A synergistic bioactive composition for controlling platelet hyperactivity and associated thrombotic risk

Abstract

The present invention is related to a synergistic bioactive composition comprising flavonoids and a mixture of long-chain alcohols for controlling platelet hyperactivity and associated thrombotic risk. The composition comprises the combination of anthocyanin(s) and policosanol. The combination of anthocyanin(s) and policosanol effectively regulates platelet hyperactivity. The composition of present invention offers a promising solution for neuro-cardiovascular and metabolic health by harnessing the synergistic effects of anthocyanin(s) and policosanol. Further, the invention provides synergistic action in controlling platelet hyperactivity associated with diseases like stroke, diabetes, atherosclerosis, dyslipidemia, stent thrombosis.

Description

[0001] A SYNERGISTIC BIOACTIVE COMPOSITION FOR CONTROLLING PLATELET HYPERACTIVITY AND ASSOCIATED THROMBOTIC RISK

[0002] RELATED APPLICATION:

[0003] The present application claims benefit of the Indian Provisional Application No. IN202421061825 filed on, August 14th, 2024 the entire contents of which are hereby incorporated by reference.

[0004] FIELD OF THE INVENTION

[0005] The present invention relates to a synergistic bioactive composition designed to improve neuro-cardiovascular and metabolic well-being through robust antiplatelet action. Specifically, the present invention is related to a synergistic bioactive composition for controlling platelet hyperactivity and associated thrombotic risk. The composition comprises the combination of anthocyanin(s) and policosanol. The combination of anthocyanin(s) and policosanol effectively regulates platelet hyperactivity. The composition of present invention offers a promising solution for neuro-cardiovascular and metabolic health by harnessing the synergistic effects of anthocyanin(s) and policosanol. Further, the invention provides synergistic action in controlling platelet hyperactivity associated with diseases like stroke, diabetes, atherosclerosis, dyslipidemia, stent thrombosis.

[0006] BACKGROUND OF THE INVENTION

[0007] There is a strong interplay between neuro-cardiovascular and metabolic health. The crucial connections between the nervous and cardiovascular systems have given rise to interdisciplinary fields focusing on neurological and cardiac diseases. Platelet aggregation emerges as a central player, responsible for thrombosis — a major complication in cardiovascular disease, leading to severe outcomes such as myocardial infarction, acute ischemic stroke, or venous thromboembolism.

[0008] Thrombosis occurs when a thrombus forms inside blood vessels, disrupting normal blood flow. Thrombi, the resulting blood clots, exhibit heterogeneity in composition. Myocardial infarction-related thrombi are predominantly composed of fibrin, along with platelets, red blood cells, leukocytes, and cholesterol crystals. In contrast, thrombi from acute ischemic stroke patients are characterized by regions rich in red blood cells and platelets. Thrombi from venous thromboembolism patients contain mainly red blood cells and fibrin, accompanied by platelets and leukocytes.

[0009] Given the prevalence of thrombosis in conditions like ischemic stroke and cardiovascular diseases such as myocardial infarction, dyslipidemia, or atherosclerosis, an invention capable of controlling thrombus formation, particularly by controlling platelet hyperactivity, could have significant positive impacts on neurocardiovascular and metabolic health.

[0010] The scope of metabolic health is defined by maintaining blood sugar, waist circumference, blood pressure, cholesterol, and triglycerides within healthy ranges. Impaired metabolic health, marked by elevated levels of these parameters, is associated with platelet hyperactivity, leading to thrombus formation. Therefore, an invention controlling thrombus formation due to platelet hyperactivity could also prove beneficial for individuals suffering from impaired metabolic conditions such as type-2 diabetes mellitus, hypertension, dyslipidemia, among others, thereby improving metabolic health.

[0011] The need for such a synergistic composition arises from the pivotal role platelets play in primary hemostasis and, conversely, their involvement in thrombus formation during conditions like atherosclerotic plaque erosion or rupture. Platelet activation is especially crucial in thrombo-inflammatory diseases like stroke, making novel therapeutic options an urgent requirement.

[0012] Thrombosis stands among the leading causes of death globally, underscoring the significance of antithrombotic therapy. Vascular dysfunction and pro-thrombotic progression in cardiovascular diseases are often linked to platelet hyper-activation and hyper-aggregation. Factors like increased oxidative stress and endothelial vessel wall damage trigger platelet adherence, activation, and aggregation at the injury site.

[0013] The activation-dependent surface receptors and thrombotic pathways associated with platelet activation, including P2Y1 / P2Y12 (ADP receptor), GPVI / a2pi (collagen receptor), cyclo-oxygenase- 1 (COX-1) arachidonic acid pathway, are crucial targets. While current antiplatelet therapeutics aim to blunt specific thrombotic pathways and reduce platelet activation, reports indicate increased resistance and side effects in target populations.

[0014] In light of these challenges, the present invention's unique contribution lies in the synergistic combination of anthocyanin(s) and policosanol, offering a comprehensive approach to controlling platelet hyperactivity. This approach extends beyond the scope of existing antiplatelet drugs, providing a promising solution for various health conditions associated with neuro-cardiovascular and metabolic health.

