JP2000344682A - Cough suppressant - Google Patents
Cough suppressantInfo
- Publication number
- JP2000344682A JP2000344682A JP11157287A JP15728799A JP2000344682A JP 2000344682 A JP2000344682 A JP 2000344682A JP 11157287 A JP11157287 A JP 11157287A JP 15728799 A JP15728799 A JP 15728799A JP 2000344682 A JP2000344682 A JP 2000344682A
- Authority
- JP
- Japan
- Prior art keywords
- antitussive
- salt
- cough
- codeine
- naproxen
- 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.)
- Withdrawn
Links
- 229940124584 antitussives Drugs 0.000 title claims abstract description 22
- 239000003434 antitussive agent Substances 0.000 title claims abstract description 7
- 230000000954 anitussive effect Effects 0.000 claims abstract description 24
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 claims abstract description 12
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229960002009 naproxen Drugs 0.000 claims abstract description 11
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 claims abstract description 11
- 229960001193 diclofenac sodium Drugs 0.000 claims abstract description 9
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229960000991 ketoprofen Drugs 0.000 claims abstract description 9
- PXWLVJLKJGVOKE-UHFFFAOYSA-N propyphenazone Chemical compound O=C1C(C(C)C)=C(C)N(C)N1C1=CC=CC=C1 PXWLVJLKJGVOKE-UHFFFAOYSA-N 0.000 claims abstract description 9
- 229960002189 propyphenazone Drugs 0.000 claims abstract description 9
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 claims abstract description 9
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 claims abstract description 8
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical compound O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 claims abstract description 7
- 229960004126 codeine Drugs 0.000 claims abstract description 5
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 claims abstract description 5
- 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 4
- 229960001985 dextromethorphan Drugs 0.000 claims abstract description 4
- 229960000278 theophylline Drugs 0.000 claims abstract description 4
- FLNXBVJLPJNOSI-UHFFFAOYSA-N 1-[2-[(4-chlorophenyl)-phenylmethoxy]ethyl]piperidine Chemical compound C1=CC(Cl)=CC=C1C(C=1C=CC=CC=1)OCCN1CCCCC1 FLNXBVJLPJNOSI-UHFFFAOYSA-N 0.000 claims abstract description 3
- CFJMRBQWBDQYMK-UHFFFAOYSA-N 1-phenyl-1-cyclopentanecarboxylic acid 2-[2-(diethylamino)ethoxy]ethyl ester Chemical compound C=1C=CC=CC=1C1(C(=O)OCCOCCN(CC)CC)CCCC1 CFJMRBQWBDQYMK-UHFFFAOYSA-N 0.000 claims abstract description 3
- 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 claims abstract description 3
- 229960003556 aminophylline Drugs 0.000 claims abstract description 3
- 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 claims abstract description 3
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- JWIXXNLOKOAAQT-UHFFFAOYSA-N tipepidine Chemical compound C1N(C)CCCC1=C(C=1SC=CC=1)C1=CC=CS1 JWIXXNLOKOAAQT-UHFFFAOYSA-N 0.000 claims abstract description 3
- UHWFVIPXDFZTFA-UHFFFAOYSA-N alloclamide Chemical compound CCN(CC)CCNC(=O)C1=CC=C(Cl)C=C1OCC=C UHWFVIPXDFZTFA-UHFFFAOYSA-N 0.000 claims abstract 2
- 229950009425 alloclamide Drugs 0.000 claims abstract 2
- 206010011224 Cough Diseases 0.000 claims description 22
- 239000003814 drug Substances 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 15
- 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 claims description 13
- RBOXVHNMENFORY-DNJOTXNNSA-N dihydrocodeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC RBOXVHNMENFORY-DNJOTXNNSA-N 0.000 claims description 5
- 229960000920 dihydrocodeine Drugs 0.000 claims description 5
- XYYVYLMBEZUESM-UHFFFAOYSA-N dihydrocodeine Natural products C1C(N(CCC234)C)C2C=CC(=O)C3OC2=C4C1=CC=C2OC XYYVYLMBEZUESM-UHFFFAOYSA-N 0.000 claims description 2
- -1 dehydrocodeine Chemical compound 0.000 abstract description 6
- 229960002819 diprophylline Drugs 0.000 abstract description 2
- KSCFJBIXMNOVSH-UHFFFAOYSA-N dyphylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1N(CC(O)CO)C=N2 KSCFJBIXMNOVSH-UHFFFAOYSA-N 0.000 abstract description 2
