JP2018076306A - 感冒薬 - Google Patents
感冒薬 Download PDFInfo
- Publication number
- JP2018076306A JP2018076306A JP2017209097A JP2017209097A JP2018076306A JP 2018076306 A JP2018076306 A JP 2018076306A JP 2017209097 A JP2017209097 A JP 2017209097A JP 2017209097 A JP2017209097 A JP 2017209097A JP 2018076306 A JP2018076306 A JP 2018076306A
- Authority
- JP
- Japan
- Prior art keywords
- hydrochloride
- cold medicine
- magnesium
- medicine according
- sodium
- 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
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims abstract description 39
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 claims abstract description 38
- 229960002009 naproxen Drugs 0.000 claims abstract description 38
- 150000003839 salts Chemical class 0.000 claims abstract description 29
- 230000003419 expectorant effect Effects 0.000 claims abstract description 20
- 239000003172 expectorant agent Substances 0.000 claims abstract description 19
- 206010039083 rhinitis Diseases 0.000 claims abstract description 17
- 230000000954 anitussive effect Effects 0.000 claims abstract description 16
- 229940124584 antitussives Drugs 0.000 claims abstract description 16
- 229940124579 cold medicine Drugs 0.000 claims description 52
- 238000002360 preparation method Methods 0.000 claims description 34
- -1 Nantenjitsu Chemical compound 0.000 claims description 32
- 239000004615 ingredient Substances 0.000 claims description 24
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims description 20
- 239000004480 active ingredient Substances 0.000 claims description 19
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 17
- 229920002678 cellulose Polymers 0.000 claims description 13
- 239000001913 cellulose Substances 0.000 claims description 13
- 229920000642 polymer Polymers 0.000 claims description 13
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 claims description 10
- 238000000975 co-precipitation Methods 0.000 claims description 10
- AKNNEGZIBPJZJG-MSOLQXFVSA-N (-)-noscapine Chemical compound CN1CCC2=CC=3OCOC=3C(OC)=C2[C@@H]1[C@@H]1C2=CC=C(OC)C(OC)=C2C(=O)O1 AKNNEGZIBPJZJG-MSOLQXFVSA-N 0.000 claims description 8
- 229940024546 aluminum hydroxide gel Drugs 0.000 claims description 8
- SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 claims description 8
- 229940005636 dl- methylephedrine Drugs 0.000 claims description 8
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims description 8
- 229960004708 noscapine Drugs 0.000 claims description 8
- WQOYJMWVNIGIQR-UHFFFAOYSA-N 3-(dithiophen-2-ylmethylidene)-1-methylpiperidine;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.C1N(C)CCCC1=C(C=1SC=CC=1)C1=CC=CS1 WQOYJMWVNIGIQR-UHFFFAOYSA-N 0.000 claims description 7
