CN1278728A - 治疗呼吸系统疾病的组合物和方法 - Google Patents
治疗呼吸系统疾病的组合物和方法 Download PDFInfo
- Publication number
- CN1278728A CN1278728A CN98811202A CN98811202A CN1278728A CN 1278728 A CN1278728 A CN 1278728A CN 98811202 A CN98811202 A CN 98811202A CN 98811202 A CN98811202 A CN 98811202A CN 1278728 A CN1278728 A CN 1278728A
- Authority
- CN
- China
- Prior art keywords
- flu
- composition
- pharmaceutical composition
- compositions
- 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.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 57
- 238000000034 method Methods 0.000 title abstract description 7
- 208000023504 respiratory system disease Diseases 0.000 title description 2
- 206010022000 influenza Diseases 0.000 claims abstract description 39
- ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 claims abstract description 17
- 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 16
- 229960001803 cetirizine Drugs 0.000 claims abstract description 16
- 229960002009 naproxen Drugs 0.000 claims abstract description 16
- 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 16
- 206010020751 Hypersensitivity Diseases 0.000 claims abstract description 7
- 208000026935 allergic disease Diseases 0.000 claims abstract description 7
- 230000007815 allergy Effects 0.000 claims abstract description 7
- -1 Alpha-hydroxy-α-phenylbenzyl Chemical group 0.000 claims description 19
- 150000001875 compounds Chemical class 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 16
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 claims description 14
- 206010011224 Cough Diseases 0.000 claims description 13
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 230000001387 anti-histamine Effects 0.000 claims description 9
- 239000000739 antihistaminic agent Substances 0.000 claims description 9
- 206010022004 Influenza like illness Diseases 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 claims description 7
- 229960001948 caffeine Drugs 0.000 claims description 7
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 claims description 7
- 206010028735 Nasal congestion Diseases 0.000 claims description 6
- 208000002193 Pain Diseases 0.000 claims description 6
- 229940124584 antitussives Drugs 0.000 claims description 6
- 239000000850 decongestant Substances 0.000 claims description 6
- 239000003172 expectorant agent Substances 0.000 claims description 6
- 230000003419 expectorant effect Effects 0.000 claims description 6
- 230000000202 analgesic effect Effects 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 4
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 4
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 claims description 4
- 239000004472 Lysine Substances 0.000 claims description 4
- 239000003434 antitussive agent Substances 0.000 claims description 4
- 229960001680 ibuprofen Drugs 0.000 claims description 4
- 229960001140 cyproheptadine Drugs 0.000 claims description 3
- JJCFRYNCJDLXIK-UHFFFAOYSA-N cyproheptadine Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2C=CC2=CC=CC=C21 JJCFRYNCJDLXIK-UHFFFAOYSA-N 0.000 claims description 3
- 230000000144 pharmacologic effect Effects 0.000 claims description 3
- LZFCSDIBLCSFAK-WLHGVMLRSA-N (e)-but-2-enedioic acid;2-[2-(dimethylamino)ethyl]-4-methyl-2,3-dihydropyrido[3,2-f][1,4]oxazepine-5-thione Chemical compound OC(=O)\C=C\C(O)=O.O1C(CCN(C)C)CN(C)C(=S)C2=CC=CN=C21 LZFCSDIBLCSFAK-WLHGVMLRSA-N 0.000 claims description 2
- JTOUASWUIMAMAD-UHFFFAOYSA-N 7-[2-hydroxy-3-[4-(3-phenylsulfanylpropyl)piperazin-1-yl]propyl]-1,3-dimethylpurine-2,6-dione Chemical compound C1=2C(=O)N(C)C(=O)N(C)C=2N=CN1CC(O)CN(CC1)CCN1CCCSC1=CC=CC=C1 JTOUASWUIMAMAD-UHFFFAOYSA-N 0.000 claims description 2
- 239000004475 Arginine Substances 0.000 claims description 2
- DBAKFASWICGISY-BTJKTKAUSA-N Chlorpheniramine maleate Chemical compound OC(=O)\C=C/C(O)=O.C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 DBAKFASWICGISY-BTJKTKAUSA-N 0.000 claims description 2
- ZCVMWBYGMWKGHF-UHFFFAOYSA-N Ketotifene Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2CC(=O)C2=C1C=CS2 ZCVMWBYGMWKGHF-UHFFFAOYSA-N 0.000 claims description 2
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 2
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 claims description 2
- HOKDBMAJZXIPGC-UHFFFAOYSA-N Mequitazine Chemical compound C12=CC=CC=C2SC2=CC=CC=C2N1CC1C(CC2)CCN2C1 HOKDBMAJZXIPGC-UHFFFAOYSA-N 0.000 claims description 2
- ISFHAYSTHMVOJR-UHFFFAOYSA-N Phenindamine Chemical compound C1N(C)CCC(C2=CC=CC=C22)=C1C2C1=CC=CC=C1 ISFHAYSTHMVOJR-UHFFFAOYSA-N 0.000 claims description 2
- UFLGIAIHIAPJJC-UHFFFAOYSA-N Tripelennamine Chemical compound C=1C=CC=NC=1N(CCN(C)C)CC1=CC=CC=C1 UFLGIAIHIAPJJC-UHFFFAOYSA-N 0.000 claims description 2
- 239000000556 agonist Substances 0.000 claims description 2
- 239000000730 antalgic agent Substances 0.000 claims description 2
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 2
- GXDALQBWZGODGZ-UHFFFAOYSA-N astemizole Chemical compound C1=CC(OC)=CC=C1CCN1CCC(NC=2N(C3=CC=CC=C3N=2)CC=2C=CC(F)=CC=2)CC1 GXDALQBWZGODGZ-UHFFFAOYSA-N 0.000 claims description 2
