CA2911983A1 - Stable bromfenac solution - Google Patents
Stable bromfenac solutionInfo
- Publication number
- CA2911983A1 CA2911983A1 CA2911983A CA2911983A CA2911983A1 CA 2911983 A1 CA2911983 A1 CA 2911983A1 CA 2911983 A CA2911983 A CA 2911983A CA 2911983 A CA2911983 A CA 2911983A CA 2911983 A1 CA2911983 A1 CA 2911983A1
- Authority
- CA
- Canada
- Prior art keywords
- solution
- bromfenac
- agent
- stable
- present
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 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 title claims abstract description 90
- 229960003655 bromfenac Drugs 0.000 title claims abstract description 86
- 239000000203 mixture Substances 0.000 claims abstract description 71
- 238000000034 method Methods 0.000 claims abstract description 37
- -1 polymorph Chemical class 0.000 claims abstract description 34
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 22
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 22
- 206010061218 Inflammation Diseases 0.000 claims abstract description 20
- 230000004054 inflammatory process Effects 0.000 claims abstract description 20
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 19
- 208000002193 Pain Diseases 0.000 claims abstract description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 16
- 229920000642 polymer Polymers 0.000 claims abstract description 14
- 235000014113 dietary fatty acids Nutrition 0.000 claims abstract description 13
- 239000000194 fatty acid Substances 0.000 claims abstract description 13
- 229930195729 fatty acid Natural products 0.000 claims abstract description 13
- 239000004721 Polyphenylene oxide Substances 0.000 claims abstract description 12
- 125000002877 alkyl aryl group Chemical group 0.000 claims abstract description 12
- 229920000570 polyether Polymers 0.000 claims abstract description 12
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000000243 solution Substances 0.000 claims description 95
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 47
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 47
- 239000002253 acid Substances 0.000 claims description 18
- 235000006708 antioxidants Nutrition 0.000 claims description 18
- 239000003755 preservative agent Substances 0.000 claims description 15
- 230000002335 preservative effect Effects 0.000 claims description 12
- 238000003860 storage Methods 0.000 claims description 12
- 239000002738 chelating agent Substances 0.000 claims description 11
- 239000006172 buffering agent Substances 0.000 claims description 10
- 239000003002 pH adjusting agent Substances 0.000 claims description 10
- 239000000872 buffer Substances 0.000 claims description 8
- 239000012929 tonicity agent Substances 0.000 claims description 8
- 239000004094 surface-active agent Substances 0.000 claims description 6
- 239000004599 antimicrobial Substances 0.000 claims description 4
- 239000007979 citrate buffer Substances 0.000 claims description 4
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims description 3
- 230000003078 antioxidant effect Effects 0.000 claims description 3
- 206010015958 Eye pain Diseases 0.000 claims description 2
- 239000003186 pharmaceutical solution Substances 0.000 claims description 2
- JDSPXIPYMUGSIJ-UHFFFAOYSA-N 7-(4-bromobenzoyl)-1,3-dihydroindol-2-one Chemical compound C1=CC(Br)=CC=C1C(=O)C1=CC=CC2=C1NC(=O)C2 JDSPXIPYMUGSIJ-UHFFFAOYSA-N 0.000 claims 2
- 238000004806 packaging method and process Methods 0.000 claims 1
- 239000007864 aqueous solution Substances 0.000 abstract description 40
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 abstract description 28
- 238000009472 formulation Methods 0.000 abstract description 25
- 239000000546 pharmaceutical excipient Substances 0.000 abstract description 20
- 206010036346 Posterior capsule opacification Diseases 0.000 abstract description 16
- 238000001356 surgical procedure Methods 0.000 abstract description 16
- 150000003839 salts Chemical class 0.000 abstract description 14
- 235000010265 sodium sulphite Nutrition 0.000 abstract description 14
- 150000002148 esters Chemical class 0.000 abstract description 13
- BHZRJJOHZFYXTO-UHFFFAOYSA-L potassium sulfite Chemical compound [K+].[K+].[O-]S([O-])=O BHZRJJOHZFYXTO-UHFFFAOYSA-L 0.000 abstract description 9
- 235000019252 potassium sulphite Nutrition 0.000 abstract description 9
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 abstract description 8
- 229920001664 tyloxapol Polymers 0.000 abstract description 8
- MDYZKJNTKZIUSK-UHFFFAOYSA-N tyloxapol Chemical compound O=C.C1CO1.CC(C)(C)CC(C)(C)C1=CC=C(O)C=C1 MDYZKJNTKZIUSK-UHFFFAOYSA-N 0.000 abstract description 8
