CN101322683B - Gel for eye containing bromfenac sodium hydrate and preparation thereof - Google Patents
Gel for eye containing bromfenac sodium hydrate and preparation thereof Download PDFInfo
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- CN101322683B CN101322683B CN 200810117363 CN200810117363A CN101322683B CN 101322683 B CN101322683 B CN 101322683B CN 200810117363 CN200810117363 CN 200810117363 CN 200810117363 A CN200810117363 A CN 200810117363A CN 101322683 B CN101322683 B CN 101322683B
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- gel
- eye
- sodium
- sodium hydrate
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- 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 title claims abstract description 82
- 238000002360 preparation method Methods 0.000 title claims abstract description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 81
- 239000008215 water for injection Substances 0.000 claims abstract description 55
- 230000003204 osmotic effect Effects 0.000 claims abstract description 20
- 239000004480 active ingredient Substances 0.000 claims abstract description 11
- 239000003963 antioxidant agent Substances 0.000 claims abstract description 11
- 230000003078 antioxidant effect Effects 0.000 claims abstract description 11
- 229910021645 metal ion Inorganic materials 0.000 claims abstract description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 78
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 58
- 238000003756 stirring Methods 0.000 claims description 56
- 235000002639 sodium chloride Nutrition 0.000 claims description 29
- 239000011780 sodium chloride Substances 0.000 claims description 28
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 27
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 26
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 26
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 26
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 26
- 230000001954 sterilising effect Effects 0.000 claims description 25
- 238000009472 formulation Methods 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 24
- 238000004659 sterilization and disinfection Methods 0.000 claims description 24
- 230000008961 swelling Effects 0.000 claims description 24
- 238000012546 transfer Methods 0.000 claims description 24
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical group [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 claims description 22
- 229960002233 benzalkonium bromide Drugs 0.000 claims description 18
- KHSLHYAUZSPBIU-UHFFFAOYSA-M benzododecinium bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 KHSLHYAUZSPBIU-UHFFFAOYSA-M 0.000 claims description 18
- 230000000844 anti-bacterial effect Effects 0.000 claims description 15
- 229940101006 anhydrous sodium sulfite Drugs 0.000 claims description 14
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 14
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 14
- 229920000642 polymer Polymers 0.000 claims description 14
- 239000003002 pH adjusting agent Substances 0.000 claims description 13
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical group [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 claims description 12
- 239000003795 chemical substances by application Substances 0.000 claims description 10
- 230000000536 complexating effect Effects 0.000 claims description 10
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical group OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 8
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 8
- 229920002125 Sokalan® Polymers 0.000 claims description 8
- 229910021538 borax Inorganic materials 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
- 239000004327 boric acid Substances 0.000 claims description 8
- 229960001631 carbomer Drugs 0.000 claims description 8
- -1 polyethylene pyrrole Polymers 0.000 claims description 8
- 235000010339 sodium tetraborate Nutrition 0.000 claims description 8
- 239000004328 sodium tetraborate Substances 0.000 claims description 8
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 6
- 239000011734 sodium Substances 0.000 claims description 6
- 229910052708 sodium Inorganic materials 0.000 claims description 6
- 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 5
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 claims description 4
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 4
- 239000007853 buffer solution Substances 0.000 claims description 4
- 229920000609 methyl cellulose Polymers 0.000 claims description 4
- 239000001923 methylcellulose Substances 0.000 claims description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 claims description 4
- 235000010262 sodium metabisulphite Nutrition 0.000 claims description 4
- 229940001482 sodium sulfite Drugs 0.000 claims description 4
- 235000010265 sodium sulphite Nutrition 0.000 claims description 4
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 claims description 4
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 claims description 4
- 229940033663 thimerosal 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
- 235000015424 sodium Nutrition 0.000 claims description 3
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 claims description 2
- QCDWFXQBSFUVSP-UHFFFAOYSA-N 2-phenoxyethanol Chemical compound OCCOC1=CC=CC=C1 QCDWFXQBSFUVSP-UHFFFAOYSA-N 0.000 claims description 2
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 2
- QZKRHPLGUJDVAR-UHFFFAOYSA-K EDTA trisodium salt Chemical class [Na+].[Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O QZKRHPLGUJDVAR-UHFFFAOYSA-K 0.000 claims description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 2
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims description 2
- JRBPAEWTRLWTQC-UHFFFAOYSA-N dodecylamine Chemical compound CCCCCCCCCCCCN JRBPAEWTRLWTQC-UHFFFAOYSA-N 0.000 claims description 2
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 claims description 2
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 claims description 2
- 235000011187 glycerol Nutrition 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 2
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 0.000 claims description 2
- 229960005323 phenoxyethanol Drugs 0.000 claims description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims description 2
