JP2011519949A5 - - Google Patents
Download PDFInfo
- Publication number
- JP2011519949A5 JP2011519949A5 JP2011508634A JP2011508634A JP2011519949A5 JP 2011519949 A5 JP2011519949 A5 JP 2011519949A5 JP 2011508634 A JP2011508634 A JP 2011508634A JP 2011508634 A JP2011508634 A JP 2011508634A JP 2011519949 A5 JP2011519949 A5 JP 2011519949A5
- Authority
- JP
- Japan
- Prior art keywords
- prg4
- protein
- eye
- lens
- ophthalmic
- 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.)
- Granted
Links
- 102100028965 Proteoglycan 4 Human genes 0.000 description 97
- 101001123332 Homo sapiens Proteoglycan 4 Proteins 0.000 description 77
- 108090000623 proteins and genes Proteins 0.000 description 51
- 238000011282 treatment Methods 0.000 description 49
- 238000005461 lubrication Methods 0.000 description 42
- 239000000203 mixture Substances 0.000 description 40
- 102000040430 polynucleotide Human genes 0.000 description 37
- 108091033319 polynucleotide Proteins 0.000 description 37
- 239000002157 polynucleotide Substances 0.000 description 37
- 102000004169 proteins and genes Human genes 0.000 description 34
- 210000004027 cell Anatomy 0.000 description 32
- 102000005962 receptors Human genes 0.000 description 25
- 108020003175 receptors Proteins 0.000 description 25
- 108090000765 processed proteins & peptides Proteins 0.000 description 23
- 238000000034 method Methods 0.000 description 21
- 239000000314 lubricant Substances 0.000 description 19
- 230000007246 mechanism Effects 0.000 description 19
- 102000004196 processed proteins & peptides Human genes 0.000 description 19
- 150000007523 nucleic acids Chemical class 0.000 description 18
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (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-carboxylic acid Chemical compound 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 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 17
- 229920002674 hyaluronan Polymers 0.000 description 17
- 229960003160 hyaluronic acid Drugs 0.000 description 17
- 102000039446 nucleic acids Human genes 0.000 description 16
- 108020004707 nucleic acids Proteins 0.000 description 16
- 229920001184 polypeptide Polymers 0.000 description 16
- 239000004094 surface-active agent Substances 0.000 description 16
- 108020004414 DNA Proteins 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 229940067631 phospholipid Drugs 0.000 description 15
- 150000003904 phospholipids Chemical class 0.000 description 15
- 125000003275 alpha amino acid group Chemical group 0.000 description 14
- 108010009030 lubricin Proteins 0.000 description 14
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
- 230000001050 lubricating effect Effects 0.000 description 12
- 239000000463 material Substances 0.000 description 12
- 125000003729 nucleotide group Chemical group 0.000 description 12
- 239000012530 fluid Substances 0.000 description 11
- 239000012634 fragment Substances 0.000 description 11
- 108020001507 fusion proteins Proteins 0.000 description 11
- 102000037865 fusion proteins Human genes 0.000 description 11
- 230000035882 stress Effects 0.000 description 11
- KILNVBDSWZSGLL-KXQOOQHDSA-N 1,2-dihexadecanoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCCCCCCCCC KILNVBDSWZSGLL-KXQOOQHDSA-N 0.000 description 10
- 102100040134 Free fatty acid receptor 4 Human genes 0.000 description 10
- 101000890672 Homo sapiens Free fatty acid receptor 4 Proteins 0.000 description 10
- 108010029485 Protein Isoforms Proteins 0.000 description 10
- 150000001413 amino acids Chemical class 0.000 description 10
- 239000003974 emollient agent Substances 0.000 description 10
- 230000033001 locomotion Effects 0.000 description 10
- 239000002773 nucleotide Substances 0.000 description 10
- 239000013598 vector Substances 0.000 description 10
- 102000001708 Protein Isoforms Human genes 0.000 description 9
- 229920002385 Sodium hyaluronate Polymers 0.000 description 9
- 230000006870 function Effects 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- 229940010747 sodium hyaluronate Drugs 0.000 description 9
- 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 9
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 8
- 101710127913 Proteoglycan 4 Proteins 0.000 description 8
- 210000002919 epithelial cell Anatomy 0.000 description 8
- 239000000178 monomer Substances 0.000 description 8
- 230000001225 therapeutic effect Effects 0.000 description 8
- 210000001519 tissue Anatomy 0.000 description 8
- -1 tris- (trimethylsilyloxysilyl) propyl vinyl Chemical group 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 7
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 7
- 150000001875 compounds Chemical class 0.000 description 7
- 210000004087 cornea Anatomy 0.000 description 7
- 239000003814 drug Substances 0.000 description 7
- 108020004999 messenger RNA Proteins 0.000 description 7
- 239000001301 oxygen Substances 0.000 description 7
- 229910052760 oxygen Inorganic materials 0.000 description 7
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 239000002299 complementary DNA Substances 0.000 description 6
- 239000003792 electrolyte Substances 0.000 description 6
- 239000000411 inducer Substances 0.000 description 6
- 150000002632 lipids Chemical class 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- JZNWSCPGTDBMEW-UHFFFAOYSA-N Glycerophosphorylethanolamin Natural products NCCOP(O)(=O)OCC(O)CO JZNWSCPGTDBMEW-UHFFFAOYSA-N 0.000 description 5
- 230000001413 cellular effect Effects 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 230000002209 hydrophobic effect Effects 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 150000008104 phosphatidylethanolamines Chemical class 0.000 description 5
- 238000001179 sorption measurement Methods 0.000 description 5
- 108090001008 Avidin Proteins 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- PEEHTFAAVSWFBL-UHFFFAOYSA-N Maleimide Chemical compound O=C1NC(=O)C=C1 PEEHTFAAVSWFBL-UHFFFAOYSA-N 0.000 description 4
