DE3825374A1 - Komplex aus mindestens einer lipophilen saeure und mitoxantron und/oder bisantren - Google Patents
Komplex aus mindestens einer lipophilen saeure und mitoxantron und/oder bisantrenInfo
- Publication number
- DE3825374A1 DE3825374A1 DE3825374A DE3825374A DE3825374A1 DE 3825374 A1 DE3825374 A1 DE 3825374A1 DE 3825374 A DE3825374 A DE 3825374A DE 3825374 A DE3825374 A DE 3825374A DE 3825374 A1 DE3825374 A1 DE 3825374A1
- Authority
- DE
- Germany
- Prior art keywords
- complex
- mitoxantrone
- bisantrene
- composition
- lipophilic acid
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- KKZJGLLVHKMTCM-UHFFFAOYSA-N mitoxantrone Chemical compound O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO KKZJGLLVHKMTCM-UHFFFAOYSA-N 0.000 title claims abstract description 50
- 229960001156 mitoxantrone Drugs 0.000 title claims abstract description 40
- 239000002253 acid Substances 0.000 title claims abstract description 27
- 229950008548 bisantrene Drugs 0.000 title claims abstract description 23
- NJSMWLQOCQIOPE-OCHFTUDZSA-N n-[(e)-[10-[(e)-(4,5-dihydro-1h-imidazol-2-ylhydrazinylidene)methyl]anthracen-9-yl]methylideneamino]-4,5-dihydro-1h-imidazol-2-amine Chemical compound N1CCN=C1N\N=C\C(C1=CC=CC=C11)=C(C=CC=C2)C2=C1\C=N\NC1=NCCN1 NJSMWLQOCQIOPE-OCHFTUDZSA-N 0.000 title claims abstract description 23
- 239000000203 mixture Substances 0.000 claims abstract description 30
- HBSXKBIYGYFNRF-JMLRMIEWSA-N n-[(z)-[10-[(z)-(4,5-dihydro-1h-imidazol-2-ylhydrazinylidene)methyl]anthracen-9-yl]methylideneamino]-4,5-dihydro-1h-imidazol-2-amine;hydrochloride Chemical compound Cl.N1CCN=C1N\N=C/C(C1=CC=CC=C11)=C(C=CC=C2)C2=C1\C=N/NC1=NCCN1 HBSXKBIYGYFNRF-JMLRMIEWSA-N 0.000 claims abstract description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 3
- 239000002502 liposome Substances 0.000 claims description 41
- PORPENFLTBBHSG-MGBGTMOVSA-N 1,2-dihexadecanoyl-sn-glycerol-3-phosphate Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP(O)(O)=O)OC(=O)CCCCCCCCCCCCCCC PORPENFLTBBHSG-MGBGTMOVSA-N 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 6
- 239000002105 nanoparticle Substances 0.000 claims description 4
- 102000004169 proteins and genes Human genes 0.000 claims description 4
- 108090000623 proteins and genes Proteins 0.000 claims description 4
- 239000003963 antioxidant agent Substances 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 2
- -1 4,5-dihydro-1H-imidazol-2-yl Chemical group 0.000 claims description 2
- XORFYWZQDMDTTN-UHFFFAOYSA-N anthracene-1,2-dione dihydrochloride Chemical compound Cl.Cl.C1=CC=C2C=C(C(C(=O)C=C3)=O)C3=CC2=C1 XORFYWZQDMDTTN-UHFFFAOYSA-N 0.000 claims description 2
- SBRUFOSORMQHES-UHFFFAOYSA-N anthracene-9,10-dialdehyde Chemical compound C1=CC=C2C(C=O)=C(C=CC=C3)C3=C(C=O)C2=C1 SBRUFOSORMQHES-UHFFFAOYSA-N 0.000 claims description 2
- 239000012050 conventional carrier Substances 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
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- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 abstract 1
- 201000009030 Carcinoma Diseases 0.000 abstract 1
- KPGNWQKJBQMNML-UHFFFAOYSA-N Cl.Cl.O=Cc1c2ccccc2c(C=NN(C2=NCCN2)C2=NCCN2)c2ccccc12 Chemical compound Cl.Cl.O=Cc1c2ccccc2c(C=NN(C2=NCCN2)C2=NCCN2)c2ccccc12 KPGNWQKJBQMNML-UHFFFAOYSA-N 0.000 abstract 1
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- ZAHQPTJLOCWVPG-UHFFFAOYSA-N mitoxantrone dihydrochloride Chemical compound Cl.Cl.O=C1C2=C(O)C=CC(O)=C2C(=O)C2=C1C(NCCNCCO)=CC=C2NCCNCCO ZAHQPTJLOCWVPG-UHFFFAOYSA-N 0.000 description 9
- 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 8
- 150000004665 fatty acids Chemical class 0.000 description 8
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 8
- 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 7
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- 108020004414 DNA Proteins 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
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- 235000012000 cholesterol Nutrition 0.000 description 3
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- 230000003013 cytotoxicity Effects 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 230000029142 excretion Effects 0.000 description 3
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 3
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- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
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- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
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- 150000008103 phosphatidic acids Chemical class 0.000 description 2
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- 230000004083 survival effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- DUXYWXYOBMKGIN-UHFFFAOYSA-N trimyristin Chemical compound CCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCC DUXYWXYOBMKGIN-UHFFFAOYSA-N 0.000 description 2
