DESC:FORM 2

THE PATENTS ACT, 1970
(39 of 1970)
&
The Patents Rules, 2003

COMPLETE SPECIFICATION
(See Section 10 and Rule 13)

TITLE

BACOSIDE FORMULATION DESIGNED FOR IMPROVED DISPERSIBILITY AND BIOAVAILABILITY

APPLICANT

Samriddh Nutractive Pvt Ltd
402 Thirath Towers, Road No.7, Banjara Hills, Hyderabad 500034

The following specification particularly describes the invention and the manner in which it is to be performed
BACOSIDE FORMULATION DESIGNED FOR IMPROVED DISPERSIBILITY AND BIOAVAILABILITY
RELATED APPLICATION
This application is related to and takes priority from the Indian Provisional Application 202441011820 filed 20th February 2024 and the PCT application PCT/IB2025/051499 filed 13th February 2025, both of which are incorporated herein in its entirety.

FIELD OF THE APPLICATION
The present invention is related to a formulation containing bacosides with enhanced dispersibility and bioavailability. It also presents a process for the preparation of dispersible bacosides form the enriched fraction of Bacopa monneri. The resultant formulation is at least 96% dispersible which is stable at room temperature. The novel formulation with improved dispersibility and bioavailability using the designed approach serves as an alternative to traditional oral formulations of poorly dispersible bacoside.

BACKGROUND
Aging reduces physical and cognitive functions. Cognitive functions such as memory, attention, language, and executive functions are essential for day-to-day activities. Aging is associated with declining of these essential cognitive functions such as processing speed, memory, language, visuospatial, and executive function abilities. Age-related cognitive decline vary considerably across individuals and cognitive domains and affects Quality of Life (QoL) and independence during old age.1–6
Studies show that cognitive function starts declining gradually in the late 20s, and it is accelerated by neurodegenerative diseases such as Alzheimer’s disease.7, 8 Early interventions help maintaining normal cognitive aging.9 Approximately 44 million people worldwide currently suffer with Alzheimer’s disease, and without the development of a cure or drugs effective at slowing the cognitive decline, this is expected to rise to 135 million by 2050. The cost of caring for patients with Alzheimer’s is equivalent to 1% of the world’s GDP, and then there is the emotional cost on those family members and caregivers who look after the patient as their cognitive ability slowly declines.10
Bacopa monnieri, commonly known as Brahmi, has a long history in traditional medicine and is known for its memory-enhancing properties as well as reducing anxiety.11 The herb is currently marketed around the world as a memory enhancer and a blood sugar regulator. The plant has a vast number of active constituents’ compounds including several alkaloids and saponins, with the main active compounds being the steroidal saponins bacosides A (a mixture of bacoside A3, bacopaside II, bacopaside X, and bacopasaponin C).12–14 Though several other medicinal properties of the plant including cardioprotective, hepatoprotective and anticancer activities have been reported. It has been widely used in Ayurveda majorly for its memory boosting property and for treatment of anxiety, epilepsy, and improvement of cognitive processes, comprehension, and recall. 15–18
Cognitive enhancers (CEs) are prescribed to improve cognitive performance in elderly individuals and those with dementia or to promote better quality of life in patients with neuropsychiatric disorders or brain trauma. However, the administration of these supplements has gone beyond clinical indications, being increasingly used by healthy individuals seeking to improve their cognitive, emotional, and motivational functioning. Students use CEs to boost attentiveness, increase vigilance, stay awake for an extended period, or do better intellectually. Healthy subjects are turning to use CEs to strengthen and increase their attention, memory, vitality, improved focus, concentration, alertness, rapid decision-making, and other measures of wellbeing.19, 20
Herbal products have gained tremendous attention for the presence of bioactive compounds with multiple physiologic functions. The bioactive compounds majorly counter the oxidative stress inside the neurons to exert their protective role.21, 22 Recently, numerous medicinal plants possessing profound central nervous system effects and antioxidant activity have received much attention as food supplement to improve cognitive function against cognitive deficit condition.23–25 B. monnieri is one such plant with desirable compounds for improving cognitive functions.11, 26, 27
The present invention provides a formulation comprising Bacopa extract, Anticaking agent/Glidant, Bioenhancer, Emulsifier and a polymer. The said formulation is found to be improving cognitive functions such as overall memory, mental alertness, reasoning skills, mental flexibility, BDNF levels, sleep quality and reduces anxiety, and serum cortisol.