- 108010067787 Proteoglycans Proteins 0.000 description 4
- 102000016611 Proteoglycans Human genes 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 108010090804 Streptavidin Proteins 0.000 description 4
- 239000000654 additive Substances 0.000 description 4
- 239000003212 astringent agent Substances 0.000 description 4
- 239000003855 balanced salt solution Substances 0.000 description 4
- 230000005540 biological transmission Effects 0.000 description 4
- 229960002685 biotin Drugs 0.000 description 4
- 235000020958 biotin Nutrition 0.000 description 4
- 239000011616 biotin Substances 0.000 description 4
- 230000003247 decreasing effect Effects 0.000 description 4
- 239000000412 dendrimer Substances 0.000 description 4
- 229920000736 dendritic polymer Polymers 0.000 description 4
- 239000013604 expression vector Substances 0.000 description 4
- 238000011068 loading method Methods 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- 230000003204 osmotic effect Effects 0.000 description 4
- 230000035699 permeability Effects 0.000 description 4
- 235000019271 petrolatum Nutrition 0.000 description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 4
- 230000006798 recombination Effects 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 239000005526 vasoconstrictor agent Substances 0.000 description 4
- 239000001993 wax Substances 0.000 description 4
- 108091008102 DNA aptamers Proteins 0.000 description 3
- 102000016943 Muramidase Human genes 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 3
- 108091028043 Nucleic acid sequence Proteins 0.000 description 3
- 239000004372 Polyvinyl alcohol Substances 0.000 description 3
- 229940083324 Selective androgen receptor modulator Drugs 0.000 description 3
- 238000007792 addition Methods 0.000 description 3
- 229940031955 anhydrous lanolin Drugs 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 210000000845 cartilage Anatomy 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 238000001704 evaporation Methods 0.000 description 3
- 230000008020 evaporation Effects 0.000 description 3
- 230000008713 feedback mechanism Effects 0.000 description 3
- 239000000017 hydrogel Substances 0.000 description 3
- 230000002706 hydrostatic effect Effects 0.000 description 3
- 238000000338 in vitro Methods 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 239000004325 lysozyme Substances 0.000 description 3
- 235000010335 lysozyme Nutrition 0.000 description 3
- 229960000274 lysozyme Drugs 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000002480 mineral oil Substances 0.000 description 3
- 235000010446 mineral oil Nutrition 0.000 description 3
- 239000000816 peptidomimetic Substances 0.000 description 3
- 229940068886 polyethylene glycol 300 Drugs 0.000 description 3
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 3
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 3
- 229920001296 polysiloxane Polymers 0.000 description 3
- 229940068968 polysorbate 80 Drugs 0.000 description 3
- 229920000053 polysorbate 80 Polymers 0.000 description 3
- 229920002451 polyvinyl alcohol Polymers 0.000 description 3
- 235000015497 potassium bicarbonate Nutrition 0.000 description 3
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 3
- 239000011736 potassium bicarbonate Substances 0.000 description 3
- 239000001103 potassium chloride Substances 0.000 description 3
- 235000011164 potassium chloride Nutrition 0.000 description 3
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000010076 replication Effects 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 239000000849 selective androgen receptor modulator Substances 0.000 description 3
- 238000010008 shearing Methods 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
- 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 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- 206010002261 Androgen deficiency Diseases 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- 108091026890 Coding region Proteins 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- 208000003556 Dry Eye Syndromes Diseases 0.000 description 2
- 108700024394 Exon Proteins 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 2
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 2
- 102100026018 Interleukin-1 receptor antagonist protein Human genes 0.000 description 2
- 101710144554 Interleukin-1 receptor antagonist protein Proteins 0.000 description 2
- 239000004166 Lanolin Substances 0.000 description 2
- 108010014251 Muramidase Proteins 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 2
- DJDFFEBSKJCGHC-UHFFFAOYSA-N Naphazoline Chemical compound Cl.C=1C=CC2=CC=CC=C2C=1CC1=NCCN1 DJDFFEBSKJCGHC-UHFFFAOYSA-N 0.000 description 2
- 239000004264 Petrolatum Substances 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 108091081024 Start codon Proteins 0.000 description 2
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 2
- 102000000852 Tumor Necrosis Factor-alpha Human genes 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 125000000539 amino acid group Chemical group 0.000 description 2
- 239000003098 androgen Substances 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 210000001188 articular cartilage Anatomy 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 230000004397 blinking Effects 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229960002713 calcium chloride Drugs 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 150000001718 carbodiimides Chemical class 0.000 description 2
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 2
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- 239000012707 chemical precursor Substances 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 238000012937 correction Methods 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 229940119743 dextran 70 Drugs 0.000 description 2
- 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 2
- 238000012377 drug delivery Methods 0.000 description 2
- 229940021013 electrolyte solution Drugs 0.000 description 2
