WO2019158736A1 - Anti-stress composition - Google Patents

Abstract

The invention relates to a composition comprising an active substance dispersed in a matrix, said active substance comprising or consisting substantially of a mixture of betaine and ascorbic acid, said matrix being a crystalline matrix consisting substantially of hydrogenated lipids.

Description

Composition against stress

The invention relates to a composition that contributes to reducing the effects of non-optimal conditions, particularly against the effects of stress in animals.

When temperatures rise and reach high thresholds, animals may be confronted with the phenomenon of heat stress and can no longer regulate their own body temperature. This results in adverse health effects, such as reduced disease resistance and decreased growth. That is why it is essential to take the necessary measures in time to avoid heat stress in animals, especially farm animals, particularly in pigs, cattle, poultry and goats. .

In order to improve and develop productivity in the tropics, to anticipate climate changes that affect or will affect more and more temperate farming areas, it is necessary to take into account the effects of heat stress in order to adapt from farming systems to a changing climate environment, regardless of the climate zone.

Adaptation in breeding describes the ability of an animal to cope with the constraints of the environment, by mobilizing its main physiological functions. The objective of the adaptive process for the animal is to maintain its well-being and to guarantee its survival (homeostasis) and that of its offspring (homeorhesis).

The thermal stress appears from the moment when the ambient temperature exceeds the zone of least effort of thermoregulation or zone of thermoneutrality.

When the ambient temperature rises beyond this zone of thermoneutrality, the mechanisms of regulation (reduction of the thermogenesis / increase of the thermolysis) are saturated and the animal is no longer able to maintain its internal temperature constant.

Thermal stress is a problem that occurs as a result of a sudden and occasional rise in temperature (heat stroke, heat wave), or a prolonged rise in temperatures over a longer period (summer, tropical climate).

The animal is no longer able to regulate its body temperature, which leads to significant performance losses in breeding and therefore economic losses. The equipment of livestock buildings is not always enough to avoid this situation.

Heat stress can be defined as the sum of forces external to a warm-blooded animal (that is, an animal that maintains a constant body temperature independently of the external environment), which act to alter its body temperature relative to the temperature of the body. normal state.

Because of their breeding mode, and their low ability to lose heat by evaporation (absence of efficient sweat glands), farmed monogastric animals are particularly sensitive to heat, and therefore to heat stress. In particular, convection and radiation play a small role in the heat dissipation in poultry because of the effective insulation of the body surface provided by the feathers. The absence of functional sweat glands and low perspiration limit the ability of poultry to maintain a temperature during a heat episode.

The effects induced by the heat stress mechanisms are:

Behavioral disorders (pecking, aggression),

Lower ingested (in quantity and / or frequency of meals) and therefore lower growth,

Hyperventilation (open beaks, alkalosis, ionic imbalance ...)

Degradation of carcass quality (in poultry: "Pale, Soft, Exudative" PSE meat or pale, soft and exudative meat in French, linked to a rapid drop in post-mortem pH), fatter meats, lack of pigmentation; in pigs: increase in lean meat rate)

In recent years, various technical, genetic or nutritional solutions have been put in place to limit mortality and promote the growth of farmed monogastric animals, particularly chickens raised in a hot environment.

Strategies put in place to reduce the negative effects of heat will depend on the type of heat stress to which the animals are exposed. During a punctual exhibition (heat stroke), the solutions are essentially technical (improvement of buildings and adaptation of breeding techniques). In the case of prolonged or chronic exposure, nutritional or genetic solutions may be considered to improve the growth of animals.

A composition described in patent FR3017778 B1 consisting of an extract of Scutellaria is known in particular. Baicalensis . This composition is prepared from a complex of natural active ingredients, selected for their synergistic effect, and in particular Baalkaline.

However, compositions aimed at limiting or combating the effects of heat stress are still under study.

The invention therefore aims to overcome these shortcomings of the prior art.

One of the objectives of the invention is to provide a composition easy to use, easy to produce, and comprising natural compounds effective thermal stress and its physiological effects.

Another object of the invention is to provide a method of manufacturing such a composition.

The invention relates to a composition comprising an active substance dispersed in a matrix, said active substance comprising or consisting essentially of a mixture of betaine and an antioxidant agent, said antioxidant agent being ascorbic acid, said matrix being a matrix crystalline essentially consisting of one or more hydrogenated lipids, especially hydrogenated oil.

The invention is based on the unexpected finding made by the inventors that a composition comprising betaine and an antioxidant such as vitamin C (ascorbic acid), in vectorized form in a crystalline matrix has very good effects on heat stress and its consequences.

The inventors have indeed observed that the composition according to the invention acts by synergy of the active compounds (betaine and antioxidant, in particular ascorbic acid or vitamin C), and promotes the resistance of monogastric animals raised to heat stress, supports the natural defenses of said animals and improves zootechnical performance.

The composition of the invention comprises betaine which is a substance of formula (CH ₃ ) ₃ N ⁺ CCOO ^- , available in liquid or crystalline form.

Anhydrous betaine of natural origin, is extracted from the molasse or vinasse plants and roots thereof, mainly beet ( Beta vulgaris ), especially derived from the manufacture of sugar or bioethanol. Betaine is separated and purified by chromatography, with or without an organic solvent (of the methanol, dichloromethane or chloroform type), in the liquid phase or in the solid phase. The anhydrous betaines are in solid or liquid form. Solid anhydrous betaines have a purity level ranging from 91 to 97%.

Synthetic betaine is obtained from chloroacetic acid and sodium carbonate, to which trimethylamine is added. The synthetic betaines are in solid or liquid form. Betaine HCl or hydrochloride (addition of hydrochloride acid after a concentration step of the mixture of chloroacetic acid and sodium carbonate) of betaine monohydrate or anhydrate. The solid HCl synthetic betaines generally have a degree of purity of between 93 and 98%, the solid monohydrates have a purity of around 91% and solid anhydrates a purity of around 96%.

