Synergistic bioactive nutraceutical composition for muscle health and sarcopenia

Abstract

The present invention relates to a synergistic bioactive composition for improving compromised muscle health and for the prevention, management or treatment of sarcopenia. The composition comprises ecdysterone, curcuminoids, and selenium, wherein the combination of these active agents exhibits a synergistic effect in enhancing muscle mass, muscle strength, and overall functional performance. The composition is intended for oral administration and may be formulated in any suitable orally administrable dosage forms including but not limited to a tablet, capsule, powder, pill, hard capsule containing liquid or solid fill, soft capsule, granule, pellet, caplet, mini-tablet, gummy, syrup, suspension, sachet or a, modified-release formulation.

Description

[0001] SYNERGISTIC BIOACTIVE NUTRACEUTICAL COMPOSITION FOR MUSCLE HEALTH AND SARCOPENIA

[0002] RELATED APPLICATION:

[0003] The present application claims benefit of the Indian Provisional Application No. IN202421081656 filed on, November 25th, 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 for improving compromised muscle health and for the prevention, management or treatment of sarcopenia. More particularly, the invention is directed to a composition comprising ecdysterone, curcuminoids, and selenium, wherein the combination of these active agents exhibits a synergistic effect in enhancing muscle mass, muscle strength and overall functional performance. The composition provides a comprehensive therapeutic approach for the prevention and treatment of sarcopenia - a progressive degenerative condition characterized by a reduction in skeletal muscle mass and strength and associated with an increased the risk of falls, physical impairment, and elevated healthcare burden. The composition is intended for oral administration and may be formulated in any suitable orally administrable dosage forms including but not limited to a tablet, capsule, powder, pill, hard capsule containing liquid or solid fill, soft capsule, granule, pellet, caplet, mini-tablet, gummy, syrup, suspension, sachet or a , modified-release formulation. Such dosage forms provide an effective and user-friendly therapeutic means for delivering the composition for mitigating muscle deterioration and reducing complications associated therewith.

[0006] BACKGROUND OF THE INVENTION

[0007] Sarcopenia is a progressive and generalized skeletal muscle disorder characterized by an accelerated decline in muscle mass and muscle function. Although predominantly, associated with aging process, the condition is also influenced by factors including but not limited to nutritional deficiencies, hormonal imbalances, physical inactivity and chronic pathological states. Sarcopenia adversely affects quality of life by increasing the likelihood of falls, functional deterioration, frailty, and mortality. Hallmark features of sarcopenia comprise reduction in skeletal muscle mass, muscle strength, and physical functional performance. These physiological impairments may result in significant clinical and socioeconomic consequences including disability, loss of independence, prolonged hospitalization and increased healthcare burden.

[0008] Skeletal muscle, which constitutes approximately 40% of total body weight and contains 50-75% of the body’s protein content, performs essential physiological functions including maintenance of posture, generation of force and power and facilitation of voluntary movement. The regulation of skeletal muscle mass is determined by the dynamic equilibrium between protein synthesis and degradation, processes that are modulated by dietary intake, physical activity, hormonal status and overall health condition. A reduction in muscle mass resulting from aging or pathological states leads to progressive muscle weakness, compromised immune function, increased susceptibility to infection delayed wound healing and impaired ability to perform routine daily activities.

[0009] With the continued expansion of the global aging population and the corresponding increase in the incidence of sarcopenia, there exists a critical need for effective therapeutic and preventive interventions. The synergistic composition described herein addresses underlying mechanisms of muscle deterioration and offers a practical solution capable of integration into existing healthcare and clinical management practices. Accordingly, the present invention represents a significant advancement in the field of muscle health support and management of sarcopenia.

[0010] KR102229177 discloses a pharmaceutical composition and a health functional food composition for the prevention or treatment of sarcopenia, the composition comprising, as an active ingredient, a mixed extract containing a rosemary extract and a soybean extract.

[0011] WO2015151066 discloses a composition comprising a combination of 20-hydroxy- ecdysone (20HE) and at least one ecdysteroid selected from the group consisting of polypodine, makisterone A, integristerone, taxisterone, lesterone, rapisterone, inokonesterone, carthamosterone, rubrosterone, leuzeasterone, ayugasterone, and turkestrone.

[0012] US 10897923 discloses a composition employing a SLIT-ROBO signaling system for prevention or treatment of sarcopenia. More specifically, the reference describes a composition comprising a gene selected from slitl, slit2, slit3, robol, robo2 or fragments thereof, or a protein expressed by any of the foregoing genes as an active ingredient for preventing or treating a muscle-related disease or for improving muscular function.

[0013] W02020210547 discloses protein substitute products that provide essential nutrients comprising amino acid compositions containing essential and non- essential amino acids in predetermined ratios, together with vitamins, nutrients and botanicals. The disclosure described such compositions as being formulated into food or beverage products intended to provide nutritional sustenance.

[0014] KR20230043061 discloses a composition for the prevention or treatment of muscle weakness-related diseases or sarcopenia, the composition comprising as an active ingredient, a Rosa davurica extract, a fraction thereof, or a fermented product derived therefrom.

[0015] CA3206020 discloses a composition for the prevention or treatment of sarcopenia or osteoporosis, the composition comprising cyclo-L-phenylalanyl-L-proline dipeptides as an active ingredient.

[0016] WO2023068747 discloses a composition comprising reboxetine as an active ingredient for prevention or treatment of sarcopenia. Current strategies for management of sarcopenia are largely confined to exercisebased regimens and nutritional interventions, as no specific pharmacological agents have yet received regulatory approval for its treatment. While such approaches may attenuate muscle loss and improve muscle strength and functional capacity, they remain insufficient to fully address the complex and multifactorial pathophysiology of the condition. Accordingly, there exists a substantial unmet need for therapeutic compositions capable of providing a more effective and comprehensive intervention. This need has prompted ongoing efforts to develop novel pharmacological solutions that can complement existing non-pharmacological strategies and deliver improved outcomes for individuals affected by sarcopenia.

