Description:TECHNICAL FIELD:
The present invention relates to a novel, stabilized, synergistic bioactive composition for improving fetal development. Particularly, the composition comprising exogenous combination of stabilized polyunsaturated fatty acids and trimethylazanium compounds along with pharmaceutically acceptable excipients. More particularly, the present invention relates to a stable synergistic bioactive composition for improving choline expression for fetal development, comprising exogenous combination of a) stabilized omega 3 fatty acid; b) at least one trimethylazanium compound; and c) at least one pharmaceutically acceptable excipient.

BACKGROUND:
Polyunsaturated fatty acids (PUFAs) provide various health benefits in the diet, such as a reduction in low-density lipoprotein and an increase in high-density lipoproteins. Some of the PUFA (omega-3 and omega-6) are essential fatty acids that the body requires but humans are not able to synthesize it.
PUFAs are of great interest in food, nutraceutical, pharmaceutical and feed applications, a growing market estimated to reach approximate USD 50 billion by 2025.
Two PUFAs families, n-6 and n-3 fatty acids, are physiologically and metabolically distinct. A pure, high-quality omega-3 fish oil should be included in a woman's supplement regimen before and during pregnancy, as well as during breastfeeding. Long-chain omega-3 polyunsaturated fatty acids like a-Linolenic acid (ALA), Stearidonic acid (SDA), Eicosatetraenoic acid (ETA), Docosapentaenoic acid (DPA), Docosahexaenoic acid (DHA), Eicosapentaenoic acid (EPA) are important, but Docosahexaenoic acid (DHA), and Eicosapentaenoic acid (EPA) are particularly important throughout pregnancy and during the early stages of an infant's life. During pregnancy, it benefits not only the mother, but also the fetus as, maternal Docosahexaenoic acid (DHA), and Eicosapentaenoic acid (EPA) intake helps prevent pre-term labor, increases birth weight and supports postpartum mood in new mothers. As for the fetus, it is necessary to support development of the baby’s brain, eyes and nervous system. During pregnancy, omega 3 fatty acid is transferred through the placenta to the fetus’ brain.
Further, it is observed that among the many reasons to get adequate water-soluble quaternary ammonium compounds like choline, acetyl choline are useful nutrients for brain and nervous system to help regulate memory, mood, muscle control and more. choline is important for fetal brain development and placental function. In the brain, choline's primary role is in the synthesis of the neurotransmitter, acetylcholine, and lipid metabolism. choline also generates a methyl group to remethylate homocysteine to methionine. Neural Regen Res. 2017 Jul; 12(7): 1075–1076.
Few studies reported that inadequate maternal choline intake may lead to congenital disabilities and impaired postnatal cognitive ability. Besides fatty liver, choline deficiency in animals before and during pregnancy can cause serious outcomes such as a low reproductive rate, fetal growth retardation, premature death, heart dysfunction, renal degeneration, and hemorrhage of the kidney of the fetus.
Essentially, the combination of two or more nutrients working together can have a more significant impact on the body than each nutrient working alone.
The combination of two or more nutrients like PUFA and essential dietary amine play a significant role in infant brain and eye development, with inadequate intakes resulting in deficits in visual and neurocognitive function. Omega fatty acids and essential dietary amine are both essential nutrients that play crucial roles in human health. When combined, they can offer a range of benefits like Cardiovascular Health, Muscle Growth and Repair, Mental Health, Immune Function, Inflammation and Oxidative Stress.
However, stabilization of omega-3 fatty acids presents several challenges due to their susceptibility to oxidation and degradation. They are highly prone to oxidation when exposed to oxygen, light, and heat. This oxidation process leads to the formation of harmful compounds, such as free radicals and peroxides, which can reduce the efficacy and safety of omega-3 supplements. The oxidative degradation of omega-3 fatty acids leads to rancidity, characterized by unpleasant odors and flavours.
Addressing to these limitations requires the development of innovative formulation strategies, such as using antioxidants, employing encapsulation technologies, optimizing manufacturing processes, and improving packaging materials to enhance the stability and bioavailability of omega-3 fatty acids in supplements.
US8945636B2 discloses a stabilized formulation of omega-3 polyunsaturated fatty acid comprising tocopherol (Vitamin E), ascorbic acid (Vitamin C), fat-soluble antioxidant selected from the group consisting of BHT (butylated hydroxytoluene), BHA (butylated hydroxyanisole), TBHQ (tertiary butyl hydroquinone), and combinations thereof.
J Agric Food Chem. 2002 Mar 27;50(7):2094-9 discloses a metal chelator, EDTA must be added at molar concentrations higher than that of iron to inhibit oxidation of foods containing long-chain PUFA from either fish or algae and fortified with iron.
Algae oil is gaining popularity as a sustainable and plant-based alternative to fish oil. Algae have gained significant attention as a source of renewable and sustainable oil that can be used for various purposes. This plant-based oil is rich in many beneficial compounds, including omega-3 fatty acids. Fish obtain their omega-3 fatty acids from eating marine algae or other organisms that have consumed algae. They do not inherently have omega-3 in their bodies.
While fish oil and krill oil are also a good omega-3 source, algal oil may provide a good alternative for vegans and those who don't eat seafood or can't tolerate fish oil emulsion and encapsulation, especially those involving micro/nano-technologies are promoted to protect omega-3 oils.
Additionally, metal chelating agents and molecular antioxidants have shown promise in reducing omega-3 fatty acid oxidation rates. Chelating agents can inhibit the oxidation of omega 3 fatty acid by binding to transition metal ions, which are known catalysts for lipid oxidation. Chelating agents can help preserve the quality of omega 3 fatty acid -containing products by preventing the development of rancidity and maintaining freshness. Further, it improves stability and bioavailability of omega 3s by facilitating its absorption in the gastrointestinal tract. Examples of chelating agents that are commonly used in food and supplement formulations include ethylenediaminetetraacetic acid (EDTA), citric acid, ascorbic acid (vitamin C), and phytic acid. These chelating agents are generally recognized as safe (GRAS) by regulatory authorities and are widely used in the food industry to preserve product quality and stability. When formulating DHA-containing products, the selection and concentration of chelating agents should be carefully considered to achieve optimal stability and efficacy.
However, there are few limitation for use of chelating agents which are non-biodegradable like EDTA which is poorly absorbed through the gastrointestinal tract. The hepatotoxicity, poor BBB penetration, and potential neurotoxicity limit the utility of chelators for cognition therapy.
Therefore, there is an unmet need of environmentally friendly, safe and reliable biodegradable chelating agents in the pharmaceutical field.
Green Chelate can be widely used as substitute for chelation agent (e.g. NTA, EDTA, etc.) in high polymer chemistry industry, household chemical industry, pharmaceuticals industry, aquaculture, oil field, water treatment industry, boiler cleaning, etc.
Moreover, plant-based biodegradable chelating agents are gaining attention in pharmaceutical applications due to their environmental friendliness and effectiveness.
The present inventors with extensive research on chelating agent and its impact on content of omega 3s stability have developed a stable pharmaceutical composition comprising biodegradable chelator mediated omega 3 fatty acid with methyl donor group which are necessary for fetal development. The composition of the present invention has good solubility in wide pH range with powerful decontamination ability and can achieve synergistic effect in a subject need thereof.

