US4547490A
Expired / Lapsed
US
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Synthetic whole blood and a method of making the same
Assignee: Quixote Corp
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Filing: 1983-07-12
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Granted: 1985-10-15
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Expires: 2003-07-12
Abstract
Abstract A composition of matter which comprises a synthetic whole blood useful as a substitute for whole natural blood and a method of making the same are disclosed. The method of manufacture yields a composition of matter comprised of a two phase coacervate system. The claimed system successfully duplicates the two phase heterogeneous physicochemical system of naturally occurring whole blood. Also, disclosed is a phase of the claimed method of manufacture which produces a composition of matter, useful as a substitute for hematocrit. Also disclosed is an embodiment employing a hemoglobin component selected from stroma free hemoglobin, synthetic liposomes containing stroma free hemoglobin, microencapsulated stroma free hemoglobin, microspheres of albumin containing stroma free hemoglobin, or emulsified droplets of the coacervate phase containing stroma free hemoglobin. It is preferred that the size of the hemoglobin component particles and the globules of the synthetic hematocrit and the synthetic whole blood range in size from 0.1 to 10 microns.
Inventors
- 👤 Charles S. Ecanow
- 👤 Bernard Ecanow
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-28 03:35
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/0012; A61K9/0019; A61K9/0026; G; G03; G03C; G03C1/00; G03C1/005; G03C1/04; G03C1/047; G03C2001/0471
Claims Analysis
Total Claims: 23
Claim 1
Independent Claim
13 words
A method of preparing a synthetic whole blood substitute comprising the steps of:
Claim 2
Independent Claim
13 words
A method of preparing a synthetic whole blood substitute comprising the steps of:
Claim 3
Dependent Claim
177 words
(A) dispersing an amount of albumin in a solution comprised of distilled water, about 0.9% weight to volume of a salt, from about 1% to about 5% weight to volume of urea and from about 0.1% to about 10% weight to volume of a phospholipid, as will result in about 5 to 25% weight to volume albumin in the final solution, (B) adding a non-polar solvent to the solution until globules of a coacervate phase of an aqueous two phase system begin to appear, (C) storing the solution, undisturbed at a temperature of from about 4° to 10° C., for at least 12 hours, thereby producing the two phase coacervate system, comprising an aqueous coacervate phase and an equilibrium bulk water phase, (D) removing said coacervate system from storage, allowing it to reach room temperature, then adding an amount of distilled water as will result in about 5 to 25% weight to volume of albumin, and (E) adding a sufficient amount of a salt to said coacervate system as will render it isotonic with whole human blood.
Claim 4
Dependent Claim
177 words
(A) dispersing an amount of albumin in a solution comprised of distilled water, about 0.9% weight to volume of a salt, from about 1% to about 5% weight to volume of urea and from about 0.1% to about 10% weight to volume of a phospholipid, as will result in about 5 to 25% weight to volume albumin in the final solution, (B) adding a non-polar solvent to the solution until globules of a coacervate phase of an aqueous two phase system begin to appear, (C) storing the solution, undisturbed at a temperature of from about 4° to 10° C., for at least 12 hours, thereby producing the two phase coacervate system, comprising an aqueous coacervate phase and an equilibrium bulk water phase, (D) removing said coacervate system from storage, allowing it to reach room temperature, then adding an amount of distilled water as will result in about 5 to 25% weight to volume of albumin, and (E) adding a sufficient amount of a salt to said coacervate system as will render it isotonic with whole human blood.
Claim 5
Dependent Claim
24 words
The method of claim 1 wherein the non polar solvent in (B) is glycerol dioleate, and the salt in (A) and (E) is NaCl.
Claim 6
Dependent Claim
21 words
A composition of matter useful as a substitute for whole blood which is prepared according to the method of claim 1.
Claim 7
Dependent Claim
15 words
The method of claim 1 wherein the two phases of the coacervate system are separated.
Claim 8
Dependent Claim
22 words
A composition of matter useful as a hematocrit substitute comprised of the coacervate phase prepared according to the method of claim 4.
Claim 9
Dependent Claim
36 words
The method of claim 1 which comprises the additional step of adding such amount of a sterol as will result in a 0.1 to 2% weight to volume concentration of the sterol in the coacervate system.
Claim 10
Dependent Claim
28 words
The method of claim 6 wherein the sterol is selected from a group consisting of cholesterol, ergosterol 7-dehydrocholesterol, α sitosterol, β sitosterol, γ sistosterol campesterol, and mixtures thereof.
