CN116761630A - 一种药物递送用隐形眼镜和眼科用药物组合物 - Google Patents
一种药物递送用隐形眼镜和眼科用药物组合物 Download PDFInfo
- Publication number
- CN116761630A CN116761630A CN202280008993.XA CN202280008993A CN116761630A CN 116761630 A CN116761630 A CN 116761630A CN 202280008993 A CN202280008993 A CN 202280008993A CN 116761630 A CN116761630 A CN 116761630A
- Authority
- CN
- China
- Prior art keywords
- drug
- contact lens
- drug delivery
- acid
- chamber portion
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 238000012377 drug delivery Methods 0.000 title claims abstract description 101
- 239000008194 pharmaceutical composition Substances 0.000 title description 4
- 239000003814 drug Substances 0.000 claims abstract description 224
- 229940079593 drug Drugs 0.000 claims abstract description 169
- 230000000903 blocking effect Effects 0.000 claims description 61
- -1 rituximab Chemical compound 0.000 claims description 32
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 27
- 238000013270 controlled release Methods 0.000 claims description 19
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 19
- 210000005252 bulbus oculi Anatomy 0.000 claims description 16
- 150000001875 compounds Chemical class 0.000 claims description 12
- 108090000765 processed proteins & peptides Proteins 0.000 claims description 12
- BYJAVTDNIXVSPW-UHFFFAOYSA-N tetryzoline Chemical compound N1CCN=C1C1C2=CC=CC=C2CCC1 BYJAVTDNIXVSPW-UHFFFAOYSA-N 0.000 claims description 12
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 claims description 11
- 229960001031 glucose Drugs 0.000 claims description 11
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 11
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 11
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 11
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 10
- 229920002125 Sokalan® Polymers 0.000 claims description 10
- 210000001508 eye Anatomy 0.000 claims description 10
- 230000004438 eyesight Effects 0.000 claims description 10
- 230000035699 permeability Effects 0.000 claims description 10
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 10
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 10
- 210000004369 blood Anatomy 0.000 claims description 9
- 239000008280 blood Substances 0.000 claims description 9
- 239000003995 emulsifying agent Substances 0.000 claims description 9
- 239000008103 glucose Substances 0.000 claims description 9
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 9
- 229960004063 propylene glycol Drugs 0.000 claims description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 9
- 239000003381 stabilizer Substances 0.000 claims description 9
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 8
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 8
- 239000002202 Polyethylene glycol Substances 0.000 claims description 8
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 8
- 229940071826 hydroxyethyl cellulose Drugs 0.000 claims description 8
- 229920001223 polyethylene glycol Polymers 0.000 claims description 8
- 235000002639 sodium chloride Nutrition 0.000 claims description 8
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 7
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 claims description 7
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 7
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 7
- 229920000053 polysorbate 80 Polymers 0.000 claims description 7
- 229940068968 polysorbate 80 Drugs 0.000 claims description 7
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 7
- 229940068984 polyvinyl alcohol Drugs 0.000 claims description 7
- MPDGHEJMBKOTSU-YKLVYJNSSA-N 18beta-glycyrrhetic acid Chemical compound C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C(O)=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](O)C1(C)C MPDGHEJMBKOTSU-YKLVYJNSSA-N 0.000 claims description 6
- CNIIGCLFLJGOGP-UHFFFAOYSA-N 2-(1-naphthalenylmethyl)-4,5-dihydro-1H-imidazole Chemical compound C=1C=CC2=CC=CC=C2C=1CC1=NCCN1 CNIIGCLFLJGOGP-UHFFFAOYSA-N 0.000 claims description 6
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 6
- 229920002307 Dextran Polymers 0.000 claims description 6
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims description 6
- VYGQUTWHTHXGQB-FFHKNEKCSA-N Retinol Palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C VYGQUTWHTHXGQB-FFHKNEKCSA-N 0.000 claims description 6
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 claims description 6
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 claims description 6
- POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 claims description 6
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 6
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 claims description 6
- RMRCNWBMXRMIRW-BYFNXCQMSA-M cyanocobalamin Chemical compound N#C[Co+]N([C@]1([H])[C@H](CC(N)=O)[C@]\2(CCC(=O)NC[C@H](C)OP(O)(=O)OC3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)C)C/2=C(C)\C([C@H](C/2(C)C)CCC(N)=O)=N\C\2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O RMRCNWBMXRMIRW-BYFNXCQMSA-M 0.000 claims description 6
- 229960001259 diclofenac Drugs 0.000 claims description 6
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 claims description 6
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 6
- LXNHXLLTXMVWPM-UHFFFAOYSA-N pyridoxine Chemical compound CC1=NC=C(CO)C(CO)=C1O LXNHXLLTXMVWPM-UHFFFAOYSA-N 0.000 claims description 6
- XOAAWQZATWQOTB-UHFFFAOYSA-N taurine Chemical compound NCCS(O)(=O)=O XOAAWQZATWQOTB-UHFFFAOYSA-N 0.000 claims description 6
- 229960000337 tetryzoline Drugs 0.000 claims description 6
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 5
- 229960001631 carbomer Drugs 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 239000007951 isotonicity adjuster Substances 0.000 claims description 5
- GGXICVAJURFBLW-CEYXHVGTSA-N latanoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1CC[C@@H](O)CCC1=CC=CC=C1 GGXICVAJURFBLW-CEYXHVGTSA-N 0.000 claims description 5
- 229960001160 latanoprost Drugs 0.000 claims description 5
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims description 5
- 239000003755 preservative agent Substances 0.000 claims description 5
- 230000002335 preservative effect Effects 0.000 claims description 5
- 239000011780 sodium chloride Substances 0.000 claims description 5
- QCHFTSOMWOSFHM-WPRPVWTQSA-N (+)-Pilocarpine Chemical compound C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C QCHFTSOMWOSFHM-WPRPVWTQSA-N 0.000 claims description 4
- BSUGIIZTULADOL-YWPYICTPSA-N (3s,4ar,5s)-4a,5-dimethyl-3-prop-1-en-2-yl-2,3,4,5,6,7-hexahydronaphthalen-1-one Chemical compound O=C1C[C@@H](C(C)=C)C[C@]2(C)[C@@H](C)CCC=C21 BSUGIIZTULADOL-YWPYICTPSA-N 0.000 claims description 4
- TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-N 0.000 claims description 4
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 4
- GSDSWSVVBLHKDQ-JTQLQIEISA-N Levofloxacin Chemical compound C([C@@H](N1C2=C(C(C(C(O)=O)=C1)=O)C=C1F)C)OC2=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-JTQLQIEISA-N 0.000 claims description 4
- ALLWOAVDORUJLA-UHFFFAOYSA-N Rebamipida Chemical compound C=1C(=O)NC2=CC=CC=C2C=1CC(C(=O)O)NC(=O)C1=CC=C(Cl)C=C1 ALLWOAVDORUJLA-UHFFFAOYSA-N 0.000 claims description 4
- QCHFTSOMWOSFHM-UHFFFAOYSA-N SJ000285536 Natural products C1OC(=O)C(CC)C1CC1=CN=CN1C QCHFTSOMWOSFHM-UHFFFAOYSA-N 0.000 claims description 4
- 229960004150 aciclovir Drugs 0.000 claims description 4
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 claims description 4
- 229960004324 betaxolol Drugs 0.000 claims description 4
- CHDPSNLJFOQTRK-UHFFFAOYSA-N betaxolol hydrochloride Chemical compound [Cl-].C1=CC(OCC(O)C[NH2+]C(C)C)=CC=C1CCOCC1CC1 CHDPSNLJFOQTRK-UHFFFAOYSA-N 0.000 claims description 4
- HCRKCZRJWPKOAR-JTQLQIEISA-N brinzolamide Chemical compound CCN[C@H]1CN(CCCOC)S(=O)(=O)C2=C1C=C(S(N)(=O)=O)S2 HCRKCZRJWPKOAR-JTQLQIEISA-N 0.000 claims description 4
- 229960000722 brinzolamide Drugs 0.000 claims description 4
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 4
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 4
- 229960000590 celecoxib Drugs 0.000 claims description 4
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 claims description 4
- 229960002086 dextran Drugs 0.000 claims description 4
- 229960003933 dorzolamide Drugs 0.000 claims description 4
- IAVUPMFITXYVAF-XPUUQOCRSA-N dorzolamide Chemical compound CCN[C@H]1C[C@H](C)S(=O)(=O)C2=C1C=C(S(N)(=O)=O)S2 IAVUPMFITXYVAF-XPUUQOCRSA-N 0.000 claims description 4
- YMTINGFKWWXKFG-UHFFFAOYSA-N fenofibrate Chemical compound C1=CC(OC(C)(C)C(=O)OC(C)C)=CC=C1C(=O)C1=CC=C(Cl)C=C1 YMTINGFKWWXKFG-UHFFFAOYSA-N 0.000 claims description 4
- 229960002297 fenofibrate Drugs 0.000 claims description 4
- 229960003376 levofloxacin Drugs 0.000 claims description 4
- 229960004114 olopatadine Drugs 0.000 claims description 4
- JBIMVDZLSHOPLA-LSCVHKIXSA-N olopatadine Chemical compound C1OC2=CC=C(CC(O)=O)C=C2C(=C/CCN(C)C)\C2=CC=CC=C21 JBIMVDZLSHOPLA-LSCVHKIXSA-N 0.000 claims description 4
- 229960001416 pilocarpine Drugs 0.000 claims description 4
- 229960002702 piroxicam Drugs 0.000 claims description 4
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 claims description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 4
- 229950004535 rebamipide Drugs 0.000 claims description 4
- 229960005404 sulfamethoxazole Drugs 0.000 claims description 4
- JLKIGFTWXXRPMT-UHFFFAOYSA-N sulphamethoxazole Chemical compound O1C(C)=CC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 JLKIGFTWXXRPMT-UHFFFAOYSA-N 0.000 claims description 4
- 229960004605 timolol Drugs 0.000 claims description 4
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 claims description 3
- 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 claims description 3
- FFTVPQUHLQBXQZ-KVUCHLLUSA-N (4s,4as,5ar,12ar)-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=C(N(C)C)C=CC(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O FFTVPQUHLQBXQZ-KVUCHLLUSA-N 0.000 claims description 3
