CA2729834A1 - Formulations for treating eye disorders - Google Patents
Formulations for treating eye disorders Download PDFInfo
- Publication number
- CA2729834A1 CA2729834A1 CA2729834A CA2729834A CA2729834A1 CA 2729834 A1 CA2729834 A1 CA 2729834A1 CA 2729834 A CA2729834 A CA 2729834A CA 2729834 A CA2729834 A CA 2729834A CA 2729834 A1 CA2729834 A1 CA 2729834A1
- Authority
- CA
- Canada
- Prior art keywords
- ocular
- solution
- nampa
- eye
- day
- 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.)
- Abandoned
Links
- 239000000203 mixture Substances 0.000 title description 101
- 238000009472 formulation Methods 0.000 title description 82
- 208000030533 eye disease Diseases 0.000 title description 13
- HPNSFSBZBAHARI-UHFFFAOYSA-N micophenolic acid Natural products OC1=C(CC=C(C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-UHFFFAOYSA-N 0.000 claims abstract description 115
- HPNSFSBZBAHARI-RUDMXATFSA-N mycophenolic acid Chemical compound OC1=C(C\C=C(/C)CCC(O)=O)C(OC)=C(C)C2=C1C(=O)OC2 HPNSFSBZBAHARI-RUDMXATFSA-N 0.000 claims abstract description 114
- 229960000951 mycophenolic acid Drugs 0.000 claims abstract description 113
- 206010013774 Dry eye Diseases 0.000 claims abstract description 54
- 208000003556 Dry Eye Syndromes Diseases 0.000 claims abstract description 53
- 206010046851 Uveitis Diseases 0.000 claims abstract description 45
- 208000009319 Keratoconjunctivitis Sicca Diseases 0.000 claims abstract description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 47
- 238000000034 method Methods 0.000 claims description 36
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 28
- 239000011734 sodium Substances 0.000 claims description 26
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 25
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 24
- 229910052708 sodium Inorganic materials 0.000 claims description 24
- 235000011187 glycerol Nutrition 0.000 claims description 23
- 206010010726 Conjunctival oedema Diseases 0.000 claims description 22
- 208000022873 Ocular disease Diseases 0.000 claims description 22
- 206010039705 Scleritis Diseases 0.000 claims description 22
- 239000003795 chemical substances by application Substances 0.000 claims description 22
- 229960001484 edetic acid Drugs 0.000 claims description 22
- 235000002639 sodium chloride Nutrition 0.000 claims description 22
- 239000003755 preservative agent Substances 0.000 claims description 21
- 206010022941 Iridocyclitis Diseases 0.000 claims description 20
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 20
- 201000004612 anterior uveitis Diseases 0.000 claims description 20
- 206010010744 Conjunctivitis allergic Diseases 0.000 claims description 19
- 208000002205 allergic conjunctivitis Diseases 0.000 claims description 19
- 208000024998 atopic conjunctivitis Diseases 0.000 claims description 19
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 18
- 201000010099 disease Diseases 0.000 claims description 18
- 230000002335 preservative effect Effects 0.000 claims description 17
- 239000000654 additive Substances 0.000 claims description 16
- 239000000314 lubricant Substances 0.000 claims description 15
- 206010020565 Hyperaemia Diseases 0.000 claims description 14
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 14
- -1 carboxymethylpropyl Chemical group 0.000 claims description 13
- KKFDCBRMNNSAAW-UHFFFAOYSA-N 2-(morpholin-4-yl)ethanol Chemical compound OCCN1CCOCC1 KKFDCBRMNNSAAW-UHFFFAOYSA-N 0.000 claims description 12
- 230000000996 additive effect Effects 0.000 claims description 12
- 239000006172 buffering agent Substances 0.000 claims description 12
- 206010011033 Corneal oedema Diseases 0.000 claims description 11
- 206010015084 Episcleritis Diseases 0.000 claims description 11
- 201000004778 corneal edema Diseases 0.000 claims description 11
- 201000004614 iritis Diseases 0.000 claims description 11
- 229960000281 trometamol Drugs 0.000 claims description 11
- 239000000080 wetting agent Substances 0.000 claims description 11
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims description 10
- 239000011780 sodium chloride Substances 0.000 claims description 10
- 230000002708 enhancing effect Effects 0.000 claims description 9
- 208000002691 Choroiditis Diseases 0.000 claims description 8
- 208000003971 Posterior uveitis Diseases 0.000 claims description 8
- 150000003904 phospholipids Chemical class 0.000 claims description 8
- 208000001344 Macular Edema Diseases 0.000 claims description 7
- 208000003435 Optic Neuritis Diseases 0.000 claims description 7
- 230000001363 autoimmune Effects 0.000 claims description 7
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 7
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 7
- 206010023332 keratitis Diseases 0.000 claims description 7
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 7
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 7
- 208000032253 retinal ischemia Diseases 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 6
- 206010010741 Conjunctivitis Diseases 0.000 claims description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 6
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 6
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 claims description 6
- 208000001445 Uveomeningoencephalitic Syndrome Diseases 0.000 claims description 6
- 239000003963 antioxidant agent Substances 0.000 claims description 6
- 208000010217 blepharitis Diseases 0.000 claims description 6
- 230000002757 inflammatory effect Effects 0.000 claims description 6
- 210000001328 optic nerve Anatomy 0.000 claims description 6
- 201000007407 panuveitis Diseases 0.000 claims description 6
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 6
- 229940068984 polyvinyl alcohol Drugs 0.000 claims description 6
- 229960004063 propylene glycol Drugs 0.000 claims description 6
- 201000000306 sarcoidosis Diseases 0.000 claims description 6
- 239000012929 tonicity agent Substances 0.000 claims description 6
- FZWBNHMXJMCXLU-UHFFFAOYSA-N 2,3,4,5-tetrahydroxy-6-[3,4,5-trihydroxy-6-[[3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxymethyl]oxan-2-yl]oxyhexanal Chemical compound OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(OCC(O)C(O)C(O)C(O)C=O)O1 FZWBNHMXJMCXLU-UHFFFAOYSA-N 0.000 claims description 5
