Blood Substitute Patents (Class 514/832)
  • Patent number: 5914352
    Abstract: Storage stable fluorocarbon emulsions having a continuous aqueous phase and a discontinuous fluorocarbon phase, in which the fluorocarbon phase comprises a major amount of a first fluorocarbon or fluorocarbon mixture, and a minor amount of a second fluorocarbon or fluorocarbon mixture, in which the second fluorocarbon has a molecular weight greater than that of the first fluorocarbon and the second fluorocarbon includes a lipophilic moiety in its structure, whereby the second fluorocarbon serves to promote particle size stability in the emulsion while simultaneously providing favorably short organ retention times when administered to animals in vivo.
    Type: Grant
    Filed: May 12, 1997
    Date of Patent: June 22, 1999
    Assignee: Alliance Pharmaceutical Corp.
    Inventors: Jeffry Greg Weers, David Henry Klein, Cindy Shizuko Johnson
  • Patent number: 5904933
    Abstract: Stable reverse water-in-fluorocarbon emulsions and water-in-fluorocarbon-in-water multiple emulsions comprising the reverse fluorocarbon emulsions. The reverse emulsions comprise a continuous phase which is a highly fluorinated or perfluorinated compound, a discontinuous aqueous phase and a fluorinated surfactant or mixture of surfactants. The multiple emulsions comprise an aqueous continuous phase and a discontinuous phase comprising globules formed of aqueous droplets dispersed into a highly fluorinated or perfluorinated compound. The emulsions can contain pharmacologically active agents, and are particularly suitable for pulmonary drug delivery.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: May 18, 1999
    Assignee: Alliance Pharmaceutical Corp.
    Inventors: Jean G. Riess, Marie-Pierre Krafft
  • Patent number: 5900477
    Abstract: A method of treating a mammal suffering from hemorrhagic shock or reducing hypotension secondary to hemorrhagic shock in a mammal suffering from hemorrhagic shock by administering intermolecularly- or intramolecularly-crosslinked stroma-free hemoglobin to the mammal.
    Type: Grant
    Filed: February 27, 1998
    Date of Patent: May 4, 1999
    Assignee: Baxter International, Inc.
    Inventor: Robert J. Przybelski
  • Patent number: 5869539
    Abstract: The present invention involves perfluoro compound emulsions including nitric oxide, their preparation and their use. These emulsions provide a new source of nitric oxide. Such nitric oxide-containing emulsions may be used for the administration of nitric oxide to individuals in need thereof. Individuals in need of nitric oxide administration can include those suffering from hypertension, preeclampsia and a number of other situations where an increased blood flow, for example, is desirable. In addition, given the long use of perfluoro compound emulsions as blood substitutes, the present invention provides a relatively safe mode for administering and distributing nitric oxide-without potential negative side effects such as toxicities due to drug metabolites.
    Type: Grant
    Filed: April 17, 1996
    Date of Patent: February 9, 1999
    Assignees: Board of Regents, The University of Texas System, The Texas A&M University System
    Inventors: R. E. Garfield, A. T. Balaban, W. A. Seitz
  • Patent number: 5846458
    Abstract: Agents for inhibiting adsorption of proteins on the liposome surface and liposomes which are agglutination-free by binding said inhibiting agent on the surface are disclosed. The above-mentioned inhibiting agents comprise a hydrophobic moiety and a hydrophilic macromolecular chain moiety. Adsorption of plasma proteins on the liposomes is inhibited due to the hydrophilic moiety exposed on the liposome surface with a result that agglutination of the liposomes in plasma is prevented. Therefore, there is no danger of embolism in blood vessels inhibiting blood flow when the liposomes are introduced into the living body. Accordingly, the liposomes are especially highly useful as artificial erythrocytes for which a large dose of liposomes is needed for administration.
    Type: Grant
    Filed: July 9, 1996
    Date of Patent: December 8, 1998
    Assignee: Terumo Kabushiki Kaisha
    Inventors: Hiroshi Yoshioka, Hiroshi Goto
  • Patent number: 5846516
    Abstract: Perfluoroalkylated amphiphilic phosphorus compounds, corresponding to the formulae: ##STR1## wherein V is O or S;R.sup.1, R.sup.2 and R.sup.3 are H or substituted or unsubstituted perfluoroalkylated or hydrocarbon radicals;provided thatR.sup.1, R.sup.2 or R.sup.3 is a perfluoroalkylated radical; and Y and Z are radicals which can bear a part derived from a sugar, a polyol, or a hydrophilic polymer such as polyethyleneglycol, a perfluoroalkylated part or a part derived from a pharmaceutically active molecule, and method for their preparation and use. These compounds can be included in preparations, emulsions, dispersions, gels, microemulsions, notably for biomedical uses.
    Type: Grant
    Filed: June 3, 1992
    Date of Patent: December 8, 1998
    Assignee: Alliance Pharmaceutial Corp.
    Inventors: Jean G. Riess, Jacques Greiner, Alain Milius, Pierre Vierling, Frederic Guillod, Sylvie Gaentzler
  • Patent number: 5817045
    Abstract: The instant invention teaches an apparatus and a method for using an apparatus for extracorporeal therapeutic treatment of a changing volume of up to at least about half of the circulating blood of a living patient at one time.
