(12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date WO 2016/125025 Al 11 August 2016 (11.08.2016) P O P C T (51) International Patent Classification: CAO, Leila Denise; 2 bis impasse Henri Mouret, 84000 A61K 36/41 (2006.01) A61P 21/00 (2006.01) Avignon (FR). A61K 36/28 (2006.01) (81) Designated States (unless otherwise indicated, for every (21) International Application Number: kind of national protection available): AE, AG, AL, AM, PCT/IB20 16/000322 AO, AT, AU, AZ, BA, BB, BG, BH, BN, BR, BW, BY, BZ, CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, (22) Date: International Filing DO, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, 3 February 2016 (03.02.2016) HN, HR, HU, ID, IL, IN, IR, IS, JP, KE, KG, KN, KP, KR, (25) Filing Language: English KZ, LA, LC, LK, LR, LS, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, NO, NZ, OM, (26) Publication Language: English PA, PE, PG, PH, PL, PT, QA, RO, RS, RU, RW, SA, SC, (30) Priority Data: SD, SE, SG, SK, SL, SM, ST, SV, SY, TH, TJ, TM, TN, 14/612,973 3 February 2015 (03.02.2015) US TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (71) Applicant: NATUREX SA [FR/FR]; 250 rue Pierre Bayle, (84) Designated States (unless otherwise indicated, for every BP 81218-8491 1, Avignon Cedex 9 (FR). kind of regional protection available): ARIPO (BW, GH, GM, KE, LR, LS, MW, MZ, NA, RW, SD, SL, ST, SZ, (72) Inventors: BILY, Antoine, Charles; 162 rue Pomme Car TZ, UG, ZM, ZW), Eurasian (AM, AZ, BY, KG, KZ, RU, dinal^ 84270 Vedene (FR). MEYER, Marjolaine; la, rue TJ, TM), European (AL, AT, BE, BG, CH, CY, CZ, DE, des Faisans, 67370 Pfettisheim (FR). CHEVALIER, Karl; DK, EE, ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, 132 chemin de Mireille, Residence Les Hauts de I'Emperi, LV, MC, MK, MT, NL, NO, PL, PT, RO, RS, SE, SI, SK, Bat A - Appt A01, 13300 Salon de Provence (FR). SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, LAURENCON, Lise; Residence Bel Air 36, Impass de GW, KM, ML, MR, NE, SN, TD, TG). Fruitiers, 84140 Montfavet (FR). FEUILLERE, Nicolas; Published: 15 rue Pierre Long, 84350 Courthezon (FR). ROLLER, Marc; 70 chemin de I'Oliveraie, 843 10 Morieres les — with international search report (Art. 21(3)) Avignon (FR). BIRTIC, Simona; 38 Grand' Rue, 84300 — before the expiration of the time limit for amending the Cavaillon (FR). FANCA-BERTHON, Pascale Elizabeth claims and to be republished in the event of receipt of Renee; 38 domaine du Verger, 84250 Le Thor (FR). FAL- amendments (Rule 48.2(h)) o (54) Title: COMPOSITIONS AND METHODS FOR IMPROVED MUSCLE METABOLISM o (57) Abstract: A composition for improving muscle metabolism in a subject and methods for manufacturing and using same. Em bodiments include compositions having an extract of Rhaponticum and an extract of Rhodiola. An extract of Rhaponticum may in clude amounts of eedysterones including 20-hydroxyecdysone. An extract of Rhodiola my include salidrosides and rosavins, includ ing rosavin. Suitable ingestion dosages of the composition may be operable to increase protein synthesis and reduce protein proteo - lysis in a subject. COMPOSITIONS AND METHODS FOR IMPROVED MUSCLE METABOLISM CROSS-REFERENCE TO RELATED APPLICATION [0001] This application claims the benefit of U.S. Patent Application Serial No.: 14/612,973, filed February 3, 2015 hereinafter incorporated by reference. FIELD OF THE INVENTION [0002] The present disclosure provides compositions and methods for increasing muscle protein synthesis, reducing muscle proteolysis, increasing muscle mass and/or strength, and improving aerobic/anaerobic sport performance. Useful compositions include, but are not limited to, Rhaponticum and Rhodiola extracts, and combinations thereof. SUMMARY OF THE INVENTION [0003] In one aspect, the invention includes a composition including a Rhaponticum extract. In some embodiments, the Rhaponticum extract comprises at least 0.01%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% ecdysteroids including, for example, about 0.1 to 10%> ecdysteroids or about 0.4% to 5% ecdysteroids. In some embodiments the Rhaponticum extract composition comprises at least 0.01%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9% , or 10% of 20-hydroxyecdysone including, for example, 0.1%> to 5.0%> of 20- hydroxyecdysone. [0004] In another aspect, the invention includes a composition including a Rhodiola extract. In some embodiments, the Rhodiola extract comprises at least 