- 229920000053 polysorbate 80 Polymers 0.000 claims description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 2
- 235000010241 potassium sorbate Nutrition 0.000 claims description 2
- 239000004302 potassium sorbate Substances 0.000 claims description 2
- 229940069338 potassium sorbate Drugs 0.000 claims description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 claims description 2
- 229940001474 sodium thiosulfate Drugs 0.000 claims description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 claims 1
- 239000001257 hydrogen Substances 0.000 claims 1
- 235000013772 propylene glycol Nutrition 0.000 claims 1
- 239000003889 eye drop Substances 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 3
- 229940012356 eye drops Drugs 0.000 abstract description 2
- 239000000758 substrate Substances 0.000 abstract description 2
- 230000001225 therapeutic effect Effects 0.000 abstract description 2
- 229940100655 ophthalmic gel Drugs 0.000 abstract 3
- 239000002738 chelating agent Substances 0.000 abstract 1
- 230000007547 defect Effects 0.000 abstract 1
- 239000000499 gel Substances 0.000 abstract 1
- 239000000017 hydrogel Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 31
- 238000000034 method Methods 0.000 description 19
- 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 14
- 229960002716 bromfenac sodium Drugs 0.000 description 14
- HLWRUJAIJJEZDL-UHFFFAOYSA-M sodium;2-[2-[bis(carboxymethyl)amino]ethyl-(carboxymethyl)amino]acetate Chemical class [Na+].OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC([O-])=O HLWRUJAIJJEZDL-UHFFFAOYSA-M 0.000 description 7
- 230000033228 biological regulation Effects 0.000 description 6
- 241000700159 Rattus Species 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
- 230000005855 radiation Effects 0.000 description 4
- 229960002668 sodium chloride Drugs 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 210000000795 conjunctiva Anatomy 0.000 description 3
- CSVGEMRSDNSWRF-UHFFFAOYSA-L disodium;dihydrogen phosphate Chemical compound [Na+].[Na+].OP(O)([O-])=O.OP(O)([O-])=O CSVGEMRSDNSWRF-UHFFFAOYSA-L 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
- 230000014759 maintenance of location Effects 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 206010010741 Conjunctivitis Diseases 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 206010030113 Oedema Diseases 0.000 description 2
- SOYCMDCMZDHQFP-UHFFFAOYSA-N amfenac Chemical class NC1=C(CC(O)=O)C=CC=C1C(=O)C1=CC=CC=C1 SOYCMDCMZDHQFP-UHFFFAOYSA-N 0.000 description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 description 2
- 208000010217 blepharitis Diseases 0.000 description 2
- 210000004087 cornea Anatomy 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 230000036512 infertility Effects 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 210000000554 iris Anatomy 0.000 description 2
- 230000007794 irritation Effects 0.000 description 2
- 150000003180 prostaglandins Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 206010013774 Dry eye Diseases 0.000 description 1
- 206010015943 Eye inflammation Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 1
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 229950008930 amfenac Drugs 0.000 description 1
- 229940114079 arachidonic acid Drugs 0.000 description 1
- 235000021342 arachidonic acid Nutrition 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229960002645 boric acid Drugs 0.000 description 1
- 229960003655 bromfenac Drugs 0.000 description 1
- 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 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000011081 inoculation Methods 0.000 description 1
- 239000002085 irritant Substances 0.000 description 1
- 231100000021 irritant Toxicity 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 231100000017 mucous membrane irritation Toxicity 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 150000007965 phenolic acids Chemical class 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 238000011552 rat model Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000004088 simulation Methods 0.000 description 1
- 239000008354 sodium chloride injection Substances 0.000 description 1
- 229940006198 sodium phenylacetate Drugs 0.000 description 1
- OZSKVIDRCKBITI-UHFFFAOYSA-M sodium;2-bromophenolate Chemical compound [Na+].[O-]C1=CC=CC=C1Br OZSKVIDRCKBITI-UHFFFAOYSA-M 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
Images
Abstract
The invention relates to an ophthalmic gel containing the active ingredient of bromfenac sodium hydrate and a preparation method thereof; the bromfenac sodium hydrate ophthalmic gel contains the active ingredient of bromfenac sodium hydrate, macromolecular hydrogel substrate, osmotic pressure regulator, bacteriostat, antioxidant, metal ion chelating agent, pH regulator and water for injection; the ophthalmic gel has convenient application and quick effect; particularly, the gel possesses certain viscosity and can stay in the eyes for a long time, thus overcoming the defect that eye drops can only stay in the eyes for a short time after being diluted by tears and achieving more effective therapeutic effect.
Description
Technical field
The present invention relates to a kind of gel for eye that contains the active ingredient bromfenac sodium hydrate and preparation method thereof, belong to medical technical field.
Background technology
Bromfenac sodium is a kind of non-steroidal antiinflammatory drugs; it is the derivant of 2-amino-3-benzoylphenylacetic acids (amfenac); mainly be by suppressing the synthetic of cyclooxygenase blocking-up prostaglandins inflammation modulators; thereby generation antiinflammatory action; prostaglandin is except having general action, or the important regulator of eye inflammation.
The bromfenac sodium chemical name is 2-amino-3-(4-benzoyl bromide)-sodium phenylacetate times semihydrate, and its chemical constitution is as follows:
Bromfenac sodium is easily molten in water, and is almost insoluble in 0.1M hydrochloric acid solution, acetonitrile and the acetone, dissolves slightly soluble in ethanol in methanol.
Bromfenac sodium is mainly used in the inflammation treatment (blepharitis, conjunctivitis, strong film scorching (comprising that strong film is scorching) and post-operation inflammatory) of outer eye and front eye at present.
