IP Library › Granted Patent US 12,285,423
Granted Patent B2
US 12,285,423 · App. 18/382,904 · Granted Apr 29, 2025

Composition for enhancing mitochondrial function

Inventors: Larisa Andreeva (London, GB); Igor Anatolievich Pomytkin (Moscow, RU); Galina Nonina Skladtchikova (Hellemp, DK)
Assignee: Mitocholine Ltd.
A61K31/455A23L33/13A23L33/15A23L33/17A61K31/194A61K31/197A61K31/706A61K47/16A61P25/24A61P25/28
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Quick Facts
Patent No.
US 12,285,423
App. No.
18/382,904
Granted
Apr 29, 2025
Kind
B2
Abstract

A method and composition for enhancing synthesis of adenosine triphosphate (ATP) in mitochondria of brain cells of a human includes providing the composition including a synergistic compound of choline cation and succinate anion (2-) in a molar ratio of choline:succinate of 2:1 in the form of dicholine succinate (DiSu) in a daily dosage that synergistically increases ATP levels in brain cells. The method and composition are formulated to affect frequency and/or severity of various conditions by regulating ATP levels in brain cells. The method and composition are formulated to reduce rate of decline in the brain under conditions of cerebral hypoxia, e.g., due to aging, injury, illness, and the similar conditions.

Claims (18)

1. A method for enhancing synthesis of adenosine triphosphate (ATP) in mitochondria of brain cells of a healthy human subject; the method comprising:

providing for oral consumption by the human subject, a nutritional composition comprising a synergistic compound of choline cation and succinate anion (2-) in a molar ratio of choline: succinate of 2:1 in the form of dicholine succinate (DiSu), wherein the composition is formulated to comprise a daily dosage of DiSu that synergistically increases ATP levels in the brain cells, wherein:

the daily dosage of the DiSu is within a range of from about 250 mg to about 2000 mg; and

the synergistic increase in ATP levels in the brain cells is relative to the sum of increases in ATP levels from choline cation and succinate anion (2-) not combined together in the molar ratio of choline: succinate of 2:1 in the form of dicholine succinate (DiSu).

2. The method of claim 1 , further comprising formulating the composition to include creatine or a creatine precursor selected from the group consisting of glycine and arginine.

3. The method of claim 1 , further comprising reducing a rate of decline of ATP levels in the brain under conditions of cerebral hypoxia by providing the composition comprising the daily dosage of the DiSu.

4. The method of claim 1 , further comprising reducing a frequency and/or a severity of lack of concentration by increasing ATP levels in the brain cells of the human subject by providing the composition comprising the daily dosage of the DiSu.

5. The method of claim 1 , further comprising reducing a frequency and/or a severity of feelings of depression by increasing ATP levels in the brain cells of the human subject by providing the composition comprising the daily dosage of the DiSu.

6. The method of claim 1 , further comprising reducing a frequency and/or a severity of fatigue by increasing ATP levels in the brain cells of the human subject by providing the composition comprising the daily dosage of the DiSu.

7. The method of claim 1 , further comprising reducing a frequency and/or a severity of mood swings by increasing ATP levels in the brain cells of the human subject by providing the composition comprising the daily dosage of the DiSu.

8. A method for enhancing cognitive function in a healthy aging human subject, the method comprising:

providing for oral consumption by the healthy aging human subject, a nutritional composition comprising a synergistic compound of choline cation and succinate anion (2-) in a molar ratio of choline: succinate of 2:1 in the form of dicholine succinate (DiSu), wherein the nutritional composition is formulated to enhance cognitive function in the human subject by including a daily dosage of DiSu that synergistically increases ATP levels in brain cells of the human subject, wherein:

the daily dosage of the DiSu is within a range of from about 250 mg to about 2000 mg; and

the synergistic increase in ATP levels in the brain cells is relative to the sum of increases in ATP levels from corresponding amounts of choline cation and succinate anion (2-) assessed separately.

9. The method of claim 8 , further comprising formulating the composition to include creatine or a creatine precursor selected from the group consisting of glycine and arginine.

10. The method of claim 8 , further comprising reducing a frequency and/or a severity of psychological stress by synergistically increasing ATP levels in the brain cells of the human subject by providing the composition comprising the daily dosage of the DiSu.