    Type: Grant
    Filed: March 17, 1997
    Date of Patent: October 6, 1998
    Inventor: Frank Sever, Jr.
  • Patent number: 5789376
    Abstract: Compositions and processes to alleviate oxygen toxicity are disclosed based on the addition of nitroxides to physiologically compatible macromolecules. In particular, hemoglobin-based red cell substitutes are described featuring stable nitroxide free radicals for use in cell-free hemoglobin solutions, encapsulated hemoglobin solutions, stabilized hemoglobin solutions, polymerized hemoglobin solutions, conjugated hemoglobin solutions, nitroxide-labelled albumin, and nitroxide-labelled immunoglobulin. The formulations described herein interact with free radicals, act as antioxidant enzyme-mimics, and alleviate oxidative stress and oxygen-related toxicity.
    Type: Grant
    Filed: January 6, 1997
    Date of Patent: August 4, 1998
    Inventor: Jen-Chang Hsia
  • Patent number: 5785950
    Abstract: This invention relates to compositions comprising highly fluorinated, chloro-substituted, non-cyclic organic compounds having 7 to 9 carbon atoms and to processes of making and using them. More particularly, this invention relates to emulsions comprising those highly fluorinated, chloro-substituted organic compounds. This invention also related to emulsion comprising noncyclic perfluorochlorethers having 7 to 10 carbon atoms, preferably 7 to 9 carbon atoms. These novel emulsions have various medical and oxygen transport applications. They are especially useful medically as contrast media, for various biological imaging modalities such as nuclear magnetic resonance, ultrasound, x-ray, computed tomography, .sup.19 F-magnetic resonance imaging, and position emission tomography, as oxygen transport agents or "artificial bloods," in the treatment of heart attack, stroke, and other vascular obstructions, as adjuvants to coronary angioplasty and in cancer radiation treatment and chemotherapy.
    Type: Grant
    Filed: October 12, 1994
    Date of Patent: July 28, 1998
    Assignees: HemaGen/PFC, Minnesota Mining & Manufacturing Co.
    Inventors: Robert J. Kaufman, Thomas J. Richard, George G. I. Moore, Richard M. Flynn
  • Patent number: 5776914
    Abstract: Disclosed are compositions and methods for preventing or substantially inhibiting the hemolytic activity of hemolysis inducing agents. The methods and compositions are based on the use of an anionic oligosaccharide, such as polysulfated cyclodextrin, to achieve the desired reduction in hemolytic active inducing agents.
    Type: Grant
    Filed: November 30, 1994
    Date of Patent: July 7, 1998
    Assignee: The Trustees of the University of Pennsylvania
    Inventors: Paul B. Weisz, Edward J. Macarak
  • Patent number: 5741893
    Abstract: Compositions and processes to alleviate free radical toxicity are disclosed based on the use of nitroxides in association with physiologically compatible macromolecules. In particular, hemoglobin-based red cell substitutes are described featuring stable nitroxide free radicals for use in cell-free hemoglobin solutions, encapsulated hemoglobin solutions, stabilized hemoglobin solutions, polymerized hemoglobin solutions, conjugated hemoglobin solutions, nitroxide-labelled albumin, and nitroxide-labelled immunoglobulin. Formulations are described herein that interact with free radicals, acting as antioxidant enzymemimics, which preserve nitroxides in their active form in vivo. Applications are described including blood substitutes, radioprotective agents, imaging agents, agents to protect against ischemia and reperfusion injury, and in vivo enzyme mimics among others.
    Type: Grant
    Filed: June 7, 1995
    Date of Patent: April 21, 1998
    Inventor: Jen-Chang Hsia
  • Patent number: 5733894
    Abstract: An artificial plasma-like substance having at least one water soluble polysaccharide oncotic agent selected from the group consisting of high molecular weight hydroxyethyl starch, low molecular weight hydroxyethyl starch, dextran 40 and dextran 70, and albumin which is buffered by lactate and has a pre-administration pH of between 5 and 6.5 is disclosed. Also disclosed is an artificial plasma-like solution having at least two water soluble polysaccharide oncotic agents one of which is eliminated from the circulation slowly and the other of which is eliminated from the circulation quickly. Supplimentation of the plasma-like solution with certain ions is described. A system for administration of the plasma-like solution to a subject wherein the system comprises a first and second solution each having particular buffers is described. The plasma-like solution including cryoprotective adducts is also disclosed.
    Type: Grant
    Filed: June 5, 1995
    Date of Patent: March 31, 1998
    Assignee: BioTime, Inc.
    Inventors: Paul E. Segall, Harold D. Waitz, Hal Sternberg, Judith M. Segall
  • Patent number: 5698536
    Abstract: An artificial plasma-like substance having at least one water soluble polysaccharide oncotic agent selected from the group consisting of high molecular weight hydroxyethyl starch, low molecular weight hydroxyethyl starch, dextran 40 and dextran 70, and albumin which is buffered by lactate and has a pre-administration pH of between 5 and 6.5 is disclosed. Also disclosed is an artificial plasma-like solution having at least two water soluble polysaccharide oncotic agents one of which is eliminated from the circulation slowly and the other of which is eliminated from the circulation quickly. Supplimentation of the plasma-like solution with certain ions is described. A system for administration of the plasma-like solution to a subject wherein the system comprises a first and second solution each having particular buffers is described. The plasma-like solution including cryoprotective adducts is also disclosed.
