NO311637B1 - Topiske oftalmiske formuleringer inneholdende doxepinderivater for behandling av öyenallergisykdommer - Google Patents
Topiske oftalmiske formuleringer inneholdende doxepinderivater for behandling av öyenallergisykdommer Download PDFInfo
- Publication number
- NO311637B1 NO311637B1 NO19970517A NO970517A NO311637B1 NO 311637 B1 NO311637 B1 NO 311637B1 NO 19970517 A NO19970517 A NO 19970517A NO 970517 A NO970517 A NO 970517A NO 311637 B1 NO311637 B1 NO 311637B1
- Authority
- NO
- Norway
- Prior art keywords
- dimethylaminopropylidene
- dihydrodibenz
- oxepin
- acetic acid
- treatment
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 17
- 238000011282 treatment Methods 0.000 title claims description 11
- 230000000699 topical effect Effects 0.000 title abstract description 13
- 238000009472 formulation Methods 0.000 title abstract description 12
- 208000026935 allergic disease Diseases 0.000 title description 4
- 206010020751 Hypersensitivity Diseases 0.000 title description 3
- 230000007815 allergy Effects 0.000 title description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title description 2
- ODQWQRRAPPTVAG-GZTJUZNOSA-N doxepin Chemical class C1OC2=CC=CC=C2C(=C/CCN(C)C)/C2=CC=CC=C21 ODQWQRRAPPTVAG-GZTJUZNOSA-N 0.000 title 1
- JBIMVDZLSHOPLA-UHFFFAOYSA-N 2-[11-[3-(dimethylamino)propylidene]-6H-benzo[c][1]benzoxepin-2-yl]acetic acid Chemical compound C1OC2=CC=C(CC(O)=O)C=C2C(=CCCN(C)C)C2=CC=CC=C21 JBIMVDZLSHOPLA-UHFFFAOYSA-N 0.000 claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 230000000172 allergic effect Effects 0.000 claims abstract description 8
- 208000010668 atopic eczema Diseases 0.000 claims abstract description 8
- 208000030533 eye disease Diseases 0.000 claims abstract description 8
- JBIMVDZLSHOPLA-LSCVHKIXSA-N olopatadine Chemical compound C1OC2=CC=C(CC(O)=O)C=C2C(=C/CCN(C)C)\C2=CC=CC=C21 JBIMVDZLSHOPLA-LSCVHKIXSA-N 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 6
- JBIMVDZLSHOPLA-QGMBQPNBSA-N Olopatadine Chemical compound C1OC2=CC=C(CC(O)=O)C=C2C(=C/CCN(C)C)/C2=CC=CC=C21 JBIMVDZLSHOPLA-QGMBQPNBSA-N 0.000 claims description 4
- OKNAWFBIOJJTDV-UHFFFAOYSA-N 2-(oxepin-2-yl)acetic acid Chemical compound OC(=O)CC1=CC=CC=CO1 OKNAWFBIOJJTDV-UHFFFAOYSA-N 0.000 claims 1
- 208000002205 allergic conjunctivitis Diseases 0.000 abstract description 9
- 206010010744 Conjunctivitis allergic Diseases 0.000 abstract description 6
- 208000024998 atopic conjunctivitis Diseases 0.000 abstract description 4
- 201000005539 vernal conjunctivitis Diseases 0.000 abstract description 2
- 208000018464 vernal keratoconjunctivitis Diseases 0.000 abstract description 2
- 206010018258 Giant papillary conjunctivitis Diseases 0.000 abstract 1
- 239000004480 active ingredient Substances 0.000 abstract 1
- 210000003630 histaminocyte Anatomy 0.000 description 42
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 30
- 229940126062 Compound A Drugs 0.000 description 19
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 19
- 239000003814 drug Substances 0.000 description 17
- 229960001340 histamine Drugs 0.000 description 15
- 229940079593 drug Drugs 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 150000001875 compounds Chemical class 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 229960005426 doxepin Drugs 0.000 description 6
- 238000002474 experimental method Methods 0.000 description 6
- 230000000087 stabilizing effect Effects 0.000 description 6
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 5
- 230000003266 anti-allergic effect Effects 0.000 description 5
- 230000001387 anti-histamine Effects 0.000 description 5
- 239000000043 antiallergic agent Substances 0.000 description 5
