DESC:TECHNICAL FIELD
[0001] The present disclosure provides a method for improving muscle strength, muscle mass, physical performance, muscle flexibility, lean body mass and body composition, and decreasing fat percentage. Aspects of the present disclosure also provides a composition, a process for preparing the composition, and use of such composition for improving muscle strength, muscle mass, physical performance, muscle flexibility, lean body mass and body composition, and decreasing fat percentage in a subject.

BACKGROUND
[0002] Background description includes information that may be useful in understanding the present invention. It is not an admission that any of the information provided herein is prior art or relevant to the presently claimed invention, or that any publication specifically or implicitly referenced is prior art.
[0003] Protein supplements are commonly used by athletes and recreationally active people along with the Resistance Exercise Training (hereinafter also referred to as “RET”) to gain muscle mass and strength. Protein supplements stimulate protein synthesis by elevating anabolic hormones such as growth hormone, insulin-like growth factor, and testosterone. Whey protein increases muscle protein synthesis, which enhances muscular growth and function, and hence, commonly finds utility as a protein supplement. mTOR regulates cellular development and survival by sensing external and internal inputs, particularly nutritional signals like insulin. Insulin promotes protein synthesis in the muscles in the post-absorptive state. Insulin is known to activate mTORC1 kinase activity leading to increase in the association of 4EBP1 and raptor with mTORC1, a major regulator of growth in human. Some studies suggest that addition of whey protein as a protein supplement stimulates insulin release, however in certain metabolic state, this effect is not sustained for a prolonged period.
[0004] A journal article authored by Morton et al (“A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults”; British journal of sports medicine, 52(6), 376-84) reports that dietary protein supplementation increases 1-RM strength and FFM (fat free mass) under prolonged RET. It further states that RET in combination with protein supplementation is more effective in enhancing FFM in young or resistance-trained people than in older or untrained people. Proteins such as whey have been shown to upregulate mTOR signaling, however, it has been widely witnessed that it takes approximately about 8 weeks for whey protein to show noticeable difference in muscle tone and/or muscle size.
[0005] There is therefore, a need in the art of a method for improving muscle strength, muscle mass, performance, lean body mass and body composition, while decreasing fat percentage. Need is also felt of a composition, a process for preparation thereof that may aid in improving muscle strength, muscle mass, performance, lean body mass and body composition while decreasing fat percentage in a subject.

SUMMARY
[0006] The present disclosure provides a method for improving muscle strength, muscle mass, physical performance, muscle flexibility, and body composition including improving lean body mass and decreasing fat percentage. Aspects of the present disclosure also provides a composition, a process for preparing the composition, and use of such composition for improving muscle strength, muscle mass, physical performance, muscle flexibility, lean body mass and body composition, and decreasing fat percentage in a subject.
[0007] An aspect of the present disclosure relates to a method for improving muscle strength and muscle mass in a subject in need thereof, the method comprising administering, to the subject, an extract of aerial parts of Phyllanthus spp..
[0008] Another aspect of the present disclosure relates to a method for increasing physical activity level in a subject in need thereof, the method comprising administering, to the subject, an extract of aerial parts of Phyllanthus spp..
[0009] Another aspect of the present disclosure relates to a method for increasing lean body mass and decreasing fat in a subject in need thereof, the method comprising administering, to the subject, an extract of aerial parts of Phyllanthus spp..
[0010] Another aspect of the present disclosure relates to a method for increasing muscle power in a subject in need thereof, the method comprising administering, to the subject, an extract of aerial parts of Phyllanthus spp..
[0011] Another aspect of the present disclosure relates to a method for improving muscle flexibility in a subject in need thereof, the method comprising administering, to the subject, an extract of aerial parts of Phyllanthus spp..
[0012] Another aspect of the present disclosure relates to a method for improving muscle endurance in a subject in need thereof, the method comprising administering, to the subject, an extract of aerial parts of Phyllanthus spp..
[0013] Further aspect of the present disclosure relates to a method for aiding/helping in post exercise muscle recovery in a subject in need thereof, the method comprising administering, to the subject, an extract of aerial parts of Phyllanthus spp..
[0014] In some embodiments, the extract comprises tannins not less than 10% w/w, corilagin not less than 1% w/w, and bitters not less than 15% w/w. In some embodiments, the extract comprises flavonoids not less than 26% w/w. In some embodiments, the extract comprises tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, and bitters in an amount ranging from 15% w/w to 30% w/w. In some embodiments, the extract comprises flavonoids in an amount ranging from 26% w/w to 36% w/w.
[0015] Another aspect of the present disclosure relates to a method for amplifying the effect of a protein supplement in one or more of: improving muscle strength, improving muscle mass, increasing muscle power, improving muscle flexibility, improving muscle endurance, increasing physical activity level and exercise capacity, improving physical performance, increasing lean body mass, improving body composition, in decreasing fat percentage, and aiding in post exercise muscle recovery in a subject, the method comprising administering, to the subject, an extract of aerial parts of Phyllanthus spp.. In some embodiments, the extract comprises tannins not less than 10% w/w, corilagin not less than 1% w/w, and bitters not less than 15% w/w. In some embodiments, the extract comprises flavonoids not less than 26% w/w. In some embodiments, the extract comprises tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, and bitters in an amount ranging from 15% w/w to 30% w/w. In some embodiments, the extract comprises flavonoids in an amount ranging from 26% w/w to 36% w/w. Another aspect of the present disclosure relates to a method for amplifying the effect of a protein supplement and maintaining the effects even upon discontinuation of said protein supplement for upto 30 days in one or more of: improving muscle strength, improving muscle mass, increasing muscle power, improving muscle flexibility, improving muscle endurance, increasing physical activity level and exercise capacity, improving physical performance, increasing lean body mass, improving body composition, in decreasing fat percentage, and aiding in post exercise muscle recovery in a subject.
[0016] Further aspect of the present disclosure relates to a formulation comprising: (a) an extract of aerial parts of Phyllanthus spp., said extract comprising tannins not less than 10% w/w, corilagin not less than 1% w/w, and bitters not less than 15% w/w; and (b) one or more pharmaceutically acceptable excipients. In some embodiments, the extract comprises tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, and bitters in an amount ranging from 15% w/w to 30% w/w. In some embodiments, the extract comprises flavonoids in an amount ranging from 26% w/w to 36% w/w.
[0017] Further aspect of the present disclosure relates to a Phyllanthus spp. extract composition, comprising tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, bitters in an amount ranging from 15% w/w to 30% w/w, and flavonoids in an amount ranging from 26% w/w to 36% w/w. In some embodiments, the Phyllanthus spp. extract composition may be enriched during the extraction process.
[0018] Still further aspect of the present disclosure relates to a process for preparing a formulation comprising an extract of aerial parts of Phyllanthus spp., and one or more pharmaceutically acceptable excipients, said process comprising the steps of: (a) taking pulverized aerial parts of Phyllanthus spp.; (b) effecting extraction of the pulverized aerial parts of Phyllanthus spp. to obtain an extract; (c) effecting drying of the extract; and (d) effecting pulverization of the dried extract with the one or more pharmaceutical acceptable excipients to obtain the formulation.
[0019] In some embodiments, the step of extraction comprises: (a) mixing the pulverized aerial parts of Phyllanthus spp. with a hydroalcoholic solvent in a ratio ranging from 1:5 to 1:25; and (b) heating the mixture at a temperature ranging from 60-70°C for a time period ranging from 10-25 hours to obtain the extract.
[0020] In some embodiments, the step of drying comprises spray drying the extract to obtain the dried extract.
[0021] In some embodiments, the pharmaceutical acceptable excipient is silicon dioxide, and the step of pulverization comprises pulverizing the dried extract with silicon dioxide to obtain the formulation.
[0022] Still further aspect of the present disclosure relates to use of an extract of aerial parts of Phyllanthus spp. comprising tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, bitters in an amount ranging from 15% w/w to 30% w/w, and flavonoids in an amount ranging from 26% w/w to 36% w/w for one or more of: improving muscle strength, improving muscle mass, increasing muscle power, improving muscle flexibility, improving muscle endurance, increasing physical activity level, improving physical performance, increasing lean body mass, improving body composition, in decreasing fat percentage, and aiding in post exercise muscle recovery in a subject.
[0023] Still further aspect of the present disclosure relates to use of an extract of aerial parts of Phyllanthus spp. comprising tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, bitters in an amount ranging from 15% w/w to 30% w/w, and flavonoids in an amount ranging from 26% w/w to 36% w/w for preparing a medication for one or more of: improving muscle strength, improving muscle mass, increasing muscle power, improving muscle flexibility, improving muscle endurance, increasing physical activity level, improving physical performance, increasing lean body mass, improving body composition, in decreasing fat percentage, and aiding in post exercise muscle recovery in a subject.
[0024] Still further aspect of the present disclosure relates to use of a formulation comprising: an extract of aerial parts of Phyllanthus spp. comprising tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, bitters in an amount ranging from 15% w/w to 30% w/w; and flavonoids in an amount ranging from 26% w/w to 36% w/w and one or more pharmaceutically acceptable excipients for one or more of: improving muscle strength, improving muscle mass, increasing muscle power, improving muscle flexibility, improving muscle endurance, increasing physical activity level, improving physical performance, increasing lean body mass, improving body composition, in decreasing fat percentage, and aiding in post exercise muscle recovery in a subject.
[0025] Various objects, features, aspects and advantages of the inventive subject matter will become more apparent from the following detailed description of preferred embodiment/s, along with the accompanying drawing figures in which like numerals represent like components.

