COMPOSITIONS FOR DELIVERY OF THERAPEUTICS AND OTHER MATERIALS, AND METHODS OF MAKING AND USING THE SAME

• US 20060239924A1
• Filed: 07/05/2006
• Published: 10/26/2006
• Est. Priority Date: 02/27/2002
• Status: Active Grant

• Current Assignee: Pharmain Corporation
• Original Assignee: Pharmain Corporation
• Inventors: Bolotin, Elijah M.
• Granted Patent: US 7,790,140 B2
• Time in Patent Office: Days
• US Class Current: 424/9.340
• CPC Class Codes: A61K 47/645 Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT

Abstract

In part, the present invention is directed to biocompatible compositions comprising a carrier with a first metal binding domain, a metal ion, an active agent with second metal binding domain and optionally a protective chain covalently attached to the polymeric carrier.

Claims

1. A biocompatible composition comprising:

a carrier with a first metal binding domain (MBD),

a metal ion chelated to the first MBD, and

an active agent with a second MBD chelated to the metal ion,

wherein after administration of the composition to a patient, the active agent is released in a sustained manner.

2. The composition of claim 1, wherein the carrier is selected from a polymer, micelle, reverse micelle, liposome, emulsion, hydrogel, microparticle, nanoparticle, microsphere, or solid surface.

3. The composition of claim 1, wherein the carrier is a polymer.

4. The composition of claim 3, further comprising one or more protective groups covalently linked to the polymer.

5. The composition of claim 4, wherein the protective groups are selected from poly(ethylene glycol), methoxy poly(ethylene glycol), dicarboxylic acid esterified poly(ethylene glycol) monoester;

dicarboxylic acid esterified poly(propylene glycol) monoester, poly(ethylene glycol)-diacid;

poly(propylene glycol)-diacid copolymer of poly(ethylene glycol), copolymer of poly(propylene glycol), poly(ethylene glycol)monoamine;

poly(propylene glycol) monoamine;

methoxy poly(ethylene glycol)monoamine;

methoxy poly(propylene glycol)monoamine, methoxy poly(ethylene glycol)hydrazide;

methoxy poly(propylene glycol)hydrazide;

methoxy poly(ethylene glycol)imidazolide, methoxy poly(proylene glycol)imidazolide, blockcopolymer of poly (ethylene glycol), poly-lactide-glycolide co-polymer, polysaccharide, polyamidoamine, and polyethyleneimine.

6. The composition of claim 4, wherein the protective side chain comprises poly(ethylene glycol).

7. The composition of claim 4, wherein the protective side chain comprises alkoxy poly(ethyleneglycol).

8. The composition of claim 4, wherein the protective side chain comprises methoxy poly(ethyleneglycol) (MPEG).

9. The composition of claim 3, wherein the polymer is not a polyamino acid polymer.

10. The composition of claim 3, wherein the polymer has a molecular mass ranging from about 100 to about 1,000,000 daltons.

11. The composition of claim 3, wherein the polymer has a molecular mass ranging from about 10,000 to about 250,000 daltons.

12. The composition of claim 3, wherein the polymer is selected from galacturonic acid, glucuronic acid, mannuronic acid, hyaluronic acid, pectic acid, neuraminic acid, alginic acid, carrageenan, oxidized dextrans, linear or branched polysaccharides, linear or branched oligosaccharides, dextran, mannan, xylan, pullulan, cellulose, chytosan, agarose, fucoidan, galactan, arabinan, fructan, fucan, chitin, pustulan, levan, or pectin.

13. The composition of claim 12, wherein the polysaccharides or oligosaccharides are aminated, carboxylated, carboxymethylated, sulfated, or phosphorylated.

14. The composition of claim 3, wherein the first or second MBD comprises a nitrogen containing poly carboxylic acid.

15. The composition of claim 3, wherein the first or second MBD comprises one or more of the following:

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″

-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

polypeptide.

16. The composition of the claim 15, wherein the first or second MBD comprises a polypeptide of formula (AxHy)_p, wherein A is any amino acid residue, 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.

17. The composition of claim 3, wherein the metal ion is a transition metal ion.

18. The composition of claim 3, wherein the metal ion is one or more of the following:

Zn²⁺, Ni²⁺, Co²⁺, Fe²⁺, Mn²⁺, C²⁺.

19. The composition of claim 3, wherein the active agent is a diagnostic, targeting moiety, antigen or therapeutic agent.

20. The composition of claim 3, wherein more than one type of active agent is present.

21. The composition of claim 3, wherein the active agent comprises one or more of the following:

a protein, peptide, peptidomimetic, antibody, chemotactic protein, or enzyme.

22. The composition of claim 3, wherein the active agent is selected from the group consisting of factor VII, factor VIII, insulin, growth factors, hormones, cytokines, growth hormones, nerve growth factor, brain-derived neurotrophic factor, endostatin, angiostatin, trombospondin, urokinase, colony stimulating factor and interferon.

23. A pharmaceutical composition comprising the composition of claim 3 and a pharmaceutically acceptable excipient or diluent.

24. The composition of claim 3, wherein the active agent is an imaging agent.

25. A kit comprising the composition of claim 3 and instructions for administering the composition to a patient.