DK2778172T3 - Stabil krystallinsk monohydrat af epirubicin hydrochlorid og fremgangsmåde til fremstilling - Google Patents
Stabil krystallinsk monohydrat af epirubicin hydrochlorid og fremgangsmåde til fremstilling Download PDFInfo
- Publication number
- DK2778172T3 DK2778172T3 DK14159462.2T DK14159462T DK2778172T3 DK 2778172 T3 DK2778172 T3 DK 2778172T3 DK 14159462 T DK14159462 T DK 14159462T DK 2778172 T3 DK2778172 T3 DK 2778172T3
- Authority
- DK
- Denmark
- Prior art keywords
- epirubicin hydrochloride
- solvent
- range
- crystalline monohydrate
- butanol
- Prior art date
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- MWWSFMDVAYGXBV-FGBSZODSSA-N (7s,9s)-7-[(2r,4s,5r,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-9-(2-hydroxyacetyl)-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione;hydron;chloride Chemical compound Cl.O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 MWWSFMDVAYGXBV-FGBSZODSSA-N 0.000 title claims description 105
- 229960003265 epirubicin hydrochloride Drugs 0.000 title claims description 103
- 150000004682 monohydrates Chemical class 0.000 title claims description 53
- 238000000034 method Methods 0.000 title claims description 32
- 238000002360 preparation method Methods 0.000 title description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 68
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 65
- 239000002904 solvent Substances 0.000 claims description 63
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 48
- 239000013078 crystal Substances 0.000 claims description 45
- 239000002245 particle Substances 0.000 claims description 43
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 34
- 239000000203 mixture Substances 0.000 claims description 25
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 23
- 239000013557 residual solvent Substances 0.000 claims description 16
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 claims description 15
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 14
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 claims description 14
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 238000002425 crystallisation Methods 0.000 claims description 11
- 230000008025 crystallization Effects 0.000 claims description 11
- 238000000634 powder X-ray diffraction Methods 0.000 claims description 10
- IBZGBXXTIGCACK-CWKPULSASA-N Adriamycinone Chemical compound C1[C@@](O)(C(=O)CO)C[C@H](O)C2=C1C(O)=C1C(=O)C(C=CC=C3OC)=C3C(=O)C1=C2O IBZGBXXTIGCACK-CWKPULSASA-N 0.000 claims description 7
- 238000010438 heat treatment Methods 0.000 claims description 7
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- 229960004592 isopropanol Drugs 0.000 claims 1
- 239000000243 solution Substances 0.000 description 42
- 238000004458 analytical method Methods 0.000 description 24
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 20
- 150000001875 compounds Chemical class 0.000 description 15
- 239000007787 solid Substances 0.000 description 15
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- 238000012512 characterization method Methods 0.000 description 8
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- 238000002411 thermogravimetry Methods 0.000 description 8
- 150000004684 trihydrates Chemical class 0.000 description 8
- 238000000113 differential scanning calorimetry Methods 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- AOJJSUZBOXZQNB-VTZDEGQISA-N 4'-epidoxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-VTZDEGQISA-N 0.000 description 6
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 6
- HTIJFSOGRVMCQR-UHFFFAOYSA-N Epirubicin Natural products COc1cccc2C(=O)c3c(O)c4CC(O)(CC(OC5CC(N)C(=O)C(C)O5)c4c(O)c3C(=O)c12)C(=O)CO HTIJFSOGRVMCQR-UHFFFAOYSA-N 0.000 description 6
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- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 4
- 239000012530 fluid Substances 0.000 description 4
- 238000003860 storage Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 description 3
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 description 3
- 206010006187 Breast cancer Diseases 0.000 description 3
- 208000026310 Breast neoplasm Diseases 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
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- 229960004679 doxorubicin Drugs 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
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- 102100027324 2-hydroxyacyl-CoA lyase 1 Human genes 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 101001009252 Homo sapiens 2-hydroxyacyl-CoA lyase 1 Proteins 0.000 description 2
