WO2014011814A1 - Tri-salt form of metformin - Google Patents
Tri-salt form of metformin Download PDFInfo
- Publication number
- WO2014011814A1 WO2014011814A1 PCT/US2013/049984 US2013049984W WO2014011814A1 WO 2014011814 A1 WO2014011814 A1 WO 2014011814A1 US 2013049984 W US2013049984 W US 2013049984W WO 2014011814 A1 WO2014011814 A1 WO 2014011814A1
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- WIPO (PCT)
- Prior art keywords
- compound
- metformin
- subject
- formula
- diabetes
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- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
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- 239000003549 soybean oil Substances 0.000 description 1
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- 230000002269 spontaneous effect Effects 0.000 description 1
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- 125000004426 substituted alkynyl group Chemical group 0.000 description 1
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- 230000035488 systolic blood pressure Effects 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004001 thioalkyl group Chemical group 0.000 description 1
- 229960000984 tocofersolan Drugs 0.000 description 1
- 229960002277 tolazamide Drugs 0.000 description 1
- OUDSBRTVNLOZBN-UHFFFAOYSA-N tolazamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NC(=O)NN1CCCCCC1 OUDSBRTVNLOZBN-UHFFFAOYSA-N 0.000 description 1
- 229960005371 tolbutamide Drugs 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 125000006168 tricyclic group Chemical group 0.000 description 1
- 229960001641 troglitazone Drugs 0.000 description 1
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 1
- GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 1
- 208000035408 type 1 diabetes mellitus 1 Diseases 0.000 description 1
- 238000009424 underpinning Methods 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 208000016261 weight loss Diseases 0.000 description 1
- 239000002676 xenobiotic agent Substances 0.000 description 1
- 125000005023 xylyl group Chemical group 0.000 description 1
- 229940051223 zetia Drugs 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
- 229910021511 zinc hydroxide Inorganic materials 0.000 description 1
- 229940007718 zinc hydroxide Drugs 0.000 description 1
- 239000002076 α-tocopherol Substances 0.000 description 1
- 235000004835 α-tocopherol Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C279/00—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C279/20—Derivatives of guanidine, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups containing any of the groups, X being a hetero atom, Y being any atom, e.g. acylguanidines
- C07C279/24—Y being a hetero atom
- C07C279/26—X and Y being nitrogen atoms, i.e. biguanides
-
- 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
- A61K31/13—Amines
- A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C229/24—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having more than one carboxyl group bound to the carbon skeleton, e.g. aspartic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C277/00—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups
- C07C277/08—Preparation of guanidine or its derivatives, i.e. compounds containing the group, the singly-bound nitrogen atoms not being part of nitro or nitroso groups of substituted guanidines
Abstract
Description
Claims
Priority Applications (12)
Application Number | Priority Date | Filing Date | Title |
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BR112015000368A BR112015000368A2 (en) | 2012-07-10 | 2013-07-10 | metformin tri-salt form |
US14/413,996 US9382187B2 (en) | 2012-07-10 | 2013-07-10 | Tri-salt form of metformin |
AU2013290168A AU2013290168A1 (en) | 2012-07-10 | 2013-07-10 | Tri-salt form of metformin |
CA2878819A CA2878819A1 (en) | 2012-07-10 | 2013-07-10 | Tri-salt form of metformin |
MX2015000408A MX2015000408A (en) | 2012-07-10 | 2013-07-10 | Tri-salt form of metformin. |
IN76KON2015 IN2015KN00076A (en) | 2012-07-10 | 2013-07-10 | |
EP13817534.4A EP2872483A4 (en) | 2012-07-10 | 2013-07-10 | Tri-salt form of metformin |
CN201380046842.4A CN104684889A (en) | 2012-07-10 | 2013-07-10 | Tri-salt form of metformin |
KR20157002264A KR20150036235A (en) | 2012-07-10 | 2013-07-10 | Tri-salt form of metformin |
JP2015521784A JP2015523382A (en) | 2012-07-10 | 2013-07-10 | The trisalt form of metformin |
IL236613A IL236613A0 (en) | 2012-07-10 | 2015-01-11 | Tri-salt form of metformin |
ZA2015/00274A ZA201500274B (en) | 2012-07-10 | 2015-01-14 | Tri-salt form of metformin |
Applications Claiming Priority (8)
Application Number | Priority Date | Filing Date | Title |
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US201261669763P | 2012-07-10 | 2012-07-10 | |
US61/669,763 | 2012-07-10 | ||
US201261670368P | 2012-07-11 | 2012-07-11 | |
US201261670376P | 2012-07-11 | 2012-07-11 | |
US61/670,376 | 2012-07-11 | ||
US61/670,368 | 2012-07-11 | ||
US13/841,970 | 2013-03-15 | ||
US13/841,970 US8765811B2 (en) | 2012-07-10 | 2013-03-15 | Tri-salt form of metformin |
Publications (1)
Publication Number | Publication Date |
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WO2014011814A1 true WO2014011814A1 (en) | 2014-01-16 |
Family
ID=49916541
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2013/049984 WO2014011814A1 (en) | 2012-07-10 | 2013-07-10 | Tri-salt form of metformin |
Country Status (12)
Country | Link |
---|---|
EP (1) | EP2872483A4 (en) |
JP (1) | JP2015523382A (en) |
KR (1) | KR20150036235A (en) |
CN (1) | CN104684889A (en) |
AU (1) | AU2013290168A1 (en) |
BR (1) | BR112015000368A2 (en) |
CA (1) | CA2878819A1 (en) |
IL (1) | IL236613A0 (en) |
IN (1) | IN2015KN00076A (en) |
MX (1) | MX2015000408A (en) |
WO (1) | WO2014011814A1 (en) |
ZA (1) | ZA201500274B (en) |
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014124141A1 (en) * | 2013-02-07 | 2014-08-14 | Mylari Banavara L | Metformin derivatives for treating diabetes |
WO2015195491A1 (en) * | 2014-06-18 | 2015-12-23 | Thetis Pharmaceuticals Llc | Mineral amino-acid complexes of active agents |
US9505709B2 (en) | 2014-05-05 | 2016-11-29 | Thetis Pharmaceuticals Llc | Compositions and methods relating to ionic salts of peptides |
US20170119841A1 (en) * | 2015-11-04 | 2017-05-04 | Thetis Pharmaceuticals Llc | Amino acid salts of unsaturated fatty acids |
US10130719B2 (en) | 2016-06-03 | 2018-11-20 | Thetis Pharmaceuticals Llc | Compositions and methods relating to salts of specialized pro-resolving mediators |
US10471963B2 (en) | 2017-04-07 | 2019-11-12 | TuSimple | System and method for transitioning between an autonomous and manual driving mode based on detection of a drivers capacity to control a vehicle |
US10737695B2 (en) | 2017-07-01 | 2020-08-11 | Tusimple, Inc. | System and method for adaptive cruise control for low speed following |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN113105367B (en) * | 2021-03-30 | 2022-08-02 | 广州大学 | Metformin salt and preparation method and application thereof |
CN114349665B (en) * | 2021-11-30 | 2023-06-09 | 潍坊博创国际生物医药研究院 | Metformin pyroglutamic acid crystal and preparation method and application thereof |
CN116999398A (en) * | 2022-06-30 | 2023-11-07 | 山东海赜生物科技有限公司 | An oral composition |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060159746A1 (en) * | 2003-03-18 | 2006-07-20 | Troup John P | Compositions comprising fatty acids and amino acids |
WO2009038396A2 (en) * | 2007-09-21 | 2009-03-26 | Hanall Pharmaceutical Company. Ltd | N,n-dimethyl imidodicarbonimidic diamide dicarboxylate, method for producing the same and pharmaceutical compositions comprising the same |
WO2010127099A2 (en) * | 2009-04-29 | 2010-11-04 | Amarin Corporation Plc | Pharmaceutical compositions comprising epa and a cardiovascular agent and methods of using the same |
US20120178813A1 (en) * | 2011-01-12 | 2012-07-12 | Thetis Pharmaceuticals Llc | Lipid-lowering antidiabetic agent |
US20130095140A1 (en) * | 2011-01-07 | 2013-04-18 | Elcelyx Therapeutics, Inc. | Biguanide Compositions and Methods of Treating Metabolic Disorders |
Family Cites Families (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP4278863B2 (en) * | 1997-12-08 | 2009-06-17 | ブリストル−マイヤーズ スクイブ カンパニー | Novel salt and method of metformin |
FR2774591B1 (en) * | 1998-02-12 | 2000-05-05 | Lipha | PHARMACEUTICAL COMPOSITION COMPRISING THE ASSOCIATION OF METFORMIN AND FIBRATE AND THE USE THEREOF FOR THE PREPARATION OF MEDICINES FOR REDUCING HYPERGLYCEMIA |
WO2002012177A1 (en) * | 2000-08-03 | 2002-02-14 | Igor Anatolievich Pomytkin | Composition of metformin with succinic acid or salts thereof and method for treating diabetes |
EP1591114A1 (en) * | 2004-03-12 | 2005-11-02 | Fournier Laboratories Ireland Limited | Use of metformin and orlistat for the treatment or prevention of obesity |
EP2229158B1 (en) * | 2007-12-20 | 2016-08-10 | Fertin Pharma A/S | Compressed chewing gum tablet |
WO2009151116A1 (en) * | 2008-06-13 | 2009-12-17 | 持田製薬株式会社 | Prophylactic/ameliorating or therapeutic agent for non-alcoholic steatohepatitis |
BR112013009635A2 (en) * | 2010-10-19 | 2016-07-12 | Elcelyx Therapeutics Inc | chemosensory receptor ligand-based therapies |
WO2014124141A1 (en) * | 2013-02-07 | 2014-08-14 | Mylari Banavara L | Metformin derivatives for treating diabetes |
-
2013
- 2013-07-10 CN CN201380046842.4A patent/CN104684889A/en active Pending
- 2013-07-10 KR KR20157002264A patent/KR20150036235A/en not_active Application Discontinuation
- 2013-07-10 AU AU2013290168A patent/AU2013290168A1/en not_active Abandoned
- 2013-07-10 JP JP2015521784A patent/JP2015523382A/en active Pending
- 2013-07-10 IN IN76KON2015 patent/IN2015KN00076A/en unknown
- 2013-07-10 BR BR112015000368A patent/BR112015000368A2/en not_active IP Right Cessation
- 2013-07-10 EP EP13817534.4A patent/EP2872483A4/en not_active Withdrawn
- 2013-07-10 CA CA2878819A patent/CA2878819A1/en not_active Abandoned
- 2013-07-10 MX MX2015000408A patent/MX2015000408A/en unknown
- 2013-07-10 WO PCT/US2013/049984 patent/WO2014011814A1/en active Application Filing
-
2015
- 2015-01-11 IL IL236613A patent/IL236613A0/en unknown
- 2015-01-14 ZA ZA2015/00274A patent/ZA201500274B/en unknown
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20060159746A1 (en) * | 2003-03-18 | 2006-07-20 | Troup John P | Compositions comprising fatty acids and amino acids |
WO2009038396A2 (en) * | 2007-09-21 | 2009-03-26 | Hanall Pharmaceutical Company. Ltd | N,n-dimethyl imidodicarbonimidic diamide dicarboxylate, method for producing the same and pharmaceutical compositions comprising the same |
WO2010127099A2 (en) * | 2009-04-29 | 2010-11-04 | Amarin Corporation Plc | Pharmaceutical compositions comprising epa and a cardiovascular agent and methods of using the same |
US20130095140A1 (en) * | 2011-01-07 | 2013-04-18 | Elcelyx Therapeutics, Inc. | Biguanide Compositions and Methods of Treating Metabolic Disorders |
US20120178813A1 (en) * | 2011-01-12 | 2012-07-12 | Thetis Pharmaceuticals Llc | Lipid-lowering antidiabetic agent |
Non-Patent Citations (1)
Title |
---|
See also references of EP2872483A4 * |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014124141A1 (en) * | 2013-02-07 | 2014-08-14 | Mylari Banavara L | Metformin derivatives for treating diabetes |
US9505709B2 (en) | 2014-05-05 | 2016-11-29 | Thetis Pharmaceuticals Llc | Compositions and methods relating to ionic salts of peptides |
US9999626B2 (en) | 2014-06-18 | 2018-06-19 | Thetis Pharmaceuticals Llc | Mineral amino-acid complexes of active agents |
WO2015195491A1 (en) * | 2014-06-18 | 2015-12-23 | Thetis Pharmaceuticals Llc | Mineral amino-acid complexes of active agents |
CN107074884A (en) * | 2014-06-18 | 2017-08-18 | 西蒂斯制药有限责任公司 | The mineral amino acid compound of activating agent |
JP2017526623A (en) * | 2014-06-18 | 2017-09-14 | テティス・ファーマシューティカルズ・エルエルシー | Mineral / amino acid complexes of active substances |
US20170119841A1 (en) * | 2015-11-04 | 2017-05-04 | Thetis Pharmaceuticals Llc | Amino acid salts of unsaturated fatty acids |
US10130719B2 (en) | 2016-06-03 | 2018-11-20 | Thetis Pharmaceuticals Llc | Compositions and methods relating to salts of specialized pro-resolving mediators |
US11135298B2 (en) | 2016-06-03 | 2021-10-05 | Thetis Pharmaceuticals Llc | Compositions and methods relating to salts of specialized pro-resolving mediators |
US11191840B2 (en) | 2016-06-03 | 2021-12-07 | Thetis Pharmaceuticals Llc | Compositions and methods relating to salts of specialized pro-resolving mediators |
US11925688B2 (en) | 2016-06-03 | 2024-03-12 | Thetis Pharmaceuticals Llc | Compositions and methods relating to salts of specialized pro-resolving mediators |
US10471963B2 (en) | 2017-04-07 | 2019-11-12 | TuSimple | System and method for transitioning between an autonomous and manual driving mode based on detection of a drivers capacity to control a vehicle |
US10737695B2 (en) | 2017-07-01 | 2020-08-11 | Tusimple, Inc. | System and method for adaptive cruise control for low speed following |
Also Published As
Publication number | Publication date |
---|---|
CN104684889A (en) | 2015-06-03 |
CA2878819A1 (en) | 2014-01-16 |
IN2015KN00076A (en) | 2015-07-31 |
EP2872483A4 (en) | 2016-03-16 |
MX2015000408A (en) | 2015-07-14 |
KR20150036235A (en) | 2015-04-07 |
EP2872483A1 (en) | 2015-05-20 |
ZA201500274B (en) | 2017-10-25 |
BR112015000368A2 (en) | 2017-06-27 |
JP2015523382A (en) | 2015-08-13 |
AU2013290168A1 (en) | 2015-02-05 |
IL236613A0 (en) | 2015-02-26 |
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