WO2009144527A1 - A new metformin glycinate salt for blood glucose control - Google Patents
A new metformin glycinate salt for blood glucose control Download PDFInfo
- Publication number
- WO2009144527A1 WO2009144527A1 PCT/IB2008/002665 IB2008002665W WO2009144527A1 WO 2009144527 A1 WO2009144527 A1 WO 2009144527A1 IB 2008002665 W IB2008002665 W IB 2008002665W WO 2009144527 A1 WO2009144527 A1 WO 2009144527A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- metformin
- salt
- glycine
- ppm
- glycinate
- Prior art date
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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
- 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
-
- 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
- A61P5/00—Drugs for disorders of the endocrine system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- 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
- C07C229/06—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 only one amino and one carboxyl group bound to the carbon skeleton
- C07C229/08—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 only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to hydrogen atoms
Definitions
- This invention relates to the metformin glycinate salt, which exhibits superior hypoglycaemic properties, greater bioavailability, a particular, safe pharmacokinetics.
- biguanides originates from the Galega officinalis plant, which has been known for several centuries for its capacity to reduce the symptoms of diabetes mellitus.
- Metformin is a compound derived from biguanides that primarily acts by reducing hepatic gluconeogenesis, but also reduces glucose absorption at the gastro-intestinal tract level and increases sensitivity to insulin by increasing the peripheral utilisation of glucose. This may be due to the fact that metformin improves the binding of insulin to its cellular receptor, which is explained by the increased activity that it induces in the tyrosine kinase postreceptor and the consequent increase in the number and activity of GLUT4 carriers.
- Metformin is not metabolised; it is directly excreted in the urine. Its half-life is 6.2 hours.
- Metformin and Metformin hydrochloride have poor intestinal absorption at the colon and the lower gastro-intestinal tract level.
- This invention relates to the development of a new biguanide salt based on Metformin conjugated with Glycine, which exhibits a better absorption and passage into the bloodstream, less gastro-intestinal adverse effects and a better pharmacokinetic profile as compared to other Metformin salts known in the prior art.
- metformin hydrochloride is hygroscopic. This hinders the industrial handling thereof to prepare solid compositions such as tablets, capsules, etc. Moreover, in its solid form, it is a corrosive crystal, which wears the tabletting machines used. Furthermore, it is an extremely bitter salt for users and the acid generated thereby often causes gastric disorders with prolonged use.
- Patent GB 1473256 discloses, for the first time, biguanide salts for treating metabolic disorders, especially diabetes mellitus, by reducing blood glucose levels, with the following formula:
- R 1 represents a hydrogen atom or a lower alkyl or a lower alkenyl group and R 2 represents a lower alkyl, aryl, aryl-(lower alkyl), or an aryloxy-(lower alkyl) group or R 1 and R 2 together represent a lower alkenyl group, R 3 represents a hydrogen atom or a group with the formula:
- R 4 and R 5 each represent a hydrogen atom or a cation or R 4 represents a hydrogen and R 5 represents a lower alkyl group, or R 4 and R 5 together represent a lower alkylene group, and n means 1 or 2.
- Metformin hydrochloride is the currently marketed salt and has the following formula:
- metformin glycinate not only reaches the maximum plasma level within the first few minutes, but these same levels remain in plasma in a sustained manner for the first 3 to 4 hours, with a gradual decrease for 10 hours following intake.
- metformin glycinate is particularly advantageous to reduce glycaemia, due to the high concentrations that it reaches in the first hour and which may be particularly useful in dealing with postprandial hyperglycaemia, which has been recognised as one of the main factors for cardiovascular risk and vascular damage.
- metformin hydrochloride since it reaches higher maximum concentrations than metformin hydrochloride, metformin glycinate requires lower doses to produce similar hypoglycaemic effects.
- metformin Glycinate a new 1 ,1-dimethylbiguanide Glycinate salt was synthesised, called metformin Glycinate.
- This salt exhibits advantages over other metformin salts. These advantages are due, in the first place, to the fact that the glycine counterion exhibits hypoglycaemic effects by itself. Moreover, this salt exhibits more rapid absorption, reaching higher plasma concentrations than those produced with metformin hydrochloride ( Figure 1 ). On the other hand, the glycine that is generated when the salt is ionised is not a strong acid; consequently, undesirable gastric effects are reduced. Finally, metformin glycinate has favourable physical characteristics for industrial-scale handling, thus facilitating the preparation of pharmaceutical compositions, since it is less corrosive, has better rheological properties and is less susceptible to compacting.