- XUBOMFCQGDBHNK-JTQLQIEISA-N (S)-gatifloxacin Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CCN[C@@H](C)C1 XUBOMFCQGDBHNK-JTQLQIEISA-N 0.000 claims description 3
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 claims description 3
- GSDSWSVVBLHKDQ-UHFFFAOYSA-N 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 claims description 3
- OPVPGKGADVGKTG-BQBZGAKWSA-N Ac-Asp-Glu Chemical compound CC(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(O)=O)CCC(O)=O OPVPGKGADVGKTG-BQBZGAKWSA-N 0.000 claims description 3
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 claims description 3
- XYLJNLCSTIOKRM-UHFFFAOYSA-N Alphagan Chemical compound C1=CC2=NC=CN=C2C(Br)=C1NC1=NCCN1 XYLJNLCSTIOKRM-UHFFFAOYSA-N 0.000 claims description 3
- DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 claims description 3
- 229930003347 Atropine Natural products 0.000 claims description 3
- MBUVEWMHONZEQD-UHFFFAOYSA-N Azeptin Chemical compound C1CN(C)CCCC1N1C(=O)C2=CC=CC=C2C(CC=2C=CC(Cl)=CC=2)=N1 MBUVEWMHONZEQD-UHFFFAOYSA-N 0.000 claims description 3
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 3
- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 claims description 3
- 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 claims description 3
- 108010036949 Cyclosporine Proteins 0.000 claims description 3
- AUNGANRZJHBGPY-UHFFFAOYSA-N D-Lyxoflavin Natural products OCC(O)C(O)C(O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-UHFFFAOYSA-N 0.000 claims description 3
- SNPLKNRPJHDVJA-ZETCQYMHSA-N D-panthenol Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCCO SNPLKNRPJHDVJA-ZETCQYMHSA-N 0.000 claims description 3
- IECPWNUMDGFDKC-UHFFFAOYSA-N Fusicsaeure Natural products C12C(O)CC3C(=C(CCC=C(C)C)C(O)=O)C(OC(C)=O)CC3(C)C1(C)CCC1C2(C)CCC(O)C1C IECPWNUMDGFDKC-UHFFFAOYSA-N 0.000 claims description 3
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 claims description 3
- 229930182566 Gentamicin Natural products 0.000 claims description 3
- MPDGHEJMBKOTSU-UHFFFAOYSA-N Glycyrrhetinsaeure Natural products C12C(=O)C=C3C4CC(C)(C(O)=O)CCC4(C)CCC3(C)C1(C)CCC1C2(C)CCC(O)C1(C)C MPDGHEJMBKOTSU-UHFFFAOYSA-N 0.000 claims description 3
- 229920002907 Guar gum Polymers 0.000 claims description 3
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 claims description 3
- ZCVMWBYGMWKGHF-UHFFFAOYSA-N Ketotifene Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2CC(=O)C2=C1C=CS2 ZCVMWBYGMWKGHF-UHFFFAOYSA-N 0.000 claims description 3
- DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 claims description 3
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 claims description 3
- RHGKLRLOHDJJDR-BYPYZUCNSA-N L-citrulline Chemical compound NC(=O)NCCC[C@H]([NH3+])C([O-])=O RHGKLRLOHDJJDR-BYPYZUCNSA-N 0.000 claims description 3
- 239000004166 Lanolin Substances 0.000 claims description 3
- VTAJIXDZFCRWBR-UHFFFAOYSA-N Licoricesaponin B2 Natural products C1C(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2)C(O)=O)C)(C)CC2)(C)C2C(C)(C)CC1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O VTAJIXDZFCRWBR-UHFFFAOYSA-N 0.000 claims description 3
- IJHNSHDBIRRJRN-UHFFFAOYSA-N N,N-dimethyl-3-phenyl-3-(2-pyridinyl)-1-propanamine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=CC=C1 IJHNSHDBIRRJRN-UHFFFAOYSA-N 0.000 claims description 3
- RHGKLRLOHDJJDR-UHFFFAOYSA-N Ndelta-carbamoyl-DL-ornithine Natural products OC(=O)C(N)CCCNC(N)=O RHGKLRLOHDJJDR-UHFFFAOYSA-N 0.000 claims description 3
- 229930193140 Neomycin Natural products 0.000 claims description 3
- NMLMACJWHPHKGR-NCOIDOBVSA-N P(1),P(4)-bis(uridin-5'-yl) tetraphosphate Chemical compound N1([C@@H]2O[C@@H]([C@H]([C@H]2O)O)COP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@H]([C@@H](O2)N2C(NC(=O)C=C2)=O)O)O)C=CC(=O)NC1=O NMLMACJWHPHKGR-NCOIDOBVSA-N 0.000 claims description 3
- TVQZAMVBTVNYLA-UHFFFAOYSA-N Pranoprofen Chemical compound C1=CC=C2CC3=CC(C(C(O)=O)C)=CC=C3OC2=N1 TVQZAMVBTVNYLA-UHFFFAOYSA-N 0.000 claims description 3
- VYGQUTWHTHXGQB-UHFFFAOYSA-N Retinol hexadecanoate Natural products CCCCCCCCCCCCCCCC(=O)OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C VYGQUTWHTHXGQB-UHFFFAOYSA-N 0.000 claims description 3
- BUGBHKTXTAQXES-UHFFFAOYSA-N Selenium Chemical compound [Se] BUGBHKTXTAQXES-UHFFFAOYSA-N 0.000 claims description 3
- 239000004098 Tetracycline Substances 0.000 claims description 3
- JZRWCGZRTZMZEH-UHFFFAOYSA-N Thiamine Natural products CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 claims description 3
- KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 claims description 3
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 claims description 3
- KIPLYOUQVMMOHB-MXWBXKMOSA-L [Ca++].CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O.CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O Chemical compound [Ca++].CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O.CN(C)[C@H]1[C@@H]2[C@@H](O)[C@H]3C(=C([O-])[C@]2(O)C(=O)C(C(N)=O)=C1O)C(=O)c1c(O)cccc1[C@@]3(C)O KIPLYOUQVMMOHB-MXWBXKMOSA-L 0.000 claims description 3
- 229960000571 acetazolamide Drugs 0.000 claims description 3
- BZKPWHYZMXOIDC-UHFFFAOYSA-N acetazolamide Chemical compound CC(=O)NC1=NN=C(S(N)(=O)=O)S1 BZKPWHYZMXOIDC-UHFFFAOYSA-N 0.000 claims description 3
- 229960001919 alcaftadine Drugs 0.000 claims description 3
- MWTBKTRZPHJQLH-UHFFFAOYSA-N alcaftadine Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2CCN2C(C=O)=CN=C21 MWTBKTRZPHJQLH-UHFFFAOYSA-N 0.000 claims description 3
- 229960000458 allantoin Drugs 0.000 claims description 3
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 claims description 3
- 235000010323 ascorbic acid Nutrition 0.000 claims description 3
- 239000011668 ascorbic acid Substances 0.000 claims description 3
- 229960005070 ascorbic acid Drugs 0.000 claims description 3
- 229960001230 asparagine Drugs 0.000 claims description 3
- 235000009582 asparagine Nutrition 0.000 claims description 3
- 235000003704 aspartic acid Nutrition 0.000 claims description 3
- 229960005261 aspartic acid Drugs 0.000 claims description 3
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 claims description 3
- 229960000396 atropine Drugs 0.000 claims description 3
- 229960004574 azelastine Drugs 0.000 claims description 3
- 229960002071 bepotastine Drugs 0.000 claims description 3
- YWGDOWXRIALTES-NRFANRHFSA-N bepotastine Chemical compound C1CN(CCCC(=O)O)CCC1O[C@H](C=1N=CC=CC=1)C1=CC=C(Cl)C=C1 YWGDOWXRIALTES-NRFANRHFSA-N 0.000 claims description 3
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 claims description 3
- AQOKCDNYWBIDND-FTOWTWDKSA-N bimatoprost Chemical compound CCNC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)CCC1=CC=CC=C1 AQOKCDNYWBIDND-FTOWTWDKSA-N 0.000 claims description 3
- 229960002470 bimatoprost Drugs 0.000 claims description 3
- 229960003679 brimonidine Drugs 0.000 claims description 3
- ZBPLOVFIXSTCRZ-UHFFFAOYSA-N bromfenac Chemical compound NC1=C(CC(O)=O)C=CC=C1C(=O)C1=CC=C(Br)C=C1 ZBPLOVFIXSTCRZ-UHFFFAOYSA-N 0.000 claims description 3
- 239000001110 calcium chloride Substances 0.000 claims description 3
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 3
- 229960002713 calcium chloride Drugs 0.000 claims description 3
- 229940105329 carboxymethylcellulose Drugs 0.000 claims description 3
- 229960005361 cefaclor Drugs 0.000 claims description 3
- QYIYFLOTGYLRGG-GPCCPHFNSA-N cefaclor Chemical compound C1([C@H](C(=O)N[C@@H]2C(N3C(=C(Cl)CS[C@@H]32)C(O)=O)=O)N)=CC=CC=C1 QYIYFLOTGYLRGG-GPCCPHFNSA-N 0.000 claims description 3
- 229960003791 cefmenoxime Drugs 0.000 claims description 3
- HJJDBAOLQAWBMH-YCRCPZNHSA-N cefmenoxime Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NN=NN1C HJJDBAOLQAWBMH-YCRCPZNHSA-N 0.000 claims description 3
- 229960002798 cetrimide Drugs 0.000 claims description 3
- 229960005091 chloramphenicol Drugs 0.000 claims description 3
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 claims description 3
- 229960003291 chlorphenamine Drugs 0.000 claims description 3
- SOYKEARSMXGVTM-UHFFFAOYSA-N chlorphenamine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 SOYKEARSMXGVTM-UHFFFAOYSA-N 0.000 claims description 3
- 229960001265 ciclosporin Drugs 0.000 claims description 3
- 229960003405 ciprofloxacin Drugs 0.000 claims description 3
- 235000013477 citrulline Nutrition 0.000 claims description 3
- 229960002173 citrulline Drugs 0.000 claims description 3
- 229960000265 cromoglicic acid Drugs 0.000 claims description 3
- 229960002104 cyanocobalamin Drugs 0.000 claims description 3
- 235000000639 cyanocobalamin Nutrition 0.000 claims description 3
- 239000011666 cyanocobalamin Substances 0.000 claims description 3
- 229930182912 cyclosporin Natural products 0.000 claims description 3
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 3
- 229960003957 dexamethasone Drugs 0.000 claims description 3
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 claims description 3
- 229950003529 diquafosol Drugs 0.000 claims description 3
- VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 0.000 claims description 3
- 229960003720 enoxolone Drugs 0.000 claims description 3
- 229960003276 erythromycin Drugs 0.000 claims description 3
- 229960002390 flurbiprofen Drugs 0.000 claims description 3
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 claims description 3
- 229960004675 fusidic acid Drugs 0.000 claims description 3
- IECPWNUMDGFDKC-MZJAQBGESA-N fusidic acid Chemical compound O[C@@H]([C@@H]12)C[C@H]3\C(=C(/CCC=C(C)C)C(O)=O)[C@@H](OC(C)=O)C[C@]3(C)[C@@]2(C)CC[C@@H]2[C@]1(C)CC[C@@H](O)[C@H]2C IECPWNUMDGFDKC-MZJAQBGESA-N 0.000 claims description 3
- 229960002963 ganciclovir Drugs 0.000 claims description 3
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 claims description 3
- 229960003923 gatifloxacin Drugs 0.000 claims description 3
- 229960002518 gentamicin Drugs 0.000 claims description 3
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 claims description 3
- 239000001685 glycyrrhizic acid Substances 0.000 claims description 3
- 229960004949 glycyrrhizic acid Drugs 0.000 claims description 3
