A clinically proven. Cognition enhancer

Transcription

1 R A clinically proven Cognition enhancer

2 What is Memory loss? Memory is the ability of the brain to store, retain and subsequently recall information. In the recent decades, it has become one of the principal pillars of a new branch of science, cognitive neuroscience. Cognition refers to the processes through which information coming from the senses is transformed, reduced, elaborated, recovered, and used. The term information, used here, refers simply to sensory input from the environment that informs us about something that is happening there. Cognitive processes are thus the mental processes involved in knowing about the world; as such, they are important in perception, attention, thinking, problem solving and memory. Causes of Memory loss Aging Alzheimer's disease Neurodegenerative illness ead trauma or injury ysteria often accompanied by confusion Seizures General anesthetics Alcoholism Stroke or transient ischemic attack (TIA) Transient global amnesia Drugs such as barbiturates or benzodiazepines Electroconvulsive therapy (especially if prolonged) Temporal lobe brain surgery Brain masses (caused by tumors or infection) erpes encephalitis ther brain infections Depression Amnesia and Dementia are the two major classes of memory disorders seen in clinical populations. Amnesia refers to a specific, acquired difficulty in learning new information and/or remembering information from the past. Dementia is a more broadly defined cognitive disorder, of which amnesia is the primary feature. Alzheimer's disease (AD) is the world's leading cause of dementia and the most prevalent Neurodegenerative disease (NDD) % of dementia is estimated to be caused by this disease AD affects the mental abilities including memory, language and cognition. AD usually arises in late middle age or the elderly but there is a rare familial subtype that occurs earlier. Global incidence Worldwide, there is a new case of dementia every seven seconds. More than 24.3 million people are currently estimated to have dementia, and 4.6 million new cases are diagnosed each year. Dementia is expected to double between 2001 and 2040 in developed nations, it is forecast to increase by more than 300 percent in India and China. Ref: Ferri et al., Global prevalence of dementia: a Delphi consensus study. The Lancet. 2005: 366: pp Prevalence of Alzheimer's disease: 4.5 million cases in America, it is expected to increase to million cases in America by 2050 (Alzheimer's Association, 2004) 1

3 erbal approach to Memory loss Bacopa monnieri (Linn.) Pennell. English name : Bacopa Local name : Brahmi Family : Scrophulariaceae Part used : Entire plant What Ayurveda says about Brahmi? Bacopa monnieri is one of the most honored medicinal plant in Ayurveda and has been used traditionally since 3000 years.. ye eefïe.. ces³ee.. mce=efleòeoe.. (Yee. Òe.) (Good for brain, enhances memory).. ye eefïe.. yegef Òeoe.. cesee³egjeqivepeveveer.. mce=efleoe.. (efve. j.) (Improves intelligence, enhances memory).. ye eefïe.. ces³ee.. (ie. efve.) (Brain tonic).. ye eefïe.. mce=efleòeoe.. (ce. ee. efve. ce. efje.) (Enhances memory) R What is? R (patent pending) is a clinically proven (both in elderly and children) enriched standardized phytochemical composition derived from the plant Bacopa monnieri, which is well known in Ayurveda as a brain tonic. Natural Remedies R is launched after an extensive research work by. R has scientific backup of multiple in vitro, animal and clinical studies to substantiate its beneficial effects as a cognition enhancer and in the management of age related neurodegenerative disorders. 2

