JP6325547B2 - Ｘ線造影剤イオホルミノールの調製 - Google Patents
Ｘ線造影剤イオホルミノールの調製 Download PDFInfo
- Publication number
- JP6325547B2 JP6325547B2 JP2015534550A JP2015534550A JP6325547B2 JP 6325547 B2 JP6325547 B2 JP 6325547B2 JP 2015534550 A JP2015534550 A JP 2015534550A JP 2015534550 A JP2015534550 A JP 2015534550A JP 6325547 B2 JP6325547 B2 JP 6325547B2
- Authority
- JP
- Japan
- Prior art keywords
- compound
- bis
- water
- preparation
- ioforminol
- 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.)
- Active
Links
- BFVVDRUCXCIALU-UHFFFAOYSA-N 5-[[3-[3,5-bis(2,3-dihydroxypropylcarbamoyl)-n-formyl-2,4,6-triiodoanilino]-2-hydroxypropyl]-formylamino]-1-n,3-n-bis(2,3-dihydroxypropyl)-2,4,6-triiodobenzene-1,3-dicarboxamide Chemical compound OCC(O)CNC(=O)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(N(CC(O)CN(C=O)C=2C(=C(C(=O)NCC(O)CO)C(I)=C(C(=O)NCC(O)CO)C=2I)I)C=O)=C1I BFVVDRUCXCIALU-UHFFFAOYSA-N 0.000 title description 20
- 229950004332 ioforminol Drugs 0.000 title description 18
- 238000002360 preparation method Methods 0.000 title description 18
- 239000002872 contrast media Substances 0.000 title description 15
- 150000001875 compounds Chemical class 0.000 claims description 65
- 238000000034 method Methods 0.000 claims description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- 238000005804 alkylation reaction Methods 0.000 claims description 12
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 12
- 230000007062 hydrolysis Effects 0.000 claims description 11
- 238000006460 hydrolysis reaction Methods 0.000 claims description 11
- 239000003795 chemical substances by application Substances 0.000 claims description 10
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 8
- 239000000243 solution Substances 0.000 claims description 7
- 238000011065 in-situ storage Methods 0.000 claims description 6
- 239000007858 starting material Substances 0.000 claims description 5
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical group ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 claims description 4
- 125000006239 protecting group Chemical group 0.000 claims description 4
- 239000003637 basic solution Substances 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 235000013312 flour Nutrition 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 239000002585 base Substances 0.000 description 8
- -1 2,3-bis (formyloxy) propan-1-ylcarbamoyl Chemical group 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- 239000008186 active pharmaceutical agent Substances 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- NBQNWMBBSKPBAY-UHFFFAOYSA-N iodixanol Chemical compound IC=1C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C(I)C=1N(C(=O)C)CC(O)CN(C(C)=O)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I NBQNWMBBSKPBAY-UHFFFAOYSA-N 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 239000000539 dimer Substances 0.000 description 4
- 238000006471 dimerization reaction Methods 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 229960004359 iodixanol Drugs 0.000 description 4
- 239000002253 acid Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- NTHXOOBQLCIOLC-UHFFFAOYSA-N iohexol Chemical compound OCC(O)CN(C(=O)C)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I NTHXOOBQLCIOLC-UHFFFAOYSA-N 0.000 description 3
- 238000010979 pH adjustment Methods 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- RIWAPWDHHMWTRA-UHFFFAOYSA-N 1,2,3-triiodobenzene Chemical compound IC1=CC=CC(I)=C1I RIWAPWDHHMWTRA-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- QZRGKCOWNLSUDK-UHFFFAOYSA-N Iodochlorine Chemical compound ICl QZRGKCOWNLSUDK-UHFFFAOYSA-N 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 2
- 239000004327 boric acid Substances 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 229940126214 compound 3 Drugs 0.000 description 2
- 229940088679 drug related substance Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000005755 formation reaction Methods 0.000 description 2
- 238000003384 imaging method Methods 0.000 description 2
- 229960001025 iohexol Drugs 0.000 description 2
- 229960000780 iomeprol Drugs 0.000 description 2