[0015] The novelty and significance of the invention are grounded in its potential applications for individuals suffering from ischemic stroke, myocardial infarction, dyslipidemia, atherosclerosis, and other conditions. The synergistic effect of the bioactive composition introduces a new paradigm in therapeutic interventions, offering improved efficacy and potentially mitigating challenges associated with existing antiplatelet therapies.

[0016] In summary, the present invention addresses a critical nexus between neurocardiovascular and metabolic health, focusing on platelet hyperactivity as a common denominator in various health conditions.

[0017] GB2349087 discloses a medicament for oral consumption by a human subject for the purpose of effecting one or more of the following in the subject: inhibition of oxidation of plasma LDL; inhibition of platelet aggregation; stimulation of fibrinolysis; and stimulation of TGF- production; comprising a plant-derived dry composition suitable for human consumption wherein at least 25% of the plant- derived material in the composition comprises polyphenols and wherein the composition as a whole comprises at least 0.01% (w / w) flavonol; and unitary doses of the composition. This prior-art does not mention anything about the combination of flavonoids and a mixture of long-chain alcohols, specifically a mixture of anthocyanin(s) and policosanol.

[0018] Maria Lourdes Arruzazabala et. al. (Clinical and Experimental Pharmacology and Physiology 29(10): 891-7, 2002) compares the impact of two doses (20 mg / day and 40 mg / day) of policosanol, a cholesterol-lowering drug, on platelet aggregation in both healthy volunteers and type II hypercholesterolaemic patients. The research, conducted under double-blind conditions, revealed that both doses of policosanol moderately but significantly reduced platelet aggregation induced by various agents. Interestingly, there were no significant differences in the effects between the two doses. Policosanol at both 20 mg / day and 40 mg / day demonstrated similar antiplatelet effects in hypercholesterolaemic patients. This prior-art does not mention anything about the combination of flavonoids and a mixture of long -chain alcohols derived from plant waxes specifically a mixture of anthocyanin(s) and policosanol.

[0019] In the specific domain of the present innovation, there exists a limited number of prior arts. Consequently, there is a discernible gap and a compelling necessity to formulate a synergistic bioactive composition aimed at enhancing neuro- cardiovascular and metabolic well-being by effectively regulating platelet hyperactivity and mitigating the associated thrombotic risk. Recognizing this unmet need, the present invention steps in to offer a comprehensive and efficacious solution to address these critical aspects of health. Through its innovative approach, the invention endeavors to contribute significantly to the advancement of strategies that positively impact neuro -cardiovascular and metabolic health, particularly by controlling platelet hyperactivity and its implications in thrombotic risk.

[0020] OBJECTIVE OF THE INVENTION

[0021] The primary objective of this invention is to provide a synergistic bioactive composition aimed at improving neuro-cardiovascular and metabolic health by controlling platelet hyperactivity and addressing the associated thrombotic risk, the composition provides a unique solution to enhance overall well-being in individuals.

[0022] Another objective of this invention is to establish a potent bioactive composition that combines flavonoids and a mixture of long-chain alcohols. Specifically, combination of anthocyanin(s) and policosanol, contributes to a formulation designed for optimal efficacy and health benefits.

[0023] Another objective of this invention is to establish a potent bioactive composition that combines flavonoids and a mixture of long-chain alcohols. Specifically, combination of anthocyanin(s) and policosanol, along with pharmaceutically acceptable excipients, contributes to a formulation designed for optimal efficacy and health benefits.

[0024] One more objective of this invention is to define precise ratios and ranges for the components within the synergistic composition. By emphasizing the importance of these proportions, the objective is to ensure that the bioactive composition achieves its intended effects, particularly in controlling platelet hyperactivity through the anti -platelet activity exerted upon oral administration of an effective dose.

[0025] Yet another objective of the present invention is to provide a pharmaceutical formulation that includes excipients such as diluents, binders, surfactants, lubricants, glidants, additives, and solvents. These excipients play a crucial role in enhancing the stability, bioavailability, and overall effectiveness of the bioactive composition for practical use and application. One more objective of the present invention is to treat specific diseases associated with platelet hyperactivity, conditions like stroke, myocardial infarction, peripheral vascular diseases, unstable angina, hypertension, diabetes mellitus, atherosclerosis, dyslipidemia, stent thrombosis etc. are targeted, showcasing the broader potential impact of the synergistic composition on public health and disease management.

[0026] One more objective of the present invention is to provide advancements in platelet- related health by providing a synergistic composition that includes anthocyanin(s) and policosanol.

[0027] SUMMARY OF THE INVENTION

[0028] The principal aspect of the present invention incorporates a potent combination of flavonoids and a mixture of long -chain alcohols. The flavonoids, specifically identified as anthocyanin(s), while the long-chain alcohols, represented by policosanol.

[0029] One aspect of the present invention is to ensure efficacy and safety by including pharmaceutically acceptable excipients. These excipients, chosen from a range of options such as diluents, binders, surfactants, lubricants, glidants, additives, solvents, or mixtures thereof, contribute to the overall formulation.

[0030] Another aspect of the present invention provides a synergistic composition explicitly designed to control diseases associated with platelet hyperactivity. These include critical health conditions such as Stroke, myocardial infarction, peripheral vascular diseases, unstable angina, hypertension, diabetes mellitus, atherosclerosis, dyslipidemia, stent thrombosis etc.

