A method for reducing diarrhea of animals

Abstract

The present invention provides a method for reducing diarrhea and / or improving fecal quality of animals, comprising administering to the animal a feed composition comprising a) at least one organic acid and / or at least one salt thereof; and b) hypophosphorous acid and / or at least one salt thereof.

Description

[0001] A method for reducing diarrhea of animals

[0002] Technical Field

[0003] The present invention relates to a method for reducing diarrhea and improving fecal quality of animals.

[0004] Background of the Invention

[0005] Acidifier products including organic acids may be used to maintain food and feed hygiene and prevent spoilage by microorganisms such as bacteria or molds. Organic acids such as benzoic acid, formic acid, propionic acid and acetic acid may be used to control microbial growth in foodstuff, food or feed with the aim to minimize the risk for foodborne diseases. To this end, acidifier products may be added pre- and / or post-production of finished feed. Additionally, acidifier products may be used to improve feed conversion rate and weight gain of animals upon ingestion.

[0006] It has now been found surprisingly that organic acids and / or salts thereof in combination with hypophosphorous acid and / or salts thereof provide additional benefits in animals.

[0007] Summary of the Invention

[0008] The present invention provides a method for reducing diarrhea and / or improving fecal quality of an animal, comprising administering to the animal a feed composition comprising a) at least one organic acid and / or at least one salt thereof; and b) hypophosphorous acid and / or at least one salt thereof.

[0009] Detailed description of the Invention

[0010] Animals: The term “animal” or “animals” refers to any animal except human. Examples of the animals include but are not limited to pigs or swine such as piglets, growing pigs and sows; poultry such as turkeys, ducks, quail, guinea fowl, geese, pigeons (including squabs) and chicken (including but not limited to broilers, chicks and layers); pets such as cats and dogs; horses; crustaceans such as shrimps and prawns; fish such as amberjack, arapaima, barb, bass, bluefish, bocachico, bream, bullhead, cachama, carp, catfish, catla, chanos, char, cichlid, cobia, cod, crappie, dorada, drum, eel, goby, goldfish, gourami, grouper, guapote, halibut, java, labeo, lai, loach, mackerel, milkfish, mojarra, mudfish, mullet, paco, pearlspot, pejerrey, perch, pike, pompano, roach, salmon, sampa, sauger, sea bass, seabream, shiner, sleeper, snakehead, snapper, snook, sole, spinefoot, sturgeon, sunfish, sweetfish, tench, terror, tilapia, trout, tuna, turbot, vendace, walleye and whitefish. Preferably, the animal is selected from the group consisting of pigs or swine (including but not limited to piglets, growing pigs and sows); poultry such as turkeys, ducks, quail, guinea fowl, geese, pigeons (including squabs) and chicken (including but not limited to broilers, chicks, layers); and pets such as cats and dogs.

[0011] Animal Feed: the term “animal feed” refers to any compound, preparation, or mixture suitable for or intended for intake by an animal and capable of maintaining life and / or promoting production of the animal without any additional substance being consumed except water.

[0012] Animal Feed Additive: the term “Animal feed additive” refers to an ingredient or combination of ingredients added to the animal feed, usually used in micro quantities and requires careful handling and mixing. Such ingredient includes but is not limited to vitamins, amino acids, minerals, enzymes, eubiotics, colouring agents, growth improving additives and aroma compounds / flavourings, polyunsaturated fatty acids (PUFAs); reactive oxygen generating species, antioxidants, antimicrobial peptides, anti-fungal polypeptides and mycotoxin management compounds etc.

[0013] Surprisingly it has been discovered that a feed composition comprising a) at least one organic acid and / or at least one salt thereof and b) hypophosphorous acid and / or at least one salt thereof provides synergistic effect in reducing diarrhea and / or improving fecal quality of animals.

[0014] Accordingly, the present invention provides a feed composition comprising a) at least one organic acid and / or at least one salt thereof and b) hypophosphorous acid and / or at least one salt thereof for reducing diarrhea and / or improving fecal quality of an animal.