4 Clinical Trials in a Nut Shell Approved Protocol Investigator selection Approval process Patient recruitment and participation Data filed and registration obtained Presentation and publication of report Statistical Analysis Data entered and reviewed Clinical evidence - Safety of Phase I Clinical trial of BacoMind in elderly volunteers Subjects Place Dose & Duration Results 15 elderly volunteers (age group between years) Ahmedabad, India BacoMind 300 mg once a day for first 14 days and 450 mg for further 14 days BacoMind was found to be safe and tolerable. No side effects were reported in any of the treated volunteers. The physical, hematological and biochemical parameters were within the normal limits. Phase I Clinical trial of BacoMind in healthy adult volunteers Subjects Place Dose & Duration Results 23 healthy adult volunteers (age group between years) Bangalore, India BacoMind 300 mg once a day for first 15 days and 450 mg for further 15 days BacoMind was found to be safe and tolerable. Though minor gastrointestinal side effects were reported in 4 out of 23 volunteers, the physical, hematological, biochemical and electrocardiographic parameters were within the normal limits. Ref: Pravina K et al., Safety evaluation of BacoMind in healthy volunteers: A phase I study, Phytomedicine, 2007, 14: pp

5 Clinical studies of in older persons Efficacy and Tolerability of BacoMind on memory improvement in older persons. A double blind placebo controlled study Subjects Place Dose & Duration 59 elderly individuals (age group between years) Ahmedabad, India BacoMind 450 mg once a day for 24 weeks BacoMind showed a significant reduction in time required for cancellation test from baseline value Improvement in Attention week 12th week 24th week BacoMind Placebo BacoMind showed a significant improvement in Delayed recall component of list learning test Improvement in Memory 50 BacoMind helped in better visual retention memory as observed in visual retention test Improvement in visual retention Memory 0 0 week 12th week 24th week BacoMind Placebo Baseline BacoMind Placebo BacoMind showed a significant improvement in Delayed recall component of paired associates dissimilar test at 24th week Improvement in Memory Baseline BacoMind Placebo 4

6 Clinical studies of in children Efficacy study of BacoMind on memory improvement in Children requiring Individual Education Programme [IEP] Subjects Place Dose & Duration Result 24 children (aged between 4-18 years) Mumbai, India BacoMind 225 mg once a day for 4 months BacoMind treatment revealed a significant improvement in various memory related tasks in the children requiring IEP Improvement in memory test scores in BacoMind treated children requiring IEP Baseline Recognition Visual reproduction Verbal retention of dissimilar word pairs Verbal retention of similar word pairs Repeating sentences Repeating words Digit span Mental control rientation Information % improvement 5

7 Pre-Clinical evidence : In vivo studies Nootropic activity of BacoMind using passive shock avoidance test in mice Animals Test material Dose & duration Results 42 albino Swiss mice (20-22 g) of either sex BacoMind 40, 60 and 80 mg/kg for 7 days. BacoMind showed significant decrease in the latency to reach Shock free zone [SFZ] and in the number of mistakes in 15 min at all the tested doses when compared to the vehicle control. BacoMind administered at the dose of 60 mg/kg in scopolamine treated mice showed significant decrease in latency to reach SFZ and in the number of mistakes in 15 min as compared to the scopolamine control Vehicle control (10 ml/kg) Scopolamine (0.3 mg/kg) BacoMind (60 mg/kg) + Scopolamine (0.3 mg/kg) Animals were placed on the electric grid (20 V with AC current of 5 ma); the latency to reach SFZ and the mistakes (descents) the animal made in 15 min were recorded Nootropic activity of BacoMind using object recognition test in rats Animals 42 albino Wistar rats ( g) of either sex Test material Dose & duration Results BacoMind 27, 40 and 54 mg/kg for 7 days. BacoMind showed a significant increase in the discrimination index at all the tested doses when compared to the vehicle control. BacoMind administered at the dose of 40 mg/kg in scopolamine treated rats showed significant increase in the discrimination index as compared to the scopolamine control Vehicle control (10 ml/kg) Scopolamine (0.3 mg/kg) BacoMind (40 mg/kg)+ Scopolamine(0.3 mg/kg) The time spent by the animals for exploration (directing nose at a distance < 2 cm to the object or touching it with nose) of the familiar (F) and new (N) objects were recorded and Discrimination Index (D) was calculated as follows; Discrimination index [D] = N-F / N+F. 6

