FR3056381B1 - COMPOSITION COMPRISING CARNOSINE - Google Patents

Abstract

The present invention relates to an orally administered composition comprising a vegetable drink having an acidic or basic pH and carnosine. The composition may be a dietary supplement or a pharmaceutical composition.

Description

Composition comprising, Carnosine

OBJECT OF THE INVENTION The invention relates to the field of solid or liquid food supplements, pharmaceutical compositions or neutraceutical compositions comprising carnosine and their method of production.

STATE OF THE ART [0002] Carnosine is a dipeptide formed from alanine and histidine, which is naturally present in mammals, in particular in the muscle tissues, the brain, the liver and the kidneys.

[0003] The meat diet is an important contribution to Carnosine, which is derived from the digestion of meat from mammals. However, carnosine is also naturally produced in the brain and muscles by an enzyme, carnosine synthetase, from beta-alanine and histidine.

[0004] Carnosine is known for its antioxidant properties and its physiological benefits. Indeed, this molecule is capable of inactivating free radicals and chelating iron (a prooxidant), thus conferring beneficial effects against cellular aging. Moreover, Carnosine has an anti-catabolic effect, by its inhibition of the attachment of saccharides to proteins and is able to reduce the level of lactic acid produced during intense muscular effort.

[0005] Plasma and tissue carnosine levels have been shown to decline with age. It is known to supplement the body with Carnosine in order to combat the effects of aging which are mainly due to oxidative stress.

[0006] EP1388339 describes a topical preparation (cream), comprising L-Carnosine and tea extracts for reducing wrinkles in the skin, and EP1285654 describes a composition comprising at a very low dose of L-carnosine for the control of the skin. autonomic nervous system. WO9636348 discloses a dietary composition containing Carnosine in combination with one or more linear or branched amino acids to potentiate the antioxidant activity of Carnosine.

However, unlike dietary compositions that are intended to substitute for a normal diet, dietary supplements are food compositions whose purpose is to supplement a normal diet. They are a concentrated source of nutrients, such as vitamins and minerals, which are usually combined with other substances, such as plants or plant preparations, having a nutritional or physiological effect alone or in combination.

However, whether it is included in a pharmaceutical composition administered orally, in a dietary composition or a nutraceutical composition or a dietary supplement, Carnosine has a low intestinal assimilation and low bioavailability.

Goals of invention.

The present invention aims to provide a composition comprising Carnosine which does not have the disadvantages of the state of the art.

The present invention aims to provide a composition capable of being administered orally, comprising a sufficient dose of carnosine to have the required therapeutic effect on the treated animal, including humans, particularly against induced diseases by oxidative stress, such as cellular aging or inflammation, while having a better absorption and a better bio-availability of the carnosine present in the composition. SUMMARY OF THE INVENTION [0011] The present invention relates to an oral composition, that is to say adapted for oral administration comprising a beverage of plant origin having an acidic or basic pH, or a composition comprising flour or a chocolate bar of the milk chocolate or dark chocolate type; said composition also comprising Carnosine, as shown in Figures 1 and any of Figures 3A to 3D.

According to preferred embodiments of the invention, the composition according to the invention comprises at least one or any suitable combination of the following characteristics: the drink of vegetable origin is, or comprises, beer or a juice or an extract of one or more fruits and / or of one or more vegetables, the drink of vegetable origin is, or includes, a juice or an extract obtained from orange, melon or asparagus or kale, - the vegetable drink or the flour-based composition or the chocolate bar is, or includes, a spice extract, in particular a cayenne pepper extract, a coffee seed extract, cocoa bean extract, vanilla bean extract, tea leaf extract or a combination of these extracts, - the composition is a beverage which is beer, - the composition, including the composition of flour or chocolate bar is, or includes, a product the - the milk composition, including the flour-based composition or the candy bar comprises lactic acid bacteria, - the pH of the composition, including the flour-based composition or the candy bar or the drink of origin plant is between (about) 4 and (about) 6.5 or between (about) 7.5 and (about) 10, preferably between (about) 4 and (about) 5 or between (about) 8 and (about 9, the composition is in dehydrated form, the composition is dehydrated. is packaged in the form of a capsule, a lozenge or a tablet, in a flexible filter paper pod, preferably pad type or a rigid watertight and airtight pod, in an airtight bag or in a cup, carnosine is present in the composition of the invention in a proportion of between (approximately) 10 mg and (approximately) 2 g, preferably between (approximately) 30 mg and (approximately) 250 mg per dose ( that is to say, 100ml of beverage or solid composition, in particular the chocolate bar of the invention.