11. The method of claim 8 , further comprising reducing a frequency and/or a severity of insomnia by synergistically increasing ATP levels in the brain cells of the human subject by providing the composition comprising the daily dosage of the DiSu.

12. The method of claim 8 , further comprising reducing a rate of decline of ATP levels in the brain of the human subject under conditions of cerebral hypoxia by providing the composition comprising the daily dosage of the DiSu.

Assignments (2)
CORRECTIVE ASSIGNMENT TO CORRECT THE ADDRESS FOR THE APPLICANT WHICH NEEDS TO BE UPDATED PREVIOUSLY RECORDED ON REEL 67324 FRAME 191. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT OF ASSIGNORS INTEREST. Recorded Mar 13, 2026
From: ANDREEVA, LARISA; POMYTKIN, IGOR ANATOLIEVICH; SKLADTCHIKOVA, GALINA NONINA
To: MITOCHOLINE LTD.
Reel/Frame 075093/0107 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 6, 2024
From: ANDREEVA, LARISA; POMYTKIN, IGOR ANATOLIEVICH; SKLADTCHIKOVA, GALINA NONINA
To: MITOCHOLINE LTD
Reel/Frame 067324/0191 →
Priority Claims (4)
GB 1710316 · Jun 28, 2017 · national
GB 1715214 · Sep 20, 2017 · national
GB 1800244 · Jan 8, 2018 · national
GB 1807733 · May 12, 2018 · national
Continuity (3)
Continuation 18051460 · Oct 31, 2022
Continuation 16624830
Related Publication 20240066019A1 · Feb 29, 2024
References Cited (38)
US 3579423A · Yamane et al. · 1971 [cited by applicant]
US 7666908B2 · Pomytkin · 2010 [cited by examiner]
US 8367121B2 · Mazzio · 2013 [cited by examiner]
US 8673977B2 · Pomytkin · 2014 [cited by applicant]
US 11571415B2 · Andreeva · 2023 [cited by examiner]
US 20060199862A1 · Pomytkin et al. · 2006 [cited by applicant]
US 20090214680A1 · Giuliano et al. · 2009 [cited by applicant]
US 20150374745A1 · Pomytkin et al. · 2015 [cited by applicant]
WO 2009022933A1 · 2009 [cited by applicant]
Rao et al, Indian Journal of Psychiatry, 2008, 50(2), 77-82. [cited by examiner]
Strozheva et al., BMC Pharmacology, 2008, 8(1), 1-13. [cited by examiner]
McCandless, Cerebral Energy Metabolism and Metabolic Encephalopathy, 1985, pp. 313-329. [cited by examiner]
AK Reeve et al., “Aggregated a-synuclein and complex I deficiency: exploration of their relationship in differentiated neurons”, Cell Death and Disease (2015) 6, e1820; doi:10.1038/cddis.2015.166, Jul. 16, 2015, pp. 1-1… [cited by applicant]
S. Ogoh et al, “Cerebral blood flow during exercise: mechanisms of regulation”, J Appl Physiol 107:. Sep. 3, 2009, pp. 1370-1380. [cited by applicant]
B. Hassel et al., “Cerebral dicarboxylate transport and metabolism studied with isotopically labelled fumarate, malate and malonate”, Journal of Neurochemistry, 2002, pp. 410-419. [cited by applicant]
SH Zeisel et al., “Choline: An Essential Nutrient for Public Health”, Nutr Rev. Author manuscript; available in PMC, Nov. 25, 2009, pp. 1-14. [cited by applicant]
MJ Valenzuela et al., “Complex mental activity and the aging brain: Molecular, cellular and cortical network mechanisms”, ScienceDirect, Brian Reserch Reviews, 2007, pp. 198-213. [cited by applicant]
ZI Storozjeva et al., “Dicholine salt of succinic acid, a neuronal insulin sensitizer, ameliorates cognitive deficits in rodent models of normal aging, chronic cerebral hypoperfusion, and beta-amyloid peptide-(25-35)-in… [cited by applicant]
T. Wallimann et al., “Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the ‘phosphocreatine circuit’ for cellular energy homeostas… [cited by applicant]
XH. Zhu et al., “In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences”, PNAS vol. 122 No. 9, Mar. 3, 2015, pp. 2876-2881. [cited by applicant]