- QNVKOSLOVOTXKF-UHFFFAOYSA-N 4-[(2-amino-3,5-dibromophenyl)methylamino]cyclohexan-1-ol;hydron;chloride Chemical compound Cl.NC1=C(Br)C=C(Br)C=C1CNC1CCC(O)CC1 QNVKOSLOVOTXKF-UHFFFAOYSA-N 0.000 claims description 7
- 229910019142 PO4 Inorganic materials 0.000 claims description 7
- NTCYWJCEOILKNG-ROLPUNSJSA-N [(1r,2s)-1-hydroxy-1-phenylpropan-2-yl]-dimethylazanium;chloride Chemical compound Cl.CN(C)[C@@H](C)[C@H](O)C1=CC=CC=C1 NTCYWJCEOILKNG-ROLPUNSJSA-N 0.000 claims description 7
- 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 claims description 7
- 229940008027 aluminum hydroxide / magnesium carbonate Drugs 0.000 claims description 7
- 229960000985 ambroxol hydrochloride Drugs 0.000 claims description 7
- 229940073563 dl- methylephedrine hydrochloride Drugs 0.000 claims description 7
- 239000011777 magnesium Substances 0.000 claims description 7
- 229910052749 magnesium Inorganic materials 0.000 claims description 7
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims description 7
- 239000001095 magnesium carbonate Substances 0.000 claims description 7
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims description 7
- 239000000347 magnesium hydroxide Substances 0.000 claims description 7
- 229910001862 magnesium hydroxide Inorganic materials 0.000 claims description 7
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 7
- 239000010452 phosphate Substances 0.000 claims description 7
- 229960000896 tipepidine Drugs 0.000 claims description 7
- PUHLHLQBIFRKRD-CSKARUKUSA-N 5-methyl-2-[(E)-2-phenylethenyl]-1,3-benzoxazole Chemical compound N=1C2=CC(C)=CC=C2OC=1\C=C\C1=CC=CC=C1 PUHLHLQBIFRKRD-CSKARUKUSA-N 0.000 claims description 6
- MKXZASYAUGDDCJ-SZMVWBNQSA-N LSM-2525 Chemical compound C1CCC[C@H]2[C@@]3([H])N(C)CC[C@]21C1=CC(OC)=CC=C1C3 MKXZASYAUGDDCJ-SZMVWBNQSA-N 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 6
- 229960001985 dextromethorphan Drugs 0.000 claims description 6
- 241000411851 herbal medicine Species 0.000 claims description 6
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 6
- 239000007787 solid Substances 0.000 claims description 6
- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 claims description 5
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 5
- 235000001453 Glycyrrhiza echinata Nutrition 0.000 claims description 5
- 235000006200 Glycyrrhiza glabra Nutrition 0.000 claims description 5
- 235000017382 Glycyrrhiza lepidota Nutrition 0.000 claims description 5
- BWZOPYPOZJBVLQ-UHFFFAOYSA-K aluminium glycinate Chemical compound O[Al+]O.NCC([O-])=O BWZOPYPOZJBVLQ-UHFFFAOYSA-K 0.000 claims description 5
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 claims description 5
- 229940024545 aluminum hydroxide Drugs 0.000 claims description 5
