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WO2025233977A1 - Nanoémulsion d'huile de poisson à oméga-3 hautement biodisponible (epa et dha) utilisée comme formulation nutraceutique pour la santé cardiovasculaire - Google Patents

Nanoémulsion d'huile de poisson à oméga-3 hautement biodisponible (epa et dha) utilisée comme formulation nutraceutique pour la santé cardiovasculaire

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Publication number
WO2025233977A1
WO2025233977A1 PCT/IN2025/050737 IN2025050737W WO2025233977A1 WO 2025233977 A1 WO2025233977 A1 WO 2025233977A1 IN 2025050737 W IN2025050737 W IN 2025050737W WO 2025233977 A1 WO2025233977 A1 WO 2025233977A1
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Prior art keywords
omega
composition
epa
dha
fatty acids
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Pending
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PCT/IN2025/050737
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English (en)
Inventor
Aswathy P Nair
Vinaya KK
Kamalika Roy Choudhury
Nandana S. KRISHNAN
Bulla Humpy
T S Gowri
Gauri Indanthuruthil KRISHNAN
Swathi BHUNIA
Rabina Punathil
Rosh Skanth Alagan
Sreedhar SANTHOSH
Jayaprakash Maddy
Chaniyilparambu Nanappan RAMCHAND
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Individual
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Individual
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Publication of WO2025233977A1 publication Critical patent/WO2025233977A1/fr
Pending legal-status Critical Current
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/107—Emulsions ; Emulsion preconcentrates; Micelles
    • A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/20—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids
    • A61K31/202—Carboxylic acids, e.g. valproic acid having a carboxyl group bound to a chain of seven or more carbon atoms, e.g. stearic, palmitic, arachidic acids having three or more double bonds, e.g. linolenic
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • A61K31/355—Tocopherols, e.g. vitamin E
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system

Definitions

  • the present invention relates to a composition comprising omega-3 fatty acids in synergy with one or more natural compounds and a surfactant, wherein the synergistic interaction among the compounds increases cardioprotective activity by promoting the reduction of triglyceride levels in blood plasma.
  • the invention further relates to a nanoemulsion formulation of omega-3 fatty acids, with one or more natural compounds and a surfactant designed to enhance bioavailability, thereby improving the absorption and efficacy of the active compounds.
  • Omega-3 polyunsaturated fatty acids including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are essential fatty acids which need to be supplied externally through diet by animals having various physiological functions.
  • PUFAs polyunsaturated fatty acids
  • EPA eicosapentaenoic acid
  • DHA docosahexaenoic acid
  • EPA and DHA are considered to be crucial for proper fetal development and maintaining health throughout aging. Beyond their physiological functions, EPA and DHA serve as biochemical precursors to various metabolites, which function as powerful lipid mediators.
  • Oxidative stress and chronic inflammation are recognized as key contributors to the development of non-communicable diseases, including cardiovascular disease, Poly unsaturated fatty acids (PUFAs) have been shown to modulate antioxidant signaling pathways and inflammatory responses, thereby influencing systemic physiological functions.
  • PUFAs Poly unsaturated fatty acids
  • PUFAs particularly DHA
  • MCI mild cognitive impairment
  • DHA is found in high concentrations in the brain cell membranes and supports nervous system function, suggesting a possible protective role in Alzheimer’s disease (AD), a serious, progressive condition with no known cure and only a few treatment choices.
  • AD Alzheimer’s disease
  • Inflammation triggered by immune cells in the brain like microglia, is believed to be a key factor in AD.
  • PUFAs are beneficial in the treatment of non-alcoholic fatty liver disease (NAFLD) and are linked to a reduced risk of colorectal cancer (CRC) in cases of high levels of FOXP3+ T cell infiltration suggesting cancer immunopresrvation by influencing the activity of regulatory T cells. Due to well known health benefits of PUFAs, various global organizations and agencies have issued guidelines recommending omega-3 intake and fish consumption to support health and prevent chronic diseases.
  • omega-3 fatty acid deficiency is through dietary supplementation such as capsules. Supplements are particularly beneficial for individuals who are unable to meet their nutritional needs through diet alone.
  • omega-3 fatty acids pharmaceutical, nutritional , and dietary products is well established.
  • One example is a concentrated form of long-chain omega-3 PUFAs derived from fish oil, containing DHA and EPA marketed under the trademark Lovaza®. This form is described in U.S. patent numbers 5502077, 5656667 and 5698594.