    Type: Grant
    Filed: June 5, 1995
    Date of Patent: December 16, 1997
    Assignee: BioTime, Inc
    Inventors: Paul E. Segall, Harold D. Waitz, Hal Sternberg, Judith M. Segall
  • Patent number: 5679777
    Abstract: The invention relates to methods and compositions for delivering drugs to the body by binding them to hemoglobin. This technique stabilizes the drug and extends its half-life in the body. The drug may be chemically coupled to or adsorbed on the hemoglobin chain(s). Therapeutics are preferably linked to an artificial hemoglobin via a cysteine located deep within a cleft in the hemoglobin molecule.
    Type: Grant
    Filed: July 12, 1994
    Date of Patent: October 21, 1997
    Assignee: Somatogen, Inc.
    Inventors: David C. Anderson, Antony James Mathews
  • Patent number: 5676971
    Abstract: Agents for inhibiting adsorption of proteins on the liposome surface and liposomes which are agglutination-free by binding said inhibiting agent on the surface are disclosed. The above-mentioned inhibiting agents comprise a hydrophobic moiety and a hydrophilic macromolecular chain moiety. Adsorption of plasma proteins on the liposomes is inhibited due to the hydrophilic moiety exposed on the liposome surface with a result that agglutination of the liposomes in plasma is prevented. Therefore, there is no danger of embolism in blood vessels inhibiting blood flow when the liposomes are introduced into the living body. Accordingly, the liposomes are especially highly useful as artificial erythrocytes for which a large dose of liposomes is needed for administration.
    Type: Grant
    Filed: May 3, 1995
    Date of Patent: October 14, 1997
    Assignee: Terumo Kabushiki Kaisha
    Inventors: Hiroshi Yoshioka, Hiroshi Goto
  • Patent number: 5674913
    Abstract: A method of assisting a mammal having a lung disorder to breathe ambient gas normally, i.e., without the assistance of a ventilator. The method includes providing an animal having a lung disorder, such as surfactant deficiency, stiff lung or hyperinflated lung syndrome, and instilling a perfluorochemical liquid into the trachea for administration in the alveolar sacs of a lung of the animal. The perfluorochemical is permeable to the ambient gas and resides substantially permanently within the alveolar sacs without inducing hyperinflated lung syndrome. The liquid is instilled in an amount sufficient to enable the animal to breathe the ambient gas normally with O.sub.2 /CO.sub.2 blood gas exchange. In another aspect of the invention, the method further includes the step of alleviating the lung disorder without inducing hyperinflated lung syndrome.
    Type: Grant
    Filed: May 13, 1994
    Date of Patent: October 7, 1997
    Assignee: Synthetic Blood International, Inc.
    Inventor: Leland C. Clark, Jr.
  • Patent number: 5661124
    Abstract: The present invention provides blood substitutes comprised of recombinantly produced mutant hemoglobin having an osmolarity greater than 303 milliosmoles per liter and less than 800 milliosmoles per liter. Such hyperosmolar blood substitute additionally comprises a physiologically acceptable molecule less diffusible than dextrose.
    Type: Grant
    Filed: March 1, 1995
    Date of Patent: August 26, 1997
    Assignee: Somatogen, Inc.
    Inventors: Stephen J. Hoffman, Kiyoshi Nagai
  • Patent number: 5635538
    Abstract: A fluorocarbon emulsion which exhibits reduced pulmonary gas-trapping properties in species-sensitive laboratory animals is disclosed. Additionally, the fluorocarbon component(s) exhibit short organ retention time(s). The emulsion includes an aqueous phase, an emulsifier, and a fluorocarbon (or fluorocarbon composition), having a vapor pressure of less than about 8 torr to reduce pulmonary gas-trapping, and having an organ retention half life of less than about 6 weeks and more preferably less than about 3 to 4 weeks.
    Type: Grant
    Filed: March 16, 1993
    Date of Patent: June 3, 1997
    Assignee: Alliance Pharmaceutical Corp.
    Inventors: Jeffry G. Weers, Ernest G. Schutt, Timothy J. Pelura, Peter E. Keipert
  • Patent number: 5613944
    Abstract: An artificial plasma-like substance having at least one water soluble polysaccharide oncotic agent selected from the group consisting of high molecular weight hydroxyethyl starch, low molecular weight hydroxyethyl starch, dextran 40 and dextran 70, and albumin which is buffered by lactate and has a preadministration pH of between 5 and 6.5 is disclosed. Also disclosed is an artificial plasma-like solution having at least two water soluble polysaccharide oncotic agents one of which is eliminated from the circulation slowly and the other of which is eliminated from the circulation quickly. Supplimentation of the plasma-like solution with certain ions is described. A system for administration of the plasma-like solution to a subject wherein the system comprises a first and second solution each having particular buffers is described. The plasma-like solution including cryoprotective adducts is also disclosed.