OBJECT OF THE INVENTION:
The primary object of the present invention is to provide novel therapeutical approach for improving fetal development.
Another object of the present invention is to provide environmentally friendly, green dietary source, safe and reliable nutritional composition.
Yet another object of the present invention is to provide bioavailable oral compositions for improving fetal brain behaviour and cognitive development.
Yet another object of the present invention is to provide cost-effective, side-effect-free supplementation for enhancing both maternal and fetal health.

SUMMARY OF THE INVENTION:
To meet the above objects, the inventors of the instant invention carried out thorough experiments to establish significant effects of the active ingredients or PUFA or vitamin or quaternary ammonium compounds or nutrients or methyl donors that ameliorate therapeutic efficacy in the treatment of fetal development.
In an aspect, the present invention provides a bioactive composition for enhancing both maternal and fetal health comprising exogenous combination of biodegradable chelators mediated polyunsaturated fatty acids and trimethylazanium along with pharmaceutically acceptable excipients.
In another aspect, the invention provides stabilized bioactive composition comprising synergistic combination of stabilized omega 3 fatty acid and methyl donor along with pharmaceutically acceptable excipients.
In another aspect, the invention provides stabilized bioactive composition wherein the stabilized omega 3 fatty acid is stabilization is carried out in presence of green or biodegradable chelators.
In yet another aspect, the invention provides stabilized bioactive composition having good solubility and synergistic effect.

Abbreviations:
PUFA: polyunsaturated fatty acids
Omega-3s: Omega-3 fatty acids
GLDA: (L-glutamic acid N,N-diacetic acid)
MGDA: (methylglycinediacetic acid)
EDDS: (ethylenediamine-N,N'-disuccinic acid)
ASDA: (L-aspartic acid N,N-diacetic acid)

BRIEF DESCRIPTION OF THE FIGURES:
Figure 1 illustrates choline plasma serum level in pg/ml for G1 to G10 test groups.

DETAILED DESCRIPTION OF THE INVENTION:
The invention will now be described in detail in connection with certain preferred and optional embodiments, so that various aspects thereof may be more fully interpreted and comprehended. However, any skilled person or artisan will appreciate the extent to which such embodiments could be generalized in practice.
It is further to be understood that all terminology used herein is for the purpose of describing particular embodiment only and is not intended to be limiting in any manner or scope. Unless defined otherwise, all technical and scientific expressions used herein have the same meaning as commonly understood by one of ordinary skill in the art to which embodiments of the invention pertain.
In describing and claiming the embodiments of the present invention, the following terminology will be used in accordance with the definitions set out below which are known in the state of art.
The singular forms “a,” “an,” and “the” include plural reference unless the context clearly dictates otherwise. Also, the term ‘composition’ does not limit the scope of the invention for multiple compositions that can be illustrated for best mode of the invention.
The term “pharmaceutically/nutraceutically acceptable salt,” as used herein, represents those salts which are within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and animals without undue toxicity, irritation, allergic response and the like and are commensurate with a reasonable benefit/risk ratio.
Particularly the term “pharmaceutically acceptable salts” refers to the relatively non-toxic, inorganic, and organic acid addition salts of compounds, amino acid salt, sugar-based salt, alkali or alkaline earth metal salts, as well as hydrates, solvates, co-crystals, polymorphs and the like of the salts.
The salts are preferably selected from chloride, bromide, calcium, sodium, hydroxide, phosphate, acetate, fumarate, lactate, maleate, sulphate, tartrate, citrate, hydrates carbonate, gluconate, mesylate, hydrochloride, hydrobromide and glucosamine.
The term ‘green chelate’ or ‘biodegradable’ chelating agents refers to chelants or sequestering agents, which is mainly prepared from plant-based raw material and forms stable complexes with metal ions through a process of chelation. These agents are environmentally friendly alternatives to traditional nonbiodegradable chelating compounds. They effectively bind and remove heavy metals and minerals from wastewater and soil, reducing pollution and environmental damage.
The ‘trimethylazanium group’ having three methyl groups attached to heteroatom nitrogen also refereed as ‘quaternary ammonium cation’. The methyl-groups are highly stable molecules involved in methylation. This process is an extremely important metabolic process that imparts a sizable influence on cellular functions. Maternal methyl-group donor availability may be associated with fetal growth and development and with different perinatal outcomes such as birth weight, congenital malformations, and later health hazards.
The term ‘exogenous substance’ is any material that is present and active in an individual organism or living cell but originated outside that organism. Moreover, ‘exogenous substance’ is introduced from or produced outside the organism or system.
All modifications and substitutions that come within the meaning of the description and the range of their legal equivalents are to be embraced within their scope. A description using the transition “comprising” allows the inclusion of other elements to be within the scope of the invention.
In an embodiment, the present invention provides the composition comprising exogenous combination of stabilized polyunsaturated fatty acids and trimethylazanium compounds along with pharmaceutically acceptable excipients.
In one embodiment, the present invention provides a stable synergistic bioactive composition for improving choline expression for fetal development comprising exogenous combination of: a) stabilized omega 3 fatty acid; b) at least one trimethylazanium compound; and c) at least one pharmaceutically acceptable excipient.
In preferred embodiment, the present invention provides stabilized synergistic bioactive composition comprising exogenous combination of biodegradable chelators mediated polyunsaturated fatty acids and trimethylazanium along with pharmaceutically acceptable excipients.
In another preferred embodiment, the polyunsaturated fatty acids are omega 3 fatty acids preferably (9Z,12Z,15Z)-octadeca-9,12,15-trienoic acid, (5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaenoic acid and (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10, 13,16,19-hexaenoic acid .
In another embodiment, the concentration of omega 3 fatty acids in the composition ranges from 1 mg to 1000 mg by weight of the total composition., preferably 10 to 600 mg.

