TR201615270A1 - OPHTHALMIC PHARMACEUTICAL COMPOSITIONS - Google Patents
OPHTHALMIC PHARMACEUTICAL COMPOSITIONS Download PDFInfo
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- TR201615270A1 TR201615270A1 TR2016/15270A TR201615270A TR201615270A1 TR 201615270 A1 TR201615270 A1 TR 201615270A1 TR 2016/15270 A TR2016/15270 A TR 2016/15270A TR 201615270 A TR201615270 A TR 201615270A TR 201615270 A1 TR201615270 A1 TR 201615270A1
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- pharmaceutical composition
- specified
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- sodium
- acid
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- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 35
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 claims abstract description 16
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 claims abstract description 16
- 238000001356 surgical procedure Methods 0.000 claims abstract description 12
- 208000002177 Cataract Diseases 0.000 claims abstract description 11
- 230000003110 anti-inflammatory effect Effects 0.000 claims abstract description 9
- 230000003637 steroidlike Effects 0.000 claims abstract description 8
- 206010061218 Inflammation Diseases 0.000 claims abstract description 7
- 230000004054 inflammatory process Effects 0.000 claims abstract description 7
- 208000001344 Macular Edema Diseases 0.000 claims abstract description 6
- 206010025415 Macular oedema Diseases 0.000 claims abstract description 6
- 201000010230 macular retinal edema Diseases 0.000 claims abstract description 6
- 230000002980 postoperative effect Effects 0.000 claims abstract description 6
- 206010015958 Eye pain Diseases 0.000 claims abstract description 5
- 208000004550 Postoperative Pain Diseases 0.000 claims abstract description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 5
- 230000000069 prophylactic effect Effects 0.000 claims abstract description 5
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 5
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 33
- 239000000203 mixture Substances 0.000 claims description 33
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 23
- 239000003795 chemical substances by application Substances 0.000 claims description 22
- 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 21
- 229960001002 nepafenac Drugs 0.000 claims description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 20
- 235000002639 sodium chloride Nutrition 0.000 claims description 18
- -1 Oksifenbutazone Chemical compound 0.000 claims description 17
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 14
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 13
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 13
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 13
- 239000011780 sodium chloride Substances 0.000 claims description 12
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 claims description 10
- 229930195725 Mannitol Natural products 0.000 claims description 10
- 235000010355 mannitol Nutrition 0.000 claims description 10
- 239000000594 mannitol Substances 0.000 claims description 10
- 239000000243 solution Substances 0.000 claims description 10
- 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 9
- 239000003995 emulsifying agent Substances 0.000 claims description 9
- 229920000136 polysorbate Polymers 0.000 claims description 9
- 229950008882 polysorbate Drugs 0.000 claims description 9
- 239000008215 water for injection Substances 0.000 claims description 9
- 239000003109 Disodium ethylene diamine tetraacetate Substances 0.000 claims description 8
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 8
- 239000004327 boric acid Substances 0.000 claims description 8
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 8
- 235000010338 boric acid Nutrition 0.000 claims description 8
- 235000019301 disodium ethylene diamine tetraacetate Nutrition 0.000 claims description 8
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 claims description 8
- 239000003755 preservative agent Substances 0.000 claims description 8
- 239000004094 surface-active agent Substances 0.000 claims description 8
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 7
- 239000003889 eye drop Substances 0.000 claims description 7
- 238000009472 formulation Methods 0.000 claims description 7
- 230000002335 preservative effect Effects 0.000 claims description 7
- 239000000725 suspension Substances 0.000 claims description 7
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 claims description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- 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 6
- 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 6
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- 235000011187 glycerol Nutrition 0.000 claims description 6
- GLDOVTGHNKAZLK-UHFFFAOYSA-N octadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCO GLDOVTGHNKAZLK-UHFFFAOYSA-N 0.000 claims description 6
- 239000003002 pH adjusting agent Substances 0.000 claims description 6
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 6
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 239000000600 sorbitol Substances 0.000 claims description 6
- 235000010356 sorbitol Nutrition 0.000 claims description 6
- 239000012929 tonicity agent Substances 0.000 claims description 6
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 claims description 5
- 239000004480 active ingredient Substances 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-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
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 4
- 239000004166 Lanolin Substances 0.000 claims description 4
- DLRVVLDZNNYCBX-UHFFFAOYSA-N Polydextrose Polymers OC1C(O)C(O)C(CO)OC1OCC1C(O)C(O)C(O)C(O)O1 DLRVVLDZNNYCBX-UHFFFAOYSA-N 0.000 claims description 4
- HVUMOYIDDBPOLL-XWVZOOPGSA-N Sorbitan monostearate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O HVUMOYIDDBPOLL-XWVZOOPGSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 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 4
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 claims description 4
- 239000002552 dosage form Substances 0.000 claims description 4
- 239000006196 drop Substances 0.000 claims description 4