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 abstract 2
- 239000000126 substance Substances 0.000 abstract 2
- 229940075420 xanthine Drugs 0.000 abstract 2
- 206010022000 influenza Diseases 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 230000000294 tussive effect Effects 0.000 abstract 1
- 229940079593 drug Drugs 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 208000024891 symptom Diseases 0.000 description 9
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 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
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 4
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 4
- AKNNEGZIBPJZJG-UHFFFAOYSA-N alpha-noscapine Natural products CN1CCC2=CC=3OCOC=3C(OC)=C2C1C1C2=CC=C(OC)C(OC)=C2C(=O)O1 AKNNEGZIBPJZJG-UHFFFAOYSA-N 0.000 description 4
- 239000000796 flavoring agent Substances 0.000 description 4
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- PLPRGLOFPNJOTN-UHFFFAOYSA-N narcotine Natural products COc1ccc2C(OC(=O)c2c1OC)C3Cc4c(CN3C)cc5OCOc5c4OC PLPRGLOFPNJOTN-UHFFFAOYSA-N 0.000 description 4
- 229960004708 noscapine Drugs 0.000 description 4
- 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 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- 101000879758 Homo sapiens Sjoegren syndrome nuclear autoantigen 1 Proteins 0.000 description 3
- 102000016943 Muramidase Human genes 0.000 description 3
- 108010014251 Muramidase Proteins 0.000 description 3
- 108010062010 N-Acetylmuramoyl-L-alanine Amidase Proteins 0.000 description 3
- 102100037330 Sjoegren syndrome nuclear autoantigen 1 Human genes 0.000 description 3
- 229960000985 ambroxol hydrochloride Drugs 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- 239000004359 castor oil Substances 0.000 description 3
- 235000019438 castor oil Nutrition 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 3
- 229960000274 lysozyme Drugs 0.000 description 3
- 235000010335 lysozyme Nutrition 0.000 description 3
- 239000004325 lysozyme Substances 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 241000700159 Rattus Species 0.000 description 2
- 206010041349 Somnolence Diseases 0.000 description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 229960002335 bromhexine hydrochloride Drugs 0.000 description 2
- 229960001948 caffeine Drugs 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- WHWZLSFABNNENI-UHFFFAOYSA-N epinastine Chemical compound C1C2=CC=CC=C2C2CN=C(N)N2C2=CC=CC=C21 WHWZLSFABNNENI-UHFFFAOYSA-N 0.000 description 2
- 229960002548 epinastine hydrochloride Drugs 0.000 description 2
- 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 2
- 235000019634 flavors Nutrition 0.000 description 2
- 235000013355 food flavoring agent Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000011812 mixed powder Substances 0.000 description 2
- 201000009240 nasopharyngitis Diseases 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 239000001509 sodium citrate Substances 0.000 description 2
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 2
- 239000004094 surface-active agent Substances 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- SFZVXTJDDOYGIS-DFWYDOINSA-N (2r)-2-(methylamino)-3-sulfanylpropanoic acid;hydrochloride Chemical compound [Cl-].C[NH2+][C@@H](CS)C(O)=O SFZVXTJDDOYGIS-DFWYDOINSA-N 0.000 description 1
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical class [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
- 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 1
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- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
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- 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 1
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
【0001】[0001]
【発明の属する技術分野】本発明は、風邪症候群等によ
る咳嗽症状に対し鎮咳効果が向上した咳止め薬に関す
る。BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a cough medicine having an improved antitussive effect against cough symptoms caused by cold syndrome and the like.
