CS214798B2 - Method of stabilization of active substances - Google Patents
Method of stabilization of active substances Download PDFInfo
- Publication number
- CS214798B2 CS214798B2 CS793373A CS337379A CS214798B2 CS 214798 B2 CS214798 B2 CS 214798B2 CS 793373 A CS793373 A CS 793373A CS 337379 A CS337379 A CS 337379A CS 214798 B2 CS214798 B2 CS 214798B2
- Authority
- CS
- Czechoslovakia
- Prior art keywords
- buffer
- solution
- prostacyclin
- amino acid
- active ingredient
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 25
- 239000013543 active substance Substances 0.000 title claims description 13
- 230000006641 stabilisation Effects 0.000 title description 2
- 238000011105 stabilization Methods 0.000 title description 2
- 229960001123 epoprostenol Drugs 0.000 claims abstract description 31
- 150000001413 amino acids Chemical class 0.000 claims abstract description 25
- 239000000203 mixture Substances 0.000 claims abstract description 5
- 238000009472 formulation Methods 0.000 claims abstract description 4
- KAQKFAOMNZTLHT-VVUHWYTRSA-N epoprostenol Chemical compound O1C(=CCCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-VVUHWYTRSA-N 0.000 claims abstract 4
- 239000000872 buffer Substances 0.000 claims description 40
- 235000001014 amino acid Nutrition 0.000 claims description 24
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 23
- 150000003839 salts Chemical class 0.000 claims description 22
- 239000004480 active ingredient Substances 0.000 claims description 21
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- 239000011780 sodium chloride Substances 0.000 claims description 12
- 239000004471 Glycine Substances 0.000 claims description 10
- 239000002904 solvent Substances 0.000 claims description 10
- 239000000654 additive Substances 0.000 claims description 8
- 239000004475 Arginine Substances 0.000 claims description 6
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims description 6
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 claims description 6
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 claims description 6
- 230000000996 additive effect Effects 0.000 claims description 6
- 235000004279 alanine Nutrition 0.000 claims description 6
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 claims description 6
- 239000004474 valine Substances 0.000 claims description 6
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 5
- 229930195725 Mannitol Natural products 0.000 claims description 5
- 239000000594 mannitol Substances 0.000 claims description 5
- 235000010355 mannitol Nutrition 0.000 claims description 5
- 159000000000 sodium salts Chemical class 0.000 claims description 5
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 claims description 4
- LMHIPJMTZHDKEW-XQYLJSSYSA-M Epoprostenol sodium Chemical group [Na+].O1\C(=C/CCCC([O-])=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 LMHIPJMTZHDKEW-XQYLJSSYSA-M 0.000 claims description 3
- 239000002253 acid Substances 0.000 claims description 3
- 230000000087 stabilizing effect Effects 0.000 claims description 3
- 230000007062 hydrolysis Effects 0.000 claims description 2
- 238000006460 hydrolysis reaction Methods 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 abstract description 11
- 239000007853 buffer solution Substances 0.000 abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 45
- 239000000243 solution Substances 0.000 description 43
- KAQKFAOMNZTLHT-OZUDYXHBSA-N prostaglandin I2 Chemical compound O1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-OZUDYXHBSA-N 0.000 description 27
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 150000001875 compounds Chemical class 0.000 description 12