Summary of the invention
The object of the invention provides the gel for eye that a kind of active ingredient is bromfenac sodium hydrate, soluble in water according to bromfenac sodium, aqueous solution is alkaline physicochemical property, and bromfenac sodium sodium salt in acid solution dissociates, become bromfenac, and further be decomposed into the bromfenac sodium precursor, and lose its drug action, affected to a great extent its stability and drug action.Therefore the bromfenac sodium gel for eye use is that bromfenac sodium is mixed in the aqueous gel substrate, by regulating pH value stability with the assurance active ingredient in alkaline range, regulate the ophthalmic preparation that the osmotic pressure scope makes by osmotic pressure regulator, so that ocular absorption and reduction ophthalmic administration to the eye mucous membrane irritation, also further increase the stability of gel by antibacterial, antioxidant and complexing of metal ion agent; And bromfenac sodium hydrate is prepared into gel for eye to have easy to use, particularly gel has certain viscosity retention time is longer within the eye, improve eye drop to be diluted by tear and caused the low and short shortcoming of the time of staying within the eye of drug level, played the therapeutical effect of continuous and effective.
Another object of the present invention provides the preparation method that a kind of active ingredient is the gel for eye of bromfenac sodium hydrate.
The zest of the size of gel for eye pH patient's eye to medicine stability with when using all can have certain influence, therefore by great many of experiments pH adjusting agent is selected in the present invention's research, so that its pH value remains on 7-10, both guarantee the stability of active ingredient bromfenac sodium hydrate, alleviated again preparation to the zest of eye.Carried out the Ocular irritation experimental study with 6 prepared samples of embodiment of the present invention in 14 days with every group of 3 single-doses of regular grade large ear rabbit and successive administration, bromine phenolic acid sodium gel for eye use single and continuous 14 days eye drips contrast as dripping same dosage 0.9% sodium chloride injection.The single-dose group after twice administration 1,2,4,24h, 48,72h, the successive administration group before administration every day and after the last administration 1,2,4,24,48 and 72h eye checked and give a mark.As a result single and continuous 14 days eye drips, the irritant reaction situation score value of animal eye cornea, iris and conjunctiva is 0, occurs without any irritation, the results are shown in Table 1.
Table 1
| Observe item | Embodiment 3 score values | Embodiment 4 score values | Embodiment 6 score values | Embodiment 13 score values | Embodiment 14 score values | Embodiment 16 score values |
| Cornea | 0 | 0 | 0 | 0 | 0 | 0 |
| |
0 | 0 | 0 | 0 | 0 | 0 |
| |
0 | 0 | 0 | 0 | 0 | 0 |
| Edema | 0 | 0 | 0 | 0 | 0 | 0 |
| |
0 | 0 | 0 | 0 | 0 | 0 |
| |
0 | 0 | 0 | 0 | 0 | 0 |
Ophthalmic preparation is very high to the requirement of osmotic pressure, hyperosmotic solution easily absorbs moisture within the eye, make eye dryness and discomfort, hypisotonic solution then can make keratectasia and produce pain, we guarantee that by the selection to osmotic pressure regulator the osmotic pressure of bromfenac sodium gel for eye use is equivalent to 0.9%NaCl solution osmotic pressure, ooze state with tear formation etc., to reduce the stimulation of eye and to promote that medicine is absorbed better.
Aseptic requirement is one of the important quality of ophthalmic preparation and security requirement, in process of the present invention by adding suitable antibacterial and sterilizing, adopt direct inoculation to carry out 14 days steriling tests and the method for inspection is verified, strict control reaches the aseptic requirement of ophthalmic preparation.
PH characteristic according to the bromfenac sodium gel for eye use, select the phosphate buffered solution of pH=7.4 as its release medium, mucosa characteristic according to eye, the semipermeable membrane bag filter of selective retention molecular weight 14000 is made simulation test, product sodium bromophenolate eye drops with 6 prepared samples of embodiment of the present invention and prior art is done contrast, the result is in identical release medium, contrast release test with eye drop in the bag filter shows that both in-vitro release are close, but the release of gel will be a little less than eye drop in the dispose procedure, and it is slower that release descends, and demonstrates the within the eye advantage of slow release effect in the long similar ophthalmic preparation of retention time of gel.The results are shown in Table 2 and accompanying drawing.
Table 2
| Time (h) | Eye drop | Embodiment 3 | Embodiment 4 | Embodiment 6 | Embodiment 13 | Embodiment 14 | Embodiment 16 |
| 0.5 | 37.93 | 28.96 | 27.82 | 29.12 | 28.15 | 27.67 | 28.95 |
| 1 | 55.38 | 46.84 | 46.17 | 47.08 | 45.97 | 43.59 | 48.17 |
| 2 | 76.51 | 66.93 | 64.89 | 66.34 | 65.61 | 64.27 | 67.29 |
| 3 | 85.03 | 77.86 | 76.18 | 76.92 | 78.03 | 76.08 | 78.13 |
| 5 | 90.19 | 83.05 | 82.56 | 83.97 | 83.99 | 82.45 | 83.32 |
| 8 | 93.20 | 86.77 | 84.48 | 85.04 | 85.37 | 83.97 | 85.95 |
| 10 | 91.06 | 80.82 | 78.85 | 79.35 | 78.65 | 77.99 | 79.89 |
| 12 | 86.98 | 76.51 | 75.13 | 75.76 | 74.92 | 74.53 | 76.54 |
| 24 | 70.27 | 73.18 | 73.49 | 74.22 | 73.86 | 72.87 | 73.96 |
The present invention relates to a kind of bromfenac sodium hydrate eye-gel preparation and preparation method thereof, it is characterized in that comprising active ingredient bromfenac sodium hydrate, polymer waterborne gel-type vehicle, osmotic pressure regulator, antibacterial, pH adjusting agent, water for injection.
