Abstract: Accordingly, the present invention is directed to biological compounds derivatized so as to contain at least one perfluoro-t-butyl moiety for use in fluorine-19 NMR and/or MRI studies. The perfluoro-t-butyl (PFTB) moiety, ##STR1## is an excellent reported group for fluorine-19 NMR/MRI. It is a source of nine magnetically equivalent fluorine nuclei which generate a single intense resonance for each detection in spectroscopy or imaging. This signal is a sharp singlet, not split by neighboring nuclei or spread over a wide frequency range and eliminates any change of ghost images which might arise from multiple resonances. These spectral properties ensure a maximum signal-to-noise ratio (S/N) for readily detecting this moiety. The foregoing allows either reduction in the concentration of the derivatized compound, ability to use MRI instruments with lower field strengths, a reduction in imaging times, or a combination of the foregoing as a result of this moiety producing a single, sharp, intense resonance.

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 organ preservative solution containing a low molecular weight dextran in a pharmacologically acceptable storage solution is suitable for storage and preservative of organs for transplantation.

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: Gas transport and bio-inert fluid administration to biological systems methods using a novel composition of matter are disclosed wherein the composition of matter comprises perfluorinated, ethyldimethyl cyclohexane. The compound has unique utilities in vapor phase heating and soldering, oxygen transport for biological fluids and other requirements for an inert, stable fluid.

Abstract: An aqueous cardioplegic solution providing significantly improved cardiac function after a period of exposure to cardioplegia, contains NaCl in the range of 70-110 mM; KCl in the range of 10-16 mM; CaCl.sub.2 in the range of 0.5-1.0 mM; MgCl.sub.2 in the range of 8-16 mM; NaHCO.sub.3 in the range of 10-20 mM; D-Glucose in the range of 5-15 mM; L-Aspartic acid in the range of 5-20 mM; and Lactobionic acid in the range of 0-15 mM.

Abstract: The present invention relates to a composition for increasing the vascular dwell-time of a particulate therapeutic or diagnostic agent in a mammal through the adjunct administration of an effective amount of the particulate therapeutic or diagnostic agent and an effective amount of a vascular dwell-time enhancing agent. Suitable therapeutic and diagnostic agents include those whose efficacy within the body is predicated on their ability to remain within or to be carried within the vascular compartment. Accordingly this method can be readily adapted for treating several diseases and disorders, including hypoxia, hypoxemia, anemia and cancer and for imaging selected regions of a mammal by various imaging techniques, including ultrasound imaging, X-ray imaging and MRI imaging.

Abstract: A method for rapidly preparing a frozen fluorocarbon emulsion for administration without degradation and having an extended shelf life is disclosed.

Abstract: .sup.19 F labelled compounds are disclosed which are useful in methods of NMR imaging and spectroscopy. The compounds comprise a .sup.19 F-containing sensor moiety, and a transport polymer or substrate, and can optionally also comprise a spacer moiety to separate the sensor moiety and the transport polymer.

Abstract: The present invention is directed to biological compounds derivatized so as to contain at least one perfluoro-t-butyl moiety for use in fluorine-19 NMR and/or MRI studies. The perfluoro-t-butyl (PFTB) moiety, ##STR1## is an excellent reporter group for fluorine-19 NMR/MRI. It is a source of nine magnetically equivalent fluorine nuclei which generate a single intense resonance for easy detection in spectroscopy or imaging. This signal is a sharp singlet, not split by neighboring nuclei or spread over a wide frequency range and eliminates any chance of ghost images which might arise from multiple resonances. These spectral properties ensure a maximum signal-to-noise ratio (S/N) for readily detecting this moiety. The foregoing allows either reduction in the concentration of the derivatized compound, ability to use MRI instruments with lower field strengths, a reduction in imaging times, or a combination of the foregoing as a result of this moiety producing a single, sharp, intense resonance.

