HU211477A9 - Bisz-indol-alkaloid-sót tartalmazó injekciós oldat - Google Patents
Bisz-indol-alkaloid-sót tartalmazó injekciós oldat Download PDFInfo
- Publication number
- HU211477A9 HU211477A9 HU95P/P00443P HU9500443P HU211477A9 HU 211477 A9 HU211477 A9 HU 211477A9 HU 9500443 P HU9500443 P HU 9500443P HU 211477 A9 HU211477 A9 HU 211477A9
- Authority
- HU
- Hungary
- Prior art keywords
- bis
- gluconate
- aqueous solution
- zinc
- hydroxybenzoic acid
- Prior art date
Links
- TYGUTURXHKSOBP-UHFFFAOYSA-N 10-bromo-5,12-dihydroindolo[2,3-g]carbazole-2,3-diol Chemical class C1=C(Br)C=C2NC3=C(C4=C(C=C(C(=C4)O)O)N4)C4=CC=C3C2=C1 TYGUTURXHKSOBP-UHFFFAOYSA-N 0.000 title description 2
- 229940102223 injectable solution Drugs 0.000 title 1
- 238000000034 method Methods 0.000 claims description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 17
- 239000007864 aqueous solution Substances 0.000 claims description 16
- 239000000203 mixture Substances 0.000 claims description 13
- 239000011701 zinc Substances 0.000 claims description 13
- 229930013930 alkaloid Natural products 0.000 claims description 12
- 229910052751 metal Inorganic materials 0.000 claims description 12
- 239000002184 metal Substances 0.000 claims description 12
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 claims description 11
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical group COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 claims description 11
- 239000003755 preservative agent Substances 0.000 claims description 11
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 10
- 239000004227 calcium gluconate Substances 0.000 claims description 10
- 229960004494 calcium gluconate Drugs 0.000 claims description 10
- 235000013927 calcium gluconate Nutrition 0.000 claims description 10
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 claims description 10
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 claims description 10
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 10
- 229910052725 zinc Inorganic materials 0.000 claims description 10
- -1 alkaloid salt Chemical class 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 229960003048 vinblastine Drugs 0.000 claims description 9
- 230000002335 preservative effect Effects 0.000 claims description 8
- 229960004528 vincristine Drugs 0.000 claims description 8
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 claims description 8
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 claims description 7
- 229940050410 gluconate Drugs 0.000 claims description 7
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 claims description 7
- AQTQHPDCURKLKT-JKDPCDLQSA-N vincristine sulfate Chemical group OS(O)(=O)=O.C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C=O)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 AQTQHPDCURKLKT-JKDPCDLQSA-N 0.000 claims description 7
- 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 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
- 229930195725 Mannitol Natural products 0.000 claims description 6
- 235000015778 magnesium gluconate Nutrition 0.000 claims description 6
- 239000000594 mannitol Substances 0.000 claims description 6
- 235000010355 mannitol Nutrition 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 6
- 150000005846 sugar alcohols Polymers 0.000 claims description 6
- 235000011478 zinc gluconate Nutrition 0.000 claims description 6
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 claims description 6
- 229960001763 zinc sulfate Drugs 0.000 claims description 6
- 229910000368 zinc sulfate Inorganic materials 0.000 claims description 6
- 229910052791 calcium Inorganic materials 0.000 claims description 5
- 239000001755 magnesium gluconate Substances 0.000 claims description 5
- 229960003035 magnesium gluconate Drugs 0.000 claims description 5
- 229960000306 zinc gluconate Drugs 0.000 claims description 5
- 239000011670 zinc gluconate Substances 0.000 claims description 5
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 4
- 229910052749 magnesium Inorganic materials 0.000 claims description 4
