[go: up one dir, main page]

WO2024200609A1 - Association de trigonelline et d'oleuropéine ou de métabolite d'oleuropéine pour le traitement ou la prévention d'états liés aux mitochondries chez un animal de compagnie - Google Patents

Association de trigonelline et d'oleuropéine ou de métabolite d'oleuropéine pour le traitement ou la prévention d'états liés aux mitochondries chez un animal de compagnie Download PDF

Info

Publication number
WO2024200609A1
WO2024200609A1 PCT/EP2024/058416 EP2024058416W WO2024200609A1 WO 2024200609 A1 WO2024200609 A1 WO 2024200609A1 EP 2024058416 W EP2024058416 W EP 2024058416W WO 2024200609 A1 WO2024200609 A1 WO 2024200609A1
Authority
WO
WIPO (PCT)
Prior art keywords
trigonelline
oleuropein
cells
composition
metabolite
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/EP2024/058416
Other languages
English (en)
Inventor
Jerome FEIGE
Umberto DE MARCHI
Aurélie HERMANT
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Societe des Produits Nestle SA
Nestle SA
Original Assignee
Societe des Produits Nestle SA
Nestle SA
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Societe des Produits Nestle SA, Nestle SA filed Critical Societe des Produits Nestle SA
Publication of WO2024200609A1 publication Critical patent/WO2024200609A1/fr
Anticipated expiration legal-status Critical
Pending legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4425—Pyridinium derivatives, e.g. pralidoxime, pyridostigmine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/075—Ethers or acetals
    • A61K31/085—Ethers or acetals having an ether linkage to aromatic ring nuclear carbon
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/351—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom not condensed with another ring
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/02—Algae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/74—Rubiaceae (Madder family)
    • A61K36/742—Coffea, e.g. coffee
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present disclosure generally relates to compositions and methods that use a combination of trigonelline and at least one oleuropein and/or metabolite thereof to produce intracellular NAD + /NADH and boost mitochondrial function.
  • NAD + is an enzyme co-factor that is essential for the function of several enzymes related to reduction-oxidation reactions and energy metabolism.
  • NAD + functions as an electron carrier in cell metabolism of amino acids, fatty acids, and carbohydrates.
  • NAD + serves as an activator and substrate for sirtuins, a family of protein deacetylases that have been implicated in metabolic function and extended lifespan in lower organisms.
  • sirtuins a family of protein deacetylases that have been implicated in metabolic function and extended lifespan in lower organisms.
  • the co-enzymatic activity of NAD + together with the tight regulation of its biosynthesis and bioavailability, makes it an important metabolic monitoring system that is clearly involved in the aging process.
  • mitochondria are the primary source of aerobic energy production in mammalian cells and also maintain a large Ca 2+ gradient across their inner membrane, providing a signaling potential for this molecule.
  • mitochondrial Ca 2+ plays a role in the mitochondria in the regulation of ATP generation and potentially contributes to the orchestration of cellular metabolic homeostasis. Specifically, activation of mitochondrial Ca2+ import increases cellular energy metabolism (Glancy & Balaban, 2012).
  • the present disclosure provides a method of treating or preventing (e.g., reducing incidence and/or severity) a mitochondria-related disease or a condition associated with altered mitochondrial function in a pet animal in need thereof or at risk thereof.
  • the method comprises orally administering to the pet animal a composition comprising trigonelline and at least one of oleuropein and/or metabolite thereof.
  • the mitochondria-related disease or condition can be selected from the group consisting of deleterious effects of aging, stress (e.g., oxidative stress), obesity, overweight, reduced metabolic rate, metabolic syndrome, diabetes mellitus, complications from diabetes, hyperlipidemia, neurodegenerative disease, cognitive disorder, stress-induced or stress-related cognitive dysfunction, mood disorder, anxiety disorder, age-related neuronal death or dysfunction, chronic kidney disease, kidney failure, trauma, infection, cancer, hearing loss, macular degeneration, myopathies and dystrophies, and combinations thereof.
  • stress e.g., oxidative stress
  • obesity e.g., obesity, overweight, reduced metabolic rate, metabolic syndrome, diabetes mellitus
  • complications from diabetes hyperlipidemia, neurodegenerative disease, cognitive disorder, stress-induced or stress-related cognitive dysfunction, mood disorder, anxiety disorder, age-related neuronal death or dysfunction, chronic kidney disease, kidney failure, trauma, infection, cancer, hearing loss, macular degeneration, myopathies and dystrophies, and combinations thereof.
  • the present invention provides a method of achieving at least one result selected from the group consisting of (i) improved mitochondrial calcium uptake in one or more cells, (ii) improved utilization of calcium in one or more cells, (iii) increased mitochondrial energy in one or more cells, (ii) improvement in a physiological state linked to metabolic fatigue in one or more cells, (iii) treatment or prevention of metabolic fatigue in one or more cells, (iv) treatment or prevention of muscle fatigue, (v) improved mobility, (vi) improved longevity (viii) increasing NAD+ levels in one or more cells and (ix) improved conditions of restrictions of NAD+ bioavailability, the method comprising orally administering to a pet animal an effective amount of a combination of trigonelline and at least one of oleuropein and/or metabolite thereof.
  • the trigonelline and at least one of oleuropein and/or metabolite thereof is in an amount effective to increase the calcium uptake in mitochondrial cells.
  • the present combination of ingredient is also particularly effective in conditions of restrictions of NAD + bioavailability. That condition has been reported in cancer and neurodegeneration, as well as the course of natural aging and, in general, during states of genotoxic stress, that accompany a growing list of diseases. In addition, loss of NAD homeostasis leads to progressive and reversible degeneration of skeletal muscle.
  • the increase in NAD + biosynthesis can provide one or more benefits to the pet animal.