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 1
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- RZVHIXYEVGDQDX-UHFFFAOYSA-N 9,10-anthraquinone Chemical compound C1=CC=C2C(=O)C3=CC=CC=C3C(=O)C2=C1 RZVHIXYEVGDQDX-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 102000004506 Blood Proteins Human genes 0.000 description 1
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- 208000003322 Coinfection Diseases 0.000 description 1
- 231100001074 DNA strand break Toxicity 0.000 description 1
- PVNIQBQSYATKKL-UHFFFAOYSA-N Glycerol trihexadecanoate Natural products CCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCC PVNIQBQSYATKKL-UHFFFAOYSA-N 0.000 description 1
- DCXXMTOCNZCJGO-UHFFFAOYSA-N Glycerol trioctadecanoate Natural products CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 1
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 1
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- 238000012404 In vitro experiment Methods 0.000 description 1
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- 239000000232 Lipid Bilayer Substances 0.000 description 1
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- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
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- 229910019142 PO4 Inorganic materials 0.000 description 1
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- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
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- 238000005259 measurement Methods 0.000 description 1
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- 239000002207 metabolite Substances 0.000 description 1
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- 229960004169 mitoxantrone hydrochloride Drugs 0.000 description 1
- 239000003471 mutagenic agent Substances 0.000 description 1
- 231100000707 mutagenic chemical Toxicity 0.000 description 1
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- 108020004707 nucleic acids Proteins 0.000 description 1
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- 238000011580 nude mouse model Methods 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
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- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/06—Phosphorus compounds without P—C bonds
- C07F9/08—Esters of oxyacids of phosphorus
- C07F9/09—Esters of phosphoric acids
- C07F9/10—Phosphatides, e.g. lecithin
- C07F9/106—Adducts, complexes, salts of phosphatides
-
- 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
- A61K9/10—Dispersions; Emulsions
- A61K9/127—Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C225/00—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones
- C07C225/24—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones the carbon skeleton containing carbon atoms of quinone rings
- C07C225/26—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones the carbon skeleton containing carbon atoms of quinone rings having amino groups bound to carbon atoms of quinone rings or of condensed ring systems containing quinone rings
- C07C225/32—Compounds containing amino groups and doubly—bound oxygen atoms bound to the same carbon skeleton, at least one of the doubly—bound oxygen atoms not being part of a —CHO group, e.g. amino ketones the carbon skeleton containing carbon atoms of quinone rings having amino groups bound to carbon atoms of quinone rings or of condensed ring systems containing quinone rings of condensed quinone ring systems formed by at least three rings
- C07C225/34—Amino anthraquinones
- C07C225/36—Amino anthraquinones the carbon skeleton being further substituted by singly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2603/00—Systems containing at least three condensed rings
- C07C2603/02—Ortho- or ortho- and peri-condensed systems
- C07C2603/04—Ortho- or ortho- and peri-condensed systems containing three rings
- C07C2603/22—Ortho- or ortho- and peri-condensed systems containing three rings containing only six-membered rings
- C07C2603/24—Anthracenes; Hydrogenated anthracenes
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Dispersion Chemistry (AREA)
- Biochemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3825374A DE3825374A1 (de) | 1988-07-26 | 1988-07-26 | Komplex aus mindestens einer lipophilen saeure und mitoxantron und/oder bisantren |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE3825374A DE3825374A1 (de) | 1988-07-26 | 1988-07-26 | Komplex aus mindestens einer lipophilen saeure und mitoxantron und/oder bisantren |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE3825374A1 true DE3825374A1 (de) | 1990-02-01 |
| DE3825374C2 DE3825374C2 (enrdf_load_stackoverflow) | 1990-06-28 |
