JP2011046692A - Medicinal preparation - Google Patents
Medicinal preparation Download PDFInfo
- Publication number
- JP2011046692A JP2011046692A JP2010167929A JP2010167929A JP2011046692A JP 2011046692 A JP2011046692 A JP 2011046692A JP 2010167929 A JP2010167929 A JP 2010167929A JP 2010167929 A JP2010167929 A JP 2010167929A JP 2011046692 A JP2011046692 A JP 2011046692A
- Authority
- JP
- Japan
- Prior art keywords
- salt
- loxoprofen
- xanthine derivative
- caffeine
- desiccant
- 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
- 238000002360 preparation method Methods 0.000 title claims abstract description 39
- 150000003839 salts Chemical class 0.000 claims abstract description 120
- 229960002373 loxoprofen Drugs 0.000 claims abstract description 81
- 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 abstract description 80
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 claims abstract description 61
- 239000007787 solid Substances 0.000 claims abstract description 33
- 239000002274 desiccant Substances 0.000 claims abstract description 29
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 claims description 36
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 26
- 229960001948 caffeine Drugs 0.000 claims description 22
- 230000003993 interaction Effects 0.000 claims description 19
- 238000004806 packaging method and process Methods 0.000 claims description 17
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 claims description 14
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 claims description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 12
- 229910021536 Zeolite Inorganic materials 0.000 claims description 12
- HNPSIPDUKPIQMN-UHFFFAOYSA-N dioxosilane;oxo(oxoalumanyloxy)alumane Chemical compound O=[Si]=O.O=[Al]O[Al]=O HNPSIPDUKPIQMN-UHFFFAOYSA-N 0.000 claims description 12
- 239000010457 zeolite Substances 0.000 claims description 12
- ODINCKMPIJJUCX-UHFFFAOYSA-N Calcium oxide Chemical compound [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- JWBPVFVNISJVEM-UHFFFAOYSA-M sodium caffeine benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1.CN1C(=O)N(C)C(=O)C2=C1N=CN2C JWBPVFVNISJVEM-UHFFFAOYSA-M 0.000 claims description 9
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 6
- 239000000292 calcium oxide Substances 0.000 claims description 6
- 235000012255 calcium oxide Nutrition 0.000 claims description 6
- 239000000499 gel Substances 0.000 claims description 6
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 4
- 229910001583 allophane Inorganic materials 0.000 claims description 4
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims description 4
- 239000001110 calcium chloride Substances 0.000 claims description 4
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 4
- 239000000395 magnesium oxide Substances 0.000 claims description 4
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 claims description 4
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 claims description 4
- 239000002808 molecular sieve Substances 0.000 claims description 4
- 239000000741 silica gel Substances 0.000 claims description 4
- 229910002027 silica gel Inorganic materials 0.000 claims description 4
- 239000000377 silicon dioxide Substances 0.000 claims description 4
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 claims description 4
- 239000000440 bentonite Substances 0.000 claims description 3
- 229910000278 bentonite Inorganic materials 0.000 claims description 3
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 claims description 3
- RCQXSQPPHJPGOF-UHFFFAOYSA-N caffeine citrate Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C RCQXSQPPHJPGOF-UHFFFAOYSA-N 0.000 claims description 3
- 229960002031 caffeine citrate Drugs 0.000 claims description 3
- LCHGOKZNRDAXEK-UHFFFAOYSA-N caffeine monohydrate Chemical group O.CN1C(=O)N(C)C(=O)C2=C1N=CN2C LCHGOKZNRDAXEK-UHFFFAOYSA-N 0.000 claims description 3
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 claims description 3
- 239000004927 clay Substances 0.000 claims description 3
- GUJOJGAPFQRJSV-UHFFFAOYSA-N dialuminum;dioxosilane;oxygen(2-);hydrate Chemical compound O.[O-2].[O-2].[O-2].[Al+3].[Al+3].O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O GUJOJGAPFQRJSV-UHFFFAOYSA-N 0.000 claims description 3
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 3
- 229910052901 montmorillonite Inorganic materials 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 238000004321 preservation Methods 0.000 claims 2
- 239000003795 chemical substances by application Substances 0.000 claims 1
- -1 loxoprofen sodium anhydride Chemical class 0.000 description 17
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 16
- 239000003826 tablet Substances 0.000 description 15
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 14
- 239000008187 granular material Substances 0.000 description 12
- 238000000034 method Methods 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 239000000203 mixture Substances 0.000 description 10
- 239000003814 drug Substances 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 230000009471 action Effects 0.000 description 7
- 229940079593 drug Drugs 0.000 description 7
- 229960000278 theophylline Drugs 0.000 description 7
- QUNWUDVFRNGTCO-UHFFFAOYSA-N 1,7-dimethylxanthine Chemical compound N1C(=O)N(C)C(=O)C2=C1N=CN2C QUNWUDVFRNGTCO-UHFFFAOYSA-N 0.000 description 6
- FQPFAHBPWDRTLU-UHFFFAOYSA-N aminophylline Chemical compound NCCN.O=C1N(C)C(=O)N(C)C2=C1NC=N2.O=C1N(C)C(=O)N(C)C2=C1NC=N2 FQPFAHBPWDRTLU-UHFFFAOYSA-N 0.000 description 6
- 230000001754 anti-pyretic effect Effects 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 6
- 239000011521 glass Substances 0.000 description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 238000003860 storage Methods 0.000 description 5
- 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 description 4
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 4
- 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
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 4
- 208000002193 Pain Diseases 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 229960003556 aminophylline Drugs 0.000 description 4
- 230000000954 anitussive effect Effects 0.000 description 4
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 239000002221 antipyretic Substances 0.000 description 4
- 229940124584 antitussives Drugs 0.000 description 4
- 239000003172 expectorant agent Substances 0.000 description 4
- 230000003419 expectorant effect Effects 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- 229960004708 noscapine Drugs 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- KYHQZNGJUGFTGR-LURJTMIESA-N 7-[(2s)-2-hydroxypropyl]-1,3-dimethylpurine-2,6-dione Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C[C@@H](O)C KYHQZNGJUGFTGR-LURJTMIESA-N 0.000 description 3
- HOKDBMAJZXIPGC-UHFFFAOYSA-N Mequitazine Chemical compound C12=CC=CC=C2SC2=CC=CC=C2N1CC1C(CC2)CCN2C1 HOKDBMAJZXIPGC-UHFFFAOYSA-N 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
- 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 description 3
- 230000000202 analgesic effect Effects 0.000 description 3
- 239000000739 antihistaminic agent Substances 0.000 description 3
- 239000003907 antipyretic analgesic agent Substances 0.000 description 3
- 229960002335 bromhexine hydrochloride Drugs 0.000 description 3
- 238000000975 co-precipitation Methods 0.000 description 3
- 229940124579 cold medicine Drugs 0.000 description 3
- PCHPORCSPXIHLZ-UHFFFAOYSA-N diphenhydramine hydrochloride Chemical compound [Cl-].C=1C=CC=CC=1C(OCC[NH+](C)C)C1=CC=CC=C1 PCHPORCSPXIHLZ-UHFFFAOYSA-N 0.000 description 3
- YRSGDLIATOURQO-UHFFFAOYSA-N ethyl 4-acetyl-5-oxohexanoate Chemical compound CCOC(=O)CCC(C(C)=O)C(C)=O YRSGDLIATOURQO-UHFFFAOYSA-N 0.000 description 3
- 241000411851 herbal medicine Species 0.000 description 3
- 235000012054 meals Nutrition 0.000 description 3
- 229960005042 mequitazine Drugs 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- PLPRGLOFPNJOTN-UHFFFAOYSA-N narcotine Natural products COc1ccc2C(OC(=O)c2c1OC)C3Cc4c(CN3C)cc5OCOc5c4OC PLPRGLOFPNJOTN-UHFFFAOYSA-N 0.000 description 3
- 229960004767 proxyphylline Drugs 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 229960004559 theobromine Drugs 0.000 description 3
- JZRWCGZRTZMZEH-UHFFFAOYSA-N thiamine Chemical compound CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N JZRWCGZRTZMZEH-UHFFFAOYSA-N 0.000 description 3
- 239000001100 (2S)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chroman-4-one Substances 0.000 description 2
- 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 description 2
- 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 description 2
- 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 description 2
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- 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 description 2
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- GQTHJBOWLPZUOI-FJXQXJEOSA-M sodium D-pantothenate Chemical compound [Na+].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O GQTHJBOWLPZUOI-FJXQXJEOSA-M 0.000 description 1
- 235000010378 sodium ascorbate Nutrition 0.000 description 1
- PPASLZSBLFJQEF-RKJRWTFHSA-M sodium ascorbate Substances [Na+].OC[C@@H](O)[C@H]1OC(=O)C(O)=C1[O-] PPASLZSBLFJQEF-RKJRWTFHSA-M 0.000 description 1
- 229960005055 sodium ascorbate Drugs 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229940068459 sodium pantothenate Drugs 0.000 description 1
- 229960004025 sodium salicylate Drugs 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
- GFWRVVCDTLRWPK-KPKJPENVSA-N sofalcone Chemical compound C1=CC(OCC=C(C)C)=CC=C1\C=C\C(=O)C1=CC=C(OCC=C(C)C)C=C1OCC(O)=O GFWRVVCDTLRWPK-KPKJPENVSA-N 0.000 description 1
- 229950004782 sofalcone Drugs 0.000 description 1
- 238000007711 solidification Methods 0.000 description 1
- 230000008023 solidification Effects 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 229960004291 sucralfate Drugs 0.000 description 1
- MNQYNQBOVCBZIQ-JQOFMKNESA-A sucralfate Chemical compound O[Al](O)OS(=O)(=O)O[C@@H]1[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](COS(=O)(=O)O[Al](O)O)O[C@H]1O[C@@]1(COS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)[C@H](OS(=O)(=O)O[Al](O)O)[C@@H](OS(=O)(=O)O[Al](O)O)O1 MNQYNQBOVCBZIQ-JQOFMKNESA-A 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 229950006156 teprenone Drugs 0.000 description 1
- 229960003495 thiamine Drugs 0.000 description 1
- 235000019157 thiamine Nutrition 0.000 description 1
- 239000011721 thiamine Substances 0.000 description 1
- 229960001385 thiamine disulfide Drugs 0.000 description 1
- 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
- UIERGBJEBXXIGO-UHFFFAOYSA-N thiamine mononitrate Chemical compound [O-][N+]([O-])=O.CC1=C(CCO)SC=[N+]1CC1=CN=C(C)N=C1N UIERGBJEBXXIGO-UHFFFAOYSA-N 0.000 description 1
- 208000023409 throat pain Diseases 0.000 description 1
- 229960000896 tipepidine Drugs 0.000 description 1
- 208000004371 toothache Diseases 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
- 229960001593 triprolidine hydrochloride Drugs 0.000 description 1
- 235000013976 turmeric Nutrition 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 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
本発明は、ロキソプロフェン又はその塩、及びキサンチン誘導体又はその塩を含む医薬製剤に関する。 The present invention relates to a pharmaceutical preparation comprising loxoprofen or a salt thereof and a xanthine derivative or a salt thereof.
