CA2618380A1 - Feed additive and uses thereof - Google Patents

Abstract

The present invention relates to a food or feed supplement composition. The composition comprised of a natural anti-inflammatory compound or plant extract, a anti-oxidant compound and a vitamin. The anti-inflammatory compound is preferably a polyphenol compound.
The composition helps to reduce the body oxidative stress, the systemic or localised inflammation, or the body temperature due to stress.

Description

FEED ADDITIVE AND USES THEREOF
Field of the invention This invention is in the area of animal feed additives.
Background of the invention Disease or undesirable condition may occur in a human and an animal subject from any one or more of a long list of causes, including microbial infection, exposure to toxins, prolonged exposure to stress, and a diet that is either deficient in one or more essential substances, contains an excess of harmful substances, such as salt, fats, cholesterol, etc., or is otherwise unbalanced.
Alternatively, or in addition, the onset and development of disease or undesirable condition may have a genetic component.

Oxidative damage is caused by the action of highly reactive species (such as free radicals or peroxides) on the cells and tissues of the body. A free radical is any atom or group of atoms, which has one or more uripaired electrons. Free radicals are uncharged high-energy species that are highly reactive. Peroxides are compounds containing linked pairs of oxygen atoms.
Organic peroxides can act as sources of free radicals.

One major source of such reactive species is molecular oxygen, which is converted into a "reactive oxygen species". The loss of an electron from molecular oxygen will produce a free radical species, which reacts with cells or tissue in the body causing damage including lipid peroxidation, which leads to cell death. Reactive oxygen species can be produced in the body of an aerobic organism during metabolism, for example by the respiratory burst of phagocytes, mitochondrial oxidative phosphorylation and the xanthine oxidase system. In addition, reactive oxygen species are produced in the environment, for example by UV light, pollutants or ionising radiation.

Exposure of the body to agents causing oxidative damage results in inflammation, auto immune diseases, cancers, muscle disorders, lung inflammation and general ageing. Oxidative damage to different parts of the body is responsible for causing or exacerbating a number of disorders. Oxidative stress occurs when the production of reactive oxygen species exceeds the removal of the reactive oxygen species. Systemic and localised inflammation most of the time involve reaction of oxidative stresses and production of inflammatory markers, such as protein kinase C, lactic acid, haptogrobin, and cortisol. Another consequence of oxidative stress, body temperature increases and/or systemic inflammation is the reduction of oxygenation of cells, particularly smooth and red muscle cells, as well as the equilibrium of the immune and hormonal systems.

Agents causing oxidative damage can be inactivated by antioxidant molecules or compounds. Antioxidants are typically highly substituted phenols, aromatic amines or sulphur containing molecules, which can occur naturally or can be produced synthetically. In addition, metal-sequestering agents can act as antioxidants by inactivating metals. The body has its own anti-oxidant defences including glutathione, vitamin C, vitamin E, catalase, copper-zinc-superoxide dismutase and uric acid.

In moderate or severe cases of body temperature decrease, systemic and localised inflammation, and oxidative -stress, it is necessary to treat with prescription medication.
Corticosteroids are most of the time used to reduce the inflammation thereby resolving the clinical signs of the disease. However, the inflammation will return following cessation of the therapy if the individual is exposed to offending products or conditions, including environmental sources of stress. The use of corticosteroids is accompanied by a number of undesirable side effects. High concentrations of the corticosteroids result in the suppression of the immune system. The long-term use of corticosteroids can lead to depression, muscle wasting, long dry hair coat, hyperglycemia, increased risk of' laminitis, polydipsia and polyuria.

Phosphodiesterase inhibitors inhibit the breakdown of intracellular cAMP in smooth muscle. The most commonly used phosphodiesterase inhibitor in mammals is theophylline.

In addition, stress causing body temperature disturbance and systemic inflammation leads to lost of performance in animal production systems and farms. Appetite reduction, weight loss, decrease survival rate at birth, reduction of delivery, reduction of lactation, and several other problems can be associated to stress effects to the body.

-2-Therefore any new treatment or therapy which allows decreasing the concentration of conventional pharmaceuticals necessary to treat stress, inflammation and body temperature will be beneficial, in addition of improving the human and animal welfare and performance.

SUMMARY OF THE INVENTION

One aim of the present invention is to provide a food supplement composition comprising at least one polyphenol compound, at least one antioxidant compound, and at least one vitamin.

The polyphenol compound can be obtained from a plant extract, and for example, but without limiting the scope of the present invention, can be a polyphenolic acid. The vitamin can be an antioxidant vitamin, or another vitamin, such as for example, vitamin D, or a vitamin B, or a vitamin f, or a combination thereof.

For example, the polyphenol can be in proportion of 0.1% (w/v or w/w) to 25%
(w/v or w/w), the anti-oxidant compound in proportion of 0.1% (w/v or w/w) to 20% (w/v or w/w), and the vitamin in proportion of 0.11ro (w/v or w/w) to 30% (w/v or w/w).

