Method for creation of biomimetic surfaces

• US 5,939,208 A
• Filed: 11/07/1997
• Issued: 08/17/1999
• Est. Priority Date: 11/07/1997
• Status: Expired due to Term

• Current Assignee: Replication Medical, Inc.
• Original Assignee: Bio-Mimetics, Inc.
• Inventors: Stoy, Patrick
• Primary Examiner(s): Dudash, Diana
• Application Number:
  US08/966,343
• Time in Patent Office: 648 Days
• Field of Search: 427/337, 427/336, 427/352, 427/353, 427/2.24, 427/2.3, 427/414, 427/2.28, 427/2.1, 427/2.12, 427/2.13, 427/333, 427/340, 428/500, 428/424.2, 428/424.7, 523/103, 523/105, 523/106, 523/108, 424/422, 424/423, 424/427, 424/487
• US Class Current: 428/500
• CPC Class Codes: A61L 2300/208 Quaternary ammonium compounds
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• 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 29/08 Materials for coatings
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/08 Materials for coatings
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C08J 2333/04 esters
• CPC Class Codes: C08J 7/12 Chemical modification
• CPC Class Codes: Y10T 428/31573 Next to addition polymer of ethylenically unsaturated monomer
• CPC Class Codes: Y10T 428/31583 Nitrile monomer type [polyacrylonitrile, etc.]
• CPC Class Codes: Y10T 428/31855 Of addition polymer from unsaturated monomers

Abstract

In the present invention method, the surface of articles made of acrylic polymers and methacrylic polymers are converted into thin biomimetic layers by using the process involving at least the following two steps:

(a) The polymer surface is contacted, in the presence of water and for a predetermined reaction time necessary to form a continuous surface layer thinner than about 500 microns, with a solution containing one or more tetraalkylammonium hydroxides of the general formula:

R.sub.1 R.sub.2 R.sub.3 R.sub.4 N.sup.+ OH.sup.-

where R₁, R₂, R₃, R₄ are the alkyl substituents, in which the sum of the number of carbon atoms is equal to or larger than 8 but smaller than 45; and,

(b) The article is removed from the aqueous reaction solution and excess of tetraalkylammonium hydroxide is removed from the polymer surface by washing the polymer with a liquid miscible with the tetraalkylammonium hydroxide.

Claims

1. A method of creating a biomimetic negatively charged, hydrated layer on the surface of an article formed primarily from polymers selected from acrylic polymers, methacrylic polymers, and copolymers or mixtures thereof, which polymers are hydrogel polymers which are capable of being swelled in water, which comprises:

(a) contacting said article at a temperature between 20°

C. and 125°

C., with tetraalkylammonium hydroxide solution of a solvent which is immiscible with water, said solution having at least one tetraalkylammonium hydroxide having a general formula;

space="preserve" listing-type="equation">R.sub.1 R.sub.2 R.sub.3 R.sub.4 N.sup.+ OH.sup.-

where R₁, R₂, R₃, R₄ are alkyl substituents, in which the sum of the number of carbon atoms is equal to or larger than 8 but less than 45, and;

(b) removing the article from said tetraalkylammonium hydroxide solution and removing the excess of the said solution by washing in an aqueous washing solution of an acid with a pK value of less than 4.5, said aqueous washing solution being miscible with said tetraalkylammonium hydroxide.

2. The method according to claim 1 wherein said tetraalkylammonium hydroxide has at least 15 but less than 25 carbon atoms.

3. The method according to claim 1 wherein said step (a) solution contains from 1% by weight to 40% by weight of said tetraalkylammonium hydroxide.

4. The method according to claim 3 wherein said solution contains from 5% by weight to 15% by weight of said tetraalkylammonium hydroxide.

5. The method according to claim 1 wherein said temperature is between 50°

C. and 90°

C.

6. The method according to claim 1 wherein said polymers are selected from polymers having ester pendant groups, polymers having amide pendant groups, polymers having nitrile pendant groups and copolymers and mixtures thereof.

7. The method according to claim 6 wherein said amide pendant groups are derived from amides of compounds selected from the group consisting of ammonia;

an alkylamine containing 1 to 4 carbons;

a dilalkylamine containing 2 to 8 carbons;

hydroxyalkylamine containing 2 to 6 carbons;

glucosamine;

arginine;

lysine;

taurine and alanine.

8. The method according to claim 6 wherein said esters are esters of hydroxy compounds selected from the group consisting of ethylene glycol;

diethylene glycol;

triethylene glycol;

glycerol;

1,2-propylene glycol;

benzylalcohol;

dihydroxybenzophenone;

borneol;

isoborneol and aliphatic alcohols containing between 1 and 8 carbon atoms.

9. The article having a product comprising a surface polymer layer created by the method according to claim 1.

10. A method of creating a biomimetic negatively charged, hydrated layer on the surface of an article formed primarily from polymers selected from acrylic polymers, methacrylic polymers, and copolymers or mixtures thereof, which polymers are hydrogel polymers which are capable of being swelled in water, which comprises:

(a) contacting said article at a temperature between 20°

C. and 125°

C., with tetraalkylammonium hydroxide aqueous solution, said solution having at least one tetraalkylammonium hydroxide having a general formula;

space="preserve" listing-type="equation">R.sub.1 R.sub.2 R.sub.3 R.sub.4 N.sup.+ OH.sup.-

where R₁, R₂, R₃, R₄ are alkyl substituents, in which the sum of the number of carbon atoms is equal to or larger than 8 but less than 45, and;

(b) removing the article from said tetraalkylammonium hydroxide solution and removing the excess of the said solution by washing in a washing liquid miscible with said tetraalkylammonium hydroxide.

11. The method according claim 10 wherein said tetraalkylammonium hydroxide has at least 15 but less than 25 carbon atoms.

12. The method according to claim 10 wherein said step (a) aqueous solution is an aqueous solution containing said tetraalkylammonium hydroxide, water, and a water-miscible solvent.

13. The method according to claim 12 wherein said water-miscible solvent is a compound selected from the group consisting of dimethylsulfoxide;

dimethylformamide;

y-butyrolactone;

tetrahydrofuran;

dioxane;

sodium thiocyanate;

glycerol;

propylene glycol;

ethylene glycol;

hydroxyalkyl amine where the alkyl substituent has 2 to 6 carbons;

diethylene glycol;

triethylene glycol;

polyethylene glycol;

methylethers of polyethylene glycols; and

copolymers of ethylene and propylene glycols.

14. The method according to claim 10 wherein said step (a) solution contains from 1% by weight to 40% by weight of said tetraalkylammonium hydroxide.

15. The method according to claim 14 wherein said solution contains from 5% by weight to 15% by weight of said tetraalkylammonium hydroxide.

16. The method according to claim 10 wherein said temperature is between 50°

C. and 90°

C.

17. The method according to claim 10 wherein said polymers are selected from polymers having ester pendant groups, polymers having amide pendant groups, polymers having nitrile pendant groups and copolymers and mixtures thereof.

18. The method according to claim 10 wherein said step (b) is an aqueous washing solution of an acid with pK value of less than 4.5.

19. The method according to claim 17 wherein said esters are esters of hydroxy compounds selected from the group consisting of ethylene glycol;

diethylene glycol;

triethylene glycol;

glycerol;

1,2-propylene glycol;

benzylalcohol;

dihydroxybenzophenone;

borneol;

isoborneol and aliphatic alcohols containing between 1 and 8 carbon atoms.

20. The article having a product comprising a surface polymer layer created by the method according to claim 10.