US4539204A — Gelatin based synthetic blood and a method of mak…

Claim 1

Independent Claim 44 words

A synthetic whole blood substitute comprising two gelatins, two modified fluid gelatins, or one gelatin and one modified fluid gelatin, having different isoelectric points, water, and sufficient alkaline substance to achieve a basic pH, said synthetic whole blood being a substantially non-polar coacervate phase.

Claim 2

Dependent Claim 44 words

A synthetic whole blood substitute comprising two gelatins, two modified fluid gelatins, or one gelatin and one modified fluid gelatin, having different isoelectric points, water, and sufficient alkaline substance to achieve a basic pH, said synthetic whole blood being a substantially non-polar coacervate phase.

Claim 3

Dependent Claim 79 words

The synthetic whole blood of claim 1, wherein one gelatin or modified fluid gelatin has an isoelectric point of 2 to 6 and the other gelatin or modified gelatin has an isoelectric point of 8 to 10; said basic pH is from 7.2 to 7.6; said alkaline substance is sodium hydroxide or sodium bicarbonate; and each of said two gelatins or modified fluid gelatins is present as starting material in an amount of 1-10% weight to volume of water.

Claim 4

Dependent Claim 37 words

The synthetic whole blood of claim 2, wherein said synthetic whole blood also includes 2-15% weight to volume of a hemoglobin selected from stroma free hemoglobin, microencapsulated stroma free hemoglobin, or synthetic liposomes containing stroma free hemoglobin.

Claim 5

Dependent Claim 54 words

The synthetic whole blood of claim 3, further including an additive to enhance oxygen transport capability selected from 1-10% weight to volume of an ionic surfactant or a non-ionic surfactant or mixtures of the surfactants; 1-10% weight to volume of an organic solvent; 1-5% weight to volume of a suitable protein; or mixtures thereof.

Claim 6

Dependent Claim 33 words

The synthetic whole blood of any of claims 1, 2, 3 or 4, further including an additive selected from nutrients, physiological entities, therapeutic entities, drugs, enzyme systems, electrolytes, O 2 or mixtures thereof.

Claim 7

Dependent Claim 56 words

A synthetic whole blood comprising two gelatins, two modified fluid gelatins or one gelatin and one modified fluid gelatin, having different isoelectric points, water, and sufficient alkaline substance to achieve a basic pH, said synthetic whole blood being a two-phase system, said phases being a substantially nonpolar coacervate phase and a substantially polar equilibrium water phase.

Claim 8

Dependent Claim 56 words

A synthetic whole blood comprising two gelatins, two modified fluid gelatins or one gelatin and one modified fluid gelatin, having different isoelectric points, water, and sufficient alkaline substance to achieve a basic pH, said synthetic whole blood being a two-phase system, said phases being a substantially nonpolar coacervate phase and a substantially polar equilibrium water phase.

Claim 9

Dependent Claim 98 words

The synthetic whole blood of claim 6, wherein one gelatin or modified fluid gelatin has an isoelectric point of 2 to 6 and the other gelatin or modified fluid gelatin has an isoelectric point of 8 to 10; said basic pH is from 7.2 to 7.6; said alkaline substance is sodium hydroxide or sodium bicarbonate; and each of said two gelatins or modified fluid gelatins is present as a starting material in an amount of 1-10% weight to volume of water; and said combination is an emulsion wherein the particle size is in the range of 0.5-9 microns.

Claim 10

Dependent Claim 37 words

The synthetic whole blood of claim 7, wherein said synthetic whole blood also includes 2-15% weight to volume of a hemoglobin selected from stroma free hemoglobin, microencapsulated stroma free hemoglobin, or synthetic liposomes containing stroma free hemoglobin.

Claim 11

Dependent Claim 54 words

The synthetic whole blood of claim 8, further including an additive to enhance oxygen transport capability selected from 1-10% weight to volume of an ionic surfactant or a non-ionic surfactant or mixtures of the surfactants, 1-10% weight to volume of an organic solvent, 1-5% weight to volume of a suitable protein, or mixtures thereof.

Claim 12

Dependent Claim 33 words

The synthetic whole blood of any of claims 6, 7, 8 or 9, further including an additive selected from nutrients, physiological entities, therapeutic entities, drugs, enzyme systems, electrolytes, O 2 or mixtures thereof.

Claim 13

Independent Claim 92 words

A method of making a synthetic whole blood, said method comprising (a) combining water and two gelatins, two modified fluid geltins, or one gelatin and one modified fluid gelatin, with different isoelectric points, (b) storing the combination at 15°-40° C., for 12-72 hours whereby said combination separates into two layers, said lower layer being a substantially non-polar coacervate phase, and said upper layer being an equilibrium water phase, (c) separating said lower phase from said upper phase and (d) adjusting the pH of said lower phase to the range of from 7.2-7.6.

Claim 14

Independent Claim 92 words

A method of making a synthetic whole blood, said method comprising (a) combining water and two gelatins, two modified fluid geltins, or one gelatin and one modified fluid gelatin, with different isoelectric points, (b) storing the combination at 15°-40° C., for 12-72 hours whereby said combination separates into two layers, said lower layer being a substantially non-polar coacervate phase, and said upper layer being an equilibrium water phase, (c) separating said lower phase from said upper phase and (d) adjusting the pH of said lower phase to the range of from 7.2-7.6.