[0015] The present invention also provides a method for reducing diarrhea and / or improving fecal quality of an animal, comprising administering to the animal a feed composition comprising a) at least one organic acid and / or at least one salt thereof; and b) hypophosphorous acid and / or at least one salt thereof.

[0016] The present invention further provides use of a feed composition comprising a) at least one organic acid and / or at least one salt thereof; and b) hypophosphorous acid and / or at least one salt thereof in the preparation of an animal feed additive or an animal feed for reducing diarrhea and / or improving fecal quality of an animal.

[0017] In the present invention, the diarrhea and fecal quality of an animal may be characterized or represented by fecal score as determined by the method as disclosed in Estefania et al., 2019. Biosystems Engineering 184: 122-129. (0 = Normal feces; 1 = Soft feces; 2 = Mild diarrhea; 3 = Severe diarrhea).

[0018] In the present invention, the fecal score is changed in a desired direction by at least 3%, such as by at least 4%, at least 5%, at least 6%, at least 7%, at least 8%, at least 9%, or at least 10%, compared to an animal feed additive wherein the at least one organic acid and / or at least one salt thereof and hypophosphorous acid and / or at least one salt thereof are not included (herein referred to as the control).

[0019] In the present invention, the at least one organic acid may be selected from the group consisting of short monocarboxylic acids having between 1 and 6 carbon atom(s), saturated dicarboxylic acids, unsaturated dicarboxylic acids, unsaturated carboxylic acids, saturated carboxylic acids, hydroxycarboxylic acids, aromatic carboxylic acids, and keto carboxylic acids, and / or at least one salt thereof. Merely for clarification, examples of the short monocarboxylic acids having between 1 and 6 carbon atom(s) include but are not limited to formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, 3-methylbutyric acid, 2-methylbutyric acid, 2-ethylbutyric acid, valeric acid, hexanoic acid. Examples of the saturated dicarboxylic acids include but are not limited to adipic acid and succinic acid. An example of the unsaturated dicarboxylic acid is fumaric acid. Examples of the unsaturated carboxylic acids include but are not limited to sorbic acid and oleic acid. Examples of the saturated carboxylic acids include but are not limited to stearic acid, octanoic acid (also referred to as caprylic acid), decanoic acid (also referred to as capric acid) and dodecanoic acid (also referred to as lauric acid). Examples of the hydroxylcarboxylic acids include but are not limited to lactic acid, malic acid (D- , or L-, or D / L-malic acid), citric acid and tartaric acid. Examples of the aromatic carboxylic acids include but are not limited to benzoic acid and cinnamic acid. An example of keto carboxylic acid is pyruvic acid.

[0020] Preferably, the at least one organic acid may be selected from the group consisting of formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, 3-methylbutyric acid, 2-metylbutyric acid, 2- ethylbutyric acid, valeric acid, hexanoic acid, adipic acid, succinic acid, fumaric acid, sorbic acid, oleic acid, stearic acid, octanoic (caprylic) acid, decanoic (capric) acid, dodecanoic (lauric) acid, lactic acid, malic acid, citric acid, tartaric acid, benzoic acid, cinnamic acid, pyruvic acid, gluconic acid, suberic acid, malonic acid, tannic acid, caffeic acid, ellagic acid, perillic acid and gallic acid, or at least one salt thereof.

[0021] More preferably, the at least one organic acid may be selected from the group consisting of acetic acid, butyric acid, citric acid, formic acid, fumaric acid, lactic acid, octanoic acid, propionic acid, pyruvic acid, benzoic acid, sorbic acid, succinic acid and valeric acid, or at least one salt thereof.

[0022] In the present invention, the at least one salt of the organic acid may be any one of metal salts such as potassium, sodium or calcium salts, and ammonium salts. Examples of the salts of the organic acid include but are not limited to ammonium formate, potassium diformate, sodium diacetate, calcium acetate, ammonium propionate, sodium propionate, calcium propionate, calcium lactate, potassium sorbate, sodium formate, calcium formate, sodium butyrate, sodium sorbate, potassium citrate, sodium citrate, calcium citrate, and benzoates such as sodium benzoate, magnesium benzoate, manganese benzoate, potassium benzoate, aluminium benzoate, calcium benzoate and ferric benzoate.