- 239000008151 electrolyte solution Substances 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- STVZJERGLQHEKB-UHFFFAOYSA-N ethylene glycol dimethacrylate Chemical compound CC(=C)C(=O)OCCOC(=O)C(C)=C STVZJERGLQHEKB-UHFFFAOYSA-N 0.000 description 2
- 239000003889 eye drop Substances 0.000 description 2
- 229940012356 eye drops Drugs 0.000 description 2
- 210000000744 eyelid Anatomy 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 210000004907 gland Anatomy 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 102000054055 human PRG4 Human genes 0.000 description 2
- 229940071826 hydroxyethyl cellulose Drugs 0.000 description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229960003943 hypromellose Drugs 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 229940039717 lanolin Drugs 0.000 description 2
- 235000019388 lanolin Nutrition 0.000 description 2
- 230000000670 limiting effect Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 210000004185 liver Anatomy 0.000 description 2
- 230000005923 long-lasting effect Effects 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229960002337 magnesium chloride Drugs 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 230000035772 mutation Effects 0.000 description 2
- 229940088644 n,n-dimethylacrylamide Drugs 0.000 description 2
- YLGYACDQVQQZSW-UHFFFAOYSA-N n,n-dimethylprop-2-enamide Chemical compound CN(C)C(=O)C=C YLGYACDQVQQZSW-UHFFFAOYSA-N 0.000 description 2
- 229960004760 naphazoline hydrochloride Drugs 0.000 description 2
- 230000017128 negative regulation of NF-kappaB transcription factor activity Effects 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 239000012188 paraffin wax Substances 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 229940066842 petrolatum Drugs 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 229960003733 phenylephrine hydrochloride Drugs 0.000 description 2
- OCYSGIYOVXAGKQ-FVGYRXGTSA-N phenylephrine hydrochloride Chemical compound [H+].[Cl-].CNC[C@H](O)C1=CC=CC(O)=C1 OCYSGIYOVXAGKQ-FVGYRXGTSA-N 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229940069328 povidone Drugs 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 238000005215 recombination Methods 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 230000003746 surface roughness Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 229940021790 tetrahydrozoline hydrochloride Drugs 0.000 description 2
- BJORNXNYWNIWEY-UHFFFAOYSA-N tetrahydrozoline hydrochloride Chemical compound Cl.N1CCN=C1C1C2=CC=CC=C2CCC1 BJORNXNYWNIWEY-UHFFFAOYSA-N 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 230000001052 transient effect Effects 0.000 description 2
- HFMRLLVZHLGNAO-UHFFFAOYSA-N trimethylsilyloxysilicon Chemical compound C[Si](C)(C)O[Si] HFMRLLVZHLGNAO-UHFFFAOYSA-N 0.000 description 2
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 2
- 238000011144 upstream manufacturing Methods 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- 239000003871 white petrolatum Substances 0.000 description 2
- 229940045860 white wax Drugs 0.000 description 2
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 2
- 229960001763 zinc sulfate Drugs 0.000 description 2
- 229910000368 zinc sulfate Inorganic materials 0.000 description 2
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 1
- BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 description 1
- UURVHRGPGCBHIC-UHFFFAOYSA-N 3-(ethenoxycarbonylamino)propanoic acid 4-[[[[[[[[[[[[[[[[[[[[[[[[[[[4-ethenoxycarbonyloxybutyl(dimethyl)silyl]oxy-dimethylsilyl]oxy-dimethylsilyl]oxy-dimethylsilyl]oxy-dimethylsilyl]oxy-dimethylsilyl]oxy-dimethylsilyl]oxy-dimethylsilyl]oxy-dimethylsilyl]oxy-dimethylsilyl]oxy-dimethylsilyl]oxy-dimethylsilyl]oxy-dimethylsilyl]oxy-dimethylsilyl]oxy-dimethylsilyl]oxy-dimethylsilyl]oxy-dimethylsilyl]oxy-dimethylsilyl]oxy-dimethylsilyl]oxy-dimethylsilyl]oxy-dimethylsilyl]oxy-dimethylsilyl]oxy-dimethylsilyl]oxy-dimethylsilyl]oxy-dimethylsilyl]oxy-dimethylsilyl]oxy-dimethylsilyl]butyl ethenyl carbonate 1-ethenylpyrrolidin-2-one ethenyl N-[3-tris(trimethylsilyloxy)silylpropyl]carbamate Chemical compound C=CN1CCCC1=O.OC(=O)CCNC(=O)OC=C.C[Si](C)(C)O[Si](CCCNC(=O)OC=C)(O[Si](C)(C)C)O[Si](C)(C)C.C[Si](C)(CCCCOC(=O)OC=C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)O[Si](C)(C)CCCCOC(=O)OC=C UURVHRGPGCBHIC-UHFFFAOYSA-N 0.000 description 1
- DBCAQXHNJOFNGC-UHFFFAOYSA-N 4-bromo-1,1,1-trifluorobutane Chemical compound FC(F)(F)CCCBr DBCAQXHNJOFNGC-UHFFFAOYSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 108091093088 Amplicon Proteins 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 description 1
- 206010006784 Burning sensation Diseases 0.000 description 1
- VPIDXLJVGVBFOW-UHFFFAOYSA-N C=1C=[C-]PC=1 Chemical class C=1C=[C-]PC=1 VPIDXLJVGVBFOW-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- 108090000994 Catalytic RNA Proteins 0.000 description 1
- 102000053642 Catalytic RNA Human genes 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 108020004705 Codon Proteins 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 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 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004163 DNA-directed RNA polymerases Human genes 0.000 description 1
- 108090000626 DNA-directed RNA polymerases Proteins 0.000 description 1
- 206010013774 Dry eye Diseases 0.000 description 1
- BALXUFOVQVENIU-GNAZCLTHSA-N Ephedrine hydrochloride Chemical compound Cl.CN[C@@H](C)[C@H](O)C1=CC=CC=C1 BALXUFOVQVENIU-GNAZCLTHSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 101001018100 Homo sapiens Lysozyme C Proteins 0.000 description 1
- 101100409185 Homo sapiens PRG4 gene Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 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 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 108091092195 Intron Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 108020004711 Nucleic Acid Probes Proteins 0.000 description 1