BRIEF DESCRIPTION OF FIGURES
Figure 1. Summary of mean change – placebo vs. Bacopa monnieri Extract (BME). (a) Digit Span Task; (b) Spatial Span Task; (c) Token Search Task; (d) Monkey Ladder Task; and (e) Paired Associates Task. *p value<0.05; #p value<0.1.
Figure 2. Summary of mean change – placebo vs. Bacopa monnieri Extract (BME). Feature Match Test ? (a) acute effects and (b) chronic effects; Sustained Attention to Response Task ? (c) acute effects and (d) chronic effects; Double Trouble Task ? (e) acute effects and (f) chronic effects. *p value<0.05.
Figure 3. Summary of mean change – placebo vs. Bacopa monnieri Extract (BME). (a) Odd One Out scores; (b) Grammatical Reasoning scores; (c) Spatial Planning scores, and (d) Rotations Task scores. *p value<0.05; #p value<0.1.
Figure 4. Mean change summary of (a) Beck Anxiety Inventory – BAI; (b) Pittsburgh sleep quality index – PSQI; (c) serum Brain Derived Neurotrophic Factor – BNDF (ng/ml), and (d) serum cortisol (mcg/dL). *p value<0.05.

DESCRIPTION OF THE INVENTION
The present invention provides a nutraceutical formulation of Bacopa extract which is at least 96% dispersible and is effective in improving cognitive skills in human subjects.
More specifically, the present invention provides a formulation comprising Bacopa extract, Anticaking agent/Glidant, Bioenhancer, Emulsifier and a polymer.
The formulation comprises, in weight/weight percentage, Bacopa extract in the range of 30-75%, anti caking agent in the range of 0.3 to 0.6%, bioenhancer in the range of 1-10%, emulsifier in the range of 10-30% and polymer in the range of 10-30%.
The formulation of the invention is prepared as a spray powder, granules or tablets, beadlets and can be consumed as a powder, granules, tablets, chewable, liquid form and the likes there of.

The said formulation is found to be improving cognitive functions such as overall memory, mental alertness, reasoning skills, mental flexibility, BDNF levels, sleep quality and reduces anxiety, and serum cortisol.
The anticaking agent in the formulation is selected from the group consisting of mannitol, sodium bicarbonate, powdered cellulose, magnesium silicate, stearic acid and any of the combination thereof.
Emulsifier in the formulation is selected from the group consisting of gum such as pectin alginate, carrageenan agar, gum arabic, gum tragacanth, locust bean gum and xanthan gum or the combination there of.
The bioenhancer is selected from the group consisting of Black cumin oil (Nigella sativa), Caraway (Carum carvi) oil, Phosphatidyl choline, MCT oil, sunflower oil, peanut oil, safflower oil, soybean oil, corn oil, rapeseed oil, Thyme oil, Olive oil and linseed oil.
The polymer in the formulation includes but not restricted to Hydroxyethyl cellulose, Hydroxypropyl cellulose or Carboxyalkyl cellulose.
The invention is further enabled by the following Examples. Examples provided herein are for illustration purposes only and are should not be construed as limiting the scope of the invention.

Example 1. Formulation prepared as spray dried powder
The emulsifier was weighed accurately and added to the suitable solvent under stirring to prepare solution. Bacopa extract was weighed accurately and added to solution under stirring. MCT oil was added slowly under stirring to above solution. Polymer was weighed and added to the said solution under continuous stirring. The final solution was sifted through #60 mesh and was spray dried to form powder. Further, the spray dried powder was sifted and blended with colloidal silicon dioxide in double cone blender. Table 1 to 3 provide formulation of the invention prepared as spray dried powder
Table 1.
S.N. Ingredients Functional role %W/W
1 Bacopa Extract Active 73.20
2 Colloidal Silicon Dioxide (Aerosil) Anticaking agent/Glidant 0.50
3 Medium-Chain Triglycerides (MCT) oil (RSPO)MB Bioenhancer 6.0
4 Sunflower Lecithin (Phosphatidylcholine) Emulsifier 2.68
5 Hydroxypropyl Methyl Cellulose E3 Polymer 17.62
Total (Solid Content) 100.00

