NO303634B1 - AnalogifremgangsmÕte for fremstilling av et farmas°ytisk aktivt inklusjonskompleks av 3-morfolino-sydnonimin og dets tautomerisomere former, spesielt SIN-1A, eller deres salter, dannet med et syklodekstrinderivat - Google Patents
AnalogifremgangsmÕte for fremstilling av et farmas°ytisk aktivt inklusjonskompleks av 3-morfolino-sydnonimin og dets tautomerisomere former, spesielt SIN-1A, eller deres salter, dannet med et syklodekstrinderivat Download PDFInfo
- Publication number
- NO303634B1 NO303634B1 NO914650A NO914650A NO303634B1 NO 303634 B1 NO303634 B1 NO 303634B1 NO 914650 A NO914650 A NO 914650A NO 914650 A NO914650 A NO 914650A NO 303634 B1 NO303634 B1 NO 303634B1
- Authority
- NO
- Norway
- Prior art keywords
- sin
- cyclodextrin
- morpholino
- complex
- cdpsi
- Prior art date
Links
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical class O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 title claims abstract description 27
- 150000003839 salts Chemical class 0.000 title claims abstract description 11
- 238000004519 manufacturing process Methods 0.000 title description 4
- 238000000034 method Methods 0.000 claims abstract description 15
- 238000002360 preparation method Methods 0.000 claims abstract description 13
- FKDHHVKWGRFRTG-UHFFFAOYSA-N linsidomine Chemical compound [N-]1OC(=N)C=[N+]1N1CCOCC1 FKDHHVKWGRFRTG-UHFFFAOYSA-N 0.000 claims abstract description 11
- 239000012736 aqueous medium Substances 0.000 claims abstract 2
- 229920000858 Cyclodextrin Polymers 0.000 claims description 37
- 229920000642 polymer Polymers 0.000 claims description 7
- 238000004108 freeze drying Methods 0.000 claims description 6
- 230000018044 dehydration Effects 0.000 claims description 3
- 238000006297 dehydration reaction Methods 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 238000001694 spray drying Methods 0.000 claims description 2
- -1 hydroxypropyl cyclodextrin Chemical compound 0.000 claims 1
- 230000008569 process Effects 0.000 abstract description 8
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 4
- 208000005156 Dehydration Diseases 0.000 abstract 1
- 238000010316 high energy milling Methods 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- 230000015556 catabolic process Effects 0.000 description 14
- 239000007864 aqueous solution Substances 0.000 description 12
- 229940097362 cyclodextrins Drugs 0.000 description 12
- 239000004480 active ingredient Substances 0.000 description 11
- 238000006731 degradation reaction Methods 0.000 description 11
- 239000012153 distilled water Substances 0.000 description 11
- 239000000126 substance Substances 0.000 description 11
- 238000003860 storage Methods 0.000 description 10
- 230000000694 effects Effects 0.000 description 9
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 8
- 239000000872 buffer Substances 0.000 description 7
- 239000002207 metabolite Substances 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 6
- 230000009918 complex formation Effects 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- XLFWDASMENKTKL-UHFFFAOYSA-N molsidomine Chemical compound O1C(N=C([O-])OCC)=C[N+](N2CCOCC2)=N1 XLFWDASMENKTKL-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 238000010521 absorption reaction Methods 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 238000005259 measurement Methods 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 230000000087 stabilizing effect Effects 0.000 description 5
- 230000009466 transformation Effects 0.000 description 5