BRIEF DESCRIPTION OF THE DRAWINGS
[0026] The accompanying drawings are included to provide a further understanding of the present disclosure, and are incorporated in and constitute a part of this specification. The drawings illustrate exemplary embodiments of the present disclosure and, together with the description, serve to explain the principles of the present disclosure.
Figure 1 illustrates change in 1-RM at day 28 from baseline in randomized in the three study arms/groups viz. EB-MS-01 group, EB-MS-02 and EB-MS-03 groups. Of the six participants in the EB-MS-03 group, five participants demonstrated 10.34% to 17.14% increase in the 1-RM at 28th day as compared to baseline.
Figure 2 illustrates increase in lean body mass, in the range of 680-2454 gm, was observed in four participants at the end of the study from baseline.
Figure 3 illustrates the muscle flexibility test results.

DETAILED DESCRIPTION
[0027] The following is a detailed description of embodiments of the disclosure depicted in the accompanying drawings. The embodiments are in such detail as to clearly communicate the disclosure. However, the amount of detail offered is not intended to limit the anticipated variations of embodiments; on the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the present disclosure as defined by the appended claims.
[0028] Each of the appended claims defines a separate invention, which for infringement purposes is recognized as including equivalents to the various elements or limitations specified in the claims. Depending on the context, all references below to the “invention” may in some cases refer to certain specific embodiments only. In other cases it will be recognized that references to the “invention” will refer to subject matter recited in one or more, but not necessarily all, of the claims.
[0029] As used in the description herein and throughout the claims that follow, the meaning of “a,” “an,” and “the” includes plural reference unless the context clearly dictates otherwise. Also, as used in the description herein, the meaning of “in” includes “in” and “on” unless the context clearly dictates otherwise.
[0030] All methods described herein can be performed in any suitable order unless otherwise indicated herein or otherwise clearly contradicted by context. The use of any and all examples, or exemplary language (e.g. “such as”) provided with respect to certain embodiments herein is intended merely to better illuminate the invention and does not pose a limitation on the scope of the invention otherwise claimed. No language in the specification should be construed as indicating any non-claimed element essential to the practice of the invention.
[0031] Various terms as used herein are shown below. To the extent a term used in a claim is not defined below, it should be given the broadest definition persons in the pertinent art have given that term as reflected in printed publications and issued patents at the time of filing.
[0032] The present disclosure provides a method for one or more of: improving muscle strength, improving muscle mass, increasing muscle power, improving muscle flexibility, improving muscle endurance, increasing physical activity level, improving physical performance, increasing lean body mass, improving body composition, in decreasing fat percentage, and aiding in post exercise muscle recovery in a subject. Aspects of the present disclosure also provides a composition, a process for preparing the composition, and use of such composition for one or more of: improving muscle strength, improving muscle mass, increasing muscle power, improving muscle flexibility, improving muscle endurance, increasing physical activity level, improving physical performance, increasing lean body mass, improving body composition, in decreasing fat percentage, and aiding in post exercise muscle recovery in a subject.
[0033] The present disclosure is on a premise of surprising observation by inventors that extract of aerial parts of Phyllanthus spp. affords dramatic improvement in muscle strength, muscle mass, muscle power, muscle flexibility, muscle endurance, physical activity level, physical performance, lean body mass and body composition, and aiding in post exercise muscle recovery, while decreasing fat percentage (e.g. body fat %, visceral fat, and android fat), especially when administered with protein supplements (particularly, whey protein) in exercising subjects.
[0034] Accordingly, an aspect of the present disclosure relates to a method for improving muscle strength and muscle mass in a subject in need thereof, the method comprising administering, to the subject, an extract of aerial parts of Phyllanthus spp..
[0035] Another aspect of the present disclosure relates to a method for increasing physical activity level in a subject in need thereof, the method comprising administering, to the subject, an extract of aerial parts of Phyllanthus spp..
[0036] Another aspect of the present disclosure relates to a method for increasing lean body mass and decreasing fat in a subject in need thereof, the method comprising administering, to the subject, an extract of aerial parts of Phyllanthus spp..
[0037] Another aspect of the present disclosure relates to a method for increasing muscle power in a subject in need thereof, the method comprising administering, to the subject, an extract of aerial parts of Phyllanthus spp..
[0038] Another aspect of the present disclosure relates to a method for improving muscle flexibility in a subject in need thereof, the method comprising administering, to the subject, an extract of aerial parts of Phyllanthus spp..
[0039] Another aspect of the present disclosure relates to a method for improving muscle endurance in a subject in need thereof, the method comprising administering, to the subject, an extract of aerial parts of Phyllanthus spp..
[0040] Further aspect of the present disclosure relates to a method for aiding/helping in post exercise muscle recovery in a subject in need thereof, the method comprising administering, to the subject, an extract of aerial parts of Phyllanthus spp..
[0041] In some embodiments, the extract comprises tannins in an amount not less than 10% w/w, corilagin not less than 1% w/w, bitters not less than 15% w/w, and flavonoids not less than 26% w/w. In some embodiments, the extract comprises tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, bitters in an amount ranging from 15% w/w to 30% w/w, and flavonoids in an amount ranging from 26% w/w to 36% w/w.
[0042] The term “corilagin” refers to a type of polyphenolic compound composed of ellagic acid linked to a glucose molecule found in a variety of medicinal plants and has been studied for its potential health benefits, including antioxidant, anti-inflammatory, antiviral, and anticancer activities.
[0043] The term “flavonoids” refers to a large group of plant-based compounds, known as polyphenols, that are widely distributed in fruits, vegetables, grains, and beverages like tea and wine. They are known for their potent antioxidant properties and have various health benefits, including anti-inflammatory, anti-cancer, anti-viral, and heart-protective effects. Phyllanthus Spp may comprise flavonoids such as but not limited to rutin, astragalin, kaempferol, quercetin.
[0044] The present disclosure also relates to a method for amplifying the effect of a protein supplement in one or more of: improving muscle strength, improving muscle mass, increasing muscle power, improving muscle flexibility, improving muscle endurance, increasing physical activity level, improving physical performance, increasing lean body mass, improving body composition, in decreasing fat percentage, and aiding in post exercise muscle recovery in a subject, the method comprising administering, to the subject, an extract of aerial parts of Phyllanthus spp..
[0045] In some embodiments, the extract comprises tannins in an amount not less than 10% w/w, corilagin not less than 1% w/w, bitters not less than 15% w/w, and flavonoids not less than 26% w/w. In some embodiments, the extract comprises tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, bitters in an amount ranging from 15% w/w to 30% w/w, and flavonoids in an amount ranging from 26% w/w to 36% w/w.
[0046] In some embodiment, the protein supplement comprises whey protein.
[0047] In some embodiments, the subject is a mammal, preferably, an adult human being. In some embodiments, the subject is an adult human being performing physical activity, preferably, performing physical activity at least on 2 days in a week, for example, performing exercise at least on 2 consecutive or non-consecutive days in a week as per American College of Sport Medicine (ASCM) guidelines (https://www.acsm.org/education-resources/trending-topics-resources/physical-activity-guidelines).
[0048] In some embodiments, the extract comprises an extract of aerial parts of Phyllanthus spp. selected from the group comprising Phyllanthus niruri, Phyllanthus amarus, Phyllanthus airy-shawii, Phyllanthus maderaspatensis, Phyllanthus urinaria, Phyllanthus fraternus, Phyllanthus corcovadensis and mixtures thereof.
[0049] In some embodiments, the extract is a hydro-alcoholic extract.
[0050] In some embodiments, the extract comprises tannins not less than about 10% w/w. For example, the exact comprises tannins more than about 17% w/w, or more than about 20% w/w, or more than about 25% w/w, more than about 30% w/w, or more than about 40% w/w, more than about 50% w/w.
[0051] In some embodiments, the extract comprises tannins not more than about 85% w/w, for example, less than about 80% w/w, or less than about 75% w/w, or less than about 70% w/w, or less than about 60% w/w, or less than about 50% w/w.
[0052] In some embodiments, the extract comprises tannins in an amount ranging from about 10% w/w to about 75% w/w, for example, from about 15% to about 70% w/w, or from about 17% to about 70% w/w, or from about 20% to about 65% w/w, or from about 20% to about 60% w/w. In a preferred embodiment, the extract comprises tannins in an amount ranging from 10% w/w to 30% w/w.
[0053] In some embodiments, the extract comprises corilagin not less than about 1% w/w. For example, the exact comprises corilagin more than about 1.5% w/w, or more than about 2% w/w, or more than about 2.5% w/w, or more than about 3% w/w, or more than about 4% w/w, or more than about 5% w/w.
[0054] In some embodiments, the extract comprises corilagin not more than about 50% w/w, for example, less than about 45% w/w, or less than about 40% w/w, or less than about 30% w/w, or less than about 20% w/w, or less than about 10% w/w.
[0055] In some embodiments, the extract comprises corilagin in an amount ranging from about 1% w/w to about 50% w/w, for example, from about 1.5% to about 45% w/w, or from about 2% to about 40% w/w, or from about 5% to about 40% w/w. In a preferred embodiment, the extract comprises corilagin in an amount ranging from 1% w/w to 4% w/w.
[0056] In some embodiments, the extract comprises bitters not less than about 15% w/w. For example, the exact comprises bitters more than about 17% w/w, or more than about 20% w/w, or more than about 25% w/w, more than about 30% w/w, or more than about 40% w/w, more than about 50% w/w.