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 5
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 5
- 229960000520 diphenhydramine Drugs 0.000 claims description 5
- 229940010454 licorice Drugs 0.000 claims description 5
- 239000000395 magnesium oxide Substances 0.000 claims description 5
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 5
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims description 5
- 239000011734 sodium Substances 0.000 claims description 5
- 229910052708 sodium Inorganic materials 0.000 claims description 5
- DKSZLDSPXIWGFO-BLOJGBSASA-N (4r,4ar,7s,7ar,12bs)-9-methoxy-3-methyl-2,4,4a,7,7a,13-hexahydro-1h-4,12-methanobenzofuro[3,2-e]isoquinoline-7-ol;phosphoric acid;hydrate Chemical compound O.OP(O)(O)=O.OP(O)(O)=O.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC.C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC DKSZLDSPXIWGFO-BLOJGBSASA-N 0.000 claims description 4
- PMGQWSIVQFOFOQ-BDUVBVHRSA-N (e)-but-2-enedioic acid;(2r)-2-[2-[1-(4-chlorophenyl)-1-phenylethoxy]ethyl]-1-methylpyrrolidine Chemical compound OC(=O)\C=C\C(O)=O.CN1CCC[C@@H]1CCOC(C)(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 PMGQWSIVQFOFOQ-BDUVBVHRSA-N 0.000 claims description 4
- FWLKKPKZQYVAFR-LVEZLNDCSA-N (e)-but-2-enedioic acid;1-(2-ethoxyethyl)-2-(4-methyl-1,4-diazepan-1-yl)benzimidazole Chemical compound OC(=O)\C=C\C(O)=O.OC(=O)\C=C\C(O)=O.N=1C2=CC=CC=C2N(CCOCC)C=1N1CCCN(C)CC1 FWLKKPKZQYVAFR-LVEZLNDCSA-N 0.000 claims description 4
- FLNXBVJLPJNOSI-UHFFFAOYSA-N 1-[2-[(4-chlorophenyl)-phenylmethoxy]ethyl]piperidine Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC=CC=1)OCCN1CCCCC1 FLNXBVJLPJNOSI-UHFFFAOYSA-N 0.000 claims description 4
- RRJFVPUCXDGFJB-UHFFFAOYSA-N Fexofenadine hydrochloride Chemical compound Cl.C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RRJFVPUCXDGFJB-UHFFFAOYSA-N 0.000 claims description 4
- HSRJKNPTNIJEKV-UHFFFAOYSA-N Guaifenesin Chemical compound COC1=CC=CC=C1OCC(O)CO HSRJKNPTNIJEKV-UHFFFAOYSA-N 0.000 claims description 4
- 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 4
- BFSMWENDZZIWPW-UHFFFAOYSA-N Isopropamide iodide Chemical compound [I-].C=1C=CC=CC=1C(C(N)=O)(CC[N+](C)(C(C)C)C(C)C)C1=CC=CC=C1 BFSMWENDZZIWPW-UHFFFAOYSA-N 0.000 claims description 4
- HOKDBMAJZXIPGC-UHFFFAOYSA-N Mequitazine Chemical group C12=CC=CC=C2SC2=CC=CC=C2N1CC1C(CC2)CCN2C1 HOKDBMAJZXIPGC-UHFFFAOYSA-N 0.000 claims description 4
- HVRLZEKDTUEKQH-NOILCQHBSA-N Olopatadine hydrochloride Chemical compound Cl.C1OC2=CC=C(CC(O)=O)C=C2C(=C/CCN(C)C)\C2=CC=CC=C21 HVRLZEKDTUEKQH-NOILCQHBSA-N 0.000 claims description 4
- GBFLZEXEOZUWRN-VKHMYHEASA-N S-carboxymethyl-L-cysteine Chemical compound OC(=O)[C@@H](N)CSCC(O)=O GBFLZEXEOZUWRN-VKHMYHEASA-N 0.000 claims description 4