In accordance with the present invention there is provided a food composition in which can be a concentration of methyl salicylate or an analog thereof at a level from 0.01 mg to 100 mg per kilogram body weight per day or above.

The food supplemenit composition of the present invention may comprosed of a probiotic microorganism. The probiotic microorganism can be a yeast, a bacteria, or a combination thereof, which can be alternatibly a living or dead probiotic microorganism.

Another aim of the present invention is to provide a food supplement for reducing systemic inflammation, localised inflammation, body temperature, or cellular oxidation, comprising a food supplement composition as described herein.

Another aim of the present invention is to provide a method for reducing body temperature, systemic inflammation, localised inflammation, or cellular oxidation, the method

-3-comprising the step of administering orally to an animal or a human the food supplement composition according to the present invention.

Another aim of the present invention is to provide a method for improving fertility of an animal or a human compris'ing giving orally to the animal or human the food supplement composition according to the present invention.

Another aim of the present invention is to provide a method for increasing the growth rate of an animal or a human comprising giving orally to an animal or a human the food supplement composition according to the present invention.

Another aim of the present invention is to provide a method for calming an animal or a human comprising giving orally to an animal or human the food supplement composition according to the present invention.

Another aim of the present invention is to provide a method for reducing body shrink of an animal or a human during a stress period comprising giving orally to an animal or human the food supplement composition according to the present invention at least before, during, or after the stress period.

Another aim of the present invention is to provide a method for increasing the number of eggs per bird comprising giving orally to a bird the food supplement composition according to the present invention.

Another aim of the present invention is to provide a method for reducing diarrhea of an animal or a human comprising giving orally to an animal or human the food supplement composition according to the present invention.

Another aim of the present invention is to provide a method for increasing wounding comprising giving orally to an animal or human the food supplement composition according to the present invention.

Another aim of the present invention is to provide a food composition for improving fertility of an animal or a human comprising the food supplement composition according to the present invention.

-4-Another aim of the present invention is to provide a food composition for increasing the growth rate of an animal or a human comprising the food supplement composition according to the present invention.

Another aim of the present invention is to provide a food composition for calming an animal or a human comprising the food supplement composition according to the present invention.

Another aim of the present invention is to provide a food composition for reducing body shrink of an animal or a human during a stress period comprising the food supplement composition according to the present invention.

Another aim of the present invention is to provide a food composition for increasing the number of eggs per bird compr:ising the food supplement composition according to the present invention.

Another aim of the present invention is to provide a food composition for reducing diarrhea of an animal or a human comprising the food supplement composition according to the present invention.

Another aim of the present invention is to provide a food composition for increasing wounding comprising the food supplement composition according to the present invention.

For the purpose of the present invention the following terms are defined below.

For the purposes of this invention, the terms "aid" and "aiding" mean to decrease or alleviate the symptoms suffered by a human or an animal individual especially the symptoms of systemic inflammation, body temperature increase, and stress effects. This aid may allow the reliance on a drug therapy to be reduced. Alternatively the individual may exhibit less symptoms or the severity of the symptoms may be reduced. The individual may exhibit an improved level of fitness or an improved level of well being.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

The present invention now will be described more fully hereinafter with reference to the accompanying drawings, in which preferred embodiments of the invention are shown. This

-5-invention, may, however, be embodied in many different forms and should not be construed as limited to the embodiments set forth herein, rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art.

In accordance with the present invention, there is provided a food supplement comprising at least one polyphenol compound, at least one antioxidant compound, and at least one vitamin.

The polyphenol compound can be a polyphenolic adic, which is generally obtained from natural sources and plants, under form, for example but not limited to, plant extracts. Again for example, polyphenol can be obtained from liquorice, wintergreen, betula, taxus, larix, rosemary, grape seeds, or combination thereof.

According to another embodiment of the present invention there is provided a food or feed supplement providing a synergistic effect of the combination of anti-inflammatory products, preferably natural, and alimentary anti-oxidant products, with vitamins.

Also, the present invention may also contain one or more flavenoids from natural and synthetic sources. The source of the flavenoid is not limiting. More preferably, the natural source of flavenoids is one or more of' wintergreen, rosemary and liquorice. The plants contain tannic acid, resin and a volatile oil, which contains Borneol, bornyl acetate and other esters and a camphor derivative. Oil of rosemary is used as a tonic, astringent, diaphoretic and stimulant.

Dried plant extract containing polyphenol or flavanoids is provided at levels of from 0.1 mg to 10 grams per kilogram body weight per day, preferably at levels of 10 mg to l gram per kilogram bodyweight per day, and above or an equivalent amount of a semi-dried or fully hydrated form of plant extract.

Among others, liquorice has been shown to contain active saponins including glycyrrhizin. These compounds have been reported to have liver-protective effects through their anti-free radical properties. Glycyrrhizin is converted into its aglycone by intestinal flora.
Flavonoid aglycones are very bio-available.