Liquid betaines have a lower purity level of between 38 and 47%.

Betaine plays an osmoregulatory role. On the one hand, the protection of the intestinal epithelium against osmotic changes promotes the absorption of nutrients and thus improves zootechnical performance. On the other hand, the maintenance of osmotic pressure protects the cells from dehydration, which is favorable to their normal metabolic functioning. An improvement in yields with betaine intake is regularly observed in the literature, and could be related to better water retention of the cells.

The composition according to the invention also contains at least one antioxidant which is ascorbic acid (oxo-3-gulofuranolactone acid or vitamin C), which is well known to those skilled in the art.

The composition according to the invention is characterized in that the betaine and the antioxidant are dispersed homogeneously in a crystalline matrix consisting essentially of one or more hydrogenated lipids.

In the invention, the term "one or more lipids" is understood to mean a lipid mixture comprising a single type of lipid or a mixture of several types of lipids of different natures (and therefore of different chemical structures). Therefore, throughout the foregoing and following description, the terms "one or more lipids" may be uniformly replaced by the terms "a mixture of one type or a mixture of several different types of lipids".

In the invention, the lipids are advantageously one or more hydrogenated lipids, in particular hydrogenated oil, or hydogenated oil derivatives, such as hydrogenated fatty acids or hydrogenated fatty alcohols, the latter being able to be in free form or in the form of hydrogenated of monoglycerol, di or polyglycerol fatty acid esters. Also, in the context of a crystalline matrix of the invention composed of lipids, this matrix is essentially composed of one or more hydrogenated lipids, in particular hydrogenated oil, or derivatives of hydogenated oil, such as acids. hydrogenated fats or hydrogenated fatty alcohols, the latter being in free form or in the form of monoglycerol, di or polyglycerol fatty acid esters

In another advantageous aspect, the lipids constituting said crystalline matrix are the lipids of an oil, especially a vegetable or animal oil. By way of example and without limiting the scope of the invention, the oils envisaged are in particular the following:

vegetable oils such as rapeseed oil, oleic rapeseed oil, sunflower oil, oleic sunflower oil, coconut oil, palm oil, palm kernel oil, olive oil, peanut oil, soybean oil, corn oil, mustard oil, castor oil, palm olein, palm stearin, oil Safflower, sesame oil, linseed oil, walnut oil, grape seed oil, hemp oil,

animal oils and fats such as fish oils, especially fatty fish,

microbial oils derived from so-called oleaginous microorganisms, that is to say capable of storing fatty acids containing more than 20% of their dry weight, originating from yeasts, bacteria, in particular the genus Streptomycès , or micro-algae,

or a by-product derived from the extraction of the above-mentioned oils comprising a mixture of fatty acids, such as esterification waters, bottoms, deodorizing condensates, washings or neutralization pastes.

The lipids in the invention are chosen so that the compositions which comprise them are solid, semi-solid or plastics at an ambient temperature, that is to say at a temperature of between 15 ° C. and 40 ° C., especially of 17 ° C to 30 ° C. These lipids are in particular hydrogenated lipids by hydrogenation, in particular catalytic.

In the context of hydrogenation, the triglycerides are treated for example in the presence of molecular hydrogen and a catalyst (in particular copper or nickel or palladium) at a temperature of 140 ° C to 250 ° C. This type of reaction is heterogeneous because there are three phases present: a gaseous phase with hydrogen, a liquid phase with the triglycerides to be hydrogenated and a solid phase with the finely divided catalyst. The reaction is exothermic and evolves on the order of 100 to 150 kJ per mole of double bond. The hydrogenation can be selective, it will be for example to specifically reduce the linolenic acid (C18: 3) of an oil to obtain linoleic acid (C18: 2). This type of hydrogenation aims to saturate in a large proportion, or sometimes totally, the double bonds of the unsaturated fatty acids contained in the triglycerides of an oil.

The hydrogenated oils according to the invention are the following: refined and hydrogenated palm oil whose melting point varies from 60 to 63 ° C., hydrogenated sunflower oil whose melting point varies from 69 to 73 ° C. , refined and hydrogenated rapeseed oil having a melting point of 68 to 74 ° C and palm stearin (comprising C16-C18 fatty acids) having a melting point of 56 to 62 ° C.

Other oils of interest in the context of the invention can be used: soybean oil (non-GMO) whose melting point varies from 68 to 71 ° C or rapeseed oil (erucic high), saturated fatty acids from C12 or C14, and whose melting point ranges from 61 to 66 ° C.

In certain aspects of the composition according to the invention it is also possible to mix lipids according to the invention having a high melting point, at above 55 ° C., with lipids according to the invention whose melting point is below 55 ° C. In this case, it must be ensured that the melting point of the mixture will be above 55 ° C.

For example, it will be possible to make a mixture of hydrogenated palm kernel oils having a melting point of 39 ° C with one or more hydrogenated oils having a melting point above 65 ° C, so that the overall melting of the palmite oil and other oils mixture is greater than 55 ° C. The same is true for hydrogenated coconut oils having a melting point of 30 to 32 ° C.

The crystallization temperatures of these same hydrogenated oils are as follows:

about 47 ° C for refined and hydrogenated palm oil,

about 49 ° C for hydrogenated sunflower oil,

about 49 ° for refined and hydrogenated rapeseed oil,

about 37 ° C for palm stearin,

about 48 ° C for soybean oil (non-GMO), and

about 55 ° C for rapeseed oil (erucic high).

Advantageously, the invention relates to the abovementioned composition, in which the ascorbic acid represents from 2.5% to 8% by weight relative to the total mass of the composition.