[0057] In some embodiments, the extract comprises bitters not more than about 85% w/w, for example, less than about 80% w/w, or less than about 75% w/w, or less than about 70% w/w, or less than about 60% w/w, or less than about 50% w/w.
[0058] In some embodiments, the extract comprises bitters in an amount ranging from about 15% w/w to about 75% w/w, for example, from about 15% to about 70% w/w, or from about 20% to about 70% w/w, or from about 20% to about 65% w/w, or from about 20% to about 60% w/w. In a preferred embodiment, the extract comprises bitters in an amount ranging from 15% w/w to 30% w/w.
[0059] In some embodiments, the extract comprises flavonoids not less than about 26% w/w. For example, the exact comprises flavonoids more than about 28% w/w, or more than about 30% w/w, or more than about 31% w/w, or more than about 32% w/w, or more than about 34% w/w, or more than about 35% w/w.
[0060] In some embodiments, the extract comprises flavonoids not more than about 36% w/w, for example, less than about 35% w/w, or less than about 32% w/w, or less than about 30% w/w, or less than about 28% w/w, or less than about 27% w/w.
[0061] In some embodiments, the extract comprises flavonoids in an amount ranging from about 30% w/w to about 31% w/w, for example, from about 27% to about 34% w/w, or from about 28% to about 33% w/w, or from about 29% to about 32% w/w. In a preferred embodiment, the extract comprises flavonoids in an amount ranging from 26% w/w to 36% w/w.
[0062] In some embodiments, the extract comprises tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, and bitters in an amount ranging from 15% w/w to 30% w/w. In some embodiments, the extract comprises flavonoids in an amount ranging from 26% w/w to 36% w/w.
[0063] In some embodiments, the extract is administered, simultaneously or before or after administration of the protein supplement. In some embodiments, the extract is administered at a dose ranging from 100 mg to 2500 mg per day in single or divided doses, for example, at a dose ranging from about 125 mg to about 2000 mg per day, or from about 150 mg to about 1500 mg per day, or from about 200 mg to about 1000 mg per day, or from about 250 mg to about 1000 mg per day, or from about 300 mg to about 750 mg per day. In some embodiments, the extract is administered by oral route. In an embodiment, the extract is administered by oral route at a dose ranging from 100 mg to 2500 mg per day in single or divided doses. In an embodiment, the extract is administered by oral route at a dose ranging from 250 mg to 1500 mg per day in single or divided doses.
[0064] In some embodiment, the extract is formulated into a solid, liquid or a semi-solid formulation/dosage form. Non-limiting examples of formulations or dosage forms includes tablet, lozenge, capsule, caplet, modified release tablet or lozenge, suspension, solution, emulsion, granules, pellets, beads, powder, aerosol sprays (oral, nasal, dermal), tablet in tablet, bilayer tablet, trilayer tablet, inlay tablet, capsule in capsule, tablet(s) in capsule, granules and/or pellets in capsule, pellets and tablet in capsules and the likes.
[0065] Further aspect of the present disclosure relates to a formulation comprising: (a) an extract of aerial parts of Phyllanthus spp., said extract comprising tannins not less than 10% w/w, corilagin not less than 1% w/w, and bitters not less than 5% w/w; and (b) one or more pharmaceutically acceptable excipients. In some embodiments, the extract comprises tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, and bitters in an amount ranging from 15% w/w to 30% w/w. In some embodiments, the extract comprises flavonoids in an amount ranging from 26% w/w to 36% w/w.
[0066] Further aspect of the present disclosure relates to an enriched Phyllanthus spp. extract composition, comprising tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, bitters in an amount ranging from 15% w/w to 30% w/w, and flavonoids in an amount ranging from 26% w/w to 36% w/w.
[0067] In some embodiments, the formulation comprises: (a) an extract of aerial parts of Phyllanthus spp., said extract comprising tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, and bitters in an amount ranging from 15% w/w to 30% w/w; and (b) one or more pharmaceutically acceptable excipients. In some embodiments, the extract comprises flavonoids in an amount ranging from 26% w/w to 36% w/w.
[0068] In some embodiments, the enriched Phyllanthus spp. extract composition, comprising tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, bitters in an amount ranging from 15% w/w to 30% w/w, and flavonoids in an amount ranging from 26% w/w to 36% w/w.
[0069] In some embodiments, the formulation comprises: (a) an extract of aerial parts of Phyllanthus spp., said extract comprising tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, and bitters in an amount ranging from 15% w/w to 30% w/w; and (b) the rest being one or more pharmaceutically acceptable excipients. In some embodiments, the extract comprises flavonoids in an amount ranging from 26% w/w to 36% w/w.
[0070] In some embodiments, present invention discloses an enriched Phyllanthus spp. extract composition, comprising tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, bitters in an amount ranging from 15% w/w to 30% w/w, and flavonoids in an amount ranging from 26% w/w to 36% w/w.
[0071] In some embodiments, the formulation consists of: (a) the extract of aerial parts of Phyllanthus spp., said extract comprising tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, and bitters in an amount ranging from 15% w/w to 30% w/w; and (b) the rest being one or more pharmaceutically acceptable excipients. In some embodiments, the extract comprises flavonoids in an amount ranging from 26% w/w to 36% w/w.
[0072] In some embodiments, the formulation comprises one or more excipients, preferably, one or more pharmaceutically acceptable excipients. The excipient can be selected from any or a combination of: a diluent, an anti-oxidant, a preservative, an alkalizing agent, a buffering agent, a disintegrant, a binder, an anti-foaming agent, a solvent, a glidant, a lubricant, a flavoring agent, a sweetener, a coating agent, a rate controlling polymer or non-polymer, an amino acid or metabolites or amino acid derivatives, a bulking agent/filler, an anti-tacking agent, an emulsifier, a surfactant, a plasticizer and a stabilizer.
[0073] In some embodiments, the excipient comprises a carrier. In some embodiments, the carrier comprises silicon dioxide.
[0074] In some embodiments, the diluent(s) include(s), but not limited to, dicalcium phosphate dihydrate, calcium sulfate, lactose, sucrose, mannitol, sorbitol, cellulose, microcrystalline cellulose, kaolin, sodium chloride, dry starch, hydrolyzed starches, pregelatinized starch, silicone dioxide, titanium oxide, and magnesium aluminum silicate and mixtures thereof.
[0075] In some embodiments, the anti-oxidant(s) and preservative(s) include(s), but not limited to, L-Carnosine, vitamin A, vitamin E, vitamin C, D-Panthenol, retinyl palmitate, and selenium, citric acid, sodium citrate, methyl paraben, propyl paraben, p-hydroxybenzoic acid esters, sorbic acid, benzoic acid, propionic acid or salts thereof; Alcohols such as benzyl alcohol, butanol or ethanol, isopropyl alcohol, and quaternary ammonium compounds such as benzalkonium chloride, sodium benzoate and mixtures thereof.
[0076] In some embodiments, the alkalizing agent(s) include(s), but not limited to, ammonia solution NF, Ammonium Carbonate NF, Diethanolamine NF, monoethanolamine, Potassium Hydroxide NF, Sodium Bicarbonate USP, Sodium Borate NF, Sodium Carbonate NF, Sodium Hydroxide NF, sodium Phosphate Dibasic USP, trolamine NF, calcium carbonate, magnesium carbonate, magnesium oxide, magnesium hydroxide, magnesium trisilicate, aluminum hydroxide, aluminum carbonate, magnesium aluminium silicate hydrate, potassium bicarbonate, sodium bicarbonate, sodium citrate, potassium citrate, aluminum sulfate, calcium carbonate and mixtures thereof.
[0077] In some embodiments, the buffering agent(s) include(s), but not limited to, a bicarbonate salt of alkali earth metal, amino acids, an acid salt of an amino acid, an alkali salt of an amino acid and mixture thereof.
[0078] In some embodiments, the disintegrant(s) include(s), but not limited to Croscarmellose sodium, microcrystalline cellulose, low-substituted hydroxypropyl cellulose, alginic acid and alginates, modified starches, sodium starch glycolate, sodium carboxy methyl cellulose, carboxymethyl cellulose calcium, polyvinylpyrrolidone, docusate sodium, guar gum and mixtures thereof.
[0079] In some embodiments, the binder(s) include(s), but not limited to, hypromellose (or hypromellose 5 cps), polyvinyl pyrrolidone, copolymers of vinyl pyrrolidone with other vinyl derivatives, hydroxypropyl cellulosic derivatives (such as methylcellulose, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxyethylmethyl cellulose, hydroxypropylcellulose etc), polyacrylates (such as Carbopol, polycarbophil, etc), Povidone (all grades), Polyox of any molecular weight or grade, irradiated or not, maize starch, povidone, copovidone, corn starch, starch, polyvinylpyrrolidone (PVP), microcrystalline cellulose, powdered acacia, gelatin, guar gum, carbomer such as carbopol, polymethacrylates, starch, heavy magnesium oxide and mixtures thereof.
[0080] In some embodiments, the anti-foaming agent(s) include(s), but not limited to, alcohols such as cetostearyl alcohol, insoluble oils such as castor oil, stearates, polydimethylsiloxanes and other silicones derivatives, ethers, paraffin oil, paraffin wax, glycols, simethicone (or simethicone 30% emulsion) and mixtures thereof.
[0081] In some embodiments, solvent(s) include(s), but not limited to, methanol, ethanol, n-propanol, isopropanol, hexane, heptane, petroleum ether, cyclohexane, diethyl ether, diisopropyl ether, ethyl acetate, methyl acetate, ethyl formate, methyl formate, isobutyl acetate, n-butyl acetate, methylene chloride, ethylene chloride, chloroform, carbon tetrachloride, acetone, ethyl methyl ketone, diisobutyl ketone, methyl isobutyl ketone, 1,4- dioxane, toluene, ammonia solution, glacial acetic acid, ammonium hydroxide, sodium hydroxide, calcium hydroxide, calcium carbonate, potassium hydroxide, potassium carbonate, water and mixtures thereof.
[0082] In some embodiments, the glidant(s) include(s), but are not limited to, colloidal silicon dioxide, stearic acid, talk, aluminium silicate and mixtures thereof.
[0083] In some embodiments, the lubricant(s) include(s), but not limited to, stearic acid, magnesium stearate, sodium stearyl fumarate, sodium lauryl sulphate, magnesium lauryl sulphate, fumaric acid, glyceryl palmitostearate, zinc stearate, calcium stearate, silica, talc, polyethylene glycol, paraffin and mixtures thereof.
[0084] In some embodiments, the flavoring agent(s) include(s), but not limited, cherry, maple, pineapple, orange, raspberry, banana-vanilla, peppermint, butterscotch, strawberry, vanilla, apricot, cinnamon, honey, lime, peach-orange, peach-rum, raspberry, wild cherry, mint and mixtures thereof.
