NL2019738B1

NL2019738B1 - Composition for use as mycotoxin binder in animals

Info

Publication number: NL2019738B1
Application number: NL2019738A
Authority: NL
Inventors: Segers Ludo; Ketels Eddy
Original assignee: Orffa Additives B V
Priority date: 2017-10-16
Filing date: 2017-10-16
Publication date: 2019-04-23
Also published as: WO2019076820A1

Abstract

The current invention concerns a composition for binding and inactivation of mycotoxins, comprising a yeast component and one or more mineral clays, characterized in that said composition further comprises betaine or a betaine derivative.

Description

COMPOSITION FOR USE AS MYCOTOXIN BINDER IN ANIMALS

TECHNICAL FIELD

The invention is directed to compositions and their use as feed additives to reduce mycotoxin contamination, preferably in animal feed.

BACKGROUND

Mycotoxins are metabolites produced by fungi that are toxic to humans and/or animals. These fungi occur on natural materials such as grains and plants, where the mycotoxins are then formed. These mycotoxins are fairly resistant to all kinds of treatments and are, in addition, difficult to detect. As a result, fungi infested plant material acts as carrier for mycotoxins, allowing them to enter the animal food chain through the feed produced thereof, where they can cause discomfort and disease. The physical effects of mycotoxins differ from reduced food intake and poor food conversion to animal disease. The observed symptoms may also vary from animal to animal. Acute mycotoxicosis is often recognizable, but chronic mycotoxicosis takes its toll as it has an impact on animal performance and a reduction in immunity with all the known economic consequences. Liver damage and deterioration is one of the main characteristics of both acute and chronic mycotoxicosis, further compromising the animals' health.

Known state of the art solutions include the addition of (myco)toxin binders to the feed, in order to inactivate the mycotoxins before being taken in by the animal, or in the animal itself. EP 1 079 696 for instance discloses a composition comprising a clay mineral and a yeast component capable of binding mycotoxins into the feed. However, once the animal has ingested the toxins, there is also a need for a composition which helps to restrain the damage caused by the toxins, limiting their toxicity, thus assisting the animal to cope with the infection. WO 2 014 014 334 A1 describes a food supplement for animals comprising a clay mineral, a yeast component and trace minerals. This food supplement, however, does not deal with the issues of mycotoxicity.

The invention aims to provide a composition that is, on the one hand, functional as a toxin binder in feed while, on the other hand, protecting liver function in the animal, thereby having a double positive influence on the well-being of the animal and its performance.

SUMMARY OF THE INVENTION

The present invention provides a composition as stated in claim 1 for binding and inactivation of mycotoxins in animals, while protecting liver function. More specifically, the composition comprises (myco)toxin binders combined with betaine, thereby having a double positive influence on the well-being of the animal and its performance.

The current invention thereto aims to provide a composition comprising one or more mineral clays and a yeast component as (myco)toxin binders, acting both in the feed and in the animal. Betaine or a betaine derivative is included in the composition, which is functional in the animal as a liver detoxifying agent due to its involvement in methylation reactions and detoxification of homocysteine.

In a second and third aspect, the present invention provides an animal feed comprising a composition as stated in claim 14 and a method as stated in claim 19.

The current invention thereto aims to provide an animal feed comprising the composition as stated above in combination with a preservative, and a method of providing this feed to animals.

DESCRIPTION OF FIGURES

Figure 1 illustrates the mycotoxin binding capacity of betaine hydrochloride in the gastric environment. The additive is added at 0.5% and comprises 0% or 3.5% betaine hydrochloride (betaine HCL). Mycotoxin binding is expressed relative to the negative controls.

Figure 2 illustrates the mycotoxin binding capacity of a feed additive in the gastrointestinal track environment. The additive is added at 0.5% and comprises 0% or 3.5% betaine hydrochloride (HCI). Mycotoxin binding is expressed relative to the negative controls.

Figure 3 illustrates the positive effect of a feed supplement containing betaine hydrochloride (HCI) on the health of pigs based on the daily measurement of the feed conversion ratio (FCR). The FCR was calculated for each experimental group as the proportion of the feed intake (g) to the daily weight gain (g).