    Type: Grant
    Filed: June 5, 1995
    Date of Patent: March 25, 1997
    Assignee: BioTime, Inc.
    Inventors: Paul E. Segall, Harold D. Waitz, Hal Sternberg, Judith M. Segall
  • Patent number: 5612310
    Abstract: The present invention is directed to administration of a nitric oxide scavenger or a nitric oxide synthase inhibitor to enhance the effectiveness of tumor therapy with hypoxic or acidic chemotherapeutic agents or hyperthermia. In a specific example, administration of cell free hemoglobin, a nitric oxide scavenger, in conjunction with mitomycin C, a hypoxic cytotoxin, results in a significant delay in tumor growth of a human tumor xenograft in a mouse compared to mitomycin C alone.
    Type: Grant
    Filed: May 24, 1993
    Date of Patent: March 18, 1997
    Assignees: Duke University, North Carolina State University, Apex Bioscience, Inc.
    Inventors: Mark W. Dewhirst, Robert E. Meyer, Joseph Bonaventura, Joseph DeAngelo
  • Patent number: 5595687
    Abstract: An injectable physiologically acceptable aqueous phase fluorocarbon emulsion, which has substantially no free fluorocarbon, has an excellent stability is prepared by a process of the invention. Typically, more than about 99.8 wt. % of the fluorocarbon remains in the size range of about 0.2 to 0.4 microns even after being stored at room temperature for one year or more in sealed containers under a non-oxidizing atmosphere. The emulsion is useful in medical applications, for example, coronary angioplasty, cancer therapy, among others.
    Type: Grant
    Filed: April 7, 1995
    Date of Patent: January 21, 1997
    Assignee: Thomas Jefferson University
    Inventors: Stuart Raynolds, Robert H. Dettre
  • Patent number: 5593622
    Abstract: Agents for inhibiting adsorption of proteins on the liposome surface and liposomes which are agglutination-free by binding said inhibiting agent on the surface are disclosed. The above-mentioned inhibiting agents comprise a hydrophobic moiety and a hydrophilic macromolecular chain moiety. Adsorption of plasma proteins on the liposomes is inhibited due to the hydrophilic moiety exposed on the liposome surface with a result that agglutination of the liposomes in plasma is prevented. Therefore, there is no danger of embolism in blood vessels inhibiting blood flow when the liposomes are introduced into the living body. Accordingly, the liposomes are especially highly useful as artificial erythrocytes for which a large dose of liposomes is needed for administration.
    Type: Grant
    Filed: June 2, 1995
    Date of Patent: January 14, 1997
    Assignee: Terumo Kabushiki Kaisha
    Inventors: Hiroshi Yoshioka, Hiroshi Goto
  • Patent number: 5591710
    Abstract: Compositions and processes to alleviate oxygen toxicity are disclosed based on the addition of nitroxides to physiologically compatible macromolecules. In particular, hemoglobin-based red cell substitutes are described featuring stable nitroxide free radicals for use in cell-free hemoglobin solutions, encapsulated hemoglobin solutions, stabilized hemoglobin solutions, polymerized hemoglobin solutions, conjugated hemoglobin solutions, nitroxide-labelled albumin, and nitroxide-labelled immunoglobulin. The formulations described herein interact with free radicals, act as antioxidant enzyme-mimics, and alleviate oxidative stress and oxygen-related toxicity.
    Type: Grant
    Filed: August 15, 1994
    Date of Patent: January 7, 1997
    Inventor: Jen-Chang Hsia
  • Patent number: 5573757
    Abstract: Compositions for topical application in gel form comprising a fluorocarbon or perfluorocarbon compound or mixtures thereof at a concentration of at least about 75% v/v, a minor quantity of a surface active agent and an aqueous phase.The compositions provide a storage-stable high concentration fluorocarbon gel that is prepared without the use of thickeners or additional stabilizing agents. The gels are useful in formulations for pharmaceutical, cosmetic purposes and for other products as well.
    Type: Grant
    Filed: October 3, 1994
    Date of Patent: November 12, 1996
    Assignee: Alliance Pharmaceutical Corp.
    Inventors: Jean G. Riess, Marie-Pierre Krafft
  • Patent number: 5574019
    Abstract: The present invention relates to the field of compositions of matter, disclosing compositions of matter which as aqueous solutions, may be used to perfuse a living or non-living subject in need of perfusion. The solutions according to the invention are typified by an aqueous solution comprising a polysaccharide oncotic agent, a physiologically compatible buffer, a simple hexose sugar, dissolved chloride salts of calcium, sodium and magnesium, and a dissolved organic salt of sodium. The solutions according to the invention are effective substitutes for blood. In addition the solution according to the invention may be used to preserve the biological integrity of the organs of a mammalian donor organism as shown by superior anatomical integrity of cryopreserved organs and tissues of subjects perfused with the solution of the invention.
    Type: Grant
    Filed: September 10, 1993
    Date of Patent: November 12, 1996
    Assignee: Biotime, Inc.
