JP2017031144A - 経口用医薬組成物 - Google Patents
経口用医薬組成物 Download PDFInfo
- Publication number
- JP2017031144A JP2017031144A JP2016146924A JP2016146924A JP2017031144A JP 2017031144 A JP2017031144 A JP 2017031144A JP 2016146924 A JP2016146924 A JP 2016146924A JP 2016146924 A JP2016146924 A JP 2016146924A JP 2017031144 A JP2017031144 A JP 2017031144A
- Authority
- JP
- Japan
- Prior art keywords
- pain
- factors
- psychogenic
- pharmaceutical composition
- caffeine
- 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
Links
- 239000008203 oral pharmaceutical composition Substances 0.000 title description 2
- 239000000203 mixture Substances 0.000 claims abstract description 37
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 claims abstract description 35
- 208000002193 Pain Diseases 0.000 claims abstract description 28
- 230000036407 pain Effects 0.000 claims abstract description 28
- 229960002373 loxoprofen Drugs 0.000 claims abstract description 22
- 229960001948 caffeine Drugs 0.000 claims abstract description 18
- 206010019233 Headaches Diseases 0.000 claims abstract description 17
- KSUUMAWCGDNLFK-UHFFFAOYSA-N apronal Chemical compound C=CCC(C(C)C)C(=O)NC(N)=O KSUUMAWCGDNLFK-UHFFFAOYSA-N 0.000 claims abstract description 17
- 229960004459 apronal Drugs 0.000 claims abstract description 17
- 231100000869 headache Toxicity 0.000 claims abstract description 17
- 208000005171 Dysmenorrhea Diseases 0.000 claims abstract description 16
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 claims abstract description 14
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 claims abstract description 14
- 230000001107 psychogenic effect Effects 0.000 claims description 21
- BAZQYVYVKYOAGO-UHFFFAOYSA-M loxoprofen sodium hydrate Chemical compound O.O.[Na+].C1=CC(C(C([O-])=O)C)=CC=C1CC1C(=O)CCC1 BAZQYVYVKYOAGO-UHFFFAOYSA-M 0.000 claims description 20
- 230000000202 analgesic effect Effects 0.000 claims description 15
- WMGSQTMJHBYJMQ-UHFFFAOYSA-N aluminum;magnesium;silicate Chemical compound [Mg+2].[Al+3].[O-][Si]([O-])([O-])[O-] WMGSQTMJHBYJMQ-UHFFFAOYSA-N 0.000 claims description 10
- CMCCHHWTTBEZNM-UHFFFAOYSA-N 2-bromo-N-carbamoyl-3-methylbutanamide Chemical compound CC(C)C(Br)C(=O)NC(N)=O CMCCHHWTTBEZNM-UHFFFAOYSA-N 0.000 claims description 4
- 239000003907 antipyretic analgesic agent Substances 0.000 claims description 3
- 239000002552 dosage form Substances 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 12
- 230000007794 irritation Effects 0.000 abstract description 4
- 230000002265 prevention Effects 0.000 abstract description 4
- 230000003449 preventive effect Effects 0.000 abstract description 3
- 230000001225 therapeutic effect Effects 0.000 abstract description 2
- JAUGGEIKQIHSMF-UHFFFAOYSA-N dialuminum;dimagnesium;dioxido(oxo)silane;oxygen(2-);hydrate Chemical compound O.[O-2].[O-2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O.[O-][Si]([O-])=O JAUGGEIKQIHSMF-UHFFFAOYSA-N 0.000 abstract 1
- YMBXTVYHTMGZDW-UHFFFAOYSA-N loxoprofen Chemical compound C1=CC(C(C(O)=O)C)=CC=C1CC1C(=O)CCC1 YMBXTVYHTMGZDW-UHFFFAOYSA-N 0.000 abstract 1
- 208000019901 Anxiety disease Diseases 0.000 description 20
- 230000036506 anxiety Effects 0.000 description 20
- 238000009472 formulation Methods 0.000 description 18
- 206010022998 Irritability Diseases 0.000 description 15
- -1 magnesium metasilicate aluminate Chemical class 0.000 description 11
- 208000024891 symptom Diseases 0.000 description 11