- GQPLMRYTRLFLPF-UHFFFAOYSA-N Nitrous Oxide Chemical compound [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 238000002441 X-ray diffraction Methods 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 229940045799 anthracyclines and related substance Drugs 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 230000015556 catabolic process Effects 0.000 description 2
- STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 2
- 238000006731 degradation reaction Methods 0.000 description 2
- -1 epirubicin hydrochlorides Chemical class 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
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- STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 1
- 229920002799 BoPET Polymers 0.000 description 1
- 102100021202 Desmocollin-1 Human genes 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 208000002250 Hematologic Neoplasms Diseases 0.000 description 1
- 101000968043 Homo sapiens Desmocollin-1 Proteins 0.000 description 1
- 101000880960 Homo sapiens Desmocollin-3 Proteins 0.000 description 1
- XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 1
- XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 206010025323 Lymphomas Diseases 0.000 description 1
- 239000005041 Mylar™ Substances 0.000 description 1
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- 102000007537 Type II DNA Topoisomerases Human genes 0.000 description 1
- 108010046308 Type II DNA Topoisomerases Proteins 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 210000001185 bone marrow Anatomy 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
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- 238000005443 coulometric titration Methods 0.000 description 1
- 238000003869 coulometry Methods 0.000 description 1
- 230000001472 cytotoxic effect Effects 0.000 description 1
- 229960000975 daunorubicin Drugs 0.000 description 1
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- 239000011888 foil Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 229960000908 idarubicin Drugs 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- APFVFJFRJDLVQX-UHFFFAOYSA-N indium atom Chemical compound [In] APFVFJFRJDLVQX-UHFFFAOYSA-N 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000009830 intercalation Methods 0.000 description 1
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- 150000002576 ketones Chemical class 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/24—Condensed ring systems having three or more rings
- C07H15/252—Naphthacene radicals, e.g. daunomycins, adriamycins
-
- 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
- A61K31/01—Hydrocarbons
- A61K31/015—Hydrocarbons carbocyclic
-
- 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
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- A61K31/381—Heterocyclic compounds having sulfur as a ring hetero atom having five-membered rings
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H1/00—Processes for the preparation of sugar derivatives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/24—Condensed ring systems having three or more rings
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Biotechnology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Saccharide Compounds (AREA)
Claims (13)
1. Fremgangsmåde til fremstilling af et krystallinsk monohydrat af epirubicin hydrochlorid, hvilken fremgangsmåde omfatter: (a) tilsætning af mindst et første opløsningsmiddel og mindst et andet opløsningsmiddel til epirubicin hydrochlorid, hvori (i) det første opløsningsmiddel er valgt fra gruppen bestående af 1-butanol, 2-butanol, iso-butanol, tert-butanol, og blandinger deraf; (ii) det andet opløsningsmiddel er valgt fra gruppen bestående af 1-propanol, iso-propanol, ethanol, og blandinger deraf; og (iii) volumenforholdet mellem det første opløsningsmiddel og det andet opløsningsmiddel er i området mellem 1:1 og 2:1 (volumen/volumen); (b) tilpasning af vandindholdet i opløsningen opnået i trin (a) til en mængde i området mellem 8 vægt-% og 11 vægt-%; og (c) opvarmning af opløsningen opnået i trin (b) til en temperatur på 70 °C til 90 °C for at opnå krystallisation; hvori det fremstillede krystallinske monohydrat har et vandindhold i området mellem 2,7 vægt-°/o og 3,5 vægt-% og er frit for rest-solventer.
2. Fremgangsmåden ifølge krav 1, hvori det første opløsningsmiddel er 1-butanol og det andet opløsningsmiddel er 1-propanol.
3. Fremgangsmåden ifølge krav 1 eller krav 2, hvilken yderligere omfatter: opvarmning af blandingen fra trin (a) til en temperatur på 40 °C til 55 °C indtil fuldstændig opløsning af reaktionsblandingen er opnået.
4. Fremgangsmåden ifølge et hvilket som helst af kravene 1 til 3, hvori den resulterende koncentration af epirubicin hydrochlorid i opløsningen i trin (b) er i området mellem 10 g/L og 100 g/L.
5. Fremgangsmåden ifølge et hvilket som helst af kravene 1 til 4, hvori opløsningen i trin (c) opvarmes til en temperatur på 75 °C til 85 °C.