- SEBMTIQKRHYNIT-UHFFFAOYSA-N azatadine Chemical compound C1CN(C)CCC1=C1C2=NC=CC=C2CCC2=CC=CC=C21 SEBMTIQKRHYNIT-UHFFFAOYSA-N 0.000 claims description 2
- 229960000383 azatadine Drugs 0.000 claims description 2
- 229960003166 bromazine Drugs 0.000 claims description 2
- NUNIWXHYABYXKF-UHFFFAOYSA-N bromazine Chemical compound C=1C=C(Br)C=CC=1C(OCCN(C)C)C1=CC=CC=C1 NUNIWXHYABYXKF-UHFFFAOYSA-N 0.000 claims description 2
- ZDIGNSYAACHWNL-UHFFFAOYSA-N brompheniramine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Br)C=C1 ZDIGNSYAACHWNL-UHFFFAOYSA-N 0.000 claims description 2
- 229960000725 brompheniramine Drugs 0.000 claims description 2
- 229960000428 carbinoxamine Drugs 0.000 claims description 2
- OJFSXZCBGQGRNV-UHFFFAOYSA-N carbinoxamine Chemical compound C=1C=CC=NC=1C(OCCN(C)C)C1=CC=C(Cl)C=C1 OJFSXZCBGQGRNV-UHFFFAOYSA-N 0.000 claims description 2
- 229960003291 chlorphenamine Drugs 0.000 claims description 2
- 238000005520 cutting process Methods 0.000 claims description 2
- ZDIGNSYAACHWNL-HNNXBMFYSA-N dexbrompheniramine Chemical compound C1([C@H](CCN(C)C)C=2N=CC=CC=2)=CC=C(Br)C=C1 ZDIGNSYAACHWNL-HNNXBMFYSA-N 0.000 claims description 2
- 229960002691 dexbrompheniramine Drugs 0.000 claims description 2
- SOYKEARSMXGVTM-HNNXBMFYSA-N dexchlorpheniramine Chemical compound C1([C@H](CCN(C)C)C=2N=CC=CC=2)=CC=C(Cl)C=C1 SOYKEARSMXGVTM-HNNXBMFYSA-N 0.000 claims description 2
- 229960001882 dexchlorpheniramine Drugs 0.000 claims description 2
- 229960001259 diclofenac Drugs 0.000 claims description 2
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 claims description 2
- 229960005178 doxylamine Drugs 0.000 claims description 2
- HCFDWZZGGLSKEP-UHFFFAOYSA-N doxylamine Chemical compound C=1C=CC=NC=1C(C)(OCCN(C)C)C1=CC=CC=C1 HCFDWZZGGLSKEP-UHFFFAOYSA-N 0.000 claims description 2
- 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 description 2
- 229960000991 ketoprofen Drugs 0.000 claims description 2
- 229960004958 ketotifen Drugs 0.000 claims description 2
- 229960004305 lodoxamide Drugs 0.000 claims description 2
- RVGLGHVJXCETIO-UHFFFAOYSA-N lodoxamide Chemical compound OC(=O)C(=O)NC1=CC(C#N)=CC(NC(=O)C(O)=O)=C1Cl RVGLGHVJXCETIO-UHFFFAOYSA-N 0.000 claims description 2
- YECBIJXISLIIDS-UHFFFAOYSA-N mepyramine Chemical compound C1=CC(OC)=CC=C1CN(CCN(C)C)C1=CC=CC=N1 YECBIJXISLIIDS-UHFFFAOYSA-N 0.000 claims description 2
- 229960005042 mequitazine Drugs 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 229960005419 nitrogen Drugs 0.000 claims description 2
- BAINIUMDFURPJM-UHFFFAOYSA-N oxatomide Chemical compound O=C1NC2=CC=CC=C2N1CCCN(CC1)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 BAINIUMDFURPJM-UHFFFAOYSA-N 0.000 claims description 2
- 229960002698 oxatomide Drugs 0.000 claims description 2
- 229960003534 phenindamine Drugs 0.000 claims description 2
- 229950004607 tazifylline Drugs 0.000 claims description 2
- 229960003223 tripelennamine Drugs 0.000 claims description 2
- 229960001128 triprolidine Drugs 0.000 claims description 2
- CBEQULMOCCWAQT-WOJGMQOQSA-N triprolidine Chemical compound C1=CC(C)=CC=C1C(\C=1N=CC=CC=1)=C/CN1CCCC1 CBEQULMOCCWAQT-WOJGMQOQSA-N 0.000 claims description 2
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims 3
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 claims 2
- MITFXPHMIHQXPI-UHFFFAOYSA-N Oraflex Chemical compound N=1C2=CC(C(C(O)=O)C)=CC=C2OC=1C1=CC=C(Cl)C=C1 MITFXPHMIHQXPI-UHFFFAOYSA-N 0.000 claims 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 2
- 239000003205 fragrance Substances 0.000 claims 2
- YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 claims 2
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 claims 2
- RJMIEHBSYVWVIN-LLVKDONJSA-N (2r)-2-[4-(3-oxo-1h-isoindol-2-yl)phenyl]propanoic acid Chemical compound C1=CC([C@H](C(O)=O)C)=CC=C1N1C(=O)C2=CC=CC=C2C1 RJMIEHBSYVWVIN-LLVKDONJSA-N 0.000 claims 1
- MDKGKXOCJGEUJW-VIFPVBQESA-N (2s)-2-[4-(thiophene-2-carbonyl)phenyl]propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C(=O)C1=CC=CS1 MDKGKXOCJGEUJW-VIFPVBQESA-N 0.000 claims 1
- WGDADRBTCPGSDG-UHFFFAOYSA-N 2-[[4,5-bis(4-chlorophenyl)-1,3-oxazol-2-yl]sulfanyl]propanoic acid Chemical compound O1C(SC(C)C(O)=O)=NC(C=2C=CC(Cl)=CC=2)=C1C1=CC=C(Cl)C=C1 WGDADRBTCPGSDG-UHFFFAOYSA-N 0.000 claims 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 claims 1
- DHHFDKNIEVKVKS-FMOSSLLZSA-N Betanin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC(C(=C1)O)=CC(C[C@H]2C([O-])=O)=C1[N+]2=C\C=C\1C=C(C(O)=O)N[C@H](C(O)=O)C/1 DHHFDKNIEVKVKS-FMOSSLLZSA-N 0.000 claims 1
- DHHFDKNIEVKVKS-MVUYWVKGSA-N Betanin Natural products O=C(O)[C@@H]1NC(C(=O)O)=C/C(=C\C=[N+]/2\[C@@H](C(=O)[O-])Cc3c\2cc(O)c(O[C@H]2[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O2)c3)/C1 DHHFDKNIEVKVKS-MVUYWVKGSA-N 0.000 claims 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims 1
- AHLPHDHHMVZTML-BYPYZUCNSA-N L-Ornithine Chemical compound NCCC[C@H](N)C(O)=O AHLPHDHHMVZTML-BYPYZUCNSA-N 0.000 claims 1
