JP4958818B2 - ピレノキシンを含有する懸濁型水性液剤 - Google Patents
ピレノキシンを含有する懸濁型水性液剤 Download PDFInfo
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- JP4958818B2 JP4958818B2 JP2008063416A JP2008063416A JP4958818B2 JP 4958818 B2 JP4958818 B2 JP 4958818B2 JP 2008063416 A JP2008063416 A JP 2008063416A JP 2008063416 A JP2008063416 A JP 2008063416A JP 4958818 B2 JP4958818 B2 JP 4958818B2
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- pirenoxine
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- aqueous solution
- suspension
- castor oil
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- OKPNYGAWTYOBFZ-UHFFFAOYSA-N Pirenoxine Chemical compound C12=NC3=CC=CC=C3OC2=CC(=O)C2=C1C(=O)C=C(C(=O)O)N2 OKPNYGAWTYOBFZ-UHFFFAOYSA-N 0.000 title claims description 65
- 229960005071 pirenoxine Drugs 0.000 title claims description 65
- 239000007864 aqueous solution Substances 0.000 title claims description 24
- -1 polyoxyethylene Polymers 0.000 claims description 33
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 27
- 239000004359 castor oil Substances 0.000 claims description 27
- 235000019438 castor oil Nutrition 0.000 claims description 27
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 claims description 27
- 238000000034 method Methods 0.000 claims description 19
- 238000002360 preparation method Methods 0.000 claims description 17
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 15
- 229960000281 trometamol Drugs 0.000 claims description 15
- 239000007788 liquid Substances 0.000 claims description 13
- 229920000609 methyl cellulose Polymers 0.000 claims description 6
- 239000001923 methylcellulose Substances 0.000 claims description 6
- 235000010981 methylcellulose Nutrition 0.000 claims description 6
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 5
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 5
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 5
- 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 5
- 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
- 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
- 238000009472 formulation Methods 0.000 description 36
- 239000000203 mixture Substances 0.000 description 36
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 230000000694 effects Effects 0.000 description 14
- 239000003889 eye drop Substances 0.000 description 14
- 238000003860 storage Methods 0.000 description 14
- 230000000052 comparative effect Effects 0.000 description 13
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 239000012085 test solution Substances 0.000 description 8
- 229920000642 polymer Polymers 0.000 description 7
- 230000001954 sterilising effect Effects 0.000 description 7
- 238000004659 sterilization and disinfection Methods 0.000 description 7
- 239000000725 suspension Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 6
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 6
- 229940068968 polysorbate 80 Drugs 0.000 description 6
- 229920000053 polysorbate 80 Polymers 0.000 description 6
- 239000008213 purified water Substances 0.000 description 6
- 239000004094 surface-active agent Substances 0.000 description 6
- 229960000686 benzalkonium chloride Drugs 0.000 description 5
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 5
- 235000011187 glycerol Nutrition 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 229940012356 eye drops Drugs 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 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
- 239000003814 drug Substances 0.000 description 3
- 238000004388 gamma ray sterilization Methods 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000003002 pH adjusting agent Substances 0.000 description 3
- 239000003755 preservative agent Substances 0.000 description 3
