Abstract: Disclosed is a multi-compartment medical device useful in the storage, processing and extended shelf life of perishable products, especially pharmaceutical, food and biological products. Particular biological materials processed according to the present methods are human blood and blood products (RBCs). Also disclosed are processes for preserving food, pharmaceutical and biological products for long-term storage and extended shelf life employing a process that reduces the hydration level of the material to less than native hydration levels of the specific product. The invention further provides stabilized biological products, such as in the form of glassified beads, prepared using a two-phase system according to the described processes that may be rehydrated and prepared for clinical use, and having essentially no loss of biological and/or pharmacological activity.

Abstract: The present invention relates to a pharmaceutical composition and the method for the preparation thereof. The composition comprises 1.5˜6.9% (w/v) of one or more substances selected from sodium chloride, sodium bicarbonate, potassium chloride, magnesium sulfate, calcium chloride, calcium gluconate, and the like, and 3˜18% (w/v) of one or more substances selected from hydroxyethylstarch, dextran, carboxymethylstarch, polyvinyl-pyrrolidone, gelatin derivatives, and the like as well as the remainder of conventional injections, as long as sodium chloride is not less than 1.5% (w/v). The pharmaceutical composition of the present invention is used to treat and save the wounded and patients, as well as to treat shock, its advantages include safe and convention use, rapid and good curative effect, long time maintenance, extensive uses and the like.

Abstract: Compositions, and methods of use thereof, for use as blood substitute products comprise aqueous mixtures of oxygen-carrying and non-oxygen carrying plasma expanders and methods for the use thereof. The oxygen-carrying component may consist of any hemoglobin-based oxygen carrier, while the non-oxygen carrying plasma expander my consist of any suitable diluent.

Abstract: In accordance with the invention there is provided a method of treating a human subject to prevent leakage of serum proteins from capillary endothelial junctions during a period of increased capillary permeability. The invention also provides a method for preventing the harmful effects of free radicals on cellular membranes and other organelles. The method comprises administering to a subject an effective amount of a composition comprising at least one polysaccharide selected from the group consisting of hydroxyethyl starch and dextran of varying molecular sizes and at least one member of the group consisting of superoxide dismutase, glutathione peroxidase, catalase, hydroxyethyl rutoside, cyclic adenosine monophosphate and vitamin C. The compositions contain the macromolecules in a molecular size and concentration to effectively stabilize the capillary membrane.

Abstract: The present invention relates to a pharmaceutical composition and the method for the preparation thereof, The composition comprises 1.5˜6.9% (w/v) of one or more substances selected from sodium chloride, sodium bicarbonate, potassium chloride, magnesium sulfate, calcium chloride, calcium gluconate, and the like, and 3˜18% (w/v) of one or more substances selected from hydroxyethylstarch, dextran, carboxymethylstarch, polyvinyl-pyrrolidone, gelatin derivatives, and the like as well as the remainder of conventional injections, as long as sodium chloride is not less than 1.5% (w/v). The pharmaceutical composition of the present invention is used to treat and save the wounded and patients, as well as to treat shock, its advantages include safe and convenient use, rapid and good curative effect, long time maintenance, extensive uses and the like.

Abstract: The present invention provides superoxygenating compositions that comprise hemoglobin and guanosine 3′:5′-cyclic monophosphate (cyclic GMP) generating compounds, and methods for treatment of diseases or medical conditions which utilize the superoxygenating compositions as biocolloids, i.e. hemodiluents, blood substitutes, plasma expanders, or resuscitative fluids. The cardiac output-increasing compositions comprise a simple mixture of hemoglobin and the cyclic GMP generating compounds or hemoglobin physically or chemically coupled to the cyclic GMP generating compounds. The invention also provides time-controlled superoxygenating compositions of hemoglobin and cyclic GMP generating compounds that would be used for treatment of specific diseases or medical conditions requiring time-dependent use of biocolloids, i.e. hemodiluents, blood substitutes, plasma expanders, or resuscitative fluids.