-6-For the purposes of this invention the plant extract may be dried or partially dried, in the fornl of a powder, in oil, liquid (either as a solution or as an oil), crushed, an extract, fresh or semi-solid. Preferred forms of clried plant extract include those containing between 0 and 40%
w/w water or between 0 and 10% or between 0 and 5%. Dried liquorice is preferably provided at a level of 2 mg to 500 mg per kilogram bodyweight per day more preferably 1 mg per kilogram bodyweight per day or above.

The first aspect of the invention relates to a food supplement which may contain herbal phenolic compounds. The source of the herbal phenolic compounds is not limiting and can include natural and synthetic sources. The herbal phenolic compounds can be provided by a natural source such as a plant, more preferably an herb plant. The phenolic compounds can be provided by one herb or by a mixture of herbs, for example, one or more of wintergreen, rosemary, nutmeg, oregano, basil and coriander. For the purposes of this invention, any part of the herb plant can be used (for exarnple, leaf, stem, bark, bulb, root, fruit, flower or seed). The herb material can be dried, semi-dried, fresh, crushed, in oil, in solution as a powder, liquid (as a solution or as an oil) or semi-soli:d.

Alternatively, the herbal phenolic compound is provided as an extract from a plant.
The phenolic compound can be extracted and partially or fully purified from the herb.

Preferably the phenolic compounds are obtained from wintergreen.

Several phenolic cornpounds extracted from plant extracts as disclosed above (and related family members such as oregano) have exhibited antioxidant effects.
Phenolics from plant extracts include, but are not limited to, carnosol, rosemanol, carnosic acid and rosemaridiphenol.
These phenolic compounds may act as antioxidants, inhibit carcinogenesis or act as anti-inflammatory agents.

Plant extracts according to the the invention may be in any form. It may be dried, fresh, crushed, in solution, in oil, as a powder, liquid (either as a solution or as an oil) or semi-solid.

Another aspect of die invention may optionally comprise proanthrocyanidins.
The proanthrocyanidins of the preser-t invention can be provided by natural or synthetic sources. The

-7-source of the proanthrocyanidins is not limiting. The proanthrocyanidins can also be provided by grape seed oil for example, without limiting the invention to this source.

The food supplement of the invention optionally contains B-vitamins including folate.
The B-vitamins can be provided by natural or synthetic sources. Definitions of natural and synthetic sources discussed in relation to the antioxidant vitamins also apply to this aspect of the invention. Natural sources of the B vitamins include brewers yeast.

Brewers yeast is provided in the food supplement in this aspect of the invention at a level from lmg to 25 grams per kilogram body weight per day.

The food supplement of the invention may be used in aiding the treatment of an animal suffering from high body temperature, systemic inflammation, localized inflammation, oxidative stress, or environmental stress effects. In particular the food supplement is used where the animal may be mammals or birds. Manimals for the purposes of this invention include bovine, porcine, ovine, caprine, feline, canine, and primate, including human being. Birds may include for example chicken, turkey or ducks.

The antioxidant vitamins of the invention are compounds which can inactivate free radical species or the sources of free radicals including reactive oxygen species and hydrogen peroxide. Examples of such antioxidant vitamins include vitamin C, vitamin E
and beta-carotene.

Vitamin C is a water-soluble substance. Vitamin C has a number of important roles in the body. It has an essential role in the maintenance of healthy teeth, gums and bones. It aids the healing of wounds, scar tissue and fractures and strengthens blood vessels.
Vitamin C also builds resistance to infection and aids in the prevention and treatment of the common cold. Vitamin C is also one of the major antioxidant nutrients.

The food supplement of the invention will optionally contain vitamin C at a level from 10 mg to 1 gram per kilogram body weight per day. The vitamin C may be in any form. It may be liquid, semi-solid or solid.

Vitamin E is a collective term for several biologically similar compounds, including those called tocopherols and tocotrienols, which share the same biological activity. The selenium-containing enzyme glutathione peroxidase together with vitamin E helps to protect cells against

-8-free radical induced damage. Vitamin E acts as a scavenger of free radicals.
Vitamin C may assist by reducing the tocopheroxyl radicals formed by the scavenging. In addition, vitamin E helps to block lipid peroxidation and may also form an important part of the membrane structure due to its interaction with membrane phospholipids. It has also been suggested that Vitamin E plays an important role in the functioning of the immune system. The most biologically active biological form of vitamin E in animal tissue is alpha-tocopherol. Vitamin E cannot be synthesised in vivo.
Forms of vitamin E for the present invention include D-alpha-tocopherol, D-alpha-tocopherol acetate, DL-alpha-tocopherol and DL-alpha-tocopherol acetate.

