NO329118B1 - Sterilt topisk oftalmisk preparat samt anvendelse av en forbindelse for fremstilling av et medikament - Google Patents
Sterilt topisk oftalmisk preparat samt anvendelse av en forbindelse for fremstilling av et medikament Download PDFInfo
- Publication number
- NO329118B1 NO329118B1 NO19993777A NO993777A NO329118B1 NO 329118 B1 NO329118 B1 NO 329118B1 NO 19993777 A NO19993777 A NO 19993777A NO 993777 A NO993777 A NO 993777A NO 329118 B1 NO329118 B1 NO 329118B1
- Authority
- NO
- Norway
- Prior art keywords
- stated
- compound
- alkyl
- formula
- topical ophthalmic
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 40
- 150000001875 compounds Chemical class 0.000 title claims description 64
- 230000000699 topical effect Effects 0.000 title claims description 22
- 239000003814 drug Substances 0.000 title claims description 11
- 238000004519 manufacturing process Methods 0.000 title claims description 8
- 230000028327 secretion Effects 0.000 claims abstract description 28
- -1 dinucleotides Chemical compound 0.000 claims abstract description 26
- PGAVKCOVUIYSFO-XVFCMESISA-N UTP Chemical compound O[C@@H]1[C@H](O)[C@@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O[C@H]1N1C(=O)NC(=O)C=C1 PGAVKCOVUIYSFO-XVFCMESISA-N 0.000 claims abstract description 23
- PGAVKCOVUIYSFO-UHFFFAOYSA-N uridine-triphosphate Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)OC1N1C(=O)NC(=O)C=C1 PGAVKCOVUIYSFO-UHFFFAOYSA-N 0.000 claims abstract description 23
- 238000011282 treatment Methods 0.000 claims abstract description 16
- 239000007788 liquid Substances 0.000 claims abstract description 10
- PCDQPRRSZKQHHS-ZAKLUEHWSA-N cytidine-5'-triphosphate Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@H](O)[C@@H](O)[C@H](CO[P@](O)(=O)O[P@@](O)(=O)OP(O)(O)=O)O1 PCDQPRRSZKQHHS-ZAKLUEHWSA-N 0.000 claims abstract description 9
- PCDQPRRSZKQHHS-UHFFFAOYSA-N Cytidine 5'-triphosphate Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)O1 PCDQPRRSZKQHHS-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000000499 gel Substances 0.000 claims abstract description 8
- ZKHQWZAMYRWXGA-KQYNXXCUSA-N Adenosine triphosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1O ZKHQWZAMYRWXGA-KQYNXXCUSA-N 0.000 claims abstract description 5
- 239000006071 cream Substances 0.000 claims abstract description 3
- 239000000829 suppository Substances 0.000 claims abstract description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 12
- 239000002245 particle Substances 0.000 claims description 12
- 125000003118 aryl group Chemical group 0.000 claims description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
- 239000001301 oxygen Substances 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- YDHWWBZFRZWVHO-UHFFFAOYSA-H [oxido-[oxido(phosphonatooxy)phosphoryl]oxyphosphoryl] phosphate Chemical compound [O-]P([O-])(=O)OP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O YDHWWBZFRZWVHO-UHFFFAOYSA-H 0.000 claims description 9
- 125000000824 D-ribofuranosyl group Chemical group [H]OC([H])([H])[C@@]1([H])OC([H])(*)[C@]([H])(O[H])[C@]1([H])O[H] 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 8
- 239000001226 triphosphate Substances 0.000 claims description 8
- 102000000033 Purinergic Receptors Human genes 0.000 claims description 7
- 108010080192 Purinergic Receptors Proteins 0.000 claims description 7
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 claims description 7
- 208000028006 Corneal injury Diseases 0.000 claims description 6
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 6
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims description 6
- 229940079593 drug Drugs 0.000 claims description 6
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 239000000243 solution Substances 0.000 claims description 6
- 235000011178 triphosphate Nutrition 0.000 claims description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
- 125000000524 functional group Chemical group 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 150000002367 halogens Chemical class 0.000 claims description 4
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 4
- 125000004426 substituted alkynyl group Chemical group 0.000 claims description 4
- 238000005406 washing Methods 0.000 claims description 4
- 229910019142 PO4 Inorganic materials 0.000 claims description 3
- 125000003435 aroyl group Chemical group 0.000 claims description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- LTVOKYUPTHZZQH-UHFFFAOYSA-N difluoromethane Chemical group F[C]F LTVOKYUPTHZZQH-UHFFFAOYSA-N 0.000 claims description 3
- 239000006194 liquid suspension Substances 0.000 claims description 3
- 230000001737 promoting effect Effects 0.000 claims description 3
- 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 239000007921 spray Substances 0.000 claims description 3
- 229940035893 uracil Drugs 0.000 claims description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 3
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 2
- 229920002683 Glycosaminoglycan Polymers 0.000 claims description 2
- 239000004166 Lanolin Substances 0.000 claims description 2
- 125000003282 alkyl amino group Chemical class 0.000 claims description 2
- 125000004414 alkyl thio group Chemical group 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 125000006367 bivalent amino carbonyl group Chemical group [H]N([*:1])C([*:2])=O 0.000 claims description 2
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 2
- DYWBDRKFYPLULC-UHFFFAOYSA-N cyano(nitrosulfonyl)sulfamic acid Chemical compound C(#N)N(S(=O)(=O)[N+](=O)[O-])S(=O)(=O)O DYWBDRKFYPLULC-UHFFFAOYSA-N 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- 229940039717 lanolin Drugs 0.000 claims description 2
