KR102446654B1 - Composition for inhibiting endotoxin in rumen of ruminant animals - Google Patents

Abstract

The present invention relates to a composition for inhibiting endotoxin in the rumen of a ruminant, and by including aronia juice as an active ingredient, endotoxin in the rumen of a mammal, preferably a ruminant, can be suppressed.

Description

Composition for inhibiting endotoxin in rumen of ruminant animals

The present invention relates to a composition capable of inhibiting endotoxin in the rumen of a mammal, preferably a ruminant.

In the livestock industry, ruminants include beef cattle for meat production and cows for milk production. Ruminants are herbivores and use plants such as grass as the main energy source, but plants such as grasses and grain feeds such as corn, barley, beet pulp and cotton are also used as energy sources for the purpose of improving productivity. In this way, a mixture of plants such as grass and grain feed to form a single feed is called a complete fiber feed.

Ruminants have a large and complex stomach unlike unit animals such as pigs and chickens. The stomach of ruminants is largely divided into four compartments, and the first and second stomachs are collectively called rumen, and various microorganisms inhabit the rumen. The microorganisms of the rumen produce short carbon chain fatty acids called volatile fatty acids by fermenting feed crops and grains such as grasses consumed by ruminants, and the produced volatile fatty acids are absorbed into the rumen wall and used as an energy source for ruminants. do. 70% of the total energy used by ruminants for maintenance, growth and production of livestock products (meat and milk) is volatile fatty acids generated in the rumen. Therefore, the production and composition of volatile fatty acids produced in the rumen have a direct effect on the productivity of beef cattle and dairy cattle.

When a high-energy feed is supplied, microorganisms are stressed in the rumen and secrete endotoxin such as lipopolysaccharide. endotoxin) is secreted.

Endotoxin produced in the rumen crosses the intestinal barrier and moves to organs other than the intestine, and endotoxemia refers to the spread of endotoxin. Endotoxins are known to cause systemic inflammatory response syndrome (SIRS) and sepsis. When endotoxemia occurs, enterobacteriaceae and various products first propagate to the mesenteric lymph nodes, move along the lymphatic system to the chest tube, and spread to distant organs such as the liver, spleen, and lungs. It is also disseminated as In this case, the production of volatile fatty acids is also affected, which affects the productivity of beef cattle and dairy cattle.

Diseases associated with endotoxemia include trauma, aortic aneurysm surgery and intestinal transplantation, obstructive jaundice, acute pancreatitis, intestinal obstruction, liver cirrhosis, heart failure, neoplastic disease, inflammatory bowel disease, extrapulmonary acute respiratory failure (ARDS), systemic inflammatory There are reactive syndromes and sepsis, and endotoxemia has been found to be correlated with infectious complications of these diseases (Adv.Exp.Med.Biol 1999;473:11-30).

Therefore, there is a need for a natural substance that can solve the problem of lowering productivity of ruminants by inhibiting the production of endotoxins in a state that does not affect the functions of the rumen microorganisms.

Republic of Korea Patent No. 1795499 Republic of Korea Patent No. 1256567

It is an object of the present invention to provide a composition capable of inhibiting endotoxin in mammals by including aronia juice as an active ingredient.

Another object of the present invention is to provide a feed composition capable of inhibiting endogenous toxins in mammals by including aronia juice as an active ingredient.

Another object of the present invention is to provide a pharmaceutical composition for animals capable of inhibiting endogenous toxins in mammals by including aronia juice as an active ingredient.

The composition for inhibiting endotoxin in mammals other than humans of the present invention for achieving the above object may include aronia juice as an active ingredient.

The aronia juice may be 13 to 20 brix.

The composition may inhibit endotoxin in the rumen of a ruminant.

The ruminant may be a camelidae, a deer family, a deer family, a giraffe family, or a bovine family, and preferably it may be at least one selected from the group consisting of Korean beef, beef cattle, dairy cows, buffalo, yak, gayal and banting.

In addition, the feed composition for inhibiting endotoxin in mammals other than humans of the present invention for achieving the above other object may include aronia juice as an active ingredient.