- HNDVDQJCIGZPNO-YFKPBYRVSA-N L-histidine Chemical compound OC(=O)[C@@H](N)CC1=CN=CN1 HNDVDQJCIGZPNO-YFKPBYRVSA-N 0.000 claims 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims 1
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 claims 1
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 claims 1
- AHLPHDHHMVZTML-UHFFFAOYSA-N Orn-delta-NH2 Natural products NCCCC(N)C(O)=O AHLPHDHHMVZTML-UHFFFAOYSA-N 0.000 claims 1
- UTJLXEIPEHZYQJ-UHFFFAOYSA-N Ornithine Natural products OC(=O)C(C)CCCN UTJLXEIPEHZYQJ-UHFFFAOYSA-N 0.000 claims 1
- TVQZAMVBTVNYLA-UHFFFAOYSA-N Pranoprofen Chemical compound C1=CC=C2CC3=CC(C(C(O)=O)C)=CC=C3OC2=N1 TVQZAMVBTVNYLA-UHFFFAOYSA-N 0.000 claims 1
- ZGUGWUXLJSTTMA-UHFFFAOYSA-N Promazinum Chemical compound C1=CC=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZGUGWUXLJSTTMA-UHFFFAOYSA-N 0.000 claims 1
- 206010040744 Sinus headache Diseases 0.000 claims 1
- 229960004663 alminoprofen Drugs 0.000 claims 1
- FPHLBGOJWPEVME-UHFFFAOYSA-N alminoprofen Chemical compound OC(=O)C(C)C1=CC=C(NCC(C)=C)C=C1 FPHLBGOJWPEVME-UHFFFAOYSA-N 0.000 claims 1
- 229940035676 analgesics Drugs 0.000 claims 1
- 229960003121 arginine Drugs 0.000 claims 1
- 235000012677 beetroot red Nutrition 0.000 claims 1
- 239000001654 beetroot red Substances 0.000 claims 1
- 229960005430 benoxaprofen Drugs 0.000 claims 1
- 235000002185 betanin Nutrition 0.000 claims 1
- 229960003184 carprofen Drugs 0.000 claims 1
- IVUMCTKHWDRRMH-UHFFFAOYSA-N carprofen Chemical compound C1=CC(Cl)=C[C]2C3=CC=C(C(C(O)=O)C)C=C3N=C21 IVUMCTKHWDRRMH-UHFFFAOYSA-N 0.000 claims 1
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims 1
- 229960001231 choline Drugs 0.000 claims 1
- HEFNNWSXXWATRW-JTQLQIEISA-N dexibuprofen Chemical compound CC(C)CC1=CC=C([C@H](C)C(O)=O)C=C1 HEFNNWSXXWATRW-JTQLQIEISA-N 0.000 claims 1
- DKYWVDODHFEZIM-NSHDSACASA-N dexketoprofen Chemical compound OC(=O)[C@@H](C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-NSHDSACASA-N 0.000 claims 1
- 229960001395 fenbufen Drugs 0.000 claims 1
- ZPAKPRAICRBAOD-UHFFFAOYSA-N fenbufen Chemical compound C1=CC(C(=O)CCC(=O)O)=CC=C1C1=CC=CC=C1 ZPAKPRAICRBAOD-UHFFFAOYSA-N 0.000 claims 1
- 229960002390 flurbiprofen Drugs 0.000 claims 1
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 claims 1
- 150000002337 glycosamines Chemical class 0.000 claims 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 claims 1
- 229960002885 histidine Drugs 0.000 claims 1
- XGIHQYAWBCFNPY-AZOCGYLKSA-N hydrabamine Chemical compound C([C@@H]12)CC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC[C@@]1(C)CNCCNC[C@@]1(C)[C@@H]2CCC3=CC(C(C)C)=CC=C3[C@@]2(C)CCC1 XGIHQYAWBCFNPY-AZOCGYLKSA-N 0.000 claims 1
- 229960004187 indoprofen Drugs 0.000 claims 1
- 229960003646 lysine Drugs 0.000 claims 1
- 125000003588 lysine group Chemical group [H]N([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 claims 1
- OJGQFYYLKNCIJD-UHFFFAOYSA-N miroprofen Chemical compound C1=CC(C(C(O)=O)C)=CC=C1C1=CN(C=CC=C2)C2=N1 OJGQFYYLKNCIJD-UHFFFAOYSA-N 0.000 claims 1
- 229950006616 miroprofen Drugs 0.000 claims 1
- 229960003104 ornithine Drugs 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 150000003053 piperidines Chemical class 0.000 claims 1
- 229960000851 pirprofen Drugs 0.000 claims 1
- PIDSZXPFGCURGN-UHFFFAOYSA-N pirprofen Chemical compound ClC1=CC(C(C(O)=O)C)=CC=C1N1CC=CC1 PIDSZXPFGCURGN-UHFFFAOYSA-N 0.000 claims 1
- 229960003101 pranoprofen Drugs 0.000 claims 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 claims 1
- 229960004919 procaine Drugs 0.000 claims 1
- 229960003598 promazine Drugs 0.000 claims 1
- 229960004492 suprofen Drugs 0.000 claims 1
- 229960004559 theobromine Drugs 0.000 claims 1
- 229930192474 thiophene Natural products 0.000 claims 1
- 229940015849 thiophene Drugs 0.000 claims 1
- 229950006150 tioxaprofen Drugs 0.000 claims 1
- 230000001976 improved effect Effects 0.000 abstract description 6
- 230000000116 mitigating effect Effects 0.000 abstract 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 208000024891 symptom Diseases 0.000 description 10
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 239000006186 oral dosage form Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 206010039085 Rhinitis allergic Diseases 0.000 description 6
- 201000010105 allergic rhinitis Diseases 0.000 description 6
- CDBRNDSHEYLDJV-FVGYRXGTSA-M naproxen sodium Chemical compound [Na+].C1=C([C@H](C)C([O-])=O)C=CC2=CC(OC)=CC=C21 CDBRNDSHEYLDJV-FVGYRXGTSA-M 0.000 description 6
- 229960003940 naproxen sodium Drugs 0.000 description 6
- 239000000375 suspending agent Substances 0.000 description 5
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 4
- 229960001138 acetylsalicylic acid Drugs 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 239000003086 colorant Substances 0.000 description 4
- 239000000796 flavoring agent Substances 0.000 description 4
- 235000013355 food flavoring agent Nutrition 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- ADVGKWPZRIDURE-UHFFFAOYSA-N 2'-Hydroxyacetanilide Chemical compound CC(=O)NC1=CC=CC=C1O ADVGKWPZRIDURE-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 206010039101 Rhinorrhoea Diseases 0.000 description 3
