TR2022007363A2 - COMPOSITION CONTAINING NONSTEROIDAL ANTI-INFLAMMATORY ACTIVE INGREDIENT - Google Patents
COMPOSITION CONTAINING NONSTEROIDAL ANTI-INFLAMMATORY ACTIVE INGREDIENTInfo
- Publication number
- TR2022007363A2 TR2022007363A2 TR2022/007363 TR2022007363A2 TR 2022007363 A2 TR2022007363 A2 TR 2022007363A2 TR 2022/007363 TR2022/007363 TR 2022/007363 TR 2022007363 A2 TR2022007363 A2 TR 2022007363A2
- Authority
- TR
- Turkey
- Prior art keywords
- eye drop
- pharmaceutically acceptable
- composition
- sodium
- combinations
- Prior art date
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 62
- 239000004480 active ingredient Substances 0.000 title claims abstract description 19
- 230000003110 anti-inflammatory effect Effects 0.000 title claims abstract description 17
- 239000003889 eye drop Substances 0.000 claims abstract description 25
- 239000000546 pharmaceutical excipient Substances 0.000 claims abstract description 15
- 206010061218 Inflammation Diseases 0.000 claims abstract description 8
- 230000004054 inflammatory process Effects 0.000 claims abstract description 8
- 230000000699 topical effect Effects 0.000 claims abstract description 7
- 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 17
- 150000003839 salts Chemical class 0.000 claims description 17
- 229960001002 nepafenac Drugs 0.000 claims description 15
- 235000002639 sodium chloride Nutrition 0.000 claims description 14
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 claims description 12
- 239000003755 preservative agent Substances 0.000 claims description 12
- 230000002335 preservative effect Effects 0.000 claims description 11
- -1 treitol Chemical compound 0.000 claims description 10
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 9
- 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 claims description 8
- 239000006172 buffering agent Substances 0.000 claims description 8
- 229960003333 chlorhexidine gluconate Drugs 0.000 claims description 8
- YZIYKJHYYHPJIB-UUPCJSQJSA-N chlorhexidine gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.C1=CC(Cl)=CC=C1NC(=N)NC(=N)NCCCCCCNC(=N)NC(=N)NC1=CC=C(Cl)C=C1 YZIYKJHYYHPJIB-UUPCJSQJSA-N 0.000 claims description 8
- 229960003194 meglumine Drugs 0.000 claims description 8
- 239000003002 pH adjusting agent Substances 0.000 claims description 8
- 239000000600 sorbitol Substances 0.000 claims description 8
- 239000004034 viscosity adjusting agent Substances 0.000 claims description 8
- 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 claims description 7
- 239000000022 bacteriostatic agent Substances 0.000 claims description 7
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- 239000013543 active substance Substances 0.000 claims description 6
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 6
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 claims description 6
- 230000003637 steroidlike Effects 0.000 claims description 6
- 229920002125 Sokalan® Polymers 0.000 claims description 5
- 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 claims description 4
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 4
- GUBGYTABKSRVRQ-CUHNMECISA-N D-Cellobiose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)OC(O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-CUHNMECISA-N 0.000 claims description 4
- 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 claims description 4
- HEBKCHPVOIAQTA-QWWZWVQMSA-N D-arabinitol Chemical compound OC[C@@H](O)C(O)[C@H](O)CO HEBKCHPVOIAQTA-QWWZWVQMSA-N 0.000 claims description 4
- 239000004386 Erythritol Substances 0.000 claims description 4
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 claims description 4
- 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 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 4
- 229930195725 Mannitol Natural products 0.000 claims description 4
- JVWLUVNSQYXYBE-UHFFFAOYSA-N Ribitol Natural products OCC(C)C(O)C(O)CO JVWLUVNSQYXYBE-UHFFFAOYSA-N 0.000 claims description 4
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 4
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 4
- 229960001631 carbomer Drugs 0.000 claims description 4
- 229910000397 disodium phosphate Inorganic materials 0.000 claims description 4
- 235000019800 disodium phosphate Nutrition 0.000 claims description 4
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 claims description 4
- 235000019414 erythritol Nutrition 0.000 claims description 4
- 229940009714 erythritol Drugs 0.000 claims description 4
- 229940093476 ethylene glycol Drugs 0.000 claims description 4
- 239000008103 glucose Substances 0.000 claims description 4
- 229960005150 glycerol Drugs 0.000 claims description 4
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 4
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 4
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 4
- 239000008101 lactose Substances 0.000 claims description 4
- 239000000845 maltitol Substances 0.000 claims description 4
- 235000010449 maltitol Nutrition 0.000 claims description 4
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 claims description 4
- 229940035436 maltitol Drugs 0.000 claims description 4
- 239000000594 mannitol Substances 0.000 claims description 4
- 235000010355 mannitol Nutrition 0.000 claims description 4
- HEBKCHPVOIAQTA-ZXFHETKHSA-N ribitol Chemical compound OC[C@H](O)[C@H](O)[C@H](O)CO HEBKCHPVOIAQTA-ZXFHETKHSA-N 0.000 claims description 4
- 239000001632 sodium acetate Substances 0.000 claims description 4
- 235000017281 sodium acetate Nutrition 0.000 claims description 4
- 239000000661 sodium alginate Substances 0.000 claims description 4
- 235000010413 sodium alginate Nutrition 0.000 claims description 4
- 229940005550 sodium alginate Drugs 0.000 claims description 4
