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US-20260124165-A1 - COMPOSITIONS COMPRISING CREATINE FOR USE IN TELOMERE LENGTHENING

US20260124165A1US 20260124165 A1US20260124165 A1US 20260124165A1US-20260124165-A1

Abstract

The present invention pertains to a pharmaceutical composition comprising creatine or its physiologically acceptable derivatives, precursors, salts, or adducts for facilitating telomere length. Another aspect of the invention concerns the utilization of a composition containing creatine or its derivatives, precursors, salts, or adducts as a dietary supplement to extend telomere length in aged subjects and smokers.

Inventors

  • Sergej Ostojic

Assignees

  • Sergej Ostojic

Dates

Publication Date
20260507
Application Date
20241101

Claims (8)

  1. 1 . The pharmaceutical compositions containing creatine or physiologically acceptable derivatives, salts, precursors and/or adducts thereof intended for telomere lengthening.
  2. 2 . The pharmaceutical composition as claimed in claim 1 , wherein insufficient telomere length results from aging, disease or environmental stress.
  3. 3 . The pharmaceutical composition according to any one of claims 1 to 2 , wherein the acceptable creatine derivative encompasses creatine, creatine hydrates, creatine esters phosphocreatine, guanidinoacetic acid, creatinol-O-phospate or a combination thereof.
  4. 4 . The pharmaceutical composition according to any one of claims 1 to 3 , wherein the acceptable creatine salts, creatine adducts, salts of physiologically acceptable creatine derivatives, and adducts of these derivatives ideally encompass acetates, aconitates, aminobutyrates, ascorbates, aspartates, chlorides, citrates, decanoates, fumarates, gluconates, hemi-sulfates, hydrochlorides isocitrates, ketoglutarates, ketoisocaproate, malates, maleates, nitrates, orotate, oxalates, oxaloacetates, phosphates, pyruvates, ribosides, succinates, sulfates, tartrates, taurinates, tetrahydrates, sodium, potassium, calcium, magnesium salts, guanidinoacetic acid adducts, or a combination thereof.
  5. 5 . The pharmaceutical composition of any one of claims 1 to 4 , wherein the daily dose of creatine in the composition is in the range of 1 gram to 4 grams.
  6. 6 . Use of a composition comprising creatine or physiologically acceptable derivatives and/or salts, precursors and or adducts thereof as dietary supplement or as a supplement for preparation of a diet supporting telomere length.
  7. 7 . The use of claim 6 , wherein insufficient telomere length is caused by aging or environmental stress (smoking).
  8. 8 . The use of any one of claims 6 to 7 , wherein the daily dose of creatine in the composition is in the range of 1 gram to 4 grams.