In the invention, the ascorbic acid contained in the composition represents, by weight relative to the total mass of the composition, 2.5%, 2.6%, 2.7%, 2.8%, 2.9%, 3%, 3.1%, 3.2%, 3.3%, 3.4%, 3.5%, 3.6%, 3.7%, 3.8%, 3.9%, 4% , 4.1%, 4.2%, 4.3%, 4.4%, 4.5%, 4.6%, 4.7%, 4.8%, 4.9%, 5%, 5% , 1%, 5.2%, 5.3%, 5.4%, 5.5%, 5.6%, 5.7%, 5.8%, 5.9%, 6%, 6.1% %, 6.2%, 6.3%, 6.4%, 6.5%, 6.6%, 6.7%, 6.8%, 6.9%, 7%, 7.1%, 7.2%, 7.3%, 7.4%, 7.5%, 7.6%, 7.7%, 7.8%, 7.9% or 8%.

Ascorbic acid, in the aforementioned proportions, can be added to the other products constituting the composition according to the invention in liquid form or in solid form.

Advantageously, the invention relates to the abovementioned composition, in which betaine represents from 13% to 40% by weight relative to the total mass of the composition.

In the invention, the betaine contained in the composition represents, by weight relative to the total weight of the composition 13%, 13.5%, 14%, 14.5%, 15%, 15.5%, 16%, 16.5%, 17%, 17.5%, 18%, 18.5%, 19%, 19.5%, 20%, 20.5%, 21%, 21.5%, 22%, 22%, 5%, 23%, 23.5%, 24%, 24.5%, 25%, 25.5%, 26%, 26.5%, 27%, 27.5%, 28%, 28.5% , 29%, 29.5%, 30%, 30.5%, 31%, 31.5%, 32%, 32.5%, 33%, 33.5%, 34%, 34.5%, 35% %, 35.5%, 36%, 36.5%, 37%, 37.5%, 38%, 38.5%, 39%, 39.5% or 40%.

Betaine with a purity greater than or equal to 91% will be preferred.

Betaine, in the aforementioned proportions, may be added to the other products constituting the composition according to the invention in liquid form or in solid form.

Advantageously, the invention relates to the aforementioned composition, wherein said crystalline matrix, consisting of one or more lipids, represents from 25% to 65% by weight relative to the total mass of the composition.

In the invention, the crystalline matrix contained in the composition represents by weight relative to the total mass of the composition 25%, 25.5%, 26%, 26.5%, 27%, 27.5%, 28% , 28.5%, 29%, 29.5%, 30%, 30.5%, 31%, 31.5%, 32%, 32.5%, 33%, 33.5%, 34%, 34% , 5%, 35%, 35.5%, 36%, 36.5%, 37%, 37.5%, 38%, 38.5%, 39%, 39.5%, 40%, 40.5% %, 41%, 41.5%, 42%, 42.5%, 43%, 43.5%, 44%, 44.5%, 45%, 45.5%, 46%, 46.5%, 47%, 47.5%, 48%, 48.5%, 49%, 49.5%, 50%, 50.5%, 51%, 51.5%, 52%, 52.5%, 53% , 53.5%, 54%, 54.5%, 55%, 55.5%, 56%, 56.5%, 57%, 57.5%, 58%, 58.5%, 59%, 59% , 5%, 60%, 60.5%, 61%, 61.5%, 62%, 62.5%, 63%, 63.5%, 64%, 64.5% or 65%.

In another advantageous aspect, the invention relates to the composition as defined above, further comprising at least one additional antioxidant agent.

The composition according to the invention may contain, besides ascorbic acid, one or more antioxidants. Antioxidants are compounds that can attenuate, inhibit or prevent the oxidation of oxidizable materials by preventing the appearance of free radicals and / or by capturing them.

Antioxidants are very diverse in terms of nature (enzymatic or not, water-soluble or fat-soluble), origin (endogenous, exogenous, natural, synthetic) or mode of action (preventive, "chain breaking").

Said at least one additional antioxidant agent is especially chosen from:

antioxidants such as palmityl-6-L-ascorbic acid, tocopherols and alpha-tocopherol, propyl gallate, buthylhydroxyanisol (BHA), butylated hydroxytoluene (BHT) and ethoxyquin,

carotenoids and xanthophyls such as beta-carotenes, capsanthin, taurine, lutein, zeaxanthin, citranaxanthin and astaxanthin,

polyphenols including flavonoids such as flavone, flavonol, flavonone, dihydroflavonol, isoflavone, isoflavanone, chalone, aurone, anthocyanin, tannins, quercetin, cyanidol, delphinidol and malvidol,

vitamins and provitamines such as palmityl-6-L-ascorbic acid, vitamin E, alphatocopheryl acetate and folic acid,

trace elements: copper, manganese, zinc, selenium (organic form) and iron,

- and plant extracts rich in antioxidants, such as extracts of ginger, sage, citrus, rosemary, clove, seeds and / or grape skin, thyme, and turmeric.

These lists are not limiting and one skilled in the art will be able to choose the appropriate additional antioxidant compound (s).

In addition, there are commercial antioxidant products, natural or synthetic, which can contain several additives or even raw materials, at least one of which has antioxidant activity.

Normally, there is a balance between the permanent production of free radicals in the body and the defense systems, the antioxidants. Oxidative stress is a break in this balance (lack of antioxidants and / or overproduction of free radicals) and is likely to cause immunodepression in animals. This imbalance can be induced by nutritional failures and / or deficiencies in antioxidants, and in some cases by excessive antioxidants.

When an animal is exposed to stress, the production of free radicals increases and its antioxidant reserves decrease, leading to oxidative stress. In the animal, the oxidative stress can appear during certain critical phases and in particular at the time of food imbalances: high food levels, food restriction, consumption of xenobiotics or toxins, micronutrient deficiency, lack of precursor nutrients antioxidants (mainly vitamin E, B-carotene, selenium, copper and zinc), metabolic disorders linked to a significant energy deficit ...; or certain physiological stages: peri-partum period, gestation (mother and fetus), neonatal period. The onset of oxidative stress is also dependent on rearing conditions: climatic variations, emotional stress (confinement, transport, ante-mortem stress); the animal's health status or linked to intense metabolic activity: production of large quantities of milk in dairy cows.