- 229940037001 sodium edetate Drugs 0.000 description 3
- QFOHBWFCKVYLES-UHFFFAOYSA-N Butylparaben Chemical compound CCCCOC(=O)C1=CC=C(O)C=C1 QFOHBWFCKVYLES-UHFFFAOYSA-N 0.000 description 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 229920003174 cellulose-based polymer Polymers 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 238000013329 compounding Methods 0.000 description 2
- 238000009826 distribution Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000007951 isotonicity adjuster Substances 0.000 description 2
- 239000000463 material Substances 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
- 239000002997 ophthalmic solution Substances 0.000 description 2
- 229940054534 ophthalmic solution Drugs 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 230000002335 preservative effect Effects 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
- 239000003381 stabilizer Substances 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 239000011800 void material Substances 0.000 description 2
- 229920000178 Acrylic resin Polymers 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 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 description 1
- 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 1
- 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 description 1
- 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 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 229920002675 Polyoxyl Polymers 0.000 description 1
- 229920002685 Polyoxyl 35CastorOil Polymers 0.000 description 1
- 229920002701 Polyoxyl 40 Stearate Polymers 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 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 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 229940067596 butylparaben Drugs 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229960001484 edetic acid Drugs 0.000 description 1
- 238000010894 electron beam technology Methods 0.000 description 1
- 229960001617 ethyl hydroxybenzoate Drugs 0.000 description 1
- 239000004403 ethyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010228 ethyl p-hydroxybenzoate Nutrition 0.000 description 1
- NUVBSKCKDOMJSU-UHFFFAOYSA-N ethylparaben Chemical compound CCOC(=O)C1=CC=C(O)C=C1 NUVBSKCKDOMJSU-UHFFFAOYSA-N 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000139 polyethylene terephthalate Polymers 0.000 description 1
- 239000005020 polyethylene terephthalate Substances 0.000 description 1
- 229940099429 polyoxyl 40 stearate Drugs 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229920000915 polyvinyl chloride Polymers 0.000 description 1
- 239000004800 polyvinyl chloride Substances 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 229960003415 propylparaben Drugs 0.000 description 1
- 201000008525 senile cataract Diseases 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
Classifications
-
- 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
- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5383—1,4-Oxazines, e.g. morpholine ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/10—Inactivation or decontamination of a medicinal preparation prior to administration to an animal or a person
- A61K41/17—Inactivation or decontamination of a medicinal preparation prior to administration to an animal or a person by ultraviolet [UV] or infrared [IR] light, X-rays or gamma rays
-
- 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
-
- 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
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
-
- 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
-
- 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
- A61K9/10—Dispersions; Emulsions
-
- 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
- A61P27/12—Ophthalmic agents for cataracts