In another embodiment, the present invention provides an algal oil which is derived from marine or freshwater algae. The algal oil is contamination-free, non-toxic, and enriched with omega 3 fatty acid, particularly (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid.
Particularly, (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid is stabilized by adding a specific quantity of biodegradable chelating agent. The stabilized (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid comprises (4Z,7Z,10Z, 13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid and biodegradable chelating agent or salts thereof in the weight ratio of 1:0.5 to 1:10.
In yet another embodiment, a biodegradable chelating agent / chelator(s) used in the composition is selected from the group consisting of GLDA (L-glutamic acid N, N-diacetic acid), MGDA (methylglycinediacetic acid), EDDS (ethylenediamine-N,N'-disuccinic acid), ASDA (L-aspartic acid N,N-diacetic acid), Sodium Gluconate, NTA (nitrilotriacetic acid), and IDS (iminodisuccinic acid).
In another embodiment, the additional biodegradable chelating agents which can be used in place of traditional nonbiodegradable chelators include Citric Acid, Tartaric Acid, Lactic Acid, Soy Protein Hydrolysates and Polyphenols.

In further embodiment, the biodegradable chelating agent is present in the range of 0.01 to 10 % of the omega 3 fatty acid.
In another embodiment, the formulations of the present application include from about 0.001% to about 0.01% by weight of the chelator relative to the omega-fatty acids (w/w), (i.e. weight of chelator/weight of omega-fatty acids), from about 0.01% to about 0.1%, from about 0.1% to about 0.5%, from about 0.5% to about 1.0%, from about 1.0% to about 2.0%, from about 2.0% to about 4.0%, from about 4.0% to about 6.0%, or about 4% of the chelator relative to the omega-fatty acids.
In another embodiment, the formulations of the present application include from about 0.1% to about 10.0% by weight of the chelator relative to the omega-fatty acids (w/w).
In yet another embodiment, the methyl donor is compounds containing trimethylazanium groups selected from the group consisting of 2-hydroxyethyl(trimethyl)azanium, 2-(trimethylazaniumyl)acetate , 2-acetyloxyethyl(trimethyl) azanium, [3-hexadecanoyloxy-2-[(Z)-hexadec-4-enoyl]oxypropyl] 2-(trimethylazaniumyl) ethyl phosphate, [(E,2S,3R)-2-[[(Z)-hexacos-17-enoyl]amino]-3-hydroxyoctadec-4-enyl] 2-(trimethylazaniumyl)ethyl phosphate and salts thereof.
In another embodiment the concentration of trimethylazanium groups in the present composition ranges from 1 mg to 1000 mg by weight of the total composition., preferably 10 to 800 mg.
Particularly, the composition comprising stabilized (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid and 2-hydroxyethyl(trimethyl)azanium and salts thereof, wherein the stabilized 4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid comprising combination of 4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid with biodegradable chelators. The biodegradable chelators are selected from hydroxyiminodisuccinic acid (HIDS), methylglycinediacetic acid (MGDA), iminodisuccinate and ethylenediamine-N,N'-disuccinic Acid (EDDS).
In another preferred embodiment, the present invention provides stabilized medicinal composition comprising exogenous combination of stabilized omega 3 fatty acid and trimethylazanium moiety along with pharmaceutically acceptable excipients, wherein stabilized omega 3 fatty acid and trimethylazanium moiety are present in the weight ratio of 1:0.1 to 1:10; preferably 1:0.5 to 1: 5 w/w of total composition.
In another preferred embodiment, the stabilized omega 3 fatty acid is present in the range of 20 to 65% w/w of the total composition.
In another preferred embodiment, the trimethylazanium containing compound is present in the range of 25 to 75% w/w of the total composition.
In another embodiment, the present invention provides a stabilized synergistic bioactive composition comprising combination of methylglycinediacetic acid (MGDA) stabilized (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid with 2-hydroxyethyl (trimethyl)azanium along with pharmaceutically acceptable excipients/carriers, wherein methylglycinediacetic acid (MGDA) stabilized (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid with 2-hydroxyethyl (trimethyl)azanium are present in the weight ratio of 1:0.1 to 1:10 w/w along with along with pharmaceutically acceptable excipients.
In another embodiment, the present invention provides a stabilized synergistic bioactive composition comprising combination of L-glutamic acid N,N-diacetic acid (GLDA) stabilized (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid with 2-hydroxyethyl (trimethyl)azanium along with pharmaceutically acceptable excipients/carriers, wherein L-glutamic acid N,N-diacetic acid (GLDA) stabilized (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid with 2-hydroxyethyl (trimethyl)azanium are present in the weight ratio of 1: 0.1 to 1:10 w/w along with along with pharmaceutically acceptable excipients.
In another embodiment, the present invention provides stable synergistic composition that provides bioactive compounds useful for fetal brain development. Moreover, the composition plays a significant role in infant brain and eye development. The combined supplementation enhances neurodevelopment in the fetal hippocampus more effectively than supplementing with either nutrient alone. The present combination enhances cognitive function and reduce oxidative stress. Further, it supports maternal well-being and reduce the risk of preterm birth.
It is further evident that supplementation with one augments the other points to synergy between the two nutrients. Infants receiving nutrition from breastmilk are provided with the present composition from the maternal intake, but those who are not breastfed can take infant formula that contains the present combination for proper growth and development.