- 235000019388 lanolin Nutrition 0.000 claims description 2
- 239000002502 liposome Substances 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- 229920000570 polyether Polymers 0.000 claims description 2
- 229920000642 polymer Polymers 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 229920006395 saturated elastomer Polymers 0.000 claims description 2
- 230000004936 stimulating effect Effects 0.000 claims description 2
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 2
- 229920002554 vinyl polymer Polymers 0.000 claims description 2
- 239000002773 nucleotide Substances 0.000 claims 5
- MWEQTWJABOLLOS-UHFFFAOYSA-L disodium;[[[5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-oxidophosphoryl] hydrogen phosphate;trihydrate Chemical compound O.O.O.[Na+].[Na+].C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP([O-])(=O)OP(O)([O-])=O)C(O)C1O MWEQTWJABOLLOS-UHFFFAOYSA-L 0.000 claims 2
- 235000021317 phosphate Nutrition 0.000 claims 2
- 125000006592 (C2-C3) alkenyl group Chemical group 0.000 claims 1
- 125000006593 (C2-C3) alkynyl group Chemical group 0.000 claims 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims 1
- 239000013078 crystal Substances 0.000 claims 1
- 239000008151 electrolyte solution Substances 0.000 claims 1
- 229940021013 electrolyte solution Drugs 0.000 claims 1
- 239000006260 foam Substances 0.000 claims 1
- 239000002674 ointment Substances 0.000 claims 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 26
- 239000012530 fluid Substances 0.000 abstract description 5
- 239000003227 purinergic agonist Substances 0.000 abstract description 5
- ZKHQWZAMYRWXGA-UHFFFAOYSA-N Adenosine triphosphate Natural products C1=NC=2C(N)=NC=NC=2N1C1OC(COP(O)(=O)OP(O)(=O)OP(O)(O)=O)C(O)C1O ZKHQWZAMYRWXGA-UHFFFAOYSA-N 0.000 abstract description 4
- 229960001456 adenosine triphosphate Drugs 0.000 abstract description 4
- 230000000638 stimulation Effects 0.000 abstract description 4
- 239000007923 nasal drop Substances 0.000 abstract description 3
- 229940100662 nasal drops Drugs 0.000 abstract description 3
- 239000007922 nasal spray Substances 0.000 abstract description 3
- 238000007910 systemic administration Methods 0.000 abstract description 3
- 238000011200 topical administration Methods 0.000 abstract description 3
- 239000012528 membrane Substances 0.000 abstract description 2
- 229940097496 nasal spray Drugs 0.000 abstract description 2
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 2
- 239000006199 nebulizer Substances 0.000 abstract 1
- 239000006187 pill Substances 0.000 abstract 1
- 210000001508 eye Anatomy 0.000 description 37
- 208000003556 Dry Eye Syndromes Diseases 0.000 description 32
- 241000283973 Oryctolagus cuniculus Species 0.000 description 26
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 22
- 206010013774 Dry eye Diseases 0.000 description 21
- 241001465754 Metazoa Species 0.000 description 17
- 210000001519 tissue Anatomy 0.000 description 16
- 210000004083 nasolacrimal duct Anatomy 0.000 description 13
- 239000011780 sodium chloride Substances 0.000 description 13
- 208000009319 Keratoconjunctivitis Sicca Diseases 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 10
- 210000002175 goblet cell Anatomy 0.000 description 10
- 102000015728 Mucins Human genes 0.000 description 8
- 108010063954 Mucins Proteins 0.000 description 8
- 239000011575 calcium Substances 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 102100028045 P2Y purinoceptor 2 Human genes 0.000 description 7
- 101710096700 P2Y purinoceptor 2 Proteins 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 239000006196 drop Substances 0.000 description 7
- 210000000744 eyelid Anatomy 0.000 description 7
- 208000000617 lacrimal duct obstruction Diseases 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 206010010071 Coma Diseases 0.000 description 6
- 206010061876 Obstruction Diseases 0.000 description 6
- 210000004561 lacrimal apparatus Anatomy 0.000 description 6
- 230000004489 tear production Effects 0.000 description 6
- 102100028070 P2Y purinoceptor 4 Human genes 0.000 description 5
- 108050009478 P2Y purinoceptor 4 Proteins 0.000 description 5
- 239000000556 agonist Substances 0.000 description 5
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 5
- 210000000795 conjunctiva Anatomy 0.000 description 5
- 210000004087 cornea Anatomy 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 208000015181 infectious disease Diseases 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 5
- 229940045145 uridine Drugs 0.000 description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- 230000005856 abnormality Effects 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 208000035475 disorder Diseases 0.000 description 4
- YFHXZQPUBCBNIP-UHFFFAOYSA-N fura-2 Chemical compound CC1=CC=C(N(CC(O)=O)CC(O)=O)C(OCCOC=2C(=CC=3OC(=CC=3C=2)C=2OC(=CN=2)C(O)=O)N(CC(O)=O)CC(O)=O)=C1 YFHXZQPUBCBNIP-UHFFFAOYSA-N 0.000 description 4
- 229940113601 irrigation solution Drugs 0.000 description 4
- 238000011555 rabbit model Methods 0.000 description 4
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 3
- 229930024421 Adenine Natural products 0.000 description 3
- GFFGJBXGBJISGV-UHFFFAOYSA-N Adenine Chemical compound NC1=NC=NC2=C1N=CN2 GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 3
- 208000009299 Benign Mucous Membrane Pemphigoid Diseases 0.000 description 3
- 208000007775 Congenital alacrima Diseases 0.000 description 3
- 208000001730 Familial dysautonomia Diseases 0.000 description 3
- 208000029462 Immunodeficiency disease Diseases 0.000 description 3
