WO2017006351A1

WO2017006351A1 - Herbal dha composition

Info

Publication number: WO2017006351A1
Application number: PCT/IN2016/050224
Authority: WO
Inventors: Chitra Vasant Savangikar; Sanjeevan Shashikant DEODHAR; Jitendra Prabhakar DAGAONKAR
Original assignee: Individual
Current assignee: Individual
Priority date: 2015-07-09
Filing date: 2016-07-07
Publication date: 2017-01-12
Anticipated expiration: 2018-01-09

Abstract

This invention comprises a composition, its use in treatment of cognitive disorders and a method of treatment of cognitive disorders in human subjects in need thereof comprising administering a composition for use in treatment of cognitive disorders, wherein the composition comprise at least: (a) an edible oil comprising some triglycerides having docosahexaenoic acid moiety (DHA), (b) an emulsifier, and (c) at least an extract of each of the following plant species: Centella asiatica L., Bacopa monnieri L., Moringa oleifera Lamk., Benincasa hispida Thunb. and Cynodon dactylon L.. The composition may further comprise an extract of each of following plant species: Convolvulus pluricaulis Choisy., Celastrus paniculata Willd., Acorus calamus L and, Nardostachys jatamansi (D.Don) DC.. The edible oil may be a DHA rich microbial oil such as DHA rich algal oil or a fish oil. The cognitive disorders include ADHD (Attention Deficit / Hyperactivity disorder), ADD (Attention Deficit Disorder).

Description

HE R BAL DHA C O MPOS ITIO N

FIE L D O F THE INVE NTION

Invention discloses pharmaceutical compositions containing plant-derived active ingredients and Docosahexaenoic acid. The invention also relates to the treatment, prevention or/and risk reduction of mental disorders comprising ADH D (Attention Deficit / Hyperactivity ¾ Disorder), ADD (Attention Deficit Disorder), people having learning disabilities, Tourette's Syndrome, oppositional defiant disorder, conduct disorder, bipolar disorder, Parkinson's disease, Alzheimer's disease, loss of memory, Asperger's syndrome, epilepsy, dyspraxia, dyslexia, ataxia, and schizophrenia.

3α DES C RIPTION OF T HE INVE NTION

^"Attention Deficit / Hyperactivity Disorder_^ abbreviated as ADH D or ADD learning disabilities, dyslexia are some of the most common childhood disorders. These disorders can continue through adolescence and adulthood. C ommon symptoms comprise difficulty in staying focused and paying attention, difficulty in controlling behavior, and hyperactivity (over- 5¾ activity),

In the following is a summary of comprehensive information available on the website link of National Institute of Mental health, USA (website link: http://Www.nimh.nih.gov/health/topics/attention-deficit-hyperactivity-disorder- adhd/index.shtml). ttl Causes for ADH D have not yet been identified with certainty.

Many international studies on twins have indicated genes as major cause since it is shown that ADH D runs in families, they have thinner brain tissue in the areas of the brain associated with attention; which may develop to a normal level of thickness in course of time accompa nied with improvement in their AD H D symptoms a lso.

S tudies indicate a potential link between ciga rette smoking and alcohol use during pregna ncy and ADH D in children. Also exposure to high levels of lead in preschoolers arising from ¾ plumbing fixtures or paint in old buildings may have a higher risk of developing ADH D.

Brain injury can be one of the causes. A possible link is indicated between consumption of certain food additives like artificial colors or preservatives, and a n increase in activity.

Inattention, hyperactivity, and impulsivity a re the key behaviors of ADH D. It is normal for all children to be inattentive, hyperactive, or impulsive sometimes, but for children with ADH D, these behaviors are more severe a nd occur more often. T o be diagnosed with the disorder, a child must have symptoms for 6 or more months and to a degree that is greater than other children of the same age.

S tudies show that the number of children being diagnosed with AD H D is increasing.

R ecognizing AD H D symptoms and seeking help early will lead to better outcomes for both¾ affected children and their families.

Adults may also have AD H D symptoms. T his is particularly possible when the ADH D symptoms begin in childhood and have continued throughout adulthood.