In yet another embodiment, the present stabilized 4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid not only improve fetal growth but also increases cellular choline uptake.
The composition is useful supplement for improving cell survival, synaptic plasticity, and normal brain development of fetus. It further reduces cortisol induced stress conditions.
In another embodiment, the present invention provides synergistic bioactive composition wherein two ingredients work intracellularly in synergistic manner.
In yet another embodiment, the present invention provides composition that is useful to improve cognitive function and memory in maternal and foetus.
The term "therapeutically effective amount " denotes an amount that reduces the risk, potential, possibility or occurrence of a disease or disorder, or provides advanced alleviation, mitigation, and/or reduction or restoration or modulation, regulation of at least one indicator/biomarker (e.g., blood or serum CRP level), and/or minimize at least one clinical symptom related to fetal development.
The term ‘subject in need thereof’ pertains to a human, preferably female. Particularly female including but not limited to adult, women planning for pregnancy, women before conception, pregnant women, conceive, lactating women, women of reproductive age.
In the context of the present invention, the term “treatment” refers to alleviate, mitigate, prophylaxis, attenuate, manage, regulate, modulate, control, minimize, lessen, decrease, downregulate, up regulate, moderate, inhibit, restore, suppress, limit, block, decrease, prevent, inhibit, stabilize, ameliorate, cure, enhance, improve fetal neurodevelopment.
Notably, the instant composition is non-hazardous, non-toxic, and safe for human consumption without any severe adverse effects, therefore the present composition can also be used as preventive therapy/ adjuvant therapy/ add-on therapy/ combination/ adjunctive therapy in a subject in need thereof.
Certain compounds of the present invention exist in unsolvated forms as well as solvated forms, including hydrated forms. Further, some compounds of the present invention exist in multiple crystalline or amorphous forms (“polymorphs”). Compounds of the present invention are formulated in isomeric, geometric, enantiomeric or stereoisomeric forms.
The active compounds may be in the hygroscopic or non-hygroscopic form based on water affinity of the compound salts.
In general, all physical forms are of use in the methods contemplated by the present invention and are intended to be within the scope of the present invention.
Compound or pharmaceutically acceptable salts includes, hydrates, halides like chloride, bromide, metal salts like calcium, sodium, potassium, hydroxide, phosphate; polymorphs, solvates, enantiomers or racemates. Some of the crystalline forms of the compound exist as polymorphs and as such are intended to be included in the present disclosure. In addition, some of the compounds may form solvates with water (i.e., hydrates) or common organic solvents, and such solvates are intended to be encompassed by some embodiments.
In one of the embodiments, the present invention provides a synergistic bioactive composition that is present in effective amount along with pharmaceutically acceptable excipients.
As used herein, the term “pharmaceutically acceptable carriers, diluents or excipients” is purported to mean, without limitation, any adjuvant, carrier, excipient, sweetening agent, diluents, preservative, dye/colorant, flavor enhancer, surfactant, wetting agent, dispersing agent, suspending agent, stabilizer, isotonic agent, solvent, emulsifier, or encapsulating agent, encapsulating polymeric delivery systems or polyethylene glycol matrix which is acceptable for use in the subject, preferably humans. Excipients may also include, for example: antiadherents, antioxidants, binders, coatings, compression aids, disintegrants, dyes (colors), emollients, emulsifiers, fillers (diluents), film formers or coatings, fragrances, glidants (flow enhancers), lubricants, preservatives, sorbents, suspending or dispersing agents, sweeteners, surfactant, anticaking agent, food additives, or waters of hydration, salts.
In another embodiment, the present invention relates to synergistic bioactive composition, which can be prepared in a manner well known in the pharmaceutical art, and can be administered by a variety of routes, depending upon whether local or systemic treatment is desired and upon the area to be treated. The preferable route of administration includes but not limited to sublingual, rectal, topical, parenteral, nasal, or oral.
In some embodiment, the present synergistic bioactive composition can be administered to the subject in need thereof, in the form which is suitable for oral use, such as a tablet, capsule (in the form of delayed release, extended release, sustained release, enteric coated release); hard gelatin capsules, hard gel, soft gelatin capsules in an oily vehicle, veg capsule, hard or soft cellulose capsule, granulate for sublingual use, effervescent or carbon tablets, aqueous or oily solution, suspension or emulsion, encapsulate, matrix, coat, beadlets, nanoparticles, caplet, granule, particulate, agglomerate, spansule, chewable tablet, lozenge, troche, solution, suspension, rapidly dissolving film, elixir, gel, tablets, pellets, granules, capsules, lozenges, aqueous or oily solutions, suspensions, emulsions, sprays or reconstituted dry powdered form with a liquid medium or syrup; infant drops; for topical use including transmucosal and transdermal use, such as a cream, ointment, gel, aqueous or oil solution or suspension, salve, parch or plaster; for nasal use, such as a snuff nasal spray or nasal drops; for vaginal or rectal use, such as a suppository; for administration by inhalation, such as a finely divided powder or a liquid aerosol; for sub-lingual or buccal use, such as a tablet, capsule, film, spray. Further, the composition can be formulated for parenteral use including intravenous, subcutaneous, intramuscular, intravascular, infusion, intraperitoneal, intracerebral, intracerebroventricular, or intradermal.
Synergistic bioactive composition of the present invention is suitable for oral administration and can be presented as discrete units such as capsules (e.g., soft-gel capsules), cachets or tablets each containing a predetermined amount of the active ingredient; as a powder or granules; as a solution or a suspension in an aqueous liquid or a non-aqueous liquid, syrup; or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsion. The active ingredients can also be presented in the form of a bolus, electuary or paste, bioactive bar, energy bars (candy bars), powder, energy drink, ready to drink, granule sachet.
Further, the present composition can be formulated in the form of age-appropriate pediatric oral dosage forms such as syrup, minitablets, chewable formulations, orodispersible films, orodispersible tablets and bioadhesive buccal tablets. It can also be prepared in the form of snack, confectionery food products, sachet, gummies.
In another embodiment, the synergistic bioactive composition of the present invention is non-toxic, cost effective, enriched with bioactive ingredients, and provides safeguard against problems associated with choline deficiency without any adverse effect.
In another embodiment of the present invention, the diluents are selected from starches, hydrolyzed starches, partially pregelatinized starches, anhydrous lactose, cellulose powder, lactose monohydrate, sugar alcohols such as sorbitol, xylitol and mannitol, silicified microcrystalline cellulose, ammonium alginate, calcium carbonate, calcium lactate, dibasic calcium phosphate (anhydrous/ dibasic dehydrate/ tribasic), calcium silicate, calcium sulphate, cellulose acetate, croscarmellose, corn starch, pregelatinized starch, dextrin, ß-cyclodextrin, methylated-ß-cyclodextrin, dextrates, dextrose, erythritol, ethyl cellulose, fructose, fumaric acid, glyceryl palmitostearate, magnesium carbonate, magnesium oxide, maltodextrin, maltose, medium-chain triglycerides, polydextrose, polymethacrylates, sodium alginate, sodium chloride, sterilizable maize, sucrose, sugar spheres, talc, trehalose, xylitol, vehicles like petrolatum, dimethyl sulfoxide and mineral oil or the like.
In some embodiment of the present invention, the diluent in the composition/formulation is present in a range of 1% to 30% by weight of the total composition/formulation.
In yet another embodiment of the present invention, the binder is selected from disaccharides such as sucrose, lactose, polysaccharides and their derivatives like starches, cellulose, or modified cellulose such as microcrystalline cellulose and cellulose ethers such as hydroxypropyl cellulose (HPC); hydroxypropyl methyl cellulose (HPMC); sugar alcohols such as xylitol, sorbitol, or mannitol; protein like gelatin; synthetic polymers such as polyvinylpyrrolidone (PVP), polyethylene glycol (PEG), starch, acacia, agar, alginic acid, calcium carbonate, calcium lactate, carbomers, carboxymethylcellulose sodium, carrageenan, cellulose acetate phthalate, chitosan, copovidone, corn starch, pregelatinized starch, cottonseed oil, dextrates, dextrin, dextrose, ethyl cellulose, guar gum, hydrogenated vegetable oil, mineral oil, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxyl ethyl methyl cellulose, hydroxypropyl cellulose, inulin, cellulose, methyl cellulose, polyvinylpyrrolidone and polyethylene glycol, lactose, liquid glucose, gum arabic, magnesium aluminium silicate, maltodextrin, maltose, methyl-cellulose, microcrystalline cellulose, pectin, poloxamer, polydextrose, polymethacrylates, povidone, sodium alginate, stearic acid, sucrose, sunflower oil, various animal vegetable oils, and white soft paraffin, paraffin, flavorants, colorants and wax.
In another embodiment, the present invention provides synergistic bioactive composition which is useful in the treatment of neural tube defects (NTDs), attention and cognitive dysfunction, nutrient deficiency, infant processing speed, visuospatial memory, congenital disabilities, and autism.