Abstract: The present invention relates to the production of lipid vesicles having a moderately volatile material such as a perfluorocarbon or a silicone oil encapsulated therein. In another aspect, lipid vesicles having a gas-filled center or core are made. The lipid vesicles having gas-filled central core are made by dehydrating vesicles having the moderately volatile liquid encapsulated in the central core. This drives off the water first, allowing the moderately volatile liquid to stabilize the vesicle structure as it dries, finally forming a central void which can refract light. The preferred vesicles of the invention are paucilamellar vesicles.

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 method of treating a subject in cardiac arrest, comprises blocking the descending aorta of the subject and then perfusing the aortic arch of the subject with a protective solution. The protective solution is one capable of delivering oxygen to the heart of said subject, such as a perfluorochemical blood substitute. Following perfusion, spontaneous circulation is restored.In an improved embodiment of the foregoing, a vasoconstrictor such as epinephrine is administered concurrently with the perfusing step in an amount effective to enhance coronary perfusion with said protective solution.

Abstract: A novel composition for the preservation of organs intended for transplantation and a method of preserving organs intended for transplantation using the composition are described. The composition contains glucuronic acid or a physiologically tolerated salt or ester thereof in a pharmaceutically acceptable organ preservation solution.

Abstract: Perfluoro derivatives of dimethyladamantane; tributylamine; dihexylether; 1-bromooctane; and tetradecahydrophenanthrene, for example, are rendered dispersable colloidally in water or other polar media without the aid of an emulsifying agent by melt spinning a mixture of the compound with a sugar. Thus, a family of new colloidal perfluoro compounds are produced.

Abstract: A method is disclosed for nuclear magnetic resonance spectroscopy wherein the improvement is the use of perfluoro 15-crown-5 ether which has 20 magnetically similar fluorine providing a superior signal to noise ratio with resultant enhanced diagnostic resolution.

Abstract: There are disclosed sterilant compositions having improved biocompatibility comprising a sterilant such as sodium chlorite, an acid such as citric acid, and a buffer such as sodium bicarbonate, the compositions forming an isotonic solution with pH of approximately 7.3.The compositions are particularly useful for cleansing and sterilizing kidney hemodialysis apparatus with minimal disruption of the protein layer which forms on the internal surface of the hollow fibers of a dialysis membrane when a patient is undergoing treatment with the apparatus thus establishing improved biocompatibility between patient and apparatus. The compositions are also useful in other areas of technology, such as, for example, food and wine making technologies.

Abstract: A method for preparing perfluorinated heterocyclic compounds corresponding to the formulas Ia and Ib ##STR1## wherein m represents 3 or 4, andX is a --CF.sub.2 --O--CF.sub.2 -- group, a --CF.sub.2 --CF.sub.2 --CF.sub.2 -- group, or a --CF(CF.sub.3)--CF.sub.2 -- group,and their mixtures, and the perfluoro-N-cyclohexylmorpholine prepared by this method. The compounds are obtained by electrochemical perfluorination starting from corresponding cycloalkenyl derivatives, and they can be used for preparing medically usable aqueous emulsions, e.g. blood substitutes.

Abstract: Improved emulsions of highly fluorinated organic compounds. The emulsions comprise a highly fluorinated organic compound, an oil, that is not substantially surface active and not significantly water soluble, and a surfactant. They are characterized by a well-defined relationship in the relative amounts of the three components.

Abstract: Disclosed here are novel compositions and methods which can be used to reduce or prevent adverse physiological effects of physical exercise or environmental exposure. The novel compositions comprise fluids containing water, sugar, electrolytes, and a substance which is non-toxic to man or animals, can be rapidly absorbed through the gastrointestinal tract, prevents decreases in blood volume, and acts as an energy source.

Abstract: A preparation for blood dialysis comprising two composition, i.e. a first powdery composition comprising (a) solid electrolytes for dialysis and a liquid acid, (b) solid electrolytes for dialysis, glucose and a liquid acid, or (c) solid inorganic salts for dialysis, glucose, sodium acetate and acetic acid, and a second composition comprising (a) sodium hydrogen carbonate and glucose, (b) sodium carbonate, or (c) sodium hydrogen carbonate and sodium acetate.

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.