DETAILED DESCRIPTION OF THE INVENTION

The present invention concerns a composition to prevent the harmful effects of ingested mycotoxins present in animal feed.

Unless otherwise defined, all terms used in disclosing the invention, including technical and scientific terms, have the meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. By means of further guidance, term definitions are included to better appreciate the teaching of the present invention.

As used herein, the following terms have the following meanings: "A", "an", and "the" as used herein refers to both singular and plural referents unless the context clearly dictates otherwise. By way of example, "a compartment" refers to one or more than one compartment. "About" as used herein referring to a measurable value such as a parameter, an amount, a temporal duration, and the like, is meant to encompass variations of +/-20% or less, preferably +/-10% or less, more preferably +/-5% or less, even more preferably +/-1% or less, and still more preferably +/-0.1% or less of and from the specified value, in so far such variations are appropriate to perform in the disclosed invention. However, it is to be understood that the value to which the modifier "about" refers is itself also specifically disclosed. "Comprise," "comprising," and "comprises" and "comprised of" as used herein are synonymous with "include", "including", "includes" or "contain", "containing", "contains" and are inclusive or open-ended terms that specifies the presence of what follows e.g. component and do not exclude or preclude the presence of additional, non-recited components, features, element, members, steps, known in the art or disclosed therein.

The recitation of numerical ranges by endpoints includes all numbers and fractions subsumed within that range, as well as the recited endpoints.

The expression "% by weight" (weight percent), here and throughout the description unless otherwise defined, refers to the relative weight of the respective component based on the overall weight of the formulation.

For the purpose of the current invention, the term betaine is to be understood as referring to trimethylglycine. Trimethylglycine is an N-trimethylated amino acid. Betaine derivatives are to be understood as the products originated by conversion of betaine by strong acids to various salts. A betaine derivative can therefore be, but is not limited to, betaine hydrochloride which is yielded by conversion of betaine by hydrochloric acid.

The present invention provides a composition that can be used to reduce the negative effects of mycotoxins to the animals' health by, on the one hand, inactivating mycotoxins present in feed or in the animal itself and, on the other hand, by supporting the detoxification function of the liver in the animal.

In a first aspect, the invention provides a composition for binding and subsequent inactivation of mycotoxins while protecting liver function, comprising a yeast component, one or more mineral clays, characterized in that said composition further comprises betaine or a betaine derivative. Mineral clays are known as (myco)toxin binders, both in the feed as in the animal itself. The absorption of the toxins by the mineral clays prevents their uptake into the animals' blood stream. The combination of mineral clays with yeast cell wall extracts in animal feeds is known to further increase the mycotoxin binding effect. Binding of mycotoxins directly interferes with their toxicity mechanism.

The yeast component in the composition is preferably present in a concentration from 5% to 10% by weight and consists specifically of a yeast cell wall extract. In particular the cell wall is extracted from a yeast selected from the group of Saccharomyces, Candida, Kluyveromyces, Torulaspora or a combination thereof. More in particular, the yeast cell wall is extracted from a Saccharomyces cerevisiae yeast. More in particular, the yeast cell wall is hydrolysed prior to extraction and is, more specifically, composed of mannan-oligosaccharides.

The clay minerals in the composition are preferably present in a concentration from 40% to 80% by weight. In particular, one or more mineral clays are selected from the group consisting of zeolites, bentonites, aluminosilicates, magnesium aluminum silicates or mixtures thereof. In a preferred embodiment of the invention the mineral clay consists of a clinoptilolite.

The composition also aims at supporting the animals' endogenous defense mechanisms once mycotoxins have been ingested. After mycotoxin ingestion, the liver is burdened with the inactivation and degradation of the mycotoxins. Accordingly, liver damage and deterioration is one of the main characteristics of both acute and chronic mycotoxicosis.

The composition thereto comprises betaine or a betaine derivative, which is involved in methylation reactions and in the detoxification of homocysteine. Betaine and betaine derivatives are used in this invention as detoxifying agents, supporting the detoxification functions of the liver, eventually contributing to the improvement of the animals' health.