In a further embodiment of the present invention, the binder in the composition/formulation is present in a range of 0.1 to 30% by weight of the composition/formulation.
In some embodiment, the antioxidant is selected from tocopherol (vitamin E), sesamol, guaiac resin, methionine, beta-carotene, lycopene, lutein, zeaxanthin, butylated hydroxy anisole (BHA), butylated hydroxytoluene (BHT), sodium ascorbate, sodium metabisulfite (SMB), l-carnosine, propyl gallate (PG), tertiary butyl hydroquinone, cysteine (CYS), citric acid, tartaric acid, phosphoric acid and ascorbic acid.
In another embodiment of the present invention, the amount of antioxidant in the composition/formulation is present in the range of 0.1 to 10% by wt. of the composition/ formulation.
In another embodiment of the present invention, the lubricant is selected from magnesium stearate, zinc stearate, calcium stearate, glycerin monostearate, glyceryl behenate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil, light mineral oil, magnesium lauryl sulphate, medium-chain triglycerides, mineral oil, myristic acid, palmitic acid, poloxamer, polyethylene glycol, sodium benzoate, sodium chloride, sodium lauryl sulphate, sodium stearyl fumarate, stearic acid, talc, potassium, or sodium benzoate or the like.
In another embodiment of the present invention, the lubricant in the composition/formulation is present in a range of 0.1% to 10.0% by weight of the total composition/formulation.
In another embodiment of the present invention, the solubilizing agent is selected from polysorbate 80, sodium lauryl sulphate, anionic emulsifying wax, nonionic emulsifying wax, glyceryl monooleate, phospholipids, polyoxyethylene alkyl ethers, polyoxyethylene castor oil derivatives, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearates, polyoxylglycerides, sorbitan esters, triethyl citrate, vitamin E, polyethylene glycol succinate, microcrystalline cellulose, carboxymethylcellulose sodium, diethanolamine, ethylene glycol palmitostearate, glycerin monostearate, gum arabic, acetate succinate, lecithin, polyethylene alkyl ethers, aluminum oxide, poly(methylvinyl ether/maleic anhydride), calcium carbonate, crospovidone, cyclodextrins, fructose, hydroxpropyl betadex, oleyl alcohol, povidone, benzalkonium chloride, benzethonium chloride, benzyl alcohol, benzyl benzoate, cetylpyridinium chloride, inulin, meglumine, poloxamer, pyrrolidone, sodium bicarbonate, starch, stearic acid, sulfobutylether beta cyclodextrin, tricaprylin, triolein, docusate sodium, glycine, alcohol, self-emulsifying glyceryl monooleate, cationic benzethonium chloride, cetrimide, xanthan gum, lauric acid, myristyl alcohol, butylparaben, ethylparaben, methylparaben, propylparaben, sorbic acid or the like.
In another embodiment of the present invention, the amount of solubilizing agent or surfactant in thecomposition/formulation ranges from 0.1% to 10% by weight of the composition/formulation.
In a preferred embodiment of the present invention, the solubilizing agent or surfactant is present in a range of 0.1% to 5.0% by weight of the composition/formulation.
In one of the embodiments of the present invention, the glidant is selected from colloidal silicon dioxide, magnesium stearate, fumed silica (colloidal silicon dioxide), starch, talc, calcium phosphate tribasic, cellulose powdered, hydrophobic colloidal silica, magnesium oxide, zinc stearate, magnesium silicate, magnesium trisilicate, silicon dioxide or the like.
In another embodiment of the present invention, the glidant in the composition/formulation is present in a range of 0.1% to 5.0% by weight of the total composition/formulation.
In some embodiment of the present invention, the stabilizers are selected from the group consisting of alginate, agar, carrageen, gelatin, guar gum, gum arabic, locust bean gum, pectin, starch, xanthan gum, trehalose and likewise.
In some embodiment of the present invention, the stabilizer in the composition/formulation is present in a range of 0.1% to 10.0% by weight of the total composition/ formulation.
In some embodiment of the present invention, the plasticizers added to coating of the formulation are selected from the group consisting of propylene glycol, glycerol, glyceryl triacetate (triacetin), triethyl citrate, acetyl triethyl citrate, diethyl phthalate, acetylated monoglycerides, castor oil, mineral oil and like thereof.
In some embodiment of the present invention, the plasticizer in the composition/formulation is present in a range of 0.1% to 5.0% by weight of the total composition/ formulation.
In some embodiment of the present invention, the solvent is selected from water, alcohol, isopropyl alcohol, propylene glycol, mineral oil, benzyl alcohol, benzyl benzoate, flavored glycol, carbon dioxide, castor oil, corn oil (maize), cottonseed oil, dimethyl ether, albumin, dimethylacetamide, ethyl acetate, ethyl lactate, medium-chain triglycerides, methyl lactate, olive oil, peanut oil, polyethylene glycol, polyoxyl, castor oil, propylene carbonate, pyrrolidone, safflower oil, sesame oil, soybean oil, sunflower oil, water-miscible solvents, organic polar or non-polar solvents or mixtures thereof.
In a preferred embodiment of the present invention, the solvent in the composition/formulation is used in a quantity sufficient to make the weight of the composition/formulation 100% by weight.
The additional additives include a polymer, a plasticizer, a sweetener, and a powdered flavor, a preservative, a colorant, a surfactant, and other excipients. The powdered flavor composition includes a flavourant associated with a solid carrier. Coating materials such as synthetic polymers, shellac, corn protein (zein) or other polysaccharides, gelatin, fatty acids, waxes, shellac, plastics, and plant fibers and like thereof are used.
In a preferred embodiment of the present invention, the additives are used in a range of 0.1 to 10% w/w of unit dose.
In yet another embodiment, the present invention provides the composition/formulation comprising a therapeutic blend of biodegradable chelators mediated omega 3 fatty acids and trimethylazanium compound thereof along with pharmaceutical excipients, wherein the pharmaceutical excipients are selected from a diluent, a binder, a lubricant, a glidant, an additive, a surfactant, a stabilizer or mixtures thereof.
In a preferred embodiment, the present invention provides the composition/formulation wherein the pharmaceutically acceptable excipients are selected from a group consisting of the diluent is present in a range of 1 to 30%; the binder present is present in a range of 0.1 to 25%; the lubricant is present in a range of 0.1 to 10.0 %; the glidant is present in a range of 0.1 to 5.0%; the additive is present in a range of 0.1 to 10%; the surfactant is present in a range of 0.1 to 5.0%; the stabilizer is present in a range of 0.1 to 5.0%; the antioxidant is present in a range of 0.1 to 5.0%; and the plasticizer is present in a range of 0.1 to 5.0%; by weight of total composition.
In further embodiment, compositions containing compounds of the present invention, can be conveniently presented in unit dosage form and prepared by any of the methods well known in the art of pharmacy. Preferred unit dosage formulations are those containing an effective dose, or an appropriate fraction thereof, of the active ingredient, or a pharmaceutically acceptable salt thereof.
The magnitude of a prophylactic or therapeutic dose typically varies with the nature and severity of the condition to be treated and the route of administration. The dose, and perhaps the dose frequency, will also vary according to the age, body weight and response of the individual patient.
In general, the total daily dose (in single or divided doses) ranges from about 1 mg per day to about 2000 mg per day, preferably about 10 mg per day to about 1500 mg per day.
In certain embodiments, the present invention provides the bioactive synergetic composition wherein the effective unit dose for an oral administration is formulated in a range of 10 to 1000 mg.
It is further recommended that women planning for pregnancy, initially receive low doses and that the dosage be titrated based on individual physiological responses and/or pharmacokinetics. It can be necessary to use dosages outside these ranges in some cases, as will be apparent to those in the art.
The present composition can be used as infant formula as well as adult formula by varying the concentration of active ingredients. Further, it is noted that the dietician or nutritionist or certified physician, medical practitioner knows how and when to interrupt, adjust or terminate therapy in conjunction with an individual patient’s response.
The use of any and all examples, or exemplary language (e.g., such as) provided herein, is intended merely to better illuminate the invention, and does not pose a limitation on the scope of the invention unless otherwise claimed.
Various other examples of compositions and modifications or adaptations thereof can be devised by a person skilled in the art after reading the foregoing preferred embodiments without departing from the spirit and scope of the invention. All such further examples, modifications and adaptations are included within the scope of the invention.
It will be appreciated by those versed in the art that the present invention makes available novel and useful bioactive compositions, which have effects in several administration forms. Also, it will be understood by those with knowledge in the dietary supplement and nutraceutical art, that many embodiments of this invention may be made without departing from the spirit and scope of the invention, and the invention is not to be construed as limited, as it embraces all equivalents therein.
The invention may be further illustrated by the following examples, which are for illustrative purposes only and should not be construed as limiting the scope of the invention in anyway.
The present disclosure is therefore to be considered as in all respects illustrative and not restrictive, the scope of the invention being indicated by the appended claims and examples, and all changes or alterations which come within the ambit of equivalency are intended to be encompassed therein.

