Synergistic composition for poor muscle health and sarcopenia

Abstract

The present invention relates to a synergistic composition for the improvement of compromised muscle health and management of sarcopenia. In particular, the invention provides a composition comprising ecdysterone, calcium hydroxy methylbutyrate, and selenium, wherein the constituents act synergistically to promote enhancement of skeletal muscle mass, muscular strength, and functional physical performance. Sarcopenia is a progressive and degenerative condition characterized by the loss of skeletal muscle mass and strength, commonly associated with aging or chronic disease and is recognized as a major contributor to increased risk of falls, mobility limitations, physical disability and elevated healthcare burden. The composition disclosed herein offers a comprehensive therapeutic approach for the prevention, delay or treatment of sarcopenia and related muscle-wasting disorders. The composition is formulated for oral administration and may be presented in various dosage forms including but not limited to powder, tablet, capsule, and syrup. The oral formulation facilitates user compliance and effective systemic delivery, thereby providing a practical and efficacious intervention for mitigating skeletal muscle deterioration and its associated physiological and functional impairments.

Description

[0001] SYNERGISTIC COMPOSITION FOR POOR MUSCLE HEALTH AND SARCOPENIA RELATED APPLICATION:

[0002] The present application claims benefit of the Indian Provisional Application No. IN202421081653 filed on, October 25th, 2024 the entire contents of which are hereby incorporated by reference.

[0003] FIELD OF THE INVENTION

[0004] The present invention relates to a synergistic composition for the improvement of compromised muscle health and management of sarcopenia. In particular, the invention provides a composition comprising ecdysterone, calcium hydroxy methylbutyrate, and selenium, wherein the constituents act synergistically to promote enhancement of skeletal muscle mass, muscular strength, and functional physical performance. Sarcopenia is a progressive and degenerative condition characterized by the loss of skeletal muscle mass and strength, commonly associated with aging or chronic disease and is recognized as a major contributor to increased risk of falls, mobility limitations, physical disability and elevated healthcare burden. The composition disclosed herein offers a comprehensive therapeutic approach for the prevention, delay or treatment of sarcopenia and related muscle-wasting disorders. The composition is formulated for oral administration and may be presented in various dosage forms including but not limited to powder, tablet, capsule, and syrup. The oral formulation facilitates user compliance and effective systemic delivery, thereby providing a practical and efficacious intervention for mitigating skeletal muscle deterioration and its associated physiological and functional impairments. BACKGROUND OF THE INVENTION

[0005] Sarcopenia is recognized as a progressive and generalized skeletal muscle disorder characterized by an accelerated decline in muscle mass, strength and functional performance. While primarily associated with advancing age, the etiology of sarcopenia is multifactorial and may be influenced by nutritional deficiencies, hormonal dysregulation, reduced physical activity, and the presence of chronic pathological conditions. This condition poses a significant public health concern due to its adverse impacts on physical function and quality of life, contributing to an increased risk of falls, frailty, morbidity and mortality. The principal clinical manifestations of sarcopenia include measurable reductions in skeletal muscle quantity, strength and performance capacity, which progressively impair mobility and daily living activities. The consequences of sarcopenia are substantial and include, but are not limited to, loss of independence, increased incidence of disability, extended hospitalizations, and elevated healthcare utilization and costs. Accordingly, there exists a critical and unmet need for effective therapeutic or preventive interventions that address the multifaceted nature of sarcopenia.

[0006] Skeletal muscle constitutes approximately 40% of total body weight and accounts for an estimated 50-75% of total body protein content. It performs essential physiological functions, including maintenance of posture, generation of force and power, and facilitation of voluntary body movement. The maintenance of muscle mass is governed by a dynamic equilibrium between protein synthesis and degradation, which is modulated by various internal and external factors such as nutritional intake, physical activity, endocrine function and general health status. With advancing age or the onset of chronic disease, this balance is often disrupted, resulting in a net loss of muscle mass. The consequent muscle atrophy contributes to a spectrum of adverse health outcomes including but not limited to reduced muscular strength, impaired immune function, increased susceptibility to infections, delayed wound healing, and diminished capacity to perform routine activities of daily living. These physiological impairments collectively exacerbate the risk of disability and dependence, highlighting the need for targeted interventions to preserve or restore skeletal muscle integrity.

[0007] KR10-2410771 discloses a pharmaceutical composition comprising blueberry extract for use in the prevention or treatment of sarcopenia. The disclosed invention targets the reduction in muscle mass and strength that occurs as a consequence of the aging process.

[0008] W02023 / 048504 discloses a composition for the prevention or treatment muscle weakness-associated diseases, including sarcopenia, comprising as an active ingredient, a Rosa davurica Pallas extract, a fraction thereof or a fermented product thereof.

[0009] KR102229177 discloses a composition for the prevention or treatment of sarcopenia, wherein the active component comprises a natural extract consisting of a mixed extract of a rosemary (Rosmarinus officinalis) and a soybean (Glycine max).

[0010] WO2023 / 068747 discloses a composition comprising reboxetine as an active ingredient for use in the prevention or treatment of sarcopenia.

[0011] IN202337052255 discloses a composition for the prevention or treatment of sarcopenia or osteoporosis, comprising cyclo-L-phenylalanyl-L-proline dipeptides as an active ingredient.

[0012] EP3470078 discloses a composition for preventing or treating sarcopenia, specifically, comprising an active ingredient selected from the group of genes of the SLIT-ROBO system, including slitl, slit2, slit3, robol, robo2, and fragments thereof, or proteins expressed therefrom. The composition is described as effective for preventing or treating a muscle disease and for improving muscular function. Current strategies for managing sarcopema are predominantly limited to exercise regimens and nutritional interventions, as no specific pharmacological agents have been approved for this condition. These approaches primarily aim to attenuate muscle loss and to enhance muscle strength and functional capacity. Nevertheless, a significant unmet medical need remains for effective pharmacological therapies capable of addressing the complex and multifactorial pathophysiology of sarcopenia. Consequently, there is an ongoing demand for novel therapeutic agents or compositions that can complement existing management strategies and provide a more comprehensive and efficacious treatment option for individuals suffering from this progressive and debilitating muscle disorder.

[0013] OBJECTIVE OF THE INVENTION

[0014] The primary objective of the present invention is to provide a synergistic composition for the management of compromised muscle health and / or sarcopenia, the composition comprising ecdysterone, calcium hydroxy methylbutyrate, and selenium as active ingredients. The composition is formulated to effectively enhance or maintain muscle mass, muscular strength, and functional physical performance, thereby addressing key clinical features associated with muscle degeneration.

[0015] One objective of the present invention is to promote and maintain muscle health through the use of a synergistic combination of ecdysterone, calcium hydroxy methylbutyrate, and selenium, thereby mitigating adverse clinical outcomes associated with sarcopenia including but not limited to increased risk of falls, functional decline, and increased healthcare utilization and costs.

[0016] One objective of the present invention is to improve muscle quality and functional performance through the synergistic action of ecdysterone, calcium hydroxyl methylbutyrate, and selenium, thereby facilitating enhanced body movement, maintenance of posture and promoting overall physical independence in individuals experiencing or at risk of muscle detenoration.

[0017] Another objective of the present invention is to prevent or reduce the risk of complications associated with muscle loss, including but not limited to impaired immune function, reduced ability to perform physical activities, and prolonged hospitalization through the administration of the synergistic composition comprising ecdysterone, calcium hydroxyl methylbutyrate and selenium.

[0018] One more objective of the present invention is to stimulate protein synthesis and promote muscle regeneration, thereby contributing to an increase in muscle mass and strength, which are crucial for counteracting the progression of sarcopenia and related muscle disorders.

[0019] A further objective of the present invention is to provide a pharmaceutical composition that enhances muscle endurance, vitality, and resistance to physiological stress, thereby promoting overall well-being and improving quality of life in individuals suffering from compromised muscle health or related muscular conditions.

[0020] One objective of the present invention is to optimize the dosage and formulation of the synergistic composition comprising ecdysterone, calcium hydroxyl methylbutyrate, and selenium to enable effective oral administration for the management of sarcopenia, thereby providing a convenient, accessible and patient-compliant therapeutic option.

