TWI599361B - 磷酸鉑（ｐｈｏｓｐｈａｐｌａｔｉｎ）化合物之合成與純化方法及其用途 - Google Patents
磷酸鉑（ｐｈｏｓｐｈａｐｌａｔｉｎ）化合物之合成與純化方法及其用途 Download PDFInfo
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- TWI599361B TWI599361B TW102111669A TW102111669A TWI599361B TW I599361 B TWI599361 B TW I599361B TW 102111669 A TW102111669 A TW 102111669A TW 102111669 A TW102111669 A TW 102111669A TW I599361 B TWI599361 B TW I599361B
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- Prior art keywords
- pyrophosphate
- platinum
- reaction mixture
- dach
- complex
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- 238000000034 method Methods 0.000 title claims description 98
- 150000001875 compounds Chemical class 0.000 title claims description 18
- YPGLWPWPVJBCEM-UHFFFAOYSA-K [Pt+3].[O-]P([O-])([O-])=O Chemical compound [Pt+3].[O-]P([O-])([O-])=O YPGLWPWPVJBCEM-UHFFFAOYSA-K 0.000 title description 4
- 230000002194 synthesizing effect Effects 0.000 title description 3
- 238000006243 chemical reaction Methods 0.000 claims description 69
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 60
- 239000011541 reaction mixture Substances 0.000 claims description 54
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 47
- 239000007787 solid Substances 0.000 claims description 37
- 235000011180 diphosphates Nutrition 0.000 claims description 36
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 34
- 229910017604 nitric acid Inorganic materials 0.000 claims description 34
- 239000002244 precipitate Substances 0.000 claims description 34
- 229910052697 platinum Inorganic materials 0.000 claims description 29
- ZZMFAAPZGBNYRP-UHFFFAOYSA-J phosphonato phosphate platinum(4+) Chemical compound [Pt+4].[O-]P([O-])(=O)OP([O-])([O-])=O ZZMFAAPZGBNYRP-UHFFFAOYSA-J 0.000 claims description 27
- 239000000203 mixture Substances 0.000 claims description 26
- -1 platinum (IV) pyrophosphate pyrophosphate compound Chemical class 0.000 claims description 24
- 238000003756 stirring Methods 0.000 claims description 22
- 238000001556 precipitation Methods 0.000 claims description 21
- 230000008569 process Effects 0.000 claims description 20
- 239000002904 solvent Substances 0.000 claims description 20
- 150000004985 diamines Chemical class 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 14
- 239000003446 ligand Substances 0.000 claims description 12
- 239000000706 filtrate Substances 0.000 claims description 11
- 150000001412 amines Chemical class 0.000 claims description 10
- 206010028980 Neoplasm Diseases 0.000 claims description 9
- 229960004316 cisplatin Drugs 0.000 claims description 9
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 claims description 9
- 239000003960 organic solvent Substances 0.000 claims description 9
- VSRXQHXAPYXROS-UHFFFAOYSA-N azanide;cyclobutane-1,1-dicarboxylic acid;platinum(2+) Chemical compound [NH2-].[NH2-].[Pt+2].OC(=O)C1(C(O)=O)CCC1 VSRXQHXAPYXROS-UHFFFAOYSA-N 0.000 claims description 8
- 229960004562 carboplatin Drugs 0.000 claims description 8
- 239000002246 antineoplastic agent Substances 0.000 claims description 7
- 239000000872 buffer Substances 0.000 claims description 7
- 201000011510 cancer Diseases 0.000 claims description 7
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 6
- 206010033128 Ovarian cancer Diseases 0.000 claims description 6
- 206010061535 Ovarian neoplasm Diseases 0.000 claims description 6
- 125000001931 aliphatic group Chemical group 0.000 claims description 6
- 150000004982 aromatic amines Chemical class 0.000 claims description 6
- 238000001816 cooling Methods 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000005233 alkylalcohol group Chemical group 0.000 claims description 5
- 229960001756 oxaliplatin Drugs 0.000 claims description 5