Although there is no cure found so far, treatments that relieve many of the disorder s symptoms focus on reducing the symptoms of ADH D and improving functioning and include medication, various types of psychotherapy, education or training, or a combination of treatments. However, need for research is recognized for developing more effective treatments and interventions, and using new tools such as brain imaging, to better understand ADH D and to find more effective ways to treat and prevent it

US81 10229 discloses a herbal composition comprising: J yotishmati seed oil (Celastrus

¾ paniculata Willd in an amount of about 5 to 50% of the total formulation; Flax seed oil (Linum usitatissium L.( in an amount of about 30 to 65%; Bacopa monnieri L.( extract in an amount of from greater than 0% to about 10%; Rosmarinus officinalis L.( extract from greater than 0% to about 10%; G inger (Zingiber officinalis Rose.) extract in an amount of from greater than 0% to about 4%; and natural Vitamin E (.alpha. Tocopherols) in an amount of from

91 greater than 0% to about 2%%, said composition being useful in the treatment of symptoms associated with Attention Deficit disorder (ADD) or Attention deficit / hyperactivity disorder (ADHD). The method comprises administering an effective amount of the above composition to the subject suffering symptoms associated with attention Deficit Disorder (ADD) and Attention Deficit Hyperactivity Disorder (ADH D) for a period of up to 3 to 12 months.

3S. US8394429 discloses a method for treating patients having conditions associated with Attention Deficit Disorder (ADD) and Attention Deficit / Hyperactivity Disorder (ADH D), comprising administering to a subject suffering from conditions associated with attention Deficit Disorder (AD D) and Attention Deficit / Hyperactivity Disorder (ADHD) for a period of up to 3 to 12 months an effective amount of a composition comprising: a) a combination of rfl supercritical fluid extracts comprising: i) a supercritical fluid extract of J yotishmati; ii) a supercritical fluid extract of Bacopa monnieri L; a supercritical fluid extract of G inger in oil form; iv) a supercritical fluid extract of Flax S eed in oil form; and v) a supercritical fluid extract of Rosemary; and optionally b) Vitamin E; said combination of supercritical fluid extracts being present in an effective amount useful in the treatment of symptoms associated with ϊ& Attention Deficit disorder (ADD) or Attention Deficit / Hyperactivity Disorder (ADH D), wherein said associated conditions are selected from the group consisting of learning disabilities, Tourette's Syndrome, oppositional defiant disorder, conduct disorder, bipolar disorder, Pa rkinson's disease, Alzheimer's disease, loss of memory, Asperger's syndrome, epilepsy, dyspraxia, dyslexia, ataxia, and schizophrenia.

T he composition of US 8394429 also comprises: a combination of supercritical fluid extracts ¾ comprising: i) a supercritical fluid extract of J yotishmati; ii) a supercritical fluid extract of Bacopa monnieri L; iii) a supercritical fluid extract of G inger in oil form; iv) a supercritica l fluid extract of F lax S eed in oil form; and v) a supercritica l fluid extract of R osemary; a nd optiona lly b) Vitamin E .

US 8394429 discloses that the method comprising the step of administering an effective 91 amount of above described herbal composition to sa id patient is applicable also for reducing oxidative stress in a patient for improving scholastic performance or intelligence quotient of a student .

US patent no. 7,923,041 discloses enhancement in the cognitive function by the use of the methylation modifying activity of the herbal extract comprising of G inkgo, C offee extract 3¾ garlic, Bacopa, butcher's broom, flaxseed oil, ginseng, grape seed, St J ohn's wort, artichoke powder, tea leaf, tobacco, and cocoa.

