Nanoparticle and polymer formulations for thyroid hormone analogs, antagonists, and formulations thereof

• US 8,668,926 B1
• Filed: 04/11/2007
• Issued: 03/11/2014
• Est. Priority Date: 09/15/2003
• Status: Active Grant

• Current Assignee: NanoPharmaceuticals LLC
• Original Assignee: NanoPharmaceuticals LLC
• Inventors: Mousa, Shaker A., Davis, Faith B., Davis, Paul J.
• Primary Examiner(s): Gulledge, Brian
• Assistant Examiner(s): Maewall, Snigdha
• Application Number:
  US11/786,723
• Time in Patent Office: 2,526 Days
• Field of Search: None
• US Class Current: 424/450
• 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 31/4365 the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
• CPC Class Codes: A61K 31/60 Salicylic acid; Derivatives thereof
• CPC Class Codes: A61K 31/65 Tetracyclines
• CPC Class Codes: A61K 31/7076 containing purines, e.g. adenosine, adenylic acid
• CPC Class Codes: A61K 31/727 Heparin; Heparan
• CPC Class Codes: A61K 39/44 Antibodies bound to carriers
• 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: A61K 47/64 Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent peptidic linkers A61K47/65
• CPC Class Codes: A61K 47/68 the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
• CPC Class Codes: A61K 47/6801 Drug-antibody or immunoglobulin conjugates defined by the pharmacologically or therapeutically active agent
• CPC Class Codes: A61K 47/6811 the drug being a protein or peptide, e.g. transferrin or bleomycin
• CPC Class Codes: A61K 47/6937 the polymer being PLGA, PLA or polyglycolic acid
• CPC Class Codes: A61K 47/6939 the polymer being a polysaccharide, e.g. starch, chitosan, chitin, cellulose or pectin
• CPC Class Codes: A61K 49/0008 Screening agents using (non-human) animal models or transgenic animal models or chimeric hosts, e.g. Alzheimer disease animal model, transgenic model for heart failure
• CPC Class Codes: A61K 49/085 : conjugated systems
• CPC Class Codes: A61K 49/10 : Organic compounds
• CPC Class Codes: A61K 49/12 : Macromolecular compounds
• CPC Class Codes: A61K 51/0402 : carboxylic acid carriers, fatty acids amino acids A61K51/0406
• CPC Class Codes: A61K 51/0497 : conjugates with a carrier being an organic compounds
• CPC Class Codes: A61K 51/065 : conjugates with carriers being macromolecules
• CPC Class Codes: A61K 9/0048 : Eye, e.g. artificial tears
• CPC Class Codes: A61K 9/5153 : Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: C07K 16/2848 : against integrin beta3-subunit-containing molecules, e.g. CD41, CD51, CD61
• CPC Class Codes: C07K 2317/76 : Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: Y10T 428/2982 : Particulate matter [e.g., sphere, flake, etc.]

Abstract

Disclosed are methods of treating subjects having conditions related to angiogenesis including administering an effective amount of a polymeric Nanoparticle form of thyroid hormone agonist, partial agonist 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. A method for treating a non-cancerous skin disorder comprising:

providing a thyroid hormone analog conjugated to a polymer via a linker, wherein the polymer is poly(lactic-co-glycolic) acid (PLGA), polylactide, polyglycolide, or co-polymers thereof, wherein said thyroid hormone analog is selected from the group consisting of tetraiodothyroacetic acid (TETRAC), triiodothyroacetic acid (TRIAC), thyroid antagonists and combinations thereof, wherein the linker is an ester linkage, anhydride linkage, thioether linkage, sulfhydryl linkage or ether linkage, wherein the conjugated thyroid hormone analog acts exclusively at the cell surface receptor and the conjugated thyroid hormone analog is a sufficient size to prevent the conjugated thyroid hormone analog from entering the cell; and

administering the thyroid hormone analog conjugated to a polymer via a linker to a portion of the skin affected by the non-cancerous skin disorder.

2. The method of claim 1, wherein said non-cancerous skin disorder is selected from the group consisting of rosacea, angiomas, telangiectasias, poikiloderma of Civatte and psoriasis by inhibiting angiogenesis.

3. The method of claim 1, wherein the step of administering includes a topical mode of administration.

4. The method of claim 3 wherein topical mode of administration comprises a topical cutaneous mode of administration selected from the group consisting of solutions, sprays, creams, ointments, soaps and incorporation into gauze pads or into synthetic sheets.

5. The method of claim 1, wherein the ratio of thyroid hormone molecules per nanoparticle ranges from 1:

1 to 30;

1.

6. The method of claim 1 further comprising a step of formulating the thyroid hormone analog conjugated to a polymer into a nanoparticle with a particle size between 1 nm and <

1000 nm.