[0021] One more objective of the present invention is to validate the efficacy of the synergistic composition comprising ecdysterone, calcium hydroxyl methylbutyrate, and selenium through in vitro studies and / or suitable animal models, thereby demonstrating its therapeutic potential for the treatment or management of sarcopenia and related muscle -degenerative conditions.

[0022] Yet another objective of the present invention is to provide a versatile composition formulated for oral administration, wherein the composition may be presented in the form of tablets, capsules, powders, pills, hard capsules filled with liquids or solids, soft capsules, granules, pellets, caplets, mini-tablets, gummies, syrups, suspensions, sachets, modified-release forms, or any other pharmaceutically acceptable oral dosage form suitable for effective delivery of the active ingredients.

[0023] These objectives collectively underscore the innovative and multifaceted approach of the present synergistic composition in effectively addressing the challenges associated compromised muscle health and sarcopenia, thereby offering novel therapeutic possibilities for enhancing muscular function, physical well-being and overall quality of life in affected individuals.

[0024] SUMMARY OF THE INVENTION

[0025] The present invention relates to a synergistic composition for the improvement of compromised muscle health and the management of sarcopenia. More particularly, the invention provides a composition comprising ecdysterone, calcium hydroxy methylbutyrate, and selenium, which act synergistically to promote the enhancement of muscle mass, muscular strength, and functional physical performance. The composition offers a comprehensive therapeutic approach for the prevention and treatment of sarcopenia - a progressive musculoskeletal disorder characterized by the decline of skeletal muscle mass and strength, conditions that substantially increase the risk of falls, physical disability, and impose a significant burden on healthcare system. The composition is intended for oral administration and may be formulated in a variety of pharmaceutically acceptable dosage forms, including but not limited to tablets, capsules, powders, pills, hard capsules filled with liquids or solids, soft capsules, granules, pellets, caplets, mini-tablets, gummies, syrups, suspensions, sachets, modified-release forms, or any other suitable oral dosage form. Such versatility in formulation provides an effective, convenient and user-friendly therapeutic option for mitigating muscle deterioration and its associated complications. The primary aspect of the present invention is its focus on addressing the multifactorial challenges associated with sarcopenia. Skeletal muscle comprises a substantial portion of the human body mass and accounts for a significant percentage of the body’s protein content. It plays a critical role in generating force, maintaining posture, and enabling voluntary bodily movements, all of which are essential for sustaining functional independence. However, with advancing age and in the presence of various pathological conditions, skeletal muscle mass and strength progressively decline. This decline results from an imbalance between protein synthesis and degradation, further exacerbated by factors including nutritional deficiencies, hormonal fluctuations, and reduced physical activity. Sarcopenia exacerbates these physiological deteriorations, thereby increasing the risks of falls, functional impairment, frailty and mortality. These challenges highlight an urgent and unmet medical need for effective therapeutic interventions to prevent, mitigate or reverse the progression of sarcopenia.

[0026] One more aspect of the present invention involves the synergistic combination comprising ecdysterone, calcium HMB, and selenium, wherein each component provides distinct and complementary pharmacological effects effective in combating sarcopenia.

[0027] Another aspect of the present invention relates to the formulation of a synergistic composition suitable for management of compromised muscle health and sarcopenia in clinical applications. The composition comprises ecdysterone, selenium, and calcium HMB, optionally in the form of their pharmaceutically acceptable salts, metabolites, derivatives, or isomers, together with suitable pharmaceutically acceptable excipients. The composition may be formulated into a wide range of pharmaceutical dosage forms to accommodate diverse patient requirements and preferences, Such dosage forms include, but are not limited to tablets, capsules, powders, pills, hard capsules fdled with liquids or solids, soft capsules, granules, pellets, caplets, mini-tablets, gummies, syrups, suspensions, sachets, modified-release forms, or any other suitable oral dosage form. This versatility in formulation ensures optimal delivery and bioavailability of active ingredients for effective therapeutic outcomes.

[0028] One more aspect of the present invention encompasses patent claims directed to critical features of the synergistic composition including but not limited to specific selenium concentrations, defined ratios of ecdysterone to calcium hydroxy methylbutyrate (calcium HMB), and key formulation parameters that are essential to achieving optimal therapeutic efficacy in the prevention and management of sarcopenia.

[0029] In summary, the synergistic composition according to the present invention represents a significant advancement in the field of muscle health management. By combining ecdysterone, calcium hydroxy methylbutyrate and selenium, the invention provides a comprehensive and effective approach for mitigating muscle loss, enhancing muscle function, and improving the overall quality of life for individuals suffering from sarcopenia and related muscle-degenerative conditions.

[0030] BRIEF DESCRIPTION OF THE DRAWINGS:

[0031] Figure 1: Grip Strength

[0032] Figure 2: Body weight

[0033] Figure 3: Gait speed

[0034] Figure 4: Step numbers

[0035] Figure 5: Rotarodtest

[0036] Figure 6: Serum IL-6

[0037] Figure 7: Serum SIRT-1

[0038] DETAILED DESCRIPTION OF THE INVENTION

[0039] The following detailed description illustrates various embodiments of the present subject matter. These embodiments are described with sufficient detail to enable those skilled in the art to make and use the invention. It is to be understood that other embodiments may be utilized and that the structural, procedural and other changes may be made without departing from the scope of the present subject matter as defined by the appended claims.

[0040] 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.

[0041] In view of the aging global population and the rising incidence of sarcopenia, the development of effective therapeutic interventions, such as the synergistic composition disclosed in the present invention, is of critical importance. By targeting the underlying physiological mechanisms responsible for muscle degradation and offering a practical, clinically applicable solution that can be seamlessly integrated into existing healthcare systems, the present invention constitutes a notable advancement in the field of muscle health and sarcopenia management. The disclosed composition provides a promising therapeutic strategy for improving muscle mass, strength, and functional performance, thereby enhancing the overall quality of life for affected individuals on a global scale. This underscores the ongoing need for continued innovation and research aimed at addressing age-related muscle decline and associated comorbidities.

[0042] The present invention relates to a synergistic composition designed specifically for the management of compromised muscle health and / or sarcopenia. The composition comprises ecdysterone, calcium hydroxy methylbutyrate (Ca HMB), and selenium, which act collectively to enhance muscle mass, strength and functionality, thereby providing an effective therapeutic approach for the prevention and treatment of sarcopenia and related muscular disorders. In one embodiment, the present invention leverages the dynamic and plastic nature of skeletal muscle, which constitutes a significant portion of total human body weight and protein content. Skeletal muscles play a critical role in force generation, posture maintenance, locomotion, and the preservation of functional independence. However, various physiological and pathological factors such as nutritional deficiencies, hormonal imbalances, physical inactivity, injuries or chronic diseases can disrupt the finely regulated balance between muscle protein synthesis and degradation leading to a net loss of muscle tissue. This imbalance contributes to the onset and progression of sarcopenia, a condition characterized by a gradual decline in skeletal muscle mass and strength. Sarcopenia is associated with increased risk of falls, functional impairment, frailty, and elevated mortality, thereby representing a significant public health concern and underscoring the need for effective therapeutic strategies.

[0043] Another embodiment of the present invention recognizes the significant clinical and economic burden associated with sarcopenia, a condition characterized by a progressive decline in skeletal muscle mass, strength and functional capacity. Sarcopenia is further associated with increased risk of adverse health outcomes, including but not limited to falls, fractures, impaired mobility and reduced quality of life. Additionally, the condition contributes to elevated healthcare resource utilization including prolonged hospitalization, increased frequency of intensive care units (ICU) admission and overall heightened healthcare expenditures. The present invention addresses complications arising from sarcopenia such as muscular weakness, impaired immune function, increased susceptibility to infection, delayed tissue repair and decreased physical performance. Accordingly, this embodiment provides for compositions and methods aimed at ameliorating sarcopenia symptoms and improving muscular health and functionality in affected individuals.