KR20040046656 discloses a composition for preventing and treating Alzheimer's syndrome is characterized by containing 2-10 parts by weight of L-carnitine, 10-30 pa rts by weight of Acorus gramineus L.S oland extract 10-30 parts by weight of Angelica gigas A. Nakai extract 10-30 parts by weight of green extract, 1 0-30 parts by weight of pine root extract, 5-20 parts by weight of lecithin, 2-10 parts by weight of taurine, 10-30 parts by weight of C urcuma Ionga L. extract, 10-3 parts by weight of F raxinus rhynchophylla L, Hance. extract 10-30 parts by weight of Polygala tenuifolia L. extract, 1 0-30 pa rts by weight of D HA and vitamins. US 8,962,042 discloses a method for treating a praxia, autism, speech impairments, tra umatic brain injury, seizure disorders, epilepsy, globa l delays, or ADH D, comprising administering to a patient in need thereof a nutrient composition that a meliorates one or more symptoms of apraxia, autism, speech impairments, traumatic brain injury, seizure ¾ disorders, epilepsy, globa l delays, or ADH D, said nutrient composition comprising an effective amount of a mixture or purified mixture thereof comprising botanical extracts selected from each of the group of bota nicals consisting of gymnema sylvestre, commiphora mukul, curcuma longa, camellia sinensis, emblica officinalis, and termina lia chebula.

In Ayurveda, the traditional system of medicine recognized as system of medicine approved 91 by Indian F DA, ingredients useful for brain disorders and brain function have been mentioned and cata logued in T he Ayurvedic P ha rmacopeia of India ..

S ince, there is a significant scientific acceptance for the fact that cure has not yet been achieved, there exists a continuing need since a long time to achieve further improvement in efficacy of the treatment either by the way of a new active ingredient, or a new composition 3S. conta ining several ingredients or by further modification of existing compositions.

S U MMA RY O F T H E INV E NTION

T his invention comprises a compos ition, its use in treatment of cognitive disorders and a method of treatment of cognitive disorders in human subjects in need thereof comprising administering a composition for use in treatment of cognitive disorders, wherein the composition comprise at least (a) an edible oil comprising some triglycerides having docosahexaenoic acid moiety (D HA), (b) an emulsifier, and (c) at least an extract of each of the following pla nt species: C entella asiatica L. , Bacopa monnieri L, Moringa oleifera La mk., Benincasa hispida Thunb., Cynodon dactylon L. T he composition may further comprise an extract of each of following plant species, C onvolvulus pluricaulis C hoisy., C elastrus paniculata Willd., Acorus calamus L, Nardostachys jata mansi (D.Don) DC.

T he edible oil comprising some triglycerides having docosahexaenoic acid moiety ( D HA) ¾ may be a D HA rich microbial oil or a fish oil. The DHA rich microbial oil has been illustrated in the insta nt invention by using DHA rich alga l oil. However, any other DHA rich edible oil may be used in its place.

T he emulsifier used in the composition is selected from the group soy-lecithin a nd polysorbate. However, a ny other edible emulsifier may be used in their place. l T he composition of this invention may further comprising excipients; which may include flavors a nd colors permitted in food and pharmaceutica l compos itions. F lavor used for substa ntia l suppression of fishy flavor/smell of DHA in the illustrative composition is extract of C innamomum zeylanicum Blume; although other natural flavors may also replace it if they are strong enough to suppress the fishy smell/flavor of DHA. ¾ T he composition of this invention has been illustrated in syrup form. However, if D HA-rich oil is microencapsulated a nd the herba l extracts of plant species mentioned above a re dried off, it is possible to envisage powder compositions for filling in sachets or capsules or tablets or any other solid dosage form.

T he cognitive disorders for which the composition of this invention may be effective comprises a group comprising, without limitation, AD H D (Attention Deficit / Hyperactivity disorder), ADD (Attention Deficit Disorder), people having learning disabilities, T ourette's Syndrome, oppositional defiant disorder, conduct disorder, bipolar disorder, Parkinson's disease, Alzheimer's disease, loss of memory, Asperger's syndrome, epilepsy, dyspraxia, dyslexia, ataxia, and schizophrenia. DETAIL E D DE S C RIPTIO N O F T HE INVE NTION

Stimulants are commonly used in medication for treating ADHD, which actually has a calming effect on children with ADHD. S ome non-stimulants which work differently than stimulants are also used as medicines for treating ADHD. It is also recognized that no single ¾ medication and dose works for all the patients. What works for one might not work for another child, sometimes a combination of medicines and dosages is required to be given. Occurrence of side effects is also variable and unpredictable.