【0002】[0002]
【従来の技術】風邪の諸症状のなかでも、咳嗽症状は、
咳嗽反射により引き起こされ、胸部関連部位の急激な運
動を伴うため消費エネルギーも多く、咳嗽症状が継続す
ると風邪症状全体の遷延化につながると考えられてい
る。したがって、如何に早く咳嗽症状を除去又は軽減す
るかが、速やかな回復のために重要な治療上のポイント
となっている。2. Description of the Related Art Among the various symptoms of colds, cough symptoms are:
It is caused by the cough reflex and involves rapid exercise of the chest-related parts, which consumes a lot of energy, and it is thought that continuing cough symptoms may lead to prolongation of the general cold symptoms. Therefore, how to eliminate or alleviate cough symptoms is an important therapeutic point for rapid recovery.
【0003】このような状況にあって、咳嗽症状に対す
る咳止め薬は、一つにはコデイン又はその類縁物質によ
る中枢性呼吸抑制作用によるものがあり、これらの薬剤
の効果は、長年の実績があるものの、多くは麻薬性を有
しており、習慣性をはじめ傾眠や幻覚等の副作用を有し
ている。もう一つはキサンチン類縁物質に代表される気
管支筋弛緩作用によるものであるが、これらの薬剤も習
慣性、呼吸亢進、不眠、頻尿等の副作用を有している。
従って、これらの薬剤の使用には、用法及び用量に厳格
な使用上の制限があり、殊に広く生活者の使用を目的と
するセルフメディケーションの領域では不便さを来して
いた。従来より鎮咳薬を配合した多種の咳止め薬が知ら
れているものの、上記副作用発現との関係で鎮咳効果が
十分でなかった。[0003] Under such circumstances, cough suppressants for cough symptoms include, for one thing, the central respiratory depression effect of codeine or its analogs, and the effects of these drugs have been proven for many years. However, many of them are narcotic and have side effects such as addiction, somnolence and hallucinations. The other is due to a bronchial muscle relaxing action typified by xanthine analogs, but these drugs also have side effects such as habit, hyperpnea, insomnia, and frequent urination.
Therefore, the use of these drugs has strict use restrictions on the usage and dosage, and has been inconvenient, especially in the area of self-medication intended for widespread use by consumers. Conventionally, various antitussives containing an antitussive have been known, but the antitussive effect was insufficient due to the above-mentioned side effects.
【0004】[0004]
【発明が解決しようとする課題】本発明は、風邪症候群
等による咳嗽症状に対し鎮咳効果が向上した咳止め薬を
提供することにある。SUMMARY OF THE INVENTION An object of the present invention is to provide a cough suppressant having an improved antitussive effect against cough symptoms such as a cold syndrome.
【0005】[0005]
【課題を解決するための手段】本発明者らは、上記目的
を解決するために鋭意研究した結果、鎮咳薬にナプロキ
セン、ケトプロフェン、ジクロフェナクナトリウム又は
イソプロピルアンチピリンを配合することにより鎮咳効
果が劇的に改善されることを見い出し、本発明を完成し
た。すなわち、本発明は(A)鎮咳薬、及び(B)ナプ
ロキセン、ケトプロフェン、ジクロフェナクナトリウム
又はイソプロピルアンチピリンを含有する咳止め薬であ
る。Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems, and as a result, the antitussive effect has been dramatically improved by adding naproxen, ketoprofen, diclofenac sodium or isopropylantipyrine to an antitussive. The inventors have found that the present invention is improved and completed the present invention. That is, the present invention is a cough medicine containing (A) an antitussive and (B) naproxen, ketoprofen, diclofenac sodium or isopropylantipyrine.
【0006】[0006]
【発明の実施の形態】本発明における鎮咳薬とは、医薬
品として使用されるものでコデイン若しくはその塩(例
えば、リン酸塩)、ジヒドロコデイン若しくはその塩
(例えば、リン酸塩)、デキストロメトルファン若しく
はその塩(例えば、臭化水素酸塩)、テオフィリン、ア
ミノフィリン、ジプロフィリン、プロキシフィリン、ク
ロペラスチン若しくはその塩(例えば、塩酸塩)、チペ
ピジン若しくはその塩(例えば、クエン酸塩)、ペント
キシベリン若しくはその塩(例えば、クエン酸塩)、又
はアロクラミド若しくはその塩(例えば、塩酸塩)を挙
げることができ、これらのいずれか1種を用いることが
できる。また本発明には上記以外の鎮咳作用を有する成
分を含んでもよい。BEST MODE FOR CARRYING OUT THE INVENTION An antitussive in the present invention is used as a medicament and is codeine or a salt thereof (for example, phosphate), dihydrocodeine or a salt thereof (for example, phosphate), dextromethorphan or Salt thereof (eg, hydrobromide), theophylline, aminophylline, diprofylline, proxyphylline, cloperastine or a salt thereof (eg, hydrochloride), tipepidine or a salt thereof (eg, citrate), pentoxiverine or a salt thereof (E.g., citrate), or allocramide or a salt thereof (e.g., hydrochloride), and any one of these can be used. Further, the present invention may contain components having an antitussive action other than the above.
