EP3506929A1 - Utilisation d'un hydrolysat de collagène pour améliorer la capacité d'endurance et stimuler le catabolisme lipidique - Google Patents

Utilisation d'un hydrolysat de collagène pour améliorer la capacité d'endurance et stimuler le catabolisme lipidique

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Publication number
EP3506929A1
EP3506929A1 EP17758489.3A EP17758489A EP3506929A1 EP 3506929 A1 EP3506929 A1 EP 3506929A1 EP 17758489 A EP17758489 A EP 17758489A EP 3506929 A1 EP3506929 A1 EP 3506929A1
Authority
EP
European Patent Office
Prior art keywords
collagen hydrolyzate
use according
collagen
hydrolyzate
per day
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
EP17758489.3A
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German (de)
English (en)
Inventor
Steffen Oesser
Stephan Hausmanns
Hans-Ulrich Frech
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.)
Gelita AG
Original Assignee
Gelita AG
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
Priority claimed from DE102017102873.0A external-priority patent/DE102017102873A1/de
Application filed by Gelita AG filed Critical Gelita AG
Publication of EP3506929A1 publication Critical patent/EP3506929A1/fr
Pending legal-status Critical Current

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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K38/012—Hydrolysed proteins; Derivatives thereof from animals
    • A61K38/014—Hydrolysed proteins; Derivatives thereof from animals from connective tissue peptides, e.g. gelatin, collagen
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    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/64—Proteins; Peptides; Derivatives or degradation products thereof
    • A61K8/65—Collagen; Gelatin; Keratin; Derivatives or degradation products thereof
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    • A61K38/39—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
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    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
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    • A61K38/43—Enzymes; Proenzymes; Derivatives thereof
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    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
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Definitions