- 208000005590 Choroidal Neovascularization Diseases 0.000 claims description 5
- 206010060823 Choroidal neovascularisation Diseases 0.000 claims description 5
- 206010011844 Dacryocystitis Diseases 0.000 claims description 5
- 206010012688 Diabetic retinal oedema Diseases 0.000 claims description 5
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 5
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 5
- 206010029113 Neovascularisation Diseases 0.000 claims description 5
- 208000004788 Pars Planitis Diseases 0.000 claims description 5
- 206010034277 Pemphigoid Diseases 0.000 claims description 5
- 206010057182 Periorbital cellulitis Diseases 0.000 claims description 5
- 229920002125 Sokalan® Polymers 0.000 claims description 5
- 206010047115 Vasculitis Diseases 0.000 claims description 5
- 208000034705 Vogt-Koyanagi-Harada syndrome Diseases 0.000 claims description 5
- 241000282485 Vulpes vulpes Species 0.000 claims description 5
- 201000009926 acute dacryocystitis Diseases 0.000 claims description 5
- 206010072959 birdshot chorioretinopathy Diseases 0.000 claims description 5
- 230000001684 chronic effect Effects 0.000 claims description 5
- 229940119743 dextran 70 Drugs 0.000 claims description 5
- 201000010476 glaucomatocyclitic crisis Diseases 0.000 claims description 5
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 5
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 5
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 claims description 5
- 208000002780 macular degeneration Diseases 0.000 claims description 5
- 229940069328 povidone Drugs 0.000 claims description 5
- 208000021165 scleral disease Diseases 0.000 claims description 5
- 230000009724 venous congestion Effects 0.000 claims description 5
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 claims description 4
- 206010025415 Macular oedema Diseases 0.000 claims description 4
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 claims description 4
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- 201000001949 Retinal Vasculitis Diseases 0.000 claims description 4
- 206010038848 Retinal detachment Diseases 0.000 claims description 4
- 208000007536 Thrombosis Diseases 0.000 claims description 4
- 206010054880 Vascular insufficiency Diseases 0.000 claims description 4
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 claims description 4
- 229940119744 dextran 40 Drugs 0.000 claims description 4
- 229920000159 gelatin Polymers 0.000 claims description 4
- 235000019322 gelatine Nutrition 0.000 claims description 4
- 201000010230 macular retinal edema Diseases 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 4
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 4
- 229940068968 polysorbate 80 Drugs 0.000 claims description 4
- 229920000053 polysorbate 80 Polymers 0.000 claims description 4
- 230000004264 retinal detachment Effects 0.000 claims description 4
- 208000023577 vascular insufficiency disease Diseases 0.000 claims description 4
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 3
- 206010058202 Cystoid macular oedema Diseases 0.000 claims description 3
- 229920002307 Dextran Polymers 0.000 claims description 3
- 108010010803 Gelatin Proteins 0.000 claims description 3
- 229910019142 PO4 Inorganic materials 0.000 claims description 3
- 230000003078 antioxidant effect Effects 0.000 claims description 3
- 201000010206 cystoid macular edema Diseases 0.000 claims description 3
- 239000008273 gelatin Substances 0.000 claims description 3
- 235000011852 gelatine desserts Nutrition 0.000 claims description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 3
- 239000010452 phosphate Substances 0.000 claims description 3
- 239000001103 potassium chloride Substances 0.000 claims description 3
- 235000011164 potassium chloride Nutrition 0.000 claims description 3
- GDTSJMKGXGJFGQ-UHFFFAOYSA-N 3,7-dioxido-2,4,6,8,9-pentaoxa-1,3,5,7-tetraborabicyclo[3.3.1]nonane Chemical compound O1B([O-])OB2OB([O-])OB1O2 GDTSJMKGXGJFGQ-UHFFFAOYSA-N 0.000 claims description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 2
- 239000001856 Ethyl cellulose Substances 0.000 claims description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims 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 claims description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- 239000004264 Petrolatum Substances 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 claims description 2
- 229920001213 Polysorbate 20 Polymers 0.000 claims description 2
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 2
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 claims description 2
- 229960001950 benzethonium chloride Drugs 0.000 claims description 2
- KHSLHYAUZSPBIU-UHFFFAOYSA-M benzododecinium bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 KHSLHYAUZSPBIU-UHFFFAOYSA-M 0.000 claims description 2
- 229940073464 benzododecinium bromide Drugs 0.000 claims description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 2
- 229960001631 carbomer Drugs 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 2
- 229960001927 cetylpyridinium chloride Drugs 0.000 claims description 2
- YMKDRGPMQRFJGP-UHFFFAOYSA-M cetylpyridinium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 YMKDRGPMQRFJGP-UHFFFAOYSA-M 0.000 claims description 2
- 229960004926 chlorobutanol Drugs 0.000 claims description 2
- 239000008121 dextrose Substances 0.000 claims description 2
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 claims description 2
- 229920001249 ethyl cellulose Polymers 0.000 claims description 2
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 2
- 239000000499 gel Substances 0.000 claims description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- 150000002500 ions Chemical class 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- 235000010981 methylcellulose Nutrition 0.000 claims description 2
- 239000002480 mineral oil Substances 0.000 claims description 2
- 235000010446 mineral oil Nutrition 0.000 claims description 2
- 229940066842 petrolatum Drugs 0.000 claims description 2
- 235000019271 petrolatum Nutrition 0.000 claims description 2
- 229940067107 phenylethyl alcohol Drugs 0.000 claims description 2
- 229960000502 poloxamer Drugs 0.000 claims description 2
