Tea catechins in sustained release formulations as cancer specific proliferation inhibitors

Abstract

The invention described herein encompasses a methods and compositions of treating cancer or solid tumors comprising the administration of a therapeutically effective amount of catechins, a group of polyphenols found in green tea, to a mammal in need of such therapy. Compositions of catechins include but not limited to, epigallocatechin gallate (EGCg), epicatechin (EC), epicatechin gallate (ECG), epigallocatechin (EGC). The unique compositions of the invention contain various combinations of the catechins, alone or in combination with each other or other therapeutic agents and are used to treat primary and metastatic cancers in humans. The invention also encompasses the varying modes of administration of the therapeutic compounds, including a sustained release formulation which may be used as a therapeutic compound for the treatment of cancer or as a dietary supplement for the prevention of cancer.

What is claimed is:  
     
         1 . A composition of a sustained release formulation of tea catechins comprising tea catechins and at least one component which controls the release of said catechins.  
     
     
         2 . The composition of  claim 1  wherein at least 30% of said catechins is EGCg.  
     
     
         3 . The composition of  claim 2  wherein EGCg comprises about 35% to about 45% of the catechins.  
     
     
         4 . The composition of  claim 2  wherein EGCg comprises about 40% of the catechins.  
     
     
         5 . The composition of  claim 1  wherein at least 30% of said catechins is EGCg and at least 5% of said catechins is ECG based on the total amount of catechins present in said formulation.  
     
     
         6 . The composition of  claim 5  wherein EGCg comprises about 35% to about 45% of the catechins and ECG comprises about 10% to about 20% of the catechins.  
     
     
         7 . The composition of  claim 5  wherein EGCg comprises about 40% of the catechins and ECG comprises about 15% of the catechins.  
     
     
         8 . The composition of  claim 1  wherein at least 30% of said catechins is EGCg and at least 3% of said catechins is EC based on the total amount of catechins present in said formulation.  
     
     
         9 . The composition of  claim 8  wherein EGCg comprises about 35% to about 45% of the catechins and EC comprises about 3% to about 15% of the catechins.  
     
     
         10 . The composition of  claim 8  wherein EGCg comprises about 40% of the total catechins and EC comprises about 7% of the catechins.  
     
     
         11 . The composition of  claim 1  wherein EGCg and EC comprise the catechins, EGCg comprises at least 0.01% of said catechins, and the EC content is at least 10 fold greater than the EGCg content.  
     
     
         12 . The composition of  claim 11  wherein the EC content is at least 100 fold greater than the EGCg content.  
     
     
         13 . The composition of  claim 11  wherein the EC content is at least 1000 fold greater than the EGCg content.  
     
     
         14 . The composition of  claim 1  wherein at least 30% of said catechins is EGCg and at least 1% of said catechins is EGC based on the total amount of catechins present in said formulation.  
     
     
         15 . The composition of  claim 14  wherein EGCg comprises about 35% to about 45% of the catechins and EGC comprises about 2% to about 5% of the catechins.  
     
     
         16 . The composition of  claim 14  wherein EGCg comprises about 40% of the total catechins and EGC comprises about 3% of the catechins.  
     
     
         17 . The composition of  claim 1  wherein at least 30% of said catechins is EGCg, at least 3% of said catechins is EC, and at least 5% of said catechins is ECG based on the total amount of catechins present in said formulation.  
     
     
         18 . The composition of  claim 17  wherein EGCg comprises about 35% to about 45% of the catechins, EC comprises about 3% to about 15% of the catechins, and ECG comprises about 10% to about 20% of the catechins.  
     
     
         19 . The composition of  claim 17  wherein EGCg comprises about 45% of the catechins, EC comprises about 7% of the catechins, and ECG comprises about 15% of said catechins in said formulation.  
     
     
         20 . The composition of  claim 1  wherein at least 30% of said catechins is EGCg, at least 3% of said catechins is EC, and at least 1% of said catechins is EGC based on the total amount of catechins present in said formulation.  
     
     
         21 . The composition of  claim 20  wherein EGCg comprises about 35% to about 45% of the catechins, EC comprises about 3% to about 15% of said catechins, and EGC comprises about 2% to about 5% of the catechins.  
     
     
         22 . The composition of  claim 20  wherein EGCg comprises about 45% of the catechins, EC comprises about 7% of the catechins, and EGC comprises about 3% of the catechins.  
     