- 229920002554 vinyl polymer Polymers 0.000 claims description 4
- 239000000811 xylitol Substances 0.000 claims description 4
- 235000010447 xylitol Nutrition 0.000 claims description 4
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 claims description 4
- 229960002675 xylitol Drugs 0.000 claims description 4
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 3
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 3
- YASYEJJMZJALEJ-UHFFFAOYSA-N Citric acid monohydrate Chemical compound O.OC(=O)CC(O)(C(O)=O)CC(O)=O YASYEJJMZJALEJ-UHFFFAOYSA-N 0.000 claims description 3
- 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 claims description 3
- 239000000440 bentonite Substances 0.000 claims description 3
- 229910000278 bentonite Inorganic materials 0.000 claims description 3
- 235000012216 bentonite Nutrition 0.000 claims description 3
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 claims description 3
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 3
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 claims description 3
- 229960001950 benzethonium chloride Drugs 0.000 claims description 3
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 3
- 229960003655 bromfenac 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
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 3
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 3
- 229940105329 carboxymethylcellulose Drugs 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 229960004926 chlorobutanol Drugs 0.000 claims description 3
- 229960004106 citric acid Drugs 0.000 claims description 3
- 229960002303 citric acid monohydrate Drugs 0.000 claims description 3
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 claims description 3
- 229960001259 diclofenac 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
- 229960000443 hydrochloric acid Drugs 0.000 claims description 3
- 239000007951 isotonicity adjuster Substances 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
- 229920000609 methyl cellulose Polymers 0.000 claims description 3
- 239000001923 methylcellulose Substances 0.000 claims description 3
- 235000010981 methylcellulose Nutrition 0.000 claims description 3
- HWPKGOGLCKPRLZ-UHFFFAOYSA-M monosodium citrate Chemical compound [Na+].OC(=O)CC(O)(C([O-])=O)CC(O)=O HWPKGOGLCKPRLZ-UHFFFAOYSA-M 0.000 claims description 3
- 239000002524 monosodium citrate Substances 0.000 claims description 3
- 235000018342 monosodium citrate Nutrition 0.000 claims description 3
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 3
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- 229940001593 sodium carbonate Drugs 0.000 claims description 3
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 3
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 3
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 3
- 229940083608 sodium hydroxide Drugs 0.000 claims description 3
- 239000001488 sodium phosphate Substances 0.000 claims description 3
- 229910000162 sodium phosphate Inorganic materials 0.000 claims description 3
- 235000011008 sodium phosphates Nutrition 0.000 claims description 3
- 239000003381 stabilizer Substances 0.000 claims description 3
- 239000004094 surface-active agent Substances 0.000 claims description 3
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 claims description 3
- 150000001875 compounds Chemical class 0.000 claims 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims 1
- 239000000243 solution Substances 0.000 description 15
- 150000005846 sugar alcohols Chemical class 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- 208000002177 Cataract Diseases 0.000 description 3
- HSHXDCVZWHOWCS-UHFFFAOYSA-N N'-hexadecylthiophene-2-carbohydrazide Chemical compound CCCCCCCCCCCCCCCCNNC(=O)c1cccs1 HSHXDCVZWHOWCS-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000002997 ophthalmic solution Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 229940054534 ophthalmic solution Drugs 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- OMDQUFIYNPYJFM-XKDAHURESA-N (2r,3r,4s,5r,6s)-2-(hydroxymethyl)-6-[[(2r,3s,4r,5s,6r)-4,5,6-trihydroxy-3-[(2s,3s,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]methoxy]oxane-3,4,5-triol 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]2[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@H](O)[C@H](O)O1 OMDQUFIYNPYJFM-XKDAHURESA-N 0.000 description 1
- 244000007835 Cyamopsis tetragonoloba Species 0.000 description 1
- 229920000926 Galactomannan Polymers 0.000 description 1
- 208000001344 Macular Edema Diseases 0.000 description 1
- 206010025415 Macular oedema Diseases 0.000 description 1
- 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 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 229950003529 diquafosol Drugs 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 229940064811 ilevro Drugs 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 201000010230 macular retinal edema Diseases 0.000 description 1
- 229940012664 nevanac Drugs 0.000 description 1
- 230000002980 postoperative effect Effects 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 229940061102 topical suspension Drugs 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Abstract
Mevcut buluş, ağrı ve/veya iltihaplanma tedavisinde kullanılmak üzere en az bir nonsteroidal antienflamatuvar etken madde ve en az bir farmasötik olarak kabul edilebilir bir yardımcı madde ihtiva eden bir topikal göz damlası bileşimi ile ilgilidir.The present invention relates to a topical eye drop composition comprising at least one nonsteroidal anti-inflammatory active ingredient and at least one pharmaceutically acceptable excipient for use in the treatment of pain and/or inflammation.