- AKNNEGZIBPJZJG-UHFFFAOYSA-N alpha-noscapine Natural products CN1CCC2=CC=3OCOC=3C(OC)=C2C1C1C2=CC=C(OC)C(OC)=C2C(=O)O1 AKNNEGZIBPJZJG-UHFFFAOYSA-N 0.000 claims description 4
- 229940043673 aluminum hydroxide / calcium carbonate Drugs 0.000 claims description 4
- 229940108858 belladonna total alkaloid Drugs 0.000 claims description 4
- 229960002335 bromhexine hydrochloride Drugs 0.000 claims description 4
- 229960000428 carbinoxamine Drugs 0.000 claims description 4
- OJFSXZCBGQGRNV-UHFFFAOYSA-N carbinoxamine Chemical compound C=1C=CC=NC=1C(OCCN(C)C)C1=CC=C(Cl)C=C1 OJFSXZCBGQGRNV-UHFFFAOYSA-N 0.000 claims description 4
- 229960000456 carbinoxamine maleate Drugs 0.000 claims description 4
- GVNWHCVWDRNXAZ-BTJKTKAUSA-N carbinoxamine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(OCCN(C)C)C1=CC=C(Cl)C=C1 GVNWHCVWDRNXAZ-BTJKTKAUSA-N 0.000 claims description 4
- 229940046978 chlorpheniramine maleate Drugs 0.000 claims description 4
- 229960002689 clemastine fumarate Drugs 0.000 claims description 4
- 229960002544 cloperastine Drugs 0.000 claims description 4
- 229960004126 codeine Drugs 0.000 claims description 4
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 claims description 4
- 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 claims description 4
- 229960000920 dihydrocodeine Drugs 0.000 claims description 4
- RBOXVHNMENFORY-DNJOTXNNSA-N dihydrocodeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC RBOXVHNMENFORY-DNJOTXNNSA-N 0.000 claims description 4
- 229960001056 dimemorfan Drugs 0.000 claims description 4
- KBEZZLAAKIIPFK-NJAFHUGGSA-N dimemorfan Chemical compound C1C2=CC=C(C)C=C2[C@@]23CCN(C)[C@@H]1[C@H]2CCCC3 KBEZZLAAKIIPFK-NJAFHUGGSA-N 0.000 claims description 4
- 229960000325 emedastine Drugs 0.000 claims description 4
- WHWZLSFABNNENI-UHFFFAOYSA-N epinastine Chemical compound C1C2=CC=CC=C2C2CN=C(N)N2C2=CC=CC=C21 WHWZLSFABNNENI-UHFFFAOYSA-N 0.000 claims description 4
- 229960002548 epinastine hydrochloride Drugs 0.000 claims description 4
- YRSGDLIATOURQO-UHFFFAOYSA-N ethyl 4-acetyl-5-oxohexanoate Chemical compound CCOC(=O)CCC(C(C)=O)C(C)=O YRSGDLIATOURQO-UHFFFAOYSA-N 0.000 claims description 4
- 229960000354 fexofenadine hydrochloride Drugs 0.000 claims description 4
- 229960002146 guaifenesin Drugs 0.000 claims description 4
- 229960001545 hydrotalcite Drugs 0.000 claims description 4
- 229910001701 hydrotalcite Inorganic materials 0.000 claims description 4
- 229960001543 isopropamide iodide Drugs 0.000 claims description 4
- YNQQEYBLVYAWNX-WLHGVMLRSA-N ketotifen fumarate Chemical compound OC(=O)\C=C\C(O)=O.C1CN(C)CCC1=C1C2=CC=CC=C2CC(=O)C2=C1C=CS2 YNQQEYBLVYAWNX-WLHGVMLRSA-N 0.000 claims description 4
- 229960003630 ketotifen fumarate Drugs 0.000 claims description 4