Family
ID=6359585
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE3825374A Granted DE3825374A1 (de) | 1988-07-26 | 1988-07-26 | Komplex aus mindestens einer lipophilen saeure und mitoxantron und/oder bisantren |
Country Status (1)
| Country | Link |
|---|---|
| DE (1) | DE3825374A1 (enrdf_load_stackoverflow) |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992001441A1 (de) * | 1990-07-21 | 1992-02-06 | Knoll Aktiengesellschaft | Stabile wirkstoff-formulierung |
| WO1993018749A1 (de) * | 1992-03-17 | 1993-09-30 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Liposomen mit negativer überschussladung |
| EP1159974A1 (en) * | 1993-07-19 | 2001-12-05 | Angiotech Pharmaceuticals, Inc. | Anti-angiogenic compositions and methods of use |
| US6846841B2 (en) | 1993-07-19 | 2005-01-25 | Angiotech Pharmaceuticals, Inc. | Anti-angiogenic compositions and methods of use |
| EP1838286B1 (de) * | 2004-12-23 | 2012-02-15 | KTB Tumorforschungsgesellschaft mbH | Herstellung von lipidbasierten nanopartikeln unter einsatz einer dualen asymmetrischen zentrifuge |
| EP3024457A4 (en) * | 2013-07-26 | 2017-06-28 | Update Pharma Inc. | Compositions to improve the therapeutic benefit of bisantrene |
| WO2019073296A1 (en) * | 2017-10-13 | 2019-04-18 | Race Oncology Ltd. | LIPOSOMAL FORMULATIONS OF BISANTRENE OR DERIVATIVES OR THE LIKE THEREOF |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19818802A1 (de) * | 1998-04-27 | 1999-10-28 | Dresden Arzneimittel | Stabile Mitoxantron-Lösungen |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3343530A1 (de) * | 1983-12-01 | 1985-06-13 | Max Planck Gesellschaft | Arzneimittel mit verbesserter penetration der gewebsmembran |
-
1988
- 1988-07-26 DE DE3825374A patent/DE3825374A1/de active Granted
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3343530A1 (de) * | 1983-12-01 | 1985-06-13 | Max Planck Gesellschaft | Arzneimittel mit verbesserter penetration der gewebsmembran |
Non-Patent Citations (4)
| Title |
|---|
| Angew. Chemie 97, 1985, S. 157-159 * |
| CA 104, 1986, 141 894 x * |
| LIST, Arzneiformenlehre 1985, 518-520 * |
| RÖMPP: Chemie-Lexikon, 1983, 2379 * |
Cited By (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1992001441A1 (de) * | 1990-07-21 | 1992-02-06 | Knoll Aktiengesellschaft | Stabile wirkstoff-formulierung |
| WO1993018749A1 (de) * | 1992-03-17 | 1993-09-30 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Liposomen mit negativer überschussladung |
| AU672600B2 (en) * | 1992-03-17 | 1996-10-10 | Max-Planck-Gesellschaft Zur Forderung Der Wissenschaften E.V. | Liposomes with excess negative charge |
| US5626867A (en) * | 1992-03-17 | 1997-05-06 | Max-Planck Gesellschaft Zur Forderung Der Wissenschaften E.V. | Liposomes with a negative excess charge |
| EP1159974A1 (en) * | 1993-07-19 | 2001-12-05 | Angiotech Pharmaceuticals, Inc. | Anti-angiogenic compositions and methods of use |
| EP1155691A3 (en) * | 1993-07-19 | 2002-05-29 | Angiotech Pharmaceuticals, Inc. | Anti-angiogenic compositions and methods of use |
| US6544544B2 (en) | 1993-07-19 | 2003-04-08 | Angiotech Pharmaceuticals, Inc. | Anti-angiogenic compositions and methods of use |
| US6846841B2 (en) | 1993-07-19 | 2005-01-25 | Angiotech Pharmaceuticals, Inc. | Anti-angiogenic compositions and methods of use |
| EP1838286B1 (de) * | 2004-12-23 | 2012-02-15 | KTB Tumorforschungsgesellschaft mbH | Herstellung von lipidbasierten nanopartikeln unter einsatz einer dualen asymmetrischen zentrifuge |
| US10662060B2 (en) | 2004-12-23 | 2020-05-26 | Ulrich Massing | Manufacture of lipid-based nanoparticles using a dual asymmetric centrifuge |
| EP3024457A4 (en) * | 2013-07-26 | 2017-06-28 | Update Pharma Inc. | Compositions to improve the therapeutic benefit of bisantrene |
| US10500192B2 (en) | 2013-07-26 | 2019-12-10 | Race Oncology Ltd. | Combinatorial methods to improve the therapeutic benefit of bisantrene and analogs and derivatives thereof |
| US10548876B2 (en) | 2013-07-26 | 2020-02-04 | Race Oncology Ltd. | Compositions to improve the therapeutic benefit of bisantrene and analogs and derivatives thereof |
| US11135201B2 (en) | 2013-07-26 | 2021-10-05 | Race Oncology Ltd. | Compositions to improve the therapeutic benefit of bisantrene and analogs and derivatives thereof |
| US11147800B2 (en) | 2013-07-26 | 2021-10-19 | Race Oncology Ltd. | Combinatorial methods to improve the therapeutic benefit of bisantrene and analogs and derivatives thereof |
| WO2019073296A1 (en) * | 2017-10-13 | 2019-04-18 | Race Oncology Ltd. | LIPOSOMAL FORMULATIONS OF BISANTRENE OR DERIVATIVES OR THE LIKE THEREOF |
Also Published As
| Publication number | Publication date |
|---|---|
| DE3825374C2 (enrdf_load_stackoverflow) | 1990-06-28 |
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