The feed composition may inhibit endotoxin in the rumen of ruminants.

In addition, the pharmaceutical composition for animals for suppressing endotoxin in mammals other than humans of the present invention for achieving the above other object may include aronia juice as an active ingredient.

The feed composition may inhibit endotoxin in the rumen of ruminants.

The composition comprising the aronia juice of the present invention as an active ingredient inhibits endotoxin in the rumen, thereby preventing the disease that may be caused by the endotoxin from occurring in the first place, so it can be used as a feed composition or a pharmaceutical composition for animals. have.

In addition, when the composition containing the aronia extract of the present invention as an active ingredient is added to the feed composition and fed, most of the feed energy can be used for the growth of ruminants.

The present invention relates to a composition capable of inhibiting endotoxin in the rumen of a mammal, preferably a ruminant.

Hereinafter, the present invention will be described in detail.

The inventors of the present invention confirmed that aronia juice inhibits endotoxin in mammals other than humans, preferably in the rumen of ruminants.

The present invention relates to a composition for inhibiting endotoxin in mammals other than humans, comprising aronia juice as an active ingredient.

The aronia juice is grape juice, grape water extract, grape seed water extract, maqui berry juice, maqui berry water extract, acai berry juice, acai berry water extract, etc. Excellent suppression of endogenous toxins.

In particular, the aronia juice of the present invention can inhibit endotoxin in the rumen better than the aronia water extract, the aronia ethanol extract, or the aronia methanol extract.

The aronia juice is a liquid substance from which solids are removed by squeezing aronia. When aronia is extracted with water, an alcohol having 1 to 4 carbon atoms, or a mixed solvent thereof, the inhibitory ability of endogenous toxins in the rumen is reduced. can be

The sugar content of the aronia juice is 13 to 20 brix, preferably 15 to 18 brix. If the sugar content of the aronia juice is less than the lower limit, the sensory properties may be reduced and the inhibitory ability of endotoxin in the rumen may be reduced. .

In addition, the present invention can provide a feed composition for suppressing endogenous toxins in mammals other than humans, including aronia juice as an active ingredient.

In the 'feed composition', in addition to aronia juice as an active ingredient, food ingredients that can be used as foods described in the standards and specifications ('Food Code') and food additives described in the Food Additives Code can be used, and used as food. Even if it is not a possible food raw material or food additive, raw materials that fall within the range of single feed in Attached Table 1 of 'Standards and Specifications for Feed, etc.' and raw materials that fall within the range of Supplementary Feed in Attached Table 2 may be used.

The 'feed composition' may be an extractant among auxiliary feeds according to the 'standards and specifications for feed, etc.', and may be a compound feed including the auxiliary feed.

When preparing a feed composition using the aronia juice as an active ingredient, the aronia juice does not need to be particularly limited as long as it has an amount capable of inhibiting endogenous toxins in the rumen, but for example, 0.1 to 99% by weight, 0.5 to 95 Weight%, 1 to 90% by weight, 2 to 80% by weight, 3 to 70% by weight, 4 to 60% by weight, 5 to 50% by weight may be included.

The aronia extract, which is an active ingredient in the feed composition, varies depending on the condition, weight, presence or extent and duration of the ingested animal, but may be appropriately selected by those skilled in the art. For example, it may be 1 to 5,000 mg, preferably 5 to 2,000 mg, more preferably 10 to 1,000 mg, still more preferably 20 to 800 mg, and most preferably 50 to 500 mg based on the daily dose. And, the number of administration does not need to be particularly limited, but can be adjusted by those skilled in the art within the range of 3 times a day to once a week. In the case of long-term intake for the purpose of health and hygiene or health control, it may be less than the above range.

The present invention can provide a pharmaceutical composition for animals for suppressing endotoxin in mammals other than humans, comprising aronia juice as an active ingredient.

The present invention also provides a treatment method for suppressing endotoxin in mammals other than humans by administering the composition to animals other than humans.

In addition, the present invention provides a novel use of aronia extract for the manufacture of a medicament for animals for the suppression of endotoxin in mammals.