[0085] In some embodiments, coating agent(s) include(s), but not limited to, Cellulosics, such as hydroxypropyl methyl cellulose (HPMC), methy ethylcellulose (MEC), carboxymethyl celluolose (CMC), carboxymethyl ethylcelluolose (CMEC), hydroxyethyl cellulose (HEC), Hydroxypropyl cellulose (HPC), cellulose acetate phthalate (CAP), hydroxypropyl methyl cellulose phthalate (HPMCP), hydroxypropyl methyl cellulose acetate succinate (HPMCAS), hypromellose, povidone, copovidone, and ethyl cellulose (EC); Vinyls, such as polyvinyl alcohol; Acrylics, such as methacrylic acid / ethylacrylate copolymers (often used for enteric or delayed release coatings), Natural derivatives, such as shellac or alginate and mixtures thereof.
[0086] In some embodiments, the rate controlling polymer(s) include(s), but not limited to, cellulose acetate, alkyl celluloses, hydroxyalkyl, acrylic polymers, copolymers dialkylphthalates, dibutyl phthalate, microcrystalline wax and mixtures thereof.
[0087] In some embodiments, the rate controlling non-polymer(s) include(s), but not limited to, fat, wax, fatty acid, fatty acid ester, long chain monohydric alcohol or their ester and mixtures thereof.
[0088] In some embodiments, the amino acids or metabolites or amino acid derivatives include(s), but not limited to, glycine, glutamine, asparagine, arginine, lysine in biologically active enantiomeric forms, L-carnosine, L-carnitine, choline, betaine, taurine, glycosaminoglycans including hyaluronic acid, chondroitin sulfate, glucosamine, L-glucosamine, heparins and mixtures thereof.
[0089] In some embodiments, the bulking agent(s) include(s), but not limited to, lactose USP, Starch 1500, mannitol, erythritol, sorbitol, maltodextrin, malitol or other non-reducing sugars; silica, microcrystalline cellulose (e.g., Avicel), dibasic calcium phosphate (anhydrous or dihydrate), sucrose, etc. and mixtures thereof.
[0090] In some embodiments, the anti-tacking agent(s) include(s), but not limited to, stearates; stearic acid; vegetable oil; waxes; a blend of magnesium stearate and sodium lauryl sulfate; sodium benzoate; sodium acetate and mixtures thereof.
[0091] In some embodiments, the surfactant(s) and emulsifier(s) include(s), but not limited to, ionic or non-ionic surfactants and emulsifiers, poloxamers, polyethylene glycols, polyethylene glycol monostearate, polysorbates, sodium lauryl sulfate, polyethoxylated, hydrogenated castor oil and mixtures thereof.
[0092] In some embodiments, the plasticizer(s) include(s), but are not limited to, diethyl phthalate, triethyl citrate, acetyl tributyl citrate, dibutyl phthalate, triacetin, propylene glycol, polyethylene glycol, dichloromethane, acetone, ethanol, methanol, isopropyl alcohol, water and mixtures thereof.
[0093] In some embodiments, the stabilizer(s) include(s), but not limited to, gums, agar, taste masking agents like acrylic polymers, copolymers of acrylates, celluloses, resins and mixtures thereof.
[0094] In some embodiments, the sweetener(s) include(s), but not limited to, mannitol, sorbitol, polyethylene glycol (PEG) 6000 and 8000, Emdex, Nu-tab, Sweetrex, Mola-tab, Hony-tab, Sugartab, non-sugar sweetening agents such as aspartame, sorbitol, xylitol, isomalt, saccharin, sodium saccharin, calcium saccharin, sucralose, acesulfame-K, steviol, steviosin, mannitol, erythritol, lactitol, and sugar sweetening agents such as sucrose, fructose, dextrose and mixtures thereof.
[0095] Although several embodiments of the present disclosure names few of the commonly used excipients, any other excipient known to or appreciated by a skilled person can also be used to realize the advantageous compositions of the present disclosure. Examples of useful excipients which can optionally be added to the composition are described in the Handbook of Pharmaceutical Excipients, 3rd edition, Edited by A. H. Kibbe, Published by: American Pharmaceutical Association, Washington DC, ISBN: 0-917330-96-X, and in Handbook of Pharmaceutical Excipients (4th edition), Edited by Raymond C Rowe - Publisher: Science and Practice.
[0096] Still further aspect of the present disclosure relates to a process for preparing a formulation comprising an extract of aerial parts of Phyllanthus spp., and one or more pharmaceutically acceptable excipients, said process comprising the steps of: (a) taking pulverized aerial parts of Phyllanthus spp.; (b) effecting extraction of the pulverized aerial parts of Phyllanthus spp. to obtain an extract; (c) effecting drying of the extract; and (d) effecting pulverization of the dried extract with the one or more pharmaceutical acceptable excipients to obtain the formulation.
[0097] In some embodiments, there is provided a process for preparing a formulation comprising an extract of aerial parts of Phyllanthus spp., said extract comprising tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, bitters in an amount ranging from 15% w/w to 30% w/w, and flavonoids in an amount ranging from 26% w/w to 36% w/w; and one or more pharmaceutically acceptable excipients, said process comprising the steps of: (a) taking pulverized aerial parts of Phyllanthus spp.; (b) effecting extraction of the pulverized aerial parts of Phyllanthus spp. to obtain an extract; (c) effecting drying of the extract; and (d) effecting pulverization of the dried extract with the with the one or more pharmaceutical acceptable excipients to obtain the formulation.
[0098] In some embodiments, the step of extraction comprises: (a) mixing the pulverized aerial parts of Phyllanthus spp. with a hydroalcoholic solvent in a ratio ranging from 1:5 to 1:25; and (b) heating the mixture at a temperature ranging from 60-70°C for a time period ranging from 10-25 hours to obtain the extract.
[0099] In some embodiments, the step of drying comprises spray drying the extract to obtain the dried extract.
[00100] In some embodiments, the pharmaceutical acceptable excipient is silicon dioxide, and the step of pulverization comprises pulverizing the dried extract with silicon dioxide to obtain the composition.
[00101] The present disclosure also relates to use of an extract of aerial parts of Phyllanthus spp. comprising tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, bitters in an amount ranging from 15% w/w to 30% w/w, and flavonoids in an amount ranging from 26% w/w to 36% w/w for one or more of: improving muscle strength, improving muscle mass, increasing muscle power, improving muscle flexibility, improving muscle endurance, increasing physical activity level, improving physical performance, increasing lean body mass, improving body composition, in decreasing fat percentage, and aiding in post exercise muscle recovery in a subject.
[00102] The present disclosure also relates to use of an extract of aerial parts of Phyllanthus spp. comprising an enriched Phyllanthus spp. extract composition, comprising tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, bitters in an amount ranging from 15% w/w to 30% w/w, and flavonoids in an amount ranging from 26% w/w to 36% w/w.
[00103] The present disclosure also relates to use of an extract of aerial parts of Phyllanthus spp. comprising tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, bitters in an amount ranging from 15% w/w to 30% w/w, and flavonoids in an amount ranging from 26% w/w to 36% w/w for preparing a medication for one or more of: improving muscle strength, improving muscle mass, increasing muscle power, improving muscle flexibility, improving muscle endurance, increasing physical activity level, improving physical performance, increasing lean body mass, improving body composition, in decreasing fat percentage, and aiding in post exercise muscle recovery in a subject.
[00104] The present disclosure also relates to use of a formulation comprising: an extract of aerial parts of Phyllanthus spp. comprising tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, bitters in an amount ranging from 15% w/w to 30% w/w, and flavonoids in an amount ranging from 26% w/w to 36% w/w; and one or more pharmaceutically acceptable excipients for one or more of: improving muscle strength, improving muscle mass, increasing muscle power, improving muscle flexibility, improving muscle endurance, increasing physical activity level, improving physical performance, increasing lean body mass, improving body composition, in decreasing fat percentage, and aiding in post exercise muscle recovery in a subject.
[00105] While the foregoing describes various embodiments of the invention, other and further embodiments of the invention may be devised without departing from the basic scope thereof. The scope of the invention is determined by the claims that follow. The invention is not limited to the described embodiments, versions or examples, which are included to enable a person having ordinary skill in the art to make and use the invention when combined with information and knowledge available to the person having ordinary skill in the art.
EXAMPLE
[00106] CAPSULE FORMULATION COMPRISING AN EXTRACT OF AERIAL PARTS OF PHYLLANTHUS SPP.
[00107] A formulation comprising hydro-alcoholic extract of Phyllanthus spp. (Phyllanthus amarus) was prepared by the following process: The dried whole aerial parts of Phyllanthus amarus was powdered and sieved through a 2 mm sieve of mesh size 9 to obtain a powder. A hydro-alcoholic solution (70% ethanolic solution in water) in an amount of about 16 times the amount of the dried whole aerial part was mixed with the powder and extraction was carried out at a temperature of about 65°C for a time period of about 16 hours to obtain an extract. The extract was then spray dried for a period of about 10 hours to obtain a powdered extract. The powdered extract was then mixed with silicon dioxide (i.e. a pharmaceutically acceptable carrier) in a weight ratio of 99.5:0.5 and the mixture was subjected to pulverization to obtain the powdered formulation. The powdered formulation was then filled in an amount of about 500 mg in hard gelatin capsules and stored in a hermetically sealed glass container.
[00108] Example 1: RANDOMIZED PILOT STUDY
[00109] A randomized pilot study was conducted to assess efficacy of the extract of Phyllanthus spp. Participants were randomized in the three study arms/groups viz. four (4) participants in EB-MS-01 group, and six (6) participants each in EB-MS-02 and EB-MS-03 groups. The mean age (standard deviation mentioned in the parenthesis) of the participants was 25 (±2.0) years, and the mean body mass index (BMI) was 25.48 (±1.18) kg/m2; the mean 1-RM of the participants was 111.25 (±29.76), 115.00 (±43.90), and 98.75 (±18.22) kg in EB-MS-01, EB-MS-02 and EB-MS-03, respectively.
[00110] Along with investigational products (placebo containing microcrystalline cellulose, or extract of Phyllanthus spp.), each participant was also provided 48 gm of whey protein isolate (WPI) in two divided doses of 24 gm dissolved in 200 ml of water with their breakfast and dinner till the end of the study. All the participants (except EB-MS-01 group) were asked to exercise under a trainer for 30 minutes of free-weight strength training, performed for two non-consecutive days per week as per American College of Sport Medicine (ACSM) guidelines. Details of the study groups, treatments and regimen is provided in Table 1.