- 230000009471 action Effects 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 229960004027 molsidomine Drugs 0.000 description 4
- 238000002798 spectrophotometry method Methods 0.000 description 4
- 238000004809 thin layer chromatography Methods 0.000 description 4
- 238000012546 transfer Methods 0.000 description 4
- 238000002211 ultraviolet spectrum Methods 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-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
- 239000003708 ampul Substances 0.000 description 3
- 230000004071 biological effect Effects 0.000 description 3
- 230000003293 cardioprotective effect Effects 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 230000003301 hydrolyzing effect Effects 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000002674 ointment Substances 0.000 description 3
- GSKDBLIBBOYOFU-UHFFFAOYSA-N oxadiazol-5-amine Chemical class NC1=CN=NO1 GSKDBLIBBOYOFU-UHFFFAOYSA-N 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 239000006069 physical mixture Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- DSDAICPXUXPBCC-MWDJDSKUSA-N trimethyl-β-cyclodextrin Chemical compound COC[C@H]([C@H]([C@@H]([C@H]1OC)OC)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COC)[C@H]([C@@H]([C@H]3OC)OC)O[C@H]3O[C@H](COC)[C@H]([C@@H]([C@H]3OC)OC)O[C@H]3O[C@H](COC)[C@H]([C@@H]([C@H]3OC)OC)O[C@H]3O[C@H](COC)[C@H]([C@@H]([C@H]3OC)OC)O3)[C@H](OC)[C@H]2OC)COC)O[C@@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@@H]3O[C@@H]1COC DSDAICPXUXPBCC-MWDJDSKUSA-N 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000007857 degradation product Substances 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 238000011835 investigation Methods 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
- 230000007935 neutral effect Effects 0.000 description 2
- 230000002040 relaxant effect Effects 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- XMPLPXUYWIJXFL-UHFFFAOYSA-N 2-morpholin-4-yliminoacetonitrile Chemical compound N#CC=NN1CCOCC1 XMPLPXUYWIJXFL-UHFFFAOYSA-N 0.000 description 1
- NCGICGYLBXGBGN-UHFFFAOYSA-N 3-morpholin-4-yl-1-oxa-3-azonia-2-azanidacyclopent-3-en-5-imine;hydrochloride Chemical compound Cl.[N-]1OC(=N)C=[N+]1N1CCOCC1 NCGICGYLBXGBGN-UHFFFAOYSA-N 0.000 description 1
- ZRFWHHCXSSACAW-UHFFFAOYSA-M 3-morpholin-4-yloxadiazol-3-ium-5-amine;chloride Chemical compound [Cl-].O1C(N)=C[N+](N2CCOCC2)=N1 ZRFWHHCXSSACAW-UHFFFAOYSA-M 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 102000004031 Carboxy-Lyases Human genes 0.000 description 1
- 108090000489 Carboxy-Lyases Proteins 0.000 description 1
- 229920000298 Cellophane Polymers 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 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
- 206010019280 Heart failures Diseases 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 206010034960 Photophobia Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
- 238000002441 X-ray diffraction Methods 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000004004 anti-anginal agent Substances 0.000 description 1
- 229940124345 antianginal agent Drugs 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000010668 complexation reaction Methods 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 239000013068 control sample Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229940080345 gamma-cyclodextrin Drugs 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000002484 inorganic compounds Chemical class 0.000 description 1
