JP2021075530A - Pharmaceutical composition - Google Patents
Pharmaceutical composition Download PDFInfo
- Publication number
- JP2021075530A JP2021075530A JP2020186453A JP2020186453A JP2021075530A JP 2021075530 A JP2021075530 A JP 2021075530A JP 2020186453 A JP2020186453 A JP 2020186453A JP 2020186453 A JP2020186453 A JP 2020186453A JP 2021075530 A JP2021075530 A JP 2021075530A
- Authority
- JP
- Japan
- Prior art keywords
- salt
- pharmaceutical composition
- examples
- mass
- dextromethorphan
- 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.)
- Pending
Links
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 50
- 150000003839 salts Chemical class 0.000 claims abstract description 65
- 229960001985 dextromethorphan Drugs 0.000 claims abstract description 37
- 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 abstract description 35
- GYDJEQRTZSCIOI-LJGSYFOKSA-N tranexamic acid Chemical compound NC[C@H]1CC[C@H](C(O)=O)CC1 GYDJEQRTZSCIOI-LJGSYFOKSA-N 0.000 claims abstract description 33
- 229960000401 tranexamic acid Drugs 0.000 claims abstract description 33
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims abstract description 29
- 229960001680 ibuprofen Drugs 0.000 claims abstract description 29
- HSRJKNPTNIJEKV-UHFFFAOYSA-N Guaifenesin Chemical compound COC1=CC=CC=C1OCC(O)CO HSRJKNPTNIJEKV-UHFFFAOYSA-N 0.000 claims abstract description 19
- 229960002146 guaifenesin Drugs 0.000 claims abstract description 19
- 239000000843 powder Substances 0.000 claims description 7
- 239000002775 capsule Substances 0.000 claims description 6
- 239000008187 granular material Substances 0.000 claims description 3
- 239000006187 pill Substances 0.000 claims description 3
- 239000002552 dosage form Substances 0.000 claims description 2
- 238000009736 wetting Methods 0.000 abstract description 7
- 230000003993 interaction Effects 0.000 abstract description 6
- 230000015556 catabolic process Effects 0.000 abstract 1
- 238000006731 degradation reaction Methods 0.000 abstract 1
- -1 dextromethorphan phenolphthaline salt Chemical class 0.000 description 20
- 239000003814 drug Substances 0.000 description 13
- 239000003826 tablet Substances 0.000 description 13
- 229940079593 drug Drugs 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- 238000009472 formulation Methods 0.000 description 9
- 201000009240 nasopharyngitis Diseases 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 8
- 239000000654 additive Substances 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 239000011248 coating agent Substances 0.000 description 8
- 239000000739 antihistaminic agent Substances 0.000 description 7
- 238000000576 coating method Methods 0.000 description 7
- 238000005516 engineering process Methods 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 230000000996 additive effect Effects 0.000 description 6
- 229960001948 caffeine Drugs 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 230000006866 deterioration Effects 0.000 description 6
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 5
- 229920002472 Starch Polymers 0.000 description 5
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 5
- 238000004090 dissolution Methods 0.000 description 5
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 5
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- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 5
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- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 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 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 206010036790 Productive cough Diseases 0.000 description 4
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 4
- 230000000954 anitussive effect Effects 0.000 description 4
- 230000001387 anti-histamine Effects 0.000 description 4
- 229940124584 antitussives Drugs 0.000 description 4
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 4
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 4
- 230000000147 hypnotic effect Effects 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 208000024794 sputum Diseases 0.000 description 4
- 239000008107 starch Substances 0.000 description 4
- 208000024891 symptom Diseases 0.000 description 4
- JWIXXNLOKOAAQT-UHFFFAOYSA-N tipepidine Chemical compound C1N(C)CCCC1=C(C=1SC=CC=1)C1=CC=CS1 JWIXXNLOKOAAQT-UHFFFAOYSA-N 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
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- 229920000881 Modified starch Polymers 0.000 description 3
- 239000004372 Polyvinyl alcohol Substances 0.000 description 3
- AUNGANRZJHBGPY-SCRDCRAPSA-N Riboflavin Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)CN1C=2C=C(C)C(C)=CC=2N=C2C1=NC(=O)NC2=O AUNGANRZJHBGPY-SCRDCRAPSA-N 0.000 description 3
- 235000010489 acacia gum Nutrition 0.000 description 3
- 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 3
- 150000004347 all-trans-retinol derivatives Chemical class 0.000 description 3
- 229940125715 antihistaminic agent Drugs 0.000 description 3
- 239000003434 antitussive agent Substances 0.000 description 3
- 229950008138 carmellose Drugs 0.000 description 3
- 239000003086 colorant Substances 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 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 description 3
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 3
- 239000001095 magnesium carbonate Substances 0.000 description 3
- 229910000021 magnesium carbonate Inorganic materials 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 229920002451 polyvinyl alcohol Polymers 0.000 description 3
- 229940083542 sodium Drugs 0.000 description 3
- 235000015424 sodium Nutrition 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 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 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- 229920002785 Croscarmellose sodium Polymers 0.000 description 2
- 240000009138 Curcuma zedoaria Species 0.000 description 2
- 235000003405 Curcuma zedoaria Nutrition 0.000 description 2
- 244000000626 Daucus carota Species 0.000 description 2
- 235000002767 Daucus carota Nutrition 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 240000006927 Foeniculum vulgare Species 0.000 description 2
- 235000004204 Foeniculum vulgare Nutrition 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 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 description 2
- 102000016943 Muramidase Human genes 0.000 description 2
- 108010014251 Muramidase Proteins 0.000 description 2
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 2
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 description 2
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 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 description 2
- 239000000205 acacia gum Substances 0.000 description 2
- 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 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- 229940024546 aluminum hydroxide gel Drugs 0.000 description 2
- SMYKVLBUSSNXMV-UHFFFAOYSA-K aluminum;trihydroxide;hydrate Chemical compound O.[OH-].[OH-].[OH-].[Al+3] SMYKVLBUSSNXMV-UHFFFAOYSA-K 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- 229940121363 anti-inflammatory agent Drugs 0.000 description 2
- 239000003907 antipyretic analgesic agent Substances 0.000 description 2
- 229940108858 belladonna total alkaloid Drugs 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
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- 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 description 2
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 2
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- 239000000812 cholinergic antagonist Substances 0.000 description 2
- 235000015165 citric acid Nutrition 0.000 description 2
- 229960001681 croscarmellose sodium Drugs 0.000 description 2
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- 239000001812 curcuma zedoaria berg. rosc. Substances 0.000 description 2
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- WBEBQCINXJDZCX-UHFFFAOYSA-M dibunate Chemical compound [O-]S(=O)(=O)C1=C(C(C)(C)C)C=CC2=CC(C(C)(C)C)=CC=C21 WBEBQCINXJDZCX-UHFFFAOYSA-M 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 229960001056 dimemorfan Drugs 0.000 description 2
- 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 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 229960000520 diphenhydramine Drugs 0.000 description 2
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- 230000000694 effects Effects 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- PFAXACNYGZVKMX-UHFFFAOYSA-N fenethazine Chemical compound C1=CC=C2N(CCN(C)C)C3=CC=CC=C3SC2=C1 PFAXACNYGZVKMX-UHFFFAOYSA-N 0.000 description 2
- 229950007454 fenethazine Drugs 0.000 description 2
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- 229960002449 glycine Drugs 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
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- 229910052700 potassium Inorganic materials 0.000 description 2
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- 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 description 2
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- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
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- 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
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- 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 description 1
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Abstract
Description
本発明は、イブプロフェンを含有する医薬組成物に関する。 The present invention relates to pharmaceutical compositions containing ibuprofen.