- 239000008103 glucose Substances 0.000 claims description 4
- 235000001727 glucose Nutrition 0.000 claims description 4
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 claims description 4
- 229940039717 lanolin Drugs 0.000 claims description 4
- 235000019388 lanolin Nutrition 0.000 claims description 4
- 239000003921 oil Substances 0.000 claims description 4
- 239000002674 ointment Substances 0.000 claims description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 4
- 239000004323 potassium nitrate Substances 0.000 claims description 4
- 235000010333 potassium nitrate Nutrition 0.000 claims description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 claims description 4
- 239000011734 sodium Substances 0.000 claims description 4
- 229910052708 sodium Inorganic materials 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 4
- 235000011076 sorbitan monostearate Nutrition 0.000 claims description 4
- 239000001587 sorbitan monostearate Substances 0.000 claims description 4
- 229940035048 sorbitan monostearate Drugs 0.000 claims description 4
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 229960001259 diclofenac 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
- 239000012153 distilled water Substances 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
- 229940075507 glyceryl monostearate Drugs 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
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 claims description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 3
- 239000004404 sodium propyl p-hydroxybenzoate Substances 0.000 claims description 3
- 235000010230 sodium propyl p-hydroxybenzoate Nutrition 0.000 claims description 3
- IXMINYBUNCWGER-UHFFFAOYSA-M sodium;4-propoxycarbonylphenolate Chemical compound [Na+].CCCOC(=O)C1=CC=C([O-])C=C1 IXMINYBUNCWGER-UHFFFAOYSA-M 0.000 claims description 3
- JNYAEWCLZODPBN-KVTDHHQDSA-N (2r,3r,4r)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical class OC[C@@H](O)[C@H]1OC[C@@H](O)[C@H]1O JNYAEWCLZODPBN-KVTDHHQDSA-N 0.000 claims description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 claims description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 2
- CXRFDZFCGOPDTD-UHFFFAOYSA-M Cetrimide Chemical compound [Br-].CCCCCCCCCCCCCC[N+](C)(C)C CXRFDZFCGOPDTD-UHFFFAOYSA-M 0.000 claims description 2
- 239000001856 Ethyl cellulose Substances 0.000 claims description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 2
- 108010010803 Gelatin Proteins 0.000 claims description 2
- 229920002907 Guar gum Polymers 0.000 claims description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 2
- 240000007472 Leucaena leucocephala Species 0.000 claims description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 claims description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 claims description 2
- 229920001100 Polydextrose Polymers 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- 229920000289 Polyquaternium Polymers 0.000 claims description 2
- 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 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
- 229920002125 Sokalan® Polymers 0.000 claims description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 2
- 229930006000 Sucrose Natural products 0.000 claims description 2
- 235000010443 alginic acid Nutrition 0.000 claims description 2
- 239000000783 alginic acid Substances 0.000 claims description 2
- 229920000615 alginic acid Polymers 0.000 claims description 2
- 229960001126 alginic acid Drugs 0.000 claims description 2
- 150000004781 alginic acids Chemical class 0.000 claims description 2
- KHSLHYAUZSPBIU-UHFFFAOYSA-M benzododecinium bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 KHSLHYAUZSPBIU-UHFFFAOYSA-M 0.000 claims description 2
- 229940073464 benzododecinium bromide Drugs 0.000 claims description 2
- 229960002645 boric acid Drugs 0.000 claims description 2
- 229960003655 bromfenac Drugs 0.000 claims description 2
- 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 2
- 229960001631 carbomer Drugs 0.000 claims description 2
- 150000001735 carboxylic acids Chemical class 0.000 claims description 2
- 235000010418 carrageenan Nutrition 0.000 claims description 2
- 239000000679 carrageenan Substances 0.000 claims description 2
- 229920001525 carrageenan Polymers 0.000 claims description 2
- 229940113118 carrageenan Drugs 0.000 claims description 2
- 229940082500 cetostearyl alcohol Drugs 0.000 claims description 2
- 229960001927 cetylpyridinium chloride Drugs 0.000 claims description 2
- 229960004926 chlorobutanol Drugs 0.000 claims description 2
- 229940075614 colloidal silicon dioxide Drugs 0.000 claims description 2
- 239000006071 cream Substances 0.000 claims description 2
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims description 2
- 229910000397 disodium phosphate Inorganic materials 0.000 claims description 2
- 235000019800 disodium phosphate Nutrition 0.000 claims description 2
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 claims description 2
- 239000003814 drug Substances 0.000 claims description 2
- 229960001484 edetic acid Drugs 0.000 claims description 2
- 239000000839 emulsion Substances 0.000 claims description 2
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 claims description 2
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 2
- 229920001249 ethyl cellulose Polymers 0.000 claims description 2
- 229940012356 eye drops Drugs 0.000 claims description 2
- 239000000499 gel Substances 0.000 claims description 2
- 239000008273 gelatin Substances 0.000 claims description 2
- 229920000159 gelatin Polymers 0.000 claims description 2
- 235000019322 gelatine Nutrition 0.000 claims description 2
- 235000011852 gelatine desserts Nutrition 0.000 claims description 2
- 239000000665 guar gum Substances 0.000 claims description 2
- 235000010417 guar gum Nutrition 0.000 claims description 2
- 229960002154 guar gum Drugs 0.000 claims description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 2
- 229960000905 indomethacin Drugs 0.000 claims description 2
- 229940040145 liniment Drugs 0.000 claims description 2
- 239000000865 liniment Substances 0.000 claims description 2
- 239000006193 liquid solution Substances 0.000 claims description 2
