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

• US 9,750,709 B2
• Filed: 02/20/2014
• Issued: 09/05/2017
• 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): Maewall, Snighda
• Application Number:
  US14/185,010
• Publication Number:
  US 20140314665A1
• Time in Patent Office: 1,293 Days
• 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. An imaging compound comprising:

a thyroid hormone analog, wherein the thyroid hormone analog is covalently bonded to a linker selected from the group consisting of diaminopropane, ether, sulfhydryl, ester and anhydride linkages, and the linker is covalently bonded to a radio-labelled tracer selected from the group consisting of iodine-123 (¹²³I), iodine-124 (¹²⁴I), iodine-125 (¹²⁵I), iodine-131 (¹³¹I), fluorine-18 (¹⁸F), technetium-99m (^99mTc), indium-111 (¹¹¹In), carbon-11 (¹¹C) and astatine-210 (²¹⁰At), wherein the imaging compound is a nanoparticle.

2. The imaging compound of claim 1, wherein the thyroid hormone analog is tetrac, triac or a combination thereof.

3. The imaging compound of claim 1, wherein the nanoparticle has a diameter between 1 nm and less than 1000 nm.

4. The imaging compound of claim 1, wherein the thyroid hormone analog is covalently bonded to a diaminopropane linker and the diamino propane linker is covalently bonded to indium-111.

5. A method for imaging tumor tissues and neovascularization using the imaging compound of claim 1 comprising the steps of:

administering the imaging compound of claim 1 to a patient, wherein the imaging compound binds to a plurality of α

vβ

3 integrin receptors;

generating an image representing a distribution of the imaging agent binding to the α

vβ

3 integrin receptors.

6. The method of claim 5, wherein the step of generating the image is performed by an imaging technique selected from the group consisting of positron emission topography (PET) and single photon emission (SPECT).

7. The method of claim 5, wherein the imaging compound of claim 1 includes a thyroid hormone analog selected from the group consisting of tetrac, triac or a combination thereof.

8. A method for diagnosing a degenerative disease comprising the steps of:

administering the imaging compound of claim 1 to a patient, wherein the imaging compound binds to a plurality of transthyretin; and

generating an image representing a distribution of the imaging compound binding to the plurality of the transthyretin.

9. The method of claim 8, wherein the thyroid hormone analog of the imaging compound of claim 1 is triac or tetrac covalently bound to a the diaminopropane linker.

10. The method of claim 8, wherein the neurodegenerative disease is Alzheimer'"'"'s disease.

11. The method of claim 8, further comprising the step of inhibiting the formation of amyloid fibrils with the imaging compound of claim 1.

12. The method of claim 8, wherein the step of generating the image is performed by positron emission topography (PET) or single photon emission (SPECT).

13. The imaging method of claim 8, wherein the image representing a distribution of the imaging compound is at least one portion of the brain.