- 229920001983 poloxamer Polymers 0.000 claims description 2
- 229920001992 poloxamer 407 Polymers 0.000 claims description 2
- 229940044476 poloxamer 407 Drugs 0.000 claims description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 claims description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 claims description 2
- 229940068977 polysorbate 20 Drugs 0.000 claims description 2
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 claims description 2
- 235000013772 propylene glycol Nutrition 0.000 claims description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 2
- 235000010234 sodium benzoate Nutrition 0.000 claims description 2
- 239000004299 sodium benzoate Substances 0.000 claims description 2
- 229960003885 sodium benzoate Drugs 0.000 claims description 2
- 229960001922 sodium perborate Drugs 0.000 claims description 2
- JXKPEJDQGNYQSM-UHFFFAOYSA-M sodium propionate Chemical compound [Na+].CCC([O-])=O JXKPEJDQGNYQSM-UHFFFAOYSA-M 0.000 claims description 2
- 235000010334 sodium propionate Nutrition 0.000 claims description 2
- 239000004324 sodium propionate Substances 0.000 claims description 2
- 229960003212 sodium propionate Drugs 0.000 claims description 2
- YKLJGMBLPUQQOI-UHFFFAOYSA-M sodium;oxidooxy(oxo)borane Chemical compound [Na+].[O-]OB=O YKLJGMBLPUQQOI-UHFFFAOYSA-M 0.000 claims description 2
- 235000010199 sorbic acid Nutrition 0.000 claims description 2
- 239000004334 sorbic acid Substances 0.000 claims description 2
- 229940075582 sorbic acid Drugs 0.000 claims description 2
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 claims description 2
- 229920001664 tyloxapol Polymers 0.000 claims description 2
- MDYZKJNTKZIUSK-UHFFFAOYSA-N tyloxapol Chemical compound O=C.C1CO1.CC(C)(C)CC(C)(C)C1=CC=C(O)C=C1 MDYZKJNTKZIUSK-UHFFFAOYSA-N 0.000 claims description 2
- 229960004224 tyloxapol Drugs 0.000 claims description 2
- 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 claims 1
- 239000001828 Gelatine Substances 0.000 claims 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 1
- 229910002651 NO3 Inorganic materials 0.000 claims 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 claims 1
- 239000001913 cellulose Substances 0.000 claims 1
- 229920002678 cellulose Polymers 0.000 claims 1
- 229940042472 mineral oil Drugs 0.000 claims 1
- 210000001508 eye Anatomy 0.000 abstract description 176
- 230000000699 topical effect Effects 0.000 abstract description 57
- 239000003814 drug Substances 0.000 abstract description 24
- 229940079593 drug Drugs 0.000 abstract description 18
- 208000027866 inflammatory disease Diseases 0.000 abstract description 10
- 150000001875 compounds Chemical class 0.000 abstract description 9
- 230000003110 anti-inflammatory effect Effects 0.000 abstract description 6
- 239000003018 immunosuppressive agent Substances 0.000 abstract description 3
- 230000000149 penetrating effect Effects 0.000 abstract description 2
- 230000000172 allergic effect Effects 0.000 abstract 1
- 208000010668 atopic eczema Diseases 0.000 abstract 1
- 229960003444 immunosuppressant agent Drugs 0.000 abstract 1
- 230000001861 immunosuppressant effect Effects 0.000 abstract 1
- 230000001766 physiological effect Effects 0.000 abstract 1
- 241001465754 Metazoa Species 0.000 description 142
- 239000000243 solution Substances 0.000 description 127
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 81
- 238000011282 treatment Methods 0.000 description 79
- 210000001519 tissue Anatomy 0.000 description 73
- 239000003981 vehicle Substances 0.000 description 59
- 108010036949 Cyclosporine Proteins 0.000 description 46
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- 238000012360 testing method Methods 0.000 description 36
- 229940053174 restasis Drugs 0.000 description 35
- 241000283973 Oryctolagus cuniculus Species 0.000 description 33
- 239000013641 positive control Substances 0.000 description 33
- 108010062580 Concanavalin A Proteins 0.000 description 32
- 229960001265 ciclosporin Drugs 0.000 description 32
- 229930182912 cyclosporin Natural products 0.000 description 32
- 229960003957 dexamethasone Drugs 0.000 description 30
- 238000002347 injection Methods 0.000 description 30
- 239000007924 injection Substances 0.000 description 30
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical group 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 29
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
- 229940090044 injection Drugs 0.000 description 27
- 239000013642 negative control Substances 0.000 description 27
- 230000009467 reduction Effects 0.000 description 27
- 210000000795 conjunctiva Anatomy 0.000 description 24
- 230000007794 irritation Effects 0.000 description 23
- 241000699670 Mus sp. Species 0.000 description 21
- 230000000694 effects Effects 0.000 description 20
- 210000004561 lacrimal apparatus Anatomy 0.000 description 20
- LRJOMUJRLNCICJ-JZYPGELDSA-N Prednisolone acetate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O LRJOMUJRLNCICJ-JZYPGELDSA-N 0.000 description 19
- 210000004087 cornea Anatomy 0.000 description 19
- 239000008213 purified water Substances 0.000 description 19
- 238000010561 standard procedure Methods 0.000 description 18
- 206010061218 Inflammation Diseases 0.000 description 17
- 210000004027 cell Anatomy 0.000 description 17
- 229920002055 compound 48/80 Polymers 0.000 description 17
- 230000004054 inflammatory process Effects 0.000 description 17
- 241000700159 Rattus Species 0.000 description 16
- 206010051625 Conjunctival hyperaemia Diseases 0.000 description 15
- 210000000744 eyelid Anatomy 0.000 description 15
- 230000035515 penetration Effects 0.000 description 15
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 14
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 14
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 14
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 14
- 229960002646 scopolamine Drugs 0.000 description 14
- 208000026935 allergic disease Diseases 0.000 description 13
- 238000004458 analytical method Methods 0.000 description 13
- 230000037396 body weight Effects 0.000 description 13
- 239000002997 ophthalmic solution Substances 0.000 description 13
- 229930105110 Cyclosporin A Natural products 0.000 description 12
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 12