8 Nootropic activity of BacoMind using elevated plus maze test in mice Animals Test material Dose & duration Results 42 albino Swiss mice (20-22 g) of either sex BacoMind 40, 60 and 80 mg/kg for 7 days. A significant decrease in the inflexion ratio was noticed in the scopolamine treated group as compared to the vehicle control. BacoMind administered at the dose of 60 mg/kg in scopolamine treated mice showed significant increase in the inflexion ratio as compared to the scopolamine control Vehicle control (10 ml/kg) Scopolamine (0.3 mg/kg) BacoMind (60 mg/kg)+ Scopolamine(0.3 mg/kg) Transfer latency (TL) [the time taken by the mouse to move into the enclosed arm of the elevated plus maze] was measured and expressed as inflexion ration [initial TL-Later TL / Later TL] In Vitro studies on BacoMind BacoMind exhibited butyrylcholinesterase activity BacoMind has up to 60 percent more affinity to 5-T6receptors than Bacoside A. BacoMind inhibited lipoxygenase (LX) activity BacoMind showed antioxidant potential in the following models DPP radical scavenging assay ABTS radical scavenging assay RAC assay Safety of A phase I clinical study on BacoMind has indicated that it is safe and well tolerated in healthy adults and elderly volunteers. No side effects were reported in any of the treated volunteers. The physical, hematological and biochemical parameters were within the normal limits. Pravina K et al., Safety evaluation of BacoMind in healthy volunteers: A phase I study, Phytomedicine, 2007, 14: pp ral administration of BacoMind (500mg/kg body weight) for 90 days did not cause any mortality and significant adverse effects in rats. LD of BacoMind was found to be 2400mg/kg in rats*. In addition, no 50 mutagenicity could be detected in the Ame's test. *Joshua Allan J et al., Safety evaluation of a standardized phytochemical composition extracted from Bacopa monnieri in Sprague Dawley rats, Food and Chemical Toxicology (In Press). 7

9 ow Bacopa works? With reference to cognition enhancement Agonist activation of 6 5-T-1A receptors Inhibits Lipoxygenase 7 activity Modulation of acetylcholine release, choline acetyl transferase and muscarinic receptor 8 & 9 Inhibits butyrylcholinesterase 10 activity May Attenuate PKC activity since it reduces norepinephrine 1 & 6 levels in ippocampus May act thro'5-t6 2 receptors Reduces amyloid levels 3 in the Brain 4 Anti-oxidant activity Agonist activation of 5 5-T-1A receptors 1. Birnbaum SG et al., Science.2004 :306 (5697): pp Natural Remedies, In house report 3. olcomb LA et al., J Alzheimers Dis :9(3): pp Bhattacharya SK et al., Phytother Res 2000 b:14: pp Parker K and Medora R. Annual meeting of the American Society of Pharmacognosy on July 24 at regon State University in Corvallis, regon. 6. Singh K and Dhawan BN. Indian J Pharmacol 1997:29: pp Dhanasekaran M et al., Phytother Res. 2007: 29 [Epub ahead of print] 8. Bhattacharya SK et al., Molecular aspects of Asian medicine. New York: PJD Publications: 2000: pp Agarwal A. A comparative study of psychotropic drugs and biofeedback therapy in the prevention and management of psychosomatic disorder. Thesis: Institute of Medical Sciences, Banaras indu University; Pravina K et al., Phytomedicine, 2007, 14: pp Publications & Presentations on Publications Pravina K et al., Safety evaluation of BacoMind in healthy volunteers: A phase I study, Phytomedicine, 2007, 14: pp Kasture SB et al., Nootropic activity of BacoMind, an enriched phytochemical composition from Bacopa monnieri, Journal of Natural Remedies, 2007: 7 (1): pp Joshua Allan J et al., Safety evaluation of a standardized phytochemical composition extracted from Bacopa monnieri in Sprague Dawley rats, Food and Chemical Toxicology (In Press). Dipanwita Dutta Deb et al., In vitro safety evaluation and Anticlastogenic Effect of BacoMind on uman Lymphocytes. Journal of Biomedical and Environmental Sciences (Communicated). Deepak M et al., Quantitative determination of the major saponins mixture bacoside A in Bacopa monnieri by PLC. Phytochem Anal. 2005: 16: pp Deepak M and Amit A. The need for establishing identities of bacoside A and B, the putative major bioactive saponins of Indian medicinal plant Bacopa monnieri. Phytomedicine. 2004: 11: pp Presentations th Proceedings of the International Conference on Toxicology, Toxicogenomics and ccupational ealth (ICTT) & 26 Annual Meeting of Society of Toxicology (STX), Gwalior, Joshua Allan J et al., Safety evaluation of BacoMind A standardized extract of Bacopa monnieri in Sprague Dawley rats. P Joshua Allan J et al., Toxicity studies on BacoMind : A standardized phytochemical composition from Bacopa Monnieri: PP: 97. th Proceedings of the International Conference on Advances in Drug Discovery Research 11 ISCBC 2007 Lucknow. Barbhaiya C et al., A double blind placebo controlled study of BacoMind on cognition enhancement in elderly volunteers. P: Kasture SB et al., Effect of BacoMind, an enriched phytochemical composition from Bacopa monnieri, on learning and memory in rats and mice. PP: Pravina K et al., Evaluation of safety and tolerability of BacoMind in healthy volunteers. PP: Dipanwita Dutta Deb et al., Antigenotoxic and Anticlastogenic Effect of BacoMind on uman Lymphocytes. International Conference on Biomarkers in ealth and Environmental Management Coimbatore. 8

