Blood Substitute Patents (Class 514/832)
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Patent number: 5914352Abstract: 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: GrantFiled: May 12, 1997Date of Patent: June 22, 1999Assignee: Alliance Pharmaceutical Corp.Inventors: Jeffry Greg Weers, David Henry Klein, Cindy Shizuko Johnson
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Patent number: 5904933Abstract: 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: GrantFiled: June 7, 1995Date of Patent: May 18, 1999Assignee: Alliance Pharmaceutical Corp.Inventors: Jean G. Riess, Marie-Pierre Krafft
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Patent number: 5900477Abstract: 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: GrantFiled: February 27, 1998Date of Patent: May 4, 1999Assignee: Baxter International, Inc.Inventor: Robert J. Przybelski
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Patent number: 5869539Abstract: 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: GrantFiled: April 17, 1996Date of Patent: February 9, 1999Assignees: Board of Regents, The University of Texas System, The Texas A&M University SystemInventors: R. E. Garfield, A. T. Balaban, W. A. Seitz
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Patent number: 5846458Abstract: 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: GrantFiled: July 9, 1996Date of Patent: December 8, 1998Assignee: Terumo Kabushiki KaishaInventors: Hiroshi Yoshioka, Hiroshi Goto
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Patent number: 5846516Abstract: 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: GrantFiled: June 3, 1992Date of Patent: December 8, 1998Assignee: Alliance Pharmaceutial Corp.Inventors: Jean G. Riess, Jacques Greiner, Alain Milius, Pierre Vierling, Frederic Guillod, Sylvie Gaentzler
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Patent number: 5817045Abstract: 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: GrantFiled: March 17, 1997Date of Patent: October 6, 1998Inventor: Frank Sever, Jr.
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Patent number: 5789376Abstract: 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: GrantFiled: January 6, 1997Date of Patent: August 4, 1998Inventor: Jen-Chang Hsia
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Patent number: 5785950Abstract: 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: GrantFiled: October 12, 1994Date of Patent: July 28, 1998Assignees: HemaGen/PFC, Minnesota Mining & Manufacturing Co.Inventors: Robert J. Kaufman, Thomas J. Richard, George G. I. Moore, Richard M. Flynn
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Patent number: 5776914Abstract: 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: GrantFiled: November 30, 1994Date of Patent: July 7, 1998Assignee: The Trustees of the University of PennsylvaniaInventors: Paul B. Weisz, Edward J. Macarak
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Patent number: 5741893Abstract: 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: GrantFiled: June 7, 1995Date of Patent: April 21, 1998Inventor: Jen-Chang Hsia
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Patent number: 5733894Abstract: 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: GrantFiled: June 5, 1995Date of Patent: March 31, 1998Assignee: BioTime, Inc.Inventors: Paul E. Segall, Harold D. Waitz, Hal Sternberg, Judith M. Segall
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Patent number: 5698536Abstract: 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: GrantFiled: June 5, 1995Date of Patent: December 16, 1997Assignee: BioTime, IncInventors: Paul E. Segall, Harold D. Waitz, Hal Sternberg, Judith M. Segall
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Patent number: 5679777Abstract: 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: GrantFiled: July 12, 1994Date of Patent: October 21, 1997Assignee: Somatogen, Inc.Inventors: David C. Anderson, Antony James Mathews
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Patent number: 5676971Abstract: 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: GrantFiled: May 3, 1995Date of Patent: October 14, 1997Assignee: Terumo Kabushiki KaishaInventors: Hiroshi Yoshioka, Hiroshi Goto
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Patent number: 5674913Abstract: 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: GrantFiled: May 13, 1994Date of Patent: October 7, 1997Assignee: Synthetic Blood International, Inc.Inventor: Leland C. Clark, Jr.