- 238000013480 data collection Methods 0.000 description 12
- 208000028659 discharge Diseases 0.000 description 12
- 238000005406 washing Methods 0.000 description 12
- 206010015548 Euthanasia Diseases 0.000 description 11
- 208000003251 Pruritus Diseases 0.000 description 11
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 11
- 239000000839 emulsion Substances 0.000 description 11
- 230000007803 itching Effects 0.000 description 11
- 239000002953 phosphate buffered saline Substances 0.000 description 11
- 230000009885 systemic effect Effects 0.000 description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 10
- 238000011887 Necropsy Methods 0.000 description 10
- 230000002146 bilateral effect Effects 0.000 description 10
- 208000035475 disorder Diseases 0.000 description 10
- 210000001339 epidermal cell Anatomy 0.000 description 10
- 229960004716 idoxuridine Drugs 0.000 description 10
- RTGDFNSFWBGLEC-SYZQJQIISA-N mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(/C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-SYZQJQIISA-N 0.000 description 10
- 229960004866 mycophenolate mofetil Drugs 0.000 description 10
- 229940054534 ophthalmic solution Drugs 0.000 description 10
- 150000003839 salts Chemical class 0.000 description 10
- 238000011200 topical administration Methods 0.000 description 10
- 206010020751 Hypersensitivity Diseases 0.000 description 9
- 206010030113 Oedema Diseases 0.000 description 9
- 230000005856 abnormality Effects 0.000 description 9
- 230000002411 adverse Effects 0.000 description 9
- 210000001742 aqueous humor Anatomy 0.000 description 9
- 230000008901 benefit Effects 0.000 description 9
- 239000000872 buffer Substances 0.000 description 9
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 9
- 230000001965 increasing effect Effects 0.000 description 9
- 210000001525 retina Anatomy 0.000 description 9
- 159000000000 sodium salts Chemical class 0.000 description 9
- 238000007619 statistical method Methods 0.000 description 9
- 208000023275 Autoimmune disease Diseases 0.000 description 8
- 210000004369 blood Anatomy 0.000 description 8
- 239000008280 blood Substances 0.000 description 8
- 210000003161 choroid Anatomy 0.000 description 8
- 230000006698 induction Effects 0.000 description 8
- 210000002540 macrophage Anatomy 0.000 description 8
- 210000003786 sclera Anatomy 0.000 description 8
- 150000003431 steroids Chemical class 0.000 description 8
- 230000008961 swelling Effects 0.000 description 8
- 241000283690 Bos taurus Species 0.000 description 7
- 230000007423 decrease Effects 0.000 description 7
- 238000011156 evaluation Methods 0.000 description 7
- 239000003889 eye drop Substances 0.000 description 7
- 229940012356 eye drops Drugs 0.000 description 7
- 210000003630 histaminocyte Anatomy 0.000 description 7
- 210000000554 iris Anatomy 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 238000011740 C57BL/6 mouse Methods 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 238000013401 experimental design Methods 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- 244000036975 Ambrosia artemisiifolia Species 0.000 description 5
- 235000003129 Ambrosia artemisiifolia var elatior Nutrition 0.000 description 5
- 208000009137 Behcet syndrome Diseases 0.000 description 5
- 108010058846 Ovalbumin Proteins 0.000 description 5
- 210000001744 T-lymphocyte Anatomy 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 230000007815 allergy Effects 0.000 description 5
- 235000006708 antioxidants Nutrition 0.000 description 5
- 210000004204 blood vessel Anatomy 0.000 description 5
- 210000004240 ciliary body Anatomy 0.000 description 5
- 244000144993 groups of animals Species 0.000 description 5
- 230000006872 improvement Effects 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 238000010253 intravenous injection Methods 0.000 description 5
- 238000011694 lewis rat Methods 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 238000011587 new zealand white rabbit Methods 0.000 description 5
- 229940092253 ovalbumin Drugs 0.000 description 5
- 229960002800 prednisolone acetate Drugs 0.000 description 5
- 230000002265 prevention Effects 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 206010003645 Atopy Diseases 0.000 description 4
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 4
- 208000010164 Multifocal Choroiditis Diseases 0.000 description 4
- 241000187479 Mycobacterium tuberculosis Species 0.000 description 4
- 108010081690 Pertussis Toxin Proteins 0.000 description 4
- 206010070834 Sensitisation Diseases 0.000 description 4
- 210000000695 crystalline len Anatomy 0.000 description 4
- 230000007159 enucleation Effects 0.000 description 4
- 210000003979 eosinophil Anatomy 0.000 description 4
- 238000007710 freezing Methods 0.000 description 4
- 230000008014 freezing Effects 0.000 description 4
- 230000003053 immunization Effects 0.000 description 4
- 238000002649 immunization Methods 0.000 description 4
- 230000008595 infiltration Effects 0.000 description 4
- 238000001764 infiltration Methods 0.000 description 4
- 210000004969 inflammatory cell Anatomy 0.000 description 4
- 238000007918 intramuscular administration Methods 0.000 description 4
- 229960003299 ketamine Drugs 0.000 description 4
- 230000005499 meniscus Effects 0.000 description 4
- 238000000386 microscopy Methods 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 238000002203 pretreatment Methods 0.000 description 4
- 230000001932 seasonal effect Effects 0.000 description 4
- 230000008313 sensitization Effects 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- 229940124597 therapeutic agent Drugs 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- 210000004127 vitreous body Anatomy 0.000 description 4
- 230000003442 weekly effect Effects 0.000 description 4
- 230000004580 weight loss Effects 0.000 description 4
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 4
- 229960001600 xylazine Drugs 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- 241000700198 Cavia Species 0.000 description 3
- 229920000858 Cyclodextrin Polymers 0.000 description 3
- 208000021386 Sjogren Syndrome Diseases 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 239000013566 allergen Substances 0.000 description 3
