Methods for treating bioprosthetic tissue using a nucleophile/electrophile in a catalytic system

• US 10,238,771 B2
• Filed: 11/07/2013
• Issued: 03/26/2019
• Est. Priority Date: 11/08/2012
• Status: Active Grant

• Current Assignee: Edwards Lifesciences Corporation
• Original Assignee: Edwards Lifesciences Corporation
• Inventors: Xu, Dengfeng, Dove, Jeffrey S.
• Primary Examiner(s): Fan, Lynn Y
• Application Number:
  US14/074,379
• Publication Number:
  US 20140127804A1
• Time in Patent Office: 1,965 Days
• Field of Search: 435375
• CPC Class Codes: A61L 2400/02 Treatment of implants to prevent calcification or mineralisation in vivo
• CPC Class Codes: A61L 2430/40 Preparation and treatment of biological tissue for implantation, e.g. decellularisation, cross-linking
• CPC Class Codes: A61L 27/3687 characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents

Abstract

Methods for treating a bioprosthetic tissue are described herein. The methods comprise contacting the bioprosthetic tissue with at least one nucleophile and/or at least one electrophile in the presence of a catalytic system comprising at least one or a combination of a fluoride-based salt, a cesium-based salt, a potassium-based salt, a rubidium-based salt, or a carbonate-based salt. The methods may be used to alter functional groups on biological tissue which represent actual and potential calcium binding sites and also processes for cross-linking bioprosthetic tissue. Both processes may be used in conjunction with known fixative techniques, such as glutaraldehyde fixation, or may be used to replace known fixative techniques.

Claims

1. A method for treating a bioprosthetic tissue comprising:

contacting the bioprosthetic tissue with a nucleophile in the presence of a catalytic system to at least partially cross-link the bioprosthetic tissue;

wherein the nucleophile directly reacts with tissue functional groups associated with the bioprosthetic tissue, and wherein the nucleophile comprises cystamine;

wherein the catalytic system comprises at least one or a combination of a fluoride-based salt, a cesium-based salt, a potassium-based salt, or a rubidium-based salt;

wherein the bioprosthetic tissue is not treated with a glutaraldehyde to at least partially cross-link the bioprosthetic tissue; and

wherein the bioprosthetic tissue has reduced antigenicity and reduced binding sites for calcium after implantation.

2. The method of claim 1, wherein the catalytic system further comprises at least one pyridinium salt.

3. The method of claim 2, wherein the pyridinium salt comprises one or more selected from the group consisting of:

2-fluoro-1-methylpyridinium p-toluenesulfonate (FMPTS), 2-fluoro-1-ethylpyridinium p-toluenesulfonate (FEPTS), 2-chloro-1-methylpyridinium p-toluenesulfonate (CEPTS), and 2-chloro-1-methylpyridinium iodide (CMPI).

4. The method of claim 3, wherein the catalytic system comprises FMPTS and CsF.

5. The method of claim 1, wherein the catalytic system comprises one or both of the fluoride-based salt and the carbonate based salt.

6. The method of claim 1, wherein the fluoride-based salt is one or a combination of CsF, RbF and KF.

7. The method of claim 1, wherein the cesium-based salt is one or a combination of CsF and Cs₂CO₃.

8. The method of claim 1, wherein the potassium-based salt is one or a combination of KF and K₂CO₃.

9. The method of claim 1, wherein the rubidium-based salt is one or a combination of RbF and Rb₂CO₃.

10. The method of claim 1, wherein the contacting is performed in a solvent system, and wherein the solvent system comprises one or more selected from the group consisting of:

an alcohol, a nitrile, a ketone, an ester, an amide, a sulfoxide, an ether, a cyclic ether, a lactone, and a lactam.

11. The method of claim 10, wherein the solvent system comprises one or more selected from the group consisting of:

acetonitrile, butyl acetate, ethyl acetate, N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), 1,4-dioxane, glycerol, 3-methyl-1-mutanol, 1-methyl-2-pyrrolidinone, pyridine, tetrahydrofuran (THF), and diglyme.

12. The method of claim 1, wherein the contacting is performed in a solvent system comprising glycerol and ethanol.

13. The method of claim 1, wherein the contacting is performed in a solvent system comprising one or more selected from the group consisting of:

water, saline, phosphate-buffered saline (PBS), buffers having a pH of 1-13, and mixtures of organic solvents with water or buffers having a pH of 1-13.

14. The method of claim 1, wherein the catalytic system comprises CsF and FMPTS;

and wherein the contacting is performed in a solvent system comprising DMSO or glycerol and ethanol.

15. The method of claim 1, wherein the catalytic system comprises CsF and FMPTS;

and wherein the contacting is performed in a solvent system comprising a buffered aqueous solution.

16. The method of claim 1, further comprising treating the bioprosthetic tissue with glycerol.

17. The method of claim 16, wherein the bioprosthetic tissue is treated with glycerol after the bioprosthetic tissue is contacted with the nucleophile in the presence of the catalytic system.