6. Fremgangsmåden ifølge et hvilket som helst af kravene 1 til 5, hvilken yderligere omfatter: podning af opløsningen opnået i trin (b) for at fremme krystallisationen.
7. Fremgangsmåden ifølge et hvilket som helst af kravene 1 til 6, hvilken yderligere omfatter: oprensning af krystallerne opnået i trin (c).
8. Fremgangsmåden ifølge et hvilket som helst af kravene 1 til 7, hvori vandindholdet i det krystallinske monohydrat af epirubicin hydrochlorid er i området mellem 2,8 vægt-% og 3,3 vægt-%.
9. Krystallinsk monohydrat af epirubicin hydrochlorid, som er fremstillet ved fremgangsmåden ifølge et hvilket som helst af kravene 1 til 8, hvori (i) gennemsnitsdiameteren af de fremstillede krystalpartikler er i området mellem 20 pm og 50 pm; og (ii) partikelstørrelsen af mindst 60 %, og især af mindst 80 % af de fremstillede krystalpartikler er inden for det område, der er givet som gennemsnitsdiameteren ± 20 %.
10. Det krystallinske monohydrat af epirubicin hydrochlorid ifølge krav 9, hvori partikelstørrelsen af mindst 60 %, og især af mindst 80 % af de fremstillede krystalpartikler er inden for det område, der er givet som gennemsnitsdiameteren ± 10 %.
11. Det krystallinske monohydrat af epirubicin hydrochlorid ifølge krav 9 eller krav 10, hvilket yderligere er kendetegnet ved en termostabilitet, som resulterer i dannelse af mindre end 0,5 vægt-% doxorubicinon efter inkubation ved 100 °C i én måned ifølge ICH-vejledningen.
12. Det krystallinske monohydrat af epirubicin hydrochlorid ifølge et hvilket som helst af kravene 9 til 11, hvilket yderligere er kendetegnet ved et pulver-røntgendiffraktionsmønster omfattende toppe ved gennemsnitsdiffraktionsvinkler (2Θ) på 5,1°, 9,1°, 13,6°, 22,1°, 22,5°, og 24,0° (hver ± 0,2°).
13. Det krystallinske monohydrat af epirubicin hydrochlorid ifølge et hvilket som helst af kravene 9 til 12 til anvendelse ved forebyggelse eller behandling af kræft.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP13159392.3A EP2778171A1 (en) | 2013-03-15 | 2013-03-15 | Crystalline monohydrate of epirubicin hydrochloride |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DK2778172T3 true DK2778172T3 (da) | 2017-04-10 |
Family
ID=48013735
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK14159462.2T DK2778172T3 (da) | 2013-03-15 | 2014-03-13 | Stabil krystallinsk monohydrat af epirubicin hydrochlorid og fremgangsmåde til fremstilling |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US20140271874A1 (da) |
| EP (2) | EP2778171A1 (da) |
| JP (1) | JP5964339B2 (da) |
| KR (1) | KR101751099B1 (da) |
| CN (1) | CN104045672B (da) |
| DK (1) | DK2778172T3 (da) |
| ES (1) | ES2623218T3 (da) |
| HU (1) | HUE034152T2 (da) |
| IN (1) | IN2014DE00737A (da) |
| PL (1) | PL2778172T3 (da) |
| PT (1) | PT2778172T (da) |
| RS (1) | RS55850B1 (da) |
| RU (2) | RU2630692C2 (da) |
| SI (1) | SI2778172T1 (da) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3279206B1 (en) * | 2015-03-30 | 2020-04-22 | Meiji Seika Pharma Co., Ltd. | Method for producing epirubicin and novel production intermediate therefor |
| CN104861014B (zh) * | 2015-06-03 | 2017-09-29 | 道中道（菏泽）制药有限公司 | 一种盐酸表阿霉素结晶的制备方法 |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1155446B (it) | 1982-12-23 | 1987-01-28 | Erba Farmitalia | Procedimento per la purificazione di glucosidi antraciclinonici mediante adsobimento selettivo su resine |