- 239000008187 granular material Substances 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 239000000654 additive Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 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 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- 230000001754 anti-pyretic effect Effects 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
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 239000000395 magnesium oxide Substances 0.000 description 3
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 3
- 235000012245 magnesium oxide Nutrition 0.000 description 3
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 3
- 239000003921 oil Substances 0.000 description 3
- 235000019198 oils Nutrition 0.000 description 3
- 208000020016 psychiatric disease Diseases 0.000 description 3
- 235000012239 silicon dioxide Nutrition 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 239000004386 Erythritol Substances 0.000 description 2
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 235000006679 Mentha X verticillata Nutrition 0.000 description 2
- 235000002899 Mentha suaveolens Nutrition 0.000 description 2
- 235000001636 Mentha x rotundifolia Nutrition 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- 206010028813 Nausea Diseases 0.000 description 2
- 206010034972 Photosensitivity reaction Diseases 0.000 description 2
- 206010047700 Vomiting Diseases 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- VJHCJDRQFCCTHL-UHFFFAOYSA-N acetic acid 2,3,4,5,6-pentahydroxyhexanal Chemical compound CC(O)=O.OCC(O)C(O)C(O)C(O)C=O VJHCJDRQFCCTHL-UHFFFAOYSA-N 0.000 description 2
- 150000008064 anhydrides Chemical class 0.000 description 2
- 208000003464 asthenopia Diseases 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 239000011575 calcium Substances 0.000 description 2
- 229960005069 calcium Drugs 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 229950008138 carmellose Drugs 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 239000007884 disintegrant Substances 0.000 description 2
- 230000000773 effect on pain Effects 0.000 description 2
- 235000019414 erythritol Nutrition 0.000 description 2
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 description 2
- 229940009714 erythritol Drugs 0.000 description 2
- 239000000796 flavoring agent Substances 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 235000010355 mannitol Nutrition 0.000 description 2
- 230000003340 mental effect Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000008693 nausea Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000036211 photosensitivity Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000035807 sensation Effects 0.000 description 2
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- 230000008673 vomiting Effects 0.000 description 2
- HDTRYLNUVZCQOY-UHFFFAOYSA-N α-D-glucopyranosyl-α-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OC1C(O)C(O)C(O)C(CO)O1 HDTRYLNUVZCQOY-UHFFFAOYSA-N 0.000 description 1
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 1
- DTGKSKDOIYIVQL-WEDXCCLWSA-N (+)-borneol Chemical compound C1C[C@@]2(C)[C@@H](O)C[C@@H]1C2(C)C DTGKSKDOIYIVQL-WEDXCCLWSA-N 0.000 description 1
- REPVLJRCJUVQFA-UHFFFAOYSA-N (-)-isopinocampheol Natural products C1C(O)C(C)C2C(C)(C)C1C2 REPVLJRCJUVQFA-UHFFFAOYSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