    Inventors: Paul E. Segall, Hal Sternberg, Harold D. Waitz
  • Patent number: 5571801
    Abstract: An artificial plasma-like substance having at least one water soluble polysaccharide oncotic agent selected from the group consisting of high molecular weight hydroxyethyl starch, low molecular weight hydroxyethyl starch, dextran 40 and dextran 70, and albumin which is buffered by lactate and has a pre-administration pH of between 5 and 6.5 is disclosed. Also disclosed is an artificial plasma-like solution having at least two water soluble polysaccharide oncotic agents one of which is eliminated from the circulation slowly and the other of which is eliminated from the circulation quickly. Supplimentation of the plasma-like solution with certain ions is described. A system for administration of the plasma-like solution to a subject wherein the system comprises a first and second solution each having particular buffers is described. The plasma-like solution including cryoprotective adducts is also disclosed.
    Type: Grant
    Filed: May 22, 1995
    Date of Patent: November 5, 1996
    Assignee: Biotime, Inc.
    Inventors: Paul E. Segall, Harold D. Waitz, Hal Sternberg, Judith M. Segall
  • Patent number: 5567765
    Abstract: This invention relates to physiologically acceptable emulsions of perfluorocarbon ether hydrides having 8 to 12 carbon atoms. These novel emulsions have various medical applications. They are especially useful medically as contrast media for various biological imaging modalities such as nuclear magnetic resonance, .sup.19 F-magnetic resonance imaging, ultrasound, x-ray, and computed tomography, as oxygen transport agents or "artificial bloods" in the treatment of heart attack, stroke, and other vascular obstructions, as adjuvants to coronary angioplasty and in cancer radiation treatment and chemotherapy.
    Type: Grant
    Filed: February 23, 1996
    Date of Patent: October 22, 1996
    Assignee: Minnesota Mining and Manufacturing Company
    Inventors: George G. I. Moore, Richard M. Flynn, Miguel A. Guerra
  • Patent number: 5565317
    Abstract: A solution for the preservation or perfusion of organs contains sodium lactobionate, sodium dihydrogenphosphate, raffinose, glutathione, allopurinol, nafamostat mesilate (mesylate) and optionally cyclodextrin, preferably 100-120 mM, 2-25 mM, 25-35 mM, 2-4 mM, 1-2 mM and 0.5-1 mM, respectively. The solution may be used for perfusion and storage of organs. Also disclosed are methods of use of the solution to perfuse and store organs.
    Type: Grant
    Filed: December 6, 1994
    Date of Patent: October 15, 1996
    Assignee: Torii Pharmaceutical Co., Ltd.
    Inventors: Kiyohiko Dohi, Takashi Urushihara, Masanori Iwata
  • Patent number: 5514536
    Abstract: A solution suitable as a hypothermic blood substitute for replacing blood in euthermic subjects during surgery are provided. The blood substitute contains a purge solution and a maintenance solution, the latter of which is useful for organ preservation. The purge solution contains an aqueous solution of electrolytes at physiological concentrations, a macromolecular oncotic agent, a biological pH buffer effective under physiological and hypothermic conditions, a simple sugar, and a substrate for the regeneration of ATP. The maintenance solution contains a second aqueous solution of electrolytes containing potassium ions at a concentration range of from 35 to 45 mM, sodium ions at a concentration range of from 80 to 120 mM, magnesium ions at a concentration range of from 2 to 10 mM, chloride ions at a concentration range of from 15 to 20 mM, and calcium ions at a concentration range of from 0.01 to 0.
    Type: Grant
    Filed: October 24, 1994
    Date of Patent: May 7, 1996
    Assignee: Cryomedical Sciences, Inc.
    Inventor: Michael Taylor
  • Patent number: 5502043
    Abstract: The use of a hydroxyethyl starch specification with a molecular weight M.sub.W of 110,000 to 150,000, a substitution level MS of 0.38 to 0.5, a substitution level DS of 0.32 to 0.45, and a C.sub.2 /C.sub.6 ratio from 8 to 20 for improvement of microcirculation in a peripheral arterial circulation disorder, in particular in already existing peripheral arterial occlusive disease in Stage II according to Fontaine. This hydroxyethyl starch specification can be used in suitable concentrations, e.g., as 6 wt.-% or 10 wt.-% solution, whereby these solutions optionally contain conventional adjuvants and additives.
    Type: Grant
    Filed: March 30, 1994
    Date of Patent: March 26, 1996
    Assignee: Fresenius AG
    Inventors: Burghard Weidler, Klaus Sommermeyer, Klaus Henning, Frank Bepperling
  • Patent number: 5502094
    Abstract: This invention relates to physiologically acceptable emulsions of perfluorocarbon ether hydrides having 8 to 12 carbon atoms. These novel emulsions have various medical applications. They are especially useful medically as contrast media for various biological imaging modalities such as nuclear magnetic resonance, .sup.19 F-magnetic resonance imaging, ultrasound, x-ray, and computed tomography, as oxygen transport agents or "artificial bloods" in the treatment of heart attack, stroke, and other vascular obstructions, as adjuvants to coronary angioplasty and in cancer radiation treatment and chemotherapy.
