A method for curing and/or improving hypoxia characterized by administering a compound represented by the general formula (1), ##STR1## said compounds have been known in prior art literatures, for example, as carbostyril derivatives in Japanese Patent Kokai No. 54-160389 (1979), etc., as benzoxazine derivatives in Japanese Patent Kokai No. 59-70675 (1984), and as benzoazepine derivatives in Japanese Patent Kokai No. 57-193461 (1982), and they have been known as central nervous system controlling agents and antihistaminic agents.The present invention was established on the basis of the findings that the compounds represented by the general formula (1) possess excellent pharmacological activities for curing and/or improving hypoxia and also possess excellent anti-oxidative activities, which could not have been anticipated from the disclosures in the prior art literatures.

Otsuka Pharmaceutical Co., Ltd.

Method for treating hypoxia

The current invention provides a new organ preservation solution, suitable for machine perfusion, for maintaining viability of organs, parts of organs and tissues. This solution has been designed to overcome a number of problems associated with hypothermic machine perfusion of donor organs, in particular organs obtained from non-heart-beating donors. The solution prevents or minimizes the adverse affects caused by ischemia, hypoxia, energy and nutrient depletion, acidification, hypothermia and reperfusion injury. The preservation solutions according to the current invention are superior to current state of the art preservation solutions, in particular for preservation and perfusion of organs obtained from non-heart-bearing donors, by supplying increased concentrations and an optimized balance of amino acids, vitamins, anti-oxidants, high molecular weight additives and enhanced buffering capacity. In addition, the preservation solution according to the invention combines optimal physical and chemical properties with the use of readily available, inexpensive and pharmaceutically tested and acceptable compounds, reducing the cost of manufacturing and facilitating medical certification of solutions according to the current invention.

Doorschodt; Benedict Marie

Bessems; Maud

Organoflush B.V.

Composition for cold preservation and perfusion of organs

According to the claims, the present invention comprises the preparation of chemically modified, cross-linked hemoglobins with improved functional properties, the cross-linked hemoglobins prepared according to this method and the use of these hemoglobins as artificial oxygen carriers. The synthesis method is characterized by technical simplicity as well as by high yields. Deoxygenated hemoglobin of high purity is conjugated covalently under the protection of an antioxidant with an effector of oxygen binding, especially with pyridoxal-5-phosphate, after which the hemoglobin is polymerized with glutardialdehyde as a bifunctional cross-linking agent. At the same time, there is a large increase in the volume of the reaction mixture and a decrease in the concentration of the hemoglobin during the addition of the cross-linking agent. Subsequently, after further dilution with water, a polyethylene oxide derivative is chemically linked to the cross-linked hemoglobins. Polymers are obtained, which are compatible with blood plasma and have optimized cooperativity and half saturation pressure values and can find use as artificial oxygen carriers and, in particular, are divided into a lower molecular weight fraction as blood substitute and a higher molecular weight fraction as blood additive, for example, for the treatment of oxygen-deficiency conditions.

Sanguibiotech GmbH

Synthetic oxygen transport made from cross-linked modified human or porcine haemoglobin with improved properties, method for a preparation thereof from purified material and use thereof

Methods and pharmaceutical compositions for preconditioning and/or providing neuroprotection to the animal central nervous system against the effects of ischemia, trauma, metal poisoning and neurodegeneration, including the associated cognitive, behavioral and physical impairments. In one embodiment, the method is accomplished by stimulating and stabilizing hypoxia-inducible factor-1.alpha. (HIF-1.alpha.). HIF-1.alpha. is known to provide a neuroprotective benefit under ischemic conditions. Patients at risk for certain diseases or disorders that are associated with risk for cerebral ischemia may benefit, e.g., those at risk for Alzheimer's disease, Parkinson's disease, Wilson's disease or stroke or those patients having head or spinal cord injury. Patients undergoing certain medical procedures that may result in ischemia may also benefit. Initially, the possibility of ischemia or neurodegeneration is recognized. Intranasal therapeutic agents are administered to the upper third of the nasal cavity to bypass the blood-brain barrier and access the central nervous system directly to avoid unwanted and potentially lethal side effects. Therapeutic agents include those substances that interact with iron and/or copper such as iron chelators, copper chelators, and antioxidants. A particular example of such therapeutic agents is the iron chelator deferoxamine (DFO). Intranasal administration of DFO is known to stimulate and/or stabilize HIF-1.alpha. and provides an efficient and safe method for pre-conditioning the brain to protect against cerebral ischemia. Moreover, DFO is shown to decrease weight loss in subjects when administered pre and/or post stroke.

antioxidant/hypoxia

Method for treating hypoxia

Composition for cold preservation and perfusion of organs

Synthetic oxygen transport made from cross-linked modified human or porcine haemoglobin with improved properties, method for a preparation thereof from purified material and use thereof

Methods for providing neuroprotection for the animal central nervous system against neurodegeneration caused by ischemia

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