[0031] One more aspect of the present invention involves the rigorous evaluation of the anti -platelet activity of the bioactive composition using an animal model. This aspect seeks to provide empirical evidence supporting the effectiveness of the composition in controlling platelet hyperactivity.

[0032] One more aspect of the present invention includes defining specific ratio of anthocyanin(s) to policosanol for the optimal synergistic effects of the bioactive components, reinforcing their potential therapeutic benefits.

[0033] Another aspect of the present invention is to provide the preferred mode of administration as oral, emphasizing the practical and accessible nature of the proposed treatment. This aspect enhances the applicability and convenience of the synergistic bioactive composition.

[0034] One more aspect of the present invention specifies potential sources of flavonoids, including anthocyanin(s). Additionally, it identifies policosanol, ensuring versatility in formulation.

[0035] Yet another aspect of the present invention is the primary objective to establish a synergistic bioactive composition that comprehensively improves neuro- cardiovascular and metabolic health. By addressing platelet hyperactivity, the composition aims to reduce the risk of associated thrombotic events.

[0036] Another aspect of the present invention is the proactive approach to addressing issues related to resistance and side effects often encountered with current antiplatelet drugs.

[0037] In summary, main aspect of the present invention represents a novel approach to health improvement by introducing a synergistic bioactive composition. This innovative formulation targets platelet hyperactivity, offering a multifaceted solution to improve neurocardiovascular and metabolic health and reduce the risk of thrombotic events.

[0038] BRIEF DESCRIPTION OF THE DRAWINGS Figure- 1: Depicts modulatory effects of test substances on serum P-Selectin levels Figure-2: Depicts modulatory effects of test substances on ADP induced platelet aggregation

[0039] Figure-3: Depicts modulatory effects of test substances on serum hs-CRP levels Figure-4: Depicts modulatory effects of test substances on serum D-Dimer levels Figure-5: Depicts modulatory effects of test substances on serum CXCL4 levels Figure-6: Depicts modulatory effects of test substances on serum CCL2 levels Figure-7: Depicts modulatory effects of test substances on serum PAI-1 levels

[0040] DETAILED DESCRIPTION OF THE INVENTION

[0041] The following is a detailed description of the present subject matter the various embodiments. These embodiments are described in sufficient detail to enable those skilled in the art to practice the present subject matter. Other embodiments may be utilized and changes may be made without departing from the scope of the present subject matter.

[0042] References to “an”, “one”, or “various” embodiments in this disclosure are not necessarily to the same embodiment, and such references contemplate more than one embodiment. The following detailed description is, therefore, not to be taken in a limiting sense, and the scope is defined only by the appended claims, along with the full scope of legal equivalents to which such claims are entitled.

[0043] One embodiment of the present invention provides a synergistic bioactive composition designed to improve neuro-cardiovascular and metabolic health by addressing platelet hyperactivity and associated thrombotic risk. This embodiment highlights the unique combination of flavonoids and long -chain alcohols.

[0044] In another embodiment, of the present invention provides a synergistic bioactive composition designed to improve neuro-cardiovascular and metabolic health by addressing platelet hyperactivity and associated thrombotic risk. This embodiment highlights the unique combination of flavonoids and long-chain alcohols, along with their pharmaceutically acceptable excipients.

[0045] In another embodiment, the present invention provides a synergistic bioactive composition comprising of flavonoids and plant waxes derived mixture of long chain alcohols along with pharmaceutically acceptable salts to improve neurocardiovascular and metabolic health through exerting anti-platelet action.

[0046] In one of the embodiment, the present invention provides a synergistic bioactive composition comprising of anthocyanin(s) and policosanol or their salts, derivatives, or isomers.

[0047] In one of the embodiment, the present invention provides a synergistic bioactive composition comprising of anthocyanin(s) and policosanol or their salts, derivatives, or isomers and one or more pharmaceutically acceptable excipients.

[0048] In one of the embodiment, the present invention provides a synergistic bioactive composition consisting essentially of anthocyanin(s) and policosanol or their salts, derivatives, or isomers and one or more pharmaceutically acceptable excipients.

[0049] The synergistic bioactive composition of the present invention improves neurocardiovascular and metabolic health by controlling platelet hyperactivity and associated thrombotic risk.

[0050] In one of the embodiment, the present invention provides a synergistic bioactive composition comprising of anthocyanin(s) and policosanol or their salts, derivatives, or isomers wherein the composition improves neuro-cardiovascular and metabolic health by controlling platelet hyperactivity and associated thrombotic risk. The synergistic bioactive composition comprising of flavonoids and plant waxes derived mixture of long chain alcohols or their salts, derivatives, or isomers to improve neurocardiovascular and metabolic health through exerting anti-platelet action.

[0051] The present invention comprises flavonoids which is anthocyanin(s) or its salts, derivatives, or isomers and the mixture of long chain alcohols which is policosanol or its salts, derivatives, or isomers along with pharmaceutically acceptable excipients.

[0052] The present invention provides a composition comprising anthocyanin(s) and policosanol, effectively addressing the challenge of poor solubility and limited bioavailability of anthocyanin(s). While conventional approaches focus on improving solubility through physical modifications or excipients, the incorporation of policosanol in the disclosed composition unexpectedly enhances the absorption of anthocyanin(s), leading to a significant increase in bioavailability. This synergistic composition maximizes therapeutic efficacy, offering a superior solution to existing limitations.