Another aspect of the present invention relates to a use of the composition according to the invention to increase the intestinal absorption or bioavailability of carnosine in a mammalian subject, particularly in a human patient.

A complementary aspect of the present invention relates to the composition of the invention as a medicament, that is to say a pharmaceutical composition comprising the composition of the invention and a suitable pharmaceutical vehicle or diluent, including a beverage composition, a flour-based composition or a chocolate bar, and its use, particularly in a treatment and / or prevention of diseases and / or syndromes induced by oxidative stress, in particular cell aging or fl ammation, in a mammalian subject, preferably che2 a human patient.

The present invention also relates to a method for preparing a dietary supplement and comprising carnosine, said method comprising a rehydration step of the dehydrated composition according to the invention, preferably by addition or spraying on said dehydrated composition of a jet of a liquid, in particular a solvent, such as water or milk, using a device for producing hot drinks and / or cold drinks.

DETAILED DESCRIPTION OF THE INVENTION [OOlfi] The composition according to the invention is an oral composition, that is to say adapted for oral administration. Preferably, it is a dietary supplement or functional food with therapeutic or prophylactic benefits on animal and / or human health, but may also be a pharmaceutical composition, in particular a neutraceutical.

The composition comprises L-Carnosine and / or D-Carnosine or a racemate or racemic mixture of L- and D-Carnosine.

The composition further comprises either a flour-based composition or a chocolate bar, in particular milk chocolate, black or white or a beverage of plant origin having a non-neutral pH, that is to say say an acidic or basic pH.

Surprisingly, it appears that carnosine is better absorbed intestinal level and its bioavailability is improved by the simultaneous absorption of a composition based on flour, a candy bar or a drink of origin vegetable comprising (poly) phenols, and even more favorably when the beverage has an acidic or basic pH.

In the composition of the invention, the pH of said beverage is not equal to 7 (neutral pH), advantageously it is between (about) 4 and (about) 6.5 or between (about) 7 , 5 and (approximately) 10.

The inventors have discovered that the non-neutral pH and the ionic sites generated on the molecule influence the solubility of the molecule in an aqueous medium. Depending on the pH of the medium, carnosine can exist in 4 forms represented in FIGS. 3A to 3D and at the pH mentioned in FIG. 2. The form represented in FIG. 3B would be the most soluble because it has a pH of 4.74 , 3 ionic sites. Under these conditions, Carnosine can advantageously be in the form of salts and / or complexes with the constituents of the vegetable drink and combine with the benefits to generate a synergy with the compounds, such as polyphenols present in the drink or the chocolate bar. .

The pH may be adjusted by acids or bases acceptable in the food field, such as in particular citric acid, lactic acid, and / or phosphoric acid and mixtures thereof or the hydroxide of a alkaline metal, ...

The drink of plant origin is preferably based on water. It may be a fermented beverage, such as beer or unfermented; therefore, she may or may not understand alcohol. Preferably, it is one or more juices and / or one or more extracts of one or more plants, preferably one or more plants used in the human or animal food, [0024] "Juice »The liquid part contained in the plant or plants, obtained by any suitable means, for example by pressing or centrifugation, all or part of the plant or plants, implemented hot or cold, under pressure or at atmospheric pressure. "Extract" means the liquid and non-neutral pH fraction obtained by maceration or prolonged contact, hot or cold, under pressure or at atmospheric pressure, of all or part of the plant or plants with a solvent allowing extraction of substances contained in the plant or plants, the solvent may be for example water, an alcohol, an oil, preferably an essential oil, or a mixture of these compounds.

