Curcumin and curcuminoid inhibition of angiogenesis

Abstract

Methods for treating diseases or disorders of the skin which are characterized by angiogenesis have been developed using curcumin and curcumin analogs. Based on the results obtained with curcumin, it has been determined that other angiogenesis inhibitors can also be used to treat these skin disorders. It has further been discovered that curcumin acts to inhibit angiogenesis in part by inhibition of basic fibroblast growth factor (bFGF), and thereby provides a means for treating other disorders characterized by elevated levels of bFGF, such as bladder cancer, using curcumin and other analogues which also inhibit bFGF. Representative skin disorders to be treated include the malignant diseases angiosarcoma, hemangioendothelioma, basal cell carcinoma, squamous cell carcinoma, malignant melanoma and Karposi's sarcoma, and the non-malignant diseases or conditions including psoriasis, lymphangiogenesis, hemangioma of childhood, Sturge-Weber syndrome, verruca vulgaris, neurofibromatosis, tuberous sclerosis, pyogenic granulomas, recessive dystrophic epidermolysis bullosa, venous ulcers, acne, rosacea, eczema, molluscum contagious, seborrheic keratosis, and actinic keratosis.

I claim:  
     
         1 . A method for inhibiting disorders characterized by elevated levels of basic fibroblast growth factor comprising administering to the individual having the disorder an effective amount of a curcuminoid to inhibit the basic fibroblast growth factor.  
     
     
         2 . The method of claim I wherein the curcuminoid is administered topically.  
     
     
         3 . The method of    claim 1    wherein the disorder is bladdar or cervical cancer.  
     
     
         4 . A method for inhibiting skin disorders selected from the group consisting of lymphangiogenesis, hemangioma of childhood, Sturge-Weber syndrome, verruca vulgaris, neurofibromatosis, tuberous sclerosis, pyogenic granulomas, recessive dystrophic epidermolysis bullosa, venous ulcers, acne, rosacea, eczema, molluscum contagious, seborrheic keratosis, and actinic keratosis comprising administering to the individual in need of treatment thereof an angiogenesis inhibitor in an amount effective to inhibit angiogenesis.  
     
     
         5 . The method of    claim 4    wherein the angiogenesis inhibitor is applied topically.  
     
     
         6 . The method of    claim 5    wherein the angiogenesis inhibitor is selected from the group consisting of collagenase inhibitors, endostatin, angiostatin, fumagillin derivatives like TNP-470, 2,5-diaryltetrahydrofurans, aminophenylphosphonic acid compounds, 3-substituted oxindole derivatives, thalidomides, penicillamine and IL12.  
     
     
         7 . The method of    claim 4    wherein the angiogenesis inhibitor is a curcuminoid.  
     
     
         8 . The method of    claim 7    wherein the angiogenesis inhibitor is curcumin.  
     
     
         9 . The method of    claim 7    wherein the angiogenesis inhibitor is demethoxycurcumin.  
     
     
         10 . A method to treat a disorder selected from the group consisting of angiosarcoma, hemangioendothelioma, basal cell carcinoma, squamous cell carcinoma, malignant melanoma and Karposi's sarcoma, and psoriasis, comprising administering to the individual in need of treatment an effective amount to inhibit angiogenesis of a curcuminoid.  
     
     
         11 . The method of    claim 10    wherein the angiogenesis inhibitor is curcumin.  
     
     
         12 . The method of    claim 10    wherein the angiogenesis inhibitor is demethoxycurcumin.  
     
     
         13 . A pharmaceutical composition comprising a curcumin in combination with a pharmaceutically acceptable carrier for topical administration, wherein the curcumin is present in a dosage effective to treat a condition selected from the group consisting of lymphangiogenesis, hemangioma of childhood, Sturge-Weber syndrome, verruca vulgaris, neurofibromatosis, tuberous sclerosis, pyogenic granulomas, recessive dystrophic epidermolysis bullosa, venous ulcers, acne, rosacea, eczema, molluscum contagious, seborrheic keratosis, and actinic keratosis.  
     
     
         14 . The composition of    claim 13    wherein the carrier is an ointment or gel.  
     
     
         15 . The composition of    claim 14    as an ointment or hydrogel containing between one-half percent (0.5%) and five percent (5%) of the curcuminoid.  
     
     
         16 . The composition of    claim 13    wherein the carrier is a polymer formulation for implantation.