Described eye-gel preparation is characterized in that comprising antioxidant, complexing of metal ion agent.
Described eye-gel preparation is characterized in that its active ingredient bromfenac sodium hydrate content is 0.1-10mg/g.
Described eye-gel preparation is characterized in that described polymer waterborne gel-type vehicle comprises carbomer, hydroxypropyl methylcellulose, polyvinyl alcohol, methylcellulose, hyaluronic acid sodium, glycerol, propylene glycol, tween 80, Sodium Tvlose, polyethylene pyrrole network alkane ketone.
Described eye-gel preparation is characterized in that the content of described polymer waterborne gel-type vehicle can be 1-100mg/g.
Described eye-gel preparation is characterized in that described osmotic pressure regulator comprises sodium chloride, mannitol, boric acid, Borax, sodium chromoglicate.
Described eye-gel preparation is characterized in that the content of described osmotic pressure regulator can be 1-50mg/g.
Described eye-gel preparation is characterized in that described antibacterial comprises benzalkonium bromide, benzalkonium chloride, methyl hydroxybenzoate, ethyl hydroxybenzoate, thimerosal, phenethanol, phenoxyethanol.
Described eye-gel preparation is characterized in that the content of described antibacterial can be 0.1-10mg/g.
Described eye-gel preparation is characterized in that described antioxidant comprises anhydrous sodium sulfite, potassium sorbate, sodium thiosulfate, sodium pyrosulfite, sodium sulfite.
Described eye-gel preparation is characterized in that the content of described antioxidant can be 0-30mg/g.
Described eye-gel preparation is characterized in that described complexing of metal ion agent comprises disodium edetate, edetic acid sodium salt, edetate trisodium salt.
Described eye-gel preparation is characterized in that the content of described complexing of metal ion agent can be 0-30mg/g.
Described eye-gel preparation, it is characterized in that described pH adjusting agent comprises sodium hydrate aqueous solution, sodium bicarbonate aqueous solution, ethylenediamine, lauryl amine, triethanolamine, diethanolamine, sodium hydrogen phosphate-phosphate sodium dihydrogen buffer solution, aqueous sodium carbonate, wherein sodium hydrate aqueous solution concentration can be the concentration of any suitable adjusting pH.
The preparation method of described eye-gel preparation is characterized in that polymer waterborne gel-type vehicle, osmotic pressure regulator and antibacterial, adds in the part water for injection, stir, make its abundant swelling, make blank gel, with bromfenac sodium hydrate be dissolved in the part water for injection in the dissolving after join in the blank gel, stir, transfer pH to 7-10 with pH adjusting agent, inject water to amount of formulation, be stirred to even gel, sterilization is filtered, and namely gets the bromfenac sodium hydrate gel for eye use; Or with polymer waterborne gel-type vehicle, osmotic pressure regulator and antibacterial, add in the part water for injection, stir, make its abundant swelling, make blank gel, bromfenac sodium hydrate is joined in the blank gel, stir, transfer pH to 7-10 with pH adjusting agent, inject water to amount of formulation, be stirred to even gel, sterilization, filter, namely get the bromfenac sodium hydrate gel for eye use; Or osmotic pressure regulator, antibacterial added in the part water for injection, stir, transfer pH to 7-10 with pH adjusting agent, add the polymer waterborne gel-type vehicle, stir, make its abundant swelling, make blank gel, bromfenac sodium hydrate is dissolved in the water for injection of part dissolving, after join in the blank gel, inject water to amount of formulation, keep pH to 7-10, be stirred to even gel, sterilization is filtered, and namely gets the bromfenac sodium hydrate gel for eye use; Or osmotic pressure regulator, antibacterial added in the part water for injection, stir, transfer pH to 7-10 with pH adjusting agent, add the polymer waterborne gel-type vehicle, stir, make its abundant swelling, make blank gel, bromfenac sodium hydrate is joined in the blank gel, inject water to amount of formulation, keep pH to 7-10 to be stirred to even gel, sterilization, filter, namely get the bromfenac sodium hydrate gel for eye use.
The preparation method of described eye-gel preparation is characterized in that also can adding in the blank gel antioxidant or complexing of metal ion agent or antioxidant and complexing of metal ion agent.