イブプロフェンは、プロピオン酸系に分類される非ステロイド系消炎鎮痛剤(NSAID)の1種であり、シクロオキシゲナーゼ(COX)を阻害することにより、プロスタグランジンの生成を抑制し、解熱鎮痛作用を示す。イブプロフェンは、医療用医薬品ばかりでなく、総合感冒薬等の一般医薬品の有効成分としても広く流通している。 Ibuprofen is a non-steroidal anti-inflammatory drug (NSAID) classified as a propionic acid system, and by inhibiting cyclooxygenase (COX), it suppresses the production of prostaglandins and exhibits an antipyretic analgesic effect. Ibuprofen is widely distributed not only as a medical drug but also as an active ingredient of over-the-counter drugs such as common cold treatments.
総合感冒薬の有効成分として使用される薬剤には、イブプロフェンの他、例えば、鎮咳剤のデキストロメトルファン、去痰剤のグアイフェネシン等が知られている。
特許文献1には、水性媒体中に迅速に懸濁する能力を有する医薬組成物の調製に用いることができる医薬担体として有用な顆粒組成物を含む水懸濁性医薬組成物が開示されており、その中に含まれる医薬有効物質の例として、イブプロフェン、デキストロメトルファン、グアイフェネシン等が挙げられている
In addition to ibuprofen, dextromethorphan, an antitussive, and guaifenesin, a sputum-removing agent, are known as agents used as active ingredients of common cold treatments.
Patent Document 1 discloses a water-suspendable pharmaceutical composition containing a granular composition useful as a pharmaceutical carrier that can be used for preparing a pharmaceutical composition capable of rapidly suspending in an aqueous medium. , Examples of pharmaceutically effective substances contained therein include ibuprofen, dextromethorphan, guaifenesin and the like.
特許文献2には、難溶性風邪薬の経口投与用マイクロエマルション濃縮液の製造方法が開示されており、難溶性風邪薬の例として、イブプロフェン、デキストロメトルファン、グアイフェネシン等が挙げられている。 Patent Document 2 discloses a method for producing a microemulsion concentrate for oral administration of a poorly soluble cold drug, and examples of the poorly soluble cold drug include ibuprofen, dextromethorphan, guaifenesin and the like.
また、特許文献3には、ジフェンヒドラミンなどの抗ヒスタミン剤の催眠作用の発現を有効に利用しつつ、カフェインの作用を際立たせ、総合感冒薬の有用性をQOLの観点から向上させることを目的とした製剤として、抗ヒスタミン剤を処方した第1の総合感冒薬と、催眠作用の発現割合が異なる別の抗ヒスタミン剤を処方した第2の総合感冒薬を含む組合せ製剤が開示されている。また、同様の目的の製剤として、特許文献4には、抗ヒスタミン剤を第1の用量で処方した第1の総合感冒薬と、該抗ヒスタミン剤を第1の用量とは異なる第2の用量で処方した第2の総合感冒薬とを含む組合せ製剤が開示されている。これらの文献には、該製剤には、イブプロフェン、デキストロメトルファン、グアイフェネシン等をさらに含んでもよいことが記載されている。 Further, Patent Document 3 aims to enhance the action of caffeine and improve the usefulness of a common cold drug from the viewpoint of QOL while effectively utilizing the hypnotic action of antihistamines such as diphenhydramine. As a preparation, a combination preparation containing a first common cold drug prescribing an antihistamine and a second common cold drug prescribing another antihistamine having a different rate of occurrence of hypnotic action is disclosed. Further, as a preparation for the same purpose, Patent Document 4 describes a first common cold treatment drug in which an antihistamine is prescribed at a first dose, and a second dose of the antihistamine, which is different from the first dose. A combination formulation containing 2 common cold treatments is disclosed. These documents describe that the preparation may further contain ibuprofen, dextromethorphan, guaifenesin and the like.
上記の文献のいずれも、総合感冒薬等の医薬品に複数の有効成分を配合し得ることを示しているが、(a)イブプロフェン、(b)デキストロメトルファン又はその塩、及び(c)グアイフェネシンを同時配合すると、これらの薬剤の相互作用により湿潤及び/又は溶解を引き起こし、外観品質を損ねる問題については全く記載も示唆もない。
本発明の課題は、上記三成分(a)〜(c)を同時配合した際の相互作用による湿潤及び/又は溶解を抑制し、外観品質の劣化を抑制した医薬組成物を提供することにある。
All of the above documents indicate that a plurality of active ingredients can be blended in a drug such as a common cold drug, but (a) ibuprofen, (b) dextromethorphan or a salt thereof, and (c) guaifenesin are used. When co-blended, the interaction of these agents causes wetting and / or dissolution, and there is no description or suggestion of a problem that impairs appearance quality.
An object of the present invention is to provide a pharmaceutical composition which suppresses wetting and / or dissolution due to interaction when the above three components (a) to (c) are simultaneously blended and suppresses deterioration of appearance quality. ..
本発明者は鋭意検討した結果、上記三成分(a)〜(c)に加えて、トラネキサム酸又はその塩を配合することで、上記問題を解決できることを見出し、本発明を完成させるに至った。
すなわち、本発明は、以下の態様を含む。
[1] イブプロフェン、デキストロメトルファン又はその塩、及びグアイフェネシン、並びにトラネキサム酸又はその塩を含有することを特徴とする医薬組成物。
[2] デキストロメトルファン又はその塩が、デキストロメトルファン臭化水素酸塩水和物である、[1]に記載の医薬組成物。
[3] トラネキサム酸又はその塩が、トラネキサム酸である、[1]または[2]に記載の医薬組成物。
[4] 感冒用に用いられる、[1]〜[3]いずれか記載の医薬組成物。
[5] 医薬組成物の剤形が、錠剤、カプセル剤、顆粒剤、散剤又は丸剤である、[1]〜[4]いずれか記載の医薬組成物。
As a result of diligent studies, the present inventor has found that the above problems can be solved by blending tranexamic acid or a salt thereof in addition to the above three components (a) to (c), and has completed the present invention. ..
That is, the present invention includes the following aspects.
[1] A pharmaceutical composition comprising ibuprofen, dextromethorphan or a salt thereof, and guaifenesin, and tranexamic acid or a salt thereof.
[2] The pharmaceutical composition according to [1], wherein dextromethorphan or a salt thereof is dextromethorphan hydrobromide hydrate.
[3] The pharmaceutical composition according to [1] or [2], wherein tranexamic acid or a salt thereof is tranexamic acid.
[4] The pharmaceutical composition according to any one of [1] to [3], which is used for the common cold.
[5] The pharmaceutical composition according to any one of [1] to [4], wherein the dosage form of the pharmaceutical composition is a tablet, a capsule, a granule, a powder or a pill.