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D489/00—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula:
- C07D489/02—Heterocyclic compounds containing 4aH-8, 9 c- Iminoethano-phenanthro [4, 5-b, c, d] furan ring systems, e.g. derivatives of [4, 5-epoxy]-morphinan of the formula: with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone
- C07D489/04—Salts; Organic complexes
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- General Health & Medical Sciences (AREA)
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- Oil, Petroleum & Natural Gas (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Ophthalmology & Optometry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Dispersion Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medical Preparation Storing Or Oral Administration Devices (AREA)
Description
しにくい、すなわち、容器への固着が抑制された、ピレノキシンを含有する懸濁型水性液
剤が要望されている。
懸濁型水性液剤中のピレノキシンの容器への固着を調べた。
1)比較処方1を次のようにして調製した。
上記に従って調製した比較処方1〜2及び処方1,3の被験液剤を5ml点眼容器各10本に充填した。該容器を正立させ、25℃/40%RHの条件で1週間保存した後、容器をゆっくりと横転させて、さらに同条件で1週間保存した。保存終了後、各処方におけるピレノキシンの容器底部への固着に対する抑制効果について検査した。
上記に従って調製した比較処方1〜2及び処方1〜3の被験液剤を5ml点眼容器各10本に充填した。該容器を正立させ、25℃/40%RHの条件で1週間保存した後、容器をゆっくりと横転させて、さらに同条件で2週間保存した。保存終了後、各処方におけるピレノキシンの容器底部への固着に対する抑制効果について検査した。
上記に従って調製した比較処方1及び処方2,3の被験液剤を5ml点眼容器各10本に充填した。該容器を正立させ、25℃/40%RHの条件で1週間保存した後、容器をゆっくりと横転させて、さらに同条件で1ヶ月間保存した。保存終了後、各処方におけるピレノキシンの容器底部への固着に対する抑制効果について検査した。
異なる滅菌処理を施したピレノキシンを用いて容器への固着に対する影響を調べた。
1)処方4を次のようにして調製した。
上記に従って調製した処方4及び5の被験液剤を5ml点眼容器に充填した(処方4:50本、処方5:40本)。該容器を正立させ、25℃/40%RHの条件で1週間保存した後、容器をゆっくりと倒立させて、さらに同条件で1日間保存した。保存終了後、各処方における固着発生率(%)を算出した。
上記に従って調製した処方4及び5の被験液剤を5ml点眼容器に充填した(処方4:30本、処方5:20本)。該容器を正立させ、25℃/40%RHの条件で1週間保存した後、容器をゆっくりと横転させて、さらに同条件で2週間保存した。保存終了後、各処方における容器底部に固着している薬物の分散性について検査した。
上記に従って調製した処方4及び5の被験液剤を5ml点眼容器に充填した(処方4:50本、処方5:40本)。該容器を正立させ、25℃/40%RHの条件で1週間保存した後、容器をゆっくりと横転させて、さらに同条件で1ヶ月間保存した。保存終了後、各処方における容器底部に固着している薬物の分散性について検査した。
ここで、固着発生サンプル数とは、サンプルを箱に入れ、緩やかに手で20回容器を回転させ、さらに手で50回容器を振盪させた後、容器底部にピレノキシンが固着しているサンプルの数を示す。なお、ピレノキシンが固着しているサンプルとは、ピレノキシンが粒子として肉眼的に観察できる状態であるサンプルを示す。
(製剤例)
実施例1に記載した調製法に準じて下記の製剤を得た。尚、下記製剤例において、各成分の配合量は100ml中の含量で記載する。
成分 含量
ピレノキシン 0.005g
ポリオキシエチレン硬化ヒマシ油60 0.01g
濃グリセリン 2.6g
塩化ベンザルコニウム 0.005g
エデト酸ナトリウム 適量
希塩酸 適量
水酸化ナトリウム 適量
滅菌精製水 適量
上記処方において、ポリオキシエチレン硬化ヒマシ油60の配合量を0.005、0.01、0.05又は0.1gに変えて製剤例1と同様な製剤を得ることができる。
成分 含量
ピレノキシン 0.005g
トロメタモール 1.8g
ポリソルベート80 0.005g
塩化ベンザルコニウム 0.005g
エデト酸ナトリウム 適量
希塩酸 適量
水酸化ナトリウム 適量
滅菌精製水 適量
上記処方において、トロメタモールの配合量を0.5、1.0、1.5、2.0又は3.0gに変えて製剤例2と同様な製剤を得ることができる。
Claims (6)
- ピレノキシンを含有する懸濁型水性液剤であって、該ピレノキシンは、ガンマ線により滅菌処理が施されたピレノキシンであり、該水性液剤がポリオキシエチレン硬化ヒマシ油及びトロメタモールからなる群より選択される少なくとも1種を含有し、かつ、該水性液剤が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、ヒドロキシエチルセルロース及びヒドロキシプロピルセルロースを含有しない、水性液剤。
- ピレノキシンの濃度が0.001〜0.01%(W/V)である請求項1記載の水性液剤。
- ポリオキシエチレン硬化ヒマシ油の濃度が0.0005%〜0.5%(W/V)である請求項1記載の水性液剤。
- ポリオキシエチレン硬化ヒマシ油の濃度が0.01%〜0.1%(W/V)である請求項1記載の水性液剤。
- トロメタモールの濃度が0.1%〜3.0%(W/V)である請求項1記載の水性液剤。
- ガンマ線により滅菌処理が施されたピレノキシンを含有する懸濁型水性液剤に、ポリオキシエチレン硬化ヒマシ油及びトロメタモールからなる群より選択される少なくとも1種を配合することにより、該水性液剤に含有されるピレノキシンの容器への固着を抑制する方法。
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JPH0737386B2 (ja) * | 1988-10-12 | 1995-04-26 | 参天製薬株式会社 | 懸濁型ピレノキシン点眼剤 |
JPH0676319B2 (ja) * | 1988-12-20 | 1994-09-28 | 大正製薬株式会社 | トコフェロール類含有液剤 |
JPH04300830A (ja) * | 1991-03-28 | 1992-10-23 | Zeria Pharmaceut Co Ltd | ビタミンe類の水溶液の製剤 |
CN1101677C (zh) * | 1997-05-30 | 2003-02-19 | 韩万愚 | 含有紫杉醇的药用注射溶液 |
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JP2005154437A (ja) * | 2003-11-07 | 2005-06-16 | Rohto Pharmaceut Co Ltd | トラニラスト含有医薬組成物 |
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KR101519673B1 (ko) | 2015-05-12 |
TW200906415A (en) | 2009-02-16 |
CN101636163A (zh) | 2010-01-27 |
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