ロキソプロフェンは、非ステロイド性消炎鎮痛剤(NSAID)の一種であり、関節リウマチ、変形性関節症、腰痛症、肩関節周囲炎、頸肩腕症候群、歯痛、急性上気道炎、手術後・外傷後・抜歯後等の消炎・鎮痛・解熱に有効なものとして知られている(非特許文献1)。 Loxoprofen is a type of non-steroidal anti-inflammatory analgesic (NSAID), including rheumatoid arthritis, osteoarthritis, low back pain, shoulder periarthritis, cervical-shoulder arm syndrome, toothache, acute upper respiratory inflammation, post-surgical / post-traumatic It is known as effective for anti-inflammatory, analgesic and antipyretic after tooth extraction (Non-patent Document 1).
ロキソプロフェンは、その優れた薬理作用から、様々な薬物と組み合せることが検討されている。当該組み合わせにより得られる作用としては、例えば、カフェイン、エテンザミドやアセトアミノフェンと組み合せることによる消炎・鎮痛・解熱効果の増強作用(特許文献1)、カルビノキサミンマレイン酸塩、クロルフェニラミンマレイン酸塩、ケトチフェンフマル酸塩、メキタジンやエピナスチン塩酸塩と組み合わせることによる鼻閉症状の改善作用(特許文献2)、アゼラスチン塩酸塩やメキタジンと組み合わせることによる杯細胞過形成抑制作用(特許文献3)などが挙げられる。
また、ロキソプロフェンをブロムヘキシン塩酸塩やアンブロキソール塩酸塩と組み合わせることによる、咳嗽症状に対する効果の増強作用(特許文献4)及び杯細胞過形成抑制作用(特許文献5)並びにロキソプロフェンをブロムヘキシン塩酸塩と組み合わせることによる消炎・鎮痛・解熱効果の増強作用(特許文献6)等が知られている。
Loxoprofen has been studied for combining with various drugs because of its excellent pharmacological action. Examples of the action obtained by the combination include enhancement of anti-inflammatory, analgesic and antipyretic effects by combining with caffeine, ethenamide and acetaminophen (Patent Document 1), carbinoxamine maleate, chlorpheniramine malee Of nasal congestion by combining with acid salt, ketotifen fumarate, mequitazine and epinastine hydrochloride (Patent Document 2), inhibitory effect on goblet cell hyperplasia by combining with azelastine hydrochloride and mequitazine (Patent Document 3), etc. Is mentioned.
Further, combining loxoprofen with bromhexine hydrochloride or ambroxol hydrochloride enhances the effect on cough symptoms (Patent Document 4) and suppresses goblet cell hyperplasia (Patent Document 5), and combines loxoprofen with bromhexine hydrochloride. There are known anti-inflammatory, analgesic and antipyretic effects (Patent Document 6).
また、ロキソプロフェンが、クロルフェニラミンマレイン酸塩やクレマスチンフマル酸塩の抗ヒスタミン作用を増強すること(特許文献6)も知られ、当該特許文献においては、ロキソプロフェンと様々な薬物との組み合せが検討されており、またロキソプロフェンと様々な薬物を組み合せた製剤例が記載されている。さらに、制酸剤及びキサンチン誘導体と組み合わせることによる、ロキソプロフェン起因の胃粘膜障害抑制作用(特許文献7)が知られている。 It is also known that loxoprofen enhances the antihistamine action of chlorpheniramine maleate and clemastine fumarate (Patent Document 6). In this patent document, combinations of loxoprofen with various drugs are studied. In addition, formulation examples in which loxoprofen and various drugs are combined are described. Furthermore, a gastric mucosal disorder inhibiting action caused by loxoprofen by combining with an antacid and a xanthine derivative is known (Patent Document 7).
一方、キサンチン誘導体としては、カフェイン、テオフィリン、パラキサンチン、テオブロミン、アミノフィリン、ジプロフィリン、プロキシフィリン等が知られ、カフェインは中枢興奮作用、強心・利尿作用、胃酸分泌亢進作用、平滑筋弛緩作用等を示し、解熱鎮痛剤、総合感冒薬や鎮咳去痰薬等に用いられる薬物である(非特許文献2ほか)。また、テオフィリンは平滑筋弛緩作用、中枢興奮作用、強心・利尿作用等を示し、鎮咳去痰薬や鎮暈薬等に用いられる薬物である。アミノフィリンはテオフィリンとエチレンジアミンの複塩であり、テオフィリンと同様の作用を示し、ジプロフィリンも、テオフィリンと同様の作用を示す(非特許文献3ほか)。プロキシフィリンもテオフィリンと同様の作用を示し(非特許文献4ほか)、パラキサンチンやテオブロミンも同様の作用を示す。 On the other hand, as xanthine derivatives, caffeine, theophylline, paraxanthine, theobromine, aminophylline, diprofylline, proxyphylline, etc. are known. It is a drug used for antipyretic analgesics, general cold medicine, antitussive expectorant and the like (Non-patent Document 2 and others). Theophylline exhibits smooth muscle relaxing action, central excitatory action, cardiotonic / diuretic action, and the like, and is a drug used for antitussive expectorant and antipruritic drug. Aminophylline is a double salt of theophylline and ethylenediamine, and exhibits the same action as theophylline, and diprofylline also exhibits the same action as theophylline (Non-patent Document 3 and others). Proxyphylline also exhibits the same action as theophylline (Non-Patent Document 4 and others), and paraxanthine and theobromine also exhibit the same action.
カフェイン又はアミノフィリンとロキソプロフェンを含有する錠剤は知られている(特許文献7、8、9ほか)が、ロキソプロフェンとキサンチン誘導体とが相互作用するか否かは知られていない。当然のことながら、その解決手段については全く知られていない。 Tablets containing caffeine or aminophylline and loxoprofen are known (Patent Documents 7, 8, 9 and others), but it is not known whether loxoprofen and xanthine derivatives interact. Of course, no solution is known about the solution.
本発明者らは、まず、ロキソプロフェン又はその塩とキサンチン誘導体又はその塩とを含有する固形製剤を開発するため、それらの保存安定性について検討したところ、ロキソプロフェン又はその塩とキサンチン誘導体又はその塩とを混合して保存すると、意外にも、これらの化合物の間に相互作用が生じ、この相互作用により、固化等が生じ、安定性に問題が生じることを見出した。
従って、本発明の課題は、ロキソプロフェン又はその塩とキサンチン誘導体又はその塩を含有する安定な固形製剤の提供である。
First, the present inventors examined the storage stability of a solid preparation containing loxoprofen or a salt thereof and a xanthine derivative or a salt thereof. As a result, the loxoprofen or a salt thereof and a xanthine derivative or a salt thereof were examined. Surprisingly, it has been found that when these are mixed and stored, an interaction occurs between these compounds, and this interaction causes solidification and the like, resulting in a problem in stability.
Accordingly, an object of the present invention is to provide a stable solid preparation containing loxoprofen or a salt thereof and a xanthine derivative or a salt thereof.
そこで、本発明者らは、この問題を解決すべくさらに検討したところ、ロキソプロフェン又はその塩、及びキサンチン誘導体又はその塩を、シリカゲル、シリカアルミナゲル(アロフェン)、天然ゼオライト、合成ゼオライト(モレキュラーシーブ)、塩化カルシウム、生石灰(酸化カルシウム)、ベントナイトクレイ(モンモリロナイト)、塩化マグネシウム、酸化マグネシウム等の乾燥剤存在下で保存することにより、当該相互作用を抑制することができることを見出した。 Then, the present inventors further studied to solve this problem. As a result, loxoprofen or a salt thereof, and a xanthine derivative or a salt thereof were converted into silica gel, silica alumina gel (allophane), natural zeolite, synthetic zeolite (molecular sieve). It was found that the interaction can be suppressed by storing in the presence of a desiccant such as calcium chloride, quicklime (calcium oxide), bentonite clay (montmorillonite), magnesium chloride, magnesium oxide.
すなわち、本発明は、ロキソプロフェン又はその塩、キサンチン誘導体又はその塩、及び乾燥剤を容器中に含む医薬製剤を提供するものである。
また、本発明は、ロキソプロフェン又はその塩、及びキサンチン誘導体又はその塩を含有する固形製剤と乾燥剤とを容器中に含む医薬製剤を提供するものである。
また、本発明は、ロキソプロフェン又はその塩、及びキサンチン誘導体又はその塩を、乾燥剤存在下で保存することを特徴とする、相互作用が抑制されたロキソプロフェン又はその塩、及びキサンチン誘導体又はその塩を含有する固形製剤の製造方法を提供するものである。
また、本発明は、ロキソプロフェン又はその塩、及びキサンチン誘導体又はその塩を含有する固形製剤を乾燥剤存在下で保存する工程を含むことを特徴とする、ロキソプロフェン又はその塩及びキサンチン誘導体又はその塩を含有する固形製剤と乾燥剤とを容器中に含む医薬製剤の製造方法を提供するものである。
That is, this invention provides the pharmaceutical formulation which contains a loxoprofen or its salt, a xanthine derivative or its salt, and a desiccant in a container.