Table 2.
S.N. Ingredients Functional role %W/W
1 Bacopa Extract Active 73.20
2 Gum Arabic powder Emulsifier 2.0
3 Colloidal Silicon Dioxide (Aerosil) Anticaking agent/Glidant 0.50
4 Medium-Chain Triglycerides (MCT) oil (RSPO)MB Bioenhancer 3.0
5 Sunflower Lecithin (Phosphatidylcholine) Emulsifier 2.68
6 Hydroxypropyl Methyl Cellulose E3 Polymer 18.62
Total (Solid Content) 100.00

Table 3.
S.N. Ingredients Functional role %W/W
1 Bacopa Extract Active 73.20
2 Gum Arabic powder Emulsifier 5.0
3 Colloidal Silicon Dioxide (Aerosil) Anti-caking agent/ Glidant 0.50
4 Medium-Chain Triglycerides (MCT) oil (RSPO)MB Bioenhancer 3.0
5 Sunflower Lecithin (Phosphatidylcholine) Emulsifier 2.68
6 Hydroxypropyl Methyl Cellulose E3 Polymer 15.62
Total 100.00

Example 2. Formulation prepared as granules
The emulsifier was weighed accurately and added to the suitable solvent under stirring to prepare solution. Further binder was added to above solution under stirring condition. Bacopa extract and diluent were weighed accurately and loaded in RMG container and dry mixed at appropriate impeller speed to form uniform dry blend. The binder solution was added gradually to the dry blend in RMG to obtain wet granules. The wet granules were loaded in tray dryer for drying to obtain desired % LOD. Dried granules were sifted through mesh to obtain desired particle size distribution. Table 4 provides formulation of the invention prepared as granules.
Table 4.
S.N. Ingredients Functional role %W/W
1 Bacopa Extract Active 73.20
2 Hydroxypropyl Methyl Cellulose E3 Binder 1.50
3 Sunflower Lecithin (Phosphatidylcholine) Emulsifier 3.00
4 Microcrystalline Cellulose 101 Diluent 22.30
Total 100.00

Example 3. Formulation prepared as beadlets
The binder was weighed accurately and added to the suitable solvent under stirring to prepare solution. Bacopa extract, colloidal silicon dioxide and Talc were added to above solution slowly under stirring. Sugar spheres were loaded in Fluidized bed processor and prepared dispersion was sprayed on the sugar spheres under optimized process parameters. After completion of spraying, dry the beadles to obtain desired LOD. Coating polymer was weighed and added to suitable solvent under stirring conditions. Stirring continued to get clear solution. Prepared solution was sprayed on the extract loaded beadlets in fluidized bed processor to get the desired weight gain. Final coated beadlets were dried to get desired LOD. Table 5 provides formulation of the invention prepared as beadlets.
Table 5.
S.N. Ingredients Functional role %W/W
1 Bacopa Extract 50% Active 40.00
2 Methocel VLV Binder 2.00
3 Sugar spheres (#60-80) Carrier 42.50
4 Talc Anti-tacking agent 3.50
5 Colloidal silicon Dioxide Anticaking agent 2.00
6 Hydroxypropyl Methyl Cellulose E3 Coating polymer 10.00
Total 100.00