- 229910010272 inorganic material Inorganic materials 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 208000013469 light sensitivity Diseases 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000003094 microcapsule Substances 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 238000010525 oxidative degradation reaction Methods 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000002085 persistent effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 238000006303 photolysis reaction Methods 0.000 description 1
- 230000015843 photosynthesis, light reaction Effects 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 239000012088 reference solution Substances 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 239000000523 sample Substances 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000000870 ultraviolet spectroscopy Methods 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08B—POLYSACCHARIDES; DERIVATIVES THEREOF
- C08B37/00—Preparation of polysaccharides not provided for in groups C08B1/00 - C08B35/00; Derivatives thereof
- C08B37/0006—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid
- C08B37/0009—Homoglycans, i.e. polysaccharides having a main chain consisting of one single sugar, e.g. colominic acid alpha-D-Glucans, e.g. polydextrose, alternan, glycogen; (alpha-1,4)(alpha-1,6)-D-Glucans; (alpha-1,3)(alpha-1,4)-D-Glucans, e.g. isolichenan or nigeran; (alpha-1,4)-D-Glucans; (alpha-1,3)-D-Glucans, e.g. pseudonigeran; Derivatives thereof
- C08B37/0012—Cyclodextrin [CD], e.g. cycle with 6 units (alpha), with 7 units (beta) and with 8 units (gamma), large-ring cyclodextrin or cycloamylose with 9 units or more; Derivatives thereof
- C08B37/0015—Inclusion compounds, i.e. host-guest compounds, e.g. polyrotaxanes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/08—Vasodilators for multiple indications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/04—1,2,3-Oxadiazoles; Hydrogenated 1,2,3-oxadiazoles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Biochemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Pharmacology & Pharmacy (AREA)
- Cardiology (AREA)
- Animal Behavior & Ethology (AREA)
- Polymers & Plastics (AREA)
- Materials Engineering (AREA)
- Heart & Thoracic Surgery (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU901869A HU212730B (en) | 1990-03-28 | 1990-03-28 | Process for producing inclusion complexes of cyclodextrine or its derivative and 3-morpholino-sydnonimine or its salt or its tautomer and pharmaceutical compositions containing them |
| PCT/HU1991/000013 WO1991014681A1 (en) | 1990-03-28 | 1991-03-28 | Inclusion complexes of 3-morpholino-sydnonimine or its salts or its tautomer isomer, process for the preparation thereof, and pharmaceutical compositions containing the same |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO914650D0 NO914650D0 (no) | 1991-11-27 |
| NO914650L NO914650L (no) | 1991-11-27 |
| NO303634B1 true NO303634B1 (no) | 1998-08-10 |
Family
ID=10956597
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO914650A NO303634B1 (no) | 1990-03-28 | 1991-11-27 | AnalogifremgangsmÕte for fremstilling av et farmas°ytisk aktivt inklusjonskompleks av 3-morfolino-sydnonimin og dets tautomerisomere former, spesielt SIN-1A, eller deres salter, dannet med et syklodekstrinderivat |
Country Status (33)
| Country | Link |
|---|---|
| US (1) | US5298496A (zh) |
| EP (1) | EP0478732B1 (zh) |
| JP (1) | JP2549961B2 (zh) |
| KR (1) | KR950004706B1 (zh) |
| CN (1) | CN1051081C (zh) |
| AT (1) | ATE170849T1 (zh) |
| AU (1) | AU635835B2 (zh) |
| BG (1) | BG61812B1 (zh) |
| BR (1) | BR9105137A (zh) |
| CA (1) | CA2054213C (zh) |
| CZ (1) | CZ285695B6 (zh) |
| DE (1) | DE69130146T2 (zh) |
