Thyroid hormone analogs and methods of use

• US 7,785,632 B2
• Filed: 09/15/2004
• Issued: 08/31/2010
• Est. Priority Date: 09/15/2003
• Status: Active Grant

• Current Assignee: NanoPharmaceuticals LLC
• Original Assignee: Albany College of Pharmacy & Health Sciences, Ordway Research Institute, Inc.
• Inventors: Davis, Paul J., Mousa, Shaker A., Davis, Faith B.
• Primary Examiner(s): Kishore; Gollamudi S
• Application Number:
  US10/943,072
• Publication Number:
  US 20050124862A1
• Time in Patent Office: 2,176 Days
• Field of Search: 424489-502
• US Class Current: 424/501
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61K 31/198 Alpha-amino acids, e.g. alanine or edetic acid [EDTA] betaine A61K31/205; proline A61K31/401; tryptophan A61K31/405; histidine A61K31/4172; peptides not degraded to individual amino acids A61K38/00
• CPC Class Codes: A61K 38/1825 Fibroblast growth factor [FGF]
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• 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 47/60 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: A61K 9/00 Medicinal preparations characterised by special physical form nuclear magnetic resonance contrast preparations or magnetic resonance imaging contrast preparations A61K49/18; preparations containing radioactive substances A61K51/12
• CPC Class Codes: A61K 9/146 with organic macromolecular compounds
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 27/02 Ophthalmic agents
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/04 specific for metastasis
• CPC Class Codes: A61P 5/14 of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/08 : Vasodilators for multiple indications
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/14 : Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers

Abstract

Disclosed are methods of treating subjects having conditions related to angiogenesis including administering an effective amount of a polymeric form of thyroid hormone, or an antagonist thereof, to promote or inhibit angiogenesis in the subject. Compositions of the polymeric forms of thyroid hormone, or thyroid hormone analogs, are also disclosed.

Claims

1. An anti-angiogenic composition consisting of tetraiodothyroacetic acid (TETRAC), wherein said TETRAC is conjugated via a covalent bond to a copolymer of polyglycolide and polylactide, wherein said copolymer is formulated into a nanoparticle, wherein said nanoparticle is less than 200 nanometers in size, and wherein said TETRAC binds to the cell surface receptor for thyroid hormone on integrin α

vβ

3 at the cell membrane level and does not activate signal transduction.

2. A pharmaceutical formulation comprising the composition of claim 1 in a pharmaceutically acceptable carrier.

3. The pharmaceutical formulation of claim 2, further comprising one or more pharmaceutically acceptable excipients.

4. The pharmaceutical formulation of claim 2, wherein said formulation is formulated for parenteral, oral, rectal, or topical administration, or combinations thereof.