The present invention also provides a pharmaceutical preparation comprising a solid preparation containing loxoprofen or a salt thereof and a xanthine derivative or a salt thereof and a desiccant in a container.
In addition, the present invention provides loxoprofen or a salt thereof and xanthine derivative or a salt thereof with suppressed interaction, characterized by storing loxoprofen or a salt thereof and a xanthine derivative or a salt thereof in the presence of a desiccant. The manufacturing method of the solid formulation to contain is provided.
The present invention also includes a step of storing a solid preparation containing loxoprofen or a salt thereof and a xanthine derivative or a salt thereof in the presence of a desiccant, wherein the loxoprofen or a salt thereof and a xanthine derivative or a salt thereof are provided. The present invention provides a method for producing a pharmaceutical preparation comprising a contained solid preparation and a desiccant in a container.
本発明によれば、ロキソプロフェン又はその塩とキサンチン誘導体又はその塩との相互作用を抑制できる。従って、保存安定性が優れた、ロキソプロフェン又はその塩、及びキサンチン誘導体又はその塩を含む固形製剤を提供することができる。
また、複雑な工程を経ることなく、簡便かつ安価に、ロキソプロフェン又はその塩、及びキサンチン誘導体又はその塩を含む、相互作用が抑制された固形製剤を提供することができる。
According to the present invention, the interaction between loxoprofen or a salt thereof and a xanthine derivative or a salt thereof can be suppressed. Therefore, a solid preparation containing loxoprofen or a salt thereof and a xanthine derivative or a salt thereof having excellent storage stability can be provided.
Moreover, the solid formulation with which interaction was suppressed including the loxoprofen or its salt, and a xanthine derivative or its salt can be provided easily and cheaply without passing through a complicated process.
本発明の医薬製剤は、ロキソプロフェン又はその塩、キサンチン誘導体又はその塩及び乾燥剤を含む。
本発明の医薬製剤に用いられるロキソプロフェン又はその塩には、ロキソプロフェンのみならず、ロキソプロフェンの薬学上許容される塩、さらには水やアルコール等との溶媒和物が含まれる。これらは公知の化合物であり、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。本発明において、ロキソプロフェン又はその塩としては、ロキソプロフェンナトリウム水和物(化学名:Monosodium 2-[4-[(2-oxocyclopentyl)methyl]phenyl]propanoate dihydrate)が好ましい。
The pharmaceutical preparation of the present invention contains loxoprofen or a salt thereof, a xanthine derivative or a salt thereof and a desiccant.
Loxoprofen or a salt thereof used in the pharmaceutical preparation of the present invention includes not only loxoprofen but also a pharmaceutically acceptable salt of loxoprofen, and further a solvate with water, alcohol or the like. These are known compounds, and can be produced by known methods, or commercially available products can be used. In the present invention, loxoprofen or a salt thereof is preferably loxoprofen sodium hydrate (chemical name: Monosodium 2- [4-[(2-oxocyclopentyl) methyl] phenyl] propanoate dihydrate).
本発明の医薬製剤におけるロキソプロフェン又はその塩の含有量は、服用者の性別、年齢、症状等に応じて、適宜検討して決定すればよいが、1日あたり、ロキソプロフェンナトリウム無水物換算で10〜300mg服用できる量が好ましく、30〜240mg服用できる量がより好ましい。60〜180mg服用できる量がさらに好ましい。 The content of loxoprofen or a salt thereof in the pharmaceutical preparation of the present invention may be determined by appropriate examination according to the sex, age, symptoms, etc. of the user, but is 10 to 10 per day in terms of loxoprofen sodium anhydride. The amount that can be taken 300 mg is preferred, and the amount that can be taken 30 to 240 mg is more preferred. The amount that can be taken 60 to 180 mg is more preferable.
本発明の医薬製剤に用いられるキサンチン誘導体としては、下記一般式(I)で表される化合物が好ましい。 As the xanthine derivative used in the pharmaceutical preparation of the present invention, a compound represented by the following general formula (I) is preferable.
[式中、R1及びR2は各々独立して水素原子又はメチル基を意味する。R3は水素原子、
メチル基、モノヒドロキシプロピル基又はジヒドロキシプロピル基を意味する。]
[Wherein, R 1 and R 2 each independently represents a hydrogen atom or a methyl group. R 3 is a hydrogen atom,
It means a methyl group, a monohydroxypropyl group or a dihydroxypropyl group. ]
上記R3において、モノヒドロキシプロピル基としては、2−ヒドロキシプロピル基が好ましい。また、ジヒドロキシプロピル基としては、2,3−ジヒドロキシプロピル基が好ましい。 In R 3 described above, the monohydroxypropyl group is preferably a 2-hydroxypropyl group. The dihydroxypropyl group is preferably a 2,3-dihydroxypropyl group.
なお、上記一般式(I)において、(1)R1がメチル基であり、R2がメチル基であり、R3がメチル基であるものは、カフェインを意味するものである。
(2)R1がメチル基であり、R2がメチル基であり、R3が水素原子であるものは、テオフィリンを意味するものである。
(3)R1が水素原子であり、R2がメチル基であり、R3がメチル基であるものは、テオブロミンを意味するものである。
(4)R1がメチル基であり、R2が水素原子であり、R3がメチル基であるものは、パラキサンチンを意味するものである。
(5)R1がメチル基であり、R2がメチル基であり、R3が2−ヒドロキシプロピル基であるものは、プロキシフィリンを意味するものである。
(6)R1がメチル基であり、R2がメチル基であり、R3が2,3−ジヒドロキシプロピル基であるものは、ジプロフィリンを意味するものである。
In the general formula (I), (1) R 1 is a methyl group, R 2 is a methyl group, and R 3 is a methyl group means caffeine.
(2) R 1 is a methyl group, R 2 is a methyl group, and R 3 is a hydrogen atom means theophylline.
(3) R 1 is a hydrogen atom, R 2 is a methyl group, and R 3 is a methyl group means theobromine.
(4) R 1 is a methyl group, R 2 is a hydrogen atom, and R 3 is a methyl group means paraxanthine.
(5) A compound in which R 1 is a methyl group, R 2 is a methyl group, and R 3 is a 2-hydroxypropyl group means proxyphylline.
(6) The case where R 1 is a methyl group, R 2 is a methyl group, and R 3 is a 2,3-dihydroxypropyl group means diprofylline.
一般式(I)の化合物、とりわけ上述の化合物は公知であり、本発明においては、公知の方法により製造したもののほか、市販のものを用いることができる。 The compounds of the general formula (I), especially the above-mentioned compounds are known, and in the present invention, commercially available products can be used in addition to those produced by known methods.
また、本発明の医薬製剤に用いられるキサンチン誘導体又はその塩には、キサンチン誘導体のみならず、キサンチン誘導体の薬学上許容される塩、さらには水やアルコール等との溶媒和物が含まれる。
なお、本発明において、カフェインやテオフィリンとしては、複塩を形成したもの(安息香酸ナトリウムカフェイン(安息香酸ナトリウムとカフェインの複塩)、アミノフィリン(テオフィリンとエチレンジアミンとの複塩))等を用いることもできる。
Moreover, the xanthine derivative or salt thereof used in the pharmaceutical preparation of the present invention includes not only a xanthine derivative but also a pharmaceutically acceptable salt of the xanthine derivative, and further a solvate with water, alcohol or the like.
In the present invention, caffeine and theophylline include double salt (sodium benzoate caffeine (double salt of sodium benzoate and caffeine), aminophylline (double salt of theophylline and ethylenediamine)) and the like. It can also be used.
本発明の医薬製剤におけるキサンチン誘導体又はその塩としては、本発明に係る固形製剤を解熱鎮痛剤や総合感冒薬として利用した場合の観点から、カフェインが好ましい。カフェインとしては、カフェイン水和物、無水カフェイン、安息香酸ナトリウムカフェイン、クエン酸カフェインが好適な具体例として挙げられる。 As the xanthine derivative or a salt thereof in the pharmaceutical preparation of the present invention, caffeine is preferable from the viewpoint of using the solid preparation of the present invention as an antipyretic analgesic or a general cold medicine. Specific examples of caffeine include caffeine hydrate, anhydrous caffeine, sodium benzoate caffeine and caffeine citrate.
本発明の医薬製剤におけるキサンチン誘導体又はその塩の含有量は、服用者の性別、年齢、症状等に応じて、適宜検討して決定すればよいが、1日あたり、10〜1000mg服用できる量が好ましく、20〜800mg服用できる量がより好ましく、30〜700mg服用できる量がさらに好ましく、40〜600mg服用できる量が特に好ましい。キサンチン誘導体又はその塩として、カフェイン水和物を用いる場合の含有量は、1日あたり、30〜300mg服用できる量が好ましく、無水カフェインを用いる場合の含有量は、1日あたり、30〜300mg服用できる量が好ましく、安息香酸ナトリウムカフェインを用いる場合の含有量は、1日あたり、30〜300mg服用できる量が好ましく、クエン酸カフェインを用いる場合の含有量は、1日あたり、60〜300mg服用できる量が好ましい。 The content of the xanthine derivative or a salt thereof in the pharmaceutical preparation of the present invention may be determined by appropriate examination according to the sex, age, symptom, etc. of the user, but there is an amount that can be taken 10 to 1000 mg per day. Preferably, the amount that can be taken 20 to 800 mg is more preferred, the amount that can be taken 30 to 700 mg is more preferred, and the amount that can be taken 40 to 600 mg is particularly preferred. As a xanthine derivative or a salt thereof, the content when caffeine hydrate is used is preferably an amount that can be taken in an amount of 30 to 300 mg per day, and the content when anhydrous caffeine is used is 30 to 30 days per day. The amount that can be taken 300 mg is preferable, the content when using sodium caffeine benzoate is preferably 30 to 300 mg per day, the content when using caffeine citrate is 60 per day. An amount that can be taken up to 300 mg is preferred.