Stimulant medications available in different forms, such as a pill, capsule, liquid, or skin patch with their short-acting, long-acting, or extended release dosage forms are made from active

3l agents that comprise amphetamine, methylphenidate, methamphetamine hydrochloride, Dextroamphetamine, dexmethylphenidate, Atomoxetine and lisdexamfetamine dimesylate. The most commonly reported side effects of these active agents includes decreased appetite, sleep problems, anxiety, and irritability. S ome children also report mild stomachaches or headaches. Most side effects are minor and disappear over time or if the

3S. dosage level is lowered.

One ADH D medication, the non-stimulant atomoxetine (Strattera), carries a warning that children are more likely to have suicidal thoughts than children and teenagers with ADH D who do not take it; and the problem may develop suddenly.

It is acknowledged that current medications do not cure ADH D. Rather, they control the tfn symptoms for as long as they are taken. Medications can help a child pay attention and complete schoolwork. It is not clear, however, whether medications can help children learn or improve their academic skills. Adding behavioral therapy, counseling, and practical support can help children with ADH D and their families to better cope with everyday problems. Other therapies, which a re recommended to be applied simultaneous to medication include psychotherapy, including behavioral therapy.

Medications for adults are same as for children with some exceptions, and this is combined with psychothera py. Although not F DA-approved specifically for the treatment of AD H D,

¾ antidepressants are sometimes used to treat adults with ADH D, which includes norepinephrine or/and dopamine affecting chemicals such as tricyclics, venlafaxine (E ffexor) and bupropion (Wellbutrin). However, adults may be taking medications for dia betes, high blood pressure, other lifestyle diseases, anxiety and depression; and since antidepressants interact with medications for these diseases very badly, careful choice and monitoring is

91 needed.

T his invention embodies a compos ition which has provided faster reduction in ADH D symptoms than reported for prior art compositions. In another embodiment, the composition of this invention has also shown improvement in academic performance concurrent to decrease in AD H D hyperactivity symptoms.

3¾

It is an embodiment of this invention that the composition comprises Docosahexaenoic acid rich algal oil and brain function improving ingredients made from Ayurvedic medicinal herbs as active ingredients. Following Ayurvedic herbs are considered essential C entella asiatica L, Bacopa monnieri L, Moringa oleifera Lamk., Benincasa hispida T hunb, Cynodon dactylon ttl L. C entella is used for Brain tonic ( Medhya), Bacopa for Brain T onic ( edhya), improves memory (Matiprada), a nd in mental disorders. Moringa is used in a ll ailments (S arvavipada Nivara ni), Benincasa In Mental Disorders ( Manasvikar). Cynodon has been reported in Ayurveda to have an efficacy in treatment of dizziness and giddiness (Murchha) and is being used for the first time in the illustrated formulation for the purpose of AD H D symptoms. ϊ& C innamomum is added for flavor and taste in the illustrated composition as one of the most effective natural flavor to mask the fishy odor of DHA. A person skilled in the art may add an alternative flavor, natural or artificial to replace C inna momum in the illustrated composition.

F urther to the extracts of above herbs, extracts from other herbs may also be added as ¾ adjuncts, such as, including, without limitation, herbs such as C onvolvulus pluricaulis C hoisy., C elastrus pa niculata W illd. , Acorus calamus L, Nardostachys jatama nsi (D.Don)DC . etc.

T he composition of this invention, as a syrup, may comprise (a) 1 to 8 % S chizochytrium Oil conta ining 40% DHA, (b) 0.1 to 2-% of soy lecithin, and (c) at least an extract of each of the 91 following pla nt species, 0.5 to 2% C entella asiatica, 0.5- to 2% Bacopa monnieri, 0.1 to 1 % C onvolvulus pluricaulis, 0.1 to 1 % C elastrus paniculata, 0.1 to 1 % Acorus calamus, 0.1 to 2% Moringa oleifera, 0.1 to 1 % Nardostachys jata ma nsi, 0.5 to 2% Benincasa hispida, and 0.01 to 1 Cynodon dactylon,

T he Alga l oil may also be replaced with any other DHA rich edible oil from other sources, 3¾ including fish oil and oil from other species of microalgae.