- 235000003484 annual ragweed Nutrition 0.000 description 3
- 230000001580 bacterial effect Effects 0.000 description 3
- 239000003855 balanced salt solution Substances 0.000 description 3
- 230000006399 behavior Effects 0.000 description 3
- 230000003139 buffering effect Effects 0.000 description 3
- 235000006263 bur ragweed Nutrition 0.000 description 3
- 235000011089 carbon dioxide Nutrition 0.000 description 3
- 238000005352 clarification Methods 0.000 description 3
- 235000003488 common ragweed Nutrition 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 229940097362 cyclodextrins Drugs 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 210000003128 head Anatomy 0.000 description 3
- 230000003118 histopathologic effect Effects 0.000 description 3
- 230000001506 immunosuppresive effect Effects 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000011159 matrix material Substances 0.000 description 3
- 238000010172 mouse model Methods 0.000 description 3
- 210000000440 neutrophil Anatomy 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 229940100654 ophthalmic suspension Drugs 0.000 description 3
- 230000000069 prophylactic effect Effects 0.000 description 3
- 235000009736 ragweed Nutrition 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 230000001954 sterilising effect Effects 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000003053 toxin Substances 0.000 description 3
- 231100000765 toxin Toxicity 0.000 description 3
- 238000011269 treatment regimen Methods 0.000 description 3
- 208000019553 vascular disease Diseases 0.000 description 3
- 230000000007 visual effect Effects 0.000 description 3
- 206010002091 Anaesthesia Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 208000002177 Cataract Diseases 0.000 description 2
- 208000006069 Corneal Opacity Diseases 0.000 description 2
- 208000010412 Glaucoma Diseases 0.000 description 2
- WZUVPPKBWHMQCE-UHFFFAOYSA-N Haematoxylin Chemical compound C12=CC(O)=C(O)C=C2CC2(O)C1C1=CC=C(O)C(O)=C1OC2 WZUVPPKBWHMQCE-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- RTGDFNSFWBGLEC-UHFFFAOYSA-N Mycophenolate mofetil Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1CC=C(C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-UHFFFAOYSA-N 0.000 description 2
- 206010052143 Ocular discomfort Diseases 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 208000017442 Retinal disease Diseases 0.000 description 2
- 206010038910 Retinitis Diseases 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- 239000003732 agents acting on the eye Substances 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 238000000540 analysis of variance Methods 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
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000004397 blinking Effects 0.000 description 2
- 229940107810 cellcept Drugs 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000001886 ciliary effect Effects 0.000 description 2
- 231100000269 corneal opacity Toxicity 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 239000006196 drop Substances 0.000 description 2
- 229940009662 edetate Drugs 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 230000006353 environmental stress Effects 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 210000002683 foot Anatomy 0.000 description 2
- 230000036449 good health Effects 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 229960001340 histamine Drugs 0.000 description 2
- 238000012744 immunostaining Methods 0.000 description 2
- 230000004968 inflammatory condition Effects 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 230000003902 lesion Effects 0.000 description 2
- 206010025135 lupus erythematosus Diseases 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 238000012544 monitoring process Methods 0.000 description 2
- 229940083410 myfortic Drugs 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 229940023490 ophthalmic product Drugs 0.000 description 2
- 238000002577 ophthalmoscopy Methods 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000000955 prescription drug Substances 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 150000003180 prostaglandins Chemical class 0.000 description 2
- 238000011555 rabbit model Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000002441 reversible effect Effects 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 229940063122 sandimmune Drugs 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 2
- 238000012353 t test Methods 0.000 description 2
- 239000008399 tap water Substances 0.000 description 2
- 235000020679 tap water Nutrition 0.000 description 2
- 230000004489 tear production Effects 0.000 description 2
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002110 toxicologic effect Effects 0.000 description 2
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 2
- JCIIKRHCWVHVFF-UHFFFAOYSA-N 1,2,4-thiadiazol-5-amine;hydrochloride Chemical compound Cl.NC1=NC=NS1 JCIIKRHCWVHVFF-UHFFFAOYSA-N 0.000 description 1
- JVTIXNMXDLQEJE-UHFFFAOYSA-N 2-decanoyloxypropyl decanoate 2-octanoyloxypropyl octanoate Chemical compound C(CCCCCCC)(=O)OCC(C)OC(CCCCCCC)=O.C(=O)(CCCCCCCCC)OCC(C)OC(=O)CCCCCCCCC JVTIXNMXDLQEJE-UHFFFAOYSA-N 0.000 description 1
- 241000224422 Acanthamoeba Species 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 241001225321 Aspergillus fumigatus Species 0.000 description 1
- 238000000846 Bartlett's test Methods 0.000 description 1
- 241000588832 Bordetella pertussis Species 0.000 description 1
- 241000589968 Borrelia Species 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 241000606153 Chlamydia trachomatis Species 0.000 description 1
- 208000028006 Corneal injury Diseases 0.000 description 1
- 241001337994 Cryptococcus <scale insect> Species 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 241000701022 Cytomegalovirus Species 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 241000243988 Dirofilaria immitis Species 0.000 description 1
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 description 1
- 241000243234 Encephalitozoon Species 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 206010052130 Episcleral hyperaemia Diseases 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 208000001860 Eye Infections Diseases 0.000 description 1