The 'pharmaceutical composition for animals' or 'medicine for animals' may further include suitable carriers, excipients and diluents commonly used in the manufacture of pharmaceutical compositions, in addition to aronia juice as an active ingredient.

The 'carrier' is a compound that facilitates the addition of the compound into a cell or tissue. The 'diluent' is a compound that is diluted in water to not only stabilize the biologically active form of the compound of interest, but also to dissolve the compound.

The carrier, excipient and diluent are not particularly limited, but for example, lactose, glucose, sugar, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia gum, alginate, gelatin, calcium phosphate, calcium silicate, cellulose , methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methyl hydroxy benzoate, propyl hydroxy benzoate, talc, magnesium stearate and mineral oil.

The amount of the pharmaceutical composition for animals or veterinary medicine used may vary depending on the age, sex, and weight of the animal to be treated, and above all, the condition of the subject to be treated, a specific category or type of disease to be treated, the route of administration, and the It will depend on the properties of the therapeutic agent.

The pharmaceutical composition for animals or pharmaceuticals for animals is appropriately selected according to the absorption rate of the active ingredient in the body, the rate of excretion, the age and weight of the animal to be treated, sex and condition, the severity of the disease to be treated, etc., but generally 0.1 to It is preferred to administer 1,000 mg/kg, preferably 1 to 500 mg/kg, more preferably 5 to 250 mg/kg, and most preferably 10 to 100 mg/kg. The unit dosage form formulated in this way can be administered several times at regular time intervals as needed.

The pharmaceutical composition for animals or pharmaceuticals for animals may be administered individually as a prophylactic or therapeutic agent, or may be administered in combination with other therapeutic agents, and may be administered sequentially or simultaneously with conventional therapeutic agents.

The pharmaceutical composition for animals or pharmaceuticals for animals may be formulated into oral formulations such as powders, granules, tablets, capsules, troches, suspensions, emulsions, syrups, and aerosols, respectively, according to a conventional method. In the case of formulation, it can be prepared using a diluent or excipient such as a filler, extender, binder, wetting agent, disintegrant, surfactant, etc. commonly used.

Solid preparations for oral administration include tablets, pills, powders, granules, capsules, troches, and the like, and such solid preparations include at least one excipient to the compound, for example, starch, calcium carbonate, sugar or lactose, gelatin. It can be prepared by mixing and the like. In addition to simple excipients, lubricants such as magnesium stearate and talc may also be used. Liquid formulations for oral use include suspensions, solutions, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, fragrances, preservatives, etc. may be included. .

The treatment method for suppressing endotoxin in a mammal is to administer the composition to an animal other than a human, particularly a mammal, for example, to administer the composition to a subject to be treated with an endotoxin.

The dosage, administration method, and frequency of administration for the treatment may refer to the dosage, administration method and frequency of administration of the pharmaceutical composition for animals or medicaments for animals.

Hereinafter, preferred examples are presented to help the understanding of the present invention, but the following examples are merely illustrative of the present invention, and it will be apparent to those skilled in the art that various changes and modifications are possible within the scope and spirit of the present invention, It goes without saying that such variations and modifications fall within the scope of the appended claims.

Example 1. Aronia juice

The washed aronia was squeezed to remove the solid, and the remaining aronia juice was obtained. The sugar content at this time is 15 brix.

Comparative Example 1. Aronia water extract

Purified water 20 times the weight of the washed aronia was added, extracted under reflux at 90 ° C. for 4 hours, filtered with a 60 mesh filter paper, and then concentrated under reduced pressure to obtain an aronia water extract. The sugar content at this time is 11 brix.

Comparative Example 2. Grape juice

The washed grapes were squeezed to remove solids, and the remaining grape juice was obtained.

Comparative Example 3 Grape Water Extract

After adding purified water 20 times the weight to the washed grapes, reflux extraction was performed at 90° C. for 4 hours, filtered with a 60 mesh filter paper, and concentrated under reduced pressure to obtain a grape seed water extract.