Description
Tarifname NONSTEROIDAL ANTIENFLAMATUVAR ETKEN MADDE IÇEREN BILESIM Bulusun Ilgili Oldugu Alan Mevcut bulus, topikal olarak kullanilmak üzere en az bir nonsteroidal antienflamatuvar etken madde ve en az bir farmasötik olarak kabul edilebilir yardimci madde ihtiva eden bir göz damlasi bilesimi ile ilgilidir. Daha özel olarak, söz konusu bilesim agri ve/veya iltihaplanma tedavisinde kullanilmak üzere sunulmaktadir. Teknigin Bilinen Durumu Nepafenak, genellikle reçeteli göz damlasi olarak %Ü.1'lik solüsyon (Nevanac®] veya %Ü.3'lük solüsyon (Ilevro®) olarak ticari adlari ile piyasada bulunabilen, nonsteroid antientlamatuvar bir ilaçtir [NSAID]. Nepafenak etken maddesinin kimyasal yapisi asagida yer alan Formül 1'de verilmektedir. Formül 1 Söz konusu ilaç, katarakt ameliyati ile iliskili olarak agri ve iltihabin tedavisinde kullanilmaktadir. Nepafenak ayrica, COX'1 ve COX*2 aktivitesinin bir inhibitörü olan amfenakin bir ön ilacidir. Avrupa Birligi'nde nepafenak, diyabetli kisilerde katarakt ameliyati ile iliskili postoperatif makula ödemi riskinin azaltilmasi için de endikedir. US 5475034 A sayili patent belgesinde, 3-benzoilfenilasetik asidin yeni ester ve amid türevleri açiklanmaktadir. Ayrica söz konusu belge kapsaminda açiklanan türevlerin, oftalmik enflamatuar bozukluklarin tedavisi için topikal olarak uygulanabilir bilesimlerde kullanimi da saglanmaktadir. EP 1819362 A2 sayili patent belgesi, nepafenak etken maddesinin topikal süspansiyon bilesimleri ile ilgilidir. Söz konusu bilesimler özellikle topikal oftalmik uygulamaya yöneliktir. EP 2586426 A1 sayili patent belgesi, bir karbomer olarak karboksivinil polimeri, bir guar olarak galaktomannayi ve bir borat bilesigi ihtiva eden süspansiyon bilesimlerine iliskindir. Teknigin bilinen durumunda yer alan nonsteroidal antienflamatuvar etken madde ihitva eden oftalmik çözeltilerinde yasanan en yaygin problem, söz konusu çözeltinin çökelti olusturmaksizinn saklanabilirlige, dayanikliliga ve stabiliteye sahip olmamasidir. Özellikle, ilacin muhafaza edilmesi sürecinde çözelti içerisinde birtakim çökeltiler meydana gelmekte ve bu çökeltiler sonrasinda uzaklastirilamamaktadir. Bilinen çözelti bilesimleri, bu sorununun üstesinden gelmeye yönelik tedbirler içerse de bilesimlerde yer alan yardimci maddelerle geçimsizlik sorunlari devam etmektedir. Ayrica 151, isik ve nem gibi dis faktörlere karsi yeterince dayaniklilik da saglanamamaktadir. Dolayisiyla teknikte çözelti içerisinde çökelti olusumunun engellendigi, stabilitesi, dayanikliligi yüksek nonsteroidal antienflamatuvar etken madde ihtiva eden oftalmik çözelti bilesimlerine yönelik ihtiyaç devam etmektedir. Yukaridaki bilgiler isiginda görülmektedir ki, ilgili teknik alanda, diquafosol içeren bilesimlerin yüksek stabilitesinin ve dayanikliliginin saglandigi, agri ve/veya iltihaplanma tedavisinde endike ve bunlara ek olarak dayanikliligi yüksek oftalmik çözelti bilesimlerine yönelik bir ihtiyaç bulunmaktadir. Mevcut bulus kapsaminda bu amaçla, topikal olarak kullanilmak üzere en az bir nonsteroidal antienilamatuvar etken madde ve en az bir farmasötik olarak kabul edilebilir bir yardimci madde ihtiva eden bir göz damlasi bilesimi sunulmaktadir. Bulusun Kisa Açiklamasi Mevcut bulus bir yönüyle, agri ve/veya iltihaplanma tedavisinde kullanilmak üzere kullanilmak üzere en az bir nonsteroidal antienflamatuvar etken madde ve en az bir farmasötik olarak kabul edilebilir yardimci madde ihtiva eden bir topikal göz damlasi bilesimi sunmaktadir. Bahsedilen non steroidal etken madde, tercihen ketorolak veya bunun farmasötik olarak kabul edilebilir bir tuzunu, bromfenak veya bunun farmasötik kabul edilebilir bir tuzunu, nepafenak, diklofenak veya bunun farmasötik olarak kabul edilebilir bir tuzunu, flubiprofen veya bunun farmasötik olarak kabul edilebilir bir tuzunu içeren bir gruptan seçilebilir. Mevcut bulusa ait bilesim, nonsteroidal antienflamatuvar etken madde nepafenak veya bunun farmasötik olarak kabul edilebilir bir tuzudur. Mevcut bulusa ait bilesim, tercihen %0.01 ila %1 araliginda, daha tercihen %0.05 ila %1 araliginda nonsteroidal antienllamatuvar etken madde ihtiva edebilir. Daha da özel olarak söz konusu bilesim ayrica, %0.1 ila %1 araliginda nonsteroidal antienflamatuvar etken madde ihtiva edebilir. Mevcut bilesimin tercih edilen yapilanmalarinda yer alan farmasötik olarak kabul edilebilir yardimci madde tamponlayici ajan, izotonik ajan, bakteriyostatik madde, pH ayarlayici ajan, tonisite ayarlayici ajan, viskozite ayarlayici ajan, yüzey aktif madde, stabilizatör, koruyucu veya bunlarin kombinasyonlarini içeren bir gruptan seçilmektedir. Bahsedilen tamponlayici ajan