- 206010015993 Eyelid oedema Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 208000007465 Giant cell arteritis Diseases 0.000 description 1
- 241000224467 Giardia intestinalis Species 0.000 description 1
- NYHBQMYGNKIUIF-UUOKFMHZSA-N Guanosine Chemical class C1=NC=2C(=O)NC(N)=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O NYHBQMYGNKIUIF-UUOKFMHZSA-N 0.000 description 1
- 208000009889 Herpes Simplex Diseases 0.000 description 1
- 208000007514 Herpes zoster Diseases 0.000 description 1
- 201000002563 Histoplasmosis Diseases 0.000 description 1
- 101000883515 Homo sapiens Chitinase-3-like protein 1 Proteins 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- GRSZFWQUAKGDAV-KQYNXXCUSA-N IMP Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(O)=O)O[C@H]1N1C(NC=NC2=O)=C2N=C1 GRSZFWQUAKGDAV-KQYNXXCUSA-N 0.000 description 1
- 206010062016 Immunosuppression Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 102000015696 Interleukins Human genes 0.000 description 1
- 108010063738 Interleukins Proteins 0.000 description 1
- 238000012313 Kruskal-Wallis test Methods 0.000 description 1
- 244000178870 Lavandula angustifolia Species 0.000 description 1
- 235000010663 Lavandula angustifolia Nutrition 0.000 description 1
- 241000222722 Leishmania <genus> Species 0.000 description 1
- 206010025421 Macule Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229930188023 Magnone Natural products 0.000 description 1
- 102000015728 Mucins Human genes 0.000 description 1
- 108010063954 Mucins Proteins 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699660 Mus musculus Species 0.000 description 1
- 208000021642 Muscular disease Diseases 0.000 description 1
- 241000186362 Mycobacterium leprae Species 0.000 description 1
- 201000009623 Myopathy Diseases 0.000 description 1
- 240000005125 Myrtus communis Species 0.000 description 1
- 235000013418 Myrtus communis Nutrition 0.000 description 1
- JCMWSVNNSPUNER-UHFFFAOYSA-N N,O-dimethyltyramine Chemical compound CNCCC1=CC=C(OC)C=C1 JCMWSVNNSPUNER-UHFFFAOYSA-N 0.000 description 1
- 241000588652 Neisseria gonorrhoeae Species 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 206010061137 Ocular toxicity Diseases 0.000 description 1
- 208000001132 Osteoporosis Diseases 0.000 description 1
- 241000282577 Pan troglodytes Species 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 241000009328 Perro Species 0.000 description 1
- BELBBZDIHDAJOR-UHFFFAOYSA-N Phenolsulfonephthalein Chemical compound C1=CC(O)=CC=C1C1(C=2C=CC(O)=CC=2)C2=CC=CC=C2S(=O)(=O)O1 BELBBZDIHDAJOR-UHFFFAOYSA-N 0.000 description 1
- 241000233872 Pneumocystis carinii Species 0.000 description 1
- 101710093543 Probable non-specific lipid-transfer protein Proteins 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 241000700157 Rattus norvegicus Species 0.000 description 1
- 206010062237 Renal impairment Diseases 0.000 description 1
- 108091006629 SLC13A2 Proteins 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 241000282898 Sus scrofa Species 0.000 description 1
- 206010044245 Toxic optic neuropathy Diseases 0.000 description 1
- 201000005485 Toxoplasmosis Diseases 0.000 description 1
- 206010052779 Transplant rejections Diseases 0.000 description 1
- 206010064996 Ulcerative keratitis Diseases 0.000 description 1
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 1
- 208000025749 Vogt-Koyanagi-Harada disease Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 229940087168 alpha tocopherol Drugs 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 229940037003 alum Drugs 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
- 229910052921 ammonium sulfate Inorganic materials 0.000 description 1
- 235000011130 ammonium sulphate Nutrition 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 229940072107 ascorbate Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229940091771 aspergillus fumigatus Drugs 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 210000003719 b-lymphocyte Anatomy 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 210000000270 basal cell Anatomy 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 229940049638 carbomer homopolymer type c Drugs 0.000 description 1
- 229940043234 carbomer-940 Drugs 0.000 description 1
- 229940031663 carbomer-974p Drugs 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 229920003174 cellulose-based polymer Polymers 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000005482 chemotactic factor Substances 0.000 description 1
- 229940038705 chlamydia trachomatis Drugs 0.000 description 1
- 201000004709 chorioretinitis Diseases 0.000 description 1
- 229910017052 cobalt Inorganic materials 0.000 description 1
- 239000010941 cobalt Substances 0.000 description 1
- GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 231100000478 corneal permeability Toxicity 0.000 description 1
- 210000003683 corneal stroma Anatomy 0.000 description 1
- 201000007717 corneal ulcer Diseases 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 229940078064 cyclosporine injection Drugs 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003112 degranulating effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000035617 depilation Effects 0.000 description 1
- 230000002951 depilatory effect Effects 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229940033055 dexamethasone ophthalmic suspension Drugs 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 229940099686 dirofilaria immitis Drugs 0.000 description 1
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 description 1
- NJDNXYGOVLYJHP-UHFFFAOYSA-L disodium;2-(3-oxido-6-oxoxanthen-9-yl)benzoate Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=CC(=O)C=C2OC2=CC([O-])=CC=C21 NJDNXYGOVLYJHP-UHFFFAOYSA-L 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 210000003038 endothelium Anatomy 0.000 description 1
- 239000003256 environmental substance Substances 0.000 description 1
- YQGOJNYOYNNSMM-UHFFFAOYSA-N eosin Chemical compound [Na+].OC(=O)C1=CC=CC=C1C1=C2C=C(Br)C(=O)C(Br)=C2OC2=C(Br)C(O)=C(Br)C=C21 YQGOJNYOYNNSMM-UHFFFAOYSA-N 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 208000011323 eye infectious disease Diseases 0.000 description 1
