JP2020002123A - レバミピドを含有するドライアイ治療用水溶性多回用点眼剤組成物、並びにその可溶化及び安定化方法 - Google Patents
レバミピドを含有するドライアイ治療用水溶性多回用点眼剤組成物、並びにその可溶化及び安定化方法 Download PDFInfo
- Publication number
- JP2020002123A JP2020002123A JP2019107703A JP2019107703A JP2020002123A JP 2020002123 A JP2020002123 A JP 2020002123A JP 2019107703 A JP2019107703 A JP 2019107703A JP 2019107703 A JP2019107703 A JP 2019107703A JP 2020002123 A JP2020002123 A JP 2020002123A
- Authority
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- Prior art keywords
- acid
- rebamipide
- preservative
- water
- eye drop
- 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.)
- Granted
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- ALLWOAVDORUJLA-UHFFFAOYSA-N Rebamipida Chemical compound C=1C(=O)NC2=CC=CC=C2C=1CC(C(=O)O)NC(=O)C1=CC=C(Cl)C=C1 ALLWOAVDORUJLA-UHFFFAOYSA-N 0.000 title claims abstract description 56
- 229950004535 rebamipide Drugs 0.000 title claims abstract description 56
- 239000000203 mixture Substances 0.000 title claims abstract description 27
- 239000003889 eye drop Substances 0.000 title claims abstract description 25
- 238000000034 method Methods 0.000 title claims abstract description 17
- 206010013774 Dry eye Diseases 0.000 title claims abstract description 16
- 208000003556 Dry Eye Syndromes Diseases 0.000 title claims abstract description 15
- 230000003381 solubilizing effect Effects 0.000 title claims abstract description 8
- 230000000087 stabilizing effect Effects 0.000 title claims abstract description 8
- 239000003755 preservative agent Substances 0.000 claims abstract description 58
- 230000002335 preservative effect Effects 0.000 claims abstract description 54
- 239000000243 solution Substances 0.000 claims abstract description 31
- 239000002738 chelating agent Substances 0.000 claims abstract description 20
- 238000004519 manufacturing process Methods 0.000 claims abstract description 12
- 239000002997 ophthalmic solution Substances 0.000 claims description 29
- 229940054534 ophthalmic solution Drugs 0.000 claims description 29
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 24
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 18
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 16
- 230000003204 osmotic effect Effects 0.000 claims description 12
- SLXKOJJOQWFEFD-UHFFFAOYSA-N 6-aminohexanoic acid Chemical compound NCCCCCC(O)=O SLXKOJJOQWFEFD-UHFFFAOYSA-N 0.000 claims description 9
- 229960002684 aminocaproic acid Drugs 0.000 claims description 9
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 claims description 9
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 claims description 9
- 229960002216 methylparaben Drugs 0.000 claims description 9
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 claims description 9
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 claims description 9
- 229960003415 propylparaben Drugs 0.000 claims description 9
- 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 8
- 229910052783 alkali metal Inorganic materials 0.000 claims description 8
- -1 alkali metal salt Chemical class 0.000 claims description 8
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 229960001484 edetic acid Drugs 0.000 claims description 8
- 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
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
- 239000000872 buffer Substances 0.000 claims description 6
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 6
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 6
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 6
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 5
- UEZVMMHDMIWARA-UHFFFAOYSA-N Metaphosphoric acid Chemical compound OP(=O)=O UEZVMMHDMIWARA-UHFFFAOYSA-N 0.000 claims description 5
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 5
- 229920000137 polyphosphoric acid Polymers 0.000 claims description 5
- 238000005063 solubilization Methods 0.000 claims description 5
- 230000007928 solubilization Effects 0.000 claims description 5
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- 239000011975 tartaric acid Substances 0.000 claims description 5
- 235000002906 tartaric acid Nutrition 0.000 claims description 5
- IMQLKJBTEOYOSI-GPIVLXJGSA-N Inositol-hexakisphosphate Chemical compound OP(O)(=O)O[C@H]1[C@H](OP(O)(O)=O)[C@@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@H](OP(O)(O)=O)[C@@H]1OP(O)(O)=O IMQLKJBTEOYOSI-GPIVLXJGSA-N 0.000 claims description 4
- IMQLKJBTEOYOSI-UHFFFAOYSA-N Phytic acid Natural products OP(O)(=O)OC1C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C(OP(O)(O)=O)C1OP(O)(O)=O IMQLKJBTEOYOSI-UHFFFAOYSA-N 0.000 claims description 4
- 239000002253 acid Substances 0.000 claims description 4
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 4
- XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical compound OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 0.000 claims description 4
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 claims description 4