sodyum fosfat, sodyum hidrojen fosfat, disodyum hidrojen fosfat, sodyum dihidrojen fosfat, sodyum asetat, monosodyum sitrat, sodyum klorür, sitrik asit monohidrat veya bunlarin kombinasyonlarini içeren bir gruptan seçilmektedir. Söz konusu bakteriyostatik madde ise, benzalkonyum klorür, klorobütanol, benzetonyum klorür, klorheksidin glukonat veya bunlarin kombinasyonlarini içeren bir gruptan seçilmektedir. Mevcut bulusa ait bilesim, farmasötik olarak kabul edilebilir en az bir koruyucu ihtiva edebilir. Söz konusu farmasötik olarak kabul edilebilir bir koruyucu tercihen, meglumin, etilen glikol, gliserol, eritritol, treitol, arabitol ksilitol, ribitol, mannitol, laktoz, sorbitol, galaktikol, glukoz anhidrat, sellobiyoz, maltitolü ve bunlarin kombinasyonlarini içeren bir gruptan seçilemekle beraber sadece bu seker alkolleri veya seker alkolü türevleri ile sinirli degildir. Daha tercihen söz konusu tasiyici, meglumin olabilir, sorbîtol olabilir, galaktikol olabilir. Söz konusu viskozite ayarlayici ajan da, karbomer, bentonit, hidroksipropil metil selüloz, metil selüloz, karboksimetil selüloz, polivinil prolidon, sodyum karboksi metil selüloz veya bunlarin kombinasyonlarini içeren bir gruptan seçilmektedir. Bahsi geçen pH ayarlayici ajan, hidroklorik asit, sodyum hidroksit, sodyum karbonat, sitrik asit, sodyum aljinat veya bunlarin kombinasyonlarini içeren bir gruptan seçilmektedir. Mevcut bilesime ait pH degeri tercihen 4 ila 8 araliginda bir degere, özellikle tercihen 6,8 pH degerindedir. Bulusun Ayrintili Açiklamasi Bu ayrintili açiklamada, mevcut bulusa göre olan agri ve/veya iltihaplanma tedavisinde kullanilmak üzere kullanilmak üzere en az bir nonsteroidal antienflamatuvar etken madde ve en az bir farmasötik olarak kabul edilebilir yardimci madde ihtiva eden bir topikal göz damlasi bilesimi konunun daha iyi anlasilmasi için açiklanmaktadir. Bahsedilen non steroidal etken madde, tercihen ketorolak veya farmasötik olarak kabul edilebilir bir tuzu, bromfenak veya farmasötik kabul edilebilir bir tuzu, nepafenak, diklofenak veya farmasötik olarak kabul edilebilir bir tuzu, flubiprofen veya farmasötik olarak kabul edilebilir bir tuzu arasindan seçilebilir. Mevcut bulusun tercih edilen yapilanmalarinda söz konusu bilesim nonsteroidal antienflamatuvar etken madde olarak nepafenak ihtiva edebilir. Bulusa ait oftalmik bilesim agirlikça %0.01 ila %1 [a/h] araliginda, tercihen %0.05 ila %1 (a/h] araliginda nepafenak ihtiva edebilir. Daha tercihen agirlikça %0.1 ila %1 (a/h) araliginda nepafenak ihtiva edebilir. Mevcut bulus sahipleri, ilgili etken maddenin bu agirlikça miktarda kullanilmasinin bulusa ait kullanima uygun göz damlasi bilesimi katarakt cerrahi ile iliskili olarak agri ve iltihaplanma tedavisinde daha etkili hale getirdigini görmüslerdir. Mevcut bulusa göre olan en az bir farmasötik olarak kabul edilebilir yardimci madde tamponlayici ajan, izotonik ajan, bakteriyostatik madde, pH ayarlayici ajan, tonisite ayarlayici ajan, viskozite ayarlayici ajan, yüzey aktif madde, stabilizatör, koruyucu veya bunlarin kombinasyonlarini içeren bir gruptan seçilebilir. Bulus kapsaminda farmasötik olarak kabul edilebilir yardimci maddeler ile tasarlanmis göz damlasi bilesimi problemlere bir çözüm sunularak ilgili teknik alanda yer alan bilesimlere kiyasla daha iyi kararliliga ve dayanikliliga sahip bir göz damlasi bilesimi saglanmaktadir. Mevcut bulusa göre olan en az bir farmasötik olarak kabul edilebilir yardimci madde tercihen en az bir koruyucu ihtiva etmektedir. Söz konusu farmasötik olarak kabul edilebilir bir koruyucu tercihen, meglumin, etilen glikol, gliserol, eritritol, treitol, arabitol ksilitol, ribitol, mannitol, laktoz, sorbitol, galaktikol, glukoz anhidrat, sellobiyoz, maltitolü ve bunlarin kombinasyonlarini içeren bir gruptan seçilemekle beraber sadece bu seker alkolleri veya seker alkolü türevleri ile sinirli degildir. Daha tercihen söz konusu tasiyici, meglumin olabilir, sorbitol olabilir, galaktikol olabilir. Mevcut bulusun tercih edilen yapilanmalarinda söz konusu bilesim en az bir etken madde, seker alkolü ve diger yardimci maddeleri ihtiva edebilir. Mevcut bulusun tercih edilen yapilanmalarinda söz konusu bilesimin seker alkolleri veya seker alkolü türevleri ile bir arada kullanilmasi ile mevcut bulusa ait bilesimin homojenligi, stabilitesi, dayanikliligi artmakta ve dolayisiyla bahsedilen bilesimin raf ömrü güçlendirilmektedir. Ayrica, mevcut bulus sahipleri, yukarida bahsedilen seker alkollerinin nepafenak etken maddesi ile bir araya getirilmesiyle beraber göz damlasi solüsyonunun saklanmasi sürecinde meydana gelen bozulmalari sürpriz bir sekilde engelleyebildigini