Medinox, Inc.

Vassil P Vassilev

Ching-San Lai

Tingmin Wang

Long-Shiuh Chen

Wei-Cheng Liaw

In accordance with the present invention, there are provided conjugates of dithiocarbamates &ldquo;DC&rdquo;) and pharmacologically active agents (e.g., NSAIDs). Invention conjugates provide a new class of pharmacologically active agents (e.g., anti-inflammatory agents) which cause a much lower incidence of side-effects due to the protective effects imparted by modifying the pharmacologically active agents as described herein.

Protected forms of pharmacologically active agents and uses therefor

The present invention provides a novel dithiocarbamamte disulfide dimer useful in various therapeutic treatments, either alone or in combination with other active agents. In one method, the disulfide derivative of a dithiocarbamate is coadministered with an agent that inactivates (or inhibits the production of) species that induce the expression of nitric oxide synthase to reduce the production of such species, while, at the same time reducing nitric oxide levels in the subject. In another embodiment, free iron ion levels are reduced in a subject by administration of a disulfide derivative of a dithiocarbamate(s) to scavenge free iron ions, for example, in subjects undergoing anthracycline chemotherapy. In another embodiment, cyanide levels are reduced in a subject by administration of a disulfide derivative of a dithiocarbamate so as to bind cyanide in the subject. In a further aspect, the present invention relates to compositions and formulations useful in such therapeutic methods.

Therapeutic methods employing disulfide derivatives of dithiocarbamates and compositions useful therefor

The preparation and use of a protected organic aldehyde is described wherein bioavailability of the orally administered therapeutic aldehyde is improved. The protected aldehyde is prepared by reacting the aldehyde with a protecting group, for example, condensing the aldehyde chemically with a thiazolidine-4-carboxylic acid. The improved bioavailability of such orally administered drugs increases the feasibility of delivering sufficient amounts of vanillin or other therapeutic organic aldehydes in vivo to prevent sickling in sickle cell anemia. Combination therapy is also described wherein a protected organic aldehyde is administered to a subject in treatment of sickle cell anemia in conjunction with one or more other drugs, such as pain killers, used in treatment of the symptoms of sickle cell anemia or sickle cell disease.

Methods for treatment of sickle cell anemia

Therapeutic methods employing disulfide derivatives of dithiocarbonates and compositions useful therefor

In accordance with the present invention, there are provided conjugates of physiologically compatible free radical scavengers (e.g., dithiocarbamate disulfides (DD)) and pharmacologically active agents (e.g., NSAIDS). Invention conjugates provide a new class of pharmacologically active agents (e.g., anti-inflammatory agents) which cause a much lower incidence of side-effects due to the protective effects imparted by modifying the pharmacologically active agents as described herein. In addition, invention conjugates are more effective than unmodified pharmacologically active agents because cells and tissues contacted by the pharmacologically active agent(s) are protected from the potentially damaging effects of free radical overproduction induced thereby as a result of the co-production of free radical scavenger (e.g., dithiocarbamate), in addition to free pharmacologically active agent, when invention conjugate is cleaved.

Conjugates of dithiocarbamate disulfides with pharmacologically active agents and uses therefor

The present invention provides methods for producing pharmaceutical-grade particulate dithiocarbamates from secondary amines by vigorously contacting at least one secondary amine and a pharmaceutically acceptable diluent that is a solvent for the carbon disulfide, but not for the secondary amine in an inert gas atmosphere, cooling the mixture so as to precipitate the dithiocarbamate therefrom, and separating the precipitated dithiocarbamate from the cooled mixture. The preferred solvent contains absolute ethanol. In alternative embodiments, the invention further provides methods for purifying a dithiocarbamate to obtain a pharmaceutical-grade dithiocarbamate particulate from a dithiocarbamate feed and methods for producing a sterile pharmaceutical-grade dithiocarbamate from a dithiocarbamate feed.

Method for preparation of pharmaceutical-grade dithiocarbamate

The present invention provides a novel dithiocarbamate disulfide dimer useful in various therapeutic treatments, either alone or in combination with other active agents. In one method, the disulfide derivative of a dithiocarbamate is coadministered with an agent that inactivates (or inhibits the production of) species that induce the expression of nitric oxide synthase to reduce the production of such species, while, at the same time reducing nitric oxide levels in the subject. In another embodiment, free iron ion levels are reduced in a subject by administration of a disulfide derivative of a dithiocarbamate(s) to scavenge free iron ions, for example, in subjects undergoing anthracycline chemotherapy. In another embodiment, cyanide levels are reduced in a subject by administration of a disulfide derivative of a dithiocarbamate so as to bind cyanide in the subject. In a further aspect, the present invention relates to compositions and formulations useful in such therapeutic methods.

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San Diego, CA, United States of America

Vassil P Vassilev