     
         23 . The composition of  claim 1  wherein at least 30% of said catechins is EGCg, at least 3% of said catechins is EC, at least 5% of said catechins is ECG, and at least 1% of said catechins is EGC based on the total amount of catechins present in said formulation.  
     
     
         24 . The composition of  claim 23  wherein EGCg comprises about 35% to about 45% of the catechins, EC comprises about 3% to about 15% of the catechins, ECG comprises about 10% to about 20% of the catechins, and EGC comprises about 2% to about 5% of the catechins.  
     
     
         25 . The composition of  claim 23  wherein EGCg comprises about 45% of the catechins, EC comprises about 7% of the catechins, ECG comprises about 15% of the catechins, and EGC comprises about 3% of the catechins.  
     
     
         26 . The composition of  claim 1  wherein at least 30% of said catechins is EGCg, at least 3% of said catechins is EC, at least 5% of said catechins is ECG, at least 1% of said catechins is EGC, and at least 5% of said catechins is C based on the total amount of catechins present in said formulation.  
     
     
         27 . The composition of  claim 26  wherein EGCg comprises about 35% to about 45% of the catechins, EC comprises about 3% to about 15% of the catechins, ECG comprises about 10% to about 20% of the catechins, EGC comprises about 2% to about 5% of the catechins, and C comprises about 10% to about 20% of the catechins.  
     
     
         28 . The composition of  claim 26  wherein EGCg comprises about 45% of the catechins, EC comprises about 7% of the catechins, ECG comprises about 15% of the catechins, EGC comprises about 3% of the catechins, and C comprises about 15% of the catechins.  
     
     
         29 . The composition of  claim 1 , which is a dietary or nutritional supplement, wherein the composition is formulated as an oral preparation comprising tablets, capsules, gelcaps, or powders.  
     
     
         30 . The composition of  claim 1 , which is a dietary or nutritional supplement, wherein the composition is formulated as a sterile preparation.  
     
     
         31 . The composition of  claim 1 , which is a dietary or nutritional supplement, wherein the composition is formulated as a parenteral solution.  
     
     
         32 . The composition of  claim 1 , which is a dietary or nutritional supplement, wherein the component is a polymer matrix, gel, permeable membrane, osmotic system, multilayer coating, microparticle, liposome, or microsphere.  
     
     
         33 . The composition of  claim 32  wherein the polymer matrix is cellulose.  
     
     
         34 . The composition of  claim 33  wherein the cellulose is hydroprophylmethyl cellulose.  
     
     
         35 . The composition of  claim 1 , which is a dietary or nutritional supplement, wherein the composition is microencapsulated.  
     
     
         36 . The composition of  claim 35  wherein the composition is microencapsulated with microcrystalline cellulose, maltodextrine, ethylcellulose, and magnesium stearate.  
     
     
         37 . The pharmaceutical composition of  claim 1  wherein the composition is formulated as an oral preparation comprising tablets, capsules, gelcaps, or powders.  
     
     
         38 . The pharmaceutical composition of  claim 1  wherein the composition is formulated as a sterile preparation.  
     
     
         39 . The pharmaceutical composition of  claim 1  wherein the composition is formulated as a parenteral solution.  
     
     
         40 . The pharmaceutical composition of  claim 1  wherein the component is a polymer matrix, gel, permeable membrane, osmotic system, multilayer coating, microparticle, liposome, or microsphere.  
     
     
         41 . The pharmaceutical composition of  claim 40  wherein the polymer matrix is cellulose.  
     
     
         42 . The pharmaceutical composition of  claim 41  wherein the cellulose is hydroprophylmethyl cellulose.  
     
     
         43 . The pharmaceutical composition of  claim 1  wherein the composition is microencapsulated.  
     
     
         44 . The pharmaceutical composition of  claim 43  wherein the composition is microencapsulated with microcrystalline cellulose, maltodextrine, ethylcellulose, and magnesium stearate.  
     
     
         45 . A method of preventing cancer in a mammal, wherein said cancer is a type having cancer cells which express tNOX, which comprises administering to a mammal desirous of preventing cancer, an effective dose of a sustained release formulation of tea catechins so that the cancer cells which express tNOX do not accumulate to a number which creates clinical symptoms associated with said cancer.  
     
     
         46 . The method of  claim 45  wherein the reduction in the number of cancer cells is a result of cell death.  
     
     
         47 . The method of  claim 45  wherein the reduction in the number of cancer cells is a result of inhibition of cell growth.  
     