Oxidative stress is expressed in animals by stimulation of the enzymes involved in its regulation (glutathione peroxidase, superoxide dismutase, catalase), oxidation of antioxidants in the body (glutathione, thiol proteins, vitamins E, C, A), and the accumulation of oxidation products. The first consequence for the body is the appearance of often irreversible damage to the cell. More broadly, oxidative stress can affect not only product quality but also animal health.

Advantageously, the invention relates to the abovementioned composition, wherein said at least one additional antioxidant agent represents, by weight, up to 2% relative to the total mass of the composition.

In the invention, the additional antioxidant agent (s) contained in the composition represent, by weight relative to the total mass of the composition, 0%, 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 1.1%, 1.2%, 1.3%, 1.4%, 1, 5%, 1.6%, 1.7%, 1.8%, 1.9% or 2%.

Advantageously, the invention relates to the aforementioned composition, further comprising at least one support.

In addition to betaine and at least one antioxidant, that is to say at least ascorbic acid, and the crystalline matrix of hydrogenated lipids, it is possible, during the manufacture of the composition of the invention, to add one or more supports described below. These supports have the effect of stabilizing and solidifying the composition and in particular to allow solidification of the crystalline matrix of hydrogenated lipids.

Said at least one support is chosen from silica, calcium carbonate, pyrogenic silica, calcium stearate, magnesium stearate and calcium sulphate, calcium formate, bentonite, calcium phosphate, dextrose or a mixture of these.

An advantageous composition according to the invention consists, in mass with respect to the total mass of said composition of:

38% hydrogenated rapeseed oil,

7.05% silica,

5% anhydrous calcium sulphate,

42% betaine anhydrous at 96%, and

7.95% of vitamin C to 97.5%.

Advantageously, another composition according to the invention consists, in mass with respect to the total mass of said composition of:

50% hydrogenated palm oil,

11.7% silica,

5% anhydrous calcium sulphate,

28% betaine anhydrous at 96%, and

5.3% of vitamin C at 97.5%,

Advantageously, another composition according to the invention consists, in mass with respect to the total mass of said composition of:

50% hydrogenated palm oil,

10.4% calcium carbonate,

5% anhydrous calcium sulphate,

28% betaine anhydrous at 96%,

5.3% of vitamin C at 97.5%, and

1.3% of vitamin E

Yet another advantageous composition of the invention consists, in mass with respect to the total mass of said composition of:

50% hydrogenated palm oil,

10.4% silica,

5% anhydrous calcium sulphate,

5.3% of vitamin C at 97.5%,

0.8% grape seed extract,

28% betaine anhydrous at 96%, and

0.5% of a folic acid premix (0.1% of 92% folic acid on a carrier, based on the total mass of the premix)

Yet another advantageous composition of the invention consists, in mass with respect to the total mass of said composition of:

50% hydrogenated palm oil,

15.6% silica,

5.5% of vitamin C at 97.5%,

28% betaine anhydrous at 96%,

0.55% vitamin E, and

0.35% turmeric extract

Another advantageous composition of the invention consists, in mass with respect to the total mass of said composition of:

62.7% hydrogenated palm oil,

15% silica,

5% anhydrous calcium sulphate,

2.65% of vitamin C at 97.5%,

14% betaine anhydrous at 96%,

0.4% vitamin E extract, and

0.25% of a folic acid premix (0.1% 92% folic acid on a carrier, based on the total weight of the premix)

The invention furthermore relates to a feed intended for the nutrition of farm animals comprising from 0.05% to 0.2% by weight of a composition as defined above with respect to the total mass of the feed.

The aforementioned composition can be added as a supplement or additive to animal feed in proportions ranging from 500g to 2kg per ton of feed. Such proportions represent from 0.05% to 0.2% by weight of composition relative to the total weight of the food. This means that the composition represents, in mass, relative to the total mass of the food, 0.05%, 0.06%, 0.07%, 0.08%, 0.09%, 0.1% , 0.11%, 0.12%, 0.13%, 0.14%, 0.15%, 0.16%, 0.17%, 0.18%, 0.19% or 0.2% .

The invention also relates to a method for preparing a composition as defined above, comprising the following steps:

a) contacting one or more hydrogenated lipids having a melting point of 55 ° C to 80 ° C, especially hydrogenated oil having a melting temperature of 55 ° C to 80 ° C, with ascorbic acid and betaine, said one or more hydrogenated lipids being brought to a temperature at least equal to the melting temperature of said one or more hydrogenated lipids so that these or these are in liquid or pasty form, the pasty form corresponding to a mixture of molten lipids and still solid lipids,

b) the mixture, especially homogeneous, of the compounds contacted in the previous step, this step taking place for a period of time sufficient for the temperature of the mixture from said homogeneous mixture to drop to a temperature below the temperature of crystallizing said one or more hydrogenated lipids to obtain a crystalline matrix consisting essentially of one or more hydrogenated lipids in which are dispersed ascorbic acid and betaine.

The composition according to the invention is thus prepared according to a simple process making use of the crystallization properties of lipids and their melting and crystallization temperature.

In the invention, the term "the homogeneous mixture", the action of mixing the various constituents of the composition so that they are distributed in a substantially uniform or uniform manner.

In order to produce the composition according to the invention, said one or more hydrogenated lipids are heated to a temperature that goes beyond the melting point (melting temperature) of the lipid (s) as defined above. Said lipid or lipids are then in liquid form or in pasty form.

It is then possible to add the active compounds (betaine and ascorbic acid) to lipids in liquid or pasty form. In order to achieve uniform dispersion or not, the lipid / betaine / ascorbic acid mixture is mixed by any means of mixing or mixing (pestles, spatulas, blades, propellers ...). The temperature of the mixture, and in particular the temperature of the lipid or lipids, will then gradually decrease until, at first, it falls below the melting temperature of the molten lipids. If the mixture is still stirred (or subjected to mixing), the temperature will decrease below the point of crystallization of said lipid or said inducing a crystallization of this or these.

