US4425334A
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Functional oxygen transport system
Assignee: University of California
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Filing: 1982-04-02
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Granted: 1984-01-10
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Expires: 2002-04-02
Abstract
Abstract Functional oxygen transport systems (OTS) have been devised which may serve as temporary blood substitutes in the circulatory system. The OTS comprises pure crystalline hemoglobin dissolved in an aqueous solution and encapsulated within a complex lipid and carbohydrate modified lipid phase. The hemoglobin encapsulated inner aqueous phase and the encapsulating lipid phase are dispensed in an outer isotonic aqueous phase to form a suspension of the multiple water-in-oil-in water emulsion type. The emulsion is suitable to transfusion into the circulatory system to assist in oxygen transport. The carbohydrate modified lipids are included in the lipid phase to "mask" the OTS from the tissue binding and take up by the reticuloendothelial system. The OTS are also suitable for use as calibrating fluids in gas analysis apparatus.
Inventors
- 👤 C. Anthony Hunt
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-26 13:08
CPC Classifications
A; A61; A61K; A61K9/00; A61K9/0012; A61K9/0019; A61K9/0026; A61K38/00; A61K38/16; A61K38/41; A61K38/42; A61P; A61P7/00; A61P7/08; G; G01; G01N; G01N33/00; G01N33/0004; G01N33/0006; Y; Y10; Y10T; Y10T436/00; Y10T436/10; Y10T436/106664
Claims Analysis
Total Claims: 33
Claim 1
Independent Claim
43 words
An oxygen transport system comprising an emulsion including an inner aqueous phase having crystalline hemoglobin dissolved therein, and an oil phase acting as an artificial membrane enclosing said inner aqueous phase, said oil phase including physiologically acceptable lipids and nonreducing carbohydrate-lipid addition products.
Claim 2
Dependent Claim
43 words
An oxygen transport system comprising an emulsion including an inner aqueous phase having crystalline hemoglobin dissolved therein, and an oil phase acting as an artificial membrane enclosing said inner aqueous phase, said oil phase including physiologically acceptable lipids and nonreducing carbohydrate-lipid addition products.
Claim 3
Dependent Claim
33 words
The oxygen transport system of claim 1 wherein an outer aqueous phase entrains said oil phase and the enclosed inner aqueous phase, said outer aqueous phase being physiologically acceptable and isotonic with blood.
Claim 4
Dependent Claim
21 words
The oxygen transport system of claim 1 wherein said outer aqueous phase is a saline solution buffered to about pH 7.4.
Claim 5
Dependent Claim
20 words
The oxygen transport system of claim 1 wherein the hemoglobin in said inner aqueous phase is essentially pure recrystallized hemoglobin.
Claim 6
Dependent Claim
30 words
The oxygen transport system of claim 4 wherein the oxygen transport action of said pure hemoglobin is stabilized by the inclusion of a glycerate or phosphate in the inner phase.
Claim 7
Dependent Claim
18 words
The oxygen transport system of claim 5 wherein said pure hemoglobin is stabilized by inclusion of an antioxidant.
Claim 8
Dependent Claim
32 words
The oxygen transport system of claim 4 wherein the inner aqueous phase is buffered to a pH of about 7.4 and is rendered isoosmolar with blood plasma by the inclusion of carbohydrate.
Claim 9
Dependent Claim
25 words
The oxygen transport system of claim 2 wherein said oil phase is a membrane separating the inner aqueous hemoglobin phase from the outer aqueous phase.
Claim 10
Dependent Claim
26 words
The oxygen transport system of claim 1 wherein the oil phase comprises a mixture of naturally occurring lipids and at least one nonreducing carbohydrate-lipid reaction product.
Claim 11
Dependent Claim
29 words
The oxygen transport system of claim 9 wherein the carbohydrate reacted with the lipid is a carbohydrate essentially inert to tissue binding and take up by mammalian reticuloendothelial systems.
Claim 12
Dependent Claim
26 words
The oxygen transport system of claim 10 wherein the carbohydrate-lipid reaction product comprises from about 1 to 50% by weight of the lipid based membrane phase.
Claim 13
Dependent Claim
29 words
The oxygen transport system of claim 10 wherein the carbohydrate is covalently bound to at least a portion of the lipids comprising the surface of said membrane oil phase.