- 229960003088 loratadine Drugs 0.000 claims description 4
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 claims description 4
- ZADYMNAVLSWLEQ-UHFFFAOYSA-N magnesium;oxygen(2-);silicon(4+) Chemical compound [O-2].[O-2].[O-2].[Mg+2].[Si+4] ZADYMNAVLSWLEQ-UHFFFAOYSA-N 0.000 claims description 4
- 229960005042 mequitazine Drugs 0.000 claims description 4
- PLPRGLOFPNJOTN-UHFFFAOYSA-N narcotine Natural products COc1ccc2C(OC(=O)c2c1OC)C3Cc4c(CN3C)cc5OCOc5c4OC PLPRGLOFPNJOTN-UHFFFAOYSA-N 0.000 claims description 4
- 229960003139 olopatadine hydrochloride Drugs 0.000 claims description 4
- BAINIUMDFURPJM-UHFFFAOYSA-N oxatomide Chemical compound O=C1NC2=CC=CC=C2N1CCCN(CC1)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 BAINIUMDFURPJM-UHFFFAOYSA-N 0.000 claims description 4
- 229960002698 oxatomide Drugs 0.000 claims description 4
- QFRKWSPTCBGLSU-UHFFFAOYSA-M potassium 4-hydroxy-3-methoxybenzene-1-sulfonate Chemical group [K+].COC1=CC(S([O-])(=O)=O)=CC=C1O QFRKWSPTCBGLSU-UHFFFAOYSA-M 0.000 claims description 4
- 229940069505 potassium guaiacolsulfonate Drugs 0.000 claims description 4
- 229960003447 pseudoephedrine hydrochloride Drugs 0.000 claims description 4
- BALXUFOVQVENIU-KXNXZCPBSA-N pseudoephedrine hydrochloride Chemical compound [H+].[Cl-].CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 BALXUFOVQVENIU-KXNXZCPBSA-N 0.000 claims description 4
- 229940083542 sodium Drugs 0.000 claims description 4
- CDQGZJGHIVUWQA-UHFFFAOYSA-N 4-[2-(4-hydroxy-3,5-dimethylphenyl)butan-2-yl]-2,6-dimethylphenol Chemical compound C=1C(C)=C(O)C(C)=CC=1C(C)(CC)C1=CC(C)=C(O)C(C)=C1 CDQGZJGHIVUWQA-UHFFFAOYSA-N 0.000 claims description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 claims description 3
- DBAKFASWICGISY-DASCVMRKSA-N Dexchlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C1([C@H](CCN(C)C)C=2N=CC=CC=2)=CC=C(Cl)C=C1 DBAKFASWICGISY-DASCVMRKSA-N 0.000 claims description 3
- 241000218657 Picea Species 0.000 claims description 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 3
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 claims description 3
- 229940015826 dihydroxyaluminum aminoacetate Drugs 0.000 claims description 3
- 229940061262 ethyl cysteine hydrochloride Drugs 0.000 claims description 3
- 229960000869 magnesium oxide Drugs 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- GRLPQNLYRHEGIJ-UHFFFAOYSA-J potassium aluminium sulfate Chemical compound [Al+3].[K+].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O GRLPQNLYRHEGIJ-UHFFFAOYSA-J 0.000 claims description 3
- 229940088417 precipitated calcium carbonate Drugs 0.000 claims description 3