本発明によれば、(a)イブプロフェン、(b)デキストロメトルファン又はその塩、及び(c)グアイフェネシンを同時配合した医薬組成物において、トラネキサム酸又はその塩をさらに配合することにより、これらの薬剤の相互作用による湿潤及び/又は溶解を抑制し、外観品質の劣化を抑制することができる。したがって、本発明によれば、上記三成分(a)〜(c)を含み、外観品質の劣化が抑制された医薬組成物を提供することができる。 According to the present invention, in a pharmaceutical composition containing (a) ibuprofen, (b) dextromethorphan or a salt thereof, and (c) guaifenesin at the same time, tranexamic acid or a salt thereof may be further added to these agents. Wetting and / or dissolution due to the interaction of the above can be suppressed, and deterioration of appearance quality can be suppressed. Therefore, according to the present invention, it is possible to provide a pharmaceutical composition containing the above three components (a) to (c) and suppressing deterioration of appearance quality.
本発明の医薬組成物は、イブプロフェン、デキストロメトルファン又はその塩、及びグアイフェネシン、並びにトラネキサム酸又はその塩を含有することを特徴とする。 The pharmaceutical composition of the present invention is characterized by containing ibuprofen, dextromethorphan or a salt thereof, and guaifenesin, and tranexamic acid or a salt thereof.
本発明における「イブプロフェン」は、公知の方法により製造できるほか、市販のものを用いることができる。例えば、日本薬局方に準拠したイブプロフェンを用いることができる。
本発明におけるイブプロフェンの投与量は、服用者の年齢、症状などに応じて、適宜検討して決定すればよいが、例えば、1日あたり、50〜600mgを1回又は2ないし3回に分けて投与するのが好ましい。
本発明の医薬組成物中に含まれるイブプロフェンの含量は、特に限定されず、上記投与量に基づいて適宜検討して決定すればよいが、例えば、医薬組成物全体の1〜60質量%、好ましくは5〜50質量%、より好ましくは10〜30質量%である。
The "ibuprofen" in the present invention can be produced by a known method, or a commercially available product can be used. For example, ibuprofen conforming to the Japanese Pharmacopoeia can be used.
The dose of ibuprofen in the present invention may be appropriately examined and determined according to the age, symptoms, etc. of the user, and for example, 50 to 600 mg per day may be divided into 1 dose or 2 to 3 doses. It is preferable to administer.
The content of ibuprofen contained in the pharmaceutical composition of the present invention is not particularly limited and may be appropriately examined and determined based on the above dose. For example, 1 to 60% by mass, preferably 1 to 60% by mass of the entire pharmaceutical composition. Is 5 to 50% by mass, more preferably 10 to 30% by mass.
本発明における「デキストロメトルファン又はその塩」は、デキストロメトルファン及びその薬学的に許容される塩、並びにデキストロメトルファン及びその薬学的に許容される塩と水やアルコール等との溶媒和物を含む。デキストロメトルファン又はその塩としては、例えば、デキストロメトルファン、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等が挙げられ、好ましくは、デキストロメトルファン臭化水素酸塩水和物である。これらは、公知の方法により製造できるほか、市販のものを用いることができる。例えば、日本薬局方に準拠したデキストロメトルファン又はその塩を用いることができる。
本発明におけるデキストロメトルファン又はその塩の投与量は、服用者の年齢、症状等に応じて、適宜検討して決定すればよいが、例えば、1日あたり、0.1〜270mg、好ましくは0.5〜180mg、より好ましくは1〜90mgを1回又は2ないし3回に分けて投与するのが好ましい。また、デキストロメトルファン又はその塩が、デキストロメトルファン臭化水素酸塩水和物である場合、1日あたり、デキストロメトルファン臭化水素酸塩水和物として6〜60mg、好ましくは15〜60mg、より好ましくは20〜60mgを投与するのが好ましい。さらに、デキストロメトルファン又はその塩がデキストロメトルファンフェノールフタリン塩である場合、1日あたり、デキストロメトルファンフェノールフタリン塩として9〜90mg、好ましくは22〜90mg、より好ましくは30〜90mgを投与するのが好ましい。
本発明の医薬組成物中に含まれる「デキストロメトルファン又はその塩」の含量は、特に限定されず、上記投与量に基づいて適宜検討して決定すればよいが、例えば、医薬組成物全体の0.1〜5質量%、好ましくは0.5〜3質量%である。
The "dextromethorphan or a salt thereof" in the present invention refers to dextromethorphan and a pharmaceutically acceptable salt thereof, and a solvate of dextromethorphan and a pharmaceutically acceptable salt thereof and water, alcohol, etc. Including. Examples of dextromethorphan or a salt thereof include dextromethorphan, dextromethorphan hydrobromide hydrate, dextromethorphan phenolphthaline salt and the like, and dextromethorphan hydrobromide hydrate is preferable. It is a thing. These can be produced by a known method, or commercially available products can be used. For example, dextromethorphan or a salt thereof according to the Japanese Pharmacopoeia can be used.
The dose of dextromethorphan or a salt thereof in the present invention may be appropriately examined and determined according to the age, symptoms, etc. of the user, and is, for example, 0.1 to 270 mg per day, preferably 0. It is preferable to administer 5 to 180 mg, more preferably 1 to 90 mg in a single dose or in 2 to 3 divided doses. When dextromethorphan or a salt thereof is dextromethorphan hydrobromide hydrate, the amount of dextromethorphan hydrobromide hydrate is 6 to 60 mg, preferably 15 to 60 mg per day. It is preferable to administer 20 to 60 mg. Further, when dextromethorphan or a salt thereof is dextromethorphanphenol phthalin salt, 9 to 90 mg, preferably 22 to 90 mg, more preferably 30 to 90 mg of dextromethorphan phenolphthalin salt is administered per day. It is preferable to do so.
The content of "dextromethorphan or a salt thereof" contained in the pharmaceutical composition of the present invention is not particularly limited and may be appropriately examined and determined based on the above dose. For example, the entire pharmaceutical composition may be determined. It is 0.1 to 5% by mass, preferably 0.5 to 3% by mass.
本発明における「グアイフェネシン」は、公知の方法により製造できるほか、市販のものを用いることができる。例えば、日本薬局方に準拠したグアイフェネシンを用いることができる。
本発明におけるグアイフェネシンの投与量は、服用者の年齢、症状などに応じて、適宜検討して決定すればよいが、例えば、1日あたり、20〜600mgを1回又は2ないし3回に分けて投与するのが好ましい。
本発明の医薬組成物中に含まれるグアイフェネシンの含量は、特に限定されず、上記投与量に基づいて適宜検討して決定すればよいが、例えば、医薬組成物全体の1〜60質量%、好ましくは2.5〜50質量%、より好ましくは5〜30質量%である。
The "guaifenesin" in the present invention can be produced by a known method, or a commercially available product can be used. For example, guaifenesin conforming to the Japanese Pharmacopoeia can be used.
The dose of guaifenesin in the present invention may be appropriately examined and determined according to the age, symptoms, etc. of the user, and for example, 20 to 600 mg per day may be divided into 1 dose or 2 to 3 doses. It is preferable to administer.
The content of guaifenesin contained in the pharmaceutical composition of the present invention is not particularly limited and may be appropriately examined and determined based on the above dose. For example, 1 to 60% by mass, preferably 1 to 60% by mass of the entire pharmaceutical composition. Is 2.5 to 50% by mass, more preferably 5 to 30% by mass.