kesfetmislerdir. Böylelikle, tamponlayici ajan, viskozite ayarlayici ajan, pH ayarlayici ajan, bakteriyostatik madde ve/veya koruyucunun bir arada kullanildigi yapilanmalarda söz konusu göz damlasi bilesiminin çevresel faktörlere olan dayanikliliginin sasirtici bir sekilde arttigi ve dolayisiyla çözeltinin muhafaza sürecinin de güçlendirildigi ortaya koyulmaktadir. Ayrica, söz konusu koruyucu da meglumin, etilen glikol, gliserol, eritritol, treitol, arabitol ksilitol, ribitol, mannitol, laktoz, sorbitol, galaktikol, glukoz anhidrat, sellobiyoz, maltitolü veya bunlarin kombinasyonlarini içeren bir gruptan seçilmektedir. Özellikle tercihen söz konusu koruyucu, meglumin olabilir, sorbitol olabilir, galaktikol olabilir. Bahsi geçen tamponlayici ajan sodyum fosfat, sodyum hidrojen fosfat, disodyum hidrojen fosfat, sodyum dihidrojen fosfat, sodyum asetat, monosodyum sitrat, sodyum klorür, sitrik asit monohidrat veya bunlarin kombinasyonlarini içeren bir gruptan seçilmektedir. Söz konusu viskozite ayarlayici ajan karbomer, bentonit, hidroksipropil metil selüloz, metil selüloz, karboksimetil selüloz, polivinil prolidon, sodyum karboksi metil selüloz veya bunlarin kombinasyonlarini içeren bir gruptan seçilmektedir. Bahsedilen pH ayarlayici ajan ise, hidroklorik asit, sodyum hidroksit, sodyum karbonat, sitrik asit, sodyum aljinat veya bunlarin kombinasyonlarini içeren bir gruptan seçilmektedir. Mevcut bulusa ait çözeltinin pH degeri 4 ila 8 araliginda bir degere, daha tercihen 6,8 pH degerine ayarlanmaktadir. Ayrica, söz konusu bakteriyostatik madde de benzalkonyum klorür, klorobütanol, benzetonyum klorür, klorheksidin glukonat veya bunlarin kombinasyonlarini içeren bir gruptan seçilmektedir. Mevcut bulusun ileri yapilanmalari, yukarida bahsedilenlerin haricinde bulusa göre sunulan kullanima uygun farmasötik olarak kabul edilebilir eksipiyanlar, çözücüler, baglayicilar, yaglayicilar, kaydiricilar, dolgu maddeleri, selatlayici ajan, islatma maddelerini de içerebilir. Söz konusu yardimci maddelerin yukarida bahsedilmeyen kombinasyonlari da mevcut bulusun kapsami disinda birakilmamalidir. Dolayisiyla, mevcut bulus çözelti içerisinde çökelti olusumunu engelleyerek daha iyi bir dayanikliliga ve kararliliga sahip bir göz damlasi bilesimi sunmasi sebebiyle avantajlidir ve bu yönüyle teknikte bir ilerleme saglamaktaclir. Mevcut bulusa ait bilesimin teknik etkisinin dayanikliliga fayda sagladigi ve bu sebeple mevcut bilesimlere kiyasla daha avantajli oldugu ortaya koyulmaktadir. ÖRNEKLER Tercih edilen yapilanmalarda, mevcut bulusa ait göz damlasi bilesimi asagidaki bilesenleri ihtiva etmektedir: Bilesen Agirlikça (%) (a/h] Nepafenak veya bunun tuzu 0,1 - 10 Tamponlayici ajan 0,1 - 10 Viskozite ayarlayici ajan 0,1 - 10 pH ayarlayici ajan 0,1 - 10 Koruyucu madde 0,001 - 0,1 Bilesen Agirlik (g) Nepafenak 0.300 Sodyum hidrojen fosfat 0.200 Hidroksipropil metil selüloz 0-420 Sodyum hidroksit Ü-17Ü Klorheksidin glukonat 0-050 Meglumin 0-003 Saf su Yeterli miktarda hidroksit, 0.05 g klorheksîdin glukonat ve 0.003 meglumin, saf su içerisinde çözünmesi saglanmistir. Böylece elde edilen çözeltinin hacmi 3 mL olmustur. Bilesen Agirlik (8] Nepafenak 0.100 Polivinil prolidon 0.320 Sitrik asit 0.120 Klorheksidin glukonat 0.5 1 Sorbitol 0.002 Saf su Yeterli miktarda g klorheksidin glukonat ve 0.002 sorbîtol, saf su içerisinde çözünmesi saglanmistir. Böylece elde edilen çözeltinin hacmi 3 mL olmustur. Bilesen Agirlik (g) Nepafenak 0.200 Sodyum asetat 0.200 Polivinil prolidon 0.320 Sodyum aljinat 0.240 Klorheksidin glukonat 0.060 Galaktikol 0.002 Saf su Yeterli miktarda klorheksidin glukonat ve 0.002 galaktikol, saf su içerisinde çözünmesi saglanmistir. Böylece elde edilen çözeltinin hacmi 3 mL olmustur. Yukarida tarif edilen örnek bilesimlerin her biri, bir cam kap içerisinde 25°C'de üç ay boyunca saklanmis ve ardindan söz konusu bilesimlerin görünüslerinde herhangi bir degisiklik olmadigi saptanmistir. Ayrica, bu süreçlerdeki çökelti içerisinde meydana gelen çökeltilerin miktarinin azaldigi da ortaya koyulmustur. Mevcut bulus, nepafenak etken maddesinin veya bunun tuzunun farmasötik olarak kabul edilebilir yardimci maddeler ile bir araya getirilerek saglanan spesifik bilesimi ile çözelti içerisinde çökelti olusumunun engellenmesi saglanarak iyi bir dayanikliliga ve kararliliga sahip ve ayrica isi, isik ve nem gibi dis faktörlere karsi yeterince dayaniklilik gösteren göz damlasi bilesimleri saglamasi bakimindan avantajlidir. Bulusun koruma kapsami ekte verilen istemlerde belirtilmis olup teknikte uzman bir kisinin, bulusun ana temasindan ayrilmadan yukarida anlatilanlar isiginda benzer yapilanmalar ortaya