  • US7652068 discloses highly purified formulations of omega-3 fatty acids comprising more than 85% omega-3 fatty acids by weight.
  • US8491953N describes designing a stable food supplement containing fish oil US9675575, US10034849 and US10172819 discloses composition, dosage forms and methods of use of DHA and EPA Natural bioactives from plants: A substantial number of plant-derived compounds and traditional remedies have been examined for their lipid-lowering effects, with over 70 medicinal plants demonstrating notable hypolipidemic activity. In recent years, particularly over the past decade, the use of these medicinal plants has grown in urban centers of developed countries. Medicinal plants are recognized as key contributors to hypolipidemic therapy, with reported benefits including high efficacy, a strong safety profile, affordability, and widespread acceptance among users.
  • Extracts from plants such as Amla (Phyllanthus emblica), Guggul (Commiphora wightii), Black cumin (Nigella sativa), Garcinia (Garcinia cambogia), Green tea (Camellia sinensis) and Frankincense (Boswellia serrata) are recognized for their diverse pharmacological properties, including antidiabetic, hypolipidemic, antibacterial, antioxidant, antiulcerogenic, hepatoprotective, gastroprotective, and chemopreventive effects.
  • This invention pertains to an orally administrable composition comprising omega-3 fatty acids, a plant extract, and at least one surfactant, specifically designed to enhance bioavailability.
  • Another aspect of the present invention relates to a composition comprising omega-3 fatty acids and one or more plant extracts, wherein the plant extracts are capable of exerting a synergistic and/or additive effect on the anti-hyperlipidemic activity of the omega-3 fatty acids.
  • Another aspect of the present invention provides a composition suitable for the prophylactic or therapeutic applications commonly associated with omega-3 fatty acids in a subject in need thereof, the composition comprising omega-3 fatty acids, at least one plant extract, and at least one surfactant, formulated for oral administration.
  • FIG 1 is an illustration of the particle size of highly bioavailable omega-3 formulation.
  • FIG 2 is an illustration of the fatty acid profiling of the highly bioavailable omega-3 formulation.
  • FIG 3 is an illustration of comparative oral pharmacokinetic profile of the omega-3 fatty acids present in unformulated fish oil with omega-3 fatty acid given as highly bioavailable formulation.
  • FIG 4 is an illustration of comparative oral pharmacokinetic profile of EPA concentration in Fast state and Fed state of highly bioavailable omega-3 formulation
  • FIG 5 is an illustration of comparative oral pharmacokinetic profile of EPA concentration in fast state with highly bioavailable omega-3 formulation vs lovaza DETAILED DESCRIPTION OF THE INVENTION
  • omega-3 fatty acids encompasses both naturally occurring and synthetically produced omega-3 fatty acids, as well as pharmaceutically acceptable forms thereof, including but not limited to esters, free acids, triglycerides, derivatives, conjugates, precursors, salts, and combinations thereof.
  • omega-3 fatty acid oils include omega- 3 polyunsaturated long-chain fatty acids such as eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), alpha-linolenic acid (ALA), heneicosapentaenoic acid (HPA), docosapentaenoic acid (DPA), eicosatetraenoic acid (ETA), eicosatrienoic acid (ETE), and octadecatetraenoic acid (also referred to as stearidonic acid, STA).
  • EPA eicosapentaenoic acid
  • DHA docosahexaenoic acid
  • ALA alpha-linolenic acid
  • HPA heneicosapentaenoic acid
  • DPA docosapentaenoic acid
  • ETA eicosatetraenoic acid
  • ETE eicosatrienoic
  • Suitable forms further include esters of omega-3 fatty acids with glycerol (e.g., mono-, di-, and triglycerides) and esters formed with primary, secondary, or tertiary alcohols, such as fatty acid methyl esters and fatty acid ethyl esters.
  • the omega-3 fatty acids, esters, triglycerides, derivatives, conjugates, precursors, salts, and/or mixtures described herein may be utilized in their isolated or pure form, or as components of oils, including but not limited to marine oils (e.g., fish oil, purified fish oil concentrates), algal oils, microbial oils, and plant-derived oils.
  • plant extract refers to an extract, juice, or concentrate derived from any part of a plant, including but not limited to the seed, leaf, fruit, flower, stem, root, tuber, or bark.