本発明における「トラネキサム酸又はその塩」は、は、トラネキサム酸及びその薬学的に許容される塩、並びにトラネキサム酸及びその薬学的に許容される塩と水やアルコール等との溶媒和物を含む。トラネキサム酸又はその塩としては、例えば、トラネキサム酸、並びにトラネキサム酸の塩酸塩、硝酸塩、硫酸塩等の鉱酸塩、メタンスルホン酸塩等の有機酸塩、ナトリウム塩、カリウム塩、カルシウム塩、マグネシウム塩等のアルカリ金属塩及びアルカリ土類金属塩等が挙げられ、好ましくは、トラネキサム酸である。これらは、公知の方法により製造できるほか、市販のものを用いることができる。例えば、日本薬局方に準拠したトラネキサム酸又はその塩を用いることができる。
本発明におけるトラネキサム酸又はその塩の投与量は、服用者の年齢、症状などに応じて、適宜検討して決定すればよいが、例えば、トラネキサム酸の場合、1日あたり、50〜2000mgを1回又は2ないし3回に分けて投与するのが好ましい。
本発明の医薬組成物中に含まれるトラネキサム酸又はその塩の含量は、特に限定されず、上記投与量に基づいて適宜検討して決定すればよいが、例えば、医薬組成物全体の1〜80質量%、好ましくは5〜60質量%、より好ましくは10〜40質量%である。
The "tranexamic acid or a salt thereof" in the present invention includes tranexamic acid and a pharmaceutically acceptable salt thereof, and a solvate of tranexamic acid and a pharmaceutically acceptable salt thereof and water, alcohol and the like. .. Examples of tranexamic acid or a salt thereof include tranexamic acid, mineral salts such as tranexamic acid hydrochloride, nitrate and sulfate, organic acid salts such as methanesulfonate, sodium salt, potassium salt, calcium salt and magnesium. Examples thereof include alkali metal salts such as salts and alkaline earth metal salts, and tranexamic acid is preferable. These can be produced by a known method, or commercially available products can be used. For example, tranexamic acid or a salt thereof according to the Japanese Pharmacopoeia can be used.
The dose of tranexamic acid or a salt thereof in the present invention may be appropriately examined and determined according to the age, symptoms, etc. of the user. For example, in the case of tranexamic acid, 50 to 2000 mg per day is 1 It is preferable to administer in divided doses or in 2 to 3 divided doses.
The content of tranexamic acid or a salt thereof contained in the pharmaceutical composition of the present invention is not particularly limited and may be appropriately examined and determined based on the above dose. For example, 1 to 80 of the entire pharmaceutical composition. It is by mass, preferably 5 to 60% by mass, and more preferably 10 to 40% by mass.
本発明の医薬組成物に含まれるイブプロフェンとデキストロメトルファン又はその塩の質量比は、特に限定されないが、例えば、イブプロフェンの1質量部に対して、デキストロメトルファン又はその塩が、例えば、その下限として0.01質量部以上、好ましくは0.02質量部以上であり、その上限として2質量部以下、好ましくは1.5質量部以下である。 The mass ratio of ibuprofen to dextromethorphan or a salt thereof contained in the pharmaceutical composition of the present invention is not particularly limited, but for example, dextromethorphan or a salt thereof is the lower limit thereof with respect to 1 part by mass of ibuprofen. It is 0.01 parts by mass or more, preferably 0.02 parts by mass or more, and the upper limit thereof is 2 parts by mass or less, preferably 1.5 parts by mass or less.
本発明の医薬組成物に含まれるイブプロフェンとグアイフェネシンの質量比は、特に限定されないが、例えば、イブプロフェンの1質量部に対して、グアイフェネシンが、例えば、その下限として0.1質量部以上、好ましくは0.5質量部以上であり、その上限として10質量部以下、好ましくは5質量部以下である。 The mass ratio of ibuprofen to guaifenecin contained in the pharmaceutical composition of the present invention is not particularly limited, but for example, guaifenecin is preferably 0.1 part by mass or more as the lower limit thereof with respect to 1 part by mass of ibuprofen. It is 0.5 parts by mass or more, and the upper limit thereof is 10 parts by mass or less, preferably 5 parts by mass or less.
本発明の医薬組成物に含まれるイブプロフェンとトラネキサム酸又はその塩の質量比は、特に限定されないが、例えば、イブプロフェンの1質量部に対して、トラネキサム酸又はその塩が、例えば、その下限として0.1質量部以上、好ましくは0.5質量部以上であり、その上限として10質量部以下、好ましくは5質量部以下である。 The mass ratio of ibuprofen to tranexamic acid or a salt thereof contained in the pharmaceutical composition of the present invention is not particularly limited, but for example, tranexamic acid or a salt thereof is 0 as the lower limit thereof with respect to 1 part by mass of ibuprofen. .1 part by mass or more, preferably 0.5 part by mass or more, and the upper limit thereof is 10 parts by mass or less, preferably 5 parts by mass or less.
本発明の医薬組成物に含まれるデキストロメトルファン又はその塩とトラネキサム酸又はその塩の質量比は、特に限定されないが、例えば、デキストロメトルファン又はその塩の1質量部に対して、トラネキサム酸又はその塩が、例えば、その下限として1質量部以上、好ましくは5質量部以上であり、その上限として100質量部以下、好ましくは20質量部以下である。 The mass ratio of dextrometholphan or a salt thereof and tranexamic acid or a salt thereof contained in the pharmaceutical composition of the present invention is not particularly limited, but for example, tranexamic acid or tranexamic acid or a salt thereof is based on 1 part by mass of dextrometholphan or a salt thereof. The lower limit of the salt is, for example, 1 part by mass or more, preferably 5 parts by mass or more, and the upper limit thereof is 100 parts by mass or less, preferably 20 parts by mass or less.
本発明の医薬組成物に含まれるグアイフェネシンとトラネキサム酸又はその塩の質量比は、特に限定されないが、例えば、グアイフェネシンの1質量部に対して、トラネキサム酸又はその塩が、例えば、その下限として0.1質量部以上、好ましくは0.5質量部以上であり、その上限として10質量部以下、好ましくは5質量部以下である。 The mass ratio of guayphenesin to tranexamic acid or a salt thereof contained in the pharmaceutical composition of the present invention is not particularly limited, but for example, tranexamic acid or a salt thereof is 0 as the lower limit thereof with respect to 1 part by mass of guayphenesin. .1 part by mass or more, preferably 0.5 part by mass or more, and the upper limit thereof is 10 parts by mass or less, preferably 5 parts by mass or less.
本発明の医薬組成物に含まれるイブプロフェン、デキストロメトルファン又はその塩及びグアイフェネシンの組合せと、トラネキサム酸又はその塩の質量比は、特に限定されないが、例えば、上記組合せ1質量部に対して、トラネキサム酸又はその塩が、例えば、その下限として0.05質量部以上、好ましくは0.1質量部であり、その上限として10質量部以下、好ましくは5質量部以下である。 The mass ratio of the combination of ibuprofen, dextrometholphan or a salt thereof and guayphenesin contained in the pharmaceutical composition of the present invention and tranexamic acid or a salt thereof is not particularly limited. The lower limit of the acid or its salt is, for example, 0.05 parts by mass or more, preferably 0.1 parts by mass, and the upper limit thereof is 10 parts by mass or less, preferably 5 parts by mass or less.