     
         48 . The method of  claim 45  wherein the reduction in the number of cancer cells is a result of cell growth arrest.  
     
     
         49 . The method of  claim 45  wherein the mammal is a human.  
     
     
         50 . The method of  claim 49  wherein the cancer is selected from a group comprising rectal carcinoma, colon carcinoma, breast carcinoma, ovarian carcinoma, small cell lung carcinoma, colon carcinoma, chronic lymphocytic carcinoma, hairy cell leukemia, osophogeal carcinoma, prostate carcinoma, breast cancer, myeloma, and lymphoma.  
     
     
         51 . The method of  claim 49  wherein the human is immunosuppressed by reason of having undergone anti-cancer therapy prior to administration of said formulation comprising catechins.  
     
     
         52 . The method of  claim 45  wherein at least 30% of said catechins is EGCg.  
     
     
         53 . The method of  claim 52  wherein EGCg comprises about 35% to about 45% of the catechins.  
     
     
         54 . The method of  claim 52  wherein EGCg comprises about 40% of the catechins.  
     
     
         55 . The method of  claim 45  wherein at least 30% of said catechins is EGCg and at least 5% of said catechins is ECG based upon the total amount of catechins present in said formulation.  
     
     
         56 . The method of  claim 55  wherein EGCg comprises about 35% to about 45% of the catechins and ECG comprises about 10% to about 20% of the catechins.  
     
     
         57 . The method of  claim 55  wherein EGCg comprises about 40% of the catechins and ECG comprises about 15% of the catechins.  
     
     
         58 . The method of  claim 45  wherein at least 30% of said catechins is EGCg and at least 3% of said catechins is EC based upon the total amount of catechins present in said formulation.  
     
     
         59 . The method of  claim 58  wherein EGCg comprises about 35% to about 45% of the catechins and EC comprises about 3% to about 15% of the catechins.  
     
     
         60 . The method of  claim 58  wherein EGCg comprises about 40% of the total catechins and EC comprises about 7% of the catechins.  
     
     
         61 . The method of  claim 45  wherein EGCg and EC comprise the catechins, EGCg comprises at least 0.01% of said catechins, and the EC content is at least 10 fold greater than the EGCg content.  
     
     
         62 . The method of  claim 61  wherein the EC content is at least 100 fold greater than the EGCg content.  
     
     
         63 . The method of  claim 61  wherein the EC content is at least 1000 fold greater than the EGCg content.  
     
     
         64 . The method of  claim 45  wherein at least 30% of said catechins is EGCg and at least 1% of said catechins is EGC based upon the total amount of catechins present in said formulation.  
     
     
         65 . The method of  claim 64  wherein EGCg comprises about 35% to about 45% of the catechins and EGC comprises about 2% to about 5% of the catechins.  
     
     
         66 . The method of  claim 64  wherein EGCg comprises about 40% of the total catechins and EGC comprises about 3% of the catechins.  
     
     
         67 . The method of  claim 45  wherein at least 30% of said catechins is EGCg, at least 3% of said catechins is EC, and at least 5% of said catechins is ECG based upon the total amount of catechins present in said formulation.  
     
     
         68 . The method of  claim 67  wherein said formulation comprises EGCg, EC, and ECG wherein EGCg comprises about 35% to about 45% of the catechins, EC comprises about 3% to about 15% of the catechins, and ECG comprises about 10% to about 20% of the catechins.  
     
     
         69 . The method of  claim 67  wherein said formulation comprises EGCg, EC, and ECG wherein EGCg comprises about 45% of the catechins, EC comprises about 7% of the catechins, and ECG comprises about 15% of the catechins.  
     
     
         70 . The method of  claim 45  wherein at least 30% of said catechins is EGCg, at least 3% of said catechins is EC, and at least 1% of said catechins is EGC in said formulation.  
     
     
         71 . The method of  claim 70  wherein said formulation comprises EGCg, EC, and EGC wherein EGCg comprises about 35% to about 45% of the catechins, EC comprises about 3% to about 15% of the catechins, and EGC comprises about 2% to about 5% of the catechins.  
     
     
         72 . The method of  claim 70  wherein said formulation comprises EGCg, EC, and EGC wherein EGCg comprises about 45% of the catechins, EC comprises about 7% of the catechins, and EGC comprises about 3% of the catechins.  
     