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% salidrosides including, for example, about 1% to 4%. In some embodiments, the Rhodiola extract composition comprises at least 0 .1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10%, rosavins including, for example, about 0.5% to 10% or 3% to 6% rosavins. In some embodiments, the composition comprises at least 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6% , 7% , 8% , 9% , or 10%, rosavin including, for example, about 0.5 to 10% rosavin or 1% to 5% rosavin. In some embodiments, the Rhodiola extract composition comprises at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 99% Rhodiola extract including, for example about 50% to 99%, 60%-95%, 70%-95% Rhodiola extract. [0005] In one aspect, the invention includes a composition including a Rhaponticum extract and a Rhodiola extract. In some embodiments, the Rhaponticum extract comprises at least 0.01%, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8% , 9% , or 10% ecdysteroids including, for example, about 0.1 to 10%> ecdysteroids or about 0 .4% to 5% ecdysteroids. In some embodiments the composition comprises at least 0.01%>, 0.05%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% of 20-hydroxyecdysone including, for example, 0.1%> to 5.0% of 20-hydroxyecdysone. [0006] In some embodiments, the Rhodiola extract comprises at least 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% salidrosides including, for example, about 1% to 4 % . In some embodiments, the composition comprises at least 0.1%>, 0.2%, 0.3%>, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10%, rosavins including, for example, about 3% to 6%> rosavins. In some embodiments, the composition comprises at least 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% , rosavin including, for example, about 2% to 5% rosavin. [0007] In some embodiments, the composition comprises at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 99% Rhodiola extract including, for example about 50% to 99%, 60%-95%, 70%-95% Rhodiola extract. [0008] In another aspect, the invention includes compositions having (i) at least 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% ecdysteroids including, for example, about 0.1 to 10% ecdysteroids or about 0.4% to 5% ecdysteroids and (ii) at least 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% salidrosides including, for example, about 1% to 4%. In some embodiments the composition comprises at least 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10% of 20-hydroxyecdysone including, for example, 0.1% to 5.0% of 20- hydroxyecdysone. In some embodiments, the composition comprises at least 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, or 10%, rosavins including, for example, about 3% to 6% rosavins. In some embodiments, the composition comprises at least 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8% , 9% , or 10% , rosavin including, for example, about 2% to 5% rosavin. [0009] In other embodiments, any of the foregoing compositions may be included in a pharmaceutical formulation. The composition may be formulated in any convenient and suitable formulation depending upon the route of intended administration. Suitable formulations for oral administration include, for example, a tablet, pill, capsule, powder, solution, suspension, syrup, or elixir. Optionally, the composition further contains a pharmaceutically-acceptable excipient or carrier, or other pharmaceutically-active or non- active ingredient. [0010] Other aspects of the invention include methods for increasing protein synthesis, increasing muscle strength, and/or reducing protein proteolysis in a subject by administering to the subject any of the compositions or pharmaceutical formulations described above. Further aspects include methods for treating conditions associated with or characterized by muscle atrophy in a subject by administering to the subject any of the compositions or pharmaceutical formulations described above. The composition or formulation may be administered to the subject by any appropriate route of administration. In one embodiment, the composition is orally administered. In some embodiments, the subject is administered a daily dose of at least 1 mg/kg/day, 5 mg/kg/day, 10 mg/kg/day, 20 mg/kg/day, 30 mg/kg/day, 40 mg/kg/day, 50 mg/kg/day, 75 mg/kg/day, 100 mg/kg/day, 200 mg/kg/day, 400 mg/kg/day, 600 mg/kg/day, 800 mg/kg/day, 1000 mg/kg/day, 2000 mg/kg/day, 3000 mg/kg/day, 5000 mg/kg/day or more per day.