Phytoestrogenic Formulations for Alleviation or Prevention of Neurodegenerative Diseases

Abstract

Select phytoestrogen pharmaceutical compositions and methods of use for promoting neurological health and prevention of age-related neurodegeneration, such as AD, have been developed. These select phytoestrogen formulations are composed of a number of plant-derived estrogenic molecules and/or their structural analogues and exhibit binding preference to ERβ over ERα and agonist activity in the brain. These ERβ-selective phytoestrogen formulations cross the blood-brain-barrier and promote estrogen-associated neurotrophism and neuroprotection mechanisms in the brain, without activating proliferative mechanisms in the reproductive tissues and are therefore devoid of other estrogen-associated problematic aspects. The select phytoestrogen formulations are therapeutically useful to both women and men for sustaining neurological health and preventing age-related cognitive decline and neurodegenerative disorders, such as AD. These are administered enterally, transdermally, transmucosally, intranasally or parenterally, in a dosage effective to prevent or alleviate neuronal damage, effect neuronal regeneration or sustain viability, increase expression of anti-apoptotic proteins, and/or decrease indicators of Alzheimer's Disease. The formulations preferably contain combinations of compounds, and can be formulated for daily, sustained, delayed or weekly/monthly administration. In a preferred embodiment, these are administered to women who are in menopause or post menopausal, most preferably early in menopausal.

1 . A formulation for administration to an individual in need of treatment or prevention of neurological disorders or aging comprising two or more naturally occurring compounds that selectively preferentially bind to estrogen receptor β, which cross the blood brain barrier.  
     
     
         2 . The formulation of  claim 1 , wherein the two or more naturally occurring compounds are selected from the group consisting of genistein, daidzein, equol, IBSO03569, and combinations thereof.  
     
     
         3 . The formulation of  claim 1 , farther comprising one or more excipients or carriers.  
     
     
         4 . The formulation of  claim 1 , further comprising one or more additional active agents selected from the group consisting of other selective estrogen receptor modulators, estrogen agonists, estrogen antagonists, antineoplastic agents, alkylating agents, antibiotics, hormones, antimetablites, anti-osteoporosis drugs, vitamins, nutritional supplements, antioxidants and coenzymes.  
     
     
         5 . The formulation of  claim 1  formulated for enteral, parenteral, or topical administration.  
     
     
         6 . A method for alleviating or preventing one or more symptoms associated with estrogen deficiency comprising administering to the patient an effective amount of the formulation of  claim 1 .  
     
     
         7 . The method of  claim 6 , wherein the patient is a postmenopausal women.  
     
     
         8 . The method of  claim 6 , wherein the estrogen-deficiency associated risks are a neurological disease or disorder.  
     
     
         9 . The method of  claim 8 , wherein the neurological disease is a neurodegenerative disease.  
     
     
         10 . The method of  claim 9 , wherein the neurodegenerative disease is cognitive deficit or memory loss.  
     
     
         11 . The method of  claim 9 , wherein the neurodegenerative disease is Alzheimer's disease.  
     
     
         12 . The method of  claim 6  further to treat or prevent hot flashes comprising administering to a subject in need thereof an effective amount of the formulation of  claim 1 .  
     
     
         13 . The method of  claim 6  to treat or prevent cognitive decline associated with estrogen deficiency comprising administering to a subject in need thereof an effective amount of the formulation of  claim 1 .  
     
     
         14 . The method of  claim 6  to treat or prevent osteoporosis associated with estrogen deficiency comprising administering to a subject in need thereof an effective amount of the formulation of  claim 1.