  • the one or more benefits can comprise at least one of increased mitochondrial energy, treatment or prevention of metabolic fatigue, treatment or prevention of muscle fatigue, improvement in a physiological state linked to metabolic fatigue in one or more cells, improved mobility or improved longevity.
  • the NAD + biosynthesis is increased in one or more cells of the pet animal, for example one or more cells that are part of at least one body part selected from the group consisting of a liver, a kidney, a brain, and a skeletal muscle.
  • At least a portion of the trigonelline is provided by a plant extract in the composition, such as one or more of a coffee extract, a hemp extract, a pumpkin seed extract and/or a fenugreek seed extract, for example a plant extract enriched in trigonelline.
  • a plant extract in the composition such as one or more of a coffee extract, a hemp extract, a pumpkin seed extract and/or a fenugreek seed extract, for example a plant extract enriched in trigonelline.
  • at least a portion of trigonelline is provided from a fenugreek extract.
  • At least a portion of the trigonelline is provided from an algae source, for example, a Laminariaceae extract.
  • the metabolite of oleuropein is selected from the group consisting of oleuropein aglycone, hydroxytyrosol, homovanillyl alcohol, isohomovanillyl alcohol, glucuronidated forms thereof, sulfated forms thereof, derivatives thereof, and mixtures thereof.
  • the composition is selected from the group consisting of a petfood product, a treat, a veterinary petfood or supplement, and combinations thereof.
  • An advantage of one or more embodiments provided by the present disclosure is to potentiate benefits on oxidative metabolism and prevent DNA damage.
  • Another advantage of one or more embodiments provided by the present disclosure is to replenish NAD + pools, which decline with age.
  • Yet another advantage of one or more embodiments provided by the present disclosure is to help off-set slowing of the metabolism associated with aging.
  • Another advantage of one or more embodiments provided by the present disclosure is to help increase fatty acids metabolism.
  • Yet another advantage of one or more embodiments provided by the present disclosure is to help the body to metabolize fat and increase lean body mass.
  • Another advantage of one or more embodiments provided by the present disclosure is to help maintain heart health.
  • Yet another advantage of one or more embodiments provided by the present disclosure is to help support healthy LDL-cholesterol and fatty acid levels in the blood.
  • Another advantage of one or more embodiments provided by the present disclosure is to treat or prevent neurodegeneration, such as age-related neurodegeneration, and/or promote neurite outgrowth.
  • FIG. 1 is a graph showing the beneficial effect of the combination of 3pM Oleuropein aglycone plus 500pM Trigonelline iodine on mitochondria activation, via mitochondrial Ca 2+ , in C2C12-derived myotubes.
  • the graph shows that Oleuropein aglycone alone (3pM) enhances mitochondrial Ca 2+ by 17%, compared with buffer (white).
  • the combination of Oleuropein aglycone (3pM) plus Trigonelline (500 pM) enhances mitochondrial Ca 2+ by 76%, compared with Trigonelline alone (buffer, black).
  • FIG. 2 is a graph showing the beneficial effect of the combination of lOpM Oleuropein aglycone plus 500pM Trigonelline iodine on mitochondria activation, via mitochondrial Ca 2+ , in C2C12-derived myotubes.
  • the graph shows that Oleuropein aglycone alone (lOpM) enhance mitochondrial Ca 2+ by 28%, compared with buffer (white).
  • the combination of Oleuropein aglycone (lOpM) plus Trigonelline (500 pM) enhances mitochondrial Ca 2+ by 67%, compared with Trigonelline alone (buffer black).
  • the data are plotted as a percentage of integrated mitochondrial calcium response obtained in presence of the buffer.
  • compositions disclosed herein may lack any element that is not specifically disclosed herein.
  • a disclosure of an embodiment using the term “comprising” includes a disclosure of embodiments “consisting essentially of’ and “consisting of’ the components identified. Any embodiment disclosed herein can be combined with any other embodiment disclosed herein.
  • a condition “associated with” or “linked with” another condition means the conditions occur concurrently, preferably means that the conditions are caused by the same underlying condition, and most preferably means that one of the identified conditions is caused by the other identified condition.
  • the terms “food,” “food product” and “food composition” mean a product or composition that is intended for ingestion by an individual such as a pet animal and provides at least one nutrient to the individual.
  • a food product typically includes at least one of a protein, a lipid, a carbohydrate and optionally includes one or more vitamins and minerals.
  • the compositions of the present disclosure can comprise, consist of, or consist essentially of the elements disclosed herein, as well as any additional or optional ingredients, components, or elements described herein or otherwise useful in a diet.
  • isolated means removed from one or more other compounds or components with which the compound may otherwise be found, for example as found in nature.
  • isolated preferably means that the identified compound is separated from at least a portion of the cellular material with which it is typically found in nature. In an embodiment, an isolated compound is free from any other compound.
  • prevention includes reduction of risk, incidence and/or severity of a condition or disorder.
  • treatment includes both prophylactic or preventive treatment (that prevent and/or slow the development of a targeted pathologic condition or disorder) and curative, therapeutic or disease-modifying treatment, including therapeutic measures that cure, slow down, lessen symptoms of, and/or halt progression of a diagnosed pathologic condition or disorder; and treatment of patients at risk of contracting a disease or suspected to have contracted a disease, as well as patients who are ill or have been diagnosed as suffering from a disease or medical condition.
  • the term does not necessarily imply that a subject is treated until total recovery.
  • treatment also refer to the maintenance and/or promotion of health in a pet animal not suffering from a disease but who may be susceptible to the development of an unhealthy condition.
  • treatment,” “treat” and “to alleviate” are also intended to include the potentiation or otherwise enhancement of one or more primary prophylactic or therapeutic measure.