Thus, by progressive cooling with stirring, the hydrogenated lipid (s) will gradually crystallize and, because of the agitation, form crystals in the middle of which betaine and ascorbic acid will be finely dispersed, homogeneously or not.

The melting and crystallization temperatures of the advantageous oils are described above.

For example, a composition according to the invention made from refined and hydrogenated rapeseed oil will be obtained according to the following process:

The refined hydrogenated rapeseed oil is heated to a temperature above 68 ° C (melting point) to obtain a liquid oil.

Betaine and ascorbic acid at room temperature are added to the liquid oil, and the mixture is stirred.

Stirring is carried out for a time sufficient for the temperature of the mixture to reach a temperature below 49 ° C. (crystallization temperature) in order to allow slow and gradual crystallization.

At the end of the process, crystals of refined and hydrogenated rapeseed oil have formed and betaine and ascorbic acid are found dispersed homogeneously or otherwise between the crystals.

The mixing can be carried out by a conventional mixer known to those skilled in the art.

If the composition comprises additional compounds (other than betaine and ascorbic acid), these compounds are added to the molten lipids or in pasty form, together with betaine and ascorbic acid.

The invention furthermore relates to a composition comprising ascorbic acid and betaine dispersed in a homogeneous or non-homogeneous manner in a crystalline matrix consisting essentially of one or more hydrogenated lipids that can be obtained, or obtained directly, by the process above.

The invention furthermore relates to a composition as defined above, or a food as defined above, for its use for the protection against the effects of heat stress of monogastric animals, especially poultry or farmed pigs. .

It is understood in the invention that a monogastric animal corresponds to any animal that does not live in the wild. "Monogastric animals" means monogastric animals raised for the purpose of animal production or conservation, as well as domestic animals.

In homeothermic animals, in the thermal comfort zone, homeothermy is maintained by means of inexpensive energy mechanisms (quieter behavior, sensible radiation losses, conduction or convection of heat). Beyond this zone, heat losses through the sensitive pathway decrease and homeothermy is ensured only by a significant increase in latent losses (evaporation and / or perspiration).

The thermoneutrality zone is defined by lower and higher critical ambient temperatures which depend on many criteria: species, physiological stage, sex, level of use for poultry, speed of growth, level of production ... but also environmental factors: relative humidity, habitat, ...

The transfers that occur in this temperature range correspond to low energy expenditure, not influenced by the environment and equal to the production of heat then due to the vital needs and the transformation of the food into muscle and fat. The thermal comfort of the animal is optimal. Farm animals effectively transform their ration in order to produce (egg, meat, milk, ...) More simply, this zone of thermoneutrality corresponds to a temperature range in which the animal uses little or no of energy to regulate its temperature.

Thus, beyond this zone of thermoneutrality, it is observed that the heat loss by radiation and contact becomes limiting in the animal and that the heat loss by evapotranspiration takes on increasing importance. In birds, absent or inefficient sweat glands play a negligible role in thermoregulation. Heat loss by evapotranspiration then takes place on the pulmonary mucosal surfaces.

In pigs, as in poultry, in the absence of sweating (sweat glands absent or non-functional), high temperature will cause respiratory hyperventilation, which ultimately has little effect on the acid-base balance of the blood. Pork adjusts cardiovascular function by increasing blood flow to the subcutaneous and respiratory systems, and by decreasing the flow to highly heat-producing tissues such as the liver, muscles or digestive tract. There is also a change in skin temperature, an improvement in heat loss by radiation and convection related to the increase in vasodilation of subcutaneous arterioles.

Heat stress in pigs also significantly affects the feeding behavior of pigs: lower consumption (reduced size of meals coupled with a reduction in the number of meals at certain physiological stages, the only way to maintain homeothermia), transfer of meals to the cooler times of the day. These impacts on feeding behavior have additional effects on the sow: nutritional deficit, mobilization of reserves to maintain piglet growth and milk production. In growing pigs, there is a reduction in growth rate, an increase in lean meat in carcasses.

High temperature increases water losses, can disturb electrolyte balance but can also increase cell oxidation.

The negative effects of heat stress in warm-blooded animals, especially poultry and pigs, do not only affect feed intake and growth, but also carcass yield and survival.

The composition according to the invention aims to remedy these disadvantages

The invention furthermore relates to the use of a composition as defined above, for the manufacture of a pharmaceutical or veterinary product, intended for protection against the effects of thermal stress on farmed monogastric animals, especially the poultry or swine.

In addition, a method for protecting against the effects of thermal stress on monogastric animals is described, said method comprising the administration to monogastric animals, in particular farmed poultry or pigs, in need, or likely to be in the need, an effective dose of a composition as defined above.

FIG. 1 represents histograms showing the activity of the plasma creatine kinase enzyme of 34J chickens, expressed in units / liter, for each of the groups studied: (1): Negative control batch without betaine (gray) dark); (2) Lot with betaine supply of synthetic anhydrous 96% non-vectorized at 500 ppm (gray); (3): batch with betaine anhydrous synthetic 96% vectorized at 500 ppm (light gray).

FIG. 2 represents histograms showing the activity of the 34 mg broiler Glutathione Peroxidase (GPx) enzyme, expressed in units / liter, for each of the groups studied: (1): Negative control batch without betaine supply ( dark gray) ; (2) Lot with betaine supply of synthetic anhydrous 96% non-vectorized at 500 ppm (gray); (3): batch with betaine anhydrous synthetic 96% vectorized at 500 ppm (light gray).