koyabilecegi açiktir. TR Description COMPOSITION CONTAINING NONSTEROIDAL ANTI-INFLAMMATORY ACTIVE INGREDIENT Field of the Invention The present invention relates to an eye drop composition containing at least one non-steroidal anti-inflammatory active ingredient and at least one pharmaceutically acceptable excipient for topical use. More specifically, the composition is provided for use in the treatment of pain and/or inflammation. State of the Art Nepafenac is a non-steroidal anti-inflammatory drug [NSAID], usually available as prescription eye drops under the trade names of 1% solution (Nevanac®) or 3% solution (Ilevro®). The chemical structure of the substance is given in Formula 1 below. Formula 1 The drug in question is used in the treatment of pain and inflammation associated with cataract surgery. It is also a prodrug of amfenacine, an inhibitor of COX'1 and COX*2 activity. In , nepafenac is also indicated for reducing the risk of postoperative macular edema associated with cataract surgery in people with diabetes. Patent document US 5475034 A discloses new ester and amide derivatives of 3-benzoylphenylacetic acid. In addition, the derivatives disclosed within the scope of this document are used for the treatment of ophthalmic inflammatory disorders. Its use in topically applicable compositions is also provided. Patent document numbered EP 1819362 A2 relates to topical suspension compositions of the active ingredient nepafenac. The compositions are particularly suitable for topical ophthalmic application. Patent document EP 2586426 A1 relates to suspension compositions containing carboxyvinyl polymer as a carbomer, galactomannan as a guar and a borate compound. The most common problem encountered in ophthalmic solutions containing nonsteroidal anti-inflammatory active substances in the state of the art is that the solution in question does not have the ability to be stored without forming a precipitate, durability and stability. In particular, during the preservation of the drug, some precipitates form in the solution and these precipitates cannot be removed afterwards. Although known solution compositions contain measures to overcome this problem, incompatibility problems with the auxiliary substances in the compositions continue. In addition, sufficient resistance against external factors such as 151, light and moisture cannot be provided. Therefore, there is still a need in the art for ophthalmic solution compositions containing nonsteroidal anti-inflammatory active substances that prevent precipitate formation in the solution and have high stability and durability. In the light of the above information, it can be seen that there is a need in the relevant technical field for ophthalmic solution compositions with high stability, which are indicated in the treatment of pain and/or inflammation, and in which the high stability and durability of diquafosol-containing compositions are provided. For this purpose, within the scope of the present invention, an eye drop composition containing at least one non-steroidal anti-inflammatory active substance and at least one pharmaceutically acceptable excipient for topical use is provided. Brief Description of the Invention In one aspect, the present invention provides a topical eye drop composition comprising at least one nonsteroidal anti-inflammatory active ingredient and at least one pharmaceutically acceptable excipient for use in the treatment of pain and/or inflammation. Said non-steroidal active ingredient is preferably from the group consisting of ketorolac or a pharmaceutically acceptable salt thereof, bromfenac or a pharmaceutically acceptable salt thereof, nepafenac, diclofenac or a pharmaceutically acceptable salt thereof, flubiprofen or a pharmaceutically acceptable salt thereof. can be selected. The composition of the present invention is the nonsteroidal anti-inflammatory active ingredient nepafenac or a pharmaceutically acceptable salt thereof. The composition of the present invention may preferably contain 0.01% to 1%, more preferably 0.05% to 1% nonsteroidal anti-inflammatory active ingredient. More specifically, the composition may further contain from 0.1% to 1% nonsteroidal anti-inflammatory active ingredient. The pharmaceutically acceptable excipient in preferred embodiments of the present composition is selected from the group consisting of buffering agent, isotonic agent, bacteriostatic agent, pH adjusting agent, tonicity adjusting agent, viscosity adjusting agent, surfactant, stabilizer, preservative, or combinations thereof. Said buffering agent is selected from the group consisting of sodium phosphate, sodium