- 208000023715 Ocular surface disease Diseases 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 108700026244 Open Reading Frames Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 description 1
- 239000004365 Protease Substances 0.000 description 1
- 229940079156 Proteasome inhibitor Drugs 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 102000009572 RNA Polymerase II Human genes 0.000 description 1
- 108010009460 RNA Polymerase II Proteins 0.000 description 1
- 108010008281 Recombinant Fusion Proteins Proteins 0.000 description 1
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- 240000004808 Saccharomyces cerevisiae Species 0.000 description 1
- 238000012300 Sequence Analysis Methods 0.000 description 1
- 108020005038 Terminator Codon Proteins 0.000 description 1
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical class O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 1
- 108020004566 Transfer RNA Proteins 0.000 description 1
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical class O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 238000000246 agarose gel electrophoresis Methods 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 210000004102 animal cell Anatomy 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000003886 aromatase inhibitor Substances 0.000 description 1
- 229940046844 aromatase inhibitors Drugs 0.000 description 1
- 239000000607 artificial tear Substances 0.000 description 1
- 238000010256 biochemical assay Methods 0.000 description 1
- 231100000704 bioconcentration Toxicity 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000002051 biphasic effect Effects 0.000 description 1
- 229960005069 calcium Drugs 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- LLSDKQJKOVVTOJ-UHFFFAOYSA-L calcium chloride dihydrate Chemical compound O.O.[Cl-].[Cl-].[Ca+2] LLSDKQJKOVVTOJ-UHFFFAOYSA-L 0.000 description 1
- 229940052299 calcium chloride dihydrate Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 239000013626 chemical specie Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000013611 chromosomal DNA Substances 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 208000037976 chronic inflammation Diseases 0.000 description 1
- 230000006020 chronic inflammation Effects 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000000295 complement effect Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 210000000795 conjunctiva Anatomy 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 239000005547 deoxyribonucleotide Substances 0.000 description 1
- 125000002637 deoxyribonucleotide group Chemical group 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 230000001687 destabilization Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 229960002179 ephedrine Drugs 0.000 description 1
- 229960002534 ephedrine hydrochloride Drugs 0.000 description 1
- 239000000328 estrogen antagonist Substances 0.000 description 1
- 238000009164 estrogen replacement therapy Methods 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 210000003527 eukaryotic cell Anatomy 0.000 description 1
- 210000003722 extracellular fluid Anatomy 0.000 description 1
- 230000007684 eye toxicity Effects 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 239000003349 gelling agent Substances 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 230000001295 genetical effect Effects 0.000 description 1
- 238000009499 grossing Methods 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- ILZDRYGMISWQJJ-UHFFFAOYSA-H hexasodium 2-hydroxypropane-1,2,3-tricarboxylate Chemical compound [Na+].[Na+].[Na+].[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O ILZDRYGMISWQJJ-UHFFFAOYSA-H 0.000 description 1
- 210000005260 human cell Anatomy 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000007803 itching Effects 0.000 description 1
- 210000005067 joint tissue Anatomy 0.000 description 1
- 210000002510 keratinocyte Anatomy 0.000 description 1
- 210000004561 lacrimal apparatus Anatomy 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 229940059904 light mineral oil Drugs 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229940050906 magnesium chloride hexahydrate Drugs 0.000 description 1
- DHRRIBDTHFBPNG-UHFFFAOYSA-L magnesium dichloride hexahydrate Chemical compound O.O.O.O.O.O.[Mg+2].[Cl-].[Cl-] DHRRIBDTHFBPNG-UHFFFAOYSA-L 0.000 description 1
- 229940091250 magnesium supplement Drugs 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 238000007726 management method Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 210000004175 meibomian gland Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000005499 meniscus Effects 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000001823 molecular biology technique Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 239000002853 nucleic acid probe Substances 0.000 description 1
- 231100000327 ocular toxicity Toxicity 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000003605 opacifier Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N p-hydroxybenzoic acid methyl ester Natural products COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000009832 plasma treatment Methods 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 230000008488 polyadenylation Effects 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000000770 proinflammatory effect Effects 0.000 description 1
- 210000001236 prokaryotic cell Anatomy 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 239000003207 proteasome inhibitor Substances 0.000 description 1
- 230000006920 protein precipitation Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000012207 quantitative assay Methods 0.000 description 1
- 238000003259 recombinant expression Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 125000002652 ribonucleotide group Chemical group 0.000 description 1
- 108020004418 ribosomal RNA Proteins 0.000 description 1
- 108091092562 ribozyme Proteins 0.000 description 1
- 229940095743 selective estrogen receptor modulator Drugs 0.000 description 1