- 230000002421 anti-septic effect Effects 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 125000004432 carbon atom Chemical group C* 0.000 description 3
- 239000003937 drug carrier Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 230000003203 everyday effect Effects 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 231100000252 nontoxic Toxicity 0.000 description 3
- 230000003000 nontoxic effect Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
- FTLYMKDSHNWQKD-UHFFFAOYSA-N (2,4,5-trichlorophenyl)boronic acid Chemical compound OB(O)C1=CC(Cl)=C(Cl)C=C1Cl FTLYMKDSHNWQKD-UHFFFAOYSA-N 0.000 description 2
- VIBOGIYPPWLDTI-UHFFFAOYSA-N 2-naphthylacetic acid Chemical compound C1=CC=CC2=CC(CC(=O)O)=CC=C21 VIBOGIYPPWLDTI-UHFFFAOYSA-N 0.000 description 2
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 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
- 206010019233 Headaches Diseases 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 241001113283 Respirovirus Species 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 125000003545 alkoxy group Chemical group 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 229940125715 antihistaminic agent Drugs 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000007894 caplet Substances 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 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 description 2
- 239000006184 cosolvent Substances 0.000 description 2
- KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 231100000869 headache Toxicity 0.000 description 2
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000008297 liquid dosage form Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 2
- 239000008108 microcrystalline cellulose Substances 0.000 description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- LHGVFZTZFXWLCP-UHFFFAOYSA-N pyrocatechol monomethyl ether Natural products COC1=CC=CC=C1O LHGVFZTZFXWLCP-UHFFFAOYSA-N 0.000 description 2
- 229940085605 saccharin sodium Drugs 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229920001027 sodium carboxymethylcellulose Polymers 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
- 239000002904 solvent Substances 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 229960005486 vaccine Drugs 0.000 description 2
- 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 1
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
- 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 description 1
- YCKSFFKKEWTLIZ-UHFFFAOYSA-N 2-(4-benzhydrylpiperazin-1-ium-1-yl)acetate Chemical compound C1CN(CC(=O)O)CCN1C(C=1C=CC=CC=1)C1=CC=CC=C1 YCKSFFKKEWTLIZ-UHFFFAOYSA-N 0.000 description 1
- RNEJAHLAXZZEPV-UHFFFAOYSA-N 2-(6-chloro-3,4-dihydronaphthalen-2-yl)propanoic acid Chemical compound C1=C(Cl)C=C2CCC(C(C(O)=O)C)=CC2=C1 RNEJAHLAXZZEPV-UHFFFAOYSA-N 0.000 description 1
- IJHVTMGVBAHGSJ-UHFFFAOYSA-N 2-(6-fluoro-3,4-dihydronaphthalen-2-yl)propanoic acid Chemical compound C1=C(F)C=C2CCC(C(C(O)=O)C)=CC2=C1 IJHVTMGVBAHGSJ-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- MBUVEWMHONZEQD-UHFFFAOYSA-N Azeptin Chemical compound C1CN(C)CCCC1N1C(=O)C2=CC=CC=C2C(CC=2C=CC(Cl)=CC=2)=N1 MBUVEWMHONZEQD-UHFFFAOYSA-N 0.000 description 1
- 208000001387 Causalgia Diseases 0.000 description 1
- 206010008469 Chest discomfort Diseases 0.000 description 1
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
- 208000023890 Complex Regional Pain Syndromes Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 206010013952 Dysphonia Diseases 0.000 description 1
- 241000709661 Enterovirus Species 0.000 description 1
- 229930091371 Fructose Natural products 0.000 description 1
- 239000005715 Fructose Substances 0.000 description 1
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- HSRJKNPTNIJEKV-UHFFFAOYSA-N Guaifenesin Chemical compound COC1=CC=CC=C1OCC(O)CO HSRJKNPTNIJEKV-UHFFFAOYSA-N 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 208000010473 Hoarseness Diseases 0.000 description 1
- 206010020565 Hyperaemia Diseases 0.000 description 1
- PWKSKIMOESPYIA-BYPYZUCNSA-N L-N-acetyl-Cysteine Chemical compound CC(=O)N[C@@H](CS)C(O)=O PWKSKIMOESPYIA-BYPYZUCNSA-N 0.000 description 1
- 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 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241001597008 Nomeidae Species 0.000 description 1
- 208000005141 Otitis Diseases 0.000 description 1
- 206010033372 Pain and discomfort Diseases 0.000 description 1
- 206010034464 Periarthritis Diseases 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 206010057190 Respiratory tract infections Diseases 0.000 description 1
- 208000036071 Rhinorrhea Diseases 0.000 description 1
- 206010061494 Rhinovirus infection Diseases 0.000 description 1
- 241000220010 Rhode Species 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 206010046306 Upper respiratory tract infection Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 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 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- JBDGDEWWOUBZPM-XYPYZODXSA-N ambroxol Chemical compound NC1=C(Br)C=C(Br)C=C1CN[C@@H]1CC[C@@H](O)CC1 JBDGDEWWOUBZPM-XYPYZODXSA-N 0.000 description 1
