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
  • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
  • A61K31/365—Lactones
  • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23L—FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES, NOT OTHERWISE PROVIDED FOR; PREPARATION OR TREATMENT THEREOF
  • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
  • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
• • 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
  • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
  • A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
  • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
  • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
  • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/0012—Galenical forms characterised by the site of application
  • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
• • 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
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
  • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
  • C07D311/78—Ring systems having three or more relevant rings
  • C07D311/80—Dibenzopyrans; Hydrogenated dibenzopyrans
• • A—HUMAN NECESSITIES
  • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
  • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
  • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

• the present disclosure relates to methods involving oral administration of urolithins according to a specific dosage regime, resulting in the provision of beneficial health effects, for example improved mitochondrial function and cellular metabolism.
• the methods are useful, e.g. for improving the health and wellbeing of subjects, particularly the elderly or frail; and for improving fitness, muscle performance and/or endurance of those engaging in exercise.
• the methods are also useful in treating or preventing various conditions, e.g. conditions associated with inadequate
• A, B, C, D, W, X, Y and Z are each independently selected from H and OH;
• Figure 12 shows the pharmacokinetic bioavailability profile of total Urolithin A
• the present disclosure provides methods involving oral administration of specific daily dosages of compounds of formula (I), i.e. urolithins, which provide beneficial health effects.
• a compound of formula (I) wherein: A, B, C, D, W, X, Y and Z are each independently selected from H and OH; or a salt thereof; wherein said compound of formula (I) is combined with at least one pharmaceutically acceptable carrier to form an oral solid dosage form, administered, wherein the compound or salt is orally administered at a dose sufficient to achieve steady state plasma levels of a compound of formula (I) and/or metabolites thereof, of 220-900ng/ml.
• the methods are for treating, preventing and/or reducing the severity of a condition, disease or disorder.
• Age-related diseases pose a burden for both the elderly and society as a whole.
• evidence has shown that dysfunction of mitochondria plays an important role in age related diseases, such as Alzheimer's and Parkinson's diseases, diabetes mellitus type 2, SIBM, intensive care unit-acquired muscle weakness (ICUAW) and sarcopenia.
• ICUAW intensive care unit-acquired muscle weakness
• sarcopenia During aging, there is a progressive decline in the cell capacity to eliminate its dysfunctional elements by autophagy, as evidenced by mutations in mitochondria and the decrease in autophagic flux.
• the endurance capacity refers to the time to fatigue when exercising at a constant workload, generally at an intensity ⁇ 80% VO2imax.
• Methods of the present disclosure may improve endurance capacity in individuals with a disease, including young and elderly individuals.
• Methods of the present disclosure may improve endurance capacity in healthy individuals, including athletes, non-athletic individuals, sedentary individuals and the elderly.
• the present disclosure provides for a method of increasing the time to fatigue while performing a specific activity, for example, fitness training, walking, running, swimming, or cycling. This improvement of endurance capacity may be assessed with objective measurements (for example, speed, oxygen consumption or heart rate) or it can be self-reported measurements (for example, using a validated questionnaire).
• the carnitine or salt thereof is administered daily to the subject by oral dosing, e.g. over a period of at least 21 days, or over a period of at least 28 days.
• the daily dosage of carnitine or salt thereof administered to the subject is in the range of from 0.5 to 50 mmol per day, or in the range of from 1 to 25 mmol per day, or in the range of from 2.5 to 15 mmol per day, or about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, about 10, about 1 1 , about 12, about 13, about 14, or about 15 mmol per day.
• the method comprises administration of a compound of formula (I) or salt thereof (e.g. urolithin A), in micronized form.
• a compound of formula (I) or salt thereof e.g. urolithin A
• the physical form of the composition can be tailored to the requirements of the product in question.
• the compositions may be pharmaceutical compositions.
• the compositions may be nutritional compositions.
• the European Pharmacopoeia describes medium-chain triglycerides as the fixed oil extracted from the hard, dried fraction of the endosperm of Cocos nucifera L.
• 'Lecithin' designates any group of fatty substances occurring in animal and plant tissues including phosphoric acid, choline, fatty acids, glycerol, glycolipids, triglycerides, and phospholipids (e.g., phosphatidylcholine,
• Long chain omega-6 fatty acids having at least 20 carbon atoms include cis-1 1 , 14-eicosadienoic acid C20:2, cis-8, 1 1 , 14-eicosatrienoic acid (Dihomo-gamma-linolenic acid) (DGLA) C20:3, cis-5,8, 1 1 , 14-eicosatetraenoic acid (Arachidonic acid) (AA) C20:4, cis-13, 16-docosadienoic acid C22:2, cis- 7, 10, 13, 16-docosatetraenoic acid (Adrenic acid) C22:4, cis-4, 7, 10, 13, 16- docosapentaenoic acid (Osbond acid) C22:5.
• compositions may be compounds that do not provide health benefits to the subject, but instead improve the composition in some other way, for example its taste, texture or shelf-life as mentioned above.
• the composition may thus further contain one or more compounds selected from emulsifiers, colorants, preservatives, gums, setting agents, thickeners, sweeteners and flavourings.
• GMS falls into two distinct grades: 40-55 percent monoglycerides, and 90 percent monoglycerides.
• 40-55 percent monoglycerides as defined by the European Pharmacopoeia describes GMS as a mixture of monoacylglycerols, mostly monostearoylglycerol, together with a quantity of di- and tri-glycerols.
• the 40-55 grade contains 40-55% monoacylglycerols, 30-45% diacylglycerols, and 5- 15% of triacylglycerols.
• the 99 percent grade contains not less than 90% of monoglycerides.
• the monoglycerides in commercial GMS products are mixtures of variable proportions of glyceryl monostearate and glyceryl monopalmitate.
• the method comprises administration of a composition comprising a medium chain triglyceride, the compound of formula (I) or a salt thereof (e.g.urolithin A), and a stabiliser, for example glycerol monostearate.
• a stabiliser for example glycerol monostearate.
• the method involves administration of a composition comprising an emulsifier and a stabiliser.
• Metal chelators or sequestrants such as sodium calcium salts of ethylenediamine tetra acetic acid (EDTA) may also be used.
• Other components that may be included in formulations of the invention include polyethylene glycols, silicon dioxide, vegetable shortening and beeswax. A flavouring may be beneficial in compositions used in the methods described herein.
• composition A is a mixture of Representative composition A:
• Cohort 2 (12 subjects): 500 mg urolithin A (9 subjects) or placebo (3 subjects) soft gel capsule formulation for 28 days.
• Metabolomics is the study of known measurable metabolites in a sample.
• each blood sample was centrifuged at 1500 g for 10 minutes at 4°C. Within 30 minutes after the centrifugation, the top layer of human plasma was transferred into pre-labelled polypropylene tube. Tubes were capped immediately from each time point and the plasma frozen in an upright position at approximately -80°C for storage. The samples were shipped on dry ice for bioavailability analysis.
• ody mass index (BMI) between 25.0 and 34.9 kg/m 2 , inclusive