[0044] Yet another embodiment of the present invention is directed to overcoming the current deficiency in targeted pharmacological therapies for the treatment and management of sarcopenia. At present, conventional management paradigms primarily focus on non-pharmacologic interventions, such as structured physical activity and dietary optimization, which, while beneficial, may not adequately address the underlying pathophysiological mechanisms of muscle atrophy and functional decline. Accordingly, this embodiment of the invention provides compositions and methods comprising a synergistic combination of ecdysterone, calcium HMB, and selenium. These ingredients when administered in combination, exhibit complementary pharmacodynamic activity conducive to enhancing muscle health, mitigating the progression of sarcopenia, and restoring skeletal muscle mass and function.

[0045] In a further embodiment, the present invention recognizes the synergistic potential of ecdysterone, calcium HMB, and selenium in promoting and maintaining muscle health. This embodiment underscores the significance of assessing the combined pharmacological effects of these ingredients in both preclinical and clinical settings to establish therapeutic efficacy. Experimental evidences support the effectiveness of the composition in enhancing muscle related health parameters, thereby demonstrating its utility as a therapeutic intervention for the prevention and / or treatment of sarcopenia and muscle degeneration. The invention further encompasses a synergistic composition comprising ecdysterone, selenium, and calcium HMB, optionally in the form of pharmaceutically acceptable salts, metabolites, derivatives, or isomers thereof, and formulated with one or more pharmaceutically acceptable excipients to facilitate optimal delivery, stability and therapeutic efficacy.

[0046] Yet another embodiment of the present invention, the nutraceutical composition is formulated into one or more pharmaceutically or nutraceutically acceptable dosage forms selected from, but not limited to tablets, capsules, powders, solutions, suspensions or other liquid formulations, in accordance with the administration preferences and physiological needs of the intended target population.

[0047] According to one embodiment of the present invention, there is provided a synergistic bioactive composition comprising Hydroxy methylbutyrate, Ecdysterone, and Selenium, or pharmaceutically or nutraceutically acceptable salts, derivatives, isomers, precursors, plant-derived sources, or metabolites thereof. The composition is formulated for oral administration and may be delivered in a variety of suitable dosage forms, including but not limited to tablets, capsules, powders, pills, hard capsules filled with liquids or solids, soft gelatin capsules, granules, pellets, caplets, mini-tablets, gummies, syrups, suspensions, sachets, modified-release forms (including sustained release, delayed release and controlled release), or any other pharmaceutically acceptable oral dosage form for human or veterinary use.

[0048] The composition further comprises one or more pharmaceutically acceptable excipients that facilitate the development of a stable and effective dosage form, as well as enhance the bioavailability and overall performance of the formulation. Such excipients may include, but are not limited to diluents, binders, surfactants, lubricants, glidants, disintegrants, solvents, additives, or combination thereof.

[0049] In certain embodiments, the diluents are included in the composition 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. The diluents are present in an amount ranging from about 1% to about 98% by weight (w / w) of the total composition.

[0050] In certain embodiments, the binders utilized in the composition 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, or mixtures thereof. The binders are present in an amount ranging from about 0.1% to about 12% by weight (w / w) of the total composition.

[0051] In certain embodiments, the lubricants included in the composition are selected from one or more of magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, talc, polyethylene glycol, colloidal silicon dioxide, glyceryl behenate, or zinc stearate, or mixtures thereof. The lubricants are present in an amount ranging from about 0.5% to about 10% by weight (w / w) of the total composition.

[0052] In certain embodiments the glidants are incorporated into the composition are selected from one or more of colloidal silicon dioxide, hydrophobic colloidal silica, silicon dioxide, talc, tribasic calcium phosphate, or mixtures thereof. The glidants are present in an amount ranging from about 0.5% to aboutlO% by weight (w / w) of the total composition.

[0053] In certain embodiments, the disintegrants employed in the composition are 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 mixtures thereof. The disintegrants are present in an amount ranging from about 0.4% to about 15% by weight (w / w) of the total composition.

[0054] In certain embodiments, the surfactants incorporated into the composition are 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, benzethomum chloride, cetylpyridinium chloride, lecithin, phosphatidylcholine, lauryl betaine, or mixtures thereof.

[0055] The composition of the present invention may be prepared using conventional techniques well known in the art for formulating oral dosage forms. Depending on the desired characteristics of the final product, the formulation may be produced by direct compression, wherein the active pharmaceutical ingredients are blended with suitable excipients including but not limited to fillers, binders, disintegrants, and lubricants, and subsequently compressed into tablets. Alternatively, the composition may be processed using granulation methods, such as wet granulation or dry granulation, to improve flowability and compressibility of the blend prior to tableting or encapsulation. The resulting formulation may be filled into unit dosage forms such as sachets or capsules for ease of administration. In further, embodiments, the composition may be provided in the form of powders or granules intended for reconstitution into an oral suspension. Other pharmaceutically or nutraceutically acceptable processing methods may also be employed, provided they achieve the desired dosage form while maintaining formulation stability, therapeutic efficacy, and patient compliance. Methods for the preparation of nutraceutical compositions suitable for oral administration are well established in the art.

[0056] The present invention provides a synergistic bioactive composition comprising Hydroxy methylbutyrate, Ecdysterone, and Selenium, wherein each active ingredient may be present in the form of their pharmaceutically or nutraceutically acceptable salts, derivatives, isomers, precursors, plant-derived sources, or metabolites thereof.

[0057] According to the present invention, hydroxy methylbutyrate (HMB) may be present in any pharmaceutically or nutraceutically acceptable salt form, preferably the suitable salt is calcium hydroxy methylbutyrate (Ca-HMB). The present invention provides a synergistic bioactive composition comprising Hydroxy methylbutyrate, Ecdysterone, and Selenium, wherein Hydroxy methylbutyrate is present in an amount ranging from 50 mg to 6500 mg, 100 mg to 6250 mg, 150 mg to 6000 mg, 200 mg to 5800 mg, 250 mg to 5750 mg, 300 mg to 5500 mg, 350 mg to 5250 mg, 400 mg to 5000 mg

[0058] The present invention provides a synergistic bioactive composition comprising Hydroxy methylbutyrate, Ecdysterone, and Selenium, wherein Ecdysterone is present in an amount ranging from 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, 2 mg to 725 mg, 2 mg to 700 mg.

[0059] The present invention provides a synergistic bioactive composition comprising Hydroxy methylbutyrate, 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 mg to 0.40, 0.01 mg to 0.38 mg, 0.01 mg to 0.35 mg, 0.01 mg to 0.30 mg, 0.01 mg to 0.25 mg.

[0060] In another embodiment, the present invention provides a synergistic bioactive composition comprising Hydroxy methylbutyrate, Ecdysterone, and Selenium, optionally in the form of their pharmaceutically or nutraceutically acceptable salts, derivatives, isomers, precursors, plant-derived sources, or metabolites thereof, wherein the. Ecdysterone, Hydroxy methylbutyrate and Selenium are present in a ratio rating from 1 : 0.0417 : 0.000008 to 1:3250:0.250, 1 : 0.0909 : 0.000009 to 1:3125:0.225, 1 : 0.1667 : 0.000011 to 1:3000:0.2100, 1 : 0.2500 : 0.000013 to 1:2900:0.2000, 1 : 0.3226 : 0.000013 to 1:2875:0.1900, 1 : 0.4000 : 0.000013 to 1:2750:0.1750, 1 : 0.5714 : 0.000014 to 1:2500:0.1250.

[0061] In another embodiment, the present invention provides a synergistic bioactive composition comprising Hydroxy methylbutyrate, Ecdysterone, and Selenium, optionally in the form of their pharmaceutically or nutraceutically acceptable salts, derivatives, isomers, precursors, plant-derived sources, or metabolites wherein Ecdysterone and Hydroxy methylbutyrate are in a ratio of 1:0.5714 to 1:2500.

[0062] In one embodiment of the present invention, the synergistic bioactive composition comprises Hydroxy methylbutyrate, Ecdysterone, and Selenium, optionally in the form of their pharmaceutically or nutraceutically acceptable salts, derivatives, isomers, precursors, plant-derived sources, or metabolites wherein Hydroxy methylbutyrate and Selenium are in a ratio of 1:0.000002 to 1:0.000625.

