Compositions for delivery of therapeutics and other materials

• US 7,635,463 B2
• Filed: 06/21/2007
• Issued: 12/22/2009
• Est. Priority Date: 02/27/2002
• Status: Expired due to Term

• Current Assignee: Pharmain Corporation
• Original Assignee: Pharmain Corporation
• Inventors: Bolotin, Elijah M., Castillo, Gerardo M.
• Primary Examiner(s): JONES, DAMERON LEVEST
• Application Number:
  US11/766,623
• Publication Number:
  US 20080015263A1
• Time in Patent Office: 915 Days
• Field of Search: 424/1.11, 424/149, 424/1.65, 424/1.69, 424/1.73, 424/9.1, 424/9.3, 424/9.36, 424/9.4, 424/9.5, 424/9.6, 424/9.7, 424/9.8, 424/1.49, 514/6, 514/54, 514/2, 514/773, 534/7, 534 10- 16
• US Class Current: 424/1.65
• 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. A composition with a metal bridge comprising:

a first molecule comprising;

a first hydrophobic group comprising a first metal binding domain (FMBD) at one end;

a metal ion chelated to the FMBD; and

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

a second molecule comprising;

a second hydrophobic group comprising a first and second end; and

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

2. The composition of claim 1 further comprising:

a targeting group covalently linked to the second end of the hydrophilic group.

3. The composition of claim 1, further comprising a third molecule comprising:

a third hydrophobic group; and

a second hydrophilic group with first and second end, with the first end covalently linked to the third hydrophobic group; and

a targeting group covalently linked to the second end of the second hydrophilic group.

4. The composition of claim 1, further comprising:

a third metal binding domain (TMBD) covalently linked to the second end of the second hydrophobic group.

5. The composition of claim 4, further comprising a third molecule comprising:

a third hydrophobic group;

a second hydrophilic group, with first and second end, with the first end, covalently linked to the third hydrophobic group; and

a targeting group covalently linked to the second end of the second hydrophilic group.

6. The composition of claim 4 further comprising:

a targeting group covalently linked to the second end of hydrophilic group.

7. The composition of claim 6 further comprising a third molecule comprising:

a third hydrophobic group comprising a first and second end;

a second hydrophilic group comprising a first and second end, with the first end covalently linked to the first end of the third hydrophobic group.

8. The composition as in one of claims 1-7, wherein the FMBD, the SMBD, or the TMBD is selected from a nitrogen containing poly carboxylic acid or a polypeptide.

9. The composition as in one of claims 1-7, wherein the metal ion is a transition metal ion.

10. The composition as in one of claims 1-7, wherein the active agent is an imaging agent or a therapeutic agent.

11. The composition as in claims 2, 3, 5, 6, or 7, wherein the targeting group is selected from the group consisting of antibody, a cell surface receptor ligand, a cell surface receptor binding drugs, a cell surface binding saccharide ligand, an extracellular matrix ligand, cytosolic receptor ligand, growth factor, cytokine, incretin, a hormones, and lectin.

12. The composition as in one of claim 1-7, wherein the FMBD, the SMBD, or the TMBD are individually selected from N-(hydroxy-ethyl)ethylenediaminetriacetic acid;

nitrilotriacetic acid (NTA);

ethylene-bis(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″

-triactic 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);

or 1,2-diaminocyclohexane-N,N,N′

,N′

-tetraacetic acid.

13. The composition as in one of claim 8, wherein the FMBD, the SMBD, or the TMBD 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.

14. The composition as in one of claims 1-7, wherein the hydrophobic group has molecular weight ranging from about 50 to about 1000 Daltons.

15. The composition as in one of claims 1-7, wherein the hydrophobic group comprises of one or more linear fatty acyl group with formula [CH₃(CH₂)_xCO—

] where x is an integer from 6-50.

16. The composition as in one of claims 1-7, wherein the hydrophobic group is a branched or straight chain C₅-C₅₀ alkyl, a substituted branched or straight chain C₅-C₅₀ alkyl, poly-glycine, 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.

17. The composition as in one of claims 1-7, 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;

z is an integer from 1-13.

18. The composition as in one of claims 1-7, 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.