DK2568987T3 - Tetracyclin-sammensætninger - Google Patents
Tetracyclin-sammensætninger Download PDFInfo
- Publication number
- DK2568987T3 DK2568987T3 DK11781314.7T DK11781314T DK2568987T3 DK 2568987 T3 DK2568987 T3 DK 2568987T3 DK 11781314 T DK11781314 T DK 11781314T DK 2568987 T3 DK2568987 T3 DK 2568987T3
- Authority
- DK
- Denmark
- Prior art keywords
- solution
- less
- minocycline
- divalent
- molar ratio
- Prior art date
Links
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- 235000019364 tetracycline Nutrition 0.000 title claims description 82
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- SOVUOXKZCCAWOJ-HJYUBDRYSA-N (4s,4as,5ar,12ar)-9-[[2-(tert-butylamino)acetyl]amino]-4,7-bis(dimethylamino)-1,10,11,12a-tetrahydroxy-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1C2=C(N(C)C)C=C(NC(=O)CNC(C)(C)C)C(O)=C2C(O)=C2[C@@H]1C[C@H]1[C@H](N(C)C)C(=O)C(C(N)=O)=C(O)[C@@]1(O)C2=O SOVUOXKZCCAWOJ-HJYUBDRYSA-N 0.000 claims description 110
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- 238000007086 side reaction Methods 0.000 description 1
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- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 229910052979 sodium sulfide Inorganic materials 0.000 description 1
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- 235000010265 sodium sulphite Nutrition 0.000 description 1
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- OFVLGDICTFRJMM-WESIUVDSSA-N tetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O OFVLGDICTFRJMM-WESIUVDSSA-N 0.000 description 1
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Classifications
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- 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
- A61K31/65—Tetracyclines
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- 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
- A61K31/04—Nitro compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/26—Iron; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/34—Copper; Compounds thereof
-
- 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
- A61K47/02—Inorganic compounds
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2121/00—Preparations for use in therapy
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Inorganic Chemistry (AREA)
- Dermatology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Claims (23)
1. Farmaceutisk sammensætning, der omfatter (A) en vandig opløsning af et 7~dimethyiamino-tetracyclin-antibiotikum og en magnesiumkation, hvor det molære forhold af magnesiumkation ti! 7-dimethylamino-tetracyclin-antibiotikum er større end 2:1, og hvor opløsningen ikke omfatter en farmaceutisk acceptabel olie, har et pH større end 4 og mindre end 7, har en osmolalitet mindre end 500 mOsmol/kg, og er egnet ti! intravenøs administration, fortrinsvis er 7-dimethylamino-tetracyciin-antibiotikumet minocydin, eller (6) omfattende en vandig opløsning af minocydin og en magnesiumkation, hvor koncentrationen af minocydin er mindst 1 mg/ml, hvor det molære forhold af magnesiumkation til minocydin er større end 2:1 og hvor opløsningen har et pH større end 4 og mindre end 5 og er egnet til intravenøs administration.
2. Farmaceutisk sammensætning ifølge krav 1, hvor opløsningen ikke omfatter en komponent valgt fra gruppen bestående af polyoxyethylen-hydrogeneret ricinusolie, en antioxidant, et pyridin-holdig forbindelse, nikotinamid, en alkohol, glycerol, polyethylenglycol, giuconat, en pyrrolidon-forbindelse , et vandblandbart lokalbedøvelsesmiddel, procain, urinstof, lactose og et dehydratiserlngs-middel valgt fra gruppen bestående af ethylacetat, eddikesyreanhydhd, absolut ethanol, ethylacetat, eddikesyreanhvdrid og blandinger deraf.
3. Farmaceutisk sammensætning ifølge krav 1, alternativ (A), hvor opløsningen har en pH på mindre end 7, fortrinsvis mindre end 8, mere fortrinsvis mindre end 5, eller hvor opløsningen har en pH større end 4 og mindre end 6, fortrinsvis større end 4 og mindre end 5.
