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Patent US4532130A successfully refreshed from Google Patents.
US4532130A
Expired / Lapsed
US
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Preparation of synthetic frythrocytes
Assignee: RUSH-PRESBYTERIAN- ST LUKE'S MEDICAL CENTER
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Filing: 1983-03-30
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Granted: 1985-07-30
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Expires: 2003-03-30
Abstract
Abstract A sterile preparation of synthetic erythrocytes consisting of hemoglobin fraction encapsulated within water-immiscible amphiphylic membranes provides a total hemoglobin of at least about 12 gm percent at a hematocrit of 50%. A lipid composition is prepared and dispersed by agitation in a sterile, stroma-free 30-45 gram percent hemoglobin fraction. The dispersion is pressurized to between about 400 to about 900 kg/cm 2 , and the pressure is substantially instantaneously released by passing the mixture to a lower pressure region through an orifice having an area of between about 0.1 and about 10.0 mm 2 , thereby forming the synthetic erythrocytes. The preparation is filtered through a filter which passes particles having a diameter less than about 0.22 micron to eliminate any monocellular organisms that may be present and to eliminate larger synthetic erythrocytes. The synthetic erythrocyte preparation, if dried under vacuum to remove the major portion of the water from the encapsulated hemoglobin fraction, substantially transforms the erythrocytes but retains the integrity of the encapsulating lipid composition membranes. In the dried form, the sterile erythrocytes are storable for extended periods.
Inventors
- 👤 Ljubomir Djordjevich
- 👤 Anthony D. Ivankovich
- 👤 William Gottschalk
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 17:26
CPC Classifications
A; A61; A61K; A61K35/00; A61K35/12; A61K35/14; A61K35/18; A61K38/00; A61K38/16; A61K38/41; A61K38/42; A61K9/00; A61K9/10; A61K9/127; A61K9/1277
Claims Analysis
Total Claims: 13
Claim 1
Independent Claim
260 words
A process for producing a sterile synthetic erythrocyte preparation providing a total hemoglobin concentration of at least 12 gram percent when suspended in a liquid medium to a hematocrit of 50 percent, the process comprising Preparing a water-immiscible composition comprising between about 60 and about 90 weight percent lipids, between about 10 and about 40 weight percent of a sterol and between 0 and about 10 weight percent of an agent that imparts a negative charge to the surface of said composition, separating from whole blood a stroma-free hemoglobin fraction, adjusting the concentration of said stroma-free hemoglobin fraction to between about 30 and about 45 gram percent, mixing said adjusted hemoglobin fraction with said water-immiscible composition at a hemoglobin fraction to lipid composition volume ratio of between about 3:1 and about 10:1, agitating said mixture to disperse globules of said water-immiscible composition within said hemoglobin fraction, pressurizing said dispersion to a gauge pressure of between about 400 kg/cm 2 and about 900 kg/cm 2 , passing said pressurized dispersion through an orifice having a cross-sectional area of between about 0.1 mm and about 10.0 mm to substantially instantaneously release the pressure and thereby to form a preparation of synthetic erythrocytes having hemoglobin fraction encapsulated within membranes of said composition, the gauge pressure being selected according to the orifice size so as to obtain synthetic erythrocytes primarily in the 0.05 micron to 0.02 micron size range, filtering said composition through a filter which passes particles having a diameter about 0.22 micron in diameter or less, thereby removing microorganisms from the preparation.
Claim 2
Dependent Claim
260 words
A process for producing a sterile synthetic erythrocyte preparation providing a total hemoglobin concentration of at least 12 gram percent when suspended in a liquid medium to a hematocrit of 50 percent, the process comprising Preparing a water-immiscible composition comprising between about 60 and about 90 weight percent lipids, between about 10 and about 40 weight percent of a sterol and between 0 and about 10 weight percent of an agent that imparts a negative charge to the surface of said composition, separating from whole blood a stroma-free hemoglobin fraction, adjusting the concentration of said stroma-free hemoglobin fraction to between about 30 and about 45 gram percent, mixing said adjusted hemoglobin fraction with said water-immiscible composition at a hemoglobin fraction to lipid composition volume ratio of between about 3:1 and about 10:1, agitating said mixture to disperse globules of said water-immiscible composition within said hemoglobin fraction, pressurizing said dispersion to a gauge pressure of between about 400 kg/cm 2 and about 900 kg/cm 2 , passing said pressurized dispersion through an orifice having a cross-sectional area of between about 0.1 mm and about 10.0 mm to substantially instantaneously release the pressure and thereby to form a preparation of synthetic erythrocytes having hemoglobin fraction encapsulated within membranes of said composition, the gauge pressure being selected according to the orifice size so as to obtain synthetic erythrocytes primarily in the 0.05 micron to 0.02 micron size range, filtering said composition through a filter which passes particles having a diameter about 0.22 micron in diameter or less, thereby removing microorganisms from the preparation.
