Covalent modification of metal surfaces

• US 20080035243A1
• Filed: 07/09/2007
• Published: 02/14/2008
• Est. Priority Date: 07/07/2006
• Status: Active Grant

• Current Assignee: Intezyne Technologies
• Original Assignee: Intezyne Technologies
• Inventors: Skaff, Habib, Breitenkamp, Kurt, Breitenkamp, Rebecca, Sill, Kevin
• Granted Patent: US 8,066,824 B2
• Time in Patent Office: Days
• US Class Current: 148/240
• CPC Class Codes: A61F 2/82 Devices providing patency to, or preventing collapsing of, tubular structures of the body, e.g. stents stent-grafts for tubular structures of the body other than blood vessels A61F2/04; stent-grafts for blood vessels A61F2/07; instruments specially adapted for placement or removal of stents or stent-grafts A61F2/95; for closing wounds, or holding wounds closed A61B17/04 - A61B17/115; dilators A61M29/00
• CPC Class Codes: A61L 2400/18 Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment
• CPC Class Codes: A61L 27/04 Metals or alloys
• 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 31/022 Metals or alloys
• CPC Class Codes: A61L 31/14 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: B05D 1/185 applying monomolecular layers B05D1/204 takes precedence
• CPC Class Codes: B05D 2202/00 Metallic substrate
• CPC Class Codes: B05D 3/102 Pretreatment of metallic substrates C23C takes precedence
• CPC Class Codes: B05D 3/142 Pretreatment
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 40/00 Manufacture or treatment of nanostructures
• CPC Class Codes: C07D 498/02 in which the condensed system contains two hetero rings

Abstract

The present invention provides modified metal surfaces, methods of preparing the same, and intermediates thereto. These materials are useful in a variety of applications including biomaterials.

Claims

1. A method for covalently modifying a metal surface, comprising the steps of introducing hydroxyl groups onto a metal substrate and covalently bonding a polymer or small molecule organic moiety onto the resulting hydrophilic metal surface.

2. The method according to claim 1, wherein the metal substrate comprises iron.

3. The method according to claim 1, wherein the metal substrate is selected from a stainless steel, a cobalt alloy, a titanium alloy, an iron alloy, steel, stainless steel, austenitic stainless steel, Type 316 stainless steel, ferritic stainless steel, martensitic stainless steel, duplex stainless steel, cobalt, a cobalt alloy, a cobalt-chromium alloy, stellite alloys, Vitallium®

, titanium, titanium alloy, or a super-alloy.

21. A method for expanding the lumen of a body passageway, comprising inserting a stent into the passageway, the stent having a generally tubular structure, at least a portion of the surface of the structure being covalently modified according to the method of claim 1, such that the passageway is expanded.

4. A method for preparing a covalently modified metal surface, comprising the steps of:

(a) modifying a metal substrate to incorporate thereon a plurality of hydroxyl groups;

(b) providing a compound of formula I;

wherein;

wherein;

R¹ is a natural or synthetic polymer or copolymer group or a small molecule organic group;

W is —

C(═

O)OH, —

C(═

O)X, —

P(═

O)(OH)₂, —

P(═

O)(X)₂, —

P(═

O)(R^a)OH, —

P(═

O)(R^a)X, —

O—

S(═

O)₂OH, —

S(═

O)₂OH, —

Si(R^a)₂OH, —

Si(OR^a)₂OH, —

Si(R^a)₂X, —

Si(R^a)(OH)₂, —

Si(R^a)X₂, —

Si(OR^a)₂X, C(═

O)H, —

N═

C═

S, —

N═

C=O, phenol, thiophenol, or an epoxide;

each X is independently Cl, Br, or I; and

each R^a is hydrogen, an alkyl group, or an aryl group; and

(c) coupling the compound of formula I to one or more of the hydroxyl groups on the metal surface.