    Type: Grant
    Filed: May 17, 1995
    Date of Patent: March 26, 1996
    Assignee: Minnesota Mining and Manufacturing Company
    Inventors: George G. I. Moore, Richard M. Flynn, Miguel A. Guerra
  • Patent number: 5496536
    Abstract: Injectable contrast agents of great clinical importance for lymphography, characterized by non-water soluble particle sizes between about 5 or 10 nm and about 500 or 900 nm, which have selective distribution to lymph nodes upon percutaneous administration and can be imaged with millimeter resolution. Also disclosed are methods for performing percutaneous lymphography using these contrast agents.
    Type: Grant
    Filed: April 25, 1995
    Date of Patent: March 5, 1996
    Inventor: Gerald Wolf
  • Patent number: 5470841
    Abstract: A metabolizable blood plasma substitute is described which contains a starch ester with a molecular weight (Mw) of>20000 Daltons and a molar substitution of 0.1 to 1.5 as a colloidal component. The starch ester is for example acetyl starch with a molecular weight (Mw) of 200000 to 230000 Daltons and a molar substitution of 0.3 to 0.5.
    Type: Grant
    Filed: January 7, 1994
    Date of Patent: November 28, 1995
    Assignee: Laevosan-Gesellschaft mbH
    Inventors: Harald Forster, Fatima Asskali, Ernst Nitsch
  • Patent number: 5464814
    Abstract: A process is disclosed for the preparation of an essentially tetramer-free, essentially stroma-free, cross-linked, polymerized, pyridoxylated hemoglobin which comprises separating red blood cell stroma from blood by means of heat treating step to remove stromal contaminants and filtration or centrifugation or both, pyridoxylating, polymerizing, and removing essentially all of the remaining unmodified tetramer.
    Type: Grant
    Filed: February 28, 1994
    Date of Patent: November 7, 1995
    Assignee: Northfield Laboratories, Inc.
    Inventors: Lakshman R. Sehgal, Richard E. De Woskin, Gerald S. Moss, Steven A. Gould, Arthur L. Rosen, Hansa Sehgal
  • Patent number: 5464634
    Abstract: A red blood cell surrogate which is composed of a nanocrystalline core particle to which an oxygen carrier such as hemoglobin is bound. An oxygen carrier anchor coating is provided between the nanocrystalline core particle and the oxygen carrier in order to provide binding of the oxygen carrier to the nanocrystalline core particle without denaturing the oxygen carrier or otherwise destroying its oxygen carrying capacity. The nanocrystalline core particle with the oxygen carrier bound thereto is coated with a layer of lipid and then an outer layer of a sugar or allosteric effector is applied.
    Type: Grant
    Filed: April 25, 1994
    Date of Patent: November 7, 1995
    Assignee: The Regents of the University of California
    Inventors: Nir Kossovsky, Andrew E. Gelman, H. James Hnatyszyn
  • Patent number: 5460800
    Abstract: A composition for use in visualizing tissues comprising a physiologically-acceptable fluorocarbon liquid and a visualizable label such as a chromophore or visible or fluorescent dye associated therewith; preferably the fluorocarbon is in the form of an emulsion and the label has a lipophilic moiety. Also disclosed are methods for labeling and visualizing cells and tissue, such as those of the reticuloendothelial system.
    Type: Grant
    Filed: August 22, 1994
    Date of Patent: October 24, 1995
    Assignee: Alliance Pharmaceutical Corp.
    Inventor: Mark A. Walters
  • Patent number: 5446030
    Abstract: Disclosed are compositions and methods for prevented or substantially inhibiting the hemolytic activity of hemolysis inducing agents. The methods and compositions are based on the use an anionic oligosaccharide, such as polysulfated cyclodextrin, to achieve the desired reduction in hemolytic active inducing agents.
    Type: Grant
    Filed: September 19, 1991
    Date of Patent: August 29, 1995
    Inventors: Paul B. Weisz, Edward J. Macarak
  • Patent number: 5439944
    Abstract: Oil and water emulsions containing alkylphosphoryl choline or alkylglycerophosphoryl choline surfactants are disclosed. The surfactants have the following general structures: ##STR1## In the above general structures, R.sub.1, R.sub.2 or R.sub.3 is alkyl, alkenyl, fluoroalkyl and alkenyl; and PC is the phosphoryl choline. The emulsions are useful as oxygen transport agents, artificial bloods or red blood cell substitutes.
    Type: Grant
    Filed: November 24, 1993
    Date of Patent: August 8, 1995
    Assignee: HemaGen/PFC
    Inventors: Robert J. Kaufman, Thomas J. Richard
  • Patent number: 5439882
    Abstract: An improved blood substitute comprises purified hemoglobin, preferably bovine, cross-linked intramolecularly with periodate-oxidized ATP (o-ATP) and intermolecularly with periodate-oxidized adenosine (o-adenosine), combined with reduced glutathione (GSH), and optionally enriched with mannitol, non-electrolytes, and/or electrolytes. The blood substitute has prolonged intravascular persistence, can sustain plasma volume, has low oxygen affinity, can work as a physiological oxygen carrier, has vasodilator activity and can reduce the vasoconstriction that follows hemorrhage. A method of treating a human afflicted with acute blood loss and/or a sickling crisis of sickle cell anemia comprises intravenously administrating to the human an effective volume of the blood substitute.
    Type: Grant
    Filed: May 14, 1993
    Date of Patent: August 8, 1995
    Assignee: Texas Tech University Health Sciences Center
    Inventors: Mario Feola, Jan S. Simoni, Peter C. Canizaro, deceased
  • Patent number: 5438041
    Abstract: A process is provided wherein hemoglobin, a fragile material, is formulated into high hemoglobin content water-in-oil-in-water multiple emulsion while maintaining high yields and high oxygen exchange activity. A multiple emulsion of aqueous oxygen carrying material in oil in outer aqueous phase is suitable for provision of oxygen for oxygen transfer processes. A hemoglobin multiple emulsion in physiologically compatible oil in an outer aqueous saline solution is provided in sufficiently small droplet size to provide oxygen flow through blood vessels to desired body tissues or organs thereby providing a blood substitute.
    Type: Grant
    Filed: March 3, 1993
    Date of Patent: August 1, 1995
    Assignees: Illinois Institute of Technology, Northfield Laboratories, Inc.
    Inventors: Shuming Zheng, Richard L. Beissinger, Darsh T. Wasan, Lakshman R. Sehgal, Arthur L. Rosen
  • Patent number: 5436232
    Abstract: A pharmaceutical composition is described as well as the use of a starch ester for the production of such a pharmaceutical composition for peritoneal dialysis (CAPD) in particular for continuous ambulatory peritoneal dialysis. Starch esters which are particularly suitable are e.g. acetyl starch with a molecular weight (Mw) of 100000 to 200000 Daltons and a molar substitution of 0.3 to 0.5. Using the compositions according to the invention it is possible to carry out peritoneal dialysis without damaging the peritoneal epithelium. In addition it is not stored in the organs.
    Type: Grant
    Filed: January 7, 1994
    Date of Patent: July 25, 1995
    Assignee: Laevosan-Gesellschaft MBH
    Inventors: Harald Forster, Fatima Asskali, Ernst Nitsch
  • Patent number: 5434191
    Abstract: A blood substitute employs combinations of fluoro or perfluorochemicals capable in the presence of emulsifying agents of forming emulsions stable at room temperature and possessing enhanced oxygen carrying capacity; the invention enables preparation of an improved blood substitute, with improved O.sub.2 carrying capacity and stability, as well as lessened anaphylactoid reaction.
    Type: Grant
    Filed: August 23, 1993
    Date of Patent: July 18, 1995
    Assignee: International Therapeutics Inc.
    Inventors: Walter B. Dandliker, W. Keith R. Watson, Thomas C. Drees
  • Patent number: 5416078
    Abstract: The invention relates to fluid resuscitation of the human or animal body by administration of deferoxamine (DFO) and a water-soluble biopolymer.The DFO and the biopolymer are preferably bonded together.The biopolymer may be a polysaccharide or a protein.The DFO and the biopolymer are preferably formulated as an aqueous solution suitable for oral administration.The fluid resuscitation may be effected for ameliorating systemic oxidant injury occurring during ischemia and subsequent reperfusion.The fluid resuscitation may be indicated in treatment of burn injury, lung injury caused by inhalation of hot and/or toxic substances, such as smoke derived from combustion, hemorrhagic shock and other types of trauma.
    Type: Grant
    Filed: November 25, 1992
    Date of Patent: May 16, 1995
    Assignee: Biomedical Frontiers, Inc.
    Inventors: Bo E. Hedlund, Philip E. Hallaway
  • Patent number: 5407676
    Abstract: Perfluoro compounds such as C.sub.12 F.sub.20 ; C.sub.12 F.sub.27 N; C.sub.12 F.sub.26 O; C.sub.8 F.sub.17 Br; and C.sub.14 F.sub.24 are rendered dispersible colloidally in water or other polar media without the aid of an emulsifying agent by providing a matrix formed by subjecting a feedstock containing perfluoro compounds and carrier materials to conditions which alter the physical and/or chemical structure of the carrier material. The matrix suspends the perfluoro compounds for delivery to a dispersible medium. Thus, a family of new colloidal perfluoro compounds is produced. Methods of producing readily dispersible perfluoro compounds in the absence of emulsifying agents and cosmetics including the same are also disclosed.
    Type: Grant
    Filed: December 24, 1992
    Date of Patent: April 18, 1995
    Assignee: Fuisz Technologies Ltd.
    Inventor: Richard C. Fuisz
  • Patent number: 5405742
    Abstract: A solution suitable as a hypothermic blood substitute for replacing blood in euthermic subjects during surgery are provided. The blood substitute contains a purge solution and a maintenance solution, the latter of which is useful for organ preservation. The purge solution contains an aqueous solution of electrolytes at physiological concentrations, a macromolecular oncotic agent, a biological pH buffer effective under physiological and hypothermic conditions, a simple sugar, and a substrate for the regeneration of ATP. The maintenance solution contains a second aqueous solution of electrolytes containing potassium ions at a concentration range of from 35 to 45 mM, sodium ions at a concentration range of from 80 to 120 mM, magnesium ions at a concentration range of from 2 to 10 mM, chloride ions at a concentration range of from 15 to 20 mM, and calcium ions at a concentration range of from 0.01 to 0.