[0063] In one embodiments of the present invention, the synergistic bioactive composition comprises Hydroxy methylbutyrate, Ecdysterone, and Selenium, optionally in the form of their pharmaceutically or nutraceutically acceptable salts, derivatives, isomers, precursors, plant-derived sources, or metabolites wherein Ecdysterone and Selenium are in a ratio of 1:0.000014 to 1:0.125.

[0064] According to present invention, hydroxy methylbutyrate or its pharmaceutically or nutraceutically acceptable salts, derivatives, isomers, precursors, or metabolites thereof, may be obtained through chemical synthesis, produced via, fermentation processes, or isolated and purified from plant-derived sources.

[0065] According to present invention, Ecdysterone or its pharmaceutically or nutraceutically acceptable salts, derivatives, isomers, precursors, or metabolites thereof, may be obtained through chemical synthesis, produced via fermentation processes, or extracted and purified from plant-derived sources.

[0066] According to present invention, Selenium or its pharmaceutically or nutraceutically acceptable salts, derivatives, isomers, precursors, or metabolites thereof, may be obtained through chemical synthesis, produced via fermentation process, or isolated from plant-derived sources. In another embodiment, the present invention provides a synergistic bioactive composition comprising Hydroxy methylbutyrate, Ecdysterone, and Selenium, optionally in the form of their pharmaceutically or nutraceutically acceptable salts, derivatives, isomers, precursors, plant-derived sources, or metabolites, wherein the composition comprises: Hydroxy methylbutyrate is present in the range of 1.54% to 99.97% w / w of the total weight of the composition, Ecdysterone is present in the range of 0.03% to 96% w / w of the total weight of the composition, and Selenium is present in the range of 0.0001% to 0.9525% w / w of the total weight of the composition.

[0067] The synergistic composition(s) as per the present invention, wherein the amount of ecdysterone is present in the range of 0.03 to 96% of the combined total weight of calcium hydroxy methylbutyrate and ecdysterone present in the composition.

[0068] The synergistic composition(s) as per the present invention, wherein the amount of calcium hydroxy methylbutyrate is present in the range of 4 to 99.97% of the combined total weight of calcium hydroxy methylbutyrate and ecdysterone present in the composition.

[0069] The synergistic composition(s) as per the present invention, wherein oral administration of an effective dose of the composition helps to manage poor muscle health and sarcopenia.

[0070] The synergistic composition(s) as per the present invention further comprise one or more pharmaceutically or nutraceutically acceptable excipients selected the group of from the group of a diluent, a binder, a surfactant, a lubricant, a glidant, an additive, a solvent or mixtures thereof.

[0071] The synergistic composition (s) of the present invention are formulated in a dosage form selected from the group consisting of a powder, tablet, capsule and syrup. The present invention provides a synergistic bioactive composition comprising Hydroxy methylbutyrate, Ecdysterone, and Selenium, optionally in the form of their pharmaceutically or nutraceutically acceptable salts, derivatives, isomers, precursors, plant-derived sources, or metabolites. In certain embodiments, the composition comprises Hydroxy methylbutyrate in an amount ranging from about 50 mg to about 6500 mg, Ecdysterone in an amount ranging from about 2 mg to about 1200 mg, and Selenium in an amount ranging from about 0.01 mg to about 0.5 mg. The composition is formulated for oral administration and exhibits a synergistic effect in enhancing muscle strength, as evidenced by an increase in grip strength by at least 22.91% relative to the combined individual effects of Hydroxy methylbutyrate, Ecdysterone, and Selenium when administered separately. The observed increase in grip strength serves as a measurable indicator of improved muscle health.

[0072] The present invention provides a synergistic bioactive composition comprising Hydroxy methylbutyrate, Ecdysterone, and Selenium, optionally in the form of their pharmaceutically or nutraceutically acceptable salts, derivatives, isomers, precursors, plant-derived sources, or metabolites. In certain embodiments, the composition comprises Hydroxy methylbutyrate in an amount ranging from about 50 mg to about 6500 mg, Ecdysterone in an amount ranging from about 2 mg to about 1200 mg, and Selenium in an amount ranging from about 0.01 mg to about 0.5 mg. The composition is formulated for oral administration and exhibits a synergistic effect in improving muscle strength, as demonstrated by increase in body weight by at least 34.86% greater than the combined individual effects of Hydroxy methylbutyrate, Ecdysterone, and Selenium administered separately. The observed increase in body weight serves as an indicator of potential improvement in sarcopenia.

[0073] The present invention provides a synergistic bioactive composition comprising Hydroxy methylbutyrate, Ecdysterone, and Selenium, optionally in the form of their pharmaceutically or nutraceutically acceptable salts, derivatives, isomers, precursors, plant sources, or metabolites. The composition comprises Hydroxy methylbutyrate in an amount ranging from about 50 mg to about 6500 mg, Ecdysterone in an amount ranging from about 2 mg to about 1200 mg, and Selenium in an amount ranging from about 0.01 mg to about 0.5 mg. The composition is formulated for oral administration and exhibits a synergistic effect by improving motor activity by increasing gait speed and reducing step number by at least 27.05% and least 27.57%, respectively, more than the combined individual effects of Hydroxy methylbutyrate, Ecdysterone, and Selenium administered separately. The observed increase in gait speed reflects improved muscle, while a decreased number of steps corresponds to better muscle function, with higher step counts generally indicating greater muscle impairment.

[0074] The present invention provides a synergistic bioactive composition comprising Hydroxy methylbutyrate, Ecdysterone, and Selenium, optionally in the form of their pharmaceutically or nutraceutically acceptable salts, derivatives, isomers, precursors, plant-derived sources, or metabolites. In certain embodiments, the composition comprises Hydroxy methylbutyrate in an amount ranging from about 50 mg to about 6500 mg, Ecdysterone in an amount ranging from about 2 mg to about 1200 mg, and Selenium in an amount ranging from about 0.01 mg to about 0.5 mg. The composition is formulated for oral administration and exhibits a synergistic effect in improving motor coordination and physical performance, as evidenced by an increase of at least 38.21% in the duration of stay on s revolving rotarod apparatus, relative to the combined individual effects of Hydroxy methylbutyrate, Ecdysterone, and Selenium administered separately. Performance in the rotarod test serves as a recognized functional assessment of neuromuscular coordination and endurance, wherein reduced performance is considered as a key indicator of functional decline associated with sarcopenia.

[0075] The present invention provides a synergistic bioactive composition comprising Hydroxy methylbutyrate, Ecdysterone, and Selenium, optionally in the form of their pharmaceutically or nutraceutically acceptable salts, derivatives, isomers, precursors, plant-derived sources, or metabolites. In certain embodiments, the composition comprises Hydroxy methylbutyrate in an amount ranging from about 50 mg to about 6500 mg, Ecdysterone in an amount ranging from about 2 mg to about 1200 mg, and Selenium in an amount ranging from about 0.01 mg to about 0.5 mg. The composition is intended for oral administration and exhibits a synergistic effect in mitigating muscle wasting as evidenced by reduction in serum interleukin-6 levels of at least 41.38% greater than the combined individual effects of Hydroxy methyl butyrate, Ecdysterone, and Selenium administered separately. Elevated serum IL-6 levels are associated with systemic inflammation and accelerated muscle degradation in sarcopenia; thus a reduction in IL-6 is indicative of therapeutic efficacy in controlling sarcopenia progression.

[0076] The present invention provides a synergistic bioactive composition comprising Hydroxy methylbutyrate, Ecdysterone, and Selenium, optionally in the form of their pharmaceutically or nutraceutically acceptable salts, derivatives, isomers, precursors, plant-derived sources, or metabolites. In certain embodiments, the composition comprises Hydroxy methylbutyrate in an amount ranging from about 50 mg to about 6500 mg, Ecdysterone in an amount ranging from about 2 mg to about 1200 mg, and Selenium in an amount ranging from about 0.01 mg to about 0.5 mg. The composition is formulated for oral administration and exhibits a synergistic effect in enhancing muscle mitochondrial content and function, as demonstrated by an increase in serum SIRT-1 levels by at least 28.14% greater than the combined individual effects of Hydroxy methylbutyrate, Ecdysterone, and Selenium administered orally. Elevated SIRT-1 levels are indicative of improved mitochondrial biogenesis and metabolic activity in muscle tissue, thereby contributing to the maintenance of muscle health and attenuation of sarcopenic progression.