本発明の医薬製剤に含まれるロキソプロフェン又はその塩、及びキサンチン誘導体又はその塩の含有比は、上述した各成分の1日あたりの服用量に応じて、適宜検討して決定すればよいが、ロキソプロフェン又はその塩を、ロキソプロフェンナトリウム無水物換算で1質量部に対し、キサンチン誘導体又はその塩を、0.03〜100質量部含有するものが好ましく、0.08〜27質量部含有するものがより好ましく、0.2〜10質量部含有するものがさらに好ましい。 The content ratio of loxoprofen or a salt thereof and xanthine derivative or a salt thereof contained in the pharmaceutical preparation of the present invention may be appropriately determined and determined according to the daily dose of each component described above. Or the salt thereof is preferably one containing 0.03 to 100 parts by mass, more preferably 0.08 to 27 parts by mass of the xanthine derivative or a salt thereof based on 1 part by mass in terms of loxoprofen sodium anhydride. What contains 0.2-10 mass parts is still more preferable.
本発明の医薬製剤に含まれるロキソプロフェン又はその塩、及びキサンチン誘導体又はその塩は、服用の簡便性や薬物服用量の管理等の点で、ロキソプロフェン又はその塩とキサンチン誘導体又はその塩を含む固形製剤であるのが好ましい。
本発明の固形製剤は、第十五改正日本薬局方製剤総則等に記載の公知の方法に基づき製造、製剤化することができる。固形製剤の剤形としては、例えば、錠剤、散剤、顆粒剤、細粒剤、丸剤、カプセル剤等が挙げられる。
当該固形製剤としては、相互作用抑制の点で、固形製剤中のロキソプロフェン又はその塩及びキサンチン誘導体又はその塩を実質的に互いに接触しないように含有せしめ、製造、製剤化したものがより好ましい。当該実質的に互いに接触しないように含有せしめて製した製剤とは、一般の製剤技術研究者であれば、容易に理解されうるものであり、公知の方法に基づき、適宜製剤添加物を用いて製造、製剤化できる。具体的には、固形製剤の形態としては、以下の(イ)−(ヘ)を例示することができ、これらは公知の方法により製造、製剤化できる。
Loxoprofen or a salt thereof, and a xanthine derivative or a salt thereof included in the pharmaceutical preparation of the present invention are a solid preparation containing loxoprofen or a salt thereof and a xanthine derivative or a salt thereof in terms of convenience of administration and management of a drug dose. Is preferred.
The solid preparation of the present invention can be produced and formulated based on a known method described in the 15th revision Japanese Pharmacopoeia General Rules for Preparations. Examples of the dosage form of the solid preparation include tablets, powders, granules, fine granules, pills, capsules and the like.
As the solid preparation, in view of interaction inhibition, it is more preferable to contain loxoprofen or a salt thereof and a xanthine derivative or a salt thereof in the solid preparation so that they do not substantially come into contact with each other. The preparations prepared so as to be substantially in contact with each other can be easily understood by general pharmaceutical technology researchers, using appropriate formulation additives based on known methods. Can be manufactured and formulated. Specifically, as the form of the solid preparation, the following (a) to (f) can be exemplified, and these can be produced and formulated by a known method.
(イ)ロキソプロフェン又はその塩、及びキサンチン誘導体又はその塩のいずれか一方を適当な方法で造粒して粒状物とし、これに他方を造粒せずに含有せしめて製した散剤や顆粒剤等、並びに当該粒状物を更に適当な方法で被覆した製剤。
(ロ)ロキソプロフェン又はその塩、及びキサンチン誘導体又はその塩をそれぞれ適当な方法で別個に造粒して粒状物とし、これらを含有せしめて製した散剤や顆粒剤等、並びに当該粒状物を更に適当な方法で被覆した製剤。
(ハ)上記(イ)又は(ロ)で製した散剤や顆粒剤等をカプセルに充填したカプセル剤。(ニ)上記(イ)又は(ロ)で製した粒状物等を製錠して得た錠剤。
(ホ)ロキソプロフェン又はその塩、及びキサンチン誘導体又はその塩が互いに接触しないように製した多層錠、並びに当該多層錠を更に適当な方法で被覆した製剤。当該多層錠としては、ロキソプロフェン又はその塩、及びキサンチン誘導体又はその塩を、互いに異なる層に位置させたものが好ましく、三層以上の多層錠として、ロキソプロフェン又はその塩を含む層とキサンチン誘導体又はその塩を含む層が互いに接しないように位置させたものがより好ましい。なお、ロキソプロフェン又はその塩、及びキサンチン誘導体又はその塩として、上記(イ)や(ロ)で製した粒状物を用いることができる。
(ヘ)ロキソプロフェン又はその塩、及びキサンチン誘導体又はその塩のいずれか一方を核錠に配置した有核錠、並びに当該有核錠を更に適当な方法で被覆した製剤。なお、ロキソプロフェン又はその塩、及びキサンチン誘導体又はその塩として、上記(イ)や(ロ)で製した粒状物を用いることができる。
(I) Powders or granules produced by granulating any one of loxoprofen or a salt thereof and xanthine derivative or a salt thereof into a granular material and containing the other without granulation. In addition, a preparation in which the granular material is further coated by an appropriate method.
(B) Loxoprofen or a salt thereof, and xanthine derivative or a salt thereof are granulated separately by an appropriate method to form a granular material, and a powder or a granule prepared by containing them, and the granular material are further suitable. Coated by various methods.
(C) A capsule filled with the powder or granule prepared in (i) or (b) above. (D) Tablets obtained by tableting the granular material produced in (b) or (b) above.
(E) A multi-layer tablet prepared so that loxoprofen or a salt thereof and a xanthine derivative or a salt thereof do not contact each other, and a preparation in which the multi-layer tablet is further coated by an appropriate method. The multi-layered tablet is preferably one in which loxoprofen or a salt thereof and xanthine derivative or salt thereof are positioned in different layers, and as a multi-layered tablet having three or more layers, a layer containing loxoprofen or a salt thereof and a xanthine derivative or the salt thereof More preferably, the salt-containing layers are positioned so as not to contact each other. In addition, as the loxoprofen or a salt thereof, and the xanthine derivative or the salt thereof, the granular material produced in the above (i) or (b) can be used.
(F) A dry-coated tablet in which any one of loxoprofen or a salt thereof, and a xanthine derivative or a salt thereof is arranged in a nuclear tablet, and a preparation in which the dry-coated tablet is further coated by an appropriate method. In addition, as the loxoprofen or a salt thereof, and the xanthine derivative or the salt thereof, the granular material produced in the above (i) or (b) can be used.
本発明の固形製剤の服用経路としては、経口及び経直腸や経膣等の非経口が挙げられ、本発明の固形製剤としては、経口投与製剤が好ましい。また、本発明に係る固形製剤は、経口投与する場合、1日につき1〜4回程度に分けて、食前、食間、食後、就寝前等に服用することができる。 Examples of the route of administration of the solid preparation of the present invention include oral and parenteral such as rectal and vaginal, and the solid preparation of the present invention is preferably an oral administration preparation. In addition, when administered orally, the solid preparation according to the present invention can be divided into about 1 to 4 times per day and taken before meals, between meals, after meals, and before going to bed.
本発明において乾燥剤は、ロキソプロフェン又はその塩、及びキサンチン誘導体又はその塩とともに保存した際に、相互作用を抑制ないし改善できるものであれば、特に限定されない。また、その形状も限定されず、例えば、板状や袋状のシート型、円柱状(錠剤型)に成形されたもの等が挙げられ、円柱状のものにペーパーラッピングやフィルムコーティングを施したものでもよい。 In the present invention, the desiccant is not particularly limited as long as it can suppress or improve the interaction when stored together with loxoprofen or a salt thereof and a xanthine derivative or a salt thereof. Also, the shape is not limited, and examples thereof include a plate-shaped or bag-shaped sheet mold, a cylinder (tablet mold), etc., and a cylinder with paper wrapping or film coating. But you can.
乾燥剤としては、例えば、シリカゲル、シリカアルミナゲル(アロフェン)、天然ゼオライト、合成ゼオライト(モレキュラーシーブ)、塩化カルシウム、生石灰(酸化カルシウム)、ベントナイトクレイ(モンモリロナイト)、塩化マグネシウム及び酸化マグネシウムから選択される1種又は2種以上を挙げられ、これらと活性炭を混合したものであってもよい。これらのうち、シリカゲル、シリカアルミナゲル(アロフェン)、合成ゼオライト(モレキュラーシーブ)及び塩化カルシウムから選択される1種又は2種以上がより好ましく、相互作用抑制の点で、合成ゼオライトが特に好ましい。 Examples of the desiccant include silica gel, silica alumina gel (allophane), natural zeolite, synthetic zeolite (molecular sieve), calcium chloride, quicklime (calcium oxide), bentonite clay (montmorillonite), magnesium chloride and magnesium oxide. 1 type or 2 types or more can be mentioned, and these and activated carbon may be mixed. Among these, one or more selected from silica gel, silica alumina gel (allophane), synthetic zeolite (molecular sieve) and calcium chloride are more preferable, and synthetic zeolite is particularly preferable from the viewpoint of interaction suppression.
乾燥剤は種々市販されており、例えば、株式会社東海化学工業所製のシブレット、MS−タブレット、MS−セラムW、トーカイゲル、デシカイト25、アルプシート、山仁薬品株式会社製のドライヤーン(登録商標)分包品、ドライヤーン(登録商標)タブレット、ドライヤーン(登録商標)シート、品川化成株式会社製のセカード、アロシート、ゼオシート、株式会社OZO化学技研製のOZO、株式会社アイディ製のアイディシート、アイディパッキング乾燥剤等が挙げられる。 Various desiccants are commercially available. For example, Shiblet, MS-Tablet, MS-Serum W, Tokai Gel, Decite Kite 25, Alp sheet, Toray Chemical Co., Ltd. ) Packaged items, Dryan (registered trademark) tablets, Dryan (registered trademark) sheets, Sekawa, Allosheet, Zeosheet, Shinzo Kasei Co., Ltd., OZO Co., Ltd. OZO, IDi Co., Ltd. IDi-packing desiccant and the like.