【0007】本発明において(A)鎮咳剤、と配合して
鎮咳効果を増強する成分としては、(B)ナプロキセ
ン、ケトプロフェン、ジクロフェナクナトリウム又はイ
ソプロピルアンチピリンである。これらは解熱鎮痛薬・
抗炎症薬として知られているものであり、これらのいず
れか1種を用いることができる。本発明では上記以外の
解熱鎮痛作用・抗炎症作用を有する成分を含んでもよ
い。In the present invention, the component which enhances the antitussive effect by being combined with (A) an antitussive is (B) naproxen, ketoprofen, diclofenac sodium or isopropylantipyrine. These are antipyretic analgesics
It is known as an anti-inflammatory drug, and any one of these can be used. In the present invention, a component having an antipyretic analgesic action / anti-inflammatory action other than the above may be included.
【0008】本発明の特徴は(A)鎮咳薬に、(B)ナ
プロキセン、ケトプロフェン、ジクロフェナクナトリウ
ム又はイソプロピルアンチピリンを配合することによ
り、鎮咳効果を増強する点にあるが、その結果鎮咳薬に
起因する副作用の発現が低減できるという利点を有す
る。A feature of the present invention resides in that the coughing effect is enhanced by adding (B) naproxen, ketoprofen, diclofenac sodium or isopropylantipyrine to (A) an antitussive, which results from the antitussive. This has the advantage that the occurrence of side effects can be reduced.
【0009】なお、必要に応じて、去痰薬、抗ヒスタミ
ン(抗アレルギー)薬、気管支拡張薬、消炎(抗炎症)
酵素薬、抗コリン薬、眠気防止薬、ビタミン類、生薬、
制酸薬等を適宜配合して、咳嗽症状以外の他の風邪症状
にも対応した薬剤とすることもできる。If necessary, expectorants, antihistamine (antiallergic) drugs, bronchodilators, anti-inflammatory (anti-inflammatory)
Enzyme drugs, anticholinergics, drowsiness drugs, vitamins, crude drugs,
An antacid or the like may be appropriately compounded to prepare a drug for other cold symptoms other than cough symptoms.
【0010】本発明の咳止め薬は通常、成人に対して1
日当たり有効成分として300〜1500mgを、1回
ないし数回に分けて経口服用することができる。この服
用量は、年齢、体重、病状により適宜増減することがで
きる。[0010] The cough medicine of the present invention is usually used for adults.
300-1500 mg as an active ingredient per day can be taken orally in one or several divided doses. This dose can be appropriately adjusted according to age, weight, and medical condition.
【0011】(A)鎮咳薬、に対する(B)成分の配合
比は、鎮咳薬の種類や服用量により広い範囲で選択で
き、(A)鎮咳薬1重量部に対して、(B)成分がナプ
ロキセン、ケトプロフェン、ジクロフェナクナトリウム
の場合には0.01〜300重量部がよく、好ましくは
0.05〜120で、更に好ましくは0.75〜100
重量部であり、(B)成分がイソプロピルアンチピリン
の場合には、0.03〜180重量部がよく、好ましく
は0.1〜60で、更に好ましくは0.2〜50重量部
である。配合比がこの範囲外となると鎮咳効果の改善が
なされない場合がある。The mixing ratio of the component (B) to the (A) antitussive can be selected in a wide range depending on the type and dosage of the antitussive, and (B) the component (B) per 1 part by weight of the antitussive. In the case of naproxen, ketoprofen, diclofenac sodium, the amount is preferably 0.01 to 300 parts by weight, preferably 0.05 to 120, more preferably 0.75 to 100.