- 206010000087 Abdominal pain upper Diseases 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 229920002785 Croscarmellose sodium Polymers 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-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
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 206010014020 Ear pain Diseases 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 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 description 1
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerol Natural products OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- ZCVMWBYGMWKGHF-UHFFFAOYSA-N Ketotifene Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2CC(=O)C2=C1C=CS2 ZCVMWBYGMWKGHF-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 206010068319 Oropharyngeal pain Diseases 0.000 description 1
- 206010033557 Palpitations Diseases 0.000 description 1
- 201000007100 Pharyngitis Diseases 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 208000036992 Psychogenic pain disease Diseases 0.000 description 1
- 239000004373 Pullulan Substances 0.000 description 1
- 229920001218 Pullulan Polymers 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 206010041349 Somnolence Diseases 0.000 description 1
- 208000013200 Stress disease Diseases 0.000 description 1
- 239000004376 Sucralose 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
- 208000008548 Tension-Type Headache Diseases 0.000 description 1
- HDTRYLNUVZCQOY-WSWWMNSNSA-N Trehalose Natural products O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-WSWWMNSNSA-N 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- YKTSYUJCYHOUJP-UHFFFAOYSA-N [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] Chemical compound [O--].[Al+3].[Al+3].[O-][Si]([O-])([O-])[O-] YKTSYUJCYHOUJP-UHFFFAOYSA-N 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010358 acesulfame potassium Nutrition 0.000 description 1
- 229960004998 acesulfame potassium Drugs 0.000 description 1
- 239000000619 acesulfame-K Substances 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- HDTRYLNUVZCQOY-LIZSDCNHSA-N alpha,alpha-trehalose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 HDTRYLNUVZCQOY-LIZSDCNHSA-N 0.000 description 1
- 229940069428 antacid Drugs 0.000 description 1
- 239000003159 antacid agent Substances 0.000 description 1
- 230000001458 anti-acid effect Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 239000000440 bentonite Substances 0.000 description 1
- 229910000278 bentonite Inorganic materials 0.000 description 1
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 229940116229 borneol Drugs 0.000 description 1
- CKDOCTFBFTVPSN-UHFFFAOYSA-N borneol Natural products C1CC2(C)C(C)CC1C2(C)C CKDOCTFBFTVPSN-UHFFFAOYSA-N 0.000 description 1
- 229960003880 bromisoval Drugs 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- MKJXYGKVIBWPFZ-UHFFFAOYSA-L calcium lactate Chemical compound [Ca+2].CC(O)C([O-])=O.CC(O)C([O-])=O MKJXYGKVIBWPFZ-UHFFFAOYSA-L 0.000 description 1
- 239000001527 calcium lactate Substances 0.000 description 1
- 235000011086 calcium lactate Nutrition 0.000 description 1
- 229960002401 calcium lactate Drugs 0.000 description 1
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 1
- 235000013539 calcium stearate Nutrition 0.000 description 1
- 239000008116 calcium stearate Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000010630 cinnamon oil Substances 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000010634 clove oil Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 229960001681 croscarmellose sodium Drugs 0.000 description 1