- 239000000333 selective estrogen receptor modulator Substances 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229940087562 sodium acetate trihydrate Drugs 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 229960000999 sodium citrate dihydrate Drugs 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000008961 swelling Effects 0.000 description 1
- 210000001258 synovial membrane Anatomy 0.000 description 1
- 210000002435 tendon Anatomy 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000005026 transcription initiation Effects 0.000 description 1
- 238000013519 translation Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 239000013638 trimer Substances 0.000 description 1
- 229940038773 trisodium citrate Drugs 0.000 description 1
- 230000003827 upregulation Effects 0.000 description 1
- LVLANIHJQRZTPY-UHFFFAOYSA-N vinyl carbamate Chemical compound NC(=O)OC=C LVLANIHJQRZTPY-UHFFFAOYSA-N 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 230000029663 wound healing Effects 0.000 description 1
- 210000005253 yeast cell Anatomy 0.000 description 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5111208P | 2008-05-07 | 2008-05-07 | |
| US61/051,112 | 2008-05-07 | ||
| PCT/US2009/043018 WO2009137603A1 (en) | 2008-05-07 | 2009-05-06 | Ophthalmic device, and method of use thereof, for increasing ocular boundary lubrication |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2011519949A JP2011519949A (ja) | 2011-07-14 |
| JP2011519949A5 true JP2011519949A5 (enExample) | 2013-08-01 |
| JP5474054B2 JP5474054B2 (ja) | 2014-04-16 |
Family
ID=41264988
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011508534A Active JP5508398B2 (ja) | 2008-05-07 | 2009-04-08 | 眼の表面潤滑の治療的補充及び強化 |
| JP2011508634A Active JP5474054B2 (ja) | 2008-05-07 | 2009-05-06 | 眼の境界潤滑を増加させるための、眼科治療の装置、及び、その使用方法、 |
| JP2011508633A Active JP5439652B2 (ja) | 2008-05-07 | 2009-05-06 | 眼の表面の潤滑性の治療的調節 |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011508534A Active JP5508398B2 (ja) | 2008-05-07 | 2009-04-08 | 眼の表面潤滑の治療的補充及び強化 |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2011508633A Active JP5439652B2 (ja) | 2008-05-07 | 2009-05-06 | 眼の表面の潤滑性の治療的調節 |
Country Status (16)
| Country | Link |
|---|---|
| US (9) | US9138457B2 (enExample) |
| EP (4) | EP2285364B1 (enExample) |
| JP (3) | JP5508398B2 (enExample) |
| CN (2) | CN105664136A (enExample) |
| CA (3) | CA2722913C (enExample) |
| CY (2) | CY1119122T1 (enExample) |
| DK (3) | DK2915529T3 (enExample) |
| ES (3) | ES2530723T3 (enExample) |
| HR (3) | HRP20150097T1 (enExample) |
| HU (2) | HUE024146T2 (enExample) |
| LT (2) | LT2915529T (enExample) |
| PL (3) | PL2285364T3 (enExample) |
| PT (2) | PT2285364E (enExample) |
| RU (1) | RU2510274C2 (enExample) |
| SI (3) | SI2915529T1 (enExample) |
| WO (3) | WO2009137217A2 (enExample) |
Families Citing this family (63)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20040082509A1 (en) | 1999-10-12 | 2004-04-29 | Christophe Bonny | Cell-permeable peptide inhibitors of the JNK signal transduction pathway |
| US9884038B2 (en) | 2004-06-07 | 2018-02-06 | University Of Tennessee Research Foundation | Selective androgen receptor modulator and methods of use thereof |
| WO2013003594A2 (en) | 2011-06-28 | 2013-01-03 | Tearscience, Inc. | Methods and systems for treating meibomian gland dysfunction using radio-frequency energy |
| US20070060988A1 (en) | 2005-07-18 | 2007-03-15 | Grenon Stephen M | Melting meibomian gland obstructions |
| US20090043365A1 (en) * | 2005-07-18 | 2009-02-12 | Kolis Scientific, Inc. | Methods, apparatuses, and systems for reducing intraocular pressure as a means of preventing or treating open-angle glaucoma |
| US8950405B2 (en) | 2006-05-15 | 2015-02-10 | Tearscience, Inc. | Treatment of obstructive disorders of the eye or eyelid |
| US20070016256A1 (en) * | 2005-07-18 | 2007-01-18 | Korb Donald R | Method and apparatus for treating gland dysfunction |
| US7981095B2 (en) * | 2005-07-18 | 2011-07-19 | Tearscience, Inc. | Methods for treating meibomian gland dysfunction employing fluid jet |
| US20080114423A1 (en) | 2006-05-15 | 2008-05-15 | Grenon Stephen M | Apparatus for inner eyelid treatment of meibomian gland dysfunction |
| US7981145B2 (en) | 2005-07-18 | 2011-07-19 | Tearscience Inc. | Treatment of meibomian glands |
| US7981146B2 (en) | 2006-05-15 | 2011-07-19 | Tearscience Inc. | Inner eyelid treatment for treating meibomian gland dysfunction |
| WO2007031098A1 (en) | 2005-09-12 | 2007-03-22 | Xigen S.A. | Cell-permeable peptide inhibitors of the jnk signal transduction pathway |
| US8128673B2 (en) | 2006-05-15 | 2012-03-06 | Tearscience, Inc. | System for inner eyelid heat and pressure treatment for treating meibomian gland dysfunction |
| US8128674B2 (en) | 2006-05-15 | 2012-03-06 | Tearscience, Inc. | System for outer eyelid heat and pressure treatment for treating meibomian gland dysfunction |
| US7981147B2 (en) | 2006-05-15 | 2011-07-19 | Tearscience, Inc. | Outer eyelid heat and pressure treatment for treating meibomian gland dysfunction |
| US8007524B2 (en) | 2006-05-15 | 2011-08-30 | Tearscience, Inc. | Heat treatment and heat loss reduction for treating meibomian gland dysfunction |
| US8137390B2 (en) | 2006-05-15 | 2012-03-20 | Tearscience, Inc. | System for providing heat treatment and heat loss reduction for treating meibomian gland dysfunction |
| US7976573B2 (en) | 2006-05-15 | 2011-07-12 | Tearscience, Inc. | Inner eyelid heat and pressure treatment for treating meibomian gland dysfunction |
| US9314369B2 (en) | 2006-05-15 | 2016-04-19 | Tearscience, Inc. | System for inner eyelid treatment of meibomian gland dysfunction |
| US7968603B2 (en) | 2007-09-11 | 2011-06-28 | University Of Tennessee Research Foundation | Solid forms of selective androgen receptor modulators |
| US8506944B2 (en) * | 2008-05-07 | 2013-08-13 | The Regents Of The University Of California | Replenishment and enrichment of ocular surface lubrication |