Parts by weight, and when the component (B) is isopropylantipyrine, the amount is preferably 0.03 to 180 parts by weight, more preferably 0.1 to 60 parts by weight, and even more preferably 0.2 to 50 parts by weight. If the compounding ratio is out of this range, the antitussive effect may not be improved.
【0012】本発明の咳止め薬は例えば錠剤、顆粒剤、
細粒剤、散剤、カプセル剤、チュアブル剤、発泡剤、ド
ロップ剤、口中瞬間溶解剤、ドライシロップ剤、内服液
剤、吸入剤、ストリーム剤等の服用形態の製剤として用
いることができる。The cough medicine of the present invention includes, for example, tablets, granules,
It can be used as a dosage form such as fine granules, powders, capsules, chewables, foaming agents, drops, instant dissolving agents in the mouth, dry syrups, oral liquids, inhalants, and streams.
【0013】これらの製剤は、常法により調製すること
ができ、特に制限されない。固形製剤の調製に際して使
用できる添加剤としては、賦形剤、結合剤、崩壊剤、界
面活性剤、抗酸化剤、滑沢剤、コーティング剤があり、
この他必要に応じて香料、色素、矯味剤などを使用する
ことができる。These preparations can be prepared by a conventional method and are not particularly limited. Excipients that can be used in the preparation of solid preparations include excipients, binders, disintegrants, surfactants, antioxidants, lubricants, coating agents,
In addition, flavors, pigments, flavoring agents, and the like can be used as needed.
【0014】また、内服液剤の調製に際しては使用でき
る添加剤としては、界面活性剤、増粘剤、pH調整剤が
あり、この他必要に応じて溶解補助剤、保存剤、甘味
剤、香料、色素、矯味剤等を使用することができる。[0014] Additives that can be used in the preparation of a liquid medicine for internal use include a surfactant, a thickener, and a pH adjuster. In addition, if necessary, a solubilizing agent, a preservative, a sweetener, a flavor, Dyes, flavoring agents and the like can be used.
【0015】その他の形態の製剤についても、通常これ
らの製剤に使用されている添加剤等を用いることができ
る。For other forms of preparations, additives and the like usually used for these preparations can be used.
【0016】[0016]
【実施例】以下に実施例及び試験例を挙げ本発明をさら
に詳しく説明するが、本発明は下記の例に限定されるも
のではない。The present invention will be described in more detail with reference to the following Examples and Test Examples, but the present invention is not limited to the following Examples.
【0017】実施例1 リン酸ジヒドロコデイン30mg、ナプロキセン300
mgを精製水に溶解し、クエン酸及びクエン酸ナトリウ
ムでpHを4.2に調整した後、精製水を加えて全量を
50mLとした。Example 1 Dihydrocodeine phosphate 30 mg, naproxen 300
mg was dissolved in purified water, the pH was adjusted to 4.2 with citric acid and sodium citrate, and purified water was added to adjust the total volume to 50 mL.
【0018】実施例2〜24 表1〜6に示す成分及び分量を秤量し、実施例1に準じ
て調製した。Examples 2 to 24 Components and amounts shown in Tables 1 to 6 were weighed and prepared according to Example 1.
【0019】実施例25 下記の各成分及び分量を秤量し均一に混合した後、得ら
れた混合粉末を2号硬カプセルに200mgずつ充填し
た。Example 25 The following components and amounts were weighed and uniformly mixed, and then 200 mg of the obtained mixed powder was filled in a No. 2 hard capsule.
【0020】 ナプロキセン 300g リン酸ジヒドロコデイン 24g ノスカピン 48g マレイン酸クロルフェニラミン 12g 塩酸メトキシフェナミン 250g 塩酸ブロムヘキシン 12g 乳糖 250g 微結晶セルロース 186g ステアリン酸マグネシウム 14g 実施例26 下記の各成分及び分量を秤量し均一に混合した後、得ら
れた混合粉末を直打法により1錠重量250mgになる
ように打錠した。Naproxen 300 g Dihydrocodeine phosphate 24 g Noscapine 48 g Chlorpheniramine maleate 12 g Methoxyphenamine hydrochloride 250 g Bromhexine hydrochloride 12 g Lactose 250 g Microcrystalline cellulose 186 g Magnesium stearate 14 g Example 26 The following components and amounts were weighed and mixed uniformly. After that, the obtained mixed powder was tableted by a direct compression method so that the weight of one tablet became 250 mg.
