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Compositions and methods using adenosine cobalamin

An adenosylcobalamin, mitochondrial technology, used in the treatment of chronic diseases, reducing their incidence and/or reducing their severity, can solve problems such as damage to mitochondrial function, reduce oxidative stress, maintain heart health, increase Effects of Fatty Acid Metabolism

Pending Publication Date: 2022-04-29
SOC DES PROD NESTLE SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Furthermore, oxidative damage to mitochondrial membranes impairs mitochondrial function due to aging and chronic disease

Method used

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  • Compositions and methods using adenosine cobalamin
  • Compositions and methods using adenosine cobalamin
  • Compositions and methods using adenosine cobalamin

Examples

Experimental program
Comparison scheme
Effect test

Embodiment approach

[0057] Vitamin B12 (also known as cobalamin) is a class of cobalt-containing water-soluble vitamins that cannot be synthesized by the human body and must therefore be obtained from food or synthesized by intestinal flora. Vitamin B12 species can refer to several chemical forms of vitamin B12, depending on the upper axial ligand of the cobalt ion. These are cyanocobalamin (R=-CN); hydroxocobalamin (R=-OH) methylcobalamin (R=-CH3) and adenosylcobalamin (R=-5'-deoxyadenosine ).

[0058] The vitamin B12 complex in humans consists of several forms: cyanocobalamin, which is inactive and requires conversion to be active; and methylcobalamin and adenosylcobalamin, which are the metabolically active forms of vitamin B12 .

[0059] Two enzymes are known to depend on vitamin B12 as a cofactor: methionine synthase and methylmalonyl-CoA mutase. Methionine synthase is a cytoplasmic enzyme that relies on methylcobalamin to convert homocysteine ​​to methionine. It thus plays a key role in...

Embodiment 1

[0125] Materials and methods

[0126] To test the role of adenosine B12 and methyl B12 in human muscle myotubes, oxygen consumption rates and ATP production were measured in human myotubes differentiated from primary adult myocytes (HSMM). HSMMs were purchased from Lonza (https: / / bioscience.lonza.com). HSMMs were isolated from upper arm or leg muscle tissue of normal donors and used after the second passage. HSMMs were seeded in 96-well plates at a density of 12000 cells per well in SKM-M medium (ZenBio). Myotubes were differentiated from HSMM by growing cells for 4 days in DMEM / F-12 (Gibco) containing 2% horse serum. From the second growth day, the medium did not contain B12.

[0127] Oxygen consumption was measured using an XF96 instrument (Seahorse Biosciences, North Billerica, MA, USA). After differentiation, respiration rate was measured every 7 min at 37°C. Myotubes were stimulated with 10 μM bombesin. Then, to measure the ATP synthase-dependent component of resp...

Embodiment 2

[0135] Materials and methods

[0136] Male Wistar rats aged 3 or 19 months were treated with adenosylcobalamin (adenosine B12) or methylcobalamin (methylcobalamin) by subcutaneous injection at a dose of 1 mg / kg three times a week during 5 months. base B12) for treatment. Control animals were injected with an equal volume of saline. After 5 months of treatment, adult rats were defined as 8-month-old rats, and aged (old) animals were defined as 24-month-old aged rodents.

[0137] Total RNA was extracted from the tibialis anterior muscle using the Agencourt RNAdvance Tissue Kit. For gene set enrichment analysis and network analysis, RNA quantity was measured with Ribogreen, and RNA quality was checked on a fragment analyzer using a standard sensitivity RNA analysis kit. All cRNA targets were synthesized using the IVT plus kit based on the Eberwine T7 program and fragmented according to the Affymetrix protocol. Briefly, 100 ng of total RNA was used to generate double-strande...

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Abstract

The present invention discloses a composition effective in restoring mitochondrial function and other cell functions and / or increasing mitochondrial energy in one or more cells, the composition containing adenosine cobalamin. Other aspects relate to methods of improving a physiological state associated with metabolic fatigue in one or more cells and / or reducing fatigue in an individual; methods of treating, reducing the morbidity and / or reducing the severity of chronic diseases and / or treating, reducing the morbidity and / or reducing the severity of mitochondrial-related diseases or conditions associated with altered mitochondrial function or reduced mitochondrial density.

Description

Background technique [0001] The present disclosure generally relates to compositions and methods for increasing cellular energy and / or treating or preventing mitochondria-related diseases or disorders, for example, by increasing ATP production in cells, reducing oxidative stress, and / or enhancing mitochondrial function in an individual. [0002] Adenosine triphosphate (ATP) is a complex organic chemical that provides energy to drive many processes in living cells, such as muscle contraction, nerve impulse propagation, and chemical synthesis. ATP is present in all life forms and is often referred to as the "molecular currency unit" of energy transfer within cells. When consumed during metabolism, it is converted to adenosine diphosphate (ADP) or adenosine monophosphate (AMP). It is also a precursor of DNA and RNA and acts as a coenzyme. ATP is also a substrate for adenylate cyclase, most commonly found in the G protein-coupled receptor signaling pathway, and is converted to t...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/714A61P3/00A61P3/04A61P3/10A61P3/06A61P25/28A61P25/22A61P13/12A61P9/04A61P9/00A61P19/08A61P17/02A61P31/00A61P35/00A61P27/02
CPCA61K31/714A61P3/00A61P3/04A61P3/10A61P3/06A61P25/28A61P25/22A61P13/12A61P9/04A61P9/00A61P19/08A61P17/02A61P31/00A61P35/00A61P27/02A61P21/00A61K9/0048
Inventor U·德马奇J·费热A·赫曼特S·卡拉兹
Owner SOC DES PROD NESTLE SA
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