[0023] Examples of commercial organic acid products are VevoVitall® (DSM Nutritional Products, Switzerland), Biotronic® (DSM Nutritional Products, Austria), Amasil®, Luprisil®, Lupro-Grain®, Lupro-Cid®, Lupro-Mix® (BASF), n-Butyric Acid AF (OXEA) and Adimix Precision (Nutriad).

[0024] In the present invention, the at least one salt of hypophosphorous acid may be selected from the group consisting of sodium hypophosphite, magnesium hypophosphite, manganese hypophosphite, potassium hypophosphite, aluminum hypophosphite, calcium hypophosphite, ammonium hypophosphite and ferric hypophosphite, preferably sodium hypophosphite, magnesium hypophosphite, manganese hypophosphite and potassium hypophosphite, more preferably sodium hypophosphite.

[0025] In the present invention, the feed composition may comprise more than one organic acid and / or the at least one salt thereof and hypophosphorous acid and / or at least one salt thereof. For example, such a feed composition may comprise two, three, four or even more organic acids in combination with hypophosphorous acid and / or at least one salt thereof. In an example, the feed composition comprises at least three organic acids, especially formic acid, acetic acid, propionic acid, and a salt of hypophosphorous acid selected from the group consisting of sodium hypophosphite, manganese hypophosphite, magnesium hypophosphite and potassium hypophosphite, preferably sodium hypophosphite and manganese hypophosphite, more preferably sodium hypophosphite. In another example, the feed composition comprises at least four organic acids, especially formic acid, acetic acid, propionic acid, benzoic acid, and a salt of hypophosphorous acid selected from the group consisting of sodium hypophosphite, manganese hypophosphite, magnesium hypophosphite and potassium hypophosphite, preferably sodium hypophosphite and manganese hypophosphite, more preferably sodium hypophosphite.

[0026] In the present invention, the feed composition may be provided in a particular manner, wherein the molar ratio of the at least one organic acid and / or the at least one salt thereof to hypophosphorous acid and / or the at least one salt thereof is from 100:0.1 to 0.1 :100, preferably from 100:1 to 1 :100, more preferably from 50:1 to 1 :50, even more preferably from 20:1 to 1 :20, and the most preferably from 10:1 to 1 :10.

[0027] Such a feed composition according to the present invention may be provided in a form wherein one or more or all of the components is / are provided in solid form (e.g. salt, powder, granulate, pellet etc.) or in liquid form (e.g. aqueous, gel, viscous). It is also considered that the feed composition may be provided in a manner, wherein one component (e.g. one or more organic acid(s)) is provided in liquid form and a second component is provided in solid form (e.g. hypophosphorous acid), and the composition is formed by combining the two components in a mixture or in a separate form.

[0028] As anticipated by any person skilled in the art, the feed composition according to the present invention may be formulated as an animal feed additive. Accordingly, the feed composition of the present invention may also include micro-ingredients.

[0029] The micro-ingredients include but are not limited to aroma compounds; antimicrobial peptides; polyunsaturated fatty acids (PUFAs); reactive oxygen generating species; at least one enzyme, and fat- and water-soluble vitamins, as well as minerals.

[0030] Examples of antimicrobial peptides (AMP's) are CAP18, leucocin A, protegrin-1 , thanatin, defensin, lactoferrin, lactoferricin, and ovispirin such as novispirin (Robert Lehrer, 2000), plectasins, and statins.

[0031] Examples of polyunsaturated fatty acids are Cis-, C20- and C22- polyunsaturated fatty acids, such as arachidonic acid, docosohexaenoic acid, eicosapentaenoic acid and gamma-linoleic acid.

[0032] Examples of reactive oxygen generating species are chemicals such as perborate, persulphate, or percarbonate; and enzymes such as an oxidase, an oxygenase or a syntethase.

[0033] Examples of enzyme are phytase (EC 3.1.3.8 or 3.1.3.26), galactanase (EC 3.2.1.89), alphagalactosidase (EC 3.2.1.22), phospholipase A 1 (EC 3.1.1.32), phospholipase A2 (EC 3.1.1.4), lysophospholipase (EC 3.1 .1 .5), phospholipase C (EC 3.1 .4.3), and / or phospholipase D (EC 3.1 .4.4).

[0034] Examples of fat-soluble vitamins include but are not limited to vitamin A, vitamin D3, and vitamin K, e.g. vitamin K3.

[0035] Examples of water-soluble vitamins include but are not limited to vitamin B12, biotin and choline, vitamin Bi, vitamin B2, vitamin Be, niacin, folic acid and panthothenate, e.g. Ca-D-panthothenate.

[0036] Examples of minerals include but are not limited to calcium, phosphorus, sodium, potassium, magnesium, chlorine, iodine, iron, manganese, copper, molybdenum, cobalt and zinc. Common mineral supplements in feed include but are not limited to limestone, Bone meal, oyster shell, sodium chloride, dicalcium phosphate, manganese sulphate, potassium iodide, and superphosphate. Sources of minerals include meat scraps, fish meal, milk products, ground limestone (calcium), ground oyster shells (calcium), dicalcium phosphate (calcium, phosphorus), defluorinated rock phosphate (phosphorus, calcium), steamed bone meal (phosphorus, calcium), salt (sodium, chlorine, iodine), manganese sulfate (manganese), manganese oxide (manganese), zinc carbonate (zinc), zinc oxide (zinc). As also anticipated by any person skilled in the art, the feed composition according to the present invention may further be formulated as an animal feed. Accordingly, the feed composition of the present invention may further include any number of components typical for an animal feed, such as proteins, carbohydrates as defined above, fats and additional additives.

[0037] Examples of suitable types of proteins that can be included in the feed include, but are not limited to, meat scraps (lysine), fish meal (lysine, methionine), poultry by-product meal (tryptophan, lysine), blood meal, liver and glandular meal, feather meal (hydrolyzed), animal tankage, milk products, cottonseed meal, peanut meal, soybean meal, sesame meal, sunflower seed meal.

[0038] Most feed ingredients (maize, barley, safflower, milo, wheat, rice, bran, etc.) contain approximately 2- 5% fat and linoleic acid. Sources of fats include animal tallow (beef), lard, corn oil, and other vegetable oils.

[0039] Additional additives include but are not limited to minerals as defined above; antioxidants like BHT (Butylated hydroxytoluene), santoquin, ethoxyquin, butylated hydroxyan isode and diphenyl paraphenyl diamine; pellet binders such as sodium bentonite (clay), liquid or solid by-products of the wood pulp industry, molasses, and guarmeal; coloring agents such as xanthophylls, synthetic carotinoid, and canthaxanthin; probiotics such as strains of lactobacillus and streptococcus; and / or antibiotics such as penicillin, streptomycin, tetracyclines, and aureomycin.

[0040] In the present invention, the at least one organic acid and / or the at least one salt thereof may be provided at a concentration of from 0.001 % to 10%, preferably from 0.01 % to 5%, more preferably from 0.05% to 1 % by weight such as 0.05%, 0.1 %, 0.2%, 0.3%, 0.4% and 0.5% by weight of the animal feed.

[0041] In the present invention, hypophosphorous acid and / or the at least one salt thereof may be provided at a concentration of from 0.0005% to 1%, preferably from 0.001% to 0.5%, more preferably from 0.002% to 0.2%, even more preferably 0.0025% to 0.1% by weight such as 0.0025%, 0.003%, 0.004%, 0.005%, 0.01%, 0.015%, 0.02%, 0.025%, 0.03%, 0.04%, 0.05%, 0.06%, 0.08% and 0.1 % by weight of the animal feed.

[0042] The present invention is further illustrated by the following examples. Examples

[0043] Example 1

[0044] Animals and Housing

[0045] The trial was carried out in a commercial farm in Lorca (Livestock Feed Test, Denmark). A total of 540 healthy piglets weaned at an average of 28 days of age with initial average body weight of 6.4 kg, were used for the trial. The environmental conditions were automatically controlled, ensuring an adequate temperature and ventilation for the age of the piglets.