4. Farmaceutisk sammensætning ifølge krav 1, hvor det molære forhold af divalent eller trivalent kation ti! minocydin er større end 3:1, fortrinsvis større end 5:1, mere fortrinsvis større end 8:1, meget mere fortrinsvis større end 10:1, eller hvor osmolaliteten af opløsningen er mindre end 400 mOsm/kg, fortrinsvis mindre end 350 mOsm/kg, eller hvor opløsningen omfatter et salt valgt fra gruppen bestående af magnesiumsulfat, magnesiumoxid, magnesiumacetat og magnesiumchlorid, eller hvor opløsningen omfatter en puffer, eller hvor opløsningen omfatter en base,
5. Farmaceutisk sammensætning ifølge krav 1, hvor koncentrationen af minocydin er mindst 5 mg/ml, mere fortrinsvis mindst 10 mg/ml.
6. Farmaceutisk sammensætning ifølge krav 4, hvor opløsningen omfatter acetat, eller hvor basen omfatter NaOH.
7. Farmaceutisk sammensætning sialge krav 1, alternativ (A), hvor 7-dimethylamino-tetracyclinet er valgt blandt PTK796, og et glycylcyclin-antibiotikum, fortrinsvis hvor glycylcyciin-antibiotikumet er tigecyclin.
8. Farmaceutisk sammensætning ifølge krav 1, alternativ (A), der omfatter: 10 mg/ml minocyclin, MgCH og NaOH, hvor det snolære forhold af Mg til minocyclin er 5:1, og pH er større end 4,5 og mindre end 5,5, eller 10 mg/ml minocyclin, MgSC>4 og natriumacetat, hvor det molære forhold af Mg til minocyclin er 5:1, pH er større end 4,5 og mindre end 5,5, og os-molaliteten er over 275 mOsm/kg og mindre end 375 mOsm/kg, eller 10 mg/ml minocyclin og MgiCkiHsCfeb, hvor det molære forhold af Mg til minocyclin er 5:1, og pH er større end 4,5 og mindre end 5,5, eller 10 mg/ml minocyclin, MgSCA og NaOH, hvor det molære forhold af Mg til minocyclin er 5:1, pH er større end 4,5 og mindre end 5,5, og osmolalite-ten er over 150 mOsm/kg og mindre end 250 mOsm/kg.
9. Farmaceutisk sammensætning ifølge krav 1 alternativ (A) omfattende 5 mg/ml tigecyclin, MgClz eller MgSC>4 og NaOH, hvor det molære forhold af Mg til tigecyclin er 5:1, og pH er større end 5,5 og mindre end 8,5, eller hvor det molære forhold af Mg til tigecyclin er 12:1, og pH er større end 5,5 og mindre end 6,5.
10. Farmaceutisk sammensætning ifølge krav 1 alternativ (A), der er egnet ti! topisk administration omfattende 5 mg/ml MgS04 og NaOH, hvor det molære forhold af Mg til tigecyclin er 5:1 eller 12:1, og pH er større end 6,0 og mindre end 7,0.
11. Vandopløselig fast sammensætning, der omfatter et 7-dimethyiamino-tetracyclin-antibiotikum eller et salt deraf og et salt omfattende et divalent eller trivalent kation, hvor det molasre forhold af divalent eller trivalent kation til 7-dimethylaminotetracyciin er større end 3:1 og hvori efter opløsning af den faste sammensætning i vand en opløsning med et pH større end 4 og mindre end 7 er dannet, fortrinsvis 7“dimethy!amino4etracyc!in-antibiotikum eller et salt deraf er minocyclin eller et salt deraf.