Comparative Example 4. Grape Seed Extract

After adding purified water 20 times the weight to the washed grape seeds, reflux extraction was performed at 90° C. for 4 hours, filtered through a 60 mesh filter paper, and concentrated under reduced pressure to obtain a grape seed water extract.

<Test Example>

Control 1 is an untreated group, Control 2 is a group treated with malvidin, and Control 3 is a group treated with N-acylhomoserine lactone (AHL).

Test Example 1. Measurement of fermentation characteristics and endotoxin

The rumen contents of slaughtered beef cattle were collected immediately after slaughter at the Livestock Slaughterhouse in Iksan. The collected rumen contents were first filtered using 4 layers of cheese cloth, and then placed in an insulated container to maintain anaerobic conditions. Before the experiment, CO ₂ was injected and the pH was adjusted to 6.5. McDougall's buffer and filtered rumen gastric juice were mixed in a volume ratio of 4:1 and used as an inoculum. The composition of McDougall's buffer is shown in Table 1 below.

Ingredients Content (g/L) NaHCO ₃ 9.80 g Na ₂ HPO ₄ ·2H ₂ O 4.62 g KCl 0.57 g NaCl 0.47 g MgSO ₄ 7H ₂ O 0.12 g CaCl ₂ 0.00004 g

100 g of common feed; After mixing 0.1 g of the substances prepared in Examples, Comparative Examples or Controls, 0.5 g of the mixture was put into a serum bottle, dispensed into 50 ml of rumen inoculum, sealed, and fermented for 24 hours.

1-1. Endotoxin (10 ⁴ EU/ml): Endotoxin was analyzed for the fermented product using the LAL Chromogenic Endotoxin Quantitation Kit (Thermo).

1-2. Fermentation gas production amount (ml): The amount of fermentation gas of the fermented product was measured using an experimental glass syringe.

1-3. pH: It was measured using a pH meter (S20 Seven Eazy ^TM , Mettler-Toledo).

1-4. Ammonia nitrogen (mg/dL): Ammonia nitrogen (NH ₃ -N) content in the rumen was measured by gas chromatography.

1-5. Total volatile fatty acids (mM): The volatile fatty acids (VFA) in the rumen were measured by gas chromatography.

division Control 1 Control 2 Control 3 Example 1 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 endotoxin 3.85 3.75 3.83 3.48 3.83 3.91 3.81 3.72 fermented gas 183.67 165.67 169.67 170.00 168.25 167.21 172.00 171.67 pH 6.07 6.13 6.10 6.11 6.09 6.05 6.14 6.15 ammonia nitrogen 13.16 12.46 11.93 12.45 12.12 13.20 12.94 11.49 total volatile fatty acids acetic acid 68.33 64.42 62.33 63.01 64.11 62.11 66.66 63.96 propionic acid 26.30 24.94 24.02 24.74 24.05 23.53 25.93 25.25 butyl acid 17.65 17.89 17.17 18.30 17.11 17.52 18.39 18.76 valeric acid 6.30 7.21 6.88 7.59 7.00 7.05 7.33 7.86 total amount 118.59 114.46 110.39 113.63 112.27 110.21 118.31 115.84

As shown in Table 2 above, it was confirmed that the aronia juice prepared according to Example 1 of the present invention had a lower amount of endotoxin in the rumen compared to Controls 1 to 3 and Comparative Examples 1 to 4. That is, it can be said that the aronia juice of Example 1 is effective in inhibiting endotoxin production in the rumen.

In addition, the fermentation gas is related to the heat of fermentation in the rumen, and the decrease in the amount of fermented gas produced in the aronia juice prepared according to Example 1 of the present invention compared to the control 1 is interpreted as having an effect in relieving stress by reducing the amount of heat generated. can

There was no significant difference in the pH of rumen gastric juice for each test group, and it was confirmed that all test groups were present between 6.0 and 7.0, which is a stable rumen pH. Through this, it can be seen that the materials prepared according to Examples and Comparative Examples do not have a negative effect on rumen fermentation.

In addition, ammonia nitrogen in the rumen is a substance that is helpful for the growth of microorganisms, and total volatile fatty acids are a substantial energy source for ruminants, and the more they are produced in the rumen, the better, and there was no significant difference between test groups.

