Photoactive biocompatible coating composition

• US 20070154518A1
• Filed: 12/29/2005
• Published: 07/05/2007
• Est. Priority Date: 12/29/2005
• Status: Abandoned Application

• Current Assignee: Cordis Corporation (Cardinal Health, Inc.)
• Original Assignee: Cordis Corporation (Cardinal Health, Inc.)
• Inventors: Falotico, Robert, Zhao, Jonathon
• Application Number:
  US11/321,424
• Publication Number:
  US 20070154518A1
• Time in Patent Office: Days
• US Class Current: 424/424
• CPC Class Codes: A61L 2300/236 Glycosaminoglycans, e.g. heparin, hyaluronic acid, chondroitin
• CPC Class Codes: A61L 2300/41 Anti-inflammatory agents, e.g. NSAIDs
• CPC Class Codes: A61L 2300/418 Agents promoting blood coagulation, blood-clotting agents, embolising agents
• CPC Class Codes: A61L 2300/434 of enzymes
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors

Abstract

The present invention discloses a biocompatible coating composition that can be photo crosslinked when exposed to long wavelength ultraviolet light. The biocompatible coating composition comprises at least one biocompatible polymer having a photoactive moiety covalently attached thereto, and a biologically active molecule having a photoactive moiety covalently attached thereto. The photoactive moiety covalently attached to the biologically active molecule and the photoactive moiety covalently attached to the at least one biocompatible polymer are the same or different, and absorb and respond to ultraviolet light having a wavelength band of about 300 nm or above. Preferably, the photoactive moiety is a chemical moiety derived from thioxanthone. The inventive biocompatible coating composition can be applied on at least a portion of one surface of an article.

Claims

1. A biocompatible coating composition for applying on at least a portion of one surface of an article, comprising at least one biocompatible polymer having a photoactive moiety covalently attached thereto, and a biologically active molecule having a photoactive moiety covalently attached thereto;

wherein the photoactive moiety covalently attached to the biologically active molecule and the photoactive moiety covalently attached to the at least one biocompatible polymer are the same or different, and absorb and respond to ultraviolet light having a wavelength band of about 300 nm or above.

2. The biocompatible coating composition of claim 1, wherein the photoactive moieties are chemical moieties having the following structure:

wherein R¹, R², R³, R⁴, R⁵, R⁶, and R⁷ are the same or different, and are hydrogen, halogen, hydroxy, amino, —

CN, —

COOH, —

NO₂, phenylsulfonyl, C1-C12 alkyl, C3-C6 cycloalkyl, C1-C12 alkoxy, C1-C12 alkylthio, —

NHR⁸, or N,N-dialkylamino having 1 to 6 carbon atoms in the alkyl moiety;

X is CH₂, O, S, NR⁸; and

R⁸ is C1-C6 alkyl.

3. The biocompatible coating composition of claim 1, wherein the at least one biocompatible polymer having a photoactive moiety covalently attached thereto is derived from a biocompatible polymer and a reactive photoinitiator, wherein the reactive photoinitiator comprises a photoactive moiety and a functional group, wherein the photoactive moiety absorbs and responds to ultraviolet light having a wavelength band of about 300 nm or above, and the functional group reacts with the biocompatible polymer forming a covalent bond.

4. The biocompatible coating composition of claim 3, wherein the biocompatible polymer is a water-soluble polymer.

5. The biocompatible coating composition of claim 1, wherein the at least one biocompatible polymer having a photoactive moiety covalently attached thereto comprising a repeating unit having the following structure:

wherein M is an alkali metal cation, n is an integer of 10 to 5000.

6. The biocompatible coating composition of claim 1, wherein the at least one biocompatible polymer having a photoactive moiety covalently attached thereto comprising a repeating unit having the following structure:

wherein R¹, R², R³, R⁴, R⁵, R⁶, and R⁷ are the same or different, and are hydrogen, halogen, hydroxy, amino, —

CN, —

COOH, —

NO₂, phenylsulfonyl, C1-C12 alkyl, C3-C6 cycloalkyl, C1-C12 alkoxy, C1-C12 alkylthio, —

NHR⁸, or N,N-dialkylamino having 1 to 6 carbon atoms in the alkyl moiety;

X is CH₂, O, S, NR⁸;

M is an alkali metal cation;

n is an integer of 10 to 5000; and

R⁸ is C1-C6 alkyl.

7. The biocompatible coating composition of claim 1, wherein the biologically active molecule having a photoactive moiety covalently attached thereto is derived from a biologically active molecule and a reactive photoinitiator, wherein the reactive photoinitiator comprises a photoactive moiety and a functional group, wherein the photoactive moiety absorbs and responds to ultraviolet light having a wavelength band of about 300 nm or above, and the functional group reacts with the biologically active molecule forming a covalent bond.

8. The biocompatible coating composition of claim 7, wherein the biologically active molecule is selected from the group consisting of anti-thrombogenic agents, immuno-suppressants, anti-neoplastic agents, anti-inflammatory agents, angiogenesis inhibitors, and protein kinase inhibitors.