  • the present invention relates to the use of collagen hydrolyzate for improving endurance performance.
  • the invention further relates to the use of collagen hydrolyzate for the stimulation of fat loss, and in particular for the reduction of body weight.
  • Collagen hydrolyzate which is produced in particular by the enzymatic hydrolysis of collagen-containing animal starting materials, consists of a mixture of peptides whose molecular weights are distributed over a certain size range depending on the starting material and production conditions.
  • the use of collagen hydrolyzate as a dietary supplement has long been known, in particular for the prevention and / or treatment of disorders associated with the bone, joints or connective tissue, especially a stimulating effect of the collagen peptides on the synthesis of the body's extracellular matrix could be shown in these types of tissues (see, e.g., Bello et al., Curr. Med. Res. Opin. 2006 (22) 2221-2232).
  • collagen hydrolyzate also leads to an increase in mitochondrial activity in human and animal cells, i. E. an increase in the mitochondrial count per cell and / or an enlargement of the individual mitochondria.
  • collagen hydrolyzate according to the present invention can be specifically used to improve endurance performance and to stimulate fat loss in humans and animals by increasing mitochondrial activity in their muscle cells.
  • the endurance capacity of the human or animal body correlates with the capacity of the aerobic metabolism to supply the muscles with the required energy in the form of ATP (adenosine triphosphate) over a longer period of time.
  • Decisive for the aerobic capacity is the oxygen uptake, which in turn is determined by three factors: the oxygen supply via the lungs, the oxygen transport via the cardiovascular system and the oxygen utilization in the muscle cells. While maximum oxygen delivery is dictated by individual anatomical conditions (total alveolar surface area), oxygen transport and utilization can be increased through training and other measures, with the final step typically being the limiting factor. Endurance capacity therefore depends essentially on the number of mitochondria (per muscle cell or in the total muscle) in which the oxygen-consuming and ATP-generating reactions of the respiratory chain take place.
  • an increase in mitochondrial activity means that the body's basal metabolic rate increases and a higher amount of nutrients are metabolized per unit of time for energy.
  • a higher catabolic metabolic activity inevitably leads (with constant nutrient intake) to an increased degradation of the body's reserves, i. to a stimulation of fat loss.
  • the degradation of the long-chain carboxylic acids released from the adipose tissue takes place essentially throughout the body and especially in the liver, so that for this aspect of the invention, as opposed to improving the endurance performance, not only the mitochondria in the muscle cells are relevant.
  • the use of collagen hydrolyzate according to the invention comprises in particular a non-therapeutic use, i. administration of the collagen hydrolyzate to persons or animals that are not in need of medical treatment in terms of their endurance performance or body weight. Rather, the use is on the one hand with the aim of a general desirable increase in endurance performance. This can contribute to an improvement in the quality of life and is particularly relevant for athletes. On the other hand, a reduction in body weight by stimulating fat loss may be desirable, especially from a cosmetic point of view, ie to improve body proportions.
  • the invention also encompasses the therapeutic use of collagen hydrolyzate for the prevention and / or treatment of a pathological condition characterized by a reduction in mitochondrial activity.
  • a pathological condition characterized by a reduction in mitochondrial activity.
  • the pathological condition may be characterized by decreased endurance performance and / or increased body weight.
  • the pathological condition is preferably selected from obesity, cardiovascular diseases, cardiac arrhythmia, cardiac insufficiency, hypotension, hypertension, metabolic disorders, diabetes mellitus, metabolic syndrome, sideroblastic anemia, kidney and liver dysfunction, neuropathy, ataxia, epileptic seizures, dementia, Alzheimer's disease, autism, depression, chronic fatigue syndrome, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, stroke-like symptoms, migraine, myoclonus, paralysis, neuralgia, hyperpathias, hyperaesthesias, dysphagia, vomiting, constipation, diarrhea, degeneration of optic nerve fibers and the retina, disturbed eye movement, ptosis, night blindness, deafness, deafness and inner ear disorders.
  • a therapeutic effect can be achieved by increasing the mitochondrial or mitochondrial activity.
  • the administration of collagen hydrolyzate may also have a positive effect in the prevention and / or treatment of cancer, i. of malignant tumors. This is based on the consideration that tumor cells have their energy requirements primarily through anaerobic metabolism (milk metabolism). acidic fermentation) and for this necessarily rely on glucose. An increased glucose consumption in the body cells would thus weaken the tumor cells.
  • collagen hydrolyzate leads to increased expression of the enzyme AMP-activated protein kinase (AMPK).
  • AMPK AMP-activated protein kinase
  • This regulatory enzyme also affects the energy metabolism of the cell, so that an increase in the AMPK amount has a positive impact on endurance performance and fat loss.
  • the collagen hydrolyzate is preferably administered enterally, especially orally.