- 229960004224 tyloxapol Drugs 0.000 abstract description 8
- 230000000699 topical effect Effects 0.000 abstract description 6
- 239000012535 impurity Substances 0.000 description 40
- 235000002639 sodium chloride Nutrition 0.000 description 18
- 239000000126 substance Substances 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 16
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 16
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 15
- 238000004128 high performance liquid chromatography Methods 0.000 description 14
- 238000003556 assay Methods 0.000 description 12
- 238000012360 testing method Methods 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 230000035882 stress Effects 0.000 description 8
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 7
- 229930195725 Mannitol Natural products 0.000 description 7
- 229960002716 bromfenac sodium Drugs 0.000 description 7
- 239000000594 mannitol Substances 0.000 description 7
- 235000010355 mannitol Nutrition 0.000 description 7
- 229940079593 drug Drugs 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- 230000032683 aging Effects 0.000 description 5
- 239000003889 eye drop Substances 0.000 description 5
- 230000007794 irritation Effects 0.000 description 5
- 229920001684 low density polyethylene Polymers 0.000 description 5
- 239000004702 low-density polyethylene Substances 0.000 description 5
- 239000008213 purified water Substances 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 235000011121 sodium hydroxide Nutrition 0.000 description 5
- BIYQNLJPABKADF-UHFFFAOYSA-M sodium;2-[2-amino-3-(4-bromobenzoyl)phenyl]acetate;hydrate Chemical compound O.[Na+].NC1=C(CC([O-])=O)C=CC=C1C(=O)C1=CC=C(Br)C=C1 BIYQNLJPABKADF-UHFFFAOYSA-M 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000006196 drop Substances 0.000 description 4
- 229940124274 edetate disodium Drugs 0.000 description 4
- 239000005022 packaging material Substances 0.000 description 4
- 229960000999 sodium citrate dihydrate Drugs 0.000 description 4
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000004285 Potassium sulphite Substances 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- HZFGMQJYAFHESD-UHFFFAOYSA-M bromfenac sodium Chemical compound [Na+].NC1=C(CC([O-])=O)C=CC=C1C(=O)C1=CC=C(Br)C=C1 HZFGMQJYAFHESD-UHFFFAOYSA-M 0.000 description 3
- PPOSVVJOVKVBPW-UHFFFAOYSA-L bromfenac sodium salt sesquihydrate Chemical compound O.O.O.[Na+].[Na+].NC1=C(CC([O-])=O)C=CC=C1C(=O)C1=CC=C(Br)C=C1.NC1=C(CC([O-])=O)C=CC=C1C(=O)C1=CC=C(Br)C=C1 PPOSVVJOVKVBPW-UHFFFAOYSA-L 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- NFDRPXJGHKJRLJ-UHFFFAOYSA-N edtmp Chemical compound OP(O)(=O)CN(CP(O)(O)=O)CCN(CP(O)(O)=O)CP(O)(O)=O NFDRPXJGHKJRLJ-UHFFFAOYSA-N 0.000 description 3
- 229920001903 high density polyethylene Polymers 0.000 description 3
- 239000004700 high-density polyethylene Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 3
- 239000001509 sodium citrate Substances 0.000 description 3
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-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-JGWLITMVSA-N 0.000 description 2
- URDCARMUOSMFFI-UHFFFAOYSA-N 2-[2-[bis(carboxymethyl)amino]ethyl-(2-hydroxyethyl)amino]acetic acid Chemical compound OCCN(CC(O)=O)CCN(CC(O)=O)CC(O)=O URDCARMUOSMFFI-UHFFFAOYSA-N 0.000 description 2
- YXSJRZBKSLLIOM-UHFFFAOYSA-N 2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetate;tris(2-hydroxyethyl)azanium Chemical compound OCCN(CCO)CCO.OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O YXSJRZBKSLLIOM-UHFFFAOYSA-N 0.000 description 2
- CFKMVGJGLGKFKI-UHFFFAOYSA-N 4-chloro-m-cresol Chemical compound CC1=CC(O)=CC=C1Cl CFKMVGJGLGKFKI-UHFFFAOYSA-N 0.000 description 2
- 239000004255 Butylated hydroxyanisole Substances 0.000 description 2
- 239000004322 Butylated hydroxytoluene Substances 0.000 description 2
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 2
- QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 description 2
- RGHNJXZEOKUKBD-SQOUGZDYSA-N D-gluconic acid Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O RGHNJXZEOKUKBD-SQOUGZDYSA-N 0.000 description 2
- 229940120146 EDTMP Drugs 0.000 description 2
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 229920002690 Polyoxyl 40 HydrogenatedCastorOil Polymers 0.000 description 2
- 239000004743 Polypropylene Substances 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 208000003251 Pruritus Diseases 0.000 description 2
