Microwave preservation of bioprostheses

• US 4,994,237 A
• Filed: 11/13/1989
• Issued: 02/19/1991
• Est. Priority Date: 10/02/1987
• Status: Expired due to Fees

• Current Assignee: BETH Israel Medical Center (Mount Sinai Beth Israel)
• Original Assignee: BETH Israel Medical Center (Mount Sinai Beth Israel)
• Inventors: Johnson, Robert G., Dvorak, Ann M., Login, Gary R.
• Primary Examiner(s): WARDEN, JILL ALICE
• Assistant Examiner(s): Johnston, Jill
• Application Number:
  US07/435,332
• Time in Patent Office: 463 Days
• Field of Search: 422/21, 422/36, 422/37, 422/40, 435/1
• US Class Current: 435/1.1
• CPC Class Codes: A01N 1/02 Preservation of living parts
• CPC Class Codes: A01N 1/0294 Electromagnetic, i.e. using electromagnetic radiation or electromagnetic fields
• CPC Class Codes: A61L 2/0011 using physical methods
• CPC Class Codes: A61L 2/0082 using chemical substances
• CPC Class Codes: A61L 2/12 Microwaves
• CPC Class Codes: A61L 2/18 Liquid substances or solutions comprising solids or dissolved gases

Abstract

A method to preserve and sterilize biological tissues by exposing the tissue to microwave irradiation, thereby limiting tissue exposure to standard organic preservatives and retaining tissue pliability and other qualities that characterize natural, unpreserved tissue.

Claims

1. A method to preserve and sterilize bioprostheses comprising the following steps:

immersing a specimen of biologic tissue in a preserving solution at room temperature (20°

C.) selected from a member of the group consisting of;

(a) 0.9% sodium chloride;

(b) 0.87% sodium chloride, 0.12% sodium phosphate dibasic, and 0.015% sodium phosphate monobasic, pH 7.3-7.6 (PBS);

(c) 20 mM Tris(hydroxymethyl)aminomethane and 0.9% sodium chloride, pH 7.3-7.6 (TRIS);

(d) 25 mM N-2-hydroxyethylpiperazine-N¹ -2-ethanesulfonic acid, pH 7.3-7.6 (HEPES);

(e) 0.001-0.1% glutaraldehyde in a solution selected from a member of the group consisting of (1) 0.9% sodium chloride, (2) PBS, (3) HEPES, and (4) TRIS;

(f) a calcium chelating agent in a solution selected from a member of the group consisting of (1) 0.9% sodium chloride, (2) PBS, (3) HEPES, and (4) TRIS; and

(g) a calcium chelating agent and 0.001-0.1% glutaraldehyde in a solution selected from a member of the group consisting of (1) 0.9% sodium chloride, (2) PBS, (3) HEPES, and (4) TRIS;

exposing the immersed specimen to microwave irradiation until the final temperature of the solution is between 35° and

50°

C.; and

,

storing the irradiated specimen in a cold sterile osmotically balanced solution selected from the group consisting of (1) 0.9% sodium chloride, (2) PBS, (3) HEPES, and (4) TRIS.

2. The method to preserve and sterilize bioprostheses as set forth in claim 1 wherein said biologic tissue is immersed in the osmotically balanced preserving solution within fifteen minutes after it is harvested from a donor animal and exposed to microwave irradiation.

3. The method to preserve and sterilize bioprostheses as set forth in claim 1 wherein said preserving solution is osmotically balanced to said biologic tissue.

4. The method to preserve and sterilize bioprostheses as set forth in claim 1 wherein said preserving solution is 1-100 mM of the calcium chelating agent ethylinediamenetetraacetic acid (EDTA) in a solution selected from the group consisting of (1) 0.9% sodium chloride, (2) PBS, (3) HEPES, and (4) TRIS.

5. The method to preserve and sterilize as set forth in claim 1 wherein said preserving solution is 1-100 mM of the calcium chelating agent EDTA and 0.001-0.1% glutaraldyde in a solution selected from the group consisting of (1) 0.9% sodium chloride, (2) PBS, (3) HEPES and (4) TRIS.

6. The method to preserve and sterilize bioprostheses as set forth in claim 1 wherein said biologic tissue is irradiated in a microwave oven for between one and fifty seconds until the solution reaches a temperature in the range of 35°

to 50°

C.

7. The method to preserve and sterilize bioprostheses as set forth in claim 1 wherein said cold sterile osmotically balanced storage solution has a temperature of 4°

C.

8. The method to preserve and sterilize bioprostheses as set forth in claim 1 wherein said cold sterile osmotically balanced storage solution further comprises an inhibitor of microbial growth.

9. The method to preserve and sterilize bioprostheses as set forth in claim 8 wherein said inhibitor of microbial growth is selected from the group consisting of 0.02% sodium azide and 0.02% thimerosal.

10. The method to preserve and sterilize bioprostheses as set forth in claim 1 wherein said cold sterile osmotically balanced storage solution further comprises a calcium chelating agent.

11. The method to preserve and sterilize bioprostheses as set forth in claim 10 wherein said calcium chelating agent is 1-100 mM EDTA.

12. The method to preserve and sterilize bioprostheses as set forth in claim 1 wherein said cold sterile osmotically balanced storage solution further comprises 0.001-0.1% glutaraldehyde.

13. A method to preserve and sterilize bioprostheses comprising the following steps:

harvesting a specimen of biologic tissue within fifteen minutes after sacrificing a donor animal;

immersing said specimen of biologic tissue within fifteen minutes of harvesting in a room temperature an osmotically balanced solution selected from the group consisting of;

(a) 0.9% sodium chloride;

(b) PBS;

(c) TRIS;

(d) HEPES;

(e) 0.001-0.1% glutaraldehyde in a solution selected from the group consisting of (1) 0.9% sodium chloride, (2) PBS, (3) HEPES, and (4) TRIS;

(f) 1-100 mM EDTA in a solution selected from group consisting of (1) 0.9% sodium chloride, (2) PBS, (3) HEPES, and (4) TRIS;

(g) 1-100 mM EDTA and 0.001-0.1% glutaraldehyde in a solution selected from the group consisting of (1) 0.9% sodium chloride, (2) PBS, (3) HEPES, and (4) TRIS;

exposing the immersed specimen to microwave irradiation within fifteen minutes of immersion in said preserving solution for 1-50 seconds until the temperature of the solution is between 35° and

50°

C.; and

,

storing the irradiated specimen within thirty seconds of irradiation at 4°

C. in a sterile osmotically balanced solution selected from the group consisting of (1) 0.9% sodium chloride, (2) PBS, (3) HEPES, and (4) TRIS.

14. The method to preserve and sterilize bioprostheses as set forth in claim 13 wherein said sterile osmotically balanced solution further comprises 1-100 mM EDTA, 0.001-0.1% glutaraldehyde, and an inhibitor of microbial growth selected from the group consisting of 0.02% sodium azide and 0.02% thimerosal.