- 229960005174 ambroxol Drugs 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 150000003863 ammonium salts Chemical class 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 239000008122 artificial sweetener Substances 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 229960004574 azelastine Drugs 0.000 description 1
- OJGDCBLYJGHCIH-UHFFFAOYSA-N bromhexine Chemical compound C1CCCCC1N(C)CC1=CC(Br)=CC(Br)=C1N OJGDCBLYJGHCIH-UHFFFAOYSA-N 0.000 description 1
- 229960003870 bromhexine Drugs 0.000 description 1
- 229940124630 bronchodilator Drugs 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- OFAIGZWCDGNZGT-UHFFFAOYSA-N caramiphen Chemical compound C=1C=CC=CC=1C1(C(=O)OCCN(CC)CC)CCCC1 OFAIGZWCDGNZGT-UHFFFAOYSA-N 0.000 description 1
- 229960004160 caramiphen Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 239000000812 cholinergic antagonist Substances 0.000 description 1
- WRCHFMBCVFFYEQ-UHFFFAOYSA-N clofedanol Chemical compound C=1C=CC=C(Cl)C=1C(O)(CCN(C)C)C1=CC=CC=C1 WRCHFMBCVFFYEQ-UHFFFAOYSA-N 0.000 description 1
- 229960004472 clofedanol Drugs 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 208000014439 complex regional pain syndrome type 2 Diseases 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 229960001985 dextromethorphan Drugs 0.000 description 1
- XYYVYLMBEZUESM-UHFFFAOYSA-N dihydrocodeine Natural products C1C(N(CCC234)C)C2C=CC(=O)C3OC2=C4C1=CC=C2OC XYYVYLMBEZUESM-UHFFFAOYSA-N 0.000 description 1
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 229960000520 diphenhydramine Drugs 0.000 description 1
- 230000008034 disappearance Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 208000019258 ear infection Diseases 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 238000009505 enteric coating Methods 0.000 description 1
- 239000002702 enteric coating Substances 0.000 description 1
- 229960002179 ephedrine Drugs 0.000 description 1
- 230000009969 flowable effect Effects 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- KSNNEUZOAFRTDS-UHFFFAOYSA-N fominoben Chemical compound ClC=1C=CC=C(NC(=O)C=2C=CC=CC=2)C=1CN(C)CC(=O)N1CCOCC1 KSNNEUZOAFRTDS-UHFFFAOYSA-N 0.000 description 1
- 229960004594 fominoben Drugs 0.000 description 1
- 235000011194 food seasoning agent Nutrition 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229960001867 guaiacol Drugs 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 235000019534 high fructose corn syrup Nutrition 0.000 description 1
- LLPOLZWFYMWNKH-CMKMFDCUSA-N hydrocodone Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)CC(=O)[C@@H]1OC1=C2C3=CC=C1OC LLPOLZWFYMWNKH-CMKMFDCUSA-N 0.000 description 1
- 229960000240 hydrocodone Drugs 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- WVLOADHCBXTIJK-YNHQPCIGSA-N hydromorphone Chemical compound O([C@H]1C(CC[C@H]23)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O WVLOADHCBXTIJK-YNHQPCIGSA-N 0.000 description 1
- 229960001410 hydromorphone Drugs 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 229960000930 hydroxyzine Drugs 0.000 description 1
- ZQDWXGKKHFNSQK-UHFFFAOYSA-N hydroxyzine Chemical compound C1CN(CCOCCO)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZQDWXGKKHFNSQK-UHFFFAOYSA-N 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 229960003088 loratadine Drugs 0.000 description 1
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- PLPRGLOFPNJOTN-UHFFFAOYSA-N narcotine Natural products COc1ccc2C(OC(=O)c2c1OC)C3Cc4c(CN3C)cc5OCOc5c4OC PLPRGLOFPNJOTN-UHFFFAOYSA-N 0.000 description 1
- 201000009240 nasopharyngitis Diseases 0.000 description 1
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 239000000820 nonprescription drug Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000008008 oral excipient Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 229960005489 paracetamol Drugs 0.000 description 1
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 1
- 229960003436 pentoxyverine Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 1
- 229960001802 phenylephrine Drugs 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Substances [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 229960003908 pseudoephedrine Drugs 0.000 description 1
- KWGRBVOPPLSCSI-WCBMZHEXSA-N pseudoephedrine Chemical compound CN[C@@H](C)[C@@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WCBMZHEXSA-N 0.000 description 1
- 229940021275 pseudoephedrine hydrochloride 60 mg Drugs 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 235000019615 sensations Nutrition 0.000 description 1
- 230000014860 sensory perception of taste Effects 0.000 description 1
- 238000011125 single therapy Methods 0.000 description 1
- 201000009890 sinusitis Diseases 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
