CA2439915A1 - New pharmaceutical compositions based on anticholinergics and nk1-receptor antagonists - Google Patents
New pharmaceutical compositions based on anticholinergics and nk1-receptor antagonists Download PDFInfo
- Publication number
- CA2439915A1 CA2439915A1 CA002439915A CA2439915A CA2439915A1 CA 2439915 A1 CA2439915 A1 CA 2439915A1 CA 002439915 A CA002439915 A CA 002439915A CA 2439915 A CA2439915 A CA 2439915A CA 2439915 A1 CA2439915 A1 CA 2439915A1
- Authority
- CA
- Canada
- Prior art keywords
- phenyl
- acid
- alkyl
- inhalable
- methyl
- 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.)
- Abandoned
Links
- 239000002464 receptor antagonist Substances 0.000 title claims abstract description 23
- 229940044551 receptor antagonist Drugs 0.000 title claims abstract description 23
- 102000002002 Neurokinin-1 Receptors Human genes 0.000 title claims abstract description 22
- 108010040718 Neurokinin-1 Receptors Proteins 0.000 title claims abstract description 22
- 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 title claims abstract description 7
- 239000000812 cholinergic antagonist Substances 0.000 title claims abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 32
- 239000000203 mixture Substances 0.000 claims abstract description 73
- 239000003814 drug Substances 0.000 claims abstract description 5
- 239000013543 active substance Substances 0.000 claims description 46
- 239000000443 aerosol Substances 0.000 claims description 40
- 239000002904 solvent Substances 0.000 claims description 38
- 125000000217 alkyl group Chemical group 0.000 claims description 30
- 239000000725 suspension Substances 0.000 claims description 28
- 238000009472 formulation Methods 0.000 claims description 26
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 26
- 239000000843 powder Substances 0.000 claims description 25
- 239000003380 propellant Substances 0.000 claims description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 20
- 150000003839 salts Chemical class 0.000 claims description 20
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 18
- -1 N-methylpiperidinyl Chemical group 0.000 claims description 18
- 239000004615 ingredient Substances 0.000 claims description 18
- 150000001875 compounds Chemical class 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 16
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 15
- 239000002775 capsule Substances 0.000 claims description 13
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 12
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- LERNTVKEWCAPOY-DZZGSBJMSA-N tiotropium Chemical class O([C@H]1C[C@@H]2[N+]([C@H](C1)[C@@H]1[C@H]2O1)(C)C)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 LERNTVKEWCAPOY-DZZGSBJMSA-N 0.000 claims description 11
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 10
- 235000011167 hydrochloric acid Nutrition 0.000 claims description 10
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- 239000002245 particle Substances 0.000 claims description 9
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 8
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 claims description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 7
- 239000003963 antioxidant agent Substances 0.000 claims description 7
- 235000006708 antioxidants Nutrition 0.000 claims description 7
- ATALOFNDEOCMKK-OITMNORJSA-N aprepitant Chemical compound O([C@@H]([C@@H]1C=2C=CC(F)=CC=2)O[C@H](C)C=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)CCN1CC1=NNC(=O)N1 ATALOFNDEOCMKK-OITMNORJSA-N 0.000 claims description 7
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 7
- HUTHJVYJUPXHDF-DEOSSOPVSA-N (2s)-n-[2-[3,5-bis(trifluoromethyl)phenyl]ethyl]-2-[4-(cyclopropylmethyl)piperazin-1-yl]-n-methyl-2-phenylacetamide Chemical compound O=C([C@@H](N1CCN(CC2CC2)CC1)C=1C=CC=CC=1)N(C)CCC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 HUTHJVYJUPXHDF-DEOSSOPVSA-N 0.000 claims description 6
- XPNMCDYOYIKVGB-CONSDPRKSA-N (2s,3s)-2-benzhydryl-n-[(2-methoxy-5-propan-2-ylphenyl)methyl]-1-azabicyclo[2.2.2]octan-3-amine Chemical compound COC1=CC=C(C(C)C)C=C1CN[C@@H]1[C@H](C(C=2C=CC=CC=2)C=2C=CC=CC=2)N2CCC1CC2 XPNMCDYOYIKVGB-CONSDPRKSA-N 0.000 claims description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 claims description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- 235000010323 ascorbic acid Nutrition 0.000 claims description 6
- 239000011668 ascorbic acid Substances 0.000 claims description 6
- 229960005070 ascorbic acid Drugs 0.000 claims description 6
- 239000001530 fumaric acid Substances 0.000 claims description 6
- OEXHQOGQTVQTAT-JRNQLAHRSA-N ipratropium Chemical class O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 OEXHQOGQTVQTAT-JRNQLAHRSA-N 0.000 claims description 6
- 239000003755 preservative agent Substances 0.000 claims description 6
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 5
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 5
- 235000015165 citric acid Nutrition 0.000 claims description 5
- 239000008139 complexing agent Substances 0.000 claims description 5
- 239000012141 concentrate Substances 0.000 claims description 5
- NVOYVOBDTVTBDX-PMEUIYRNSA-N oxitropium Chemical class CC[N+]1(C)[C@H]2C[C@@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)[C@H](CO)C1=CC=CC=C1 NVOYVOBDTVTBDX-PMEUIYRNSA-N 0.000 claims description 5
- 239000003381 stabilizer Substances 0.000 claims description 5
- ZIWFCOIGUNPHPM-HKUYNNGSSA-N (2s,3s)-n-[[2-methoxy-5-(trifluoromethoxy)phenyl]methyl]-2-phenylpiperidin-3-amine Chemical compound COC1=CC=C(OC(F)(F)F)C=C1CN[C@@H]1[C@H](C=2C=CC=CC=2)NCCC1 ZIWFCOIGUNPHPM-HKUYNNGSSA-N 0.000 claims description 4
- XILNRORTJVDYRH-HKUYNNGSSA-N (2s,3s)-n-[[2-methoxy-5-[5-(trifluoromethyl)tetrazol-1-yl]phenyl]methyl]-2-phenylpiperidin-3-amine Chemical compound C1([C@@H]2NCCC[C@@H]2NCC2=CC(=CC=C2OC)N2C(=NN=N2)C(F)(F)F)=CC=CC=C1 XILNRORTJVDYRH-HKUYNNGSSA-N 0.000 claims description 4
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 4
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 claims description 4
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 4
- 229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 150000001298 alcohols Chemical class 0.000 claims description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 4
- 201000010099 disease Diseases 0.000 claims description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 4
- 235000019253 formic acid Nutrition 0.000 claims description 4
- 150000004677 hydrates Chemical class 0.000 claims description 4
- 230000002757 inflammatory effect Effects 0.000 claims description 4
- NNPPMTNAJDCUHE-UHFFFAOYSA-N isobutane Chemical compound CC(C)C NNPPMTNAJDCUHE-UHFFFAOYSA-N 0.000 claims description 4
- VSKQRMHRWDXZPR-UHFFFAOYSA-N n-[2-[3,5-bis(trifluoromethyl)phenyl]ethyl]-2-[4-(1,3-dihydroxypropan-2-ylamino)piperidin-1-yl]-n-methyl-2-phenylacetamide Chemical compound C1CC(NC(CO)CO)CCN1C(C=1C=CC=CC=1)C(=O)N(C)CCC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 VSKQRMHRWDXZPR-UHFFFAOYSA-N 0.000 claims description 4
- XMAVVCOSFCHLNQ-UHFFFAOYSA-N n-[2-[3,5-bis(trifluoromethyl)phenyl]ethyl]-2-[4-[2-hydroxyethyl(3-hydroxypropyl)amino]piperidin-1-yl]-n-methyl-2-phenylacetamide Chemical compound C1CC(N(CCO)CCCO)CCN1C(C=1C=CC=CC=1)C(=O)N(C)CCC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 XMAVVCOSFCHLNQ-UHFFFAOYSA-N 0.000 claims description 4
- GIALVDJQVZLCEJ-UHFFFAOYSA-N n-[2-[3,5-bis(trifluoromethyl)phenyl]ethyl]-2-[4-[cyclopropylmethyl(3-hydroxypropyl)amino]piperidin-1-yl]-n-methyl-2-phenylacetamide Chemical compound C1CC(N(CCCO)CC2CC2)CCN1C(C=1C=CC=CC=1)C(=O)N(C)CCC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 GIALVDJQVZLCEJ-UHFFFAOYSA-N 0.000 claims description 4
- ASBGMDZIWCEVNG-UHFFFAOYSA-N n-[2-[3,5-bis(trifluoromethyl)phenyl]ethyl]-2-[4-[cyclopropylmethyl(methyl)amino]piperidin-1-yl]-n-methyl-2-phenylacetamide Chemical compound C1CN(C(C(=O)N(C)CCC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)C=2C=CC=CC=2)CCC1N(C)CC1CC1 ASBGMDZIWCEVNG-UHFFFAOYSA-N 0.000 claims description 4
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 claims description 4
- 230000000414 obstructive effect Effects 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 210000002345 respiratory system Anatomy 0.000 claims description 4
- 235000011149 sulphuric acid Nutrition 0.000 claims description 4
- 239000004094 surface-active agent Substances 0.000 claims description 4
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 3
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 3
- 235000011054 acetic acid Nutrition 0.000 claims description 3
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims description 3
- 150000002016 disaccharides Chemical class 0.000 claims description 3
- 239000000796 flavoring agent Substances 0.000 claims description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 150000002772 monosaccharides Chemical class 0.000 claims description 3
- NJGRIQCLLOJEHU-UHFFFAOYSA-N n-[2-[3,5-bis(trifluoromethyl)phenyl]ethyl]-2-[4-[3-hydroxypropyl(methyl)amino]piperidin-1-yl]-n-methyl-2-phenylacetamide Chemical compound C1CC(N(CCCO)C)CCN1C(C=1C=CC=CC=1)C(=O)N(C)CCC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 NJGRIQCLLOJEHU-UHFFFAOYSA-N 0.000 claims description 3
- 239000012453 solvate Substances 0.000 claims description 3
- 239000001117 sulphuric acid Substances 0.000 claims description 3
- 239000011975 tartaric acid Substances 0.000 claims description 3
- 235000002906 tartaric acid Nutrition 0.000 claims description 3
- 238000002604 ultrasonography Methods 0.000 claims description 3
- 229930003231 vitamin Natural products 0.000 claims description 3
- 239000011782 vitamin Substances 0.000 claims description 3
- 235000013343 vitamin Nutrition 0.000 claims description 3
- 229940088594 vitamin Drugs 0.000 claims description 3
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 2
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 2
- FPIPGXGPPPQFEQ-UHFFFAOYSA-N 13-cis retinol Natural products OCC=C(C)C=CC=C(C)C=CC1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000005711 Benzoic acid Substances 0.000 claims description 2
- PMPVIKIVABFJJI-UHFFFAOYSA-N Cyclobutane Chemical class C1CCC1 PMPVIKIVABFJJI-UHFFFAOYSA-N 0.000 claims description 2
- LVZWSLJZHVFIQJ-UHFFFAOYSA-N Cyclopropane Chemical class C1CC1 LVZWSLJZHVFIQJ-UHFFFAOYSA-N 0.000 claims description 2
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical class CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 claims description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims description 2
- FPIPGXGPPPQFEQ-BOOMUCAASA-N Vitamin A Natural products OC/C=C(/C)\C=C\C=C(\C)/C=C/C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-BOOMUCAASA-N 0.000 claims description 2
- 229930003427 Vitamin E Natural products 0.000 claims description 2
- FPIPGXGPPPQFEQ-OVSJKPMPSA-N all-trans-retinol Chemical compound OC\C=C(/C)\C=C\C=C(/C)\C=C\C1=C(C)CCCC1(C)C FPIPGXGPPPQFEQ-OVSJKPMPSA-N 0.000 claims description 2
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
- 235000010233 benzoic acid Nutrition 0.000 claims description 2
- 229960004365 benzoic acid Drugs 0.000 claims description 2
- 150000001558 benzoic acid derivatives Chemical class 0.000 claims description 2
- 239000001273 butane Chemical class 0.000 claims description 2
- YMKDRGPMQRFJGP-UHFFFAOYSA-M cetylpyridinium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+]1=CC=CC=C1 YMKDRGPMQRFJGP-UHFFFAOYSA-M 0.000 claims description 2
- 229960001927 cetylpyridinium chloride Drugs 0.000 claims description 2
- 235000014113 dietary fatty acids Nutrition 0.000 claims description 2
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims description 2
- 239000000194 fatty acid Substances 0.000 claims description 2
- 229930195729 fatty acid Natural products 0.000 claims description 2
- 235000011087 fumaric acid Nutrition 0.000 claims description 2
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 claims description 2
- 150000004676 glycans Chemical class 0.000 claims description 2
- 150000002334 glycols Chemical class 0.000 claims description 2
- 150000005826 halohydrocarbons Chemical class 0.000 claims description 2
- 229930195733 hydrocarbon Natural products 0.000 claims description 2
- 150000002430 hydrocarbons Chemical class 0.000 claims description 2
- 239000001282 iso-butane Substances 0.000 claims description 2
- 239000000314 lubricant Substances 0.000 claims description 2
- 239000001630 malic acid Substances 0.000 claims description 2
- 235000011090 malic acid Nutrition 0.000 claims description 2
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical class C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 claims description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Chemical class CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- 150000002482 oligosaccharides Polymers 0.000 claims description 2
- 229920001223 polyethylene glycol Polymers 0.000 claims description 2
- 229920001451 polypropylene glycol Polymers 0.000 claims description 2
- 229920001282 polysaccharide Polymers 0.000 claims description 2
- 239000005017 polysaccharide Substances 0.000 claims description 2
- 239000001294 propane Chemical class 0.000 claims description 2
- 235000019260 propionic acid Nutrition 0.000 claims description 2
- 229960004063 propylene glycol Drugs 0.000 claims description 2
- 235000013772 propylene glycol Nutrition 0.000 claims description 2
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 claims description 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 2
- 125000004076 pyridyl group Chemical group 0.000 claims description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 2
- 150000005846 sugar alcohols Polymers 0.000 claims description 2
- 229930003799 tocopherol Natural products 0.000 claims description 2
- 239000011732 tocopherol Substances 0.000 claims description 2
- 235000019149 tocopherols Nutrition 0.000 claims description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 claims description 2
- 235000019155 vitamin A Nutrition 0.000 claims description 2
- 239000011719 vitamin A Substances 0.000 claims description 2
- 235000019165 vitamin E Nutrition 0.000 claims description 2
- 239000011709 vitamin E Substances 0.000 claims description 2
- 229940046009 vitamin E Drugs 0.000 claims description 2
- 229940045997 vitamin a Drugs 0.000 claims description 2
- QUEDXNHFTDJVIY-UHFFFAOYSA-N γ-tocopherol Chemical class OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1 QUEDXNHFTDJVIY-UHFFFAOYSA-N 0.000 claims description 2
- OWOHLURDBZHNGG-YFKPBYRVSA-N (8ar)-hexahydropyrrolo[1,2-a]pyrazine-1,4-dione Chemical compound O=C1CNC(=O)[C@@H]2CCCN12 OWOHLURDBZHNGG-YFKPBYRVSA-N 0.000 claims 2
- OVBJJZOQPCKUOR-UHFFFAOYSA-L EDTA disodium salt dihydrate Chemical compound O.O.[Na+].[Na+].[O-]C(=O)C[NH+](CC([O-])=O)CC[NH+](CC([O-])=O)CC([O-])=O OVBJJZOQPCKUOR-UHFFFAOYSA-L 0.000 claims 2
- 229940037001 sodium edetate Drugs 0.000 claims 2
- VSKQRMHRWDXZPR-DEOSSOPVSA-N (2s)-n-[2-[3,5-bis(trifluoromethyl)phenyl]ethyl]-2-[4-(1,3-dihydroxypropan-2-ylamino)piperidin-1-yl]-n-methyl-2-phenylacetamide Chemical compound O=C([C@@H](N1CCC(CC1)NC(CO)CO)C=1C=CC=CC=1)N(C)CCC1=CC(C(F)(F)F)=CC(C(F)(F)F)=C1 VSKQRMHRWDXZPR-DEOSSOPVSA-N 0.000 claims 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims 1
- 239000006184 cosolvent Substances 0.000 claims 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims 1
- 239000011976 maleic acid Substances 0.000 claims 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 11
- 208000018569 Respiratory Tract disease Diseases 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 72
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 42
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- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 239000002274 desiccant Substances 0.000 description 1
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- 125000004990 dihydroxyalkyl group Chemical group 0.000 description 1
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- 229960001361 ipratropium bromide Drugs 0.000 description 1
- KEWHKYJURDBRMN-ZEODDXGYSA-M ipratropium bromide hydrate Chemical compound O.[Br-].O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 KEWHKYJURDBRMN-ZEODDXGYSA-M 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
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- 229910052751 metal Inorganic materials 0.000 description 1
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
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- ZGMCKRSPXWWEAO-UHFFFAOYSA-N n-(cyclopropylmethyl)-n-methylpiperidin-4-amine Chemical compound C1CNCCC1N(C)CC1CC1 ZGMCKRSPXWWEAO-UHFFFAOYSA-N 0.000 description 1
- FCSOWUBSHSLEHV-UHFFFAOYSA-N n-(cyclopropylmethyl)-n-methylpiperidin-4-amine;dihydrochloride Chemical compound Cl.Cl.C1CNCCC1N(C)CC1CC1 FCSOWUBSHSLEHV-UHFFFAOYSA-N 0.000 description 1
- JXDKAWGCUBTYFX-BMPTZRATSA-N n-[(1s,2r)-2-[[(2r)-2-[methyl-[2-(4-methylphenyl)acetyl]amino]-3-naphthalen-2-ylpropanoyl]amino]cyclohexyl]-1h-indole-3-carboxamide Chemical compound CN([C@H](CC=1C=C2C=CC=CC2=CC=1)C(=O)N[C@H]1[C@H](CCCC1)NC(=O)C=1C2=CC=CC=C2NC=1)C(=O)CC1=CC=C(C)C=C1 JXDKAWGCUBTYFX-BMPTZRATSA-N 0.000 description 1
- CVXJAPZTZWLRBP-MUUNZHRXSA-N n-[(2r)-1-[acetyl-[(2-methoxyphenyl)methyl]amino]-3-(1h-indol-3-yl)propan-2-yl]-2-(4-piperidin-1-ylpiperidin-1-yl)acetamide Chemical compound COC1=CC=CC=C1CN(C(C)=O)C[C@H](NC(=O)CN1CCC(CC1)N1CCCCC1)CC1=CNC2=CC=CC=C12 CVXJAPZTZWLRBP-MUUNZHRXSA-N 0.000 description 1
- IGAXDMFXJYIUIV-XIFFEERXSA-N n-[1-[[(2s)-1-[benzyl(methyl)amino]-3-naphthalen-2-yl-1-oxopropan-2-yl]carbamoyl]cyclohexyl]-1h-indole-3-carboxamide Chemical compound O=C([C@H](CC=1C=C2C=CC=CC2=CC=1)NC(=O)C1(CCCCC1)NC(=O)C=1C2=CC=CC=C2NC=1)N(C)CC1=CC=CC=C1 IGAXDMFXJYIUIV-XIFFEERXSA-N 0.000 description 1
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- 229960001609 oxitropium bromide Drugs 0.000 description 1
- LCELQERNWLBPSY-KHSTUMNDSA-M oxitropium bromide Chemical compound [Br-].C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3[N+]([C@H](C2)[C@@H]2[C@H]3O2)(C)CC)=CC=CC=C1 LCELQERNWLBPSY-KHSTUMNDSA-M 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
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- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
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- 229940068965 polysorbates Drugs 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
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- 230000036515 potency Effects 0.000 description 1
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- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 239000002002 slurry Substances 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
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
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- 229960004793 sucrose Drugs 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/0075—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a dry powder inhaler [DPI], e.g. comprising micronized drug mixed with lactose carrier particles
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
-
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
- A61K9/008—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy comprising drug dissolved or suspended in liquid propellant for inhalation via a pressurized metered dose inhaler [MDI]
-
- 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
-
- 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
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Pulmonology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Otolaryngology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10111058.8 | 2001-03-08 | ||
| DE10111058A DE10111058A1 (de) | 2001-03-08 | 2001-03-08 | Neue Arzneimittelkompositionen auf der Basis von Anticholinergika und NK¶1¶-Rezeptor-Antagonisten |
| PCT/EP2002/001987 WO2002069944A2 (de) | 2001-03-08 | 2002-02-26 | Neue arzneimittelkompositionen auf der basis von anticholinergika und nk1-rezeptor-antagonisten |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2439915A1 true CA2439915A1 (en) | 2002-09-12 |
Family
ID=7676673
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002439915A Abandoned CA2439915A1 (en) | 2001-03-08 | 2002-02-26 | New pharmaceutical compositions based on anticholinergics and nk1-receptor antagonists |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP1370293A2 (enExample) |
| JP (1) | JP2004519484A (enExample) |
| AU (1) | AU2002251010A1 (enExample) |
| CA (1) | CA2439915A1 (enExample) |
| DE (1) | DE10111058A1 (enExample) |
| MX (1) | MXPA03008051A (enExample) |
| WO (1) | WO2002069944A2 (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10214264A1 (de) * | 2002-03-28 | 2003-10-16 | Boehringer Ingelheim Pharma | HFA-Suspensionsformulierungen eines Anhydrats |
| US7244415B2 (en) | 2002-03-28 | 2007-07-17 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | HFA suspension formulations of an anhydrate |
| DE10230750A1 (de) * | 2002-07-09 | 2004-01-22 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Neue Arzneimittelkompositionen auf der Basis neuer Anticholonergika und NK1-Rezeptor-Antagonisten |
| WO2005004875A1 (ja) * | 2003-07-14 | 2005-01-20 | Sankyo Company, Limited | 経肺投与用医薬組成物 |
| JP2006160639A (ja) * | 2004-12-06 | 2006-06-22 | Sankyo Co Ltd | ニューロキニン受容体拮抗剤と抗コリン剤の併用 |
| ITRM20120331A1 (it) * | 2012-07-12 | 2014-01-13 | Guidotti & C Spa Labor | Composizioni pediatriche orali liquide contenenti nepadutant. |
| WO2015111627A1 (ja) * | 2014-01-21 | 2015-07-30 | 味の素株式会社 | 糖アミノ酸およびその用途 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3429338B2 (ja) * | 1992-07-27 | 2003-07-22 | 杏林製薬株式会社 | 新規なアリールグリシンアミド誘導体及びその製造法 |
| US5545617A (en) * | 1993-11-12 | 1996-08-13 | The Schepens Eye Research Institute, Inc. | Therapeutic regulation of abnormal conjunctival goblet cell mucous secretion |
| DE19608665A1 (de) * | 1996-03-06 | 1997-09-11 | Boehringer Ingelheim Kg | Neue Arylglycinamidderivate, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende pharmazeutische Zusammensetzungen |
| US6124319A (en) * | 1997-01-21 | 2000-09-26 | Merck & Co., Inc. | 3,3-disubstituted piperidines as modulators of chemokine receptor activity |
| AU4279699A (en) * | 1998-06-11 | 1999-12-30 | Merck Sharp & Dohme Limited | Use of a nk-1 receptor antagonist for treating psychiatric disorders |
-
2001
- 2001-03-08 DE DE10111058A patent/DE10111058A1/de not_active Withdrawn
-
2002
- 2002-02-22 MX MXPA03008051A patent/MXPA03008051A/es not_active Application Discontinuation
- 2002-02-26 AU AU2002251010A patent/AU2002251010A1/en not_active Abandoned
- 2002-02-26 CA CA002439915A patent/CA2439915A1/en not_active Abandoned
- 2002-02-26 WO PCT/EP2002/001987 patent/WO2002069944A2/de not_active Ceased
- 2002-02-26 JP JP2002569121A patent/JP2004519484A/ja active Pending
- 2002-02-26 EP EP02719915A patent/EP1370293A2/de not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| JP2004519484A (ja) | 2004-07-02 |
| AU2002251010A1 (en) | 2002-09-19 |
| WO2002069944A2 (de) | 2002-09-12 |
| EP1370293A2 (de) | 2003-12-17 |
| WO2002069944A3 (de) | 2003-10-02 |
| MXPA03008051A (es) | 2003-12-04 |
| DE10111058A1 (de) | 2002-09-12 |
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