Betaine is used in the liver as a methyl group donor. The liver is the major organ within which methylation reactions occur. Dietary intake of methyl donors like betaine could influence the methylation of DNA and histones, thereby altering the epigenetic regulation of gene expression. Many of the hepatic genes involved in pathways for the development of fatty liver, hepatic fibrosis, and hepatocarcinomas are epigenetically regulated. In addition, methylation reactions are also important for several metabolic processes such as the synthesis of creatine and carnitine.

Betaine or a betaine derivative is preferably present in the composition in a concentration from 0.001% to 5% by weight of the composition. In a particularly preferred embodiment of the invention, the betaine derivative included in the composition is betaine hydrochloride.

The inventors of the present invention have found that a composition as described above is exceptionally suited to counteract the harmful effects of a broad range of toxins. The binding and inactivation of in particular Ochra toxin, zearalenones, deoxynivalenol (DON), fumonisins, aflatoxins, HT-2 toxins, T-2 toxins or enniatins contributes to the protection of the animals' health.

In a preferred embodiment, the composition described in the present invention or a feed supplement comprising the composition described in the present invention comprises a preservative composed of a calcium, sodium or ammonium salt of propionate. This preservative prevents bacterial and fungal growth in the composition or in the animal feed or drinking water upon addition of the composition. More in particular, the preservative is present in a concentration from between 5% to 10% by weight of the composition.

In a second aspect, the composition of the present invention as described above has a remarkable positive effect on the animal when taken in and is thus well suited as a feed supplement or as addition to the animals' feed. Addition of the composition to feed directly or as (part of) a feed supplement therefore results in healthier animals. In one embodiment, the composition or supplement is a powder. In a different embodiment, the composition or supplement is a liquid. In yet another embodiment, the composition or additive is added to the animals' drinking water. In a preferred embodiment of the invention, the effective amount of the composition comprises from 0.5% to 1% by weight of the feed.

In particular the composition according to the present invention is suited for administration to animals selected from the group consisting of avian, bovine, porcine, equine, ovine, and caprine species

In a third aspect, the present invention also describes a method of feeding animals with a feed supplemented with a feed supplement according to the present invention, wherein the animal obtains the feed additive in a content of between 5 g/kg and 10 g/kg bodyweight/ day. In a specific embodiment of the invention, the composition is admixed with the animal feed prior to feeding. In an alternative embodiment, the composition is admixed with the animal's drinking water before it is provided to the animal.

The present invention may be described by the following embodiments: 1. A composition for binding and inactivation of mycotoxins, comprising a yeast component and one or more mineral clays, characterized in that said composition further comprises betaine or a betaine derivative. 2. The composition of embodiment 1, wherein the yeast component comprises a yeast cell wall extract. 3. The composition of any of the embodiments 1 to 2, wherein the yeast component comprises a yeast cell wall extract from a yeast selected from the group consisting of Saccharomyces, Candida, Kluyveromyces, Torulaspora or a combination thereof. 4. The composition of any of the embodiments 1 to 3, wherein the yeast component comprises a yeast cell wall extract from a Saccharomyces cerevisiae yeast. 5. The composition of any of the embodiments 1 to 4, wherein the yeast component comprises a yeast cell wall extract composed of mannan-oligosaccharides. 6. The composition of embodiment 1, wherein said one or more mineral clays are selected from the group consisting of zeolites, bentonites, aluminosilicates, magnesium aluminum silicates or mixtures thereof. 7. The composition of any of embodiments 1 to 6, wherein said mineral clay is clinoptilolite. 8. The composition of embodiment 1, wherein said betaine derivative is betaine hydrochloride. 9. The composition of embodiment 1, wherein said composition has a total concentration of mineral clay of between 40% and 80% by weight of the composition. 10. The composition of embodiment 1, wherein said composition comprises between 5% and 10% yeast component by weight of the composition. 11. The composition of embodiment 1, wherein said composition comprises between 0.001% to 5% betaine or betaine derivative by weight of the composition. 12. A composition for use as toxin binder in animals and animal feed, said composition is a composition according to any of the embodiments 1 to 11. 13. The composition of embodiment 12, wherein said toxin is selected from the group consisting of Ochra toxin, zearalenones, deoxynivalenol (DON), fumonisins, aflatoxins, HT-2 toxins, T-2 toxins and enniatins. 14. An animal feed comprising a composition according to any of the embodiments 1 to 11. 15. The animal feed of embodiment 14, wherein the effective amount of the composition comprises from 0.5% to 1% by weight of the feed. 16. The animal feed of embodiment 14, wherein the animal is selected from the group consisting of avian, bovine, porcine, equine, ovine, and caprine species. 17. The animal feed of any of embodiments 14 or 16, wherein said composition comprises a preservative that is composed of a calcium, sodium or ammonium salt of propionate. 18. A method for feeding animals, where the animals consume a feed comprising a composition as stated in any of embodiments 1 to 11 or an animal feed as stated in any of embodiments 14 to 18, wherein the effective amount of the composition comprises from 5g/kg to 10g/kg bodyweight/day. 19. The method of embodiment 19, wherein the composition is admixed with the animal feed prior to feeding.