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Patent number: 5661124Abstract: 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: GrantFiled: March 1, 1995Date of Patent: August 26, 1997Assignee: Somatogen, Inc.Inventors: Stephen J. Hoffman, Kiyoshi Nagai
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Patent number: 5635538Abstract: 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: GrantFiled: March 16, 1993Date of Patent: June 3, 1997Assignee: Alliance Pharmaceutical Corp.Inventors: Jeffry G. Weers, Ernest G. Schutt, Timothy J. Pelura, Peter E. Keipert
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Patent number: 5613944Abstract: 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: GrantFiled: June 5, 1995Date of Patent: March 25, 1997Assignee: BioTime, Inc.Inventors: Paul E. Segall, Harold D. Waitz, Hal Sternberg, Judith M. Segall
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Patent number: 5612310Abstract: 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: GrantFiled: May 24, 1993Date of Patent: March 18, 1997Assignees: Duke University, North Carolina State University, Apex Bioscience, Inc.Inventors: Mark W. Dewhirst, Robert E. Meyer, Joseph Bonaventura, Joseph DeAngelo
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Patent number: 5595687Abstract: 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: GrantFiled: April 7, 1995Date of Patent: January 21, 1997Assignee: Thomas Jefferson UniversityInventors: Stuart Raynolds, Robert H. Dettre
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Patent number: 5593622Abstract: 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: GrantFiled: June 2, 1995Date of Patent: January 14, 1997Assignee: Terumo Kabushiki KaishaInventors: Hiroshi Yoshioka, Hiroshi Goto
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Patent number: 5591710Abstract: 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: GrantFiled: August 15, 1994Date of Patent: January 7, 1997Inventor: Jen-Chang Hsia
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Patent number: 5573757Abstract: 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: GrantFiled: October 3, 1994Date of Patent: November 12, 1996Assignee: Alliance Pharmaceutical Corp.Inventors: Jean G. Riess, Marie-Pierre Krafft
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Patent number: 5574019Abstract: 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: GrantFiled: September 10, 1993Date of Patent: November 12, 1996Assignee: Biotime, Inc.Inventors: Paul E. Segall, Hal Sternberg, Harold D. Waitz
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Patent number: 5571801Abstract: 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: GrantFiled: May 22, 1995Date of Patent: November 5, 1996Assignee: Biotime, Inc.Inventors: Paul E. Segall, Harold D. Waitz, Hal Sternberg, Judith M. Segall
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Patent number: 5567765Abstract: 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: GrantFiled: February 23, 1996Date of Patent: October 22, 1996Assignee: Minnesota Mining and Manufacturing CompanyInventors: George G. I. Moore, Richard M. Flynn, Miguel A. Guerra
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Patent number: 5565317Abstract: 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: GrantFiled: December 6, 1994Date of Patent: October 15, 1996Assignee: Torii Pharmaceutical Co., Ltd.Inventors: Kiyohiko Dohi, Takashi Urushihara, Masanori Iwata
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Patent number: 5514536Abstract: 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: GrantFiled: October 24, 1994Date of Patent: May 7, 1996Assignee: Cryomedical Sciences, Inc.Inventor: Michael Taylor
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Patent number: 5502043Abstract: 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: GrantFiled: March 30, 1994Date of Patent: March 26, 1996Assignee: Fresenius AGInventors: Burghard Weidler, Klaus Sommermeyer, Klaus Henning, Frank Bepperling
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Patent number: 5502094Abstract: 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: GrantFiled: May 17, 1995Date of Patent: March 26, 1996Assignee: Minnesota Mining and Manufacturing CompanyInventors: George G. I. Moore, Richard M. Flynn, Miguel A. Guerra
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Patent number: 5496536Abstract: 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: GrantFiled: April 25, 1995Date of Patent: March 5, 1996Inventor: Gerald Wolf
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Patent number: 5470841Abstract: 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: GrantFiled: January 7, 1994Date of Patent: November 28, 1995Assignee: Laevosan-Gesellschaft mbHInventors: Harald Forster, Fatima Asskali, Ernst Nitsch