- 210000004027 cell Anatomy 0.000 description 5
- 229960000265 cromoglicic acid Drugs 0.000 description 5
- VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 description 5
- -1 inorganic acid salts Chemical class 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 241000700159 Rattus Species 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- 210000000795 conjunctiva Anatomy 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 108010058846 Ovalbumin Proteins 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000006196 drop Substances 0.000 description 3
- 239000003889 eye drop Substances 0.000 description 3
- 229940012356 eye drops Drugs 0.000 description 3
- 229940092253 ovalbumin Drugs 0.000 description 3
- 238000003127 radioimmunoassay Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 210000003491 skin Anatomy 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 239000012980 RPMI-1640 medium Substances 0.000 description 2
- 241000700157 Rattus norvegicus Species 0.000 description 2
- 241000283984 Rodentia Species 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- 150000001242 acetic acid derivatives Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000003110 anti-inflammatory 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
- 239000000739 antihistaminic agent Substances 0.000 description 2
- 239000006285 cell suspension Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 230000005455 negative regulation of mast cell degranulation Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000002335 preservative effect Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 239000008213 purified water Substances 0.000 description 2
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 2
- 241000894007 species Species 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000012353 t test Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- PIGCSKVALLVWKU-UHFFFAOYSA-N 2-Aminoacridone Chemical compound C1=CC=C2C(=O)C3=CC(N)=CC=C3NC2=C1 PIGCSKVALLVWKU-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- VKJGBAJNNALVAV-UHFFFAOYSA-M Berberine chloride (TN) Chemical compound [Cl-].C1=C2CC[N+]3=CC4=C(OC)C(OC)=CC=C4C=C3C2=CC2=C1OCO2 VKJGBAJNNALVAV-UHFFFAOYSA-M 0.000 description 1
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 1
- COXVTLYNGOIATD-HVMBLDELSA-N CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O Chemical compound CC1=C(C=CC(=C1)C1=CC(C)=C(C=C1)\N=N\C1=C(O)C2=C(N)C(=CC(=C2C=C1)S(O)(=O)=O)S(O)(=O)=O)\N=N\C1=CC=C2C(=CC(=C(N)C2=C1O)S(O)(=O)=O)S(O)(=O)=O COXVTLYNGOIATD-HVMBLDELSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000283707 Capra Species 0.000 description 1
- 241000700198 Cavia Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 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
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- 241000557626 Corvus corax Species 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 238000001061 Dunnett's test Methods 0.000 description 1
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 101000637792 Homo sapiens Solute carrier family 35 member G5 Proteins 0.000 description 1
- 108010003272 Hyaluronate lyase Proteins 0.000 description 1
- 102000009066 Hyaluronoglucosaminidase Human genes 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 102000016943 Muramidase Human genes 0.000 description 1
- 108010014251 Muramidase Proteins 0.000 description 1
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 1
- DJDFFEBSKJCGHC-UHFFFAOYSA-N Naphazoline Chemical compound Cl.C=1C=CC2=CC=CC=C2C=1CC1=NCCN1 DJDFFEBSKJCGHC-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 206010070834 Sensitisation Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 102100032019 Solute carrier family 35 member G5 Human genes 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 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 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