Abstract: New blood substitutes are described having osmolarities greater than normal blood. The new blood substitues typically comprise a physiologically acceptable fluid electrolyte solution, a physiologically acceptable agent capable of increasing the osmolarity of the blood substitute to a value greater than normal blood, an oxygen carrying substance, and a sufficient amount of water to achieve the desired osmolarity. The blood substitutes of the present invention have osmolarities in the range of 500-800 milliosmoles per liter.

Abstract: The present invention is concerned with improved aqueous asanguineous perfusates, blood substitutes for profound hypothermia, and method of using the same. The perfusates comprise:______________________________________ Component Molar Conc., mM Grams/liter ______________________________________ Hydroxyethyl starch, 40 to 60 gms MW = 500,000 Glucose 5-15 0.9-2.7 Sodium bicarbonate 5-20 0.42-1.68 Potassium chloride 15-40 1.15-3.33 Calcium chloride 0.5-2.04 0.074-0.294 Magnesium chloride 0.25-2.5 0.051-0.510 HEPES or THAM 7.2-15 1.72-3.90 Sodium phosphate, 7.2-15 monobasic, MW = 120.0 Mannitol or sucrose 0-170 0-30.97.

Abstract: Methods of (a) improving the quality of the bones and/or increasing the bone strength and/or the blood quality of and/or (b) treating ascites and/or fatty liver syndrome in animals, including humans, cattle, sheep, goats, swine, cats, dogs and poultry without deleterious effects on the animals or products of the animals by adding small effective amounts of zeolite to the feed of the animals or directly to the animals in the form of a capsule, tablet or the like.

Abstract: The foregoing emergency replacement procedure or method for rapid and drastic reduction of the body burden of AIDS virus residing primarily in the formed elements of the blood involves the removal of all blood from the patient and replacement with an emulsion of a perfluorocarbon chemical or other blood substitute, several exchanges of blood substitute in order to attempt a "scrubbing" in totality of the AIDS containing blood from all of the tissues and organs served by vascular beds and then replacement of the emulsion of perfluorocarbon chemical or other blood substitute with whole blood of the same type as the patient; and wherein the above replacement procedure is carried out using antiviral agents or other agents currently shown to reduce, mitigate or destroy the AIDS virus during and after the above said replacement procedure.

Abstract: Biocompatible fluorcarbon emulsions having fluorocarbon in concentrations of from 75% weight per volume to 125% weight per volume have small, biocompatible particle size stability through heat sterilization with one emulsifying agent, including phospholipids, in concentrations of from 3% to 7% weight per volume. The single emulsifying agent can be hydrogenated lecithins and synthesized lecithins. Fluorocarbon emulsions having fluorocarbon in concentrations of from 40% weight per volume to 125% weight per volume have stability of partial pressure of oxygen and of partial pressure of carbon dioxide through heat sterilization and storage for extended periods of time after having been oxygenated with dissolved oxygen.

Abstract: A method is disclosed for nuclear magnetic resonance spectroscopy wherein the improvement is the use of perfluoro 15-crown-5 ether which has 20 magnetically similar fluorine providing a superior signal to noise ratio with resultant enhanced diagnostic resolution.

Abstract: 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. A process is provided wherein hemoglobin, a fragile material, is formulated into high hemoglobin content water-in-oil-in-water multiple emulsions while maintaining high yields and high oxygen exchange activity.

Abstract: A stable perfluorochemical emulsion is provided which comprises perfluorochemical particles in stabilized vesicles. The vesicles comprise a biocompatible polymer formed by coating the perfluorochemical particles with one or more phospholipid monomer(s) and polymerizing the monomer(s).

Abstract: Solutions of mutant hemoglobins having a lower oxygen affinity than that of native hemoglobin are used as blood substitutes. The mutant hemoglobins are preferably obtained by recombinant DNA techniques. Both alpha and beta globin chains can now be so prepared, making possible the production of wholly artificial hemoglobin, whether conventional or mutant in form. Solutions of wholly artificial hemoglobins are also used as blood substitutes.