- 229960002110 vincristine sulfate Drugs 0.000 claims description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical group [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 3
- WHMDKBIGKVEYHS-IYEMJOQQSA-L Zinc gluconate Chemical compound [Zn+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O WHMDKBIGKVEYHS-IYEMJOQQSA-L 0.000 claims description 3
- 239000008351 acetate buffer Substances 0.000 claims description 3
- 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 claims description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 2
- IAKLPCRFBAZVRW-XRDLMGPZSA-L magnesium;(2r,3s,4r,5r)-2,3,4,5,6-pentahydroxyhexanoate;hydrate Chemical compound O.[Mg+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O IAKLPCRFBAZVRW-XRDLMGPZSA-L 0.000 claims description 2
- 239000000600 sorbitol Substances 0.000 claims description 2
- KDQAABAKXDWYSZ-PNYVAJAMSA-N vinblastine sulfate Chemical compound OS(O)(=O)=O.C([C@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 KDQAABAKXDWYSZ-PNYVAJAMSA-N 0.000 claims description 2
- 229960004982 vinblastine sulfate Drugs 0.000 claims description 2
- 150000003797 alkaloid derivatives Chemical class 0.000 claims 2
- 239000000243 solution Substances 0.000 description 17
- 239000007924 injection Substances 0.000 description 13
- 238000002347 injection Methods 0.000 description 13
- NEEHYRZPVYRGPP-UHFFFAOYSA-L calcium;2,3,4,5,6-pentahydroxyhexanoate Chemical compound [Ca+2].OCC(O)C(O)C(O)C(O)C([O-])=O.OCC(O)C(O)C(O)C(O)C([O-])=O NEEHYRZPVYRGPP-UHFFFAOYSA-L 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000003708 ampul Substances 0.000 description 3
- 239000007853 buffer solution Substances 0.000 description 3
- 239000011575 calcium Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 239000012153 distilled water Substances 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- GBABOYUKABKIAF-IELIFDKJSA-N vinorelbine Chemical compound C1N(CC=2C3=CC=CC=C3NC=22)CC(CC)=C[C@H]1C[C@]2(C(=O)OC)C1=CC([C@]23[C@H]([C@@]([C@H](OC(C)=O)[C@]4(CC)C=CCN([C@H]34)CC2)(O)C(=O)OC)N2C)=C2C=C1OC GBABOYUKABKIAF-IELIFDKJSA-N 0.000 description 3
- OCUCCJIRFHNWBP-IYEMJOQQSA-L Copper gluconate Chemical class [Cu+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O OCUCCJIRFHNWBP-IYEMJOQQSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 229960005069 calcium Drugs 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 150000003839 salts Chemical group 0.000 description 2
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 2
- NDMPLJNOPCLANR-UHFFFAOYSA-N 3,4-dihydroxy-15-(4-hydroxy-18-methoxycarbonyl-5,18-seco-ibogamin-18-yl)-16-methoxy-1-methyl-6,7-didehydro-aspidospermidine-3-carboxylic acid methyl ester Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 NDMPLJNOPCLANR-UHFFFAOYSA-N 0.000 description 1
- ALEVUYMOJKJJSA-UHFFFAOYSA-N 4-hydroxy-2-propylbenzoic acid Chemical compound CCCC1=CC(O)=CC=C1C(O)=O ALEVUYMOJKJJSA-UHFFFAOYSA-N 0.000 description 1
- 229940090248 4-hydroxybenzoic acid Drugs 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- QOSMNYMQXIVWKY-UHFFFAOYSA-N Propyl levulinate Chemical compound CCCOC(=O)CCC(C)=O QOSMNYMQXIVWKY-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 235000001465 calcium Nutrition 0.000 description 1
- 201000011510 cancer Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 229940091250 magnesium supplement Drugs 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 229940085991 phosphate ion Drugs 0.000 description 1
- 230000001850 reproductive effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 229960004355 vindesine Drugs 0.000 description 1
- UGGWPQSBPIFKDZ-KOTLKJBCSA-N vindesine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(N)=O)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1N=C1[C]2C=CC=C1 UGGWPQSBPIFKDZ-KOTLKJBCSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Claims (12)
- SZABADALMI IGÉNYPONTOK1. Bisz-indolvázas alkaloidot tartalmazó gyógyászati készítmény, azzal jellemezve, hogy egy bisz-indolvázas alkaloid-só cink-komplexét, kétértékű fémglükonátot és egy- vagy többértékű alkoholban oldott konzerválószert tartalmaz vizes oldatban, mannit vagy szorbit lényegi vagy teljes távollétében és acetát-puffer lényegi vagy teljes távollétében.
