# US 5,702,880 A · Blood substitute comprising 0-5 mM K.sup.+

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- Number: US 5,702,880 A
- Document ID: US5702880A
- Status: Granted
- Kind: A
- Application number: 08/253,384
- Filed: 1994-06-03
- Granted: 1997-12-30
- Earliest claimed: 1993-06-04
- Assignees: BioTime, Inc.
- Inventors: Paul E. Segall; Hal Sternberg; Harold D. Waitz; Judith M. Segall
- Web page: https://patentgrep.com/patent/US5702880A

## CPC

- A01N 1/125: Freeze protecting agents, e.g. cryoprotectants or osmolarity regulators
- A01N 1/162: Temperature processes, e.g. following predefined temperature changes over time
- A61K 9/0026: {Blood substitute; Oxygen transporting formulations; Plasma extender}
- A61K 33/10: Carbonates; Bicarbonates
- A61K 33/14: Alkali metal chlorides; Alkaline earth metal chlorides
- A61P 7/08: Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock (artificial tears A61P27/04)
- A01N: PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF (preservation of food or foodstuff A23); BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES (preparations for medical, dental or toiletry purposes which kill or prevent the growth or proliferation of unwanted organisms A61K); PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Aqueous solutions comprising a polysaccharide oncotic agent, a physiologically compatible buffer, a simple hexose sugar, dissolved chloride salts of calcium, sodium and magnesium, and a dissolved organic salt of sodium are disclosed. The solutions are effective substitutes for blood and may be used to preserve the biological integrity of the organs of a mammalian donor organism as shown by superior anatomical integrity of cryopreserved organs and tissues of subjects perfused with the solution. The solutions may be used for maintaining a partially or substantially completely exsanguinated subject at normal temperatures and at temperatures substantially below those normally maintained by a mammal and may be used in conjunction with hypobaric environments to maintain such partially or completed exsanguinated subjects alive without infusing blood back into the subject.

## Claims

### Claim 1

An aqueous blood substitute solution comprising:
0-5 mM K.sup.+ ;
130-150 mM Na.sup.+ ;
0.2-0.45 mM Mg.sup.++ ;
2.0-2.5 mM Ca.sup.++ ;
70-160 mM Cl.sup.- ;
6% wt/wt ofhy&oxyethyl starch;
2-50 mM glucose;
and lactate in a concentration sufficient to provide in vivo buffering in a physiological range;
with the proviso that said aqoeous blood substitute solution does not include a conventional biological buffer.

### Claim 2 (depends on 1)

The aqueous blood substitute solution of claim 1 wherein K.sup.+ is present in the concentration range of 2-3 mM.

### Claim 3

An aqueous blood substitute solution consisting essentially of:
0-5 mM K.sup.+ ;
130-150 mM Na.sup.+ ;
0.2-0.45 mM Mg.sup.++ ;
2.0-2.5 mM Ca.sup.++ ;
70-160 mM Cl.sup.- ;
a blood plasma expander in a concentration sufficient to provide a colloid osmotic pressure about 2 g mm Hg in said solution;
a simple sugar selected from the group consisting of glucose, fructose and galactosc;
and an organic carboxylic acid, salt or ester thereof selected from the group consisting of lactate, acetate citrate, glueonate, pyruvate and succinate in a concentration sufficient to provide in vivo buffering in a physiological range;
with the proviso that said aqueous blood substitute solutioa does not include a conventional biological buffer.

### Claim 4 (depends on 3)

The aqueous blood substitute solution of claim 3 wherein K.sup.30 is present in the concentration range of 2-3 mM.

### Claim 5

A method for providing a heat sterilized blood substitute comprising:
placing a solution comprised of:
0-5 mM K.sup.+ ;
130-150 mM Na.sup.+ ;
0.2-0.45 mM Mg.sup.++ ;
2.0-2.5 mM Ca.sup.++ ;
70-160 mM Cl.sup.- ;
6% wt/wt of hydroxyethyl starch;
2-50 mM glucose;
and lactate in a concentration sufficient to provide in vivo buffering in a physiological range;
with the proviso that said solution does not include a conventional biological buffer, in a heat sterilizable container; and
raising the temperature of said solution under pressure and for a period of time sufficient to kill all or substantially kill all bacteria and iaactivate all or substantially all viruses in the solution.

### Claim 6 (depends on 5)

The method of claim 5 wherein said temperature of said solution is raised under pressure to 120.degree. C. for 15 minutes.

### Claim 7 (depends on 5)

The method according to claim 5 wherein said solution is placed in an autoclave.

### Claim 8

A method for providing a heat sterilized blood substitute comprising:
placing a solution consisting essentially of:
0-5 mM K.sup.+ ;
130-150 mM Na.sup.+ ;
0.2-0.45 mM Mg.sup.++ ;
2.0-2.5 mM Ca.sup.++ ;
70-160 mM Cl.sup.- ;
a blood plasma expander in a concentration sufficient to providc a colloid osmotic pressure about 28 mm Hg in the solution;
a simple sugar selected from the group consisting of glucose, fructose and galactose;
and an organic carboxylic acid, salt or ester thereof selected from the group consisting of lactate, acetate, citrate, gluconate, pyruvale and succinate in a concentration sufficient to provide in vivo buffering in a physiological range;
with the proviso that said solution does not include a conventional biological buffer, in a heat sterilizable container; and
raising the temperature of said solution under pressure and for a period of time sufficient to kill all or substantially kill all bacteria and inactivate all or substantially all viruses in the solution.

### Claim 9 (depends on 8)

The method of claim 8 wherein said temperature of said solution is raised under pressure to 120.degree. C. for 15 minutes.

### Claim 10 (depends on 8)

The method according to claim 8 wherein said solution is placed in an autoclave.