Abstract: Diacetylinic phosophocholines have distinctly different endothermic and exothermic transition temperatures. Lipid tubules are formed by hydrating a diacetylinic phosphocholine at a temperature above its endothermic transition temperature. The hydrated lipid is then cooled slowly to a formation temperature 1.degree. to 10.degree. C. below the exothermic transition temperature to form tubule structures. The tubules structures can be polymerized to form permanent tubules. The tubules can be used in the same manner as a liposome vesicle or they can be metal coated for a variety of applications.

Abstract: Microemulsions based on perfluoropolyethers, comprising:an aqueous medium,a perfluoropolyether having a mean molecular weight from 400 to 10,000, and perfluoroalkyl end groups;a fluorinated surfactant, and optionally also a short-chain hydrogenated alcohol or a fluoroalkanol, or a water-soluble salt, said microemulsions being permanently stable in a certain temperature range, in which they are preparable by simple mixing of the components.

Abstract: An up to 125% fluorocarbon emulsion for use in or with animal bodies and organs thereof, maintains emulsion stability through normal sterilization procedures with selective osmotic and buffering agents, maintains the emulsion at within predetermined osmolarity levels and, when desired, free of excessive calcium precipitation, reduces in vivo and in vitro red blood cell injury, reduces adverse anemia effects, reduces viscosity and reduces the rate of oxidation, and tends to equilibrate its distribution in major body organs thereby reducing toxicity. The osmotic agents may buffer and may provide nutrient in the form of sugars.

Abstract: Compounds having a polyhydroxylated hydrophilic moiety, a highly fluorinated moiety and a functional junction group linking said moieties together, wherein said hydrophilic moiety is derived from a polyol or an aminopolyol, and wherein said highly fluorinated moiety consists of a fluorocarbon group wherein at lest 50% of the atoms bonded to the carbon skeleton are fluorine atoms, the other atoms bonded to the carbon skeleton being hydrogen, chlorine or bromine atoms, said highly fluorinated moiety containing at least 4 fluorine atoms; as well as the internal ethers and ketals thereof; process for their preparation; and a compositions containing said compounds as surfactants, together with non polar compounds, for use as gas carriers.

Abstract: Novel nonionic perfluoroalkylthioglycosides of the formula, R.sub.f -E-S-saccharide are described, wherein R.sub.f is a straight or branched chain perfluoroalkyl of 1 to 18 carbon atoms or said perfluoroalkyl substituted by perfluoroalkoxy of 2 to 6 carbon atoms, E is a connecting group, and the saccharide is a mono-, di-, or higher oligosaccharide, comprising 1 to 30 units of 5, 6 or 7 carbon-membered sugars.

Abstract: A single-phase, either isotropic or anisotropic formulation is disclosed, which contains perfluorinated oil and one or more surfactant(s), is useful as an excipient for cosmetic and dermatologic formulations and is characterized in that at least one surfactant is selected from those having the following general formula: ##STR1## wherein: R.sub.F is an F--(CF.sub.2 --CF.sub.2).sub.i -- group;X is a group selected from: ##STR2## --(CH.sub.2 --O).sub.K --; and --(CH.sub.2 --S).sub.K --; wherein R.sup.I is a (C.sub.1 -C.sub.4)-alkyl;Y is a group selected from: NH.sub.2 (R.sup.II).sub.2 and N(R.sup.II).sub.4 ; wherein R.sup.II is a hydrogen atom, or a group selected from --CH.sub.2 --CH.sub.2 --OH and (C.sub.1 -C.sub.4)-alkyl;i is an integer comprised within the range of from 3 to 8;i is zero or 1;K is 2.l;l is an integer comprised within the range of from 1 to 10;m is 1 or 2.Such composition is spontaneously formed when the components are simply placed into contact with one another.

Abstract: A single-vessel method is provided for preparing liposomes in commercial quantities by forming a homogeneous and uniform lipid film in a thin-film evaporator by evaporation of the organic solvent, followed by in situ hydration of the film in an aqueous phase by agitation with the rotor.