- 206010023644 Lacrimation increased Diseases 0.000 description 3
- 206010029315 Neuromuscular blockade Diseases 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 201000001638 Riley-Day syndrome Diseases 0.000 description 3
- 206010042033 Stevens-Johnson syndrome Diseases 0.000 description 3
- 231100000168 Stevens-Johnson syndrome Toxicity 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 229960000643 adenine Drugs 0.000 description 3
- 125000000304 alkynyl group Chemical group 0.000 description 3
- 230000003444 anaesthetic effect Effects 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 239000000607 artificial tear Substances 0.000 description 3
- 230000001363 autoimmune Effects 0.000 description 3
- 208000010217 blepharitis Diseases 0.000 description 3
- 208000036549 congenital autosomal dominant alacrima Diseases 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000007812 deficiency Effects 0.000 description 3
- 201000010099 disease Diseases 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- 210000000981 epithelium Anatomy 0.000 description 3
- 230000000762 glandular Effects 0.000 description 3
- 230000036541 health Effects 0.000 description 3
- 239000000644 isotonic solution Substances 0.000 description 3
- 230000004317 lacrimation Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 210000003097 mucus Anatomy 0.000 description 3
- 208000015200 ocular cicatricial pemphigoid Diseases 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 239000000779 smoke Substances 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 239000011782 vitamin Substances 0.000 description 3
- 235000013343 vitamin Nutrition 0.000 description 3
- 229940088594 vitamin Drugs 0.000 description 3
- 229930003231 vitamin Natural products 0.000 description 3
- UHDGCWIWMRVCDJ-UHFFFAOYSA-N 1-beta-D-Xylofuranosyl-NH-Cytosine Natural products O=C1N=C(N)C=CN1C1C(O)C(O)C(CO)O1 UHDGCWIWMRVCDJ-UHFFFAOYSA-N 0.000 description 2
- 206010002091 Anaesthesia Diseases 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- UHDGCWIWMRVCDJ-PSQAKQOGSA-N Cytidine Natural products O=C1N=C(N)C=CN1[C@@H]1[C@@H](O)[C@@H](O)[C@H](CO)O1 UHDGCWIWMRVCDJ-PSQAKQOGSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- 208000002720 Malnutrition Diseases 0.000 description 2
- 208000029549 Muscle injury Diseases 0.000 description 2
- 208000028389 Nerve injury Diseases 0.000 description 2
- 208000023715 Ocular surface disease Diseases 0.000 description 2
- 235000019483 Peanut oil Nutrition 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 2
- 230000037005 anaesthesia Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000004321 blink reflex Effects 0.000 description 2
- 210000005252 bulbus oculi Anatomy 0.000 description 2
- 229910000019 calcium carbonate Inorganic materials 0.000 description 2
- 235000010216 calcium carbonate Nutrition 0.000 description 2
- 239000001506 calcium phosphate Substances 0.000 description 2
- 229910000389 calcium phosphate Inorganic materials 0.000 description 2
- 235000011010 calcium phosphates Nutrition 0.000 description 2
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 2
- 230000005284 excitation Effects 0.000 description 2
- 239000003889 eye drop Substances 0.000 description 2
- 229940012356 eye drops Drugs 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 210000000259 harderian gland Anatomy 0.000 description 2
- 230000036571 hydration Effects 0.000 description 2
- 238000006703 hydration reaction Methods 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000003834 intracellular effect Effects 0.000 description 2
- 210000000554 iris Anatomy 0.000 description 2
- 210000004072 lung Anatomy 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 230000008764 nerve damage Effects 0.000 description 2
- 208000030212 nutrition disease Diseases 0.000 description 2
- 239000000312 peanut oil Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000002571 phosphodiesterase inhibitor Substances 0.000 description 2
- 239000002504 physiological saline solution Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 230000003248 secreting effect Effects 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000010186 staining Methods 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 150000005621 tetraalkylammonium salts Chemical class 0.000 description 2
- 229940100613 topical solution Drugs 0.000 description 2
- 230000002110 toxicologic effect Effects 0.000 description 2
- 231100000759 toxicological effect Toxicity 0.000 description 2
- 238000002627 tracheal intubation Methods 0.000 description 2
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 2
- QCHFTSOMWOSFHM-WPRPVWTQSA-N (+)-Pilocarpine Chemical compound C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C QCHFTSOMWOSFHM-WPRPVWTQSA-N 0.000 description 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- WWJWZQKUDYKLTK-UHFFFAOYSA-N 1,n6-ethenoadenine Chemical compound C1=NC2=NC=N[C]2C2=NC=CN21 WWJWZQKUDYKLTK-UHFFFAOYSA-N 0.000 description 1
- 125000006325 2-propenyl amino group Chemical group [H]C([H])=C([H])C([H])([H])N([H])* 0.000 description 1
- APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 1
- GICKXGZWALFYHZ-UHFFFAOYSA-N 3,N(4)-ethenocytosine Chemical compound O=C1NC=CC2=NC=CN12 GICKXGZWALFYHZ-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 240000002470 Amphicarpaea bracteata Species 0.000 description 1
- JGLMVXWAHNTPRF-CMDGGOBGSA-N CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O Chemical compound CCN1N=C(C)C=C1C(=O)NC1=NC2=CC(=CC(OC)=C2N1C\C=C\CN1C(NC(=O)C2=CC(C)=NN2CC)=NC2=CC(=CC(OCCCN3CCOCC3)=C12)C(N)=O)C(N)=O JGLMVXWAHNTPRF-CMDGGOBGSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 206010051625 Conjunctival hyperaemia Diseases 0.000 description 1