| SI2915529T1 (sl) | 2008-05-07 | 2017-09-29 | The Regents Of The University Of California | Terapevtska regeneracija in obogatitev lubrikacije okularne površine |
| WO2009143864A1 (en) | 2008-05-30 | 2009-12-03 | Xigen S.A. | Use of cell-permeable peptide inhibitors of the jnk signal transduction pathway for the treatment of chronic or non-chronic inflammatory digestive diseases |
| WO2009143865A1 (en) | 2008-05-30 | 2009-12-03 | Xigen S.A. | Use of cell-permeable peptide inhibitors of the jnk signal transduction pathway for the treatment of various diseases |
| WO2010072228A1 (en) | 2008-12-22 | 2010-07-01 | Xigen S.A. | Novel transporter constructs and transporter cargo conjugate molecules |
| CA3110817C (en) | 2009-05-22 | 2023-08-15 | Lubris, Llc | Application and uses of prg4 and therapeutic modulation thereof |
| US8791158B2 (en) | 2010-01-11 | 2014-07-29 | Gtx, Inc. | Methods of treating meibomian gland dysfunction |
| WO2011160653A1 (en) | 2010-06-21 | 2011-12-29 | Xigen S.A. | Novel jnk inhibitor molecules |
| CA2807036C (en) | 2010-10-14 | 2018-01-16 | Xigen S.A. | Use of cell-permeable peptide inhibitors of the jnk signal transduction pathway for the treatment of chronic or non-chronic inflammatory eye diseases |
| WO2012174123A1 (en) * | 2011-06-13 | 2012-12-20 | Allergan, Inc. | Treatment of psychological trauma |
| ES2780182T3 (es) * | 2011-06-29 | 2020-08-24 | Allergan Inc | Formulaciones de 15-hidroxiestearato de macrogol |
| US20130029919A1 (en) | 2011-07-26 | 2013-01-31 | Allergan, Inc. | Two part formulation system for opthalmic delivery |
| AU2012344299A1 (en) * | 2011-11-30 | 2014-05-29 | Xigen Inflammation Ltd. | Use of cell-permeable peptide inhibitors of the JNK signal transduction pathway for the treatment of dry eye syndrome |
| WO2013091670A1 (en) | 2011-12-21 | 2013-06-27 | Xigen S.A. | Novel jnk inhibitor molecules for treatment of various diseases |
| US9827250B2 (en) * | 2012-07-31 | 2017-11-28 | Johnson & Johnson Vision Care, Inc. | Lens incorporating myopia control optics and muscarinic agents |
| US10842670B2 (en) | 2012-08-22 | 2020-11-24 | Johnson & Johnson Vision Care, Inc. | Apparatuses and methods for diagnosing and/or treating lipid transport deficiency in ocular tear films, and related components and devices |
| ES2942724T3 (es) | 2013-04-30 | 2023-06-06 | Alcon Inc | Sistemas para el tratamiento de enfermedades del ojo |
| US9763827B2 (en) | 2013-04-30 | 2017-09-19 | Tear Film Innovations, Inc. | Systems and methods for the treatment of eye conditions |
| WO2015197097A1 (en) | 2014-06-26 | 2015-12-30 | Xigen Inflammation Ltd. | New use for jnk inhibitor molecules for treatment of various diseases |
| WO2014206427A1 (en) | 2013-06-26 | 2014-12-31 | Xigen Inflammation Ltd. | New use of cell-permeable peptide inhibitors of the jnk signal transduction pathway for the treatment of various diseases |
| AU2014301631A1 (en) | 2013-06-26 | 2015-08-27 | Xigen Inflammation Ltd. | New use of cell-permeable peptide inhibitors of the JNK signal transduction pathway for the treatment of various diseases |
| US9982027B2 (en) | 2013-10-22 | 2018-05-29 | Lubris Llc | Control of rheological properties of mixed hyaluronate/lubricin solutions |
| US9668916B2 (en) | 2013-11-04 | 2017-06-06 | Vance M. Thompson | Conjunctival cover and methods therefor |
| US20150141328A1 (en) * | 2013-11-18 | 2015-05-21 | The Schepens Eye Research Institute | Stimulation of human meibomian gland function |
| JP6571101B2 (ja) | 2013-11-26 | 2019-09-04 | ルブリス，エルエルシー． | 細胞間相互作用を阻害するための組成物及び方法 |
| US10940111B2 (en) | 2014-06-15 | 2021-03-09 | Yeda Research And Development Co. Ltd. | Surface treatment by water-soluble polymers and lipids/liposomes |
| IL234929B (en) * | 2014-10-01 | 2021-01-31 | Yeda Res & Dev | Liposomes-containing antifouling compositions and uses thereof |
| US9395557B2 (en) | 2014-11-12 | 2016-07-19 | Vance M. Thompson | Partial corneal conjunctival contact lens |
| MA53108A (fr) * | 2015-01-26 | 2021-05-12 | Lubris Llc | Utilisation de prg4 comme agent anti-inflammatoire |
| US9869883B2 (en) | 2015-03-11 | 2018-01-16 | Vance M. Thompson | Tear shaping for refractive correction |
| HK1246644A1 (zh) * | 2015-04-03 | 2018-09-14 | 参天制药株式会社 | 以诺龙或其酯、美替诺龙或其酯作为有效成分的乾眼症治疗剂 |
| DK3300482T3 (da) | 2015-05-19 | 2021-10-18 | Lubris Llc | Brug af prg4 til at forbedre dynamisk synsstyrke og højere ordens aberrationer |
| JP6718608B2 (ja) * | 2016-05-25 | 2020-07-08 | 国立大学法人愛媛大学 | 眼表面・眼瞼摩擦係数測定装置および眼表面・眼瞼摩擦係数評価方法 |
| US10974063B2 (en) | 2016-06-30 | 2021-04-13 | Alcon Inc. | Light therapy for eyelash growth |
| US10353220B2 (en) | 2016-10-17 | 2019-07-16 | Vance M. Thompson | Tear shaping for refractive correction |
| US10678067B2 (en) | 2018-04-06 | 2020-06-09 | Vance M. Thompson | Tear shaping for refractive correction |
| MX2020013869A (es) * | 2018-06-21 | 2021-03-02 | Lubris Llc | Lubricina para uso en curacion de heridas referencia cruzada con solicitudes relacionadas. |
| US20220008518A1 (en) * | 2018-11-08 | 2022-01-13 | The Schepens Eye Research Institute, Inc. | Therapeutic approaches for tissue reconstruction and wound healing treatment |
| EP3900787A4 (en) | 2018-12-21 | 2022-02-23 | Kyoto University | LUBRICIN-LOCALIZED CARTILE-LIKE TISSUE, METHOD OF MANUFACTURE THEREOF AND COMPOSITION THEREOF FOR TREATMENT OF ARTICULATE-CARTILAGE DEFECTS |
| US20220127319A1 (en) | 2019-01-15 | 2022-04-28 | Cornell University | Recombinant mucins, and compositions and methods for using the same |
| US20220273844A1 (en) * | 2019-07-26 | 2022-09-01 | Pandorum Technologies Private Limited | Bio-ink formulations, bio-printed corneal lenticule, and applications thereof |
| WO2021067823A2 (en) * | 2019-10-05 | 2021-04-08 | The Schepens Eye Research Institute, Inc. | A new treatment for meibomian gland dysfunction |
| US11609438B2 (en) * | 2019-10-31 | 2023-03-21 | Menicon Singapore Pte Ltd. | Ocular lens with friction control structures |
