Oxigene, Inc.

Optigenex, Inc.

Other

Campamed Corp.

Baylor University

Preventive Medicine Institute

Ronald W Pero

David J Chaplin

David I Sherris

Alan N Schwartz

Kevin G Pinney

Zhi Chen

Francis Y F Lee

Vani P Mocharla

Daniel G Miller

Hans Olov Sj&ouml;gren

Klaus Edvardsen

Anders Olsson

Tomas Ekberg

The disclosure provides a method for isolating the bioactive component of the water-soluble extract ofknown as C-MED-100&#xae;, comprising (i) precipitating the spray drying carrier from C-MED-100&#xae;; (ii) using the resulting C-MED-100&#xae; to obtain a spotting mixture for thin layer chromatography (TLC); (iii) spotting the C-MED-100&#xae; spotting mixture on pre-run TLC plates and eluting the plates to obtain the fluorescing band with R=0.2-0.3; (iv) scraping off the R=0.2-0.3 band, eluting it in ammonia and freeze drying the eluted band to form a powder; and (v) extracting the powder with methanol to remove solubilized silica gel, concentrating the methanol solution and crystalizing the concentrated solution to obtain the bioactive component. The isolated bioactive component in vitro is a quinic acid analog, preferably quinic acid lactone. By contrast, the disclosure further shows the isolated bioactive component in vivo is quinic acid, whether as free acid or as a quinic acid salt, including quinic acid ammonium salt. The disclosure then provides for a pharmaceutical composition comprising a pharmaceutically effective amount of the bioactive component and a nontoxic inert carrier or diluent. The pharmaceutical composition and bioactive component may be used to enhance immune competency, treat disorders associated with the immune system, inhibit the inflammatory response, treat disorders associated with the inflammatory response, enhance the anti-tumor response, and treat disorders associated with the response to tumor formation and growth, all in mammals.

Method for enhancing the DNA repair process, treating disorders associated with the DNA repair process, enhancing antitumor response and treating disorders associated with anti-tumor response in mammals by administering pruified quinic acid and/or carboxy alkyl ester

For use in mammals, methods for enhancing the anti-tumor response and treating disorders associated with anti-tumor response. The methods generally comprise non-topical administration of purified, isolated quinic acid alkyl acid or a carboxy alkyl ester with a non-toxic carrier or diluent.

Method for enhancing the DNA repair process, treating disorders associated with the DNA repair process, enhancing antitumor response and treating disorders associated with anti-tumor response in mammals by administering purified quinic acid and/or carboxy alkyl ester

For use in mammals, methods for enhancing the DNA repair process, treating disorders associated with the DNA repair process, enhancing anti-tumor response and treating disorders associated with anti-tumor response. The methods generally comprise non-topical administration of purified, isolated quinic acid alkyl acid or a carboxy alkyl ester with a non-toxic carrier or diluent.

The disclosure provides a method for isolating the bioactive component of the water-soluble extract ofknown as C-MED-100&#xae;, comprising (i) precipitating the spray drying carrier from C-MED-100&#xae;; (ii) using the resulting C-MED-100&#xae; to obtain a spotting mixture for thin layer chromatography (TLC); (iii) spotting the C-MED-100&#xae; spotting mixture on pre-run TLC plates and eluting the plates to obtain the fluorescing band with R=0.2-0.3; (iv) scraping off the R=0.2-0.3 band, eluting it in ammonia and freeze drying the eluted band to form a powder; and (v) extracting the powder with methanol to remove solubilized silica gel, concentrating the methanol solution and crystallizing the concentrated solution to obtain the bioactive component. The isolated bioactive component in vitro is a quinic acid analog, preferably quinic acid lactone. By contrast, the disclosure further shows the isolated bioactive component in vivo is quinic acid, whether as free acid or as a quinic acid salt, including quinic acid ammonium salt. The disclosure then provides for a pharmaceutical composition comprising a pharmaceutically effective amount of the bioactive component and a nontoxic inert carrier or diluent. The pharmaceutical composition and bioactive component may be used to enhance immune competency, treat disorders associated with the immune system, inhibit the inflammatory response, treat disorders associated with the inflammatory response, enhance the anti-tumor response, and treat disorders associated with the response to tumor formation and growth, all in mammals.