Example 4. Clinical Studies to establish efficacy of the formulation
Method:
A prospective, randomized, double-blind, placebo-controlled, parallel group study was conducted to assess the safety and efficacy of the formulation of the invention. Healthy male and/or female subjects aged between 18-55 years with normal cognition profile assessed by Mini-Mental State Examination (MMSE) and meeting the eligibility criteria were enrolled in the study. There were six study visits for each subject – Screening/Baseline Visit (Day -7 to Day 0), Randomization Visit (Day 1), Three Follow-Up Visits (Day 14±3 days; Day 28±3 days; Day 56±3 days) and End of Study Visit (Day 84±3 days). During randomization visit, eligible subjects were randomly assigned in double-blinded fashion into two treatment groups to receive placebo or B. monneri extract (bacopa formulation of the invention) in 1:1 ratio. The subjects were asked to consume one capsule every morning after breakfast for 84 days. The B. monneri extract (BME) was given as capsules that contained 300 mg of bacopa extract (30% total bacosides) providing 90 mg of total bacosides and the placebo capsules were made of Microcrystalline Cellulose.
Fasting blood samples were collected for biomarker analysis; serum Brain-Derived Neurotrophic Factor (BDNF), serum cortisol as well as safety assessments which included complete blood count (CBC), alanine transaminase (ALT), aspartate transaminase (AST), total bilirubin (TB) and alkaline phosphatase (ALP) for liver function and serum creatinine and blood urea nitrogen (BUN) for renal function. After blood sample collection, subjects were evaluated for memory and cognitive functions.
The following tests were done:
Creyos Cognitive Battery
The specific tasks include domains like verbal short-term memory, spatial short-term memory, visuospatial working memory, working memory, episodic memory, concentration, alertness, sustained attention, reasoning, planning and mental flexibility.
Beck Anxiety Inventory
Beck Anxiety Inventory (BAI) is a tool for assessing the severity of an individual's anxiety symptoms. It has 21 questions that can be self-administered or given verbally by a practitioner.
Pittsburgh Sleep Quality Index (PSQI)
The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire that measures sleep quality and disruptions over a one-month period. It includes 19 self-reported items and 5 additional questions for the bed partner. It is divided into seven domains: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, the use of sleeping medication, and daytime dysfunction.
Serum BDNF and cortisol was analyzed using ELISA kits by the central laboratory.
Endpoints Evaluation
Efficacy endpoints: Primary efficacy endpoints included mean change in verbal short-term memory assessed by Digit Span task, visuospatial working assessed by Monkey Ladder task, working memory assessed by Token Search task, episodic memory assessed by Paired Associates task, and spatial short-term memory assessed by Spatial Span task using Creyos Assessment (formerly Cambridge Brain Sciences) from baseline to Days 28, 56 and 84.
Secondary efficacy endpoints were mean change in cognitive skills parameters - alertness and sustained attention through Feature Match task and Sustained Attention to Response Task; concentration assessed by Double Trouble task; reasoning assessed by Odd One Out and Grammatical Reasoning task; planning assessed by Spatial planning task and mental flexibility assessed by Rotations task using Creyos on Day 0 (baseline) and Days 14, 28, 56 and 84. Concentration assessed by Double Trouble task, alertness and sustained attention assessed by Feature Match task and Sustained Attention to Response Task were also evaluated at 1, 3 and 5 hours post dose on Day 1 by Creyos Assessment.
Mean change in serum BDNF (baseline, Day 84), serum cortisol levels (baseline, Day 56 and 84), BAI scores for evaluation of anxiety levels, PSQI scores for evaluation of sleep quality (baseline, Days 28, 56 and 84), and safety (incidence of adverse events) from baseline to Day 84 were evaluated.
Results
Efficacy Evaluation
Primary Endpoints
The primary objective of the study was to evaluate the effect of BME versus placebo on memory from baseline to Day 84.
Verbal Short-term Memory Assessed by Digit Span Task
Summary of mean change for verbal short-term memory assessed by Digit Span Task by visit and treatment for per protocol (PP) population is presented in Figure 1a. For the BME group, the change from baseline in the Digit Span Task scores was significant (p<0.05) on Day 28 (BME=1.26±2.09, placebo=0.22±1.99), Day 56 (BME=1.82±2.01, placebo=0.14±2.84) and Day 84 (BME=2.45±2.57, placebo=0.17±2.48) versus placebo.
Spatial Short-term Memory Assessed by Spatial Span Task
Summary of mean change for spatial short-term memory assessed by Spatial Span Task by visit and treatment for PP population is presented in Figure 1b. For the BME group, the change from baseline for the Spatial Span Task score was non-significant on Day 28 (BME=0.34±0.99, placebo=0.17±1.28). However, the change from baseline was significant (p<0.05) on Day 56 (BME=0.79±0.91, placebo=0.17±1.21) and Day 84 (BME=1.21±1.04, placebo=0.22±1.48) when compared to the placebo.
Working Memory Assessed by Token Search Task
Summary of working memory assessed by Token Search Task by visit and treatment for PP population is presented in Figure 1c. For the BME group, the change from baseline for the Token Search Task showed an increasing trend (p=0.0533) on Day 28 (BME=0.79±1.34, placebo=0.08±1.52). However, the change from baseline was significant (p<0.05) at Day 56 (BME=1.05±1.54, placebo=0.19±1.33) and Day 84 (BME=1.55±2.02, placebo=0.25±1.38) compared to the placebo.
Visuospatial Working Assessed by Monkey Ladder Task
Summary of mean change for visuospatial working assessed by Monkey Ladder Task by visit and treatment for PP population is presented in Figure 1d. For the BME group, the change from baseline in the Monkey Ladder Task scores was non-significant on Day 28 (BME=1.05±2.32, placebo=0.28±2.09). However, the change from baseline was significant (p<0.05) on Day 56 (BME=1.37±1.76, placebo=0.22±1.27) and Day 84 (BME=2.00±2.77, placebo=0.33±1.55) as compared to the placebo.