[0077] The composition of the present invention is intended for use in the treatment, prevention or management of sarcopenia, frailty, muscle atrophy, muscle weakness, muscle injury, or other disorders associated with impaired muscle health. The present invention provides a synergistic bioactive composition comprising Hydroxy methylbutyrate, Ecdysterone, and Selenium, wherein the composition comprises: Hydroxy methylbutyrate in an amount ranging from about 50 mg to about 6500 mg; Ecdysterone in an amount ranging from about 2 mg to about 1200 mg; and Selenium in an amount ranging from about 0.01 mg to about 0.5 mg; wherein Ecdysterone. Hydroxyl methylbutyrate and selenium are present in a ratio ranging from 1 : 0.2914 : 0.000008 to 1:2500:0.400 ; wherein the composition is intended for oral administration; and wherein oral administration of the composition: i) improves muscle strength, as evidenced by an increase in grip strength by at least 22.91% relative to the combined individual effects of hydroxy methylbutyrate, ecdysterone, and selenium administered separately; and ii) enhances muscle mitochondrial content and function as evidenced by an increase in serum Sirtuin-1 (SIRT-1) levels of at least 28.14% relative to the combined individual effects of Hydroxy methylbutyrate, Ecdysterone, and Selenium administered separately.

[0078] The present invention provides a synergistic bioactive composition comprising Hydroxy methylbutyrate, Ecdysterone, and Selenium, wherein the composition comprises: Hydroxy methylbutyrate in an amount ranging from about 1.54% to about 99.97% w / w of the total composition; Ecdysterone in an amount ranging from about 0.03 % to about 96.00 % w / w of the total composition; and Selenium in an amount ranging from about 0.0001 % to about 0.9524 % w / w of the total composition. The composition is formulated for oral administration and upon such administration, exhibits a synergistic effect by: (i) improving muscle strength, as demonstrated by an increase in grip strength of at least 22.91% compared to the combined individual effects of Hydroxy methylbutyrate, Ecdysterone, and Selenium; and (ii) enhancing muscle mitochondrial content and function, as evidenced by an increase in serum Sirtuin-1 (SIRT-1) levels of at least 28.14% compared to the combined individual effects of the individual components. The composition is indicated for use in the treatment or management of sarcopenia. According to the present invention, the composition may alternatively be provided as a combination of three separate compositions, wherein a first composition comprises Hydroxy methylbutyrate, a second composition comprises ecdysterone, and a third composition comprises selenium, each optionally in the form of their pharmaceutically or nutraceutically acceptable salts, derivatives, isomers, precursors, or plant-derived sources or metabolites, and wherein the three compositions are intended for simultaneous or sequential administration to a subject in need thereof. In certain embodiments, the present invention further provides a kit comprising the three individual compositions in separate dosage forms, optionally accompanied by instructions for administration.

[0079] The development of the composition of the present invention addresses a significant unmet medical need in managing sarcopenia, a progressive muscle-wasting condition that adversely affects the quality of life, physical function and independence in affected individuals. The composition offers a pharmacological intervention that complements existing non-pharmacological approaches such as nutritional supplementation and physical exercise, thereby enhancing the overall effectiveness of sarcopenia management strategies. The synergistic inclusion of ecdysterone, along with calcium hydroxy methylbutyrate, and selenium provides a multifactorial therapeutic approach targeting various physiological pathways involved in muscle maintenance, regeneration and function.

[0080] In summary, the present invention provides a novel and comprehensive approach for addressing the multifactorial challenges associated with poor muscle health and sarcopenia. The invention offers an integrated therapeutic strategy designed to enhance muscle mass, strength, and functional performance. Through rigorous experimental evaluation and validation, the composition of the present invention has demonstrated significant potential in improving overall muscle health and quality of life in individuals affected by sarcopenia. Accordingly, the invention represents a substantial advancement the field of muscle health management and therapeutic development.

[0081] EXAMPLES

[0082] The invention described herein encompasses various embodiments, features and processes as set forth above, with respect to their characteristics and methods of implementation. While certain aspects and embodiments have been emphasized, it is to be understood that modifications, equivalents and variations thereof may be made without departing from the spirit and the scope of the invention as defined by the appended claims.

[0083] EXAMPLE-1: COMPOSITION: Following is a general composition formula as per the present invention:

[0084] Ex. 1A Ex. IB Ex. 1C Ingredients % in w / w % in w / w In milligram Calcium hydroxy

[0085] 50 to 99 % 1.54 to 99.97% 50 to 6500 mg methylbutyrate

[0086] Ecdysterone 0.01 to 60 % 0.03 to 96.00% 2 to 1200 mg 0.0001 to

[0087] Selenium 0.00003 to 0.01% 0.01 to 0.5 mg 0.9524%

[0088] Excipients Q.s. Q.s. Q.s.

[0089]

[0090] Process for preparation of example 1 :

[0091] 1. Accurately weigh each ingredient in separate containers.

[0092] 2. Sift the previously weighed active ingredients and excipients through a sieve.

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

[0094] S Q Eldttampexy..

[0095] / i1t mgnu - S.No

[0096] Ingredients

[0097] S Q Eldttampexy..

[0098] / i2t mgnu - Hydroxy

[0099] 1 3000 1500 5250 5000 5500 5750 5800 6000 6250 6500 Methylbutyrate S Q Eldttampexy..

[0100] 2 Ecdysterone 12 6 72 / i53t mgnu - 700 750 775 800 900 1100 1200 3 Selenium 0.04 0.02 0.3 0.25 0.35 0.38 0.4 0.42 0.45 0.5

[0101] S Qdtty..

[0102] Microcrystalline 994.9 2497. 2007. 2 El1ampex49.8 1799. 1744. 1739. 1709. 1584. 1474.5 4

[0103] 8 / it mgnu

[0104] cellulose 49 1 84 - 81 66 67 74 73 3 Polyvinylpyrrolidon 149.8 120.4 107.9 104.6 104.3 102.5

[0105] 5 59.7 128.99 95.08 88.47 e 5 3 S Q Eldttampexy.. 9 8 8 8

[0106] 6 Magnesium stearate 9.95 24.97 20.07 21.5 18 / i5t mgnu - 17.45 17.4 17.1 15.85 14.75 Colloidal silicon

[0107] 7 5.97 14.99 12.04 12.9 10.8 1 S Q Eldttampexy0...47 10.44 10.26 9.51 8.85 dioxide / i6t mgnu - 149.8 120.4 107.9 104.6 104.3 102.5

[0108] 8 Hypromellose 59.7 128.99 95.08 88.47

[0109] 5 3 9 8 S Q Eldttampexy.. 8 8

[0110] 9 Polysorbate 80 9.95 24.97 20.07 21.5 18 17.45 17. / i7t4 mgnu - 17.1 15.85 14.75 10 Talc 19.9 49.95 40.14 42.99 35.99 34.9 34.79 34.2 31.7 29.5

[0111] S Q Eldttampexy..

[0112] 11 Zinc stearate 9.95 24.97 20.07 21.5 18 17.45 17.4 17.1 15.85 14.75

[0113] / i8t mgnu - 1498. 1204. 1289.9 1079. 1044. 1043. 1025.

[0114] 12 Dicalcium phosphate 597 950.8 884.74

[0115] 5 27 3 86 68 81 81 S Qdtt Elyampex..