FIG. 3 represents histograms showing the corrected consumption index of the weight of broilers, expressed in g / g, over the period 21-34j for each of the groups studied: (1): Negative control batch without betaine supply ( dark gray) ; (2) Lot with betaine supply of synthetic anhydrous 96% non-vectorized at 500 ppm (gray); (3): batch with betaine anhydrous synthetic 96% vectorized at 500 ppm (light gray).

FIG. 4 represents histograms showing the Daily Average Gain (GMQ) of broilers, expressed in g / day, over the period 21-34j, for each of the groups studied: (1): Negative control batch without betaine supply ( dark gray) ; (2) Lot with betaine supply of synthetic anhydrous 96% non-vectorized at 500 ppm (gray); (3): batch with betaine anhydrous synthetic 96% vectorized at 500 ppm (light gray).

FIG. 5 shows curves showing the evolution of the average broiler weight, expressed in% of the control group (1), over the period 7-42j for each of the groups studied: (1): Negative control lot (black spots ); (2): Batch with vitamin C and other non-vectorized antioxidants (light gray dots); (3): Lot with contribution of the composition according to the invention (dark gray triangle).

FIG. 6 represents a histogram comparing the index of consumption of broilers, expressed in% of the control group (1), over the period 0-45j for each of the groups studied: (1): negative control lot (black); (2): Batch with vitamin C and other non-vectorized antioxidants (dark gray); (3): batch with contribution of the composition according to the invention (light gray).

FIG. 7 represents a histogram showing the weight-corrected consumption index (ICC) of broilers at 37j, expressed in g / g, for each of the groups studied: (1): Negative control batch without betaine supplementation or antioxidant (dark gray) ; (2): Lot with betaine HCl synthetic 95% non-vectorized allowing a contribution of 700ppm pure betaine (gray); (3): Batch of betaine HCl synthetic 95% vectorized with hydrogenated palm oil allowing a supply of 350ppm pure betaine (light gray); (4): batch with contribution of the composition according to the invention for a supply of 200 ppm of pure betaine (scratches).

Figure 8 represents a histogram showing the weight of the fillets of broilers, expressed in g, the 0-36j period for each of the groups studied: (1): Lot negative control without supplementation betaine or antioxidant (dark gray); (2): Lot with betaine HCl synthetic 95% non-vectorized allowing a contribution of 700ppm pure betaine (gray); (3): Batch of betaine HCl synthetic 95% vectorized with hydrogenated palm oil allowing a supply of 350ppm pure betaine (light gray); (4): batch with contribution of the composition according to the invention for a supply of 200 ppm of pure betaine (scratches).

EXAMPLES

Example 1 : Effects of supplementation betaine  and in food antioxidants vectorized on growth performance, oxidative stress and carcass carcass quality maintained at high temperatures

The growth performance of broilers and the meat yield are altered by high temperature.

This deficiency is attributable to a reduction in food consumption and an increase in oxidative stress, which leads to hemolysis and a lower quality of the carcass. Betaine supplementation can reduce these negative effects by virtue of its osmoprotective properties and its role as a methyl donor. In addition, vitamin C and other antioxidants can protect against oxidative stress and hemolysis. Since betaine and vitamins are aggressive or sensitive active ingredients, a specific vectorization process with a selected vegetable fat has been applied. The purpose of this study was to evaluate the effect of the composition according to the invention on growth performance, carcass quality and blood hemolysis in broilers reared under hot conditions. A total of 192 male Ross 308 broilers were distributed in a randomized complete block comprising 3 groups: T- (negative control, no composition according to the invention), B1 (T- + 750 g / ton of composition according to the invention). invention) and B2 (T + 1300 g / ton of composition according to the invention), each repeated 16 times with 4 birds per cage. From day 21 to day 35, the temperature was changed daily to simulate high summer temperatures of up to 30 ° C. Growth performance was measured throughout the experiment. At 36 days, the birds were slaughtered. Plasma markers of oxidative stress, as well as blood hemolysis status, were compared between T- and B2. Water loss and yield nets were compared. The data were analyzed using univariate analysis of variance and Tukey's test as a post-hoc test. The composition according to the invention tested in B1 and B2 had a significant effect on body weight gain, consumption and feed efficiency between 0 and 36 days (P <0.05). A post hoc analysis revealed that B1 gave the best results for the above parameters (P <0.05). The net yield was significantly increased by supplementation via the composition according to the invention, and even more so for B1 (P <0.01). Markers of oxidative stress were not significantly affected by dietary intervention. In addition, B2 had a hemolysis score lower than that of T- (4.12 g / L vs. 4.44 g / L, p <0.05). These results indicate that the composition according to the invention has a positive effect on the growth performance and the integrity of the erythrocytes of broilers, showing better resistance when the thermal environment exceeds the thermoneutrality zone of the animals.

In this example, the term "composition according to the invention" means:

50% hydrogenated palm oil,

10.4% silica,

5% anhydrous calcium sulphate,

5.3% of vitamin C at 97.5%,

0.8% grape seed extract,

28% betaine anhydrous at 96%, and

0.5% of a folic acid premix (0.1% 92% folic acid on a carrier, based on the total weight of the premix).

Example 2 Effect of betaine vectorization under thermal challenge conditions

The objective of this trial was to test a vectorized form of synthetic anhydrous betaine, compared to a non-vectorized form of anhydrous betaine, made in the broiler feed under hot conditions, from 21 to 34 days.

 The inventors compared:

(1): negative control lot without betaine supply,

(2): Batch test with betaine anhydrous synthetic 96% not vectorized at 500 ppm,

(3): Batch test with an injection of betaine anhydrous synthesis 96% vectorized at 500 ppm.

The following parameters have been noted:

zootechnical performance throughout the trial,

Plasma concentration of the creatine kinase enzyme (CK) as an indicator of muscle damage related to a deterioration of the function and membrane permeability of muscle cells, at 34j,

blood antioxidant status via the activity of the enzyme Glutathione Peroxidase (GPx), at 34j.