    Type: Grant
    Filed: July 16, 1993
    Date of Patent: April 11, 1995
    Assignee: Cyromedical Sciences, Inc.
    Inventor: Michael J. Taylor
  • Patent number: 5403575
    Abstract: This invention relates to compositions comprising highly fluorinated, chloro-substituted, non-cyclic organic compounds having 7 to 9 carbon atoms and to processes of making and using them. More particularly, this invention relates to emulsions comprising those highly fluorinated, chloro-substituted organic compounds. These novel emulsions have various medical and oxygen transport applications. They are especially useful medically as contrast media, for various biological imaging modalities such as nuclear magnetic resonance, ultrasound, x-ray, computed tomography, .sup.19 F-magnetic resonance imaging, and position emission tomography, as oxygen transport agents or "artificial bloods," in the treatment of heart attack, stroke, and other vascular obstructions, as adjuvants to coronary angioplasty and in cancer radiation treatment and chemotherapy.
    Type: Grant
    Filed: December 12, 1991
    Date of Patent: April 4, 1995
    Assignee: HemaGen/PFC
    Inventors: Robert J. Kaufman, Thomas J. Richard
  • Patent number: 5401493
    Abstract: Organic compounds for diagnostic imaging which contain at least one aryl group which has been derivatized to contain at least one perfluoro-1H,1H-neopentyl moiety are provided. The perfluoro-1H,1H-neopentyl groups produce a single magnetic resonance to insure a maximum signal to noise ratio. One compound disclosed is 2-O-oleoylglycerol 1,3-bis(7'-{3",5"-di[2"',2"'-di(trifluoromethyl)3"', 3"',3"'-trifluoropropyl]phenyl}heptanoate). In the preferred embodiment, a lipid emulsion is provided as a carrier vehicle to deliver the derivitized analog to a mammalian recipient. Methods to use these compounds in MRI and computerized tomography are provided.
    Type: Grant
    Filed: March 26, 1993
    Date of Patent: March 28, 1995
    Assignee: Molecular Biosystems, Inc.
    Inventors: Rolf Lohrmann, Ashwin Krishnan
  • Patent number: 5397562
    Abstract: Oxygen tension of tissue in a living subject may be determined non-invasively by a method which involves: administering to a living mammalian subject a biologically compatible perfluorocarbon emulsion in an amount effective to generate a measurable .sup.19 F spectrum under .sup.19 F NMR spectroscopy; allowing sufficient time to elapse for substantially all of the perfluorocarbon emulsion to be cleared from the vascular system of the subject, with a portion of the perfluorocarbon emulsion becoming sequestered in tissue of the subject; subjecting the tissue in which the perfluorocarbon emulsion has become sequestered to a .sup.19 F magnetic resonance spectroscopy procedure in which simultaneous measurements are made of spin-lattice relaxation rates for at least two separate resonances of the perfluorocarbon emulsion; and comparing the at least two spin-lattice relaxation rates measured in the .sup.
    Type: Grant
    Filed: July 15, 1993
    Date of Patent: March 14, 1995
    Assignee: Board of Regents, The University of Texas System
    Inventors: Ralph P. Mason, Peter P. Antich
  • Patent number: 5393513
    Abstract: A non-toxic, brominated perfluorocarbon emulsion for internal and intravenous use in animals (including humans) is disclosed, for use as an oxygen transport medium and as a contrast enhancement medium capable of facilitating the detection of tumors and other elements within the body. This emulsion is stable and maintains its very small particle size characteristics for extended periods of time, often exceeding eighteen months after sterilization, and further may include a stabilizing component selected from the group consisting of steroids, tocopherols, cholesterols, and combinations thereof. An anti-oxidizing component enhances delivery in oxygen transport.
    Type: Grant
    Filed: July 30, 1993
    Date of Patent: February 28, 1995
    Assignee: Alliance Pharmaceutical Corp.
    Inventor: David M. Long, Jr.
  • Patent number: 5362477
    Abstract: Methods and compositions are disclosed for enhancing .sup.19 F magnetic resonance imaging which utilize .sup.19 F magnetic resonance contrast media having enhanced .sup.19 F relaxivity. Fluorine-containing compounds having enhanced .sup.19 F relaxation properties resulting from direct association with an unpaired spin are disclosed. The fluorine-containing compound is associated with the unpaired spin by covalent attachment of a stable free radical, by complexation of a fluorinated complexing agent with a paramagnetic metal ion, or by salt formation or charge neutralization of a paramagnetic ion.
    Type: Grant
    Filed: December 1, 1992
    Date of Patent: November 8, 1994
    Assignee: Mallinckrodt Medical, Inc.
    Inventors: Dennis A. Moore, Max D. Adams, William P. Cacheris, David H. White, Muthunadar P. Periasamy, Raghavan Rajagopalan, Lynn A. deLearie, Steven R. Woulfe