Children's Hospital Medical Center

Synthetic Blood International, Inc.

Suntech, Inc.

Hemagen/pfc

Other

Children's Hospital Research Foundation

Implanted Biosystems, Inc.

Children's Hospital Research Foundation, a Division of Children's

University of Cincinnati

Sun Ventures, Inc.

Adamantech, Inc.

Oxygen Biotherapeutics, Inc.

Leland C Clark, Jr

Robert F Shaw

Gholam A Peyman

Richard J Lagow

Robert E Moore

Lawrence A Shimp

Christ Tamborski

Jerome L Ackerman

Stephen R Thomas

Richard E Hoffmann

The sensitivity of enzyme-based polarographic electrodes to oxygen concentration can be significantly reduced or eliminated by providing an oxygen-reservoir in intimate contact with the oxidative enzyme. This is achieved by making a stabilized emulsion between the enzyme and a compound in which oxygen is extremely soluble. An aqueous glucose oxidase solution is emulsified with a perfluorocarbon liquid, and the resulting emulsion is stabilized by chemically crosslinking the mixture to form a gel. Thin layers of the emulsion are fabricated by spreading a layer of the liquid emulsion before gelation occurs. Additional carrier proteins such as albumin may be added to the enzyme prior to crosslinking to protect enzymatic activity and enhance gel strength. Additional electron transport compounds may be added to further reduce sensitivity to oxygen concentration.

Implantable glucose sensor

The sensitivity of enzyme-based polarographic electrodes to oxygen concentration can be significantly reduced or eliminated by providing an oxygen-reservoir in intimate contact with the oxidative enzyme. This is achieved by making a stabilized emulsion between the enzyme and a compound in which oxygen is extremely soluble. An aqueous glucose oxidase solution is emulsified with a perfluorocarbon liquid, and the resulting emulsion is stabilized by chemically crosslinking the mixture to form a gel. Thin layers of the emulsion are fabricated by spreading a layer of the liquid emulsion before gelation occurs. Additional carrier proteins such as albumin may be added to the enzyne prior to crosslinking to protect enzymatic activity and enhance gel strength. Additional electron transport compounds may be added to further reduce sensitivity to oxygen concentration.

Perfluorinated alkylcyclohexane and alkyl cyclopentane derivatives of the empirical formula C,F,boil at atmospheric pressure in the range of 144-146&deg; C. and are utilized as mediums for gas transport in liquid ventilation and in artificial blood. Compounds of the C,F,formula which can exist only as a single stereoisomer are preferred as mediums for gas transport.

Selected C-10 perfluorinated hydrocarbons for liquid ventilation and artificial blood

Perfluorotetramethylcyclohexane shows improved properties for use in biological gas exchange, both as a blood substitute and as perfluorocarbon for intra-pulmonary applications. The material has an adequately low vapor pressure to completely avoid causing hyperinflated lung damage and to increase the interval between required applications. However, the compound has a sufficiently high vapor pressure to produce acceptably brief residence time within the body. A method has been developed for using this novel compound to accelerate the exhalation of very low vapor pressure compounds such as perfluorophenanthrene from the lungs. The addition of perfluorotetramethylcyclohexane, along with perfluorophenanthrene, greatly increases the rate at which the perfluorophenanthrene is exhaled.

Perfluorocarbons for biological gas exchange and method

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 minimum effective dose of a perfluorochemical liquid or emulsion through the trachea for coating the alveolar sacs of a lung of the mammal. The preferred perfluorochemicals have a very low vapor pressure to avoid inducing hyperinflated lung syndrome and are supplied in a minimum effective dosage sufficient to coat the inner lung surfaces. The perfluorochemicals are permeable to the ambient gas and reside 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. Effective coating of the lungs with a small (generally &lt;0.1 ml/kg) dose of very low vapor pressure perfluorochemical is achieved through administration of an aqueous emulsion of the perfluorochemical or a mixture of the very low vapor pressure compound in a larger volume of a higher vapor pressure carrier perfluorochemical.