- 239000006210 lotion Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 229920000609 methyl cellulose Polymers 0.000 claims description 2
- 235000010981 methylcellulose Nutrition 0.000 claims description 2
- 239000001923 methylcellulose Substances 0.000 claims description 2
- 229960002900 methylcellulose Drugs 0.000 claims description 2
- GOQYKNQRPGWPLP-UHFFFAOYSA-N n-heptadecyl alcohol Natural products CCCCCCCCCCCCCCCCCO GOQYKNQRPGWPLP-UHFFFAOYSA-N 0.000 claims description 2
- 229940049964 oleate Drugs 0.000 claims description 2
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 claims description 2
- 229940067107 phenylethyl alcohol Drugs 0.000 claims description 2
- 239000002504 physiological saline solution Substances 0.000 claims description 2
- 229960002702 piroxicam Drugs 0.000 claims description 2
- 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 2
- 239000001259 polydextrose Substances 0.000 claims description 2
- 235000013856 polydextrose Nutrition 0.000 claims description 2
- 229940035035 polydextrose Drugs 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 229920000259 polyoxyethylene lauryl ether Polymers 0.000 claims description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 claims description 2
- 229940069328 povidone Drugs 0.000 claims description 2
- 229960003101 pranoprofen Drugs 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 claims description 2
- 229960004889 salicylic acid Drugs 0.000 claims description 2
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 claims description 2
- 239000004299 sodium benzoate Substances 0.000 claims description 2
- 235000010234 sodium benzoate Nutrition 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 229940046303 sodium cetostearyl sulfate Drugs 0.000 claims description 2
- 239000001509 sodium citrate Substances 0.000 claims description 2
- 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 claims description 2
- 239000001488 sodium phosphate Substances 0.000 claims description 2
- JXKPEJDQGNYQSM-UHFFFAOYSA-M sodium propionate Chemical compound [Na+].CCC([O-])=O JXKPEJDQGNYQSM-UHFFFAOYSA-M 0.000 claims description 2
- 239000004324 sodium propionate Substances 0.000 claims description 2
- 235000010334 sodium propionate Nutrition 0.000 claims description 2
- 229960003212 sodium propionate Drugs 0.000 claims description 2
- UPUIQOIQVMNQAP-UHFFFAOYSA-M sodium;tetradecyl sulfate Chemical compound [Na+].CCCCCCCCCCCCCCOS([O-])(=O)=O UPUIQOIQVMNQAP-UHFFFAOYSA-M 0.000 claims description 2
- 239000004334 sorbic acid Substances 0.000 claims description 2
- 235000010199 sorbic acid Nutrition 0.000 claims description 2
- 229940075582 sorbic acid Drugs 0.000 claims description 2
- 229960002920 sorbitol Drugs 0.000 claims description 2
- 229940012831 stearyl alcohol Drugs 0.000 claims description 2
- 239000005720 sucrose Substances 0.000 claims description 2
- 229960004793 sucrose Drugs 0.000 claims description 2
- OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 claims description 2
- 239000000230 xanthan gum Substances 0.000 claims description 2
- 235000010493 xanthan gum Nutrition 0.000 claims description 2
- 229920001285 xanthan gum Polymers 0.000 claims description 2
- 229940082509 xanthan gum Drugs 0.000 claims description 2
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical class [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 claims description 2
- 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 claims description 2
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Landscapes
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Mevcut buluş, oküler ağrı, katarakt cerrahisi ile ilişkili postoperatif ağrı ve inflamasyonun profilaktik ve/veya semptomatik ve/veya terapötik tedavisinde; diyabetik hastalarda katarakt cerrahisi ile ilişkili postoperatif maküler ödem riskinin azaltılmasında kullanılmak üzere steroid yapılı olmayan antiinflamatuvar (NSAID) özellikteki uygun etken maddeyi ve/veya farmasötik olarak kabul edilebilir türevlerini içeren farmasötik bileşim/ler ile ilgilidir.The present invention relates to prophylactic and / or symptomatic and / or therapeutic treatment of ocular pain, postoperative pain and inflammation associated with cataract surgery; The present invention relates to pharmaceutical composition (s) containing suitable non-steroidal anti-inflammatory (NSAID) active agent and / or pharmaceutically acceptable derivatives thereof for use in reducing the risk of postoperative macular edema associated with cataract surgery in diabetic patients.
Description
TARIFNAME OFTALMIK FARMASÖTIK BILESIMLER BULUSUN ILGILI OLDUGU ALAN Mevcut bulus, oküler agri, katarakt cerrahisi ile iliskili postoperatif agri ve inflamasyonun profilaktik ve/veya semptoinatik ve/veya terapötik tedavisinde; diyabetik hastalarda katarakt cerrahisi ile iliskili postoperatif maküler ödem riskinin azaltilmasinda kullanilmak üzere steroid yapili olmayan antiinflamatuvar (NSAID) özellikteki uygun etken maddeyi ve/veya farmasötik olarak kabul edilebilir türevlerini içeren farmasötik bilesim/ler ile Mevcut bulus; steroid yapili olmayan antiinflamatuvar (NSAID) özellikteki etken maddenin Nepafenak, 2-(2-Amino-3-benzoilfenil) asetamit (Formül 1) ve/veya farmasötik olarak kabul edilebilir türevleri oldugu ve uygun farmasötik formlarda etken madde olarak kullanildigi farmasötik bilesimler ile ilgilidir. DESCRIPTION OPHTHALMIC PHARMACEUTICAL COMPOSITIONS FIELD OF THE INVENTION The present invention is related to ocular pain, postoperative pain and inflammation associated with cataract surgery. prophylactic and/or symptomatic and/or therapeutic treatment; in diabetic patients To be used to reduce the risk of postoperative macular edema associated with cataract surgery Appropriate active substance with non-steroidal anti-inflammatory (NSAID) properties, such as and/or pharmaceutical composition(s) containing pharmaceutically acceptable derivatives The present invention; non-steroidal anti-inflammatory (NSAID) agent Nepafenac, 2-(2-Amino-3-benzoylphenyl) acetamide (Formula 1) and/or pharmaceutical as an active ingredient in suitable pharmaceutical forms. relates to the pharmaceutical compositions in which it is used.