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 claims description 3
- 235000019410 glycyrrhizin Nutrition 0.000 claims description 3
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 claims description 3
- 235000010417 guar gum Nutrition 0.000 claims description 3
- 239000000665 guar gum Substances 0.000 claims description 3
- 229960002154 guar gum Drugs 0.000 claims description 3
- 229920002674 hyaluronan Polymers 0.000 claims description 3
- 229960003160 hyaluronic acid Drugs 0.000 claims description 3
- 108010076560 isospaglumic acid Proteins 0.000 claims description 3
- 229960004752 ketorolac Drugs 0.000 claims description 3
- OZWKMVRBQXNZKK-UHFFFAOYSA-N ketorolac Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 OZWKMVRBQXNZKK-UHFFFAOYSA-N 0.000 claims description 3
- 229960004958 ketotifen Drugs 0.000 claims description 3
- 229940039717 lanolin Drugs 0.000 claims description 3
- 235000019388 lanolin Nutrition 0.000 claims description 3
- IXHBTMCLRNMKHZ-LBPRGKRZSA-N levobunolol Chemical compound O=C1CCCC2=C1C=CC=C2OC[C@@H](O)CNC(C)(C)C IXHBTMCLRNMKHZ-LBPRGKRZSA-N 0.000 claims description 3
- 229960000831 levobunolol Drugs 0.000 claims description 3
- 229960004305 lodoxamide Drugs 0.000 claims description 3
- RVGLGHVJXCETIO-UHFFFAOYSA-N lodoxamide Chemical compound OC(=O)C(=O)NC1=CC(C#N)=CC(NC(=O)C(O)=O)=C1Cl RVGLGHVJXCETIO-UHFFFAOYSA-N 0.000 claims description 3
- 229960002422 lomefloxacin Drugs 0.000 claims description 3
- ZEKZLJVOYLTDKK-UHFFFAOYSA-N lomefloxacin Chemical compound FC1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNC(C)C1 ZEKZLJVOYLTDKK-UHFFFAOYSA-N 0.000 claims description 3
- 229960001798 loteprednol Drugs 0.000 claims description 3
- YPZVAYHNBBHPTO-MXRBDKCISA-N loteprednol Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)OCCl)[C@@H]4[C@@H]3CCC2=C1 YPZVAYHNBBHPTO-MXRBDKCISA-N 0.000 claims description 3
- 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 claims description 3
- 229960004083 methazolamide Drugs 0.000 claims description 3
- FLOSMHQXBMRNHR-DAXSKMNVSA-N methazolamide Chemical compound CC(=O)\N=C1/SC(S(N)(=O)=O)=NN1C FLOSMHQXBMRNHR-DAXSKMNVSA-N 0.000 claims description 3
- 229960003702 moxifloxacin Drugs 0.000 claims description 3
- FABPRXSRWADJSP-MEDUHNTESA-N moxifloxacin Chemical compound COC1=C(N2C[C@H]3NCCC[C@H]3C2)C(F)=CC(C(C(C(O)=O)=C2)=O)=C1N2C1CC1 FABPRXSRWADJSP-MEDUHNTESA-N 0.000 claims description 3
- 229960005016 naphazoline Drugs 0.000 claims description 3
- 229960004927 neomycin Drugs 0.000 claims description 3
- 229960002362 neostigmine Drugs 0.000 claims description 3
- LULNWZDBKTWDGK-UHFFFAOYSA-M neostigmine bromide Chemical compound [Br-].CN(C)C(=O)OC1=CC=CC([N+](C)(C)C)=C1 LULNWZDBKTWDGK-UHFFFAOYSA-M 0.000 claims description 3
- 229960001002 nepafenac Drugs 0.000 claims description 3
- QEFAQIPZVLVERP-UHFFFAOYSA-N nepafenac Chemical compound NC(=O)CC1=CC=CC(C(=O)C=2C=CC=CC=2)=C1N QEFAQIPZVLVERP-UHFFFAOYSA-N 0.000 claims description 3
- 229960001180 norfloxacin Drugs 0.000 claims description 3
- OGJPXUAPXNRGGI-UHFFFAOYSA-N norfloxacin Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 OGJPXUAPXNRGGI-UHFFFAOYSA-N 0.000 claims description 3
- 229960001699 ofloxacin Drugs 0.000 claims description 3
- 229940101267 panthenol Drugs 0.000 claims description 3
- 235000020957 pantothenol Nutrition 0.000 claims description 3
- 239000011619 pantothenol Substances 0.000 claims description 3
- 229960001190 pheniramine Drugs 0.000 claims description 3
- 239000004584 polyacrylic acid Substances 0.000 claims description 3
- 229920001184 polypeptide Polymers 0.000 claims description 3
- 229960004839 potassium iodide Drugs 0.000 claims description 3
- 229960003101 pranoprofen Drugs 0.000 claims description 3
- 229960005205 prednisolone Drugs 0.000 claims description 3
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 claims description 3
- 235000008160 pyridoxine Nutrition 0.000 claims description 3
- 239000011677 pyridoxine Substances 0.000 claims description 3
- 229960003471 retinol Drugs 0.000 claims description 3
- 235000020944 retinol Nutrition 0.000 claims description 3
- 239000011607 retinol Substances 0.000 claims description 3
- 229940108325 retinyl palmitate Drugs 0.000 claims description 3
- 235000019172 retinyl palmitate Nutrition 0.000 claims description 3
- 239000011769 retinyl palmitate Substances 0.000 claims description 3
- 235000019192 riboflavin Nutrition 0.000 claims description 3
- 229960002477 riboflavin Drugs 0.000 claims description 3
- 239000002151 riboflavin Substances 0.000 claims description 3
- 229960001487 rimexolone Drugs 0.000 claims description 3
- QTTRZHGPGKRAFB-OOKHYKNYSA-N rimexolone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CC)(C)[C@@]1(C)C[C@@H]2O QTTRZHGPGKRAFB-OOKHYKNYSA-N 0.000 claims description 3
- 229960004641 rituximab Drugs 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 229910052711 selenium Inorganic materials 0.000 claims description 3
- 239000011669 selenium Substances 0.000 claims description 3
- 229960002668 sodium chloride Drugs 0.000 claims description 3
- 235000009518 sodium iodide Nutrition 0.000 claims description 3
- 229940083599 sodium iodide Drugs 0.000 claims description 3
- 229960004458 tafluprost Drugs 0.000 claims description 3
- WSNODXPBBALQOF-VEJSHDCNSA-N tafluprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\C(F)(F)COC1=CC=CC=C1 WSNODXPBBALQOF-VEJSHDCNSA-N 0.000 claims description 3
- 229960003080 taurine Drugs 0.000 claims description 3
- 229940063650 terramycin Drugs 0.000 claims description 3
- 229960002180 tetracycline Drugs 0.000 claims description 3
- 229930101283 tetracycline Natural products 0.000 claims description 3
- 235000019364 tetracycline Nutrition 0.000 claims description 3
- 150000003522 tetracyclines Chemical class 0.000 claims description 3
- 229960003495 thiamine Drugs 0.000 claims description 3
- 235000019157 thiamine Nutrition 0.000 claims description 3
- KYMBYSLLVAOCFI-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SCN1CC1=CN=C(C)N=C1N KYMBYSLLVAOCFI-UHFFFAOYSA-N 0.000 claims description 3
- 239000011721 thiamine Substances 0.000 claims description 3
- 235000010384 tocopherol Nutrition 0.000 claims description 3
- 229960001295 tocopherol Drugs 0.000 claims description 3
- 229930003799 tocopherol Natural products 0.000 claims description 3
- 239000011732 tocopherol Substances 0.000 claims description 3
- 229960004394 topiramate Drugs 0.000 claims description 3
- 229960005342 tranilast Drugs 0.000 claims description 3
- NZHGWWWHIYHZNX-CSKARUKUSA-N tranilast Chemical compound C1=C(OC)C(OC)=CC=C1\C=C\C(=O)NC1=CC=CC=C1C(O)=O NZHGWWWHIYHZNX-CSKARUKUSA-N 0.000 claims description 3
- MKPLKVHSHYCHOC-AHTXBMBWSA-N travoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)COC1=CC=CC(C(F)(F)F)=C1 MKPLKVHSHYCHOC-AHTXBMBWSA-N 0.000 claims description 3
- 229960002368 travoprost Drugs 0.000 claims description 3
- 229940074410 trehalose Drugs 0.000 claims description 3
- 229960005294 triamcinolone Drugs 0.000 claims description 3
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 claims description 3
- 229960004317 unoprostone Drugs 0.000 claims description 3
- TVHAZVBUYQMHBC-SNHXEXRGSA-N unoprostone Chemical compound CCCCCCCC(=O)CC[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(O)=O TVHAZVBUYQMHBC-SNHXEXRGSA-N 0.000 claims description 3
- 229960002004 valdecoxib Drugs 0.000 claims description 3
- LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 claims description 3
- 229960003895 verteporfin Drugs 0.000 claims description 3
- ZQFGRJWRSLZCSQ-ZSFNYQMMSA-N verteporfin Chemical compound C=1C([C@@]2([C@H](C(=O)OC)C(=CC=C22)C(=O)OC)C)=NC2=CC(C(=C2C=C)C)=NC2=CC(C(=C2CCC(O)=O)C)=NC2=CC2=NC=1C(C)=C2CCC(=O)OC ZQFGRJWRSLZCSQ-ZSFNYQMMSA-N 0.000 claims description 3
- 229940011671 vitamin b6 Drugs 0.000 claims description 3
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 claims description 3
- 229920002567 Chondroitin Polymers 0.000 claims description 2
- 108010078777 Colistin Proteins 0.000 claims description 2
- HSRJKNPTNIJEKV-UHFFFAOYSA-N Guaifenesin Chemical compound COC1=CC=CC=C1OCC(O)CO HSRJKNPTNIJEKV-UHFFFAOYSA-N 0.000 claims description 2
- 108010093965 Polymyxin B Proteins 0.000 claims description 2
- 240000000851 Vaccinium corymbosum Species 0.000 claims description 2
- 235000003095 Vaccinium corymbosum Nutrition 0.000 claims description 2
- 235000017537 Vaccinium myrtillus Nutrition 0.000 claims description 2
- OENHQHLEOONYIE-UKMVMLAPSA-N all-trans beta-carotene Natural products CC=1CCCC(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C OENHQHLEOONYIE-UKMVMLAPSA-N 0.000 claims description 2
- 235000013734 beta-carotene Nutrition 0.000 claims description 2
- 239000011648 beta-carotene Substances 0.000 claims description 2
- TUPZEYHYWIEDIH-WAIFQNFQSA-N beta-carotene Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CCCC1(C)C)C=CC=C(/C)C=CC2=CCCCC2(C)C TUPZEYHYWIEDIH-WAIFQNFQSA-N 0.000 claims description 2
- 229960002747 betacarotene Drugs 0.000 claims description 2
- 229960000397 bevacizumab Drugs 0.000 claims description 2
- 235000021014 blueberries Nutrition 0.000 claims description 2
- LWAFSWPYPHEXKX-UHFFFAOYSA-N carteolol Chemical compound N1C(=O)CCC2=C1C=CC=C2OCC(O)CNC(C)(C)C LWAFSWPYPHEXKX-UHFFFAOYSA-N 0.000 claims description 2
- 229960001222 carteolol Drugs 0.000 claims description 2
- DLGJWSVWTWEWBJ-HGGSSLSASA-N chondroitin Chemical compound CC(O)=N[C@@H]1[C@H](O)O[C@H](CO)[C@H](O)[C@@H]1OC1[C@H](O)[C@H](O)C=C(C(O)=O)O1 DLGJWSVWTWEWBJ-HGGSSLSASA-N 0.000 claims description 2
- 229960003346 colistin Drugs 0.000 claims description 2
- 229960003449 epinastine Drugs 0.000 claims description 2
- WHWZLSFABNNENI-UHFFFAOYSA-N epinastine Chemical compound C1C2=CC=CC=C2C2CN=C(N)N2C2=CC=CC=C21 WHWZLSFABNNENI-UHFFFAOYSA-N 0.000 claims description 2
- 229960004945 etoricoxib Drugs 0.000 claims description 2
- MNJVRJDLRVPLFE-UHFFFAOYSA-N etoricoxib Chemical compound C1=NC(C)=CC=C1C1=NC=C(Cl)C=C1C1=CC=C(S(C)(=O)=O)C=C1 MNJVRJDLRVPLFE-UHFFFAOYSA-N 0.000 claims description 2