  • Bioavailability refers to the measurement of the rate and extent to which a drug or active ingredient reaches the systemic circulation.
  • bioavailability refers to the “relative bioavailability” between the composition of the present invention, which includes omega-3 fatty acids and plant extracts, and an unformulated omega-3 fatty acid.
  • a composition is provided that includes omega-3 fatty acids, a herbal extract, an essential oil, an antioxidant and at least one surfactant suitable for oral administration.
  • the omega-3 fatty acids may be sourced from marine species, such as fish oil or crustaceans. Examples of fish rich in omega-3 fatty acids include “oily fish” such as salmon, tuna, swordfish, halibut, tilefish, cod (including cod liver oil), and sardines.
  • the composition comprises from about 10% to about 70% (w/w) of omega-3 fatty acids relative to the total composition.
  • the composition contains about 30% (w/w) omega-3 fatty acids, and more preferably about 60% (w/w) omega-3 fatty acids.
  • the omega-3 fatty acid used herein is preferably eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or a combination thereof.
  • omega-3 fatty acids including “EPA” and “DHA”, used herein may be of esterified, triglyceride, phospholipid or free fatty acid forms.
  • the omega-3 fatty acids comprising EPA and DHA used herein are preferably in an esterified form.
  • the combined content of EPA and DHA constitutes at least 10% w/w, 20% w/w, 30% w/w, 40% w/w,50% w/w, 60% w/w, 70% w/w or preferably about 50% w/w of the total omega-3 fatty acids in the composition.
  • the content of EPA alone is at least 22% w/w of the total composition.
  • the composition comprises a herbal extract selected from the group consisting of black cumin extract, resveratrol, garcinia extract, green tea extract, and boswellia serrata extract.
  • the herbal extract may exhibit an additive and/or synergistic effect on the antihyperlipidemic activity of omega-fatty acids.
  • the herbal extract comprises from about 1% to about 25% (w/w) of the total composition.
  • the composition comprises omega-3 fatty acids, a herbal extract, an antioxidant and at least one surfactant.
  • a surfactant may, for example, reduce the surface tension of a liquid or the interfacial tension between two liquids.
  • surfactants may be used to lower the surface tension between the fatty acid oil mixture and an aqueous solution.
  • surfactants are molecules that possess at least one hydrophilic (water-attracting) region and at least one hydrophobic (lipophilic or oil-attracting) region.
  • HLB hydrophilic-lipophilic balance
  • the HLB scale typically ranges from 0 to 20, where a value closer to 0 indicates a predominantly hydrophilic character, while a value closer to 20 indicates a predominantly lipophilic character.
  • the surfactant is selected from the group consisting of nonionic surfactants, cationic surfactants, anionic surfactants, zwitterionic surfactants, or combinations thereof.
  • surfactants or emulsifiers are employed in the formulation to enhance the stability, solubility, and bioavailability of the active components.
  • Suitable surfactants include, but are not limited to, polysorbates such as polysorbate 20 (polyoxyethylene (20) sorbitan monolaurate), polysorbate 40 (polyoxyethylene (20) sorbitan monopalmitate), polysorbate 60 (polyoxyethylene (20) sorbitan monostearate), and polysorbate 80 (polyoxyethylene (20) sorbitan monooleate).
  • Additional suitable surfactants include sorbitan fatty acid esters (Spans), poloxamers, and phospholipids such as egg lecithin, soy lecithin, and phosphatidylcholine.
  • nonionic surfactants include polyoxyethylene glycol sorbitan alkyl esters, polyoxyethylene stearates, polyoxyethylene castor oil derivatives, polyoxylglycerides, sucrose fatty acid esters, block copolymers of polyethylene glycol and polypropylene glycol, fatty acid esters of ethylene glycol, propylene glycol derivatives (e.g., propylene glycol monolaurate), polyethylene glycol, polypropylene glycol, glycol, trimethylolpropane, and pentaerythritol.
  • polyoxyethylene glycol sorbitan alkyl esters polyoxyethylene stearates, polyoxyethylene castor oil derivatives, polyoxylglycerides, sucrose fatty acid esters, block copolymers of polyethylene glycol and polypropylene glycol, fatty acid esters of ethylene glycol, propylene glycol derivatives (e.g., propylene glycol monolaurate), polyethylene glycol, polypropylene glyco
  • Additional surfactant classes may include glucoside derivatives, glycerin alkyl ether fatty acid esters, trimethylolpropane oxyethylene alkyl ethers, fatty acid amides, alkylolamides, alkylamine oxides, lanolin and its derivatives, castor oil and hardened castor oil derivatives, sterols and their derivatives, polyoxyethylene alkyl ethers, polyoxyethylene alkyl allyl ethers, polyoxyethylene alkylamines, polyoxyethylene fatty acid amides, polyoxyethylene alkylolamides, polyoxyethylene diethanolamine fatty acid esters, polyoxyethylene trimethylolpropane fatty acid esters, polyoxyethylene alkyl ether fatty acid esters, polyoxyethylene-polyoxypropylene glycols, polyoxyethylene-polyoxypropylene alkyl ethers, polyoxyethylene-polyoxypropylene polyhydric alcohol ethers, glycerin fatty acid esters, poly
  • At least one surfactant is selected from the group consisting of polyoxyethylene glycol sorbitan alkyl esters, such as polysorbate 20 (Tween 20), polysorbate 60 (Tween 60), and polysorbate 80 (Tween 80).
  • the total amount of surfactant(s) present in the composition does not exceed about 30% w/w of the total composition.
  • the formulation may further comprise an antioxidant to enhance the stability of omega-3 fatty acids.
  • Suitable antioxidants include, but are not limited to, ascorbic acid (vitamin C), tocopherols (e.g., ⁇ -tocopherol or vitamin E), butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), propyl gallate, citric acid, sodium ascorbate, ascorbyl palmitate, rosemary extract, and tert-butylhydroquinone (TBHQ).
  • added an essential oil for flavor masking and HDL modulation include, but are not limited to, lemon oil, orange oil, turmeric oil,ginger oil, bergamot oil, basil oil,lemon grass oil and clove oil.
  • the composition comprising omega-3 fatty acids, at least one herbal extract, and at least one surfactant may optionally further include one or more co-surfactants, and/or at least one antioxidant.
  • PARTICLE SIZE In one embodiment, the composition may be in the form of a preconcentrate or an emulsion, which facilitates dispersion in an aqueous solution. In another embodiment composition the composition forms micelles in aqueous medium having, hydrodynamic diameter less than 700nm more preferably hydrodynamic diameter less than 300 nm. In one embodiment composition comprising omega-3 fatty acids and a herbal extract and an antioxidant and atleast one surfactant for oral administration, wherein the composition forms particle size more preferably hydrodynamic diameter less than 300 nm in aqueous medium.
  • the composition pertains to a process for preparing a formulation comprising omega-3 fatty acids, a herbal extract, an antioxidant and at least one surfactant.
  • the method of preparation involves mixing the omega-3 fatty acids with a surfactant, followed by the addition of herbal extract and the antioxidant, such as vitamin E to the mixture with thorough mixing.
  • the pharmaceutical composition of the present invention is encapsulated, preferably in gelatin capsules, which may be either soft or hard. Soft gelatin capsules are typically manufactured and filled in a single, continuous operation.
  • Another aspect of the invention provides a composition suitable for the therapeutic treatment for conditions known to benefit from omega-3 fatty acids, intended for a subject in need thereof, wherein the composition comprises omega-3 fatty acids, a herbal extract, an antioxidant and at least one surfactant, and is formulated for oral administration.
  • Another aspect of the invention provides an omega-3 fatty acid composition comprising herbal extracts, wherein the herbal extracts may exert a synergistic and/or additive effect on the antihyperlipidemic properties of the omega-3 fatty acids.
  • the synergistic composition provides both herbal extracts and omega- 3 fatty acids together in a stable formulation.
  • the embodiment provides a composition in which the herbal extracts and antioxidant serve to protect the highly labile omega-3 fatty acid molecules from oxidation, as well as from the detrimental effects of light and air.
  • the omega-3 fatty acid in the composition is formulated to be highly palatable, effectively minimizing or eliminating unpleasant odor, aftertaste, and/or burping in the patient.
  • BIOAVAILABILITY The absorption of omega-3 fatty acids in the gastrointestinal tract relies heavily on their emulsification and breakdown into smaller micellar droplets. Bile salts play a crucial role in dispersing large fat globules into these finer droplets.
  • pancreatic lipase acts on the triglycerides within the droplets, breaking them down into free fatty acids. These smaller, more soluble molecules can then easily pass through the phospholipid bilayer of intestinal cells, facilitating efficient absorption.