The food crop or plants may be cereals, starch plants, oleaginous plants, including oleaginous plants or oleaginous trees, fruit plants, including citrus fruits and other fresh fruit plants, such as orange or melon or dried fruit, vegetables, including vegetables, such as asparagus or cabbage, preferably kale and seasoning plants, spice plants, especially cayenne pepper, plants beverages, including unfermented beverage plants and fermented beverage plants, for example beer or edible seaweed.

In a preferred embodiment, the drink comprises the juice of one or more fruits, such as for example melon, orange, grape, strawberry, lychee or apple, or a vegetable such as artichoke or cabbage, especially kale. Preferably, the pH of this extract or juice is between about (4) and (about) or between (about) 8 and (about) 10.

In another preferred embodiment, the beverage or the flour-based composition or the chocolate bar comprises cayenne pepper extract, coffee bean seeds, preferably previously terrified seeds. Preferably, the pH of this extract is between (about) 4 and (about) 5.

In another preferred embodiment, the beverage or the flour-based composition or the chocolate bar comprises cocoa bean extract, preferably previously torrified beans. Preferably, the pH of this extract is between (about) 4 and (about) 5.

In another preferred embodiment, the beverage or the flour-based composition or the chocolate bar comprises the vanilla pod extract, preferably previously dried pods.

In another preferred embodiment, the beverage or flour-based composition or chocolate bar comprises tea leaf extract, preferably previously dried leaves. Preferably, the pH of this extract is between (approximately) 4 and (approximately) 5. Preferably, and whatever the food plant or plants, the drink may be, or include, a milk product, fermented or not fermented. Advantageously, the milk product may comprise lactic acid bacteria. Preferably, the drink is based on milk or cream. Advantageously, it may be a dessert cream or a liquid yoghurt.

Preferably, and whatever the food plant or plants, the drink may further comprise food additives, such as texturizing agents, thickeners, sweeteners, preservatives, flavors, dyes, essential oils. or a mixture of these products.

The composition according to the invention is preferably in liquid form, preferably packaged in a suitable container, such as a bottle, a bottle or a bulb. It can also be in a form of a liquid concentrate. It may also, in liquid or concentrate form, be added to or present in a solid food carrier (such as a chocolate bar with milk, dark chocolate or white).

In another embodiment of the invention, the liquid composition such as a drink, according to the invention is subjected to a dehydration process, for example by freeze drying to be present and marketed in a dry form. and solid, preferably in pulverulent form, compacted or not.

Preferably, the composition in solid form is packaged in the form of a capsule, a tablet or a tablet, in a flexible filter paper pod, in particular pad type or a rigid pod or leakproof capsule water and air, disposable or reusable, in an airtight bag, or even in a cup, arranged at the bottom of the latter and protected by a cover.

Whatever its conditioning, the composition in solid form can recover its liquid form by the addition, preferably by spraying under pressure of a liquid or solvent, hot or cold, such as water or water. milk.

Preferably, for packages in flexible or rigid pods, the composition in solid form is suitable for use by beverage production devices, such as coffee machines, able to prepare a drink from a product percolation or infusion. Advantageously, the beverage production apparatus is equipped with a recognition device for example a bar code reader or the like, so-called pods in order to add the appropriate liquid, at the appropriate temperature and pressure.