Family Cites Families (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4550022A (en) * | 1981-10-05 | 1985-10-29 | Alcon Laboratories, Inc. | Tissue irrigating solution |
| SE8501723L (sv) | 1985-04-09 | 1986-10-10 | Pharmacia Ab | Preparation att anvendas vid behandling av ledinflammation |
| US4964206A (en) * | 1988-03-15 | 1990-10-23 | Minnesota Mining And Manufacturing Company | Intraocular lens anchoring filament to lens element fixation method |
| US4964205A (en) * | 1988-06-13 | 1990-10-23 | Rampart Packaging Inc. | Method for making screw cap jar |
| US6433142B1 (en) | 1989-08-08 | 2002-08-13 | Genetics Institute, Llc | Megakaryocyte stimulating factors |
| US5326558A (en) | 1989-08-08 | 1994-07-05 | Genetics Institute, Inc. | Megakaryocytopoietic factor |
| RU2033165C1 (ru) * | 1989-10-13 | 1995-04-20 | Межотраслевой научно-технический комплекс "Микрохирургия глаза" | Способ получения пластичного материала из коллагена |
| US5688765A (en) * | 1992-04-21 | 1997-11-18 | The Schepens Eye Research Institute, Inc. | Ocular therapy in Sjogren's syndrome using topically applied androgensor TGF-β |
| ATE185697T1 (de) * | 1992-04-21 | 1999-11-15 | Schepens Eye Res Inst | Androgentherapie am auge beim sjögrensyndrom |
| US6107289A (en) * | 1992-04-21 | 2000-08-22 | The Schepens Eye Research Institute, Inc. | Ocular therapy in keratoconjunctivitis sicca using topically applied androgens or TGF-β |
| IL106922A (en) * | 1992-09-14 | 1998-08-16 | Novartis Ag | Composite materials with one or more wettable surfaces and process for their preparation |
| US5351100A (en) * | 1992-12-09 | 1994-09-27 | Bmc Industries, Inc. | Glass multifocal ophthalmic lens with polarizing element and method of making |
| WO1995013827A1 (en) * | 1993-11-19 | 1995-05-26 | The University Of Sydney | A method for preventing or controlling cataract |
| US5515590A (en) * | 1994-07-19 | 1996-05-14 | University Of Kentucky Research Foundation | Method for reducing the generation of wear particulates from an implant |
| US5518732A (en) * | 1995-02-14 | 1996-05-21 | Chiron Vision, Inc. | Bio-erodible ophthalmic shield |
| DE69629230D1 (de) * | 1995-03-24 | 2003-09-04 | Ocular Res Of Bonton Inc | Hydrogellinse mit Lipid-Vorbeschichtigung |
| RU2207885C2 (ru) * | 1995-08-30 | 2003-07-10 | Фармация Аб | Способ подачи небольшого объема лечебного раствора к целевому месту |
| US6689748B1 (en) * | 1998-04-08 | 2004-02-10 | Theoharis C. Theoharides | Method of treating mast cell activation-induced diseases with a proteoglycan |
| WO2000027421A2 (en) * | 1998-11-06 | 2000-05-18 | The Schepens Eye Research Institute, Inc. | LOCAL USE OF SOLUBLE TUMOR NECROSIS RECEPTOR I (sTNFRI) FOR PROPHYLAXIS AND TREATMENT OF CORNEAL TRANSPLANT REJECTION AND OTHER DISORDERS OF THE EYE |
| CA2349168C (en) * | 1998-11-10 | 2009-01-06 | Denki Kagaku Kogyo Kabushiki Kaisha | Hyaluronic acid gel, method of its production and medical material containing it |
| US6960562B2 (en) | 1999-04-23 | 2005-11-01 | Rhode Island Hospital, A Lifespan Partner | Tribonectin polypeptides and uses thereof |
| US6743774B1 (en) | 1999-04-23 | 2004-06-01 | Rhode Island Hospital | Tribonectins |
| CA2399039C (en) * | 2000-02-03 | 2009-09-22 | Denki Kagaku Kogyo Kabushiki Kaisha | Hyaluronic acid gel, method of its production and medical material containing it |
| US6989156B2 (en) | 2001-04-23 | 2006-01-24 | Nucryst Pharmaceuticals Corp. | Therapeutic treatments using the direct application of antimicrobial metal compositions |
| US7026500B2 (en) * | 2000-08-24 | 2006-04-11 | University Of Tennessee Research Foundation | Halogenated selective androgen receptor modulators and methods of use thereof |
| PT1343474E (pt) * | 2000-12-20 | 2010-04-19 | Alcon Inc | Solução de irrigação intra-ocular com características de fluidez aperfeiçoadas |
| AU2002232437A1 (en) * | 2000-12-20 | 2002-07-01 | Alcon Universal Ltd. | Ophthalmic lubricating solution adapted for use in lasik surgery |
| US6815074B2 (en) | 2001-05-30 | 2004-11-09 | Novartis Ag | Polymeric materials for making contact lenses |
| CN1980582B (zh) * | 2001-08-17 | 2010-12-22 | 美你康株式会社 | 用于用后即弃式软隐形眼镜的包装 |
| US20030134810A1 (en) * | 2001-10-09 | 2003-07-17 | Chris Springate | Methods and compositions comprising biocompatible materials useful for the administration of therapeutic agents |
| TWI255224B (en) * | 2002-01-09 | 2006-05-21 | Novartis Ag | Polymeric articles having a lubricious coating and method for making the same |
| AR038926A1 (es) | 2002-03-13 | 2005-02-02 | Novartis Ag | Materiales con contenido de multiples capas de vesiculas |
| SE0201479D0 (sv) * | 2002-05-16 | 2002-05-16 | Pharmacia Groningen Bv | Kit and method in eye surgery |
| US20050196370A1 (en) | 2003-03-18 | 2005-09-08 | Zhi-Jian Yu | Stable ophthalmic oil-in-water emulsions with sodium hyaluronate for alleviating dry eye |
| US20050074497A1 (en) | 2003-04-09 | 2005-04-07 | Schultz Clyde L. | Hydrogels used to deliver medicaments to the eye for the treatment of posterior segment diseases |
| NZ545145A (en) * | 2003-08-06 | 2009-07-31 | Nirmal Mulye | Pharmaceutical composition containing water soluble drug |
| KR101078202B1 (ko) * | 2003-08-14 | 2011-11-01 | 와이어쓰 엘엘씨 | 재조합 루브리신 분자 및 이의 용도 |
| US7087237B2 (en) * | 2003-09-19 | 2006-08-08 | Advanced Ocular Systems Limited | Ocular solutions |
| WO2005027933A1 (en) | 2003-09-23 | 2005-03-31 | The Corporation Of The Trustees Of The Order Of The Sisters Of Mercy In Queensland | Unsaturated phosphatidylcholines and uses thereof |
| US20070275032A1 (en) * | 2004-03-05 | 2007-11-29 | Synthes (U.S.A.) | Use Of A Mixture For The Production Of An Agent For Treating Defective Or Degenerated Cartilage In The Production Of Natural Cartilage Replacement In Vitro |
| US20090060933A1 (en) | 2004-06-14 | 2009-03-05 | Estell David A | Proteases producing an altered immunogenic response and methods of making and using the same |
| US20050287223A1 (en) * | 2004-06-23 | 2005-12-29 | Peyman Gholam A | Use of amniotic membrane as biocompatible devices |