- 206010010726 Conjunctival oedema Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 206010011844 Dacryocystitis Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- QRLVDLBMBULFAL-UHFFFAOYSA-N Digitonin Natural products CC1CCC2(OC1)OC3C(O)C4C5CCC6CC(OC7OC(CO)C(OC8OC(CO)C(O)C(OC9OCC(O)C(O)C9OC%10OC(CO)C(O)C(OC%11OC(CO)C(O)C(O)C%11O)C%10O)C8O)C(O)C7O)C(O)CC6(C)C5CCC4(C)C3C2C QRLVDLBMBULFAL-UHFFFAOYSA-N 0.000 description 1
- 231100000635 Draize test Toxicity 0.000 description 1
- 241000909851 Epiphora Species 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- SXRSQZLOMIGNAQ-UHFFFAOYSA-N Glutaraldehyde Chemical compound O=CCCCC=O SXRSQZLOMIGNAQ-UHFFFAOYSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 241001281199 Jaoa Species 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
- 206010023642 Lacrimation decreased Diseases 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- 208000019693 Lung disease Diseases 0.000 description 1
- 229910021380 Manganese Chloride Inorganic materials 0.000 description 1
- GLFNIEUTAYBVOC-UHFFFAOYSA-L Manganese chloride Chemical compound Cl[Mn]Cl GLFNIEUTAYBVOC-UHFFFAOYSA-L 0.000 description 1
- 239000000637 Melanocyte-Stimulating Hormone Substances 0.000 description 1
- 108010007013 Melanocyte-Stimulating Hormones Proteins 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 208000009344 Penetrating Wounds Diseases 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
- 208000037581 Persistent Infection Diseases 0.000 description 1
- 241000276498 Pollachius virens Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 206010061926 Purulence Diseases 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 206010040844 Skin exfoliation Diseases 0.000 description 1
- 229920002385 Sodium hyaluronate Polymers 0.000 description 1
- 240000006394 Sorghum bicolor Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 229960004308 acetylcysteine Drugs 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000004397 blinking Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- OJGDCBLYJGHCIH-UHFFFAOYSA-N bromhexine Chemical compound C1CCCCC1N(C)CC1=CC(Br)=CC(Br)=C1N OJGDCBLYJGHCIH-UHFFFAOYSA-N 0.000 description 1
- 229960003870 bromhexine Drugs 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 239000007978 cacodylate buffer Substances 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 229940096529 carboxypolymethylene Drugs 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- 229940104302 cytosine Drugs 0.000 description 1
- 230000035618 desquamation Effects 0.000 description 1
- 230000001687 destabilization Effects 0.000 description 1
- PFBUKDPBVNJDEW-UHFFFAOYSA-N dichlorocarbene Chemical group Cl[C]Cl PFBUKDPBVNJDEW-UHFFFAOYSA-N 0.000 description 1
- UVYVLBIGDKGWPX-KUAJCENISA-N digitonin Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)C[C@@H](O)[C@H](O[C@H]5[C@@H]([C@@H](O)[C@@H](O[C@H]6[C@@H]([C@@H](O[C@H]7[C@@H]([C@@H](O)[C@H](O)CO7)O)[C@H](O)[C@@H](CO)O6)O[C@H]6[C@@H]([C@@H](O[C@H]7[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O7)O)[C@@H](O)[C@@H](CO)O6)O)[C@@H](CO)O5)O)C[C@@H]4CC[C@H]3[C@@H]2[C@@H]1O)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 UVYVLBIGDKGWPX-KUAJCENISA-N 0.000 description 1
- UVYVLBIGDKGWPX-UHFFFAOYSA-N digitonine Natural products CC1C(C2(CCC3C4(C)CC(O)C(OC5C(C(O)C(OC6C(C(OC7C(C(O)C(O)CO7)O)C(O)C(CO)O6)OC6C(C(OC7C(C(O)C(O)C(CO)O7)O)C(O)C(CO)O6)O)C(CO)O5)O)CC4CCC3C2C2O)C)C2OC11CCC(C)CO1 UVYVLBIGDKGWPX-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000002919 epithelial cell Anatomy 0.000 description 1
- 210000003560 epithelium corneal Anatomy 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000003172 expectorant agent Substances 0.000 description 1
- 210000001723 extracellular space Anatomy 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 210000004907 gland Anatomy 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- 229940075529 glyceryl stearate Drugs 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 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 description 1
- 206010020718 hyperplasia Diseases 0.000 description 1
- 230000028993 immune response Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000009434 installation Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 208000016747 lacrimal apparatus disease Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 210000000867 larynx Anatomy 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 239000011565 manganese chloride Substances 0.000 description 1
- 235000002867 manganese chloride Nutrition 0.000 description 1
- WPBNNNQJVZRUHP-UHFFFAOYSA-L manganese(2+);methyl n-[[2-(methoxycarbonylcarbamothioylamino)phenyl]carbamothioyl]carbamate;n-[2-(sulfidocarbothioylamino)ethyl]carbamodithioate Chemical compound [Mn+2].[S-]C(=S)NCCNC([S-])=S.COC(=O)NC(=S)NC1=CC=CC=C1NC(=S)NC(=O)OC WPBNNNQJVZRUHP-UHFFFAOYSA-L 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 238000000386 microscopy Methods 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 235000010446 mineral oil Nutrition 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 230000000420 mucociliary effect Effects 0.000 description 1
- 229940066491 mucolytics Drugs 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 210000003928 nasal cavity Anatomy 0.000 description 1
- 208000012028 nasolacrimal duct disease Diseases 0.000 description 1
- 238000011587 new zealand white rabbit Methods 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 210000001331 nose Anatomy 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 230000000050 nutritive effect Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000003209 petroleum derivative Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 150000004804 polysaccharides Chemical class 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000000306 recurrent effect Effects 0.000 description 1