- AJZJIYUOOJLBAU-CEAXSRTFSA-N (2r,3r)-2,3-dihydroxybutanedioic acid;n,n,2-trimethyl-3-phenothiazin-10-ylpropan-1-amine Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.C1=CC=C2N(CC(CN(C)C)C)C3=CC=CC=C3SC2=C1.C1=CC=C2N(CC(CN(C)C)C)C3=CC=CC=C3SC2=C1 AJZJIYUOOJLBAU-CEAXSRTFSA-N 0.000 claims description 2
- CIVCELMLGDGMKZ-UHFFFAOYSA-N 2,4-dichloro-6-methylpyridine-3-carboxylic acid Chemical compound CC1=CC(Cl)=C(C(O)=O)C(Cl)=N1 CIVCELMLGDGMKZ-UHFFFAOYSA-N 0.000 claims description 2
- ZKLPARSLTMPFCP-OAQYLSRUSA-N 2-[2-[4-[(R)-(4-chlorophenyl)-phenylmethyl]-1-piperazinyl]ethoxy]acetic acid Chemical compound C1CN(CCOCC(=O)O)CCN1[C@@H](C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-OAQYLSRUSA-N 0.000 claims description 2
- FSSICIQKZGUEAE-UHFFFAOYSA-N 2-[benzyl(pyridin-2-yl)amino]ethyl-dimethylazanium;chloride Chemical compound Cl.C=1C=CC=NC=1N(CCN(C)C)CC1=CC=CC=C1 FSSICIQKZGUEAE-UHFFFAOYSA-N 0.000 claims description 2
- QOLHOCYZKJILAV-UHFFFAOYSA-N 5-[(3-carboxy-4-hydroxyphenyl)methyl]-2-hydroxybenzoic acid;n,n-dimethyl-1-phenothiazin-10-ylpropan-2-amine Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1.C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1.C1=C(O)C(C(=O)O)=CC(CC=2C=C(C(O)=CC=2)C(O)=O)=C1 QOLHOCYZKJILAV-UHFFFAOYSA-N 0.000 claims description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 2
- ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 claims description 2
- BALXUFOVQVENIU-GNAZCLTHSA-N Ephedrine hydrochloride Chemical compound Cl.CN[C@@H](C)[C@H](O)C1=CC=CC=C1 BALXUFOVQVENIU-GNAZCLTHSA-N 0.000 claims description 2
- 229920000881 Modified starch Polymers 0.000 claims description 2
- FFFPYJTVNSSLBQ-UHFFFAOYSA-N Phenolphthalin Chemical class OC(=O)C1=CC=CC=C1C(C=1C=CC(O)=CC=1)C1=CC=C(O)C=C1 FFFPYJTVNSSLBQ-UHFFFAOYSA-N 0.000 claims description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 2
- 229920002472 Starch Polymers 0.000 claims description 2
- 229960005174 ambroxol Drugs 0.000 claims description 2
- JBDGDEWWOUBZPM-XYPYZODXSA-N ambroxol Chemical compound NC1=C(Br)C=C(Br)C=C1CN[C@@H]1CC[C@@H](O)CC1 JBDGDEWWOUBZPM-XYPYZODXSA-N 0.000 claims description 2
- 229960002071 bepotastine Drugs 0.000 claims description 2
- YWGDOWXRIALTES-NRFANRHFSA-N bepotastine Chemical compound C1CN(CCCC(=O)O)CCC1O[C@H](C=1N=CC=CC=1)C1=CC=C(Cl)C=C1 YWGDOWXRIALTES-NRFANRHFSA-N 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
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 claims description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 2
- 229940105329 carboxymethylcellulose Drugs 0.000 claims description 2
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 claims description 2
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- 235000019192 riboflavin Nutrition 0.000 description 1
- 239000002151 riboflavin Substances 0.000 description 1
- 229960002477 riboflavin Drugs 0.000 description 1