Abstract: Fluorinated triethylenediamine compounds such as perfluorotriethylenediamine and the novel compounds undecafluorotriethylenediamine and decafluorotriethylenediamine, prepared by indirect fluorination of triethylenediamine by passing triethylenediamine over, e.g., cobalt trifluoride (CoF.sub.3), are useful as a material capable of carrying oxygen in an aqueous emulsion for lifesaving a patient suffering from massive hemorrhage and for preserving internal organs in transplantation. The compounds undergo rapid biological elimination due to their low molecular weight.

Abstract: A highly concentrated solution is provided which is both hyperosmotic and hyperoncotic with respect to blood plasma and has utility in treating patients experiencing or threatening to experience hypodynamic shock. The physiologically acceptable solution comprises a crystalloid to provide a osmolarity in excess of 5000 mOsms and a colloid to provide an oncocity in excess of 200 mm Hg. The solution is easily transported and administered by a single, rapid infusion of about less than about 1 ml/kg of body weight and results in a rapid and sustained normalization of circulatory function.

Abstract: Biocompatible fluorocarbon emulsions having fluorocarbon in concentrations of from 75% weight per volume to 125% weight per volume have small, biocompatible particle size stability through heat sterilization with one emulsifying agent, including phospholipids, in concentrations of from 3% to 7% weight per volume. The single emulsifying agent can be hydrogenated lecithins and synthesized lecithins. Fluorocarbon emulsions having fluorocarbon in concentrations of from 40% weight per volume to 125% weight per volume have stability of partial pressure of oxygen and of partial pressure of carbon dioxide through heat sterilization and storage for extended periods of time after having been oxygenated with dissolved oxygen.

Abstract: The invention consists in making an emulsion of a fluorinated product, in the presence of a derivative of morpholine. The derivative of morpholine may be the morpholine itself, a saturated derivative or a non-saturated derivative, for example morpholinoethyl methacrylate. The fluorinated product may be a fluorinated monomer, for example 3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl methacrylate. Placing in emulsion is effected by adding to the fluorinated product the derivative of morpholine in the presence of a surface-active agent, and by adjusting, with mechanical stirring, the desired quantity of liquid.

Abstract: Compositions having enhanced gas and drug transporting capability, are prepared by providing a perfluoro compound dispersed in an aqueous medium with a surfactant to form an aqueous initial dispersion, concentrating the perfluoro compound phase of the dispersion as by centrifugation or filtration, wherein a portion of the surfactant remains complexed with the particles of the perfluoro compound phase and the balance of the surfactant is in the aqueous phase, separating the phases, and redispersing the particles of the concentrated perfluoro compound phase to form a final dispersion in which greater than 65% by weight, and preferably at least 75%, of the surfactant present is complexed with the perfluoro compound particles.

Abstract: Sterile liposome-encapsulated hemoglobin having an oxygen carrying capacity of 20 vol/%, a half life of 15-20 hours as measured in mice, with the liposome made from chloroform, HSPC, cholesterol, negatively charged DMPG and alpha-tocopherol.

Abstract: Novel compositions include compounds of the formula: ##STR1## wherein the carbon rings are fully fluorinated.

Abstract: In accordance with the present invention a method of preserving organs using a perfusate or storage solution containing a specific synthetic hydroxyethyl starch in place of human serum albumin is disclosed. A suitable composition is provided. Disclosed is a cold-storage solution and perfusate that has provided 72 hour preservation for the pancreas, 48 hour storage for the kidney and at least 24 hour preservation for the liver.

Abstract: Novel compositions include compounds of the formula: ##STR1## wherein the carbon rings are fully fluorinated and R is selected from the group consisting of fluorine, --CF.sub.3 or --CF(CF.sub.3).sub.2.

Abstract: The present invention relates to new compositions for the preservation of organs prior to implantation comprising hydroxyethyl starch substantially free of ethylene glycol, ethylene chlorohydrin and acetone in a pharmaceutically acceptable organ perfusate.

Abstract: A stable aqueous emulsion of perfluorochemical, a phospholipid and a triglyceride of fatty acids has been demonstrated which has enhanced stability, diminished particle size and heightened tolerance by biological systems. The emulsion has utility as an oxygen transport medium, such as artificial blood.