T he composition of this invention also contains pharmaceutically acceptable excipients. T he pharmaceutical excipients include, without limitation, sweeteners, flavors, emulsifiers including soy lecithin and polysorbate.

In the illustrated exa mple, sugar is used as sweetener. A person skilled in the art would understand that sugar may be replaced with a ny other sweetener, natural or artificial and the sweetener may be a low intensity sweetener i.e. with a sweetness delivery within a couple of multiples or a fraction of sweetness delivery of cane sugar or the same may be high-intensity sweetener having sweetness delivery of a few hundred times the sweetness of the same bulk density of same weight of cane sugar. T he flavor may also be a ny or a mixture of pharmaceutically permitted flavors. Other pharmaceutically permitted excipients may also be added. Emulsifier may also comprise soy lecithin, Polysorbate or any other one or more of pharmaceutically permitted emulsifiers. In the above, depending on the context, a singular may also include plural and vice versa; for example, an emulsifier. may, if context permits, ¾ shall also mean and include ^"emulsifiers. and vice versa.

The dosage form of the composition of this invention is made very conveniently as a syrup, since DHA rich oil is a liquid. However, by using microcapsules of DHA rich edible oil, it is possible to envisage use of solid dosage forms including, without limitation, powders, tablets, capsules, microspheres, microcapsules and the like.

91 In the following are described non-limiting example of working of this invention. A person skilled in the art shall readily recognize equivalents and variations in the composition which are obvious and all of them are included within the scope of this invention.

EXAMPLES

EXAMPLE 1

3R RESPONSE OF ADHD AFFECTED CHILD TO A PRIOR ART COMPOSITION

Following are the indications as disclosed in The Ayurvedic Pharmacopeia of India _ on which the ingredients used herein are known to be effective on brain function improvement Ayurveda is a traditional system of medicine in India which is recognized by Food and Drug Administration of India as an authentic system of medicine. Its knowledge is considered to f l have been validated for efficacy through thousands of years of experience on their application. Table 1

Based on the above available information, a syrup (composition 1) was made as described in the following:

Composition 1: Syrup

Table 2:

All parts^*: Entire plant with its roots, stem and leaves.

The extracts of plants/plant parts as mentioned in Table 1 were weighed in indicated quantities as per formulation in Table 1 and added to 12.5 litres of water. Accurately weighed quantity of juice of Benincasa hispida Thunb. is added to the mixture. Sugar 10 kg, is added to the mixture which is stirred well to dissolve to get a syrup. The syrup is filtered and made up to 15 liters by adding water and the permitted flavor/s and preservative/s are added in the syrup.

T he composition 1 was administered to a child aged 1 1 years, who had following problems as reported by his parents:

¾ 1. T he child used to have incomplete books from school.

2. T he child used to get bored very quickly when completing the work or doing homework and used to start fidgeting and losing focus. Attention span was not more tha n a few minutes.

3. W hen asked about concepts, he showed a good understanding of the same

91 4. S olving jigsaw puzzles, drawing / coloring a nd other sitting activities did not interest him at a II.

5. G et quickly bored of coaching even games. H is Badminton coach got frustrated and reported that this boy has a brilliant game, naturally graceful and technically correct strokes; but simply does not s how the willingness to persevere.

3S. 6. G etting him to sleep at night was an uphill task, slept very late and, consequently, had leading difficulty in waking up, would have deep sleep a nd slept till late if allowed to.

7. E ating was also a problem, because though he showed good appetite, he would not sit to eat his full mea l. If he did sit down to ea each meal used to take a n hour to complete.

8. F or a long time, he had not shown any increase in his height due to his poor food intake.

O n DS -V criteria [T he Diagnostic and S tatistical Ma nual of Mental Disorders ( DS M), published by the American Psychiatric Association (APA)] with 4 point Likert scale was applied for determining his AD H D score. In compliance of DS M-V criteria, as with all DS M-V diagnoses, other conditions that may be the true cause of symptoms were ruled out. Based on the frequent and severe presence of six or more characteristics of inattentive presentation as well as Hyperactive-Impulsive presentation when compared to children of same age, this child was diagnosed as a case of ¾ C ombined presentation. These symptoms were present for more than six months and

affected his life adversely at home, social settings as well as school.