10 Phytochemistry BacoMind is an enriched phytochemical composition with true claims on the optimum levels of nine bioactive constituents Bacoside A 3 Bacopaside II Jujubogenin isomer of bacopasaponin C Bacopasaponin C Bacopaside I Bacosine C 2 S C3 Apigenin Luteolin β-sitosterol-d-glucoside 9

11 C3 Standardization of PLC and PTLC Chromatograms 0.4 Luteolin Bacoside A Bacopaside II 0.2 S Bacopaside I Jujubogenin isomer of bacopasaponin C Apigenin Bacopasaponin C C β-sitosterol-d-glucoside

12 Why? Availability BacoMind is clinically proven. Chemical standardization involving assay of 9 different bioactive compounds by PLC*. Biological standardization using, Lipoxygenase inhibition, Butyryl cholinesterase inhibition, ABTS radical scavenging, RAC and DPP assays for each batch*. Supported with phytochemical reference standards (with spectroscopic and chromatographic characterization). Manufactured in a GMP and IS certified manufacturing facility. The Product is Kosher certified. BacoMind is available as a free flowing powder with a unique chemical and biological quality control support. Recommended Dose* For adult mg /day/adult for 12 weeks. For children - 225mg /day/child for 12 weeks. BacoMind is recommended for incorporation in dietary / nutraceutical formulations intended for improving memory and age related neuro-degenerative disorders. Corporate ffice : Ashwathlakshmi Mansion, No. 364, II Floor, 16th Main, 4th 'T' Block, Jayanagar, Bangalore INDIA Ph : / Fax : / R & D Centre : Plot No. 5B, Veerasandra Industrial Area, 19th K. M. Stone, osur Road, Electronic City Post, Bangalore INDIA Ph : / 98 / 97 / 96 Fax : / madhu@naturalremedy.com Website : Disclaimer : These statements have not been evaluated by the Food and Drug Administration or any other regulatory body. This product is not intended to diagnose, treat, cure or prevent any disease. "Natural Remedies calls to readers' attention that some of the products, protocols and uses of the product/s described herein are or may be subject to various restrictions or limitations because of patents, exclusive or nonexclusive licenses, confidentiality agreements and other intellectual property or equivalent rights. Readers are advised to make an early and thorough investigation and inquiry into any product, protocol or use in which they may be interested, to see if any such rights might be applicable".