Units of vitamin E can be expressed as International Units (IU), where 1 IU of alpha-tocopherol approximates to 1 mg of alpha-tocopherol. Other vitamin E compounds have their IU
determined by their biopotency :in comparison to alpha-tocopherol as described in McDowell, L.
R (1989) Vitamin E: In vitamins in Animal Nutrition, Chapter 4, page 96, Academic Press, UK.

Vitamin E is a major anti-oxidant nutrient and acts in the body as a free radical scavenger. Alpha-tocopherol is the most active anti-oxidant biological form of vitamin E.

The food supplement of the first aspect of the invention may contain vitamin E
at a level from 1 IU to 100 IU per kilogram body weight per day.

A further useful point: in relation to the use of vitamin E in combination with vitamin C
is their potential to act synergistically, and more again when in combination with anti-inflammatory plant extract, such as these containing polyphenolic acids. This may be assisted by the fact that vitamin E is lipid soluble and vitamin C is water-soluble. Alpha-tocopherol is known to sit in the lipid membrane. Ascorbate and alpha-tocopherol, for example, interact at the interface between cell membranes or lipoproteins and water. Ascorbic acid rapidly reduces alpha-tocopherol radicals in membranes to regenerate alpha-tocopherol.

Beta-carotene has strong antioxidant properties and has been shown to be beneficial against selected cancers, cardiovascular diseases, cataracts and age related macular degeneration.
Beta-carotene is particularly effective at scavenging peroxyl radicals and is a very potent singlet oxygen quencher at low oxygen tensions. Supplementation of the diet with beta-carotene has been reported to reduce lipid peroxidation.

-9-The food supplement of the invention may contain beta-carotene as a level of from 1 mg to 50 mg per kilogram body weight per day.

The antioxidant vitamins (including sources of such vitamins, such as beta-carotene) of the invention are provided in combination with one or more compounds, which exhibit antioxidant or anti-inflammatory properties. These compounds include polyphenol, polyphenolic acid, eugenol, selenium, carotenoids, flavenoids, phyto-oestrogens, proanthrocyanidins, herbal phenolic compounds or ubiquinone.

Without limiting the present invention, there is some evidence that reactive oxygen species may have a role in high body temperature, stress related and inflammatory diseases. Work has indicated that mammals and birds suffering from recurrent airway obstruction demonstrate oxidative stress. The food supplement of the invention has provided a cocktail of antioxidant compounds derived from natural sources which decreases the level of inflammation in mammals and birds suffering from high body temperature, systemic and localized inflammations, and related conditions.

Administration of the food supplement of the invention to an animal will provide an increased level of compounds with antioxidant activity thus reducing oxidative stress to the body.
This will be particularly beneficial where an animal has been or will be or is subjected to an increase growth, or where an animal is exposed to free radicals due to environment. The food supplement may help in maintaining the healthy respiratory system of an animal by supporting or improving the natural defenses of the body.

Controlling the systemic or localized inflammation, or body temperature increase in farm animals by giving the animals a composition according to the present invenitori involves preventing further attacks by erivironmental management or the use of prescription medication which can be costly and involves the risk of unwanted side effects.
Administration of the food supplement of the invention cani reduce the need for prescription medication thereby decreasing the risk of side effects to that medication.

A second aspect of the invention provides a food supplement, which provides an effective prophylaxis or adjunct treatment for inflammation, stresses, stress effects or body

-10-temperature increase. The food supplement may be manufactured from natural sources and provides a more natural treatment for this condition.

A further aspect of the invention provides a food supplement, which provides a contribution to the effective prophylaxis or treatment of systemic inflammation, body increase temperature, and stress effects. Administration of the food supplement of the invention to an individual suffering from these diseases will decrease, thus decreasing the severity of the symptoms.

According to anothei- embodiment of the current invention, it involves a method of contributing to the prophylaxis or treatment of an animal susceptible to or suffering from damages dues to oxidative stress, body temperature increase, systemic or localized inflammation. The invention also relates to a method of contributing to the prophylaxis or treatment of an animal susceptible to or suffering froni an environmental stress effect. In particular this relates to a method of treatment where the stress effect involves an inflammation of the body. It is clear that the method may have more general effects throughout the body. In each case, the method comprises administering to the animal a food supplement of of the invention.
The animal is preferably in need of the prophylaxis or treatment.

The present invention will be more readily understood by referring to the following examples which are given to illustrate the invention rather than to limit its scope.

-11-EXEMPLE I

EFFET DES POLYPHENOLS ISSU DES HUILES DE THE DES BOIS, MENTHE
POIVRE ET DE CANNELLE COMME ADDITIF DE CONTROLE DES STRESS
D'ELEVAGE PORCIN

Abstract : Le stress est un probleme de production extremement grave. Le stress semble le principal element responsable de la majorite des pertes de production. Le stress est une reaction naturelle de l'organisme. Le stress est un mecanisme inflammatoire qui inhibe la production toutes les autres fonctions du corps pour permettre dans un premier temps de produire du sucre et ainsi etre en mesure de repondre aux attaques externes. (The mechanisms of body function 1984). Les quatre dernieres annees ont favorise des nouvelles approches de production animale et I'ajout de nouvelles alternatives qui permettent de reduire les problemes du stress. (Bristol University UK, animal welfare guide 2005). L'alimentation est aussi un moyen de reduire les stress ou du moins a aide de les controler.
L'acquisition de connaissance sur les plantes aux proprietes anti-inflammatoires nous semble une voie interessante pour favoriser un meilleur equilibre metabolique. L'objectif de cet ouvrage etait de demontrer si il est possible par I'alimentation d'augmenter la tolerance ou resistance aux differents stress d'elevage chez le porc.