     
         73 . The method of  claim 45  wherein at least 30% of said catechins is EGCg, at least 3% of said catechins is EC, at least 5% of said catechins is ECG, and least 1% of said catechins is EGC based upon the total amount of catechins present in said formulation.  
     
     
         74 . The method of  claim 73  wherein said formulation comprises EGCg, EC, and ECG wherein EGCg comprises about 35% to about 45% of the catechins, EC comprises about 3% to about 15% of the catechins, ECG comprises about 10% to about 20% of the catechins, and EGC comprises about 2% to about 5% of the catechins.  
     
     
         75 . The method of  claim 73  wherein said formulation comprises EGCg, EC, and ECG wherein EGCg comprises about 45% of said catechins, EC comprises about 7% of said catechins, ECG comprises about 15% of said catechins, and EGC comprises about 3% of said catechins in said formulation.  
     
     
         76 . The method of  claim 45  wherein at least 30% of said catechins is EGCg, at least 3% of said catechins is EC, at least 5% of said catechins is ECG, at least 1% of said catechins is EGC, and at least 5% of said catechins is C based upon the total amount of catechins present in said formulation.  
     
     
         77 . The method of  claim 76  wherein said formulation comprises EGCg, EC, and ECG wherein EGCg comprises about 35% to about 45% of the catechins, EC comprises about 3% to about 15% of the catechins, ECG comprises about 10% to about 20% of the catechins, EGC comprises about 2% to about 5% of the catechins, and C comprises about 10% to about 20% of the catechins.  
     
     
         78 . The method of  claim 76  wherein said formulation comprises EGCg, EC, and ECG wherein EGCg comprises about 45% of the catechins, EC comprises about 7% of the catechins, ECG comprises about 15% of the catechins, EGC comprises about 3% of the catechins, and C comprises about 15% of the catechins.  
     
     
         79 . The method of  claim 45  wherein said formulation is an ionic aqueous solution of the composition comprising tea catechins.  
     
     
         80 . The method of  claim 45  wherein the total daily amount administered is from about 10 to about 100,000 mg of the composition comprising tea catechins.  
     
     
         81 . The method of  claim 45  wherein the formulation is provided at constant levels in the sera for at least 48 hours.  
     
     
         82 . The method of  claim 45  wherein the formulation is provided at constant levels in the sera for at least 72 hours.  
     
     
         83 . A method for treating cancer in a mammal which comprises administering to a mammal in need of cancer treatment, wherein said cancer is a type having cancer cells which express tNOX, a therapeutically effective dose of a sustained release formulation of tea catechins so that there is a reduction in the number of cancer cells in the body.  
     
     
         84 . The method of  claim 83  wherein the reduction in the number of cancer cells is a result of cell death.  
     
     
         85 . The method of  claim 83  wherein the reduction in the number of cancer cells is a result of inhibition of cell growth.  
     
     
         86 . The method of  claim 83  wherein the reduction in the number of cancer cells is a result of cell growth arrest.  
     
     
         87 . The method of  claim 83  wherein the mammal is a human.  
     
     
         88 . The method of  claim 87  wherein the cancer is selected from a group comprising rectal carcinoma, colon carcinoma, breast carcinoma, ovarian carcinoma, small cell lung carcinoma, colon carcinoma, chronic lymphocytic carcinoma, hairy cell leukemia, osophogeal carcinoma, prostate carcinoma, breast cancer, myeloma, and lymphoma.  
     
     
         89 . The method of  claim 87  wherein the human is immunosuppressed by reason of having undergone anti-cancer therapy prior to administration of said formulation comprising catechins.  
     
     
         90 . A method for treating a solid tumor in a mammal, wherein the solid tumor comprises cancer cells which express tNOX, which comprises administering to a mammal, a therapeutically effective dose of a sustained release formulation of tea catechins so that there is a reduction in the number of cancer cells in the tumor.  
     
     
         91 . The method of  claim 90  wherein the reduction in the number of cancer cells is a result of cell death.  
     
     
         92 . The method of  claim 90  wherein the reduction in the number of cancer cells is a result of inhibition of cell growth.  
     
     
         93 . The method of  claim 90  wherein the reduction in the number of cancer cells is a result of cell growth arrest.  
     
     
         94 . The method of  claim 90  wherein the mammal is a human.  
     
     
         95 . The method of  claim 94  wherein the tumor is a tumor of epithelial tissue, lymphoid tissue, connective tissue, bone, or central nervous system.  
     