5. The method according to claim 4, wherein step (c) is performed by condensation or dehydration reaction.

6. The method according to claim 4, wherein R¹ is poly(ethylene glycol) (PEG), a heterobifunctional PEG, a branched PEG, PEG-b-PAA-b-PAA block copolymers, PEG-b-PAA-b-PEG block copolymers, PEG-b-polyester-b-PEG block copolymers, PEG-b-PAA block copolymers, dextran, chitosan, amylose, amylopectin, glycogen, xanthan, gellan, or pullulun.

7. The method according to claim 4, wherein R¹ is a monosaccharide, a disaccharide, a phosphorylcholine, a phosoplipid, a cyclodextran, or a small molecule drug.

8. A method for preparing a covalently modified metal surface, comprising the steps of:

(a) providing a metal surface having a plurality of hydroxyl groups;

(b) providing a compound of formula I;

wherein;

R¹ is a natural or synthetic polymer or copolymer group or a small molecule organic group;

W is —

C(═

O)OH, —

C(═

O)X, —

P(═

O)(OH)₂, —

P(═

O)(X)₂, —

P(═

O)(R^a)OH, —

P(═

O)(R^a)X, —

O—

S(═

O)₂OH, —

S(═

O)₂OH, —

Si(R^a)₂OH, —

Si(OR^a)₂OH, —

Si(R^a)₂X, —

Si(R^a)(OH)₂, —

Si(R^a)X₂, —

Si(OR^a)₂X, C(═

O)H, —

N═

C═

S, —

N═

C=O, phenol, thiophenol, or an epoxide;

each X is independently Cl, Br, or I; and

each R^a is hydrogen, an alkyl group, or an aryl group; and

(c) coupling the compound of formula I to one or more of the hydroxyl groups on the metal surface.

9. The method according to claim 8, wherein R¹ is a group of formula II:

10. The method according to claim 9, wherein R¹ is a group of formula II-d:

11. The method according to claim 9, further comprising the step of coupling the azide-terminal end to a suitable group via Click chemistry.

12. The method according to claim 8, wherein R¹ is a block copolymer group of formula III:

13. The method according to claim 8, wherein R¹ is a block copolymer group of formula IV:

14. The method according to claim 8, wherein R¹ is a group of formula V:

15. The method according to claim 8 wherein R¹ is selected from any of the groups depicted in Tables 2 and 3.

16. A compound of formula II-e:

17. An implantable device, wherein at least a portion of said device is a covalently modified metal surface.

18. The implantable device according to claim 17, wherein said device is PEGylated.

19. The implantable device according to claim 17, wherein said device is selected from cardiovascular devices (e.g., implantable venous catheters, venous ports, tunneled venous catheters, chronic infusion lines or ports, including hepatic artery infusion catheters, pacemaker wires, implantable defibrillators);

neurologic/neurosurgical devices (e.g., ventricular peritoneal shunts, ventricular atrial shunts, nerve stimulator devices, dural patches and implants to prevent epidural fibrosis post-laminectomy, devices for continuous subarachnoid infusions);

gastrointestinal devices (e.g., chronic indwelling catheters, feeding tubes, portosystemic shunts, shunts for ascites, peritoneal implants for drug delivery, peritoneal dialysis catheters, implantable meshes for hernias, suspensions or solid implants to prevent surgical adhesions, including meshes);

genitourinary devices (e.g., uterine implants, including intrauterine devices (IUDs) and devices to prevent endometrial hyperplasia, fallopian tubal implants, including reversible sterilization devices, fallopian tubal stents, artificial sphincters and periurethral implants for incontinence, ureteric stents, chronic indwelling catheters, bladder augmentations, or wraps or splints for vasovasostomy);

otolaryngology devices (e.g., ossicular implants, Eustachian tube splints or stents for glue ear or chronic otitis as an alternative to transtempanic drains); and

orthopedic implants (e.g., cemented orthopedic prostheses).

20. The implantable device according to claim 19, wherein said device is a stent.