Formül 1: Ayrica bulus, Nepafenak ve/veya farmasötik olarak kabul edilebilir türevlerini içeren farmasötik bilesimlerin oftalmik uygulama için uygun olan formülasyonlarini ve profilaktik, semptomatik veya terapötik kullanimlarini da kapsamaktadir. ÖNCEKI TEKNIK (TEKNIGIN BILINEN DURUMU) NSAID'ler, oküler yanginin kontrol altina alinmasinda siklikla kullanilmaktadir. Bu ajanlarin, alerjik konjunktivitis semptomlarinin hafifletilmesi, intra-operatif miyozisin önlenmesi, pre ve post-operatif oküler yangi ve katarakt cerrahisi ile iliskili cystoid macular ödemin tedavisi ve refraktif cerrahi sonrasinda sekillenebilecek agrinin azaltilmasi gibi birçok kullanim alani vardir. Formula 1: In addition, the invention includes Nepafenac and/or its pharmaceutically acceptable derivatives. formulations of pharmaceutical compositions suitable for ophthalmic administration and includes prophylactic, symptomatic or therapeutic uses. PRIOR ART (KNOWN STATE OF THE ART) NSAIDs are frequently used to control ocular inflammation. This agents, relief of symptoms of allergic conjunctivitis, intra-operative miosis cystoid associated with prevention, pre- and post-operative ocular inflammation and cataract surgery Treatment of macular edema and reduction of pain that may occur after refractive surgery It has many uses such as
NSAID'lerin steroid tedavisinden kaynaklanan potansiyel komplikasyonlardan sakinmak için özellikle kuru göz sendromu (KGS) gibi kronik yangisal göz hastaliklarinin tedavisinde kortikosteroidlere alternatif olarak kullanilmasi önerilmektedir (Lekhanont K, Park CY, Smith JA, et al. Effects of T0pical Anti-inflainniatory Agents in a Botulinuni Toxin B-Induced bromfeiiak, diklofenak, flurbiprofen, indometazin, ketorolak, nepafenak ve suprofen gibi ajanlar Slkllkla kullanilmaktadir (Schalnus R. Topical Nonsteroidal Aiiti-Inflammatory Therapy in Nepafenak oküler agri, katarakt cerrahisi ile iliskili postoperatif agri ve intlamasyonun önlenmesi ve tedavi edilmesi, diyabetik hastalarda katarakt cerrahisi ile iliskili postoperatif maküler ödem riskinin azaltilmasinda kullanilan steroid yapili olmayan antiinflamatuvar (NSAID) topikal bir ön ilaçtir. Ön ilaç özelligine sahip ilk oftalmik NSAID“tir. avoid potential complications from steroid therapy of NSAIDs especially for chronic inflammatory eye diseases such as dry eye syndrome (KGS) It is recommended to be used as an alternative to corticosteroids in the treatment of Park CY, Smith JA, et al. Effects of T0pical Anti-inflainniatory Agents in a Botulinuni Toxin B-Induced such as brompheiac, diclofenac, flurbiprofen, indomethacin, ketorolac, nepafenac, and suprofen agents are used frequently (Schalnus R. Topical Nonsteroidal Drug-Inflammatory Therapy in Nepafenac ocular pain, postoperative pain and inflammation associated with cataract surgery prevention and treatment of postoperative cataract surgery in diabetic patients Non-steroidal anti-inflammatory drug used to reduce the risk of macular edema (NSAID) is a topical prodrug. It is the first ophthalmic NSAID with prodrug properties.
Nepafenakin ön ilaç seklindeki yapisi, bir yandan korneaya hizli penctrasyonuna ve hedef bölgelere dagilima olanak tanirken, diger yandan yüzeyde akümülasyonu ve oküler yüzey komplikasyonlarini azaltir. içeren oftalmik bilesimlerden bahsedilmektedir. Nepafenacine's prodrug form allows, on the one hand, its rapid penetration into the cornea and targeted while allowing distribution to regions, on the other hand, surface accumulation and ocular surface reduces complications. ophthalmic compositions containing
BULUSUN AÇIKLAMASI Mevcut bulus, oküler agri, katarakt cerrahisi ile iliskili postoperatif agri ve inflamasyonun profilaktik ve/veya semptomatik ve/veya terapötik tedavisinde; diyabetik hastalarda katarakt cerrahisi ile iliskili postoperatif maküler ödem riskinin azaltilmasinda kullanilmak üzere steroid yapili olmayan antiintlamatuvar (NSAID) özellikteki uygun etken maddeyi ve/veya farmasötik olarak kabul edilebilir türevlerini içeren farmasötik bilesim/ler ile Mevcut bulusun bir diger yönü; oftalrnik kullanilmak üzere steroid yapili olmayan antiinflamatuvar (NSAID) özellikteki uygun etken maddeyi ve/veya farmasötik olarak kabul edilebilir türevlerini ve farmasötik olarak kabul edilebilir yardimci maddeleri içeren farmasötik bilesimler ile ilgilidir. DESCRIPTION OF THE INVENTION The present invention is related to ocular pain, postoperative pain and inflammation associated with cataract surgery. prophylactic and/or symptomatic and/or therapeutic treatment; in diabetic patients To be used to reduce the risk of postoperative macular edema associated with cataract surgery Appropriate active substance with non-steroidal anti-inflammatory (NSAID) properties, such as and/or pharmaceutical composition(s) containing pharmaceutically acceptable derivatives Another aspect of the present invention is; non-steroidal for ophthalmological use Appropriate anti-inflammatory (NSAID) active substance and/or pharmaceutical containing acceptable derivatives and pharmaceutically acceptable excipients. relates to pharmaceutical compositions.
Bulusta steroid yapili olmayan antiintlamatuvar (NSAID) özellikteki uygun etken madde bunlarla sinirli olmamakla birlikte, bromfenak, nepafenak, pranoprofen, salisilik asit, bendazak, piroksikam, ketorolak, flurbiprofen, diklofenak, oksifenbütazon, indoinetasin ve/veya farmasötik olarak kabul edilebilir türevlerinin arasindan tercihen Nepafenak olarak seçilir. In the invention, suitable active substance with non-steroidal anti-inflammatory (NSAID) properties including but not limited to bromfenac, nepafenac, pranoprofen, salicylic acid, bendazac, piroxicam, ketorolac, flurbiprofen, diclofenac, oxyphenbutazone, indoinethacin and/or pharmaceutically acceptable derivatives, preferably Nepafenac. is selected.