EXAMPLES:
Having described the basic aspects of the present invention, the following non-limiting examples illustrate specific embodiments thereof. Those skilled in the art will appreciate that many modifications may be made in the invention without changing the essence of invention.
Example 1: Various compositions/formulations.
i. Composition 1: Tablet / Capsule
Ingredient mg per unit dose
(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid 150
2-hydroxyethyl(trimethyl)azanium 450
L-glutamic acid N,N-diacetic acid 100
Magnesium Stearate 0.1-10
Hydroxypropyl Methylcellulose 0.5-10
Microcrystalline Cellulose 0.1-10
Polyvinylpyrrolidone 0.1-10
Starch 0.1-5
Talc 0.1-5
Mannitol 0.1-2
Propylene Glycol QS
Water QS
Average weight 710-750 mg

ii. Composition 2: Tablet / Capsule
Ingredient mg per unit dose
(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid 100
2-hydroxyethyl(trimethyl)azanium 550
L-glutamic acid N,N-diacetic acid 90
Magnesium Stearate 0.1-5
Ascorbic acid 0.1-5
Microcrystalline Cellulose 0.1-10
Colloidal Silicon dioxide 0.1-5
Hydroxypropyl Methylcellulose 0.1-5
PVPP 0.1-5
Talc 0.1-5
Tween 80 0.1-5
Mannitol 0.1-1
Water QS
Average weight 750-800 mg

iii. Composition 3: Tablet / Capsule
Ingredient mg per unit dose
(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid 100
2-hydroxyethyl(trimethyl)azanium 250
Methylglycinediacetic acid 100
Microcrystalline Cellulose 0.1-10
Silicon dioxide 0.1-5
Hydroxypropyl Methylcellulose 0.1-5
Stearic acid 0.1-5
Pregelatinized starch 0.1-10
Talc 0.1-5
Tween 80 0.1-5
Starch 0.1-5
PEG QS
Water QS
Average weight 455-520 mg