Tableau 1 Matieres actives Nom de Ia plante Forme Origine Matiere active globale Matiere active physiqu desirer pour Ia e formulation INGREDIENTS AUX PROPRIETES ANTI-INFLAMMATOIRES
Reglisse de chine Poudre Asie isoflavones, liquiritine, isoliquirie et Ortho acethyle salicylate formoneitine, ortho acetyle salicylate de (Glucosides sodium phenoliques) Huile de the des bois Huile Europe et Methyle salicylate Methyl salicylate Asie (Glucosides phenoliques) Menthe poivree Poudre Europe et Menthol, acides phenoliques Acide phenolique Asie Vitamine E Poudre Asie Alpha tocopherol Vitamine E
INGREDIENTS AUX PROPRIETES regularisation du sucre sanguin Tripicolinate de Poudre USA Chrome Chrome chrome INGREDIENTS SIALAGOGUE ET BACTERIOSTATIQUES
Huile de cannelle Huile Amerique Aldehyde cinnamique, eugenol, tanins, Aldehyde cinnamique, du sud, coumarines coumarines Europe et Asie

-12-Tableau 2 Formulation en pourcentage d'ingredients utilises.

Ingredients Formule avant Formule A: Groupe A Formule Placebo substitution % % %
Composantes Methyle salicylate de I'huile de 0,0% 4,0% AUCUN
phytoactives the O-salicylate de la reglisse 12,5% 4,5%
Acide phenolique 0,5% 2,5%
Aldehyde cinnamique 0,5% 1,0%
Coumarines 0,25% 1,0%
Tanin 0,25% 1,0%
Composantes Vitamine E 64 K U.I. ou en premix 12,8%
actives Tripicolinate de chrome 200 PPB en premix 10%
Acide folique 4000 mg/kg en premix 1%
Composantes Argile accessoires Aluminosilicate Variation pour Ia maniabilite : Ingredients inertes : 10%
Aromate Remplissage Remplissage avec du mais moulu. 76% 90%
TOTAL 100% 100%
100%
Notes I. Formulation avant substitution : 14% d'activite poids/poids de polyphenols de deux sources, reglisse (12,5%) et cannelle (1,5%).
2. Formulation A: 14% d'activite poids/poids de polyphenols de 4 sources de polyphenols, rdglisse (4,5%), huile de th6(4,0%), menthe (2,5%) et cannelle (3,0%).
3. Les coumarines sont des acides phenoliques anticoagulantes.
4. Le tanin est un polyphdnol astringent 2.3.0) PROTOCOLE EXPERIMENTAL : La preparation du melange ses effectues en plusieurs etapes. L'etape 1 est la preparation d'un petit echantillon qui servait a evaluer les caracteristiques de base des ingredients. (Couleur, odeur, fluidite, densite, palatabilite).
L'etape 2 etait de verifier comment les ingredients pouvaient se manipuler en production laboratoire.
L'etape 3 etait la production d'echantillon test pour obtenir un seuil d'acceptabilite d'appetence pour les animaux.
Cet etape pouvait necessite plusieurs voyages aller retour entre la ferme et la cuisine laboratoire.
Lorsque le seuil d'acceptabilite etait atteint, un plus gros echantillon etait produit pour faire les tests d'experimentation sur les animaux. Les formules sont au tableau 2.

PROJET CHEZ LE PORC et LES STRESS NORMAUX:
LE PROJET: Le projet a trois phases, une phase 1 qui consiste a substituer des molecules actives anti-inflammatoires de la reglisse de chine (isoflavones, liquiritine, isoliquirie et formoneitine, ortho acetyle salicylate de sodium) par d'autres sources en provenance de 1'huile de the des bois, menthe poivre et cannelle (methyle salicylate, tannin, menthol, acide phenolique, aldehyde de cannelle). Et une deuxieme phase qui consiste a experimenter le melange sur des

-13-pores en engraissement en conditions normale. La troisieme phase consiste a ajuste les ingredients accessoires inertes afin d'ameliorer sa maniabilite.
= La formulation est un additif alimentaire utilise a un ratio 1/1000 dans 1'aliment complet.
= La formulation a comme but d'essayer de demontrer l'effet inflammatoire peut-elle etre benefique chez des pores non challenges.
= L'efficacite de la formulation est evaluee par la presence de proteine inflammatoire dans le sang, et des resultats de performances zootechniques sur la mortalite et 1'efficacite alimentaire.