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000002048 spasmolytic effect Effects 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 238000009495 sugar coating Methods 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- LLPOLZWFYMWNKH-UHFFFAOYSA-N trans-dihydrocodeinone Natural products C1C(N(CCC234)C)C2CCC(=O)C3OC2=C4C1=CC=C2OC LLPOLZWFYMWNKH-UHFFFAOYSA-N 0.000 description 1
- RBNWAMSGVWEHFP-UHFFFAOYSA-N trans-p-Menthane-1,8-diol Chemical compound CC(C)(O)C1CCC(C)(O)CC1 RBNWAMSGVWEHFP-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 208000011479 upper respiratory tract disease Diseases 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/14—Antitussive agents
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Pulmonology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Otolaryngology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
本发明涉及通过给予安全有效量的包括萘普生和西替利嗪的组合物来提供治疗、处理或缓解感冒、类感冒、窦和/或流感症状的组合物和方法。
Description
技术领域
本发明涉及通过给予安全有效量的包括萘普生或相关化合物和西替利嗪或相关化合物的组合物来提供治疗、处理或缓解感冒、类感冒、变态反应、窦和／或流感症状的组合物和方法。
发明的背景
感冒虽然并不总是严重的疾病，却是高度流行、不舒服和令人烦恼的病痛。术语“感冒”用于各种不同的呼吸道病毒引起的较次要的呼吸系疾病。鼻病毒是已知的主要感冒病因，在成人中约占30％，其它一些组中的病毒也是重要的。由于出现免疫反应，因此一些呼吸道病毒的感染可用疫苗预防，但开发覆盖所有可能病毒的多型疫苗是不可实施的。因此，防治急性上呼吸道疾病的问题提出了复杂的挑战，长期期待的发现对感冒的单一治疗是一种不切实际的期望。
早期症状可能是轻微的，只有轻度不适、喉痛和鼻部症状。鼻病毒感染时，通常生病的第一天开始流鼻涕、鼻充血和打喷嚏，第二天或第三天进展到最严重的程度。与鼻部症状相伴随的可以是喉痛、干燥或痒，及声音嘶哑和咳嗽。其它症状可包括眼睛轻度灼痛、嗅觉和味觉消失、窦或耳受压或塞满感、头痛和嗓音受损。可以但不常出现发热。流感通常包括发热，常常是突然发作，持续数日，程度严重；全身疼痛和不适；疲劳和虚弱；以及胸部不适。
目前，对感冒只有对症治疗。在美国用以治疗感冒的非处方药费用估计每年超过15亿美元。门诊病人的直接治疗费用估计约为40亿美元。根据因活动受限工资减少的量计算，间接费用实质上更高。
治疗咳嗽、感冒、类感冒、变态反应、窦和／或流感症状和所伴随的不适、疼痛、发热和全身不适的现有技术配方的示例一般包括镇痛药(阿斯匹林或对乙酰氨基酚)，及一种或几种抗组胺药、减充血剂、咳嗽抑制剂-止咳药和祛痰药。
使用非甾类抗炎药对付炎症及其伴随的疼痛是可接受的医学实践。非甾类化合物通常用于减轻诸如粘膜囊炎、关节炎所伴有的疼痛和炎症、头痛等。最常用的非麻醉性镇痛药是阿斯匹林、乙酰氨基酚、布洛芬、酮洛芬、双氯芬酸和萘普生及其盐(如赖氨酸、精氨酸、钠和钾的盐)。在此，将阿斯匹林、乙酰氨基酚和布洛芬作为疼痛缓解剂和退热成分包括在缓解咳嗽／感冒多重症状的常规组合物中。除了阿斯匹林、乙酰氨基酚、布洛芬外，这些市售产品一般包含一种或几种抗组胺药、减充血剂、咳嗽抑制剂-止咳药和祛痰药。
本发明者发现，包括萘普生和西替利嗪的选择的组合物对感冒、类感冒、变态反应、窦和／或流感症状(包括鼻充血)提供了改善的治疗、处理或缓解。
因此，本发明的目的是提供在需要进行治疗的哺乳动物机体治疗咳嗽、感冒、类感冒、变态反应、窦和／或流感症状的方法，包括对这些机体投予本发明的组合物。此处所用的这些“症状”指鼻卡他、鼻充血、窦充血、窦疼痛、上呼吸道感染、耳炎、窦炎等。
发明的概述
本发明涉及通过给予安全有效量的含萘普生和西替利嗪的组合物对感冒、类感冒、窦和／或流感症状(包括鼻充血)提供改善的治疗、处理或缓解的组合物和方法。
本说明书所用的所有百分比和比例均为重量比，除非另指。此外，所有测定均在25℃进行，除非另指。
发明的详细描述
本发明涉及通过给予安全有效量的主要由含萘普生和西替利嗪组成的组合物对感冒、类感冒、变态反应、窦和／或流感症状(包括鼻充血)提供改善的治疗、处理或缓解的组合物和方法。
西替利嗪
本发明涉及在还包含萘普生的组合物中使用2-[4-(二苯基-甲基)-1-哌嗪基]-乙酸及其酰胺和无毒的药学上可接受的盐。
西替利嗪和相关的化合物具有如下通式：
其中，
Y为羟基或-NH2基；
X和X’各自独立地代表氢原子、卤原子、直链或支链低级烷氧基或三氟甲基；
M为1或2；
N为1或2，较佳为2，
及其无毒的药学上可接受的盐。
本说明书所用的术语“低级烷氧基”指具有1-4个碳原子的直链或支链脂肪醇，如甲氧基、乙氧基、丙氧基等。卤原子以氯或氟原子为佳。
本说明书所用的术语“无毒的药学上可接受的盐”不仅指通式所示酸和酰胺与药学上可接受的酸(如乙酸、柠檬酸、琥珀酸、抗坏血酸、盐酸、氢溴酸和磷酸)的加成盐，而且指通式所示酸的药学上可接受的盐，如金属盐(例如钠和钾盐)、铵盐、胺盐和氨基酸盐。
本发明的优选的化合物为：
2-[2-[4[(4-氯苯基)苯基甲基]-1-哌嗪基]乙氧基]-乙酸及其二盐酸盐：
2-[2-[4[(4-氯苯基)苯基甲基]-1-哌嗪基]乙氧基]-乙酸钾；
2-[2-[4[(4-二苯基甲基)-1-哌嗪基]乙氧基]-乙酸及其二盐酸盐；
2-[2-[4[(4-氟苯基)苯基甲基]-1-哌嗪基]乙氧基]-乙酸及其水合物。
通式所示西替利嗪化合物具有有趣的药理学性质。特别是，它们可用作抗变态反应剂、抗组胺剂、支气管扩张剂和解痉剂，其用量为约5-20mg。
优选的化合物为3，4-二氢-6-氟-2-萘基-α-甲基乙酸，其烷酯(其中烷基具有1-12个碳原子)，及其药学上可接受的加成盐。特别优选的为3，4-二氢-6-氯-2-萘基-α-甲基乙酸，其烷酯(其中烷基具有1-12个碳原子)，及其药学上可接受的加成盐。
这些化合物在美国专利No．4，525，358(1985年6月25日)中作了详细描述，其全文在此引为参考。
萘普生
萘普生及类似的化合物为2-萘乙酸，可用下式表示的化合物：
阿拉伯数字和α符号表示本说明书中所用的2-萘乙酸衍生物命名法中的位置。这是萘普生及其相关化合物的通式。
它们在美国专利No．3，896，157中有进一步描述，在此处全文引作参考。萘普生本身是(S)-6-甲氧基-2-甲基-2-萘乙酸，较佳为钠盐。
萘普生及其相关化合物通常用量为50-660mg，较佳为约100-330mg，更佳为约150-220mg。
另外的药物活性成分
本发明的组合物还可包括选自以下类型的至少一种其它药理活性成分：(a)减充血剂：(b)祛痰剂；(c)外加的抗组胺药；和(d)镇咳剂。本发明组合物中有用的减充血剂包括伪麻黄碱、苯丙胺醇、苯福林和麻黄碱，它们的药学上可接受的盐和混合物。本发明组合物中有用的镇咳剂包括诸如右美沙芬、氯苯达诺、喷托维林、卡拉美芬、那可丁、苯海拉明、可待因、氢可酮、氢吗啡酮、福米诺苯，它们的药学上可接受的盐和混合物。本发明组合物中有用的外加的抗组胺药包括诸如氯苯那敏、溴苯那敏、右氯苯那敏、右溴苯那敏、曲普利啶、阿札他定、多西拉敏、曲吡那敏、赛庚啶(cyproheptadine)、羟嗪、吡氯苄氧胺、苯茚胺、溴苯海拉明、新安替根，它们的药学上可接受的盐，以及非镇静性抗组胺药，包括阿伐斯订、AHR-11325、阿斯咪唑，阿扎他定、氮斯汀(azelastine)，依巴斯订、酮替芬、洛草氨酸、洛雷替定(loratidine)，左卡巴斯订、美喹他嗪、奥沙米特、司他斯订、他齐茶碱和替美斯订，它们的药学上可接受的盐和混合物。本发明组合物中有用的祛痰剂(也称作解粘剂)包括愈疮木酚甘油酯(glyceryl guaiacolate)、萜品醇、氯化铵、N-乙酰半胱氨酸和溴己新，氨溴索，它们的药学上可接受的盐和混合物。所有这些成分及其可接受的剂量范围在以下文献中有描述：1988年11月8日授予Sunshine等的美国专利No．4，783，465；1986年10月28日授予Sunshine等的美国专利No．4，619，934，它们均在此引为参考。
被发现在本发明的组合物中有用的其它药物是α-激动剂，如1995年12月26日授权的美国专利No．5，478，858，其全文在此引为参考。
可使用各种口服剂型，包括诸如片剂、胶囊型片剂(caplet)、胶囊、颗粒、糖锭和疏松粉剂的固体剂型，及诸如糖浆、悬浮剂等液体剂型。提供这些活性成分控制释放的控释剂型也是有用的。这些口服剂型包含安全有效量、通常至少约5％的活性成分。固体口服剂型较佳包含约5％-95％、更佳包含约10％-95％、最佳包含约25％-95％的活性成分。液体口服剂型较佳包含约1％-50％、更佳包含约1％-25％、最佳包含约3％-10％的活性成分。
片剂可压制、研制、进行肠溶包衣、包糖衣、包薄膜或多层压制，包含合适的粘合剂、润滑剂、稀释剂、崩解剂、着色剂、调味剂、防腐剂和促流动剂。还有有用的是软明胶胶囊。
液体口服剂型包括水性和非水性溶液、乳剂、假乳剂、悬浮液和溶液和／或从非泡腾颗粒重建的悬浮液，它们包含合适的溶剂、防腐剂、乳化剂、悬浮剂、稀释剂、甜味剂、遮味剂、着色剂和矫味剂。可用于配制口服剂型的药学上可接受的载体和赋形剂的具体例子在1975年9月2日授予Robert的美国专利No．3，903，297中有描述，在此引为参考。制备固体口服剂型的技术和组成在Marshall的“固体口服剂型”，Modern Pharmaceutics，Vol．7，(Banker和Rhodes编著)，第359-427页(1979)中有描述，在此引为参考。制备片剂(压制和模压)、胶囊(硬和软明胶)和丸剂的技术和组成在Remington’s Pharmaceutical Sciences(Arthur Osol编著)，第1553-1593页(1980)中有描述，在此引为参考。
被发现在本发明的组合物中有用的另外的药物是咖啡因。咖啡因被发现能减轻西替利嗪的轻度镇静作用。咖啡因的用量通常为约20mg-500mg，较佳为约50mg-200mg，最佳为约65mg-100mg。
制备液体口服剂型时，按照常规的药剂实践，将活性成分掺入水基口服可接受的药物载体中。“水基口服可接受的药物载体”是其中全部或主要溶剂是水的一种载体。典型的载体包括单纯水溶液、糖浆、分散液和悬浮液，及水基乳剂如水包油型。最佳的载体是药物组合物在含合适的悬浮剂的水性赋形剂中的悬浮液。合适的悬浮剂包括Avicel RC-591(一种购自FMC的微晶纤维素／羧甲基纤维素钠混合物)、瓜耳树胶等。这些悬浮剂是本领域技术人员熟知的。根据活性成分和其它任选的非活性成分的总重量和体积，本发明组合物中水的量可在很大范围内变化，基于最终组合物的重量，水的总量一般可在约20-75％，较佳为约20-40％(w／v)。
虽然水本身可构成全部载体，但典型的液体剂型以含助溶剂(例如，丙二醇、甘油、山梨醇溶液等)为佳，以帮助水不溶性成分(如调味油等)增溶和掺入组合物中。因此，一般说来，本发明的组合物以包含约5-25％(v／v)助溶剂为佳，以约10-25％(v／v)为最佳。