  • treatment,” “treat” and “to alleviate” are further intended to include the dietary management of a disease or condition or the dietary management for prophylaxis or prevention a disease or condition.
  • a treatment can be patient- or doctor-related.
  • unit dosage form refers to physically discrete units suitable as unitary dosages for pet animal subjects, each unit containing a predetermined quantity of the composition disclosed herein in an amount sufficient to produce the desired effect, in association with a pharmaceutically acceptable diluent, carrier or vehicle.
  • the specifications for the unit dosage form depend on the particular compounds employed, the effect to be achieved, and the pharmacodynamics associated with each compound in the host.
  • an “effective amount” is an amount that prevents a deficiency, treats a disease or medical condition in a pet animal, or, more generally, reduces symptoms, manages progression of the disease, or provides a nutritional, physiological, or medical benefit to the pet animal.
  • the relative terms “improve,” “increase,” “enhance,” “promote” and the like refer to the effects of the composition disclosed herein, namely a composition comprising trigonelline, relative to a composition not having trigonelline but otherwise identical.
  • "promoting” refers to enhancing or inducing relative to the level before administration of the composition disclosed herein.
  • a "subject” or “individual” is a pet animal.
  • “Pet animal” includes, but is not limited to, mammals, which includes but is not limited to rodents; aquatic mammals; domestic animals such as dogs, cats and other pets; farm animals such as sheep, pigs, cows and horses.
  • an “older adult” or “ageing individual” has exceeded 50% of the average lifespan for its particular species and/or breed within a species.
  • the term “elderly” means a pet animal subject that has reached 60% of its likely lifespan, in some embodiments at least 70%, at least 80% or at least 90% of its likely lifespan.
  • a determination of lifespan may be based on actuarial tables, calculations, or estimates, and may consider past, present, and future influences or factors that are known to positively or negatively affect lifespan. Consideration of species, gender, size, genetic factors, environmental factors and stressors, present and past health status, past and present nutritional status, and stressors may be taken into consideration when determining lifespan.
  • An ageing cat or dog has an age from birth of at least about 5 years.
  • An elderly or senior cat or dog has an age from birth of at least about 7 years.
  • Muscle fatigue means a reduced contractile force in one or more muscles due to a shortage of substrates within the muscle fiber and/or an accumulation of metabolites within the muscle fiber which interfere either with the release of calcium or with the ability of calcium to stimulate muscle contraction.
  • metabolic syndrome refers to a combination of medical disorders that, when occurring together, increase the risk of developing cardiovascular disease and diabetes. Its prevalence increases with age.
  • neurodegenerative disease or " neurodeg enerative disorder” refers to any condition involving progressive loss of functional neurons in the central nervous system.
  • the neurodegenerative disease is associated with age-related cell death.
  • Non-limiting examples of neurodegenerative diseases include mild cognitive impairment, Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis (also known as ALS and as Lou Gehrig's disease), peripheral neuropathy, AIDS dementia complex, adrenoleukodystrophy, Alexander disease, Alper's disease, ataxia telangiectasia, Batten disease, bovine spongiform encephalopathy (BSE), Canavan disease, corticobasal degeneration, Creutzfeldt-Jakob disease, dementia with Lewy bodies, fatal familial insomnia, frontotemporal lobar degeneration, Kennedy's disease, Krabbe disease, Lyme disease, Machado-Joseph disease, multiple sclerosis,
  • cognitive function refers to any mental process that involves symbolic operations, e.g., perception, memory, attention, speech comprehension, speech generation, reading comprehension, creation of imagery, learning, and reasoning, preferably at least memory.
  • Methods for measuring cognitive function are well-known and can include, for example, individual or battery tests for any aspect of cognitive function.
  • One such test is the Prudhoe Cognitive Lunction Test by Margallo-Lana et al. (2003) J. Intellect. Disability Res. 47:488-492.
  • Another such test is the Mini Mental State Exam (MMSE), which is designed to assess orientation to time and place, registration, attention and calculation, recall, language use and comprehension, repetition, and complex commands. Folstein et al. (1975) J. Psych. Res. 12:189-198.
  • Such tests can be used to assess cognitive function in an objective manner, so that changes in cognitive function, for example in response to treatment in accordance with methods disclosed herein, can be measured and compared.
  • a “cognitive disorder” refers to any condition that impairs cognitive function.
  • Non-limiting examples of a cognitive disorder include delirium, dementia, learning disorder, attention deficit disorder (ADD), and attention deficit hyperactivity disorder (ADHD).
  • a "neurite” refers to any projection from the cell body of a neuron, such as an axon or a dendrite.
  • the term is frequently used when speaking of immature or developing neurons, especially of cells in culture, because axons can be difficult to differentiate from dendrites before differentiation is complete.
  • Neurites are often packed with microtubule bundles, the growth of which is stimulated by nerve growth factor (NGF), as well as tau proteins, microtubule associated protein 1 (MAPI), and microtubule associated protein 2 (MAP2).
  • NNF nerve growth factor
  • MPI microtubule associated protein 1
  • MAP2 microtubule associated protein 2
  • the neural cell adhesion molecule N-CAM simultaneously combines with another N-CAM and a fibroblast growth factor receptor to stimulate the tyrosine kinase activity of that receptor to induce the growth of neurites.
  • Mobility is the ability to move independently and safely from one place to another.
  • Metal fatigue means reduced mitochondrial function in one or more cells (e.g., one or more of liver, kidney, brain, skeletal muscle) due to a shortage of substrates within the one or more cells and/or due to an accumulation of metabolites within the one or more cells which interfere with mitochondrial function.
  • trigonelline is any compound comprising 1-methylpyridin-l- ium-3 -carboxylate including, for example, any salt thereof (e.g., Chloride or Iodide salt) and/or a form in which the ring therein may be reduced.
