Pre-loadable dried biological heart valve and preparation method thereof

Patent metadata

Field	Value
Publication number	US-12064531-B2
Application number	US-202117313877-A
Country	US
Kind code	B2
Filing date	May 6, 2021
Priority date	Sep 19, 2018
Publication date	Aug 20, 2024
Grant date	Aug 20, 2024

Abstract

A pre-loadable dried biological heart valve and a preparation method thereof. The preparation method includes: Step A: soaking a fresh animal pericardium in an aqueous solution of soluble elastin or glycosaminoglycan, and then subjecting the pericardium to a first cross-linking reaction in a mixed solution of carbodiimide or N-hydroxysuccinimide to allow the soluble elastin or glycosaminoglycan to bind to the pericardium via a chemical bond; and Step B: subjecting the pericardium after the first cross-linking to a second cross-linking reaction in an aqueous glutaraldehyde solution, and then drying the pericardium after the second cross-linking, to obtain the pre-loadable dried biological heart valve. The dried biological heart valve obtained by the above preparation method has good toughness, and is rapidly flattened out in a simulated folding and pressing test.

First claim

What is claimed is:

1. A method for preparing a pre-loadable dried biological heart valve, comprising:
Step A: soaking a fresh animal pericardium in an aqueous solution of soluble elastin or glycosaminoglycan, and then subjecting the pericardium to a first cross-linking reaction in a mixed solution of carbodiimide or N-hydroxysuccinimide to allow the soluble elastin or glycosaminoglycan to bind to the pericardium via a chemical bond; and
Step B: subjecting the pericardium after the first cross-linking to a second cross-linking reaction in an aqueous glutaraldehyde solution, and then drying the pericardium after the second cross-linking, to obtain the pre-loadable dried biological heart valve.

2. The method for preparing a pre-loadable dried biological heart valve according to claim 1 , wherein in Step A, the pericardium is soaked for 2 to 24 hrs in a 0.1 to 10 wt % aqueous solution of soluble elastin or glycosaminoglycan at 25 to 37° C. with shaking.

3. The method for preparing a pre-loadable dried biological heart valve according to claim 1 , wherein in Step A, the pericardium is subjected to the first cross-linking reaction by soaking in a 0.1 to 1 M mixed solution of carbodiimide or N-hydroxysuccinimide at 25 to 37° C. with shaking for 2 to 24 hrs.

4. The method for preparing a pre-loadable dried biological heart valve according to claim 1 , wherein in Step B, the pericardium after the first cross-linking is subjected to cross-linking reaction by soaking in a 0.25 to 1 vol % aqueous glutaraldehyde solution at 25 to 37° C. with shaking for 1 to 7 days.

5. The method for preparing a pre-loadable dried biological heart valve according to claim 1 , wherein in Step B, the drying is dehydration and drying in an alcohol solvent.

6. The method for preparing a pre-loadable dried biological heart valve according to claim 5 , wherein in Step B, the pericardium after the second cross-linking is dehydrated and dried over gradient concentrations of an alcohol solvent.

7. The method for preparing a pre-loadable dried biological heart valve according to claim 5 , wherein in Step B, the alcohol solvent comprises one or more of methanol, ethanol, isopropanol, glycerol, n-propanol, n-butanol, n-pentanol, n-undecanol, n-dodecanol, 2-propanol, 2-butanol, 2-hexanol, cyclohexanol and tert-butanol.

8. The method for preparing a pre-loadable dried biological heart valve according to claim 6 , wherein in Step B, the pericardium after the secondary crosslinking is sequentially soaked in 50% isopropanol or 50% glycerol for 20-30 hrs, and then in 90% isopropanol or 10% glycerol for 20 to 30 hrs at 25 to 37° C. to accomplish the dehydration and drying.

9. The method for preparing a pre-loadable dried biological heart valve according to claim 1 , wherein in Step A, the soluble elastin or glycosaminoglycan solution is selected from a group consisting of: soluble elastin, hyaluronic acid, chondroitin sulfate, dermatan sulfate, keratan sulfate, heparan sulfate, heparin, and a mixture of any combination thereof.

10. The method for preparing a pre-loadable dried biological heart valve according to claim 1 , wherein in Step A, the method further comprises a step of washing the fresh animal pericardium before soaking the fresh animal pericardium in the aqueous solution of soluble elastin or glycosaminoglycan.

11. The method for preparing a pre-loadable dried biological heart valve according to claim 10 , wherein the step of washing the fresh animal pericardium comprises washing the fresh animal pericardium with distilled water at 3 to 5° C. with shaking at 80 to 120 rpm for 1.5 to 3 hrs.

12. The method for preparing a pre-loadable dried biological heart valve according to claim 10 , wherein the step of washing the fresh animal pericardium comprises a cell removal treatment.

13. A pre-loadable dried biological heart valve, prepared by the method according to claim 1 .

Assignees

• Venus Medtech Hangzhou Inc
• Univ Sichuan

Inventors

• Wang Yunbing
• Lei Yang
• Li Gaocan
• Yang Li
• Lim Hou-Sen
• Kuang Dajun
• Yu Jincheng

Classifications

• A61L2430/20

  for reconstruction of the heart, e.g. heart valves · CPC title

• A61L27/3641

  characterised by the site of application in the body (materials for artificial blood vessels A61L27/507; materials for use in artificial skin A61L27/60) · CPC title

• A61L27/3625 Primary

  Vascular tissue, e.g. heart valves · CPC title

• A61L2400/18

  Modification of implant surfaces in order to improve biocompatibility, cell growth, fixation of biomolecules, e.g. plasma treatment · CPC title

• A61L27/3687 Primary

  characterised by the use of chemical agents in the treatment, e.g. specific enzymes, detergents, capping agents, crosslinkers, anticalcification agents · CPC title