- 229960004308 acetylcysteine Drugs 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- UREZNYTWGJKWBI-UHFFFAOYSA-M benzethonium chloride Chemical compound [Cl-].C1=CC(C(C)(C)CC(C)(C)C)=CC=C1OCCOCC[N+](C)(C)CC1=CC=CC=C1 UREZNYTWGJKWBI-UHFFFAOYSA-M 0.000 description 2
- 229960001950 benzethonium chloride Drugs 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- 235000019282 butylated hydroxyanisole Nutrition 0.000 description 2
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical compound COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 description 2
- 229940043253 butylated hydroxyanisole Drugs 0.000 description 2
- 235000010354 butylated hydroxytoluene Nutrition 0.000 description 2
- 229940095259 butylated hydroxytoluene Drugs 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 239000007857 degradation product Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 229940012356 eye drops Drugs 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 230000007803 itching Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 231100000647 material safety data sheet Toxicity 0.000 description 2
- 238000002483 medication Methods 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 230000017074 necrotic cell death Effects 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 229920001983 poloxamer Polymers 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 229920001155 polypropylene Polymers 0.000 description 2
- 229940068968 polysorbate 80 Drugs 0.000 description 2
- 229920000053 polysorbate 80 Polymers 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 238000010926 purge Methods 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 2
- 229940001584 sodium metabisulfite Drugs 0.000 description 2
- 235000010262 sodium metabisulphite Nutrition 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 229940001474 sodium thiosulfate Drugs 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- 229910001220 stainless steel Inorganic materials 0.000 description 2
- 239000010935 stainless steel Substances 0.000 description 2
- 239000008174 sterile solution Substances 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical compound [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 2
- 229940033663 thimerosal Drugs 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 239000003981 vehicle Substances 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- JCIIKRHCWVHVFF-UHFFFAOYSA-N 1,2,4-thiadiazol-5-amine;hydrochloride Chemical compound Cl.NC1=NC=NS1 JCIIKRHCWVHVFF-UHFFFAOYSA-N 0.000 description 1
- OOSZCNKVJAVHJI-UHFFFAOYSA-N 1-[(4-fluorophenyl)methyl]piperazine Chemical compound C1=CC(F)=CC=C1CN1CCNCC1 OOSZCNKVJAVHJI-UHFFFAOYSA-N 0.000 description 1
- QWAOZPAYELXRIH-UHFFFAOYSA-N 2-[3-(4-bromobenzoyl)phenyl]acetic acid Chemical compound OC(=O)CC1=CC=CC(C(=O)C=2C=CC(Br)=CC=2)=C1 QWAOZPAYELXRIH-UHFFFAOYSA-N 0.000 description 1
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- LZZYPRNAOMGNLH-UHFFFAOYSA-M Cetrimonium bromide Chemical compound [Br-].CCCCCCCCCCCCCCCC[N+](C)(C)C LZZYPRNAOMGNLH-UHFFFAOYSA-M 0.000 description 1
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
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- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- RGHNJXZEOKUKBD-UHFFFAOYSA-N D-gluconic acid Natural products OCC(O)C(O)C(O)C(O)C(O)=O RGHNJXZEOKUKBD-UHFFFAOYSA-N 0.000 description 1
- AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 0.000 description 1
- RUPBZQFQVRMKDG-UHFFFAOYSA-M Didecyldimethylammonium chloride Chemical compound [Cl-].CCCCCCCCCC[N+](C)(C)CCCCCCCCCC RUPBZQFQVRMKDG-UHFFFAOYSA-M 0.000 description 1
- OJIYIVCMRYCWSE-UHFFFAOYSA-M Domiphen bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CCOC1=CC=CC=C1 OJIYIVCMRYCWSE-UHFFFAOYSA-M 0.000 description 1
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- MCSINKKTEDDPNK-UHFFFAOYSA-N propyl propionate Chemical compound CCCOC(=O)CC MCSINKKTEDDPNK-UHFFFAOYSA-N 0.000 description 1
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- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
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- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
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- 229940074545 sodium dihydrogen phosphate dihydrate Drugs 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
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- PESXGULMKCKJCC-UHFFFAOYSA-M sodium;4-methoxycarbonylphenolate Chemical compound [Na+].COC(=O)C1=CC=C([O-])C=C1 PESXGULMKCKJCC-UHFFFAOYSA-M 0.000 description 1