本発明の課題である(a)イブプロフェン、(b)デキストロメトルファン又はその塩、及び(c)グアイフェネシンを同時配合した際の湿潤及び/又は溶解、それに基づく外観品質の劣化は、成分(a)〜(c)が物理的に接触することにより生じていると考えられる。したがって、本発明の医薬組成物としては、特に、成分(a)〜(c)が物理的に分離されておらず、接触し得る状態で含まれる医薬組成物が挙げられる。このような医薬組成物としては、例えば、これらの成分を、同群で混合・造粒し、打錠して得られる錠剤、あるいはこれらの成分を、別群で造粒後、それらの造粒末を混合し、打錠して得られる錠剤等が含まれる。 Wetting and / or dissolution when (a) ibuprofen, (b) dextromethorphan or a salt thereof, and (c) guaifenesin are co-blended, which are the subjects of the present invention, and the deterioration of the appearance quality based on the mixture are the components (a). It is considered that ~ (c) is caused by physical contact. Therefore, examples of the pharmaceutical composition of the present invention include pharmaceutical compositions in which the components (a) to (c) are not physically separated and are contained in a state where they can come into contact with each other. As such a pharmaceutical composition, for example, tablets obtained by mixing and granulating these components in the same group and tableting, or granulating these components in another group and then granulating them. Includes tablets and the like obtained by mixing powders and tableting.
本発明の医薬組成物には、本発明の効果を阻害しない限り、上記有効成分以外の有効成分、例えば、解熱鎮痛剤、鼻炎用薬、抗ヒスタミン剤、鎮咳剤、去痰剤、気管支拡張剤、胃粘膜保護剤、ビタミン類、催眠鎮静薬、喀痰溶解剤、抗炎症剤、抗コリン剤、生薬類、漢方処方などを配合してもよい。 The pharmaceutical composition of the present invention contains active ingredients other than the above active ingredients, for example, antihypertensive analgesics, rhinitis drugs, antihistamines, antitussives, sputum agents, bronchial dilators, gastric mucosa protection, as long as the effects of the present invention are not inhibited. Agents, vitamins, hypnotic sedatives, sputum-dissolving agents, anti-inflammatory agents, anticholinergic agents, crude drugs, Chinese herbal prescriptions, etc. may be blended.
解熱鎮痛剤としては、例えば、アスピリン(アセチルサリチル酸)、アスピリンアルミニウム、アセトアミノフェン、サリチルアミド、サリチル酸ナトリウム、エテンザミド、サザピリン、ラクチルフェネチジン、ケトプロフェン、イソプロピルアンチピリン、ロキソプロフェンナトリウムなどが例示できる。
鼻炎用薬として、塩酸プソイドエフェドリン、dl−マレイン酸クロルフェニラミン、d−クロルフェニラミンマレイン酸塩、ベラドンナ総アルカロイド、ヨウ化イソプロパミド、グリチルリチン酸ジカリウム等が挙げられる。
抗ヒスタミン剤としては、例えば、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、タンニン酸ジフェンヒドラミン、酒石酸アリメマジン、塩酸イソチペンジル、プロメタジンメチレン二サリチル酸塩、ジフェニルピラリン塩酸塩、ジフェニルピラリンテオクル酸塩、塩酸イソチペンジル、塩酸ジフェテロール、リン酸ジフェテロール、トリプロリジン塩酸塩水和物、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、ジフェニルジスルホン酸カルビノキサミン、ナパジシル酸メブヒドロリン、マレイン酸カルビノキサミン、塩酸イプロヘプチン、塩酸プロメタジン、ジフェニルジスルホン酸カルビノキサミン、酒石酸アリメマジン、タンニン酸フェネタジン、プロメタジンメチレン二サリチル酸塩、クレマスチンフマル酸塩、メキタジンなどが例示できる。
麻薬性鎮咳剤としては、例えば、コデインリン酸塩水和物、ジヒドロコデインリン酸塩などが例示できる。
非麻薬性鎮咳剤としては、例えば、アロクラミド、イソアミニル、エプラジノン、オキセラジン、クロフェダノール、クロブチノール、クロペラスチン、ジブナート、ジメモルファン、チペピジン、ノスカピン、ヒドロコタルニン、ペントキシベリン、ベンプロペリン及びホミノベン、並びにそれらの塩及び水和物が挙げられ、それらの塩及び水和物としては、例えば、塩酸アロクラミド、クロペラスチン塩酸塩、クロペラスチンフェンジゾ酸塩、ジブナートナトリウム、ジメモルファンリン酸塩、チペピジンヒベンズ酸塩、チペピジンクエン酸塩、ペントキシベリンクエン酸塩及びそれらの水和物が例示できる。
去痰剤としては、グアヤコールスルホン酸カリウム、ブロムヘキシン塩酸塩、クエン酸チペピジン、L−カルボシステイン、塩化アンモニウム、l−メントール、アンモニア・ウイキョウ精、クレゾールスルホン酸カリウムなどが例示できる。
気管支拡張剤としては、例えば、dl−メチルエフェドリン塩酸塩、dl−メチルエフェドリンサッカリン塩、塩酸トリメトキノール、塩酸フェニルプロパノールアミン、塩酸メトキシフェナミン、l−塩酸メチルエフェドリン、塩酸プソイドエフェドリン、アミノフィリン、ジプロフィリン、テオフィリン、プロキシフィリンなどが例示できる。
胃粘膜保護剤としては、例えば、グリシン、アミノ酢酸、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、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、炭酸マグネシウムなどが例示できる。
ビタミン類としては、例えば、ビタミンB1類またはその誘導体若しくはそれらの塩、ビタミンB2類またはその誘導体若しくはそれらの塩、ビタミンC類またはその誘導体若しくはそれらの塩、ビタミンP(ヘスペリジン)またはその誘導体若しくはそれらの塩などが例示できる。
催眠鎮静薬として、アリルイソプロピルアセチル尿素、ブロムワレリル尿素などが例示できる。
喀痰溶解剤としては、塩化リゾチーム、L−エチルシステイン塩酸塩、塩酸メチルシステインなどが例示できる。
抗炎症剤としては、塩化リゾチーム、セラプターゼ、及びグリチルリチン酸及びその塩などが例示できる。
抗コリン剤としては、ベラドンナ総アルカロイド、ヨウ化イソプロパミドなどが例示できる。
生薬類としては、マオウ、ナンテンジツ、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、セキサン、セネガ、バイモ、ウイキョウ、オウバク、オウレン、ガジュツ、カミツレ、ケイヒ、ゲンチアナ、ゴオウ、獣胆(ユウタン含む)、シャジン、ショウキョウ、ソウジュツ、チョウジ、チンピ、ビャクジュツ、ジリュウ、チクセツニンジン、ニンジンなどが例示できる。
漢方処方としては、根湯、根湯加桔梗、桂皮湯、香蘇散、柴胡桂皮湯、小柴胡湯、小青竜湯、麦門冬湯、半夏厚朴湯、麻黄湯などが例示できる。
Examples of the antipyretic analgesic include aspirin (acetylsalicylic acid), aspirin aluminum, acetaminophen, salicylamide, sodium salicylate, ethenzamide, sazapyrine, lactylphenetidine, ketoprofen, isopropylantipyrine, sodium loxoprofen and the like.