- FIG 1- Figure 1 shows the plasma concentrations of metformin glycinate
- FIG 2 A- Figure 2 A shows the Nuclear Magnetic Resonance (NMR) proton spectrum for metformin glycinate.
- FIG 2 B- Figure 2 B shows the carbon-13 spectrum for metformin glycinate.
- FIG 3- Figure 3 shows the infrared (IR) spectrum for metformin glycinate.
- FIG 4- Figure 4 shows the mass spectrum obtained by the FAB + technique.
- FIG 5- Figure 4 shows the mass spectrum obtained by the FAB ' technique
- FIG 6- Figure 5 shows the unit cell obtained by monocrystal X-ray diffraction.
- FIG 7- Figure 6 shows the crystalline arrangement.
- the salt produced was identified by means of nuclear magnetic resonance, infrared spectrometry, mass spectrometry and, finally, Monocrystal X-ray Diffraction. The analysis of the spectra indicated that the new salt produced is different from other Metformin compounds.
- the Nuclear Magnetic Resonance (RMN) proton spectrum showed displacements at 2,814 ppm, 2,916 ppm, 4,677 ppm.
- the infrared spectrum showed characteristic absorption signals at 3,367.34 cm-1 , 3,175.88 cm-1 , 1 ,618.78 cm-1 , and 1 ,573.96 cm-1.
- Metformin glycinate a) Full chemical name: N.N-dimethylimidodicarbonimidic diamide glycinate. b) Condensed formula: C 6 H 16 N 6 O 2 c) Molecular weight: 204.24 d) Storage requirements:
- compositions to be administered which may be in the form of a tablet, caplet, gel, paste, powder, prolonged-release granules, capsule, prolonged-release tablet, liquid with buffer agent, effervescent tablets, suspension, syrup, aerosol and others, or the administration route, which may be oral, intravenous injectable, intramuscular injectable, nasal, intraperitoneal, sublingual, etc.
- administration route which may be oral, intravenous injectable, intramuscular injectable, nasal, intraperitoneal, sublingual, etc.
- Hepatic origin cells CCL13, ATCC (American Type Culture Collection).
- Kidney origin cells CRL 1633, ATCC (American Type Culture Collection).
- MTT Assay Methylthiazoltetrazolium reduction assay
- Metformin glycinate evaluated was not cytotoxic for any of the cell types used in this study in the two exposure periods evaluated (24 and 72 hours).
- the oral-route 50 Lethal Dose (LD 50 ) assay in Wistar rats was performed in compliance with international regulations and the specifications for the care and use of laboratory animals. The entire procedure was conceived as stipulated in
- Randomisation 12 batches with 8 animals per batch. Four batches were used for the preliminary studies to find the dose interval and eight batches were used for the final study. Method: After fasting, different doses of the product were orally administered using an orogastric tube. During the development of the study, a control group was used in parallel.
- volume 3.8 ⁇ 0.4 ml (corresponding to a volume not greater than 2 ml for every 100 g of rat body weight). Observation period: 24 hours.
- the oral LD 50 obtained for Metformin glycinate 2.4625 ⁇ 0.195 g/kg.
- the LD 50 of Metformin hydrochloride is 1.45 g/kg.
- the OECD defines LD 50 as the "statistically derived single dose of a substance that can be expected to cause death in 50% of the laboratory animals.”
- the Subacute Toxicity test at 28 days was performed in compliance with international regulations and the specifications for the care and use of laboratory animals.
- the extrapolation of a probable dose to determine the non-observable adverse effect could be set between 0.5 and 1.0 g/kg.
- Metformin glycinate tablets equivalent to 850 mg of metformin hydrochloride were administered to 12 healthy volunteers and were compared to the response of 12 other volunteers who received metformin hydrochloride 850 mg.
- Samples were taken from the 24 volunteers in order to perform a pharmacokinetic curve, with the following resulting pharmacokinetic parameters: maximum concentration (C max ) 591 ng/ml, maximum time (t max ) 2.5 hours, area under the curve for 10 minutes at 24 hours (ABC (10 . 24 )) 26.811 ⁇ g ⁇ nl/h, with a relative bioavailability of 2.8 ⁇ g/ml (see results in Figure 1 ).