- 239000000284 extract Substances 0.000 claims description 2
- 229960002146 guaifenesin Drugs 0.000 claims description 2
- 229920003063 hydroxymethyl cellulose Polymers 0.000 claims description 2
- 229940031574 hydroxymethyl cellulose Drugs 0.000 claims description 2
- OEXHQOGQTVQTAT-JRNQLAHRSA-N ipratropium Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 OEXHQOGQTVQTAT-JRNQLAHRSA-N 0.000 claims description 2
- 229960001888 ipratropium Drugs 0.000 claims description 2
- JORAUNFTUVJTNG-BSTBCYLQSA-N n-[(2s)-4-amino-1-[[(2s,3r)-1-[[(2s)-4-amino-1-oxo-1-[[(3s,6s,9s,12s,15r,18s,21s)-6,9,18-tris(2-aminoethyl)-3-[(1r)-1-hydroxyethyl]-12,15-bis(2-methylpropyl)-2,5,8,11,14,17,20-heptaoxo-1,4,7,10,13,16,19-heptazacyclotricos-21-yl]amino]butan-2-yl]amino]-3-h Chemical compound CC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@H]([C@@H](C)O)CN[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O.CCC(C)CCCCC(=O)N[C@@H](CCN)C(=O)N[C@H]([C@@H](C)O)CN[C@@H](CCN)C(=O)N[C@H]1CCNC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCN)NC(=O)[C@H](CCN)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CCN)NC1=O JORAUNFTUVJTNG-BSTBCYLQSA-N 0.000 claims description 2
- 229960001802 phenylephrine Drugs 0.000 claims description 2
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 claims description 2
- 229920000024 polymyxin B Polymers 0.000 claims description 2
- XDJYMJULXQKGMM-UHFFFAOYSA-N polymyxin E1 Natural products CCC(C)CCCCC(=O)NC(CCN)C(=O)NC(C(C)O)C(=O)NC(CCN)C(=O)NC1CCNC(=O)C(C(C)O)NC(=O)C(CCN)NC(=O)C(CCN)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(CCN)NC1=O XDJYMJULXQKGMM-UHFFFAOYSA-N 0.000 claims description 2
- KNIWPHSUTGNZST-UHFFFAOYSA-N polymyxin E2 Natural products CC(C)CCCCC(=O)NC(CCN)C(=O)NC(C(C)O)C(=O)NC(CCN)C(=O)NC1CCNC(=O)C(C(C)O)NC(=O)C(CCN)NC(=O)C(CCN)NC(=O)C(CC(C)C)NC(=O)C(CC(C)C)NC(=O)C(CCN)NC1=O KNIWPHSUTGNZST-UHFFFAOYSA-N 0.000 claims description 2
- 229960005266 polymyxin b Drugs 0.000 claims description 2
- OENHQHLEOONYIE-JLTXGRSLSA-N β-Carotene Chemical compound CC=1CCCC(C)(C)C=1\C=C\C(\C)=C\C=C\C(\C)=C\C=C\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C OENHQHLEOONYIE-JLTXGRSLSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims 2
- NXLOLUFNDSBYTP-UHFFFAOYSA-N retene Chemical compound C1=CC=C2C3=CC=C(C(C)C)C=C3C=CC2=C1C NXLOLUFNDSBYTP-UHFFFAOYSA-N 0.000 claims 2
- FBHJUBZJKYKXJM-BAFYGKSASA-N (3R)-2-chloro-3,5-dihydroxy-3-methylpentanoic acid Chemical compound OCC[C@](O)(C)C(Cl)C(O)=O FBHJUBZJKYKXJM-BAFYGKSASA-N 0.000 claims 1
- BOVGTQGAOIONJV-BETUJISGSA-N 1-[(3ar,6as)-3,3a,4,5,6,6a-hexahydro-1h-cyclopenta[c]pyrrol-2-yl]-3-(4-methylphenyl)sulfonylurea Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1C[C@H]2CCC[C@H]2C1 BOVGTQGAOIONJV-BETUJISGSA-N 0.000 claims 1
- 229960000548 alemtuzumab Drugs 0.000 claims 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims 1
- 229960000346 gliclazide Drugs 0.000 claims 1
- 229960004023 minocycline Drugs 0.000 claims 1
- 239000003889 eye drop Substances 0.000 abstract description 30
- 229940012356 eye drops Drugs 0.000 abstract description 20
- 210000004877 mucosa Anatomy 0.000 abstract description 4
- 230000007794 irritation Effects 0.000 abstract description 3
- 238000002360 preparation method Methods 0.000 abstract description 3
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 description 30
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 17
- 210000004087 cornea Anatomy 0.000 description 13
- 238000011156 evaluation Methods 0.000 description 13
- 210000000795 conjunctiva Anatomy 0.000 description 12
- 229920000642 polymer Polymers 0.000 description 12
- WOBHKFSMXKNTIM-UHFFFAOYSA-N Hydroxyethyl methacrylate Chemical compound CC(=C)C(=O)OCCO WOBHKFSMXKNTIM-UHFFFAOYSA-N 0.000 description 11
- 230000004888 barrier function Effects 0.000 description 11
- 210000003786 sclera Anatomy 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- 210000001742 aqueous humor Anatomy 0.000 description 10
- 239000004359 castor oil Substances 0.000 description 10
- 235000019438 castor oil Nutrition 0.000 description 10
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 10
- 210000001519 tissue Anatomy 0.000 description 10
- 238000007599 discharging Methods 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 238000013268 sustained release Methods 0.000 description 9
- 239000012730 sustained-release form Substances 0.000 description 9
- 229940124597 therapeutic agent Drugs 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 229920002675 Polyoxyl Polymers 0.000 description 7
- 238000002474 experimental method Methods 0.000 description 7
- 238000009472 formulation Methods 0.000 description 7
- 238000003860 storage Methods 0.000 description 7
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 235000011187 glycerol Nutrition 0.000 description 6
- 229940069328 povidone Drugs 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 description 4
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- 229960002684 aminocaproic acid Drugs 0.000 description 4
- 229910021538 borax Inorganic materials 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 4
- 229920000609 methyl cellulose Polymers 0.000 description 4
- 235000010981 methylcellulose Nutrition 0.000 description 4
- 239000001923 methylcellulose Substances 0.000 description 4
- 239000001509 sodium citrate Substances 0.000 description 4
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 4
- 235000010339 sodium tetraborate Nutrition 0.000 description 4
- 239000012085 test solution Substances 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- 239000002562 thickening agent Substances 0.000 description 4
- 229920001664 tyloxapol Polymers 0.000 description 4
- 229960004224 tyloxapol Drugs 0.000 description 4
- MDYZKJNTKZIUSK-UHFFFAOYSA-N tyloxapol Chemical compound O=C.C1CO1.CC(C)(C)CC(C)(C)C1=CC=C(O)C=C1 MDYZKJNTKZIUSK-UHFFFAOYSA-N 0.000 description 4
- QRIMLDXJAPZHJE-UHFFFAOYSA-N 2,3-dihydroxypropyl 2-methylprop-2-enoate Chemical compound CC(=C)C(=O)OCC(O)CO QRIMLDXJAPZHJE-UHFFFAOYSA-N 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 3
- YSDQQAXHVYUZIW-QCIJIYAXSA-N Liraglutide Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCNC(=O)CC[C@H](NC(=O)CCCCCCCCCCCCCCC)C(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=C(O)C=C1 YSDQQAXHVYUZIW-QCIJIYAXSA-N 0.000 description 3
- 108010019598 Liraglutide Proteins 0.000 description 3
- RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 3
- 235000010443 alginic acid Nutrition 0.000 description 3
- 229920000615 alginic acid Polymers 0.000 description 3
- 239000000783 alginic acid Substances 0.000 description 3
- 229960001126 alginic acid Drugs 0.000 description 3
- 150000004781 alginic acids Chemical class 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000001276 controlling effect Effects 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000000017 hydrogel Substances 0.000 description 3
- 229920001477 hydrophilic polymer Polymers 0.000 description 3
- 229920001600 hydrophobic polymer Polymers 0.000 description 3
- 229960002701 liraglutide Drugs 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 3
- 229950004354 phosphorylcholine Drugs 0.000 description 3
- PYJNAPOPMIJKJZ-UHFFFAOYSA-N phosphorylcholine chloride Chemical compound [Cl-].C[N+](C)(C)CCOP(O)(O)=O PYJNAPOPMIJKJZ-UHFFFAOYSA-N 0.000 description 3
- 229920001983 poloxamer Polymers 0.000 description 3
- 229960000502 poloxamer Drugs 0.000 description 3
- 229940057838 polyethylene glycol 4000 Drugs 0.000 description 3
- 239000002861 polymer material Substances 0.000 description 3
- 229920001296 polysiloxane Polymers 0.000 description 3
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 3
- 229960002920 sorbitol Drugs 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 229920001285 xanthan gum Polymers 0.000 description 3
- 235000010493 xanthan gum Nutrition 0.000 description 3
- 239000000230 xanthan gum Substances 0.000 description 3
- 229940082509 xanthan gum Drugs 0.000 description 3
- WMFHUUKYIUOHRA-UHFFFAOYSA-N (3-phenoxyphenyl)methanamine;hydrochloride Chemical compound Cl.NCC1=CC=CC(OC=2C=CC=CC=2)=C1 WMFHUUKYIUOHRA-UHFFFAOYSA-N 0.000 description 2
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 2
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
- OVYMWJFNQQOJBU-UHFFFAOYSA-N 1-octanoyloxypropan-2-yl octanoate Chemical compound CCCCCCCC(=O)OCC(C)OC(=O)CCCCCCC OVYMWJFNQQOJBU-UHFFFAOYSA-N 0.000 description 2
- SPSPIUSUWPLVKD-UHFFFAOYSA-N 2,3-dibutyl-6-methylphenol Chemical compound CCCCC1=CC=C(C)C(O)=C1CCCC SPSPIUSUWPLVKD-UHFFFAOYSA-N 0.000 description 2
- FUWVMBCPMRAWPG-UHFFFAOYSA-N 2,3-dihydroxypropyl 2-hydroxyoctadecanoate Chemical compound CCCCCCCCCCCCCCCCC(O)C(=O)OCC(O)CO FUWVMBCPMRAWPG-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 2
- WUWFMDMBOJLQIV-UHFFFAOYSA-N 7-(3-aminopyrrolidin-1-yl)-1-(2,4-difluorophenyl)-6-fluoro-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid Chemical compound C1C(N)CCN1C(C(=C1)F)=NC2=C1C(=O)C(C(O)=O)=CN2C1=CC=C(F)C=C1F WUWFMDMBOJLQIV-UHFFFAOYSA-N 0.000 description 2
- 201000009487 Amblyopia Diseases 0.000 description 2
- 208000002177 Cataract Diseases 0.000 description 2
- 206010010744 Conjunctivitis allergic Diseases 0.000 description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
- 208000003556 Dry Eye Syndromes Diseases 0.000 description 2
- 206010013774 Dry eye Diseases 0.000 description 2
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 2
- 239000001856 Ethyl cellulose Substances 0.000 description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
- 208000010412 Glaucoma Diseases 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 229930195725 Mannitol Natural products 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 208000001140 Night Blindness Diseases 0.000 description 2
- 241000283973 Oryctolagus cuniculus Species 0.000 description 2
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 2
- 229920002690 Polyoxyl 40 HydrogenatedCastorOil Polymers 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