- IXMINYBUNCWGER-UHFFFAOYSA-M sodium;4-propoxycarbonylphenolate Chemical compound [Na+].CCCOC(=O)C1=CC=C([O-])C=C1 IXMINYBUNCWGER-UHFFFAOYSA-M 0.000 description 1
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- 239000000600 sorbitol Substances 0.000 description 1
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- 238000013112 stability test Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000012496 stress study Methods 0.000 description 1
- 238000009662 stress testing Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- HWCKGOZZJDHMNC-UHFFFAOYSA-M tetraethylammonium bromide Chemical compound [Br-].CC[N+](CC)(CC)CC HWCKGOZZJDHMNC-UHFFFAOYSA-M 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- FYZXEMANQYHCFX-UHFFFAOYSA-K tripotassium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxymethyl)amino]acetate Chemical compound [K+].[K+].[K+].OC(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O FYZXEMANQYHCFX-UHFFFAOYSA-K 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 229910000406 trisodium phosphate Inorganic materials 0.000 description 1
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/12—Carboxylic acids; Salts or anhydrides thereof
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Ophthalmology & Optometry (AREA)
- Molecular Biology (AREA)
- Inorganic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN1816/DEL/2013 | 2013-06-19 | ||
| IN1816DE2013 | 2013-06-19 | ||
| PCT/US2014/042724 WO2014204952A1 (en) | 2013-06-19 | 2014-06-17 | Stable bromfenac solution |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2911983A1 true CA2911983A1 (en) | 2014-12-24 |
Family
ID=51136842
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2911983A Abandoned CA2911983A1 (en) | 2013-06-19 | 2014-06-17 | Stable bromfenac solution |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US20160143869A1 (enExample) |
| EP (1) | EP3010485A1 (enExample) |
| JP (1) | JP2016522257A (enExample) |
| CA (1) | CA2911983A1 (enExample) |
| EA (1) | EA201591910A1 (enExample) |
| WO (1) | WO2014204952A1 (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2017002042A (ja) * | 2015-06-10 | 2017-01-05 | 参天製薬株式会社 | 点眼剤、及び点眼剤防腐効力維持方法 |
| KR20200099547A (ko) * | 2017-12-14 | 2020-08-24 | 산텐 세이야꾸 가부시키가이샤 | 2-아미노-3-(4-브로모벤조일)페닐아세트산 또는 그의 염을 함유하는 점안제 |
| CN114224830A (zh) * | 2021-12-24 | 2022-03-25 | 辰欣药业股份有限公司 | 一种单剂量无抑菌剂的眼用制剂及其制备方法 |
| CN115887366A (zh) * | 2022-11-21 | 2023-04-04 | 山东诺明康药物研究院有限公司 | 一种溴芬酸钠离子敏感型原位凝胶滴眼液及其制备方法和应用 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE400966B (sv) | 1975-08-13 | 1978-04-17 | Robins Co Inc A H | Forfarande for framstellning av 2-amino-3-(eller 5-)bensoyl-fenylettiksyror |
| CA1325382C (en) | 1988-01-27 | 1993-12-21 | Takahiro Ogawa | Locally administrable therapeutic composition for inflammatory disease |
| US5603929A (en) | 1994-11-16 | 1997-02-18 | Alcon Laboratories, Inc. | Preserved ophthalmic drug compositions containing polymeric quaternary ammonium compounds |
| US8129431B2 (en) * | 2003-01-21 | 2012-03-06 | Senju Pharmaceutical Co., Ltd. | Aqueous liquid preparation containing 2-amino-3-(4-bromobenzoyl)phenylacetic acid |
| CA2560559C (en) * | 2004-11-05 | 2013-07-02 | Senju Pharmaceutical Co., Ltd. | Aqueous intraocular penetration-promoting eye drop |
| US8778999B2 (en) * | 2009-03-05 | 2014-07-15 | Insite Vision Incorporated | Non-steroidal anti-inflammatory ophthalmic compositions |
| US20130023575A1 (en) * | 2011-07-22 | 2013-01-24 | Kamran Hosseini | Compositions and methods for the treatment of ocular surface allergies |
| PL2765988T3 (pl) | 2011-10-12 | 2025-02-10 | Bausch & Lomb Incorporated | Kompozycja okulistyczna zawierająca bromofenak o zwiększonej biodostępności |
| ES2664053T3 (es) * | 2012-11-19 | 2018-04-18 | Bausch & Lomb Incorporated | Composición líquida acuosa que contiene ácido 2-amino-3-(4-bromobenzoil)fenil-láctico |
-
2014
- 2014-06-17 EA EA201591910A patent/EA201591910A1/ru unknown
- 2014-06-17 JP JP2016521511A patent/JP2016522257A/ja active Pending
- 2014-06-17 US US14/898,268 patent/US20160143869A1/en not_active Abandoned
- 2014-06-17 WO PCT/US2014/042724 patent/WO2014204952A1/en not_active Ceased
- 2014-06-17 EP EP14736572.0A patent/EP3010485A1/en not_active Withdrawn
- 2014-06-17 CA CA2911983A patent/CA2911983A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP3010485A1 (en) | 2016-04-27 |
| WO2014204952A1 (en) | 2014-12-24 |
| EA201591910A1 (ru) | 2016-05-31 |
| JP2016522257A (ja) | 2016-07-28 |
| US20160143869A1 (en) | 2016-05-26 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |
Effective date: 20190618 |