  • any salt thereof e.g., Chloride or Iodide salt
  • trigonelline is represented by the structure of formula 1, being able to establish a salt with an anion (X-), such as a halogen, for example, iodide or chloride.
  • X- anion
  • the structure of formula 1 is also known as 3 -carboxy- 1 -methylpyridinium, N-Methylnicotinic acid, l-methylpyridine-3 -carboxylic acid, l-methylpyridin-l-ium-3 -carboxylic acid, Pyridinium 3 -carboxy- 1 -methyl- hydroxide inner salt (8CI), 1 -methylnicotinic acid, Pyridinium 3-carboxy-l- methyl-.
  • trigonelline is represented by the structure of formula 2 in its inner salt form.
  • the structure of formula 2 is also known as Caffearine, Gynesine, N-Methylnicotinate, Trigenolline, Coffearine, Trigonellin, Coffearin, Betain nicotinate, Betaine nicotinate, 1- methylpyridinium-3-carboxylate, Nicotinic acid N-methylbetaine, l-Methylpyridinio-3-carboxylate, 1- Methyl-3-pyridiniumcarboxylate, N-Methylnicotinic acid, Trigenelline, Caffearin, 3-Carboxy-l- methylpyridinium hydroxide inner salt, N'-Methylnicotinate, l-methylpyridin-l-ium-3-carboxylate, 3- Carboxy-1 -methylpyridinium hydroxide inner salt, Pyridinium 3-carboxy-l -
  • optionally “trigonelline” can include metabolites and pyrolysis products thereof, such as nicotinamide, nicotinamide riboside, 1 -methylnicotinamide, l-methyl-2- pyridone-5-carboxamide (Me2PY), l-methyl-4-pyridone-5 -carboxamide (Me4PY), and alkylpyridiniums, such as 1-methyl-pyridinium (NMP) and 1,4-dimethylpyridinium; although as noted later herein, some embodiments exclude one or more of these metabolites and pyrolysis products of trigonelline.
  • metabolites and pyrolysis products thereof such as nicotinamide, nicotinamide riboside, 1 -methylnicotinamide, l-methyl-2- pyridone-5-carboxamide (Me2PY), l-methyl-4-pyridone-5 -carboxamide (Me4PY), and alky
  • the present disclosure provides a method for increasing intracellular NAD+ in a pet animal, the method comprising administering to the pet animal a composition comprising trigonelline and at least one of oleuropein and/or metabolite thereof in an amount effective to increase NAD + biosynthesis.
  • the present disclosure provides a method of treating or preventing (e.g., reducing incidence and/or severity) a mitochondria-related disease or a condition associated with altered mitochondrial function in a pet animal in need thereof or at risk thereof.
  • the method comprises orally administering to the pet animal a composition comprising trigonelline and at least one of oleuropein and/or metabolite thereof in an amount effective to increase NAD + biosynthesis.
  • the mitochondria-related disease or condition can be selected from the group consisting of deleterious effects of aging, stress, obesity, overweight, reduced metabolic rate, metabolic syndrome, diabetes mellitus, complications from diabetes, hyperlipidemia, neurodegenerative disease, cognitive disorder, stress-induced or stress-related cognitive dysfunction, mood disorder, anxiety disorder, age-related neuronal death or dysfunction, chronic kidney disease, kidney failure, trauma, infection, cancer, hearing loss, macular degeneration, myopathies and dystrophies, and combinations thereof.
  • the increase in NAD + biosynthesis can provide one or more benefits to the individual (e.g., a pet animal undergoing medical treatment).
  • the one or more benefits can comprise at least one of increased mitochondrial energy, treatment or prevention of metabolic fatigue, treatment or prevention of muscle fatigue, improvement in a physiological state linked to metabolic fatigue in one or more cells, improved mobility or improved longevity.
  • the NAD + biosynthesis is increased in one or more cells of the human, for example one or more cells that are part of at least one body part selected from the group consisting of a liver, a kidney, a brain, and a skeletal muscle.
  • the composition is administered to an older adult or an elderly individual.
  • the composition can comprise a pharmacologically effective amount of trigonelline in a pharmaceutically suitable carrier.
  • the trigonelline concentration preferably ranges from about 0.05 wt.% to about 4 wt.%, or from about 0.5 wt.% to about 2 wt.% or from about 1.0 wt.% to about 1.5 wt.% of the aqueous liquid composition.
  • the method can comprise administering daily trigonelline in the weight range of 0.05 mg - 1 g per kg body weight of the pet animal, preferably 1 mg -200 mg per kg body weight, more preferably 5 mg - 150 mg per kg body weight, even more preferably 5 mg - 80 mg per kg body weight, or most preferably 5 mg - 20 mg per kg body weight.
  • At least a portion of the trigonelline is isolated. Additionally or alternatively, at least a portion of trigonelline can be chemically synthesized.
  • the composition comprises trigonelline which is chemically synthesized which is at least about 90% trigonelline, preferably at least about 98% trigonelline.
  • At least a portion of the trigonelline is provided by a plant or algae extract, for example an extract from one or more of coffee bean (e.g., a green coffee extract), Japanese radish, fenugreek seed, garden pea, hemp seed, oats, potato, dahlia, Stachys species, Strophanthus species, Laminariaceae species (especially Laminaria and Saccharina), Postelsia palmaeformis, Pseudochorda nagaii, Akkesiphycus or Dichapetalum cymosum.
  • coffee bean e.g., a green coffee extract
  • Japanese radish radish
  • fenugreek seed e.g., Japanese radish
  • fenugreek seed e.g., garden pea, hemp seed, oats, potato, dahlia, Stachys species, Strophanthus species, Laminariaceae species (especially Laminaria and Sac
  • the plant extract is preferably enriched in trigonelline, i.e., the starting plant material comprises one or more other compounds in addition to the trigonelline, and the enriched plant material has a ratio of the trigonelline relative to at least one of the one or more other compounds that is higher than the ratio in the starting plant material.
  • compositions comprise plant sources and/or enriched plant sources that provide at least a portion of the trigonelline in the composition.
  • the composition comprises enriched fenugreek extract which provides at least about 25 - 50% trigonelline in the composition. In a more preferred embodiment, the composition comprises enriched fenugreek extract which provides at least about 28 - 40% trigonelline.
  • composition consisting essentially of trigonelline contains trigonelline and is substantially free or completely free of any additional compound that affects NAD + production other than the trigonelline.