[0017] OBJECTIVE OF THE INVENTION

[0018] The primary objective of the present invention is to provide a synergistic composition for improving compromised muscle health and / or for the prevention, management, or treatment of sarcopenia, the composition comprising Ecdysterone, Curcuminoids and Selenium, optionally in the form of their pharmaceutically acceptable salts, derivatives, isomers, precursors, plant sources, or metabolites.

[0019] Another objective of the present invention is to provide a synergistic composition for improving compromised muscle health and / or addressing sarcopenia, the composition comprising Ecdysterone, Curcuminoids, and Selenium, optionally in the form of their pharmaceutically acceptable salts, derivatives, isomers, precursors, plant sources, or metabolites, wherein the composition is effective in enhancing muscle mass, muscle strength, and functional performance.

[0020] Another objective of the present invention is to improve muscle health through the provision of a strategic combination of ecdysterone, Curcuma species derived curcuminoids and selenium. The composition is intended to counteract the adverse consequences of sarcopenia, including reduced physical function, a higher risk of falls, and escalating healthcare expenses. Another objective of the present invention is to prevent or minimize complications arising from muscle loss, such as weakened immunity, diminished physical mobility, and extended hospitalizations through the synergistic effects of ecdysterone, Curcuma species derived curcuminoids, and selenium.

[0021] A further objective of the present invention is to enhance protein synthesis and promote muscle regeneration, thereby contributing to increased muscle mass and strength which are essential for mitigating the effects of sarcopenia and other related muscle-related conditions.

[0022] Another objective of the present invention is to provide a synergistic bioactive composition comprising Ecdysterone, Curcuminoids and Selenium, wherein Ecdysterone, Curcuminoids and Selenium, are present in a ratio ranging from 1:0.000833:0.000008 to 1: 1000:0.25.

[0023] Yet another objective of the present invention is to provide a synergistic bioactive composition comprising Ecdysterone, Curcuminoids and Selenium, wherein the Curcuminoids is in an amount ranging from 0.0312% to 99.4031% w / w, based on the total weight of the composition; the Ecdysterone is present in an amount ranging from 0.0500% to 99.0908% w / w, based on the total weight of the composition; and the amount of Selenium is in the range of 0.0002% to 3.7037% w / w, based on the total weight of the composition.

[0024] Yet another object of the invention is to provide a synergistic bioactive composition comprising Curcuminoids, Ecdysterone, and Selenium, wherein Curcuminoids are present in an amount ranging from 1 mg to 2000 mg; Ecdysterone is present in an amount ranging from 2 mg to 1200 mg; and Selenium is present in an amount ranging from 0.01 mg to 0.5 mg.

[0025] Yet another object of the invention is to provide a synergistic bioactive composition comprising Curcuminoids, Ecdysterone, and Selenium for the treatment or management of sarcopenia, frailty, muscle atrophy, muscle weakness, muscle injury, or other related muscle health-related disorders.

[0026] Another object of the present invention is to provide a kit comprising Ecdysterone, Curcuminoids, and Selenium, wherein Ecdysterone, Curcuminoids, and Selenium, are provided either: as separate compositions within the kit, or as a single composition comprising any combination of two or more of these compounds. The kit is formulated for oral administration and is intended for use in the treatment or management of sarcopenia, frailty, muscle atrophy, muscle weakness, muscle injury, or other muscle health-related disorders.

[0027] Yet another objective of the present invention is to provide a versatile formulation that is adapted into variety of pharmaceutical dosage forms, including but not limited to a tablet, capsule, powder, pill, hard capsule containing liquid or solid fill, soft capsule, granule, pellet, caplet, mini-tablet, gummy, syrup, suspension, sachet, modified-release formulation, or any other orally administrable dosage form.

[0028] These objectives collectively underscore the innovative nature of the present synergistic composition in addressing the challenges associated with compromised muscle health and sarcopenia, thereby providing new and effective possibilities for enhancing muscular function, overall well-being and quality of life.

[0029] SUMMARY OF THE INVENTION

[0030] The present invention relates to a synergistic composition for improving muscle health and / or for the prevention, management or treatment of sarcopenia. The composition comprises ecdysterone, curcuminoids, and selenium as key active components. Each component contributes to enhancing muscle function and counteracting the detrimental effects of sarcopenia, a condition characterized by progressive skeletal muscle loss and a corresponding decline in functional capacity.

[0031] A primary aspect of the present invention lies in its targeted approach to addressing the multifactorial challenges associated with sarcopenia. Skeletal muscle, which is essential for force generation, posture maintenance, and movement facilitation, represents a substantial portion of the total body mass and protein content. With advancing age or in the presence of certain pathological conditions, skeletal muscle mass and strength progressively decline as a result of disruptions in the balance between protein synthesis and degradation, as well as influences such as nutritional deficiencies, hormonal changes, and decreased physical activity. Sarcopenia exacerbates these impairments leading to an increased risks of falls, functional decline, frailty, and mortality, thereby underscoring the critical need for effective therapeutic interventions..

[0032] Another aspect of the e present invention pertains to the synergistic combination of ecdysterone, curcuminoids, and selenium, wherein each component contributes distinct pharmacological benefits that collectively enhances the management and mitigation of sarcopenia.