With meeting Chinese Pharmacopoeia the examination requirements of bromfenac sodium hydrate eye-gel preparation carried out embodiments of the invention the check of pH, uniformity, viscosity, sterility test, wherein 6 embodiment the results are shown in Table 3:
Table 3
| Inspection item | Embodiment 3 | Embodiment 4 | Embodiment 6 | Embodiment 13 | Embodiment 14 | Embodiment 16 |
| PH value | 8.2 | 8.0 | 7.9 | 8.0 | 7.8 | 7.9 |
| Uniformity | Evenly, exquisiteness | Evenly, exquisiteness | Evenly, exquisiteness | Evenly, exquisiteness | Evenly, exquisiteness | Evenly, exquisiteness |
| Viscosity mPa.s | 28.8 | 27.5 | 28.1 | 26.9 | 30.2 | 29.6 |
| Sterility test | Meet the pharmacopeia regulation | Meet the pharmacopeia regulation | Meet the pharmacopeia regulation | Meet the pharmacopeia regulation | Meet the pharmacopeia regulation | Meet the pharmacopeia regulation |
Description of drawings
Accompanying drawing: release in vitro curve
The specific embodiment
The embodiment that to enumerate several active substances of the present invention be the bromfenac sodium hydrate eye-gel preparation is used for further specifying the present invention, but the present invention does not mean and only is confined to following examples.
Embodiment 1
Bromfenac sodium hydrate: 0.1g
Carbomer: 15.0g
Thimerosal: 0.5g
Boric acid: 10.0g
Borax: 5.0g
Sodium carbonate liquor: an amount of
Water for injection adds to 1000g
Make 1000g
Method for making: with carbomer, thimerosal, boric acid and Borax, add in the part water for injection, stir, make its abundant swelling, make blank gel, bromfenac sodium hydrate is joined in the blank gel, stir, transfer about pH to 8.0 with sodium carbonate liquor, inject water to amount of formulation, be stirred to even gel, radiation sterilization, filter, namely get the bromfenac sodium hydrate gel for eye use.
Embodiment 2
Bromfenac sodium hydrate: 10.00g
Methylcellulose: 10.00g
Hyaluronic acid sodium: 10.00g
Benzalkonium bromide: 0.25g
Edetic acid sodium salt 1.0g
Sodium chloride: 9.00g
0.1mol/L sodium hydroxide solution: an amount of
Water for injection adds to 1000g
Make 1000g
Method for making: with methylcellulose, hyaluronic acid sodium, benzalkonium bromide, edetic acid sodium salt and sodium chloride, add in the part water for injection, stir, make its abundant swelling, make blank gel, bromfenac sodium hydrate is dissolved in the water for injection of part, join after the dissolving in the blank gel, stir, transfer about pH to 8.0 with the 0.1mol/L sodium hydroxide solution, inject water to amount of formulation, be stirred to even gel, dry heat sterilization is filtered, and namely gets the bromfenac sodium hydrate gel for eye use.
Embodiment 3
Bromfenac sodium hydrate: 10.00g
Hydroxypropyl methylcellulose: 14.00g
Benzalkonium bromide: 0.25g
Disodium edetate 1.0g
Sodium chloride: 9.00g
0.1mol/L sodium hydroxide solution: an amount of
Water for injection adds to 1000g
Make 1000g
Method for making: with benzalkonium bromide, disodium edetate and sodium chloride, add in the part water for injection, stir, transfer about pH to 8.0 with the 0.1mol/L sodium hydroxide solution, add the hydroxypropyl methylcellulose stirring and make its abundant swelling, make blank gel, bromfenac sodium hydrate is joined in the blank gel, stir, inject water to amount of formulation, be stirred to even gel, moist heat sterilization, filter, namely get the bromfenac sodium hydrate gel for eye use.
Embodiment 4
Bromfenac sodium hydrate: 1.00g
Hydroxypropyl methylcellulose: 12.00g
Benzalkonium chloride: 0.05g
Sodium chloride: 9.00g
0.1mol/L sodium hydroxide solution: an amount of
Water for injection adds to 1000g
Make 1000g
Method for making: with hydroxypropyl methylcellulose, benzalkonium chloride and sodium chloride, add in the part water for injection, stir, make its abundant swelling, make blank gel, bromfenac sodium hydrate is dissolved in the water for injection of part, join after the dissolving in the blank gel, stir, transfer about pH to 8.0 with the 0.1mol/L sodium hydroxide solution, inject water to amount of formulation, be stirred to even gel, moist heat sterilization filters, and namely gets the bromfenac sodium hydrate gel for eye use.
Bromfenac sodium hydrate: 1.00g
Hydroxypropyl methylcellulose: 12.00g
Benzalkonium chloride: 0.05g
Sodium chloride: 9.00g
0.1mol/L sodium hydroxide solution: an amount of
Water for injection adds to 1000g
Make 1000g
Method for making: with benzalkonium chloride and sodium chloride, add in the part water for injection, stir, transfer about pH to 8.0 with the 0.1mol/L sodium hydroxide solution, add hydroxypropyl methylcellulose and stir, make its abundant swelling, make blank gel, bromfenac sodium hydrate is dissolved in the water for injection of part, join after the dissolving in the blank gel, stir, inject water to amount of formulation, be stirred to even gel, moist heat sterilization, filter, namely get the bromfenac sodium hydrate gel for eye use.