  • the collagen hydrolyzate is administered in the form of a dietary supplement.
  • a dietary supplement particularly advantageous is the administration in the form of a solution, e.g. in the form of finished ampoules, or in the form of a powder. Due to its good solubility, the collagen hydrolyzate can also be added to various beverages without causing turbidity. By using tasteless collagen hydrolyzate, user acceptance can be increased.
  • the dietary supplement according to a preferred embodiment of the invention contains no further proteins or protein hydrolysates in addition to the collagen hydrolyzate.
  • Various proteins are used in known dietary supplements for muscle building and muscle maintenance, especially in athletes, with the aim of replacing carbohydrates and fats as energy suppliers to a large extent by proteins.
  • the use according to the invention is not based on the function of collagen hydrolyzate as an energy source, but on the specific effect on mitochondrial activity described above.
  • the dietary supplement contains no further physiologically active constituents in addition to the collagen hydrolyzate.
  • the invention also includes the case that the collagen hydrolyzate is administered as part of a (food) composition with various other ingredients.
  • the collagen hydrolyzate may be added to a food or beverage, e.g. A chocolate bar, protein bar or cereal bar (so-called functional food), or in milk, milk products (e.g., yoghurt) and milk substitutes (e.g., soymilk, almond milk, and coconut milk).
  • the collagen hydrolyzate is typically administered in an amount of from 1 to 40 grams per day, preferably from 2.5 to 30 grams per day, more preferably from 10 to 25 grams per day, and most preferably from 12.5 to 20 grams per day .
  • collagen hydrolyzate is used as the only physiologically active ingredient of a nutritional supplement, it may be combined for use in the present invention with one or more other components that have a positive effect on overall health and, more particularly, endurance performance.
  • Such components are preferably selected from vitamin C, vitamins of the B, D, E and K series, conjugated linolenic acids, caffeine and its derivatives, guaranea extract, green tea extract, epigallocatechin gallate, creatine, L-carnitine, L-citrulline, L-carnitine Arginine, ⁇ -lipoic acid, N-acetylcysteine, NADH, D-ribose, magnesium aspartate, antioxidants such as anthocyanins, carotenoids, flavonoids, resveratol, glutathione, superoxide dismutase and xanthans such as mangiferin, minerals such as iron, magnesium, calcium, zinc, selenium and Phosphorus, and other proteins, hydrolys
  • a further advantageous embodiment of the invention relates to the combination of the collagen hydrolyzate with ubiquinone-10 and / or ubiquinol, ie. the oxidized or reduced form of the coenzyme Qi 0 , wherein ubiquinol is preferred because of its better bioavailability.
  • ubiquinol is preferred because of its better bioavailability.
  • a daily intake of 50 to 100 mg of ubiquinol a positive effect on physical performance was observed, whereby promotion of mitochondrial activity is assumed by the antioxidant action of ubiquinol.
  • the effect of the collagen hydrolyzate in the above indications associated with mitochondrial dysfunction can be promoted in this way.
  • a combination of the collagen hydrolyzate with pyrroloquinoline quinone (PQQ) is possible, which has recently been discovered as an important redox cofactor.
  • the administration of collagen hydrolyzate is combined with endurance training or altitude training.
  • Endurance training can increase the aerobic capacity of the metabolism.
  • a physical training under relative lack of oxygen hyperoxia training
  • hypoxia training has a strong effect on the endurance performance, so that when co-administration of collagen hydrolyzate in each case a synergistic effect is assumed. This is of particular interest to athletes.
  • collagen hydrolyzate takes place in the absence of endurance training, altitude training or muscle training.
  • the molecular weight of the collagen hydrolyzate used may vary over a wide range according to the invention, with an upper limit imposed by the fact that collagen hydrolyzate, unlike denatured collagen or gelatin, has a sufficiently high degree of hydrolysis to be water-soluble at room temperature and not gelled.
  • the soluble peptides of the collagen hydrolyzate can be well absorbed in the body.
  • the collagen hydrolyzate has an average molecular weight of from 200 to 25,000 Da, preferably from 1,000 to 6,000 Da, more preferably from 1,200 to 4,000 Da, even more preferably from 1,500 to 3,500 Da, and most preferably from 2,800 to 3,300 Da.
  • the collagen hydrolyzate is conveniently prepared by enzymatic hydrolysis of a collagen-containing starting material.
  • endopeptidases and / or exopeptidases of microbial or plant origin are used for this hydrolysis.
  • the collagen-containing starting material is usually selected from the skin or bones of vertebrates, preferably from mammals, and in particular from the skin of cattle or pigs (cattle slit or pork rind).
  • the collagen hydrolyzate can be prepared from these starting materials either in a one-step process or gelatin via the intermediate, in which case both Type A and Type B gelatin can be used.
  • the collagen hydrolyzate for use in the invention may be produced by recombinant gene expression.
  • natural collagen sequences in particular from cattle or pigs, and their expression in genetically modified cells (eg yeasts, bacteria or plant cells, especially tobacco)
  • products can be produced which are substantially identical to the hydrolysis products of the corresponding collagen-containing raw materials are . It is possible to obtain a narrower or exactly predetermined molecular weight distribution.