Preferably, the composition according to the invention is a pharmaceutical composition comprising a suitable pharmaceutical vehicle or diluent used in the treatment and / or prevention of diseases and syndromes related to a deficiency, that is to say a carnosine deficiency, in particular in the prevention or treatment of pathologies induced by oxidative stress, in the prevention or minimization of aging processes and associated pathologies, in the prevention or treatment of metabolic syndromes, such as hypertriglyceridemia , hypercholesterolemia. Advantageously, the composition according to the invention is used for the prevention and / or treatment of cancer, autoimmune diseases, fibrous diseases, inflammatory diseases, neurodegenerative diseases, infectious diseases, pulmonary diseases and / or heart and vascular diseases.

Example: Phase 2 clinical study of L-Carnosine associated with coffee and tea [0039] The study is conducted on a sample of 15 people (M / F) distributed as follows: 3 healthy subjects aged between 18 and 30 years , 6 between 40 and 60 years old and 6 over 60 years old.

The measurements are made by analysis of the concentration of MDA (Malondialdehyde) in the urine of the subjects. It appears that the MDA level is inversely proportional to that of L-Carnosine *.

Kits are distributed to them for testing at their place of work or at home. For 6 days, without taking L-Carnosine, the urine is measured within 5 hours after breakfast and as many times as necessary. The next six days, a first urine test is performed on an empty stomach in the morning, and at breakfast, 500 mg of L-Carnosine are ingested in capsule form. The urine is measured within 5 hours and as many times as necessary. Then you must stop taking the treatment for 2 days to eliminate (wash-out) its concentration in the urine **. The urine is measured on an empty stomach and after breakfast. After, during the next 6 days, during breakfast, 500 mg of L-Carnosine are dissolved in the morning hot drink (tea or coffee). The urine is measured within 5 hours and as many times as necessary. Finally, for the next 6 days, the urine is measured within 5 hours after breakfast and as many times as necessary, but without any further intake of L-Carnosine.

The correspondence of the color codes of the tabs is not given to the subjects so as not to alter the test. Subjects note each time the date and time taken and test and the color code obtained, This test can determine whether carnosine is better ingested once dissolved in a hot drink type coffee or tea.

The difference in the level of MDA indicates that L-Carnosine is better assimilated in one test than in the other. * Ww. antiaging-systems. com / articles / 1 gi-carnosine-can-reduce-urinary-mda-concentration ** The half-life of L-Carnosine is between 1 hour and 5 hours.

Claims (9)

1. A composition suitable for oral administration and comprising Carnosine and a vegetable drink having an acidic or basic pH in which the beverage of plant origin is or comprises, a juice or an extract of one or several fruits and / or one or more vegetables, - in which the juice or extract is obtained from orange, melon, asparagus, or kale, - in which the drink of vegetable origin is or includes a cayenne pepper extract, a cocoa bean extract, a vanilla bean extract, or a combination of these extracts, - wherein the beverage is beer or - in which the composition is a chocolate bar of the milk chocolate or dark chocolate type. 2. The composition of any one of the preceding claims, wherein the pH of the beverage is between 4 and 6.5 or between 7.5 and 10. 3. The composition of claim 8, wherein the pH of the beverage is between 4 and 5 or between 8 and 9. 4. The composition according to any one of the preceding claims, in dehydrated form (It is possible that this claim No. 4 and the following claims No. 5 and No. 9 should be deleted). 5. The composition according to claim 10, packaged in the form of a capsule, a pellet or a tablet, in a flexible filter paper pod or a rigid watertight and air-tight pod, in a hermetic bag, or in a cup. A pharmaceutical composition comprising a suitable pharmaceutical carrier or diluent and the composition of any one of the preceding claims 1 to 10. 7. The composition of claim 12, used in the treatment or prevention of diseases or syndromes induced by oxidative stress. 8. The composition of claim 12 for increasing the intestinal absorption or bioavailability of carnosine in a mammalian subject, particularly in a human patient. 9. A method for preparing a dietary supplement comprising carnosine, said method comprising a step of rehydrating the dehydrated composition according to claim 10, by addition or spraying on said dehydrated composition of a liquid jet to the using an apparatus for producing hot and / or cold drinks.