Ambient stored blood plasma expanders containing keratose
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.
1. A liquid plasma expander composition for use in a subject in need thereof, consisting essentially of:
(a) from 0.1 to 10 percent by weight of basic alpha keratose; said basic alpha keratose produced by the process of separating basic alpha keratose from a mixture of acidic and basic alpha keratose by ion exchange chromatography; and with 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 composition of claim 1 which when contacted to red blood cells forms aggregates of said blood cells of less than 25 microns in diameter.
3. The composition of claim 1 , 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.
4. The composition of claim 3 , wherein said denaturing solution comprises a buffer solution.
5. The composition of claim 4 , wherein said denaturing solution comprises a TRIS buffer solution.
6. The composition of claim 1 , wherein said composition is sterile.
7. A medical product comprising the composition of claim 1 packaged in a sterile container.
8. The product of claim 7 , said composition having a shelf life of at least 4 months at room temperature.
9. The composition 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.
10. The composition 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.
11. The composition 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.
12. The composition of claim 1 , wherein said composition 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.
13. The composition of claim 1 , wherein said composition 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.
14. A blood substitute composition for use in a subject in need thereof, comprising:
(a) a plasma expander of claim 1 ; combined with
(b) red blood cells (RBCs).
15. The blood substitute of claim 14 , wherein said red blood cells are mammalian.
16. The blood substitute of claim 14 , wherein said red blood cells are human.
17. The blood substitute of claim 14 , where said RBCs form an essentially single cell suspension of RBCs.
18. A method of making a liquid plasma expander composition for use in a subject in need thereof, comprising:
mixing a dry powder composition comprising keratin derivative in dry powder form with an aqueous solution to produce the homogeneous liquid plasma expander composition of claim 1 .
19. The method of claim 18 , said dry powder composition further comprising at least a portion of the constituents that form said electrolyte solution when combined with said aqueous solution.