12. Sammensætning ifølge krav 11, hvor det molære forhold af divalent eller trivalent kation H 7-dimethyiamino-tetracyciin-antibiotikumet er større end 5:1, fortrinsvis større end 8:1, fortrinsvis større end 10:1, eller hvor sammensætningen er i form af en lyofil, eller hvor sammensætningen omfatter natriumacetat, eller hvor sammensætningen omfatter NaOH, eller hvor saltet er valgt blandt mag-nesiumchlorid, magnesiumbromid, magnesiumsulfat, calciumchlorid, calcium-bromid, calciumsulfat, zinkchiorid, galliumchlorid, magnesiummalat, magnesium citrat, magnesiumacetat, calciumcitrat, zinkacetat og zinkcitrat, eller hvor sammensætningen ikke omfatter en bestanddel valgt fra gruppen bestående af en antioxidant, en pyridin-holdig forbindelse, nicotinamid, giuconat, eller hvor 7- dimethylamino-tetracydin er valgt blandt PTK796, og et glycylcyciin- antiblotikum.
13. Fremgangsmåde til fremstilling af en farmaceutisk sammensætning omfattende: at opløse den vandopiøselige faste sammensætning ifølge ethvert af kravene 11 til 12 i vand for at danne en opløsning.
14. Fremgangsmåde til fremstilling af en farmaceutisk sammensætning omfattende: at opløse et 7-dimethyiamino-tetracyclin i en opløsning omfattende en divalent eller trivalent kation, hvor det molære forhold af divalent eller trivalent kation til 7-dimethylaminotetracyctin i opløsningen er større end 3:1, at indstille pH af opløsningen til at være større end 4 og mindre end 7; og at frysetørre sammensætningen, 7-dimethylamino-tetracyclin er fortrinsvis valgt blandt minocyclin, PTK796, og et glycylcyclin.
15. Fremgangsmåden ifølge krav 14, hvor pH i opløsningen indstilles til at være mindre end 6, fortrinsvis mindre end 5, eller hvor pH i opløsningen indstilles til at være større end 4 og mindre end 6, fortrinsvis større end 4 og mindre end 5, eller hvor justering af pH omfatter at tilsætte en syre eller at tilsætte en base eller at danne en puffer, syren er fortrinsvis HCI eller basen er NaOH, eller pufferen omfatter at tilsætte natriumacetat, eller hvori den divalente eller trivalenie kation er valgt blandt jern, kobber, zink, mangan, nikkel, cobalt, aluminium, calcium, magnesium og gallium.
16. Kit, der omfatter: en første beholder omfattende et fortyndingsmiddel, der omfatter en vandig opløsning af en divalent eller trivalent kation; og en anden beholder omfattende en fast sammensætning, der er opløselig i fortyndingsmidlet, hvor den faste sammensætning omfatter (C) minocyclin i en sådan mængde, at det molære forhold af den divalente eller trivalent© kation til minocyclin er større end 2:1, eller hvori den faste sammensætning omfatter (D) et 7-dimethylamino-tetracyclin antibiotikum i en sådan mængde, at det molære forhold af den divalente eller trivalente kation til 7-dimethylamino-tetracyclin-antibiotikum er større end 3:1, og hvor opløsning af den faste sammensastning i fortyndingsmidiet frembringer en opløsning med en pH storre end 4 og mindre end 7.
17. Kittet ifølge krav 16, hvor fortyndingsmidiet omfatter en syre eller en base, eller en puffer; fortrinsvis er syren MCI eller basen er NaOH eller fortyndings-midlet omfatter natriumacetat, eller hvor pH af fortyndingsmidlet er større end pH 6 og mindre end pH 8, eller hvori den divalente eller trivalente kation er valgt blandt jern, kobber, zink, mangan, nikkel, cobalt, aluminium, calcium, magnesium og gallium, eller hvor molforhoidet af divalent eller trivalent kation til minocyciin er større end 3:1, eller hvor 7-dimethyiamlno-tetracyc!Snet af alternativ (D) er valgt fra minocyciin, PTK796, og en giycylcyclin.