[0033] Another aspect of the present invention relates to the development of a versatile formulation for improving compromised muscle health and / or managing sarcopenia. The formulation comprises ecdysterone, selenium, Curcuminoids and one or more pharmaceutically acceptable excipients. The composition may be adapted into a wide range of pharmaceutical dosage forms including but not limited to a tablet, capsule, powder, pill, hard capsule containing liquid or solid fill, soft capsule, granule, pellet, caplet, mini-tablet, gummy, syrup, suspension, sachet, modified-release formulation, or any other orally administrable dosage form thereby accommodating diverse patient needs.

[0034] In summary, the synergistic composition of the present invention represents a substantial advancement in the field of muscle health management. Through the combined use of ecdysterone, Curcuminoids and selenium, the present invention offers a comprehensive and effective approach to mitigating muscle loss, enhancing muscle function, and improving overall quality of life in individuals suffering from sarcopenia or other muscle -related conditions. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1: Grip Strength

[0036] Figure 2: Body weight

[0037] Figure 3: Gait speed

[0038] Figure 4: Step numbers

[0039] Figure 5: Rotarod test

[0040] Figure 6: Serum IL-6

[0041] Figure 7: Serum SIRT-1

[0042] DETAILED DESCRIPTION OF THE INVENTION

[0043] The following detailed description sets forth various embodiments of the present subject matter. These embodiments are described in sufficient detail to enable those skilled in the art to practice the present subject matter. It will be understood, however, that the additional embodiments may be utilized and modifications may be made without departing from the scope of the present subject matter.

[0044] References to “an”, “one”, or “various” embodiments herein are not intended to refer to the same embodiment, and such references contemplate the possibility of multiple, distinct embodiments. Accordingly, the following detailed description should not be construed as limiting, and the scope of the present subject matter is defined solely by the appended claims and the full range of legal equivalents to which such claims are entitled.

[0045] The present invention relates to a synergistic composition designed specifically to improve muscle health and manage conditions associated sarcopenia. This composition comprises ecdysterone, curcuminoids, and selenium, which collectively work to enhance muscle strength and mitigate the progression of sarcopenia.

[0046] The present invention provides a synergistic bioactive composition for improving poor muscle health and / or managing sarcopenia. The composition comprises Curcuminoids, Ecdysterone, and Selenium, optionally in the form of their pharmaceutically acceptable salts, derivatives, isomers, precursors, plant sources, or metabolites.

[0047] In one embodiment, the present invention provides a synergistic bioactive composition for improving poor muscle health and / or managing sarcopenia, the composition comprising Curcuminoids, Ecdysterone, and Selenium, optionally in the form of their pharmaceutically acceptable salts, derivatives, isomers, precursors, plant sources, or metabolites, to effectively manage muscle mass, strength and functional performance.

[0048] In one embodiment, the present invention is directed towards addressing the adaptable and malleable properties of skeletal muscle, which constitutes a major component of the human body’s total weight and protein reserves. Skeletal muscles are vital for force generation, posture maintenance, movement facilitation, and preserving functional autonomy. However, factors such as nutritional deficiencies, hormonal imbalances, physical inactivity, injuries and various disease conditions can disrupt the equilibrium between muscle protein synthesis and breakdown. Such disruptions contribute to Sarcopenia, a progressive condition characterized by a gradual decline in muscle mass and strength, which in turn increases the risk of falls, functional impairment, frailty and mortality.

[0049] Another embodiment of the present invention addresses the critical clinical burden of sarcopenia, a condition characterized by reduced muscle mass, diminished muscle strength, impaired physical performance, and increased vulnerability to falls and fractures. Sarcopenia is further associated with substantial healthcare implications, including higher medical resource utilization, prolonged hospital stays, intensive care admissions and elevated overall healthcare expenditures. Complications such as muscle weakness, compromised immune functions, heightened infection risks, delayed would healing and mobility limitations underscore the urgent need for effective interventions to mitigate sarcopenic symptoms and enhance overall muscle function.

[0050] One more embodiment of the present invention focuses on the current lack of targeted pharmacological treatments for sarcopenia. Existing management strategies primarily rely on physical exercise and nutritional interventions, highlighting the unmet need for novel therapeutic solutions capable of addressing the underlying mechanism of muscle deterioration and functional decline. The present invention aims to fdl this gap by utilizing the synergistic combination of ecdysterone, curcuminoids, and selenium, which collectively offer substantial pharmacological benefits for enhancing muscle health and mitigating the progression of sarcopenia.

[0051] According to present invention, there is provided a synergistic bioactive composition comprising Curcuminoids, Ecdysterone, and Selenium, wherein the composition is formulated for oral administration and is presented in one or more dosage forms selected from tablet, capsule, powder, pill, hard capsule containing liquid or solid fill, soft capsule, granule, pellet, caplet, mini-tablet, gummy, syrup, suspension, sachet, modified-release formulation, or any other orally administrable dosage form suitable for the preferences and needs of the target population.

[0052] According to present invention, there is provided a synergistic bioactive composition comprising Curcuminoids, Ecdysterone, and Selenium further comprising one or more pharmaceutically acceptable excipients selected from: a bulking agents (diluents), disintegrants, binders, solubilizing agents, lubricants, glidants, or any combination thereof.

[0053] Diluents are selected from one or more from 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, and are present in amount ranging from 1% to 98% w / w of the total composition.

[0054] Disintegrants are selected from one or more from 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 mixtures thereof, and are present in amount ranging from 0.4% to 15% w / w of the total composition.

[0055] Binders are selected from one or more from 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, or tragacanth, and are present in an amount ranging from 0.1% to 12% w / w of the total composition.