Method of preparation and composition of a water soluble extract of the bioactive component of the plant species Uncaria for enhancing immune, anti-inflammatory, anti-tumor and DNA repair processes of warm blooded animals

A method for isolating the bioactive component of the water-soluble extract ofknown as C-MED-100&#xae;, comprising (i) precipitating the spray drying carrier from C-MED-100&#xae;; (ii) using the resulting C-MED-100&#xae; to obtain a spotting mixture for thin layer chromatography (TLC); (iii) spotting the C-MED-100&#xae; spotting mixture on pre-run TLC plates and eluting the plates to obtain the fluorescing band with R=0.2-0.3; (iv) scraping off the R=0.2-0.3 band, eluting it in ammonia and freeze drying the eluted band to form a powder; and (v) extracting the powder with methanol to remove solubilized silica gel, concentrating the methanol solution and crystallizing the concentrated solution to obtain the bioactive component. The isolated bioactive component in vitro is a quinic acid analog, preferably quinic acid lactone. By contrast, the isolated bioactive component in vivo is quinic acid, whether as free acid or as a quinic acid salt, including quinic acid ammonium salt. A pharmaceutical composition comprising a pharmaceutically effective amount of the bioactive component and a nontoxic inert carrier or diluent. The bioactive component may be used to enhance immune competency, treat disorders associated with the immune system, inhibit the inflammatory response, treat disorders associated with the inflammatory response, enhance the anti-tumor response, and treat disorders associated with the response to tumor formation and growth, all in mammals.

A method for isolating the bioactive component of the water-soluble extract ofknown as C-MED-100&#xae;, comprising (i) precipitating the spray drying carrier from C-MED-100&#xae;; (ii) using the resulting C-MED-100&#xae; to obtain a spotting mixture for thin layer chromatography (TLC); (iii) spotting the C-MED-100&#xae; spotting mixture on pre-run TLC plates and eluting the plates to obtain the fluorescing band with R=0.2-0.3; (iv) scraping off the R=0.2-0.3 band, eluting it in ammonia and freeze drying the eluted band to form a powder; and (v) extracting the powder with methanol to remove solubilized silica gel, concentrating the methanol solution and crystalizing the concentrated solution to obtain the bioactive component. The isolated bioactive component is a quinic acid analog, preferably quinic acid lactone. A pharmaceutical composition comprising a pharmaceutically effective amount of the bioactive component and a nontoxic inert carrier or diluent. The bioactive component may be used to enhance immune competency, treat disorders associated with the immune system, inhibit the inflammatory response, treat disorders associated with the inflammatory response, enhance the anti-tumor response, and treat disorders associated with the response to tumor formation and growth, all in mammals.

METHOD OF PREPARATION AND COMPOSITION OF A WATER SOLUBLE EXTRACT OF THE BIOACTIVE COMPONENT OF THE PLANT SPECIES UNCARIA FOR ENHANCING IMMUNE, ANTI-INFLAMMATORY, ANTI-TUMOR AND DNA REPAIR PROCESSES OF WARM BLOODED ANIMALS

Treatment of warm-blooded animals having a tumor or non-malignant hypervascularation, by administering a sufficient amount of a cytotoxic agent formulated into a phosphate prodrug form having substrate specificity for microvessel phosphatases, so that microvessels are destroyed preferentially over other normal tissues, because the less cytotoxic prodrug form is converted to the highly cytotoxic dephosphorylated form.