- 210000004739 secretory vesicle Anatomy 0.000 description 1
- 229920000260 silastic Polymers 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229910001467 sodium calcium phosphate Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 229940010747 sodium hyaluronate Drugs 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000032258 transport Effects 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229950010342 uridine triphosphate Drugs 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 150000003722 vitamin derivatives Chemical class 0.000 description 1
- 230000002618 waking effect Effects 0.000 description 1
- 229910052724 xenon Inorganic materials 0.000 description 1
- FHNFHKCVQCLJFQ-UHFFFAOYSA-N xenon atom Chemical compound [Xe] FHNFHKCVQCLJFQ-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/06—Pyrimidine radicals
- C07H19/10—Pyrimidine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7084—Compounds having two nucleosides or nucleotides, e.g. nicotinamide-adenine dinucleotide, flavine-adenine dinucleotide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- 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
- A61P27/04—Artificial tears; Irrigation solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
- C07H19/20—Purine radicals with the saccharide radical esterified by phosphoric or polyphosphoric acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H21/00—Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Epidemiology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Ophthalmology & Optometry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/797,472 US5900407A (en) | 1997-02-06 | 1997-02-06 | Method of treating dry eye disease with uridine triphosphates and related compounds |
| PCT/US1998/002701 WO1998034593A1 (en) | 1997-02-06 | 1998-02-06 | Method of treating dry eye disease with purinergic receptor agonists |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO993777D0 NO993777D0 (no) | 1999-08-04 |
| NO993777L NO993777L (no) | 1999-10-05 |
| NO329118B1 true NO329118B1 (no) | 2010-08-30 |
Family
ID=25170925
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19993777A NO329118B1 (no) | 1997-02-06 | 1999-08-04 | Sterilt topisk oftalmisk preparat samt anvendelse av en forbindelse for fremstilling av et medikament |
Country Status (19)
| Country | Link |
|---|---|
| US (6) | US5900407A (enExample) |
| EP (1) | EP1003474B1 (enExample) |
| JP (3) | JP3652707B2 (enExample) |
| KR (1) | KR100378443B1 (enExample) |
| CN (1) | CN1151775C (enExample) |
| AT (1) | ATE428400T1 (enExample) |
| AU (1) | AU735684B2 (enExample) |
| BR (1) | BR9809562A (enExample) |
| CA (1) | CA2280183C (enExample) |
| DE (1) | DE69840746D1 (enExample) |
| DK (1) | DK1003474T3 (enExample) |
| ES (1) | ES2325892T3 (enExample) |
| ID (1) | ID23375A (enExample) |
| MY (1) | MY120023A (enExample) |
| NO (1) | NO329118B1 (enExample) |
| NZ (1) | NZ337405A (enExample) |
| PT (1) | PT1003474E (enExample) |
| WO (1) | WO1998034593A1 (enExample) |
| ZA (1) | ZA98979B (enExample) |
Families Citing this family (88)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6423694B1 (en) * | 1996-02-21 | 2002-07-23 | Inspire Pharmaceuticals, Inc. | Method of treating otitis media with uridine triphosphates and related compounds |
| US5900407A (en) * | 1997-02-06 | 1999-05-04 | Inspire Pharmaceuticals, Inc. | Method of treating dry eye disease with uridine triphosphates and related compounds |
| US6673779B2 (en) * | 1996-03-27 | 2004-01-06 | Inspire Pharmaceuticals, Inc. | Method of treating ciliary dyskinesia with dinucleoside polyphosphate compounds or UTP analogues |
| US6420347B1 (en) * | 1997-03-27 | 2002-07-16 | Inspire Pharmaceuticals, Inc. | Method of treating ciliary dyskinesia with uridine triphosphates and related compounds |
| US6319908B1 (en) | 1996-07-03 | 2001-11-20 | Inspire Pharmaceuticals, Inc. | Method for large-scale production of di(uridine 5′-tetraphosphate) and salts thereof |
| US5763447C1 (en) * | 1996-07-23 | 2002-05-07 | Inspire Pharmaceuticals | Method of preventing or treating pneumonia in immobilized patients with uridine triphosphates and related compounds |
| US6921755B2 (en) * | 1998-02-06 | 2005-07-26 | Inspire Pharmaceuticals, Inc. | Method of treating dry eye disease with purinergic receptor agonists |
| US6696425B2 (en) * | 1997-02-06 | 2004-02-24 | Inspire Pharmaceuticals, Inc. | Method of treating dry eye disease with purinergic receptor agonists |
| US7223744B2 (en) * | 1997-02-10 | 2007-05-29 | Inspire Pharmaceuticals, Inc. | Pharmaceutical formulation comprising dinucleoside polyphosphates and salts thereof |
| US6596725B2 (en) | 1997-02-10 | 2003-07-22 | Inspire Pharmaceuticals, Inc. | Use of certain dinucleotides to stimulate removal of fluid in retinal detachment and retinal edema |
| US7078391B2 (en) | 1997-02-10 | 2006-07-18 | Inspire Pharmaceuticals, Inc. | Method of treating edematous retinal disorders |
| US6462028B2 (en) | 1997-07-25 | 2002-10-08 | Inspire Pharmaceuticals, Inc. | Method of promoting cervical and vaginal secretions |
| TW593331B (en) | 1997-07-25 | 2004-06-21 | Inspire Pharmaceuticals Inc | Method for large-scale production of di(uridine 5')-tetraphosphate and salts thereof |
| EP1012154B1 (en) | 1997-07-25 | 2004-03-17 | Inspire Pharmaceuticals, Inc. | Salts of di(uridine 5'-tetraphosphate), method for preparation and uses thereof |