Episodic Memory Assessed by Paired Associates Task
Summary of episodic memory assessed by Paired Associates Task by visit and treatment for PP population is presented in Figure 1e. For the BME group, the change from baseline for the Paired Associates Task scores was significant (p<0.05) on Day 28 (BME=0.66±0.99, placebo= -0.03±1.13), Day 56 (BME=0.90±1.31, placebo=0.03±0.91) and Day 84 (BME=1.50±1.62, placebo=0.14±1.29) as compared to the placebo.
Secondary Endpoints
The secondary objectives of the study was to evaluate the effect of BME on cognitive skills, anxiety, sleep quality, serum cortisol and BDNF levels from baseline to Day 84.
Cognitive Skills Parameters - Feature Match Task
Acute Effect - Featured Match Task (Baseline to 1, 3 and 5 hours Post-dose)
Summary of acute effect on alertness and sustained attention assessed by Feature Match Task by visit and treatment for PP population is presented in Figure 2a. For the BME group, the change from baseline for the Feature Match Task scores was non-significant at 1-hour post-dose (BME=15.80±34.45, placebo=15.30±35.00), 3-hour post-dose (BME=15.85±29.87, placebo=10.13±27.28) and 5-hour post-dose (BME=26.00±34.04, placebo=19.13±29.76) as compared to the placebo.
Chronic Effect - Featured Match Task (Baseline to Week 12)
Summary of chronic effect on alertness and sustained attention assessed by Feature Match Task by visit and treatment for PP population is presented in Figure 2b. For the BME group, the change from baseline for the Feature Match Task scores was significant (p<0.05) on Day 14 (BME=21.79±31.19, placebo=5.92±24.88), Day 28 (BME=25.79±28.86, placebo=8.39±20.91) Day 56 (BME=24.42±30.15, placebo=6.44±25.36) and Day 84 (BME=27.74±26.75, placebo=7.25±26.64) as compared to the placebo.
Cognitive Skills Parameters - Sustained Attention to Response Task (SART)
Acute Effect - Sustained Attention to Response Task (Baseline to 1, 3 and 5 hours Post-dose)
Summary of acute effect on alertness and sustained attention assessed by Sustained Attention to Response Task by visit and treatment for PP population is presented in Figure 2c. For the BME group, the change from baseline for the Sustained Attention to Response Task scores was non-significant at 1-hour post-dose (BME=7.18±30.84, placebo=4.88±21.36), 3-hour post-dose (BME=13.15±21.57, placebo=5.78±12.49) and 5-hour post-dose (BME=12.65±20.75, placebo=5.18±13.83) compared to the placebo.
Chronic Effect - Sustained Attention to Response Task (Baseline to Week 12)
Summary of chronic effect on sustained attention assessed by Sustained Attention to Response Task by visit and treatment for PP population is presented in Figure 2d. For the BME group, the change from baseline for the Sustained Attention to Response Task scores was non-significant on Day 14 (BME=13.66±25.99, placebo=11.06±13.15), Day 28 (BME=13.05±24.15, placebo=6.14±17.01) Day 56 (BME=16.29±21.59, placebo=7.19±16.33) and Day 84 (BME=11.21±22.45, placebo=4.06±16.97) compared to the placebo.
Cognitive Skills Parameters - Concentration Assessed by Double Trouble Task
Acute Effect - Double Trouble Task (Baseline to 1, 3 and 5 hrs Post-dose)
Summary of acute effect on concentration assessed by Double Trouble Task by visit and treatment for PP population is presented in Figure 2e. For the BME group, the change from baseline for the Double Trouble Task scores was non-significant at 1-hour post-dose (BME=10.35±9.25, placebo=8.25±11.07). The change from baseline was significant (p<0.05) at 3-hour post-dose (BME=14.50±9.15, placebo=8.70±11.09) and 5-hour post-dose (BME=16.23±11.69, placebo=10.30±9.54) as compared to the placebo.
Chronic Effect - Double Trouble Task (from Baseline to Week 12)
Summary of chronic effect on concentration assessed by Double Trouble Task by visit and treatment for PP population is presented in Figure 2f. For the BME group, the change from baseline for the Double Trouble Task scores was significant (p<0.05) on Day 14 (BME=19.68±10.13, placebo=9.69±12.57), Day 28 (BME=22.97±11.96, placebo=16.33±12.75), Day 56 (BME=24.24±14.22, placebo=16.08±13.98) and Day 84 (BME=27.11±14.41, placebo=15.39±16.87) as compared to the placebo.
Odd One Out Task
Summary of reasoning assessed by Odd One Out Task by visit and treatment for PP population is presented in Figure 3a. For the BME group, the change from baseline for the Odd One Out Task scores was non-significant on Day 14 (BME=1.13±3.14, placebo= -0.08±3.94). The change from baseline was significant (p<0.05) on Day 28 (BME=0.87±3.63, placebo= -0.11±3.12) at Day 56 (BME=1.68±2.73, placebo= -0.03±3.45) and Day 84 (BME=2.08±2.58, placebo=0.03±4.55) as compared to the placebo.
Grammatical Reasoning Task
Summary of reasoning assessed by Grammatical Reasoning Task by visit and treatment for PP population is presented in Figure 3b. For the BME group, the change from baseline for the Grammatical Reasoning Task score showed an increasing trend on Day 14 (BME=3.55±6.03, placebo=1.14±4.95; p=0.0633). The change from baseline were significant (p<0.05) on Day 28 (BME=4.47±5.80, placebo=2.47±4.00), Day 56 (BME=5.90±6.60, placebo=2.19±6.69) and Day 84 (BME=7.42±6.45, placebo=4.08±5.89) as compared to the placebo.
Spatial Planning Task
Summary of planning assessed by Spatial Planning Task by visit and treatment for PP population is presented in Figure 3c. For the BME group, the change from baseline for the Spatial Planning Task scores was non-significant on Day 14 (BME=7.45±13.70, placebo=5.14±14.32), Day 28 (BME=8.79±13.93, placebo=7.97±15.89), and Day 56 (BME=14.03±18.76, placebo=9.75±17.07), and showed an increasing trend on Day 84 (BME=16.03±15.14, placebo=10.00±16.57; p=0.0968) as compared to the placebo.
Rotations Task
Summary of mental flexibility assessed by Rotations Task by visit and treatment for PP population is presented in Figure 3d. For the BME group, the change from baseline for the Rotations Task scores was non-significant (p>0.05) at Day 14 (BME=35.61±40.41, placebo=17.28±53.24), Day 56 (BME=41.16±58.50, placebo=18.61±53.83) and an increasing trend at Day 28 (BME=33.74±48.62, placebo=19.86±46.80, p=0.0886) compared to the placebo. The change from baseline was significant (p<0.05) at Day 84 (BME=49.74±48.00, placebo=20.08±42.78) compared to the placebo.