[0046] At weaning piglets were classified by body weight into 5 groups (60 pens in total, 9 animals (4 barrows and 5 gilts) per pen). Subsequently they were randomly assigned to one of the 5 experimental treatments (CTR, VEV, BIO, SH1 and SH2).

[0047] Experimental Diets

[0048] A 2-phase feeding plan (dO-14 and d14-42) was used. The experimental diets for each of the study phases were formulated using BRILL Software (linear programming method) and FEDNA 2019 composition tables. Same nutrient and ingredient restrictions were used with the only exception of the inclusion of the test products (VEVOVITALL® (DSM Nutritional Products, Switzerland) and BIOTRONIC® TOP 3 (DSM Nutritional Products, Austria) or sodium hypophosphite).

[0049] The inclusion levels of the test products as well as the ingredient of the experimental diets are shown in Tables 1 and 2.

[0050] Table 1. 0-14d diet composition (%, as fed basis)

[0051] 1Premix piglets: vitamin premix provides compound feed per kg: vitamin A, 4800 IU; Vitamin Ds, 576 IU; Vitamin E, 76 8 mg; Vitamin Ks, 1 44 mg; Vitamin Bi, 1 44 mg; Vitamin Be, 1 92 mg; Vitamin B12, 19 g; Niacin, 19 2 mg; Pantothenic acid, 96 mg; Biotin, 0 121 mg

[0052] Table 2. 14-42d diet composition (%, as fed basis) 1Premix piglets: vitamin premix provides compound feed per kg: vitamin A, 4800 IU; Vitamin Ds, 576 IU; Vitamin E, 76 8 mg; Vitamin Ks, 1 44 mg; Vitamin Bi , 1 44 mg; Vitamin Be, 1 92 mg; Vitamin B12, 19 pg; Niacin, 19 2 mg; Pantothenic acid, 9 6 mg; Biotin, 0 121 mg

[0053] Experimental parameters and analyses • Diarrhea status: average fecal score value daily or weekly and fecal score distribution.

[0054] Results and Discussion

[0055] Table 3 lists the average fecal scores of treatments in every day during the trial period. As shown, compared to the CTR treatment and VEV treatment, SH1 treatment provided comparable or even improved average fecal score at d1 , d3, d5, d9, d12-13, d17 and d20-24, and SH2 treatment provided even more improved average fecal score in most of the days during the trial period, such as at d2-10, d13-14 and d17-24. Table 3. Average Fecal score of piglets during the trial period a, ab, b: P<0.05

[0056] 5 Table 4 lists the facel score distribution at different periods of the trial. As shown, compared to the CTR treatment and VEV treatment, SH1 treatment significantly increased the percentages of score 1 at dO-14 and score 0 at d14-28, shows more normal or soft feces during the trial, and SH2 provided more improved results, i.e., significantly increased the percentage of scores 0 and 1 at dO-14, score 0 at d14-28 and also scores 0 and 1 at the whole period of dO-42, shows significantly w higher percentage of normal or soft feces and significantly lower percentage of mild diarrhea feces during the trial.

[0057] Table 4. Fecal score frequency of piglets at different trial period a, ab, b: P<0.05

[0058] 15

[0059] Conclusion

[0060] The combination of organic acids and sodium hypophosphite reduced diarrhea and improved fecal quality of piglets at the stage of d 0-42.

Claims

Claims1. A method for reducing diarrhea and / or improving fecal quality of animals, comprising administering to the animal a feed composition comprising a) at least one organic acid and / or at least one salt thereof; and b) hypophosphorous acid and / or at least one salt thereof.

2. The method of claim 1 , wherein the at least one organic acid is selected from the group consisting of short monocarboxylic acids having between 1 and 6 carbon atom(s), saturated dicarboxylic acids, unsaturated dicarboxylic acids, unsaturated carboxylic acids, saturated carboxylic acids, hydroxycarboxylic acids, aromatic carboxylic acids and keto carboxylic acids.