Claim 3
Dependent Claim
25 words
A process according to claim 1 wherein said dispersion is pressurized to a gage pressure of between about 450 and about 700 kg/cm 2 .
Claim 4
Dependent Claim
46 words
A process according to claim 1 including adjusting said gage pressure according to the diameter of said orifice to produce a synthetic erythrocyte preparation wherein at least about 80 percent of said synthetic erythrocytes have diameters between about 0.05 micron and about 0.2 micron in diameter.
Claim 5
Dependent Claim
20 words
A process according to claim 1 including filtering said preparation to separate free hemoglobin fraction from said synthetic erythrocytes preparation.
Claim 6
Dependent Claim
22 words
A process according to claim 4 including recovering hemoglobin from said separated hemoglobin fraction by filtering said medium through a hemoglobin-impermeable membrane.
Claim 7
Dependent Claim
24 words
A process according to claim 1 wherein said dispersion is pressurized by reducing the volume of the vessel in which said dispersion is contained.
Claim 8
Dependent Claim
25 words
A process according to claim 1 wherein said dispersion is pressurized by introducing a pressurized gas into the vessel wherein said lipid composition is contained.
Claim 9
Dependent Claim
23 words
A process according to claim 6 including drying said synthetic erythrocytes under vacuum to reduce the water content of said encapsulated hemoglobin fraction.
Claim 10
Dependent Claim
52 words
A process according to claim 1, said dispersion having a viscosity at 4° C. of between about 1500 centipoise and about 3200 centipoise as measured with a Brookfield cone plate viscometer with a CP-42 cone and a cone angle of 1.565 degrees, and using a shear rate of 1.15 sec -1 .
Claim 11
Dependent Claim
20 words
A process according to claim 5 including mixing said recovered hemoglobin with said stroma-free hemoglobin fraction to recycle unencapsulated hemoglobin.
Claim 12
Dependent Claim
91 words
A process for producing a dried reconstitutable synthetic erythrocytes comprising separating from whole blood a stroma-free hemoglobin fraction, mixing said stroma-free hemoglobin fraction with a lipid composition in a vessel, pressurizing the resulting mixture, substantially instantaneously releasing said pressure to form a suspension of synthetic erythrocytes in a portion of said hemoglobin fraction, said synthetic erythrocytes having hemoglobin fraction encapsulated in lipid membranes, separating said synthetic erythrocytes from said aqueous medium, and reducing the water content of said synthetic erythrocytes to less than 10% by weight of said encapsulated hemoglobin fraction.
Claim 13
Dependent Claim
91 words
A process for producing a dried reconstitutable synthetic erythrocytes comprising separating from whole blood a stroma-free hemoglobin fraction, mixing said stroma-free hemoglobin fraction with a lipid composition in a vessel, pressurizing the resulting mixture, substantially instantaneously releasing said pressure to form a suspension of synthetic erythrocytes in a portion of said hemoglobin fraction, said synthetic erythrocytes having hemoglobin fraction encapsulated in lipid membranes, separating said synthetic erythrocytes from said aqueous medium, and reducing the water content of said synthetic erythrocytes to less than 10% by weight of said encapsulated hemoglobin fraction.
References Cited (Backward Citations)
No citation records indexed.
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1988-07-29 | 1989-01-28 | 1989-07-30 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1992-07-29 | 1993-01-28 | 1993-07-30 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1996-07-29 | 1997-01-28 | 1997-07-30 | $7700.00 | Window Closed / Lapsed |