     
         96 . The method of  claim 90  in which said administration is made parenterally, orally, or directly into the tumor.  
     
     
         97 . A method for treating metastases in a human which comprises administering to a human having a primary cancer, wherein said cancer is a type having cancer cells which express tNOX, a therapeutically effective dose of a sustained release formulation of tea catechins so that there is a reduction in the number of cancer cells in the body.  
     
     
         98 . The method of  claim 97  wherein the reduction in the number of cancer cells is a result of cell death.  
     
     
         99 . The method of  claim 97  wherein the reduction in the number of cancer cells is a result of inhibition of cell growth.  
     
     
         100 . The method of  claim 97  wherein the reduction in the number of cancer cells is a result of cell growth arrest.  
     
     
         101 . A method for treating cancer in a mammal which comprises administering to a mammal in need of cancer treatment, wherein said cancer is a type having cancer cells which express tNOX, a therapeutically effective dose of a sustained release formulation of tea catechins, or a pharmaceutically acceptable salt thereof, in combination with an effective amount of at least one other chemotherapeutic agent so that there is a reduction in the number of cancer cells in the body.  
     
     
         102 . The method of  claim 101  in which said other anti-cancer agent is selected from the group consisting of adriamycin and adriamycin conjugates, mechlorethamine, cyclophosphamide, ifosfamide, melphalan, chlorambucil, hexamethylmelamine, thiotepa, busulfan, carmustine, lomustine, semustine, streptozocin, dacarbazine, methotrexate, fluorouacil, floxuridie, cytarabine, mercaptopurine, thioguanine, pentostatin, vinblastine, vincristine, etoposide, teniposide, actinomycin D, daunorubicin, doxorubicin, bleomycin, plicamycin, mitomycin, L-asparaginase, interferon-alpha, cisplatin, carboplatin, mitoxantrone, hydroxyurea, procarbazine, mitotane, aminoglutethimide, prednisone, hydroxyprogesterone caproate, medroxyprogesterone acetate, megestrol acetate, diethylstilbestrol, ethinyl estradiol, tamoxifen, testosterone propionate, fluoxymesterone, flutamide, leuprolide, acetogenins, e.g., bullatacin, and quassanoids, e.g. simalikalactone D and glaucarubolone, and pharmaceutically acceptable derivatives thereof.  
     
     
         103 . The method of  claim 89 ,  90 ,  97  or  101  in which said administration is made via an implantation device.  
     
     
         104 . The method of  claim 89 ,  90 ,  97  or  101  wherein at least 30% of said catechins is EGCg.  
     
     
         105 . The method of  claim 104  wherein EGCg comprises about 35% to about 45% of the catechins.  
     
     
         106 . The method of  claim 104  wherein EGCg comprises about 40% of the catechins.  
     
     
         107 . The method of  claim 89 ,  90 ,  97  or  101  wherein at least 30% of said catechins is EGCg and at least 5% of said catechins is ECG based upon the total amount of catechins present in said formulation.  
     
     
         108 . The method of  claim 107  wherein EGCg comprises about 35% to about 45% of the catechins and ECG comprises about 10% to about 20% of the catechins.  
     
     
         109 . The method of  claim 107  wherein EGCg comprises about 40% of the catechins and ECG comprises about 15% of the catechins.  
     
     
         110 . The method of  claim 89 ,  90 ,  97  or  101  wherein at least 30% of said catechins is EGCg and at least 3% of said catechins is EC based upon the total amount of catechins present in said formulation.  
     
     
         111 . The method of  claim 110  wherein EGCg comprises about 35% to about 45% of the catechins and EC comprises about 3% to about 15% of the catechins.  
     
     
         112 . The method of  claim 110  wherein EGCg comprises about 40% of the total catechins and EC comprises about 7% of the catechins.  
     
     
         113 . The method of  claim 89 ,  90 ,  97  or  101  wherein EGCg and EC comprise the catechins, EGCg comprises at least 0.01% of said catechins, and the EC content is at least 10 fold greater than the EGCg content.  
     
     
         114 . The method of  claim 113  wherein the EC content is at least 100 fold greater than the EGCg content.  
     
     
         115 . The method of  claim 113  wherein the EC content is at least 1000 fold greater than the EGCg content.  
     
     
         116 . The method of  claim 89 ,  90 ,  97  or  101  wherein at least 30% of said catechins is EGCg and at least 1% of said catechins is EGC based upon the total amount of catechins present in said formulation.  
     