Examples of the drug for rhinitis include pseudoephedrine hydrochloride, chlorpheniramine dl-chlorpheniramine, d-chlorpheniramine maleate, belladonna total alkaloid, isopropamide iodide, dipotassium glycyrrhizinate and the like.
Antihistamines include, for example, diphenhydramine hydrochloride, diphenhydramine salicylate, diphenhydramine tannate, alimemazine tartrate, isotipendyl hydrochloride, promethazine methylene disalicylate, diphenylpyraline hydrochloride, diphenylpyraline theocrate, isotipendyl hydrochloride, diferrol hydrochloride, phosphoric acid. Dipheterol, triprolysine hydrochloride hydrate, tryperenamine hydrochloride, tonsylamine hydrochloride, phenetazine hydrochloride, metodylazine hydrochloride, carbinoxamine diphenyldisulfonate, mebuhydrolin napadisylate, carbinoxamine maleate, iproheptin hydrochloride, promethazine hydrochloride, carbinoxamine diphenyldisulfonate Examples thereof include phenetazine, promethazine methylene disalicylate, cremastine fumarate, and mekitadine.
Examples of narcotic antitussives include codeine phosphate hydrate and dihydrocodeine phosphate.
Non-pharmaceutical antitussives include, for example, allocramid, isoamynyl, epradinone, oxerazine, clofedanol, clobutinol, cloperastin, dibunato, dimemorphan, tipepidin, noscapine, hydrocotarnin, pentoxyberin, beneproperin and hominoben, and salts and water thereof. Examples thereof include Japanese products, and examples of the salts and hydrates thereof include alloclamid hydrochloride, cloperastine hydrochloride, cloperastinfendizoate, dibunato sodium, dimemorphan phosphate, tipepidin hibenzate, and the like. Examples thereof include tipepidin citrate, pentoxyberin silicate and their hydrates.
Examples of the expectorant include potassium guayacol sulfonate, bromhexine hydrochloride, tipepidin citrate, L-carbocisteine, ammonium chloride, l-menthol, ammonia / uikyosei, potassium cresol sulfonate, and the like.
Bronchial dilators include, for example, dl-methylephedrine hydrochloride, dl-methylephedrine saccharin salt, trimetokinol hydrochloride, phenylpropanolamine hydrochloride, methoxyphenamine hydrochloride, l-methylephedrine hydrochloride, pseudoephedrine hydrochloride, aminophylline, diprophylline, Examples include theophylline and proxiphylline.
Examples of the gastromucosal protective agent include glycine, aminoacetic acid, magnesium silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum / aminoacetate, aluminum hydroxide gel, dry aluminum hydroxide gel, and water. Aluminum oxide / magnesium carbonate mixed dry gel, co-precipitated product of aluminum hydroxide / sodium hydrogen carbonate, co-precipitated product of aluminum hydroxide / calcium carbonate / magnesium carbonate, co-precipitated product of magnesium hydroxide / potassium aluminum sulfate, Examples include magnesium carbonate.
Examples of vitamins include vitamin B 1 or a derivative thereof or a salt thereof, vitamin B 2 or a derivative thereof or a salt thereof, vitamin C or a derivative thereof or a salt thereof, vitamin P (hesperidin) or a derivative thereof. Alternatively, those salts and the like can be exemplified.
Examples of hypnotic sedatives include allylisopropylacetylurea and bromvalerylurea.
Examples of the sputum solubilizer include lysozyme chloride, L-ethylcysteine hydrochloride, and methylcysteine hydrochloride.
Examples of the anti-inflammatory agent include lysozyme chloride, seraptase, glycyrrhizic acid and salts thereof.
Examples of the anticholinergic agent include belladonna total alkaloids and isopropamide iodide.
Herbal medicines include Maou, Nantenjitsu, Ohi, Onji, Kanzo, Kikyo, Shazenshi, Shazensou, Sexan, Senega, Baimo, Fennel, Oubaku, Coptis chinensis, Zedoary, Kamitsure, Keihi, Gentiana, Goou, Beast (including Yutan). Examples thereof include shajin, fennel, licorice, clove, chimpi, zedoary, jiryu, chikusetsu carrot, and carrot.
Examples of Chinese medicine prescriptions include Neto, Neyu Kakikyo, Keikinto, Kososan, Saiko Keikinto, Shosaikoto, Shoseiryuto, Bakumondoto, Hangekobokuto, and Maoto.
本発明の医薬組成物は、好ましくはカフェイン類を含まない。
カフェイン類としては、カフェイン、カフェイン水和物、無水カフェイン、カフェインの薬学的に許容される塩(安息香酸ナトリウムカフェイン等)等が挙げられる。
The pharmaceutical composition of the present invention preferably does not contain caffeine.
Examples of caffeine include caffeine, caffeine hydrate, anhydrous caffeine, and pharmaceutically acceptable salts of caffeine (sodium benzoate caffeine, etc.).
本発明の医薬組成物は、上記有効成分と製剤技術分野において慣用の薬学的に許容される担体又は添加剤とともに製剤化された形態であり得る。
上記担体又は添加剤としては、例えば賦形剤、崩壊剤、結合剤、流動化剤、滑沢剤、着色剤、pH調整剤、界面活性剤、安定化剤、矯味剤、香料などが挙げられる。これら添加剤は、製剤技術分野において慣用の量が用いられる。
The pharmaceutical composition of the present invention may be in a form formulated with the above active ingredient and a pharmaceutically acceptable carrier or additive commonly used in the field of pharmaceutical technology.
Examples of the carrier or additive include excipients, disintegrants, binders, fluidizers, lubricants, colorants, pH adjusters, surfactants, stabilizers, flavoring agents, fragrances and the like. .. These additives are used in amounts commonly used in the field of pharmaceutical technology.