[0056] Surfactants are selected from one or more of polysorbates, sorbitan esters, polyethylene glycol esters, polyoxyethylene stearates, polyoxyethylene stearate, , poloxamers, sodium lauryl sulfate, sodium dodecyl sulfate, sodium stearate, sodium dioctyl sulfosuccinate, benzalkonium chloride, benzethonium chloride, cetylpyridinium chloride, lecithin, phosphatidylcholine, lauryl betaine, or mixtures thereof.

[0057] Lubricants are selected from one or more from magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, talc, polyethylene glycol, colloidal silicon dioxide, glyceryl behenate, or zinc stearate, and are present in an amount ranging from 0.5% to 10% w / w of the total composition.

[0058] Glidants are selected from one or more from colloidal silicon dioxide, hydrophobic colloidal silica, silicon dioxide, talc, tribasic calcium phosphate, or mixtures thereof, and are present in an amount ranging from 0.5% to 10% w / w of the total composition.

[0059] The composition of the present invention can be prepared using conventional methods known in the art for formulation of oral dosage forms. Depending on the intended final product, the formulation may be prepared by direct compression, in which the active pharmaceutical ingredients are blended with suitable excipients including fillers, binders, disintegrants, and lubricants, followed by compression into tablets. Alternatively, the composition may be prepared using granulation techniques, including wet or dry granulation, to enhance flow properties and compressibility. The resulting formulation can be filled into sachets or capsules to facilitate administration. Additionally, the composition can be provided as a powder or granules for reconstitution into an oral suspension. Other suitable manufacturing 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.

[0060] A synergistic composition for the management of muscle health and / or associated sarcopenia, according to the present invention, comprises ecdysterone, selenium and Curcuminoids optionally in the form of their pharmaceutically acceptable salts, derivatives, isomers, precursors, plant sources, or metabolites, along with pharmaceutically acceptable excipients.

[0061] According to present invention, there is provided a synergistic bioactive composition comprising Curcuminoids, Ecdysterone, and Selenium, wherein, Curcuminoids are present in an amount ranging from 1 mg to 2000 mg, 5 mg to 1900 mg, 10 mg to 1800 mg, 15 mg to 1700 mg, 20 mg to 1600 mg, 25 mg to 1500 mg and 10 mg to 1000 mg and 25 to 1000 mg.

[0062] According to present invention, there is provided a synergistic bioactive composition comprising Curcuminoids, Ecdysterone, and Selenium, wherein, Ecdysterone is present in an amount ranging from 2 mg to 1400 mg, 2 mg to 1200 mg, 2 mg to 1100 mg, 2 mg to 900 mg, 2 mg to 800 mg, 2 mg to 775 mg, 2 mg to 750 mg and 2 mg to 500 mg.

[0063] According to present invention, there is provided a synergistic bioactive composition comprising Curcuminoids, Ecdysterone, and Selenium, wherein, Selenium is present in an amount ranging from 0.01 mg to 0.5 mg, 0.01 mg to 0.45 mg, 0.01 mg to 0.42 mg, 0.01 to 0.40 mg, 0.01 mg to 0.38 mg and 0.01 mg to 0.35 mg.

[0064] In another embodiment, the present invention provides a synergistic bioactive composition comprising Curcuminoids, Ecdysterone, and Selenium, optionally in the form of their pharmaceutically acceptable salts, derivatives, isomers, precursors, plant-derived sources, or metabolites, wherein ecdysterone, curcuminoids, selenium are present in a ratio ranging from 1:0.000833:0.000008 to 1: 1000:0.25, 1:0.004545:0.000009 to 1:950:0.225, 1:0.011111:0.000011 to 1:900:0.21,

[0065] 1:0.018750:0.000013 to 1:850:0.2, 1:0.025806:0.000013 to 1:800:0.19,

[0066] 1:0.033333:0.000013 to 1:750:0.175 and 1:0.05:0.000020 to 1:500:0.175.

[0067] According to present invention, there is provided a synergistic bioactive composition comprising Curcuminoids, Ecdysterone, and Selenium, wherein the Curcuminoids are present in an amount ranging from 0.03% to 99.40% w / w based on the total weight of the composition.

[0068] According to present invention, there is provided a synergistic bioactive composition comprising Curcuminoids, Ecdysterone, and Selenium, wherein the Ecdysterone is present in an amount ranging from 0.05% to 99.09% w / w, based on the total weight of the composition.

[0069] According to present invention, there is provided a synergistic bioactive composition comprising Curcuminoids, Ecdysterone, and Selenium, wherein the Selenium is present in an amount ranging from 0.0002% to 3.70% w / w, based on the total weight of the composition. Curcuminoids, or their pharmaceutically acceptable salts, derivatives, isomers, precursors, or metabolites, may be obtained through chemical synthesis, fermentation processes, or isolated from plant sources.

[0070] Ecdysterone, or its pharmaceutically acceptable salts, derivatives, isomers, precursors, or metabolites, may be obtained by chemical or biological synthesis , or extracted from suitable plant sources.

[0071] Selenium, or its pharmaceutically acceptable salts, derivatives, isomers, precursors, or metabolites, may also be obtained via chemical synthesis, fermentation process, or extraction from natural plant sources.

[0072] The synergistic composition(s) as per the present invention, wherein oral administration of an effective dose of the composition helps to manage muscle health and the prevention, treatment or mitigation of sarcopenia.

[0073] In another embodiment of the present invention provides a synergistic bioactive composition comprising Curcuminoids, Ecdysterone, and Selenium, optionally in the form of their pharmaceutically acceptable salts, derivatives, isomers, precursors, plant-derived sources, or metabolites, wherein the composition is used for the treatment or management of sarcopenia, frailty, muscle atrophy, muscle weakness, muscle injury, or other related muscle health disorders.