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Patent number: 5464814Abstract: 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: GrantFiled: February 28, 1994Date of Patent: November 7, 1995Assignee: Northfield Laboratories, Inc.Inventors: Lakshman R. Sehgal, Richard E. De Woskin, Gerald S. Moss, Steven A. Gould, Arthur L. Rosen, Hansa Sehgal
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Patent number: 5464634Abstract: 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: GrantFiled: April 25, 1994Date of Patent: November 7, 1995Assignee: The Regents of the University of CaliforniaInventors: Nir Kossovsky, Andrew E. Gelman, H. James Hnatyszyn
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Patent number: 5460800Abstract: 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: GrantFiled: August 22, 1994Date of Patent: October 24, 1995Assignee: Alliance Pharmaceutical Corp.Inventor: Mark A. Walters
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Patent number: 5446030Abstract: 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: GrantFiled: September 19, 1991Date of Patent: August 29, 1995Inventors: Paul B. Weisz, Edward J. Macarak
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Patent number: 5439944Abstract: 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: GrantFiled: November 24, 1993Date of Patent: August 8, 1995Assignee: HemaGen/PFCInventors: Robert J. Kaufman, Thomas J. Richard
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Patent number: 5439882Abstract: 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: GrantFiled: May 14, 1993Date of Patent: August 8, 1995Assignee: Texas Tech University Health Sciences CenterInventors: Mario Feola, Jan S. Simoni, Peter C. Canizaro, deceased
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Patent number: 5438041Abstract: 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: GrantFiled: March 3, 1993Date of Patent: August 1, 1995Assignees: Illinois Institute of Technology, Northfield Laboratories, Inc.Inventors: Shuming Zheng, Richard L. Beissinger, Darsh T. Wasan, Lakshman R. Sehgal, Arthur L. Rosen
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Patent number: 5436232Abstract: 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: GrantFiled: January 7, 1994Date of Patent: July 25, 1995Assignee: Laevosan-Gesellschaft MBHInventors: Harald Forster, Fatima Asskali, Ernst Nitsch
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Patent number: 5434191Abstract: 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: GrantFiled: August 23, 1993Date of Patent: July 18, 1995Assignee: International Therapeutics Inc.Inventors: Walter B. Dandliker, W. Keith R. Watson, Thomas C. Drees
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Patent number: 5416078Abstract: 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: GrantFiled: November 25, 1992Date of Patent: May 16, 1995Assignee: Biomedical Frontiers, Inc.Inventors: Bo E. Hedlund, Philip E. Hallaway
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Patent number: 5407676Abstract: 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: GrantFiled: December 24, 1992Date of Patent: April 18, 1995Assignee: Fuisz Technologies Ltd.Inventor: Richard C. Fuisz
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Patent number: 5405742Abstract: 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: GrantFiled: July 16, 1993Date of Patent: April 11, 1995Assignee: Cyromedical Sciences, Inc.Inventor: Michael J. Taylor
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Patent number: 5403575Abstract: 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: GrantFiled: December 12, 1991Date of Patent: April 4, 1995Assignee: HemaGen/PFCInventors: Robert J. Kaufman, Thomas J. Richard
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Patent number: 5401493Abstract: 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: GrantFiled: March 26, 1993Date of Patent: March 28, 1995Assignee: Molecular Biosystems, Inc.Inventors: Rolf Lohrmann, Ashwin Krishnan
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Patent number: 5397562Abstract: 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: GrantFiled: July 15, 1993Date of Patent: March 14, 1995Assignee: Board of Regents, The University of Texas SystemInventors: Ralph P. Mason, Peter P. Antich
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Patent number: 5393513Abstract: 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: GrantFiled: July 30, 1993Date of Patent: February 28, 1995Assignee: Alliance Pharmaceutical Corp.Inventor: David M. Long, Jr.
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Patent number: 5362477Abstract: 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: GrantFiled: December 1, 1992Date of Patent: November 8, 1994Assignee: 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