ES2619412T3 - Métodos de síntesis y de purificación para compuestos de fosfaplatino y usos de los mismos - Google Patents
Métodos de síntesis y de purificación para compuestos de fosfaplatino y usos de los mismos Download PDFInfo
- Publication number
- ES2619412T3 ES2619412T3 ES13793812.2T ES13793812T ES2619412T3 ES 2619412 T3 ES2619412 T3 ES 2619412T3 ES 13793812 T ES13793812 T ES 13793812T ES 2619412 T3 ES2619412 T3 ES 2619412T3
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- ES
- Spain
- Prior art keywords
- platinum
- pyrophosphate
- reaction mixture
- dach
- monomeric
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 106
- 150000001875 compounds Chemical class 0.000 title claims abstract description 31
- 230000015572 biosynthetic process Effects 0.000 title description 24
- 238000003786 synthesis reaction Methods 0.000 title description 23
- 238000000746 purification Methods 0.000 title description 17
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims abstract description 70
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 62
- 239000011541 reaction mixture Substances 0.000 claims abstract description 61
- 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 abstract description 42
- 239000002244 precipitate Substances 0.000 claims abstract description 38
- 229910052697 platinum Inorganic materials 0.000 claims abstract description 37
- 229910001868 water Inorganic materials 0.000 claims abstract description 30
- 239000002904 solvent Substances 0.000 claims abstract description 19
- 150000003839 salts Chemical class 0.000 claims abstract description 14
- 239000003960 organic solvent Substances 0.000 claims abstract description 10
- 238000002156 mixing Methods 0.000 claims abstract description 4
- XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical class [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 claims abstract 4
- 238000006243 chemical reaction Methods 0.000 claims description 66
- 239000007787 solid Substances 0.000 claims description 42
- -1 aliphatic amines Chemical class 0.000 claims description 34
- 239000002253 acid Substances 0.000 claims description 30
- 239000000203 mixture Substances 0.000 claims description 27
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 26
- 238000001556 precipitation Methods 0.000 claims description 26
- 229910052799 carbon Inorganic materials 0.000 claims description 23
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 22
- 238000001914 filtration Methods 0.000 claims description 22
- 229910017604 nitric acid Inorganic materials 0.000 claims description 22
- 238000003756 stirring Methods 0.000 claims description 21
- 239000003446 ligand Substances 0.000 claims description 12
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- SSJXIUAHEKJCMH-UHFFFAOYSA-N cyclohexane-1,2-diamine Chemical compound NC1CCCCC1N SSJXIUAHEKJCMH-UHFFFAOYSA-N 0.000 claims description 9
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- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical group NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 claims description 7
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- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- 125000001931 aliphatic group Chemical group 0.000 claims description 6
- NUNLBVUVTXONII-UHFFFAOYSA-J phosphonato phosphate;platinum(2+) Chemical compound [Pt+2].[Pt+2].[O-]P([O-])(=O)OP([O-])([O-])=O NUNLBVUVTXONII-UHFFFAOYSA-J 0.000 claims description 5
- HRGDZIGMBDGFTC-UHFFFAOYSA-N platinum(2+) Chemical compound [Pt+2] HRGDZIGMBDGFTC-UHFFFAOYSA-N 0.000 claims description 5
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- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims description 4
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 claims description 4
- 239000003463 adsorbent Substances 0.000 claims description 4
- 150000001412 amines Chemical class 0.000 claims description 4
- 125000003118 aryl group Chemical group 0.000 claims description 4
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 claims description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 4
- 239000011707 mineral Substances 0.000 claims description 4
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- WGYKZJWCGVVSQN-UHFFFAOYSA-N propylamine Chemical compound CCCN WGYKZJWCGVVSQN-UHFFFAOYSA-N 0.000 claims description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 4
- 150000004984 aromatic diamines Chemical class 0.000 claims description 3
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 claims description 2
- 150000003222 pyridines Chemical class 0.000 claims description 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
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 1
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- 239000000047 product Substances 0.000 description 69
- 239000000243 solution Substances 0.000 description 55
- 239000012535 impurity Substances 0.000 description 30
- XPPKVPWEQAFLFU-UHFFFAOYSA-N diphosphoric acid Chemical compound OP(O)(=O)OP(O)(O)=O XPPKVPWEQAFLFU-UHFFFAOYSA-N 0.000 description 28
- 239000008367 deionised water Substances 0.000 description 27
- 229910021641 deionized water Inorganic materials 0.000 description 27
- 235000011180 diphosphates Nutrition 0.000 description 21
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- 238000004128 high performance liquid chromatography Methods 0.000 description 18
- 238000001953 recrystallisation Methods 0.000 description 17
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
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- 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 12
- 239000000725 suspension Substances 0.000 description 11
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- 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
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- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
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- 206010028980 Neoplasm Diseases 0.000 description 7
- 239000007853 buffer solution Substances 0.000 description 7
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 7
- 229960004316 cisplatin Drugs 0.000 description 7
- 239000000539 dimer Substances 0.000 description 7
- 150000003057 platinum Chemical class 0.000 description 7
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- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 229910002651 NO3 Inorganic materials 0.000 description 6
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- IYNIYQPKWZYHRQ-UHFFFAOYSA-N azane;phosphono dihydrogen phosphate Chemical class N.OP(O)(=O)OP(O)(O)=O IYNIYQPKWZYHRQ-UHFFFAOYSA-N 0.000 description 6
- 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 description 6
- 230000008901 benefit Effects 0.000 description 6
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- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
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- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 1
- 229940011051 isopropyl acetate Drugs 0.000 description 1
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 210000005265 lung cell Anatomy 0.000 description 1
- 208000020816 lung neoplasm Diseases 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- MUTQTHUBSRXFQO-UHFFFAOYSA-L oxalate;platinum(2+) Chemical class [Pt+2].[O-]C(=O)C([O-])=O MUTQTHUBSRXFQO-UHFFFAOYSA-L 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- 230000001376 precipitating effect Effects 0.000 description 1
- 230000002685 pulmonary effect Effects 0.000 description 1
- 229940005657 pyrophosphoric acid Drugs 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000035945 sensitivity Effects 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000004317 sodium nitrate Substances 0.000 description 1
- 235000010344 sodium nitrate Nutrition 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002411 thermogravimetry Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 235000011178 triphosphate Nutrition 0.000 description 1
- 239000001226 triphosphate Substances 0.000 description 1
- UNXRWKVEANCORM-UHFFFAOYSA-N triphosphoric acid Chemical compound OP(O)(=O)OP(O)(=O)OP(O)(O)=O UNXRWKVEANCORM-UHFFFAOYSA-N 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 238000005406 washing 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
Landscapes
- 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 (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261651200P | 2012-05-24 | 2012-05-24 | |
| US201261651200P | 2012-05-24 | ||
| PCT/US2013/031885 WO2013176764A1 (en) | 2012-05-24 | 2013-03-15 | Synthetic and purification methods for phosphaplatin compounds and uses thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2619412T3 true ES2619412T3 (es) | 2017-06-26 |
Family
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES13793812.2T Active ES2619412T3 (es) | 2012-05-24 | 2013-03-15 | Métodos de síntesis y de purificación para compuestos de fosfaplatino y usos de los mismos |
| ES16203851T Active ES2751668T3 (es) | 2012-05-24 | 2013-03-15 | Método de purificación para compuestos de fosfaplatino |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES16203851T Active ES2751668T3 (es) | 2012-05-24 | 2013-03-15 | Método de purificación para compuestos de fosfaplatino |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US8846964B2 (enExample) |
| EP (2) | EP2855496B1 (enExample) |
| JP (1) | JP5833795B2 (enExample) |
| CN (2) | CN106967124B (enExample) |
| CY (2) | CY1118746T1 (enExample) |
| DK (2) | DK3202769T3 (enExample) |
| ES (2) | ES2619412T3 (enExample) |
| HR (2) | HRP20170416T1 (enExample) |
| HU (2) | HUE032197T2 (enExample) |
| IN (1) | IN2014KN02722A (enExample) |
| LT (2) | LT3202769T (enExample) |
| PL (2) | PL3202769T3 (enExample) |
| PT (2) | PT3202769T (enExample) |
| RS (2) | RS59725B1 (enExample) |
| SI (2) | SI3202769T1 (enExample) |
| SM (2) | SMT201700168T1 (enExample) |
| TW (2) | TWI599361B (enExample) |
| WO (1) | WO2013176764A1 (enExample) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SMT201700168T1 (it) * | 2012-05-24 | 2017-05-08 | Phosplatin Therapeutics Llc | Metodi di sintesi e di purificazione per composti di fosfaplatino e utilizzi degli stessi |
| TWI798175B (zh) * | 2016-04-06 | 2023-04-11 | 美商弗斯普萊汀治療股份有限公司 | 磷酸鉑(phosphaplatin)液態調配物 |
| US10668080B2 (en) | 2017-01-06 | 2020-06-02 | Phosplatin Therapeutics Llc | Phosphaplatin compounds as therapeutic agents for treatment of bone or blood cancers |
| JP7381083B2 (ja) * | 2017-09-08 | 2023-11-15 | フォスプラティン テラピューティクス インコーポレイテッド | 免疫調節剤としてのホスファプラチン化合物およびその治療的使用 |
| 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 |
Family Cites Families (8)
| 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 |
| JP4463274B2 (ja) | 2003-06-27 | 2010-05-19 | 明 小谷 | ビスホスホネート錯体 |
| RU2008135369A (ru) * | 2006-01-30 | 2010-03-10 | Платко Текнолоджис (Проприэтэри) Лимитед (Za) | Получение комплексов платины(ii) |
| RU2482841C2 (ru) * | 2007-05-18 | 2013-05-27 | ТиТиАй Эллебо, Инк. | Устройства для трансдермальной доставки, обеспечивающие улучшенное высвобождение действующего начала через биологическую поверхность |
| DK2173337T3 (da) * | 2007-08-06 | 2014-09-15 | Univ Ohio | Phosphaplatiner og deres anvendelse i behandlingen af cancer, der er resistent over for cisplatin og carboplatin |
| SI2575802T1 (sl) * | 2010-06-04 | 2017-03-31 | Ohio University | Fosfaplatini in njihova uporaba za zdravljenje raznih vrst raka |
| EP2763537B1 (en) * | 2011-10-05 | 2018-01-10 | Rathindra N. Bose | Efficient processes for large scale preparation of phosphaplatins antitumor agents |
| SMT201700168T1 (it) * | 2012-05-24 | 2017-05-08 | Phosplatin Therapeutics Llc | Metodi di sintesi e di purificazione per composti di fosfaplatino e utilizzi degli stessi |
-
2013
- 2013-03-15 SM SM20170168T patent/SMT201700168T1/it unknown
- 2013-03-15 WO PCT/US2013/031885 patent/WO2013176764A1/en not_active Ceased
- 2013-03-15 PT PT162038517T patent/PT3202769T/pt unknown
- 2013-03-15 PL PL16203851T patent/PL3202769T3/pl unknown
- 2013-03-15 LT LT16203851T patent/LT3202769T/lt unknown
- 2013-03-15 LT LTEP13793812.2T patent/LT2855496T/lt unknown
- 2013-03-15 RS RS20191364A patent/RS59725B1/sr unknown
- 2013-03-15 JP JP2015514010A patent/JP5833795B2/ja active Active
- 2013-03-15 SM SM20190617T patent/SMT201900617T1/it unknown
- 2013-03-15 ES ES13793812.2T patent/ES2619412T3/es active Active
- 2013-03-15 PL PL13793812T patent/PL2855496T3/pl unknown
- 2013-03-15 CN CN201710071127.6A patent/CN106967124B/zh active Active
- 2013-03-15 EP EP13793812.2A patent/EP2855496B1/en active Active
- 2013-03-15 SI SI201331598T patent/SI3202769T1/sl unknown
- 2013-03-15 HR HRP20170416TT patent/HRP20170416T1/hr unknown
- 2013-03-15 IN IN2722KON2014 patent/IN2014KN02722A/en unknown
- 2013-03-15 DK DK16203851T patent/DK3202769T3/da active
- 2013-03-15 SI SI201330565A patent/SI2855496T1/sl unknown
- 2013-03-15 HU HUE13793812A patent/HUE032197T2/en unknown
- 2013-03-15 PT PT137938122T patent/PT2855496T/pt unknown
- 2013-03-15 ES ES16203851T patent/ES2751668T3/es active Active
- 2013-03-15 CN CN201380026289.8A patent/CN104540839B/zh active Active
- 2013-03-15 HU HUE16203851A patent/HUE046327T2/hu unknown
- 2013-03-15 DK DK13793812.2T patent/DK2855496T3/en active
- 2013-03-15 EP EP16203851.7A patent/EP3202769B1/en active Active
- 2013-03-15 RS RS20170272A patent/RS55806B1/sr unknown
- 2013-04-01 TW TW102111669A patent/TWI599361B/zh active
- 2013-04-01 TW TW106122720A patent/TWI653237B/zh active
- 2013-09-20 US US14/032,704 patent/US8846964B2/en active Active
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2014
- 2014-03-18 US US14/217,883 patent/US8859796B1/en active Active
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2017
- 2017-03-13 CY CY20171100317T patent/CY1118746T1/el unknown
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2019
- 2019-10-21 HR HRP20191904TT patent/HRP20191904T1/hr unknown
- 2019-11-21 CY CY20191101227T patent/CY1122316T1/el unknown
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