【0021】 ケトプロフェン 100g 塩酸エピナスチン 20g デキストロメトルファン 24g ノスカピン 48g 塩酸アンブロキソール 45g 塩化リゾチーム 90g(力価) 乳糖 340g 微結晶セルロース 300g ステアリン酸マグネシウム 18g 硬化ヒマシ油 15g 実施例27 下記の各成分及び分量を秤量し均一に混合した後、実施
例26に準拠し1錠重量300mgになるように打錠し
た。Ketoprofen 100 g Epinastine hydrochloride 20 g Dextromethorphan 24 g Noscapine 48 g Ambroxol hydrochloride 45 g Lysozyme chloride 90 g (titer) Lactose 340 g Microcrystalline cellulose 300 g Magnesium stearate 18 g Hardened castor oil 15 g Example 27 The following components and amounts After weighing and mixing uniformly, tableting was performed so that the weight per tablet was 300 mg according to Example 26.
【0022】 ジクロフェナクナトリウム 75g フマル酸ケトチフェン 2g テオフィリン 450g ノスカピン 48g 塩酸トリメトキノール 6g 塩酸アンブロキソール 45g 塩化リゾチーム 60g(力価) 乳糖 400g 微結晶セルロース 375g ステアリン酸マグネシウム 20g 硬化ヒマシ油 19g 実施例28 下記の各成分及び分量を秤量し均一に混合した後、実施
例26に準拠し1錠重量300mgになるように打錠し
た。Diclofenac sodium 75 g Ketotifen fumarate 2 g Theophylline 450 g Noscapine 48 g Trimethoxinol hydrochloride 6 g Ambroxol hydrochloride 45 g Lysozyme chloride 60 g (titer) Lactose 400 g Microcrystalline cellulose 375 g Magnesium stearate 20 g Hardened castor oil Example 19 g of the following: After weighing and uniformly mixing the components and amounts, the tablets were compressed to a tablet weight of 300 mg according to Example 26.
【0023】 イソプロピルアンチピリン 150g フマル酸ケトチフェン 2g ジプロフィリン 325g ノスカピン 48g 塩酸アンブロキソール 45g 塩酸メチルシステイン 300g 塩酸トリメトキノール 6g プロキシフィリン 210g 無水カフェイン 75g ビタミンB1硝酸塩 8g ビタミンB2 4g 乳糖 300g 微結晶セルロース 290g ステアリン酸マグネシウム 20g 硬化ヒマシ油 17g 実施例29 蒸留水に下記成分を加え撹拌し均一にした。その後、p
H調整剤(クエン酸緩衝液)にてpH4.2に調整し、蒸
留水を加えて全量を50Lにして製した。[0023] Ketotifen isopropyl antipyrine 150g Fumaric acid 2g diprophylline 325g noscapine 48g ambroxol hydrochloride 45g hydrochloride methylcysteine 300g hydrochloride trimetoquinol Nord 6g proxy Villingen 210g anhydrous caffeine 75g Vitamin B 1 nitrate 8g vitamin B 2 4g Lactose 300g Microcrystalline cellulose 290g Magnesium stearate 20 g Hardened castor oil 17 g Example 29 The following components were added to distilled water, and the mixture was stirred to be uniform. Then p
The pH was adjusted to 4.2 with an H adjuster (citrate buffer), and distilled water was added to make the total volume 50 L.
【0024】 ナプロキセン 300g リン酸ジヒドロコデイン 24g 塩酸エピナスチン 20g dl−塩酸メチルエフェドリン 60g 塩酸ブロムヘキシン 12g 塩化リゾチーム 60g(力価) 無水カフェイン 50g ビタミンC 100g D−ソルビトール 50g クエン酸ナトリウム 5g ポリオキシエチレン硬化ヒマシ油 1g 香料 微 量 比較例1〜10 表7〜8に示す成分及び分量を秤量し、実施例1に準じ
て調製した。Naproxen 300 g Dihydrocodeine phosphate 24 g Epinastine hydrochloride 20 g dl-Methylephedrine hydrochloride 60 g Bromhexine hydrochloride 12 g Lysozyme chloride 60 g (titer) Anhydrous caffeine 50 g Vitamin C 100 g D-sorbitol 50 g Sodium citrate 5 g Polyoxyethylene cured g Fragrance Fine amount Comparative examples 1 to 10 Components and amounts shown in Tables 7 to 8 were weighed and prepared according to Example 1.
