PHARMACEUTICAL COMPOSITIONS COMPRISING POH DERIVATIVES
The present invention provides for a derivative of monoterpene or sesquiterpene, such as a perillyl alcohol derivative. For example, the perillyl alcohol derivative may be a perillyl alcohol carbamate. The perillyl alcohol derivative may be perillyl alcohol conjugated with a therapeutic agent such as a chemotherapeutic agent. The present invention also provides for a method of treating a disease such as a primary cutaneous lymphoma which may be a cutaneous T cell lymphoma (CTCL). The CTCL may be mycosis fungoides, primary cutaneous anaplastic large cell lymphoma (ALCL), or Sezary syndrome. A patient may be administered a therapeutically effective amount of a derivative of monoterpene (or sesquiterpene).
1 . A method for treating a primary cutaneous lymphoma mycosis fungoides in a mammal, the method comprising administering to the mammal a therapeutically effective amount of a perillyl alcohol carbamate.
2 . The method of claim 1 , wherein the primary cutaneous lymphoma is a cutaneous T cell lymphoma (CTCL).
3 . The method of claim 2 , wherein the cutaneous T cell lymphoma (CTCL) is mycosis fungoides, primary cutaneous anaplastic large cell lymphoma (ALCL), or Sezary syndrome.
4 . The method of claim 2 , wherein the cutaneous T cell lymphoma (CTCL) is mycosis fungoides.
5 . The method of claim 1 , wherein the perillyl alcohol carbamate is perillyl alcohol conjugated with a therapeutic agent.
6 . The method of claim 5 , wherein the therapeutic agent is a chemotherapeutic agent.
7 . The method of claim 6 , wherein the chemotherapeutic agent is selected from the group consisting of a DNA alkylating agent, a topoisomerase inhibitor, an endoplasmic reticulum stress inducing agent, a platinum compound, an antimetabolite, an enzyme inhibitor, and a receptor antagonist.
8 . The method of claim 5 , wherein the therapeutic agent is selected from the group consisting of dimethyl celecoxib (DMC), temozolomide (TMZ) and rolipram.
9 . The method of claim 1 , wherein the perillyl alcohol carbamate is selected from the group consisting of (a) 4-(bis-N,N′-4-isopropenyl cyclohex-1-enylmethyloxy carbonyl [5-(2,5-dimethyl phenyl)-3-trifluoromethyl pyrazol-1-yl] benzenesulfonamide; (b) 4-(3-cyclopentyloxy-4-methoxy phenyl)-2-oxo-pyrrolidine-1-carboxylic acid 4-isopropenyl cyclohex-1-enylmethyl ester; and (c) 3-methyl 4-oxo-3,4-dihydroimidazo[5,1-d][1,2,3,5]tetrazine-8-carbonyl)-carbamic acid-4-isopropenyl cyclohex-1-enylmethyl ester.
10 . The method of claim 1 , further comprising treating the mammal with radiation.
11 . The method of claim 1 , further comprising administering to the mammal a chemotherapeutic agent.
12 . The method of claim 1 , wherein the perillyl alcohol carbamate is administered by inhalation, intranasally, orally, intravenously, subcutaneously or intramuscularly.
13 . The method of claim 1 , wherein the mammal is a human.