[0074] One embodiment of the present invention provides a synergistic bioactive composition comprising Curcuminoids, Ecdysterone, and Selenium, wherein oral administration of the composition results in a significant improvement in muscle strength, as demonstrated by an increase in grip strength of at least 24.06% compared to the combined individual effects of Curcuminoids, Ecdysterone, and Selenium.

[0075] One embodiment of the present invention provides a synergistic bioactive composition comprising Curcuminoids, Ecdysterone, and Selenium, wherein oral administration of the composition improves body weight by at least 22.20% more than the combined individual effects of curcuminoids, ecdysterone and selenium.

[0076] One embodiment of the present invention provides a synergistic bioactive composition comprising Curcuminoids, Ecdysterone, and Selenium, wherein oral administration of the composition improves motor activity, as evidenced by an increase gait speed of at least 41.47% and a reduction in step number of at least 16.35% more than the combined individual effects of curcuminoids, ecdysterone and selenium.

[0077] One embodiment of the present invention provides a synergistic bioactive composition comprising Curcuminoids, Ecdysterone, and Selenium, wherein oral administration of the composition enhances motor coordination and performance as demonstrated by an increase in staying time on revolving rotarod of at least by at least 21.38% more than the combined individual effects of curcuminoids, ecdysterone and selenium.

[0078] One embodiment of the present invention provides a synergistic bioactive composition comprising Curcuminoids, Ecdysterone, and Selenium, wherein oral administration of the composition reduces muscle wasting as evidence by a decrease in serum interleukin-6 levels of at least 51.56% more than the combined individual effects of curcuminoids, ecdysterone and selenium.

[0079] One embodiment of the present invention provides a synergistic bioactive composition comprising Curcuminoids, Ecdysterone, and Selenium, wherein oral administration of the composition improves muscle mitochondrial content and functions, as demonstrated by an increase in serum SIRT-1 levels by at least 26.77% more than the combined individual effects of curcuminoids, ecdysterone and selenium.

[0080] In another embodiment of the present invention provides a synergistic bioactive composition comprising Curcuminoids, Ecdysterone, and Selenium, optionally in the form of their pharmaceutically acceptable salts, derivatives, isomers, precursors, plant-derived sources, or metabolites, wherein the Curcuminoids are in an amount ranging from 0.0312% to 99.403 l%w / w, the Ecdysterone is in an amount ranging from 0.0500% to 99.0908% w / w, and the Selenium is present in an amount ranging from 0.0002% to 3.7037% w / w, each based on the total weight of the composition.

[0081] In another embodiment, the present invention provides a synergistic bioactive composition comprising Curcuminoids, Ecdysterone, and Selenium, optionally in the form of their pharmaceutically acceptable salts, derivatives, isomers, precursors, plant-derived sources, or metabolites, wherein Curcuminoids are present in an amount ranging from 1 mg to 2000 mg; Ecdysterone is present in an amount ranging from 2 mg to 1200 mg; and Selenium is present in an amount ranging from 0.01 mg to 0.5 mg.

[0082] In another embodiment, the present invention provides a synergistic bioactive composition comprising Curcuminoids, Ecdysterone, and Selenium, optionally in the form of their pharmaceutically acceptable salts, derivatives, isomers, precursors, plant-derived sources, or metabolites, wherein the composition comprises Curcuminoids in an amount ranging from 1 mg to 2000 mg; Ecdysterone in an amount ranging from 2 mg to 1200 mg; Selenium in an amount ranging from 0.01 mg to 0.5 mg; wherein Ecdysterone, Curcuminoids and Selenium are present in a ratio ranging from 1:0.000833:0.000008 to 1: 1000:0.25; wherein the composition is formulated for oral administration; and wherein oral administration of the composition: improves muscle strength by increasing grip strength by at least 24.06% more than the combined individual effects of curcuminoids, ecdysterone and selenium; and improves muscle mitochondrial content and function by increasing serum SIRT-1 levels by at least 26.77% more than the combined individual effects of curcuminoids, ecdysterone and selenium.

[0083] In another embodiment of the present invention provides a kit comprising: Ecdysterone, Curcuminoids, and Selenium, optionally in the form of their pharmaceutically acceptable salts, derivatives, isomers, precursors, plant sources, or metabolites, wherein Ecdysterone, Curcuminoids, and Selenium, are provided either: as separate compositions within the kit, or as a single composition comprising a combination of two or more of compounds Ecdysterone, Curcuminoids, and Selenium, wherein the kit is formulated for oral administration and is intended for use in the treatment or management of sarcopenia, frailty, muscle atrophy, muscle weakness, muscle injury, or other muscle health-related disorders.

[0084] According to the present invention, the active ingredients Curcuminoids, Ecdysterone, and Selenium may be present in their original form or in the form of any of their pharmaceutically acceptable salts, derivatives, isomers, precursors, metabolites, or as components derived from natural sources, including plant extracts.

[0085] In summary, the present invention provides a novel approach to addressing the complex challenges of poor muscle health and sarcopenia. The invention offers a comprehensive therapeutic strategy aimed at enhancing muscle mass, strength, and functional performance.

[0086] EXAMPLES

[0087] 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.

[0088] EXAMPLE-1: COMPOSITION: Following is a general composition formula as per the present invention:

[0089] Process for preparation of example 1 :

[0090] 1. Accurately weigh each ingredient in separate containers.

[0091] 2. Sift the previously weighed active ingredients and excipients through a

[0092] 5 sieve.

[0093] 3. Combine the contents from step 2 to prepare suitable oral dosage form.