The test was carried out on male chicks, Ross PM3 strain, distributed in 20 cages of 4 animals each (or 6 or 7 repetitions per group).

The following thermal program was applied from 21 days of age: from 18h to 8h, the chickens are placed at 24 ° C, from 8h to 11h at 28 ° C, from 11h to 15h at 30 ° C and 15h at 18h at 28 ° C.

Results

Maintaining the integrity of muscle cells :

The results are shown in Figure 1 . The plasma creatine kinase enzyme is one of the indicators of muscle damage related to a degradation of the function and membrane permeability of muscle cells, which can result in a degradation of meat quality.

More specifically, myopathy related to hyperthermia is characterized in particular by an increase in the plasma activity of this enzyme.

In this assay, the betaine supply (2) and (3) numerically reduced the plasma level of CK compared to the negative control (1) and the betaine vectorized (3) reduced more strongly CK (-20% compared to the control negative) that betain non-vectorized (2) (-9% compared to the negative control).

Improvement of oxidative status:

The results are shown in Figure 2 . The increased activity of the enzyme Glutathione Peroxidase (GPx) promotes a stable antioxidant system according to the literature.

The provision of betaine (2) or (3) numerically increases the activity of the GPx enzyme relative to the control group (1), especially for the betaine-vectorized group (3) (+ 12% compared with the negative control ( 1) versus 7% for non-vectorized Betaine (2)).

Improvement of zootechnical performances:

The results are shown in Figures 3 and 4 . Betaine intake (2) and (3) improved the weight-corrected intake index compared with the control group (1), either via the non-vectorized form (2) (-0.03 points) or the vectorized form (3) (-0.05 points). Same observation for the Daily Mean Gain (GMQ) between 21 and 34 days: + 3.1% and + 3.6% compared to the control group respectively for the free Betaine 500 ppm group (2) and the Betaine vectorized group 500 ppm (3).

Conclusion

This trial demonstrates the interest of the beta- neability of betaine anhydrous which makes it possible to obtain better zootechnical performances compared to free betaine under conditions of thermal challenge, with a numerical improvement of the oxidative stress markers and the integrity of the cells. muscle.

Example 3 Effect of Vectorization of Antioxidants in Hot Conditions

The objective of this test is to compare the effects of the composition according to the invention (3) with a contribution of non-vectorized antioxidants (2) on the growth performance of meat fowl raised under tropical temperatures.

The test was carried out at an experimental station in Dakar, Senegal, in hot conditions (maximum temperature of 30 ° C). 810 Cobb500 chickens were allotted to 0 days at the rate of 54 chickens per floor, and 5 floors per group.

The following groups have been tested:

(1): Negative control lot without supplementation,

(2): Batch with vitamin C (5%) and other non-vectorized antioxidants (vitamins and trace elements) (12%), supported on calcium carbonate (83%) at 2000 g / tonne of feed, from 0 to 42 days,

(3): Batch with addition of the composition according to the invention (28% anhydrous betaine 96%, 5.5% vitamin C, 0.9% other antioxidants, 15.6% carrier, 50% crystalline matrix based on hydrogenated palm oil), at 750 g / ton of food from 0 to 20 days (start-up phase), then 915 g / ton of food from 20 to 42 days (growth phase). duration of the test:

Weekly: the individual weights, the quality of the litter and legs,

On a daily basis: food and water consumption, mortality.

Results

The results are presented in Figures 5 and 6 .

The contribution of non-vectorized antioxidants (2) and of the composition according to the invention (3) in the broiler chickens reared under the conditions of rearing of the tropical zones makes it possible to significantly improve the weights of the chickens compared with the control. negative (1), respectively by 5% and 7% at 42 days.

This improvement in the weight of the animals is explained by a drop in feed consumption, hence a positive trend in the consumption indices (IC in g / g) for the 2 test groups: -2% for the batch ( 2) and -5% for lot (3).

Furthermore, the viability of the animals is improved with the addition of non-vectorized antioxidants (2) and the composition according to the invention (3), since the mortality decreases by 47% and 52% respectively relative to the negative control (1). .

No effect of the composition according to the invention (3) on the quality of the litters and legs compared to the control group (1).

conclusions

This trial confirms the importance of an antioxidant intake against the effects of heat stress in broiler poultry, a contribution that allows the improvement of zootechnical performances (slaughter weight, consumption index) and the improvement of the viability of farm animals.

This beneficial effect versus thermal stress is all the more important with the composition according to the invention (3) in which the antioxidants are vectorized and combined with betaine, although the antioxidants are provided in a smaller quantity (up to three times less) than batch (2) not containing betaine,

Example 4 Comparison of the effects of the composition according to the invention on simple additions of free betaine or vectorized, in conditions of thermal challenge

The objective of the test is to compare the effects of the composition according to the invention (4) in comparison with a supply of free betaine (2) and betaine vectorized (3) on growth performance, stress markers. oxidation and the quality of broiler carcasses subjected to high ambient temperatures compared to the seasonal norm.

Materials and methods

The test was carried out in experimental station. The 256 chickens were allotted at 0 days at the rate of 4 Ross 308 male chickens per module, divided into 4 groups of 16 modules, ie 64 chickens per group.

Batching was done according to the average weight per module at the finish.

The following groups were tested throughout the trial period:

(1): Negative control lot without betaine or antioxidant supplementation;

(2): Positive control lot with betaine HCl synthetic 95% non-vectorized allowing a contribution of 700ppm pure betaine;

(3): Batch of betaine synthesis HCl 95% vectorized with hydrogenated palm oil allowing a supply of 350ppm pure betaine;

(4): Lot with composition according to the invention, distributed at 1500 g / T of food:

62.7% hydrogenated palm oil,

15% silica,

5% anhydrous calcium sulphate,

2.65% of vitamin C at 97.5%,

14% betaine anhydrous at 96%,

0.4% vitamin E extract, and

0.25% of a folic acid premix (0.1% 92% folic acid on a carrier, based on the total weight of the premix)

An adaptation period of 20 days at standard temperature was first respected.