Embodiment 6
Bromfenac sodium hydrate: 1.00g
Hydroxypropyl methylcellulose: 12.00g
Benzalkonium bromide: 0.05g
Sodium chloride: 9.00g
0.1mol/L sodium hydroxide solution: an amount of
Water for injection adds to 1000g
Make 1000g
Method for making: with benzalkonium bromide and sodium chloride, add in the part water for injection, stir, transfer about pH to 8.0 with the 0.1mol/L sodium hydroxide solution, add hydroxypropyl methylcellulose and stir, make its abundant swelling, make blank gel, bromfenac sodium hydrate is joined in the blank gel, stir, inject water to amount of formulation, be stirred to even gel, dry heat sterilization is filtered, and namely gets the bromfenac sodium hydrate gel for eye use.
Embodiment 7
Bromfenac sodium hydrate: 10.00g
Hydroxypropyl methylcellulose: 14.00g
Benzalkonium bromide: 0.25g
Disodium edetate 1.0g
Sodium chloride: 9.00g
0.1mol/L sodium hydroxide solution: an amount of
Water for injection adds to 1000g
Make 1000g
Method for making: with benzalkonium bromide, disodium edetate and sodium chloride, add in the part water for injection, stir, transfer about pH to 8.0 with the 0.1mol/L sodium hydroxide solution, add the hydroxypropyl methylcellulose stirring and make its abundant swelling, make blank gel, bromfenac sodium hydrate is dissolved in the water for injection of part, join after the dissolving in the blank gel, stir, inject water to amount of formulation, be stirred to even gel, radiation sterilization is filtered, and namely gets the bromfenac sodium hydrate gel for eye use.
Embodiment 8
Bromfenac sodium hydrate: 10.00g
Carbomer 18.00g
Benzalkonium bromide: 0.25g
Edetic acid sodium salt 1.2g
Sodium chloride: 9.00g
Sodium bicarbonate solution: an amount of
Water for injection adds to 1000g
Make 1000g
Method for making: with carbomer, benzalkonium bromide, edetic acid sodium salt and sodium chloride, add in the part water for injection, stir, make its abundant swelling, make blank gel, bromfenac sodium hydrate is joined in the blank gel, stir, transfer about pH to 8.0 with sodium bicarbonate solution, inject water to amount of formulation, be stirred to even gel, dry heat sterilization, filter, namely get the bromfenac sodium hydrate gel for eye use.
Embodiment 9
Bromfenac sodium hydrate: 1.00g
Carbomer: 15.00g
Benzalkonium bromide: 0.2g
Sodium sulfite: 1.5g
Sodium chloride: 9.00g
Sodium hydrogen phosphate-phosphate sodium dihydrogen buffer solution is an amount of
Water for injection adds to 1000g
Make 1000g
Method for making: with carbomer, benzalkonium bromide, sodium sulfite and sodium chloride, add in the part water for injection, stir, make its abundant swelling, make blank gel, bromfenac sodium hydrate is joined in the blank gel, stir, transfer about pH to 8.0 with sodium hydrogen phosphate-phosphate sodium dihydrogen buffer solution, inject water to amount of formulation, be stirred to even gel, moist heat sterilization, filter, namely get the bromfenac sodium hydrate gel for eye use.
Bromfenac sodium hydrate: 5.00g
Hydroxypropyl methylcellulose: 10.00g
Polyethylene pyrrole network alkane ketone: 2.0g
Benzalkonium bromide: 0.2g
Anhydrous sodium sulfite: 1.5g
Edetic acid sodium salt 1.0g
Boric acid: 5.0g
Borax: 5.0g
0.1mol/L sodium hydroxide solution: an amount of
Water for injection adds to 1000g
Make 1000g
Method for making: with hydroxypropyl methylcellulose, polyethylene pyrrole network alkane ketone, benzalkonium bromide, anhydrous sodium sulfite, edetic acid sodium salt, boric acid and Borax, add in the part water for injection, stir, make its abundant swelling, make blank gel, bromfenac sodium hydrate is joined in the blank gel, stir, transfer about pH to 8.0 with the 0.1mol/L sodium hydroxide solution, inject water to amount of formulation, be stirred to even gel, moist heat sterilization, filter, namely get the bromfenac sodium hydrate gel for eye use.
Embodiment 11
Bromfenac sodium hydrate: 5.00g
Hydroxypropyl methylcellulose: 14.00g
Phenethanol: 0.6g
Sodium pyrosulfite: 1.5g
Disodium edetate 1g
Boric acid: 5.0g
Borax: 5.0g
Ethylenediamine: an amount of
Water for injection adds to 1000g
Make 1000g
Method for making: with hydroxypropyl methylcellulose, phenethanol, sodium pyrosulfite, disodium edetate, boric acid and Borax, add in the part water for injection, stir, make its abundant swelling, make blank gel, bromfenac sodium hydrate is dissolved in the water for injection of part, join after the dissolving in the blank gel, stir, transfer about pH to 8.0 with ethylenediamine, inject water to amount of formulation, be stirred to even gel, radiation sterilization is filtered, and namely gets the bromfenac sodium hydrate gel for eye use.
