Claims
- 1. A synthetic whole blood substitute comprising effective amounts of lecithin and either one gelatin or one modified fluid gelatin, water, sufficient alkaline substance to achieve a pH within the range of human blood, and sufficient electrolyte to achieve an isotonicity equal to that of physiological saline solution, said synthetic whole blood comprising essentially a substantially non-polar coacervate phase of an aqueous two-phase coacervate system.
- 2. The synthetic whole blood substitute of claim 1, wherein said gelatin or modified fluid gelatin has an isoelectric point of from about 2 to 10; said pH is from about 7.2 to 7.6; said alkaline substances is sodium hydroxide or sodium bicarbonate; said lecithin is present as a starting material in an amount of about 0.5-10% weight to volume of water; said gelatin or modified fluid gelatin is present as starting material in an amount of about 1-10% weight to volume of water; and said electrolyte is a salt of Na, K, Ca, or Mg.
- 3. The synthetic whole blood substitute of claim 2, wherein said synthetic whole blood also includes about 2-25% weight to volume stroma free heloglobin, about 1-10% weight to volume of an ionic surfactant or a non-ionic surfactant or mixtures of the surfactants, about 1-10% weight to volume of an organic solvent, about 1-5% weight to volume of a suitable protein, or mixtures thereof.
- 4. The synthetic whole blood substitute of any of claims 1, 2, or 3, further including an additive selected from physiological entities.
- 5. A synthetic whole blood substitute comprising effective amounts of lecithin and either one gelatin or one modified fluid gelatin, water, sufficient alkaline substance to achieve a pH within the range of human blood, and sufficient electrolyte to achieve an isotonicity equal to that of physiological saline solution, said synthetic whole blood comprising a two-phase system, including a substantially non-polar coacervate phase and a substantially polar equilibrium water phase.
- 6. The synthetic whole blood substitute of claim 5, wherein said gelatin or modified fluid gelatin has an isoelectric point of from about 2 to 10; said pH is from about 7.2 to 7.6; said alkaline substance is sodium hydroxide or sodium bicarbonate; said lecithin is present as a starting material in an amount of about 0.5-10% weight to volume of water; said gelatin or modified fluid gelatin is present as a starting material in an amount of about 1-10% weight to volume of water; said electrolyte is a salt of Na, K, Ca, or Mg; and said blood substitute composition being in the form of an emulsion wherein the particle size is in the range of about 0.5-9 microns.
- 7. The synthetic whole blood substitute of claim 6, wherein said synthetic whole blood also includes about 2-15% weight to volume stroma free hemoglobin, about 1-10% weight to volume of an ionic surfactant or a non-ionic surfactant or mixtures of the surfactants, about 1-10% weight to volume of an organic solvent, about 1-5% weight to volume of a suitable protein, or mixtures thereof.
- 8. The synthetic whole blood substitute of any of claims 5, 6, or 7, further including an additive selected from physiological entities.
- 9. A method of making a synthetic whole blood substitute, said method comprising the steps of: (a) combining water and effective amounts of lecithin and either one gelatin or modified fluid gelatin, (b) mixing in sufficient electrolyte to achieve an isotonicty equal to that of physiological saline solution, (c) storing the combination at a temperature of about 15.degree.-50.degree. C., for about 12-72 hours whereby said combination separates into two layers, the lower layer being a substantially non-polar concervate phase, and the upper layer being a substantially polar equilibrium water phase, (d) separating said lower phase from said upper phase, and (e) adjusting the pH of said lower phase to the range of from about 7.2-7.6.
- 10. The method of claim 9, wherein in step (a) said gelatin or modified fluid gelatin is combined with water to form a 1-10% weight to volume solution, said lecithin is combined with water to form a 0.5-10% weight to volume solution, and then said two solutions are combined; and said gelatin or modified gelatin has an isoelectric point of 2 to 10, and in step (b) said electrolyte is a salt of Na, K, Ca, or Mg.
- 11. The method of claim 10, wherein said pH is adjusted to 7.4 by the dropwise addition of an alkaline substance, selected from sodium bicarbonate or sodium hydroxide.
- 12. The method of claim 11, wherein after said pH adjustment, 1-5% weight to volume of a suitable protein is added.
