IP Library Granted Patent US 10,433,539
Granted Patent B2
US 10,433,539 · App. 15/521,484 · Granted Oct 8, 2019

Composition and solution with controlled calcium ion level, and related method and use for reperfusion

Inventors: Christopher White (Edmonton, CA); Darren Freed (Edmonton, CA); Larry Hryshko (Edmonton, CA)
Assignee: TEVOSOL, INC.
A01N1/0226A61K31/167
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Quick Facts
Patent No.
US 10,433,539
App. No.
15/521,484
Granted
Oct 8, 2019
Kind
B2
Abstract

A solution comprises a preservation mixture comprising a calcium ion source; and a buffer for maintaining a pH of the solution. The molar concentration of calcium ion (Ca 2+ ) in the solution is from 0.18 to 0.26 mmol/L, and the pH is lower than 7.4 and higher than 6.6. A composition for preparing the solution may comprise adenosine, lidocaine, and a calcium source, wherein the molar ratio of adenosine:calcium is from 0.3:0.26 to 0.45:0.18, and the molar ratio of lidocaine:calcium is from 0.04:0.26 to 0.09:0.18. A donor heart may be reperfused with the solution. The solution may be used for reperfusion of a donor heart, such as at a temperature from about 25 to about 37° C. The donor may be a donor after circulatory death.

Claims (48)

1. A solution comprising:

a cardioplegia mixture comprising a calcium ion source and lidocaine; and

a buffer for maintaining a pH of the solution,

wherein the solution comprises 0.04 to 0.09 mmol/L of lidocaine and 0.18 to 0.26 mmol/L of calcium ion (Ca 2+ ), and the pH is lower than 7.4 and higher than 6.6.

2. The solution of claim 1 , wherein the molar concentration of calcium ion (Ca 2+ ) is 0.22 mmol/L.

3. The solution of claim 1 , wherein the pH is from 6.8 to 7.0.

4. The solution of claim 1 , wherein the pH is 6.9.

5. The solution of claim 1 , wherein the cardioplegia mixture further comprises adenosine and a magnesium ion source.

6. The solution of claim 5 , comprising 0.3 to 0.45 mmol/L of adenosine, and 11 to 15 mmol/L of Mg 2+ .

7. The solution of claim 1 , further comprising a sodium ion source and a potassium ion source.

8. The solution of claim 7 , comprising about 130 to about 160 mmol/L of Na + and 4 to 7 mmol/L of K + .

9. The solution of claim 1 , further comprising chloride, an osmotic buffer and a reducing agent.

10. The solution of claim 1 , further comprising 70 to 180 mmol/L chloride, 8 to 12.5 mmol/L of glucose, 7.5 to 12.5 IU/L of insulin, 100 to 140 mmol/L of D-mannitol, 0.75 to 1.25 mmol/L of pyruvate, and 2.5 to 3.5 mmol/L of reduced glutathione.

11. The solution of claim 1 , wherein the solution is oxygenated.

12. The solution of claim 1 , comprising:

0.3 to 0.45 mmol/L of adenosine;

0.04 to 0.09 mmol/L of lidocaine;

8 to 12.5 mmol/L of glucose;

110 to 130 mmol/L of NaCl;

4 to 7 mmol/L of KCl;

16 to 24 mmol/L of NaHCO 3 ;

0.9 to 1.4 mmol/L of NaH 2 PO 4 ;

0.18 to 0.26 mmol/L of CaCl 2 ;

11 to 15 mmol/L of MgCl 2 ;

7.5 to 12.5 IU/L of insulin;

100 to 140 mmol/L of D-mannitol;

0.75 to 1.25 mmol/L of pyruvate; and

2.5 to 3.5 mmol/L of reduced glutathione.

13. The solution of claim 1 , comprising:

0.4 mmol/L of adenosine;

0.05 mmol/L of lidocaine;

10 mmol/L of glucose;

123.8 mmol/L of NaCl;

5.9 mmol/L of KCl;

20 mmol/L of NaHCO 3 ;

1.2 mmol/L of NaH 2 PO 4 ;

0.22 mmol/L of CaCl 2 ;

13 mmol/L of MgCl 2 ;

10 IU/L of insulin;

120 mmol/L of D-mannitol;

1 mmol/L of pyruvate; and

3 mmol/L of reduced glutathione.

14. A method comprising reperfusing a donor heart with the solution of claim 1 .

15. The method of claim 14 , wherein the heart is reperfused with the solution during removal of the heart from a donor of the heart.

16. The method of claim 14 , wherein the heart is reperfused with the solution in a reperfusion device.

17. The method of claim 16 , wherein the heart is reperfused with the solution for at least 3 minutes immediately after removal of the heart from a donor of the heart.

18. The method of claim 14 , wherein the heart is removed from a donor after circulatory death.

19. The method of claim 14 , wherein the heart is at a temperature above about 25° C. and below about 37° C.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 17, 2023
From: BRIDGE TO LIFE LTD.; TEVOSOL, INC.
To: TRANSMEDICS, INC.
Reel/Frame 064617/0106 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 25, 2019
From: FREED, DARREN H
To: TEVOSOL, INC.
Reel/Frame 048994/0647 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 13, 2017
From: THE UNIVERSITY OF MANITOBA
To: FREED, DARREN
Reel/Frame 043000/0231 →
Priority Claims (1)
CA PCT/CA2015/050297 · Apr 10, 2015 · national
Continuity (4)
Continuation In Part 15302593
Provisional Application 62068524 · Oct 24, 2014
Provisional Application 61978132 · Apr 10, 2014
Related Publication 20180192640A1 · Jul 12, 2018
Cited By (4)
US 12,185,718 US 12,207,649 US 12,317,888 US 12,396,454