Methods and compositions for the delivery of biologically active agents

• US 8,574,604 B2
• Filed: 04/14/2006
• Issued: 11/05/2013
• Est. Priority Date: 04/15/2005
• Status: Active Grant

• Current Assignee: Interface Biologics, Inc.
• Original Assignee: Interface Biologics, Inc.
• Inventors: Esfand, Roseita, Santerre, Paul J., Yang, Meilin
• Primary Examiner(s): ROGERS, JAMES WILLIAM
• Application Number:
  US11/404,290
• Publication Number:
  US 20070037891A1
• Time in Patent Office: 2,762 Days
• Field of Search: 424/405
• US Class Current: 424/405
• CPC Class Codes: A61K 47/30 Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
• CPC Class Codes: A61K 9/7007 Drug-containing films, membranes or sheets A61K9/0041, A61K9/0043, A61K9/006, A61K9/0063 take precedence
• CPC Class Codes: A61L 2300/80 characterised by a special chemical form
• CPC Class Codes: A61L 27/14 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 31/041 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/04 Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C08G 18/2885 containing halogen atoms
• CPC Class Codes: C08G 18/4854 Polyethers containing oxyalkylene groups having four carbon atoms in the alkylene group
• CPC Class Codes: C08G 18/771 oxygen

Abstract

The invention features polymers noncovalently complexed with a biologically active agent. The polymer complexes include at least one shielding moiety covalently tethered to at least one complexing moiety, which is complexed with at least one biologically active agent.

Claims

1. A polymer described by the formula:

F_T−

LINK A[−

(oligo)_a−

(LINK A)_b]_c−

T_d(Bio)_e,

wherein

F_T is a polyfluoroorgano group;

Bio is one or more biologically active agents capable of being complexed to LINK A;

each LINK A is, independently, an organic moiety comprising a complexing moiety that is tri-hydroxymethyl aminoethane (Tris);

oligo is an oligomeric segment;

T is a terminal group;

a is 0 or 1;

b, c, d, and e are integers greater than 0; and

wherein at least one Bio is complexed via hydrogen bonding interactions to at least one LINK A, and

wherein each Bio is selected from the group consisting of antibiotics, antiproliferative agents, rapamycin macrolides, analgesics, anesthetics, antiangiogenic agents, antithrombotic agents, vasoactive agents, anticoagulants, immunomodulators, cytotoxic agents, antiviral agents, psychoactive drugs, vitamins, lipids, and prodrugs thereof.

2. The polymer of claim 1, wherein F_T is a polyfluoroalkyl.

3. The polymer of claim 1, wherein F_T has a molecular weight of between 100-1,500 Da.

4. The polymer of claim 1, wherein F_T is selected from the group consisting of radicals of the general formula CF₃(CF₂)_rCH₂CH₂—

wherein r is 2-20, and CF₃(CF₂)_s(CH₂CH₂O)_χ

wherein χ

is 1-10 and s is 1-20.

5. The polymer of claim 1, wherein said Oligo is a branched or non-branched oligomeric segment with 20 or more repeating units.

6. The polymer of claim 1, wherein said LINK A is a monomeric segment.

7. The polymer of claim 1, wherein a is 0.

8. The polymer of claim 1, wherein said oligomeric segment comprises polyurethane, polyurea, polyamides, polyalkylene oxide, polycarbonate, polyester, polylactone, polysilicone, polyethersulfone, polyolefin, polyvinyl derivative, polypeptide, polysaccharide, polysiloxane, polydimethylsiloxane, polyethylene-butylene, polyisobutylene, polybutadiene, polypropylene oxide, polyethylene oxide, polytetramethyleneoxide, or polyethylenebutylene segments.

9. The polymer of claim 1, wherein said oligomeric segment has an absolute molecular weight of greater than about 10 kDa.

10. The polymer of claim 1, wherein said polyfluoroorgano group comprises from about 0.01 to 5 weight % of said polymer.

11. The polymer of claim 1, wherein said oligomeric segment has an absolute molecular weight of less than about 10 kDa.

12. An admixture comprising a polymer of claim 1 admixed with a base polymer.

13. The admixture of claim 12, wherein said base polymer is selected from polyurethanes, polysulfones, polycarbonates, polysaccharide, polyesters, polyethylene, polypropylene, polystyrene, poly(acrylonitrile-butadienestyrene), polybutadiene, polyisoprene, styrenebutadiene-styrene block copolymers, styrene-iso-prenestyrene block copolymers, poly-R-methylpentene, polyisobutylene, polymethyl-methacrylate, polyvinylacetate-polyacrylonitrile, polyvinyl chloride, polyethylene terephthalate, cellulose and its esters, polyamides, polyester-polyethers, styrene-isoprenes, styrene butadienes, thermoplastic polyolefins, styrene-saturated olefins, polyester-polyester, ethylene-vinyl acetate ethylene-ethyl acrylate, ionomers, thermoplastic polydienes, and combinations thereof.

14. A shaped article formed from a polymer of claim 1.

15. A shaped article formed from an admixture of claim 12.

16. The shaped article of claim 14 or 15, wherein said article is an implantable medical device.

17. The shaped article of claim 14 or 15, wherein said article is a cardiac-assist device, a catheter, a stent, a prosthetic implant, an artificial sphincter, or a drug delivery device.

18. The shaped article of claim 14 or 15, wherein 80% of the biologically active agent is released within 2 years.

19. The shaped article of claim 18, wherein t₁₀ is greater than 1/10 of t₅₀.

20. A composition for the controlled release of a biologically active agent comprising a polymer of claim 1, wherein said composition is formulated as a cream, gel, or lotion.

21. A composition for controlling the proliferation of pests comprising a polymer of claim 1, wherein said biologically active agent is an pesticide or herbicide.

22. A composition for reducing microbial growth on a surface comprising a polymer of claim 1, wherein said biologically active agent is an antimicrobial agent.

23. A shaped article comprising a polymer of claim 1.

24. The shaped article of claim 23, wherein said article is coated with said polymer.