乾燥剤の含有量は、適宜検討して決定すればよいが、ロキソプロフェン又はその塩1質量部に対して、0.05〜35質量部が好ましく、0.15〜17質量部がより好ましい。
また、ロキソプロフェン又はその塩、及びキサンチン誘導体又はその塩を含有する固形製剤1質量部に対しては、0.001〜1質量部が好ましく、0.004〜1質量部がより好ましく、0.004〜0.4質量部がさらに好ましい。
The content of the desiccant may be determined as appropriate, but is preferably 0.05 to 35 parts by mass, more preferably 0.15 to 17 parts by mass with respect to 1 part by mass of loxoprofen or a salt thereof.
Moreover, 0.001-1 mass part is preferable with respect to 1 mass part of solid preparation containing a loxoprofen or its salt, and a xanthine derivative or its salt, 0.004-1 mass part is more preferable, 0.004 -0.4 mass part is further more preferable.
本発明の医薬製剤には、医薬成分として、ロキソプロフェン又はその塩とキサンチン誘導体又はその塩以外の薬物、例えば、解熱鎮痛剤、抗ヒスタミン剤、鎮咳剤、ノスカピン類、気管支拡張剤、去痰剤、催眠鎮静剤、ビタミン類、抗炎症剤、胃粘膜保護剤、抗コリン剤、生薬類、漢方処方等からなる群より選ばれる1種又は2種以上を含んでいても良い。これら成分は、上記固形製剤中に含有させるのが好ましい。 In the pharmaceutical preparation of the present invention, as a pharmaceutical ingredient, a drug other than loxoprofen or a salt thereof and a xanthine derivative or a salt thereof, for example, an antipyretic analgesic agent, an antihistamine, an antitussive, a noscapine, a bronchodilator, an expectorant, a hypnotic sedative, It may contain one or more selected from the group consisting of vitamins, anti-inflammatory agents, gastric mucosa protective agents, anticholinergic agents, herbal medicines, Kampo prescriptions and the like. These components are preferably contained in the solid preparation.
解熱鎮痛剤としては、例えば、アスピリン、アスピリンアルミニウム、アセトアミノフェン、イソプロピルアンチピリン、イブプロフェン、エテンザミド、サザピリン、サリチルアミド、サリチル酸ナトリウム、チアラミド塩酸塩、ラクチルフェネチジン等が挙げられる。 Examples of antipyretic analgesics include aspirin, aspirin aluminum, acetaminophen, isopropylantipyrine, ibuprofen, ethenzamide, sazapyrine, salicylamide, sodium salicylate, thiaramide hydrochloride, lactylphenetidine, and the like.
抗ヒスタミン剤としては、例えば、アゼラスチン塩酸塩、アリメマジン酒石酸塩、イソチペンジル塩酸塩、イプロヘプチン塩酸塩、エピナスチン塩酸塩、エメダスチンフマル酸塩、カルビノキサミンジフェニルジスルホン酸塩、カルビノキサミンマレイン酸塩、クレマスチンフマル酸塩、dl−クロルフェニラミンマレイン酸塩、d−クロルフェニラミンマレイン酸塩、ケトチフェンフマル酸塩、ジフェテロール塩酸塩、ジフェテロールリン酸塩、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、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、ジフェンヒドラミンタンニン酸塩、トリプロリジン塩酸塩、トリペレナミン塩酸塩、トンジルアミン塩酸塩、フェネタジン塩酸塩、プロメタジン塩酸塩、プロメタジンメチレン二サリチル酸塩、メキタジン、メトジラジン塩酸塩、メブヒドロリンナパジシル酸塩等が挙げられる。 Antihistamines include, for example, azelastine hydrochloride, alimemazine tartrate, istipendil hydrochloride, iproheptin hydrochloride, epinastine hydrochloride, emedastine fumarate, carbinoxamine diphenyl disulfonate, carbinoxamine maleate, clemastine fumarate. Acid salt, dl-chlorpheniramine maleate, d-chlorpheniramine maleate, ketotifen fumarate, dipheterol hydrochloride, dipheterol phosphate, diphenylpyraline hydrochloride, diphenylpyraline theocrate, diphenhydramine Hydrochloride, diphenhydramine salicylate, diphenhydramine tannate, triprolidine hydrochloride, tripelenamine hydrochloride, tondilamine hydrochloride, phenetazine hydrochloride, promethazine hydrochloride, promethad Methylene two salicylates, mequitazine, methdilazine hydrochloride, main blanking hydro Linna Paji sill acid salts.
鎮咳剤としては、例えば、アロクラミド塩酸塩、エプラジノン塩酸塩、カルベタペンタンクエン酸塩、クロペラスチン塩酸塩、クロペラスチンフェンジゾ酸塩、コデインリン酸塩、ジヒドロコデインリン酸塩、ジブナートナトリウム、ジメモルファンリン酸塩、デキストロメトルファン臭化水素酸塩、デキストロメトルファン・フェノールフタリン塩、チペピジンクエン酸塩、チペピジンヒベンズ酸塩等が挙げられる。 Antitussives include, for example, aloclamide hydrochloride, eprazinone hydrochloride, carbetapentane enoate, cloperastine hydrochloride, cloperastine phendizoate, codeine phosphate, dihydrocodeine phosphate, dibutarate sodium, dimemorphan Examples thereof include phosphate, dextromethorphan hydrobromide, dextromethorphan / phenol phthaline salt, tipepidine citrate, and tipepidine hibenzate.
ノスカピン類としては、例えば、ノスカピン塩酸塩、ノスカピン等が挙げられる。
気管支拡張剤としては、例えば、トリメトキノール塩酸塩、フェニルプロパノールアミン塩酸塩、フェニレフリン塩酸塩、プソイドエフェドリン塩酸塩、プソイドエフェドリン硫酸塩、メチルエフェドリン、dl−メチルエフェドリン塩酸塩、l−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、メトキシフェナミン塩酸塩等が挙げられる。
Examples of noscapine include noscapine hydrochloride and noscapine.
Examples of bronchodilators include trimethquinol hydrochloride, phenylpropanolamine hydrochloride, phenylephrine hydrochloride, pseudoephedrine hydrochloride, pseudoephedrine sulfate, methylephedrine, dl-methylephedrine hydrochloride, l-methylephedrine hydrochloride, dl -Methylephedrine saccharin salt, methoxyphenamine hydrochloride, etc. are mentioned.
去痰剤としては、例えば、アンブロキソール塩酸塩、アンモニア・ウイキョウ精、エチルシステイン塩酸塩、塩化アンモニウム、カルボシステイン、グアイフェネシン、グアヤコールスルホン酸カリウム、クレゾールスルホン酸カリウム、ブロムヘキシン塩酸塩、メチルシステイン塩酸塩、l−メントール、リゾチーム塩酸塩等が挙げられる。 As an expectorant, for example, ambroxol hydrochloride, ammonia fennel, ethylcysteine hydrochloride, ammonium chloride, carbocysteine, guaifenesin, potassium guaiacolsulfonate, potassium cresolsulfonate, bromhexine hydrochloride, methylcysteine hydrochloride, Examples thereof include l-menthol and lysozyme hydrochloride.
催眠鎮静剤としては、例えば、アリルイソプロピルアセチル尿素やブロムワレリル尿素等が挙げられる。
ビタミン類としては、例えば、ビタミンB1、ビタミンB2、ビタミンB5、ビタミンB6、ビタミンB12、ビタミンC、ヘスペリジン及びその誘導体並びにそれらの塩類等(例えば、チアミン、チアミン塩化物塩酸塩、チアミン硝化物、ジセチアミン塩酸塩、セトチアミン塩酸塩、フルスルチアミン、フルスルチアミン塩酸塩、オクトチアミン、シコチアミン、チアミンジスルフィド、ビスイブチアミン、ビスベンチアミン、プロスルチアミン、ベンフォチアミン、リボフラビン、リボフラビンリン酸エステル、リボフラビン酪酸エステル、リン酸リボフラビンナトリウム、パンテノール、パンテチン、パントテン酸カルシウム、パントテン酸ナトリウム、ピリドキシン塩酸塩、ピリドキサールリン酸エステル、シアノコバラミン、メコバラミン、アスコルビン酸、アスコルビン酸ナトリウム、アスコルビン酸カルシウム、ヘスペリジン等)が挙げられる。
Examples of the hypnotic sedative include allyl isopropyl acetyl urea and bromovalerylurea.
Examples of vitamins include vitamin B 1 , vitamin B 2 , vitamin B 5 , vitamin B 6 , vitamin B 12 , vitamin C, hesperidin and derivatives thereof, and salts thereof (for example, thiamine, thiamine chloride hydrochloride, Thiamine nitrate, dicetiamine hydrochloride, sethiamine hydrochloride, fursultiamine, fursultiamine hydrochloride, octothiamine, chicotiamine, thiamine disulfide, bisibutamine, bisbenchamine, prosultiamine, benfotiamine, riboflavin, riboflavinline Acid ester, riboflavin butyrate, sodium riboflavin phosphate, panthenol, pantethine, calcium pantothenate, sodium pantothenate, pyridoxine hydrochloride, pyridoxal phosphate, cyanocobalamin, mecoba Lamin, ascorbic acid, sodium ascorbate, calcium ascorbate, hesperidin, etc.).