Embodiment 12
Bromfenac sodium hydrate: 5.00g
Hydroxypropyl methylcellulose: 12.00g
Benzalkonium bromide: 0.2g
Anhydrous sodium sulfite: 1.5g
Disodium edetate: 1.0g
Sodium chloride: 9.00g
0.1mol/L sodium hydroxide solution: an amount of
Water for injection adds to 1000g
Make 1000g
Method for making: with benzalkonium bromide, anhydrous sodium sulfite, disodium edetate, sodium chloride, add in the part water for injection, stir, transfer about pH to 8.0 with the 0.1mol/L sodium hydroxide solution, add the hydroxypropyl methylcellulose stirring and make its abundant swelling, make blank gel, bromfenac sodium hydrate is joined in the blank gel, stir, inject water to amount of formulation, be stirred to even gel, dry heat sterilization, filter, namely get the bromfenac sodium hydrate gel for eye use.
Embodiment 13
Bromfenac sodium hydrate: 5.00g
Hydroxypropyl methylcellulose: 12.00g
Benzalkonium chloride: 0.2g
Anhydrous sodium sulfite: 1.5g
Disodium edetate: 1.0g
Sodium chloride: 9.00g
0.1mol/L sodium hydroxide solution: an amount of
Water for injection adds to 1000g
Make 1000g
Method for making: with benzalkonium chloride, anhydrous sodium sulfite, disodium edetate, sodium chloride, add in the part water for injection, stir, transfer about pH to 8.0 with the 0.1mol/L sodium hydroxide solution, add the hydroxypropyl methylcellulose stirring and make its abundant swelling, make blank gel, bromfenac sodium hydrate is dissolved in the water for injection of part, join after the dissolving in the blank gel, stir, inject water to amount of formulation, be stirred to even gel, moist heat sterilization filters, and namely gets the bromfenac sodium hydrate gel for eye use.
Embodiment 14
Bromfenac sodium hydrate: 2.00g
Hydroxypropyl methylcellulose: 15.00g
Benzalkonium chloride: 0.1g
Anhydrous sodium sulfite: 2.0g
Sodium chloride: 9.00g
0.1mol/L sodium hydroxide solution: an amount of
Water for injection adds to 1000g
Make 1000g
Method for making: with hydroxypropyl methylcellulose, benzalkonium chloride, anhydrous sodium sulfite and sodium chloride, add in the part water for injection, stir, make its abundant swelling, make blank gel, bromfenac sodium hydrate is dissolved in the water for injection of part, join after the dissolving in the blank gel, stir, transfer about pH to 8.0 with the 0.1mol/L sodium hydroxide solution, inject water to amount of formulation, be stirred to even gel, moist heat sterilization filters, and namely gets the bromfenac sodium hydrate gel for eye use.
Bromfenac sodium hydrate: 2.00g
Hydroxypropyl methylcellulose: 15.00g
Benzalkonium chloride: 0.1g
Anhydrous sodium sulfite 2.0g
Sodium chloride: 9.00g
0.1mol/L sodium hydroxide solution: an amount of
Water for injection adds to 1000g
Make 1000g
Method for making: with benzalkonium chloride, anhydrous sodium sulfite and sodium chloride, add in the part water for injection, stir, transfer about pH to 8.0 with the 0.1mol/L sodium hydroxide solution, add the hydroxypropyl methylcellulose stirring and make its abundant swelling, make blank gel, bromfenac sodium hydrate is joined in the blank gel, stir, inject water to amount of formulation, be stirred to even gel, radiation sterilization, filter, namely get the bromfenac sodium hydrate gel for eye use.
Embodiment 16
Bromfenac sodium hydrate: 2.00g
Hydroxypropyl methylcellulose: 15.00g
Benzalkonium chloride: 0.1g
Anhydrous sodium sulfite 2.0g
Sodium chloride: 9.00g
0.1mol/L sodium hydroxide solution: an amount of
Water for injection adds to 1000g
Make 1000g
Method for making: with benzalkonium chloride, anhydrous sodium sulfite and sodium chloride, add in the part water for injection, stir, transfer about pH to 8.0 with the 0.1mol/L sodium hydroxide solution, add the hydroxypropyl methylcellulose stirring and make its abundant swelling, make blank gel, bromfenac sodium hydrate is dissolved in the water for injection of part, join after the dissolving in the blank gel, stir, inject water to amount of formulation, be stirred to even gel, dry heat sterilization is filtered, and namely gets the bromfenac sodium hydrate gel for eye use.
Embodiment 17
With 32 uniform rats of body weight, prepare sample and 2 rats of the every group model of prior art eye drop with 6 embodiment of the present invention, two each 1 of rat, 4 rats of normal saline blank, adopt arachidonic acid profile and carrageenin model to carry out the comparative study of rat model antiinflammatory experimental observation, difference result shows that embodiment of the invention sample all can obviously suppress rat conjunctiva edema, has significant antiinflammatory action, the results are shown in Table 4.
Table 4
The preparation method of above-mentioned bromfenac sodium gel for eye also is applicable to the preparation of the bromfenac sodium gel for eye of other prescription.
Therefore, bromfenac sodium gel for eye zest of the present invention is low, safety good, and (blepharitis, conjunctivitis, strong film scorching (comprising that strong film is scorching) and the treatment of post-operation inflammatory have lasting definite curative effect to be used for the inflammation treatment of outer eye and front eye.