- DWAFYCQODLXJNR-BNTLRKBRSA-L oxaliplatin Chemical compound O1C(=O)C(=O)O[Pt]11N[C@@H]2CCCC[C@H]2N1 DWAFYCQODLXJNR-BNTLRKBRSA-L 0.000 claims description 5
- 206010041067 Small cell lung cancer Diseases 0.000 claims description 4
- 208000024313 Testicular Neoplasms Diseases 0.000 claims description 4
- 206010057644 Testis cancer Diseases 0.000 claims description 4
- JMILYKIVBZFXGN-UHFFFAOYSA-F [O-]P([O-])(=O)OP(=O)([O-])[O-].[O-]P([O-])(=O)OP(=O)([O-])[O-].[Pt+4].[Pt+4] Chemical compound [O-]P([O-])(=O)OP(=O)([O-])[O-].[O-]P([O-])(=O)OP(=O)([O-])[O-].[Pt+4].[Pt+4] JMILYKIVBZFXGN-UHFFFAOYSA-F 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 230000001376 precipitating effect Effects 0.000 claims description 4
- 208000000587 small cell lung carcinoma Diseases 0.000 claims description 4
- 201000003120 testicular cancer Diseases 0.000 claims description 4
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 claims description 3
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims description 3
- 201000010536 head and neck cancer Diseases 0.000 claims description 3
- 208000014829 head and neck neoplasm Diseases 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 3
- 208000016691 refractory malignant neoplasm Diseases 0.000 claims description 3
- 150000004984 aromatic diamines Chemical class 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 239000003463 adsorbent Substances 0.000 claims 3
- ZMSQRDFHWWEUJY-UHFFFAOYSA-L [O-]P([O-])(=O)OP(=O)(O)O.OP(O)(=O)OP(=O)(O)O.[Pt+2] Chemical compound [O-]P([O-])(=O)OP(=O)(O)O.OP(O)(=O)OP(=O)(O)O.[Pt+2] ZMSQRDFHWWEUJY-UHFFFAOYSA-L 0.000 claims 2
- 229910052794 bromium Inorganic materials 0.000 claims 2
- 229910052801 chlorine Inorganic materials 0.000 claims 2
- 229910052736 halogen Inorganic materials 0.000 claims 2
- 125000005843 halogen group Chemical group 0.000 claims 2
- 229910052740 iodine Inorganic materials 0.000 claims 2
- 239000003125 aqueous solvent Substances 0.000 claims 1
- 239000000571 coke Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- MHAJPDPJQMAIIY-UHFFFAOYSA-M hydrogenperoxide(1-) Chemical compound [O-]O MHAJPDPJQMAIIY-UHFFFAOYSA-M 0.000 claims 1
- PVGAVTXIFQJKJI-UHFFFAOYSA-H platinum(2+);diphosphate Chemical compound [Pt+2].[Pt+2].[Pt+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O PVGAVTXIFQJKJI-UHFFFAOYSA-H 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
- 239000000047 product Substances 0.000 description 64
- 239000000243 solution Substances 0.000 description 54
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 49
- 229940048084 pyrophosphate Drugs 0.000 description 34
- XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical compound OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 0.000 description 32
- 239000012535 impurity Substances 0.000 description 26
- 230000015572 biosynthetic process Effects 0.000 description 25
- 238000003786 synthesis reaction Methods 0.000 description 23
- 239000008367 deionised water Substances 0.000 description 22
- 229910021641 deionized water Inorganic materials 0.000 description 22
- STPOWJQGUGBHQJ-UHFFFAOYSA-F [O-]P([O-])(=O)OP(=O)([O-])[O-].[O-]P([O-])(=O)OP(=O)([O-])[O-].[Pt+2].[Pt+2].[Pt+2].[Pt+2] Chemical compound [O-]P([O-])(=O)OP(=O)([O-])[O-].[O-]P([O-])(=O)OP(=O)([O-])[O-].[Pt+2].[Pt+2].[Pt+2].[Pt+2] STPOWJQGUGBHQJ-UHFFFAOYSA-F 0.000 description 19
- 239000002253 acid Substances 0.000 description 18
- 238000001914 filtration Methods 0.000 description 18
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- 238000004128 high performance liquid chromatography Methods 0.000 description 16
- 238000001953 recrystallisation Methods 0.000 description 16
- 238000000746 purification Methods 0.000 description 13