HYPOTHESE:
= Un additif alimentaire contenant suffisamment d'acides polyphenoliques anti-inflammatoire ainsi que du tripicolinate de chrome, aide a controler la reaction inflammatoire peut-il avoir un effet positif sur les parametres zootechniques.
= Il est possible de substituer des sources et molecules differentes en autant que les substituant ont les memes proprietes biologiques.
= Un animal expose a des ingredients differents, mais a de meme fonction devrait repondre de la meme maniere.
= Si les molecules anti-inflammatoires de la reglisse sont efficaces et que nous les substituons par d'autres rnolecules de meme nature, nous devrions avoir la meme reponse biologique.

Les ingredients a substitue sont : La reglisse Les ingredients substituant sont : Huiles de the des bois, menthe poivre et cannelle.

La principale raison de substitution est: La reglisse a forte concentration cree un melange qui fait des precipites.

MATERIELS ET METHODES

Dosages de 1'additif en fonction du sexe Animals EVP-COMBI
Truies 2 kg / tm Verrats 1 k / tm Porcelets 2 kg / tm

-14-Parametres d'evaluation de la reponse experimentale Parametres de mesure Su lement pol henoli ue Biochimie a. Haptoglobine (oxidation cellulaire) Oui b. CPK: (degenerescence musculaire) Oui c. Lactate: duree du stress) Oui Zootechnique :
a. Gain quotidien : Non b. Consommation alimentaire : Oui c. Consommation d'eau : Oui d. Fertilite : Oui Intervalle sevrage-saillie Oui Taux de reussite des inseminations Oui Taux de gestations (et de retours en chaleur) Oui Viabilite des porcelets au sevrage Oui e. Mortalite Oui Comportement :
a. Niveau d'agitation Oui b. Niveau d'a ressivite Oui Presence de maladie a. Types PRRS (porc) b. Incidences Oui c. Duree Oui RESULTATS

Tableau 5 Nombres d'animaux en Pouponniere Ferme :
Total Testes Contr6le Tableau 6 Nombre d'animaux en Engraissement Ferme Total Testes Contr6le

-15-RESULTATS ZOOTECHNIOUES

Tableau 7 Gain en pouponniere sur de porcelet EVPP Contrale-Placebo Poids d'entree 5,55 kg 5,56 kg Poids de sortie 29,25 kg 24,21 kg Nbrs de 'ours 54 54 Gain / 'our 438 345 % de mortalft 4,98% 9,62%
Tableau 8 Gain en engraissement EVPP Controle-Placebo Poids d'entr6e 21,67 kg 21,88 kg Poids de sortie 108,90 kg 107,12 kg Nbrs de 'ours 92 94 Index 110,04 109,80 % de mortalite 4,59% 11,90%
Gain/jour 948 907 3.0) CONCLUSION ET COMMENTAIRES : Nos resultats confirment nos hypotheses sur l'importance du contr6le de I'inflammation chez le porc avec nos melanges antioxydants, polyphenols et vitamines.
Comme il apparalt que le porc est en inflammation chronique, celle-ci serait 1'element declencheur de plusieurs problemes de resistance aux maladies. Puisque nos resultats d6montrent un taux de proteine inflammatoire plus bas. Nos nouveaux melanges (formulations) di~montrent un effet aussi nouveau innatendu.

-16-EXEMPLE II

EFFET DES POLYPHENOLS ISSU DES HUILES DE THE DES BOIS, MENTHE
POIVRE ET DE CANNELLE COMME ADDITIF DE CONTRO^LE DES STRESS CHEZ
LE VEAU DE GRAIN

Abstract : Le stress est un probleme de production extremement grave. Le stress semble le principal element responsable de la majorite des pertes de production. Le stress est une reaction naturelle de l'organisme. Le stress est un mecanisme inflammatoire qui inhibe la production toutes les autres fonctions du corps pour permettre dans un premier temps de produire du sucre et ainsi etre en mesure de repondre aux attaques externes. (The mechanisms of body function 1984).
Les quatre dernieres annees ont favorise des nouvelles approches de production animale et 1'ajout de nouvelles alternatives qui permettent de reduire les problemes du stress.
(Bristol University UK, animal welfare guide 2005). L'alimentation est aussi un moyen de reduire les stress ou du moins a aide de les controler. L,'acquisition de connaissance sur les plantes aux proprietes anti-inflammatoires nous semble une voie interessante pour favoriser un meilleur equilibre metabolique. L'objectif de cet ouvrage etait de demontrer si il est possible par I'alimentation d'augmenter la tolerance ou resistance aux differents stress d'elevage chez le veau.