[0116] Lactose 401.4 359.9 348.2 347.9 341.9 317.1 13 199 499.5 429.98 / it9 mgnu - 294.91 monohydrate 2 5 3 4 4 2 Sodium starch

[0117] 14 23.88 59.85 48.88 52.19 43.19 41.87 41.65 40.65 37.71 3 S Qdtty5.38 glycolate Elampe..x / it mgnu 5002. 6500. 9990. 10000. 9849. 1001 1007 1031 10519 1064109 -. Average weight

[0118]

[0119] 02 91 22 6 93 1.9 9.66 9.48 .73 6

[0120] Manufacturing process of Sachet:

[0121] 1. All the active ingredients (Hydroxy Methylbutyrate, Ecdysterone, 5 Selenium) and excipients were accurately weighed as per the batch formula and passed through an appropriate mesh sieve to remove lumps and ensure uniform particle size.

[0122] 2. Selenium and Ecdysterone, were pre-blended with a portion of diluent to ensure uniform distribution and prevent segregation.

[0123] 10 3. Hydroxy Methylbutyrate and remaining excipients were added to the blender along with the pre-blend and mixed thoroughly to achieve a homogeneous blend.

[0124] 4. Lubricants and glidants were added and mixed gently to improve flow properties without overmixing.

[0125] 5 5. The blend underwent in-process checks including blend uniformity and flow properties.

[0126] 6. The blended powder was filled into pre-formed sachets.

[0127] 7. Sachets were sealed and packed into suitable packs, labelled, and stored under recommended conditions.

[0128] 10

[0129] Example 3 - Tablets

[0130] Example-1 Example-2 Example-3 Example-4 Example-5 Std. Qty. Std. Qty. Std. Qty. Std. Qty. Std. Qty. S.No. Ingredients

[0131] mg / unit mg / unit mg / unit mg / unit mg / unit 1 Hydroxy Methylbutyrate 350 400 300 250 200 2 Ecdysterone 2 2 2 2 2 3 Selenium 0.04 0.04 0.35 0.38 0.03 4 Microcrystalline cellulose 114 140 110 104 99.54 5 Polyvinylpyrrolidone 10.33 11 9.87 9.45 9.11 6 Magnesium stearate 3.11 3.17 2.64 2.39 2.27 7 Colloidal silicon dioxide 2.64 2.87 2.19 1.94 1.73 8 Hypromellose 9.11 9.43 8.94 8.71 8.69 9 Polysorbate 80 1.87 1.93 1.71 1.63 1.58 10 Talc 1.81 1.89 1.68 1.59 1.51 11 Zinc stearate 1.75 1.95 1.71 1.53 1.34 12 Dicalcium phosphate 89.69 94.32 78.39 52.22 41.79 13 Lactose mono hydrate 68.52 75.18 61.13 58.31 49.34 14 Sodium starch glycolate 11.14 13.35 9.21 9.14 9.11

[0132]

[0133] Average weight 666.01 757.13 589.82 503.29 428.04

[0134] Manufacturing process of Tablets:

[0135] 1. All the active ingredients and excipients were accurately weighed as per the 15 batch formula and passed through a #40 sieve to remove lumps and ensure uniform particle size.

[0136] 2. Selenium and Ecdysterone were pre-blended with a portion of diluent to ensure uniform distribution and prevent segregation.

[0137] 3. Hydroxy Methylbutyrate and remaining excipients were added to the blender along with the pre-blend and mixed thoroughly to achieve a homogeneous blend.

[0138] 4. A binder solution was prepared and added to the blend while mixing to form uniform granules, which were passed through a suitable sieve and then

[0139] 5 dried.

[0140] 5. The dried granules were passed through a 20# mesh sieve to break lumps.

[0141] Lubricants and glidants were added and blended gently for 3-5 minutes to avoid over-lubrication.

[0142] 6. The blend from Step 5 was compressed to form tablets and hypromellose- 10 based film coating solution uniformly was applied over compressed tablets using a perforated coating pan.

[0143] 7. The finished products were packed into moisture-protective packaging, labelled, and stored under recommended conditions.

[0144] 15 Example 4 - Capsules

[0145] Example-1 Example-2 Example-3 Example-4 Example-5 Example-6 Std. Qty. Std. Qty. Std. Qty. Std. Qty. Std. Qty. Std. Qty. S.No. Ingredients

[0146] mg / unit mg / unit mg / unit mg / unit mg / unit mg / unit 1 Hydroxy Methylbutyrate 150 100 50 150 100 50 2 Ecdysterone 2 2 2 12 12 12 3 Selenium 0.04 0.04 0.01 0.5 0.35 0.38 4 Microcrystalline cellulose 89.11 84.79 82.43 89.11 84.79 82.43 5 Polyvinylpyrrolidone 9 8.74 8.19 9 8.74 8.19 6 Magnesium stearate 2.21 2.19 2.14 2.21 2.19 2.14 7 Colloidal silicon dioxide 1.65 1.59 1.47 1.65 1.59 1.47 8 Hypromellose 8.43 8.21 8.05 8.43 8.21 8.05 9 Polysorbate 80 1.42 1.31 1.14 1.42 1.31 1.14 10 Talc 1.39 1.25 1.09 1.39 1.25 1.09 11 Zinc stearate 1.29 1.17 1.04 1.29 1.17 1.04 12 Dicalcium phosphate 34.64 29.13 21.73 34.64 29.13 21.73 13 Lactose mono hydrate 38.27 33.32 31.39 38.27 33.32 31.39 14 Sodium starch glycolate 8.82 8.71 8.31 8.82 8.71 8.31

[0147]

[0148] Average weight 348.27 282.45 218.99 358.73 292.76 229.36

[0149] Manufacturing process of Capsules:

[0150] 1. All the active ingredients and excipients were accurately weighed as per the batch formula and passed through a #40 sieve to remove lumps and ensure uniform particle size.

[0151] 2. Selenium and Ecdysterone were pre-blended with a portion of diluent to ensure uniform distribution and prevent segregation.

[0152] 3. Hydroxy Methylbutyrate and remaining diluents, disintegrant, and binder were added to the blender along with the pre-blend and mixed thoroughly to achieve a homo S Qdttyg El..ampex -eneous blend.

[0153] / it mgnu

[0154] 4. Lubricants and glidan 1t 5ls ner m were added and blended gently for 3-5 minutes to avoid over-lubrication. S Qdtt Elyampex.. - / it mgn 2u

[0155] 5. The blend from Step 4 the fina C 1l _ _ blend into hard gelatin or HPMC capsules.

[0156] S Qdtty..

[0157] 6. The finished products were pac Elkampex -e / it 3 mgndu into moisture-protective packaging,

[0158] C 1 _ _

[0159] labelled, and stored under recommended conditions.

[0160] S Qdtty..

[0161] Elampex - / it mgnu

[0162] 45l per m

[0163] Example 5 - Syrup

[0164] S Qdtt Elyampex.. - / it 5 mgnu

[0165] C 1 _ _

[0166] S Qdtty..

[0167] Elampex - / it mgnu

[0168] 65l per m

[0169] S Qdtt Elyampex.. - S.No. Ingredients / it 7 mgnu

[0170] S Qdtty.. Hydroxy Elampex - 1 150 100 50 350 400 300 250 20 / it mgnu0 Methylbutyrate 85l per m 2 Ecdysterone 2 12 5 150 250 350 500 400 3 Selenium 0.04 0.04 0.01 0.5 0.35 0.38 0.04 0.04 4 Citric acid 10.86 10.41 10.22 13.29 14.32 12.24 11.97 11.13 5 Sodium benzoate 10.71 10.32 10.11 13.21 14.29 12.19 11.84 11.12 6 Methylparaben 1.34 1.39 1.21 1.67 1.79 1.58 1.53 1.47 7 Propylparaben 0.23 0.23 0.21 0.37 0.4 0.32 0.29 0.27 8 Glycerin 862 613 549 581 955 932 927 911 9 Sorbitol solution 1174 1169 1157 1149 1417 1312 1214 1198 10 Sweetener 321 319 311 325 447 421 411 399 11 Flavour 2.1 1.9 1.7 4.9 4.5 3.2 3.1 2.9 12 Colour 0.1 0.11 0.12 0.2 0.21 0.2 0.21 0.19

[0171] Up to Up to Up to Up to 5 Up to Up to 5 Up to Up to 5 13 Purified water

[0172] 5 ml 5 ml 5 ml ml 5 ml ml 5 ml ml

[0173]

[0174] Average weight 150 100 50 350 400 300 250 200 Manufacturing process of Syrup:

[0175] 1. All the active ingredients and excipients were accurately weighed as per the batch formula and passed through an appropriate mesh sieve to remove lumps and ensure uniform particle size.