  • the composition consists of the trigonelline and one or more excipients.
  • substantially free means that any of the other compound present in the composition is no greater than 1.0 wt.% relative to the amount of trigonelline, preferably no greater than 0.1 wt.% relative to the amount of trigonelline, more preferably no greater than 0.01 wt.% relative to the amount of trigonelline, most preferably no greater than 0.001 wt.% relative to the amount of trigonelline.
  • At least a portion of the oleuropein is obtained by extraction, e.g., by extraction from a plant such as a plant belonging to the Oleaceae family, preferably one or more of the stems, the leaves, the fruits or the stones of a plant belonging to the Oleaceae family such as Olea europaea (olive tree), a plant of genus Ligustrum, a plant of genus Syringa, a plant of genus Fraximus, a plant of genus Jasminum and a plant of genus Osmanthus.
  • at least a portion of the oleuropein can be obtained by argan oil, produced from kernels of the argan tree (Argania spinosa) or by chemical synthesis.
  • Non-limiting examples of suitable metabolites of oleuropein include oleuropein aglycone, hydroxytyrosol, homovanillyl alcohol, isohomovanillyl alcohol, and mixtures thereof.
  • the effective amount of the combination of oleuropein and/or metabolite thereof varies with the particular composition, the age and condition of the recipient, and the particular disorder or disease being treated. Nevertheless, in a general embodiment, 0.001 mg to 1.0 g of the at least one of oleuropein and/or metabolite thereof can be administered to the individual per day, preferably from 0.01 mg to 0.9 g of the at least one of oleuropein and/or metabolite thereof per day, more preferably from 0.1 mg to 750 mg of the at least one of oleuropein and/or metabolite thereof per day, more preferably from 0.5 mg to 500 mg of the at least one of oleuropein and/or metabolite thereof per day, and most preferably from 1.0 mg to 200 mg of the at least one of oleuropein and/or metabolite thereof per day.
  • the at least one of oleuropein and/or metabolite thereof is the only polyphenol in the composition and/or the only polyphenol administered to the individual.
  • Another aspect of the present disclosure is a method of treating or preventing (e.g., reducing incidence and/or severity) a mitochondria-related disease or a condition associated with altered mitochondrial function in a pet animal in need thereof or at risk thereof.
  • the method comprises orally administering to a pet animal an effective amount of a combination of trigonelline and at least one of oleuropein and/or metabolite thereof.
  • the mitochondria-related disease or condition can be selected from the group consisting of deleterious effects of aging, stress (e.g., oxidative stress), obesity, overweight, reduced metabolic rate, metabolic syndrome, diabetes mellitus, complications from diabetes, hyperlipidemia, neurodegenerative disease, cognitive disorder, stress-induced or stress-related cognitive dysfunction, mood disorder, anxiety disorder, age-related neuronal death or dysfunction, chronic kidney disease, kidney failure, trauma, infection, cancer, hearing loss, macular degeneration, myopathies and dystrophies, and combinations thereof.
  • stress e.g., oxidative stress
  • obesity e.g., obesity, overweight, reduced metabolic rate, metabolic syndrome, diabetes mellitus
  • complications from diabetes hyperlipidemia, neurodegenerative disease, cognitive disorder, stress-induced or stress-related cognitive dysfunction, mood disorder, anxiety disorder, age-related neuronal death or dysfunction, chronic kidney disease, kidney failure, trauma, infection, cancer, hearing loss, macular degeneration, myopathies and dystrophies, and combinations thereof.
  • Yet another aspect of the present disclosure is a method of achieving at least one result selected from the group consisting of (i) improved mitochondrial calcium uptake in one or more cells, (ii) improved utilization of calcium in one or more cells, (iii) increased mitochondrial energy in one or more cells, (ii) improvement in a physiological state linked to metabolic fatigue in one or more cells, (iii) treatment or prevention of metabolic fatigue in one or more cells, (iv) treatment or prevention of muscle fatigue, (v) improved mobility, (vi) improved longevity (viii) increasing NAD+ levels in one or more cells and (ix) improved conditions of restrictions of NAD+ bioavailability, the method comprising orally administering to a pet animal an effective amount of a combination of trigonelline and at least one of oleuropein and/or metabolite thereof.
  • the trigonelline and at least one of oleuropein and/or metabolite thereof are in an amount effective to increase the calcium uptake in mitochondrial cells.
  • Aging is a condition that can be linked to one of the following: oxidative stress, reduced level of glutathione, and lower redox ratio NAD + /NADH.
  • the compositions disclosed herein can treat or prevent these deleterious effects of aging. For example, trigonelline increases NAD + , and the present inventors believe that the increased NAD + may lead to enhancement of glutathione through redox recycling.
  • oxidative stress is involved in many diseases. Examples include atherosclerosis, Parkinson's disease, heart failure, myocardial infarction, Alzheimer's disease, schizophrenia, bipolar disorder, fragile X syndrome, and chronic fatigue syndrome.
  • One source of reactive oxygen under normal conditions in pet animals is the leakage of activated oxygen from mitochondria during oxidative phosphorylation.
  • Other enzymes capable of producing superoxide (O2-) are xanthine oxidase, NADPH oxidases and cytochromes P450.
  • Hydrogen peroxide another strong oxidizing agent, is produced by a wide variety of enzymes including several oxidases.
  • Reactive oxygen species play important roles in cell signaling, a process termed redox signaling. Thus, to maintain proper cellular homeostasis a balance must be struck between reactive oxygen production and consumption.
  • Oxidative stress contributes to tissue injury following irradiation and hyperoxia. It is also suspected to be important in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and Huntington's disease.
  • ALS amyotrophic lateral sclerosis