Claim 14
Dependent Claim
15 words
The oxygen transport system of claim 1 wherein the lipids are a mixture of lipids.
Claim 15
Dependent Claim
16 words
The oxygen transport system of claim 13 wherein an anti-oxidant is included in the lipid mixture.
Claim 16
Dependent Claim
12 words
The oxygen transport system of claim 14 wherein the anti-oxidant is α-tocopherol.
Claim 17
Dependent Claim
16 words
The oxygen transport system of claim 13 wherein a phosphatidyl ethanolamine is one of the lipids.
Claim 18
Dependent Claim
15 words
The oxygen transport system of claim 13 wherein phosphatidic acid is one of the lipids.
Claim 19
Dependent Claim
14 words
The oxygen transport system of claim 13 wherein one of the lipids is cholesterol.
Claim 20
Dependent Claim
15 words
The oxygen transport system of claim 13 wherein one of the lipids is phosphatidyl choline.
Claim 21
Dependent Claim
12 words
The oxygen transport system of claim 12 wherein the carbohydrate is sucrose.
Claim 22
Dependent Claim
12 words
The oxygen transport system of claim 12 wherein the carbohydrate is raffinose.
Claim 23
Dependent Claim
12 words
The oxygen transport system of claim 12 wherein the carbohydrate is malabiose.
Claim 24
Dependent Claim
12 words
The oxygen transport system of claim 12 wherein the carbohydrate is inulin.
Claim 25
Dependent Claim
12 words
The oxygen transport system of claim 12 wherein the carbohydrate is dextran.
Claim 26
Dependent Claim
40 words
An oxygen transport system comprising an emulsion including an inner aqueous phase having pure crystalline hemoglobin dissolved therein, a lipid oil phase enclosing said aqueous phase and a nonreducing carbohydrate covalently bound to a lipid included in said oil phase.
Claim 27
Dependent Claim
40 words
An oxygen transport system comprising an emulsion including an inner aqueous phase having pure crystalline hemoglobin dissolved therein, a lipid oil phase enclosing said aqueous phase and a nonreducing carbohydrate covalently bound to a lipid included in said oil phase.
Claim 28
Dependent Claim
20 words
The oxygen transport system of claim 25 wherein said carbohydrate reduces take up by tissues of the immune defense system.
Claim 29
Dependent Claim
13 words
The oxygen transport system of claim 25 wherein said carbohydrate reduces tissue binding.
Claim 30
Independent Claim
86 words
A method for supplementing the transport of oxygen in the circulatory system comprising transfusing into a mammal a multiple water-oil-water emulsion comprising an inner aqueous phase including dissolved pure crystalline hemoglobin, an oil phase functioning as a membrane and comprising a mixture of physiologically acceptable lipids and nonreducing physiologically acceptable carbohydrates covalently bound to at least a portion of said lipids enclosing said inner aqueous phase, and an outer physiologically acceptable isotonic aqueous phase in which said oil phase and enclosed inner aqueous phase is entrained.
Claim 31
Independent Claim
86 words
A method for supplementing the transport of oxygen in the circulatory system comprising transfusing into a mammal a multiple water-oil-water emulsion comprising an inner aqueous phase including dissolved pure crystalline hemoglobin, an oil phase functioning as a membrane and comprising a mixture of physiologically acceptable lipids and nonreducing physiologically acceptable carbohydrates covalently bound to at least a portion of said lipids enclosing said inner aqueous phase, and an outer physiologically acceptable isotonic aqueous phase in which said oil phase and enclosed inner aqueous phase is entrained.
Claim 32
Dependent Claim
23 words
The method of claim 28 wherein said aqueous phases are buffered to a pH of about 7.4 and are isoosmolar with blood plasma.
Claim 33
Dependent Claim
34 words
The method of claim 28 wherein said carbohydrate-lipid component of said oil phase reduces the uptake of said oil phase and enclosed hemoglobin aqueous phase by the tissues and immune system of said mammal.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1987-01-09 | 1987-07-11 | 1988-01-10 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1991-01-09 | 1991-07-11 | 1992-01-10 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1995-01-09 | 1995-07-11 | 1996-01-10 | $7700.00 | Window Closed / Lapsed |