Bulusta “farmasötik olarak kabul edilebilir türevleri” terimi ile farmasötik olarak kabul edilebilir uygun tuzlar, esterler, solvatlar, hidratlar, kompleksler, polimorflar, enantiyomerler, önilaçlar, asit adisyon tuzlari, analoglar, izomerler, rasematlar, amidler, enantiyomer tuzlari, bazik tuzlar, konjugeler, tautomerler, anhidratlar, anhidritler, bazlar, asitler, eterler, kristal ve amorf formlar veya serbest formlarindan bir veya daha fazlasi ifade edilmektedir. In the invention, the term "pharmaceutically acceptable derivatives" is defined as pharmaceutically acceptable. Suitable salts, esters, solvates, hydrates, complexes, polymorphs, enantiomers, prodrugs, acid addition salts, analogs, isomers, racemates, amides, enantiomer salts, basic salts, conjugates, tautomers, anhydrates, anhydrides, bases, one or more of acids, ethers, crystalline and amorphous forms or free forms is expressed.
Oftalmik uygulama için hazirlanan farmasötik bilesim/ler damla (solüsyon, süspansiyon), krem, jel, merhem, losyon, liniment (sivi merhem), solüsyon, süspansiyon, emülsiyon (su/yag, yag/su) ve sivi Çözelti gibi dozaj formlarinda olabilir. Pharmaceutical composition(s) prepared for ophthalmic administration, drops (solution, suspension), cream, gel, ointment, lotion, liniment (liquid ointment), solution, suspension, emulsion It can be in dosage forms such as (water/oil, oil/water) and liquid solution.
Bulusta kullanilan oftalmik uygulamaya yönelik farmasötik göz damlasi foimülasyonu; uygun etken madde/ler yaninda en az bir viskozite ajani, en az bir izotoni ayarlayici ajan, en az bir tonisite ajani, en az bir surfaktant, en az bir emülsifiyer, en az bir koruyucu madde, gerekli görüldügü durumda en az bir pH ayarlayici ajan ve çözücünün de dahil oldugu gruptan seçilen bir veya daha fazla yardimci madde içerebilen bir bilesimi tanimlar. The formulation of pharmaceutical eye drops for ophthalmic administration used in the invention; In addition to the appropriate active ingredient/s, at least one viscosity agent, at least one isotonia adjusting agent, at least one tonicity agent, at least one surfactant, at least one emulsifier, at least one preservative substance, including at least one pH adjusting agent and solvent where necessary Defines a composition that may contain one or more excipients selected from the group it is in.
Bulusta “viskozite ajani” terimi, sivinin kalinligini arttirarak yavas akmasini saglayan bir ajan veya ajan karisimini belirtmektedir. Viskozite ajani olarak karbomer, ksantan gami, guar gam, akasya, povidon, aljinik asit, etilselüloz, jelatin, hidroksietil selüloz, hidroksipropil selüloz, polivinil pirolidon, hidroksipropil metilselüloz (HPMC), polidekstroz, karragenan, metil selüloz, sukroz, sorbitol, ksilitol, polivinil alkol, ketearil alkol, kolloidal silikon dioksit ve bunlarin karisimlari kullanilabilir. Bulusta tercihen hidroksipropil metilselüloz (HPMC) kullanilmaktadir. Bulusta kullanilan viskozite ajani miktari %0.0 1 -1 0 agirlik/hacim oranindadir. In the invention, the term “viscosity agent” is a liquid that increases the thickness of the liquid and makes it flow slowly. denotes an agent or a mixture of agents. Carbomer, xanthan gum as viscosity agent, guar gum, acacia, povidone, alginic acid, ethylcellulose, gelatin, hydroxyethyl cellulose, hydroxypropyl cellulose, polyvinyl pyrrolidone, hydroxypropyl methylcellulose (HPMC), polydextrose, carrageenan, methyl cellulose, sucrose, sorbitol, xylitol, polyvinyl alcohol, ketaryl alcohol, colloidal silicon dioxide and their mixtures can be used. preferably in the invention hydroxypropyl methylcellulose (HPMC) is used. Viscosity agent used in the invention the amount is 0.0% 1 -1 0 weight/volume.
Bulusta ”izotoni ayarlayici ajan” olarak, polivinilpirolidon, sodyum klorür, sodyum dihidrojen fosfat moiiohidrat, disodyum fosfat anhidrus, mannitol, sorbitol, gliserin, borik asit, potasyum nitrat, glukoz veya bunlarin karisimlari kullanilabilir. Bulusta tercihen sodyum klorür kullanilmaktadir. Bulusta kullanilan izotoni ayarlayici ajan miktari %0.05-8 agirlik/hacim, tercihen %0.l-1 agirlik/hacim oranindadir. Polyvinylpyrrolidone, sodium chloride, sodium as "isotonia adjusting agent" in the invention dihydrogen phosphate moiiohydrate, disodium phosphate anhydrous, mannitol, sorbitol, glycerine, boric acid, potassium nitrate, glucose or their mixtures can be used. preferably in the invention sodium chloride is used. The amount of isotonia adjusting agent used in the invention is 0.05-8% weight/volume, preferably at a ratio of 0.1-1% weight/volume.