- Metformin glycinate begins its biodegradation and its release during the first few minutes; consequently, there is rapid absorption, with the appearance of plasma levels between 0.00 and 0.13 h. These levels remain in circulation for over 10.00 hours. The circulating remnant (levels below 200 ⁇ g/ml) is present and tends to decrease within the next 12 hours and disappears when the drug is not administered the following morning.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Endocrinology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Obesity (AREA)
- Epidemiology (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
Abstract
Description
Claims
Priority Applications (28)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
SI200831163T SI2303838T1 (en) | 2008-06-26 | 2008-06-26 | A new metformin glycinate salt for blood glucose control |
AU2008357111A AU2008357111B2 (en) | 2008-06-26 | 2008-06-26 | A new metformin Glycinate salt for blood glucose control |
BRPI0822909A BRPI0822909B8 (en) | 2008-06-26 | 2008-06-26 | metformin glycinate salt for blood glucose control |
PT88072186T PT2303838E (en) | 2008-06-26 | 2008-06-26 | A new metformin glycinate salt for blood glucose control |
PCT/IB2008/002665 WO2009144527A1 (en) | 2008-06-26 | 2008-06-26 | A new metformin glycinate salt for blood glucose control |
PL08807218T PL2303838T3 (en) | 2008-06-26 | 2008-06-26 | A new metformin glycinate salt for blood glucose control |
ES08807218.6T ES2450148T3 (en) | 2008-06-26 | 2008-06-26 | A new salt of metformin glycinate for blood glucose control |
CN200880130084.3A CN102159539B (en) | 2008-06-26 | 2008-06-26 | A new metformin glycinate salt for blood glucose control |
MX2011000135A MX2011000135A (en) | 2008-06-26 | 2008-06-26 | A new metformin glycinate salt for blood glucose control. |
CA2729035A CA2729035C (en) | 2008-06-26 | 2008-06-26 | A new metformin glycinate salt for blood glucose control |
DK08807218.6T DK2303838T3 (en) | 2008-06-26 | 2008-06-26 | New metforminglycinatsalt for blood glucose control |
KR1020117000071A KR101522066B1 (en) | 2008-06-26 | 2008-06-26 | A new metformin glycinate salt for blood glucose control |
EP08807218.6A EP2303838B1 (en) | 2008-06-26 | 2008-06-26 | A new metformin glycinate salt for blood glucose control |
JP2011515639A JP5551691B2 (en) | 2008-06-26 | 2008-06-26 | A novel metformin salt of glycinate for blood glucose control |
PE2009000908A PE20100257A1 (en) | 2008-06-26 | 2009-06-25 | METFORMIN GLYCINATE SALT AS HYPOGLYCEMIANT |
JO2009233A JO2884B1 (en) | 2008-06-26 | 2009-06-25 | A new metformin glycinate salt for blood glucose control |
CL2009001484A CL2009001484A1 (en) | 2008-06-26 | 2009-06-25 | Glycinate salt of metformin; pharmaceutical composition comprising the salt; and its use to treat hyperglycemia. |
ARP090102388A AR074159A1 (en) | 2008-06-26 | 2009-06-26 | A METFORMIN GLYCINATE SALT FOR THE CONTROL OF GLUCOSE IN BLOOD, PROCESS FOR OBTAINING AND USE |
UY0001031945A UY31945A (en) | 2008-06-26 | 2009-06-26 | A NEW METFORMIN GLYCINATE SALT FOR THE CONTROL OF GLUCOSE IN BLOOD |
NI201000234A NI201000234A (en) | 2008-06-26 | 2010-12-23 | A NEW METFORMIN GLYCINATE SALT FOR THE CONTROL OF GLUCOSE IN BLOOD. |
EC2010010719A ECSP10010719A (en) | 2008-06-26 | 2010-12-24 | A NEW METFORMIN GLYCINATE SALT FOR THE CONTROL OF GLUCOSE IN BLOOD |
US12/928,985 US8703183B2 (en) | 2008-06-26 | 2010-12-24 | Metformin glycinate salt for blood glucose control |
TNP2010000607A TN2010000607A1 (en) | 2008-06-26 | 2010-12-27 | A new metroformin glycinate salt for blood glucose control |
TNP2010000604A TN2010000604A1 (en) | 2008-06-26 | 2010-12-27 | A new metformin glycinate salt for blood glucose control |
MA33460A MA32418B1 (en) | 2008-06-26 | 2010-12-27 | NEW SALT OF METFORMIN GLYCINATE FOR REGULATION OF GLYCEMIA |
CY20141100150T CY1115098T1 (en) | 2008-06-26 | 2014-02-25 | NEW METALFORMIN GLYCIN SALT FOR BLOOD GLUCOSE CONTROL |
HRP20140194AT HRP20140194T1 (en) | 2008-06-26 | 2014-03-03 | A new metformin glycinate salt for blood glucose control |
US15/135,018 USRE46496E1 (en) | 2008-06-26 | 2016-04-21 | Metformin glycinate for blood glucose control |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
PCT/IB2008/002665 WO2009144527A1 (en) | 2008-06-26 | 2008-06-26 | A new metformin glycinate salt for blood glucose control |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/928,985 Continuation-In-Part US8703183B2 (en) | 2008-06-26 | 2010-12-24 | Metformin glycinate salt for blood glucose control |
Publications (1)
Publication Number | Publication Date |
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WO2009144527A1 true WO2009144527A1 (en) | 2009-12-03 |
Family
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Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IB2008/002665 WO2009144527A1 (en) | 2008-06-26 | 2008-06-26 | A new metformin glycinate salt for blood glucose control |
Country Status (26)
Country | Link |
---|---|
US (2) | US8703183B2 (en) |
EP (1) | EP2303838B1 (en) |
JP (1) | JP5551691B2 (en) |
KR (1) | KR101522066B1 (en) |
CN (1) | CN102159539B (en) |
AR (1) | AR074159A1 (en) |
AU (1) | AU2008357111B2 (en) |
BR (1) | BRPI0822909B8 (en) |
CA (1) | CA2729035C (en) |
CL (1) | CL2009001484A1 (en) |
CY (1) | CY1115098T1 (en) |
DK (1) | DK2303838T3 (en) |
EC (1) | ECSP10010719A (en) |
ES (1) | ES2450148T3 (en) |
HR (1) | HRP20140194T1 (en) |
JO (1) | JO2884B1 (en) |
MA (1) | MA32418B1 (en) |
MX (1) | MX2011000135A (en) |
NI (1) | NI201000234A (en) |
PE (1) | PE20100257A1 (en) |
PL (1) | PL2303838T3 (en) |
PT (1) | PT2303838E (en) |
SI (1) | SI2303838T1 (en) |
TN (2) | TN2010000607A1 (en) |
UY (1) | UY31945A (en) |
WO (1) | WO2009144527A1 (en) |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
USRE46496E1 (en) | 2008-06-26 | 2017-08-01 | Laboratorios Silanes S.A. De C.V. | Metformin glycinate for blood glucose control |
US11185516B2 (en) | 2016-09-30 | 2021-11-30 | Laboratorios Silanes S.A. De C.V. | Metformin glycinate, pharmaceutical compositions comprising the same, and methods of using the same |
US11510886B2 (en) | 2016-09-30 | 2022-11-29 | Laboratorios Silanes, S.A. De C.V. | Metformin amino acid compounds and methods of using the same |
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US8765811B2 (en) | 2012-07-10 | 2014-07-01 | Thetis Pharmaceuticals Llc | Tri-salt form of metformin |
US9382187B2 (en) | 2012-07-10 | 2016-07-05 | Thetis Pharmaceuticals Llc | Tri-salt form of metformin |
US9171343B1 (en) | 2012-09-11 | 2015-10-27 | Aseko, Inc. | Means and method for improved glycemic control for diabetic patients |
US9897565B1 (en) | 2012-09-11 | 2018-02-20 | Aseko, Inc. | System and method for optimizing insulin dosages for diabetic subjects |
CN103263405B (en) * | 2013-05-08 | 2015-04-22 | 南京医科大学 | Medicinal composition for treating diabetes, and its application |
US9815777B2 (en) | 2013-09-22 | 2017-11-14 | Jiva Pharma, Inc. | Metformin salts to treat Type2 diabetes |
US9898585B2 (en) | 2014-01-31 | 2018-02-20 | Aseko, Inc. | Method and system for insulin management |
US9486580B2 (en) | 2014-01-31 | 2016-11-08 | Aseko, Inc. | Insulin management |
WO2015171516A1 (en) | 2014-05-05 | 2015-11-12 | Thetis Pharmaceuticals Llc | Compositions and methods relating to ionic salts of peptides |
WO2015183794A1 (en) * | 2014-05-27 | 2015-12-03 | City Of Hope | Tgr5 agonist complexes for treating diabetes and cancer |
US9242008B2 (en) | 2014-06-18 | 2016-01-26 | Thetis Pharmaceuticals Llc | Mineral amino-acid complexes of fatty acids |
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 |
US11081226B2 (en) | 2014-10-27 | 2021-08-03 | Aseko, Inc. | Method and controller for administering recommended insulin dosages to a patient |
AU2015339576B2 (en) | 2014-10-27 | 2020-02-06 | Glytec, Llc | Subcutaneous outpatient management |
CN105030745A (en) * | 2015-07-08 | 2015-11-11 | 南京医科大学 | Use of amidation product of glycine and metformin in preparation of drug for treating diabetes |
AU2016308953B2 (en) | 2015-08-20 | 2020-09-10 | Glytec, Llc | Diabetes management therapy advisor |
CA3026264A1 (en) | 2016-06-03 | 2017-12-07 | Thetis Pharmaceuticals Llc | Compositions and methods relating to salts of specialized pro-resolving mediators |
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 |
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MX2011000135A (en) | 2008-06-26 | 2011-02-25 | Silanes Sa De Cv Lab | A new metformin glycinate salt for blood glucose control. |
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2008
- 2008-06-26 MX MX2011000135A patent/MX2011000135A/en active IP Right Grant
- 2008-06-26 JP JP2011515639A patent/JP5551691B2/en not_active Expired - Fee Related
- 2008-06-26 SI SI200831163T patent/SI2303838T1/en unknown
- 2008-06-26 ES ES08807218.6T patent/ES2450148T3/en active Active
- 2008-06-26 PT PT88072186T patent/PT2303838E/en unknown
- 2008-06-26 CN CN200880130084.3A patent/CN102159539B/en active Active
- 2008-06-26 EP EP08807218.6A patent/EP2303838B1/en not_active Not-in-force
- 2008-06-26 BR BRPI0822909A patent/BRPI0822909B8/en active IP Right Grant
- 2008-06-26 DK DK08807218.6T patent/DK2303838T3/en active
- 2008-06-26 AU AU2008357111A patent/AU2008357111B2/en not_active Ceased
- 2008-06-26 PL PL08807218T patent/PL2303838T3/en unknown
- 2008-06-26 WO PCT/IB2008/002665 patent/WO2009144527A1/en active Application Filing
- 2008-06-26 CA CA2729035A patent/CA2729035C/en not_active Expired - Fee Related
- 2008-06-26 KR KR1020117000071A patent/KR101522066B1/en active IP Right Grant
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2009
- 2009-06-25 PE PE2009000908A patent/PE20100257A1/en active IP Right Grant
- 2009-06-25 JO JO2009233A patent/JO2884B1/en active
- 2009-06-25 CL CL2009001484A patent/CL2009001484A1/en unknown
- 2009-06-26 AR ARP090102388A patent/AR074159A1/en unknown
- 2009-06-26 UY UY0001031945A patent/UY31945A/en not_active Application Discontinuation
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2010
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- 2010-12-24 EC EC2010010719A patent/ECSP10010719A/en unknown
- 2010-12-24 US US12/928,985 patent/US8703183B2/en not_active Ceased
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2014
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- 2014-03-03 HR HRP20140194AT patent/HRP20140194T1/en unknown
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2016
- 2016-04-21 US US15/135,018 patent/USRE46496E1/en active Active
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
USRE46496E1 (en) | 2008-06-26 | 2017-08-01 | Laboratorios Silanes S.A. De C.V. | Metformin glycinate for blood glucose control |
US11185516B2 (en) | 2016-09-30 | 2021-11-30 | Laboratorios Silanes S.A. De C.V. | Metformin glycinate, pharmaceutical compositions comprising the same, and methods of using the same |
US11510886B2 (en) | 2016-09-30 | 2022-11-29 | Laboratorios Silanes, S.A. De C.V. | Metformin amino acid compounds and methods of using the same |
US11951081B2 (en) | 2016-09-30 | 2024-04-09 | Laboratorios Silanes S.A. De C.V. | Metformin glycinate, pharmaceutical compositions comprising the same, and methods of using the same |
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