The invention is further described by the following non-limiting examples which further illustrate the invention, and are not intended to, nor should they be interpreted to, limit the scope of the invention.

The present invention will be now described in more details, referring to examples that are not limitative.

It is supposed that the present invention is not restricted to any form of realization described previously and that some modifications can be added to the presented example of fabrication without reappraisal of the appended claims.

EXAMPLES

Example 1: (simulation of the gastric environment)

The following experiment demonstrates betaine hydrochloride does not have mycotoxin binding activity in the gastric environment.

Sample combinations were prepared in citrate buffer pH 3 (cf. gastric pH). After a 1 hour incubation at 37°C while shaking, the mycotoxins were extracted according to a solvent-switch method and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Internal standards were therefore included in each sample. Mycotoxin binding is expressed relative to the negative controls in % and is shown in Figure 1.

Sample combinations consisted of: negative control 1: mycotoxin standard mixture containing deoxynivalenol, zearalenone, Aflatoxin BI, Aflatoxin B2, Aflatoxin Gl, Aflatoxin G2, Ochratoxin A, HT-2 toxin, T-2 toxin, Enniatin B, Fumonisin BI and Fumonisin B2. negative control 2: 0.5% feed additive (Table 1) mycotoxin inhibitor: 0.5% feed additive (Table 1) + mycotoxin standard mixture containing deoxynivalenol, zearalenone, Aflatoxin BI, Aflatoxin B2, Aflatoxin Gl, Aflatoxin G2, Ochratoxin A, HT-2 toxin, T-2 toxin, Enniatin B, Fumonisin BI and Fumonisin B2.

Table 1: Feed additive composition

Without betaine HCI With betaine HCI

Component (%) (%)

Betaine hydrochloride 0 3.5

Mineral clays 80 76.5

Yeast component 10 10

Preservative 10 10

Addition of a feed additive comprising betaine hydrochloride (HCI) to the feed did not lead to increased mycotoxin binding in the gastric environment when compared to a feed additive without betaine HCI.

Example 2: (simulation of the gastro-intestinal track)

The following experiment demonstrates betaine hydrochloride does not have mycotoxin binding activity in the gastro-intestinal track environment.

Sample combinations were first prepared in citrate buffer pH 3 (cf. gastro-intestinal pH-range). After a 1 hour incubation at 37°C while shaking, the pH was brought to pH 7. Following a subsequent incubation of 3 hours at 37 °C while shaking, the mycotoxins were extracted according to a solvent-switch method and analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Internal standards were therefore included in each sample. Mycotoxin binding is expressed relative to the negative controls in % and is shown in Figure 2.

Addition of a feed additive comprising betaine hydrochloride (HCI) to the feed did not lead to increased mycotoxin binding in the gastro-intestinal track environment when compared to a feed additive without betaine HCI.