- VZWGHDYJGOMEKT-UHFFFAOYSA-J sodium pyrophosphate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O VZWGHDYJGOMEKT-UHFFFAOYSA-J 0.000 description 13
- 239000003795 chemical substances by application Substances 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- 238000007792 addition Methods 0.000 description 10
- FQENQNTWSFEDLI-UHFFFAOYSA-J sodium diphosphate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O FQENQNTWSFEDLI-UHFFFAOYSA-J 0.000 description 10
- 235000019818 tetrasodium diphosphate Nutrition 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 239000007853 buffer solution Substances 0.000 description 9
- 238000002425 crystallisation Methods 0.000 description 9
- 230000008025 crystallization Effects 0.000 description 9
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 7
- 239000000539 dimer Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 239000002002 slurry Substances 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- 239000000080 wetting agent Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 238000004255 ion exchange chromatography Methods 0.000 description 6
- HRGDZIGMBDGFTC-UHFFFAOYSA-N platinum(2+) Chemical compound [Pt+2] HRGDZIGMBDGFTC-UHFFFAOYSA-N 0.000 description 6
- 229940048086 sodium pyrophosphate Drugs 0.000 description 6
- 239000001577 tetrasodium phosphonato phosphate Substances 0.000 description 6
- 238000000354 decomposition reaction Methods 0.000 description 5
- 238000002955 isolation Methods 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
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- 238000010790 dilution Methods 0.000 description 4
- 239000012895 dilution Substances 0.000 description 4
- 238000005580 one pot reaction Methods 0.000 description 4
- 150000003057 platinum Chemical class 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 238000010268 HPLC based assay Methods 0.000 description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 3
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- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000010979 pH adjustment Methods 0.000 description 3
- LKMWMZZOSMBNJI-UHFFFAOYSA-J phosphono phosphate platinum(4+) Chemical compound [Pt+4].OP(O)(=O)OP([O-])([O-])=O.OP(O)(=O)OP([O-])([O-])=O LKMWMZZOSMBNJI-UHFFFAOYSA-J 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 238000005204 segregation Methods 0.000 description 3
- ATRRKUHOCOJYRX-UHFFFAOYSA-N Ammonium bicarbonate Chemical compound [NH4+].OC([O-])=O ATRRKUHOCOJYRX-UHFFFAOYSA-N 0.000 description 2
- 229910000013 Ammonium bicarbonate Inorganic materials 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
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- NUNLBVUVTXONII-UHFFFAOYSA-J phosphonato phosphate;platinum(2+) Chemical class [Pt+2].[Pt+2].[O-]P([O-])(=O)OP([O-])([O-])=O NUNLBVUVTXONII-UHFFFAOYSA-J 0.000 description 2
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- 230000014759 maintenance of location Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- HNKLPNDFOVJIFG-UHFFFAOYSA-N oxalic acid;platinum Chemical compound [Pt].OC(=O)C(O)=O HNKLPNDFOVJIFG-UHFFFAOYSA-N 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- BMMGVYCKOGBVEV-UHFFFAOYSA-N oxo(oxoceriooxy)cerium Chemical compound [Ce]=O.O=[Ce]=O BMMGVYCKOGBVEV-UHFFFAOYSA-N 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- KGRJUMGAEQQVFK-UHFFFAOYSA-L platinum(2+);dibromide Chemical compound Br[Pt]Br KGRJUMGAEQQVFK-UHFFFAOYSA-L 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 229940005657 pyrophosphoric acid Drugs 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000002594 sorbent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- VKKIJPPZWGZEFC-UHFFFAOYSA-J tetrasodium phosphonato phosphate tetrahydrate Chemical compound O.O.O.O.[Na+].[Na+].[Na+].[Na+].[O-]P([O-])(=O)OP([O-])([O-])=O VKKIJPPZWGZEFC-UHFFFAOYSA-J 0.000 description 1
- 238000002411 thermogravimetry Methods 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
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
- C07F15/00—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table
- C07F15/0006—Compounds containing elements of Groups 8, 9, 10 or 18 of the Periodic Table compounds of the platinum group
- C07F15/0086—Platinum compounds
- C07F15/0093—Platinum compounds without a metal-carbon linkage
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261651200P | 2012-05-24 | 2012-05-24 |
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| Publication Number | Publication Date |
|---|---|
| TW201347765A TW201347765A (zh) | 2013-12-01 |
| TWI599361B true TWI599361B (zh) | 2017-09-21 |
Family
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| TW102111669A TWI599361B (zh) | 2012-05-24 | 2013-04-01 | 磷酸鉑（ｐｈｏｓｐｈａｐｌａｔｉｎ）化合物之合成與純化方法及其用途 |
| TW106122720A TWI653237B (zh) | 2012-05-24 | 2013-04-01 | 磷酸鉑（ｐｈｏｓｐｈａｐｌａｔｉｎ）化合物之合成與純化方法及其用途 |
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| Application Number | Title | Priority Date | Filing Date |
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| TW106122720A TWI653237B (zh) | 2012-05-24 | 2013-04-01 | 磷酸鉑（ｐｈｏｓｐｈａｐｌａｔｉｎ）化合物之合成與純化方法及其用途 |
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Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2619412T3 (es) * | 2012-05-24 | 2017-06-26 | Phosplatin Therapeutics Llc | Métodos de síntesis y de purificación para compuestos de fosfaplatino y usos de los mismos |
| JP7634341B2 (ja) * | 2016-04-06 | 2025-02-21 | プロモントリー・セラピューティクス・インコーポレイテッド | ホスファプラチン液体製剤 |
| JP7023968B2 (ja) * | 2017-01-06 | 2022-02-22 | フォスプラティン・セラピューティクス・インコーポレーテッド | 骨がんまたは血液がんの治療のための治療薬としてのホスファプラチン化合物 |
| CA3074020A1 (en) * | 2017-09-08 | 2019-03-14 | Phosplatin Therapeutics Llc | Phosphaplatin compounds as immuno-modulatory agents and therapeutic uses thereof |
| CN113861036B (zh) * | 2021-11-08 | 2024-04-02 | 合肥工业大学 | 一种乙二胺高氯酸铜配合物的制备及用途 |
| US11673904B1 (en) | 2021-12-09 | 2023-06-13 | L'air Liquide, Societe Anonyme Pour L'etude Et L'exploitation Des Procedes Georges Claude | Low pressure process for synthesis of Pt(PF3)4 involving a soluble intermediate and storage of obtained Pt(PF3)4 |
| CN119822568B (zh) * | 2025-02-19 | 2025-08-19 | 扬州宏鑫环保科技有限公司 | 一种高效纯化水制备装置及制备方法 |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4234500A (en) * | 1979-03-07 | 1980-11-18 | Engelhard Minerals & Chemicals Corporation | Ethylenediamine platinum(II) and 1,2-diamino-cyclohexane platinum(II) pyrophosphate complexes |
| CA2530279A1 (en) | 2003-06-27 | 2005-01-06 | Akira Odani | Bisphosphonate complexes |
| MX2008009774A (es) * | 2006-01-30 | 2008-10-17 | Platco Technologies Proprietar | Preparacion de complejos de platino (ii). |
| KR20100020008A (ko) * | 2007-05-18 | 2010-02-19 | 티티아이 엘뷰 가부시키가이샤 | 생물학적 인터페이스를 통한 활성 성분의 방출을 개선한 경피 전달 장치 |
| PL2173337T3 (pl) * | 2007-08-06 | 2014-11-28 | Univ Ohio | Fosfaplatyny i ich zastosowanie w leczeniu raków opornych na cisplatynę i karboplatynę |
| PH12012502394A1 (en) * | 2010-06-04 | 2013-02-04 | Univ Ohio | Phosphaplatins and their use for treatment of cancers |
| US9012669B2 (en) * | 2011-10-05 | 2015-04-21 | The University Of Houston System | Efficient processes for large scale preparation of phosphaplatins antitumor agents |
| ES2619412T3 (es) * | 2012-05-24 | 2017-06-26 | Phosplatin Therapeutics Llc | Métodos de síntesis y de purificación para compuestos de fosfaplatino y usos de los mismos |
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