[0053] In another embodiment, the present invention provides a synergistic composition of bioactive ingredients designed to enhance neuro-cardiovascular and metabolic health by controlling platelet hyperactivity and the associated thrombotic risk. This composition comprises a synergistic combination of flavonoids and a mixture of long-chain alcohols, bolstered by pharmaceutically acceptable excipients. Specifically, the flavonoids are anthocyanin(s), and the long-chain alcohol is policosanol.

[0054] According to present invention, anthocyanin(s) and policosanol or its salts, derivatives, or isomers of the present invention are present in a ratio of 1:0.0001 to 1: 16000, 1:0.0005 to 1:3500, 1:0.0011 to 1: 1500, 1:0.0012 to 1: 1000, 1:0.0029 to 1:400, or 1:0.0010 to 1:22.5. According to the present invention, the amount of anthocyanin(s) or its salts, derivatives, or isomers thereof is present in the range of 0.0042 to 99.4901% w / w, 0.0182 to 99.4244% w / w, 0.0400 to 99.3377% w / w, 0.0500 to 99.2991% w / w, 0. 1248 to 99. 1254% w / w, or 0.3656 to 99.3789% w / w of the total composition.

[0055] According to the present invention, the amount of policosanol or its salts, derivatives, isomers is present in the range of 0.0062 to 99.7444% w / w, 0.0256 to 99.6867% w / w, 0.0526 to 99.6016% w / w, 0.0540 to 99.4036% w / w, 0.1350 to 99.2556% w / w, or 0.0510 to 90.9091% w / w of the total composition.

[0056] According to the present invention, the amount of anthocyanin(s) or its salts, derivatives, isomers is present ranges from 0.25 mg to 2000 mg, 1 mg to 1900 mg, 2 mg to 1800 mg, 2 mg to 1700 mg, 5 mg to 1700 mg and 8 mg to 1920 mg. According to the present invention the amount of policosanol or its salts, derivatives, isomers is present ranges from 0.25 mg to 4000 mg, 1 mg to 3500 mg, 2 mg to 3000 mg, 2 mg to 2000 mg, 5 mg to 2000 mg and 2 mg to 180 mg, according to present invention, the dose is calculated based on body weight of the patient in need thereof.

[0057] According to the present invention, the effective amount of active ingredients is the amount required for the therapeutic effect which can be administered at a time or in divided doses per day.

[0058] In one of the embodiment, the present invention provides, a synergistic composition comprising: anthocyanin(s) or its salts, derivatives, or isomers thereof in the range of 0.0042 to 99.4901 % w / w of the total composition, policosanol or its salts, derivatives, isomers is present in the range of 0.0062 to 99.7444 % w / w of the total composition, wherein anthocyanin(s) and policosanol or their salts, derivatives, or isomers of the present invention are present in a ratio of 1:0.0001 to 1: 16000. This composition effectively controls platelet hyperactivity, and the addition of pharmaceutically acceptable excipients makes it suitable dosage form. The composition is suitable for oral administration, delivering an effective dose that exhibits anti-platelet activity to counteract thrombus formation.

[0059] Anthocyanin(s), derived / extracted / isolated from the natural plant sources like Acai, Black currant, Aronia, Apple, Bilberry, Black bean, Turmeric, Black olives, Black rice, Blackberry, Blueberry, Bog whortleberry, Cherry, Chokeberry, Cranberry, Crowberry, Eggplant, Elderberry, Goji, Gooseberry, Grapefruit, Lettuce, Nectarine peach, Pear, Plum, Pomegranate, Purple com, Raspberry, Red cabbage, Red currant, Red grape, Red onion, Red raddish, Red wine, Rhubarb, Rowanberry, Sakatoon berry, Straw berry, Fig, Banana, Potato, Black gram, Carrot, Beans, Sweet potato, Mango, Butterfly Pea, Red Rose, Allamanda cathartic, Hibiscus, Roselle red flower, Rhoeospathacea, Turmeric or from any other plants or animals or chemically synthesized, purified or mixture thereof. These compounds have demonstrated the ability to reduce thrombosis risk through free radical scavenging activity, lowering platelet aggregation, fibrinogen levels, and mean platelet volume.

[0060] The flavonoids as per present invention is anthocyanidins, wherein anthocyanin(s) is derived from Acai, Blackcurrant, Aronia, Marion blackberry, Black crowberry, Black raspberry, Raspberry, Wild blue berry, Cherry, Queen Garnet plum, Redcurrant, Black rice, Black bean, Blue com, Purple com, Purple tomato, Concord grape, Norton grape, Red cabbage or any other berry fruits or any other plant source or synthesized through chemical or fermentation process or mixture thereof.

[0061] Policosanol, a mixture of higher aliphatic primary alcohols purified from sugarcane, also plays a role in reducing platelet aggregation and addressing dyslipidemia. However, the synergistic effect of combining anthocyanin(s) and policosanol to control platelet hyperactivity for improving neurocardiovascular and metabolic health has not been explored or discovered.

[0062] The synergistic bioactive composition comprises of plant wax, wherein the plant wax derived mixture of long chain alcohol is policosanol, wherein the policosanol is derived from sugar cane wax, rice bran, wheat bran, com kernel, green tea leaves, grain sorghum, perilla seeds, bee wax, Cochineal wax, grape seed, grains, fruits or nuts or any other plant source or synthesized through chemical or fermentation process.

[0063] The oral administration of an effective dose of the composition as per the present invention exerts anti -platelet activity to control platelet hyperactivity. These include critical health conditions such as stroke, diabetes, atherosclerosis, dyslipidemia, and stent thrombosis.

[0064] The present invention involves the rigorous evaluation of the anti-platelet activity of the bioactive composition using an animal model. This aspect seeks to provide empirical evidence supporting the effectiveness of the composition in controlling platelet hyperactivity.

[0065] The study design of the present invention provides insights into the effectiveness of the bioactive composition in controlling platelet hyperactivity. These outcomes contribute to the body of evidence supporting the overall objectives of the invention.

[0066] The antiplatelet therapeutic use of the composition of the present invention can be established through various tests, including the evaluation of Serum P-Selectin level, Adenosine Diphosphate (ADP)-induced platelet aggregation, Serum High- Sensitivity C-Reactive Protein (hs-CRP), Serum D-Dimer, Serum C-X-C Motif Ligand 4 (CXCL4) level, Serum C-C Motif Ligand 2 (CCL2) level, and Serum Plasminogen Activator Inhibitor- 1 (PAI-1). These biomarkers and functional assays provide comprehensive insights into the platelet activity, inflammatory response, and coagulation status, thereby supporting the therapeutic potential of the composition in antiplatelet applications which in turn improves neurocardiovascular and metabolic health. The present invention provides the proactive approach to addressing issues related to resistance and side effects often encountered with current antiplatelet drugs.

[0067] The synergistic bioactive composition further comprises of pharmaceutically acceptable excipients which are selected from a diluent, a binder, a surfactant, a lubricant, a glidant, a solvent or mixtures thereof. Further, the composition of the present invention optionally comprises one or more stabilizers, preservatives, anticaking agents, or a mixture thereof.

[0068] Diluent is selected from one or more of calcium carbonate, dicalcium phosphate, tricalcium phosphate, magnesium carbonate, calcium sulfate, magnesium oxide, microcrystalline cellulose, cellulose powder, maltodextrin, lactose anhydrous, lactose monohydrate, sucrose, mannitol, sorbitol, xylitol, starch, pregelatinized starch, hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyethylene glycol, polyvinylpyrrolidone, xanthan gum, or a mixture thereof. According to the present invention, the composition may comprise a diluent in an amount ranging from 1% to 98% by w / w of the total composition.

[0069] Binder is selected from one or more of microcrystalline cellulose, carboxymethylcellulose sodium, hydroxypropyl cellulose, hydroxypropyl methylcellulose, Hypromellose, low-substituted hydroxypropyl cellulose, methylcellulose, pregelatinized starch, starch, povidone, Polyvinylpyrrolidone, copovidone, carbomer, sodium alginate, acacia, agar, guar gum, maltodextrin, pectin, tragacanth, or a mixture thereof. According to the present invention, the composition may comprise a binder in an amount ranging from 0.1% to 12% by w / w of the total composition.

[0070] Disintegrant is selected from one or more of alginic acid, calcium alginate, carboxymethylcellulose calcium, carboxymethylcellulose sodium, microcrystalline cellulose, chitosan, com starch, pregelatinized starch, croscarmellose sodium, crospovidone, docusate sodium, low-substituted hydroxypropyl cellulose, methylcellulose, povidone, sodium alginate, sodium starch glycolate, cross-linked hydroxypropyl cellulose, or a mixture thereof. According to the present invention, the composition may comprise a disintegrant in an amount ranging from 0.4% to 15% by w / w of the total composition.

[0071] Surfactant is selected from one or more of polysorbates, sorbitan esters, polyethylene glycol esters, polyoxyethylene stearates, polyoxyethylene castor oil derivatives, poloxamers, sodium lauryl sulfate, sodium dodecyl sulfate, sodium stearate, sodium dioctyl sulfosuccinate, benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, lecithin, phosphatidylcholine, lauryl betaine, or a mixture thereof.

[0072] Lubricant is selected from one or more of magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, talc, polyethylene glycol, colloidal silicon dioxide, or glyceryl behenate, zinc stearate or a mixture thereof. According to the present invention, the composition may comprise a lubricant in an amount ranging from 0.5% to 10% by w / w of the total composition.

[0073] Glidant is selected from one or more of colloidal silicon dioxide, hydrophobic colloidal silica, silicon dioxide, talc, tribasic calcium phosphate, or a mixture thereof. According to the present invention, the composition may comprise a glidant in an amount ranging from 0.5% to 10% by w / w of the total composition.

[0074] Stabilizer is selected from one or more of ascorbic acid, sodium ascorbate, tocopherols, butylated hydroxyanisole, butylated hydroxytoluene, disodium edetate, calcium disodium EDTA, citric acid, tartaric acid, phosphoric acid, sodium citrate, potassium citrate, sodium bicarbonate, monobasic sodium phosphate, dibasic sodium phosphate, acetic acid, sodium acetate, benzyl alcohol, sodium benzoate, potassium sorbate, methylparaben, propylparaben, poloxamers, polysorbates, sorbitan esters, polyethylene glycol, hydroxypropyl methylcellulose, or a mixture thereof.

[0075] Preservative is selected from one or more of methylparaben, propylparaben, butylparaben, ethylparaben, sodium benzoate, potassium benzoate, benzoic acid, sorbic acid, potassium sorbate, benzyl alcohol, phenethyl alcohol, phenoxyethanol, benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, chlorhexidine, chlorhexidine gluconate, thiomersal, dehydroacetic acid, formic acid, or a mixture thereof.

[0076] Anti-caking agent is selected from one or more of colloidal silicon dioxide, silicon dioxide, hydrophobic colloidal silica, dicalcium phosphate, tricalcium phosphate, sodium calcium aluminum silicate, magnesium phosphate, magnesium stearate, magnesium trisilicate, magnesium carbonate, magnesium oxide, pregelatinized starch, com starch, rice starch, tapioca starch, calcium silicate, calcium carbonate, sodium ferrocyanide, sodium silicoaluminate, kaolin, or a mixture thereof.

[0077] The composition of the present invention can be prepared using conventional methods known in the art for formulating oral dosage forms. Depending on the desired final product, the formulation may be prepared through direct compression, wherein the active pharmaceutical ingredient is blended with suitable excipients such as fillers, binders, disintegrants, and lubricants, followed by compression into tablets. Alternatively, the composition may be processed through granulation techniques, including wet or dry granulation, to enhance flow properties and compressibility. The prepared formulation can be filled into sachets or capsules for ease of administration. Additionally, the composition can be supplied as a powder or granules for reconstitution into an oral suspension. Other suitable processes may also be employed to achieve the desired dosage form while ensuring stability, efficacy, and patient compliance. The processes for the preparation of nutraceutical compositions are well known in the art.

[0078] In another embodiment the present invention provides a pharmaceutical composition comprising a combination of Anthocyanin(s) and Policosanol their salts, derivatives, or isomers which can be formulated as wherein the composition is in the form of tablets, capsules, powder, pill, hard capsule filled with liquid or solids, soft capsules, granules, pellets, caplets, mini-tablets, syrup, suspension, sachet or modified release formulations, gummies or any other suitable oral dosage forms. According to present invention, oral dosage form is the preferred dosage form.

[0079] In another embodiment the present invention provides a synergistic bioactive composition comprising anthocyanin(s), policosanol, wherein the composition improves neurocardiovascular and metabolic health through exerting anti-platelet action.

[0080] In another embodiment the present invention provides a synergistic bioactive composition comprising anthocyanin(s), policosanol, a pharmaceutically acceptable excipient; wherein the composition is for oral administration; and wherein oral administration of the composition reduces platelet activation and aggregation by reducing thrombo-inflammatory molecule P-selectin by 30.50% more than the sum of individual effects of anthocyanin(s) and policosanol.

[0081] Furthermore, the invention also encompasses a kit comprising comprises at least two ingredients Anthocyanin(s) and Policosanol or their salt, derivative, or isomer. Additionally, each of the ingredients may be present in a separate composition within the kit.

[0082] In another embodiment the present invention provides a kit comprising anthocyanin(s), policosanol, wherein the kit improves neurocardiovascular and metabolic health through exerting anti-platelet action.

[0083] The composition of the present invention remains stable at room temperature.

[0084] EXAMPLES The invention described herein comprises in various objects and their description as mentioned above, with respect to characteristics and processes adopted. While these aspects are emphasized in the invention, any variations of the invention described above are not to be regarded as departure from the spirit and scope of the invention as described.

[0085] EXAMPLE-1: COMPOSITION

[0086] Following is a general composition formula as per the present invention: EXAMPLE 1A: COMPOSITION

[0087] EXAMPLE-2: COMPOSITION

[0088] Following is a general composition formula as per the present invention: EXAMPLE-3-7: COMPOSITION:

[0089] EXAMPLE S: ANIMAL STUDY:

[0090] Objective of the animal study: To evaluate the synergistic antiplatelet effect of anthocyanin(s) and policosanol in high fat diet fed rats.

[0091] Materials and Method: Female Wistar rats, aged 8-9 weeks and weighing 190-240 gram at the start of the experiments, were divided into different groups, each group containing 6 rats. Platelet aggregation induction method: Platelet aggregation was induced by feeding high fat diet (HFD) orally at a dose of 3 ml / 200 g b.wt per day for 8 weeks in all the groups except normal control group.

[0092] Animal grouping: Group N served as a normal control group whereas remaining all groups (D, Tl, T2 & T3) were fed high fat diet orally for 8 weeks to induced platelet aggregation as mentioned above.

[0093] Experimental design of the study was as follow:

[0094] Treatment was started from the starting of the 9thweek (i.e. after completion of 8 weeks of high fat diet feeding) as per the details mentioned in Table 1.