iv. Composition 4: Tablet / Capsule
Ingredient mg per unit dose
(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid 100
2-hydroxyethyl(trimethyl)azanium 500
L-glutamic acid N,N-diacetic acid 75
Microcrystalline Cellulose 0.1-5
Silicon dioxide 0.1-5
Dicalcium Phosphate 0.1-5
Cross Carmellose Sodium 0.1-2
Hydroxypropyl Methylcellulose 0.1-10
Magnesium Stearate 0.1-5
Polyvinylpolypyrrolidone 0.1-10
Talc 0.1-5
Polysorbate 20 0.1-2
Mannitol 0.1-2
Water QS
Average weight 675-700 mg

v. Composition 5: Tablet / Capsule
Ingredient mg per unit dose
(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid 150
2-hydroxyethyl(trimethyl)azanium 500
Ethylenediamine-N,N'-disuccinic acid 100
Silicon Dioxide 0.1-2
Microcrystalline Cellulose 0.1-10
Magnesium Stearate 0.1-5
Polyvinylpyrrolidone 0.1-5
Talc 0.1-5
Corn Starch 0.1-5
Sodium ascorbate 0.1-2
Propylene glycol 0.1-1
Water QS
Average weight 755-820 mg

vi. Composition 6: Tablet / Capsule.
Ingredient mg per unit dose
(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid 150
2-hydroxyethyl(trimethyl)azanium 250
L-glutamic acid N,N-diacetic acid 100
Microcrystalline Cellulose 0.1-10
Colloidal silicon dioxide 0.1-5
Hydroxypropyl Methylcellulose 0.1-5
Magnesium Stearate 0.1-5
Polyvinylpyrrolidone 0.1-5
Calcium Phosphate 0.1-5
Ascorbic Acid 0.1-1
Polysorbate 20 0.1-2
Talc 0.1-5
Sucrose 0.1-1
Mannitol 0.1-1
Glycerol 0.1-2
Average weight 510-560 mg

vii. Composition 7: Tablet / Capsule.
Ingredient mg per unit dose
(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid 100
2-(trimethylazaniumyl)acetate 250
L-glutamic acid N,N-diacetic acid 75
Microcrystalline Cellulose 0.1-5
Silicon dioxide 0.1-5
Hydroxypropyl Methylcellulose 0.1-10
Magnesium Stearate 0.1-2
Zinc Stearate 0.1-5
Polyvinylpyrrolidone 0.1-3
Sodium benzoate 0.1-1
Ascorbic Acid 0.1-2
Polysorbate 20 0.1-1
Talc 0.1-1
Dextrose 0.1-1
Mannitol 0.1-1
Water QS
Average weight 430-470 mg

viii. Composition 8: Tablet / Capsule.
Ingredient mg per unit dose
(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid 100
2-acetyloxyethyl(trimethyl) azanium, 250
Soy Protein Hydrolysates 100
Microcrystalline Cellulose 0.5-5
Silicon dioxide 0.1-5
Hydroxypropyl Methylcellulose 0.1-5
Magnesium Stearate 0.1-5
Zinc Stearate 0.1-5
Polyvinylpyrrolidone 0.1-5
Sodium ascorbate 0.1-2
Polysorbate 20 0.1-2
Starch 0.1-2
Talc 0.1-5
Mannitol 0.1-1
Water QS
Average weight 460-500 mg

ix. Composition 9: Tablet / Capsule
Ingredient mg per unit dose
(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid 150
2-hydroxyethyl(trimethyl)azanium 125
L-glutamic acid N,N-diacetic acid 100
Microcrystalline Cellulose 1-5
Silicon dioxide 0.1-5
Hydroxypropyl Methylcellulose 0.1-5
Magnesium Stearate 0.1-5
Zinc Stearate 0.1-5
Dicalcium Phosphate 0.1-5
Polyvinylpyrrolidone 0.1-5
Sodium Ascorbate 0.1-2
Polysorbate 20 0.1-1
Talc 0.1-5
Mannitol 0.1-1
Water QS
Average weight 380-420 mg

x. Composition 10: Tablet / Capsule.
Ingredient mg per unit dose
(4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid 100
2-hydroxyethyl(trimethyl)azanium 450
Methylglycinediacetic acid 100
Microcrystalline Cellulose 0.1-5
Silicon dioxide 0.1-5
Hydroxypropyl Methylcellulose 0.1-5
Magnesium Stearate 0.1-5
Zinc Stearate 0.1-5
Polyvinylpyrrolidone 0.1-5
Sodium benzoate 0.1-1
Ascorbic Acid 0.1-2
Cross carmellose sodium 0.1-2
Polysorbate 20 0.1-1
Talc 0.1-5
Mannitol 0.1-1
Water QS
Average weight 660-700 mg

Animal Study
Example: 2 Measurement of Choline level.
a) Biochemical Assay: Choline
Evaluation of test substance on pregnant female mice.
Test system details:
Test Species: Mice.
Strain: Pregnant Swiss Albino Mice.
Sex: Female.
Age:10-12 Weeks.
Body Weight: 20-30gms.
Total No. of Animals: 60 Animals (10 groups of 6 animals each).
Animal House conditions
Lighting: 12 / 12-hour light-dark cycle.
Temperature: 22 ± 3°C.
Relative Humidity: 30 to 70%.
Feed: Normal chow diet.
Drinking water: Mice were provided with ad libitum drinking water passed through water filter system.
Vehicle details : 0.5% of Carboxy Methyl Cellulose sodium was used as a vehicle for test formulation.
Group, Designation and Dose Levels:
Table-1
Group No. Group description Equivalent Human Dose and Treatment Observations
G1 Control No treatment Normal Level
G2 (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid 100 mg No significant change in Choline
G3 (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid (Stabilized) 100 mg Changes in Choline Level
G4 2-hydroxyethyl(trimethyl)azanium 100 mg Changes in Choline Level
G5 (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid + 2-hydroxyethyl (trimethyl)azanium Low Dose
[250 mg :125 mg] No significant change in Choline level
G6 (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid (Stabilized) + 2-hydroxyethyl (trimethyl)azanium Low Dose
[250 mg: 125 mg] Significant change in Choline level
G7 (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid + 2-hydroxyethyl (trimethyl)azanium Optimum Dose
[250 mg :450 mg] No significant change in Choline level
G8 (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid (Stabilized) + 2-hydroxyethyl (trimethyl) azanium Optimum Dose
[250mg :450mg] Significant change in Choline level
G9 (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid + 2-hydroxyethyl (trimethyl)azanium High Dose
[190 mg :550 mg] No significant change in Choline level
G10 (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid (Stabilized) + 2-hydroxyethyl (trimethyl) azanium High Dose Ratio
[190 mg :550mg] Significant change in Choline level