- ZFOZVQLOBQUTQQ-UHFFFAOYSA-N Tributyl citrate Chemical compound CCCCOC(=O)CC(O)(C(=O)OCCCC)CC(=O)OCCCC ZFOZVQLOBQUTQQ-UHFFFAOYSA-N 0.000 description 2
- MECHNRXZTMCUDQ-UHFFFAOYSA-N Vitamin D2 Natural products C1CCC2(C)C(C(C)C=CC(C)C(C)C)CCC2C1=CC=C1CC(O)CCC1=C MECHNRXZTMCUDQ-UHFFFAOYSA-N 0.000 description 2
- JVFGXECLSQXABC-UHFFFAOYSA-N ac1l3obq Chemical compound O1C(C(C2O)O)C(COCC(C)O)OC2OC(C(C2O)O)C(COCC(C)O)OC2OC(C(C2O)O)C(COCC(C)O)OC2OC(C(C2O)O)C(COCC(C)O)OC2OC(C(C2O)O)C(COCC(C)O)OC2OC(C(O)C2O)C(COCC(O)C)OC2OC(C(C2O)O)C(COCC(C)O)OC2OC2C(O)C(O)C1OC2COCC(C)O JVFGXECLSQXABC-UHFFFAOYSA-N 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
- 208000002205 allergic conjunctivitis Diseases 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 208000024998 atopic conjunctivitis Diseases 0.000 description 2
- 229960000686 benzalkonium chloride Drugs 0.000 description 2
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 2
- 229960001950 benzethonium chloride Drugs 0.000 description 2
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
- 229960004926 chlorobutanol Drugs 0.000 description 2
- 229960002242 chlorocresol Drugs 0.000 description 2
- 238000012937 correction Methods 0.000 description 2
- 230000006735 deficit Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 229960002061 ergocalciferol Drugs 0.000 description 2
- 235000019325 ethyl cellulose Nutrition 0.000 description 2
- 229920001249 ethyl cellulose Polymers 0.000 description 2
- 229960004667 ethyl cellulose Drugs 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 229960001048 fluorometholone Drugs 0.000 description 2
- FAOZLTXFLGPHNG-KNAQIMQKSA-N fluorometholone Chemical compound C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@]2(F)[C@@H](O)C[C@]2(C)[C@@](O)(C(C)=O)CC[C@H]21 FAOZLTXFLGPHNG-KNAQIMQKSA-N 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- LHGVFZTZFXWLCP-UHFFFAOYSA-N guaiacol Chemical compound COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 2
- JFOZKMSJYSPYLN-QHCPKHFHSA-N lifitegrast Chemical compound CS(=O)(=O)C1=CC=CC(C[C@H](NC(=O)C=2C(=C3CCN(CC3=CC=2Cl)C(=O)C=2C=C3OC=CC3=CC=2)Cl)C(O)=O)=C1 JFOZKMSJYSPYLN-QHCPKHFHSA-N 0.000 description 2
- 208000002780 macular degeneration Diseases 0.000 description 2
- DHRRIBDTHFBPNG-UHFFFAOYSA-L magnesium dichloride hexahydrate Chemical compound O.O.O.O.O.O.[Mg+2].[Cl-].[Cl-] DHRRIBDTHFBPNG-UHFFFAOYSA-L 0.000 description 2
- 239000000594 mannitol Substances 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 2
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 2
- 229960002216 methylparaben Drugs 0.000 description 2
- 210000003928 nasal cavity Anatomy 0.000 description 2
- 229960003255 natamycin Drugs 0.000 description 2
- 235000010298 natamycin Nutrition 0.000 description 2
- 239000004311 natamycin Substances 0.000 description 2
- NCXMLFZGDNKEPB-FFPOYIOWSA-N natamycin Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C[C@@H](C)OC(=O)/C=C/[C@H]2O[C@@H]2C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 NCXMLFZGDNKEPB-FFPOYIOWSA-N 0.000 description 2
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 description 2
- 239000003002 pH adjusting agent Substances 0.000 description 2
- 239000008055 phosphate buffer solution Substances 0.000 description 2
- 229920000747 poly(lactic acid) Polymers 0.000 description 2
- 229920001610 polycaprolactone Polymers 0.000 description 2
- 239000004632 polycaprolactone Substances 0.000 description 2
- 229920006254 polymer film Polymers 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 2
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 2
- 238000005070 sampling Methods 0.000 description 2
- 229940091258 selenium supplement Drugs 0.000 description 2
- 239000001632 sodium acetate Substances 0.000 description 2
- 235000017281 sodium acetate Nutrition 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 2
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 2
- 229940037001 sodium edetate Drugs 0.000 description 2
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 2
- 239000004289 sodium hydrogen sulphite Substances 0.000 description 2
- 235000011121 sodium hydroxide Nutrition 0.000 description 2
- 235000011088 sodium lactate Nutrition 0.000 description 2
- 239000001540 sodium lactate Substances 0.000 description 2
- 229940005581 sodium lactate Drugs 0.000 description 2
- 229940001584 sodium metabisulfite Drugs 0.000 description 2
- 235000010262 sodium metabisulphite Nutrition 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 239000004328 sodium tetraborate Substances 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- 229960000707 tobramycin Drugs 0.000 description 2
- NLVFBUXFDBBNBW-PBSUHMDJSA-N tobramycin Chemical compound N[C@@H]1C[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N NLVFBUXFDBBNBW-PBSUHMDJSA-N 0.000 description 2
- 229950008187 tosufloxacin Drugs 0.000 description 2
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 2
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 2
- 229960000281 trometamol Drugs 0.000 description 2
- MECHNRXZTMCUDQ-RKHKHRCZSA-N vitamin D2 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)/C=C/[C@H](C)C(C)C)=C\C=C1\C[C@@H](O)CCC1=C MECHNRXZTMCUDQ-RKHKHRCZSA-N 0.000 description 2
- 235000001892 vitamin D2 Nutrition 0.000 description 2
- 239000011653 vitamin D2 Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- OKMWKBLSFKFYGZ-UHFFFAOYSA-N 1-behenoylglycerol Chemical compound CCCCCCCCCCCCCCCCCCCCCC(=O)OCC(O)CO OKMWKBLSFKFYGZ-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- 239000000263 2,3-dihydroxypropyl (Z)-octadec-9-enoate Substances 0.000 description 1
- UIAGMCDKSXEBJQ-IBGZPJMESA-N 3-o-(2-methoxyethyl) 5-o-propan-2-yl (4s)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate Chemical compound COCCOC(=O)C1=C(C)NC(C)=C(C(=O)OC(C)C)[C@H]1C1=CC=CC([N+]([O-])=O)=C1 UIAGMCDKSXEBJQ-IBGZPJMESA-N 0.000 description 1
- RZRNAYUHWVFMIP-GDCKJWNLSA-N 3-oleoyl-sn-glycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-GDCKJWNLSA-N 0.000 description 1
- 239000010963 304 stainless steel Substances 0.000 description 1
- SQDAZGGFXASXDW-UHFFFAOYSA-N 5-bromo-2-(trifluoromethoxy)pyridine Chemical compound FC(F)(F)OC1=CC=C(Br)C=N1 SQDAZGGFXASXDW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- QZCLKYGREBVARF-UHFFFAOYSA-N Acetyl tributyl citrate Chemical compound CCCCOC(=O)CC(C(=O)OCCCC)(OC(C)=O)CC(=O)OCCCC QZCLKYGREBVARF-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 229940122072 Carbonic anhydrase inhibitor Drugs 0.000 description 1
- 102000003846 Carbonic anhydrases Human genes 0.000 description 1
- 108090000209 Carbonic anhydrases Proteins 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 240000008886 Ceratonia siliqua Species 0.000 description 1
- 235000013912 Ceratonia siliqua Nutrition 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- 229920001287 Chondroitin sulfate Polymers 0.000 description 1
- 102100026735 Coagulation factor VIII Human genes 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 229920000045 Dermatan sulfate Polymers 0.000 description 1
- PYGXAGIECVVIOZ-UHFFFAOYSA-N Dibutyl decanedioate Chemical compound CCCCOC(=O)CCCCCCCCC(=O)OCCCC PYGXAGIECVVIOZ-UHFFFAOYSA-N 0.000 description 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 1
- CTKXFMQHOOWWEB-UHFFFAOYSA-N Ethylene oxide/propylene oxide copolymer Chemical compound CCCOC(C)COCCO CTKXFMQHOOWWEB-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 229920000569 Gum karaya Polymers 0.000 description 1
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- OMCPLEZZPVJJIS-UHFFFAOYSA-N Hypadil (TN) Chemical compound C1C(O[N+]([O-])=O)COC2=C1C=CC=C2OCC(O)CNC(C)C OMCPLEZZPVJJIS-UHFFFAOYSA-N 0.000 description 1
- 206010020675 Hypermetropia Diseases 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 229920000161 Locust bean gum Polymers 0.000 description 1
- 208000022873 Ocular disease Diseases 0.000 description 1
- 108010038807 Oligopeptides Proteins 0.000 description 1
- 102000015636 Oligopeptides Human genes 0.000 description 1
- 244000046052 Phaseolus vulgaris Species 0.000 description 1
- 235000010627 Phaseolus vulgaris Nutrition 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229920000954 Polyglycolide Polymers 0.000 description 1
- 108010040201 Polymyxins Proteins 0.000 description 1
- 229920001710 Polyorthoester Polymers 0.000 description 1
- 229910000589 SAE 304 stainless steel Inorganic materials 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002385 Sodium hyaluronate Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 241000934878 Sterculia Species 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 229920002494 Zein Polymers 0.000 description 1
- 229940081735 acetylcellulose Drugs 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 229960002833 aflibercept Drugs 0.000 description 1
- 108010081667 aflibercept Proteins 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 229940023476 agar Drugs 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 239000003732 agents acting on the eye Substances 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 201000009310 astigmatism Diseases 0.000 description 1
- YTLQFZVCLXFFRK-UHFFFAOYSA-N bendazol Chemical compound N=1C2=CC=CC=C2NC=1CC1=CC=CC=C1 YTLQFZVCLXFFRK-UHFFFAOYSA-N 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 201000005668 blepharoconjunctivitis Diseases 0.000 description 1
- 230000004397 blinking Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 229940055416 blueberry extract Drugs 0.000 description 1
- 235000019216 blueberry extract Nutrition 0.000 description 1
- 229960003655 bromfenac Drugs 0.000 description 1
- 239000003489 carbonate dehydratase inhibitor Substances 0.000 description 1
- 239000004203 carnauba wax Substances 0.000 description 1
- 235000013869 carnauba wax Nutrition 0.000 description 1
- 229940082483 carnauba wax Drugs 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 239000007765 cera alba Substances 0.000 description 1
- 239000007766 cera flava Substances 0.000 description 1