Bulusta “tonisite ajani” terimi, standart referans madde ile ayni osmotik basinca sahip maddeleri ifade etmektedir. Tonisite ajani olarak; sodyum klorür, mannitol, sorbitol, gliserin, borik asit, potasyum nitrat, glukoz veya bunlarin karisimlari kullanilabilir. Bulusta belirtilen göz. damlasinin izotonik olmasi tercih edilir, izotonik sivilar gözyasi ile ayni ozinotik basinca sahip oldugundan gözde yanma batma gibi yan etkilere ve lakrimal drenaja neden olmaz. Bulusta tercihen mannitol kullanilmaktadir. Bulusta kullanilan tonisite ajani miktari %0.02-15 agirlik/hacim oranindadir. In the invention, the term "tonicity agent" means having the same osmotic pressure as the standard reference substance. means items. As a tonicity agent; sodium chloride, mannitol, sorbitol, glycerin, boric acid, potassium nitrate, glucose or their mixtures can be used. in the find specified eye. it is preferable that the drops are isotonic, the isotonic liquids are the same as tears Since it has ozinotic pressure, it has side effects such as burning and stinging in the eye and lacrimal pressure. does not cause drainage. Mannitol is preferably used in the invention. used in the invention The amount of tonicity agent is 0.02-15% w/v.
Bulusta “surfaktant” terimi suda veya sulu bir çözeltide çözündügünde yüzey gerilimini etkileyen kimyasal bilesigi ifade etmektedir. Surfaktant olarak sodyum lauril sülfat, sodyum setostearil sülfat ve sodyum tetradesil sülfat gibi uzun Zincirli alkil sülfonat esterlerinin tuzlari, stearatlar gibi uzun Zincirli karboksilik asitlerinin tuzlari, benzalkonyum klorür, tetradesiltrimetil amonyum bromür ve setilpiridinyum klorür gibi piridinyum bilesikleri ya da kuatemer amonyum, soya lesitin gibi lesitinleri ve lauril-l- karboksiglisin, polisorbat, gliseril monostearat gibi gliserol esterleri ve glikol, sorbitan tristearat gibi sorbitan ve mannitan esterleri (polioksietilen sorbitan mono-oleat), sorbitan esterlerinin polioksietilen türevleri veya bunlarin karisimlari kullanilabilir. Bulusta tercihen polisorbat kullanilmaktadir. Bulusta kullanilan surfaktant miktari %0.001-5 agirlik/hacim oranindadir. In the invention, the term "surfactant" increases the surface tension when dissolved in water or an aqueous solution. refers to the chemical compound that affects it. Sodium lauryl sulfate as surfactant, Long Chain alkyl sulfonate such as sodium cetostearyl sulfate and sodium tetradecyl sulfate esters, salts of long-chain carboxylic acids such as stearates, such as benzalkonium chloride, tetradecyltrimethyl ammonium bromide, and cetylpyridinium chloride pyridinium compounds or lecithins such as quaternary ammonium, soy lecithin, and lauryl-l- esters of glycerol such as carboxyglycine, polysorbate, glyceryl monostearate, and glycol, sorbitan esters of sorbitan and mannitan such as tristearate (polyoxyethylene sorbitan mono-oleate), sorbitan Polyoxyethylene derivatives of esters or mixtures thereof can be used. preferably in the invention polysorbate is used. The amount of surfactant used in the invention is 0.001-5% w/v is in the ratio.
Bulusta “emülsifiyer” terimi, birbiri içerisinde karismayan iki sivi faz arasinda homojen dagilimi saglayan maddeler olarak ifade edilmektedir. Emülsifiyer olarak polietilen glikol stearat, polisorbat, poligliseril oleat, polioksietilen lauril eter, lanolin, etoksilenmis lanolin, stearil alkol, setostearil alkol, setomakrogol, gliseril moiiostearat, seti] alkol, polioksietilen lauril alkol, polioksi etileri sorbitan monostearat, polioksietilen stearat, sorbitan monostearat, sodyum lauril sülfat, disodyum EDTA veya bunlarin karisimlari kullanilabilir. Bulusta tercihen disodyum EDTA kullanilmaktadir. Bulusta kullanilan emülsifiyer miktari %0.001-l agirlik/hacim tercihen %0.005-0.l agirlik/hacim oranindadir. In the invention, the term "emulsifier" means a homogeneous mixture between two immiscible liquid phases. are expressed as substances that provide dispersion. Polyethylene glycol as emulsifier stearate, polysorbate, polyglyceryl oleate, polyoxyethylene lauryl ether, lanolin, ethoxylated lanolin, stearyl alcohol, cetostearyl alcohol, cetomacrogol, glyceryl moiiostearate, cete] alcohol, polyoxyethylene lauryl alcohol, polyoxyethylenes sorbitan monostearate, polyoxyethylene stearate, sorbitan monostearate, sodium lauryl sulfate, disodium EDTA or mixtures thereof can be used. Disodium EDTA is preferably used in the invention. used in the invention emulsifier amount 0.001%-1% w/v preferably 0.005-0.1% w/v is in the ratio.
Bulusta “koruyucu madde” terimi mikrobiyal aktiviteye karsi koruyan maddeleri ifade etmektedir. Koruyucu madde olarak; p- hidroksibeiizoik asit ester, sodyum benzoat, sodyuin metil para hidroksibenzoat, sodyum propil para hidroksibenzoat, beiizoik asit, borik asit, etilendiamintetraasetik asit, sorbik asit, klorobütanol, `benzetonyum klorür, benzododesinyum bromür, feniletil alkol, benzalkonyum klorür, parabenler, sodyum propionat, propilen glikol, sorbatlar, polikuaterniyum veya bunlarin karisimlari kullanilabilir. Bulusta tercihen benzalkonyum klorür kullanilmaktadir. Bulusta kullanilan koruyucu madde miktari %0.0001-1 agirlik/hacim oranindadir. In the invention, the term "preservative" refers to substances that protect against microbial activity. is doing. As a preservative; p-hydroxybeisoic acid ester, sodium benzoate, sodium propyl para hydroxybenzoate, sodium propyl para hydroxybenzoate, beisoic acid, boric acid, ethylenediaminetetraacetic acid, sorbic acid, chlorobutanol, `benzethonium chloride, benzododecinium bromide, phenylethyl alcohol, benzalkonium chloride, parabens, sodium propionate, propylene glycol, sorbates, polyquaternium or mixtures thereof can be used. Benzalkonium chloride is preferably used in the invention. used in the invention the amount of preservative is 0.0001-1% weight/volume.