- 229950001574 riboflavin phosphate Drugs 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 238000007391 self-medication Methods 0.000 description 1
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- 229960005055 sodium ascorbate Drugs 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- PPASLZSBLFJQEF-RXSVEWSESA-M sodium-L-ascorbate Chemical compound [Na+].OC[C@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RXSVEWSESA-M 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
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- 230000008961 swelling Effects 0.000 description 1
- 229940061367 tamiflu Drugs 0.000 description 1
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- 239000006068 taste-masking agent Substances 0.000 description 1
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- DPJRMOMPQZCRJU-UHFFFAOYSA-M thiamine hydrochloride Chemical compound Cl.[Cl-].CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N DPJRMOMPQZCRJU-UHFFFAOYSA-M 0.000 description 1
- 235000019190 thiamine hydrochloride Nutrition 0.000 description 1
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- YXVCLPJQTZXJLH-UHFFFAOYSA-N thiamine(1+) diphosphate chloride Chemical compound [Cl-].CC1=C(CCOP(O)(=O)OP(O)(O)=O)SC=[N+]1CC1=CN=C(C)N=C1N YXVCLPJQTZXJLH-UHFFFAOYSA-N 0.000 description 1
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- JWIXXNLOKOAAQT-UHFFFAOYSA-N tipepidine Chemical compound C1N(C)CCCC1=C(C=1SC=CC=1)C1=CC=CS1 JWIXXNLOKOAAQT-UHFFFAOYSA-N 0.000 description 1
- 229940042585 tocopherol acetate Drugs 0.000 description 1
- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 description 1
- 229960000401 tranexamic acid Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
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- 238000009736 wetting Methods 0.000 description 1
- ARAIBEBZBOPLMB-UFGQHTETSA-N zanamivir Chemical compound CC(=O)N[C@@H]1[C@@H](N=C(N)N)C=C(C(O)=O)O[C@H]1[C@H](O)[C@H](O)CO ARAIBEBZBOPLMB-UFGQHTETSA-N 0.000 description 1
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- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
2-yl)propanoic acid)は、プロピオン酸系の非ステロイド性消炎鎮痛剤としてすでに公知の消炎鎮痛剤であり、関節リウマチ、変形性関節症、痛風発作、強直性脊椎炎、腰痛症、肩関節周囲炎、頸肩腕症候群、腱・腱鞘炎、月経困難症、帯状疱疹の疾患の消炎、鎮痛、解熱や、外傷後並びに手術後の消炎、鎮痛、歯科・口腔外科領域における抜歯並びに小手術後の消炎、鎮痛などを目的として広く使用されているものである。
( 錠 剤 )
1錠当たり、以下の処方により、常法に従って、速放部と徐放部を調製した。次いでこれらを用い、二層錠として錠剤を製造した。
( 錠 剤 )
1錠当たり、以下の処方により、常法に従って速放部と徐放部を調製した。次いで、これらを用い、二層錠として錠剤を製造した。
( 顆粒剤 )
1包当たり、以下の処方により、常法に従って、顆粒剤を製造した。
( 顆粒剤 )
1包当たり、以下の処方により、常法に従って、顆粒剤を製造した。
( 顆粒剤 )
1包当たり、以下の処方により、常法に従って、顆粒剤を製造した。
( 錠 剤 )
1錠当たり、以下の処方となるように配合した粉剤を、常法に従って打錠し、錠剤、得た。この錠剤を1錠あたり10mgのヒプロメロースでコーティングし、フィルムコーティング錠を製造した。
( 硬カプセル剤 )
1カプセル当たり、常法に従って以下の処方となるよう速放部と徐放部を調製し、これを硬カプセルに充填し、硬カプセル剤を製造した。