- NJKDOADNQSYQEV-UHFFFAOYSA-N iomeprol Chemical compound OCC(=O)N(C)C1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I NJKDOADNQSYQEV-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- KIHQZLPHVZKELA-UHFFFAOYSA-N 1,3-dibromopropan-2-ol Chemical compound BrCC(O)CBr KIHQZLPHVZKELA-UHFFFAOYSA-N 0.000 description 1
- 229940051269 1,3-dichloro-2-propanol Drugs 0.000 description 1
- DEWLEGDTCGBNGU-UHFFFAOYSA-N 1,3-dichloropropan-2-ol Chemical compound ClCC(O)CCl DEWLEGDTCGBNGU-UHFFFAOYSA-N 0.000 description 1
- TVCINXHQUODERO-UHFFFAOYSA-N 1-n,3-n-bis(2,3-dihydroxypropyl)-5-formamido-2,4,6-triiodobenzene-1,3-dicarboxamide Chemical compound OCC(O)CNC(=O)C1=C(I)C(NC=O)=C(I)C(C(=O)NCC(O)CO)=C1I TVCINXHQUODERO-UHFFFAOYSA-N 0.000 description 1
- HUHDYASLFWQVOL-WZTVWXICSA-N 3-[[2-[[3-[acetyl(methyl)amino]-2,4,6-triiodo-5-(methylcarbamoyl)benzoyl]amino]acetyl]amino]-5-(2-hydroxyethylcarbamoyl)-2,4,6-triiodobenzoic acid;(2r,3r,4r,5s)-6-(methylamino)hexane-1,2,3,4,5-pentol Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO.CNC(=O)C1=C(I)C(N(C)C(C)=O)=C(I)C(C(=O)NCC(=O)NC=2C(=C(C(=O)NCCO)C(I)=C(C(O)=O)C=2I)I)=C1I HUHDYASLFWQVOL-WZTVWXICSA-N 0.000 description 1
- KAEGSAWWVYMWIQ-UHFFFAOYSA-N 5-amino-1-n,3-n-bis(2,3-dihydroxypropyl)-2,4,6-triiodobenzene-1,3-dicarboxamide Chemical compound NC1=C(I)C(C(=O)NCC(O)CO)=C(I)C(C(=O)NCC(O)CO)=C1I KAEGSAWWVYMWIQ-UHFFFAOYSA-N 0.000 description 1
- JEZJSNULLBSYHV-UHFFFAOYSA-N 5-amino-2,4,6-triiodobenzene-1,3-dicarboxylic acid Chemical compound NC1=C(I)C(C(O)=O)=C(I)C(C(O)=O)=C1I JEZJSNULLBSYHV-UHFFFAOYSA-N 0.000 description 1
- NBDAHKQJXVLAID-UHFFFAOYSA-N 5-nitroisophthalic acid Chemical compound OC(=O)C1=CC(C(O)=O)=CC([N+]([O-])=O)=C1 NBDAHKQJXVLAID-UHFFFAOYSA-N 0.000 description 1
- 206010048610 Cardiotoxicity Diseases 0.000 description 1
- 206010029155 Nephropathy toxic Diseases 0.000 description 1
- 241000282887 Suidae Species 0.000 description 1
- OZXJFUAPUQMTCF-UHFFFAOYSA-N [3-[[3-(2,3-diformyloxypropylcarbamoyl)-5-formamido-2,4,6-triiodobenzoyl]amino]-2-formyloxypropyl] formate Chemical compound IC1=C(NC=O)C(I)=C(C(=O)NCC(COC=O)OC=O)C(I)=C1C(=O)NCC(COC=O)OC=O OZXJFUAPUQMTCF-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- YVPYQUNUQOZFHG-UHFFFAOYSA-N amidotrizoic acid Chemical compound CC(=O)NC1=C(I)C(NC(C)=O)=C(I)C(C(O)=O)=C1I YVPYQUNUQOZFHG-UHFFFAOYSA-N 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 238000002583 angiography Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 239000012296 anti-solvent Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 231100000259 cardiotoxicity Toxicity 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940039231 contrast media Drugs 0.000 description 1
- 239000012050 conventional carrier Substances 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 229960005423 diatrizoate Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 230000022244 formylation Effects 0.000 description 1
- 238000006170 formylation reaction Methods 0.000 description 1
- 125000000592 heterocycloalkyl group Chemical class 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000000193 iodinated contrast media Substances 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- XQZXYNRDCRIARQ-LURJTMIESA-N iopamidol Chemical compound C[C@H](O)C(=O)NC1=C(I)C(C(=O)NC(CO)CO)=C(I)C(C(=O)NC(CO)CO)=C1I XQZXYNRDCRIARQ-LURJTMIESA-N 0.000 description 1
- 229960004647 iopamidol Drugs 0.000 description 1
- 125000005647 linker group Chemical group 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 238000001728 nano-filtration Methods 0.000 description 1
- 230000007694 nephrotoxicity Effects 0.000 description 1
- 231100000417 nephrotoxicity Toxicity 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 208000003663 ventricular fibrillation Diseases 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/04—X-ray contrast preparations
- A61K49/0433—X-ray contrast preparations containing an organic halogenated X-ray contrast-enhancing agent
- A61K49/0438—Organic X-ray contrast-enhancing agent comprising an iodinated group or an iodine atom, e.g. iopamidol
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/46—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having carbon atoms of carboxamide groups, amino groups and at least three atoms of bromine or iodine, bound to carbon atoms of the same non-condensed six-membered aromatic ring
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO20121103 | 2012-09-27 | ||
| NO20121103 | 2012-09-27 | ||
| PCT/US2013/060092 WO2014052092A1 (en) | 2012-09-27 | 2013-09-17 | Preparation of ioforminol, an x-ray contrast agent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2015530415A JP2015530415A (ja) | 2015-10-15 |
| JP6325547B2 true JP6325547B2 (ja) | 2018-05-16 |
Family
ID=49237721
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2015534550A Active JP6325547B2 (ja) | 2012-09-27 | 2013-09-17 | Ｘ線造影剤イオホルミノールの調製 |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US9827334B2 (enExample) |
| EP (1) | EP2900631B1 (enExample) |
| JP (1) | JP6325547B2 (enExample) |
| KR (1) | KR20150061634A (enExample) |
| AU (1) | AU2013323982B2 (enExample) |
| BR (1) | BR112015004580A2 (enExample) |
| CA (1) | CA2881853A1 (enExample) |
| ES (1) | ES2702275T3 (enExample) |
| IN (1) | IN2015DN01186A (enExample) |
| MX (1) | MX365249B (enExample) |
| RU (1) | RU2642436C2 (enExample) |
| WO (1) | WO2014052092A1 (enExample) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP6325547B2 (ja) | 2012-09-27 | 2018-05-16 | ジーイー・ヘルスケア・アクスイェ・セルスカプ | Ｘ線造影剤イオホルミノールの調製 |
| EP2900632B1 (en) * | 2012-09-27 | 2019-10-30 | Ge Healthcare As | Preparation of an intermediate compound of ioforminol |
| CA3009649A1 (en) * | 2015-12-23 | 2017-06-29 | Brown University | Thermal accelerant compositions and methods of use |
Family Cites Families (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5698739A (en) | 1989-07-05 | 1997-12-16 | Schering Aktiengesellschaft | Carboxamide non-ionic contrast media |
| IL94718A (en) | 1989-07-05 | 1994-10-21 | Schering Ag | Non-ionic carboxamide contrast agent and method of preparation |
| NO20043305D0 (no) | 2004-08-09 | 2004-08-09 | Amersham Health As | Preparation of lodixanol |
| US20080267884A1 (en) | 2005-11-10 | 2008-10-30 | Oskar Axelsson | Contrast Agents and Diagnostic Compositions Based on Iodine-Containing Cyanuric Acid Derivatives |
| KR20100033405A (ko) | 2007-07-12 | 2010-03-29 | 지이 헬스케어 에이에스 | 조영제 |
| MX2013000476A (es) * | 2010-07-12 | 2013-02-11 | Ge Healthcare As | Generacion de imagenes de rayos x en bajas concentraciones de agente y/o dosis de radiacion. |
| CN102816085B (zh) * | 2012-08-20 | 2013-08-14 | 浙江司太立制药股份有限公司 | 碘海醇杂质的制备方法 |
| JP6325547B2 (ja) | 2012-09-27 | 2018-05-16 | ジーイー・ヘルスケア・アクスイェ・セルスカプ | Ｘ線造影剤イオホルミノールの調製 |
-
2013
- 2013-09-17 JP JP2015534550A patent/JP6325547B2/ja active Active
- 2013-09-17 AU AU2013323982A patent/AU2013323982B2/en not_active Ceased
- 2013-09-17 WO PCT/US2013/060092 patent/WO2014052092A1/en not_active Ceased
- 2013-09-17 US US14/430,148 patent/US9827334B2/en not_active Expired - Fee Related
- 2013-09-17 BR BR112015004580A patent/BR112015004580A2/pt not_active IP Right Cessation
- 2013-09-17 EP EP13766870.3A patent/EP2900631B1/en not_active Not-in-force
- 2013-09-17 RU RU2015107017A patent/RU2642436C2/ru not_active IP Right Cessation
- 2013-09-17 KR KR1020157007423A patent/KR20150061634A/ko not_active Ceased
- 2013-09-17 CA CA2881853A patent/CA2881853A1/en not_active Abandoned
- 2013-09-17 MX MX2015003913A patent/MX365249B/es active IP Right Grant
- 2013-09-17 ES ES13766870T patent/ES2702275T3/es active Active
-
2015
- 2015-02-13 IN IN1186DEN2015 patent/IN2015DN01186A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2013323982B2 (en) | 2017-11-23 |
| EP2900631A1 (en) | 2015-08-05 |
| MX2015003913A (es) | 2015-08-05 |
| EP2900631B1 (en) | 2018-11-14 |
| RU2015107017A (ru) | 2016-11-20 |
| CN104661995A (zh) | 2015-05-27 |
| US9827334B2 (en) | 2017-11-28 |
| US20150265727A1 (en) | 2015-09-24 |
| IN2015DN01186A (enExample) | 2015-06-26 |
| JP2015530415A (ja) | 2015-10-15 |
| AU2013323982A1 (en) | 2015-03-05 |
| BR112015004580A2 (pt) | 2017-07-04 |
| RU2642436C2 (ru) | 2018-01-25 |
| ES2702275T3 (es) | 2019-02-28 |
| WO2014052092A1 (en) | 2014-04-03 |
| KR20150061634A (ko) | 2015-06-04 |
| CA2881853A1 (en) | 2014-04-03 |
| MX365249B (es) | 2019-05-28 |
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