Bulusta pH ayarlayici ajan olarak; sülfürik asit, sodyum hidroksit, hidroklorik asit, sodyum klorit, asetik asit, borik asit, anhidröz sodyum sülfit, sodyum sitrat, sodyum karbonat veya bunlarin karisimlari kullanilabilir. Bulusta tercihen sodyum hidroksit ve/veya hidroklorik asit kullanilmaktadir. As a pH adjusting agent in the invention; sulfuric acid, sodium hydroxide, hydrochloric acid, sodium chloride, acetic acid, boric acid, anhydrous sodium sulfite, sodium citrate, sodium carbonate or mixtures of these can be used. In the invention preferably sodium hydroxide and/or hydrochloric acid is used.
Bulusta çözücü olarak; saf su, enjeksiyoiiluk su, fizyolojik serum, sterilize damitilmis su gibi uygun sulu çözeltiler kullanilabilir. Bulusta tercihen enjeksiyonluk su kullanilmaktadir. As a solvent in the invention; pure water, injectable water, physiological saline, sterilized distilled water Suitable aqueous solutions such as In the invention preferably water for injection is used.
Bulusta, Nepafenak ve/veya farmasötik olarak kabul edilebilir türevlerinin kullanildigi farmasötik bilesimlerin oftalmik uygulamasina yönelik göz damlasi formülasyonu asagidakileri içermektedir; - yaklasik %0.01 -4 agirlik/hacim oraninda Nepafenak - yaklasik %001 -l 0 agirlik/hacim oraninda bir veya daha fazla viskozite ajani - yaklasik %0.05-8 agirlik/hacim oraninda bir veya daha fazla izotoni ayarlayici ajan - yaklasik %0.02-15 agirlik/hacim oraninda bir veya daha fazla tonisite ajani - yaklasik %0.001-5 agirlik/hacim oraninda bir veya daha fazla surfaktaiit - yaklasik %0.001-1 agirlik/hacim oraninda bir veya daha fazla emülsifiyer - yaklasik %0.0001-1 agirlik/hacim oraninda bir veya daha fazla koruyucu madde - gerekli görüldügü durumda kafi miktar pH ayarlayici ajan - kafi miktar Çözücü. Nepafenac and/or pharmaceutically acceptable derivatives are used in the invention. eye drop formulation for ophthalmic administration of pharmaceutical compositions It includes the following; - ca. 0.01 -4 % w/v Nepafenac - one or more viscosity agents in a weight/volume ratio of approximately 001 to 10% - one or more isotonia adjusting agents at a weight/volume ratio of approximately 0.05-8% - one or more tonicity agents at a weight/volume ratio of approximately 0.02-15% - one or more surfactants in a weight/volume ratio of approximately 0.001-5% - one or more emulsifiers at a weight/volume ratio of approximately 0.001-1% - one or more preservatives at a weight/volume ratio of approximately 0.0001-1% - sufficient amount of pH adjusting agent if necessary - enough Solvent.
Bulus esas olarak oftalmik kullanilmak üzere steroid yapili olmayan antiinflamatuvar (NSAID) özellikteki Nepafeiiak ve/veya farmasötik olarak kabul edilebilir türevlerini ve farmasötik olarak kabul edilebilir uygun yardimci maddeleri içeren farmasötik bilesim/lerin hazirlanmasi ile ilgilidir. Bulusun farmasötik bilesimlerinin oftalmik göz damlasi (solüsyon, süspansiyon) formunda olmasi temeldir. Böylece Nepafenak ve/veya farmasötik olarak kabul edilebilir türevlerini ve farmasötik olarak kabul edilebilir uygun yardimci maddeleri içeren farmasötik dozaj form/lari tahris edici özelliklerinin düsük olmasi, Çabuk etki etmesi, gözde kuruluk yapmamasi, kullanimlarinin daha kolay olmasi gibi üstünlüklere sahiptir ve bu farmasötik bilesimler fiziksel ve kimyasal kararlilik açisindan oldukça stabil bir davranis sergilemistir. The invention is primarily a non-steroidal anti-inflammatory drug for ophthalmic use. (NSAID) Nepafeliac and/or pharmaceutically acceptable derivatives, and pharmaceutical containing suitable pharmaceutically acceptable excipients relates to the preparation of the composition(s). Ophthalmic eye medicine compositions of the invention It is essential that it be in the form of drops (solution, suspension). Thus, Nepafenac and/or pharmaceutically acceptable derivatives and pharmaceutically acceptable Pharmaceutical dosage form(s) containing excipients have low irritant properties to be effective, to act quickly, not to dry the eyes, to be easier to use These pharmaceutical compositions have advantages such as physical and chemical stability. It has exhibited a very stable behavior in terms of
Asagidaki örnekler bulusu açiklamaktadir, fakat hiçbir suretle kisitlamamaktadirlar. The following examples illustrate the invention, but in no way limit it.
