Methods of stimulating fat mobilization using a polymer conjugated polyphenol

• US 9,272,049 B2
• Filed: 06/08/2011
• Issued: 03/01/2016
• Est. Priority Date: 09/16/2005
• Status: Active Grant

• Current Assignee: NanoPharmaceuticals LLC
• Original Assignee: NanoPharmaceuticals LLC
• Inventors: Alexander-Bridges, Maria, Mousa, Shaker A., Davis, Paul J.
• Primary Examiner(s): Mertz, Prema
• Application Number:
  US13/156,047
• Publication Number:
  US 20120258069A1
• Time in Patent Office: 1,728 Days
• Field of Search: 514/546, 514/909, 424/725, 424/776
• US Class Current: 1/1
• CPC Class Codes: A61K 47/58 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
• CPC Class Codes: A61K 47/593 Polyesters, e.g. PLGA or polylactide-co-glycolide
• CPC Class Codes: A61K 47/60 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
• CPC Class Codes: A61K 47/61 the organic macromolecular compound being a polysaccharide or a derivative thereof
• CPC Class Codes: A61P 3/00 Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/48 of the pancreatic hormones
• CPC Class Codes: C12N 15/1086 Preparation or screening of expression libraries, e.g. reporter assays
• CPC Class Codes: G01N 33/5023 on expression patterns

Abstract

Provided herein are compositions and methods for preventing and treating diseases and risk factors associated with metabolic syndrome by targeting the RGD-binding site of selected intra- and extracellular proteins. Exemplary compositions include RGD-polyphenol conjugates via an ester linkage; polyphenol polymer conjugated to RGD analogs or mimetics; and RGD polymer conjugates linked to polyphenol.

Claims

1. A method of stimulating fat mobilization, the method comprising the steps of:

providing a polyphenol;

conjugating the polyphenol to a polymer selected from the group consisting of polyethylene glycol, polyglycolide, polylactide, polyvinyl alcohol, polyacrylic acid, hyaluronic acid and polyamidoamine;

administering to a subject suffering from dyslipidemia, the polyphenol conjugated to the polymer; and

binding the polyphenol conjugated to the polymer to a protein comprising an amino acid sequence Arg-Gly-Asp (RGD) recognition site, leading to increased phosphorylation of AMP kinase (AMPK), stimulating fat mobilization.

2. The method of claim 1, wherein the polyphenol is resveratrol.

3. The method of claim 1, wherein the polyphenol conjugated to the polymer inhibits the synthesis of new proteins comprising the amino acid sequence Arg-Gly-Asp.

4. The method of claim 1, wherein the polyphenol conjugated to the polymer regulates fat cell differentiation and/or fat accumulation by inhibiting a regulatory component involved in the activity or synthesis of the protein comprising the amino acid sequence Arg-Gly-Asp.

5. The method of claim 1, wherein the polymer is a nanoparticle between 100-300 nm.