FR3056381A1 - 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

Holder (s): FUTUR OPTIMAL Limited liability company.

Extension request (s)

Agent (s): PRONOVEM-OFFICE VAN MALDEREN.

(M) COMPOSITION COMPRISING CARNOSINE.

The invention relates to a composition administered orally comprising a drink of plant origin having an acidic or basic pH and Carnosine. The composition can be a food supplement or a pharmaceutical composition.

FR 3 056 381 - A1

300

A3 ©

ί AH, * = Ah AT ...................... E ........ 2.64 4.74 Ί ............ 6.83 8.1 7 9 _T 5 f ρΉ

Composition comprising Carnosine

OBJECT OF THE INVENTION tOOQl] L ⁷ relates to the field of solid or liquid food supplements, pharmaceutical compositions or neutraceutical compositions comprising Carnosine and their method of obtaining.

STATE OF THE ART Carnosine is a dipeptide formed from alanine and histidine, which is present naturally in mammals, especially in muscle tissue, the brain, the liver and the kidneys.

Meat food constitutes a significant intake of Carnosine, which comes 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.

Carnosine is known for its antioxidant properties and its physiological benefits. In fact, this molecule is capable of inactivating free radicals and chelating iron (a pro-oxidizing agent), thus giving it beneficial effects against cell aging. Furthermore, Carnosine has an anti-catabolic effect, by its inhibition of the binding of saccharides to proteins and is able to reduce the level of lactic acid produced during intense muscular effort.

It has been shown that plasma and tissue Carnosine levels 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.

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

However, unlike dietetics which are intended to replace a normal diet, food 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 dietetic composition or a neutraceutical composition or a food supplement, Carnosine has a low intestinal assimilation and a low bioavailability.

potentiate compositions

Aims of 1 ¹ invention.

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

The present invention aims to provide a composition suitable for oral administration, comprising a sufficient dose of carnosine to have the required therapeutic effect on the treated animal, including humans, in particular against induced diseases by oxidative stress, such as cell aging or inflammation / while having better absorption and better bioavailability of the carnosine present in the composition.

Summary of the Invention The present invention relates to an oral composition, that is to say adapted for oral administration comprising a drink of plant origin having an acidic or basic pH, or a composition comprising flour or a chocolate bar such as milk chocolate or dark chocolate; 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

a combination any appropriate, of following features: - the original drink vegetable East, or understands, of the beer or a juice or a extract of a or many fruits and or one or more vegetables, - the original drink vegetable East, or understands, a juice

or an extract obtained from orange, melon, asparagus or kale,

the vegetable-based drink or the flour-based composition or the chocolate bar is, or includes, a spice extract, in particular a chilli extract

cayenne, an extract of seeds of coffee tree, an extract of 5 beans cocoa tree, a extract of vanilla pods, a extract leaves of tea tree or a combination of these

extracts,

- the composition is a drink which is beer,

the composition, including the flour-based composition or the chocolate bar is, or includes, a milk product,

- the milk composition, including the flour-based composition or the chocolate bar comprises lactic acid bacteria,

the pH of the composition, including the flour-based composition or the chocolate bar or the drink of vegetable origin is between (approximately) 4 and (approximately) 6.5 or between (approximately) 7.5 and (approximately) 10, preferably between (approximately) 4 and (approximately) 5 or between (approximately) 8 and (approximately) 9,

- the composition is in dehydrated form,

- the dehydrated composition. is packaged in the form of a capsule, a lozenge or a tablet, in a flexible pod made of filter paper, preferably of the pad type or a rigid pod sealed against water and air, in an airtight sachet , or else in a beaker, 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 per 100 ml of drink or of the 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 for increasing the intestinal absorption or the bioavailability of Carnosine in a mammalian subject, in particular in a human patient.

An additional 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 carrier or diluent, including a composition in the form of a drink, a flour-based composition or a chocolate bar, and its use, in particular in the treatment and / or prevention of diseases and / or syndromes induced by oxidative stress, in particular cell aging or inflammation, in a mammalian subject, preferably in a human patient.