9. The biocompatible coating composition of claim 7, wherein the biologically active molecule is an anti-thrombogenic agent, or an immuno-suppressant.

10. The biocompatible coating composition of claim 7, wherein the biologically active molecule is heparin, or sirolimus.

11. The biocompatible coating composition of claim 3 or 7, wherein the reactive photoinitiator has the following structure:

wherein R¹, R², R³, R⁴, R⁵, R⁶, and R⁷ are the same or different, and are hydrogen, halogen, hydroxy, amino, —

CN, —

COOH, —

NO₂, phenylsulfonyl, C1-C12 alkyl, C3-C6 cycloalkyl, C1-C12 alkoxy, C1-C12 alkylthio, —

NHR⁸, or N,N-dialkylamino having 1 to 6 carbon atoms in the alkyl moiety;

X is CH₂, O, S, NR⁸; and

R⁸ is C1-C6 alkyl.

12. The biocompatible coating composition of claim 3 or 7, wherein the reactive photoinitiator has the following structure:

13. The biocompatible coating composition of claim 1, wherein the biologically active molecule having a photoactive moiety covalently attached thereto has the following structure:

wherein R¹, R², R³, R⁴, R⁵, R⁶, and R⁷ are the same or different, and are hydrogen, halogen, hydroxy, amino, —

CN, —

COOH, —

NO₂;

phenylsulfonyl, C1-C12 alkyl, C3-C6 cycloalkyl, C1-C12 alkoxy, C1-C12 alkylthio, —

NHR′

, or N,N-dialkylamino having 1 to 6 carbon atoms in the alkyl moiety;

X is CH₂, O, S, NR⁸;

m is an integer of 10 to 5000;

R⁸ is C1-C6 alkyl; and

m is an integer of 1 and 20.

14. The biocompatible coating composition of claim 1, wherein the coating composition has a thickness of about 1 nanometer to about 10 micrometer.

15. An article having a biocompatible coating thereon, the biocompatible coating comprising at least one biocompatible polymer having a photoactive moiety covalently attached thereto, and a biologically active molecule having a photoactive moiety covalently attached thereto;

wherein the photoactive moiety covalently attached to the biologically active molecule and the photoactive moiety covalently attached to the at least one biocompatible polymer are the same or different, and absorb and respond to ultraviolet light having a wavelength band of about 300 nm or above.

16. The article of claim 15, wherein the article is a medical device or a component of a medical device.

17. The article of claim 16, wherein the medical device or the component of a medical device is implantable.

18. The article of claim 15, wherein the photoactive moieties are chemical moieties having the following structure:

wherein R¹, R², R³, R⁴, R⁵, R⁶, and R⁷ are the same or different, and are hydrogen, halogen, hydroxy, amino, —

CN, —

COOH, —

NO₂, phenylsulfonyl, C1-C12 alkyl, C3-C6 cycloalkyl, C1-C12 alkoxy, C1-C12 alkylthio, —

NHR⁸, or N,N-dialkylamino having 1 to 6 carbon atoms in the alkyl moiety;

X is CH₂, O, S, NR⁸; and

R⁸ is C1-C6 alkyl.

19. The article of claim 15, wherein the at least one 10 biocompatible polymer having a photoactive moiety covalently attached thereto comprising a repeating unit having the following structure:

wherein M is an alkali metal cation, n is an integer of 10 to 5000.

20. The article of claim 15, wherein the at least one biocompatible polymer having a photoactive moiety covalently attached thereto comprising a repeating unit having the following structure:

wherein R¹, R², R³, R⁴, R⁵, R⁶, and R⁷ are the same or different, and are hydrogen, halogen, hydroxy, amino, —

CN, —

COOH, —

NO₂, phenylsulfonyl, C1-C12 alkyl, C3-C6 cycloalkyl, C1-C12 alkoxy, C1-C12 alkylthio, —

NHR⁸, or N,N-dialkylamino having 1 to-6 carbon atoms in the alkyl moiety;

X is CH₂, O, S, NR⁸;

M is an alkali metal cation;

n is an integer of 10 to 5000; and

R⁸ is C1-C6 alkyl.

21. The article of claim 15, wherein the biologically active molecule having a photoactive moiety covalently attached thereto has the following structure:

wherein R¹, R², R³, R⁴, R⁵, R⁶, and R⁷ are the same or different, and are hydrogen, halogen, hydroxy, amino, —

CN, —

COOH, —

NO₂, phenylsulfonyl, C1-C12 alkyl, C3-C6 cycloalkyl, C1-C12 alkoxy, C1-C12 alkylthio, —

NHR⁸, or N,N-dialkylamino having 1 to 6 carbon atoms in the alkyl moiety;

X is CH₂, O, S, NR⁸;

m is an integer of 10 to 5000;

R⁸ is C1-C6 alkyl; and

m is an integer of 1 and 20.

22. The article of claim 15, wherein the coating composition has a thickness of about 1 nanometer to about 10 micrometers.