  • Oxidative stress is also thought to be linked to certain cardiovascular diseases, since oxidation of low-density lipoprotein (LDL) in the vascular endothelium is a precursor to plaque formation. Oxidative stress also plays a role in the ischemic cascade due to oxygen reperfusion injury following hypoxia. This cascade includes both strokes and heart attacks. Oxidative stress has also been implicated in chronic fatigue syndrome. [0079] Moreover, the free radical theory of aging suggests that the biological process of aging results in increased oxidative stress in elderly pet animals. The ability of a cell to resist the damaging potential of oxidative stress is determined by a vital balance between generation of oxidant free radicals and the defensive array of antioxidants available to the cell.
  • LDL low-density lipoprotein
  • GSH glutathione
  • compositions disclosed herein can treat or prevent this condition.
  • Another aspect of the present disclosure is a unit dosage form of a composition comprising trigonelline and at least one of oleuropein and/or metabolite thereof, and the composition contains the trigonelline and at least one of oleuropein and/or metabolite thereof in an amount effective for treatment or prevention of at least condition selected from the group consisting of deleterious effects of aging, diabetes (type I or type II), complications from diabetes (e.g., diabetic dyslipidemia and/or diabetic microvascular complications such as nephropathy, retinopathy, and/or neuropathy), insulin resistance, metabolic syndrome, dyslipidemia, overweight, obesity, overweight, raised cholesterol levels, raised triglyceride levels, elevated fatty acid levels, fatty liver disease (e.g., non-alcoholic fatty liver disease, including with or without inflammation), cardiovascular disease (e.g., heart failure and/or impaired cardiac contractile function), neurodegenerative disease (e.g., from aging), depression, anxiety, decreased/low motivation, impaired cognitive function, myopathy
  • Yet another aspect of the present disclosure is a method of delaying off-set of metabolic decline, decreasing oxidative stress, maintaining immune function and/or maintaining cognitive function in a healthy older adult.
  • the method comprises administering an effective amount of a composition comprising trigonelline and at least one of oleuropein and/or metabolite thereof to the pet animal.
  • the cognitive function can be selected from the group consisting of perception, memory, attention, speech comprehension, speech generation, reading comprehension, creation of imagery, learning, reasoning, and combinations thereof.
  • the pet animal does not have a cognitive disorder; alternatively, the individual has a cognitive disorder.
  • the pet animal can be elderly and/or can have cognitive decline associated with aging. and/or metabolite
  • the composition can be administered at least one day per week, preferably at least two days per week, more preferably at least three or four days per week (e.g., every other day), most preferably at least five days per week, six days per week, or seven days per week.
  • the time period of administration can be at least one week, preferably at least one month, more preferably at least two months, most preferably at least three months, for example at least four months.
  • dosing is at least daily; for example, a subject may receive one or more doses daily, in an embodiment a plurality of doses per day.
  • the administration continues for the remaining life of the individual.
  • the administration occurs until no detectable symptoms of the medical condition remain.
  • the administration occurs until a detectable improvement of at least one symptom occurs and, in further cases, continues to remain ameliorated.
  • the composition includes petfood compositions to supply the necessary dietary requirements for an animal, animal treats (e.g., biscuits), dietary supplements, veterinary petfood or supplement, and combinations thereof.
  • the compositions may be a dry composition (e.g., kibble), semimoist composition, wet composition, or any mixture thereof.
  • the composition is a dietary supplement such as a gravy, drinking water, beverage, yogurt, powder, granule, paste, suspension, chew, morsel, treat, snack, pellet, pill, capsule, tablet, or any other suitable delivery form.
  • the composition may contain additional components such as proteins, carbohydrates and fats.
  • the dietary supplement can comprise a high concentration of the UFA and NORC, and B vitamins and antioxidants. This permits the supplement to be administered to the animal in small amounts, or in the alternative, can be diluted before administration to an animal.
  • the dietary supplement may require admixing, or can be admixed with water or other diluent prior to administration to the animal.
  • pet food or pet treat compositions comprise from about 15% to about 50% crude protein.
  • the crude protein material may comprise vegetable proteins such as soybean meal, soy protein concentrate, com gluten meal, wheat gluten, cottonseed, and peanut meal, or animal proteins such as casein, albumin, and meat protein.
  • meat protein useful herein include pork, lamb, equine, poultry, fish, and mixtures thereof.
  • the food composition is a pet food composition such as a premium or super-premium pet food composition.
  • the pet food is formulated for canines and has a protein content of about 20-30%, preferably about 24-28%, and more preferably about 25-27%.
  • the protein content of a dog food composition is about 26% by weight.
  • the formulation is for felines and has a protein content of about 35-45%, preferably about 37-42%, and more preferably about 39-41%.
  • the protein content of a cat food composition is about 40%.
  • the composition is a food product comprising about 15% to about 50% protein, about 5% to about 40% fat, about 5% to about 10% ash content, and having a moisture content of about 5% to about 20%.
  • at least a portion of the protein is selected from the group consisting of (i) protein from an animal source, (ii) protein from a plant source and (iii) a mixture thereof.
  • the protein is selected from the group consisting of (i) free form amino acids, (ii) unhydrolyzed protein, (iii) partially hydrolyzed protein, (iv) extensively hydrolyzed protein, and (v) mixtures thereof.
  • the protein can comprise essential amino acids and/or conditionally essential amino acids, e.g., such amino acids that may be insufficiently delivered due to low caloric intake or illness.
  • the protein can comprise one or more essential amino acids selected from the group consisting of histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine; and each of these amino acids (if present) may be administered in the composition in a daily dose from about 0.0476 to about 47.6 mg amino acid/kg body weight.
  • each of these amino acids may be administered in the composition in a daily dose from about 0.0476 to about 47.6 mg amino acid/kg body weight.