[0094] EXAMPLE 2A:

[0095] 10 EXAMPLE 2B:

[0096] EXAMPLE 2C: | 1985.02 | 990.04 | 1004.04 | 1036.1 | 1147.2 | 1353.3 | 1559.4 | 1705.5 |

[0097] Manufacturing process of example 2A, 2B and 2C:

[0098] 1. Accurately weigh each ingredient in separate containers.

[0099] 2. Sift the previously weighed Curcuminoids, Ecdysterone, Selenium, diluent(s), and disintegrating agent(s) separately through a #40 sieve.

[0100] 3. Combine the contents from step 2 in a rapid mixer granulator (RMG) using a slow-speed impeller.

[0101] 4. Binder solution preparation: Weigh the binding agent(s) and optionally solubilizing agent(s) in a separate container, dissolve them in the solvent(s), and then add the Ecdysterone to the same solution.

[0102] 5. Add the binder solution to the mixture from step 3 in the RMG, using a slow impeller speed.

[0103] 6. Sift and dry the granulated wet mass in a fluid bed dryer at 50°C ± 5 °C until the blend's level of dryness (LOD) is reduced to below 1.5% w / w.

[0104] 7. Sift the semi-dried granules through sieve #20, followed by sieve #30.

[0105] 8. Sift the previously weighed lubricant(s) or glidant(s) separately through sieve #40, then mix them with the material from Step 7.

[0106] 9. Compress the blend from Step 8 to form tablets containing Curcuminoids, Ecdysterone, and Selenium.

[0107] EXAMPLE 3: ANIMAL STUDY

[0108] Objective of the animal study: To Evaluate the Synergistic Effects of Curcuminoids, Ecdysterone, and Selenium in Sarcopenic Wistar Rats.

[0109] Materials and Method: Female Wistar rats, aged 9-10 weeks and weighing 210- 300 g at the start of the experiment, were divided into groups of six.

[0110] All animals were divided into groups as described below. The normal control group, disease control group, and test groups (Test Group-1, Test Group-2, Test Group-3, and Test Group-4) are denoted as N, D, Tl, T2, T3, and T4, respectively. All animals were provided with a normal diet and fresh potable drinking water throughout the study. Animals in Group N did not receive any treatment. Animals in all other groups (D, Tl, T2, T3, and T4) received intraperitoneal injections of dexamethasone (800 pg / kg, i.p.) for five consecutive days (Day 0 to Day 4) to induce sarcopenia. Treatments, as outlined in the table below, were administered from Day 0 to Day 28.

[0111] BID: Twice daily

[0112] CMC: Carboxy Methyl Cellulose

[0113] At the end of Week 4, all animals were anesthetized with ketamine at a dose of lOO mg / kg body weight via intraperitoneal (i.p.) injection. Blood samples were collected from the abdominal aorta, taking care to avoid hemolysis. Serum was separated from the blood by centrifugation at 4000 rpm for 10 minutes using a centrifuge machine (Make: DLAB, Model: D3024R) and analyzed for the respective serum parameters.

[0114] Evaluation parameters:

[0115] Anthropometric parameters:

[0116] • Body weight Behavioral parameters:

[0117] • Grip strength

[0118] • Gait speed

[0119] • Step number

[0120] • Rota rod test

[0121] ELISA parameters:

[0122] Serum SIRT-1 Serum IL-6

[0123] Test Parameters details:

[0124] Body weight: The body weight of each animal was measured using a weighing balance. Body weight serves as an important supportive parameter in the assessment and management of sarcopenia, particularly when considered alongside body composition. Sarcopenia is characterized by a loss of skeletal muscle mass, frequently resulting in reductions in overall and lean body weight. Unintentional weight loss in older adults is indicative of undemutrition, frailty, and muscle atrophy, reflecting progression of sarcopenia. A decline in body weight acts as a marker of muscle loss and functional deterioration, whereas stabilization or increase in body weight, especially lean mass, signifies effective intervention. Gains in body weight through muscle accretion represent a beneficial outcome in the management of sarcopenia.

[0125] Grip strength: Grip strength was used to evaluate muscular strength. For the assessment, each animal was held by the tail and allowed to grasp a grid attached to a force transducer. The animal was then gently pulled by the tail with increasing firmness until it released its grip. At this point, the peak force was recorded by the equipment. A higher peak force indicates greater grip strength. Grip strength is a well-established, reliable, and clinically validated measure of muscle strength and serves as a critical parameter in the diagnosis of sarcopenia, a progressive, age- related condition characterized by muscle wasting. Reductions in grip strength are closely associated with impaired mobility, diminished functional capacity, increased frailty and loss of independence. Grip strength also correlates strongly with slower gait speed and reduced overall physical performance, which are hallmark features of moderate to severe sarcopenia. Conversely, an increase in grip strength reflects enhanced neuromuscular function and improved muscle integrity

[0126] Average gait speed (cm / s): average speed of a run: Animals were placed on a glass lane with tangential illumination, and each step was recorded by detecting light diffraction using a camera placed below the lane . At least three runs per animal were recorded, with a 10-minute break between each run. Locomotion patterns and gait speed were then analyzed from smooth runs, which were defined as those during which the rat maintained a constant speed for at least 3-4 paw prints, using the automated Catwalk analysis software. A higher value indicates that the rat covered more distance, reflecting an improvement in sarcopenia. Gait speed is a critical functional parameter for evaluating sarcopenia, as it reflects muscle strength, coordination, and overall mobility. Reduced gait speed is closely associated with muscle weakness, functional decline, and an elevated risk of falls and disability. It serves as a reliable predictor of sarcopenia severity and progression, as well as overall health outcomes in elderly individuals. Improvements in gait speed indicate enhanced muscle function and physical performance, making it a valuable metric for assessing the effectiveness of interventions targeting sarcopenia.