- 229960003942 amphotericin b Drugs 0.000 description 1
- 230000002052 anaphylactic effect Effects 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 230000001088 anti-asthma Effects 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 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
- 239000001045 blue dye Substances 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 235000010338 boric acid Nutrition 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 229910002091 carbon monoxide Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 229910000397 disodium phosphate Inorganic materials 0.000 description 1
- 235000019800 disodium phosphate Nutrition 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000006862 enzymatic digestion Effects 0.000 description 1
- 238000001976 enzyme digestion Methods 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 229960003699 evans blue Drugs 0.000 description 1
- 230000000763 evoking effect Effects 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000004744 fabric Substances 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229940070818 glycyrrhizate Drugs 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 229960002773 hyaluronidase Drugs 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- YWXYYJSYQOXTPL-SLPGGIOYSA-N isosorbide mononitrate Chemical compound [O-][N+](=O)O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-SLPGGIOYSA-N 0.000 description 1
- 239000004325 lysozyme Substances 0.000 description 1
- 229960000274 lysozyme Drugs 0.000 description 1
- 235000010335 lysozyme Nutrition 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 229960004760 naphazoline hydrochloride Drugs 0.000 description 1
- RQTOOFIXOKYGAN-UHFFFAOYSA-N nedocromil Chemical compound CCN1C(C(O)=O)=CC(=O)C2=C1C(CCC)=C1OC(C(O)=O)=CC(=O)C1=C2 RQTOOFIXOKYGAN-UHFFFAOYSA-N 0.000 description 1
- 229960004398 nedocromil Drugs 0.000 description 1
- 230000005868 ontogenesis Effects 0.000 description 1
- 229940100655 ophthalmic gel Drugs 0.000 description 1
- 229940023490 ophthalmic product Drugs 0.000 description 1
- 239000002997 ophthalmic solution Substances 0.000 description 1
- 229940054534 ophthalmic solution Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 239000004584 polyacrylic acid Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000580 secretagogue effect Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000008313 sensitization Effects 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 229940037001 sodium edetate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- GEYJUFBPCGDENK-UHFFFAOYSA-M sodium;3,8-dimethyl-5-propan-2-ylazulene-1-sulfonate Chemical compound [Na+].CC(C)C1=CC=C(C)C2=C(S([O-])(=O)=O)C=C(C)C2=C1 GEYJUFBPCGDENK-UHFFFAOYSA-M 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000000528 statistical test Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 229950003937 tolonium Drugs 0.000 description 1
- HNONEKILPDHFOL-UHFFFAOYSA-M tolonium chloride Chemical compound [Cl-].C1=C(C)C(N)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 HNONEKILPDHFOL-UHFFFAOYSA-M 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
-
- 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
-
- 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
- A61P37/08—Antiallergic agents
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- Pulmonology (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
- Pyrane Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/469,729 US5641805A (en) | 1995-06-06 | 1995-06-06 | Topical ophthalmic formulations for treating allergic eye diseases |
