IP Library Granted Patent US 8,637,231
Granted Patent B2
US 8,637,231 · App. 13/207,992 · Granted Jan 28, 2014

Method for increasing the volume of a blood substitute with an expander comprising basic alpha keratose

Inventor: Mark E. Van Dyke (Winston Salem, NC)
Assignee: Wake Forest University Health Sciences
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Quick Facts
Patent No.
US 8,637,231
App. No.
13/207,992
Granted
Jan 28, 2014
Kind
B2
Abstract

A liquid plasma expander or resuscitation fluid composition for use in a subject in need thereof, comprising, consisting of, or consisting essentially of: (a) a keratin derivative (preferably alpha keratose, gamma keratose, or combinations thereof, and with basic alpha keratose preferred over acidic alpha keratose); and (b) an electrolyte solution, with the keratin derivative solubilized in the electrolyte solution to form a homogeneous liquid composition. Blood substitutes formed therefrom and methods of making and using the same are also described.

Claims (31)

1. A method of increasing the volume of available blood substitute for treatment in a subject in need thereof, comprising:

obtaining a volume of donor blood;

determining the hematocrit (Hct) of said donor blood;

isolating red blood cells (RBCs) from said donor blood; and

diluting said isolated RBCs with a plasma expander to a final Hct of not less than 10% but not greater than 70%, wherein said plasma expander consists essentially of:

(a) from 0.1 to 10 percent by weight of basic alpha keratose; said basic alpha keratose having an average molecular weight of from 10 to 100 kilodaltons;

(b) from 0 to 5 percent by weight of gamma keratose; and

(c) from 90 to 99.9 percent by weight of an electrolyte solution; with said basic alpha keratose and said gamma keratose solubilized in said electrolyte solution to form a homogeneous liquid composition having:

(i) a pH of 7-8;

(ii) an osmolarity of 200 to 500 milliosmoles/Liter; and

(iii) a viscosity of 2 to 20 centipoise at a temperature of 37 degrees Celsius as determined with a Brookfield viscometer having a cone and plate geometry with a cone angle of 0.02 radians at a constant frequency of 30 rotations per minute.

2. The method of claim 1 , wherein said donor blood is autologous blood.

3. The method of claim 1 , wherein said composition has a viscosity of 4 to 20 centipoise at a temperature of 37 degrees Celsius using a cone and plate geometry with a cone angle of 0.02 radians and a constant frequency of 30 rotations per minute.

4. The method of claim 1 , wherein said composition has a viscosity of 10 to 20 centipoise at a temperature of 37 degrees Celsius using a cone and plate geometry with a cone angle of 0.02 radians and a constant frequency of 30 rotations per minute.

5. The method of claim 1 , wherein said composition has a viscosity of 10 to 15 centipoise at a temperature of 37 degrees Celsius using a cone and plate geometry with a cone angle of 0.02 radians and a constant frequency of 30 rotations per minute.

6. The method of claim 1 , wherein said plasma expander consists essentially of:

(a) from 0.1 to 5 percent by weight of said basic alpha keratose;

(b) from 0 to 5 percent by weight of gamma keratose; and

(c) from 90 to 99.9 percent by weight of an electrolyte solution.

7. The method of claim 1 , wherein said plasma expander consists essentially of:

(a) from 0.1 to 4 percent by weight of said basic alpha keratose;

(b) from 0 to 4 percent by weight of gamma keratose; and

(c) from 92 to 99.9 percent by weight of an electrolyte solution.

8. The method of claim 1 , wherein said composition is sterile.

9. The method of claim 1 , wherein when said plasma expander is contacted to red blood cells forms aggregates of said blood cells of less than 25 microns in diameter.

10. The method of claim 1 , wherein said RBCs are mammalian.

11. The method of claim 1 , wherein said RBCs are human.

12. The method of claim 1 , wherein said basic alpha keratose is produced by the process of separating basic alpha keratose from a mixture of acidic and basic alpha keratose by ion exchange chromatography.

13. The method of claim 12 , wherein said process further comprises the steps of precipitating said basic alpha keratose; re-dissolving said basic alpha keratose in a denaturing solution, optionally in the presence of a chelating agent to complex trace metals; and re-precipitating said basic alpha keratose from said denaturing solution.

14. The method of claim 13 , wherein said denaturing solution comprises a buffer solution.

15. The method of claim 13 , wherein said denaturing solution comprises a TRIS buffer solution.

Assignments (1)
CONFIRMATORY LICENSE Recorded Nov 11, 2011
From: WAKE FOREST UNIVERSITY HEALTH SCIENCES
To: US ARMY, SECRETARY OF THE ARMY
Reel/Frame 027215/0228 →
Continuity (4)
Division 12209773 · Sep 12, 2008
Division 11205800 · Aug 17, 2005
Provisional Application 60602207 · Aug 17, 2004
Related Publication 20110300193A1 · Dec 8, 2011