[0127] Step Numbers: number of steps to perform the run: It measures the number of steps required to cover a specific distance. Animals were placed on a glass lane with tangential illumination, and each step was recorded by detecting light diffraction using a camera positioned below the lane. At least three runs per animal were performed, with a 10-minute break between each run. A lower number of steps indicates less time needed to complete the distance, suggesting improved mobility and quicker movement due to better muscle health. Conversely, a higher number of steps indicates that more steps are required to cover the same distance, reflecting reduced improvement in sarcopenia. Step count is an important functional parameter in the assessment of sarcopenia. An increased step count over a given distance often reflects shorter stride length and compensatory gait patterns arising from muscle weakness and impaired mobility, indicating reduced muscle efficiency and greater frailty. Conversely, a lower step count per distance is indicative of improved muscle function and more efficient movement. Monitoring step count provides valuable insight into the severity of sarcopenia and the efficacy of interventions aimed at improving muscle health. Rotarod test: Motor coordination and performance were assessed using the accelerating rotarod test. This test measures the time animals can remain on a revolving rod. Rats were trained to walk on the rod at a constant low-speed rotation (4 rpm) for 3 days, with one trial per day. For the accelerating test (4-40 rpm over 600 seconds), three trials were conducted on the test day, with 20-minute intervals between trials. The time until each rat fell from the rod was recorded. A longer time spent on the revolving rod indicates better motor coordination and suggests an improvement in muscle health, and vice versa. Rotarod mean time is a key functional parameter for assessing sarcopenia, as it reflects motor coordination, balance, and muscle endurance. A reduction in rotarod time indicates impaired neuromuscular function and muscle weakness, which are hallmark features of sarcopenia. Conversely, an increase in rotarod mean time signifies enhanced muscle performance and coordination. Accordingly, rotarod mean time serves as a valuable metric for evaluating the severity of sarcopenia and the efficacy of interventions aimed at improving muscle health and functional capacity.

[0128] ELISA parameters:

[0129] ELISA parameters like Serum IL-6 and Serum SIRT1 were measured on week-4 on ELISA kit, according to the ELISA kit insert.

[0130] Interleukin-6 (IL-6) is a pro-inflammatory cytokine associated with the onset and progression of sarcopenia. Elevated IL-6 levels contribute to chronic inflammation, resulting in muscle degradation, impaired regeneration, and loss of muscle mass. High IL-6 levels are correlated with reduced muscle strength and function, establishing it as a key biomarker for inflammation-mediated muscle deterioration. Accordingly, a reduction in IL-6 levels serves as an important indicator of the effectiveness of interventions for treating sarcopenia.

[0131] SIRT1 is a key protein that regulates metabolism, mitochondrial function, and muscle health. In sarcopenia, reduced SIRT1 activity leads to impaired muscle regeneration and increased aging. Elevated SIRT1 levels support muscle maintenance and energy metabolism, making it an important biomarker and therapeutic target for sarcopenia.

[0132] All the data are represented as mean ± standard deviation and are statistically 5 analyzed by two-way ANOVA followed by Tukey’s multiple comparison test. P- value <0.05 indicates a statistically significant difference between two groups.

[0133] Animal Study results:

[0134] 10 Table 1:

[0135] The sum of changes in grip strength for groups Tl, T2, and T3 was 185.33 g, whereas the invention group (T4) showed an increase of 237.33 g. This indicates 15 that the invention group (T4) exhibited a 28.06% greater increase in grip strength compared to the combined changes in groups Tl, T2, and T3, confirming the synergistic effect of the invention group.

[0136] Table 2:

[0137] 20 T2 264.83 ± 11.44 11.83

[0138] The combined change in body weight for groups Tl, T2, and T3 was 73.83 g, while the invention group (T4) showed an increase of 93.17 g. This corresponds to a 26.20% greater gain in body weight for the invention group (T4) compared to the 5 sum of groups Tl, T2, and T3, supporting the synergistic effect of the invention.

[0139] Table 3:

[0140] The combined change in gait speed for groups Tl, T2, and T3 was 14.67, whereas 10 the invention group (T4) exhibited an increase of 21.34. This represents a 45.47% greater improvement in gait speed for the invention group (T4) compared to the combined changes in groups Tl, T2, and T3, demonstrating the synergistic effect of the invention.

[0141] 15 Table 4:

[0142] The total reduction in step numbers for groups Tl, T2, and T3 was 21.33, whereas the invention group (T4) showed a decrease of 25.67. This corresponds to a 20.35% greater improvement in step numbers for the invention group (T4) compared to the 5 combined changes in groups Tl, T2, and T3, demonstrating the synergistic effect of the invention.

[0143] Table 5:

[0144] 10

[0145] The combined increase in rotarod mean time for groups Tl, T2, and T3 was 34. 16 seconds, whereas the invention group (T4) exhibited an increase of 42.83 seconds. This represents a 25.38% greater improvement in rotarod mean time for the invention group (T4) compared to the combined changes in groups Tl, T2, and T3, 15 demonstrating the synergistic effect of the invention.

[0146] Table 6: T2 3.17 ± 0.22 -0.15

[0147] The combined change in IL-6 for groups Tl, T2, and T3 was a decrease of 1.44 pg / ml, whereas the invention group (T4) showed a reduction of 2.24 pg / ml. This corresponds to a 55.56% greater decrease in IL-6, indicating reduced muscle

[0148] 5 inflammation and degradation in the invention group (T4) compared to the combined changes in groups Tl, T2, and T3, demonstrating the synergistic effect of the invention.