- 13. The method of claim 12, wherein after said pH adjustment, 2-15% weight to volume of stroma free hemoglobin is added.
- 14. The method of claim 12, wherein after said pH adjustment, 1-10% weight to volume of an ionic surfactant or a non-ionic surfactant or mixtures of the surfactants is added.
- 15. The method of claim 14, wherein after said pH adjustment, 1-10% weight to volume of an organic solvent is added.
- 16. The method of any of claims 9, 10, 11, 12, 13, 14, or 15, further including the addition of an additive selected from, physiological entities.
- 17. The method of claim 9, including the additional step of: (f) recombining said non-polar coacervate phase with said previously separated polar equilibrium water phase.
- 18. The method of claim 17, wherein in step (f), said combining is achieved by emulsification, thereby forming an emulsion.
- 19. The method of claim 18, wherein the particles of said emulsion range in size from about 0.5-9 microns.
- 20. The synthetic whole blood substitute of any of claims 1, 2 or 3, further including an additive selected from nutrients or therapeutic entities.
- 21. The synthetic whole blood substitute of any of claims 1, 2, or 3, further including an additive selected from drugs, enzyme systems, electrolytes, O.sub.2 or mixtures thereof.
- 22. The synthetic whole blood substitute of any of claims 5, 6, or 7, further including an additive selected from nutrients or therapeutic entities.
- 23. The synthetic whole blood substitute of any of claims 5, 6, or 7, further including an additive selected from drugs, enzyme systems, electrolytes, O.sub.2 or mixtures thereof.
- 24. The method of any of claims 9, 10, 11, 12, 13, 14 or 15, further including the addition of an additive selected from nutrients or therapeutic entities.
- 25. The method of any of claims 9, 10, 11, 12, 13, 14 or 15, further including the addition of an additive selected from drugs, enzyme systems, electrolytes, O.sub.2 or mixtures thereof.
Parent Case Info
This application is a division of application Ser. No. 464,704, filed Feb. 7, 1983, now U.S. Pat. No. 4,539,204, and a continuation-in-part of Ser. No. 437,823 filed Oct. 29, 1982, now abandoned, which is a continuation-in-part of Ser. No. 336,061 filed Dec. 31, 1981, now abandoned, which is a continuation-in-part of Ser. No. 222,364 filed Jan. 5, 1981, now U.S. Pat. No. 4,343,797, which is a continuation-in-part of Ser. No. 146,029 filed May 2, 1980, now abandoned, which is a continuation-in-part of Ser. No. 47,021 filed June 11, 1979, now abandoned.
US Referenced Citations (4)
Foreign Referenced Citations (2)
Number |
Date |
Country |
2940184 |
Apr 1981 |
DEX |
742594 |
Dec 1955 |
GBX |
Non-Patent Literature Citations (8)
Entry |
Watanabe et al.-Chemical Abstracts, vol. 81, (1974), p. 16715v. |
A. Veis & C. Aranyi, "Phase Separation in Polyelectrolyte Systems. I. Complex Coacervates of Gelatin", Journal of Physical Chemistry, vol. 64, (1960) pp. 1203-1210. |
G. Hawley, Ed., The Condensed Chemical Dictionary, 9th Ed., (New York: Van Nostrand Reinhold, 1977), p. 213. |
A. Osol, Ed., Remington's Pharmaceutical Sciences, (Easton, PA: Mack Publishing Co., 1975), p. 315. |
J. McMullen et al, "Pectin-Gelatin Complex Coacervates", Journal of Pharmaceutical Sciences, vol. 71, No. 6 (Jun. 1982), pp. 628-633. |
R. A. Kahn et al., "Alternative Sources and Substitutes for Therapeutic Blood Components", Blood, The Journal of the American Society of Hemotology, vol. 66-1 (Jul. 1985, pp. 1-12. |
Blood Policy & Technology, Jan. 1985, Office of Technology Assessment, pp. 136-150. |
A. Osol, ed., Remington's Pharmaceutical Sciences, 15th ed.: (Easton, PA: Mack Publishing Co., 1975), pp. 240-241. |
Divisions (1)
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464704 |
Feb 1983 |
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Continuation in Parts (4)
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336061 |
Dec 1981 |
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222364 |
Jan 1981 |
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146029 |
May 1980 |
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47021 |
Jun 1979 |
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