Table 1: Details of the study groups, treatments and regimen
Study Arms Arm 1
(Open label) Arm 2
(Blinded) Arm 3
(Blinded)
Product Code EB-MS-01 EB-MS-02 EB-MS-03
Ingredients Microcrystalline Cellulose (MCC) Microcrystalline Cellulose (MCC) Extract of Phyllanthus spp.
Ingredient Dose/ day 600 mg 600 mg 500 mg
Capsule Composition 300 mg of MCC 300 mg of MCC 500 mg of extract of Phyllanthus spp.
Daily IP Regimen 2 Capsules of Placebo 2 Capsules of Placebo 1 Cap of IP + 1 Cap of Placebo
Daily Exercise Regimen No Exercise Exercise as per ASCM guidelines Exercise as per ASCM guidelines
* Capsules were taken 30 minutes before breakfast daily with whey protein.
* On testing and exercise days, WPI with IP was taken 30 minutes prior to testing without breakfast.
[00111] The study was terminated for the participants in the open label arm (EB-MS-01 - placebo without resistance training) on Day 28 irrespective of improvement in weight in 1-RM leg press. In rest of the study groups, the study was terminated for the participants who achieved =10% increase in 1-RM at Day 28 as compared to baseline. For rest of the participants the study continued till Day 56. The participants continued to exercise as per the ASCM guidelines throughout the study period.
[00112] On the day of assessment, the participants were asked to visit the site after at least 8 hours of fasting. They were asked to start the exercise with a warm up session consisting of 8 inward hip rotations, and 8 outward hip rotations (each side), 10 deep reverse lunges to knee raise, and 10 squats. Further to determine the 1-RM, the participants were asked to start the bench press with an initial weight of 50 kg for 3 repetitions. Subsequently, weight was increased by 5 kg till 60 kg, and there onwards, the weight was increased by 2.5 kg for each 3 completed repetitions till the subject failed to complete. A rest period of 2 minutes was provided between sets. The participants were asked to perform the bench press at the same speed of movement and with same range of motion throughout the study. Participants were provided water-ad-lib during exercise and were asked to breath deep. The bench press weight that participants lifted successfully for at least 1 repetition but could not complete 3 repetitions was recorded as 1-RM. The study was considered complete for the participants showing >10% increase in the 1-RM at Day 28 (D28) and rest were followed till Day 56 (D56).
[00113] All participants were evaluated at baseline (D0) and at Day 28 (D28) for muscle strength as indicated by increase in 1-RM leg press weight from Day 0 to Day 28. Participants were also assessed for the following at the end of study visit: (i) Muscle mass as indicated by increase in lean muscle mass by Dual-energy x-ray absorptiometry (DXA) from Day 0 to end of the study; (ii) Mid-thigh muscle girth measured (prior to exercise) at midpoint between inguinal fold and superior border of patella, from baseline to Day 28/56; (iii) Fatigue level as assessed by 11-point VAS scale for Fatigue (VAS-F); (iv) Change in total body fat percentage and the android fat percent using Dual-energy x-ray absorptiometry (DXA).
[00114] After 28 days of whey protein consumption, the participants in the EB-MS-01 group (i.e. placebo group, without resistance exercise) had no increase in 1-RM. Based on the DXA, it was noted that: the lean muscle mass showed varied results as two participants showed increase, and two participants reported decrease in values at the end of the study from baseline. Three participants in this group reported decrease in body fat % and one reported increase in body fat %. One participant reported decrease in VAS fatigue score. Detailed results of EB-MS-01 group are presented in Table 2.