[0149] Table 7:

[0150] 10

[0151] The combined change in SIRT-1 for groups Tl, T2, and T3 was an increase of 0.26 pg / ml, whereas the invention group (T4) exhibited an increase of 0.34 pg / ml. This represents a 30.77% greater enhancement in SIRT-1 levels in the invention group 15 (T4) compared to the combined changes in groups Tl, T2, and T3, demonstrating the synergistic effect of the invention.

[0152] The results presented in the foregoing examples and tables clearly establish that the composition comprising components Curcuminoids, Ecdysterone, and Selenium 20 exhibits synergistic therapeutic benefits, surpassing the effects observed with the individual components alone. Specifically, the composition demonstrates a marked enhancement in efficacy for improving muscle health parameters. In conclusion, the present invention discloses a scientifically substantiated synergistic composition for the management of compromised muscle health, including but not limited to sarcopenia. Through comprehensive animal study, the inventors have shown that the combination of Curcuminoids, Ecdysterone, and

[0153] Selenium yields unexpected and superior outcomes in promoting muscle mass, strength, and overall functional performance.

[0154] The composition of the present invention therefore represents a significant advancement in the field of muscle health therapeutics. It offers a novel, non- obvious, and efficacious solution for addressing a critical unmet need associated with age-related and disease-induced muscle degeneration.

Claims

I / We Claim:

1. A synergistic bioactive composition comprising: a. Curcuminoids, b. Ecdysterone, and c. Selenium, optionally in the form of their pharmaceutically acceptable salts, derivatives, isomers, precursors, plant sources, or metabolites.

2. The synergistic bioactive composition as claimed in claim 1, wherein Ecdysterone, Curcuminoids and Selenium are present in a ratio ranging from 1:0.000833:0.000008 to 1: 1000:0.25 .

3. The synergistic bioactive composition as claimed in claim 1, wherein: a. the amount of Curcuminoids is in the range of 0.03% to 99.40% w / w, based on the total weight of the composition; b. the amount of Ecdysterone is in the range of 0.05% to 99.09% w / w, based on the total weight of the composition; and c. the amount of Selenium is in the range of 0.0002% to 3.7037% w / w, based on the total weight of the composition.

4. The synergistic bioactive composition as claimed in claim 1, wherein: a. Curcuminoids are present in an amount ranging from 1 to 2000 mg; b. Ecdysterone is present in an amount ranging from 2 to 1200 mg; and c. Selenium is present in an amount ranging from 0.01 to 0.5 mg.

5. The synergistic bioactive composition as claimed in claim 1, wherein the composition is formulated for oral administration and is in the form of one or more of: tablet, capsule, powder, pill, hard capsule fdled with liquid or solids, soft capsule, granule, pellet, caplet, mini-tablet, gummy, syrup, suspension, sachet, modified-release formulation, or any other orally administrable dosage form.

6. The synergistic bioactive composition as claimed in claim 1, further comprising one or more pharmaceutically acceptable excipients selected from: a bulking agent, disintegrant, binder, solubilizing agent, lubricant, glidant, or a mixture thereof.

7. The synergistic bioactive composition claimed in claim 1, wherein oral administration of the composition provides enhanced effects compared to the combined individual effects of curcuminoids, ecdysterone and selenium, as evidenced by at least one of the following: a. improves muscle strength by increasing grip strength by at least 24.06% more than the combined individual effects of curcuminoids, ecdysterone and selenium; or b. improves body weight by at least 22.20% more than the combined individual effects of curcuminoids, ecdysterone and selenium; or c. improves motor activity by increasing gait speed and reducing step number by at least 41.47% and at least 16.35% respectively more than the combined individual effects of curcuminoids, ecdysterone and selenium; or d. improves motor coordination and performance by increasing staying time on revolving rotarod by at least 21.38% more than the combined individual effects of curcuminoids, ecdysterone and selenium; or e. reduces muscle wasting by reducing serum interleukin-6 levels by at least 51.56% more than the combined individual effects of curcuminoids, ecdysterone and selenium; or f. improves muscle mitochondrial content and functions by increasing serum SIRT-1 levels by at least 26.77% more than the combined individual effects of curcuminoids, ecdysterone and selenium.

8. The synergistic bioactive composition as claimed in claim 1, wherein the composition is used for the treatment or management of sarcopenia, frailty, muscle atrophy, muscle weakness, muscle injury, or other related muscle health disorders.

9. The synergistic bioactive composition as claimed in claim 1, wherein the composition comprises: a. Curcuminoids in an amount ranging from 1 mg to 2000 mg; b. Ecdysterone in an amount ranging from 2 mg to 1200 mg; c. Selenium in an amount ranging from 0.01 mg to 0.5 mg; wherein Ecdysterone, Curcuminoids and Selenium are present in a ratio ranging from 1:0.000833:0.000008 to 1: 1000:0.25; wherein the composition is formulated for oral administration; and wherein oral administration of the composition: improves muscle strength by increasing grip strength by at least 24.06% more than the combined individual effects of curcuminoids, ecdysterone and selenium; or improves muscle mitochondrial content and function by increasing serum SIRT-1 levels by at least 26.77% more than the combined individual effects of curcuminoids, ecdysterone and selenium.

10. A kit comprising: a. Ecdysterone, b. Curcuminoids, and c. Selenium, optionally in the form of their pharmaceutically acceptable salts, derivatives, isomers, precursors, plant sources, or metabolites, wherein Ecdysterone, Curcuminoids, and Selenium, are provided either: a. as separate compositions within the kit, or b. as a single composition comprising a combination of two or more of Ecdysterone, Curcuminoids, and Selenium, wherein the kit is formulated for oral administration and is intended for use in the treatment or management of sarcopenia, frailty, muscle atrophy, muscle weakness, muscle injury, or other muscle health-related disorders.

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