- 239000007924 injection Substances 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 238000001802 infusion Methods 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 239000008215 water for injection Substances 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 239000011734 sodium Substances 0.000 description 6
- 238000004108 freeze drying Methods 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 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 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000007983 Tris buffer Substances 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- 239000003708 ampul Substances 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 3
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- ZMANZCXQSJIPKH-UHFFFAOYSA-N N,N-Diethylethanamine Substances CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 229910004298 SiO 2 Inorganic materials 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000006172 buffering agent Substances 0.000 description 2
- 230000002612 cardiopulmonary effect Effects 0.000 description 2
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
- 238000000502 dialysis Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 150000004702 methyl esters Chemical class 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- -1 potassium chloride Chemical class 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 239000008174 sterile solution Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- WGTYBPLFGIVFAS-UHFFFAOYSA-M tetramethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)C WGTYBPLFGIVFAS-UHFFFAOYSA-M 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- DZUXGQBLFALXCR-UHFFFAOYSA-N (+)-(9alpha,11alpha,13E,15S)-9,11,15-trihydroxyprost-13-en-1-oic acid Natural products CCCCCC(O)C=CC1C(O)CC(O)C1CCCCCCC(O)=O DZUXGQBLFALXCR-UHFFFAOYSA-N 0.000 description 1
- FGOJCPKOOGIRPA-UHFFFAOYSA-N 1-o-tert-butyl 4-o-ethyl 5-oxoazepane-1,4-dicarboxylate Chemical compound CCOC(=O)C1CCN(C(=O)OC(C)(C)C)CCC1=O FGOJCPKOOGIRPA-UHFFFAOYSA-N 0.000 description 1
- 101100294115 Caenorhabditis elegans nhr-4 gene Proteins 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 206010053567 Coagulopathies Diseases 0.000 description 1
- 239000004593 Epoxy Substances 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 101710129448 Glucose-6-phosphate isomerase 2 Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- DKNPRRRKHAEUMW-UHFFFAOYSA-N Iodine aqueous Chemical compound [K+].I[I-]I DKNPRRRKHAEUMW-UHFFFAOYSA-N 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- UAGJVSRUFNSIHR-UHFFFAOYSA-N Methyl levulinate Chemical compound COC(=O)CCC(C)=O UAGJVSRUFNSIHR-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- QYKIQEUNHZKYBP-UHFFFAOYSA-N Vinyl ether Chemical compound C=COC=C QYKIQEUNHZKYBP-UHFFFAOYSA-N 0.000 description 1
- 238000002835 absorbance Methods 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000002429 anti-coagulating effect Effects 0.000 description 1
- 239000012062 aqueous buffer Substances 0.000 description 1
- 235000010357 aspartame Nutrition 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000008366 buffered solution Substances 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 230000035602 clotting Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000006704 dehydrohalogenation reaction Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- UQGFMSUEHSUPRD-UHFFFAOYSA-N disodium;3,7-dioxido-2,4,6,8,9-pentaoxa-1,3,5,7-tetraborabicyclo[3.3.1]nonane Chemical compound [Na+].[Na+].O1B([O-])OB2OB([O-])OB1O2 UQGFMSUEHSUPRD-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229910000043 hydrogen iodide Inorganic materials 0.000 description 1
- VKOBVWXKNCXXDE-UHFFFAOYSA-N icosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCC(O)=O VKOBVWXKNCXXDE-UHFFFAOYSA-N 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical group II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000014508 negative regulation of coagulation Effects 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 229940020414 potassium triiodide Drugs 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- DZUXGQBLFALXCR-CDIPTNKSSA-N prostaglandin F1alpha Chemical compound CCCCC[C@H](O)\C=C\[C@H]1[C@H](O)C[C@H](O)[C@@H]1CCCCCCC(O)=O DZUXGQBLFALXCR-CDIPTNKSSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000013074 reference sample Substances 0.000 description 1
- 239000013049 sediment Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000004328 sodium tetraborate Substances 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
- PYJJCSYBSYXGQQ-UHFFFAOYSA-N trichloro(octadecyl)silane Chemical compound CCCCCCCCCCCCCCCCCC[Si](Cl)(Cl)Cl PYJJCSYBSYXGQQ-UHFFFAOYSA-N 0.000 description 1
- 239000005051 trimethylchlorosilane Substances 0.000 description 1
- 229920002554 vinyl polymer Polymers 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
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/183—Amino acids, e.g. glycine, EDTA or aspartame
-
- 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
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Dermatology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB2017578 | 1978-05-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CS214798B2 true CS214798B2 (en) | 1982-05-28 |
Family
ID=10141640
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS793373A CS214798B2 (en) | 1978-05-17 | 1979-05-16 | Method of stabilization of active substances |
Country Status (28)
| Country | Link |
|---|---|
| US (1) | US4335139A (ja) |
| EP (1) | EP0005768B1 (ja) |
| JP (1) | JPS54163809A (ja) |
| KR (1) | KR830000527B1 (ja) |
| AT (2) | AT365926B (ja) |
| AU (1) | AU525695B2 (ja) |
| BE (1) | BE876296A (ja) |
| CA (1) | CA1141661A (ja) |
| CH (1) | CH641044A5 (ja) |
| CS (1) | CS214798B2 (ja) |
| DE (2) | DE2966046D1 (ja) |
| DK (1) | DK156004C (ja) |
| ES (1) | ES480597A1 (ja) |
| FI (1) | FI68359C (ja) |
| FR (1) | FR2425856A1 (ja) |
| GR (1) | GR68452B (ja) |
| HU (1) | HU182746B (ja) |
| IL (1) | IL57298A (ja) |
| IT (1) | IT1116840B (ja) |
| LU (1) | LU81272A1 (ja) |
| MC (1) | MC1265A1 (ja) |
| NL (1) | NL7903871A (ja) |
| NZ (1) | NZ190462A (ja) |
| PH (1) | PH15850A (ja) |
| PL (1) | PL134004B1 (ja) |
| SE (1) | SE450930B (ja) |
| SU (1) | SU978715A3 (ja) |
| ZA (1) | ZA787353B (ja) |
Families Citing this family (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3010002A1 (de) * | 1980-03-15 | 1981-10-01 | Hoechst Ag, 6000 Frankfurt | Prostaglandine enthaltende pharmazeutische zubereitung |
| GB8814438D0 (en) * | 1988-06-17 | 1988-07-20 | Wellcome Found | Compounds for use in medicine |
| EP0347243B1 (en) * | 1988-06-17 | 1993-01-13 | The Wellcome Foundation Limited | Prostaglandin analogues for use in medicine |
| JP3421330B2 (ja) * | 2000-11-02 | 2003-06-30 | 持田製薬株式会社 | ビダラビン注射用乾燥製剤 |
| EP1238670A1 (en) * | 2001-03-07 | 2002-09-11 | Bruce Daniels | Composition and method for treating and preventing cardiovascular disease and hypertension. |
| US7491263B2 (en) | 2004-04-05 | 2009-02-17 | Technology Innovation, Llc | Storage assembly |
| ES2323286T3 (es) * | 2005-06-29 | 2009-07-10 | Verisfield (Uk) Ltd. | Composiciones farmaceuticas de risperidona en disolucion acuosa. |
| SI1993557T1 (sl) | 2006-02-03 | 2016-01-29 | Actelion Pharmaceuticals Ltd. | Nova formulacija epoprostenola in postopek izdelave le-te |
| JP2010538092A (ja) | 2007-09-07 | 2010-12-09 | ユナイテッド セラピューティクス コーポレーション | グラム陰性菌に対して選択的殺菌活性を有するバッファー溶液およびそれを使用する方法 |
| HU231031B1 (hu) | 2016-03-23 | 2019-12-30 | CHINOIN Gyógyszer és Vegyészeti Termékek Gyára Zrt. | Megnövelt stabilitású epoprostenol nátrium és eljárás előállítására |
| DE202024100435U1 (de) | 2023-02-14 | 2024-02-22 | Tomasz Dąbrowski | Zaunfeld zum Aufbau einer Reitbande |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4036954A (en) | 1973-11-02 | 1977-07-19 | Yamanouchi Pharmaceutical Co., Ltd. | Stable prostaglandin E group-containing formulation |
| GB1504437A (en) | 1974-03-08 | 1978-03-22 | Dunlop Ltd | Rubberplastics composites |
| DE2515001C2 (de) * | 1975-04-04 | 1986-10-02 | Schering AG, 1000 Berlin und 4709 Bergkamen | Prostaglandin enthaltende gefriergetrocknete Pulver |
| US3997587A (en) | 1975-06-26 | 1976-12-14 | Syntex (U.S.A.) Inc. | D1- and 8R-9-fluoro-prostadienoic acid derivatives |
| US4005133A (en) | 1975-10-14 | 1977-01-25 | The Upjohn Company | PGF2.sub.α, L-Arginine salt |
| FR2351112A1 (fr) * | 1975-10-21 | 1977-12-09 | Wellcome Found | Derive de prostaglandine et medicament contenant ce derive |
| US4062964A (en) | 1975-12-03 | 1977-12-13 | Ciba-Geigy Corporation | Antifertility-combinations |
| GB1583961A (en) * | 1976-05-11 | 1981-02-04 | Wellcome Found | Prostacyclin and derivatives thereof |
| CH643458A5 (en) * | 1977-05-20 | 1984-06-15 | Wellcome Found | Pharmaceutical composition and a process for its production |
-
1978
- 1978-12-28 ZA ZA787353A patent/ZA787353B/xx unknown
-
1979
- 1979-05-16 GR GR59108A patent/GR68452B/el unknown
- 1979-05-16 MC MC791380A patent/MC1265A1/xx unknown
- 1979-05-16 HU HU79WE596A patent/HU182746B/hu unknown
- 1979-05-16 AT AT0363479A patent/AT365926B/de not_active IP Right Cessation
- 1979-05-16 DK DK201879A patent/DK156004C/da not_active IP Right Cessation
- 1979-05-16 FI FI791565A patent/FI68359C/fi not_active IP Right Cessation
- 1979-05-16 SU SU792772851A patent/SU978715A3/ru active
- 1979-05-16 SE SE7904284A patent/SE450930B/sv not_active IP Right Cessation
- 1979-05-16 AU AU47042/79A patent/AU525695B2/en not_active Expired
- 1979-05-16 KR KR1019790001567A patent/KR830000527B1/ko active
- 1979-05-16 CA CA000327760A patent/CA1141661A/en not_active Expired
- 1979-05-16 JP JP6024479A patent/JPS54163809A/ja active Granted
- 1979-05-16 ES ES480597A patent/ES480597A1/es not_active Expired
- 1979-05-16 IT IT49064/79A patent/IT1116840B/it active
- 1979-05-16 BE BE0/195196A patent/BE876296A/xx not_active IP Right Cessation
- 1979-05-16 CS CS793373A patent/CS214798B2/cs unknown
- 1979-05-16 PH PH22508A patent/PH15850A/en unknown
- 1979-05-16 PL PL1979215627A patent/PL134004B1/pl unknown
- 1979-05-16 NL NL7903871A patent/NL7903871A/xx not_active Application Discontinuation
- 1979-05-16 LU LU81272A patent/LU81272A1/xx unknown
- 1979-05-16 IL IL57298A patent/IL57298A/xx unknown
- 1979-05-17 AT AT79101516T patent/ATE4411T1/de not_active IP Right Cessation
- 1979-05-17 DE DE7979101516T patent/DE2966046D1/de not_active Expired
- 1979-05-17 DE DE19792920020 patent/DE2920020A1/de active Granted
- 1979-05-17 NZ NZ190462A patent/NZ190462A/xx unknown
- 1979-05-17 EP EP79101516A patent/EP0005768B1/en not_active Expired
- 1979-05-17 FR FR7912583A patent/FR2425856A1/fr active Granted
- 1979-05-17 CH CH460379A patent/CH641044A5/de not_active IP Right Cessation
-
1980
- 1980-08-28 US US06/182,054 patent/US4335139A/en not_active Expired - Lifetime
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