Example 3: Study of the clinical effect of mycotoxins in pigs 50 pigs of either sex with average initial weight of 8.2 kg and average age 29 days were selected for the study. The animals were divided in 12 experimental groups. Half of the groups were fed with a feed that was contaminated with mycotoxins while the other half was fed with mycotoxin-free feed. Additionally, the feed of each group further differed in the presence or absence of a 0.5% feed supplement comprising 0%, 2.5% or 5% betaine hydrochloride (HCI). The feed supplement (see Table 2 for feed supplement composition) was admixed with the animal feed prior to feeding. The feed was administered 4 times per day and water was available ad libitum. The feed intake and weight gain was measured daily for 30 days. The Feed Conversion Rate (FCR) was calculated for each experimental group as the proportion of the feed intake (g) to the daily weight gain (g) and is used as a measure for pig health: the lower the FCR, the healthier the pigs.

Table 2: Feed supplement compositions used in example 3.

The results of the study are shown in Figure 3. A surprising effect was found when pigs were fed with mycotoxin contaminated feed that was provided with the feed supplement comprising betaine HCI. The FCR of pigs fed with the feed according to the current invention was much lower, indicating these pigs were much healthier due to the liver supporting function of betaine HCI. Notably, the positive effect on pig's health was larger than what could have been expected of the combination of feed supplement and betaine HCI based on the results of the feed supplement alone (0.5% supplement and 0% betaine HCI) or the betaine HCI alone (0% supplement and 0.0125% or 0.025% betaine HCI).

Claims

Composition for binding and inactivating mycotoxins comprising a yeast component and one or more clay minerals, characterized in that the composition further comprises betaine or a betaine derivative.

The composition of claim 1, wherein the yeast component comprises a yeast cell wall extract.

The composition of any one of claims 1 to 2, wherein the yeast component comprises a yeast cell wall extract derived from a yeast selected from the group of Saccharomyces, Candida, Kluyveromyces, Torulaspora or a combination thereof.

The composition of any one of claims 1 to 3, wherein the yeast component comprises a yeast cell wall extract derived from Saccharomyces cerevisiae.

The composition of any one of claims 1 to 4, wherein the yeast component comprises a yeast cell wall extract consisting of mannan oligosaccharides.

The composition of claim 1, wherein said one or more clay minerals is selected from the group of zeolites, bentonites, aluminosilicates, magnesium aluminum silicates or a mixture thereof.

The composition of any one of claims 1 to 6, wherein said clay mineral is a clinoptilolite.

The composition of claim 1, wherein betaine hydrochloride is the derivative of betaine.

The composition of claim 1, wherein said clay minerals are present in a weight content between 40% and 80% of the total weight of the composition.

The composition of claim 1, wherein said yeast component is present in a weight content between 5% and 10% on the total weight of the composition.

The composition of claim 1, wherein the betaine or betaine derivative is present in a weight content between 0.001% and 5% on the total weight of the composition.

A composition for use as a mycotoxin binder in animals and in feed, wherein the composition is a composition according to any of claims 1 to 11.

The composition of claim 12, wherein said mycotoxins are selected from the group of ochratoxin, zearalenones, deoxynivalenol (DON), fumonisins, aflatoxins, HT-2 toxins, T-2 toxins, and enniantines.

A feed comprising a composition according to any one of claims 1 to 11.

The feed according to claim 14, wherein the composition is present in the feed at a level between 0.5% and 1% of the total weight of the feed.

The feed according to claim 14, wherein the feed is suitable for feeding birds, cattle, pigs, horses, sheep and goats.

The feed according to any of claims 14 to 17, wherein the composition is provided with a preservative consisting of the calcium, sodium and / or ammonium salt of propanoic acid.

A method for feeding animals, wherein the animals are fed with a feed provided with a composition according to claims 1 to 11 or a feed according to any one of claims 14 to 18, wherein the animals have the composition at a level between 5 g / kg and 10g / kg body weight / day.

The method of claim 19, wherein the composition is mixed with the feed prior to feeding.