賦形剤としては、例えば、トウモロコシデンプン、馬鈴薯デンプン、コムギコデンプン、コメデンプン、部分アルファー化デンプン、アルファー化デンプン、有孔デンプンなどのデンプン類;乳糖水和物、精製白糖、果糖、ブドウ糖、マンニトール、ソルビトール、エリスリトール、キシリトール、トレハロース、マルチトール、粉末還元麦芽糖水アメ、ラクチトールなどの糖又は糖アルコール類;無水リン酸水素カルシウム、結晶セルロース、粉末セルロース、沈降炭酸カルシウム、炭酸カルシウムなどが挙げられる。
崩壊剤としては、例えば、カルメロース、カルメロースカルシウム、カルボキシメチルスターチナトリウム、カルボキシメチルセルロース、カルボキシメチルセルロースカルシウム、カルボキシメチルスターチナトリウム、クロスカルメロースナトリウム、クロスポビドン、低置換度ヒドロキシプロピルセルロース(L−HPC)、ヒドロキシプロピルスターチなどが用いられ、好ましくは、クロスカルメロースナトリウム、L−HPCである。
結合剤としては、例えば、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、ポリビニルピロリドン、コポリビドン、ポリビニルアルコール、アラビアゴム末、メチルセルロース、低置換度ヒドロキシプロピルセルロース、ヒプロメロース、カルメロースナトリウム、デキストリン、部分アルファー化デンプン、プルラン、アラビアゴム、カンテン、ゼラチン、トラガント、アルギン酸ナトリウムなどが用いられ、好ましくは、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロースである。
流動化剤としては、例えば、軽質無水ケイ酸、含水二酸化ケイ素、ケイ酸カルシウム、メタケイ酸アルミン酸マグネシウム、カオリン、タルク等が挙げられる。
滑沢剤としては、例えば、ステアリン酸、ステアリン酸マグネシウム、ステアリン酸カルシウム、タルク、ショ糖脂肪酸エステルなどが挙げられる。
着色剤としては、例えば、黄色三二酸化鉄、三二酸化鉄、食用青色1号、食用青色2号、食用黄色4号、食用黄色5号、食用緑色3号、食用赤色2号、食用赤色3号、食用赤色102号、食用赤色104号、食用赤色105号、食用赤色106号、食用レーキ色素、リボフラビン、リボフラビンリン酸エステルナトリウム、酸化チタンなどが挙げられる。
pH調整剤としては、例えば、クエン酸、リン酸、炭酸、酒石酸、フマル酸、酢酸、アミノ酸及びそれらの塩などが挙げられる。
界面活性剤として、ラウリル硫酸ナトリウム、ポリソルベート80、ポリオキシエチレン(160)ポリオキシプロピレン(30)グリコールなどが挙げられる。
安定化剤としては、例えばトコフェロール、エデト酸四ナトリウム、ニコチン酸アミド、シクロデキストリン類などが挙げられる。
矯味剤としては、例えば、アスコルビン酸、クエン酸、酒石酸、リンゴ酸、スクラロース、ステビアエキスなどが挙げられる。
香料としては、例えば、L−メントール、ハッカ油、レモン油、バニリンなどが挙げられる。
上記した担体又は添加剤は、1種であっても、2種以上を適宜、混合して用いてもよい。
Excipients include, for example, starches such as corn starch, potato starch, wheat costarch, rice starch, partially pregelatinized starch, pregelatinized starch, perforated starch; lactose hydrate, refined sucrose, fructose, glucose, mannitol. , Sorbitol, erythritol, xylitol, trehalose, martitol, powdered reduced starch sugar, sugars or sugar alcohols such as lactitol; anhydrous calcium hydrogen phosphate, crystalline cellulose, powdered cellulose, precipitated calcium carbonate, calcium carbonate and the like.
Examples of the disintegrant include carmellose, carmellose calcium, carboxymethyl starch sodium, carboxymethyl cellulose, carboxymethyl cellulose calcium, carboxymethyl starch sodium, croscarmellose sodium, crospovidone, and low degree of substitution hydroxypropyl cellulose (L-HPC). Hydroxypropyl starch or the like is used, preferably croscarmellose sodium, L-HPC.
Examples of the binder include hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinylpyrrolidone, copolyvidone, polyvinyl alcohol, gum arabic powder, methyl cellulose, low-substituted hydroxypropyl cellulose, hypromellose, sodium carmellose, dextrin, partially pregelatinized starch, and purulan. , Arabic gum, canten, gelatin, tragant, sodium alginate and the like are used, and hydroxypropyl cellulose and hydroxypropyl methyl cellulose are preferable.
Examples of the fluidizing agent include light anhydrous silicic acid, hydrous silicon dioxide, calcium silicate, magnesium aluminometasilicate, kaolin, talc and the like.
Examples of the lubricant include stearic acid, magnesium stearate, calcium stearate, talc, and sucrose fatty acid ester.
Examples of colorants include yellow sesquioxide, iron sesquioxide, edible blue No. 1, edible blue No. 2, edible yellow No. 4, edible yellow No. 5, edible green No. 3, edible red No. 2, and edible red No. 3. , Edible red No. 102, edible red No. 104, edible red No. 105, edible red No. 106, edible lake pigment, riboflavin, sodium riboflavin phosphate, titanium oxide and the like.
Examples of the pH adjuster include citric acid, phosphoric acid, carbonic acid, tartaric acid, fumaric acid, acetic acid, amino acids and salts thereof.
Examples of the surfactant include sodium lauryl sulfate, polysorbate 80, polyoxyethylene (160) polyoxypropylene (30) glycol and the like.
Examples of the stabilizer include tocopherol, tetrasodium edetate, nicotinamide, cyclodextrins and the like.
Examples of the flavoring agent include ascorbic acid, citric acid, tartaric acid, malic acid, sucralose, stevia extract and the like.
Examples of the fragrance include L-menthol, peppermint oil, lemon oil, vanillin and the like.
The above-mentioned carrier or additive may be used alone or in combination of two or more as appropriate.
本発明の医薬組成物の製剤化は、造粒ハンドブック(日本粉体工業技術協会編、オーム社)、経口投与製剤の処方設計(京都大学大学院薬学研究科教授橋田充編、薬業時報社)、粉体の圧縮成形技術(粉体工学・製剤と粒子設計部会編、日刊工業新聞社)、製剤機械技術ハンドブック(第2版、製剤機械技術研究会設立20周年記念出版編集委員会編、製剤機械技術研究会)のような刊行物に記載されている一般的な方法を用いればよく、特別な制限はない。 The formulation of the pharmaceutical composition of the present invention is described in the Granulation Handbook (edited by Japan Powder Industry Technology Association, Ohm Co., Ltd.), Prescription design of oral administration preparations (edited by Mitsuru Hashida, Professor, Graduate School of Pharmaceutical Sciences, Kyoto University, Pharmaceutical Industry Time Report) , Powder compression molding technology (powder engineering / formulation and particle design subcommittee edition, Nikkan Kogyo Shimbun), formulation machine technology handbook (2nd edition, formulation machine technology study group 20th anniversary publication editorial committee edition, formulation The general method described in publications such as the Mechanical Technology Study Group) may be used, and there are no special restrictions.
例えば、本発明の医薬組成物を錠剤に製剤化する場合、上記有効成分と慣用の薬学的に許容される担体又は添加剤を混合・造粒した後、製剤一般に用いられる各種打錠機(例えば、ロータリー式打錠機など)を使用して打錠し、錠剤とすることができる。また、本発明の医薬組成物をカプセル剤に製剤化する場合、上記有効成分と慣用の薬学的に許容される担体又は添加剤を混合・造粒した後、造粒物をカプセルに充填しカプセル剤とすることができる。 For example, when the pharmaceutical composition of the present invention is formulated into a tablet, after mixing and granulating the above active ingredient with a conventional pharmaceutically acceptable carrier or additive, various tableting machines generally used for the formulation (for example, , Rotary tableting machine, etc.) can be used to tablet and form tablets. When the pharmaceutical composition of the present invention is formulated into a capsule, the active ingredient and a conventional pharmaceutically acceptable carrier or additive are mixed and granulated, and then the granulated product is filled in a capsule to form a capsule. It can be used as an agent.