F. Bartolome et al., “Measurement of Mitochondrial NADH and FAD Autofl uorescence in Live Cells”, Mitochondrial Medicine: vol. I, Probing Mitochondrial Function, 2015, pp. 263-270. [cited by applicant]
LD. Lukyanova et al., “Mitochondria-controlled signaling mechanisms of brain protection in hypoxia”, Frontiers in Nueroscience, Oct. 1, 2015, pp. 1-15. [cited by applicant]
X. Chen et al., “Molecular and functional analysis of SDCT2, a novel rat sodium-dependent dicarboxylate transporter”. The Journal of Clinical Investigation vol. 103, No. 8, Apr. 1999, pp. 1159-1168. [cited by applicant]
V. Knott et al., “Neurocognitive effects of acute choline supplementation in low, medium and high performer healthy volunteers”, ScienceDirect, Pharmacology, Biochemistry and Behavior, Feb. 12, 2015, pp. 119-129. [cited by applicant]
PK.Shetty et al., “Nicotinamide pre-treatment ameliorates NAD(H) hyperoxidation and improves neuronal function after severe hypoxia”, Neurobiol Dis Vo. 62, Feb. 2014, pp. 1-21. [cited by applicant]
B. Gong et al., “Nicotinamide riboside restores cognition through an upregulation of proliferator-activated receprot-y coactivator 1a regulated B-secretase 1 degradation and mitochondrial gene expression in Alzheimer's … [cited by applicant]
A. Vaarmann et al., “Novel pathway for an old neurotransmitter: Dopamine-induced neuronal calcium signalling via receptor-independent mechanisms”, ScienceDirect, Cell Calcium vol. 48, Sep. 16, 2010, pp. 176-182. [cited by applicant]
C. Rae et al., “Oral creatine monohydrate supplementation improves brain performance: a double-blind, placebo-controlled, cross-over trial”, The Royal Society, Aug. 13, 2003, pp. 2147-2150. [cited by applicant]
AP. Wojtovich et al., “Physiological consequences of complex II inhibition for aging, disease, and the mKATP channel”, Biochim Biophys Acta, NIH Public Access, May 1, 2014, pp. 1-32. [cited by applicant]
PC. Hinkle, “P/O ratios of mitochondrial oxidative phosphorylation”, ScienceDirect, Biochimica et Biophysica Acta, Sep. 2004, pp. 1-11. [cited by applicant]
A. Pomytkin et al., “Study of the Effect of Preconditioning with Succinic Acid Salt of Choline (1:2) on the Disturbances of Energy Metabolism in the Brain during Ischemia by 31 P NMR In vivo”, Doklady Biochemistry and B… [cited by applicant]
BH. Cline et al., “The neuronal insulin sensitizer dicholine succinate reduces stress-induced depressive traits and memory deficit: possible role of insulin-like growth factor 2”, BMC Neuroscience, 2002, pp. 1-14. [cited by applicant]
H. Imamura et al., “Visualization of ATP levels inside single living cells with fluorescence resonance energy transfer-based genetically encoded indicators”, PNAS vol. 106 No. 37, Sep. 15, 2009, pp. 15651-15656. [cited by applicant]
“WHO Model List of Essential Medicines” 19th Edition, Apr. 2015, pp. 1-51 (55). [cited by applicant]
M. Gerlach et al., Altered Brain Metabolism of Iron as a Cause of Neurodegenerative Diseases?, Journal of Neurochemistry vol. 63, No. 3, 1994, pp. 793-807. [cited by applicant]
D. Kapogiannis et al., “Disrupted energy metabolism and neuronal circuit dysfunction in cognitive impairment and Alzheimer's disease”, Lancet Neurology vol. 10, Feb. 2011, pp. 187-198. [cited by applicant]
McCandless et al., “Cerebral Energy Metabolism and Metabolic Encephalopathy”, Departments of Anesthesia and Physiology, The Milton S. Hershey Medical Center, The Pennsylvania State University College of Medicine, Hershe… [cited by applicant]
Rao et al., “Understanding nutrition, depression and mental illnesses”, Indian J. Psychiatry, Apr.-Jun. 2008, pp. 77-82. [cited by applicant]