IP Library Granted Patent US 11,033,021
Granted Patent B2
US 11,033,021 · App. 16/551,324 · Granted Jun 15, 2021

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 11,033,021
App. No.
16/551,324
Granted
Jun 15, 2021
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 (46)

1. A composition for preparing a solution, the composition comprising:

adenosine;

lidocaine; and

a calcium source,

wherein the molar ratio of adenosine:calcium in the composition is from 0.3:0.26 to 0.45:0.18, and the molar ratio of lidocaine:calcium in the composition is from 0.04:0.26 to 0.09:0.18,

wherein the solution comprises a cardioplegia mixture and a buffer for maintaining a pH of the solution, the cardioplegia mixture comprises 0.3 to 0.45 mmol/L of adenosine, 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 composition of claim 1 , wherein the molar ratio of adenosine:calcium is 0.4:0.22, and the molar ratio of lidocaine:calcium is 0.05:0.22.

3. The composition of claim 1 , further comprising a sodium source, a potassium source and a magnesium source, wherein the molar ratio of calcium:sodium is from 0.26:130 to 0.18:160, the molar ratio of calcium:potassium is from 0.26:4 to 0.18 to 7, and the molar ratio of calcium:magnesium is from 0.26:11 to 0.18:15.

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

5. The composition of claim 1 , wherein the pH is from 6.8 to 7.0.

6. The composition of claim 1 , wherein the pH is 6.9.

7. The composition of claim 1 , further comprising a magnesium ion source.

8. The composition of claim 7 , wherein the solution comprises 11 to 15 mmol/L of Mg 2+ .

9. The composition of claim 1 , further comprising a sodium ion source and a potassium ion source.

10. The composition of claim 9 , wherein the solution comprises about 130 to about 160 mmol/L of Na + and 4 to 7 mmol/L of K + .

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

12. The composition of claim 11 , 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.

13. The composition of claim 1 , wherein the composition is oxygenated.

14. The composition of claim 1 , wherein the solution comprises:

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.

15. The composition of claim 1 , wherein the solution comprises:

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.

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 Jul 17, 2020
From: THE UNIVERSITY OF MANITOBA
To: FREED, DARREN
Reel/Frame 053245/0595 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 17, 2020
From: FREED, DARREN H.
To: TEVOSOL, INC.
Reel/Frame 053245/0645 →
Continuity (5)
Continuation 15521484
Continuation In Part 15302593
Provisional Application 62068524 · Oct 24, 2014
Provisional Application 61978132 · Apr 10, 2014
Related Publication 20200022362A1 · Jan 23, 2020
Cited By (2)
US 12,317,888 US 12,396,454