Compositions and methods of use of phorbol esters

Details Compositions and methods of use of phorbol esters Compositions and methods of use of phorbol esters

A - Human Necessities

61

K

A61K 31/23 (2006.01) A61P 31/18 (2006.01) A61P 35/00 (2006.01)

Patent

CA 2676551

Methods and compositions containing a phorbol ester or a derivative of a phorbol ester are provided for the treatment of cytopathic diseases. Cytopathic diseases may be caused by a variety means such as viral infections like HIV and AIDS, or the development of neoplasms in a mammalian subject. The methods and compositions of the invention are effective for inhibiting de novo HIV infection, upregulating viral expression from latent provirus, inhibiting HIV-induced cytopathic effects, down regulating the HIV receptor, increasing ThI cytokine expression, decreasing Th2 cytokine expression, increasing ERK phosphorylation, inducing apoptosis in malignant cells, inducing remission, maintaining remission, as chemotherapeutic agents, as well as for decreasing symptoms of cytopathic diseases and opportunistic infections that may accompany such diseasesl. Additional compositions and methods are provided which employ a phorbol ester or derivative compound in combination with at least one additional agent such as those used in HAART protocols, therapeutic agents used to treat opportunistic infections due to HIV, or chemotherapeutic agents to yield more effective treatment tools against cytopathic diseases in mammalian subjects.

Des procédés et compositions contenant un ester de phorbol ou un dérivé d'ester de phorbol sont proposés pour le traitement de maladies cytopathiques. Les maladies cytopathiques peuvent être provoquées par une variété de raisons comme des infections virales, telles que le HIV et le SIDA, ou le développement de néoplasmes chez un sujet mammifère. Les procédés et compositions de l'invention sont efficaces pour inhiber de novo l'infection HIV, réguler positivement l'expression virale provenant d'un provirus latent, inhiber les effets cytopathiques induits par le HIV, réguler négativement le récepteur HIV, augmenter l'expression de la cytokine ThI, diminuer l'expression de la cytokine Th2, augmenter la phosphorylation ERK, provoquer l'apoptose dans des cellules malignes, provoquer une rémission, maintenir la rémission, comme des agents chimiothérapeutiques, ainsi que pour diminuer les symptômes de maladies cytopathiques et des infections opportunistes qui peuvent accompagner ces maladies. Des compositions et procédés additionnels sont fournis qui utilisent un ester de phorbol ou un compose dérivé en combinaison avec au moins un agent additionnel, tel que ceux utilisés dans les protocoles HAART, des agents thérapeutiques utilisés pour traiter les infections opportunistes dues au HIV, ou des agents chimiothérapeutiques, afin de donner davantage d'outils efficaces contre les maladies cytopathiques chez les sujets mammifères.

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