[0176] 2. A syrup base was prepared by adding sorbitol solution and glycerin to required quantity of purified water while stirring. The solution was heated to around 40-50°C to aid dissolution and reduce viscosity.

[0177] 3. To the syrup base of step 2, citric acid, sodium benzoate, methylparaben, and propylparaben were sequentially added while mixing until completely dissolved.

[0178] 4. The active ingredients were dissolved separately in in a small volume of warm purified water and glycerin, and then added to the syrup base with continuous stirring.

[0179] 5. Flavoring agent, color and sweetener were added to the solution of step 4, and final volume was adjusted with adding purified water.

[0180] 6. After mixing the final product of step-5 is filled in suitable containers and sealed;

[0181] 7. The containers were packed, labelled, and stored under recommended conditions.

[0182] EXAMPLE 3: ANIMAL STUDY

[0183] Objective of the animal study: To Evaluate the Synergistic Effects of Calcium Hydroxy methylbutyrate, Ecdysterone, and Selenium in Sarcopenic Wistar Rats.

[0184] 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.

[0185] All animals were divided into groups as described below.

[0186] 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.

[0187] Table 1:

[0188] Group Treatment Dose and Route (From week 0 to 4) N Normal control group No Treatment

[0189] D Disease control group 0.5% CMC BID Per Oral

[0190] Tl Ca-HMB CaHMB 155 mg / kg BID Per Oral

[0191] T2 Ecdysterone Ecdysterone 10.33 mg / kg BID Per Oral Elemental Selenium 2.07 mcg / kg BID Per T3 Selenium

[0192] Oral

[0193] CaHMB 155 mg / kg BID per oral + Ca-HMB + Ecdysterone Ecdysterone 10.33 mg / kg BID per oral + T4

[0194] + Selenium Elemental Selenium 2.07 mcg / kg BID Per

[0195]

[0196] Oral

[0197] Ca-HMB: Calcium hydroxy methylbutyrate

[0198] BID: Twice daily

[0199] CMC: Carboxy Methyl Cellulose

[0200] At the end of Week 4, all animals were anesthetized with ketamine at a dose of lOOmg / 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.

[0201] Evaluation parameters:

[0202] • Anthropometric parameters:

[0203] o Body weight

[0204] • Behavioral parameters:

[0205] o Grip strength o Gait speed

[0206] o Step number

[0207] o Rota rod test

[0208] • ELISA parameters:

[0209] o Serum SIRT-1

[0210] o Serum IL-6

[0211] Test Parameters details:

[0212] Body weight: The body weight of each animal was measured using a weighing balance.

[0213] 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.

[0214] 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.

[0215] 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.

[0216] 5

[0217] 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 10 600 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.

[0218] 15 ELISA parameters: ELISA parameters like Serum IL-6 and Serum SIRT1 were measured on week -4 on ELISA kit, according to the ELISA kit insert.

[0219] All the data are represented as mean ± standard deviation and are statistically analyzed by two-way ANOVA followed by Tukey’s multiple comparison test. P- 20 value <0.05 indicates statistically significant difference between two groups.

[0220] Animal study results:

[0221] Table 2:

[0222] Grip strength (g)

[0223] Incremental improvement Sum of change in (%) in combination group Week 4 Change at Week individual Test Change in

[0224] Group combination

[0225] 4 vs. Control groups (T4) compared to the sum of (T1±T2±T3) group (T4) change in individual test groups (T1±T2±T3) N 994.67 ± 4.27 468.67

[0226] D 526.00 ± 5.55 0.00

[0227] T1 192.00 588.50 ± 4.93 62.50 243.67 26.91%

[0228] T2 614.17 ± 5.49 88.17

[0229] T3 567.33 ± 3.88 41.33

[0230]

[0231]

[0232] T4 769.67 ± 7.00 243.67 Grip strength is a widely recognized, reliable, and clinically validated indicator for assessing muscle strength and plays a key role in the diagnosis of sarcopenia; a progressive, age-related muscle -wasting condition. Declines in grip strength are 5 closely linked to impaired mobility, decreased functional capacity, increased frailty

[0233] and loss of independence. It also shows strong correlation with slower gait speed and diminished physical performance, both of which are defining characteristics of moderate to severe sarcopenia. An increase in grip strength indicates improved neuromuscular function and enhanced muscle integrity.

[0234] 10

[0235] Table 3:

[0236] Body weight (g)

[0237] Incremental improvement Sum of change in (%) in combination group Week 4 Change at Week individual Test Change in

[0238] Group combination

[0239] 4 vs. Control groups (T4) compared to the sum group (T4) of change in individual test (T1±T2±T3) groups (T1±T2±T3) N 376.33 ± 6.83 123.33

[0240] D 253.00 ± 5.83 0.00

[0241] T1 278.00 ± 8.00 25.00

[0242] 72.50 100.67 38.86%

[0243] T2 288.67 ± 4.23 35.67

[0244] T3 264.83 ± 11.44 11.83

[0245] T4 353.67 ± 10.25 100.67

[0246]

[0247] Body weight is a key supportive measure in assessing and managing sarcopenia, 15 especially when evaluated with body composition. Sarcopenia involves loss of skeletal muscle mass, often leading to reduced overall and lean body weight. Unintentional weight loss in older adults signals undemutrition, frailty, and muscle atrophy, indicating worsening sarcopenia. Declining body weight serves as a marker for muscle loss and functional decline, while restoration or maintenance of 20 weight particularly lean mass indicates effective treatment. Increased body weight through muscle gain is a positive outcome in sarcopenia management. Table 4:

[0248] Gait speed (cm / s)

[0249] Sum of change in Incremental improvement (%) in combination group roup Week 4 Change at Week individual Test Change in

[0250] combination

[0251] 4 vs. Control groups (T4) compared to the sum (T1±T2±T3) group (T4) of change in individual test groups (T1±T2±T3) N 33.00 ± 5.10 20.67

[0252] D 12.33 ± 2.16 0.00

[0253] T1 17.67 ± 4.55 5.34

[0254] 15.01 19.67 31.05% T2 19.50 ± 5.24 7.17

[0255] T3 14.83 ± 4.07 2.50

[0256]

[0257] T4 32.00 ± 2.97 19.67

[0258] Gait speed is a key functional measure in the evaluation of sarcopenia, reflecting 5 muscle strength, coordination, and mobility. A slower gait speed is closely linked

[0259] to muscle weakness, physical decline, and a higher risk of falls and disability. It reliably predicts the severity and progression of sarcopenia, as well as overall health outcomes in elderly individuals. Increases in gait speed signify improved muscle function and physical performance, making it an important metric for assessing the 10 efficacy of sarcopenia interventions.

[0260] Table 5:

[0261] Step numbers

[0262] Sum of change in Incremental improvement (%) in combination group r Week 4 Change at Week individual Test Change in

[0263] oup combination

[0264] 4 vs. Control groups (T4) compared to the sum of (T1±T2±T3) group (T4) change in individual test groups (T1±T2±T3) N 49.17 ± 4.88 -26.33

[0265] D 75.50 ± 3.51 0.00

[0266] T1 68.33 ± 4.55 -7.17

[0267] -22.17 -29.17 31.57%

[0268] T2 64.33 ± 4.32 -11.17

[0269] T3 71.67 ± 5.13 -3.83

[0270]

[0271] T4 46.33 ± 4.13 -29.17

[0272] 15 Step count is a key functional measure in sarcopenia assessment. A higher step count often indicates shorter stride length and compensatory gait due to muscle weakness and impaired mobility, reflecting reduced muscle efficiency and increased frailty. Conversely, fewer steps per distance suggest better muscle function and more efficient movement. Tracking step count aids in evaluating sarcopenia severity and treatment effectiveness.