Claim 11
Dependent Claim
22 words
The method of claim 6 which comprises the additional step of adding calcium chloride to a concentration of 1 to 5 mg%.
Claim 12
Dependent Claim
22 words
The method of claim 6 which comprises the additional step of adding potassium chloride to a concentration of 1 to 3 mg%.
Claim 13
Dependent Claim
29 words
The method of claim 9 which comprises the additional step or titrating the coacervate system by adding sodium bicarbonate to adjust the pH to that of whole human blood.
Claim 14
Dependent Claim
71 words
The method of claim 1 which comprises the additional step of adding a hemoglobin component selected from stroma free hemoglobin, synthetic liposomes containing stroma free hemoglobin, microencapsulated stroma free hemoglobin, microspheres of albumin containing stroma free hemoglobin, or emulsified droplets made with the coacervate phase and containing stroma free hemoglobin, or mixtures thereof to said coacervate phases to that the final product contains 1-20% weight to volume of stroma free hemoglobin.
Claim 15
Dependent Claim
29 words
The method of claim 1 wherein the phospholipid is selected from the group consisting of lecithin, isolecithin, caphalin, sphingomyelin, phosphatidyl serine, phosphatidylinositol, phosphatidic acid, phosphatidyl choline and mixtures thereof.
Claim 16
Dependent Claim
27 words
The method of claim 1, including the step of emulsifying said two phase coacervate system to produce droplets ranging in size from about 0.1 to 10 microns.
Claim 17
Dependent Claim
94 words
A synthetic whole blood substitute comprising an aqueous solution of about 0.9% weight to volume of a salt, from about 1% to about 5% weight to volume urea, from about 0.1% to about 10% weight to volume of a phospholipid, and from about 5 to 25% by weight to volume albumin, said components forming a two phase coacervate system having a coacervate phase and an equilibrium bulk water phase, and including a non-polar solvent selected from alcohols, esters, ketones, substituted glycerols or substituted hydrocarbons sufficient to promote formation of said two phase coacervate system.
Claim 18
Dependent Claim
94 words
A synthetic whole blood substitute comprising an aqueous solution of about 0.9% weight to volume of a salt, from about 1% to about 5% weight to volume urea, from about 0.1% to about 10% weight to volume of a phospholipid, and from about 5 to 25% by weight to volume albumin, said components forming a two phase coacervate system having a coacervate phase and an equilibrium bulk water phase, and including a non-polar solvent selected from alcohols, esters, ketones, substituted glycerols or substituted hydrocarbons sufficient to promote formation of said two phase coacervate system.
Claim 19
Dependent Claim
31 words
The synthetic whole blood substitute of claim 14, wherein the solvent is selected from butanol, ethyl acetate, dibutanol ketone, glycerol mono-acetate, glycerol diacetate, glycerol triacetate, glycerol dioleate, dichloromethylene, or mixtures thereof.
Claim 20
Dependent Claim
29 words
The synthetic whole blood substitute of claim 14, wherein the phospholipid is selected from lecithin, cephalin, isolecithin, sphingomyelin, phosphatidyl serine, phosphatidic acid, phosphatidyl inositol, phosphatidyl choline or mixtures thereof.
Claim 21
Dependent Claim
78 words
The synthetic whole blood substitute according to claim 14, including a sterol, CaCl 2 , KCl, enzymes, proteins, a hemoglobin component selected from stroma free hemoglobin, synthetic liposomes containing stroma free hemoglobin, microencapsulated stroma free hemoglobin, microspheres of albumin containing stroma free hemoglobin, or emulsified droplets made with the coacervate phase and containing stroma free hemoglobin, or mixtures thereof, so that the final product contains from about 1% to about 20% weight to volume of stroma free hemoglobin.
Claim 22
Dependent Claim
18 words
The synthetic whole blood substitute of claim 14, having a pH equivalent to that of whole human blood.
Claim 23
Dependent Claim
31 words
The synthetic whole blood of claim 14, in the form of an emulsion of said coacervate phase in said equilibrium phase having droplets from about 0.1 to 10 microns in size.
References Cited (Backward Citations)
US2591133A
Cited
GB742594A
Cited
US4001401A
Cited
US4002739A
Cited
US4133874A
Cited
DE2940184A1
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1988-10-14 | 1989-04-15 | 1989-10-15 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1992-10-14 | 1993-04-15 | 1993-10-15 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1996-10-14 | 1997-04-15 | 1997-10-15 | $7700.00 | Window Closed / Lapsed |