MATERIELS ET METHODES
INTRANTS : Comme a l'exemple 1 FORMULATIONS : Comme a 1'exemple 1 EVP(B) = supplement anti-inflarnmatoire vegetal bOVIN (porc) PROTOCOLE EXPERIMENTAL
Comme a 1'exemple 1.

Tableau 1 Concentrations EVP-COMBI
Veaux lait 2 / jour Veaux Grairi 1 / our

-17-PARAMETRES : Comme 6 I'exemple 1 sauf biochimie du sang 3.0) RESULTATS

3.1) ECHANTILLONNAGE

Tableau 2 Echantillonnage d'animaux utilise en fonction de la pouponniere Ferme Total Testes Contr8le Les fermes sur lequel nous avons fait 1'experimentation avaient une rotation de 2 pour les deux groupes testes. Chaque test a ete repete 12 fois dans 1'annee.

RESULTATS ZOOTECHNIQUES

Tableau 3 Gain en engraissement : 2 grammes par veaux par jour EVPB Controle-Placebo Poids d'entree 130,66 kg 131,18 kg Poids de sortie 349,7 kg 344,9 kg Nbrs de 'ours 145 145 Conversion 3,20 3,62 % de mortaiite 5,52% 10,55%
Gain quotidien 1.51 kg 1,47 kg Tableau 4 Gain en engraissement : 2 grammes par veaux par jour EVPB Controle-Placebo Poids d'entree 130,66 kg 131,18 kg Poids de sortie 349,7 kg 344,9 kg Nbrs de jours 145 145 Conversion 3,20 3,62 % de mortalite 5,52% 10,55%
Gain quotidien 1.51 kg 1,47 kg

-18-CONCLUSION ET COMMENTAIRES : Les resultats zootechniques demontrent que les veaux repondent de maniere similaire aux pores aux differents formulations polyphenols anti-inflammatoires. La conversion alimentaire semble beaucoup ameliorer. Nous pensons que cette amelioration est liee au principe de controle du stress en limitant la surproduction d'hormone lie au stress. Ainsi un animal ayant requ le melange polyphenols aurait un systeme digestif en mode optimum sur la digestion. Cependant nous devons faire des etudes afin de demontrer cet aspect.
Nous avons dtudie le lactate et le CPK pour demontrer que les taux de ses parametres sanguins sont plus faibles chez les animaux ayant re~u le melange polyphenols.

EXEMPLE III
Effet des polyphenols issu des huiles de the des bois, menthe poivre et cannelle de chine comme additif de controle des stress de la vache en relation avec le compte des cellules somatiques et la qualite de lait.

Abstract : La production laitiere moderne fait face a des problemes emergents tels que l'inflammation chronique des glandes mammaires. L'acquisition de connaissance sur les plantes aux proprietes anti-inflammatoires nous semble une voie interessante pour favoriser une meilleure sante des glandes. Le phenomene qu'engendre l'inflammation des glandes mammaire est une sur production des globules blancs. L'aliment.ation de polyphdnols aux proprietes anti-inflammatoire nous semble une voie a la reduction de compte somatique.
L'objectif de cet ouvrage etait de demontrer si il est possible par l'utilisation de polyphenols anti-inflammatoire de controler l'inflammation et de reduire le compte somatique.

LE PROJET: Le projet a deux phases, une phase 1 qui consiste a a substituer des molecules actives anti-inflammatoires de la reglisse de chine (isoflavones, liquiritine, isoliquirie et formoneitine, ortho acdtyle salicylate de sodium) par d'autres sources en provenance de I'huile de the des bois, menthe poivre et cannelle (methyle salicylate, tannin, menthol, acide phenolique, aldehyde de cannelle). Et une deuxieme phase qui consiste a experimenter le melange sur des vaches en conditions commerciale typique.

HYPOTHESE
La formulation anti-inflammatoire peut-elle fonctionne sur les probleme chronique de l'inflammation de la glande mammaire.

MATERIELS ET METHODES
INTRANTS : Comme a 1'exemple 1.
FORMULATIONS: Comme a 1'exemple 1.

-19-PROTOCOLE

LES DOSAGES:
Tableau 1 Dosages EVPB
~ VACHE 5 a 60 grammes jour.

Tableau 2 EVPB PROGRAMME DU DOSAGE

Semaine 1 2 3 4 5 6 Quantite journaliere en 60g 40g 30g 20g 20g 5g grammes PARAMETRES:

Parametres de mesure Su lement ol hLsnoli ue : EVPB
COMPTE SOMATIQUE I
PRODUCTION DE LAIT
PROTEINE DU LAIT
GRAS DU LAIT

-20-RESULTATS

Tableau 4 Evolution de la productivite des vaches recevant 5 grammes par jour de melange anti-inflammatoire.
Pourcentage de vache par groupe de production Production faible 28,32% 24,98% 30,67% 30,11% 25,65%

(501b et moins) Production 69,26% 70,84% 66,84 % 66,84% 73,24%
moyenne a forte (51 a 101 + Ib) Nombre de 537 549 538 558 538 vache