| PCT/US1996/006289 WO1996039147A2 (en) | 1995-06-06 | 1996-05-03 | Topical ophthalmic formulations containing doxepin derivatives for treating allergic eye diseases |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO970517D0 NO970517D0 (no) | 1997-02-05 |
| NO970517L NO970517L (no) | 1997-04-03 |
| NO311637B1 true NO311637B1 (no) | 2001-12-27 |
Family
ID=23864859
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19970517A NO311637B1 (no) | 1995-06-06 | 1997-02-05 | Topiske oftalmiske formuleringer inneholdende doxepinderivater for behandling av öyenallergisykdommer |
Country Status (20)
| Country | Link |
|---|---|
| US (1) | US5641805A (zh) |
| EP (1) | EP0799044B1 (zh) |
| JP (1) | JP3068858B2 (zh) |
| KR (1) | KR100202155B1 (zh) |
| CN (1) | CN1082367C (zh) |
| AT (1) | ATE220906T1 (zh) |
| AU (1) | AU698854B2 (zh) |
| CA (1) | CA2195094C (zh) |
| DE (2) | DE10299034I2 (zh) |
| DK (1) | DK0799044T3 (zh) |
| ES (1) | ES2179198T3 (zh) |
| FI (1) | FI970489A0 (zh) |
| LU (1) | LU90969I2 (zh) |
| MX (1) | MX9701013A (zh) |
| MY (1) | MY116651A (zh) |
| NL (1) | NL300101I2 (zh) |
| NO (1) | NO311637B1 (zh) |
| PT (1) | PT799044E (zh) |
| TW (1) | TW438588B (zh) |
| WO (1) | WO1996039147A2 (zh) |
Families Citing this family (31)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5859000A (en) * | 1995-06-07 | 1999-01-12 | University Of Utah Research Foundation | Method for reducing mast cell mediated allergic reactions |
| BR9906772A (pt) * | 1998-07-14 | 2000-09-26 | Alcon Lab Inc | Uso de ácido 11-(3-dimetilamino-propilideno)-6,11diidrodibenz[b,e]o xepin-2-acético para a fabricação de um medicamento para tratamento de desordens inflamatórias oftálmicas não-alérgicas e para prevenção de neovascularização ocular |
| US6174914B1 (en) | 1999-06-15 | 2001-01-16 | Alcon Laboratories, Inc. | Method of inhibiting cytokine release from human ocular cells |
| DE60008730T2 (de) | 1999-06-18 | 2004-08-05 | Alcon Manufacturing Ltd., Fort Worth | Methode zur konzentrationsbestimmung einer amphipathischen antihistaminischen verbindung durch bestimmung ihrer oberflächen aktivitäts einstufung |
| DE60109742T2 (de) | 2000-01-25 | 2005-08-18 | Alcon Inc. | Antiallergische ophthalmische zubereitungen, geeignet zur anwendung mit kontaktlinsen |
| BR0110943A (pt) | 2000-05-19 | 2004-01-06 | Alcon Inc | Derivados de dissulfeto úteis para o tratamento de doenças alérgicas |
| KR20020093981A (ko) | 2000-05-19 | 2002-12-16 | 알콘, 인코퍼레이티드 | 알레르기성 질환 치료를 위한 벤즈아미드 디설파이드유도체를 포함하는 조성물 |
| US6372802B2 (en) | 2000-05-19 | 2002-04-16 | Alcon Universal Ltd. | Aniline disulfide derivatives for treating allergic diseases |
| EP1387696A2 (en) * | 2001-05-03 | 2004-02-11 | Novartis AG | Anti-ige antibody to treat ocular allergies |
| TWI231759B (en) * | 2001-06-27 | 2005-05-01 | Alcon Inc | Olopatadine formulations for topical administration |
| US7977376B2 (en) | 2001-06-27 | 2011-07-12 | Novartis Ag | Olopatadine formulations for topical nasal administration |
| CA2468749A1 (en) * | 2001-12-05 | 2003-06-19 | Alcon, Inc. | Use of an h1 antagonist and a safe steroid to treat rhinitis |
| US20050209312A1 (en) * | 2004-03-19 | 2005-09-22 | Bausch & Lomb Incorporated | Carboxylic acid derivatives of doxepin formulations preserved with low-irritation preservative |
| EP1761259A2 (en) * | 2004-06-28 | 2007-03-14 | Alcon Inc. | Topical formulations for treating allergic diseases |
| KR101158603B1 (ko) * | 2004-11-24 | 2012-07-09 | 알콘, 인코퍼레이티드 | 비강용 스프레이를 전달하는 방법 |
| WO2007007863A1 (en) | 2005-07-08 | 2007-01-18 | Senju Pharmaceutical Co., Ltd. | Percutaneously absorptive ophthalmic preparation comprising olopatadine |