| WO2006088491A2 (en) * | 2004-06-29 | 2006-08-24 | Massachusetts Institute Of Technology | Methods and compositions related to the modulation of intercellular junctions |
| JP2008507553A (ja) * | 2004-07-23 | 2008-03-13 | ミューコサル セラピューティクス リミテッド ライアビリディ カンパニー | 粘性補給のための組成物および方法 |
| US7662509B2 (en) * | 2004-10-29 | 2010-02-16 | Medtronic, Inc. | Lithium-ion battery |
| CN101252936A (zh) * | 2005-03-02 | 2008-08-27 | 奈森特医药公司 | 眼用组合物的药学可接受的载体 |
| AU2006247136C1 (en) * | 2005-05-17 | 2020-01-16 | Bausch + Lomb Ireland Limited | Compositions and methods for treatment of eye disorders |
| US20080213274A1 (en) | 2005-10-28 | 2008-09-04 | Sabbadini Roger A | Compositions and methods for the treatment and prevention of fibrotic, inflammatory, and neovascularization conditions of the eye |
| JP5549045B2 (ja) * | 2006-01-13 | 2014-07-16 | 大正製薬株式会社 | 蒸発亢進型ドライアイの予防又は改善用水性点眼剤 |
| US20080094573A1 (en) * | 2006-04-04 | 2008-04-24 | Vermette Patrick | Surface-modified materials, such as contact lenses, methods and kits for their preparation, and uses thereof |
| US9539202B2 (en) * | 2006-04-28 | 2017-01-10 | Universidad Complutense De Madrid | Formulation of liposomal vesicles in aqueous solutions with lachrymal film characteristics |
| US20070264226A1 (en) * | 2006-05-10 | 2007-11-15 | Karagoezian Hampar L | Synergistically enhanced disinfecting solutions |
| PT2054049E (pt) * | 2006-08-24 | 2016-06-02 | Univ Tennessee Res Found | Acilanilidas substituídas e métodos de utilização das mesmas |
| US20080097606A1 (en) * | 2006-10-19 | 2008-04-24 | Cragg Andrew H | Knee joint prosthesis and hyaluronate compositions for treatment of osteoarthritis |
| US20080197324A1 (en) * | 2007-02-20 | 2008-08-21 | Fang Zhao | Ophthalmic composition containing a polyol-acid copolymer |
| US20090068247A1 (en) * | 2007-09-12 | 2009-03-12 | Mucosal Therapeutics | Biocompatible devices coated with a tribonectin and methods for their production |
| RU2488863C2 (ru) * | 2007-12-20 | 2013-07-27 | Новартис Аг | Способ изготовления контактных линз |
| SI2915529T1 (sl) * | 2008-05-07 | 2017-09-29 | The Regents Of The University Of California | Terapevtska regeneracija in obogatitev lubrikacije okularne površine |
| US8506944B2 (en) * | 2008-05-07 | 2013-08-13 | The Regents Of The University Of California | Replenishment and enrichment of ocular surface lubrication |
-
2009
- 2009-04-08 SI SI200931699T patent/SI2915529T1/sl unknown
- 2009-04-08 RU RU2010147935/15A patent/RU2510274C2/ru active
- 2009-04-08 LT LTEP15151634.1T patent/LT2915529T/lt unknown
- 2009-04-08 WO PCT/US2009/039887 patent/WO2009137217A2/en not_active Ceased
- 2009-04-08 DK DK15151634.1T patent/DK2915529T3/en active
- 2009-04-08 EP EP09743204.1A patent/EP2285364B1/en active Active
- 2009-04-08 PL PL09743204T patent/PL2285364T3/pl unknown
- 2009-04-08 JP JP2011508534A patent/JP5508398B2/ja active Active
- 2009-04-08 CN CN201610003437.XA patent/CN105664136A/zh active Pending
- 2009-04-08 ES ES09743204T patent/ES2530723T3/es active Active
- 2009-04-08 HR HRP20150097AT patent/HRP20150097T1/hr unknown
- 2009-04-08 EP EP15151634.1A patent/EP2915529B1/en active Active
- 2009-04-08 ES ES15151634.1T patent/ES2633792T3/es active Active
- 2009-04-08 SI SI200931129T patent/SI2285364T1/sl unknown
- 2009-04-08 HU HUE09743204A patent/HUE024146T2/en unknown
- 2009-04-08 DK DK09743204.1T patent/DK2285364T3/en active
- 2009-04-08 PL PL15151634T patent/PL2915529T3/pl unknown
- 2009-04-08 PT PT97432041T patent/PT2285364E/pt unknown
- 2009-04-08 PT PT151516341T patent/PT2915529T/pt unknown
- 2009-04-08 CA CA2722913A patent/CA2722913C/en active Active
- 2009-04-08 CN CN200980126381.5A patent/CN102164593B/zh active Active
- 2009-05-06 JP JP2011508634A patent/JP5474054B2/ja active Active
- 2009-05-06 WO PCT/US2009/043015 patent/WO2009137602A1/en not_active Ceased
- 2009-05-06 HR HRP20191732 patent/HRP20191732T1/hr unknown
- 2009-05-06 JP JP2011508633A patent/JP5439652B2/ja active Active
- 2009-05-06 EP EP09743589.5A patent/EP2276497B1/en active Active
- 2009-05-06 WO PCT/US2009/043018 patent/WO2009137603A1/en not_active Ceased
- 2009-05-06 CA CA2723144A patent/CA2723144C/en active Active
- 2009-05-06 PL PL09743588T patent/PL2276496T3/pl unknown
- 2009-05-06 HU HUE09743588A patent/HUE045686T2/hu unknown
- 2009-05-06 LT LT09743588T patent/LT2276496T/lt unknown
- 2009-05-06 CA CA2722944A patent/CA2722944A1/en not_active Abandoned
- 2009-05-06 DK DK09743588.7T patent/DK2276496T3/da active
- 2009-05-06 EP EP09743588.7A patent/EP2276496B1/en active Active
- 2009-05-06 ES ES09743588T patent/ES2748139T3/es active Active
- 2009-05-06 SI SI200932001T patent/SI2276496T1/sl unknown
-
2010
- 2010-11-05 US US12/940,425 patent/US9138457B2/en active Active
- 2010-11-05 US US12/940,370 patent/US9393285B2/en active Active
- 2010-11-05 US US12/940,454 patent/US8563028B2/en active Active
-
2013
- 2013-09-20 US US14/032,233 patent/US8945604B2/en active Active
-
2014
- 2014-05-08 US US14/272,634 patent/US9248161B2/en active Active
-
2015
- 2015-08-20 US US14/831,317 patent/US9421241B2/en active Active
- 2015-12-18 US US14/974,055 patent/US9585936B2/en active Active
-
2016
- 2016-04-06 US US15/091,665 patent/US9730978B2/en active Active
-
2017
- 2017-07-10 US US15/645,561 patent/US20180028598A1/en not_active Abandoned
- 2017-07-13 HR HRP20171079TT patent/HRP20171079T1/hr unknown
- 2017-07-14 CY CY20171100751T patent/CY1119122T1/el unknown
-
2019
- 2019-10-03 CY CY20191101037T patent/CY1122638T1/el unknown
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP2011519949A5 (enExample) | ||
| JP5474054B2 (ja) | 眼の境界潤滑を増加させるための、眼科治療の装置、及び、その使用方法、 | |
| US8506944B2 (en) | Replenishment and enrichment of ocular surface lubrication | |
| EP3347034B1 (en) | A hepatocyte growth factor receptor (hgfr)-binding composition for use in a method of treating corneal haze or scarring | |
| EP3096777B1 (en) | Goblet cell replacement therapy | |
| US20210169990A9 (en) | Compostions for Treating Dry Eye Disease |