| DK (1) | DK0478732T3 (zh) |
| ES (1) | ES2121780T3 (zh) |
| FI (1) | FI104882B (zh) |
| GE (1) | GEP19991743B (zh) |
| HK (1) | HK1011688A1 (zh) |
| HR (1) | HRP920560B1 (zh) |
| HU (2) | HU211648A9 (zh) |
| LT (1) | LT3257B (zh) |
| LV (1) | LV10087B (zh) |
| MC (1) | MC2186A1 (zh) |
| MD (1) | MD776C2 (zh) |
| MW (1) | MW6891A1 (zh) |
| NO (1) | NO303634B1 (zh) |
| OA (1) | OA09522A (zh) |
| PL (1) | PL165866B1 (zh) |
| RO (1) | RO109336B1 (zh) |
| RU (1) | RU2107695C1 (zh) |
| SI (1) | SI9110909B (zh) |
| TJ (1) | TJ189R3 (zh) |
| UA (1) | UA27242C2 (zh) |
| WO (1) | WO1991014681A1 (zh) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU210921B (en) * | 1990-03-28 | 1995-09-28 | Chinoin Gyogyszer Es Vegyeszet | Process for preparing inclusion complexes of n-ethoxycarbonyl-3-morpholino-sydnonimine formed with cyclodextrines and pharmaceutical compositions containing them |
| DE4117249C2 (de) * | 1991-05-27 | 1998-05-14 | Christian Dr Stief | Linsidomin zur Behandlung erektiler Dysfunktionen |
| HU213200B (en) | 1993-05-12 | 1997-03-28 | Chinoin Gyogyszer Es Vegyeszet | The cyclodextrin or cyclodextrin derivative cluster complexes of taxol, taxotere, or taxus, pharmaceutical preparations containing them and process for their production |
| HU218280B (en) * | 1994-04-26 | 2000-07-28 | Cyclodextrin inclusion complexes containing sin-1a which are stable intheir solid state, process for their preparation and pharmaceutical compositions containing the comlexes | |
| GB9915231D0 (en) | 1999-06-29 | 1999-09-01 | Pfizer Ltd | Pharmaceutical complex |
| FR2805462B1 (fr) * | 2000-02-24 | 2003-08-15 | Therabel Res | Nouvelle forme galenique orale a liberation prolongee de la molsidomine |
| WO2001085218A2 (en) * | 2000-05-11 | 2001-11-15 | Eastman Chemical Company | Acylated cyclodextrin guest inclusion complexes |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR1496056A (fr) * | 1964-06-08 | 1967-09-29 | Takeda Chemical Industries Ltd | Nouveaux composés chimiques du type sydnonimine |
| DE3221425A1 (de) * | 1982-06-07 | 1983-12-08 | Boehringer Ingelheim KG, 6507 Ingelheim | Hydrolyseempfindlichen wirkstoff enthaltende, lagerstabile tablette |
| DE3346638A1 (de) * | 1983-12-23 | 1985-07-04 | Cassella Ag, 6000 Frankfurt | Photostabilisierung von molsidomin |
| GB8506792D0 (en) * | 1985-03-15 | 1985-04-17 | Janssen Pharmaceutica Nv | Derivatives of y-cyclodextrin |
| DE3522191A1 (de) * | 1985-06-21 | 1987-01-15 | Cassella Ag | Photostabilisierung von sydnoniminen |
| GB8613688D0 (en) * | 1986-06-05 | 1986-07-09 | Euro Celtique Sa | Pharmaceutical composition |
| JPH0819004B2 (ja) * | 1986-12-26 | 1996-02-28 | 日清製粉株式会社 | 徐放性医薬製剤 |
| IT1204725B (it) * | 1987-06-17 | 1989-03-10 | Edmond Pharma Srl | Complessi di inclusione del dipiridamolo con ciclodestrine |
| SE8904296D0 (sv) * | 1989-12-21 | 1989-12-21 | Pharmacia Ab | Transdermal system |
| WO1991015346A1 (de) * | 1990-04-06 | 1991-10-17 | Gerhard Blatt | Anlage zur behandlung von betonsteinen |
-
1990
- 1990-03-28 HU HU90P/P00224P patent/HU211648A9/hu unknown
- 1990-03-28 HU HU901869A patent/HU212730B/hu unknown
-
1991
- 1991-03-28 DK DK91907217T patent/DK0478732T3/da active
- 1991-03-28 RU SU5010582A patent/RU2107695C1/ru active
- 1991-03-28 JP JP3506356A patent/JP2549961B2/ja not_active Expired - Lifetime
- 1991-03-28 CZ CS91852A patent/CZ285695B6/cs not_active IP Right Cessation
- 1991-03-28 MD MD94-0334A patent/MD776C2/ro active IP Right Grant
- 1991-03-28 UA UA93060611A patent/UA27242C2/uk unknown
- 1991-03-28 MC MC@@@@D patent/MC2186A1/xx unknown