Beck Anxiety Inventory (BAI)
Summary of anxiety assessed by BAI by visit and treatment for PP population is presented in Figure 4a. For the BME group, the change from baseline for BAI scores was significant (p<0.05) on Day 28 (BME= -1.45±1.03, placebo= -0.19±0.67), Day 56 (BME= -2.00±1.27, placebo= -0.44±0.77) and Day 84 (BME= -2.37±1.42, placebo= -0.36±1.07) as compared to the placebo.

Pittsburgh Sleep Quality Index (PSQI)
Summary of sleep quality assessed by PSQI by visit and treatment for PP population is presented in Figure 4b. For the BME group, the change from baseline for the PSQI scores were significant (p<0.05) on Day 28 (BME= -0.90±1.11, placebo= -0.17±1.13), Day 56 (BME= -1.42±1.27, placebo= -0.28±1.34) and Day 84 (BME= -1.71±1.49, placebo= -0.06±1.26) as compared to the placebo.
Serum Levels of Brain Derived Neurotrophic Factor (BDNF)
Summary of BDNF by visit and treatment for PP population is presented in Figure 4c. For the BME group, the change from baseline for the BDNF was significant (p<0.05) on Day 84 (BME=2.03±3.00 ng/ml, placebo= -0.14±1.62 ng/ml) as compared to the placebo.