- 229940045110 chitosan Drugs 0.000 description 1
- 229940059329 chondroitin sulfate Drugs 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- AVJBPWGFOQAPRH-FWMKGIEWSA-L dermatan sulfate Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@H](OS([O-])(=O)=O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](C([O-])=O)O1 AVJBPWGFOQAPRH-FWMKGIEWSA-L 0.000 description 1
- 229940051593 dermatan sulfate Drugs 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 229940031954 dibutyl sebacate Drugs 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 239000003885 eye ointment Substances 0.000 description 1
- 210000000744 eyelid Anatomy 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229940014259 gelatin Drugs 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229940049654 glyceryl behenate Drugs 0.000 description 1
- 229940075507 glyceryl monostearate Drugs 0.000 description 1
- FETSQPAGYOVAQU-UHFFFAOYSA-N glyceryl palmitostearate Chemical compound OCC(O)CO.CCCCCCCCCCCCCCCC(O)=O.CCCCCCCCCCCCCCCCCC(O)=O FETSQPAGYOVAQU-UHFFFAOYSA-N 0.000 description 1
- 229940046813 glyceryl palmitostearate Drugs 0.000 description 1
- 229960001867 guaiacol Drugs 0.000 description 1
- 230000000004 hemodynamic effect Effects 0.000 description 1
- 239000008172 hydrogenated vegetable oil Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
- 229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
- 201000006318 hyperopia Diseases 0.000 description 1
- 230000004305 hyperopia Effects 0.000 description 1
- XZZXIYZZBJDEEP-UHFFFAOYSA-N imipramine hydrochloride Chemical compound [Cl-].C1CC2=CC=CC=C2N(CCC[NH+](C)C)C2=CC=CC=C21 XZZXIYZZBJDEEP-UHFFFAOYSA-N 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- XUGNVMKQXJXZCD-UHFFFAOYSA-N isopropyl palmitate Chemical compound CCCCCCCCCCCCCCCC(=O)OC(C)C XUGNVMKQXJXZCD-UHFFFAOYSA-N 0.000 description 1
- 235000010494 karaya gum Nutrition 0.000 description 1
- 239000000231 karaya gum Substances 0.000 description 1
- 229940039371 karaya gum Drugs 0.000 description 1
- 229960005381 lifitegrast Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000001294 liquid chromatography-tandem mass spectrometry Methods 0.000 description 1
- 235000010420 locust bean gum Nutrition 0.000 description 1
- 239000000711 locust bean gum Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 235000013379 molasses Nutrition 0.000 description 1
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 1
- RZRNAYUHWVFMIP-UHFFFAOYSA-N monoelaidin Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-UHFFFAOYSA-N 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 239000002637 mydriatic agent Substances 0.000 description 1
- 208000001491 myopia Diseases 0.000 description 1
- 230000004379 myopia Effects 0.000 description 1
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 description 1
- 229920005615 natural polymer Polymers 0.000 description 1
- 229960000715 nimodipine Drugs 0.000 description 1
- 229950000754 nipradilol Drugs 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
- 229940023490 ophthalmic product Drugs 0.000 description 1
- WRUUGTRCQOWXEG-UHFFFAOYSA-N pamidronate Chemical compound NCCC(O)(P(O)(O)=O)P(O)(O)=O WRUUGTRCQOWXEG-UHFFFAOYSA-N 0.000 description 1
- 229940046231 pamidronate Drugs 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 229920001993 poloxamer 188 Polymers 0.000 description 1
- 229940044519 poloxamer 188 Drugs 0.000 description 1
- 239000002745 poly(ortho ester) Substances 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229940068918 polyethylene glycol 400 Drugs 0.000 description 1
- 239000004633 polyglycolic acid Substances 0.000 description 1
- 229920002338 polyhydroxyethylmethacrylate Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 229920000193 polymethacrylate Polymers 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- FASDKYOPVNHBLU-ZETCQYMHSA-N pramipexole Chemical compound C1[C@@H](NCCC)CCC2=C1SC(N)=N2 FASDKYOPVNHBLU-ZETCQYMHSA-N 0.000 description 1
- 229960003089 pramipexole Drugs 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 210000001747 pupil Anatomy 0.000 description 1
- 208000022749 pupil disease Diseases 0.000 description 1
- 229960003876 ranibizumab Drugs 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 229960001634 ritodrine Drugs 0.000 description 1
- IOVGROKTTNBUGK-SJCJKPOMSA-N ritodrine Chemical compound N([C@@H](C)[C@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJCJKPOMSA-N 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 239000002210 silicon-based material Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229960004599 sodium borate Drugs 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 229940010747 sodium hyaluronate Drugs 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
- 239000008117 stearic acid Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229960005158 sulfamethizole Drugs 0.000 description 1
- VACCAVUAMIDAGB-UHFFFAOYSA-N sulfamethizole Chemical compound S1C(C)=NN=C1NS(=O)(=O)C1=CC=C(N)C=C1 VACCAVUAMIDAGB-UHFFFAOYSA-N 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 description 1
- 239000001069 triethyl citrate Substances 0.000 description 1
- 235000013769 triethyl citrate Nutrition 0.000 description 1
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 1
- 229920003169 water-soluble polymer Polymers 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 229940023106 xiidra Drugs 0.000 description 1
- 239000005019 zein Substances 0.000 description 1
- 229940093612 zein Drugs 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
- A61F9/0008—Introducing ophthalmic products into the ocular cavity or retaining products therein
- A61F9/0017—Introducing ophthalmic products into the ocular cavity or retaining products therein implantable in, or in contact with, the eye, e.g. ocular inserts
-
- 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
- A61K9/0051—Ocular inserts, ocular implants
-
- 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
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
- A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
-
- 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
- A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
- A61K31/215—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids
- A61K31/22—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin
- A61K31/222—Esters, e.g. nitroglycerine, selenocyanates of carboxylic acids of acyclic acids, e.g. pravastatin with compounds having aromatic groups, e.g. dipivefrine, ibopamine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/22—Hormones
- A61K38/26—Glucagons
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
-
- G—PHYSICS
- G02—OPTICS
- G02C—SPECTACLES; SUNGLASSES OR GOGGLES INSOFAR AS THEY HAVE THE SAME FEATURES AS SPECTACLES; CONTACT LENSES
- G02C7/00—Optical parts
- G02C7/02—Lenses; Lens systems ; Methods of designing lenses
- G02C7/04—Contact lenses for the eyes
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Emergency Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Biomedical Technology (AREA)
- Endocrinology (AREA)
- Zoology (AREA)
- Gastroenterology & Hepatology (AREA)
- Immunology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
本发明涉及一种药物递送用隐形眼镜,其具有改善的药物递送效率和生物利用度。根据本发明的药物递送用隐形眼镜可以稳定地释放药物,与现有已知的滴眼液相比,减少了剂量和给药次数,从而生物利用度有望得到改善。另外,根据本发明的药物递送用隐形眼镜可以容易地应用于各种药物,对眼粘膜的刺激较小,制备方法简单,适合大量生产。
Description
技术领域
本发明涉及一种药物递送用隐形眼镜,其具有改善的药物递送效率和生物利用度。
背景技术
用于治疗眼病的药物有滴眼液(或眼药水)和眼药膏等。就这些现有的眼病药物而言,只有约7%的滴眼液被有效利用,其余在排出到鼻腔(nasal cavity)
之前仅在泪液循环中停留约2分钟(Expert opinion on drug delivery 2006
3(2)275-287)。另外,与滴眼液相比,眼药膏具有药物停留时间更长的优点,但其问题在于,由于剂型的性质,异物感或所使用的赋形剂可能会刺激眼睛,并且在眨眼时干扰视力。
因此,需要开发药物停留时间较长且管理方便的药物递送手段,并且作为基于这些需求的技术,已经开发了药物递送用隐形眼镜。然而,目前正在开发的代表性药物递送用隐形眼镜在将聚合物材料膜(drug polymer film)放置在隐形眼镜中并使用的形式方面仍然存在问题。具体地,为了成型为薄膜形式,需要使用高浓度聚合物,但美国食品药品监督管理局(FDA)限制用作药物的聚合物的量。因此,可使用的聚合物的选择是有限的,或者只有通过非常严格的毒性测试才能使用高浓度的聚合物。另外,当使用高浓度聚合物时,存在镜片成型困难,例如在涂覆过程中不能保持镜片的形状,不能很好地粘附在镜片上,就水溶性聚合物而言,溶解可能对眼粘膜造成刺激。
尤其,重要的是,药物递送用隐形眼镜要确保药物在所需时间段内以恒定速率释放,但在聚合物膜隐形眼镜中,聚合物暴露于眼粘膜的面积大,药物被泪液溶解,从而出现初始药物释放量迅速增加的现象。此外,每个人的泪液分泌量不同,这会导致不同的药物释放模式。即,药物释放模式受泪液量的影响很大。
因此,为了解决上述现有问题,本发明的发明人实现了一种不同于现有药物递送用隐形眼镜的结构,与滴眼液相比,这种结构可以通过持续释放药物来减少给药剂量和频率,并且使药物释放比现有的药物递送用隐形眼镜更稳定,本发明人发现,本发明的药物递送用隐形眼镜可以针对眼病的治疗进行优化,从而完成了本发明。
发明内容
技术问题
本发明的一方面提供一种药物递送用隐形眼镜,其包括:镜体部;腔室部,其与所述镜体部的中央部间隔开并储存药物;和阻挡部,其与所述腔室部的一部分结合并控制药物释放,所述腔室部包括通道部,药物通过所述通道部从所述腔室部移动并释放到眼球。
本发明的另一方面提供一种眼科用组合物,其包括:药物,其在眼科药学上具有活性;和用于控释药物的赋形剂,其为粘稠剂、乳化剂、稳定剂中的任意一种或多种。
技术方案
本发明的一方面提供一种药物递送用隐形眼镜,其包括:镜体部;腔室部,其与所述镜体部的中央部间隔开并储存药物;和阻挡部,其与所述腔室部的一部分结合并控制药物释放,所述腔室部包括通道部,药物通过所述通道部从所述腔室部移动并释放到眼球。
与现有的滴眼液和药物递送用隐形眼镜相比,根据本发明的药物递送用隐形眼镜,其特征在于,可以通过改进结构来控制药物释放,提高生物利用度,使药物稳定释放。
具体地,根据本发明一实施例的药物递送用隐形眼镜如图1或图2所示。
参见图1,本发明的药物递送用隐形眼镜包括腔室部,所述腔室部在镜体部内部具有特定形状(例如,直线形式等)并且是少量眼科药学上具有活性的药物的储存空间,所述腔室部的一部分上结合有阻挡部,作为所述腔室部的一部分包括通道部,药物通过所述通道部从所述腔室部移动并释放到眼球。所述通道部可以包括释放药物的排出口。将眼科药学上具有活性的药物注入腔室部所述中。
参见图2,本发明的药物递送用隐形眼镜还可以在通道部中包括排出路径,存储在腔室部中的药物可以通过所述排出路径移动到排出口。当需要更精细地控制药物释放时,可以应用所述排出路径。因此,根据腔室部的形状,药物递送用隐形眼镜可以包括也可以不包括所述排出路径。
如本文所用,术语“镜体部”是指具有球面以便可以戴在眼球上。镜体部的材料由通常使用的镜头材料制成,具体地,其可以为亲水性聚合物或疏水性聚合物,但不特别限于此,并且可以由本领域技术人员适当地选择。
所述亲水性聚合物可以包括选自金合欢、琼脂、海藻酸、卡波姆、角叉菜胶、醋酸纤维素、长角豆、壳聚糖、硫酸软骨素、硫酸皮肤素、葡聚糖、乙基纤维素、明胶、瓜尔胶、羟乙基纤维素、羟丙基-β-环糊精、羟丙基纤维素、羟丙甲纤维素、醋酸羟丙甲纤维素琥珀酸酯、羟丙甲纤维素邻苯二甲酸酯、刺梧桐胶、刺槐豆胶、甲基纤维素、糖蜜、果胶、聚丙烯酰胺、聚己内酯、聚环氧乙烷、聚乙二醇、聚甲基丙烯酸羟乙酯、聚原酸酯、聚乙烯醇、聚乙烯吡咯烷酮、海藻酸钠、羧甲基纤维素、透明质酸钠、西黄蓍胶和柠檬酸三乙酯、黄原胶中的任意一种或多种。
所述疏水性聚合物可以包括选自乙酰醇、乙酰酯蜡、乙酰柠檬酸三丁酯、单硬脂酸铝、巴西棕榈蜡、醋酸纤维素、邻苯二甲酸醋酸纤维素、癸二酸二丁酯、乙基纤维素、单硬脂酸甘油酯、甘油山嵛酸酯、单油酸甘油酯、棕榈酰硬脂酸甘油酯、氢化蓖麻油、氢化植物油型1、棕榈酸异丙酯、聚己内酯、聚乙醇酸、聚乳酸、聚丙交酯、聚甲基丙烯酸酯、聚氧甘油酯、虫胶、硬脂酸、硬脂醇、柠檬酸三丁酯、白蜂蜡、黄蜂蜡和玉米朊中的任意一种或多种。
更具体地,其可以为选自甲基丙烯酸2-羟乙酯(2-hydroxyethylmethacrylate,
2-HEMA)、甲基丙烯酸甘油酯、硅水凝胶和磷酰胆碱中的任意一种或多种,但不限于此。
根据需要,所述镜体部还可以包括视力矫正部(视力矫正镜片部)。所述视力矫正部位于镜体部的中央部,其位于角膜上,可以通过折射入射到瞳孔的光线来调节屈光度(diopter),从而矫正近视、远视、散光等。本发明的药物递送用隐形眼镜不仅可以通过药物释放表现出改善、预防或治疗眼科疾病的效果,而且还可以起到矫正视力的作用,这是隐形眼镜的独特功能。
如本文所用,术语“腔室部”是指定位成与镜体部的中央部间隔开,并且存储暴露于眼球的药物,具体地,眼科药学上具有活性的药物的部分。所述腔室部可以形成为隐形眼镜内部的凹陷结构(concave structure)。另外,一个或多个所述腔室部可以形成在单个隐形眼镜中,并且多个腔室部可以储存相同的药物或多种不同的药物。
图3具体示出了本发明的药物递送用隐形眼镜的腔室部的形状。参见图3,腔室部可以实现为以多个直线形式存储少量药物的空间(参见图3(a))、存储三种单独药物的空间(参见图3(b))、存储一种大容量药物的空间(参见图3(c))和融合型(参见图3(d))的形式,但不限于此,只要能够有效地存储药物即可。