【0025】試験例 配合製剤の咳嗽症状に対する作
用 試験方法 ddY系雄性ラットを用い、各群5匹に実施例1〜2
4、比較例1〜10の薬剤を、下記の気体暴露前24時
間、12時間、1時間の3回に毎回3mLを経口投与し
た。その後、亜硫酸ガスを2.5%混合した気体中にd
dY系雄性ラットを5秒間暴露させ人工的に発生した咳
嗽反応の1分間当たりの反応回数を測定した。この値と
精製水3mLにつき同様に操作して得た値から抑制率を
算出し、比較評価した。これらの結果をまとめて表1〜
8に示した。これらの結果から、明らかなように、鎮咳
薬にナプロキセン、ケトプロフェン、ジクロフェナクナ
トリウムを配合した製剤にあっては、咳嗽反応に対する
著しい抑制効果が認められた。同様な結果がイソプロピ
ルアンチピリンを配合した場合にも認められた。Test Example Effect of the Combined Preparation on Cough Symptoms Test Method Using ddY male rats, Examples 1 to 2
4. The drug of Comparative Examples 1 to 10 was orally administered 3 mL every 24 hours, 12 hours, and 1 hour before the following gas exposure. Then, d was mixed in a gas containing 2.5% sulfur dioxide.
The dY male rats were exposed for 5 seconds and the number of artificially generated coughing reactions per minute was measured. The inhibition rate was calculated from this value and a value obtained by performing the same operation for 3 mL of purified water, and the results were compared and evaluated. Table 1 summarizes these results.
8 is shown. From these results, it is clear that the preparation containing naproxen, ketoprofen, and diclofenac sodium combined with an antitussive had a remarkable inhibitory effect on the cough reaction. Similar results were observed when isopropylantipyrine was added.
【0026】[0026]
【表1】 [Table 1]
【0027】[0027]
【表2】 [Table 2]
【0028】[0028]
【表3】 [Table 3]
【0029】[0029]
【表4】 [Table 4]
【0030】[0030]
【表5】 [Table 5]
【0031】[0031]
【表6】 [Table 6]
【0032】[0032]
【表7】 [Table 7]
【0033】[0033]
【表8】 [Table 8]
【0034】[0034]
【発明の効果】本発明により、鎮咳薬の咳嗽抑制効果が
著しく向上した結果、風邪症候群等に対して有用な咳止
め薬を提供することが可能となった。According to the present invention, the cough suppressing effect of the antitussive has been remarkably improved. As a result, it has become possible to provide a cough medicine useful for cold syndrome and the like.
───────────────────────────────────────────────────── フロントページの続き (51)Int.Cl.7 識別記号 FI テーマコート゛(参考) A61K 31/215 A61K 31/215 31/415 601 31/415 601 31/445 601 31/445 601 613 613 31/485 31/485 31/52 601 31/52 601 C07D 409/14 C07D 409/14 // C07D 295/08 295/08 Z 473/08 473/08 Fターム(参考) 4C063 AA03 BB03 CC92 DD10 EE01 4C084 AA18 MA02 NA06 NA14 ZA081 ZA621 ZA622 ZB111 4C086 AA01 AA02 CB07 CB23 GA04 GA07 MA02 NA06 NA14 ZA62 4C206 AA01 AA02 DA22 DA23 DA25 FA03 GA07 MA02 NA06 NA14 ZA62 ──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. 7 Identification symbol FI Theme court ゛ (Reference) A61K 31/215 A61K 31/215 31/415 601 31/415 601 31/445 601 31/445 601 613 613 31 / 485 31/485 31/52 601 31/52 601 C07D 409/14 C07D 409/14 // C07D 295/08 295/08 Z 473/08 473/08 F term (reference) 4C063 AA03 BB03 CC92 DD10 EE01 4C084 AA18 MA02 NA06 NA14 ZA081 ZA621 ZA622 ZB111 4C086 AA01 AA02 CB07 CB23 GA04 GA07 MA02 NA06 NA14 ZA62 4C206 AA01 AA02 DA22 DA23 DA25 FA03 GA07 MA02 NA06 NA14 ZA62
Claims (4)
ケトプロフェン、ジクロフェナクナトリウム又はイソプ
ロピルアンチピリンを含有する咳止め薬。(1) an antitussive, (B) naproxen,
A cough medicine containing ketoprofen, diclofenac sodium or isopropylantipyrine.