  • the present invention pertains to a self-emulsifying nanoemulsion composition comprising omega-3 fatty acids, at least one herbal extract, and one or more pharmaceutically acceptable surfactants and/or co-surfactants.
  • This nanoemulsification facilitates the presentation of lipophilic bioactives in a pre-dissolved form, significantly enhancing their solubility, dispersion, and absorption.
  • the resulting nano-sized droplets provide a substantially increased surface area, improving the rate and extent of drug release across the gastrointestinal membrane.
  • the enhanced bioavailability conferred by the nanoemulsion system is attributed to: (i) improved transcellular transport through increased membrane fluidity (ii) modulation of tight junctions to permit paracellular diffusion (iii) inhibition of P-glycoprotein (P-gp) and cytochrome P450 (CYP450) enzymes by selected surfactants, thereby reducing efflux and first-pass metabolism (iv) promotion of chylomicron and lipoprotein formation by the lipid component, enhancing lymphatic transport and systemic delivery of the active constituents.
  • P-gp P-glycoprotein
  • CYP450 cytochrome P450
  • the formulation upon oral administration of the pharmaceutical formulation to a mammal, demonstrates a pharmacokinetic absorption profile— characterized by parameters such as maximum plasma concentration (C_max), area under the plasma concentration-time curve (AUC), and optionally time to reach maximum concentration (T_max)—under fed conditions that is comparable to, or bioequivalent with, the pharmacokinetic profile observed under fasting conditions.
  • C_max maximum plasma concentration
  • AUC area under the plasma concentration-time curve
  • T_max time to reach maximum concentration
  • the mammal is a human.
  • omega-3 fatty acids comprising eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—for example, from omega-3-acid ethyl esters containing EPA ethyl ester and DHA ethyl ester—the increase in the concentration of EPA and/or DHA in plasma or in serum phospholipids may serve as a reliable indicator of absorption.
  • EPA eicosapentaenoic acid
  • DHA docosahexaenoic acid
  • the invention provides a method for enhancing the bioavailability of an omega-3 fatty acid in a subject in need thereof, the method comprising orally administering to the subject nanoemulsion composition as described herein, wherein the oral absorption and/or oral bioavailability of the omega-3 fatty acid is improved relative to that of an unformulated omega-3 fatty acid administered under comparable conditions.
  • enhanced absorption is evidenced by an increase in the area under the plasma concentration-time curve (AUC) of total omega-3 fatty acids, as measured following oral administration of the composition.
  • AUC plasma concentration-time curve
  • Example 1 The present invention is further illustrated by representative compositions comprising omega- 3 fatty acids in varying ratios of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in combination with one or more surfactants, natural bioactive from plant extracts, and pharmaceutically acceptable excipients.
  • EPA eicosapentaenoic acid
  • DHA docosahexaenoic acid
  • surfactants natural bioactive from plant extracts
  • pharmaceutically acceptable excipients Non-limiting examples of such formulations are set forth in Tables 1.
  • These compositions may be prepared by standard nanoemulsion formulation techniques, including but not limited to, homogenization, low- or high-energy emulsification, solvent evaporation, ultrasonication or spontaneous emulsification methods.
  • the omega-3 fatty acid source is blended with surfactants, co-surfactants, an antioxidant , an essential oil and plant extracts under gentle mixing to yield a formulation, which upon dilution with an aqueous medium, forms a fine emulsion or nanoemulsion suitable for oral administration.
  • the invention is further illustrated by the following examples, which are not intended to limit the scope or composition of the present invention.
  • Example 1 The following examples illustrate compositions containing omega-3 fatty acids with varying amounts of EPA and DHA, along with surfactants, natural bioactives from plants, and other excipients, as detailed in Tables 1–7.
  • DPPH radical was reduced to diphenylpicrylhydrazine upon interaction with omega 3 formulation.
  • Decolourization was measured at 517nm and percentage of radical scavenging activity was calculated. Comparative analysis of IC50 values are calculated for standard – ascorbic acid and omega 3 formulation in correspondence to their specific graphs..
  • Table 8-In vitro biochemical antioxidant assay DPPH- 1,1-diphenyl-2-picrylhydrazyl
  • the antioxidant capacity was expressed in ferric ion reducing ability or Fe 2+ equivalence from standard graph of ferrous sulphate.
  • the ferric ion-reducing ability of the omega 3 formulation is equivalent to 146.5 ⁇ M of ferrous ions.
  • RELATIVE BIOAVAILABILITY STUDIES Example 4 Enhanced bioavailability (FIG 3) A comparative pharmacokinetic study of the omega-3 formulation in the invention against fish oil with similar omega-3 fatty acid content was carried out in Sprague dawley rats at unimolar dose i.e similar amount of omega-3 fatty acid was administered to the different groups treated with omega-3 formulation and the unformulated fish oil.
  • the design of study offered a weight-to-weight comparison of the omega-3 fatty acid bioavailability given as novel formulated omega-3 and unformulated fatty acid.
  • the collection of the blood carried out at defined time interval and plasma separated from it by centrifuging at 4000 rpm speed for 10 min.
  • the plasma samples were analyzed using a validated LC-MS/MS method.
  • Table 9 -Results in Table 9 shows improvement in Cmax for the omega 3 formulation prepared according to our invention.
  • Omega – 3 formulation 0.5g capsules
  • Omega – 3 formulation 0.5g capsules (under fasting conditions) (under fed conditions)
  • Example 6 Relative bioavailability in fasting condition
  • Relative bioavailability studies of omega-3 formulation 0.5g prepared according to given examples and lovaza® (omega-3-acid ethyl esters) capsules 1 g of Glaxosmithkline, RTP, NC 27709 (four capsules as single dose) in health, adult, human subjects under fasting condition is studied. The statistical analysis was not performed as there are no EPA concentrations obtained for lovaza under fasting conditions.
  • EPA concentration of lovaza® vs omega-3 formulation in fasting condition is illustrated in FIG: 5

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Abstract

La présente invention concerne une composition nutraceutique administrable par voie orale comprenant des acides gras oméga-3, au moins un extrait d'origine végétale présentant une activité hypolipidémique et un antioxydant. La composition est formulée sous la forme d'une nanoémulsion pour améliorer la biodisponibilité, améliorer l'absorption gastro-intestinale et augmenter l'efficacité thérapeutique des composés actifs. L'interaction synergique entre les acides gras oméga-3 et le composant bioactif de l'extrait végétal favorise une réduction importante des taux de triglycérides plasmatiques sanguins, améliorant la santé cardiovasculaire. La formulation démontre des caractéristiques pharmacocinétiques améliorées, y compris une meilleure exposition systémique de l'acide eicosapentaénoïque (EPA) et de l'acide docosahexaénoïque (DHA), par comparaison avec les suppléments oméga-3 disponibles dans le commerce, ainsi qu'une biodisponibilité accrue à jeun ou après avoir mangé. La présente invention offre une nouvelle stratégie pour améliorer l'efficacité thérapeutique d'acides gras oméga-3 dans la lutte contre les maladies cardiovasculaires.
PCT/IN2025/050737 2024-05-10 2025-05-10 Nanoémulsion d'huile de poisson à oméga-3 hautement biodisponible (epa et dha) utilisée comme formulation nutraceutique pour la santé cardiovasculaire Pending WO2025233977A1 (fr)

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IN202441036872 2024-05-10
IN202441036872 2024-05-10

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2382262C (fr) * 1999-08-30 2004-12-07 Ocean Nutrition Canada Ltd. Supplement nutritionnel destine a abaisser le taux de cholesterol et de triglycerides seriques
WO2012112527A1 (fr) * 2011-02-16 2012-08-23 Pivotal Therapeutics, Inc. Préparations à base d'oméga-3 comprenant epa, dha et dpa pour le traitement des facteurs de risque dans la maladie cardiovasculaire
US20200060321A1 (en) * 2018-08-22 2020-02-27 Rachelle MACSWEENEY Nanoformulations containing encapsulted omega-3 fatty acids

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2382262C (fr) * 1999-08-30 2004-12-07 Ocean Nutrition Canada Ltd. Supplement nutritionnel destine a abaisser le taux de cholesterol et de triglycerides seriques
WO2012112527A1 (fr) * 2011-02-16 2012-08-23 Pivotal Therapeutics, Inc. Préparations à base d'oméga-3 comprenant epa, dha et dpa pour le traitement des facteurs de risque dans la maladie cardiovasculaire
US20200060321A1 (en) * 2018-08-22 2020-02-27 Rachelle MACSWEENEY Nanoformulations containing encapsulted omega-3 fatty acids

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