  • the sequences can be altered by mutations to affect certain properties of the product.
  • An object of the present invention is further a method of improving endurance performance and / or stimulating fat loss, and more particularly, reducing body weight by increasing mitochondrial activity.
  • the method preferably comprises the enteral, in particular oral, administration of collagen hydrolyzate to a human or to an animal.
  • the method can be both a therapeutic and a non-therapeutic method.
  • Figure 1 fluorescence micrographs of SH-SY5Y cells, which were incubated in the presence of collagen hydrolyzate.
  • the SH-SY5Y cells were incubated in culture media with different concentrations of collagen hydrolyzate of 0.05% by weight, 0.2% by weight and 2.5% by weight.
  • collagen hydrolyzate A a collagen hydrolyzate of pork rind gelatin having an average molecular weight in the range of 3,000 Da prepared by enzymatic hydrolysis (hereinafter referred to as collagen hydrolyzate A) was used.
  • the molecular weight distribution of the peptides which was determined by gel permeation chromatography, is given in the following Table 1: Table 1: MG distribution collagen hydrolyzate A
  • TOM20 mitochondrial protein component TOM20 was fluorescently labeled.
  • TOM20 is a subunit of a receptor complex in the outer membrane of the mitochondria, which has the function to transfer cytosolic precursor proteins (prepeptides) into the mitochondria. There, the proteins, which are enzymes of the respiratory chain or the citric acid cycle, are activated by cleavage of the presequence.
  • the amount of fluorescently labeled TOM20 visible in the fluorescence microscope is thus a measure of the mitochondrial number in the cell.
  • the cells incubated with 0.05% by weight, 0.2% by weight and 2.5% by weight of collagen hydrolyzate are shown in FIGS. 1A, 1B and 1C respectively, with an increase of the light (in the original green) with increasing concentration. Fluorescence in the areas around the nucleus (blue in the original) is clearly visible.
  • the collagen hydrolyzate thus causes an increase in the mitochondrial count in the SH-SY5Y cells, and thus an increase in the total mitochondrial activity.
  • AMP-activated protein kinase is involved in energy delivery in both adipose tissue and muscle. Since AMP is formed when consuming ATP, it can be considered as an indicator of energy shortage become. The expression of AMPK thus serves to activate energy reserves from the fat depot and in the context of glycolysis.
  • AMPK RNA was significantly increased (by a factor of over 600). This finding also results in a stimulating influence of collagen hydrolyzate on the energy metabolism of the cell.
  • mice were fed daily with a quantity of collagen hydrolyzate corresponding to a human equivalence dose of 10 g over a period of 3 months. After the mice had been euthanized, the quadriceps were completely excised, snap frozen and ground. From the muscle tissue, the soluble proteins were extracted and the amount of AMPK determined by means of an immunoassay (ELISA).
  • ELISA immunoassay
  • the amount of AMPK was increased by a factor between 1.5 and 2.
  • the test group and the control group each comprised six animals.
  • a fine needle biopsy was taken from the four-headed thigh muscle (quadriceps femoris) in each rat.
  • the animals of the test groups were then given a daily dose of 200 mg of the respective collagen hydrolyzate (see below) per kg of the current body weight (corresponding to a daily dose of 15 g in a 75 kg person) over a period of four weeks.
  • the collagen hydrolyzate was added at a concentration of 20 mg / ml in an appropriate amount dissolved in tap water and administered via a nasogastric tube.
  • the animals of the control group each received the identical amount of tap water without collagen hydrolyzate.
  • a collagen hydrolyzate B from bovine cleavage gelatin having an average molecular weight of 2,000 Da was used in further test groups, and a collagen hydrolyzate C from bovine cleavage gelatin having an average molecular weight of 3,500 Da, each produced by enzymatic hydrolysis.
  • the molecular weight distributions of all three hydrolysates are given in the following Table 2:
  • the value "Cohen's d" as a measure of the effect size is more than 2.5 for all test groups, which is a very strong effect.

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Abstract

La présente invention concerne l'utilisation d'un hydrolysat de collagène pour améliorer la capacité d'endurance par augmentation de l'activité mitochondriale. L'invention concerne en outre l'utilisation d'un hydrolysat de collagène pour stimuler le catabolisme lipidique, et en particulier réduire le poids corporel, par augmentation de l'activité mitochondriale.
EP17758489.3A 2016-08-30 2017-08-23 Utilisation d'un hydrolysat de collagène pour améliorer la capacité d'endurance et stimuler le catabolisme lipidique Pending EP3506929A1 (fr)

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DE102016116160 2016-08-30
DE102017102873.0A DE102017102873A1 (de) 2016-08-30 2017-02-14 Verwendung von Kollagenhydrolysat zur Verbesserung der Ausdauerleistungsfähigkeit und zur Stimulation des Fettabbaus
PCT/EP2017/071184 WO2018041684A1 (fr) 2016-08-30 2017-08-23 Utilisation d'un hydrolysat de collagène pour améliorer la capacité d'endurance et stimuler le catabolisme lipidique

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US11180541B2 (en) 2017-09-28 2021-11-23 Geltor, Inc. Recombinant collagen and elastin molecules and uses thereof
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