尤其,腔室部的形状可以根据所施加的药物的量来选择,并且可以调整其大小。
所述调整大小是指改变所选腔室部的直径和/或深度、通道的长度等。即,选择所述腔室部的形状以制备隐形眼镜模具,在用其制备隐形眼镜形状后,可以通过注射药物并结合阻挡部来制备药物递送用隐形眼镜(图4)。
所述腔室部由通常使用的镜片材料制成,具体地,可以为选自甲基丙烯酸2-羟乙酯(2-hydroxyethylmethacrylate,2-HEMA)、甲基丙烯酸甘油酯、硅水凝胶和磷酰胆碱中的任意一种或多种,但不限于此。
如本文所用,术语“通道部”是指药物移动并暴露于眼球和/或泪液的区域,并用于供应药物。此时,药物可以从暴露于眼球和/或泪液的通道部缓慢释放。所述通道部可以包括排出口和/或排出路径,具体地,可以仅包括排出口,也可以包括排出口和排出路径。
如本文所用,术语“排出口”是指释放药物的部位,“排出路径”是指为了排放药物而药物从腔室部移动到通道部(排出口)的通道。此时,排出路径可以使得存储在腔室部中的药物以恒定速率通过通道部(排出口)释放到眼球。排出路径的长度和通道部的大小可以通过腔室部的形状和覆盖其的阻挡部的大小调节,
并且药物释放的量和速率可以通过调整排出路径的长度和通道部的大小来确定。
如本文所用,术语“阻挡部”可以是指可调节药物释放的速率和模式的部分。所述阻挡部由通常使用的镜片材料制成。具体地,其可以为选自甲基丙烯酸2-羟乙酯(2-hydroxyethylmethacrylate,2-HEMA)、甲基丙烯酸甘油酯、硅水凝胶和磷酰胆碱中的任意一种或多种,但不限于此。
所述阻挡部的特征可以在于,其形成为可以覆盖腔室部的50面积%至95面积%的大小,优选可以形成为可以覆盖腔室部的70面积%至95面积%的大小,但不限于此。具体地,当所述阻挡部的大小或阻挡率在所述范围内时,可以确保目标药物释放模式。
所述腔室部的阻挡率可以根据阻挡部覆盖腔室部的面积控制,阻挡部覆盖腔室部的面积%可以表示腔室部的阻挡率。所述阻挡部的腔室部阻挡率可以大于等于50%且小于100%,具体可以表示50%至99%、50%至97%、50%至95%、50%至93%、60%至99%、60%至97%、60%至95%、60%至93%、70%至99%、70%至97%、
70%至95%、70%至93%、75%至99%、75%至97%、75%至95%、75%至93%、80%至99%、80%至97%、80%至95%、80%至93%、85%至99%、85%至97%、85%至95%、
85%至93%、90%至99%、90%至97%、90%至95%或90%至93%的腔室部阻挡率。
所述药物递送用隐形眼镜可以用于以恒定速率释放药物。根据一实施例,在本发明的药物递送用隐形眼镜中,可以通过阻挡部控制腔室部阻挡率(阻挡部覆盖腔室部的面积%)以控制腔室部中储存的药物的释放速率,具体地,所述释放速率的控制可以是指控制腔室部中存储的药物以恒定速率释放。因此,本发明的药物递送用隐形眼镜的特征在于,药物可以以受控的模式释放,而不是初期一次性释放。所述受控的模式包括零级模型(Zeroorder model)、一级模型(First order model)、Higuchi模型、Noyes-Whitney模型、Korsmeyer-
Peppas模型等,但不限于此。
所述药物递送用隐形眼镜可以为缓释型药物递送用隐形眼镜。如本文所用,术语“缓释”是指通过控制药物的释放机制/模式来使药物在体内长时间缓慢释放。
具体地,所述缓释可以通过所述阻挡部控制腔室部阻挡率来实现。
所述阻挡部的平均厚度可以为30μm至80μm,优选可以为40μm至60μm,但不限于此。
所述腔室部可以包括药物和用于控释药物的赋形剂。所述用于控释药物的赋形剂可以包括选自粘稠剂、乳化剂、稳定剂、pH调节剂、等渗剂和保存剂中的任意一种或多种。
所述粘稠剂可以包括选自黄原胶、卡波姆、卡波普、聚乙烯醇、羟乙基纤维素、羟丙基甲基纤维素、甲基纤维素、羧甲基纤维素钠、聚维酮、聚乙二醇、聚乙二醇400、聚乙二醇4000,甘油、葡聚糖、海藻酸、葡萄糖、右旋糖和丙二醇二辛酸酯中的任意一种或多种,但不限于此。
相对于含有药物的眼科用组合物的总含量,以重量体积百分比(w/v%)计算,
所述粘稠剂的含量可以为黄原胶0.0015%至0.15%、卡波姆0.005%至0.5%、卡波普0.002%至0.2%、聚乙烯醇0.018%至1.8%、羟乙基纤维素0.005%至0.5%、羟丙基甲基纤维素0.02%至2.0%、甲基纤维素0.014%至1.4%、羧甲基纤维素钠0.005%至0.5%、聚维酮0.04%至4.0%、聚乙二醇0.04%至4.0%、聚乙二醇400
0.08%至8.0%、聚乙二醇4000 0.02%至2.0%,甘油0.025%至2.5%、葡聚糖0.001%至0.1%、海藻酸0.01%至1.0%、葡萄糖0.0009%至0.09%、右旋糖0.00065%至0.065%和丙二醇二辛酸酯0.0005%至0.05%。
所述乳化剂可以包括选自聚氧40硬化蓖麻油、聚氧40氢化蓖麻油、聚氧乙烯硬化蓖麻油、聚氧乙烯硬化蓖麻油60、聚氧乙烯氢化蓖麻油、聚氧35蓖麻油、丙二醇、泊洛沙姆、聚山梨酯80、泰洛沙泊、聚乙二醇4000、聚维酮、聚乙二醇甘油羟基硬脂酸酯和蓖麻油中的任意一种或多种,但不限于此。
相对于含有药物的眼科用组合物的总含量,以重量体积百分比(w/v%)计算,
所述乳化剂的含量可以为聚氧40硬化蓖麻油0.0005%至0.05%、聚氧40氢化蓖麻油0.002%至0.2%、聚氧乙烯硬化蓖麻油0.001%至0.1%、聚氧乙烯硬化蓖麻油600.003%至0.3%、聚氧乙烯氢化蓖麻油0.001%至0.1%、聚氧35蓖麻油0.05%至5.0%、丙二醇0.03%至3.0%、泊洛沙姆0.0005%至0.05%、聚山梨酯80
0.01%至1.0%、泰洛沙泊0.005%至0.5%、聚乙二醇4000 0.02%至2.0%、聚维酮0.04%至4.0%、聚乙二醇甘油羟基硬脂酸酯0.05%至5.0%、蓖麻油0.0126%
至1.26%。
所述稳定剂可以包括选自依地酸钠水合物、柠檬酸钠、聚维酮、聚乙烯醇、羟乙基纤维素、甲基纤维素、羟丙基甲基纤维素、聚山梨酯80、泰洛沙泊、氨丁三醇、丙二醇、亚硫酸氢钠、二丁基羟基甲苯、硫代硫酸钠、羟丙基-γ-环糊精和氨基己酸中的任意一种或多种,但不限于此。
相对于含有药物的眼科用组合物的总含量,以重量体积百分比(w/v%)计算,
所述稳定剂的含量可以为依地酸钠水合物0.005%至0.5%、柠檬酸钠0.00294%
至0.294%、聚维酮0.04%至4.0%、聚乙烯醇0.018%至1.8%、羟乙基纤维素0.005%至0.5%、甲基纤维素0.014%至1.4%、羟丙基甲基纤维素0.02%至2.0%、聚山梨酯80 0.01%至1.0%、泰洛沙泊0.005%至0.5%、氨丁三醇0.006%至0.6%、丙二醇0.03%至3.0%、亚硫酸氢钠0.001%至0.1%、二丁基羟基甲苯0.00005%
至0.005%、硫代硫酸钠0.002%至0.2%、羟丙基-γ-环糊精0.015%至1.5%和氨基己酸0.002%至0.2%中的任意一种或多种,但不限于此。
所述pH调节剂可以包括选自盐酸、磷酸、无水磷酸氢二钠、硫酸钠、柠檬酸、柠檬酸钠、乙酸酐、乙酸钠、碳酸氢钠、氢氧化钠、单乙醇胺、硼砂、硼酸、干燥亚硫酸钠、焦亚硫酸钠、硼酸钠和乳酸钠中的任意一种或多种,但不限于此。
相对于含有药物的眼科用组合物的总含量,以重量体积百分比(w/v%)计算,
所述pH调节剂的含量可以为盐酸0.0027%至0.27%、磷酸0.00288%至0.288%、无水磷酸氢二钠0.00474%至0.474%、硫酸钠0.012%至1.2%、柠檬酸0.00005%
至0.005%、柠檬酸钠0.00294%至0.294%、乙酸酐0.00007%至0.007%、乙酸钠0.029%至2.9%、碳酸氢钠0.0005%至0.05%、氢氧化钠0.00716%至0.716%、单乙醇胺0.00052%至0.052%、硼砂0.011%至1.1%、硼酸0.02%至2.0%、干燥亚硫酸钠0.002%至0.2%、焦亚硫酸钠0.004%至0.4%、硼酸钠0.00019%至0.019%
和乳酸钠0.0002%至0.02%中的任意一种或多种,但不限于此。
所述等渗剂可以包括选自葡萄糖、甘油、浓缩甘油、甘露醇、氯化钾、氯化钠、氯化钙水合物、氯化镁水合物、D-山梨醇、D-山梨醇溶液、葡萄糖和丙二醇中的任意一种或多种,但不限于此。
相对于含有药物的眼科用组合物的总含量,以重量体积百分比(w/v%)计算,
所述等渗剂的含量可以为葡萄糖0.00065%至0.065%、甘油0.025%至2.5%、浓缩甘油0.026%至2.6%、甘露醇0.05%至5.0%、氯化钾0.0037%至0.37%、氯化钠0.0655%至6.55%、氯化钙水合物0.00048%至0.048%、氯化镁水合物0.0003%
至0.03%、D-山梨醇0.05%至5.0%、D-山梨醇溶液0.066%至6.6%、葡萄糖0.0009%至0.09%和丙二醇0.03%至3.0%中的任意一种或多种,但不限于此。
所述保存剂可以包括选自苄索氯铵、对羟基苯甲酸甲酯、对羟基苯甲酸丙酯、氯丁醇、苯扎氯铵和氯甲酚中的任意一种或多种,但不限于此。
相对于含有药物的眼科用组合物的总含量,以重量体积百分比(w/v%)计算,
所述保存剂的含量可以为苄索氯铵0.002%至0.1%、对羟基苯甲酸甲酯0.0005%
至0.05%、对羟基苯甲酸丙酯0.0005%至0.05%、氯丁醇0.25%至0.05%、苯扎氯铵0.002%至0.1%和氯甲酚0.0005%至0.05%中的任意一种或多种,但不限于此。
根据一实施例,本发明的药物递送用隐形眼镜可以通过阻挡部控制腔室部阻挡率(阻挡部覆盖腔室部的面积%)和用于控释药物的赋形剂的组成/比例的组合来调节腔室部中储存的药物的释放速率,具体地,所述“释放速率的调节”可以是指调节腔室部中储存的药物以恒定速率释放。因此,本发明的药物递送用隐形眼镜的特征在于,药物可以以恒定速率释放,而不是初期一次性释放。
所述药物递送用隐形眼镜可以为缓释型药物递送用隐形眼镜,具体地,所述缓释可以通过所述阻挡部控制腔室部阻挡率和用于控释药物的赋形剂的组成/比例的组合来实现。
与滴眼液相比,所述药物递送用隐形眼镜可以有效地调节药物的释放速率和/
或实现缓释效果,具体地,由于与滴眼液相比,所述隐形眼镜可以有效且恒定地释放药物,因此即使使用比滴眼液更少的药量也能发挥有效的治疗效果。例如,以重量百分比计算,相对于滴眼液,即使使用0.5%至50%的药物,所述药物递送用隐形眼镜也可以表现出有效的治疗效果,具体地,即使使用0.5%至40%、0.5%至30%、0.5%至20%、0.5%至10%、0.5%至8%、0.5%至6%、0.5%至4%、0.5%至2%、1%至40%、1%至30%、1%至20%、1%至10%、1%至8%、1%至6%、1%至4%、1%至2%、2%至40%、2%至30%、2%至20%、2%至10%、2%至8%、2%至6%或2%至4%的药物,也可以表现出有效的治疗效果,但不限于此。根据一实施例,使用包括相同/相似组成的药物的本发明的药物递送用隐形眼镜制剂和滴眼剂评估了药物释放,结果证实所述隐形眼镜制剂显示出比滴眼剂明显更优异的药物释放结果(以恒定速率释放药物)(表7至表9和图13至图15),由此可见,当使用本发明的药物递送用隐形眼镜时,可以以恒定速率有效地递送药物。
另外,根据一实施例,使用包括相同/相似组成的药物的本发明的药物递送用隐形眼镜制剂和滴眼剂对血液和眼球组织进行了药代动力学评估,结果证实,与滴眼剂相比,当使用药物递送用隐形眼镜制剂时,血液、角膜、结膜、巩膜或眼房水中的生物利用度分别增加了约14倍、37倍、11倍、11倍或133倍(表10至表14和图16至图20)。因此,可以看出,当使用本发明的药物递送用隐形眼镜制剂时,与滴眼液相比,即使时使用0.5重量%至10重量%(血液:约7.1%,角膜:约2.7%,结膜:约9.1%,巩膜:约9.1%,或眼房水:约0.75%)的药物也可以显示出有效的治疗效果。
所述药物可以为眼科药学上具有活性的药物。
所述药物可以由选自低分子化合物、高分子化合物、肽和多肽中的至少一种组成,但不限于此。
所述药物可以包括选自干眼症治疗剂、青光眼治疗剂、降眼压剂、视力损伤治疗剂、抗菌剂、过敏性结膜炎治疗剂、睑结膜炎治疗剂、夜盲症治疗剂、弱视治疗剂、眼部炎症治疗剂、白内障治疗剂、抗病毒剂、散瞳药、碳酸酐酶抑制剂和黄斑变性抑制剂中的至少一种,但不限于此。
所述低分子化合物通常可以是指分子量小于等于1000的物质。所述低分子化合物可以包括选自下列的至少一种:透明质酸、氯化钙、氯化钠、葡萄糖、海藻糖、牛磺酸、丙二醇、西曲溴胺、天冬酰胺、维生素A棕榈酸酯、地夸磷索、瑞巴派特、立他司特、噻吗洛尔、多佐胺、拉坦前列腺素、溴莫尼定、他氟前列素、布林佐胺、曲伏前列素、比马前列素、倍他洛尔、卡替洛尔、尼普地洛、阿可乐定、毛果芸香碱、左布诺洛尔、异丙乌诺前列酮、贝夫洛尔、乙酰唑胺、醋甲唑胺、双氯芬胺、乌诺前列酮、维替泊芬、左氧氟沙星、氧氟沙星、妥布霉素、莫西沙星、加替沙星、土霉素、磺胺甲恶唑、甘草酸、妥舒沙星、洛美沙星、氯霉素、地塞米松、四氢唑啉、氯苯那敏、那他霉素、环丙沙星、甘草次酸、夫西地酸、愈创奥、奥苷菊环、红霉素、庆大霉素、磺胺甲噻二唑、头孢甲肟、诺氟沙星、小诺霉素、四环素、奥洛他定、酮替芬、阿卡他定、贝他斯汀、氮卓斯汀、新斯的明、吡哆醇、依匹斯汀、萘甲唑啉、泛醇、视黄醇、非尼拉敏、尿囊素、天冬氨酸、氰钴胺素、阿扎司特、色甘酸、曲尼司特、非尼拉敏、洛度沙胺、N-乙酰天冬氨酰谷氨酸、越橘干提取物、β-胡萝卜素、抗坏血酸、瓜氨酸、生育酚、核黄素、呋喃硫胺、锰、硒、麦角钙化醇、头孢克洛、氟米龙、四氢唑啉、泼尼松龙、氯替泼诺、瑞美松龙、曲安西龙、溴芬酸、酮咯酸、苄达酸、双氯芬酸、普拉洛芬、氟比洛芬、培比洛芬、新霉素、碘化钾、碘化钠、吡诺克辛、硫胺素、氮杂并五苯、苄达赖氨酸、奈帕芬胺、阿昔洛韦、更昔洛韦、曲氟尿苷、托吡卡胺、苯肾上腺素、氨基己酸、阿托品、环喷托酯、后马托品、唑泊司他、非诺贝特、塞来昔布、艾瑞昔布、帕马考昔、罗美昔布、依托考昔、伐地考昔,但不限于此。
所述高分子化合物同城可以是指聚合体(polymer),可分为合成聚合物和天然聚合物。另外,所述高分子化合物可以是指除所述低分子化合物以外的化合物、聚合物等。所述高分子化合物形式的药物可以包括选自羧甲基纤维素、羟丙基甲基纤维素、聚乙烯吡咯烷酮、聚丙烯酸、羊毛脂、葡聚糖、羟乙基纤维素、聚山梨酯80、聚乙烯醇、聚乙二醇、卡波姆、瓜尔胶和羟甲基纤维素中的至少一种,但不限于此。
所述肽是指氨基酸单元被人工或天然连接的聚合物。根据氨基酸残基的数量,
所述肽可分为二肽、三肽、寡肽、多肽等。在本发明中,所述肽形式的药物可以单独由一个肽组成,也可以由两个或多个肽组成,具体地,可以单独由一个肽组成,也可以由两个、三个或四个肽组合而成。所述肽形式的药物可以包括选自软骨素、环孢菌素、雷珠单抗、阿柏西普、多粘菌素B、粘菌素、贝伐珠单抗、利拉鲁肽和索马鲁肽中的至少一种,但不限于此。
作为一例,所述药物可以包括选自立他司特、噻吗洛尔、多佐胺、拉坦前列腺素、唑泊司他、左氧氟沙星、毛果芸香碱、瑞巴派特、非诺贝特、奥洛他定、氟米龙、吡诺克辛、阿昔洛韦、利拉鲁肽,索马鲁肽、环孢菌素或其药学上可接受的盐中的至少一种。
所述药物递送用隐形眼镜可以提高所释放的药物对眼球血液或眼球组织(角膜、结膜、巩膜和眼房水)的渗透率,具体此,与滴眼液相比,可以提高药物对眼球血液或眼球组织(角膜、结膜、巩膜和眼房水)的渗透率。因此,所述药物递送用隐形眼镜可以提高所释放药物的生物利用度。
所述药物可以包括选自下列的至少一种:透明质酸、氯化钙、氯化钠、葡萄糖、海藻糖、牛磺酸、丙二醇、西曲溴胺、天冬酰胺、维生素A棕榈酸酯、地夸磷索、瑞巴派特、立他司特、噻吗洛尔、多佐胺、拉坦前列腺素、溴莫尼定、他氟前列素、布林佐胺、曲伏前列素、比马前列素、倍他洛尔、卡替洛尔、尼普地洛、阿可乐定、毛果芸香碱、左布诺洛尔、异丙乌诺前列酮、贝夫洛尔、乙酰唑胺、醋甲唑胺、双氯芬胺、乌诺前列酮、维替泊芬、左氧氟沙星、氧氟沙星、妥布霉素、莫西沙星、加替沙星、土霉素、磺胺甲恶唑、甘草酸、妥舒沙星、氨基己酸、洛美沙星、氯霉素、地塞米松、四氢唑啉、氯苯那敏、那他霉素、环丙沙星、甘草次酸、夫西地酸、愈创奥、奥苷菊环、红霉素、庆大霉素、磺胺甲噻二唑、头孢甲肟、诺氟沙星、小诺霉素、四环素、奥洛他定、酮替芬、阿卡他定、贝他斯汀、氮卓斯汀、新斯的明、吡哆醇、依匹斯汀、萘甲唑啉、泛醇、视黄醇、非尼拉敏、尿囊素、天冬氨酸、氰钴胺素、阿扎司特、色甘酸、曲尼司特、非尼拉敏、洛度沙胺、N-乙酰天冬氨酰谷氨酸、越橘干提取物、β
-胡萝卜素、抗坏血酸、瓜氨酸、生育酚、核黄素、呋喃硫胺、锰、硒、麦角钙化醇、头孢克洛、氟米龙、四氢唑啉、泼尼松龙、氯替泼诺、瑞美松龙、曲安西龙、溴芬酸、酮咯酸、苄达酸、双氯芬酸、普拉洛芬、氟比洛芬、培比洛芬、新霉素、碘化钾、碘化钠、吡诺克辛、硫胺素、氮杂并五苯、苄达赖氨酸、奈帕芬胺、阿昔洛韦、更昔洛韦、曲氟尿苷、托吡卡胺、苯肾上腺素、阿托品、环喷托酯、后马托品、唑泊司他、非诺贝特、塞来昔布、艾瑞昔布、帕马考昔、罗美昔布、依托考昔、伐地考昔、羧甲基纤维素、羟丙基甲基纤维素、聚乙烯吡咯烷酮、聚丙烯酸、羊毛脂、葡聚糖、羟乙基纤维素、聚山梨酯80、聚乙烯醇、聚乙二醇、卡波姆、瓜尔胶、羟甲基纤维素、软骨素、环孢菌素、雷珠单抗、阿柏西普、多粘菌素B、粘菌素、贝伐珠单抗、利拉鲁肽、索马鲁肽及其药学上可接受的盐。
与滴眼液相比,所述药物递送用隐形眼镜可以提高所施用的药物对眼球血液或眼球组织(角膜、结膜、巩膜和眼房水)的渗透率。
根据一实施例,使用包括相同/相似组成的药物的本发明的药物递送用隐形眼镜制剂和滴眼剂评估了生物利用度,结果证实,与滴眼剂相比,所述隐形眼镜制剂显着提高药物的生物利用度和药物浓度维持时间(表10至表14和图16至图20),由此可见,当使用本发明的药物递送用隐形眼镜时,可将药物有效地递送到眼球血管和组织中。
本发明的另一方面提供一种眼科用组合物,其包括:药物,其在眼科药学上具有活性;和用于控释药物的赋形剂,其为粘稠剂、乳化剂、稳定剂中的任意一种或多种。与上述内容相同的部分也适用于所述组合物。
相对于眼科用组合物的总含量,所述眼科药学上具有活性的药物的含量可以为5w/v%至20w/v%,但不限于此。
所述眼科用组合物还可以包括pH调节剂、等渗剂或保存剂等。
所述眼科用组合物可用于改善、预防或治疗眼科疾病,优选可用于改善、预防或治疗干眼症、青光眼、眼压下降、视力损伤、细菌/病毒、过敏性结膜炎、睑结膜炎、夜盲症、弱视、眼部炎症、白内障、瞳孔障碍、与碳酸酐酶和/或黄斑变性相关的疾病,或障碍,但不限于此。
如本文所用,术语“改善”是指通过施用根据本发明的眼科用组合物来减轻眼科疾病的症状。
如本文所用,术语“预防”是指通过施用根据本发明的眼科用组合物来抑制或延迟眼科疾病症状的任何行为。
如本文所用,术语“治疗”是指通过施用根据本发明的眼科用组合物来有利地改变眼科疾病的症状。
【实现例】
下面,将参照图6至图10描述本发明的药物递送用隐形眼镜的具体实现例。根据本实现例的隐形眼镜包括药物储存结构,其与所述隐形眼镜的中央部间隔开并储存药物,并将药物提供给隐形眼镜使用者的眼球。另外,还可以包括视力矫正镜片部,其位于隐形眼镜的中央部以折射光线。
第一实现例
下面将参照图6描述根据本发明隐形眼镜的一实现例。然而,可以省略与上述元件相同或相似的元件的描述。图6为根据本发明隐形眼镜的一实现例的剖视示意图。参见图6,所述隐形眼镜包括:腔室部122,其以凹陷结构形成在隐形眼镜并将药物储存在凹陷结构;和阻挡部124,其至少覆盖腔室部122的一部分;和通道部,其形成在阻挡部124并将药物提供给眼球。
腔室部122可以以凹陷结构形成在隐形眼镜12的内部。作为一实施例,多个腔室部122可以形成在单个隐形眼镜12,并且多个腔室部122可以储存多种不同的药物。在另一实施例中,多个腔室部122可以储存相同的药物。
腔室部122可以形成为具有预定体积。作为一例,腔室部122可以形成为储存1μl至2μl体积的药物。作为另一例,药腔室部122可以形成为对应于所存储的药物的单剂量的体积。
作为上述实现例的一例,阻挡部124可以由硅材料制成。阻挡部124可以由与镜片相同的聚合物材料、所述亲水性聚合物材料和疏水性聚合物材料中的任意一种形成。
第二实现例
下面将参照图7至图9描述根据本发明隐形眼镜的另一实现例。然而,可以省略与上述元件相同或相似的元件的描述。图7为所述隐形眼镜的另一实现例的俯视示意图。图8为沿图7的A-A'线截取的剖视示意图。参见图7和图8,隐形眼镜13包括药物储存结构140。药物储存结构140包括:腔室部142+146+148,其以凹陷结构形成并将药物储存在凹陷结构;排出路径146,其为以凹陷结构形成在隐形眼镜的通道,腔室部142+146+148中包括的药物可以通过所述通道移动到所述排出口以释放药物;和阻挡部144,其覆盖腔室部142+146+148的一部分,阻挡部144打开药物排出路径的端部以形成排出口148。
排出路径146包括在腔室部142+146+148中,并且将腔室部142+146+148中包括的药物D引导到排出口148。图8示出了排出路径146和腔室部的一部分142形成为具有相同高度的示例,但在未图示的例子中,排出路径146可以形成为具有比腔室部一部分142的高度更小的高度。
如图7所示,阻挡部144可以形成为覆盖隐形眼镜13的后面,并且可以通过打开排出路径146的下端部来形成排出口148。
图9(a)为从图7中B方向观察隐形眼镜的断面时的排出口148的例子的示意图,图9(b)为排出口148的另一例子的示意图。参见图7至图9(a),阻挡部144暴露出排出路径146的下端部以形成排出口148。因此,根据图9(a)所示的例子,排出口148向隐形眼镜13的下面排出药物D。
然而,根据图9(b)所示的药物排出口的例子,阻挡部144可以形成为覆盖排出路径146的整个下面,但由于打开排出路径146的侧端部,因此排出口148可以形成在排出路径146的端部,如图9(b)所示。
人们不自觉地眨眼。所示例的隐形眼镜13的使用者可能会不自觉地眨眼,通过眼睑在移动隐形眼镜13的上部时施加的压力,储存在腔室部142+146+148中的药物D可以通过排出口148排出并提供给使用者的眼球。
第三实现例
下面将参照图10描述根据本发明隐形眼镜的另一实现例。然而,可以省略与上述元件相同或相似的元件的描述。图10为所述隐形眼镜的另一实现例的俯视示意图。参见图10,隐形眼镜14包括药物储存结构150。药物储存结构150包括:腔室部152+156+158,其以凹陷结构形成并将药物储存在凹陷结构;排出路径156,其以凹陷结构形成在隐形眼镜,并包括在腔室部152+156+158以释放药物;和阻挡部154,其覆盖腔室部152+156+158的一部分,阻挡部154打开排出路径的端部以形成排出口158。
根据图示的示例,腔室部152+156+158可以沿着隐形眼镜14的中心形成为圆形。因此,单一药物可以大容量储存。
在图示的隐形眼镜14中,与上述示例一样,排出口158可以形成在隐形眼镜14的下面以排出药物D,排出口158可以形成在排出路径156的侧面部以将药物排放到隐形眼镜14的端部。
有益效果
根据本发明的药物递送用隐形眼镜可以恒定且持续地释放药物,与现有已知的滴眼液相比,减少了剂量和给药次数,从而生物利用度有望得到改善,可以减少给药剂量产生的副作用,并且可以提高药物对组织的渗透率。另外,根据本发明的药物递送用隐形眼镜可以容易地应用于各种药物,对眼粘膜的刺激较小,制备方法简单,适合大量生产。