Table 2: Details of participants in EB-MS-01 group
Participant 1 2 3 4
Days D0 D28 D0 D28 D0 D28 D0 D28
Max weight 1-RM, kg 107.5 107.5 110 110 77.5 77.5 150 147.5
VAS fatigue 3 0 3 3 6 6 4 4
Mid-thigh girth, cm - - 45.5 43 54.5 54.5 52 52
Lean body mass, g 36922 36080 44248 47173 50078 48827 43956 45262
Body fat, % 31.6 33.4 23.5 19.8 39.4 38.7 29.6 28.1
Fat free mass, g 39024 38238 46773 49633 53032 51708 46520 47814
Visceral fat, g 788 891 276 281 1228 1115 318 286
Android fat, g 39 39.9 24.6 20.5 48.6 46.7 31.4 29.2

[00115] Within the six participants randomized in EB-MS-02 group, which consumed whey protein with placebo and exercised as per the ASCM guidelines, only three participants reported marginal increase in 1-RM weight on Day 28 (2.56-5 % of baseline). Three participants reported increase in fatigue and two of the participants reported decrease in fatigue as assessed by VAS fatigue. Two participants reported increase in mid-thigh girth at the end of the study compared to baseline (increase of 0.5 and 4.5 cm in participant 3 and 4). All the participants in this group reported increase in the lean body mass ranged from 236-1832 gm at the end of the study as compared to baseline (Figure 2). An increase in fat free mass ranging from 249-1838 gm was also observed in all the participants. Detailed data are presented in Table 3 and 4 below.

Table 3: Details of participants 1-3 in EB-MS-02 group
Participant 1 2 3
Days D0 D56 D0 D56 D0 D56
Max weight 1-RM, kg 75 87.5 97.5 107.5 67.5 82.5
VAS fatigue 3 3 7 5 5 3
Mid-thigh girth, cm 49 49 51 50 43.5 44
Lean body mass, g 47932 48168 41508 43340 44959 45538
Body fat, % 33.3 33.7 40.9 40.5 23.6 24.8
Fat free mass, g 50686 50935 43864 45702 47439 48065
Visceral fat, g 1150 1064 703 934 398 507
Android fat, g 39.6 39.4 42.8 45.8 27 28.3

Table 4: Details of participants 4-6 in EB-MS-02 group
Participant 4 5 6
Days D0 D56 D0 D56 D0 D56
Max weight 1-RM, kg 120 127.5 150 147.5 180 187.5
VAS fatigue 2 3 3 5 3 8
Mid-thigh girth, cm 42 46.5 53 53 46 46
Lean body mass, g 43934 45180 49214 50663 43078 44470
Body fat, % 31 27.1 40.2 39.8 29.1 27.8
Fat free mass, g 46174 47422 51815 53198 45523 46898
Visceral fat, g 463 315 1189 1194 604 589
Android fat, g 34.4 28.6 45.3 45 33.5 33.2

[00116] Of the six participants in the EB-MS-03 group, five participants demonstrated 10.34% to 17.14% increase in the 1-RM (as can be seen from Figure 1) at 28th day as compared to baseline. Four participants reported decrease in fatigue as assessed by VAS fatigue and other two reported no change. Mid-thigh girth increased, from 44-53.5 to 47-55 cm, in three participants at the end of the study from baseline. As can be seen from Figure 2, increase in lean body mass, in the range of 680-2454 gm, was observed in four participants at the end of the study from baseline. Four participants reported increase in fat free mass, ranging from 649-2386 gm, at follow-up from baseline. In this group, five participants reported decrease in visceral and android fat at the end of the study from baseline. The data are represented in the Table 5 and 6.

Table 5: Details of participants 1-3 in EB-MS-03 group
Participant 1 2 3
Days D0 D28 D0 D28 D0 D28
Max weight 1-RM, kg 122.5 140 100 112.5 87.5 102.5
Insomnia severity index 3 0 3 4 3 4
VAS fatigue 7 5 4 3 6 5
Mid-thigh girth, cm 49 49 47 46 53.5 55
Lean body mass, g 41204 40914 48726 49406 52355 54117
Body fat, % 33.6 33.8 29.3 28.4 35.5 33.7
Fat free mass, g 43445 43145 51215 51864 54913 56688
Visceral fat, g 643 587 760 711 1490 1443
Android fat, g 42.1 41.8 35 32.8 46.9 43.7

Table 6: Details of participants 4-6 in EB-MS-03 group
Participant 4 5 6
Days D0 D28 D0 D28 D0 D56
Max weight 1-RM, kg 95 107.5 72.5 80 115 127.5
Insomnia severity index 5 5 4 4 2 2
VAS fatigue 6 3 4 4 7 7
Mid-thigh girth, cm 44 48 46.5 47 49 49
Lean body mass, g 40614 43068 49569 51724 46370 45304
Body fat, % 33.2 30.9 25.5 23 31.2 32.1
Fat free mass, g 42812 45198 52463 54621 48683 47687
Visceral fat, g 1055 823 438 362 648 661
Android fat, g 42.8 38.9 29.7 26.4 34.9 35.6

[00117] Based on the results from the pilot study, it could be noted that: (i) the participants in the EB-MS-03 group, who consumed extract of Phyllanthus spp., showed dramatic improvement in the muscle strength as assessed by 1-RM weight (>10% increase in the 1-RM weight) as compared to the participants in EB-MS-01 and EB-MS-02 groups (which showed increase of less than 5%); (ii) within the participants in the EB-MS-03 group, majority of participants reported decrease in body fat %, visceral and android fat at Day 28; and (iii) participants in the EB-MS-03 group also showed dramatic improvement in lean body mass as compared to the participants in EB-MS-01 and EB-MS-02 groups. Accordingly, it could be concluded that, extract of aerial parts of Phyllanthus spp. affords improved muscle strength, muscle mass, performance, lean body mass and body composition while reducing fat percentage (e.g. body fat %, visceral fat, and android fat), especially when administered with protein supplements (particularly, whey protein) in exercising subjects. Without wishing to be bound by the theory, it is believed that the extract of Phyllanthus spp. when supplemented with whey protein, it amplifies the effect of whey protein in individuals/subjects undergoing/undertaking exercise providing a faster and higher increase in body mass and strength.
[00118] Example 2: RANDOMIZED STUDY 2
[00119] Another randomized study was conducted to assess the efficacy of EB-PA supplementation with WPI on muscle strength, endurance, flexibility, grip strength, and mass in exercising males. 121 healthy male participants aged 20 to 35 years were randomly assigned to three arms: Placebo (MCC capsule and maltodextrin sachet), WPI (40 g WPI and MCC capsule), and EB-PA + WPI (40 g WPI and 500 mg EB-PA capsule). All participants underwent resistance training twice a week for 30 days. The primary outcome was the improvement in muscle strength, measured by one repetition maximum (1-RM) for upper and lower body. Secondary outcomes included muscle endurance, muscle flexibility, muscle mass, and grip strength.
[00120] The mean age (standard deviation mentioned in the parenthesis) of the participants was 24.4 (±4.7) years, 25 (±4.7) years, and 25.5 (±4.6) years, respectively. The mean height was 1.7 (±0.1) meters, 1.7 (±0.1) meters, and 1.7 (±0.1) meters, respectively. The mean weight was 72 (±9) kg, 72 (±8) kg, and 72 (±8) kg, respectively. The mean BMI was 25 (±2) kg/m², 25 (±2) kg/m², and 25 (±2) kg/m², respectively. The mean waist circumference was 92 (±7) cm, 93 (±6) cm, and 93 (±7) cm, respectively. conducted in compliance with the International Conference on Harmonization (ICH) recommendation on Good Clinical Practice (GCP) - E6 (R2), 2016, and National Ethical Guidelines for Biomedical and Health Research involving Human Participants, 2017.
[00121] The study included participants with a minimum 1-RM strength of 25 kg for the upper body and 100 kg for the lower body. Participants were required to have at least one month of endurance training and avoid caffeinated products and intense strength exercises for 24 hours before the study visit. Individuals with TSH levels between 0.4 and 4.9 mIU/L were eligible. Participants who consumed whey or other supplements within the past 3 months, had significant weight fluctuations, or had chronic diseases, hypertension, diabetes, or other health conditions were excluded. Details of the study groups, treatments and regimen is provided in Table 7.
Groups Study products Ingredients
Group 1 Placebo MCC capsule (500 mg) and maltodextrin sachet (40 g)
Group 2 WPI WPI (40 g) and MCC capsule (500 mg)
Group 3 EB-PA + WPI WPI (40 g) and EB-PA capsule (500 mg of extract of Phyllanthus spp)
Dose regimen One sachet of WPI or Maltodextrin twice daily (morning and evening) and one capsule 30 minutes after WPI in the morning