Claim 15

Dependent Claim 81 words

The method of claim 11, wherein in step (a) one of said gelatins is combined with water to form a 1-10% weight to volume solution, the other said gelatin is combined with water to form a 1-10% weight to volume solution, and then said two solutions are combined; and one of said gelatins or modified gelatins has an isoelectric point of 2 to 6, and the other of said gelatins or modified gelatins has an isoelectric point of 8 to 10.

Claim 16

Dependent Claim 27 words

The method of claim 12, wherein said pH is adjusted to 7.4 by the dropwise addition of an alkaline substance, selected from sodium bicarbonate or sodium hydroxide.

Claim 17

Dependent Claim 20 words

The method of claim 13, wherein after said pH adjustment, 1-5% weight to volume of a suitable protein is added.

Claim 18

Dependent Claim 35 words

The method of claim 14, wherein after adjusting said pH, adding from 2-15% weight to volume of a hemoglobin selected from stroma free hemoglobin, synthetic liposomes containing stroma free hemoglobin or microencapsulated stroma free hemoglobin.

Claim 19

Dependent Claim 31 words

The method of claim 15, wherein after adjusting said pH, adding from 1-10% weight to volume of an ionic surfactant or a non-ionic surfactant or mixtures of the surfactants is added.

Claim 20

Dependent Claim 20 words

The method of claim 16, wherein after said pH adjustment, 1-10% weight to volume of an organic solvent is added.

Claim 21

Independent Claim 37 words

The method of any of claims 11, 12, 13, 14 15, 16, or 17, further including the addition of an additive selected from nutrients, physiological entities, therapeutic entities, drugs, enzyme systems, electrolytes, O 2 or mixtures thereof.

Claim 22

Independent Claim 115 words

A method to make a synthetic whole blood, said method comprising (a) combining water and two gelatins, two modified fluid gelatins, or one gelatin and one modified fluid gelatin, with different isoelectric points, (b) storing the combination at 15°-40° C., for 12-72 hours, whereby said combination separates into two layers, said lower layer being a substantially nonpolar coacervate phase, and said upper layer being a substantially polar equilibrium water phase, (c) separating said lower phase from said upper phase, (d) adjusting the pH of said lower phase to the range of 7.2-7.6 and (e) combining said lower coacervate phase of step (c) with said previously separated upper equilibrium water phase, thereby forming a two-phase system.

Claim 23

Independent Claim 115 words

A method to make a synthetic whole blood, said method comprising (a) combining water and two gelatins, two modified fluid gelatins, or one gelatin and one modified fluid gelatin, with different isoelectric points, (b) storing the combination at 15°-40° C., for 12-72 hours, whereby said combination separates into two layers, said lower layer being a substantially nonpolar coacervate phase, and said upper layer being a substantially polar equilibrium water phase, (c) separating said lower phase from said upper phase, (d) adjusting the pH of said lower phase to the range of 7.2-7.6 and (e) combining said lower coacervate phase of step (c) with said previously separated upper equilibrium water phase, thereby forming a two-phase system.

Claim 24

Dependent Claim 82 words

The method of claim 19, wherein in step (a) one of said gelatins is combined with water to form a 1-10% weight to volume solution, the other said gelatin is combined with water to form a 1-10% weight to volume solution, and then said two solutions are combined; and one of said gelatins or modified fluid gelatins has an isoelectric point of 2 to 6, and the other of said gelatins or modified gelatins has an isoelectric point of 8 to 10.

Claim 25

Dependent Claim 19 words

The method of claim 19, wherein in step (e), said combining is achieved by emulsification, thereby forming an emulsion.

Claim 26

Dependent Claim 17 words

The method of claim 20, wherein the particles of said emulsion range in size from 0.5-9 microns.

Claim 27

Dependent Claim 28 words

The method of claim 19, including the addition of 2-15% weight to volume of a hemoglobin selected from stroma free hemoglobin, or synthetic liposomes containing stroma free hemoglobin.

Claim 28

Dependent Claim 87 words

The method of claim 23, including the further steps of (f) adding, a 1-5% solution of formaldehyde, until the desired degree of shell structuring of the emulsion particles is achieved, (g) storing for 5-40 hours at 20°-40° C., whereby the preparation separates into two layers, an upper equilibrium liquid water layer, and a lower layer containing microencapsulated globules containing stroma free hemoglobin and (h) washing said microencapsulated globules containing stroma free hemoglobin with said upper equilibrium liquid water, until substantially all traces of the formaldehyde are removed.

Claim 29

Dependent Claim 41 words

The method of claim 24, further including the steps of (i) dispersing said microencapsulated stroma free hemoglobin in physiological saline solution, in the coacervate phase and then (j) emulsifying the resultant preparation, to obtain particles of from 0.5-9 microns in size.

Claim 30

Dependent Claim 57 words

The method of claim 19, including the addition of 1-10% weight to volume of an ionic surfactant or a non-ionic surfactant or mixtures of the surfactants, 1-10% weight to volume of an organic solvent, 1-5% weight to volume of a suitable protein, or mixtures thereof, to said lower coacervate layer after the pH adjustment of step (d).

Claim 31

Dependent Claim 27 words

The method of claim 26, including the addition of an additive selected from nutrients, physiological entities, therapeutic entities, drugs, enzyme systems, electrolytes, O 2 or mixtures thereof.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	1988-09-02	1989-03-04	1989-09-03	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	1992-09-02	1993-03-04	1993-09-03	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	1996-09-02	1997-03-04	1997-09-03	$7700.00	Window Closed / Lapsed

Gelatin based synthetic blood and a method of making the same

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