- 1991-03-28 CA CA002054213A patent/CA2054213C/en not_active Expired - Lifetime
- 1991-03-28 BR BR919105137A patent/BR9105137A/pt not_active Application Discontinuation
- 1991-03-28 SI SI9110909A patent/SI9110909B/sl unknown
- 1991-03-28 PL PL91293020A patent/PL165866B1/pl unknown
- 1991-03-28 RO RO148828A patent/RO109336B1/ro unknown
- 1991-03-28 CN CN91102699A patent/CN1051081C/zh not_active Expired - Fee Related
- 1991-03-28 DE DE69130146T patent/DE69130146T2/de not_active Expired - Lifetime
- 1991-03-28 WO PCT/HU1991/000013 patent/WO1991014681A1/en active IP Right Grant
- 1991-03-28 US US07/793,389 patent/US5298496A/en not_active Expired - Lifetime
- 1991-03-28 EP EP91907217A patent/EP0478732B1/en not_active Expired - Lifetime
- 1991-03-28 AU AU75493/91A patent/AU635835B2/en not_active Expired
- 1991-03-28 AT AT91907217T patent/ATE170849T1/de not_active IP Right Cessation
- 1991-03-28 KR KR1019910701671A patent/KR950004706B1/ko not_active IP Right Cessation
- 1991-03-28 ES ES91907217T patent/ES2121780T3/es not_active Expired - Lifetime
- 1991-11-08 OA OA60095A patent/OA09522A/en unknown
- 1991-11-13 MW MW6891A patent/MW6891A1/xx unknown
- 1991-11-26 FI FI915570A patent/FI104882B/fi active
- 1991-11-27 NO NO914650A patent/NO303634B1/no not_active IP Right Cessation
- 1991-11-27 BG BG95530A patent/BG61812B1/bg unknown
-
1992
- 1992-09-28 HR HRP-909/91A patent/HRP920560B1/xx not_active IP Right Cessation
- 1992-12-30 LV LVP-92-588A patent/LV10087B/lv unknown
-
1993
- 1993-03-05 LT LTIP387A patent/LT3257B/lt not_active IP Right Cessation
- 1993-06-16 GE GEAP1993880A patent/GEP19991743B/en unknown
-
1994
- 1994-11-28 TJ TJ94000008A patent/TJ189R3/xx unknown
-
1998
- 1998-12-07 HK HK98112917A patent/HK1011688A1/xx not_active IP Right Cessation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6287603B1 (en) | Cyclodextrin flavor delivery systems | |
| US5512306A (en) | Smoking substitute | |
| KR19980702962A (ko) | 차의 폴리페놀 분획물, 그의 용도 및 그를 함유한 제제 | |
| EP0776329A1 (en) | Water-soluble polyene conjugate | |
| NO303634B1 (no) | AnalogifremgangsmÕte for fremstilling av et farmas°ytisk aktivt inklusjonskompleks av 3-morfolino-sydnonimin og dets tautomerisomere former, spesielt SIN-1A, eller deres salter, dannet med et syklodekstrinderivat | |
| Domb et al. | Nystatin—dextran conjugates: Synthesis and characterization | |
| KR950004705B1 (ko) | 시클로덱스트린 유도체와 n-에톡시카르보닐-3-모르폴리노-시드노니민 또는 그 염들에 의해 형성된 함유복합체 및 그 제조방법과 이들을 함유하는 약제학적 조성물 | |
| FR3042412A1 (fr) | Formulation pharmaceutique stabilisee et prete a l'emploi d'ivermectine dans le traitement des parasitoses humaines et animales | |
| EP1469823B1 (fr) | Utilisation cosmetique ou dermatologique de la vitamine a ou de ses esters, en association avec une beta-cyclodextrine partiellement methylee | |
| KR20150126382A (ko) | 위 내의 알데하이드에 결합하는 캡슐화된 조성물 | |
| SK278809B6 (sk) | Inklúzny komplex 3-morfolinosydnonimínu alebo jeho | |
| Watanabe et al. | Development and pharmaceutical properties of a new oral dosage form of theophylline using sodium caseinate for the possible use in elderly patients | |
| Kreaz et al. | Freeze-dried complexes of furosemide with β-cyclodextrin derivatives | |
| WO2006002887A1 (en) | Aqueous drink solution of indibulin (d-24851) and an organic acid | |
| CZ20003366A3 (cs) | Způsob výroby cyklodextrinových inklusních komplexů | |
| IL111723A (en) | Nimesulide salt/cyclodextrin inclusion complexes, process for their preparation and pharmaceutical compositions containing them |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1K | Patent expired |