抗炎症剤としては、例えば、グリチルリチン酸及びその誘導体並びにそれらの塩類(例えば、グリチルリチン酸二カリウム、グリチルリチン酸モノアンモニウム等)、セアプローゼ、セミアルカリプロティナーゼ、セラペプターゼ、トラネキサム酸、プロクターゼ、プロナーゼ、ブロメライン等が挙げられる。 Examples of the anti-inflammatory agent include glycyrrhizic acid and its derivatives and salts thereof (for example, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate), seaprose, semi-alkaline proteinase, serrapeptase, tranexamic acid, proctase, pronase, bromelain and the like. Can be mentioned.
胃粘膜保護剤としては、例えば、アミノ酢酸、アルジオキサ、ケイ酸マグネシウム、ゲファルナート、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、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、スクラルファート、セトラキサート塩酸塩、ソファルコン、炭酸マグネシウム、テプレノン、銅クロロフィリンカリウム、銅クロロフィリンナトリウム、メタケイ酸アルミン酸マグネシウム、メチルメチオニンスルホニウムクロリド等が挙げられる。 Examples of the gastric mucosa protective agent include aminoacetic acid, aldioxa, magnesium silicate, gefarnate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium oxide, dihydroxyaluminum aminoacetate (aluminum glycinate), aluminum hydroxide gel, Aluminum hydroxide / magnesium carbonate mixed dry gel, aluminum hydroxide / sodium bicarbonate coprecipitation product, aluminum hydroxide / calcium carbonate / magnesium carbonate coprecipitation product, magnesium hydroxide / potassium aluminum sulfate coprecipitation product , Sucralfate, cetraxate hydrochloride, sofalcone, magnesium carbonate, teprenone, copper chlorophyllin potassium, copper chlorophyllin sodium, magnesium metasilicate aluminate, methylmethionine sulfate Niumukurorido, and the like.
抗コリン薬としては、例えば、オキシフェンサイクリミン塩酸塩、ジサイクロミン塩酸塩、メチキセン塩酸塩、スコポラミン臭化水素酸塩、ダツラエキス、チペピジウム臭化物、メチルアトロピン臭化物、メチルアニソトロピン臭化物、メチルスコポラミン臭化物、メチル−l−ヒヨスチアミン臭化物、メチルベナクチジウム臭化物、ピレンゼピン塩酸塩、ブチルスコポラミン臭化物、ベラドンナアルカロイド、ベラドンナエキス、ベラドンナ総アルカロイド、ヨウ化イソプロパミド、ヨウ化ジフェニルピペリジノメチルジオキソラン、ロートエキス、ロート根、ロート根総アルカロイドクエン酸塩等が挙げられる。 Anticholinergic agents include, for example, oxyphencyclimine hydrochloride, dicyclomine hydrochloride, methixene hydrochloride, scopolamine hydrobromide, datsura extract, chipepidium bromide, methyl atropine bromide, methyl anisotropin bromide, methyl scopolamine bromide, methyl- 1-hyostiamine bromide, methylbenactidium bromide, pirenzepine hydrochloride, butyl scopolamine bromide, belladonna alkaloid, belladonna extract, belladonna total alkaloid, iodopropamide iodide, diphenylpiperidinomethyldioxolane, funnel extract, funnel root, funnel Examples include root total alkaloid citrate.
生薬類としては、例えば、アカメガシワ(赤芽柏)、アセンヤク(阿仙薬)、インヨウカク(淫羊霍)、ウイキョウ(茴香)、ウコン(鬱金)、エンゴサク(延胡索)、エンメイソウ(延命草)、オウゴン(黄岑)、オウセイ(黄精)、オウバク(黄柏)、オウヒ(桜皮)、オウレン(黄連)、オンジ(遠志)、ガジュツ(我朮)、カノコソウ(鹿子草)、カミツレ、カロニン(か楼仁)、カンゾウ(甘草)、キキョウ(桔梗)、キョウニン(杏仁)、クコシ(枸杞子)、クコヨウ(枸杞葉)、ケイガイ(荊芥)、ケイヒ(桂皮)、ケツメイシ(決明子)、ゲンチアナ、ゲンノショウコ(現証拠)、コウブシ(香附子)、ゴオウ(牛黄)、ゴミシ(五味子)、サイシン(細辛)、サンショウ(山椒)、シオン(紫苑)、ジコッピ(地骨皮)、シャクヤク(芍薬)、ジャコウ(麝香)、シャジン(沙参)、シャゼンシ(車前子)、シャゼンソウ(車前草)、獣胆(ユウタン(熊胆)を含む)、ショウキョウ(生姜)、ジリュウ(地竜)、シンイ(辛夷)、セキサン(石蒜)、セネガ、センキュウ(川きゅう)、ゼンコ(前胡)、センブリ(千振)、ソウジュツ(蒼朮)、ソウハクヒ(桑白皮)、ソヨウ(蘇葉)、タイサン(大蒜)チクセツニンジン(竹節人参)、チョウジ(丁子)、チンピ(陳皮)、トウキ(当帰)、トコン(吐根)、ナンテンジツ(南天実)、ニンジン(人参)、バイモ(貝母)、バクモンドウ(麦門冬)、ハッカ(薄荷)、ハンゲ(半夏)、バンコウカ(番紅花)、ハンピ(反鼻)、ビャクシ(白し)、ビャクジュツ(白朮)、ブクリョウ(茯苓)、ボタンピ(牡丹皮)、ボレイ(牡蠣)、マオウ(麻黄)、ロクジョウ(鹿茸)等の生薬及びこれらの抽出物(エキス、チンキ、乾燥エキス等)等が挙げられる。 Herbal medicines include, for example, akamegashiwa (red buds), asenyaku (asenyaku), inyokaku (horny sheep), fennel (mushrooms), turmeric (depressed gold), engosaku (yenkogong), enmeisou (extended herb), ogon (yellow jade) ), Ousei (yellow spirit), Oubak (yellow twilight), Spruce (cherry skin), Auren (yellow ream), Onji (distant), Gajutsu (we), Ganoderma (deer herb), Chamomile, Caronin (Karojin), Licorice (licorice), Kyo-kyo (kikyo), Kyo-nin (Kyojin), Kukoshi (coconut), Kuko-yo (Kashiwa), Keihi (Kinko), Ketsumeishi (Katsumeko), Gentiana, Gennoshouko (current evidence), Koubushi (Kosuke), Gooh (Gyuhuang), Goshi (Gomiko), Saishin (Spicy), Salamander (Sambu), Zion (Purple), Zykopi (Peel), Peonies (Glue), Ji Jakkou, Shajin, Shazenshi (car forerunner), Shazenso (car forerunner), Beast gall (including yutan (gum gal)), Shakyo (ginger), Giryu (land dragon), Xinyi ), Sexan (Sekiyu), Senega, Senkyu (Ryukyu), Zenko (Mae-Hu), Senburi (Senshu), Sojutsu (蒼朮), Sohakuhi (Mulberry white skin), Soyo (Soba), Taisan (Otsuchi) Chiku Ginseng (bamboo ginseng), clove (clove), chimpi (Chen), Toki (to home), Tokon (root), Nantenjitsu (southern), carrot (carrot), baimo (shellfish mother), Bakumondou (baramon) Winter), mint (thin load), Hange (half-summer), bankouka (banka), hampi (anti-nose), juniper (white bean), juniper (white moth), bukkuri (茯苓), button pi (peony skin), volley ( Oyster), Maou (mao), Rokjo (deer moth) And herbal medicines such as these and extracts thereof (extracts, tinctures, dry extracts, etc.).
漢方処方としては、例えば、葛根湯、桂枝湯、香蘇散、柴胡桂枝湯、小柴胡湯、小青竜湯、麦門冬湯、半夏厚朴湯、麻黄湯等が挙げられる。 The Kampo prescription includes, for example, Kakkon-to, Katsue-yu, Koso-san, Saiko-Kei-to, Sho-saiko-to, Shosei-ryu, Mumon-tou-yu, Hanka-kopaku-to, Mao-to, etc.
本発明の医薬製剤に用いられる容器は、食品、サプリメント、医薬品や健康食品等の容器として使用可能なものであれば特に限定されないが、定形容器、不定形容器のいずれも用いることができ、密閉可能なものが好ましい。当該定形容器としては、例えば、瓶、缶、箱等が挙げられる。不定形容器としては、例えば、袋(ピロー包装、スティック包装、PTP包装、SP包装等)等が挙げられる。これら容器のうち、具体的には瓶、袋が好ましい。 The container used for the pharmaceutical preparation of the present invention is not particularly limited as long as it can be used as a container for foods, supplements, pharmaceuticals, health foods, and the like, but any of a fixed container and an amorphous container can be used and sealed. What is possible is preferred. Examples of the fixed container include bottles, cans, and boxes. Examples of the amorphous container include bags (pillow packaging, stick packaging, PTP packaging, SP packaging, etc.) and the like. Of these containers, specifically, bottles and bags are preferable.
容器の形成部材は、特に限定されるものではなく、例えば、紙、ガラス、樹脂若しくは樹脂フィルム、又は金属若しくは金属フィルム等の部材を挙げることができ、これら部材を適宜組み合わせた複合構造や多層構造としたものでもよい。また、紙などの透湿性を有する部材については透湿防止処理が施されていることが好ましい。
当該容器は透明、半透明、不透明のいずれでもよい。
The forming member of the container is not particularly limited, and examples thereof include paper, glass, a resin or a resin film, or a member such as a metal or a metal film, and a composite structure or a multilayer structure in which these members are appropriately combined. It may be a thing. Moreover, it is preferable that moisture permeation prevention processing is performed about the member which has moisture permeability, such as paper.
The container may be transparent, translucent, or opaque.
本発明に用いられる、ロキソプロフェン又はその塩、キサンチン誘導体又はその塩、及び乾燥剤を容器中へ収納する方法は、特に限定されるものではなく、いずれをも容器内へ投入等の適当な手段により配置することで達成できる。 The method of storing loxoprofen or a salt thereof, xanthine derivative or salt thereof, and a desiccant used in the present invention in a container is not particularly limited, and any of them may be performed by appropriate means such as charging into the container. This can be achieved by arranging.