The present invention also relates to a method of preparing a food supplement and comprising Carnosine, said method comprising a step of rehydrating the dehydrated composition according to the invention, preferably by addition or by spraying onto said dehydrated composition of a jet of a liquid, in particular a solvent, such as water or milk, using an apparatus for producing hot drinks and / or cold drinks.

Detailed description of the invention [0016] The composition according to the invention composition per os, that is to say adapted oral administration of a food supplement is one for one Preferably, it is or functional food having 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 drink 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 in the intestine and its bioavailability is improved by the simultaneous absorption of a composition based on flour, a chocolate bar or an original drink. vegetable comprising (poly) phenols, and even more favorably when the drink has an acidic or basic pH.

In the composition of the invention, the pH of said drink is not equal to 7 (neutral pH), advantageously it is between (approximately) 4 and (approximately) 6.5 or between (approximately) 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 shown in Figures 3 & to 3D and at the pH mentioned in Figure 2. The form shown in Figure 3B would be the most soluble, because it has a pH of 4.74 , 3 ionic sites. Under these conditions, the

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 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 sector, such as in particular citric acid, lactic acid, and / or phosphoric acid and their mixtures or the hydroxide of a alkali metal, ...

t0023] The vegetable-based drink is preferably water-based. It can be a fermented drink, such as beer or unfermented; therefore, it may or may not include alcohol. Preferably, it is one or more juices and / or one or more extracts from one or more plants, preferably one or more plants used in human or animal food, [0024] The term "juice" »The liquid part contained in the plant or plants, obtained by any suitable means, for example by pressing or centrifugation, of all or part of the plant or plants, used hot or cold, under pressure or at atmospheric pressure. The term "extract" means the liquid portion and at non-neutral pH 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 the extraction of substances contained in the plant or plants, the solvent possibly being for example water, an alcohol, an oil, preferably an essential oil, or a mixture of these compounds.

The food plant or plants may be cereals, starchy plants, oil plants, including oil seed plants or oil trees, fruit plants, including citrus fruits and other fresh fruit plants, such as l orange or melon or dried fruits, vegetable plants, including vegetables, such as asparagus or cabbage, preferably kale and condiment plants, spice plants, in particular cayenne pepper, plants beverage plants, 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 (approximately) 4 and (approximately) 5 or between (approximately) 8 and (approximately) 10.

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

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

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

In another preferred embodiment, the drink or the flour-based composition or the chocolate bar comprises the extract of tea leaves, preferably leaves that have been dried beforehand. Preferably, the pH of this extract is between (approximately) 4 and (approximately) 5.

Preferably, and whatever the food plant or plants, the drink can be, or comprise, a milk product, fermented or unfermented. Advantageously, the milk product may include lactic acid bacteria. Preferably, the drink is based on milk or cream. Advantageously, it can be a dessert cream or a liquid yogurt.

Preferably, and whatever the food plant or plants, the drink can also comprise food additives, such as texturing agents, thickeners, sweeteners, preservatives, flavors, colorings, 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 an ampoule. It can also be in the form of a liquid concentrate. It can also, in liquid or concentrated form, be added to or present in a solid food carrier (such as a milk chocolate bar, with dark or white chocolate).

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 lyophilization in order to be present and sold in dry form and solid, preferably in a pulverulent form, compacted or not.

Preferably, the composition in solid form is packaged in the form of a capsule, a pastille or a tablet, in a flexible pod of filter paper, in particular of pad type or a rigid pod or sealed capsule. with water and air, disposable or reusable, in an airtight sachet, or even in a cup, placed at the bottom of the latter and protected by a seal.

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

Preferably, for packaging in flexible or rigid pods, the composition in solid form is suitable for use by beverage production devices, such as coffee machines, capable of preparing 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, of said 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 carrier or diluent used in the treatment and / or prevention of diseases and syndromes linked to a deficit, that is to say a Camosine 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 , high cholesterol. 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 The study is carried out on a sample of 15 people (M / F) distributed as follows;

healthy subjects aged between 18 and 30 years, 6 between 40 years and € 0 years and 6 over 60 years.