| US6872710B2 (en) * | 1997-07-25 | 2005-03-29 | Inspire Pharmaceuticals, Inc. | Di(uridine 5′)-tetraphosphate and salts thereof |
| US6548658B2 (en) * | 1997-07-25 | 2003-04-15 | Inspire Pharmaceuticals, Inc. | Di-(uridine 5′)-tetraphosphate and salts thereof |
| CN1301168A (zh) * | 1998-05-22 | 2001-06-27 | 印斯拜尔药品股份有限公司 | 治疗性二核苷酸和衍生物 |
| EP1140967A1 (en) * | 1998-12-23 | 2001-10-10 | University Of North Carolina At Chapel Hill | Targeted gene transfer using g protein coupled receptors |
| AR023088A1 (es) * | 1999-02-26 | 2002-09-04 | Inspire Pharmaceuticals Inc | Uso de disfosfatos de uridina, adenina y citidina y analogos de los mismos para la manufactura de un medicamento para la estimulacion de la hidratacion delas mucosas. |
| BR0012205A (pt) * | 1999-06-30 | 2002-05-28 | Yamasa Corp | Cristais de dinucleótido |
| US20020061281A1 (en) * | 1999-07-06 | 2002-05-23 | Osbakken Robert S. | Aerosolized anti-infectives, anti-inflammatories, and decongestants for the treatment of sinusitis |
| US6576224B1 (en) * | 1999-07-06 | 2003-06-10 | Sinuspharma, Inc. | Aerosolized anti-infectives, anti-inflammatories, and decongestants for the treatment of sinusitis |
| US6723737B1 (en) * | 1999-10-20 | 2004-04-20 | Eliezer Rapaport | Methods, pharmaceutical and therapeutic compostions for administering adenosine |
| AU8028600A (en) * | 1999-10-20 | 2001-04-30 | Eliezer Rapaport | Methods, pharmaceutical and therapeutic compositions for administering adenosine |
| US6277855B1 (en) | 2000-04-21 | 2001-08-21 | Inspire Pharmaceuticals, Inc. | Method of treating dry eye disease with nicotinic acetylcholine receptor agonists |
| US6864243B1 (en) | 2000-05-12 | 2005-03-08 | Inspire Pharmaceuticals, Inc. | Method for treating retinal degeneration with purinergic receptor agonists |
| KR100832821B1 (ko) * | 2000-05-30 | 2008-05-28 | 산텐 세이야꾸 가부시키가이샤 | 각막 상피 신장 촉진제 |
| US7452870B2 (en) * | 2000-08-21 | 2008-11-18 | Inspire Pharmaceuticals, Inc. | Drug-eluting stents coated with P2Y12 receptor antagonist compound |
| US7132408B2 (en) * | 2000-08-21 | 2006-11-07 | Inspire Pharmaceuticals, Inc. | Composition and method for inhibiting platelet aggregation |
| US6867199B2 (en) | 2000-08-21 | 2005-03-15 | Inspire Pharmaceuticals, Inc. | Dinucleoside polyphosphate compositions and their therapeutic use |
| US7018985B1 (en) | 2000-08-21 | 2006-03-28 | Inspire Pharmaceuticals, Inc. | Composition and method for inhibiting platelet aggregation |
| US7115585B2 (en) | 2000-08-21 | 2006-10-03 | Inspire Pharmaceuticals, Inc. | Compositions for treating epithelial and retinal tissue diseases |
| US6555675B2 (en) | 2000-08-21 | 2003-04-29 | Inspire Pharmaceuticals, Inc. | Dinucleoside polyphosphate compositions and their therapuetic use as purinergic receptor agonists |
| JP3945625B2 (ja) * | 2001-03-30 | 2007-07-18 | 株式会社イーエムアイ | 角膜上皮障害モデル動物及びそのモデル動物を用いた薬剤の評価方法並びにその評価方法を用いて選択された薬剤 |
| US7629329B2 (en) | 2001-06-04 | 2009-12-08 | Tsi Health Sciences, Inc. | Method for increasing muscle mass and strength through administration of adenosine triphosphate |
| GB2394419B (en) | 2001-06-25 | 2005-09-07 | Inspire Pharmaceuticals Inc | Joint lubrication with p2y purinergic receptor agonists |
| WO2003022858A2 (de) * | 2001-09-11 | 2003-03-20 | Nascacell Gmbh | Verfahren zum screenen von inhibitoren für die protein-protein-wechselwirkung sowie ribozyme hierzu |
| CN1228053C (zh) * | 2001-09-11 | 2005-11-23 | 参天制药株式会社 | 含有二尿苷磷酸的滴眼液 |
| WO2003028712A2 (en) * | 2001-09-28 | 2003-04-10 | Universite Libre De Bruxelles | Purinergic and pyrimidinergic receptor agonists for the treatment of activated cd4+ t lymphocyte-mediated immune diseases |
| US20030109508A1 (en) * | 2001-10-11 | 2003-06-12 | Alcon, Inc. | Methods for treating dry eye |
| JP2005505592A (ja) * | 2001-10-11 | 2005-02-24 | アルコン，インコーポレイテッド | 抗炎症性ステロイドとｍｕｃ−１分泌促進薬との組み合わせによる、ドライアイを処置するための方法 |
| WO2003030892A1 (en) * | 2001-10-11 | 2003-04-17 | Alcon, Inc. | Methods for treating dry eye |
| CA2465894A1 (en) * | 2001-11-06 | 2003-05-15 | Inspire Pharmaceuticals, Inc. | Method for treating or preventing inflammatory diseases |
| US7084128B2 (en) * | 2002-01-18 | 2006-08-01 | Inspire Pharmaceuticals, Inc. | Method for reducing intraocular pressure |
| US7435724B2 (en) | 2002-02-27 | 2008-10-14 | Inspire Pharmaceutical, Inc. | Degradation-resistant mononucleoside phosphate compounds |
| CA2502600A1 (en) * | 2002-10-18 | 2004-05-06 | Molichem Medicines, Inc. | Methods of treating dry eye disease with lantibiotics |
| US6984628B2 (en) * | 2003-07-15 | 2006-01-10 | Allergan, Inc. | Ophthalmic compositions comprising trefoil factor family peptides |
| EP1750740A4 (en) * | 2004-05-06 | 2009-06-10 | Molichem Medicines Inc | TREATMENT OF MEMBRANE-ASSOCIATED DISEASES AND DISORDERS USING COMPOSITIONS CONTAINING LANTIBIOTICS |
| EP1753445A4 (en) * | 2004-05-06 | 2009-05-20 | Molichem Medicines Inc | TREATMENT OF EYE DISEASES AND EYE TREATMENTS WITH LANTIBIOTIC COMPOSITIONS |
| US20080233053A1 (en) * | 2005-02-07 | 2008-09-25 | Pharmalight Inc. | Method and Device for Ophthalmic Administration of Active Pharmaceutical Ingredients |
| RU2287159C1 (ru) * | 2005-03-14 | 2006-11-10 | Уральская государственная медицинская академия дополнительного образования | Способ прогнозирования течения синдрома "сухого глаза" |
| RU2271184C1 (ru) * | 2005-06-02 | 2006-03-10 | Федеральное государственное учреждение "Всероссийский центр глазной и пластической хирургии Федерального агентства по здравоохранению и социальному развитию" | Способ хирургического лечения синдрома сухого глаза |
| US7368439B2 (en) * | 2005-06-15 | 2008-05-06 | Bar - Ilan University | Dinucleoside poly(borano)phosphate derivatives and uses thereof |