容器内への収納は、例えば、容器が瓶の場合、乾燥剤(好ましくは、円柱状(錠剤型))を瓶内に配置、又は瓶蓋の裏側(内キャップ)に格納するとともに、ロキソプロフェン又はその塩、及びキサンチン誘導体又はその塩を瓶内に格納する等により達成できる。瓶内に格納するに際して、ロキソプロフェン又はその塩、及びキサンチン誘導体又はその塩は、これらを含む固形製剤としたものが好ましい。 For example, when the container is a bottle, a desiccant (preferably a cylindrical shape (tablet shape)) is placed in the bottle or stored in the back side (inner cap) of the bottle lid, and loxoprofen or This can be achieved by storing the salt and xanthine derivative or the salt thereof in a bottle. When storing in a bottle, loxoprofen or a salt thereof, and a xanthine derivative or a salt thereof are preferably solid preparations containing these.
また、容器が袋の場合は、乾燥剤(好ましくは、板状や袋状のシート型)とロキソプロフェン又はその塩、及びキサンチン誘導体又はその塩を袋内に格納する等により達成できる。袋内に格納するに際して、ロキソプロフェン又はその塩、及びキサンチン誘導体又はその塩は、これらを含む固形製剤としたものが好ましい。 In the case where the container is a bag, it can be achieved by storing a desiccant (preferably, a plate-type or bag-shaped sheet type), loxoprofen or a salt thereof, and a xanthine derivative or a salt thereof in the bag. When storing in a bag, the loxoprofen or a salt thereof and the xanthine derivative or a salt thereof are preferably solid preparations containing these.
さらに、本発明の固形製剤をSP包装、PTP包装や袋等により一旦包装し、次いで包装された固形製剤と乾燥剤を袋に同封した形態とすることもできる。例えば、スティック包装、SP包装又はPTP包装した、ロキソプロフェン又はその塩及びキサンチン誘導体又はその塩を含有する固形製剤と、ピロー包装又はスティック包装された乾燥剤とを含む形態が挙げられる。より具体的には、SP包装又はPTP包装した前記固形製剤と、板状や袋状のシート型乾燥剤とを併せてピロー包装する形態等が挙げられる。さらに当該ピロー包装形態のものは箱等に格納されてもよい。 Furthermore, the solid preparation of the present invention may be once packaged by SP packaging, PTP packaging, a bag or the like, and then the packaged solid preparation and a desiccant may be enclosed in a bag. For example, a form containing loxoprofen or a salt thereof and a xanthine derivative or a salt thereof in stick packaging, SP packaging or PTP packaging and a desiccant packaged in pillow packaging or stick packaging. More specifically, a form in which the solid preparation packed in SP or PTP and a plate-like or bag-like sheet-type desiccant are combined in a pillow package is included. Further, the pillow packaging form may be stored in a box or the like.
本発明の医薬製剤は、NSAIDの一種であるロキソプロフェン又はその塩、及び中枢興奮作用、強心・利尿作用、胃酸分泌亢進作用、平滑筋弛緩作用等を有するキサンチン誘導体を含有することから、頭痛・歯痛・抜歯後の疼痛・咽頭痛・耳痛・関節痛・神経痛・腰痛・筋肉痛・肩こり痛・打撲痛・骨折痛・ねんざ痛・月経痛(生理痛)・外傷痛の鎮痛、悪寒・発熱時の解熱、かぜの諸症状(のどの痛み、悪寒、発熱、頭痛、関節の痛み、筋肉の痛み)等に効能又は効果を有し、かぜ薬、解熱鎮痛剤等として有用である。 The pharmaceutical preparation of the present invention contains loxoprofen or a salt thereof, which is a kind of NSAID, and a xanthine derivative having a central excitatory action, cardiotonic / diuretic action, gastric acid secretion enhancing action, smooth muscle relaxing action, etc. -Pain after tooth extraction-Sore throat-Ear pain-Joint pain-Neuralgia-Back pain-Muscle pain-Stiff shoulder pain-Brute pain-Fracture pain-Pneumonia pain-Menstrual pain-Menstrual pain-Pain relief, chills, fever It is effective or effective for antipyretic and cold symptoms (throat pain, chills, fever, headache, joint pain, muscle pain), etc., and is useful as a cold medicine, antipyretic analgesic and the like.
以下に実施例を挙げて本発明を詳細に説明するが、本発明はこれら実施例に何ら限定されるものではない。
[試験例1]相互作用の検討
ロキソプロフェンナトリウム水和物0.5g(大和薬品工業製:商品名 日本薬局方 ロキソプロフェンナトリウム水和物)及び無水カフェイン0.61g(静岡カフェイン工業所製:商品名 無水カフェイン)を混合し、ガラス瓶(3K規格瓶)に入れ、40℃75%RHで保存した。別途、さらに乾燥剤として合成ゼオライト1g(新越化成工業製:商品名 MS−W1506)を入れ、同様に40℃75%RHで保存した。各々につき、保存開始直後、1週間後、1ヶ月後、2ヶ月後の混合物の状態、すなわち相互作用の有無を評価し、結果を表1に示した。
EXAMPLES The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples.
[Test Example 1] Study of interaction Loxoprofen sodium hydrate 0.5 g (manufactured by Yamato Pharmaceutical Co., Ltd .: trade name, Japanese Pharmacopoeia Loxoprofen sodium hydrate) and anhydrous caffeine 0.61 g (manufactured by Shizuoka Caffeine Kogyosho: product) Name anhydrous caffeine) was mixed, put into a glass bottle (3K standard bottle), and stored at 40 ° C. and 75% RH. Separately, 1 g of synthetic zeolite (manufactured by Shin-Etsu Chemical Co., Ltd .: trade name MS-W1506) was further added as a desiccant and similarly stored at 40 ° C. and 75% RH. For each, the state of the mixture immediately after the start of storage, one week later, one month later, and two months later, ie, the presence or absence of interaction, was evaluated, and the results are shown in Table 1.
表1から明らかなように、ロキソプロフェンと無水カフェインを混合しただけで保存したものは、相互作用が生じた結果、混合物は1週間後に固化状態に変化した。これに対し、乾燥剤を加えたものは、混合しただけのものと比べ、当該相互作用が抑制され、2ヶ月経過しても粉体状態が保持されることが判明した。 As is apparent from Table 1, the mixture of loxoprofen and anhydrous caffeine that had been preserved by mixing had an interaction, and as a result, the mixture changed to a solidified state after one week. On the other hand, it was found that the addition of the desiccant suppressed the interaction and maintained the powder state even after 2 months as compared with the case of just mixing.
[試験例2]相互作用の検討
ロキソプロフェンナトリウム水和物0.5g(大和薬品工業製:商品名 日本薬局方 ロキソプロフェンナトリウム水和物)及び安息香酸ナトリウムカフェイン0.74g(静岡カフェイン工業所製:商品名 安息香酸ナトリウムカフェイン)を混合し、ガラス瓶(3K規格瓶)に入れ、40℃75%RHで保存した。別途、さらに乾燥剤として合成ゼオライト1g(新越化成工業製:商品名 MS−W1506)を入れ、同様に40℃75%RHで保存した。各々につき、保存開始直後、1週間後、1ヶ月後、2ヶ月後の混合物の状態、すなわち相互作用の有無を評価し、結果を表2に示した。
[Test Example 2] Study of interaction Loxoprofen sodium hydrate 0.5 g (manufactured by Yamato Pharmaceutical Co., Ltd .: trade name, Japanese Pharmacopoeia Loxoprofen sodium hydrate) and sodium benzoate caffeine 0.74 g (manufactured by Shizuoka Caffeine Industry) : Brand name Sodium benzoate caffeine) was mixed, put into a glass bottle (3K standard bottle), and stored at 40 ° C. and 75% RH. Separately, 1 g of synthetic zeolite (manufactured by Shin-Etsu Chemical Co., Ltd .: trade name MS-W1506) was further added as a desiccant and similarly stored at 40 ° C. and 75% RH. For each, the state of the mixture immediately after the start of storage, one week later, one month later, two months later, ie, the presence or absence of interaction, was evaluated, and the results are shown in Table 2.
表2から明らかなように、ロキソプロフェンと安息香酸ナトリウムカフェインを混合しただけで保存したものは、相互作用が生じた結果、混合物は1ヶ月後には固化状態に変化した。これに対し、乾燥剤を加えたものは、2ヶ月経過しても開始時と同じ状態を保ち、当該相互作用を抑制し、改善できることが判明した。 As is apparent from Table 2, the mixture of loxoprofen and sodium caffeine benzoate stored as a result of interaction caused the mixture to change to a solid state after one month. On the other hand, it was found that the addition of a desiccant can maintain the same state as at the start even after 2 months and suppress and improve the interaction.