hydrogen phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, sodium acetate, monosodium citrate, sodium chloride, citric acid monohydrate or combinations thereof. The bacteriostatic agent in question is selected from a group including benzalkonium chloride, chlorobutanol, benzethonium chloride, chlorhexidine gluconate or combinations thereof. The composition of the present invention may contain at least one pharmaceutically acceptable preservative. Preferably, the pharmaceutically acceptable preservative in question is selected from the group consisting of meglumine, ethylene glycol, glycerol, erythritol, treitol, arabitol xylitol, ribitol, mannitol, lactose, sorbitol, galacticol, glucose anhydrate, cellobiose, maltitol and combinations thereof. It is not limited to sugar alcohols or sugar alcohol derivatives. More preferably, the carrier may be meglumine, sorbitol or galacticol. Said viscosity adjusting agent is selected from the group consisting of carbomer, bentonite, hydroxypropyl methyl cellulose, methyl cellulose, carboxymethyl cellulose, polyvinyl prolidone, sodium carboxy methyl cellulose, or combinations thereof. Said pH adjusting agent is selected from the group consisting of hydrochloric acid, sodium hydroxide, sodium carbonate, citric acid, sodium alginate or combinations thereof. The pH value of the present composition is preferably in the range of 4 to 8, particularly preferably pH 6.8. Detailed Description of the Invention In this detailed description, a topical eye drop composition comprising at least one nonsteroidal anti-inflammatory active ingredient and at least one pharmaceutically acceptable excipient for use in the treatment of pain and/or inflammation according to the present invention is described. is explained. Said non-steroidal active ingredient may preferably be selected from ketorolac or a pharmaceutically acceptable salt thereof, bromfenac or a pharmaceutically acceptable salt thereof, nepafenac, diclofenac or a pharmaceutically acceptable salt thereof, flubiprofen or a pharmaceutically acceptable salt thereof. In preferred embodiments of the present invention, the composition may contain nepafenac as a nonsteroidal anti-inflammatory active ingredient. The ophthalmic composition of the invention may contain nepafenac in the range of 0.01% to 1% [w/v], preferably in the range of 0.05% to 1% (w/v), more preferably in the range of 0.1% to 1% (w/v). The present inventors have found that the use of this weight amount of the active ingredient makes the inventive eye drop composition more effective in treating pain and inflammation associated with cataract surgery, at least one pharmaceutically acceptable excipient buffering agent according to the present invention. The eye drop composition designed with pharmaceutically acceptable excipients within the scope of the invention can be selected from a group including isotonic agent, bacteriostatic agent, pH adjusting agent, tonicity adjusting agent, viscosity adjusting agent, surfactant, stabilizer, preservative or combinations thereof, providing a solution to the problems. An eye drop composition with better stability and durability compared to compositions in the relevant art is provided. At least one pharmaceutically acceptable excipient according to the present invention preferably contains at least one preservative. Preferably, the pharmaceutically acceptable preservative in question is selected from the group consisting of meglumine, ethylene glycol, glycerol, erythritol, treitol, arabitol xylitol, ribitol, mannitol, lactose, sorbitol, galacticol, glucose anhydrate, cellobiose, maltitol and combinations thereof. It is not limited to sugar alcohols or sugar alcohol derivatives. More preferably, the carrier may be meglumine, sorbitol or galacticol. In preferred embodiments of the present invention, the composition in question may contain at least one active ingredient, sugar alcohol and other excipients. In preferred embodiments of the present invention, by using the composition in question together with sugar alcohols or sugar alcohol derivatives, the homogeneity, stability and durability of the composition of the present invention increases and therefore the shelf life of the said composition is strengthened. Moreover, the present inventors have discovered that the above-mentioned sugar alcohols combined with the active ingredient nepafenac can surprisingly prevent the deterioration that occurs during the storage of the eye drop solution. Thus, it is revealed that in embodiments where buffering agent, viscosity adjusting agent, pH adjusting agent, bacteriostatic agent and/or preservative