本発明の医薬組成物は、種々の製剤の形態をとり得るが、固形製剤の形態が好ましい。固形製剤としては、例えば、錠剤(素錠、コーティング錠、フィルムコーティング錠、糖衣錠、薄層糖衣錠、口腔内崩壊錠、チュアブル錠などを含む)、カプセル剤(軟カプセル剤、硬カプセル剤などを含む)、顆粒剤、散剤、丸剤が挙げられ、好ましくは、錠剤が挙げられる。 The pharmaceutical composition of the present invention may take various pharmaceutical forms, but a solid pharmaceutical composition is preferable. Examples of the solid preparation include tablets (including uncoated tablets, coated tablets, film-coated tablets, sugar-coated tablets, thin-layer sugar-coated tablets, orally disintegrating tablets, chewable tablets, etc.) and capsules (soft capsules, hard capsules, etc.). ), Granules, powders, pills, and preferably tablets.
上記固形製剤は、通常配合されるコーティング基剤を用いて常法によりコーティングされてもよい。例えば、錠剤を、コーティング基剤を用いてコーティングし、フィルムコーティング錠としてもよい。
コーティング基剤としては、例えば、ヒドロキシプロピルメチルセルロース(ヒプロメロース)、ヒドロキシプロピルセルロース、メチルセルロース、ポビドン、コポリビドン、ポリビニルアルコール、ポリビニルアルコール共重合体、マクロゴールなどの水溶性基剤、エチルセルロースなどの水不溶性基剤、ヒドロキシプロピルメチルセルロースフタレート、ヒドロキシプロピルメチルセルロースアセテートサクシネート、カルボキシメチルエチルセルロース、酢酸フタル酸セルロース、ヒドロキシプロピルメチルセルロースアセテートサクシネート、メタクリル酸コポリマー、アクリル酸コポリマー、カルボキシビニルポリマーなどの腸溶性基剤、ポリビニルアセタールジエチルアミノアセテート、アミノアルキルメタアクリレートコポリマー、ポリビニルアセタートジエチルアミノアセテートなどの胃溶性基剤、アラビアゴム、プルラン、カルナウバロウ、セラック、マクロゴール類、グリセリン脂肪酸エステル、ステアリン酸マグネシウムなどが挙げられる。
また、本発明において、コーティング基剤は、1種であっても2種以上であってもよい。
さらに、コーティングにコーティング添加剤を用いてもよい。コーティング添加剤としては、例えば、遮光剤、流動化剤、着色剤、可塑剤などが挙げられる。
可塑剤としては、例えば、コポリビドン、ポリエチレングリコール、クエン酸トリエチル、ヒマシ油、ポリソルベートなどが挙げられる。
The solid preparation may be coated by a conventional method with a coating base which is usually blended. For example, the tablet may be coated with a coating base to form a film-coated tablet.
Examples of the coating base include a water-soluble base such as hydroxypropylmethyl cellulose (hypromellose), hydroxypropyl cellulose, methyl cellulose, povidone, copolyvidone, polyvinyl alcohol, polyvinyl alcohol copolymer, macrogol, and a water-insoluble base such as ethyl cellulose. , Hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carboxymethylethylcellulose, cellulose acetate phthalate, hydroxypropylmethylcellulose acetate succinate, methacrylic acid copolymer, acrylic acid copolymer, enteric base such as carboxyvinyl polymer, polyvinyl acetal diethylamino Examples thereof include gastrosoluble bases such as acetate, aminoalkyl methacrylate copolymer, polyvinyl acetate diethylaminoacetate, gum arabic, purulan, carnauba wax, cellac, macrogol, glycerin fatty acid ester, magnesium stearate and the like.
Further, in the present invention, the coating base may be one kind or two or more kinds.
In addition, coating additives may be used for coating. Examples of the coating additive include a light-shielding agent, a fluidizing agent, a coloring agent, a plasticizer, and the like.
Examples of the plasticizer include copolyvidone, polyethylene glycol, triethyl citrate, castor oil, polysorbate and the like.
また、本発明は、(a)イブプロフェン、(b)デキストロメトルファン又はその塩、及び(c)グアイフェネシンを含む医薬組成物の外観劣化を抑制する方法であって、トラネキサム酸又はその塩を配合することを特徴とする方法についても提供するものである。この方法における各要件(各成分、その使用量、その使用割合等)は、本発明の医薬組成物について記載したとおりである。 The present invention is a method for suppressing deterioration of the appearance of a pharmaceutical composition containing (a) ibuprofen, (b) dextromethorphan or a salt thereof, and (c) guaifenesin, and contains tranexamic acid or a salt thereof. It also provides a method characterized by this. Each requirement (each component, the amount used thereof, the ratio used thereof, etc.) in this method is as described for the pharmaceutical composition of the present invention.
以下に実施例を挙げて本発明をさらに詳しく説明するが、本発明はこれらに限定されない。 Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited thereto.
(実施例1〜2および比較例1〜2)
表1に示す主薬成分を所定量秤量し、少量の精製水を用いて乳鉢にて造粒後、乾燥することで造粒物を得た。
A predetermined amount of the main ingredient shown in Table 1 was weighed, granulated in a mortar using a small amount of purified water, and then dried to obtain a granulated product.
(試験例)
上記で得られた造粒物(実施例1〜2および比較例1〜2)をガラス瓶に入れ密栓し、60℃条件下で1週間保存した。保存後の造粒物の性状について保存開始直後と比較評価を行った。
The granulated products obtained above (Examples 1 and 2 and Comparative Examples 1 and 2) were placed in a glass bottle, sealed tightly, and stored under 60 ° C. conditions for 1 week. The properties of the granulated product after storage were compared and evaluated with those immediately after the start of storage.
表2に示すとおり、トラネキサム酸配合群では60℃1週間保存でも造粒物の状態が保たれることを確認した(実施例1、2)。その一方で、トラネキサム酸非配合群では造粒物の湿潤ならびに溶融が認められ、造粒物として状態の保持が困難であった(比較例1、2)。
以上から、トラネキサム酸又はその塩がイブプロフェン、デキストロメトルファン又はその塩、及びグアイフェネシンの相互作用を抑制する効果を有することが明らかとなった。
As shown in Table 2, it was confirmed that in the tranexamic acid-containing group, the state of the granulated product was maintained even when stored at 60 ° C. for 1 week (Examples 1 and 2). On the other hand, in the tranexamic acid-free group, wetting and melting of the granulated product were observed, and it was difficult to maintain the state of the granulated product (Comparative Examples 1 and 2).
From the above, it was clarified that tranexamic acid or a salt thereof has an effect of suppressing the interaction between ibuprofen, dextromethorphan or a salt thereof, and guaifenesin.
(製造例1〜5)
下表3の区分Aに示した処方および配合比にしたがって各成分を混合し、打錠して素錠を得た。得られた素錠を、区分Bに示した処方にしたがってコーティングし、コーティング剤を得た。
Each component was mixed according to the formulation and compounding ratio shown in Category A of Table 3 below, and tableted to obtain an uncoated tablet. The obtained uncoated tablets were coated according to the formulation shown in Category B to obtain a coating agent.
本発明によれば、トラネキサム酸又はその塩によって、(a)イブプロフェン、(b)デキストロメトルファン又はその塩、及び(c)グアイフェネシンの相互作用による湿潤及び/又は溶解が抑制され、外観品質の劣化が抑制された医薬組成物を提供することができる。 According to the present invention, tranexamic acid or a salt thereof suppresses wetting and / or dissolution due to the interaction of (a) ibuprofen, (b) dextromethorphan or a salt thereof, and (c) guaifenesin, resulting in deterioration of appearance quality. It is possible to provide a pharmaceutical composition in which is suppressed.
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