The gum resin of Boswellia serrata(Burseraceae) plant has long been in use for the treatment of several diseases by the practitioners of Ayurvedic medicines in the Indian system of medicine. The extract of Boswellia was found to be a potent anti-inflammatory and anti-arthritic agent. The origin of anti-inflammatory actions of Boswellia gum resin and its extracts has been attributed to a group of triterpene acids called boswellic acids that were isolated from the gum resin of Boswellia serrata. Boswellic acids exert anti-inflammatory actions by inhibiting 5-lipoxygenase (5-LOX). 5-LOX is a key enzyme for the biosynthesis of leukotrienes from arachidonic acid. 3-O-Acetyl-11-keto-β-boswellic acid (AKBA) is biologically the most active component among its congeners, it being able to inhibit 5-LOX with an IC50 of 1.5 μM.
Boswellia gum resin and its extracts also demonstrated significant therapeutic improvements in human clinical trials confirming the anti-inflammatory effects shown in vitro and in vivo.
Worldwide aging of the population has increased the incidents of cognitive deficits, such as age-associated memory impairment and senile dementias, and this causes great disruptive impact on the life of the affected individuals. The “cholinergic hypothesis of learning” played a pivotal role in the development of drugs for degenerative diseases.
A disturbance of the cortical cholinergic system accompanied by a reduction of choline acetylase (reduced acetylcholine synthesis) is inter alia detectable biochemically in case of neurological diseases. Hence, there is a demand for a medicament whose active substance can ameliorate this disturbance and highly available at the target organ (brain) and which is well tolerated, particularly in long-term therapy.
Acetylcholinesterase (AChE) is an important enzyme to hydrolyze acetylcholine, a neurotransmitter mediating the activity of parasympathetic nerve, into choline and acetate. AChE is formed in the endoplasmic reticulum, and moves and functions in the cell membrane. AChE is distributed around cholinergic nerve, particularly much at the myoneural junction, and is found in the serum, liver and other tissues.
A wide range of evidence shows that acetylcholinesterase (AChE) inhibition can improve cognitive and mental functions through enhancing cortical cholinergic neurotransmission. The acetylcholinesterase (AChE) inhibitors increase the concentration of acetylcholine and help nerve cells to communicate better. The longer acetylcholine remains in the brain, the longer those cells can call up memories. The earliest known AChE inhibitors are physostigmine and tacrine.
However, clinical studies show that physostigmine has poor oral activity, brain penetration and pharmacokinetic parameters while tacrine has hepatotoxic side effects. Studies were thus focused on finding new types of acetylcholinesterase inhibitors that would overcome the disadvantages of these two compounds.
Donepezil and Rivastigmin inaugurate a new class of AChE inhibitors with longer and more selective action with manageable adverse effects but still small improvement of cognitive impairment. Galanthamine (Reminyl), an alkaloid isolated from Galanthus nivalis, is another recently approved AChE inhibitor for the treatment of Alzheimer's. It is selective, long acting, and reversible. Galanthamine produces beneficial effects in patients. Similarly, huperzine A, a novel Lycopodium alkaloid discovered from the Chinese medicinal plant Huperzia serratais a potent, reversible and selective inhibitor of AChE with a rapid absorption and penetration into the brain in animal tests. It exhibits memory-enhancing activities in animal and also in clinical trials.
Dementia with Lewy bodies (DLB) is a common cause of dementia. Changes in the acetylcholine system have been reported in brains of patients with DLB, which provides a rational basis for trials of acetylcholinesterase inhibitors in DLB.
Current treatment of dementia in Parkinson's disease (PD) is based on the compensation of profound cholinergic deficiency, as in recent studies with the cholinesterase inhibitors galantamine, donepezil and rivastigmine. It has also been shown that cholinesterase inhibitors can improve motor function in PD. The beneficial effect of cholinesterase inhibitors has been studied on patients suffering from Parkinson's disease and dementia.
Studies show that Wernicke-Korsakoff syndrome is associated with a persisting severe anterograde amnesia in which memory is not transferred from short-to long-term storage. It is believed to be a consequence of a thiamine-deficient state often found in alcohol abusers. The memory deficit has been attributed to a number of brain lesions (corpus mamillare and dorsomedial nucleus of the thalamus), loss of cholinergic forebrain neurons and serotonin-containing neurons. Many studies and case-reports suggest efficacy of acetylcholinesterase inhibitors in the Wernicke-Korsakoff-associated memory deficit. Studies also suggest that neurons in the nucleus basalis are at risk in thiamine deficient alcoholic.
The U.S. Pat. No. 5,720,975 relates to the use of incense (olibanum), incense extracts, substances contained in incense, their physiologically acceptable salts, their derivatives and their physiological salts, pure boswellic acid, of physiologically acceptable salts, of a derivative, of a salt of the derivative, for production of a medicament for the prevention or treatment of Alzheimer's disease.
US publication US20060177467A1 relates to the use of the hydrogenation products of frankincense (olibanum), its hydrogenated ingredients as well as physiologically acceptable salts and derivatives thereof and hydrogenated frankincense extracts for the production of a medicament for the prophylactic and/or therapeutic treatment of cerebral ischemia, cranial/brain trauma and/or Alzheimer's disease.
There is currently no prior art, to the best of the Applicants' knowledge, relating to the use of Boswellia non-acidic oil fractions and their compositions for the prevention, control and treatment of Memory and Cognition related diseases and enhancing brain functions.
Additionally, there are numerous pharmaceutical ingredients, herbal ingredients and biologically active molecules that are effective in vitro against a disease condition or disorder. However, several of these ingredients are not effective or not bioavailable in vivo, i.e., after administration to warm blooded animals. It is thus important to explore and identify safe and effective agents that help to increase the bioavailability of such ingredients. As set forth in the present disclosure, Boswellia non-acidic oil fractions have been found to increase bioavailability of a number of extracts, fractions, phytochemicals and compounds originating from plant, animal or microorganism sources.
There is currently no prior art, to the best of the Applicants' knowledge, relating to the use of Boswellia non-acidic oil fractions and their compositions for increasing the bioavailability of biological agents in warm blooded animals.
USPTO Backgrounds
USPTO Backgrounds