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Compositions and methods using combination of calcium and at least one of oleuropein or metabolite thereof

A technology of oleuropein and metabolites, applied in compositions for improving and maintaining muscle function or reducing loss of muscle function, at least one combination to enhance the field, capable of solving problems such as difficulty in taking preventive or therapeutic measures

Pending Publication Date: 2021-11-19
SOC DES PROD NESTLE SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Unfortunately, the etiology and pathophysiology of sarcopenia remain poorly understood, making effective preventive or therapeutic measures difficult

Method used

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  • Compositions and methods using combination of calcium and at least one of oleuropein or metabolite thereof
  • Compositions and methods using combination of calcium and at least one of oleuropein or metabolite thereof
  • Compositions and methods using combination of calcium and at least one of oleuropein or metabolite thereof

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Experimental program
Comparison scheme
Effect test

Embodiment approach

[0073] Oleuropein is a polyphenol present in the fruits, roots, trunks and more particularly leaves of plants belonging to the family Oleaceae, and especially olives. figure 1 The chemical structure of oleuropein is shown. Oleuropein is 3,4-dihydroxyphenylethanol (also known as hydroxytyrosol, in figure 1 marked "A") and olive acid (in figure 1 marked "B" in ), which contain glucose molecules (in figure 1 marked as "C"). figure 2 The metabolic pathways of oleuropein by mammalian and microbial enzymes of the present invention are shown based on findings reported in the literature.

[0074] One aspect of the present disclosure is a method of achieving at least one result selected from (i) improving mitochondrial calcium uptake in muscle cells, (ii) improving calcium utilization in muscle cells, (iii) increasing muscle cell Mitochondrial energy in, (iv) improving at least one of muscle function, muscle performance, or muscle strength, (v) reducing muscle fatigue or weakness,...

Embodiment 1

[0115] To test the effects of oleuropein, its metabolites, and calcium supplementation / deficiency in living cells, the inventors measured mitochondrial calcium elevation in HeLa cells and myotubes differentiated from mouse C2C12 cells and human primary adult muscle cells . HeLa cells and C2C12 cells were purchased from ATCC. Human skeletal muscle myoblasts (HSMM) were purchased from Lonza. HSMMs were isolated from upper arm or leg muscle tissue of normal donors and used after the second passage. HeLa cells were seeded in a 96-well plate at a density of 50,000 cells / well in minimal essential medium (DMEM, Gibco), high glucose+10% fetal bovine serum. C2C12 cells were seeded in 96-well plates at a density of 8000 cells / well in DMEM high glucose (Gibco) + 10% fetal calf serum. Myotubes were differentiated from C2C12 cells by growing cells in DMEM containing 2% horse serum for 4 days. HSMMs were seeded in 96-well plates at a density of 8000 cells / well in DMEM / F-12 (Gibco). Myo...

Embodiment 2

[0120] To test the effects of oleuropein and hydroxytyrosol on mitochondrial respiration and to assess the effects of these compounds on the ATP synthase-dependent component of respiration, the inventors measured oxygen consumption in human skeletal muscle myotubes. For respiration experiments, oxygen consumption in myotubes was measured using an XF96 instrument (Seahorse Biosciences, MA). On and after day 2, human myotubes were inoculated into polyornithine-coated Seahorse tissue plates, and the cells were incubated with (in mM) 140NaCl, 3.6KCl, 0.5NaH 2 PO 4 , 0.5MgSO 4 , 1.5CaCl 2 , 10Hepes, 5NaHCO 3 , 10 glucose and Krebs-Ringer bicarbonate Hepes buffer (KRBH) pH 7.4 and washed twice. Respiration rate was measured every 6 minutes at 37°C. ATP synthase-dependent respiration was calculated as the difference in respiration rate before and after addition of oligomycin. Experiments were performed at 37°C.

[0121] Such as Figure 9 showed that oleuropein and hydroxytyro...

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Abstract

A combination of calcium and at least one of oleuropein or metabolite thereof can be orally administered to an individual in an amount effective to achieve at least one result that is (i) improved mitochondrial calcium uptake in muscle cells, (ii) improved utilization of calcium in muscle cells, (iii) increased mitochondrial energy in muscle cells, (iv) improvement in at least one of muscle functionality, muscle performance, or muscle strength, (v) decreased muscle fatigue, (vi) increased mobility, and / or (vii) treatment of a muscle disorder linked to calcium depletion or deficiency. The individual can be at least one of an aging subject; an elderly subject; a subject with muscle fatigue or muscle weakness; a subject with impaired mobility; a frail subject; a pre-frail subject; a sarcopenic subject; a subject recovering from pre-frailty, frailty, sarcopenia or impaired mobility; a subject undergoing physical rehabilitation; a sportsman; or a pet.

Description

Background technique [0001] The present disclosure generally relates to compositions and methods using calcium in combination with at least one of oleuropein or its metabolites. More specifically, the present disclosure relates to enhancing bioenergetics and mitochondrial function by combining calcium with at least one of oleuropein or its metabolites to promote mitochondrial calcium import, which in turn can enhance muscle contraction and muscle performance, thereby improving . Compositions and methods for maintaining muscle function or reducing loss of muscle function. [0002] Sarcopenia is defined as age-related loss of muscle mass and function, including muscle strength and walking speed. Muscle function and physical capacity decline with loss of muscle mass. The incidence of loss of mobility, disability, and death at advanced age is highly predicted by impaired muscle function. Sarcopenia is becoming more prevalent with a growing geriatric population, with 45% of the ...

Claims

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Application Information

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IPC IPC(8): A61K31/05A61K31/085A61K31/351A61K31/7048A61P21/00A23K20/111A23K20/121A23L33/105A23L33/16A23L33/00
CPCA61K31/7048A61K31/351A61K31/05A61K31/085A61P21/00A23K20/111A23K20/121A23L33/105A23L33/16A23L33/40A23V2200/33A23V2200/316A23V2250/1578A23V2250/2131A23V2250/2132A23K50/50A23K50/40A61K33/06A61K2300/00
Inventor U·德马奇M·N·霍尔卡加达J·费热
Owner SOC DES PROD NESTLE SA
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