药剂师熟知的其它任选的成分也可以其一般所知的量包括在内，例如，天然或人工甜味剂、调味剂、着色剂等以提供口味好、外观好的成品，抗氧化剂如丁基化羟基苯甲醚或丁基化羟基甲苯，及防腐剂如羟苯甲酸甲酯或丙酯或苯甲酸钠，以延长和增加货架寿命。极佳的任选组份为咖啡因。
治疗方法
药物组合物的给药量根据配方中活性成分百分率而定，是如下参数的函数：西替利嗪和萘普生及任何选择成分如减充血剂、镇咳剂、祛痰剂、咖啡因和／或外加的抗组胺药每剂所需量，稳定性、释放特性和其它药学参数、
如本说明书所述，药物组合物的给药量通常约为每天1mg／kg至50mg／kg，较佳约为每天2mg／kg至30mg／kg，最佳约为每天3mg／kg至20mg／kg。此量可以单剂、或较佳为多剂(2-6剂)反复给药或整个疗程中的缓释剂量的方式给药。一般来说，本发明的药物组合物的单个剂量约为1mg／kg至25mg／kg，较佳约为2mg／kg至15mg／kg，最佳约为3mg／kg至10mg／kg。尽管高于前述剂量能有效地减轻咳嗽、感冒样、流感、流感样和变应性鼻炎症状，但任何药物对于某些个体均须小心，以防止副作用。
下面的实施例用于阐述本发明的实施方案，其中兼有必须和任选的成分。
实施例Ⅰ
合并如下成分，制备口服给药的硬明胶胶囊组合物：
成分 用量
萘普生钠 220-440mg
盐酸伪麻黄碱 60mg(120mg，缓释)
西替利嗪* 5mg
将活性成分和适量乳糖研制并装入选定大小的胶囊。
*西替利嗪是2-[2-[4[(4-氯苯基)苯基甲基]-1-哌嗪基]乙氧基]-乙酸。
对需要进行治疗的人每4-12小时给予1或2个上述胶囊，其减轻咳嗽、感冒样、流感、流感样和变应性鼻炎症状的作用改善。
实施例Ⅱ
合并如下成分，制备口服给药的压制胶囊型片剂(caplet)组合物：
成分 用量
萘普生钠 220或440mg
西替利嗪 5mg
预凝胶化淀粉 20．0mg
玉米淀粉 80．0mg
交联羧甲基纤维素钠 10．0mg
二氧化硅，胶态 1．5mg
硬脂酸，TP细粉 2．0mg
十二烷基硫酸钠 0．5mg
Opadry clear／Colorcon 5．0mg
(含羟丙基甲基纤维素)
对需要进行治疗的人每12小时给予2个胶囊型片剂，其减轻咳嗽、感冒样、流感、流感样和变应性鼻炎症状的作用改善。
实施例Ⅲ
合并如下成分，制备口服给药的压制片剂组合物：
成分 用量
萘普生钠 220或440mg
西替利嗪 5mg
微晶纤维素 110mg
聚乙烯吡咯烷酮 10mg
滑石粉 12mg
硬脂酸镁 2mg
Opadry clear／Colorcon 5．0mg
(含羟丙基甲基纤维素)
对需要进行治疗的人每12小时给予1片上述片剂，其减轻咳嗽、感冒样、流感、流感样和变应性鼻炎症状的作用改善。
实施例Ⅳ合并如下成分，制备口服给药的液体组合物：
成分 ％W／V
萘普生钠 2．200
西替利嗪 0．050
高果糖玉米糖浆(55％) 55．000
聚乙二醇400 10．000
丙二醇 10．000
乙醇(95％) 8．500
柠檬酸钠二水合物 0．470
柠檬酸 0．180
糖精钠 0．700
调味剂 0．015
色素 0．005
纯水 适量至100％
将纯水(约为最终批量体积的10％)倒入装有lightnin’混合器的批量容器内。相继加入柠檬酸钠、柠檬酸、糖精钠和除萘普生钠外的其它活性成分，搅拌溶解。然后加入高果糖。在另一个容器内将着色剂加入纯水(约最终批量体积的0．5％)中。然后将此着色剂溶液加入第一个批量容器中。在另一个容器中边搅拌边将萘普生钠加入乙醇中。将丙二醇、聚乙二醇和调味剂加入此醇预混合物中，所得的混合物搅拌至均匀，然后加到第一个容器中。将剩余的纯水加到所得的混合物中并搅拌。
对需要进行治疗的人每12小时给予10-20ml(2-4茶匙)，其减轻咳嗽、感冒样、流感、流感样和变应性鼻炎症状的作用改善。
对需要进行治疗的人每8-12小时给予20ml(4茶匙)，其咳嗽、感冒样、流感、流感样和变应性鼻炎症状的作用改善。
Claims (10)
1．通过给予安全有效量组合物对感冒、类感冒、变态反应、窦和／或流感症状提供改善的治疗、处理或缓解的组合物，所述组合物包含：
(a)一种镇痛剂，萘普生或相关化合物或其药学上可接受的盐；
(b)西替利嗪或相关化合物。
2．如权利要求l所述的药物组合物，其中所述西替利嗪或相关化合物选自：4-[1-羟基-4-(4-羟基二苯基甲基-1-哌啶基)丁基]-α，a-二甲基苯乙酸甲酯、4-[1-羟基-4-(4-羟基二苯基甲基-1-哌啶基)丁基]-α，α-二甲基苯乙酸、1-[p-(2-羟基甲基-2-丙基)苯基]-4-[4(α-羟基-α-苯基苄基)-1-哌啶基]丁醇及其混合物。
3．如权利要求2所述的药物组合物，其中包含另一种镇痛药，选自：布洛芬、苯噁洛芬、氟比洛芬、酮洛芬、菲诺洛芬、芬布芬、吲哚洛芬、吡洛芬、卡洛芬、噁丙嗪、普拉洛芬、咪洛芬、硫噁洛芬、舒洛芬、阿明洛芬、噻洛芬和双氯芬酸。
4．如权利要求3所述的药物组合物，其中所述萘普生或相关化合物或另外的镇痛药是氨基酸盐，选自三乙胺、三丙胺、2-二甲基氨基乙醇、2-二乙基氨基乙醇、赖氨酸、鸟氨酸、精氨酸、组氨酸、咖啡因、普鲁卡因、N-乙基哌啶、海巴明(hydrabamine)、胆碱、甜菜碱、乙二胺、葡糖胺、methylglycamine、可可碱、嘌呤、哌嗪和哌啶，以及它们的混合物。
5．如权利要求3所述的药物组合物，其中还包含选自减充血剂、祛痰剂、外加的抗组胺药镇咳剂及其混合物的药理活性成分。
6．如权利要求3所述的药物组合物，其中所述另外的抗组胺药选自：氯苯那敏、溴苯那敏、右氯苯那敏、右溴苯那敏、曲普利啶、多西拉敏、曲吡那敏、赛庚啶、吡氯苄氧胺、溴苯海拉明、新安替根、阿伐斯订、AHR-11325、苯茚胺、阿斯咪唑，阿扎他定、氮斯汀依巴斯订、酮替芬、洛草氨酸、洛雷替定，左卡巴斯订、美喹他嗪、奥沙米特、司他斯订、他齐茶碱、替美斯订，及其混合物或药学上可接受的盐。
7．如权利要求5所述的药物组合物，包含萘普生或相关化合物或另外的镇痛药的S(+)-对映体。
8．如权利要求8所述的药物组合物，其中所述另外的药物的S(+)-对映体选自赖氨酸S(+)-酮洛芬、赖氨酸S(+)-布洛芬及其混合物。
9．如权利要求1所述的药物组合物，其中还包含α-激动剂化合物、咖啡因及其混合物。
10．镇痛药和抗组胺药用于制备在需要治疗的哺乳动物机体治疗窦压力、窦疼痛、窦流液、鼻充血、咳嗽、感冒、感冒样或流感症状的药物的用途，所述治疗包括将权利要求1所述组合物给药于所述机体。
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US93403397A | 1997-09-19 | 1997-09-19 | |
| US08/934,033 | 1997-09-19 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1278728A true CN1278728A (zh) | 2001-01-03 |
Family
ID=25464848
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN98811202A Pending CN1278728A (zh) | 1997-09-19 | 1998-08-28 | 治疗呼吸系统疾病的组合物和方法 |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP1014983A1 (zh) |
| JP (1) | JP2001517626A (zh) |
| KR (1) | KR20010024187A (zh) |
| CN (1) | CN1278728A (zh) |
| AU (1) | AU8744398A (zh) |
| BR (1) | BR9812660A (zh) |
| CA (1) | CA2304005A1 (zh) |
| CO (1) | CO5011084A1 (zh) |
| HU (1) | HUP0004813A2 (zh) |
| NO (1) | NO20001412D0 (zh) |
| PE (1) | PE118999A1 (zh) |
| WO (1) | WO1999015173A1 (zh) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101073563B (zh) * | 2007-02-07 | 2010-10-06 | 西安利君制药有限责任公司 | 一种含有右旋布洛芬和左旋西替利嗪的手性组合物及其缓速释双层片 |
| CN103251590A (zh) * | 2013-05-13 | 2013-08-21 | 中国科学院武汉病毒研究所 | 一种琥珀酸多西拉敏在制备治疗或预防流感病毒药物中的应用 |
| CN103446587A (zh) * | 2011-12-28 | 2013-12-18 | 汪明 | 肥大细胞抑制剂在制备抗流感病毒感染药物中的应用 |
| WO2019047283A1 (zh) * | 2017-09-08 | 2019-03-14 | 中国科学院微生物研究所 | 调控a型和b型流感病毒核蛋白出核的关键氨基酸位点及其作为抗流感病毒药物靶点的用途 |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2001279999A1 (en) * | 2000-09-08 | 2002-03-22 | Warner-Lambert Compan Llc | Prevention of acute sinusitis and sinus attack |
| MXPA03011705A (es) * | 2001-06-20 | 2004-03-19 | Schering Corp | Antihistaminas para el tratamiento de congestion nasal y obstruccion nasal. |
| US6863901B2 (en) | 2001-11-30 | 2005-03-08 | Collegium Pharmaceutical, Inc. | Pharmaceutical composition for compressed annular tablet with molded triturate tablet for both intraoral and oral administration |
| US6827946B2 (en) * | 2001-12-05 | 2004-12-07 | Collegium Pharmaceutical, Inc. | Compositions containing both sedative and non-sedative antihistamines |
| US7166641B2 (en) * | 2002-10-02 | 2007-01-23 | Yung Shin Pharmaceutical Industrial Co., Ltd. | Pharmaceutically acceptable salts containing local anesthetic and anti-inflammatory activities and methods for preparing the same |
| US7863287B2 (en) | 2002-12-18 | 2011-01-04 | Wyeth Llc | Compositions of non-steroidal anti-inflammatory drugs, decongestants and anti-histamines |