C riteria considered for analyzing this child in the context of the three primary presentations were:

ADHD - Predomi nantly Inattentive P resentation

9 I Fails to give close attention to details or makes careless mistakes.

I Has difficulty sustaining attention.

I Does not appear to listen.

I Struggles to follow through on instructions.

I Has difficulty with organization.

3¾ i Avoids or dislikes tasks requiring sustained mental effort.

I Loses things.

I Is easily distracted.

I Is forgetful in daily activities.

ADHD - Predomi nantly Hyperactive/Impulsive P resentation f l i Fidgets with hands or feet or squirms in chair.

i Has difficulty remaining seated.

I R uns about or climbs excessively in children; extreme restlessness in adults.

I Difficulty engaging in activities quietly. I Acts as if driven by a motor; adults will often feel internally as if they were driven by a motor.

I Talks excessively.

I Blurts out answers before questions have been completed.

¾ i Difficulty waiting or taking turns.

I Interrupts or intrudes upon others.

ADHD - Combined Presentation

I This child met both sets of inattention and hyperactive/impulsive criteria.

The Likert scale used to score the occurrence of the above mentioned criteria in this child 9 was a four point scale as follows: (1) Never or rarely, (2) Sometimes, (3) Often, (4) Very

often.

Accordingly, before start of the treatment his ADHD score was 57.

This child was administered the Composition 1 for two and a half months from start of January 2015 to Mid-March 2015. The formulation was in syrup form and everyday

3¾ administration was 5 ml in morning and 10 ml in night. During that period, the child had started showing noticeable improvement in his studies: his books were not as incomplete as they used to be, and a small, but noticeable improvement was also seen in his grades. The biggest improvement was considered as he started taking, for the first time, an active interest in assembling toys such as cars, animals, buildings etc. and display them with interest in ttl drawing room. This improvement reflected in drop on his ADHD score from 57 to 46.

EXAMPLE 2

RESPONSE OF ADHD AFFECTED CHILD TO IMPROVED PRIOR ART COMPOSITION In case of the same child in above Example 1 , on account of negligence, the treatment got discontinued for next three months after he reached reduction of ADHD score to 46 on Likert scale; and the child returned to his original status which also reflected in increasing the ADHD score to 53 by mid J une, 2015.

¾ Thereafter, from mid-J une, he was again put on the treatment but this time, with a difference that three more ingredients were added to the Composition 1 : (a) DHA (Docosahexaenoic acid) 40% oil extracted from S chizochytrium sp., (b) extract of Cynodon dactylon, and (3) extract of Cinnamon. T he formulation is in syrup form and everyday administration was 5 ml in morning and 10 ml in night.

3t DHA is known for its relation to brain development in initial few months of breast feeding period when mother s milk provides the requirement of DHA at that stage of growth and development. Cynodon dactylon is known in Ayurveda for its efficacy in Dizziness and giddiness (Murchha) (The Ayurvedic Pharmacopeia of India ^" F irst E dition, Vol. 4, Part 1 , Page ^" 29). However, none of them are known to be effective individually on patients having

5¾ ADHD symptoms. C innamon was added mainly for the purpose of improving flavor of the formulation (The Ayurvedic P harmacopeia of India ^" First E dition Vol. 1 , Part i , Page ^" 1 13). The dominant fishy flavor/odor of DHA was a problem that was very difficult to overcome. This flavor/odor is an extremely unfavorable feature for considering use of DHA as an ingredient in oral compositions since it would be very repulsive for strict vegetarians, and tfl more so for children. Its masking is regarded as extremely difficult unless it is microencapsulated. S everal natural flavors were required to be tried, and C innamon worked to be the best.

With this addition, the composition of the Composition 2 is given in the following: Composition 2: Herbal DHA syrup

Table.3

All parts : Entire plant with its roots, stem and leaves.