-21-Tableau 5 Amelioration de la pualite du lait (SCC) produits par des vaches recevant 5 grammes par iour de melange anti-inflammatoire Pourcentage de vache par groupe de compta somatique cellulaire Compte SCC moins de 200,000 70,10% 69,02% 68,21% 68,63% 75,48%
(Producteur reVoit une prime de qualite.) Compte SCC plus de 200,000 27,57% 26,90% 28,82 % 28,32% 23,41%
Nombre de vache 537 549 538 558 538 CONCLUSION

Les resultats demontrent les effets benefiques de nos nouvelles formulations sur les comptes cellulaires (SCC) dans le lait chez la vache. L'administration orale de nos formulations demontre une reduction significative des SCC dans les echantillons de lait dans le pis, ce qui reflete donc une amelioration du statut immunitaire de 1'animal et de la reduction de 1'inflammation de la glande mammaire et des infections de celle-ci.

While the invention has been described in connection with specific embodiments thereof, it will be understood that it is capable of further modifications and this application is intended to cover any variations, uses, or adaptations of the invention following, in general, the principles of the invention and including such departures from the present disclosure as come within known or customary practice within the art to which the invention pertains and as may be applied to the essential features hereinbefore set forth, and as follows in the scope of the appended claims.

-22-

Claims (28)

I CLAIM:

1. A food supplement composition comprising at least one polyphenol compound, at least one antioxidant compound, and at least one vitamin.

2. The food supplement composition of claim 1, wherein said polyphenol compound is obtained from a plant extract.

3. The food supplement composition of claim 1, wherein said polyphenol compound is a polyphenolic acid.

4. The food supplement composition of claim 1, wherein said plant extract antioxidant is

5. The food supplement composition of claim 1, wherein said vitamin is an antioxidant vitamin.

6. The food supplement composition of claim 1, wherein said vitamin is vitamin D.

7. The food supplement composition of claim 1, wherein said said polyphenol is in proportion of 0.1% (w/v or w/w) to 25% (w/v or w/w), said anti-oxidant compound in proportion of 0.1% (w/v or w/w) to 20% (w/v or w/w), and said vitamin in proportion of 0.1%(w/v or w/w) to 30% (w/v or w/w).

8. A food supplement composition as claimed in any one of claims 1 to 7 which provides a concentration of methyl salicylate or an analog thereof at a level from 0.01 mg to 100 mg per kilogram body weight per day or above.

9. A food supplement composition as claimed in any one of claims 1 to 8, comprising a probiotic microorganism.

10. The food supplement composition of claim 9, wherein said probiotic microorganism is a yeast, a bacteria, or a combination thereof.

11. The food supplement composition of claim 8 or 9, wherein said probiotic microorganism is living or dead.

12. A food supplement as claimed in anyone of claims 1 to 11, wherein a portion of the anti-oxidant is provided by a natural source and a portion of the anti-oxidant is provided by a synthetic source.

13. A food supplement for reducing systemic inflammation, localised inflammation, body temperature, or cellular oxidation, comprising a food supplement composition as described in anyone of claims 1 to 12.

14. A method for reducing body temperature, systemic inflammation, localised inflammation, or cellular oxidation, said method comprising the step of administering orally to said animal or a human a composition as described in anyone of claims 1 to 13.

15. A method for improving fertility of an animal or a human comprising giving orally to said animal or human the food composition of anyone of claims 1 to 13.

16. A method for increasing the growth rate of an animal or a human comprising giving orally to said animal or a human the food composition of anyone of claims 1 to 13.

17. A method for calming an animal or a human comprising giving orally to said animal or human the food composition of anyone of claims 1 to 13.

18. A method for reducing body shrink of an animal or a human during a stress period comprising giving orally to said animal or human the food composition of anyone of claims 1 to 13 at least before, during, or after said stress period.

19. A method for increasing the number of eggs per bird comprising giving orally to said bird the food composition of anyone of claims 1 to 13.

20. A method for reducing diarrhea of an animal or a human comprising giving orally to said animal or human the food composition of anyone of claims 1 to 13.

21. A method for increasing wounding comprising giving orally to said animal or human the food composition of anyone of claims 1 to 13.

22. A food composition for improving fertility of an animal or a human comprising the food composition of anyone of claims 1 to 13.

23. A food composition for increasing the growth rate of an animal or a human comprising the food composition of anyone of claims 1 to 13.

24. A food composition for calming an animal or a human comprising the food composition of anyone of claims 1 to 13.

25. A food composition for reducing body shrink of an animal or a human during a stress period comprising the food composition of anyone of claims 1 to 13.

26. A food composition for increasing the number of eggs per bird comprising the food composition of anyone of claims 1 to 13.

27. A food composition for reducing diarrhea of an animal or a human comprising the food composition of anyone of claims 1 to 13.

28. A food composition for increasing wounding comprising the food composition of anyone of claims 1 to 13.