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

Kits are distributed to them to carry out the tests at their workplace or at home. For 6 days, without taking L-Carnosine, urine is measured within 5 hours of breakfast and as many times as necessary. The following six days, a first urine test is carried out on an empty stomach in the morning, then during breakfast, 500 mg of L-Carnosine are ingested in the form of a capsule. 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 **. Urine is still measured on an empty stomach and after breakfast. Afterwards, during the next 6 days, during breakfast, 500 mg of L-Carnosine is dissolved in the hot morning drink (tea or coffee). Urine is measured within 5 hours and as many times as necessary. Finally, for the next 6 days, urine is measured within 5 hours of breakfast and as many times as necessary, but no more L-Carnosine is taken.

Days 1 to 6 Days 7 to 12 Days 13 to 14 Days 15 to 20 Days 21 to 26 Measurement of urine (second jet) on an empty stomach before breakfast- lunch Breakfast Breakfast + 500 mg L- Carnosine in water Small- lunch Breakfast + 500 mg L- Carnosine in cafe or tea Breakfast Urine measurements (second jet) during the 5 hours which follow the taking of L-Carnosine. You are asked not to take anything between meal if possible

The correspondence of the color codes of the tongues is not given to the subjects in order not to alter the test. The subjects note each time the date and time of taking and testing as well as the color code obtained. This test determines if carnosine is better ingested once dissolved in a hot coffee or tea drink.

The difference in MDA level indicates that L10 Carnosine is better assimilated in one test than in the other.

* ww.antiaging-systems. com / articles / 191-carnosine-canreduce-urinary-mda-concentration ** The half-life of L-Carnosine is between 1 hour and

5 hours.

Claims (14)

1. A composition suitable for oral administration and comprising a drink of plant origin having an acidic or basic pH and Carnosine. 2. The composition according to claim 1, in which the drink of vegetable origin is or comprises, a juice or an extract of one or more fruits and / or of one or more vegetables. 3. The composition according to claim 2, in which the juice or the extract is obtained from orange, melon, asparagus, or kale. 4. The composition according to claim 1, in which the drink of vegetable origin is or comprises, an extract of cayenne pepper, an extract of seeds of the coffee tree, an extract of cocoa beans, an extract of vanilla pods, a tea leaf extract or a combination of these extracts. 5. The composition according to claim 1, wherein the drink is beer. 6. The composition according to any one of the preceding claims, being or comprising a milk product. 7. The composition according to claim 6, in which the drink of vegetable origin comprises lactic acid bacteria. 8. The composition according to any one of the preceding claims, in which the pH of the drink is between 4 and 6.5 or between 7.5 and 10. 9. The composition according to claim 8, in which the pH of the drink is between 4 and 5 or between 8 and 9. _z ,,, "," wt "w" W "i"> Jt- (- "t- WJ 1 VV 3056381 14 10. The composition according to 1 'any of claims previous, under form dehydrated. 11. The composition according to the claim 10, packaged in the form of a capsule, lozenge or 5 of a tablet, in a flexible pod of filter paper or a rigid pod waterproof against water and air, in an airtight sachet, or else in a cup. 12. A pharmaceutical composition comprising a suitable pharmaceutical carrier or diluent and the 10 composition according to any one of the preceding claims 1 to 10. 13. The composition according to claim 12, used in the treatment or prevention of diseases or syndromes induced by oxidative stress. 14. The composition according to claim 12, for increasing the intestinal absorption or the bioavailability of Carnosine in a mammalian subject, in particular in a human patient. 15. A method of preparing a supplement Food comprising carnosine, said method comprising a step of rehydrating the dehydrated composition according to claim 10, by adding or spraying on said dehydrated composition of a liquid jet using a beverage production apparatus 25 hot and / or cold. 1/2