[00122] Participants were screened based on physical activity and 1-RM strength. Muscle strength, endurance, flexibility, mass, and grip strength were assessed using 1-RM, V sit-and-reach, DEXA, and hand grip dynamometer. Safety was monitored through vital signs and adverse event recording. The primary outcome was 1-RM for upper and lower body, while secondary outcomes included muscle endurance, flexibility, mass, and grip strength.
[00123] The study assessed the primary outcome, the impact of EB-PA on muscle strength using 1-RM for upper and lower body. 1-RM is a reliable measure of muscle strength. Participants were included if they matched their baseline 1-RM. All groups showed significant increases in lower body 1-RM compared to baseline. The EB-PA + WPI group exhibited the greatest improvement, with a twofold increase compared to the WPI group and an almost seven-fold increase compared to the placebo group. Similar to lower body 1-RM, all groups showed significant increases. The EB-PA + WPI group again demonstrated the greatest improvement, with a twofold increase compared to the WPI group and an almost four-fold increase compared to the placebo group. The EB-PA + WPI group exhibited significantly higher composite body strength (sum of upper and lower body 1-RM) compared to the placebo and WPI groups. Overall, the EB-PA + WPI group consistently demonstrated superior improvements in muscle strength compared to the other groups, highlighting the effectiveness of this combination.
[00124] It was found that EB-PA supplementation with WPI significantly improved muscle endurance, as measured by exercise volume. Participants in the EB-PA + WPI group demonstrated a substantial increase in exercise volume (196.88 kg) compared to the placebo (68.93 kg) and WPI (102.94 kg) groups. While improvements were observed in all groups, the EB-PA + WPI group consistently showed the greatest enhancements. Table 8 below shows the details of the participants.
Parameter Categories Placebo (N=42) WPI (N=36) EB-PA + WPI (N=43)
Mean (SD) 95% CI Min, Max Mean (SD) 95% CI Min, Max Mean (SD) 95% CI Min, Max
Muscle
endurance Day 0 846.79
(95.95) (816.88, 876.69) 650.00,
1030.00 897.75
(152.59) (846.12,
949.38) 660.00,
1375.00 859.98
(129.66) (820.07,
899.88) 540.00,
1100.00
Day 30
915.71
(124.56) (876.90,
954.53) 710.00,
1220.00 1000.69
(148.38) (950.49,
1050.90) 680.00,
1250.00 1056.86
(165.66) (1005.88,
1107.84) 755.00,
1425.00
Change
from baseline
at day 30
Day 37 68.93 (115.37) (32.98, 104.88) - 135.00,
310.00 102.94
(142.23) (54.82, 151.07) - 215.00,
390.00 196.88
(162.50) (146.87, 246.89) - 100.00,
631.00
885.00
(119.35) (847.81,
922.19) 655.00,
1170.00 1003.33
(153.77) (951.31, 1055.36) 765.00, 1370.00 979.19
(147.61) (933.76, 1024.61) 705.00,
1300.00
Change from baseline at
day 37 38.21
(119.06) (1.11, 75.32) - 165.00,
325.00 105.58
(157.36) (52.34,
158.83) - 355.00,
365.00 119.21
(177.38) (64.62,
173.80) - 255.00,
760.00

[00125] It was also demonstrated that EB-PA supplementation with WPI improved muscle flexibility. The EB-PA + WPI group showed the greatest improvement in muscle flexibility, with a mean change of 1.42 cm compared to the placebo group (0.46 cm) and the WPI group (0.91 cm). A statistically significant difference was observed between the EB-PA + WPI group and the placebo group. The Figure 3 shows the muscle flexibility test results.
[00126] The lean muscle mass (LMM) and fat-free mass (FFM) increased in the EB-PA + WPI group. In contrast, the placebo and WPI groups showed reductions in these parameters. Table 9 below shows the details of changes in lean body mass and decrease in fat composition the participants.
Parameter Categories Placebo (N=42) WPI (N=36) EB-PA + WPI (N=43)
Mean (SD) 95% CI Min, Max Mean (SD) 95% CI Min, Max Mean (SD) 95% CI Min, Max
Lean body mass (g) Day 0 49298.21 (5960.98) (47440.64, 51155.79) 38975.00, 61911.00 50079.56 (5917.31) (48077.42, 52081.69) 41756.0, 64573.00 48737.30
(4826.39) (47251.96, 50222.65) 40281.00, 60726.00
Day 30 49257.33
(5889.51) (47422.03,
51092.63) 39428.00, 62683.00 49892.08 (5675.89) (47971.64, 51812.53) 42980.0, 63132.00 48790.77
(4803.37) (47312.51, 50269.03) 39872.00,
60756.00
Change from baseline at day 30 -40.88 (1099.44) (-383.49,
301.73) -2667.00, 1771.00 -187.47(1321.26)
(-634.52,259.58) -3346.00,
2513.00 53.47
(813.22) (- 196.81,
303.74) -2023.00, 1724.00
Fat free mass (g) Day 0 51948.48
(6118.85) (50041.71,
53855.24) 41380.00, 65098.00 52786.14 (612 8.40) (50712.59, 54859.69) 44219.00
, 67642.0
0 51430.53 (5013.74) (49887.5
3, 52973.54) 42615.00,
63558.00
Day 30 51905.52 (6023.21) (50028.56, 53782.49) 41836.00,65492.00 52614.75 (5891.84) (50621.24, 54608.26) 45165.00
, 66298.00 51484.84 (4969.49) (49955.4
5, 53014.22) 42193.0
0, 63542.0
0
Change from baseline at day
30 - 42.95 (1086.52) (- 381.53, 295.63) - 2661.00, 1757.00 -171.39 (1285.95) (- 606.49,263.71) -3267.00,2390.00 54.30 (803.28) (- 192.91, 301.51) - 2005.00, 1737.00
Android Fat (%) Day 0 34.87 (13.66) (30.62, 39.13) 10.10, 54.70 35.00 (8.14) (32.24,37.75) 16.80, 48.80 34.99 (9.31) (32.13, 37.85) 14.50, 51.90
Day 30 34.81 (13.98) (30.45, 39.17) 7.50,
55.00 35.93 (8.33) (33.11,
38.75) 15.00,
50.30 35.07 (9.21) (32.23, 37.90) 14.80, 51.20
Change from baseline at day 30 - 0.06 (1.71) (-0.60, 0.47) -3.80, 3.80 0.93
(3.18) (-0.15, 2.01) -3.20,
16.20 0.07 (1.40) (-0.36, 0.50) - 2.60, 3.50

[00127] EB-PA supplementation with WPI significantly improved handgrip strength. The EB-PA + WPI group demonstrated the most substantial improvement, with a mean increase of 5.12 kg. This was significantly higher compared to the WPI (2.44 kg) and placebo groups (0.85 kg). Table 10 below shows the details of changes in grip strength.
Parameter Categories Placebo (N=42) WPI (N=36) EB-PA + WPI (N=43)
Mean (SD) 95% CI Min,
Max Mean (SD) 95% CI Min,
Max Mean (SD) 95% CI Min,
Max
Grip strength Day 0 31.25
(6.14) (29.34, 33.17) 21.67, 52.67 34.11 (7.26) (31.66, 36.57) 21.67, 52.67 32.93 (7.63) (30.58,
35.28) 20.00, 50.67
Day 30 32.10
(5.65) (30.34, 33.86) 21.67, 52.00 36.56 (6.35) (34.40, 38.71) 26.00, 53.00 38.05 (7.05) (35.88, 40.23) 27.67, 53.33
Change
from
baseline at day 30 0.85
(2.97) (-0.07, 1.78) -5.00, 10.16 2.44(2.50) (1.60, 3.29) - 4.00, 8.33 5.12
(3.28) (4.12, 6.13) -4.00, 12.67