| WO2004082662A1 (en) * | 2003-03-21 | 2004-09-30 | Dsm Ip Assets B.V. | Amoxicillin trihydrate |
| WO2005004805A2 (en) * | 2003-07-02 | 2005-01-20 | Solux Corporation | Thermally stable crystalline epirubicin hydrochloride and method of making the same |
| US20090099346A1 (en) * | 2003-07-02 | 2009-04-16 | Victor Matvienko | Thermally stable crystalline epirubicin hydrochloride |
| GB0902009D0 (en) * | 2009-02-09 | 2009-03-11 | Innospec Ltd | Improvements in fuels |
| ES2351494B1 (es) * | 2009-06-30 | 2011-11-28 | Consejo Superior De Investigaciones Cientificas (Csic) (85,7%) | Material organo-inorganico microporoso cristalino basado en cationes alcalinoterreos, procedimiento de preparacion y usos |
| KR101125460B1 (ko) * | 2010-03-24 | 2012-03-28 | 동아제약주식회사 | 에피루비신 염산염의 신규한 결정형 |
| CN102120750B (zh) * | 2011-01-30 | 2013-04-03 | 山东新时代药业有限公司 | 一种盐酸表柔比星的纯化方法 |
| DE102011103751A1 (de) * | 2011-05-31 | 2012-12-06 | Heraeus Precious Metals Gmbh & Co. Kg | Kristallisierung von Epirubicinhydrochlorid |
-
2013
- 2013-03-15 EP EP13159392.3A patent/EP2778171A1/en not_active Withdrawn
-
2014
- 2014-03-13 DK DK14159462.2T patent/DK2778172T3/da active
- 2014-03-13 PL PL14159462T patent/PL2778172T3/pl unknown
- 2014-03-13 HU HUE14159462A patent/HUE034152T2/en unknown
- 2014-03-13 ES ES14159462.2T patent/ES2623218T3/es active Active
- 2014-03-13 JP JP2014049587A patent/JP5964339B2/ja active Active
- 2014-03-13 RS RS20170359A patent/RS55850B1/sr unknown
- 2014-03-13 PT PT141594622T patent/PT2778172T/pt unknown
- 2014-03-13 CN CN201410092353.9A patent/CN104045672B/zh active Active
- 2014-03-13 US US14/208,133 patent/US20140271874A1/en not_active Abandoned
- 2014-03-13 EP EP14159462.2A patent/EP2778172B1/en active Active
- 2014-03-13 IN IN737DE2014 patent/IN2014DE00737A/en unknown
- 2014-03-13 KR KR1020140029344A patent/KR101751099B1/ko active Active
- 2014-03-13 SI SI201430193A patent/SI2778172T1/sl unknown
- 2014-03-13 RU RU2014109682A patent/RU2630692C2/ru active
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2017
- 2017-05-23 RU RU2017117890A patent/RU2700683C2/ru active
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2019
- 2019-07-24 US US16/520,767 patent/US20190382432A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| JP2014181235A (ja) | 2014-09-29 |
| RU2014109682A (ru) | 2015-09-20 |
| RS55850B1 (sr) | 2017-08-31 |
| PT2778172T (pt) | 2017-05-03 |
| SI2778172T1 (sl) | 2017-07-31 |
| PL2778172T3 (pl) | 2017-08-31 |
| RU2017117890A3 (da) | 2018-11-26 |
| EP2778172B1 (en) | 2017-02-01 |
| CN104045672B (zh) | 2017-09-15 |
| HUE034152T2 (en) | 2018-01-29 |
| EP2778171A1 (en) | 2014-09-17 |
| ES2623218T3 (es) | 2017-07-10 |
| US20190382432A1 (en) | 2019-12-19 |
| JP5964339B2 (ja) | 2016-08-03 |
| HK1199264A1 (en) | 2015-06-26 |
| US20140271874A1 (en) | 2014-09-18 |
| RU2630692C2 (ru) | 2017-09-12 |
| RU2017117890A (ru) | 2018-11-26 |
| EP2778172A1 (en) | 2014-09-17 |
| KR20140113441A (ko) | 2014-09-24 |
| RU2700683C2 (ru) | 2019-09-19 |
| CN104045672A (zh) | 2014-09-17 |
| KR101751099B1 (ko) | 2017-06-26 |
| IN2014DE00737A (da) | 2015-06-19 |
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