Abstract: An emulsion of perfluoroorganic compounds (PFOC) comprises a rapidly eliminable perfluorocarbon (PFC) and a slowly eliminable perfluorinated cyclic tertiary amine, perfluoro-N-4-(methylcyclohexyl)-piperidine and additionally comprises not less then three rapidly eliminable and three slowly eliminable PFOC admixtures with the critical temperature of dissolution in hexane (CTDH) close to that of main PFOC. The PFOC emulsion is stabilized with a polyoxyethylene-polyoxypropylene copolymer having low viscosity to provide high dynamic oxygen capacity and enhancing oxygen delivery to tissues. To prepare the emulsion the stabilizing agent is heated up to 75° C., all components are saturated with carbon dioxide gas to minimize the reactogenicity in intravessel injection as a means of compensation for mass blood loses, perfusion of organs cut of blood flow, treating air-and fat embolism, obliterating vascular injuries of extremities and preventing toxic injuries caused by various xenobiotics.

Abstract: Compositions, and methods of use thereof, for use as blood substitute products comprise aqueous mixtures of oxygen-carrying and non-oxygen carrying plasma expanders and methods for the use thereof. The oxygen-carrying component may consist of any hemoglobin-based oxygen carrier, while the non-oxygen carrying plasma expander my consist of any suitable diluent.

Abstract: Methods for time-regulated prophylaxis or treatment of animals or humans for limited circulatory oxygen delivery induced by the inhibitory effects of a plasma-borne hemoglobin-based material on L-arginine→nitric oxide→cGMP pathways in the arteriovenous vasculature. The properties of the invention restore and increase circulatory oxygen delivery by increasing circulatory flow of the blood-hemoglobin-based material through selective activation of L-arginine→nitric oxide→cGMP pathways in the arterial rather than venous vasculature. A method of the invention utilizes oxygen-carrying biocolloid compositions that consist of a hemoglobin-based material and a guanosine 3′:5′-cyclic monophosphate (cGMP) generating entity, for treatment of animals and humans in need thereof for diseases or medical conditions which utilize the biocolloids as hemodiluents, blood substitutes, plasma expanders, or resuscitative fluids.

Abstract: A method of treating a mammal suffering from hypotension by administering intermolecularly- or intramolecularly-crosslinked stroma-free hemoglobin to the mammal.

Abstract: Fluorocarbon emulsions comprising a stabilizing, particle size controlling fluorophilic/hydrophilic compound which can have the formulaR.sub.F.sup.1 --W--R.sub.H.sup.1 (I)whereinR.sub.F.sup.1 is a linear, branched or cyclic C.sub.2-14 fluorocarbon group;R.sub.H.sup.1 is a linear, branched or cyclic C.sub.2-18 saturated or unsaturated hydrocarbon group; andW is absent or is a bivalent species chosen from the group consisting of --O--, --S--, or various fluorinated structures. Use of the fluorophilic/lipophilic compound in the dispersions of the invention provides stable particle size and efficient emulsification. The dispersions of the invention can comprise biologically useful additive and can be used for various purposes, as oxygen carriers, contrast agents, or diagnostic agents.

Abstract: Therapeutic treatment of septic shock comprises administering to an animal stroma-free hemoglobin, typically at a dose ranging from the least amount effective to increase perfusion, up to a dosage of about 2500 milligrams kilograms per of body weight.

Abstract: The present invention relates to compositions for use in medicine, e.g. as infusion or surgical rinse solutions, and to processes for their preparation. The compositions of the invention comprise an aqueous solution of physiologically inert PVP having a weight average molecular weight in the range of from 3,000 to 14,000 daltons.

Abstract: Compositions, and methods of use thereof, for use as blood substitute products comprise aqueous mixtures of oxygen-carrying and non-oxygen carrying plasma expanders and methods for the use thereof. The oxygen-carrying component may consist of any hemoglobin-based oxygen carrier, while the non-oxygen carrying plasma expander my consist of any suitable diluent.

Abstract: A method for increasing perfusion in a mammal suffering from cardiogenic shock by administering a perfusion-increasing effective amount of intermolecularly- or intramolecularly-crosslinked stroma-free hemoglobin to the mammal.