| US20050192355A1 (en) * | 2004-02-17 | 2005-09-01 | Wyeth | Compositions of non-steroidal anti-inflammatory drugs and decongestants or anti-histamines |
| GB0719518D0 (en) * | 2007-10-05 | 2007-11-14 | Therapeutics Ltd E | Therapy |
| US8246988B2 (en) | 2009-01-05 | 2012-08-21 | Mcneil-Ppc, Inc. | Three layer tablet containing cetirizine, pseudoephedrine, and naproxen |
| CA2748728C (en) | 2009-01-05 | 2017-01-03 | Mcneil-Ppc, Inc. | Tablet containing cetirizine, pseudoephedrine, and naproxen containing a barrier layer |
| US8252330B2 (en) | 2009-01-05 | 2012-08-28 | Mcneil-Ppc, Inc. | Tablet containing coated particles of cetirizine, pseudoephedrine, and/or naproxen |
| GB0905954D0 (en) * | 2009-04-06 | 2009-05-20 | E Therapeutics Plc | Treatment of exacerbations of asthma |
| CN115887456A (zh) * | 2015-03-26 | 2023-04-04 | 杰奎琳·M·艾弗森 | 抑制与宿醉相关的症状的方法和组合物 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4783465A (en) * | 1984-04-09 | 1988-11-08 | Analgesic Associates | Cough/cold mixtures comprising non-sedating antihistamine drugs |
| US4871733A (en) * | 1984-04-09 | 1989-10-03 | Analgesic Associates | Cough/cold mixtures comprising non-sedating antihistamine drugs |
| US5260073A (en) * | 1990-05-21 | 1993-11-09 | Norwich Eaton Pharmaceuticals, Inc. | Use of phenylpropanolamine as a mucus secretogogue in the upper airways |
| CA2170488A1 (en) * | 1993-09-07 | 1995-03-16 | Sekhar Mitra | Compositions containing an amino acid salt of propionic acid non-steroidal anti-inflammatory agent and at least one of a decongestant, an expectorant, an antihistamine and an antitussive |
| EP0841947A1 (en) * | 1995-07-28 | 1998-05-20 | The Procter & Gamble Company | Compositions containing analgesics and antihistamines and methods for treating respiratory disorders |
| US5648358A (en) * | 1996-03-05 | 1997-07-15 | Mitra; Sekhar | Compositions and methods for treating respiratory disorders |
-
1998
- 1998-08-28 CN CN98811202A patent/CN1278728A/zh active Pending
- 1998-08-28 KR KR1020007002958A patent/KR20010024187A/ko not_active Application Discontinuation
- 1998-08-28 WO PCT/IB1998/001339 patent/WO1999015173A1/en not_active Application Discontinuation
- 1998-08-28 EP EP98938852A patent/EP1014983A1/en not_active Withdrawn
- 1998-08-28 JP JP2000512542A patent/JP2001517626A/ja not_active Withdrawn
- 1998-08-28 AU AU87443/98A patent/AU8744398A/en not_active Abandoned
- 1998-08-28 CA CA002304005A patent/CA2304005A1/en not_active Abandoned
- 1998-08-28 BR BR9812660-1A patent/BR9812660A/pt not_active Application Discontinuation
- 1998-08-28 HU HU0004813A patent/HUP0004813A2/hu unknown
- 1998-09-17 PE PE1998000885A patent/PE118999A1/es not_active Application Discontinuation
- 1998-09-21 CO CO98054352A patent/CO5011084A1/es unknown
-
2000
- 2000-03-17 NO NO20001412A patent/NO20001412D0/no unknown
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101073563B (zh) * | 2007-02-07 | 2010-10-06 | 西安利君制药有限责任公司 | 一种含有右旋布洛芬和左旋西替利嗪的手性组合物及其缓速释双层片 |
| CN103446587A (zh) * | 2011-12-28 | 2013-12-18 | 汪明 | 肥大细胞抑制剂在制备抗流感病毒感染药物中的应用 |
| CN103251590A (zh) * | 2013-05-13 | 2013-08-21 | 中国科学院武汉病毒研究所 | 一种琥珀酸多西拉敏在制备治疗或预防流感病毒药物中的应用 |
| WO2019047283A1 (zh) * | 2017-09-08 | 2019-03-14 | 中国科学院微生物研究所 | 调控a型和b型流感病毒核蛋白出核的关键氨基酸位点及其作为抗流感病毒药物靶点的用途 |
Also Published As
| Publication number | Publication date |
|---|---|
| BR9812660A (pt) | 2000-08-22 |
| HUP0004813A2 (hu) | 2001-08-28 |
| WO1999015173A1 (en) | 1999-04-01 |
| PE118999A1 (es) | 2000-02-03 |
| JP2001517626A (ja) | 2001-10-09 |
| AU8744398A (en) | 1999-04-12 |
| NO20001412D0 (no) | 2000-03-17 |
| KR20010024187A (ko) | 2001-03-26 |
| CA2304005A1 (en) | 1999-04-01 |
| CO5011084A1 (es) | 2001-02-28 |
| EP1014983A1 (en) | 2000-07-05 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1130354A (zh) | 含有丙酸类非甾体消炎药氨基酸盐和减充血药、祛痰药、抗组胺药和镇咳药中至少一种的组合物 | |
| CN1278728A (zh) | 治疗呼吸系统疾病的组合物和方法 | |
| CA2146637C (en) | Pharmaceutical compositions and methods for treating cold symptoms | |
| CN106413717A (zh) | 药物组合物 | |
| JP2000506167A (ja) | 呼吸障害を治療するためのカフェイン及びクレマスチン | |
| JP2005511711A (ja) | 鎮静性抗ヒスタミン剤と非鎮静性抗ヒスタミン剤とを両方含む組成物 | |
| JPH08509725A (ja) | コートされた医薬組成物 | |
| CN101073563A (zh) | 一种含有右旋布洛芬和左旋西替利嗪的手性组合物及其缓速释双层片 | |
| CN1538837A (zh) | 含有对乙酰氨基酚的吞咽片 | |
| JPH11510168A (ja) | 呼吸障害を処理するための鎮痛剤及び抗ヒスタミン剤を含有する組成物及び方法 | |
| JPH09502202A (ja) | プロピオン酸非ステロイド系抗炎症剤のアミノ酸塩とカフェインを含有した組成物 | |
| US20020132002A1 (en) | Sustained release pharmaceutical formulation | |
| WO1992004022A1 (en) | Use of compositions containing 2-(6'-substituted-2'-naphthyl)-acetic acid derivatives for the treatment of respiratory disorders | |
| JP6654426B2 (ja) | 医薬組成物 | |
| JP2008115168A (ja) | 抗アデノウイルス剤 | |
| WO2009112874A1 (en) | Modified release composition comprising doxofylline | |
| JP6260736B1 (ja) | 固形製剤 | |
| JP2008285475A (ja) | ロキソプロフェンを含有する抗アデノウイルス剤 | |
| CN1634082A (zh) | 阿司匹林肠溶口腔崩解片 | |
| JP2007137896A (ja) | イブプロフェン含有医薬製剤 | |
| JP6616968B2 (ja) | 医薬組成物 | |
| JP2008285474A (ja) | 抗アデノウイルス剤を含有する医薬組成物 | |
| JP2008056701A (ja) | イブプロフェン含有医薬製剤 | |
| JP2006327993A (ja) | 鎮痛薬 | |
| JP2012246260A (ja) | 粒状物 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |