Compositions for Delivery of Therapeutics and Other Materials

• US 20100221184A1
• Filed: 11/23/2009
• Published: 09/02/2010
• Est. Priority Date: 02/27/2002
• Status: Active Grant

• Current Assignee: Pharmain Corporation
• Original Assignee: Pharmain Corporation
• Inventors: Bolotin, Elijah M., Castillo, Gerardo M.
• Granted Patent: US 8,231,859 B2
• Time in Patent Office: Days
• US Class Current: 424/9.100
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/34 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers A61K47/10 takes precedence
• CPC Class Codes: A61K 47/42 Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein oligopeptides having up to five amino acids A61K47/183; polyamino acids A61K47/34
• CPC Class Codes: A61K 47/6911 the form being a liposome
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]

Abstract

This disclosure relates to compositions for delivering agents to a subject, and in particular, to compositions for delivery of therapeutic agents or diagnostic agents in the presence or absence of targeting moieties. In part, this disclosure relates to compositions comprising a hydrophobic group with a first end and a second end, a first metal binding domain linked to the hydrophobic group, a metal ion capable of being chelated to the first metal binding domain, and an agent linked to a second metal binding domain capable of chelating to the metal ion.

Claims

1-14. -14. (canceled)

15. A composition comprising:

a hydrophobic group;

a hydrophilic group comprising a first end and a second end, wherein the first end is covalently linked to the hydrophobic group;

a first metal binding domain (FMBD) covalently linked to the second end of the hydrophilic group;

a metal ion chelated to the FMBD;

and an active agent with a second metal binding domain (SMBD) coordinately bonded to the said metal ion.

16. The composition of claim 15, wherein the FMBD or the SMBD is selected from a nitrogen containing poly carboxylic acid, a polypeptide, or a bisphosphonate derivative.

17. The composition of claim 15, wherein the metal ion is a transition metal ion (d-block of the periodic table).

18. The composition of claim 15, wherein the active agent is an imaging agent or a therapeutic agent.

20. The composition of claim 15, wherein the FMBD or the SMBD is individually selected from N-(hydroxy-ethyl)ethylenediaminetriacetic acid;

nitrilotriacetic acid (NTA);

ethylenebis(oxyethylene-nitrilo)tetraacetic acid;

1,4,7,10-tetraazacyclodo-decane-N,N′

,N″

,N″

′

-tetraacetic acid;

1,4,7,10-tetraaza-cyclododecane-N,N′

,N″

-triacetic acid;

1,4,7-tris(carboxymethyl)-10-(2′

-hydroxypropyl)-1,4,7,10-tetraazocyclodecane;

1,4,7-triazacyclonane-N,N′

,N″

-triacetic acid;

1,4,8,11-tetraazacyclotetra-decane-N,N′

,N″

,N″

′

-tetraacetic acid;

diethylenetriamine-pentaacetic acid (DTPA);

ethylenedicysteine;

bis(aminoethanethiol)carboxylic acid;

triethylenetetraamine-hexaacetic acid;

ethylenediamine-tetraacetic acid (EDTA);

1,2-diaminocyclohexane-N,N,N′

N′

-tetraacetic acid;

or a metal binding polypeptide.

21. The composition of claim 15 herein the FMBD or the SMBD is a metal binding polypeptide of formula:

(AxHy)p where A is any amino acid, H is histidine, x is an integer from 0-6;

y is an integer from 1-6; and

p is an integer from 1-6.

22. The composition of claim 15, wherein the hydrophobic group has a molecular weight ranging from about 50 to about 1000 Daltons.

23. The composition of claim 15, wherein the hydrophobic group comprises one or more linear fatty acyl groups with the formula [CH₃(CH₂)_xCO—

] where x is an integer from 6-50.

24. The composition of claim 15, wherein the hydrophobic group is a branched or straight chain C₅-C₅₀ alkyl, a substituted branched or straight chain C₅-C₅₀ alkyl, apoly-glycine, a substituted poly-glycine, poly-alanine, poly-valine, poly-leucine, poly-isoleucine, poly-phenylalanine, poly-proline, poly-methionine, phenyl, napthyl, cholesterol, vitamin D, or vitamin E.

25. The composition of claim 15, wherein the hydrophobic group has a general formula [P_vN_wC_xH_yO_z—

] where v is an integer from 0-3, w is an integer from 0-3, x is an integer from 8-48, y is an integer from 15-95, and z is an integer from 1-13.

26. The composition of claim 15, wherein the hydrophilic group comprises of a polymer selected from poly(ethylene glycol);

alkoxy poly(ethyleneglycol);

methoxy poly(ethylene glycol);

dicarboxylic acid esterified poly(ethylene glycol) monoester;

poly(ethylene glycol)-diacid;

copolymer of poly(ethylene glycol);

poly(ethylene glycol) monoamine;

methoxy poly(ethylene glycol) monoamine;

methoxy poly(ethylene glycol) hydrazide;

methoxy poly(ethylene glycol) imidazolide;

blockcopolymer of poly(ethylene glycol);

poly-lactide-glycolide co-polymer;

polysaccharide;

oligosaccharides;

polyamidoamine; and

polyethyleneimine.

19. (canceled)

27. A method of treatment or diagnosis of a subject in need of such treatment or diagnosis comprising administering a composition to the subject, the composition comprising:

a hydrophobic group;

a hydrophilic group comprising a first end and a second end, wherein the first end is covalently linked to the hydrophobic group;

a first metal binding domain (FMBD) covalently linked to the second end of the hydrophilic group;

a metal ion chelated to the FMBD; and

an active agent with a second metal binding domain (SMBD) coordinately bonded to the said metal ion;

wherein after administration of the composition to the subject, the active agent is released in a sustained manner, and wherein the active agent is a therapeutic or diagnostic agent.

28. The method of claim 27 wherein the administration is oral.