The extracts of plants/plant parts as mentioned in Table 2 were weighed in indicated quantities as per formulation in Table 1 and added to 12.5 litres of water. Accurately weighed quantity of juice of Benincasa hispida Thunb. is added to the mixture. Sugar 10 kg is added to the mixture which is stirred well to dissolve to get a syrup. The syrup is filtered and made up to 15 liters by adding water and the permitted flavor/s and preservative/s are added in the syrup.

It was an extremely surprising and unexpected observation that whereas the Composition 1 took a long period of about 3 months to show noticeable improvement, after a clear break of

¾ about 3 months in the treatment, which in effect can be considered as an effective wash out period_. as reflected in increase in the ADH D score to 53, the Composition 2 showed striking effect in just four days after starting the C omposition 2. Wherein not only the earlier improvements shown by him with Composition 1 reverted back, but, surprisingly, additional substantial improvements were also seen. He started showing signs of sitting in one place

91 and doing his homework. He surprised even himself one day at his tuition class by sitting continuously for almost 2 hours and concentrating on studies. His work at school has shown good improvement, books are slightly more complete, though not with all books and not for all the time. His appetite has been normal as usual, but the intake has improved and also the time taken for each meal has reduced by about 10%.

3S. Hence, the treatment was continued and his improvements have been noted to progressively further improve in next 21 days. At 25th day after resumption of his treatment with replacement of C omposition 1 with Composition 2, his ADHD score has dropped to 33.

In view of the established record of ADH D to require at least 3 to 12 months ^"treatment to show a very slow effect with a very slow pace, the rapid pace of improvement in substantially rfl less time is surprising. S ince the C omposition 1 and all other known reported chemical as well as natural remedies on ADH D work very slow, and also neither DHA alone nor Cynodon dactylon are known for their noticeable effect on ADH D, the above effect is nothing less than synergistic and is surprising. Treatment to this child was continued thereafter without a break, wherein, after 11 months the child^'s ADHD score on Likert scale 11 months after starting administration of the Composition 2 was 33. It was surprising that the scholastic performance increased from not answering the question paper to writing excellent essays and letters. ( J D: PI add other ¾ improvements which you feel are important). Since, the prior art indicates that although it may be possible to improve the Likert score after considerable period of time, much more than reported here, it has been acknowledge that it is very difficult to get an improvement in scholastic performance in hyperactive children. Hence, performance of the inventive composition reported here is truly surprising. EXAMPLE 3

EFFECT OF COMPOSITION 2 ON 15 CHILDREN

The composition 2 was administered to 15 children diagnosed for having cognitive disorders and their ADHD score on Likert scale before starting administration and after administration for a certain period of time has been given in below.

5¾ Case Study Details

SSubjects ^" 15

SAge G roup ^" 2 to 16 yrs

itl SCenters ^" 3

δ Method ^" DSM-5 Criteria based questionnaire

SEvaluation of Symptoms ^" By 4 point Likert Scale

δ Duration ^" 1 to 1.5 Months (2 Visits)

3 Dose ^" 10 ml each time two times a day

Observations and Results ^" SS ex Ratio = Boys 13 : G irls 2

SAge G roup = 0 to 4 = 1 , 4 to 8 = 9, 8 to 12 = 3, 12 to 16 = 2

SOverall additive symptomatic index = Visit 1 = 809, Visit 2 = 643

QAverage overall individual reading = Visit 1 = 54, Visit 2 = 43

¾ SAverage improvement in attention deficit symptoms Visit 1 =25, Visit 2 =22

3Average improvement in Hyperactivity = Visit 1 = 29, Visit 2 = 22 δ Percentile Improvement in Symptoms =

Overall = 20, Attention Deficit = 12, Hyperactivity = 24.

Additional Observations

S Decrease in enuresis

δ Improvement in scholastic performance

S. SImprovement in speech in autistic child

SIncrease in confidence in parents about the child^'s performance

Claims

C lai ms :

1. A composition comprising at least: (a) an edible oil comprising some of the triglycerides having docosahexaenoic acid moiety (DHA), (b) an emulsifier, a nd (c) at least an extract of each of the following plant s pecies: C entella asiatica L. , Bacopa

¾ monnieri L, Moringa oleifera La mk., Benincasa hispida Thunb., Cynodon dactylon L.