Serum Cortisol
Summary of serum cortisol levels by visit and treatment for PP population is presented in Figure 4d. For the BME group, the change from baseline for the serum cortisol levels were significant (p<0.05) on Day 56 (BME= -4.84±3.98 mcg/dL, placebo=0.93±4.46 mcg/dL) and Day 84 (BME= -8.80±4.80 mcg/dL, placebo=1.20±5.40 mcg/dL) as compared to the placebo.

The studies carried out with the bacopa formulation of the invention with extensive measures on memory, cognitive skills, anxiety, sleep, biomarkers, and acute effects. Our battery of cognitive functions test results show that the BME improves cognitive health, promotes concentration as early as 3 hours post dose on Day 1, increases overall memory, mental alertness, reasoning skills, mental flexibility, BDNF levels, sleep quality and reduces anxiety, and serum cortisol.
Dated: 14th February 2025

Kausalya Santhanam
Agent for the Applicant, IN/PA/1183
digitally signed for e-filing

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,CLAIMS:Claims
I Claim:
1. A nutraceutical formulation of bacosides comprising enriched fraction of bacopa, anticaking agent or a glidant, bioenhancer, emulsifier and a polymer and wherein the said formulation is stable at room temperature and exhibits at least 96% dispersibility.
2. The nutraceutical formulation of bacosides as claimed in claim 1 wherein the said anticaking agent is selected from the group consisting of mannitol, sodium bicarbonate, powdered cellulose, magnesium silicate, stearic acid and a combination thereof.
3. The nutraceutical formulation of bacosides as claimed in claim 1 wherein the said emulsifier is selected from the group consisting of pectin alginate, carrageenan agar, gum arabic, gum tragacanth, locust bean gum and xanthan gum and a combination there of.
4. The nutraceutical formulation of bacosides as claimed in claim 1 wherein the said bioenhancer is selected from the group consisting of Black cumin oil (Nigella sativa), Caraway (Carum carvi) oil, Phosphatidyl choline, MCT oil, sunflower oil, peanut oil, safflower oil, soybean oil, corn oil, rapeseed oil, Thyme oil, Olive oil and linseed oil.
5. The nutraceutical formulation of bacosides as claimed in claim 1 wherein the said polymer is selected from the group consisting of Hydroxyethyl cellulose, Hydroxypropyl cellulose and Carboxyalkyl cellulose.
6. The nutraceutical formulation of bacosides as claimed in claim 1 wherein the said formulation is processed as a spray powder, granules or tablets.
7. A nutraceutical formulation of bacosides comprising bacopa extract in the range of 30-75%, anti caking agent in the range of 0.3 to 0.6%, bioenhancer in the range of 1-10%, emulsifier in the range of 10-30% and polymer in the range of 10-30%.
8. Use of a nutraceutical formulation of bacosides comprising enriching extract of bacopa and formulation excipients for improving cognitive functions selected from memory, mental alertness, reasoning skills, mental flexibility, BDNF levels, sleep quality and reducing anxiety, and serum cortisol.