     
         117 . The method of  claim 116  wherein EGCg comprises about 35% to about 45% of the catechins and EGC comprises about 2% to about 5% of the catechins.  
     
     
         118 . The method of  claim 116  wherein EGCg comprises about 40% of the total catechins and EGC comprises about 3% of the catechins.  
     
     
         119 . The method of  claim 89 ,  90 ,  97  or  101  wherein at least 30% of said catechins is EGCg, at least 3% of said catechins is EC, and at least 5% of said catechins is ECG based upon the total amount of catechins present in said formulation.  
     
     
         120 . The method of  claim 119  wherein said formulation comprises EGCg, EC, and ECG wherein EGCg comprises about 35% to about 45% of the catechins, EC comprises about 3% to about 15% of the catechins, and ECG comprises about 10% to about 20% of the catechins.  
     
     
         121 . The method of  claim 119  wherein said formulation comprises EGCg, EC, and ECG wherein EGCg comprises about 45% of the catechins, EC comprises about 7% of the catechins, and ECG comprises about 15% of the catechins.  
     
     
         122 . The method of  claim 89 ,  90 ,  97  or  101  wherein at least 30% of said catechins is EGCg, at least 3% of said catechins is EC, and at least 1% of said catechins is EGC in said formulation.  
     
     
         123 . The method of  claim 122  wherein said formulation comprises EGCg, EC, and EGC wherein EGCg comprises about 35% to about 45% of the catechins, EC comprises about 3% to about 15% of the catechins, and EGC comprises about 2% to about 5% of the catechins.  
     
     
         124 . The method of  claim 122  wherein said formulation comprises EGCg, EC, and EGC wherein EGCg comprises about 45% of the catechins, EC comprises about 7% of the catechins, and EGC comprises about 3% of the catechins.  
     
     
         125 . The method of  claim 89 ,  90 ,  97  or  101  wherein at least 30% of said catechins is EGCg, at least 3% of said catechins is EC, at least 5% of said catechins is ECG, and least 1% of said catechins is EGC based upon the total amount of catechins present in said formulation.  
     
     
         126 . The method of  claim 125  wherein said formulation comprises EGCg, EC, and ECG wherein EGCg comprises about 35% to about 45% of the catechins, EC comprises about 3% to about 15% of the catechins, ECG comprises about 10% to about 20% of the catechins, and EGC comprises about 2% to about 5% of the catechins.  
     
     
         127 . The method of  claim 125  wherein said formulation comprises EGCg, EC, and ECG wherein EGCg comprises about 45% of said catechins, EC comprises about 7% of said catechins, ECG comprises about 15% of said catechins, and EGC comprises about 3% of said catechins in said formulation.  
     
     
         128 . The method of  claim 89 ,  90 ,  97  or  101  wherein at least 30% of said catechins is EGCg, at least 3% of said catechins is EC, at least 5% of said catechins is ECG, at least 1% of said catechins is EGC, and at least 5% of said catechins is C based upon the total amount of catechins present in said formulation.  
     
     
         129 . The method of  claim 128  wherein said formulation comprises EGCg, EC, and ECG wherein EGCg comprises about 35% to about 45% of the catechins, EC comprises about 3% to about 15% of the catechins, ECG comprises about 10% to about 20% of the catechins, EGC comprises about 2% to about 5% of the catechins, and C comprises about 10% to about 20% of the catechins.  
     
     
         130 . The method of  claim 128  wherein said formulation comprises EGCg, EC, and ECG wherein EGCg comprises about 45% of the catechins, EC comprises about 7% of the catechins, ECG comprises about 15% of the catechins, EGC comprises about 3% of the catechins, and C comprises about 15% of the catechins.  
     
     
         131 . The method of  claim 89 ,  90 ,  97  or  101  wherein said formulation is an ionic aqueous solution of the composition comprising tea catechins.  
     
     
         132 . The method of  claim 89 ,  90 ,  97  or  101  wherein the total daily amount administered is from about 10 to about 100,000 mg of the composition comprising tea catechins.  
     
     
         133 . The method of  claim 89 ,  90 ,  97  or  101  wherein the formulation is provided at constant levels in the sera for at least 48 hours.  
     
     
         134 . The method of  claim 89 ,  90 ,  97  or  101  wherein the formulation is provided at constant levels in the sera for at least 72 hours.