[0095] Table 1:

[0096] OD: Once a day b.wt: Body weight

[0097] Evaluation parameters:

[0098] Synergistic antiplatelet efficacy was evaluated on parameters like P-Selectin, ADP- induced platelet aggregation, hs-CRP, D-Dimer, CXCL-4, CCL2 and PAI-1 through ELISA based analysis. Multimode Reader (Biotek Instruments), Cytation 5 model serial no. 1909161E was used to measure the above mentioned biomarkers using respective ELISA kit (of Krishgen Biosystem) leaflet under biosafety cabinet.

[0099] Tests parameters: P-Selectin: P-selectin, a member of the selectin family of adhesion molecules, is an integral membrane glycoprotein located in both the alpha-granules of platelets and the Weibel-Palade bodies of endothelial cells. It plays an important role in arterial thrombogenesis by forming large, stable platelet-leukocyte aggregates. P-se lectin stabilizes initial platelet aggregates formed by glycoprotein Ilb / IIIa-fibrinogen interactions, allowing for the formation of larger platelet aggregates. In clinical research, increased levels of soluble P-selectin have been observed in several diseases, such as thrombotic thrombocytopenic purpura, atherosclerosis, unstable angina, and hypertension. Lowering P-selectin levels helps to reduce platelet aggregation. The study results are provided in table 2 and figure 1.

[0100] Adenosine Diphosphate (ADP) induced platelet aggregation: ADP was the first low-molecular-weight platelet aggregating agent to be identified. ADP -induced platelet aggregation plays a major role in the development and extension of arterial thrombosis. ADP not only causes primary aggregation of platelets but is also responsible for secondary aggregation induced by ADP and other agonists. ADP induces a change in the shape of platelets, transforming them from their normal disc form into a more spherical shape, on which pseudopodia appear. These shape- changed platelets immediately begin to aggregate. Subsequently, many hundreds of thousands of platelets participate in the platelet aggregates that form. ADP interacts directly with two purinergic receptors, known as P2Y1 and P2Y12, and it is the combined effect of ADP at these two receptors that leads to platelet activation, followed by platelet aggregation. Reduced ADP-induced platelet aggregation indicates a reduced risk of thrombus / clot formation. The study results are provided in table 3 and figure 2. high-sensitivity C-Reactive Protein (hs-CRP): As an inflammatory factor, hs-CRP is considered an important marker of atherosclerotic rupture. hs-CRP not only promotes an increase in plasma von Willebrand factor concentration but also stimulates the expression of Matrix Metalloproteinase (MMP)-2 and Matrix Metalloproteinase (MMP)-9, which are directly involved in the rupture of atherosclerotic plaques. Ruptured plaques can promote the adhesion of the von Willebrand factor and reduce platelet velocity, thereby stimulating the activation of platelet function, enhancing platelet adhesion and aggregation, and forming thrombosis. Reduced hs-CRP levels indicate a reduced risk of platelet adhesion, aggregation, and thrombus formation. The study results are provided in table 4 and figure 3.

[0101] D-Dimer: D-Dimer has become one of the most commonly requested coagulation test and is a generic term referring to multiple peptide fragments deriving from plasmin-mediated degradation of cross-linked fibrin. Elevated D-dimer levels occur in various disorders in which the coagulation system is activated, such as acute venous thromboembolism, ischemic cardiovascular disease. Lower D-Dimer levels suggest a decreased risk of platelet formation. The study results are provided in table 5 and figure 4.

[0102] C-X-C Motif Ligand 4 (CXCL4): It is also known as platelet factor 4 (PL4). It is released from the a-granules of platelets during aggregation. PL4 is also referred to as the platelet antiheparin protein due to its ability to neutralize heparin. It promotes thrombus formation through its inherent prothrombotic potential and by attracting monocytes with tissue factor expression. Increased level of CXCL4 is an indicator of platelet activity and aggregation. The release of PL4 in large molar amounts neutralizes the negatively charged surfaces of platelets and endothelial cells, allowing closer approximation of platelets to each other and to the endothelium, thereby enhancing thrombus formation. Lower CXCL4 levels reduce the risk of thrombus formation. The study results are provided in table 6 and figure 5.

[0103] C-C Motif Ligand 2 (CCL2): It is also known as monocyte chemoattractant protein 1 (MCP-1). It has been implicated as a key player in aspects of thrombosis. CCL2 induced tissue factor, the initiator of coagulation and a critical mediator of arterial thrombosis. It contributes to thrombin generation and thrombus formation by generating tissue factor. It responsible for the migration of monocytes to the subendothelium and attracting leucocytes to the site of injury, thus facilitating atherogenic and thromboembolic potential. Lower CCL2 indicates reduced risk of platelet aggregation. The study results are provided in table 7 and figure 6.

[0104] Plasminogen activator inhibitor 1 (PAI-1): PAI-1 is a specific inhibitor of both tissue-type and urokinase-type plasminogen activators. When the active form of PAI-1 enters the bloodstream, it works to suppress plasminogen activators, thereby reducing the amount of plasminogen in the blood. This, in turn, inhibits fibrin degradation and creates a favorable condition for thrombus formation. Inhibition of fibrinolysis by PAI-1 promotes a prothrombotic state by reducing fibrin degradation. PAI-1 is a key protein in the progression of vascular events and is linked to both arterial and venous thrombosis. Reduced PAI-1 levels decrease the risk of thrombus formation. The study results are provided in table 8 and figure 7.