3. The method of claim 1 , wherein the at least one organic acid is selected from the group consisting of formic acid, acetic acid, propionic acid, butyric acid, isobutyric acid, 3-methylbutyric acid, 2- metylbutyric acid, 2-ethylbutyric acid, valeric acid, hexanoic acid, adipic acid, succinic acid, fumaric acid, sorbic acid, oleic acid, stearic acid, octanoic (caprylic) acid, decanoic (capric) acid, dodecanoic (lauric) acid, lactic acid, malic acid, citric acid, tartaric acid, benzoic acid, cinnamic acid, pyruvic acid, gluconic acid, suberic acid, malonic acid, tannic acid, caffeic acid, ellagic acid, perillic acid and gallic acid, or at least one salt thereof.

4. The method of claim 1 , wherein the at least one organic acid is selected from the group consisting of acetic acid, butyric acid, citric acid, formic acid, fumaric acid, lactic acid, octanoic acid, propionic acid, pyruvic acid, benzoic acid, sorbic acid, succinic acid and valeric acid, or at least one salt thereof.

5. The method any one of claims 1-4, wherein the at least one salt of the organic acid is any one of metal salts such as potassium, sodium or calcium salts, and ammonium salts, including but not limited to ammonium formate, potassium diformate, sodium diacetate, calcium acetate, ammonium propionate, sodium propionate, calcium propionate, calcium lactate, potassium sorbate, sodium formate, calcium formate, sodium butyrate, sodium sorbate, potassium citrate, sodium citrate, calcium citrate, and benzoates such as sodium benzoate, magnesium benzoate, manganese benzoate, potassium benzoate, aluminium benzoate, calcium benzoate and ferric benzoate.

6. The method of claim 1 , wherein the at least one salt of hypophosphorous acid is selected from the group consisting of sodium hypophosphite, magnesium hypophosphite, manganese hypophosphite, potassium hypophosphite, aluminum hypophosphite, calcium hypophosphite, ammonium hypophosphite and ferric hypophosphite, preferably sodium hypophosphite, magnesium hypophosphite, manganese hypophosphite and potassium hypophosphite, more preferably sodium hypophosphite.

7. The method of any one of claims 1-6, wherein wherein the molar ratio of the at least one organic acid and / or the at least one salt thereof to the hypophosphorous acid and / or the at least one salt thereof is from 100:0.1 to 0.1 :100, preferably from 100:1 to 1 :100, more preferably from 50:1 to 1 :50, even more preferably from 20:1 to 1 :20, and the most preferably from 10:1 to 1 :10.

8. The method of any one of claims 1-6, wherein the at least one organic acid and / or the at least one salt thereof is provided at a concentration of from 0.001 % to 10%, preferably from 0.01% to 5%, more preferably from 0.05% to 1% by weight such as 0.05%, 0.1 %, 0.2%, 0.3%, 0.4% and 0.5% by weight of the animal feed.

9. The method of any one of claims 1 -6, wherein hypophosphorous acid and / or the at least one salt thereof is provided at a concentration of from 0.0005% to 1%, preferably from 0.001 % to 0.5%, more preferably from 0.002% to 0.2%, even more preferably 0.0025% to 0.1 % by weight such as 0.0025%, 0.003%, 0.004%, 0.005%, 0.01 %, 0.015%, 0.02%, 0.025%, 0.03%, 0.04%, 0.05%, 0.06%, 0.08% and 0.1% by weight of the animal feed.

10. The method of any one of claims 1-6, wherein the animal is selected from the group consisting of pigs or swine such as piglets, growing pigs and sows; poultry such as turkeys, ducks, quail, guinea fowl, geese, pigeons and chicken; pets such as cats and dogs; and horses.11 . Use of a feed composition comprising a) at least one organic acid and / or at least one salt thereof; and b) hypophosphorous acid and / or at least one salt thereof in the preparation of an animal feed additive or animal feed for reducing diarrhea and / or improving fecal quality of animals.

12. The use of claim 11 , wherein the animal is selected from the group consisting of pigs or swine such as piglets, growing pigs and sows; poultry such as turkeys, ducks, quail, guinea fowl, geese, pigeons and chicken; pets such as cats and dogs; and horses.

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