Then, from 21 days of age, every day during the test and up to 36 days, the chickens were subjected to the following thermal program: 28 ° C from 8h to 11h, 30 ° C from 11h to 15h, 28 ° C from 15h to 18h, 24 ° C from 18h to 8h.

The animals were slaughtered at 37 days of age, and the net quality was raised.

Zootechnical performance was measured throughout the trial period: animal weight, feed consumption, water consumption, scoring and dry matter of droppings, mortality (number, cause).

Results

Over the entire period of the trial, no significant group effect was observed on animal mortality (p-value = 0.534).

The results are presented in figure s 7 and 8 .

The weight-adjusted consumption index (ICC) 0-36j is improved numerically by the addition of the 3 solutions (1), (2) and (3) compared to the negative control (1).

The addition of 700 ppm of betaine in free form (2) and 350 ppm of betaine in vectorized form (3) gives comparable ICCs.

The ICC is significantly improved by -0.06 points with respect to the negative control (1) for the group with the composition according to the invention (4).

There is also a significant group effect on the variable net weight (g) at 37j.

No significant difference in net weight for groups (1), (2) and (3).

The group Composition according to the invention (4) improves the weight of nets of + 46.8g compared to the negative control (1).

conclusions

This test makes it possible to demonstrate the positive effect of betaine on the performance of poultry meat subjected to high temperatures, with betaine vectorized or not, and with the composition according to the invention.

The vectorization of betaine makes it possible to obtain results comparable to a betaine free double-dose (3) dose: 350 ppm vs (2): 700 ppm.

The composition according to the invention (4), for a lesser betaine equivalent dose (200 ppm), makes it possible to further improve performance with respect to a simple provision of betaine, vectorized (3) or not (2).

This test therefore confirms, under heat stress conditions:

the interest of the betaine vectorization demonstrated in point 2.1 above,

the interest of betaine and antioxidants provided via the composition according to the invention. The composition according to the invention is the product which shows the best zootechnical performance and the best slaughtering performance with a significant net weight gain.

Other performance criteria such as water consumption, droppings quality and mortality are not affected by the food.

Example 5 Mass Test in Field and Summer Conditions

The objective of this test was to test the effectiveness of the composition according to the invention, under summer conditions, on broilers between 29 and 33 days of age.

The composition according to the invention was incorporated into the last food at 1 kg / T and distributed to 47 000 broilers distributed in 1 control building (20 000 chickens) and 1 test building (27 000 chickens) in the same farm, located in the northwestern France, end of August.

For this test, the composition according to the invention consisted of:

50% hydrogenated palm oil,

10.4% calcium carbonate,

5% anhydrous calcium sulphate,

5.3% of vitamin C at 97.5%,

28% betaine anhydrous at 96%, and

1.3% of vitamin E

Heat-related mortalities have been reported; zootechnical performance and slaughter results were measured.

The animals in the control group did not receive any supplement to the feed usually used by the farmer.

The animals of the test group received, in addition to the food, the composition according to the invention at 1 kg / ton of food of 29 to 33 days of age.

Results

The results obtained are presented in the following Table 1: Witness Trial Variation (%) Average Daily Gain GMQ (g / d) 55,05 56.67 2.94 I ndice of Consumption 0-3 3 days 1.63 1.53 -6.13 Mortality (%) 3.97 1.93 -51.39

On average, at 35 days, +1.62 g / day of GMQ is obtained and -0.10 points of consumption index with the composition according to the invention compared to the negative control. The mortality (in%) is reduced by 2 points, which represents a halving of the mortality rate.

Conclusion

This test confirms that the contribution of the composition according to the invention to 1 kg / T, 5 days before slaughter, improves rearing performance (GMQ and feed efficiency) and reduces mortality, in broilers subjected to temperatures summer.

Claims (10)

A composition comprising an active substance dispersed in a matrix, said active substance comprising or consisting essentially of a mixture of betaine and an antioxidant, said antioxidant being ascorbic acid, said matrix being a crystalline matrix consisting essentially of one or more hydrogenated lipids, especially hydrogenated oil. The composition of claim 1, wherein the ascorbic acid is from 2.5% to 8% by weight based on the total weight of the composition. The composition of claim 1 or claim 2, wherein the betaine is from 13% to 40% by weight based on the total weight of the composition. Composition according to any one of claims 1 to 3, wherein said crystalline matrix, consisting of one or more lipids, represents from 25% to 65% by weight relative to the total mass of the composition. The composition of any one of claims 1 to 4, further comprising at least one additional antioxidant. The composition of claim 5, wherein said at least one additional antioxidant represents by weight, up to 2% based on the total weight of the composition. The composition of any one of claims 1 to 6, further comprising at least one carrier. Feed intended for the nutrition of farm animals comprising from 0.05% to 0.2% by weight of a composition as defined above relative to the total mass of the feed. A process for the preparation of a composition according to any one of claims 1 to 7, comprising the following steps:
a) contacting one or more hydrogenated lipids having a melting point of 55 ° C to 80 ° C, especially hydrogenated oil having a melting temperature of 55 ° C to 80 ° C, with ascorbic acid and betaine, said one or more hydrogenated lipids being brought to a temperature at least equal to the melting temperature of said one or more hydrogenated lipids so that they are in liquid or pasty form,
b) the mixture of the compounds contacted in the preceding step, this step taking place during a period of time sufficient for the temperature of the mixture resulting from said homogeneous mixture to drop to a temperature below the crystallization temperature of said one or several hydrogenated lipids to obtain a crystalline matrix consisting essentially of one or more hydrogenated lipids in which are dispersed ascorbic acid and betaine. Composition as defined in any one of Claims 1 to 7, or food according to Claim 8, for its use for protection against the effects of heat stress of monogastric animals, in particular farmed poultry or pigs.

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