[00128] Example 3: RANDOMIZED STUDY 3
[00129] The study investigated the effects of EB-PA on muscle strength, flexibility, and protein synthesis in young exercising adults. Participants received either a placebo or EB-PA for 30 days while engaging in resistance training. The study was a randomized, double-blind, placebo-controlled trial designed to evaluate the efficacy of EB-PA on muscle strength, flexibility, and protein synthesis in young exercising adults. Participants, aged 18-35, were randomly assigned to receive either EB-PA or a placebo for 30 days while engaging in moderate physical activity. Body Mass Index (BMI) of 25.71 (±2.07) kg/m2 and an average waist circumference of 95.6 (±1.29) cms. The participants as well as the researchers were blinded to the treatment. The study aimed to assess changes in muscle strength, measured by jump and throw distances and isokinetic peak torque; muscle mass, measured by DEXA scan; muscle flexibility, measured by the sit-and-reach test; and protein synthesis, measured by serum insulin levels. The study was conducted in compliance with ethical guidelines, including the Declaration of Helsinki, and participants provided informed consent before participating. Overall, the study aimed to determine if EB-PA supplementation, combined with resistance training, could improve muscle strength, flexibility, and protein synthesis in young adults.
[00130] Results showed that EB-PA supplementation significantly improved both upper and lower body strength compared to the placebo. The average distance achieved in the medicine ball throw test was significantly greater in the IP phase (548.26 cm) than in the placebo phase (519.05 cm). Additionally, the vertical jump performance also improved more in the IP phase (45.45 cm) compared to the placebo phase (44.83 cm). These findings suggest that EB-PA is effective in enhancing muscle strength.
[00131] The study evaluated muscle flexibility using the V sit and reach test. Results showed that EB-PA supplementation significantly improved muscle flexibility compared to the placebo. The mean change in flexibility increased threefold in the IP phase (2.08 cm) compared to the placebo phase (0.65 cm). Additionally, the study examined muscle protein synthesis activity through serum insulin levels. While there were no significant changes in muscle mass or isokinetic peak torque, the findings suggest that EB-PA may stimulate muscle protein synthesis through increased serum insulin levels.
[00132] Results showed that EB-PA significantly improved jump and throw distances, muscle flexibility, and serum insulin levels compared to the placebo. However, no significant changes were observed in muscle mass, fat percentage, or isokinetic peak torque. Overall, the study suggests that EB-PA supplementation can enhance muscle strength and flexibility in young adults when combined with resistance training.

ADVANTAGES
[00133] The present disclosure provides a method for one or more of: improving muscle strength, improving muscle mass, increasing muscle power, improving muscle flexibility, improving muscle endurance, increasing physical activity level, improving physical performance, increasing lean body mass, improving body composition, in decreasing fat percentage, and aiding in post exercise muscle recovery in a subject. Even upon discontinuation of administration of an extract of aerial parts of Phyllanthus spp. for upto 30 days the improved effects remain.
[00134] The present disclosure provides a formulation for one or more of: improving muscle strength, improving muscle mass, increasing muscle power, improving muscle flexibility, improving muscle endurance, increasing physical activity level, improving physical performance, increasing lean body mass, improving body composition, in decreasing fat percentage, and aiding in post exercise muscle recovery in a subject that is effective and economical.
,CLAIMS:1. A method for improving muscle strength in a subject in need thereof, the method comprising administering, to the subject, an extract of aerial parts of Phyllanthus spp..
2. A method for improving muscle mass in a subject in need thereof, the method comprising administering, to the subject, an extract of aerial parts of Phyllanthus spp..
3. A method for increasing physical activity level and exercise capacity in a subject in need thereof, the method comprising administering, to the subject, an extract of aerial parts of Phyllanthus spp..
4. A method for increasing lean body mass and decreasing fat in a subject in need thereof, the method comprising administering, to the subject, an extract of aerial parts of Phyllanthus spp..
5. A method for increasing muscle power in a subject in need thereof, the method comprising administering, to the subject, an extract of aerial parts of Phyllanthus spp..
6. A method for improving muscle flexibility in a subject in need thereof, the method comprising administering, to the subject, an extract of aerial parts of Phyllanthus spp..
7. A method for improving muscle endurance in a subject in need thereof, the method comprising administering, to the subject, an extract of aerial parts of Phyllanthus spp..
8. A method for aiding in post exercise muscle recovery in a subject in need thereof, the method comprising administering, to the subject, an extract of aerial parts of Phyllanthus spp..
9. The method as claimed in any of the preceding claims, wherein the extract comprises tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, and bitters in an amount ranging from 15% w/w to 30% w/w.
10. The method as claimed in any of the preceding claims, wherein the extract comprises an extract of aerial parts of Phyllanthus spp. selected from the group comprising Phyllanthus niruri, Phyllanthus amarus, Phyllanthus airy-shawii, Phyllanthus maderaspatensis, Phyllanthus urinaria, Phyllanthus fraternus, Phyllanthus corcovadensis and mixtures thereof.
11. The method as claimed in any of the preceding claims, wherein the extract is a hydro-alcoholic extract.
12. The method as claimed in any of the preceding claims, wherein the extract is administered by oral route at a dose ranging from 100 mg to 2500 mg per day in single or divided doses.
13. A method for amplifying effect of a protein supplement in one or more of: improving muscle strength, improving muscle mass, increasing muscle power, improving muscle flexibility, improving muscle endurance, increasing physical activity level, improving physical performance, increasing lean body mass, improving body composition, in decreasing fat percentage, and aiding in post exercise muscle recovery in a subject, the method comprising administering, to the subject, an extract of aerial parts of Phyllanthus spp..
14. The method as claimed in claim 13, wherein the extract comprises tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, and bitters in an amount ranging from 15% w/w to 30% w/w.
15. The method as claimed in claims 13 or 14, wherein the extract comprises an extract of aerial parts of Phyllanthus spp. selected from the group comprising Phyllanthus niruri, Phyllanthus amarus, Phyllanthus airy-shawii, Phyllanthus maderaspatensis, Phyllanthus urinaria, Phyllanthus fraternus, Phyllanthus corcovadensis and mixtures thereof.
16. The method as claimed in claims 14 or 15, wherein the extract is a hydro-alcoholic extract.
17. The method as claimed in claims 13-16, wherein the extract is administered by oral route at a dose ranging from 100 mg to 2500 mg per day in single or divided doses.
18. A formulation comprising:
a. an extract of aerial parts of Phyllanthus spp., said extract comprising tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, and bitters in an amount ranging from 15% w/w to 30% w/w; and
b. one or more pharmaceutically acceptable excipients.
19. The formulation as claimed in claim 18, wherein the one or more pharmaceutically acceptable excipient comprises a carrier, and wherein the carrier comprises silicon dioxide.
20. A process for preparing a formulation comprising an extract of aerial parts of Phyllanthus spp., and a pharmaceutically acceptable excipient, said process comprising the steps of:
a. taking pulverized aerial parts of Phyllanthus spp.;
b. effecting extraction of the pulverized aerial parts of Phyllanthus spp. to obtain an extract;
c. effecting drying of the extract; and
d. effecting pulverization of the dried extract with the one or more pharmaceutical acceptable excipients to obtain the formulation.
21. The process as claimed in claim 20, wherein the step of extraction comprises:
a. mixing the pulverized aerial parts of Phyllanthus spp. with a hydroalcoholic solvent in a ratio ranging from 1:5 to 1:25; and
b. heating the mixture at a temperature ranging from 60-70°C for a time period ranging from 10-25 hours to obtain the extract.
22. The process as claimed in claims 20 or 21, wherein the step of drying comprises spray drying the extract to obtain the dried extract.
23. The process as claimed in claims 20-22, wherein the pharmaceutical acceptable excipient is silicon dioxide, and wherein the step of pulverization comprises pulverizing the dried extract with silicon dioxide to obtain the formulation.
24. Use of an extract of aerial parts of Phyllanthus spp. comprising tannins in an amount ranging from 10% w/w to 30% w/w, corilagin in an amount ranging from 1% w/w to 4% w/w, and bitters in an amount ranging from 15% w/w to 30% w/w for preparing a medication for one or more of: improving muscle strength, improving muscle mass, increasing muscle power, improving muscle flexibility, improving muscle endurance, increasing physical activity level, improving physical performance, increasing lean body mass, improving body composition, in decreasing fat percentage, and aiding in post exercise muscle recovery in a subject.
25. An enriched Phyllanthus spp. extract composition comprising:
a) tannins in an amount ranging from 10% w/w to 30% w/w;
b) corilagin in an amount ranging from 1% w/w to 4% w/w;
c) bitters in an amount ranging from 15% w/w to 30% w/w; and
d) flavonoids in an amount ranging from 26% to 36%.