮抗剂和安全类固醇治疗鼻炎的用途 |
| GB2389530B (en) * | 2002-06-14 | 2007-01-10 | Cipla Ltd | Pharmaceutical compositions |
| CA2504200A1 (en) | 2002-11-12 | 2004-05-27 | Alcon, Inc. | The use of an anti-allergy agent and a steroid to treat allergic rhinitis |
-
2003
- 2003-08-29 KR KR1020057002903A patent/KR101067795B1/ko active IP Right Grant
- 2003-08-29 JP JP2004532150A patent/JP4746318B2/ja not_active Expired - Lifetime
- 2003-08-29 BR BR0313611-6A patent/BR0313611A/pt not_active IP Right Cessation
- 2003-08-29 ES ES10167527T patent/ES2393864T3/es not_active Expired - Lifetime
- 2003-08-29 DE DE60333205T patent/DE60333205D1/de not_active Expired - Lifetime
- 2003-08-29 WO PCT/EP2003/009622 patent/WO2004019955A1/en active Application Filing
- 2003-08-29 DK DK03755551.3T patent/DK1545548T3/da active
- 2003-08-29 CA CA2495830A patent/CA2495830C/en not_active Expired - Fee Related
- 2003-08-29 AT AT03755551T patent/ATE472329T1/de active
- 2003-08-29 BR BRPI0313611-6A patent/BRPI0313611B1/pt unknown
- 2003-08-29 MX MXPA05001885A patent/MXPA05001885A/es active IP Right Grant
- 2003-08-29 AU AU2003273396A patent/AU2003273396B2/en not_active Expired
- 2003-08-29 PT PT03755551T patent/PT1545548E/pt unknown
- 2003-08-29 CN CNA038198606A patent/CN1674916A/zh active Pending
- 2003-08-29 US US10/524,821 patent/US7879832B2/en active Active
- 2003-08-29 NZ NZ538954A patent/NZ538954A/en not_active IP Right Cessation
- 2003-08-29 PL PL03373433A patent/PL373433A1/xx not_active Application Discontinuation
- 2003-08-29 EP EP03755551A patent/EP1545548B1/en not_active Expired - Lifetime
- 2003-08-29 EP EP10167527A patent/EP2295062B1/en not_active Expired - Lifetime
- 2003-08-29 ES ES03755551T patent/ES2348034T3/es not_active Expired - Lifetime
- 2003-08-29 SI SI200331870T patent/SI1545548T1/sl unknown
-
2005
- 2005-01-25 ZA ZA200500719A patent/ZA200500719B/xx unknown
- 2005-01-25 IL IL166483A patent/IL166483A/en active IP Right Grant
- 2005-03-22 NO NO20051521A patent/NO335400B1/no not_active IP Right Cessation
-
2010
- 2010-11-05 JP JP2010248760A patent/JP2011021043A/ja active Pending
- 2010-12-20 US US12/973,414 patent/US8486923B2/en not_active Expired - Lifetime
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103269687A (zh) * | 2011-01-04 | 2013-08-28 | 伊斯塔制药公司 | 贝托斯汀组合物 |
| CN103269687B (zh) * | 2011-01-04 | 2016-09-14 | 伊斯塔制药公司 | 贝托斯汀组合物 |
| CN106692115A (zh) * | 2015-11-13 | 2017-05-24 | 天津金耀集团有限公司 | 一种环索奈德混悬鼻喷剂组合物 |
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8486923B2 (en) | Use of the combination of ciclesonide and antihistamines for the treatment of allergic rhinitis | |
| US10617695B2 (en) | Ophthalmic compositions containing alcaftadine | |
| KR101546596B1 (ko) | 베포타스틴 조성물 | |
| US6436924B2 (en) | Antihistamine leukotriene combinations | |
| AU2005210086A1 (en) | Treatment of rhinitis with anticholinergics alone in combination with antihistamines phosphodiesterase 4 inhibitors, or corticosteroids | |
| US20080234285A1 (en) | Combination of Organic Compounds | |
| CA2337571C (en) | Antihistamine leukotriene combinations | |
| KR20100112293A (ko) | 데스로라타딘을 포함하는 안과용 조성물 | |
| MXPA06008295A (en) | Combination of organic compounds | |
| MXPA06008935A (en) | Treatment of rhinitis with anticholinergics alone in combination with antihistamines phosphodiesterase 4 inhibitors, or corticosteroids |
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: 1080744 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: 20050928 |
|
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: WD Ref document number: 1080744 Country of ref document: HK |