18. Kittet iføige krav 16, hvor det molære forhold af divalent eller trivalent kation til minocyciin eller /-dimethyiamino-tetracyclin-antibiotikum er større end 5:1, fortrinsvis større end 8:1, mere fortrinsvis større end 10:1.
19. Kittet ifølge krav 18, sammensætningen ifølge krav 12 og fremgangsmåden iføige krav 15, hvor giycyicyclinet er tigecyclin,
20. Farmaceutisk sammensætning ifølge ethvert af kravene 1 til 10 til anvendelse ved behandling eller forebyggelse af en bakteriel infektion i et individ, hvor den farmaceutiske sammensætning indgives via en intravenøs vej eller via en topisk vej.
21. Farmaceutisk sammensætning fremstillet ifølge fremgangsmåden ifølge ethvert af kravene 13 til 15 til anvendelse ved behandling eller forebyggelse af en bakteriel infektion i et individ, hvor den farmaceutiske sammensætning indgives via en intravenøs vej eller via en topisk vej.
22. Farmaceutisk sammensætning iføige ethvert af kravene 20 til 21, hvor en intravenøs dosis omfatter mindre end 200 ml af sammensætningen eller hvor sammensætningen indgives i mindre end 60 minutter via en intravenøs vej.
23. Sammensætning omfattende en vandig opløsning af tigecyclin og en divalent eller trivalent kation, hvor molforholdet af nævnte divalente eller trivalente kation til nævnte tigecyclin er større end 2:1 og hvor opløsningen har et pH større end 4 og mindre end 7, fortrinsvis hvor molforhoidet af nævnte divalente eller trivalente kation ti! nævnte tigecyclin er større end 3:1.
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| US39230410P | 2010-10-12 | 2010-10-12 | |
| PCT/US2011/036351 WO2011143503A2 (en) | 2010-05-12 | 2011-05-12 | Tetracycline compositions |
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| DK2568987T3 true DK2568987T3 (da) | 2017-02-20 |
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| JP (2) | JP6025712B2 (da) |
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| ES2613738T3 (es) | 2010-05-12 | 2017-05-25 | Rempex Pharmaceuticals, Inc. | Composiciones de tetraciclina |
| CN102697739B (zh) * | 2012-05-31 | 2014-10-29 | 丽珠医药集团股份有限公司 | 一种减少替加环素差向异构体化的粉针剂制备方法 |
| IN2013MU01127A (da) * | 2013-03-26 | 2015-05-01 | Astron Res Ltd | |
| WO2014167575A2 (en) | 2013-03-26 | 2014-10-16 | Astron Research Limited | Stable tigecycline composition |
| US20140323443A1 (en) * | 2013-04-30 | 2014-10-30 | Fresenius Kabi Usa, Llc | Tigecycline formulations |
| BR112017020358A2 (pt) | 2015-03-23 | 2018-07-17 | Biopharmx Inc | composição farmacêutica de tetraciclina para uso dermatológico |
| PT108978B (pt) * | 2015-11-24 | 2020-03-09 | Hovione Farm S A | Sais de tetraciclinas |
| GB201904851D0 (en) | 2019-04-05 | 2019-05-22 | Katholieke Univ Leven | Melanoma treatment |
| WO2021063468A1 (en) * | 2019-10-02 | 2021-04-08 | Anfarm Hellas S.A. | Stable parenteral pharmaceutical composition containing tigecycline and process for the preparation thereof |
| CN113101371A (zh) * | 2021-04-07 | 2021-07-13 | 中国科学院大学温州研究院(温州生物材料与工程研究所) | 一种基于阳离子-π作用的疏水药物的增溶方法 |
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| US2736725A (en) | 1954-03-11 | 1956-02-28 | American Cyanamid Co | Complexes of tetracycline antibiotics and preparation of same |
| GB812138A (en) | 1954-06-17 | 1959-04-22 | American Cyanamid Co | Improvements relating to antibiotic composition |
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