  • lower intake of methionine leads to lower levels of protein translation and ultimately muscle synthesis.
  • the protein can comprise one or more conditionally essential amino acids (e.g., amino acids conditionally essential in illness or stress) selected from the group consisting of arginine, cysteine, glutamine, glycine, proline, ornithine, serine and tyrosine; and each of these amino acids (if present) may be administered in the composition in a daily dose from about 0.0476 to about 47.6 mg amino acid/kg body weigth.
  • conditionally essential amino acids e.g., amino acids conditionally essential in illness or stress
  • the composition comprises branched chain amino acids in at least one form selected from the group consisting of (i) free form, (ii) bound to at least one additional amino acid, and (iii) mixtures thereof.
  • the branched chain amino acids can comprise leucine, isoleucine and/or valine in an amount effective to activate mTOR in the individual.
  • at least a portion of the protein is 5 to 95% hydrolyzed.
  • the protein has a formulation selected from the group consisting of (i) at least 50% of the protein has a molecular weight of 1-5 kDa, (ii) at least 50% of the protein has a molecular weight of 5-10 kDa and (iii) at least 50% of the protein has a molecular weight of 10-20 kDa.
  • the composition may include a source of carbohydrates.
  • Any suitable carbohydrate may be used in the composition including, but not limited to, starch (e.g., modified starch, amylose starch, tapioca starch, com starch), sucrose, lactose, glucose, fructose, com syrup solids, maltodextrin, xylitol, sorbitol or combinations thereof.
  • the source of carbohydrates is preferably not greater than 50 energy % of the composition, more preferably not greater than 36 energy % of the composition, and most preferably not greater than 30 energy % of the composition.
  • the composition can have a high protein: carbohydrate energy ratio, for example greater than 0.66, preferably greater than 0.9 and more preferably greater than 1.2.
  • the composition may include a source of fat.
  • the source of fat may include any suitable fat or fat mixture.
  • suitable fat sources include vegetable fat, such as olive oil, com oil, sunflower oil, high-oleic sunflower, rapeseed oil, canola oil, hazelnut oil, soy oil, palm oil, coconut oil, blackcurrant seed oil, borage oil, lecithins, and the like, animal fats such as milk fat; or combinations thereof.
  • the food composition is a wet food, such as a canned food, frozen food, or fresh food product.
  • the food composition is shelf stable. In other embodiments, it must be refrigerated. In other embodiments, the food composition is an intermediate moisture product or a dry food product as described above.
  • the composition is administered to the animal in conjunction with one or more drugs.
  • the composition is administered to the animal on a daily basis, preferably in a single dose.
  • the compounds may be administered as their pharmaceutically acceptable salts. They may also be used in appropriate association with other pharmaceutically active compounds.
  • the following methods and excipients are merely exemplary and are in no way limiting.
  • C2C12 cells were purchased from ATCC. C2C12 cells were seeded in 384-well plates at a density of 4500 cells per well in DMEM medium, high glucose (Gibco) + 10% fetal calf serum. Myotubes were differentiated from C2C12 cells by growing the cells in DMEM containing 2% horse serum, for 6 days.
  • Mitochondrial calcium measurements were carried out using myotubes infected with the adenovirus (from Sirion biotech) expressing the luminescent mitochondrially-targeted calcium sensor mitochondrial aequorin (Montero et al., 2000).
  • myotubes were incubated for 2h at room temperature (22°C) in standard Aequorin buffer (145 mM NaCl, 5 mM KC1, 1 mM MgCh, 1 mM CaCh, 10 mM glucose and 10 mM Hepes, pH 7.4) with 1 pM wild type coelenterazine.
  • Trigonelline Iodine (0 pM, buffer, or 500 pM, as indicated in the figures) and Oleuropein aglycone (3 pM or 10 pM, as indicated in the figures) were incubated for 2h in Aequorin buffer.
  • Myotubes were stimulated with 5 mM of caffeine and the total calcium transiting during stimulation was calculated as the area under the curve, during caffeine stimulation.
  • Luminescence was measured at the FLIPR cell imaging reader (Molecular devices). Calibration of the luminescence data into Calcium concentration was carried out using an algorithm as described previously (Bonora et al., 2013). Custom module analysis based on Excel (Microsoft) and GraphPad Prism 7.02 (GraphPad) software was used for quantification.
  • the combination of Trigonelline plus Oleuropein promotes the beneficial effects of the 2 compounds by boosting the calcium uptake into the mitochondria.
  • Bonora M., Giorgi, C., Bononi, A., Marchi, S., Patergnani, S., Rimessi, A., Rizzuto, R., and Pinton, P. (2013). Subcellular calcium measurements in mammalian cells using jellyfish photoprotein aequorin-based probes. Nature Protocols 8, 2105-2118.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Epidemiology (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Biotechnology (AREA)
  • Organic Chemistry (AREA)
  • Medical Informatics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Botany (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Diabetes (AREA)
  • Toxicology (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Neurology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne des compositions comprenant de la trigonelline et au moins une oleuropéine et/ou un métabolite de celle-ci qui peuvent être administrées à un animal de compagnie pour traiter ou prévenir une maladie liée aux mitochondries ou une affection associée à une fonction mitochondriale altérée chez un animal de compagnie en ayant besoin ou à risque de celle-ci ou dans des conditions de restrictions de biodisponibilité de NAD+ ou d'absorption de calcium mitochondrial modifiée. Les compositions peuvent être administrées à un animal de compagnie pour favoriser l'augmentation des taux intracellulaires de nicotinamide adénine dinucléotide (« NAD+ ») dans des cellules et des tissus afin d'améliorer la survie cellulaire et tissulaire ou la santé globale des cellules et des tissus.
PCT/EP2024/058416 2023-03-30 2024-03-28 Association de trigonelline et d'oleuropéine ou de métabolite d'oleuropéine pour le traitement ou la prévention d'états liés aux mitochondries chez un animal de compagnie Pending WO2024200609A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202363455685P 2023-03-30 2023-03-30
US63/455,685 2023-03-30