| KR100870104B1 (ko) * | 2005-11-28 | 2008-11-26 | 주식회사 머젠스 | 안구건조증 치료 및 예방용 조성물 |
| BRPI0621052A2 (pt) * | 2006-01-27 | 2012-07-17 | Can Fite Biopharma Ltd | uso de um agonista de receptor de adenosina a3 (a3ar) |
| US20080107713A1 (en) * | 2006-11-08 | 2008-05-08 | Orilla Werhner C | Contact lens as a sustained drug delivery implant |
| US20080317819A1 (en) * | 2007-06-21 | 2008-12-25 | Orilla Werhner C | Iop lowering drug combination or non-combination loaded contact lens with zonal drug delivery areas |
| US20090004244A1 (en) * | 2007-06-27 | 2009-01-01 | Orilla Werhner C | Iris design as a drug depot for zonal drug delivery by contact lens |
| US20090004245A1 (en) * | 2007-06-28 | 2009-01-01 | Orilla Werhner C | Use of an iris simulated layer to allow aesthetic appearance drug loaded contact lens |
| CA2749537C (en) * | 2009-01-09 | 2018-11-20 | The Schepens Eye Research Institute, Inc. | Il-1 antagonist compositions for corneal nerve regeneration and protection |
| WO2011106697A1 (en) | 2010-02-25 | 2011-09-01 | Schepens Eye Research Institute | Therapeutic compositions for the treatment of dry eye disease |
| US10413506B2 (en) | 2010-04-03 | 2019-09-17 | Praful Doshi | Medical devices including medicaments and methods of making and using same including enhancing comfort, enhancing drug penetration, and treatment of myopia |
| CA2794956C (en) | 2010-04-03 | 2017-05-02 | Praful Doshi | Medical devices including medicaments and methods of making and using same |
| PH12013500424B1 (en) * | 2010-09-10 | 2018-07-11 | Santen Pharmaceutical Co Ltd | Agent for treatment of dry eye characterized by combining p2y2 receptor agonist and hyaluronic acid or salt thereof, method for treating dry eye, and use of the p2y2 receptor agonist and hyaluronic acid or salt thereof |
| US9821159B2 (en) | 2010-11-16 | 2017-11-21 | The Board Of Trustees Of The Leland Stanford Junior University | Stimulation devices and methods |
| ES2739490T3 (es) | 2010-11-16 | 2020-01-31 | Univ Leland Stanford Junior | Sistemas para el tratamiento del ojo seco |
| MY161032A (en) * | 2010-12-28 | 2017-04-03 | Santen Pharmaceutical Co Ltd | Ophthalmic solution comprising diquafosol, method for producing the same, and method for inhibiting formation of insoluble precipitate |
| EP2694983B1 (en) * | 2011-04-06 | 2020-06-03 | KLA-Tencor Corporation | Method and system for providing a quality metric for improved process control |
| MY169816A (en) | 2012-03-26 | 2019-05-16 | Santen Pharmaceutical Co Ltd | Ophthalmic solution comprising diquafosol |
| EP2967817B1 (en) | 2013-03-12 | 2021-03-10 | Oculeve, Inc. | Implant delivery devices and systems |
| NZ704579A (en) | 2013-04-19 | 2018-10-26 | Oculeve Inc | Nasal stimulation devices and methods |
| ES2812752T3 (es) | 2014-02-25 | 2021-03-18 | Oculeve Inc | Formulaciones de polímeros para estimulación nasolagrimal |
| US9687652B2 (en) | 2014-07-25 | 2017-06-27 | Oculeve, Inc. | Stimulation patterns for treating dry eye |
| EP3209370A4 (en) | 2014-10-22 | 2018-05-30 | Oculeve, Inc. | Contact lens for increasing tear production |
| EP3209371A4 (en) | 2014-10-22 | 2018-10-24 | Oculeve, Inc. | Implantable nasal stimulator systems and methods |
| WO2016065215A1 (en) | 2014-10-22 | 2016-04-28 | Oculeve, Inc. | Stimulation devices and methods for treating dry eye |
| HK1245651A1 (en) | 2015-06-05 | 2018-08-31 | Santen Pharmaceutical Co., Ltd. | Therapeutic agent for dry eye characterized by being to be dropped into eye of dry eye patient wearing soft contact lens |
| US10426958B2 (en) | 2015-12-04 | 2019-10-01 | Oculeve, Inc. | Intranasal stimulation for enhanced release of ocular mucins and other tear proteins |
| US10252048B2 (en) | 2016-02-19 | 2019-04-09 | Oculeve, Inc. | Nasal stimulation for rhinitis, nasal congestion, and ocular allergies |
| AU2017260237A1 (en) | 2016-05-02 | 2018-11-22 | Oculeve, Inc. | Intranasal stimulation for treatment of meibomian gland disease and blepharitis |
| JP2020500609A (ja) | 2016-12-02 | 2020-01-16 | オキュリーブ， インコーポレイテッド | ドライアイ予測及び治療勧告のための装置及び方法 |
| KR102472773B1 (ko) | 2018-02-28 | 2022-11-30 | 산텐 세이야꾸 가부시키가이샤 | 디쿠아포솔 및 양이온성 폴리머를 함유하는 안과용 조성물 |
| CN113518646B (zh) | 2019-02-27 | 2023-12-12 | 参天制药株式会社 | 含有地夸磷索或其盐，乙烯基系高分子及纤维素系高分子的眼科用组合物 |
| EP3962493A2 (en) | 2019-05-03 | 2022-03-09 | Flagship Pioneering Innovations V, Inc. | Methods of modulating immune activity/level of irf or sting or of treating cancer, comprising the administration of a sting modulator and/or purinergic receptor modulator or postcellular signaling factor |
| KR102656181B1 (ko) * | 2019-08-27 | 2024-04-08 | 산텐 세이야꾸 가부시키가이샤 | 디쿠아포솔 또는 그 염 및 폴리비닐피롤리돈을 함유하는 수성 안과용 조성물 |
| KR20210110055A (ko) * | 2020-02-28 | 2021-09-07 | 주식회사 종근당바이오 | P1, p4-디(우리딘 5'-)테트라포스페이트 나트륨염 4 수화물 결정형 a의 제조방법 |
| KR102548710B1 (ko) | 2020-12-24 | 2023-06-28 | 주식회사 종근당 | 디쿠아포솔 또는 이의 약제학적으로 허용가능한 염과 토코페롤을 함유하는 건성안 예방 또는 치료용 약제학적 조성물 |
| JP2025528009A (ja) | 2022-07-15 | 2025-08-26 | ドーシ，プラフル | 医薬品と薬剤などの不安定な構成要素の安定剤とを含むコンタクトレンズを作製及び使用する方法 |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2330902A1 (de) * | 1973-06-18 | 1975-03-20 | Helmut Dr Med Zander | Heilungsfoerderndes und vorbeugendes, zur aeusserlichen oertlichen anwendung auf der haut und im auge fuer mensch und tier bestimmtes arznei- bzw. hautpflegemittel |
| US4380239A (en) | 1979-12-20 | 1983-04-19 | The Hospital For Sick Children | Intubation of lacrimal ducts |
| US4658816A (en) | 1984-11-14 | 1987-04-21 | Concept Incorporated | Lighted canaliculus intubation sets |
| US4868154A (en) * | 1986-02-19 | 1989-09-19 | Eye Research Institute Of Retina Foundation | Stimulation of tear secretion with melanocyte stimulating hormones |