2. T he composition of cla im 1 further comprising a n extract of each of following pla nt species, C onvolvulus pluricaulis C hoisy., C elastrus paniculata Willd., Acorus calamus L, Nardostachys jatamansi (D.Don) DC.

3. T he composition of cla im 1 wherein the edible oil is either a DHA rich microbial oil or 91 a fish oil.

4. T he composition of claim 3 wherein the D HA rich microbial oil is DHA rich algal oil.

5. T he composition of cla im 1 wherein the emulsifier is selected from the group soy- lecithin and polysorbate.

6. T he composition of claim 1 further comprising excipients.

3¾ 7. T he composition of cla im 1 wherein the excipients comprise extract of C innamomum zeylanicum Blume as natural flavor or other flavours and colours

8. A composition for use in treatment of cognitive disorders, wherein the composition comprises at least: (a) an edible oil comprising some of the triglycerides having docosahexaenoic acid moiety (DHA), (b) a n emulsifier, and (c) at least an extract of til each of the following plant species, Centella asiatica, Bacopa monnieri, Moringa oliefera , Benincasa hispida, Cynodon dactylon.

9. T he composition for use according to claim 8 further comprising a n extract of each of following plant species, C onvolvulus pluricaulis C elastrus paniculata, Acorus calamus, Nardostachys jatamansi .

tfk 10. T he composition of claim 1 or claim 8 in syrup dosage form.

1 1. T he composition of claim 1 or claim 8 wherein cognitive disorders comprise a group consisting of AD H D (Attention deficit / hyperactivity disorder), AD D (Attention Deficit Disorder), people having learning disabilities, Tourette's Syndrome, oppositional defiant disorder, conduct disorder, bipolar disorder, Parkinson's disease, Alzheimer's disease, loss of memory, Asperger's syndrome, epilepsy, dyspraxia, dyslexia, ataxia, a nd schizophrenia.

12. A method of treatment of cognitive disorders in huma n s ubjects in need thereof comprising administering a compos ition for use in treatment of cognitive disorders, wherein the composition comprises at least: (a) an edible oil comprising some of the triglycerides having docosahexaenoic acid moiety (DHA), (b) an emulsifier, a nd (c) at least a n extract of each of the following plant species, C entella asiatica, Bacopa monnieri, , Moringa oliefera,, Benincasa hispida, Cynodon dactylon, .

13. T he method claim 12 wherein the composition further comprising an extract of each of following plant species, C onvolvulus pluricaulis, C elastrus paniculata, Acorus calamus, Nardostachys jatamansi,

14. T he method of claim 12 wherein the composition is a syrup.

15. T he composition of claim 1 or claim 2 or claim 8 or claim 9 as a syrup comprising (a) 1 to 8 % S chizochytrium Oil containing 40% DHA, (b) 0.1 to 2-% of soy lecithin, and (c) at least an extract of each of the following plant species, 0.5 to 2% C entella asiatica, 0.5- to 2% Bacopa monnieri, 0.1 to 1 % C onvolvulus pluricaulis, 0.1 to 1 % C elastrus paniculata, 0.1 to 1 % Acorus ca lamus, 0.1 to 2% Moringa oleifera, 0.1 to 1 % Nardostachys jatamansi, 0.5 to 2% Benincasa hispida, and 0.01 to 1 Cynodon dactylon,

16. T he composition according to claims 1 , 8 and 12 wherein flavoring agent is a n extract of, C innamomum zeyla nicum B lume or a ny other natura l flavoring agent; or a permitted artificial flavour.

17. T he method of claim 12 wherein the cognitive disorder is selected from the group consisting of AD H D (Attention deficit / hyperactivity disorder), AD D (Attention Deficit Disorder), people having learning disabilities, Tourette's Syndrome, oppositional defiant disorder, conduct disorder, bipolar disorder, Parkinson's disease, Alzheimer's disease, loss of memory, Asperger's syndrome, epilepsy, dyspraxia, dyslexia, ataxia, a nd schizophrenia.