[0105] Animal study results:

[0106] Table 2: * - in combination group (T3) compared to the sum of change in individual test groups (T1+T2)

[0107] Table 3:

[0108] * - in combination group (T3) compared to the sum of change in individual test groups (T1+T2) Table 4:

[0109] * - in combination group (T3) compared to the sum of change in individual test groups (T1+T2)

[0110] Table 5: * - in combination group (T3) compared to the sum of change in individual test groups (T1+T2)

[0111] Table 6:

[0112] * - in combination group (T3) compared to the sum of change in individual test groups (T1+T2) Table 7:

[0113] * - in combination group (T3) compared to the sum of change in individual test groups (T1+T2)

[0114] Table 8:

[0115] * - in combination group (T3) compared to the sum of change in individual test groups (T1+T2)

[0116] The study results, as presented in the tables above, confirm that the combination of the present invention leads to a significant improvement in efficacy. The experiment and efficacy parameters were designed to accurately mimic disease- related factors, ensuring that outcomes can be clearly determined based on scientifically proven parameters and criteria. The recorded observations demonstrate the animals' responses to the induced disease and their reaction to the composition. The data clearly establishes that the present composition, comprising anthocyanin(s) and Policosanol effectively regulates platelet hyperactivity. Therefore, the composition of present invention offers a promising solution for neuro-cardiovascular and metabolic health by harnessing the synergistic effects of anthocyanin(s) and policosanol. Further, the invention provides synergistic action in controlling diseases associated with Stroke, myocardial infarction, peripheral vascular diseases, unstable angina, hypertension, diabetes mellitus, atherosclerosis, dyslipidemia, stent thrombosis etc.

Claims

I / WE CLAIM:

1. A synergistic bioactive composition comprising:(a) anthocyanin(s),(b) policosanol, or pharmaceutically acceptable salts, derivatives, or isomers thereof.

2. The synergistic bioactive composition as claimed in claim 1, wherein anthocyanin(s), and policosanol are present in a ratio of 1 :0.0001 to 1: 16000.

3. The synergistic bioactive composition as claimed in claim 1, wherein;(a) anthocyanin(s) or pharmaceutically acceptable salts, derivatives, or isomers thereof is present in the range of 0.0042 to 99.4901 % w / w of the total composition.(b) policosanol or pharmaceutically acceptable salts, derivatives, or isomers thereof is present in the range of 0.0062 to 99.7444 % w / w of the total composition.

4. The synergistic bioactive composition as claimed in claim 1, wherein;(a) anthocyanin(s) or pharmaceutically acceptable salts, derivatives, or isomers thereof is present in the range of 0.25 mg to 2000 mg.(b) policosanol or pharmaceutically acceptable salts, derivatives, or isomers thereof is present in the range of 0.25 mg to 4000 mg.

5. The synergistic bioactive composition as claimed in claim 1, wherein the composition further comprises one or more pharmaceutically acceptable excipients selected from a diluent, a binder, a lubricant, a glidant, or mixtures thereof.

6. The synergistic bioactive composition as claimed in claim 1, wherein the composition is in the form of tablets, capsules, powder, pill, hard capsulefilled with liquid or solids, soft capsules, granules, pellets, caplets, minitablets, syrup, suspension, sachet, gummies or modified release formulations or any other suitable oral dosage forms.

7. The synergistic bioactive composition as claimed in claim 1, wherein;(a) the composition reduces platelet activation and aggregation by reducing thrombo-inflammatory molecule P-selectin by 30.50% more than the sum of individual effects of anthocyanin(s) and policosanol; or(b) the composition reduces adenosine diphosphate (ADP) induced platelet aggregation by 21.02% more than the sum of individual effects of anthocyanin(s) and policosanol; or(c) the composition reduces thrombo-inflammation by reducing serum high-sensitive C-Reactive Protein (hs-CRP) by 23.91% more than the sum of individual effects of anthocyanin(s) and policosanol; or(d) the composition reduces serum levels of fibrin formation biomarker D- dimer by 32.53% more than the sum of individual effects of anthocyanin(s) and policosanol; or(e) the composition reduces compact blood clot structure formation by reducing serum C-X-C Motif Ligand 4 (CXCL-4) by 24.25% more than the sum of individual effects of anthocyanin(s) and policosanol; or(f) the composition regulates platelet activity and arterial thrombosis by reducing serum C-C Motif Ligand 2 (CCL2) by 30.68% more than the sum of individual effects of anthocyanin(s) and policosanol; or(g) the composition reduces vascular thrombosis by reducing serum plasminogen activator inhibitor 1 (PAI-1) by 37.77% more than the sum of individual effects of anthocyanin(s) and policosanol.

8. The synergistic bioactive composition as claimed in claim 1, wherein the composition improves neurocardiovascular and metabolic health through exerting anti-platelet action.

9. A kit comprising:(a) anthocyanin(s),(b) policosanol, wherein the kit improves neurocardiovascular and metabolic health through exerting anti-platelet action.

10. The synergistic bioactive composition as claimed in claim 1, wherein the composition comprises:(a) anthocyanin(s),(b) policosanol; wherein the composition is for oral administration; and wherein oral administration of the composition reduces adenosine diphosphate (ADP) induced platelet aggregation by 21.02% more than the sum of individual effects of anthocyanin(s) and policosanol.

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