Hereinafter, a formulation example of a composition containing the extract of the present invention will be described, but the present invention is not intended to limit the present invention, but merely to describe it in detail.

Formulation Example 1: Preparation of powder

20 mg of extract powder of Example 1

Lactose 100 mg

talc 10 mg

The above ingredients are mixed and filled in an airtight bag to prepare a powder.

Formulation Example 2: Preparation of tablets

10 mg of extract powder of Example 1

100 mg cornstarch

Lactose 100 mg

2 mg magnesium stearate

After mixing the above ingredients, tablets are prepared by tableting according to a conventional manufacturing method of tablets.

Formulation Example 3: Preparation of capsules

10 mg of extract powder of Example 1

3 mg of crystalline cellulose

Lactose 14.8 mg

0.2 mg magnesium stearate

According to a conventional capsule preparation method, the above ingredients are mixed and filled in a gelatin capsule to prepare a capsule.

Formulation Example 4: Preparation of granules

1,000 mg of extract powder of Example 1

appropriate amount of vitamin mixture

70 μg vitamin A acetate

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

Vitamin B2 0.15 mg

0.5 mg of vitamin B6

0.2 μg of vitamin B12

Vitamin C 10 mg

Biotin 10 μg

Nicotinamide 1.7 mg

50 μg of folic acid

Calcium pantothenate 0.5 mg

Mineral mixture appropriate amount

ferrous sulfate 1.75 mg

Zinc Oxide 0.82 mg

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Dibasic calcium phosphate 55 mg

Potassium citrate 90 mg

100 mg calcium carbonate

Magnesium chloride 24.8 mg

The composition ratio of the vitamin and mineral mixture is mixed with ingredients suitable for health functional food in a preferred embodiment, but the blending ratio may be arbitrarily modified, and the ingredients are mixed according to a conventional health functional food manufacturing method. Next, the granules can be prepared and used in the preparation of a health functional food composition according to a conventional method.

Formulation Example 5: Preparation of feed composition

0.1 kg of extract powder of Example 1, 25.5 kg of corn, 15.04 kg of wheat, 8.15 kg of wheat flour, 7.4 kg of rice bran, 18 kg of soybean meal, 1 kg of okgurten, 14 kg of chicken by-product, 9 kg of animal fat, 0.3 kg of processed salt, phosphoric acid An animal (ruminant) feed composition was prepared by mixing 0.3 kg of tricalcium, 1 kg of limestone, 0.01 kg of choline chloride, 0.05 kg of vitamins, 0.05 kg of minerals and 0.1 kg of digestive enzymes.

Claims (9)

As an inhibitor of endotoxin in the rumen of ruminants by including aronia juice as an active ingredient,
The amount of the inhibited endotoxin is 3.48X10 ⁴ EU/ml, the aronia juice is 13 to 20 brix, and the ruminant is 1 selected from the group consisting of Korean cattle, beef cattle, dairy cows, buffalo, yak, gayal and banting. A composition for inhibiting endotoxin in the rumen of a ruminant, characterized in that there are more than one species. delete delete delete delete As an inhibitor of endotoxin in the rumen of ruminants by including aronia juice as an active ingredient,
The amount of the inhibited endotoxin is 3.48X10 ⁴ EU/ml, the aronia juice is 13 to 20 brix, and the ruminant is 1 selected from the group consisting of Korean cattle, beef cattle, dairy cows, buffalo, yak, gayal and banting. Feed composition for suppressing endotoxin in the rumen of ruminants, characterized in that there are more than one species. delete As an inhibitor of endotoxin in the rumen of ruminants by including aronia juice as an active ingredient,
The amount of the inhibited endotoxin is 3.48X10 ⁴ EU/ml, the aronia juice is 13 to 20 brix, and the ruminant is 1 selected from the group consisting of Korean cattle, beef cattle, dairy cows, buffalo, yak, gayal and banting. A pharmaceutical composition for animals for suppressing endotoxin in the rumen of a ruminant, characterized in that there are more than one species.

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