| EP3150209B1 (en) | 2006-03-31 | 2019-07-24 | Vistakon Pharmaceuticals, LLC | Ocular allergy treatments |
| US20080139531A1 (en) * | 2006-12-04 | 2008-06-12 | Alcon Manufacturing Ltd. | Use of connective tissue mast cell stabilizers to facilitate ocular surface re-epithelization and wound repair |
| EP2114367B1 (en) | 2007-02-07 | 2015-11-04 | Novartis AG | Olopatadine formulations for topical nasal administration |
| US20080254029A1 (en) * | 2007-04-11 | 2008-10-16 | Alcon Research, Ltd. | Use of an Inhibitor of TNFa Plus an Antihistamine to Treat Allergic Rhinitis and Allergic Conjunctivitis |
| US20090182035A1 (en) * | 2007-04-11 | 2009-07-16 | Alcon Research, Ltd. | Use of a combination of olopatadine and cilomilast to treat non-infectious rhinitis and allergic conjunctivitis |
| EP2189157A4 (en) * | 2007-09-06 | 2012-10-31 | Kyowa Hakko Kirin Co Ltd | EYE DROPPING WITH DIBENZO [b, e] OXEPINE DERIVATIVE |
| US10517839B2 (en) * | 2008-06-09 | 2019-12-31 | Cornell University | Mast cell inhibition in diseases of the retina and vitreous |
| IT1397503B1 (it) | 2009-04-21 | 2013-01-16 | F S I Fabbrica Italiana Sint | Processo per la preparazione di olopatadina |
| EP2453872B1 (en) | 2009-07-17 | 2013-08-21 | Alcon Research, Ltd. | Olopatadine nasal spray regimen for children |
| WO2011027322A1 (en) | 2009-09-03 | 2011-03-10 | Ranbaxy Laboratories Limited | Extended release dosage form containing olopatadine for oral administration |
| WO2011041640A1 (en) * | 2009-10-01 | 2011-04-07 | Alcon Research, Ltd. | Olopatadine compositions and uses thereof |
| TW201206936A (en) | 2010-07-19 | 2012-02-16 | Alcon Res Ltd | Methods and compositions for the treatment of allergy |
| TWI544922B (zh) * | 2011-05-19 | 2016-08-11 | 愛爾康研究有限公司 | 高濃度歐羅派特錠（ｏｌｏｐａｔａｄｉｎｅ）眼用組成物 |
| CN103202833A (zh) * | 2012-12-25 | 2013-07-17 | 常州市亚邦医药研究所有限公司 | 一种奥洛他定或其盐的药用组合物及其制备方法 |
| CA2929074A1 (en) * | 2013-10-31 | 2015-05-07 | Nephron Pharmaceuticals Corporation | Formulation of olopatadine |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4370324A (en) * | 1980-09-17 | 1983-01-25 | Bernstein Joel E | Method and composition for treating and preventing irritation of the eyes |
| GB8520662D0 (en) * | 1985-08-17 | 1985-09-25 | Wellcome Found | Tricyclic aromatic compounds |
| US4923892A (en) * | 1985-08-17 | 1990-05-08 | Burroughs Wellcome Co. | Tricyclic aromatic compounds |
| JPS6310784A (ja) * | 1986-03-03 | 1988-01-18 | Kyowa Hakko Kogyo Co Ltd | 抗アレルギー剤 |
-
1995
- 1995-06-06 US US08/469,729 patent/US5641805A/en not_active Expired - Lifetime
-
1996
- 1996-05-03 CN CN96190605A patent/CN1082367C/zh not_active Ceased
- 1996-05-03 CA CA002195094A patent/CA2195094C/en not_active Expired - Lifetime
- 1996-05-03 AU AU57261/96A patent/AU698854B2/en not_active Expired
- 1996-05-03 KR KR1019970700721A patent/KR100202155B1/ko active IP Right Review Request
- 1996-05-03 DE DE2002199034 patent/DE10299034I2/de active Active
- 1996-05-03 PT PT96915500T patent/PT799044E/pt unknown
- 1996-05-03 AT AT96915500T patent/ATE220906T1/de active
- 1996-05-03 DK DK96915500T patent/DK0799044T3/da active
- 1996-05-03 MX MX9701013A patent/MX9701013A/es unknown
- 1996-05-03 ES ES96915500T patent/ES2179198T3/es not_active Expired - Lifetime
- 1996-05-03 JP JP9500510A patent/JP3068858B2/ja not_active Expired - Lifetime
- 1996-05-03 WO PCT/US1996/006289 patent/WO1996039147A2/en active IP Right Grant
- 1996-05-03 DE DE69622527T patent/DE69622527T2/de not_active Expired - Lifetime
- 1996-05-03 EP EP96915500A patent/EP0799044B1/en not_active Expired - Lifetime
- 1996-05-14 MY MYPI96001818A patent/MY116651A/en unknown
- 1996-06-04 TW TW085106668A patent/TW438588B/zh not_active IP Right Cessation