Abstract: A method for increasing perfusion in a mammal suffering from stroke by admninistering a perfusion-increasing effective amount of intermolecularly- or intramolecularly-crosslinked stroma-free hemoglobin to the mammal.

Abstract: The present invention is directed to the use of an inhibitor of NO activity, such as a nitric oxide scavenger or an NO synthase inhibitor, as as an adjunct to treatment of inappropriate tissue vascularization disorders.

Abstract: A family of compounds has been found to be useful for right-shifting hemoglobin towards a low oxygen affinity state. The effect has particular application in a wide variety of treatments including hypoxia, hypothermia, ischemia, stroke, ARDS, COPD, surgical blood loss, acute nonvolemic hemodilutions, wounds, diabetic ulcers, chronic leg ulcers, pressure sores, tissue transplants, and sepsis. The compounds are capable of acting on hemoglobin in whole blood.

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.

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.

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.

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.

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.

Abstract: A family of compounds has been found to be useful for right-shifting hemoglobin towards a low oxygen affinity state. The effect has particular application in radiation oncology applications. The compounds are capable of acting on hemoglobin in whole blood.

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.

Abstract: A family of compounds has been found to be useful for right-shifting hemoglobin towards a low oxygen affinity state. The effect has particular application in a wide variety of treatments including hypoxia, hypothermia, ischemia, stroke, ARDS, COPD, surgical blood loss, acute nonvolemic hemodilutions, wounds, diabetic ulcers, chronic leg ulcers, pressure sores, tissue transplants, and sepsis. The compounds are capable of acting on hemoglobin in whole blood.

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.

Abstract: Drug compounds are used as allosteric modifiers of hemoglobin present in red blood cells. The compounds bind to only a single pair of symmetry related sites in the central water cavity of hemoglobin at the Lys 99.alpha., Arg 141.alpha., and Asn 108 .beta. residues. When one of the drug compounds is bound to hemoglobin, it will join three separate sub-units of the hemoglobin molecule and stabilize the hemoglobin in a lower oxygen affinity state. Because the compounds used in this method are either not bound by serum albumin or only interact to small degrees with serum albumin, the compounds are active in whole blood and in vivo. The process of allosterically modifying hemoglobin towards a low oxygen affinity state in whole blood and in vivo could be used in a wide variety of applications including in treatments for ischemia, heart disease, wound healing, Alzheimer's, depression, schizophrenia, adult respiratory distress syndrome (ARDS), etc.

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.

Abstract: Allosteric hemoglobin modifier compound activity on p50 is potentiated by using the compound in combination with a hydrophobic compound such as an anesthetic.

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.

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.

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.

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.

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.

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.

Abstract: The present invention provides a novel one-stage assay which uses soluble thrombomodulin for directly determining the functional status in plasma of the vitamin K-dependent coagulation-inhibiting proteins, protein C and protein S. The method comprises combining a blood plasma test sample and a coagulation-activating substance in a calcium-free solution, then adding soluble thrombomodulin and calcium ions to initiate a coagulation reaction, measuring the time required for the test plasma sample to clot, comparing the measured clot time to that of standard control plasma samples, including protein C- and protein S-deficient plasma controls, and then using the compared clot time values for determining the functional status of protein C and protein S in the individual from whom the test plasma sample was taken. The functional status of the vitamin K-dependent coagulation-inhibiting proteins is used to determine the risk of thrombosis in the host individual.

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.

Abstract: Disclosed is a method for increasing the number of platelets in a mammal, which comprises administering to the mammal a platelet number increasing effective amount of an unbound, preferably a soluble, MPL receptor.

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.

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.

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.

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.

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.

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.

Abstract: A family of compounds has been found to be useful for right-shifting hemoglobin towards a low oxygen affinity state. The compounds are capable of acting on hemoglobin in whole blood. In addition, the compounds can maintain the oxygen affinity in blood during storage and can restore the oxygen affinity of outdated blood.

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.

Abstract: A composition for removing or inactivating harmful components including virus from blood or other extracellular liquids comprises a crownether compound substituted on a polysaccharide, preferably dextrane. The composition may be soluble in water, preferably for intraveneous application, or insoluble for extracorporeal application.

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 an exterior layer of lipid.

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.