- 229960000913 crospovidone Drugs 0.000 description 1
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000003001 depressive effect Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- GDVKFRBCXAPAQJ-UHFFFAOYSA-A dialuminum;hexamagnesium;carbonate;hexadecahydroxide Chemical compound [OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[OH-].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Mg+2].[Al+3].[Al+3].[O-]C([O-])=O GDVKFRBCXAPAQJ-UHFFFAOYSA-A 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- DTGKSKDOIYIVQL-UHFFFAOYSA-N dl-isoborneol Natural products C1CC2(C)C(O)CC1C2(C)C DTGKSKDOIYIVQL-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 210000004211 gastric acid Anatomy 0.000 description 1
- 239000004083 gastrointestinal agent Substances 0.000 description 1
- 229940127227 gastrointestinal drug Drugs 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 235000013905 glycine and its sodium salt Nutrition 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- 229960001545 hydrotalcite Drugs 0.000 description 1
- 229910001701 hydrotalcite Inorganic materials 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 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 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008274 jelly Substances 0.000 description 1
- 229960004958 ketotifen Drugs 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 description 1
- 229960003511 macrogol Drugs 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 229940041616 menthol Drugs 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 230000003040 nociceptive effect Effects 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 230000001473 noxious effect Effects 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229940068984 polyvinyl alcohol Drugs 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 229920003124 powdered cellulose Polymers 0.000 description 1
- 235000019814 powdered cellulose Nutrition 0.000 description 1
- 229940088417 precipitated calcium carbonate Drugs 0.000 description 1
- 210000002243 primary neuron Anatomy 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 235000019423 pullulan Nutrition 0.000 description 1
- 239000010666 rose oil Substances 0.000 description 1
- 235000019719 rose oil Nutrition 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 235000019408 sucralose Nutrition 0.000 description 1
- BAQAVOSOZGMPRM-QBMZZYIRSA-N sucralose Chemical compound O[C@@H]1[C@@H](O)[C@@H](Cl)[C@@H](CO)O[C@@H]1O[C@@]1(CCl)[C@@H](O)[C@H](O)[C@@H](CCl)O1 BAQAVOSOZGMPRM-QBMZZYIRSA-N 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 208000004371 toothache Diseases 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
1)ロキソプロフェンナトリウムとケトチフェンを併用すると、ロキソプロフェンナトリウムの解熱作用が増強する(特許文献1参照)。
2)ロキソプロフェンナトリウムにアリルイソプロピルアセチル尿素を併用すると、ロキソプロフェンナトリウムの鎮痛作用がさらに増強する(特許文献2参照)。さらに、同文献には、ロキソプロフェンナトリウム、アリルイソプロピルアセチル尿素、カフェインを含有する組成物が開示されている。
3)ロキソプロフェンナトリウムに、アリルイソプロピルアセチル尿素とカフェインを配合すると、保存安定性が向上される(特許文献3参照)。
痛みに対する優れた効果を発現する旨の記載はない。さらに、ロキソプロフェンナトリウム、アリルイソプロピルアセチル尿素、メタケイ酸アルミン酸マグネシウム及びカフェインの配合は知られておらず、これら組成物に、心因的要因(イライラ感、不安感、ゆううつ感など)を伴う優れた鎮痛作用が発現することは示唆もされていない。
(1)以下の(a)、(b)、(c)および(d)を含有する解熱鎮痛剤組成物;
(a)ロキソプロフェン又はその塩
(b)アリルイソプロピルアセチル尿素、およびブロムワレリル尿素から選択される1種以上
(c)メタケイ酸アルミン酸マグネシウム
(d)カフェイン又は無水カフェイン
(2)心因的要因を伴う痛みを改善することを特徴とする、上記(1)に記載の鎮痛用組成物;
(3)心因的要因を伴う痛みが生理痛である、上記(1)又は(2)に記載の鎮痛用組成物;