-
1997
- 1997-02-05 NO NO19970517A patent/NO311637B1/no not_active IP Right Cessation
- 1997-02-05 FI FI970489A patent/FI970489A0/fi unknown
-
2002
- 2002-09-19 NL NL300101C patent/NL300101I2/nl unknown
- 2002-10-02 LU LU90969C patent/LU90969I2/fr unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ES2179198T3 (es) | 2003-01-16 |
| LU90969I2 (fr) | 2002-12-02 |
| WO1996039147A2 (en) | 1996-12-12 |
| ATE220906T1 (de) | 2002-08-15 |
| PT799044E (pt) | 2002-11-29 |
| CN1161000A (zh) | 1997-10-01 |
| JPH09510235A (ja) | 1997-10-14 |
| KR970704452A (ko) | 1997-09-06 |
| WO1996039147A3 (en) | 1997-02-20 |
| NL300101I1 (nl) | 2002-12-02 |
| DE69622527T2 (de) | 2002-12-05 |
| FI970489A (fi) | 1997-02-05 |
| DE10299034I1 (de) | 2003-01-23 |
| NO970517D0 (no) | 1997-02-05 |
| MY116651A (en) | 2004-03-31 |
| AU698854B2 (en) | 1998-11-12 |
| FI970489A0 (fi) | 1997-02-05 |
| DE10299034I2 (de) | 2005-07-07 |
| CA2195094A1 (en) | 1996-12-12 |
| CA2195094C (en) | 2002-02-26 |
| DE69622527D1 (de) | 2002-08-29 |
| NL300101I2 (nl) | 2003-01-06 |
| EP0799044B1 (en) | 2002-07-24 |
| EP0799044A2 (en) | 1997-10-08 |
| MX9701013A (es) | 1997-05-31 |
| JP3068858B2 (ja) | 2000-07-24 |
| KR100202155B1 (ko) | 1999-06-15 |
| US5641805A (en) | 1997-06-24 |
| TW438588B (en) | 2001-06-07 |
| DK0799044T3 (da) | 2002-10-14 |
| AU5726196A (en) | 1996-12-24 |
| NO970517L (no) | 1997-04-03 |
| CN1082367C (zh) | 2002-04-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO311637B1 (no) | Topiske oftalmiske formuleringer inneholdende doxepinderivater for behandling av öyenallergisykdommer | |
| US4599353A (en) | Use of eicosanoids and their derivatives for treatment of ocular hypertension and glaucoma | |
| CN1943577B (zh) | (2-咪唑啉-2-基氨基)喹喔啉在制备用于治疗视神经损伤的药物中的应用 | |
| TWI578990B (zh) | 眼睛過敏之治療 | |
| AU742237B2 (en) | Use of 11-(3-dimenthylaminopropylidene)-6,11-dihydrodibenz (B,E)oxepin-2-acetic acid for the manufacture of medicament for treating non-allergic opthalmic inflammatory disorders and for the prevention of ocular neovascularization | |
| WOODWARD et al. | The pruritogenic and inflammatory effects of prostanoids in the conjunctiva | |
| AU667613B2 (en) | Ophthalmic compositions comprising emedastine and their use for treating allergic conjunctivitis | |
| US5196449A (en) | Methods and pharmaceutical compositions for the treatment of ophthalmic diseases | |
| McLaren et al. | Effect of ibopamine on aqueous humor production in normotensive humans | |
| Friedlaender | The current and future therapy of allergic conjunctivitis | |
| TW200927169A (en) | Complement Clq inhibitors for the prevention and treatment of glaucoma | |
| AU2008289347B2 (en) | Compositions and methods for modulating endophthalmitis using fluoroquinolones | |
| EA029157B1 (ru) | Терапия макулярной дегенерации на основе баклофена и акампросата | |
| US6174914B1 (en) | Method of inhibiting cytokine release from human ocular cells | |
| JPH10203982A (ja) | 視機能障害の予防・治療剤 | |
| JP2010047567A (ja) | 加齢黄斑変性の予防又は治療剤 | |
| US20110166126A1 (en) | Compositions and Methods for Modulating Endophthalmitis Using Fluoroquinolones | |
| WO2024163858A1 (en) | Haloperidol derivatives, pharmaceutical composition comprising said derivatives, and therapeutic uses thereof | |
| de ROETTH | Ophthalmic Pharmacology and Toxicology | |
| B’ANN TRUE et al. | Cholinergic Drugs | |
| MXPA00004061A (en) | Use of 11-(3-dimethylaminopropylidene)- 6,1 -dihydrodibenz[b,e]oxepin-2-acetic acid for the manufacture of a medicament for treating non-allergic ophthalmic inflammatory disorders and for the prevention of ocular neovascularization |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1K | Patent expired |