are used together, the resistance of the eye drop composition in question to environmental factors increases surprisingly and therefore the preservation process of the solution is strengthened. Additionally, said preservative is selected from a group including meglumine, ethylene glycol, glycerol, erythritol, treitol, arabitol xylitol, ribitol, mannitol, lactose, sorbitol, galacticol, glucose anhydrate, cellobiose, maltitol, or combinations thereof. Particularly preferably, said preservative may be meglumine, sorbitol or galacticol. Said buffering agent is selected from the group consisting of sodium phosphate, sodium hydrogen phosphate, disodium hydrogen phosphate, sodium dihydrogen phosphate, sodium acetate, monosodium citrate, sodium chloride, citric acid monohydrate or combinations thereof. The viscosity adjusting agent in question is selected from the group consisting of carbomer, bentonite, hydroxypropyl methyl cellulose, methyl cellulose, carboxymethyl cellulose, polyvinyl prolidone, sodium carboxy methyl cellulose, or combinations thereof. Said pH adjusting agent is selected from a group including hydrochloric acid, sodium hydroxide, sodium carbonate, citric acid, sodium alginate or combinations thereof. The pH of the solution of the present invention is adjusted to a value in the range of 4 to 8, more preferably to a pH of 6.8. Additionally, the bacteriostatic agent in question is selected from the group consisting of benzalkonium chloride, chlorobutanol, benzethonium chloride, chlorhexidine gluconate, or combinations thereof. Further embodiments of the present invention may include, in addition to those mentioned above, pharmaceutically acceptable excipients, solvents, binders, lubricants, lubricants, fillers, chelating agents, wetting agents suitable for use according to the invention. Combinations of these excipients not mentioned above should not be excluded from the scope of the present invention. Therefore, the present invention is advantageous as it provides an eye drop composition with better durability and stability by preventing precipitate formation in solution, and in this respect it provides an advance in the technique. It is revealed that the technical effect of the composition of the present invention benefits durability and is therefore more advantageous compared to existing compositions. EXAMPLES In preferred embodiments, the eye drop composition of the present invention contains the following ingredients: Component By Weight (%) (w/v] Nepafenac or salt thereof 0.1 - 10 Buffering agent 0.1 - 10 Viscosity adjusting agent 0.1 - 10 pH adjusting agent 0.1 - 10 Preservative 0.001 - 0.1 Component Weight (g) Nepafenac 0.300 Sodium hydrogen phosphate 0.200 Hydroxypropyl methyl cellulose 0-420 Sodium hydroxide U-17U Chlorhexidine gluconate 0-050 Meglumin 0-003 Purified water Sufficient amount hydroxide, 0.05 g chlorhexidine gluconate and 0.003 meglumine were dissolved in pure water. Thus, the volume of the solution obtained was 3 mL. water Sufficient g chlorhexidine Gluconate and 0.002 sorbitol were dissolved in pure water. Thus, the volume of the solution obtained was 3 mL. Component Weight (g) Nepafenac 0.200 Sodium acetate 0.200 Polyvinyl prolidone 0.320 Sodium alginate 0.240 Chlorhexidine gluconate 0.060 Galacticol 0.00. 2 Pure water Sufficient amount of chlorhexidine gluconate and 0.002 galacticol , was ensured to dissolve in pure water. Thus, the volume of the solution obtained was 3 mL. Each of the exemplary compositions described above were stored in a glass container at 25°C for three months and thereafter it was determined that there was no change in the appearance of the compositions. It has also been revealed that the amount of precipitates formed in the sediment in these processes decreases. The present invention provides eye protection that has good durability and stability and is also sufficiently resistant to external factors such as heat, light and moisture by preventing the formation of precipitates in solution with the specific composition of the active ingredient nepafenac or its salt combined with pharmaceutically acceptable excipients. It is advantageous in terms of providing droplet compositions. The protection scope of the invention is specified in the attached claims, and it is clear that a person skilled in the art can produce similar structures in the light of what is explained above, without departing from the main theme of the invention. TR
Claims (1)
Publications (1)
| Publication Number | Publication Date |
|---|---|
| TR2022007363A2 true TR2022007363A2 (en) | 2023-11-21 |
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