Method of assisting normal breathing in a mammal having a lung disorder

Stable emulsions of highly fluorinated organic compounds for use as oxygen transport agents, 'artificial bloods' or red blood cell substitutes and as contrast agents for biological imaging. The emulsions comprise a highly fluorinated organic compound, an oil that is not substantially surface active and not significantly soluble in water, a surfactant and water.

Stable emulsions of highly fluorinated organic compounds

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.

Method for assisting normal breathing in a mammal having a lung disorder

Perfluoroindane is used as a gas transport agent in animals without causing gas or vapor pulmonary embolism. Emulsions containing perfluoroindane as the oxygen carrying component are made and infused into an animal and the perfluoroindane escapes at a very rapid rate from the animal body. The perfluoroindane-containing liquids or emulsions are considered valuable for angioplasty and as a blood substitute.

Stable perfluorocarbon and oil emulsions

A vitreous substitute is disclosed which is introduced into the eye by injection in a liquid form to form a gel in the eye to replace the vitreous. The substitute comprises a silicone liquid which is allowed to gel in the eye. Methods involving the use of these gels during retinal surgery are also disclosed.

Vitreous replacement

A combination of perfluorocarbon liquid and silicone is used to treat ophthalmological disorders of the eye. Perfluorocarbon liquid and silicone are injected into the eye to treat detached or torn retinas. A method of treating ophthalmological disorder of the eye with the combination of perfluorocarbon liquid and silicone is also disclosed.

Combination of perfluorocarbon liquid and silicone and method of

Novel polarographic (voltametric) methods for measuring in vivo or in vitro analytes in an animal tissue and oxygen in the sensor enzymatic reaction layer with an electroenzymatic sensor are disclosed. The new and vastly improved methods are directed to generating from the electroenzymatic sensor at a suitable voltage an anodic current derived from an anodically active product generated by enzymatic activity on an analyte for measuring the analyte and a cathodic current derived from reducing the oxygen in the sensor enzymatic reaction layer for measuring the oxygen. Additionally, the method contemplates switching the voltage between anodic and cathodic potentials to generate anodic and cathodic currents or applying the voltage at a fixed rate. Advantageously, the methods of this invention may be utilized with implanted sensors in an animal including a human. The sensors may be implanted in blood or non-blood sites. Finally, the methods of this invention further contemplate analyzing the type of conditions around the implanted sensor site to improve the reliability of the sensor as well as the detection of the analyte by the sensor.

Polarographic method for measuring both analyte and oxygen with the same

A novel and improved method to detect and/or measure indirectly at least one gas, particularly dissolved gases, of an animal employing nuclear magnetic resonance techniques (NMR). The method examines an NMR spectrum to determine chemical shift relaxation times or spin-spin couplings for an element of an animal influenced by at least one gas of the animal. Uniquely, the gas detected according to the principles of this invention may be insensitive to present NMR techniques. Further, the present invention discloses a novel method to determine and monitor gaseous physiological states of an animal. Because of the unique and advantageous non-invasive, non-destructive and non-ionizing properties, the present invention may be employed in an animal continuously and in vivo. Still further, the present invention provides for the imaging of at least one-, two-, or three-dimensional projections reconstructed from a chemical shift, relaxation times, or spin-spin couplings for an element of an animal influenced by at least one gas in the animal. Novel compounds directed to providing radio-frequency reference signals in which chemical shifts may be determined therefrom are also disclosed.

NMR compositions for indirectly detecting a dissolved gas in an animal

The present invention relates to a novel implantable biosensor and method for sensing products, such as hydrogen peroxide, generated from an enzymatic reaction between an analyte, like glucose, and an enzyme in the presence of oxygen. The novel implantable biosensor is uniquely equipped with an enclosed chamber for containing oxygen and can be adapted for extracting oxygen from animal tissue adjacent the container. The reservoir of oxygen contained in the enclosed chamber is supplied to the enzymatic reaction from both sides of a membrane. The enclosed chamber is uniquely designed to be impermeable to substances, like liquid and cells, that possibly can interfere with the supply of the oxygen permeating through the membrane to the enzymatic reaction. Also, the implantable biosensor is designed to optically or electrically sense products generated from the enzymatic reaction which serve as a function of the analyte.

Growing community of inventors

Cincinnati, OH, United States of America

Leland C Clark, Jr