Nepafenak ve/veya farmasötik olarak kabul edilebilir türevlerinin kullanildigi farmasötik bilesimlerin oftalmik uygulamasina yönelik göz damlasi forrnülasyonu asagidakileri içermektedir; - yaklasik %001-4 agirlik/hacim oraninda Nepafenak - yaklasik %001-10 agirlik/hacim oraninda hidroksipropil metilselüloz - yaklasik %005-8 agirlik/hacim oraninda sodyum klorür - yaklasik %002-15 agirlik/hacim oraninda mannitol - yaklasik %0001-5 agirlik/hacim oraninda polisorbat - yaklasik %0001-1 agirlik/hacim oraninda disodyum EDTA - yaklasik %0.0001-l agirlik/hacim oraninda benzalkonyum klorür - gerekli görüldügü durumda kafi miktar sodyum hidroksit ve/Veya hidroklorik asit - kafi miktar en jeksiyoiiluk su. Pharmaceutical use of Nepafenac and/or its pharmaceutically acceptable derivatives eye drop formulation for ophthalmic administration of the compositions includes; - approximately 001-4% w/v Nepafenac - approx. 001-10% w/v hydroxypropyl methylcellulose - sodium chloride at a weight/volume ratio of approximately 005-8% - mannitol in a weight/volume ratio of about 002-15% - polysorbate ca. 0001-5% w/v - approximately 0001-1% w/v disodium EDTA - benzalkonium chloride approx. 0.0001-l wt% - a sufficient amount of sodium hydroxide and/or hydrochloric acid if deemed necessary - Enough amount of water at the most injection.
Nepafenak ve/veya farmasötik olarak kabul edilebilir türevlerinin kullanildigi farmasötik bilesimlerin oftalmik uygulamasina yönelik göz damlasi formülasyonu asagidakileri içermektedir (mg/ 1 m1); - yaklasik 0.1-10mg Nepafenak - yaklasik 0.5-30mg hidroksipropil metilselüloz - yaklasik 0.1-15mg sodyum klorür - yaklasik 0.1-75mg mannitol - yaklasik 0.01-5mg disodyuin EDTA - yaklasik 0.001-3mg benzalkonyum klorür - gerekli görüldügü durumda kafi miktar sodyum hidroksit ve/Veya hidroklorik asit - kafi miktar en jeksiyonluk su. Üretim prosesi: Belirli bir miktar enjeksiyonluk su bir kazana alinir ve karistirma altinda Disodyum EDTA, Polisorbat ve Benzalkonyuin Klorür ilave edilir, homojen bir karisim elde edilene kadar karistirilir. pH degeri HC] ve/Veya NaOH çözeltisi ile pH 7.5”e ayarlanir ve uygun araliktaki filtreden geçirilir. Üzerine Nepafenak ilave edilir ve karistirilir. Karisim homojenizatör yardimi ile homojen hale getirilir (Karisim l). Belirli bir miktar enjeksiyonluk su ayri bir kazana alinir ve karistirma altinda, yavasça Hidroksipropil metilselüloz (HPMC) ilave edilir. Homojen bir karisim elde edilene kadar karistirma devam eder. pH degeri HCl ve/veya NaOH çözeltisi ile pH 7.5”e ayarlanir. Otoklavda steril hale getirilir (Karisim ll). Belirli bir miktar enjeksiyonluk su ayri bir kazana alinir ve karistirma altinda Mannitol ve Sodyum Klorür ilave edilir, homojen bir karisim elde edilene kadar karistirilir. pH degeri HCl ve/veya NaOH çözeltisi ile pH 7.5”e ayarlanir ve uygun araliktaki filtreden geçirilir (Karisim III). Karisim-I, Karisim-11° ye ilave edilir, karistirilir. Üzerine Karisim-III ilave edilir ve homojen karisim elde edene kadar karistirilir. Eger gerekli ise pH degeri HC] ve/veya NaOH çözeltisi ile pH 7.5'e ayarlanir. Pharmaceutical use of Nepafenac and/or its pharmaceutically acceptable derivatives eye drop formulation for ophthalmic administration of the compounds contains (mg/ 1 m1); - about 0.1-10mg of Nepafenac - about 0.5-30mg hydroxypropyl methylcellulose - about 0.1-15mg sodium chloride - about 0.1-75mg of mannitol - about 0.01-5mg of disodium EDTA - about 0.001-3mg of benzalkonium chloride - a sufficient amount of sodium hydroxide and/or hydrochloric acid if deemed necessary - Enough amount of water for injection. Production process: A certain amount of water for injection is taken into a boiler and under mixing, Disodium EDTA, Polysorbate and Benzalkonyuin Chloride are added until a homogeneous mixture is obtained. is mixed. The pH value is adjusted to pH 7.5 with HC] and/or NaOH solution and appropriate passed through the filter in the range. Add Nepafenac and mix it. Mixture It is homogenized with the help of a homogenizer (Mixture 1). a certain amount The water for injection is taken into a separate vessel and slowly mixed with Hydroxypropyl methylcellulose (HPMC) is added. Mixing until a homogeneous mixture is obtained. continues. The pH value is adjusted to pH 7.5 with HCl and/or NaOH solution. sterile in autoclave (Mix ll). A certain amount of water for injection is taken into a separate boiler and Mannitol and Sodium Chloride are added under mixing, a homogeneous mixture is obtained. stirred until it is. The pH value is adjusted to pH 7.5 with HCl and/or NaOH solution and filtered in the appropriate range (Mixture III). Mixture-I is added to Mixture-11°, is mixed. Mixture-III is added on it and until a homogeneous mixture is obtained. is mixed. If necessary, the pH value is adjusted to pH 7.5 with HC] and/or NaOH solution.
Hazirlanan süspansiyon kalan enjeksiyonluk su ile hacmine tamamlanir. pH degeri 7.5 civarinda olmalidir. Uygun ambalajina doldurulur. The prepared suspension is made up to its volume with the remaining water for injection. pH value 7.5 should be around. It is filled in its appropriate packaging.
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