Normal control (G1) group receiving vehicle, all treatment groups were administered with test substances; (G2) (G3) (G4) are individual test samples (G5) [Lower dose] (G6) Stabilized [Lower dose], (G9) [Higher dose] and (G10) Stabilized [Higher dose]. G7 and G8 are optimum dose in regular and stabilized formulation respectively.
All the treatments were administered daily for 02 weeks. After the completion of two weeks animals were anesthetized and blood was collected for biochemical parameter analysis.
All data including body weight, feed consumption, were analyzed statistically using Graph-Pad Prism Software, version 5.01. All values were expressed as Average Mean. The significant difference between the treatment and control group were estimated using one-way analysis of variance (ANOVA) with Dunnett’s test. All results of the statistical analysis were summarized in below table.

Results:
Table 2: Choline Expression in Treated Groups (pg/ml)
Animal 1 2 3 4 5 6 Mean
Groups
Group 1 (G1) 40.47 40.18 41.06 41.27 40.67 41.45 40.85
Group 2 (G2) 43.25 44.47 45.26 45.58 44.28 44.12 44.49
Group 3 (G3) 48.15 48.63 49.02 48.87 48.55 48.28 48.58
Group 4 (G4) 53.25 52.99 53.12 53.58 53.26 52.55 53.13
Group 5 (G5) 62.12 61.89 62.23 62.16 62.56 61.88 62.14
Group 6 (G6) 71.2 70.37 70.67 71.24 70.25 70.58 70.72
Group 7 (G7) 98.25 98.34 99.12 98.43 99.1 98.54 98.63
Group 8 (G8) 115.24 116.65 115.76 115.24 115.36 115.2 115.58
Group 9 (G9) 92.24 92.45 93.21 92.35 93.13 92.28 92.61
Group 10 (G10) 102.23 101.88 102.36 102.45 102.34 101.92 102.20

Discussion and Conclusion:
In the present disclosure, the compositions G6, G8 and G10 shows significant increase in choline level which is useful for fetal development. Moreover, the present disclosure indicates that the combination in specific ratio where stabilized (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid plays important role for enhancing choline expression as compared with normal or regular (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid. In combination with 2-hydroxyethyl (trimethyl) azanium, the stabilized (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid composition give synergistic effect. , Claims:1. A stable synergistic bioactive composition for improving choline expression for fetal development, comprising exogenous combination of:
a) stabilized omega 3 fatty acid;
b) at least one trimethylazanium compound; and
c) at least one pharmaceutically acceptable excipient.

2. The stable synergistic bioactive composition as claimed in claim 1, wherein the stabilized omega 3 fatty acid and at least one trimethylazanium compound are present in the weight ratio of 1: 0.5 to 1:5 by weight of the total composition.

3. The stable synergistic bioactive composition as claimed in claim 1, wherein the stabilized omega 3 fatty acid is present in the range of 20 to 65% w/w of the total composition.

4. The stable synergistic bioactive composition as claimed in claim 1, wherein the trimethylazanium compound is present in the range of 25 to 75% w/w of the total composition.

5. The stable synergistic bioactive composition as claimed in claim 1, wherein the stabilized omega 3 fatty acid is a complex of omega 3 fatty acid and biodegradable chelator with about 0.01% to about 10% by weight of the biodegradable chelator relative to the omega 3 fatty acid.

6. The stable synergistic bioactive composition as claimed in claim 5, wherein the omega 3 fatty acid is selected from the group consisting of (9Z,12Z,15Z)-octadeca-9,12,15-trienoic acid, (5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaenoic acid and (4Z,7Z,10Z, 13Z, 16Z, 19Z)-docosa-4,7,10, 13,16,19-hexaenoic acid.

7. The stable synergistic bioactive composition as claimed in claim 5, wherein the biodegradable chelator is selected from the group consisting of L-glutamic acid N,N-diacetic acid, methylglycinediacetic acid, ethylenediamine-N,N'-disuccinic acid, L-aspartic acid N,N-diacetic acid, sodium gluconate, nitrilotriacetic acid and iminodisuccinic acid.

8. The stable synergistic bioactive composition as claimed in claim 1, wherein the trimethylazanium compound is selected from the group consisting of 2-hydroxyethyl(trimethyl)azanium, 2-(trimethylazaniumyl)acetate, 2-acetyloxyethyl (trimethyl) azanium, [3-hexadecanoyloxy-2-[(Z)-hexadec-4-enoyl]oxypropyl] 2-(trimethylazaniumyl) ethyl phosphate, [(E,2S,3R)-2-[[(Z)-hexacos-17-enoyl]amino]-3-hydroxyoctadec-4-enyl] 2-(trimethylazaniumyl)ethyl phosphate and salts thereof.

9. The stable synergistic bioactive composition as claimed in claim 1, wherein the composition comprising exogenous combination of stabilized (4Z,7Z,10Z,13Z,16Z,19Z)-docosa-4,7,10,13,16,19-hexaenoic acid and 2-hydroxyethyl(trimethyl)azanium and pharmaceutically acceptable salts thereof.

10. The stable synergistic bioactive composition as claimed in claim 1, wherein effective unit dose of the composition is formulated in solid form in the range of 10 to 1000 mg.

11. The stable synergistic bioactive composition as claimed in claim 1, wherein the pharmaceutically acceptable excipients are selected from the group consisting of diluent, binder, lubricant, glidant, additive, surfactant, stabilizer, antioxidant and plasticizer; wherein the diluent is present in a range of 1 to 30%; the binder present is present in a range of 0.1 to 25%; the lubricant is present in a range of 0.1 to 10.0 %; the glidant is present in a range of 0.1 to 5.0%; the additive is present in a range of 1 to 10%; the surfactant is present in a range of 0.1 to 5.0%; the stabilizer is present in a range of 0.1 to 10.0%; %; the antioxidant is present in a range of 0.1 to 5.0%; and the plasticizer is present in a range of 0.1 to 5.0%; by weight of total composition.