| US4753945A (en) * | 1986-02-19 | 1988-06-28 | Eye Research Institute Of Retina Foundation | Stimulation of tear secretion with phosphodiesterase inhibitors |
| US5062831A (en) | 1988-09-28 | 1991-11-05 | Griffiths John D | Catheter for use in the surgical correction of a nasolacrimal duct obstruction |
| US4921485A (en) | 1988-09-28 | 1990-05-01 | Griffiths John D | Catheter for use in the surgical correction of a nasolacrimal duct obstruction |
| US5169386A (en) | 1989-09-11 | 1992-12-08 | Bruce B. Becker | Method and catheter for dilatation of the lacrimal system |
| US5021043A (en) | 1989-09-11 | 1991-06-04 | C. R. Bard, Inc. | Method and catheter for dilatation of the lacrimal system |
| US5292498A (en) * | 1991-06-19 | 1994-03-08 | The University Of North Carolina At Chapel Hill | Method of treating lung disease with uridine triphosphates |
| US5345948A (en) | 1993-04-08 | 1994-09-13 | Donnell Jr Francis E O | Method of performing translactrimal laser dacryocystorhinostomy |
| CA2250188C (en) * | 1996-03-27 | 2008-12-09 | Inspire Pharmaceuticals, Inc. | Method of treating ciliary dyskinesia with uridine triphosphates and related compounds |
| US5900407A (en) * | 1997-02-06 | 1999-05-04 | Inspire Pharmaceuticals, Inc. | Method of treating dry eye disease with uridine triphosphates and related compounds |
| US5789391A (en) * | 1996-07-03 | 1998-08-04 | Inspire Pharmaceuticals, Inc. | Method of treating sinusitis with uridine triphosphates and related compounds |
| US5763447C1 (en) * | 1996-07-23 | 2002-05-07 | Inspire Pharmaceuticals | Method of preventing or treating pneumonia in immobilized patients with uridine triphosphates and related compounds |
| US6921755B2 (en) | 1998-02-06 | 2005-07-26 | Inspire Pharmaceuticals, Inc. | Method of treating dry eye disease with purinergic receptor agonists |
| US6696425B2 (en) * | 1997-02-06 | 2004-02-24 | Inspire Pharmaceuticals, Inc. | Method of treating dry eye disease with purinergic receptor agonists |
| TW567456B (en) * | 2001-02-15 | 2003-12-21 | Au Optronics Corp | Apparatus capable of improving flicker of thin film transistor liquid crystal display |
| FR2904554B1 (fr) * | 2006-08-04 | 2010-11-05 | Zheng Xu | Lipides moleculaires heterogenes cytotropes (lmhc), procede de preparation, et methodes de traitement de patients porteurs de cancers multiples |
-
1997
- 1997-02-06 US US08/797,472 patent/US5900407A/en not_active Expired - Lifetime
-
1998
- 1998-02-06 EP EP98907434A patent/EP1003474B1/en not_active Expired - Lifetime
- 1998-02-06 AT AT98907434T patent/ATE428400T1/de active
- 1998-02-06 US US09/171,169 patent/US6887858B1/en not_active Expired - Lifetime
- 1998-02-06 CA CA002280183A patent/CA2280183C/en not_active Expired - Lifetime
- 1998-02-06 DE DE69840746T patent/DE69840746D1/de not_active Expired - Lifetime
- 1998-02-06 DK DK98907434T patent/DK1003474T3/da active
- 1998-02-06 ID IDW990977A patent/ID23375A/id unknown
- 1998-02-06 MY MYPI98000483A patent/MY120023A/en unknown
- 1998-02-06 CN CNB988032619A patent/CN1151775C/zh not_active Expired - Lifetime
- 1998-02-06 AU AU63241/98A patent/AU735684B2/en not_active Expired
- 1998-02-06 WO PCT/US1998/002701 patent/WO1998034593A1/en not_active Ceased
- 1998-02-06 PT PT98907434T patent/PT1003474E/pt unknown
- 1998-02-06 NZ NZ337405A patent/NZ337405A/en not_active IP Right Cessation
- 1998-02-06 JP JP53505498A patent/JP3652707B2/ja not_active Expired - Lifetime
- 1998-02-06 ZA ZA98979A patent/ZA98979B/xx unknown
- 1998-02-06 ES ES98907434T patent/ES2325892T3/es not_active Expired - Lifetime
- 1998-02-06 BR BR9809562-5A patent/BR9809562A/pt not_active Application Discontinuation
- 1998-02-06 KR KR10-1999-7007113A patent/KR100378443B1/ko not_active Expired - Lifetime
-
1999
- 1999-08-04 NO NO19993777A patent/NO329118B1/no not_active IP Right Cessation
-
2002
- 2002-01-03 US US10/041,826 patent/US6916794B2/en not_active Expired - Lifetime
-
2004
- 2004-09-13 JP JP2004265998A patent/JP4664027B2/ja not_active Expired - Lifetime
-
2005
- 2005-04-25 US US11/114,957 patent/US7235535B2/en not_active Expired - Fee Related
-
2007
- 2007-06-20 US US11/821,091 patent/US7759322B2/en not_active Expired - Lifetime
-
2009
- 2009-12-11 JP JP2009281951A patent/JP5373576B2/ja not_active Expired - Lifetime
-
2010
- 2010-06-28 US US12/825,051 patent/US8097600B2/en not_active Expired - Fee Related
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO329118B1 (no) | Sterilt topisk oftalmisk preparat samt anvendelse av en forbindelse for fremstilling av et medikament | |
| EP1161246B1 (en) | Use of certain dinucleotidetriphosphate, cytidinediphosphate and adeninediphosphate for preparing a pharmaceutical composition for stimulating mucosal hydration | |
| US6596725B2 (en) | Use of certain dinucleotides to stimulate removal of fluid in retinal detachment and retinal edema | |
| US6696425B2 (en) | Method of treating dry eye disease with purinergic receptor agonists | |
| US20050009778A1 (en) | Method for treating retinal degeneration with purinergic receptor agonists | |
| US6921755B2 (en) | Method of treating dry eye disease with purinergic receptor agonists | |
| US20030125299A1 (en) | Method for treating or preventing inflammatory diseases | |
| MXPA99007235A (en) | Method of treating dry eye disease with purinergic receptor agonists | |
| HK1025915B (en) | Method of treating dry eye disease with purinergic receptor agonists |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| CHAD | Change of the owner's name or address (par. 44 patent law, par. patentforskriften) |
Owner name: MERCK SHARP & DOHME CORP, US |
|
| MK1K | Patent expired |