附图简单说明
图1为根据本发明一实施例的药物递送用隐形眼镜的结构。
图2为根据本发明另一实施例的药物递送用隐形眼镜的结构。
图3为根据本发明的药物递送用隐形眼镜的腔室部的具体形状。
图4为用于制备根据本发明的药物递送用隐形眼镜的隐形眼镜形状。
图5为根据阻挡部的腔室部阻挡率的药物递送用隐形眼镜。
图6为根据本发明的药物递送用隐形眼镜的第一实现例的俯视示意图。
图7为根据本发明的药物递送用隐形眼镜的第二实现例的俯视示意图。
图8为沿图7的A-A'线截取的剖视示意图。
图9(a)为从图7中B方向观察隐形眼镜的断面时的药物排出口148的例子的示意图,图9(b)为药物排出口148的另一例子的示意图。
图10为根据本发明的药物递送用隐形眼镜的第三实现例的俯视示意图。
图11为根据腔室部阻挡率的药物递送用隐形眼镜的药物释放试验的评价结果。
图12至图15为根据腔室部中包括的用于控释药物的赋形剂的组成的药物释放试验的评价结果。
图16为使用本发明的药物递送用隐形眼镜释放的药物在血液中的生物药代动力学的评价结果。
图17为使用本发明的药物递送用隐形眼镜释放的药物在角膜中的生物药代动力学的评价结果。
图18为使用本发明的药物递送用隐形眼镜释放的药物在结膜中的生物药代动力学的评价结果。
图19为使用本发明的药物递送用隐形眼镜释放的药物在巩膜中的生物药代动力学的评价结果。
图20为使用本发明的药物递送用隐形眼镜释放的药物在眼房水中的生物药代动力学的评价结果。
具体实施方式
下面将通过实施例或实验例进行更详细的描述。然而,这些实施例或实验例等仅用于描述目的,本发明的范围不限于这些实施例。
实验例1:制备包括可储存药物的腔室部和阻挡部等的用于储存药物的隐形眼镜
为了制备本发明的药物递送用隐形眼镜,进行了如下实验。
具体地,为了制备包括各种类型腔室部的药物递送用隐形眼镜的主体部,制备了模具(阴模和阳模)。模具由304级不锈钢制成,并使用铣床(CNC machine
850)加工。
接下来,将15mL的甲基丙烯酸2-羟乙酯(2-hydroxyethylmethacrylate,2-
HEMA)涂抹到模具的阴模上后,将阳模组合在2-HEMA上以制成隐形眼镜形状。然后,使用强制对流烘箱(Forced convection oven)OF-02在80℃下固化1小时后,将2-HEMA与阴模和阳模分离,除去隐形眼镜以外的部分以完成主体部。
接下来,将阻挡部结合到主体部的上部。阻挡部使用2-HEMA,并制成各种大小,
以便能够阻挡腔室部面积的部分或全部(25%、50%、75%、85%、95%、100%)
(图5)。
实验例2:根据阻挡部(阻挡膜)的大小评估药物释放特性
为了根据阻挡部(阻挡膜)的大小评估药物释放特性,准备了如图4所示具有各种阻挡率的药物递送用隐形眼镜,其中所述阻挡部结合到用于存储药物的腔室部,以阻挡腔室部中存储的药物的释放。
具体地,准备了药物递送用隐形眼镜,其中,多个直线形式的腔室部结合到阻挡部(阻挡膜),基于腔室部的总面积,所述阻挡部可以阻挡腔室部面积的0%、
25%、50%、75%、85%、95%和100%,将药物注入到每个腔室部,并评估了药物的释放特性。
药物释放试验通过将所述药物递送用隐形眼镜放入弗兰兹扩散池(Franzdiffusion cell)来进行评估,并使用pH7.4的磷酸盐缓冲溶液将温度保持在37.0±0.5℃以进行试验。将立他司特溶解于蒸馏水的溶液注入药物递送用隐形眼镜的腔室部中,并将其安装在供体(donor)上以执行。另外,通过在预定的采样时间(0.5小时、1小时、1.5小时、2小时、3小时、4小时、5小时、6小时)用注射器从每个容器中收集5mL释放药物的溶液并填充相同量的缓冲溶液的方式来进行实验,将含有所收集药物的溶液5mL用注射器过滤器过滤后,分别取2mL装入小瓶中作为试验液,使用高效液相色谱法(HPLC)对所获得的试验液进行分析。
经所述实验结果证实,药物释放模式根据药物递送用隐形眼镜的阻挡部的大小(阻挡部的阻挡比率)而不同,具体地,药物的释放率受腔室部的阻挡比率影响,药物在50%至95%的阻挡比率下表现出持续释放效果,而在100%的阻挡比率下没有观察到持续释放效果(表1和图11)。由以上结果可知,对本发明的药物递送用隐形眼镜而言,可以通过使用阻挡部(阻挡膜)调节腔室部的阻挡比率来控制一定水平的药物释放,具体地,可以调节药物以恒定速率释放。
【表1】
实验例3:使用用于控释药物的赋形剂的控释药物的评价
3-1:药物释放控制评价1
在本发明的药物递送用隐形眼镜中,为了确认是否可以使用用于控释药物的赋形剂来控制注入腔室部中的药物的释放,进行了如下实验。
具体地,将用于控释药物的赋形剂与药物一起注入到腔室部,所述腔室部为药物递送用隐形眼镜的药物储库。使用如图3(a)所示形状的腔室部,并且使用可以阻断腔室部总面积的75%的大小的阻挡部(阻挡膜)。
以粘稠剂、乳化剂和/或稳定剂作为用于控释药物的赋形剂。以羟丙基甲基纤维素(HPMC)作为粘稠剂,以泊洛沙姆(Poloxamer 188)作为乳化剂,以聚山梨酯80作为稳定剂,按照下表2所示的比率制备样品后,进行了药物释放试验。
【表2】
药物释放试验通过将所述药物递送用隐形眼镜放入弗兰兹扩散池(Franzdiffusion cell)来进行评估,并使用pH7.4的磷酸盐缓冲溶液将温度保持在37.0±0.5℃以进行试验。将包括立他司特(Lifitegrast)和药物递送用隐形眼镜的液体组合物注入药物递送用隐形眼镜的腔室部中,并将其安装在供体(donor)上以执行。另外,通过在预定的采样时间(0.5小时、1小时、1.5小时、2小时、3小时、4小时、5小时、6小时)用注射器从每个容器中收集5mL释放药物的溶液并填充相同量的缓冲溶液的方式来进行实验,将含有所收集药物的溶液5mL用注射器过滤器过滤后,分别取2mL装入小瓶中作为试验液,使用高效液相色谱法(HPLC)对所获得的试验液进行分析。
经所述实验结果证实,根据注入药物递送用隐形眼镜的腔室部中的粘稠剂、乳化剂和/或稳定剂的组成和比例,可以实现持续释放药物的效果(表3和图12)。
【表3】
因此,由以上结果可知,可以通过同时应用阻挡部的腔室部阻挡比率和用于控释药物的赋形剂来实现目标药物释放模式。
3-2:药物释放控制评价2
为了确认用于控释药物的赋形剂是否可以对多种药物进行控释药物,进行了如下实验。
具体地,将用于控释药物的赋形剂与多种药物一起注入到腔室部,所述腔室部为药物递送用隐形眼镜的药物储库。使用如图3(d)所示形状的腔室部,并且使用可以阻断腔室部总面积的92%的大小的阻挡部(阻挡膜)。药物释放试验根据所述实验例3-1所述方法进行,定时(1小时、2小时、4小时、6小时)
取样,使用HPLC对其进行分析,并将实施例与滴眼剂进行比较。
以立他司特、拉坦前列腺素和利拉鲁肽作为靶点药物,注入腔室部的药物组合物溶液由下表4至表6所示的成分组成。
【表4】
/>
【表5】
【表6】
经所述实验结果证实,对于各种类型的药物,也可以根据药物组合物溶液中赋形剂的比例来控制药物释放模式。另外,经证实,当使用本发明的药物递送用隐形眼镜时,与滴眼液相比,可以以恒定速率释放药物(表7至表9和图13至图15)。
【表7】
【表8】
【表9】
因此,由以上结果可知,可以通过同时应用阻挡部的腔室部阻挡比率和用于控释药物的赋形剂来实现目标药物释放模式。
实验例4:生物利用度改善试验
为了进行使用本发明的药物递送用隐形眼镜释放的药物的生物药代动力学评价,
进行了如下实验。
具体地,使用可以佩戴隐形眼镜的约6月龄兔子作为试验动物,给药前一周,
使试验动物在23±2℃温度、50±10%湿度和12/12小时光照/黑暗循环的饲养条件下经受适应期。将实验例3-1中实施例6组成的药物递送用隐形眼镜作为实验组(实施例12),作为对照组(比较例4),将Xiidra滴眼液给药一次并进行比较。为了确认药物在药物作用部位即角膜、结膜、巩膜和眼房水中的分布,在给药后的不同时间处死兔子并取出眼球。每个时间点处死的个体为两只,眼球组织的数量设置为四个。从取出的眼球中分离角膜、结膜、巩膜等,在蒸馏水中匀浆后,使用LC-MS/MS分析样本中的药物浓度。由眼球组织中的药物浓度计算浓度-时间曲线下面积(AUC)和平均浓度,并且与对照组相比,对实验组的给药剂量与组织分布率的增加或减少进行了评估。
从血液药代动力学分析可以看出,当使用本发明的药物递送用隐形眼镜时,与滴眼剂相比,生物利用度增加了14倍(表10和图16)。
【表10】
参数 | 比较例4 | 实施例12 |
t1/2(h) | 1.98 | 3.30 |
Tmax(h) | 0.25 | 0.33 |
Cmax(ng/mL) | 67.77 | 909.00 |
AUClast(ng·h/mL) | 45.36 | 980.28 |
AUClast/剂量 | 9.07 | 122.54 |
相对BA(%) | - | 1,351.05 |
接着,从角膜内的药代动力学分析结果可以看出,当使用本发明的药物递送用隐形眼镜时,与对照组(滴眼剂)相比,药物向角膜的渗透率增加了37倍,并且角膜中的药物浓度维持至给药后3小时(表11和图17)。
【表11】
参数 | 比较例4 | 实施例12 |
t1/2(h) | 5.38 | 3.90 |
Tmax(h) | 0.25 | 0.50 |
Cmax(μg/mL) | 6.04 | 270.03 |
AUClast(μg·h/mL) | 22.90 | 1351.68 |
AUClast/剂量 | 4.58 | 168.96 |
相对BA(%) | - | 3,689.08 |
接着,从结膜内的药代动力学分析结果可以看出,当使用本发明的药物递送用隐形眼镜时,与对照组(滴眼剂)相比,药物向结膜的渗透率增加了11倍,并且结膜内药物浓度的维持时间较长(表12和图18)。
【表12】
参数 | 比较例4 | 实施例12 |
t1/2(h) | 3.67 | 3.65 |
Tmax(h) | 0.25 | 0.50 |
Cmax(μg/mL) | 13.06 | 278.43 |
AUClast(μg·h/mL) | 17.04 | 299.93 |
AUClast/剂量 | 3.41 | 37.49 |
相对BA(%) | - | 1099.41 |
接着,从巩膜内的药代动力学分析结果可以看出,当使用本发明的药物递送用隐形眼镜时,与对照组(滴眼剂)相比,药物向巩膜的渗透率增加了11倍(表13和图19)。
【表13】
参数 | 比较例4 | 实施例12 |
t1/2(h) | 2.66 | 4.12 |
Tmax(h) | 0.25 | 0.50 |
Cmax(μg/mL) | 4.85 | 25.32 |
AUClast(μg·h/mL) | 6.50 | 114.06 |
AUClast/剂量 | 1.30 | 14.26 |
相对BA(%) | - | 1096.92 |
接着,从眼房水内的药代动力学分析结果可以看出,当使用本发明的药物递送用隐形眼镜时,与对照组(滴眼剂)相比,药物向眼房水的渗透率增加了133倍,并且药物浓度的维持时间较长(表14和图20)。
【表14】
综上所述,当使用本发明的药物递送用隐形眼镜时,与现有的滴眼液相比,药物在血液和眼球的各种组织(角膜、结膜、巩膜和眼房水)中的渗透率和生物利用度可以显着提高,从而所述药物递送用隐形眼镜可以有效地用于眼科药学上的药物递送,由此还可以有效用于眼科疾病的治疗/预防。
以上对本发明的描述仅用于示例,本领域的技术人员可以理解,在不改变本发明的技术精神或本质特征的情况下,可以容易地将其修改为其他具体形式。因此,应当理解,上述实施例在所有方面都是示例性的,而不是限制性的。
【符号说明】
12、13、14:隐形眼镜
140、150:药物储存结构
122、142+146+148、152+156+158:腔室部
124、144、154:阻挡部
146、156:排出路径
148、158:排出口
200:视力矫正镜片部
D:药物
Claims (10)
1.一种药物递送用隐形眼镜,其包括:
镜体部;
腔室部,其与所述镜体部的中央部间隔开并储存药物;和
阻挡部,其与所述腔室部的一部分结合并控制药物释放,
所述腔室部包括通道部,药物通过所述通道部从所述腔室部移动并释放到眼球。
2.根据权利要求1所述的药物递送用隐形眼镜,其特征在于,所述通道部包括释放药物的排出口。
3.根据权利要求1所述的药物递送用隐形眼镜,其特征在于,所述通道部包括:
排出口,其释放药物;以及
排出路径,药物通过所述排出路径移动而排出。
4.根据权利要求1至3中任一项所述的药物递送用隐形眼镜,其特征在于,所述阻挡部形成为可以覆盖腔室部的50面积%至95面积%的大小。
5.根据权利要求1至3中任一项所述的药物递送用隐形眼镜,其特征在于,所述腔室部包括药物和用于控释药物的赋形剂。
6.根据权利要求5所述的药物递送用隐形眼镜,其特征在于,
所述用于控释药物的赋形剂为选自粘稠剂、乳化剂、稳定剂、pH调节剂、等渗剂和保存剂中的任意一种或多种。
7.根据权利要求1至3中任一项所述的药物递送用隐形眼镜,其特征在于,所述药物由选自低分子化合物、高分子化合物、肽和多肽中的至少一种组成。
8.根据权利要求1至3中任一项所述的药物递送用隐形眼镜,其特征在于,
所述药物包括选自下列的至少一种:透明质酸、氯化钙、氯化钠、葡萄糖、海藻糖、牛磺酸、丙二醇、西曲溴胺、天冬酰胺、维生素A棕榈酸酯、地夸磷索、瑞巴派特、立他司特、噻吗洛尔、多佐胺、拉坦前列腺素、溴莫尼定、他氟前列素、布林佐胺、曲伏前列素、比马前列素、倍他洛尔、卡替洛尔、尼普地洛、阿可乐定、毛果芸香碱、左布诺洛尔、异丙乌诺前列酮、贝夫洛尔、乙酰唑胺、醋甲唑胺、双氯芬胺、乌诺前列酮、维替泊芬、左氧氟沙星、氧氟沙星、妥布霉素、莫西沙星、加替沙星、土霉素、磺胺甲恶唑、甘草酸、妥舒沙星、氨基己酸、洛美沙星、氯霉素、地塞米松、四氢唑啉、氯苯那敏、那他霉素、环丙沙星、甘草次酸、夫西地酸、愈创奥、奥苷菊环、红霉素、庆大霉素、磺胺甲噻二唑、头孢甲肟、诺氟沙星、小诺霉素、四环素、奥洛他定、酮替芬、阿卡他定、贝他斯汀、氮卓斯汀、新斯的明、吡哆醇、依匹斯汀、萘甲唑啉、泛醇、视黄醇、非尼拉敏、尿囊素、天冬氨酸、氰钴胺素、阿扎司特、色甘酸、曲尼司特、非尼拉敏、洛度沙胺、N-乙酰天冬氨酰谷氨酸、越橘干提取物、β-胡萝卜素、抗坏血酸、瓜氨酸、生育酚、核黄素、呋喃硫胺、锰、硒、麦角钙化醇、头孢克洛、氟米龙、四氢唑啉、泼尼松龙、氯替泼诺、瑞美松龙、曲安西龙、溴芬酸、酮咯酸、苄达酸、双氯芬酸、普拉洛芬、氟比洛芬、培比洛芬、新霉素、碘化钾、碘化钠、吡诺克辛、硫胺素、氮杂并五苯、苄达赖氨酸、奈帕芬胺、阿昔洛韦、更昔洛韦、曲氟尿苷、托吡卡胺、苯肾上腺素、阿托品、环喷托酯、后马托品、唑泊司他、非诺贝特、塞来昔布、艾瑞昔布、帕马考昔、罗美昔布、依托考昔、伐地考昔、羧甲基纤维素、羟丙基甲基纤维素、聚乙烯吡咯烷酮、聚丙烯酸、羊毛脂、葡聚糖、羟乙基纤维素、聚山梨酯80、聚乙烯醇、聚乙二醇、卡波姆、瓜尔胶、羟甲基纤维素、软骨素、环孢菌素、雷珠单抗、阿柏西普、多粘菌素B、粘菌素、贝伐珠单抗、利拉鲁肽、索马鲁肽及其药学上可接受的盐。
9.根据权利要求1至3中任一项所述的药物递送用隐形眼镜,其特征在于,提高所释放的药物进入眼球血液或组织内的渗透率。
10.根据权利要求1至3中任一项所述的药物递送用隐形眼镜,其特征在于,
所述隐形眼镜还包括视力矫正镜片部。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
KR10-2021-0002689 | 2021-01-08 | ||
KR20210002689 | 2021-01-08 | ||
PCT/KR2022/000314 WO2022149914A1 (ko) | 2021-01-08 | 2022-01-07 | 약물전달용 콘택트렌즈 및 안과용 약학적 조성물 |
Publications (1)
Publication Number | Publication Date |
---|---|
CN116761630A true CN116761630A (zh) | 2023-09-15 |
Family
ID=82358269
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN202280008993.XA Pending CN116761630A (zh) | 2021-01-08 | 2022-01-07 | 一种药物递送用隐形眼镜和眼科用药物组合物 |
Country Status (9)
Country | Link |
---|---|
US (1) | US20240033124A1 (zh) |
EP (1) | EP4275675A1 (zh) |
JP (1) | JP2024502964A (zh) |
KR (1) | KR20220100541A (zh) |
CN (1) | CN116761630A (zh) |
AU (1) | AU2022205341A1 (zh) |
CA (1) | CA3204104A1 (zh) |
MX (1) | MX2023008097A (zh) |
WO (1) | WO2022149914A1 (zh) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
KR102631008B1 (ko) * | 2023-12-27 | 2024-01-30 | 이하리 | 화장료 조성물 및 이의 제조방법 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2010068281A2 (en) * | 2008-12-11 | 2010-06-17 | Massachusetts Institute Of Technology | Contact lens drug delivery device |
KR101877031B1 (ko) * | 2016-12-30 | 2018-07-11 | 주식회사 윈스 | 약물이 담지된 콘택트렌즈 |
KR101860667B1 (ko) | 2017-04-12 | 2018-05-24 | 조선대학교산학협력단 | 라소자임 감응 약물 전달용 하이드로겔 콘택트렌즈 및 그 제조방법 |
CN114296256A (zh) * | 2017-05-01 | 2022-04-08 | 普雷斯拜视力有限公司 | 动态泪液透镜 |
KR102009571B1 (ko) * | 2017-11-06 | 2019-08-09 | 대구가톨릭대학교산학협력단 | 온도감응성 약물전달용 하이드로겔 콘택트렌즈 및 그 제조방법 |
-
2022
- 2022-01-07 EP EP22736891.7A patent/EP4275675A1/en active Pending
- 2022-01-07 AU AU2022205341A patent/AU2022205341A1/en active Pending
- 2022-01-07 US US18/268,614 patent/US20240033124A1/en active Pending
- 2022-01-07 WO PCT/KR2022/000314 patent/WO2022149914A1/ko active Application Filing
- 2022-01-07 CN CN202280008993.XA patent/CN116761630A/zh active Pending
- 2022-01-07 MX MX2023008097A patent/MX2023008097A/es unknown
- 2022-01-07 KR KR1020220002785A patent/KR20220100541A/ko not_active Application Discontinuation
- 2022-01-07 CA CA3204104A patent/CA3204104A1/en active Pending
- 2022-01-07 JP JP2023540096A patent/JP2024502964A/ja active Pending
Also Published As
Publication number | Publication date |
---|---|
EP4275675A1 (en) | 2023-11-15 |
US20240033124A1 (en) | 2024-02-01 |
WO2022149914A1 (ko) | 2022-07-14 |
CA3204104A1 (en) | 2022-07-14 |
AU2022205341A1 (en) | 2023-06-29 |
JP2024502964A (ja) | 2024-01-24 |
KR20220100541A (ko) | 2022-07-15 |
MX2023008097A (es) | 2023-07-14 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20200323685A1 (en) | Sustained release delivery of active agents to treat glaucoma and ocular hypertension | |
TWI454285B (zh) | 治療青光眼及高眼壓之活性劑之持續釋放輸送 | |
US20090318549A1 (en) | Combination treatment of glaucoma | |
US20190091066A1 (en) | Drug Delivery System and Methods of Treating Open Angle Glaucoma and Ocular Hypertension | |
Castro-Balado et al. | New ophthalmic drug delivery systems | |
KR20220127186A (ko) | 콘택트렌즈 및 이를 제조하기 위한 몰드 | |
CN116761630A (zh) | 一种药物递送用隐形眼镜和眼科用药物组合物 | |
KR20220139901A (ko) | 사전 활성화된 티오머를 기반으로 하는 점막 접착성 고체 또는 반고체 안과용 전달 시스템 | |
EP2844224B1 (en) | Drug delivery system for treating open angle glaucoma and ocular hypertension |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PB01 | Publication | ||
PB01 | Publication | ||
SE01 | Entry into force of request for substantive examination | ||
SE01 | Entry into force of request for substantive examination |