イン類縁物質若しくはその塩、キサンチン類縁物質、ク
ロペラスチン若しくはその塩、チペピジン若しくはその
塩、ペントキシベリン若しくはその塩、又はアロクラミ
ド若しくはその塩である請求項1に記載の咳止め薬。2. The antitussive agent is codeine or a salt thereof, codeine analog or a salt thereof, xanthine analog, cloperastine or a salt thereof, tipepidine or a salt thereof, pentoxiverine or a salt thereof, or alloclamide or a salt thereof. Item 4. The cough medicine according to item 1.
しくはその塩、又はデキストロメトルファン若しくはそ
の塩である請求項2に記載の咳止め薬。3. The cough medicine according to claim 2, wherein the codeine analog is dihydrocodeine or a salt thereof, or dextromethorphan or a salt thereof.
ミノフィリン、ジプロフィリン、又はプロキシフィリン
である請求項2に記載の咳止め薬。4. The cough remedy according to claim 2, wherein the xanthine analog is theophylline, aminophylline, diprofylline or proxyphylline.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP11157287A JP2000344682A (en) | 1999-06-04 | 1999-06-04 | Cough suppressant |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP11157287A JP2000344682A (en) | 1999-06-04 | 1999-06-04 | Cough suppressant |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2000344682A true JP2000344682A (en) | 2000-12-12 |
Family
ID=15646368
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP11157287A Withdrawn JP2000344682A (en) | 1999-06-04 | 1999-06-04 | Cough suppressant |
Country Status (1)
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JP (1) | JP2000344682A (en) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011016534A1 (en) | 2009-08-06 | 2011-02-10 | 一般財団法人化学及血清療法研究所 | Plasma protein having antitussive effect |
CN104434789A (en) * | 2014-12-27 | 2015-03-25 | 昆明振华制药厂有限公司 | Preparing method of citron pentoxyverine syrup |
JP2018076306A (en) * | 2016-10-31 | 2018-05-17 | エスエス製薬株式会社 | Cold remedy |
CN113288878A (en) * | 2021-04-15 | 2021-08-24 | 地奥集团成都药业股份有限公司 | Cloperidine hydrochloride tablet and preparation method thereof |
-
1999
- 1999-06-04 JP JP11157287A patent/JP2000344682A/en not_active Withdrawn
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2011016534A1 (en) | 2009-08-06 | 2011-02-10 | 一般財団法人化学及血清療法研究所 | Plasma protein having antitussive effect |
US8569238B2 (en) | 2009-08-06 | 2013-10-29 | The Chemo-Sero-Therapeutic Research Institute | Plasma protein effective for suppressing cough |
CN104434789A (en) * | 2014-12-27 | 2015-03-25 | 昆明振华制药厂有限公司 | Preparing method of citron pentoxyverine syrup |
CN104434789B (en) * | 2014-12-27 | 2017-04-26 | 昆明振华制药厂有限公司 | Preparing method of citron pentoxyverine syrup |
JP2018076306A (en) * | 2016-10-31 | 2018-05-17 | エスエス製薬株式会社 | Cold remedy |
JP7163014B2 (en) | 2016-10-31 | 2022-10-31 | エスエス製薬株式会社 | cold medicine |
CN113288878A (en) * | 2021-04-15 | 2021-08-24 | 地奥集团成都药业股份有限公司 | Cloperidine hydrochloride tablet and preparation method thereof |
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A761 | Written withdrawal of application |
Free format text: JAPANESE INTERMEDIATE CODE: A761 Effective date: 20060518 |