Landscapes

• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Organic Chemistry (AREA)
• Epidemiology (AREA)
• Engineering & Computer Science (AREA)
• General Chemical & Material Sciences (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Nutrition Science (AREA)
• Diabetes (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• Obesity (AREA)
• Hematology (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Polymers & Plastics (AREA)
• Physiology (AREA)
• Food Science & Technology (AREA)
• Mycology (AREA)
• Oil, Petroleum & Natural Gas (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Coloring Foods And Improving Nutritive Qualities (AREA)
• Medicinal Preparation (AREA)
• Pyrane Compounds (AREA)

Priority Applications (3)

Applications Claiming Priority (6)

Publications (1)

Family

ID=61691936

Family Applications (1)

Country Status (4)

Cited By (9)

Families Citing this family (9)

Citations (2)

Family Cites Families (6)

• 2018
  • 2018-03-08 US US15/915,773 patent/US20180256538A1/en not_active Abandoned
  • 2018-03-08 EP EP25165087.5A patent/EP4553071A3/en active Pending
  • 2018-03-08 EP EP18712106.6A patent/EP3592424A1/en active Pending
  • 2018-03-08 WO PCT/EP2018/055788 patent/WO2018162650A1/en not_active Ceased
  • 2018-03-08 JP JP2019548663A patent/JP7761371B2/ja active Active
• 2023
  • 2023-05-08 JP JP2023076848A patent/JP2023100869A/ja active Pending

Patent Citations (2)

Non-Patent Citations (6)

Also Published As

Similar Documents

Legal Events