- 2. Az 1. igénypont szerinti készítmény, azzal jellemezve, hogy bisz-indolvázas alkaloidként vinkrisztint vagy vinblasztint tartalmaz.
- 3. Az 1. vagy 2. igénypontok szerinti készítmény, azzal jellemezve, hogy kétértékű fém-glükonátként kalcium-, vagy cink-, vagy magnézium-glükonátot tartalmaz.
- 4. Az 1-3. igénypontok bármelyike szerinti készítmény, azzal jellemezve, hogy konzerválószerként 4hidroxi-benzoesav-metilésztert és/vagy 4-hidroxi-benzoesav-propilésztert tartalmaz.
- 5. Az 1—4. igénypontok bármelyike szerinti készítmény, azzal jellemezve, hogy alkoholként etanolt, npropanolt, i-propanolt vagy etilénglikolt tartalmaz.
- 6. Eljárás az 1. igénypontban definiált bisz-indolvázas alkaloidokat tartalmazó gyógyászati készítmény előállítására, azzal jellemezve, hogy egy bisz-indolvázas alkaloid-sót vízben oldunk, cink-szulfát vizes oldatával összekeverjük, majd a kapott alkaloid-cinkkomplexet kétértékű fém-glükonát vizes oldatával kezeljük és a kapott vizes oldatot egy- vagy többértékű alkoholban oldott konzerválószerrel egészítjük ki.
- 7. A 6. igénypont szerinti eljárás, azzal jellemezve, hogy bisz-indolvázas alkaloid-sóként vinkrisztin-szulfátot vagy vinblasztin-szulfátot alkalmazunk.
- 8. A 6. vagy 7. igénypontok szerinti eljárás, azzal jellemezve, hogy kétértékű fém-glükonátként kalcium-, vagy magnézium-, vagy cink-glükonátot használunk.
- 9. A 6-8. igénypontok bármelyike szerinti eljárás, azzal jellemezve, hogy egy- vagy többértékű alkoholként etanolt, n-propanolt, i-propanolt vagy etilén-glikolt alkalmazunk.
- 10. A 6-9. igénypontok szerinti eljárás, azzal jellemezve, hogy konzerválószerként 4-hidroxi-benzoesavmetilésztert és/vagy 4-hidroxi-benzoesav-propilésztert alkalmazunk.
- 11. Gyógyászati készítmény úgy, ahogy az 1. igénypontban és a leírásban szerepel.
- 12. Eljárás egy gyógyászati készítmény előállítására, ahogy az a 6. igénypontban és a leírásban szerepel.Kiadja az Országos Találmányi Hivatal, Budapest A kiadásért felel: Gyurcsekné Philipp Clarisse osztályvezető
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU95P/P00443P HU211477A9 (hu) | 1989-11-07 | 1995-06-27 | Bisz-indol-alkaloid-sót tartalmazó injekciós oldat |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| HU895804A HU204995B (en) | 1989-11-07 | 1989-11-07 | Process for producing pharmaceutical composition comprising alkaloid with bis-indole skeleton, with antitumour activity and suitable fr parenteral purposes |
| HU95P/P00443P HU211477A9 (hu) | 1989-11-07 | 1995-06-27 | Bisz-indol-alkaloid-sót tartalmazó injekciós oldat |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HU211477A9 true HU211477A9 (hu) | 1995-11-28 |
Family
ID=26317847
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU95P/P00443P HU211477A9 (hu) | 1989-11-07 | 1995-06-27 | Bisz-indol-alkaloid-sót tartalmazó injekciós oldat |
Country Status (1)
| Country | Link |
|---|---|
| HU (1) | HU211477A9 (hu) |
-
1995
- 1995-06-27 HU HU95P/P00443P patent/HU211477A9/hu unknown
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