(4)心因的要因を伴う痛みが頭痛である、上記(1)又は(2)に記載の鎮痛用組成物;
(5)剤形が経口用である、上記(1)〜(4)のいずれか1項に記載の鎮痛用組成物;
を提供するものである。
以下の組成で、常法により錠剤を製造した。
以下の組成で、常法により顆粒剤を製造した。
1.試験方法
頭痛と診断された62人を対象として、心因的要因(イライラ感、不安感、ゆううつ感など)などを伴った頭痛に対して効果があるかについて確認した。ロキソプロフェンナトリウム、アリルイソプロピルアセチル尿素、メタケイ酸アルミン酸マグネシウム及びカフェインを主成分とした上記製剤例1又は製剤例2のいずれかの製剤を水又はぬるま湯にて服用した。服用の際は、なるべく空腹時を避けて服用し、さらに服用する場合は4時間以上の間隔をおいて服用した。通常1日2回までとするが、再度症状があらわれた場合には3回目を服用し、その場合も服用間隔は4時間以上おき、心因的要因(イライラ感、不安感、ゆううつ感など)などを伴う頭痛の、とくに初回服用120分後の改善率を求めた。
結果を表3に示す。心因反応が関与する頭痛に対する軽度改善率は、悪心93.8%、不安感83.3%、イライラ感81.0%、嘔吐77.8%、倦怠感75.6%、眼の疲労感77.1%であり、軽度改善率が70%以上と高く改善されることが確認された。また、光過敏、音過敏、臭い過敏を伴う頭痛に対しても高く改善されることが確認された。
1.試験方法
生理痛と診断された57人を対象として、心因的要因(イライラ感、不安感、ゆううつ感など)などを伴った生理痛に対して効果があるかについて確認した。ロキソプロフェンナトリウム、アリルイソプロピルアセチル尿素、メタケイ酸アルミン酸マグネシウム及びカフェインを主成分とした上記製剤例1又は製剤例2のいずれかの製剤を水又はぬるま湯にて服用した。服用の際は、なるべく空腹時を避けて服用し、さらに服用する場合は4時間以上の間隔をおいて服用した。通常1日2回までとするが、再度症状があらわれた場合には3回目を服用し、その場合も服用間隔は4時間以上おき、心因的要因(イライラ感、不安感、ゆううつ感など)を伴う生理痛の、とくに初回服用120分後の改善率を求めた。
結果を表4に示す。心因反応が関与する頭痛に対する軽度改善率は、悪心93.8%、不安感83.3%、イライラ感81.0%、嘔吐77.8%、倦怠感75.6%、眼の疲労感77.1%であり、軽度改善率が70%以上と高く改善されることが確認された。また、光過敏、音過敏、臭い過敏を伴う頭痛に対しても高く改善されることが確認された。
Claims (5)
- 以下の(a)〜(d)を含有する解熱鎮痛剤組成物。
(a)ロキソプロフェン又はその塩
(b)アリルイソプロピルアセチル尿素、およびブロムワレリル尿素から選択される1種以上
(c)メタケイ酸アルミン酸マグネシウム
(d)カフェイン又は無水カフェイン - 心因的要因を伴う痛みを改善することを特徴とする、請求項1に記載の鎮痛用組成物。
- 心因的要因を伴う痛みが生理痛である、請求項1又は請求項2に記載の鎮痛用組成物。
- 心因的要因を伴う痛みが頭痛である、請求項1又は請求項2に記載の鎮痛用組成物。
- 剤形が経口用である、請求項1〜4のいずれか1項に記載の鎮痛用組成物。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2015148778 | 2015-07-28 | ||
JP2015148778A JP2016056166A (ja) | 2015-07-28 | 2015-07-28 | 経口用医薬組成物 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021017086A Division JP7123205B2 (ja) | 2015-07-28 | 2021-02-05 | 経口用医薬組成物 |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2017031144A true JP2017031144A (ja) | 2017-02-09 |
JP2017031144A5 JP2017031144A5 (ja) | 2019-08-15 |
JP6914626B2 JP6914626B2 (ja) | 2021-08-04 |
Family
ID=55757540
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015148778A Pending JP2016056166A (ja) | 2015-07-28 | 2015-07-28 | 経口用医薬組成物 |
JP2016146924A Active JP6914626B2 (ja) | 2015-07-28 | 2016-07-27 | 経口用医薬組成物 |
JP2021017086A Active JP7123205B2 (ja) | 2015-07-28 | 2021-02-05 | 経口用医薬組成物 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2015148778A Pending JP2016056166A (ja) | 2015-07-28 | 2015-07-28 | 経口用医薬組成物 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2021017086A Active JP7123205B2 (ja) | 2015-07-28 | 2021-02-05 | 経口用医薬組成物 |
Country Status (1)
Country | Link |
---|---|
JP (3) | JP2016056166A (ja) |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2018090549A (ja) * | 2016-12-07 | 2018-06-14 | 第一三共ヘルスケア株式会社 | ロキソプロフェンとジヒドロコデインリン酸塩を含有する固形製剤 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011168580A (ja) * | 2010-01-19 | 2011-09-01 | Daiichi Sankyo Healthcare Co Ltd | 医薬組成物 |
-
2015
- 2015-07-28 JP JP2015148778A patent/JP2016056166A/ja active Pending
-
2016
- 2016-07-27 JP JP2016146924A patent/JP6914626B2/ja active Active
-
2021
- 2021-02-05 JP JP2021017086A patent/JP7123205B2/ja active Active
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2011168580A (ja) * | 2010-01-19 | 2011-09-01 | Daiichi Sankyo Healthcare Co Ltd | 医薬組成物 |
Non-Patent Citations (4)
Title |
---|
クミアイ解熱鎮痛錠 添付文書, JPN6020017411, May 2013 (2013-05-01), ISSN: 0004385546 * |
新薬と臨床, vol. 32, no. 1, JPN6020043343, 1983, pages 83 - 97, ISSN: 0004385548 * |
薬理と治療, vol. 10, no. 3, JPN6020043344, 1982, pages 513 - 520, ISSN: 0004385549 * |