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 claims description 4
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 claims description 4
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 claims description 4
- 229920000609 methyl cellulose Polymers 0.000 claims description 4
- 239000001923 methylcellulose Substances 0.000 claims description 4
- 235000010981 methylcellulose Nutrition 0.000 claims description 4
- 235000002949 phytic acid Nutrition 0.000 claims description 4
- 239000000467 phytic acid Substances 0.000 claims description 4
- 229940068041 phytic acid Drugs 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 3
- 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 3
- 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 3
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 3
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 3
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 3
- 229930195725 Mannitol Natural products 0.000 claims description 3
- 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 3
- 229930006000 Sucrose Natural products 0.000 claims description 3
- 239000002585 base Substances 0.000 claims description 3
- 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 3
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 3
- 239000004327 boric acid Substances 0.000 claims description 3
- 239000008121 dextrose Substances 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 235000011187 glycerol Nutrition 0.000 claims description 3
- 150000004677 hydrates Chemical class 0.000 claims description 3
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 3
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 3
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 3
- 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 3
- 239000001630 malic acid Substances 0.000 claims description 3
- 235000011090 malic acid Nutrition 0.000 claims description 3
- 239000000594 mannitol Substances 0.000 claims description 3
- 235000010355 mannitol Nutrition 0.000 claims description 3
- 229940005657 pyrophosphoric acid Drugs 0.000 claims description 3
- 239000000600 sorbitol Substances 0.000 claims description 3
- 230000006641 stabilisation Effects 0.000 claims description 3
- 238000011105 stabilization Methods 0.000 claims description 3
- 239000005720 sucrose Substances 0.000 claims description 3
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 2
- 239000002357 osmotic agent Substances 0.000 claims 2
- 229920000388 Polyphosphate Polymers 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- 235000011180 diphosphates Nutrition 0.000 claims 1
- 229940049920 malate Drugs 0.000 claims 1
- 125000005341 metaphosphate group Chemical group 0.000 claims 1
- 239000001205 polyphosphate Substances 0.000 claims 1
- 235000011176 polyphosphates Nutrition 0.000 claims 1
- 229940048084 pyrophosphate Drugs 0.000 claims 1
- 229940012356 eye drops Drugs 0.000 abstract description 8
- 238000003860 storage Methods 0.000 abstract description 6
- 238000001556 precipitation Methods 0.000 abstract 1
- 230000000052 comparative effect Effects 0.000 description 20
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000000725 suspension Substances 0.000 description 15
- 238000012360 testing method Methods 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- 239000012153 distilled water Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 239000003814 drug Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 229960002920 sorbitol Drugs 0.000 description 4
- 230000001954 sterilising effect Effects 0.000 description 4
- 238000004659 sterilization and disinfection Methods 0.000 description 4
- 229960003943 hypromellose Drugs 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 208000002193 Pain Diseases 0.000 description 2
- 239000006172 buffering agent Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000007774 longterm Effects 0.000 description 2
- 230000007721 medicinal effect Effects 0.000 description 2
- 210000004400 mucous membrane Anatomy 0.000 description 2
- 210000003097 mucus Anatomy 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 239000011148 porous material Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 229940124597 therapeutic agent Drugs 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
- 201000004569 Blindness Diseases 0.000 description 1
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- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- OVBJJZOQPCKUOR-UHFFFAOYSA-L EDTA disodium salt dihydrate Chemical compound O.O.[Na+].[Na+].[O-]C(=O)C[NH+](CC([O-])=O)CC[NH+](CC([O-])=O)CC([O-])=O OVBJJZOQPCKUOR-UHFFFAOYSA-L 0.000 description 1
- NMLMACJWHPHKGR-NCOIDOBVSA-N P(1),P(4)-bis(uridin-5'-yl) tetraphosphate Chemical compound N1([C@@H]2O[C@@H]([C@H]([C@H]2O)O)COP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@@H]2[C@H]([C@H]([C@@H](O2)N2C(NC(=O)C=C2)=O)O)O)C=CC(=O)NC1=O NMLMACJWHPHKGR-NCOIDOBVSA-N 0.000 description 1
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- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