Claims (9)
1. bromfenac sodium hydrate eye-gel preparation, it is characterized in that comprising the active ingredient bromfenac sodium hydrate, the polymer waterborne gel-type vehicle, osmotic pressure regulator, antibacterial, pH adjusting agent, water for injection, its active ingredient bromfenac sodium hydrate content is 0.1-10mg/g, described polymer waterborne gel-type vehicle is selected from carbomer, hydroxypropyl methylcellulose, polyvinyl alcohol, methylcellulose, hyaluronic acid sodium, glycerol, propylene glycol, tween 80, Sodium Tvlose, polyethylene pyrrole network alkane ketone, the content of described polymer waterborne gel-type vehicle is 1～100 mg/g.
2. eye-gel preparation claimed in claim 1 is characterized in that also can comprising antioxidant, complexing of metal ion agent.
3. eye-gel preparation claimed in claim 1 is characterized in that described osmotic pressure regulator is selected from sodium chloride, mannitol, boric acid, Borax or sodium chromoglicate.
4. eye-gel preparation claimed in claim 1 is characterized in that described antibacterial is selected from benzalkonium bromide, benzalkonium chloride, methyl hydroxybenzoate, ethyl hydroxybenzoate, thimerosal, phenethanol or phenoxyethanol.
5. eye-gel preparation claimed in claim 2 is characterized in that described antioxidant is selected from anhydrous sodium sulfite, potassium sorbate, sodium thiosulfate, sodium pyrosulfite or sodium sulfite.
6. eye-gel preparation claimed in claim 2 is characterized in that described complexing of metal ion agent is selected from disodium edetate or edetate trisodium salt.
7. eye-gel preparation claimed in claim 1 is characterized in that described pH adjusting agent is selected from sodium hydrate aqueous solution, sodium bicarbonate aqueous solution, ethylenediamine, lauryl amine, triethanolamine, diethanolamine, Lin acid hydrogen Er Na – phosphate sodium dihydrogen buffer solution or aqueous sodium carbonate.
8. the preparation method of eye-gel preparation claimed in claim 1, it is characterized in that polymer waterborne gel-type vehicle, osmotic pressure regulator and antibacterial, add in the part water for injection, stir, make its abundant swelling, make blank gel, with bromfenac sodium hydrate be dissolved in the part water for injection in the dissolving after join in the blank gel, stir, transfer pH to 7 – 10 with pH adjusting agent, inject water to amount of formulation, be stirred to even gel, sterilization is filtered, and namely gets the bromfenac sodium hydrate gel for eye use; Or with polymer waterborne gel-type vehicle, osmotic pressure regulator and antibacterial, add in the part water for injection, stir, make its abundant swelling, make blank gel, bromfenac sodium hydrate is joined in the blank gel, stir, transfer pH to 7 – 10 with pH adjusting agent, inject water to amount of formulation, be stirred to even gel, sterilization, filter, namely get the bromfenac sodium hydrate gel for eye use; Or osmotic pressure regulator, antibacterial added in the part water for injection, stir, transfer pH to 7 – 10 with pH adjusting agent, add the polymer waterborne gel-type vehicle, stir, make its abundant swelling, make blank gel, bromfenac sodium hydrate is dissolved in the water for injection of part dissolving, after join in the blank gel, inject water to amount of formulation, keep pH to 7 – 10, be stirred to even gel, sterilization is filtered, and namely gets the bromfenac sodium hydrate gel for eye use; Or osmotic pressure regulator, antibacterial added in the part water for injection, stir, transfer pH to 7 – 10 with pH adjusting agent, add the polymer waterborne gel-type vehicle, stir, make its abundant swelling, make blank gel, bromfenac sodium hydrate is joined in the blank gel, inject water to amount of formulation, keep pH to 7 – 10 to be stirred to even gel, sterilization, filter, namely get the bromfenac sodium hydrate gel for eye use.
9. the preparation method of eye-gel preparation claimed in claim 8 is characterized in that also can adding in the blank gel antioxidant or complexing of metal ion agent or antioxidant and complexing of metal ion agent.
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| CN104523587A (en) * | 2014-12-31 | 2015-04-22 | 辰欣药业股份有限公司 | Bromfenac sodium eye drops and preparation method thereof |
| CN106727621A (en) * | 2016-11-22 | 2017-05-31 | 郑州仁宏医药科技有限公司 | A kind of Western medicine powder for treating toothache |
| CN110538138B (en) * | 2019-10-10 | 2021-02-02 | 合肥华威药业有限公司 | Sustained-release bromfenac sodium ophthalmic preparation |
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| CN1456161A (en) * | 2002-05-10 | 2003-11-19 | 刘继东 | Eye gel for atropine sulfate |
| CN1823754A (en) * | 2006-03-28 | 2006-08-30 | 卢秀莲 | Sodium bromophenolate eye drops and its preparation method |
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| CN1456161A (en) * | 2002-05-10 | 2003-11-19 | 刘继东 | Eye gel for atropine sulfate |
| CN1823754A (en) * | 2006-03-28 | 2006-08-30 | 卢秀莲 | Sodium bromophenolate eye drops and its preparation method |
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