[製造例1]
ロキソプロフェンナトリウム水和物1123.7g(大和薬品工業製:商品名 日本薬局方 ロキソプロフェンナトリウム水和物)、無水カフェイン1375g(静岡カフェイ
ン工業所製:商品名 無水カフェイン)、ヒドロキシプロピルセルロース123.8g(日本曹達製:商品名 HPC−M)、カルメロースカルシウム412.5g(五徳薬品製:商品名 ECG505)、結晶セルロース1048.7g(旭化成ケミカルズ製:商品名 セオラスPH−101)を高速攪拌造粒機(深江工業製:FS−10型)に投入して混合後、精製水206.3gを添加して練合した。この造粒物を流動層乾燥機(フロイント産業製:FLO−5型)に投入して乾燥後、整粒機(岡田精工製:ND−10型)を用いて整粒した。この整粒物4083.7g及びステアリン酸マグネシウム41.3g(太平化学工業製:商品名 ステアリン酸マグネシウム(植物性))を混合機(コトブキ製:PM50型)に投入して混合した後、直径8.0mmの杵を取り付けた打錠機(畑鉄工所製:HT−AP18SS型)を用いて打錠し、1錠の質量が250mgの錠剤16500錠を得た。
[Production Example 1]
Loxoprofen sodium hydrate 1123.7 g (manufactured by Yamato Pharmaceutical Co., Ltd .: trade name, Japanese Pharmacopoeia Loxoprofen sodium hydrate), 1375 g of anhydrous caffeine (manufactured by Shizuoka Caffeine Industry: trade name: anhydrous caffeine), hydroxypropylcellulose 123. 8 g (manufactured by Nippon Soda: trade name HPC-M), carmellose calcium 412.5 g (product name: ECG505), and crystalline cellulose 1048.7 g (product name: Asahi Kasei Chemicals: trade name Theolas PH-101) After putting into a granulator (Fukae Kogyo Co., Ltd .: FS-10 type) and mixing, 206.3 g of purified water was added and kneaded. The granulated product was put into a fluidized bed dryer (Freund Sangyo: FLO-5 type), dried, and then granulated using a granulator (Okada Seiko: ND-10 type). 4083.7 g of this sized product and 41.3 g of magnesium stearate (manufactured by Taihei Kagaku Kogyo: trade name magnesium stearate (vegetable)) were introduced into a mixer (manufactured by Kotobuki: PM50 type) and mixed, and then the diameter 8 Tableting was performed using a tableting machine (manufactured by Hata Iron Works: HT-AP18SS type) equipped with a 0.0 mm punch, and 16500 tablets each having a mass of 250 mg were obtained.
[製造例2]
ロキソプロフェンナトリウム水和物1123.7g(大和薬品工業製:商品名 日本薬局方 ロキソプロフェンナトリウム水和物)、安息香酸ナトリウムカフェイン1650g(静岡カフェイン工業所製:商品名 安息香酸ナトリウムカフェイン)、ヒドロキシプロピルセルロース123.8g(日本曹達製:商品名 HPC−M)、カルメロースカルシウム412.5g(五徳薬品製:商品名 ECG505)、結晶セルロース773.7g(旭化成ケミカルズ製:商品名 セオラスPH−101)を高速攪拌造粒機(深江工業製:FS−10型)に投入して混合後、精製水206.3gを添加して練合した。この造粒物を流動層乾燥機(フロイント産業製:FLO−5型)に投入して乾燥後、整粒機(岡田精工製:ND−10型)を用いて整粒した。この整粒物4083.7g及びステアリン酸マグネシウム41.3g(太平化学工業製:商品名 ステアリン酸マグネシウム(植物性))を混合機(コトブキ製:PM50型)に投入して混合した後、直径8.0mmの杵を取り付けた打錠機(畑鉄工所製:HT−AP18SS型)を用いて打錠し、1錠の質量が250mgの錠剤16500錠を得た。
[Production Example 2]
Loxoprofen sodium hydrate 1123.7 g (manufactured by Daiwa Pharmaceutical Co., Ltd., trade name: Japanese Pharmacopoeia Loxoprofen sodium hydrate), sodium benzoate caffeine 1650 g (manufactured by Shizuoka Caffeine Industry Co., Ltd .: trade name sodium benzoate caffeine), hydroxy 123.8 g of propylcellulose (Nippon Soda: trade name HPC-M), 412.5 g of carmellose calcium (trade name: ECG505), 773.7 g of crystalline cellulose (trade name: Theolas PH-101) Was put into a high-speed stirring granulator (Fukae Kogyo Co., Ltd .: FS-10 type) and mixed, and then 206.3 g of purified water was added and kneaded. The granulated product was put into a fluidized bed dryer (Freund Sangyo: FLO-5 type), dried, and then granulated using a granulator (Okada Seiko: ND-10 type). 4083.7 g of this sized product and 41.3 g of magnesium stearate (manufactured by Taihei Kagaku Kogyo: trade name magnesium stearate (vegetable)) were introduced into a mixer (manufactured by Kotobuki: PM50 type) and mixed, and then the diameter 8 Tableting was performed using a tableting machine (manufactured by Hata Iron Works: HT-AP18SS type) equipped with a 0.0 mm punch, and 16500 tablets each having a mass of 250 mg were obtained.
[実施例1]
製造例1で得た錠剤30錠及び合成ゼオライト1g(新越化成工業製:商品名 MS−W1506)をガラス瓶(3K規格瓶)に入れ、医薬製剤を製した。
[Example 1]
Thirty tablets obtained in Production Example 1 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Chemical Co., Ltd .: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.
[実施例2]
製造例2で得た錠剤30錠及び合成ゼオライト1g(新越化成工業製:商品名 MS−W1506)をガラス瓶(3K規格瓶)に入れ、医薬製剤を製した。
[Example 2]
30 tablets obtained in Production Example 2 and 1 g of synthetic zeolite (manufactured by Shin-Etsu Chemical Co., Ltd .: trade name MS-W1506) were placed in a glass bottle (3K standard bottle) to prepare a pharmaceutical preparation.
本発明によれば、ロキソプロフェン又はその塩とキサンチン誘導体又はその塩との相互作用を抑制できる。従って、保存安定性が優れた、ロキソプロフェン又はその塩、及びキサンチン誘導体又はその塩を含む固形製剤を提供することができる。 According to the present invention, the interaction between loxoprofen or a salt thereof and a xanthine derivative or a salt thereof can be suppressed. Therefore, a solid preparation containing loxoprofen or a salt thereof and a xanthine derivative or a salt thereof having excellent storage stability can be provided.
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Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012153827A1 (en) * | 2011-05-11 | 2012-11-15 | 興和株式会社 | Stable drug composition |
WO2012157752A1 (en) * | 2011-05-18 | 2012-11-22 | 興和株式会社 | Pharmaceutical composition containing loxoprofen |
JP2012254977A (en) * | 2011-05-18 | 2012-12-27 | Kowa Co | Drug preparation |
WO2013018765A1 (en) * | 2011-07-29 | 2013-02-07 | 興和株式会社 | Pharmaceutical composition containing loxoprofen |
WO2013047869A1 (en) * | 2011-09-29 | 2013-04-04 | 興和株式会社 | Pharmaceutical composition containing loxoprofen or salt thereof |
Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH11139971A (en) * | 1997-09-05 | 1999-05-25 | Sankyo Co Ltd | Medicinal preparation containing loxoprofen |
JPH11206850A (en) * | 1998-01-29 | 1999-08-03 | Dai Ichi Seiyaku Co Ltd | Drug packaging body |
JPH11206849A (en) * | 1998-01-29 | 1999-08-03 | Dai Ichi Seiyaku Co Ltd | Drug drying body and drug packaging body |
JP2000016936A (en) * | 1998-06-30 | 2000-01-18 | Ryukakusan Co Ltd | Solid preparation containing loxoprofen sodium |
JP2001031565A (en) * | 1999-07-19 | 2001-02-06 | Nisshin Flour Milling Co Ltd | Capsule preparation containing loxoprofen sodium |
JP2006052210A (en) * | 2004-07-13 | 2006-02-23 | Sankyo Co Ltd | Loxoprofen-containing oral composition |
JP2007185488A (en) * | 2005-12-16 | 2007-07-26 | Ono Pharmaceut Co Ltd | Medication package |
JP2007314517A (en) * | 2006-04-27 | 2007-12-06 | Daiichi Sankyo Healthcare Co Ltd | Antitussive or expectorant pharmaceutical composition comprising loxoprofen |
-
2010
- 2010-07-27 JP JP2010167929A patent/JP5739626B2/en active Active
Patent Citations (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH11139971A (en) * | 1997-09-05 | 1999-05-25 | Sankyo Co Ltd | Medicinal preparation containing loxoprofen |
JPH11206850A (en) * | 1998-01-29 | 1999-08-03 | Dai Ichi Seiyaku Co Ltd | Drug packaging body |
JPH11206849A (en) * | 1998-01-29 | 1999-08-03 | Dai Ichi Seiyaku Co Ltd | Drug drying body and drug packaging body |
JP2000016936A (en) * | 1998-06-30 | 2000-01-18 | Ryukakusan Co Ltd | Solid preparation containing loxoprofen sodium |
JP2001031565A (en) * | 1999-07-19 | 2001-02-06 | Nisshin Flour Milling Co Ltd | Capsule preparation containing loxoprofen sodium |
JP2006052210A (en) * | 2004-07-13 | 2006-02-23 | Sankyo Co Ltd | Loxoprofen-containing oral composition |
JP2007185488A (en) * | 2005-12-16 | 2007-07-26 | Ono Pharmaceut Co Ltd | Medication package |
JP2007314517A (en) * | 2006-04-27 | 2007-12-06 | Daiichi Sankyo Healthcare Co Ltd | Antitussive or expectorant pharmaceutical composition comprising loxoprofen |
Non-Patent Citations (1)
Title |
---|
"お薬の保存方法と有効期限", お薬のしおり, JPN6015013125, 2005, ISSN: 0003043538 * |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012153827A1 (en) * | 2011-05-11 | 2012-11-15 | 興和株式会社 | Stable drug composition |
JP6042806B2 (en) * | 2011-05-11 | 2016-12-14 | 興和株式会社 | Stable pharmaceutical composition |
WO2012157752A1 (en) * | 2011-05-18 | 2012-11-22 | 興和株式会社 | Pharmaceutical composition containing loxoprofen |
JP2012254977A (en) * | 2011-05-18 | 2012-12-27 | Kowa Co | Drug preparation |
JPWO2012157752A1 (en) * | 2011-05-18 | 2014-07-31 | 興和株式会社 | Loxoprofen-containing pharmaceutical composition |
WO2013018765A1 (en) * | 2011-07-29 | 2013-02-07 | 興和株式会社 | Pharmaceutical composition containing loxoprofen |
WO2013047869A1 (en) * | 2011-09-29 | 2013-04-04 | 興和株式会社 | Pharmaceutical composition containing loxoprofen or salt thereof |
JPWO2013047869A1 (en) * | 2011-09-29 | 2015-03-30 | 興和株式会社 | Pharmaceutical composition containing loxoprofen or a salt thereof |
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