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- YZIYKJHYYHPJIB-UUPCJSQJSA-N chlorhexidine gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C(O)=O.C1=CC(Cl)=CC=C1NC(=N)NC(=N)NCCCCCCNC(=N)NC(=N)NC1=CC=C(Cl)C=C1 YZIYKJHYYHPJIB-UUPCJSQJSA-N 0.000 description 1
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- 229930182912 cyclosporin Natural products 0.000 description 1
- 238000013461 design Methods 0.000 description 1
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Classifications
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- 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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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4704—2-Quinolinones, e.g. carbostyril
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- 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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- 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
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- 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
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- 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
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- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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- A61P27/00—Drugs for disorders of the senses
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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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Abstract
Description
Claims (6)
- 有効成分としてレバミピドを含む点眼液の製造方法であって、
(a)エチルパラベン、メチルパラベン及びプロピルパラベンからなる群から選ばれた一つ以上の防腐剤;レバミピド又はその薬学的に許容される塩;並びにヒドロキシプロピルメチルセルロース、メチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシエチルセルロース及びカルボキシメチルセルロースからなる群から選ばれた一つ以上の安定化剤;に塩基を加えた後、水に溶解させて、pH10〜11の水溶液点眼液を得る工程;
(b)アミノカプロン酸又はアミノカプロン酸とホウ酸の混合物から選ばれたいずれかの緩衝剤;並びにソルビトール、マンニトール、デキストロース、スクロース及びグリセリンからなる非イオン性浸透圧調節剤から選ばれた一つ以上の浸透圧調節剤;を加え、溶解させて、エデト酸、クエン酸、メタリン酸、ピロリン酸、ポリリン酸、リンゴ酸、酒石酸及びフィチン酸からなるアルカリ金属塩又はこれらの水和物から選ばれる一つ以上のキレート剤を添加し、溶解させて、酸でpH7〜8に調整する工程;
(c)工程(b)から得られた透明な溶液をシリンジフィルターでろ過して、無菌性に製造する工程;
を含むことを特徴とする、レバミピドを含有するドライアイ治療用水溶性多回用点眼剤の可溶化及び安定化方法。 - レバミピドは、0.5〜2.0w/v%の濃度で無色透明に可溶化されることを特徴とする、請求項1に記載のレバミピドを含有するドライアイ治療用水溶性多回用点眼剤の可溶化及び安定化方法。
- 前記防腐剤の濃度は、0.001〜0.1w/v%であることを特徴とする、請求項1に記載のレバミピドを含有するドライアイ治療用水溶性多回用点眼剤の可溶化及び安定化方法。
- 前記防腐剤は、高温水で溶解して使用することを特徴とする、請求項1に記載のレバミピドを含有するドライアイ治療用水溶性多回用点眼剤の可溶化及び安定化方法。
- 前記キレート剤の濃度は、0.01〜5w/v%であることを特徴とする、請求項1に記載のレバミピドを含有するドライアイ治療用水溶性多回用点眼剤の可溶化及び安定化方法。
- 請求項1に記載の方法に従って製造された、
エチルパラベン、メチルパラベン及びプロピルパラベンからなる群から選ばれた一つ以上の防腐剤;
レバミピド又はその薬学的に許容可能な塩;
ヒドロキシプロピルメチルセルロース、メチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシエチルセルロース及びカルボキシメチルセルロースからなる群から選ばれた一つ以上の安定化剤;
アミノカプロン酸又はアミノカプロン酸とホウ酸の混合物から選ばれたいずれかの緩衝剤;
ソルビトール、マンニトール、デキストロース、スクロース、グリセリンからなる非イオン性浸透圧調節剤から選ばれた一つ以上の浸透圧調節剤;及び
エデト酸、クエン酸、メタリン酸、ピロリン酸、ポリリン酸、リンゴ酸、酒石酸、フィチン酸からなるアルカリ金属塩又はこれらの水和物から選ばれる一つ以上のキレート剤;
を含むことを特徴とする、レバミピドを含有するドライアイ治療用水溶性多回用点眼剤組成物。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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KR10-2018-0073486 | 2018-06-26 | ||
KR1020180073486A KR101923519B1 (ko) | 2018-06-26 | 2018-06-26 | 레바미피드를 함유하는 안구 건조증 치료용 수용성 다회용 점안제 조성물 및 이의 가용화 및 안정화 방법 |
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JP2020002123A true JP2020002123A (ja) | 2020-01-09 |
JP6861440B2 JP6861440B2 (ja) | 2021-04-21 |
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JP2019107703A Active JP6861440B2 (ja) | 2018-06-26 | 2019-06-10 | レバミピドを含有するドライアイ治療用水溶性多回用点眼剤組成物、並びにその可溶化及び安定化方法 |
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JP (1) | JP6861440B2 (ja) |
KR (1) | KR101923519B1 (ja) |
CN (1) | CN110638748B (ja) |
WO (1) | WO2020004784A1 (ja) |
Cited By (1)
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JP2020534321A (ja) * | 2017-09-21 | 2020-11-26 | ダエウー ファーマシューティカル インダストリー カンパニー リミテッドDaewoo Pharmaceutical Ind. Co., Ltd. | レバミピドを含有する新規ドライアイ治療用点眼組成物及びその可溶化及び安定化方法 |
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KR102615076B1 (ko) * | 2021-07-14 | 2023-12-19 | 대우제약 주식회사 | 안정한 레바미피드 점안제의 대용량 제조 방법 |
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JP2016027025A (ja) * | 2014-06-26 | 2016-02-18 | ロート製薬株式会社 | 局所粘膜適用水性組成物 |
KR101840256B1 (ko) * | 2017-09-21 | 2018-03-21 | 대우제약 주식회사 | 레바미피드를 함유하는 새로운 안구건조증 치료용 점안 조성물 및 이의 가용화 및 안정화 방법 |
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- 2018-06-26 KR KR1020180073486A patent/KR101923519B1/ko active
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- 2019-06-10 JP JP2019107703A patent/JP6861440B2/ja active Active
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JP2016027025A (ja) * | 2014-06-26 | 2016-02-18 | ロート製薬株式会社 | 局所粘膜適用水性組成物 |
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CN110638748B (zh) | 2021-12-14 |
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CN110638748A (zh) | 2020-01-03 |
WO2020004784A1 (ko) | 2020-01-02 |
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