( 顆粒剤 )
1包当たり、以下の処方により、常法に従って、顆粒剤を製造した。
( 錠 剤 )
1錠当たり、以下の処方により、常法に従って、速放部と徐放部を調製した。次いでこれらを用い、二層錠として錠剤を製造した。
アレルギー性鼻炎抑制試験:
アレルギー性鼻炎モデルを用い、鼻腔抵抗の増加に対するナプロキセン(NPX)、クロルフェニラミンマレイン酸塩(CF)、NPXとCFの併用、dl−メチルエフェドリン塩酸塩(MF)、NPXとMFの併用による抑制効果を検討した。アレルギー性鼻炎モデルとしては、モルモットを、抗原(ovalbumin,OVA)で能動感作し、その鼻腔内に抗原投与して鼻炎反応を誘発させたものを使用した。
を算出した。
nRaw(0); 誘発前のnRaw値
nRaw(2); 誘発2時間後のnRaw値
ΔnRaw(con.); 対照群のnRaw増加率
ΔnRaw(2) ; 各検体の誘発2時間後のnRaw増加率
塩基性成分存在下でのナプロキセンと去痰成分の相互作用の検討:
表12示す分量でナプロキセン、去痰成分(アンブロキソール塩酸塩)、塩基性成分(酸化マグネシウム、水酸化マグネシウム、炭酸水素カリウム、炭酸水素ナトリウム)を秤量し、全重量の10%の精製水を添加して混練して、1〜30の混合物を調製した。これら混合物を、ガラス瓶に入れ50 ℃ で保存し、60日後の混合物の状態を評価し、変色の有無を確認した。結果を表12に合わせて示した。
(評価) (内容)
−: 変色が全くない
±: 変色がほとんどない
+: 変色がある
表12に示すように、ナプロキセンと去痰成分であるアンブロキソール塩酸塩を配合すると配合変化を生じ、これらを配合した感冒薬では、有効性が減じ、商品価値が著しく低下することが示唆された。一方でナプロキセンとアンブロキソール塩酸塩を配合し、さらに、塩基性成分を配合することで、配合変を生じなかった。ナプロキセンと去痰成分の配合変化を塩基性成分により防止でき、感冒薬としての効力を十分に発揮できることが示唆された。
Claims (10)
- ナプロキセンまたはその薬学的に許容される塩と、抗鼻炎作用成分、鎮咳成分及び去痰成分から選ばれる医薬成分とを含有する感冒薬。
- 抗鼻炎作用成分が、メキタジン、クレマスチンフマル酸塩、ケトチフェンフマル酸塩、オキサトミド、フェキソフェナジン塩酸塩、エピナスチン塩酸塩、エバスチン、セチリジン塩酸塩、レボセチリジン塩酸塩、ベポタスチンベシル酸塩、エメダスチンフマル酸塩、オロパタジン塩酸塩、ロラタジン、クロルフェニラミンマレイン酸塩、5,dークロルフェニラミンマレイン酸塩、マレイン酸カルビノキサミン、ジフェニルジスルホン酸カルビノキサミン、塩酸イソチベンジル、ジフェンヒドラミン、タンニン酸ジフェンヒドラミン、ジフェンヒドラミン塩酸塩、ジフェンヒドラミンサリチル酸塩、塩酸ジフェテロール、塩酸トリペレナミン、塩酸トンジルアミン、塩酸フェネタジン、塩酸メトジラジン、ジフェニルピラリン塩酸塩、ジフェニルピラリンテオル酸塩、酒石酸アリメマジン、トリプロリジン塩酸塩水和物、ナパジルシル酸メブヒドリン、プロメタジンメチレン二サリチル酸塩、プロメタジン塩酸塩、リン酸ジフェテロール、プソイドエフェドリン塩酸塩、ベラドンナ総アルカロイドおよびヨウ化イソプロパミドから選ばれる化合物である請求項1記載の感冒薬。
- 鎮咳成分が、塩酸アロクラミド、クロペラスチン塩酸塩、ペントキシベリンクエン酸塩、ジブナートナトリウム、デキストロメトルファン臭化水素酸塩水和物、デキストロメトルファン・フェノールフタリン塩、クロペラスチンフェンジゾ酸塩、コデインリン酸塩水和物、ジヒドロコデインリン酸塩、ノスカピン、ノスカピン塩酸塩水和物、ジメモルファンリン酸塩、エプラジノン塩酸塩、ナンテンジツ、チペピジンクエン酸塩、チペピジンヒベンズ酸塩、dl−メチルエフェドリン塩酸塩およびdl−メチルエフェドリンサッカリン塩から選ばれる化合物である請求項1または2記載の感冒薬。
- 去痰成分が、グアヤコールスルホン酸カリウム、グアイフェネシン、ブロムヘキシン塩酸塩、L-エチルシステイン塩酸塩、L-カルボシステイン、クレゾールスルホン酸カリウム、アンブロキソール塩酸塩、クエン酸チペピジン、チペピジンヒベンズ酸塩、dl−メチルエフェドリン塩酸塩およびdl−メチルエフェドリンサッカリン塩から選ばれる化合物並びにマオウ、オウヒ、オンジ、カンゾウ、キキョウ、シャゼンシ、シャゼンソウ、石蒜、セネガおよびバイモから選ばれる生薬またはそのエキスから選ばれるものである請求項1ないし3の何れかの項記載の感冒薬。
- さらに塩基性成分を含有する請求項1ないし4の何れかの項記載の感冒薬。
- 塩基性成分が、ケイ酸マグネシウム、合成ケイ酸アルミニウム、合成ヒドロタルサイト、酸化マグネシウム、ジヒドロキシアルミニウム・アミノ酢酸塩(アルミニウムグリシネート)、水酸化アルミニウムゲル、乾燥水酸化アルミニウムゲル、水酸化アルミニウム・炭酸マグネシウム混合乾燥ゲル、水酸化アルミニウム・炭酸水素ナトリウムの共沈生成物、水酸化アルミニウム・炭酸カルシウム・炭酸マグネシウムの共沈生成物、水酸化マグネシウム・硫酸アルミニウムカリウムの共沈生成物、炭酸マグネシウム、メタケイ酸アルミン酸マグネシウム、ケイ酸アルミン酸マグネシウム、水酸化アルミナマグネシウム、水酸化マグネシウム、炭酸水素ナトリウム、沈降炭酸カルシウム、無水リン酸水素カルシウムおよびリン酸水素カルシウムよりなる群から選ばれた化合物である請求項5に記載の感冒薬。
- さらにセルロース系水膨潤性高分子を含有する請求項1ないし6の何れかの項記載の感冒薬。
- セルロース系水膨潤性高分子が、低置換度ヒドロキシプロピルセルロース、クロスカルメロースナトリウム、カルボキシメチルセルロースナトリウム、カルボキシメチルセルロースカルシウム、カルボキシメチルセルロース、結晶セルロース、アルファー化デンプンおよびカルボキシメチルスターチナトリウムよりなる群から選ばれたものである請求項7に記載の感冒薬。
- 固形製剤である請求項1ないし8の何れかの項記載の感冒薬。
- ナプロキセンまたはその薬学的に許容される塩、ブロムヘキシン若しくはアンブロキソールまたはその薬学的に許容される塩及び塩基性成分を含有する医薬組成物。
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