[0273] 5 Table 6:

[0274] Rotarod Mean time (s)

[0275] Sum of change in Incremental improvement (%) in combination group r Week 4 Change at Week individual Test Change in

[0276] oup combination

[0277] 4 vs. Control groups (T4) compared to the sum of (T1+T2+T3) group (T4) change in individual test groups (T1+T2+T3) N 146.17 ± 4.88 104.67

[0278] D 41.50± 4.14 0.00

[0279] T1 52.33 ± 5.05 10.83

[0280] 35.16 50.00 42.21%

[0281] T2 58.50 ± 4.04 17.00

[0282] T3 48.83 ± 3.60 7.33

[0283]

[0284] T4 91.50 ± 4.04 50.00

[0285] Rotarod mean time is an important functional metric for assessing sarcopenia, as it reflects motor coordination, balance, and muscle endurance. A decrease in rotarod 10 time indicates compromised neuromuscular function and muscle weakness, hallmark characteristics of sarcopenia. Conversely, an increase in rotarod mean time signifies improved muscle performance and coordination. Therefore, rotarod mean time is a valuable parameter for gauging sarcopenia severity and the effectiveness of treatments targeting muscle health and functional improvement.

[0286] 15

[0287] Table 7:

[0288] Serum IL-6 (pg / ml)

[0289] Sum of change in Incremental improvement (%) in combination group r Week 4 Change at Week individual Test Change in

[0290] oup combination

[0291] 4 vs. Control groups (T4) compared to the sum of (T1+T2+T3) group (T4) change in individual test groups (T1+T2+T3) N 0.87 ± 0.33 -2.45

[0292] D 3.32 ± 0.42 0.00

[0293] -1.30 -1.89 45.38%

[0294] T1 2.74 ± 0.21 -0.58

[0295]

[0296] T2 2.75 ± 0.19 -0.57 T3 3.17 ± 0.22 -0.15

[0297]

[0298] 1.43 ± 0.19 -1.89

[0299] Interleukin-6 (IL-6) is a pro-inflammatory cytokine linked to the onset and progression of sarcopenia. Elevated IL-6 levels promote chronic inflammation, leading to muscle breakdown, impaired regeneration, and muscle loss. High IL-6 5 correlates with decreased muscle strength and function, making it a key biomarker

[0300] for inflammation-driven muscle degeneration. Reducing IL-6 is thus an important indicator of effective sarcopenia treatment.

[0301] Table 8:

[0302] Serum SIRTl(pg / ml)

[0303] Incremental improvement Sum of change in (%) in combination group Week 4 Change at Week individual Test Change in

[0304] Group 4 vs. Control groups combination (T4) compared to the sum of group (T4) change in individual test (T1±T2±T3) groups (T1±T2±T3) N 0.72 ± 0.15 0.51

[0305] D 0.21 ± 0.09 0.00

[0306] T1 0.31 ± 0.07 0.10

[0307] 0.28 0.37 32.14%

[0308] T2 0.32 ± 0.12 0.11

[0309] T3 0.28 ± 0.10 0.07

[0310] T4 0.58 ± 0.06 0.37

[0311]

[0312] 10

[0313] 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 15 therapeutic target for sarcopenia.

[0314] The results of the study as illustrated in the foregoing tables, clearly demonstrate that the composition comprising Hydroxy methylbutyrate, Ecdysterone, and Selenium exhibits synergistic therapeutic effects when compared to the 20 administration of the individual components alone. The composition demonstrates enhanced efficacy in promoting and improving muscle health. In summary, the present invention provides a scientifically validated synergistic composition for managing poor muscle health and sarcopenia. Extensive research and experimental, data demonstrate that the combination of ecdysterone, calcium hydroxy methylbutyrate, and selenium produces significant improvements in skeletal muscle mass, strength, and functional performance. The composition constitutes a novel and effective therapeutic solution in the field of muscle health, addressing a prevalent and challenging condition. The development and optimization of this composition have the potential to substantially advance the treatment of sarcopenia and related muscle-wasting disorders, thereby enhancing clinical outcomes and quality of life for affected individuals.

Claims

I / WE CLAIM:

1. A synergistic bioactive composition comprising:a) Hydroxy methylbutyrate,b) Ecdysterone, andc) Selenium,wherein each of the components is optionally present in the form of their pharmaceutically acceptable salts, derivatives, isomers, precursors, plant-derived sources, or metabolites.

2. The synergistic bioactive composition as claimed in claim 1, wherein Ecdysterone, Hydroxymethylbutyrate and Selenium are present in a ratio ranging from 1:0.4:0.000013 to 1:2750:0.175.

3. The synergistic bioactive composition as claimed in claim 1, wherein:a) the amount of Hydroxy methylbutyrate is in the range of 1.54 to 99.97% w / w of the total composition;b) the amount of Ecdysterone is in the range of 0.03 to 96.00 % w / w of the total composition; andc) the amount of Selenium is in the range of 0.0001 to 0.9524 % w / w of the total composition.

4. The synergistic bioactive composition as claimed in claim 1, wherein:a) Hydroxy methylbutyrate is present in an amount ranging from 50 mg to 6500 mg; b) Ecdysterone is present in an amount ranging from 2 mg to 1200 mg; and c) Selenium is present in an amount ranging from 0.01 mg to 0.5 mg.

5. The synergistic bioactive composition as claimed in claim 1, wherein the composition is formulated for oral administration and is provided in the form of tablets, capsules, powders, pills, hard capsules filled with liquids or solids, soft capsules, granules, pellets, caplets, mini-tablets, gummies, syrups, suspensions, sachets, modified-release forms, or any other suitable oral dosage form.

6. The synergistic bioactive composition as claimed in claim 1, further comprising one or more pharmaceutically acceptable excipients selected from the group consisting of bulking agents, disintegrants, binders, solubilizing agents, lubricants, glidants, or a mixture thereof.

7. The synergistic bioactive composition as claimed in claim 1, wherein oral administration of the composition results in one or more of the following:a) improves muscle strength by increasing grip strength by at least 22.91% more than the combined individual effects of Hydroxy methylbutyrate, Ecdysterone, and Selenium; orb) improves body weight by at least 34.86% more than the combined individual effects of Hydroxy methylbutyrate, Ecdysterone, and Selenium;c) improves motor activity by increasing gait speed and reducing step number by at least 27.05% and least 27.57%, respectively, more than the combined individual effects of Hydroxy methylbutyrate, Ecdysterone, and Selenium;d) improves motor coordination and performance by increasing staying time on a revolving rotarod by at least 38.21% more than the combined individual effects of Hydroxy methylbutyrate, Ecdysterone, and Selenium;e) reduces muscle wasting by reducing serum interleukin-6 levels by at least 41.38% more than the combined individual effects of Hydroxy methylbutyrate, Ecdysterone, and Selenium; orf) improves muscle mitochondrial content and function by increasing serum SIRT-1 levels by at least 28.14% more than the combined individual effects of Hydroxy methylbutyrate, 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) Hydroxy methylbutyrate in an amount ranging from 50 mg to 6500 mg;b) Ecdysterone in an amount ranging from 2 mg to 1200 mg; andc) Selenium in an amount ranging from 0.01 mg to 0.5 mg;wherein Ecdysterone, Hydroxy methylbutyrate and Selenium are present in a ratio ranging from 1:0.4:0.000013 to 1:2750:0.175wherein the composition is intended for oral administration; andwherein oral administration of the composition:i) improves muscle strength by increasing grip strength by at least 22.91%; and ii) enhances muscle mitochondrial content and function by increasing serum SIRT-1 levels by at least 28.14%,each compared to the combined individual effects of Hydroxy methylbutyrate, Ecdysterone, and Selenium.

10. A kit comprising:a) Hydroxy methylbutyrate,b) Ecdysterone, andc) Selenium,or pharmaceutically acceptable salts, derivatives, isomers, precursors, plant sources, or metabolites thereof;wherein the kit for the treatment or management of sarcopenia, frailty, muscle atrophy, muscle weakness, muscle injury, or other related muscle health disorders.

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