- 239000000834 fixative Substances 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 229940085435 giardia lamblia Drugs 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 210000002175 goblet cell Anatomy 0.000 description 1
- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 1
- 102000054350 human CHI3L1 Human genes 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 229920001477 hydrophilic polymer Polymers 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 238000010166 immunofluorescence Methods 0.000 description 1
- 230000002163 immunogen Effects 0.000 description 1
- 230000007233 immunological mechanism Effects 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 229940125721 immunosuppressive agent Drugs 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 235000013902 inosinic acid Nutrition 0.000 description 1
- 229940047122 interleukins Drugs 0.000 description 1
- 230000004410 intraocular pressure Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000005977 kidney dysfunction Effects 0.000 description 1
- 239000001102 lavandula vera Substances 0.000 description 1
- 235000018219 lavender Nutrition 0.000 description 1
- 231100000636 lethal dose Toxicity 0.000 description 1
- 150000002617 leukotrienes Chemical class 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002634 lipophilic molecules Chemical class 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000003141 lower extremity Anatomy 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 239000003120 macrolide antibiotic agent Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 238000007431 microscopic evaluation Methods 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 231100000324 minimal toxicity Toxicity 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 229940051875 mucins Drugs 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 206010028417 myasthenia gravis Diseases 0.000 description 1
- 210000002850 nasal mucosa Anatomy 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000000826 nictitating membrane Anatomy 0.000 description 1
- 231100000327 ocular toxicity Toxicity 0.000 description 1
- 238000001543 one-way ANOVA Methods 0.000 description 1
- 238000011017 operating method Methods 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 238000002638 palliative care Methods 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 230000003071 parasitic effect Effects 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 238000005192 partition Methods 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 229960003531 phenolsulfonphthalein Drugs 0.000 description 1
- 229940096826 phenylmercuric acetate Drugs 0.000 description 1
- PDTFCHSETJBPTR-UHFFFAOYSA-N phenylmercuric nitrate Chemical compound [O-][N+](=O)O[Hg]C1=CC=CC=C1 PDTFCHSETJBPTR-UHFFFAOYSA-N 0.000 description 1
- 238000010149 post-hoc-test Methods 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 239000011241 protective layer Substances 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000004289 sodium hydrogen sulphite Substances 0.000 description 1
- 229910001415 sodium ion Inorganic materials 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 239000004296 sodium metabisulphite Substances 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000003319 supportive effect Effects 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 210000000457 tarsus Anatomy 0.000 description 1
- 206010043207 temporal arteritis Diseases 0.000 description 1
- DHCDFWKWKRSZHF-UHFFFAOYSA-L thiosulfate(2-) Chemical compound [O-]S([S-])(=O)=O DHCDFWKWKRSZHF-UHFFFAOYSA-L 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 229960001005 tuberculin Drugs 0.000 description 1
- 230000002227 vasoactive effect Effects 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
-
- 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
- A61K9/0048—Eye, e.g. artificial tears
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US7941308P | 2008-07-09 | 2008-07-09 | |
| US61/079,413 | 2008-07-09 | ||
| PCT/IB2009/006683 WO2010004435A2 (en) | 2008-07-09 | 2009-07-09 | Formulations for treating eye disorders |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2729834A1 true CA2729834A1 (en) | 2010-01-14 |
Family
ID=41505728
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2729834A Abandoned CA2729834A1 (en) | 2008-07-09 | 2009-07-09 | Formulations for treating eye disorders |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US20100010082A1 (https=) |
| EP (1) | EP2310008A4 (https=) |
| JP (1) | JP2011527339A (https=) |
| CN (1) | CN102099029A (https=) |
| CA (1) | CA2729834A1 (https=) |
| WO (1) | WO2010004435A2 (https=) |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2746527A1 (en) | 2008-09-22 | 2010-03-25 | Rxi Pharmaceuticals Corporation | Rna interference in skin indications |
| US9745574B2 (en) | 2009-02-04 | 2017-08-29 | Rxi Pharmaceuticals Corporation | RNA duplexes with single stranded phosphorothioate nucleotide regions for additional functionality |
| US20100331430A1 (en) * | 2009-06-30 | 2010-12-30 | Allergan, Inc. | Pharmaceutical compositions containing propionic preservative components |
| CN106074591B (zh) | 2010-03-24 | 2020-01-14 | 菲奥医药公司 | 眼部症候中的rna干扰 |
| 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 |
| US8829053B2 (en) * | 2011-12-07 | 2014-09-09 | Rochal Industries Llp | Biocidal compositions and methods of using the same |
| PL2968650T3 (pl) * | 2013-03-14 | 2019-05-31 | Panoptica Inc | Preparaty do oczu do dostarczania leku do tylnego fragmentu oka |
| US11279934B2 (en) | 2014-04-28 | 2022-03-22 | Phio Pharmaceuticals Corp. | Methods for treating cancer using nucleic acids targeting MDM2 or MYCN |
| WO2015168605A1 (en) | 2014-05-01 | 2015-11-05 | Rxi Pharmaceuticals Corporation | Methods for treatment of disorders in the front of the eye utilizing nucleic acid molecules |
| KR20170043655A (ko) * | 2014-09-09 | 2017-04-21 | 아르투로 솔리스 헤레라 | 멜라닌 및 멜라닌 유사체, 전구체, 및 유도체로 안과 질병, 질환, 및 증상의 치료 및 예방을 위한 방법 |
| US9789080B2 (en) * | 2015-09-04 | 2017-10-17 | Insite Vision Incorporated | Ophthalmic formulations of mycophenolic acid |
| WO2019060696A1 (en) * | 2017-09-25 | 2019-03-28 | Surface Pharmaceuticals, Inc. | OPTHALMIC PHARMACEUTICAL COMPOSITIONS AND METHODS FOR THE TREATMENT OF OCULAR SURFACE DISEASE |
| US20230158045A1 (en) * | 2017-09-25 | 2023-05-25 | Surface Ophthalmics, Inc. | Pharmaceutical compositions of mycophenolic acid and/or betamethasone for the treatment of ocular disorders |
