Yale University

Plough, Inc.

John M Pawelek

Seth J Orlow

Michael P Osber

David Gordon Bermudes

Kenneth Brooks Low

Patricia P Agin

Stefano A Sodi

Jean L Bolognia

James T Platt

The present invention provides compositions and methods for reducing skin pigmentation. The invention comprises inhibitors of sialyltransferase, inhibitors of oligosaccharide formation or oligosaccharide activity, and methods of using such inhibitors. In certain embodiments, the invention comprises inhibiting the formation and/or activity of Neu5Ac(&#x3b1;2,6)Gal/GalNAc-containing oligosaccharides.

Compositions and methods for reducing skin pigmentation

The present invention is directed to the isolation and use of super-infective, tumor-specific vectors that are strains of parasites including, but not limited to bacteria, fungi and protists. In certain embodiments the parasites include, but are not limited to, the bacterium Salmonella spp., such as , the bacterium and the protozoan . In other embodiments, the present invention is concerned with the isolation of super-infective, tumor-specific, suicide gene-containing strains of parasites for use in treatment of solid tumors.

Vectors for the diagnosis and treatment of solid tumors including melanoma

The present invention is directed to the isolation and use of super-infective, tumor-specific vectors that are strains of parasites including, but not limited to bacteria, fungi and protists. In certain embodiments the parasites include, but are not limited to, the bacterium Salmonella spp., such as,the bacterium,and the protozoan,In other embodiments, the present invention is concerned with the isolation of super-infective, tumor-specific, suicide gene-containing strains of parasites for use in treatment of solid tumors.

Disclosed are cosmetic melanins of different colors produced by procedures involving oxidative polymerization of monomeric precursors of melanin and/or co-monomers that enhance substantivity or adherence of the melanins to the skin and hair. Also disclosed are methods for preparing cosmetic melanins and methods for using these compositions topically to produce a natural-appearing tan and to prevent damage to skin caused by UV exposure.

Cosmetic melanins

A melanin that is soluble in an aqueous solution at a pH of at least 5 to 9 at a temperature of 0.degree. to 100.degree. C. The melanin is further characterized by being capable of being filtered through at least a 0.45 micron size filter. Still further, the melanin is characterized by having a molecular weight of greater than 10,000 kilodaltons. The melanin is useful for providing a naturally-appearing tan to mammalian skin and hair. Such melanin can be produced by combining dopachrome and 5,6-dihydroxyindole (or allowing dopachrome to spontaneously form 5,6-dihydroxyindole) and an appropriate enzyme or by combining 5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid or by incubating 5,6-dihydroxyindole-2-carboxylic acid alone. The melanin is also useful for providing a sun-screen to mammalian skin and hair.

Soluble melanin

A skin-whitening and suntan-inhibiting composition comprising (a) a compound which depletes glutathione, and (b) hydroquinone or an alkyl or aralkyl ether of hydroquinone.

Composition and method for whitening skin

A melanin that is soluble in an aqueous solution at a pH between 5 and 9 at a temperature of 0.degree. to 100.degree. C. Advantageously, the melanin is capable of being filtered through at least a 0.45 micron size filter, and has a molecular weight of greater than 10,000 kilodaltons. The melanin is useful for providing a naturally-appearing tan to mammalian skin and hair. Such melanin can be produced by combining dopachrome and an appropriate enzyme, or by incubating 5,6-dihydroxyindole-2-carboxylic acid alone or with 5,6-dihydroxyindole, or with 3-amino-tyrosine. The melanin is also useful for providing a sun-screen to mammalian skin and hair, to treat post-inflammatory hypo- and hyperpigmentation, to tint glass and plastic, to protect industrial materials against ultraviolet damage, and as a coloring agent in foodstuffs such as coffee, tea, soda, whiskey and liquors.

Synthetic melanin as a sunscreen and tanning agent

Synthetic melanin

A melanin that is soluble in an aqueous solution at a pH of at least 5 to 9 at a temperature of 0 to 100.degree. C. The melanin is further characterized by being capable of being filtered through at least a 0.45 micron size filter. Still further, the melanin is characterized by having a molecular weight of greater than 10,000 kilodaltons. The melanin is useful for providing a naturally-appearing tan to mammalian skin and hair. Such melanin can be produced by combining dopachrome and 5,6-dihydroxyindole (or allowing dopachrome to spontaneously form 5,6-dihydroxyindole) and an appropriate enzyme or by combining 5,6-dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid or by incubating 5,6-dihydroxyindole-2-carboxylic acid alone. The melanin is also useful for providing a sun-screen to mammalian skin and hair, to treat post-inflammatory hypo- and hyperpigmentation, to tint glass and plastic, to protect industrial materials against ultraviolet damage, and as a coloring agent in foodstuffs such as coffee, tea, soda, whiskey and liquors.

A melanin that is soluble in an aqueous solution at a pH of at least 5 to 9 at a temperature of 0.degree. to 100.degree. C. The melanin is further characterized by being capable of being filtered through at least a 0.45 micron size filter. Still further, the melanin is characterized by having a molecular weight of greater than 10,000 kilodaltons. The melanin is useful for providing a naturally-appearing tan to mammalian skin and hair. The melanin is also useful for providing a sun-screen to mammalian skin and hair.

A method of decreasing the melanin content in mammalian skin and hair by administering to a mammal a composition comprising an effective amount of one or more derivatives of 5,6-dihydroxyindole, the derivatives having one or more substituents which are capable of being removed enzymatically, in admixture with a pharmaceutically acceptable carrier, the amount being 0.5% to 20% wt/wt based on the composition.

Decreasing the melanin content in mammalian skin and hair using

A phosphorylated derivative of L-dopa of the formula ##STR1## wherein when X is ##STR2## wherein Z is --CH.sub.2, N, S or a linkage other than oxygen which renders the phosphate group resistant to hydrolysis by phosphatase enzymes in tissues and biological fluids, then Y is OQ, wherein Q is H or an alkyl with one to twelve carbon atoms, or wherein X is OQ, then Y is ##STR3## wherein R' is hydrogen or a pharmaceutically acceptable cation and R is a moiety which increases hydropobicity. The phosphorylated derivative of L-dopa is useful as an agent to increase the melanin content in mammalian skin and hair.

Phosphorylated derivatives of L-dopa and compositions and methods for

A composition and method for the treatment of melanomas in human beings wherein the composition comprises at least one O-phosphorylated derivative of 3-(3,4-dihydroxy)phenylalanine.

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Hamden, CT, United States of America

John M Pawelek