Description

REFERENCES CITED U.S. Patent Documents 11007210 B2 5/2021 Ramunas et al. Other Publications Astuti Y, Wardhana A, Watkins J, Wulaningsih W; PILAR Research Network. Cigarette smoking and telomere length: A systematic review of 84 studies and meta-analysis. Environ Res. 2017 Oct;158:480-489. doi: 10.1016/j.envres.2017.06.038. Balestrino M, Adriano E. Beyond sports: Efficacy and safety of creatine supplementation in pathological or paraphysiological conditions of brain and muscle. Med Res Rev. 2019 Nov;39(6): 2427-2459. doi: 10.1002/med.21590. Brosnan M E, Brosnan J T. The role of dietary creatine. Amino Acids. 2016 Aug;48(8):1785-91. doi: 10.1007/s00726-016-2188-1. Candow D G, Chilibeck P D, Forbes S C, Fairman C M, Gualano B, Roschel H. Creatine supplementation for older adults: Focus on sarcopenia, osteoporosis, frailty and Cachexia. Bone. 2022 Sep;162:116467. doi: 10.1016/j. bone.2022.116467. Forbes S C, Cordingley D M, Cornish S M, Gualano B, Roschel H, Ostojic S M, Rawson E S, Roy B D, Prokopidis K, Giannos P, Candow D G. Effects of Creatine Supplementation on Brain Function and Health. Nutrients. 2022 February 22;14(5):921. doi: 10.3390/nu14050921. Galié S, Canudas S, Muralidharan J, García-Gavilán J, Bulló M, Salas-Salvadó J. Impact of Nutrition on Telomere Health: Systematic Review of Observational Cohort Studies and Randomized Clinical Trials. Adv Nutr. 2020 May 1;11(3):576-601. doi: 10.1093/advances/nmz107. Gao X, Yu X, Zhang C, Wang Y, Sun Y, Sun H, Zhang H, Shi Y, He X. Telomeres and Mitochondrial Metabolism: Implications for Cellular Senescence and Age-related Diseases. Stem Cell Rev Rep. 2022 Oct;18(7):2315-2327. doi: 10.1007/s12015-022-10370-8. Epub 2022 April 23. Herrmann M, Pusceddu I, März W, Herrmann W. Telomere biology and age-related diseases. Clin Chem Lab Med. 2018 July 26;56(8):1210-1222. doi: 10.1515/cclm-2017-0870. Institute of Medicine. 2006. Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Washington, D C: The National Academies Press. https://doi.org/10.17226/11537. Jaskelioff M, Muller F L, Paik J H, Thomas E, Jiang S, Adams A C, Sahin E, Kost-Alimova M, Protopopov A, Cadiñanos J, Horner J W, Maratos-Flier E, Depinho R A. Telomerase reactivation reverses tissue degeneration in aged telomerase-deficient mice. Nature. 2011 January 6;469(7328):102-6. doi: 10.1038/nature09603. Kreider R B, Stout J R. Creatine in Health and Disease. Nutrients. 2021 Jan. 29;13(2):447. doi: 10.3390/nu13020447. McCall W, Persky A M. Pharmacokinetics of creatine. Subcell Biochem. 2007;46:261-73. Ostojic S M, Ostojic J, Drid P, Vranes M, Jovanov P. Dietary guanidinoacetic acid increases brain creatine levels in healthy men. Nutrition. 2017 Jan;33:149-156. doi: 10.1016/j.nut.2016.06.001. Ostojic S M, Forbes S C. Perspective: Creatine, a Conditionally Essential Nutrient: Building the Case. Adv Nutr. 2022 Feb. 1;13(1):34-37. doi: 10.1093/advances/nmab111. Ostojic S M. Creatine as a food supplement for the general population. Journal of Functional Foods. 2021 Aug. 1;83:104568. Ostojic S M. Low Tissue Creatine: A Therapeutic Target in Clinical Nutrition. Nutrients. 2022 Mar. 15;14(6):1230. doi: 10.3390/nu14061230. Wang Q, Zhan Y, Pedersen NL, Fang F, Hägg S. Telomere Length and All-Cause Mortality: A Meta-analysis. Ageing Res Rev. 2018 Dec;48:11-20. doi: 10.1016/j.arr.2018.09.002. FIELD OF THE INVENTION The current invention pertains to pharmaceutical compositions containing creatine and its derivatives useful in the extension of telomeres in a subject in need thereof. Such subjects include those with shortened telomeres as a consequence of aging, stress exposure, chronic inflammation, or other illnesses. Another objective of the invention involves employing creatine and creatine derivatives as food supplements to prepare a diet aimed at lengthening telomeres. DESCRIPTION OF THE PRIOR ART Telomeres are repetitive sequences of DNA found at the ends of chromosomes. They function as protective caps, preserving the integrity of the genetic material during cell division and preventing the loss of genetic information. As cells divide and replicate, their telomeres gradually shorten, acting as a biological clock that tracks cellular aging and replication limit. Maintaining adequate telomere length is essential for healthy cell function and longevity. Telomere shortening has been shown to accompany physical disease states that are associated with aging and stress exposure, including diabetes mellitus, obesity, heart disease, chronic obstructive pulmonary disease (COPD), asthma, as well as psychiatric illnesses, such as depression, anxiety, post-traumatic stress disorder (PTSD), bipolar disorder, and schizophrenia. Shorter telomeres have been associated with increased incidence of diseases and poor survival. Telomere length typically shortens with age, demonstrated by an average annual reduction of approximately 30-35 base pairs, as found in a study by Herrmann, M. et al (Clin. Chem. Lab. Med. 20