薬理と治療, vol. 26, no. 4, JPN6020043342, 1998, pages 179 - 186, ISSN: 0004385547 * |
Also Published As
Publication number | Publication date |
---|---|
JP2016056166A (ja) | 2016-04-21 |
JP7123205B2 (ja) | 2022-08-22 |
JP2021066751A (ja) | 2021-04-30 |
JP6914626B2 (ja) | 2021-08-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP5442178B2 (ja) | ロキソプロフェン含有経口用組成物 | |
JP7090616B2 (ja) | カルバメート化合物を含む口腔内崩壊錠 | |
JP6192751B2 (ja) | ロキソプロフェン含有経口用組成物5 | |
JP7123205B2 (ja) | 経口用医薬組成物 | |
RU2464023C2 (ru) | Лекарственное средство для лечения фибромиалгии | |
JP2007023026A (ja) | イブプロフェン含有経口用医薬組成物 | |
JP4913359B2 (ja) | イブプロフェン含有医薬組成物 | |
JP2008143856A (ja) | 非ステロイド系抗炎症剤配合医薬 | |
AU2012276476B2 (en) | Pharmaceutical composition for treating premature ejaculation and method for treating premature ejaculation | |
JP6940265B2 (ja) | 止瀉剤組成物 | |
JP7366108B2 (ja) | ロキソプロフェン又はその塩及びビタミンb12類を含有する経口用医薬組成物 | |
Billa et al. | Comparative Efficacy and Safety Evaluation of Tramadol plus Diclofenac versus Tramadol plus Paracetamol in a Subgroup of Indian Patients with Moderate to Severe Acute Musculoskeletal Pain: A Phase III, 5 Day Open Label Study. J Exerc Sports Orthop 4 (1): 1-6 | |
JP7346205B2 (ja) | ロキソプロフェン又はその塩とボウイとを含有する経口医薬組成物 | |
JP4993998B2 (ja) | イブプロフェンを含有する医薬組成物 | |
JP2018076312A (ja) | アセトアミノフェン、イソプロピルアンチピリン及びショウガ由来成分を含有する医薬組成物 | |
Al-Najjar et al. | Comparative study among gabapentin, midazolam and granisetron for prevention of postoperative nausea and vomiting after middle ear surgery | |
JP2006342188A (ja) | 口中溶解型又は咀嚼型鼻炎治療用固形内服医薬組成物 | |
Rodríguez-Sánchez et al. | Fixed dose combination of magaldrate plus domperidone is more effective than domperidone alone in the treatment of patients with gastroesophageal reflux symptoms: a randomized double-blind study | |
JP6804190B2 (ja) | 医薬組成物 | |
JP2019043935A (ja) | 鎮痛剤 | |
JP2020196710A (ja) | 月経困難症の予防及び/又は治療のための組合せ医薬 | |
JP2013032408A (ja) | 口中溶解型又は咀嚼型鼻炎治療用固形内服医薬組成物 | |
JP2020172475A (ja) | メロキシカム又はその薬学的に許容される塩を含有する内服治療剤 | |
JP2012046540A (ja) | イブプロフェン含有医薬組成物 | |
JP2014162750A (ja) | 唾液分泌促進用組成物 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20190704 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20190704 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20200603 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20200708 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20200929 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20201111 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210205 |
|
C60 | Trial request (containing other claim documents, opposition documents) |
Free format text: JAPANESE INTERMEDIATE CODE: C60 Effective date: 20210205 |
|
C11 | Written invitation by the commissioner to file amendments |
Free format text: JAPANESE INTERMEDIATE CODE: C11 Effective date: 20210218 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20210317 |
|
C21 | Notice of transfer of a case for reconsideration by examiners before appeal proceedings |
Free format text: JAPANESE INTERMEDIATE CODE: C21 Effective date: 20210326 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20210422 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20210602 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20210623 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20210714 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6914626 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |