NO320303B1 - Tablettformulering med vedvarende frigivelse for behandling av Parkinsons sykdom - Google Patents
Tablettformulering med vedvarende frigivelse for behandling av Parkinsons sykdom Download PDFInfo
- Publication number
- NO320303B1 NO320303B1 NO20001624A NO20001624A NO320303B1 NO 320303 B1 NO320303 B1 NO 320303B1 NO 20001624 A NO20001624 A NO 20001624A NO 20001624 A NO20001624 A NO 20001624A NO 320303 B1 NO320303 B1 NO 320303B1
- Authority
- NO
- Norway
- Prior art keywords
- pharmaceutical preparation
- usp
- preparation according
- mixture
- hydroxypropylmethylcellulose
- Prior art date
Links
- 239000007939 sustained release tablet Substances 0.000 title claims abstract description 4
- 239000000203 mixture Substances 0.000 title claims description 47
- 208000018737 Parkinson disease Diseases 0.000 title abstract description 6
- 238000009472 formulation Methods 0.000 title description 6
- 239000003826 tablet Substances 0.000 claims description 27
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 17
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 17
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 16
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 claims description 16
- 229920002472 Starch Polymers 0.000 claims description 14
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 14
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 14
- 235000019698 starch Nutrition 0.000 claims description 14
- 239000008107 starch Substances 0.000 claims description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 12
- 229940031702 hydroxypropyl methylcellulose 2208 Drugs 0.000 claims description 11
- 235000019359 magnesium stearate Nutrition 0.000 claims description 7
- 229940075614 colloidal silicon dioxide Drugs 0.000 claims description 6
- 229940031705 hydroxypropyl methylcellulose 2910 Drugs 0.000 claims description 5
- 229920002261 Corn starch Polymers 0.000 claims description 4
- 229920000881 Modified starch Polymers 0.000 claims description 3
- 239000008120 corn starch Substances 0.000 claims description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 239000002904 solvent Substances 0.000 description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 13
- 150000001875 compounds Chemical class 0.000 description 11
- 229940032147 starch Drugs 0.000 description 11
- 239000007916 tablet composition Substances 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000000034 method Methods 0.000 description 9
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 7
- 235000019341 magnesium sulphate Nutrition 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 5
- 239000012141 concentrate Substances 0.000 description 5
- 238000003818 flash chromatography Methods 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000002480 mineral oil Substances 0.000 description 5
- 235000010446 mineral oil Nutrition 0.000 description 5
- 239000004480 active ingredient Substances 0.000 description 4
- 239000000538 analytical sample Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000013268 sustained release Methods 0.000 description 4
- 239000012730 sustained-release form Substances 0.000 description 4
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 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 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 3
- 239000010409 thin film Substances 0.000 description 3
- 238000004809 thin layer chromatography Methods 0.000 description 3
- PEZNEXFPRSOYPL-UHFFFAOYSA-N (bis(trifluoroacetoxy)iodo)benzene Chemical compound FC(F)(F)C(=O)OI(OC(=O)C(F)(F)F)C1=CC=CC=C1 PEZNEXFPRSOYPL-UHFFFAOYSA-N 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- 229920000856 Amylose Polymers 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 240000008042 Zea mays Species 0.000 description 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 2
- LDECUSDQMXVUMP-UHFFFAOYSA-N benzyl 3-[6-[[2-(butylamino)-1-[3-methoxycarbonyl-4-(2-methoxy-2-oxoethoxy)phenyl]-2-oxoethyl]-hexylamino]-6-oxohexyl]-4-methyl-2-oxo-6-(4-phenylphenyl)-1,6-dihydropyrimidine-5-carboxylate Chemical compound O=C1NC(C=2C=CC(=CC=2)C=2C=CC=CC=2)C(C(=O)OCC=2C=CC=CC=2)=C(C)N1CCCCCC(=O)N(CCCCCC)C(C(=O)NCCCC)C1=CC=C(OCC(=O)OC)C(C(=O)OC)=C1 LDECUSDQMXVUMP-UHFFFAOYSA-N 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000036765 blood level Effects 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 235000005822 corn Nutrition 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- 238000007907 direct compression Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 2
- UPCAUQHSJMAOFY-SNVBAGLBSA-N methyl n-[(2r)-1-(methoxyamino)-1-oxo-3-phenylpropan-2-yl]carbamate Chemical compound CONC(=O)[C@H](NC(=O)OC)CC1=CC=CC=C1 UPCAUQHSJMAOFY-SNVBAGLBSA-N 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 229960000278 theophylline Drugs 0.000 description 2
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 2
- 238000005550 wet granulation Methods 0.000 description 2
- QGICDLYPUUZBIV-SECBINFHSA-N (2r)-2-(methoxycarbonylamino)-3-phenylpropanoic acid Chemical compound COC(=O)N[C@@H](C(O)=O)CC1=CC=CC=C1 QGICDLYPUUZBIV-SECBINFHSA-N 0.000 description 1
- IQDMUSPYIULEGD-SECBINFHSA-N (3r)-n-methyl-1,2,3,4-tetrahydroquinolin-3-amine Chemical compound C1=CC=C2C[C@@H](NC)CNC2=C1 IQDMUSPYIULEGD-SECBINFHSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 1
- COLNVLDHVKWLRT-MRVPVSSYSA-N D-phenylalanine Chemical compound OC(=O)[C@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-MRVPVSSYSA-N 0.000 description 1
- 229930182832 D-phenylalanine Natural products 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 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 1
- 239000005909 Kieselgur Substances 0.000 description 1
- 229920003091 Methocel™ Polymers 0.000 description 1
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- WMCSOLODEMCLIL-MRVPVSSYSA-N [(3R)-1-methoxy-2-oxo-3,4-dihydroquinolin-3-yl]carbamic acid Chemical compound C1=CC=C2N(OC)C(=O)[C@H](NC(O)=O)CC2=C1 WMCSOLODEMCLIL-MRVPVSSYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000012223 aqueous fraction Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- MJSHDCCLFGOEIK-UHFFFAOYSA-N benzyl (2,5-dioxopyrrolidin-1-yl) carbonate Chemical compound O=C1CCC(=O)N1OC(=O)OCC1=CC=CC=C1 MJSHDCCLFGOEIK-UHFFFAOYSA-N 0.000 description 1
- VSTVPNVVKXAOLZ-QGZVFWFLSA-N benzyl n-[(3r)-1-(methoxycarbamoyl)-3,4-dihydro-2h-quinolin-3-yl]-n-methylcarbamate Chemical compound CN([C@H]1CN(C2=CC=CC=C2C1)C(=O)NOC)C(=O)OCC1=CC=CC=C1 VSTVPNVVKXAOLZ-QGZVFWFLSA-N 0.000 description 1
- CNRFRMQVMVEMAF-MRXNPFEDSA-N benzyl n-methyl-n-[(3r)-1,2,3,4-tetrahydroquinolin-3-yl]carbamate Chemical compound CN([C@@H]1CC2=CC=CC=C2NC1)C(=O)OCC1=CC=CC=C1 CNRFRMQVMVEMAF-MRXNPFEDSA-N 0.000 description 1
- CCDWGDHTPAJHOA-UHFFFAOYSA-N benzylsilicon Chemical compound [Si]CC1=CC=CC=C1 CCDWGDHTPAJHOA-UHFFFAOYSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- MCQRPQCQMGVWIQ-UHFFFAOYSA-N boron;methylsulfanylmethane Chemical compound [B].CSC MCQRPQCQMGVWIQ-UHFFFAOYSA-N 0.000 description 1
- 239000012159 carrier gas Substances 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 229920003086 cellulose ether Polymers 0.000 description 1
- 238000000451 chemical ionisation Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000007908 dry granulation Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000010408 film Substances 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 230000014509 gene expression Effects 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 239000001307 helium Substances 0.000 description 1
- 229910052734 helium Inorganic materials 0.000 description 1
- SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- -1 hydroxypropyl Chemical group 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 150000002689 maleic acids Chemical class 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 1
- 239000002831 pharmacologic agent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229920001921 poly-methyl-phenyl-siloxane Polymers 0.000 description 1
- 229940069328 povidone Drugs 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 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
- A61K31/435—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
-
- 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
-
- 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
- A61K31/4741—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having oxygen as a ring hetero atom, e.g. tubocuraran derivatives, noscapine, bicuculline
-
- 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
- A61K31/495—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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US6082797P | 1997-09-30 | 1997-09-30 | |
| PCT/US1998/017992 WO1999016442A2 (fr) | 1997-09-30 | 1998-09-03 | Formulation de comprimes a degagement prolonge pour le traitement de la maladie de parkinson |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO20001624D0 NO20001624D0 (no) | 2000-03-29 |
| NO20001624L NO20001624L (no) | 2000-03-29 |
| NO320303B1 true NO320303B1 (no) | 2005-11-21 |
Family
ID=22031996
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20001624A NO320303B1 (no) | 1997-09-30 | 2000-03-29 | Tablettformulering med vedvarende frigivelse for behandling av Parkinsons sykdom |
Country Status (23)
| Country | Link |
|---|---|
| US (2) | US6197339B1 (fr) |
| EP (1) | EP1017391B1 (fr) |
| JP (1) | JP2001517701A (fr) |
| KR (1) | KR100516095B1 (fr) |
| CN (1) | CN1195518C (fr) |
| AT (1) | ATE297208T1 (fr) |
| AU (1) | AU742941B2 (fr) |
| BR (1) | BR9812687A (fr) |
| CA (1) | CA2301869A1 (fr) |
| DE (1) | DE69830503T2 (fr) |
| DK (1) | DK1017391T3 (fr) |
| ES (1) | ES2242296T3 (fr) |
| FI (1) | FI20000720A (fr) |
| HK (1) | HK1030163A1 (fr) |
| HU (1) | HUP0004586A2 (fr) |
| NO (1) | NO320303B1 (fr) |
| NZ (1) | NZ504221A (fr) |
| PL (1) | PL191125B1 (fr) |
| PT (1) | PT1017391E (fr) |
| RU (1) | RU2205007C2 (fr) |
| SI (1) | SI1017391T1 (fr) |
| SK (1) | SK3612000A3 (fr) |
| WO (1) | WO1999016442A2 (fr) |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2358865A1 (fr) | 1999-02-05 | 2000-08-10 | Pharmacia & Upjohn Company | Procede de preparation de (5r)-(methylamino)-5,6-dihydro-4h-imidazo[4,5,1-ij]-quinoline-2(1h)-one |
| US6667060B1 (en) | 1999-03-31 | 2003-12-23 | Janssen Pharmaceutica N.V. | Pregelatinized starch in a controlled release formulation |
| AR031152A1 (es) * | 2000-10-31 | 2003-09-10 | Upjohn Co | Tratamientos nuevos para el sindrome de piernas inquietas |
| FR2825705B1 (fr) | 2001-06-08 | 2005-05-20 | Aventis Pharma Sa | Nouveaux composes heterocycliques, leur preparation et leur utilisation comme medicaments, notamment comme anti-bacteriens |
| US20060281797A1 (en) * | 2001-12-11 | 2006-12-14 | University Of Virginia Patent Foundation | Neurorestoration with R(+) Pramipexole |
| ATE480235T1 (de) * | 2001-12-11 | 2010-09-15 | Univ Virginia | Verwendung von pramipexol zur behandlung von amyotrophischer lateralsklerose |
| FR2835186B1 (fr) | 2002-01-28 | 2006-10-20 | Aventis Pharma Sa | Nouveaux composes heterocycliques, actifs comme inhibiteurs de beta-lactamases |
| US20030203055A1 (en) * | 2002-03-15 | 2003-10-30 | Cypress Bioscience, Inc. | Methods of treating visceral pain syndromes |
| US20050079217A1 (en) * | 2002-07-25 | 2005-04-14 | Ganorkar Loksidh D. | Sustained-release tablet composition comprising a dopamine receptor agonist |
| US20050226926A1 (en) | 2002-07-25 | 2005-10-13 | Pfizer Inc | Sustained-release tablet composition of pramipexole |
| MY136318A (en) * | 2002-07-25 | 2008-09-30 | Pharmacia Corp | Sustained-release tablet composition |
| AR040682A1 (es) * | 2002-07-25 | 2005-04-13 | Pharmacia Corp | Forma de dosificacion una vez al dia de pramipexol |
| FR2844273B1 (fr) | 2002-09-05 | 2008-04-04 | Aventis Pharma Sa | Nouveaux composes heterocycliques, procede et intermediaires de preparation et utilisation comme medicament, notamment comme inhibiteurs de beta-lactamases et anti-bacteriens. |
| MXPA05003513A (es) * | 2002-10-04 | 2005-06-03 | Pharmacia Corp | Composiciones farmaceuticas para tratamiento de enfermedad de parkinson. |
| CA2500919A1 (fr) * | 2002-10-04 | 2004-04-22 | Pharmacia Corporation | Compositions et methodes permettant le traitement des dysfonctions sexuelles |
| US20060003004A1 (en) * | 2002-10-25 | 2006-01-05 | Collegium Pharmaceutical, Inc. | Pulsatile release compositions of milnacipran |
| CN1728998A (zh) * | 2002-10-25 | 2006-02-01 | 法玛西雅厄普约翰有限责任公司 | 杂环胺类化合物作为神经保护剂的用途 |
| US20040132826A1 (en) * | 2002-10-25 | 2004-07-08 | Collegium Pharmaceutical, Inc. | Modified release compositions of milnacipran |
| WO2004067039A1 (fr) * | 2003-01-28 | 2004-08-12 | Collegium Pharmaceutical, Inc. | Compositions multiparticulaires de milnacipran destinees a etre administrees par voie orale |
| US20050020589A1 (en) * | 2003-06-18 | 2005-01-27 | Pfizer Inc. | Sustained-release tablet composition comprising a dopamine receptor agonist |
| JP4971159B2 (ja) * | 2004-08-13 | 2012-07-11 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | プラミペキソール又はその薬学的に許容しうる塩を含有する徐放性ペレット製剤、その製法及び使用 |
| CN101849921A (zh) * | 2004-08-13 | 2010-10-06 | 贝林格尔·英格海姆国际有限公司 | 包含普拉克索或其可药用盐的延长释放片剂 |
| JP2009504748A (ja) * | 2005-08-15 | 2009-02-05 | ユニバーシティ オブ バージニア パテント ファウンデーション | Ｒ（＋）プラミペキソールを用いた神経回復 |
| WO2007090883A1 (fr) * | 2006-02-10 | 2007-08-16 | Boehringer Ingelheim International Gmbh | Formulation à libération prolongée |
| CA2641665A1 (fr) * | 2006-02-10 | 2007-08-16 | Boehringer Ingelheim International Gmbh | Formulation a liberation modifiee |
| US8518926B2 (en) * | 2006-04-10 | 2013-08-27 | Knopp Neurosciences, Inc. | Compositions and methods of using (R)-pramipexole |
| KR20090021169A (ko) | 2006-05-16 | 2009-02-27 | 크놉 뉴로사이언시스 인코포레이티드 | Ｒ(+) 및 ｓ(-) 프라미펙솔을 포함하는 조성물 및 이의 사용 방법 |
| US8524695B2 (en) * | 2006-12-14 | 2013-09-03 | Knopp Neurosciences, Inc. | Modified release formulations of (6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazole-diamine and methods of using the same |
| WO2008113056A2 (fr) | 2007-03-14 | 2008-09-18 | Knopp Neurosciences, Inc. | Synthèse de benzothiazole diamines substituées et purifiées du point de vue chiral |
| EP2334185A4 (fr) * | 2008-08-19 | 2011-09-21 | Knopp Neurosciences Inc | Compositions et procédés employant du (r)-pramipexole |
| CA2845147A1 (fr) | 2011-09-23 | 2013-03-28 | Roche Glycart Ag | Anticorps bispecifiques anti-egf/anti-igf-1r |
| WO2013096816A1 (fr) | 2011-12-22 | 2013-06-27 | Biogen Idec Ma Inc. | Synthèse améliorée de composés substitués par amine de 4,5,6,7-tétrahydrobenzothiazole |
| US9662313B2 (en) | 2013-02-28 | 2017-05-30 | Knopp Biosciences Llc | Compositions and methods for treating amyotrophic lateral sclerosis in responders |
| WO2014172372A1 (fr) | 2013-04-15 | 2014-10-23 | Northwestern University | Traitement de troubles dopaminergiques |
| PL3019167T3 (pl) | 2013-07-12 | 2021-06-14 | Knopp Biosciences Llc | Leczenie podwyższonych poziomów eozynofili i/lub bazofili |
| US9468630B2 (en) | 2013-07-12 | 2016-10-18 | Knopp Biosciences Llc | Compositions and methods for treating conditions related to increased eosinophils |
| ES2813674T3 (es) | 2013-08-13 | 2021-03-24 | Knopp Biosciences Llc | Composiciones y métodos para el tratamiento de trastornos de células plasmáticas y trastornos prolinfocíticos de células b |
| HUE055850T2 (hu) | 2013-08-13 | 2022-01-28 | Knopp Biosciences Llc | Készítmények és módszerek a krónikus urticaria (csalánkiütés) kezelésére |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4389393A (en) | 1982-03-26 | 1983-06-21 | Forest Laboratories, Inc. | Sustained release therapeutic compositions based on high molecular weight hydroxypropylmethylcellulose |
| CA2051697C (fr) * | 1989-06-09 | 1996-10-08 | Malcolm Wilson Moon | Amines heterocycliques ayant une activite sur le systeme nerveux central |
| US5273975A (en) | 1989-06-09 | 1993-12-28 | The Upjohn Company | Heterocyclic amines having central nervous system activity |
| US5000962A (en) | 1989-08-25 | 1991-03-19 | Schering Corporation | Long acting diltiazem formulation |
| GB9605857D0 (en) | 1996-03-20 | 1996-05-22 | Tester Richard F | Polysaccharides as chemical release systems |
| CA2173818A1 (fr) | 1996-04-10 | 1997-10-11 | Francois Chouinard | Comprime pharmaceutique a liberation controlee contenant un support a base d'amylose reticule et d'hydroxypropylmethylcellulose |
-
1998
- 1998-03-09 US US09/146,090 patent/US6197339B1/en not_active Expired - Fee Related
- 1998-09-03 CA CA002301869A patent/CA2301869A1/fr not_active Abandoned
- 1998-09-03 PT PT98945805T patent/PT1017391E/pt unknown
- 1998-09-03 KR KR10-2000-7003349A patent/KR100516095B1/ko not_active IP Right Cessation
- 1998-09-03 ES ES98945805T patent/ES2242296T3/es not_active Expired - Lifetime
- 1998-09-03 NZ NZ504221A patent/NZ504221A/en unknown
- 1998-09-03 RU RU2000111506/14A patent/RU2205007C2/ru not_active IP Right Cessation
- 1998-09-03 AU AU92964/98A patent/AU742941B2/en not_active Ceased
- 1998-09-03 DK DK98945805T patent/DK1017391T3/da active
- 1998-09-03 JP JP2000513578A patent/JP2001517701A/ja not_active Withdrawn
- 1998-09-03 CN CNB988087170A patent/CN1195518C/zh not_active Expired - Fee Related
- 1998-09-03 BR BR9812687-3A patent/BR9812687A/pt not_active Application Discontinuation
- 1998-09-03 AT AT98945805T patent/ATE297208T1/de not_active IP Right Cessation
- 1998-09-03 HU HU0004586A patent/HUP0004586A2/hu unknown
- 1998-09-03 WO PCT/US1998/017992 patent/WO1999016442A2/fr active IP Right Grant
- 1998-09-03 EP EP98945805A patent/EP1017391B1/fr not_active Expired - Lifetime
- 1998-09-03 PL PL339946A patent/PL191125B1/pl not_active IP Right Cessation
- 1998-09-03 SI SI9830770T patent/SI1017391T1/sl unknown
- 1998-09-03 DE DE69830503T patent/DE69830503T2/de not_active Expired - Fee Related
- 1998-09-03 SK SK361-2000A patent/SK3612000A3/sk unknown
-
2000
- 2000-03-29 NO NO20001624A patent/NO320303B1/no unknown
- 2000-03-29 FI FI20000720A patent/FI20000720A/fi unknown
-
2001
- 2001-01-11 US US09/759,286 patent/US20010053386A1/en not_active Abandoned
- 2001-02-21 HK HK01101251A patent/HK1030163A1/xx not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0004586A2 (hu) | 2001-06-28 |
| AU9296498A (en) | 1999-04-23 |
| CN1268890A (zh) | 2000-10-04 |
| ATE297208T1 (de) | 2005-06-15 |
| SI1017391T1 (sl) | 2005-12-31 |
| JP2001517701A (ja) | 2001-10-09 |
| NZ504221A (en) | 2004-11-26 |
| CN1195518C (zh) | 2005-04-06 |
| WO1999016442A2 (fr) | 1999-04-08 |
| NO20001624D0 (no) | 2000-03-29 |
| AU742941B2 (en) | 2002-01-17 |
| PL339946A1 (en) | 2001-01-15 |
| PT1017391E (pt) | 2005-09-30 |
| KR20010030776A (ko) | 2001-04-16 |
| KR100516095B1 (ko) | 2005-09-23 |
| SK3612000A3 (en) | 2000-09-12 |
| US20010053386A1 (en) | 2001-12-20 |
| CA2301869A1 (fr) | 1999-04-08 |
| FI20000720A (fi) | 2000-03-29 |
| BR9812687A (pt) | 2000-08-22 |
| ES2242296T3 (es) | 2005-11-01 |
| RU2205007C2 (ru) | 2003-05-27 |
| WO1999016442A3 (fr) | 1999-06-17 |
| NO20001624L (no) | 2000-03-29 |
| US6197339B1 (en) | 2001-03-06 |
| DE69830503D1 (de) | 2005-07-14 |
| EP1017391B1 (fr) | 2005-06-08 |
| PL191125B1 (pl) | 2006-03-31 |
| EP1017391A2 (fr) | 2000-07-12 |
| DK1017391T3 (da) | 2005-08-22 |
| HK1030163A1 (en) | 2001-04-27 |
| DE69830503T2 (de) | 2006-03-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| NO320303B1 (no) | Tablettformulering med vedvarende frigivelse for behandling av Parkinsons sykdom | |
| EP1737847B1 (fr) | Nebivolol et ses sels pharmaceutiquement acceptables, procede de preparation et compositions pharmaceutiques de nebivolol | |
| JPWO2006030826A1 (ja) | 医薬組成物 | |
| JP2001506600A (ja) | α―２アドレナリン受容体作動薬として有用なグアニジニル複素環式化合物 | |
| CA2328085C (fr) | Dispersion solide contenant un derive d'acide sialique | |
| KR20210042042A (ko) | 페놀라민 g형 결정, 제조 방법과 그의 조성물 및 용도 | |
| NO177262B (no) | Analogifremgangsmåte for fremstilling av terapeutisk aktive, O-substituerte oximer | |
| EP3653601A1 (fr) | Forme cristalline b de fenlean (flz), procédé de préparation, composition et utilisation de celle-ci | |
| EP2882711B1 (fr) | Sels de pipéridinium quartenaire | |
| JPH04178356A (ja) | 光学活性なベンジルアルコール誘導体及びその用途 | |
| TW201317240A (zh) | 用於治療疾病之組胺受體的雜環抑制劑 | |
| MXPA00002986A (en) | Sustained release tablet formulation to treat parkinson disease | |
| JP2001506599A (ja) | アルファ−２アドレナリン受容体アゴニストとして有効な２−イミダゾリニルアミノインダゾール化合物 | |
| CZ20001102A3 (cs) | Tabletová formulace pro trvalé uvolňování látky k léčbě Parkinsouovy nemoci | |
| US20230174525A1 (en) | Polymorphs of a hydrochloride salt of pn6047 | |
| JPS58146585A (ja) | 置換チエノベンゾジアゼピノン | |
| CN104478879B (zh) | 一种作为二肽基肽酶-4抑制剂的化合物 | |
| CN105367572A (zh) | 一种制备作为二肽基肽酶-4抑制剂的化合物的中间体 | |
| KR20240095294A (ko) | 실로시빈 유사체의 제형 및 사용 방법 | |
| JPS6110558A (ja) | 新規なデカハイドロキノリノール誘導体、その製造法及び医薬 | |
| AU2016344309A1 (en) | Ethylene glycol ether of buprenorphine | |
| JPH07285868A (ja) | ピロリジン誘導体を含有する医薬品製剤 | |
| CN104592234A (zh) | 一种作为二肽基肽酶-4抑制剂的化合物的制备方法 | |
| NO164028B (no) | Analogifremgangsm te for fremstilling av terapeutisk aktive allopurinol-derivater. |