Compositions and methods for use in targeting vascular destruction

A method of treating immune suppression in a warm-blooded animal bearing a tumor, by administering to the animal an amount of combretastatin A4 and/or a prodrug thereof effective to enhance immune responsiveness without causing vascular destruction. Immunotherapy treatment to inhibit or kill tumor cells includes administering to the animal an immune-response-stimulating agent such as a vaccine of tumor cells genetically modified to produce an immune-response-enhancing cytokine while counteracting tumor-induced immune suppression in the animal by administering combretastatin A4 and/or a prodrug thereof.

Use of combretastatin A4 and its prodrugs as an immune enhancing therapy

Methods of killing tumor or cancer cells in human patients using an aryl N-substituted carboxamide having one or more aryl halo or one or more aromatic nitrogens, and/or acid addition salts thereof. The carboxamide may be an N-substituted nicotinamide or an N-substituted benzamide having such features, and may be used directly as a chemotherapeutic agent, or as a sensitizer for radiation or other chemotherapeutic agents. New compositions for such use include N-(2-diethylamino-ethyl)-4-amino-3-chlorobenzamide, N-(2-diethylamino-ethyl) nicotinamide, and their acid addition salts, e.g. hydrochlorides.

Use of aryl N-substituted carboxamides directly and as radio-and chemosensitizers for killing tumor and cancer cells and novel compounds for such use

The present invention is directed to a method of preparation and the composition of a water soluble extract of the plant species Uncaria. The present invention is also directed to the pharmaceutical use of the composition for the enhancement of the immune, anti-inflammatory, anti-tumor and DNA repair processes of warm blooded animals. The present preparation of the water soluble extract of the plant species Uncaria results in the depletion of many of the ingredients which lead to various toxic side effects associated with other extracts or compositions derived from Uncaria. Also, the present preparation leads to the depletion of many of the active ingredients commonly associated with other extracts and compositions of the plant species Uncaria. Therefore, the present invention teaches that the hot water extraction of the crude plant parts of Uncaria and the subsequent dialysis of the solubilized products yields a low molecular weight composition which maintains a high degree of the anti-tumor, inflammatory and immune stimulatory activities associated with the crude plant parts.

Method of preparation and composition of a water soluble extract of the plant species uncaria for enhancing immune, anti-inflammatory, anti-tumor and DNA repair processes of warm blooded animals

This invention provides a method of killing tumor cells or microorganisms which comprises contacting the tumor cells or the microorganisms with an amount of nicotinamide adenine dinucleotide (NAD) or its analogs effective to increase clonogenic toxicity of cells. This invention also provides a method of killing tumor cells or microoganisms in a subject which comprises administering an amount of nicotinamide adenine dinucleotide or its analogs effective to increase clonogenic toxicity of cells to the subject.

Uses of nicotinamide adenine dinucleotide and its derivatives for treatment of malignant and infectious diseases

The present invention is directed to a method of preparation and the composition of a water soluble extract of the plant species,. The present invention is also directed to the pharmaceutical use of the composition for the enhancement of the immune, anti-inflammatory, anti-tumor and DNA repair processes of warm blooded animals. The present preparation of the water soluble extract of the plant species,results in the depletion of many of the ingredients which lead to various toxic side effects associated with other extracts or compositions derived from,. Also, the present preparation leads to the depletion of many of the active ingredients commonly associated with other extracts and compositions of the plant species,. Therefore, the present invention teaches that the hot water extraction of the crude plant parts of,and the subsequent dialysis of the solubilized products yields a low molecular weight composition which maintains a high degree of the anti-tumor, inflammatory and immune stimulatory activities associated with the crude plant parts.

Method of preparation and composition of a water soluble extract of the plant species Uncaria for enhancing immune, anti-inflammatory and anti-tumor processes of warm blooded animals

N-acetyl-3-chloroprocainamide, its acid addition salts, mixtures thereof, formulations containing the same for therapeutic administration to a human or other animal, and uses thereof in methods of inhibiting or killing tumor or cancer cells and in methods of treating inflammatory disorders.

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Arlington, VT, United States of America

Ronald W Pero