Bioactive surface modifiers for polymers and articles made therefrom

• US 6,770,725 B2
• Filed: 06/05/2002
• Issued: 08/03/2004
• Est. Priority Date: 06/07/2001
• Status: Expired due to Term

• Current Assignee: Interface Biologics, Inc.
• Original Assignee: Interface Biologics, Inc.
• Inventors: Santerre, Paul J.
• Primary Examiner(s): Moore, Margaret G.
• Application Number:
  US10/162,084
• Publication Number:
  US 20030097120A1
• Time in Patent Office: 790 Days
• Field of Search: 528/70, 528/38, 528/29, 528/65, 528/66, 528/335, 528/359, 528/401, 528/44, 528/391, 528/390, 530/300, 530/345
• US Class Current: 528/29
• CPC Class Codes: A61L 33/0017 using a surface active agent
• CPC Class Codes: C08G 18/2805 Compounds having only one group containing active hydrogen vinylpolymers having terminal groups containing active hydrogen C08G18/62
• CPC Class Codes: C08G 18/2885 containing halogen atoms
• CPC Class Codes: C08G 18/44 Polycarbonates
• CPC Class Codes: C08G 18/4854 Polyethers containing oxyalkylene groups having four carbon atoms in the alkylene group
• CPC Class Codes: C08G 18/6446 Proteins and derivatives thereof
• CPC Class Codes: C08G 18/6484 Polysaccharides and derivatives thereof
• CPC Class Codes: C08G 18/771 oxygen
• CPC Class Codes: C08G 65/007 containing fluorine

Abstract

This invention relates to macromolecule modifiers containing biologically active drugs/biomolecules, or precursors thereof, and fluoroligomers; compositions comprising the macromolecules containing the drugs and fluoroligomers in admixture with polymers, particularly biomedical polymers; articles made from the admixtures, particularly medical devices. Specifically, the modifier has the general formula

is a central portion comprising an oligomeric polymeric segment having a theoretical molecular weight of less than 15,000, and being compatible with said base polymer; wherein

[oligo] is a first oligomeric segment;

[link A] is a second coupling segment linking one [oligo] to another [oligo] within said central portion;

n is 0 to 20;

[fluoro] is a polyfluoro oligomeric group; and

[link B] is a first coupling segment linking said central portion to said [fluoro] through said first coupling segment; and coupled to a bioactive moiety [Bio] or precursor thereof; and

m is 1 to 20.

Claims

1. A bioactive fluoroalkyl surface modifier for use in admixture with a compatible base polymer, said modifier having the general formula

is a central portion comprising an oligomeric polymeric segment having a theoretical molecular weight of less than 15,000, and being compatible with said base polymer;

wherein

[oligo] is a first oligomeric segment;

[link A] is a second coupling segment linking one [oligo] to another [oligo] within said central portion;

n is 0 to 20;

[fluoro] is a polyfluoro oligomeric group; and

[link B] is a first coupling segment linking said central portion to said [fluoro] through said first coupling segment; and

coupled to a bioactive moiety [Bio] or precursor thereof; and

m is 1 to 20.

2. A modifier as defined in claim 1 having the general formula

wherein

n is 0-20; and

m is 1-20;

provided that when n is 0, m is 1.

3. A modifier as defined in claim 1 wherein said oligomeric polymeric segment has an absolute molecular weight of less than 10,000.

4. A modifier as defined in claim 3 wherein said oligomeric polymeric segment has an absolute molecular weight of less than 5,000.

5. A modifier as defined in claim 1 wherein said [oligo] is selected from the group consisting of polyurethane, polyurea, polyamides, polyalkylene oxide, polycarbonate, polyester, polylactone, polysilicone, polyethersulfone, polyolefin, polyvinyl derivative, polypeptide and polysaccharide segments.

6. A modifier as defined in claim 1 wherein said [link A] and [link B] are selected from the group consisting of an oligoamide;

oligourethane;

oligourea;

oligosulphonate;

oligosulphonamide;

oligoester;

oligoacetal oligoimine segment, and combinations thereof.

7. A modifier as defined in claim 1 wherein said [fluoro] has a molecular weight selected from 100 to 1500.

8. A modifier as defined in claim 1 wherein said [fluoro] is selected from the group consisting of radicals of the general formula CF₃(CF₂)_pCH₂CH₂—

wherein p is 2-20 and CF₃(CF₂)_m(CH₂CH₂O)_q- wherein q is 1-10 and m is 1-20.

9. A modifier as defined in claim 8 wherein said [fluoro] is C₈F₁₇CH₂CH₂-.

10. A modifier as defined in claim 1 wherein said bioactive moiety [Bio] is selected from the group consisting of an anti-inflammatory, anti-coagulant, anti-oxidant, antibiotic, cell receptor ligand, bioadhesive molecular, oligonucleic acid and phospholipid compound.

11. A modifier as defined in claim 10 wherein said bioactive material is selected from the group consisting of fluoroquinolone, Heparin, Hyaluronic acid, Vitamin E, peptide, hydrocortisone and L-α

glycerophosphoryl choline.

12. A modifier as defined in claim 11 wherein said peptide is selected from GGRGD (SEQ ID NO:

5), YRGDG (SEQ ID NO;

     3) and RGDSPASSKP (SEQ ID NO;

     4).

13. A modifier as defined in claim 1 wherein n is 2 to 10.

14. A composition comprising a bioactive fluoroalkyl surface modifier as defined in claim 1 in admixture with said compatible base polymer.

15. A composition as defined in claim 14 wherein said base polymer is selected from the group consisting of 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 and derivatives, polyamides, polyester-polyethers, styrene-isoprenes, styrene butadienes, thermoplastic polyolefins, styrene-saturated olefins, polyester-polyester, ethylene-vinyl acetate ethylene-ethyl acrylate, ionomers, and thermoplastic polydienes.

16. A composition as defined in claim 15 wherein said base polymer is segmented polyurethane.

17. A composition as defined in claim 15 wherein said base polymer is selected from the group consisting of a polysilicone, a polyester, and a polysaccharide.

18. A composition as defined in claim 14 comprising 0.5 to 10 w/w % of said modifier.

19. A composition as defined in claim 18 comprising 1 to 5 w/w % of said modifier.

20. A composition as defined in claim 14 in the form of a shaped article.

21. A shaped article as defined in claim 20 in the form of an implantable medical device, self-supporting film, or fiber.

22. A modifier having the general formula

wherein [[oligo]-(link A-[oligo])_n] is a central portion comprising an oligomeric polymeric segment having a theoretical molecular weight of less than 15,000, and being compatible with said base polymer;

[oligo] is a first oligomeric segment;

[link A] is a second coupling segment linking one [oligo] to another [oligo] within said central portion;

n is 0 to 20;

[fluoro] is a polyfluoro oligomeric group; and

[link B] is a first coupling segment linking said central portion to said [fluoro] through said first coupling segment; and

coupled to a bioactive moiety [Bio] or precursor thereof; and

m is 1 to 20.