| AU2018380300B2 (en) * | 2017-12-08 | 2022-06-16 | The Johns Hopkins University | Hypotonic hydrogel formulations for enhanced transport of active agents at mucosal surfaces |
| CA3124945A1 (en) | 2018-12-27 | 2020-07-02 | Surface Ophthalmics, Inc. | Ophthalmic pharmaceutical compositions and methods for treating ocular surface disease |
| CN116133639A (zh) * | 2019-12-20 | 2023-05-16 | 维奥梅治疗公司 | 用于治疗炎性疾病的制剂和方法 |
| US12310981B2 (en) | 2021-05-10 | 2025-05-27 | Surface Ophthalmics, Inc. | Use of chondroitin sulfate for relieving ocular pain |
| US12440510B2 (en) | 2021-05-10 | 2025-10-14 | Surface Ophthalmics, Inc. | Use of chondroitin sulfate for relieving ocular pain |
| CN113519461A (zh) * | 2021-07-06 | 2021-10-22 | 江西中洪博元生物技术有限公司 | 伴刀豆球蛋白a诱导的小鼠干眼症模型的构建方法及应用 |
| CN114028334B (zh) * | 2021-12-10 | 2023-08-29 | 卓和药业集团股份有限公司 | 一种肺部给药的免疫抑制剂的制备方法 |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3880995A (en) * | 1973-05-14 | 1975-04-29 | Lilly Co Eli | Treatment of arthritis with mycophenolic acid and derivatives |
| US4686234A (en) * | 1985-11-27 | 1987-08-11 | Syntex (U.S.A) Inc. | Mycophenolic acid derivatives in the treatment of inflammatory diseases, in particular rheumatoid arthritis |
| US4753935A (en) * | 1987-01-30 | 1988-06-28 | Syntex (U.S.A.) Inc. | Morpholinoethylesters of mycophenolic acid and pharmaceutical compositions |
| KR920003601B1 (ko) * | 1987-09-03 | 1992-05-04 | 유니버시티 어브 죠지아 리서취 화운데이션 인코포레이티드 | 점안 싸이클로스포린(cyclosporin)의 조성물 |
| US5283257A (en) * | 1992-07-10 | 1994-02-01 | The Board Of Trustees Of The Leland Stanford Junior University | Method of treating hyperproliferative vascular disease |
| US5455045A (en) * | 1993-05-13 | 1995-10-03 | Syntex (U.S.A.) Inc. | High dose formulations |
| CZ301771B6 (cs) * | 1993-10-01 | 2010-06-16 | Syntex (U.S.A.) Llc. | Farmaceutický prostredek ve forme suchého granulátu obsahující mofetil mykofenolát nebo kyselinu mykofenolovou a zpusob jeho prípravy |
| JPH0930966A (ja) * | 1995-07-24 | 1997-02-04 | Gakuzo Tamura | 眼科用新規製剤 |
| ID18663A (id) * | 1996-04-12 | 1998-04-30 | Novartis Ag | Komposisi farmasi berlapis enterik |
| US6670398B2 (en) * | 1997-05-14 | 2003-12-30 | Atherogenics, Inc. | Compounds and methods for treating transplant rejection |
| US6239113B1 (en) * | 1999-03-31 | 2001-05-29 | Insite Vision, Incorporated | Topical treatment or prevention of ocular infections |
| US7063857B1 (en) * | 1999-04-30 | 2006-06-20 | Sucampo Ag | Use of macrolide compounds for the treatment of dry eye |
| US6482799B1 (en) * | 1999-05-25 | 2002-11-19 | The Regents Of The University Of California | Self-preserving multipurpose ophthalmic solutions incorporating a polypeptide antimicrobial |
| US6489335B2 (en) * | 2000-02-18 | 2002-12-03 | Gholam A. Peyman | Treatment of ocular disease |
| US20030018044A1 (en) * | 2000-02-18 | 2003-01-23 | Peyman Gholam A. | Treatment of ocular disease |
| GB0124953D0 (en) * | 2001-10-17 | 2001-12-05 | Novartis Ag | Organic Compounds |
| GB0307553D0 (en) * | 2003-04-01 | 2003-05-07 | Novartis Ag | Organic compounds |
| US7087237B2 (en) * | 2003-09-19 | 2006-08-08 | Advanced Ocular Systems Limited | Ocular solutions |
| US7083803B2 (en) * | 2003-09-19 | 2006-08-01 | Advanced Ocular Systems Limited | Ocular solutions |
| US20050181018A1 (en) * | 2003-09-19 | 2005-08-18 | Peyman Gholam A. | Ocular drug delivery |
| US8372814B2 (en) * | 2004-06-07 | 2013-02-12 | Ista Pharmaceuticals, Inc. | Ophthalmic formulations and uses thereof |
| US20060069150A1 (en) * | 2004-07-20 | 2006-03-30 | Sandor Molnar | Processes for preparation of crystalline mycophenolate sodium |
-
2009
- 2009-07-09 US US12/500,399 patent/US20100010082A1/en not_active Abandoned
- 2009-07-09 JP JP2011517270A patent/JP2011527339A/ja active Pending
- 2009-07-09 WO PCT/IB2009/006683 patent/WO2010004435A2/en not_active Ceased
- 2009-07-09 CN CN2009801265755A patent/CN102099029A/zh active Pending
- 2009-07-09 CA CA2729834A patent/CA2729834A1/en not_active Abandoned
- 2009-07-09 EP EP09794066.2A patent/EP2310008A4/en not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| US20100010082A1 (en) | 2010-01-14 |
| WO2010004435A3 (en) | 2010-06-24 |
| EP2310008A4 (en) | 2014-03-05 |
| CN102099029A (zh) | 2011-06-15 |
| JP2011527339A (ja) | 2011-10-27 |
| WO2010004435A2 (en) | 2010-01-14 |
| EP2310008A2 (en) | 2011-04-20 |
| WO2010004435A9 (en) | 2010-08-26 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20100010082A1 (en) | Formulations for treating eye disorders | |
| AU2017380769B2 (en) | Compositions comprising tacrolimus for the treatment of intraocular inflammatory eye diseases | |
| US20220184057A1 (en) | Combination treatment of ocular inflammatory disorders and diseases | |
| US6579901B2 (en) | Pharmaceutical compositions and methods for treating immune-response associated diseases of the surface and the anterior segment of the eye | |
| US9937225B2 (en) | Topical formulations and uses thereof | |
| Pisella et al. | Comparison of the effects of preserved and unpreserved formulations of timolol on the ocular surface of albino rabbits | |
| RU2582609C2 (ru) | Соединения для лечения/профилактики воспалительных глазных заболеваний | |
| KR101778004B1 (ko) | 이마티닙을 유효성분으로 포함하는 안구 건조 질환 예방 및 치료용 약학 조성물 | |
| US20180092927A1 (en) | Topical formulations and uses thereof | |
| CN114126580A (zh) | 用于治疗眼部过敏的眼用组合物 | |
| CN118403054A (zh) | 用于控制和/或降低近视发展的药物组合物 | |
| JP2012107053A (ja) | ドライアイ障害およびブドウ膜炎を処置するための方法 | |
| US20140322193A1 (en) | Therapies for Disorders of the Cornea and Conjunctiva | |
| Zhou et al. | Subconjunctival injection of microcrystalline prodrug of dexamethasone for long-acting anti-inflammation after phacoemulsification surgery | |
| JP4475802B2 (ja) | 緑内障の局所治療用フルナリジンの使用法 | |
| CN116459251B (zh) | 一种含西维美林的眼用制剂及其制备方法和应用 | |
| CN114040783A (zh) | 可用于治疗干眼症的组合物和方法 | |
| US20260115172A1 (en) | Compositions comprising tacrolimus for the treatment of intraocular inflammatory eye diseases | |
| CN118873493A (zh) | 一种他克莫司眼用纳米乳的制备方法及用途 | |
| HK40070050A (en) | Compositions and methods useable for treatment of dry eye |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20140625 |
|
| FZDE | Discontinued |
Effective date: 20160711 |