Publications (1)

Publication Number Publication Date
WO2024200609A1 true WO2024200609A1 (fr) 2024-10-03

Family

ID=90719148

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2024/058416 Pending WO2024200609A1 (fr) 2023-03-30 2024-03-28 Association de trigonelline et d'oleuropéine ou de métabolite d'oleuropéine pour le traitement ou la prévention d'états liés aux mitochondries chez un animal de compagnie

Country Status (1)

Country Link
WO (1) WO2024200609A1 (fr)

Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022106407A1 (fr) * 2020-11-18 2022-05-27 Société des Produits Nestlé S.A. Compositions et procédés utilisant une combinaison d'oleuropéine et de nicotinamide riboside pour l'énergie cellulaire
WO2022106408A1 (fr) * 2020-11-18 2022-05-27 Société des Produits Nestlé S.A. Compositions et procédés utilisant une combinaison d'oleuropéine et de quercétine pour l'énergie cellulaire
US20220202842A1 (en) * 2019-05-13 2022-06-30 Societe Des Produits Nestle S.A. Compositions and methods to treat or prevent metabolic fatigue using at the compound oleuropein or a metabolite thereof
US20220211750A1 (en) * 2019-05-13 2022-07-07 Societe Des Produits Nestle S.A. Compositions and methods using a combination of calcium and at least one of oleuropein or metabolite thereof
US20220249453A1 (en) * 2019-07-05 2022-08-11 Societe Des Produits Nestle S.A. Compositions and methods using trigonelline to produce intracellular nicotinamide adenine dinucleotide (nad+) for treating or preventing physiological disorders or states
US20220256888A1 (en) * 2019-05-13 2022-08-18 Société des Produits Nestlé S.A. Compositions and methods using at least one of oleuropein or a metabolite thereof to treat or prevent muscle fatigue from exercise and/or for resistance to muscle fatigue from exercise
WO2022180116A1 (fr) * 2021-02-26 2022-09-01 Société des Produits Nestlé S.A. Compositions et procédés utilisant une combinaison d'oleuropéine et de vitamine b6
WO2022180119A1 (fr) * 2021-02-26 2022-09-01 Société des Produits Nestlé S.A. Compositions et procédés utilisant une combinaison d'oleuropéine et de magnésium

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20220202842A1 (en) * 2019-05-13 2022-06-30 Societe Des Produits Nestle S.A. Compositions and methods to treat or prevent metabolic fatigue using at the compound oleuropein or a metabolite thereof
US20220211750A1 (en) * 2019-05-13 2022-07-07 Societe Des Produits Nestle S.A. Compositions and methods using a combination of calcium and at least one of oleuropein or metabolite thereof
US20220256888A1 (en) * 2019-05-13 2022-08-18 Société des Produits Nestlé S.A. Compositions and methods using at least one of oleuropein or a metabolite thereof to treat or prevent muscle fatigue from exercise and/or for resistance to muscle fatigue from exercise
US20220249453A1 (en) * 2019-07-05 2022-08-11 Societe Des Produits Nestle S.A. Compositions and methods using trigonelline to produce intracellular nicotinamide adenine dinucleotide (nad+) for treating or preventing physiological disorders or states
WO2022106407A1 (fr) * 2020-11-18 2022-05-27 Société des Produits Nestlé S.A. Compositions et procédés utilisant une combinaison d'oleuropéine et de nicotinamide riboside pour l'énergie cellulaire
WO2022106408A1 (fr) * 2020-11-18 2022-05-27 Société des Produits Nestlé S.A. Compositions et procédés utilisant une combinaison d'oleuropéine et de quercétine pour l'énergie cellulaire
WO2022180116A1 (fr) * 2021-02-26 2022-09-01 Société des Produits Nestlé S.A. Compositions et procédés utilisant une combinaison d'oleuropéine et de vitamine b6
WO2022180119A1 (fr) * 2021-02-26 2022-09-01 Société des Produits Nestlé S.A. Compositions et procédés utilisant une combinaison d'oleuropéine et de magnésium

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
BONORA, M.GIORGI, C.BONONI, A.MARCHI, S.PATERGNANI, S.RIMESSI, A.RIZZUTO, R.PINTON, P.: "Subcellular calcium measurements in mammalian cells using jellyfish photoprotein aequorin-based probes", NATURE PROTOCOLS, vol. 8, 2013, pages 2105 - 2118
FOLSTEIN ET AL., J. PSYCH. RES., vol. 12, 1975, pages 189 - 198
GLANCY, B.R. S. BALABAN: "Role of mitochondrial Ca2+ in the regulation of cellular energetics", BIOCHEMISTRY, vol. 51, no. 14, 2012, pages 2959 - 2973, XP093030682, DOI: 10.1021/bi2018909
MARGALLO-LANA ET AL., J. INTELLECT. DISABILITY RES., vol. 47, 2003, pages 488 - 492
MONTERO, M.ALONSO, M.T.CARNICERO, E.CUCHILLO-IBANEZ, I.ALBILLOS, A.GARCIA, A.G.GARCIA-SANCHO, J.ALVAREZ, J.: "Chromaffin-cell stimulation triggers fast millimolar mitochondrial Ca2+ transients that modulate secretion", NATURE CELL BIOLOGY, vol. 2, 2000, pages 57 - 61

Similar Documents

Publication Publication Date Title
EP3873442B1 (fr) Composition pour la perte de poids ou la gestion du poids comprenant du bêta-hydroxybutyrate et du cannabidiol
US20120148685A1 (en) Methods and compositions for treating insulin resistance, diabetes mellitus type 2, metabolic syndrome and related disorders
US20220241259A1 (en) Compositions and methods using trigonelline and vitamins for preventing or treating conditions or disorders in skeletal muscle
US20220249453A1 (en) Compositions and methods using trigonelline to produce intracellular nicotinamide adenine dinucleotide (nad+) for treating or preventing physiological disorders or states
US6733793B2 (en) Oral composition with insulin-like activities and methods of use
TW201836669A (zh) 抑制肌纖維變性用組成物
US20220241266A1 (en) Compositions and methods using trigonelline and high protein for preventing or treating conditions or disorders in skeletal muscle
US20230172232A1 (en) Compositions and methods using an amino acid blend for providing a health benefit in an animal
US20230095374A1 (en) Meroterpenoid compounds for use in the prevention and treatment of a neurological disorder
US20220265625A1 (en) Compositions and methods using trigonelline and minerals for preventing or treating conditions or disorders in skeletal muscle
WO2024200609A1 (fr) Association de trigonelline et d'oleuropéine ou de métabolite d'oleuropéine pour le traitement ou la prévention d'états liés aux mitochondries chez un animal de compagnie
US20230346818A1 (en) Compositions and methods containing n-acetylcystein and nicotinamide riboside for prevention and treatment of neurological diseases and conditions
US12171735B2 (en) Administration of butyrate, beta-hydroxybutyrate, cannabidiol, and related compounds in humans
WO2024200611A1 (fr) Association de trigonelline et d'oleuropéine ou de métabolite d'oleuropéine pour le traitement ou la prévention d'états liés aux mitochondries
WO2024200613A1 (fr) Compositions et procédés utilisant de la trigonelline et de l'oleuropéine pour prévenir ou traiter des pathologies ou des troubles du muscle squelettique chez un animal de compagnie

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 24716686

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE