JPH0545221B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a feed additive, and more particularly to a feed additive in which a biologically active substance suitable for use in ruminants is coated with a protective substance.

[Conventional technology]

Biologically active substances such as amino acids and their derivatives such as methionine and lysine, vitamins such as vitamin A, vitamin E and carotene, feather powder, proteins such as potato protein, glucose and carbohydrates such as glucose, antibiotics, Veterinary medicines such as anthelmintics are often finely powdered products, and when they are mixed into compounded feed as feed additives, they have the disadvantage of separating during transport, etc. There are drawbacks such as a large amount of powder produced during mixing, which worsens the working environment. Furthermore, when directly orally administered to ruminants such as cows and sheep, it is degraded by microorganisms, enzymes, etc. present in the ruminal fluid, and most of its activity is lost. A protective substance that protects biologically active substances from ruminal fluid and is used as a feed additive to orally administer biologically active substances to ruminants and use them effectively for weight gain, milk production increase, disease treatment, etc. Various feed additives have been proposed that are designed to protect animals and allow the biologically active substances to be effectively absorbed by disintegrating or digesting the protective substances in the digestive tract starting from the abomasum. For example, a feed additive for ruminants in which a biologically active substance is granulated by surrounding it with a protective substance such as triglyceride, hydrogenated animal or vegetable fat, or bran wax is available.
No. 12785 describes biologically active substances as linear or branched substituted or unsubstituted saturated aliphatic monocarboxylic acids having at least 14 carbon atoms or salts thereof; A feed additive for ruminants coated or surrounded by a mixture of the salt thereof and a linear or branched substituted or unsubstituted unsaturated aliphatic monocarboxylic acid having at least 14 carbon atoms or a salt thereof is particularly provided. Kosho 56
-1057 publication further describes an aliphatic monocarboxylic acid having 14 to 22 carbon atoms, ricinoleic acid, a hydrogenated vegetable oil or a hydrogenated animal oil, and an aliphatic monocarboxylic acid having 14 to 22 carbon atoms, or ricinoleic acid. A feed additive for ruminants in which a mixture with sodium, potassium or calcium salts of B. However, these feed additives focus too much on suppressing the elution of biologically active substances in the ruminal juice, and thus have poor disintegration in the abomasum and beyond, leaving the biologically active substances not being effectively utilized. It has the disadvantage of being excreted. Furthermore, when mixed with pellets of concentrate feed, which is the usual feeding method for ruminants, it has the disadvantage that the protection is destroyed by heating during pelletization. Additionally, biologically active substances in feed additives
It has a low defect content of less than 40% by weight.

[Problem to be solved by the invention]

The present invention has improved the above-mentioned drawbacks, that is, the content of biologically active substances is high, the biologically active substances are sufficiently protected from the ruminal fluid when administered orally to ruminants, and the abomasum The object of the present invention is to provide a feed additive that is easily disintegrated in the subsequent gastrointestinal tract and whose protective substances are not destroyed during pelletization, particularly a feed additive suitable for ruminants.

[Means to solve the problem]

As a result of intensive research to achieve the above-mentioned objective, the present inventors have discovered a feed additive in which granulated biologically active substances are coated with a film that is sparingly soluble in neutral or alkaline water and easily soluble in acidic water. The agent has a low dissolution rate of biologically active substances into McDougall's artificial saliva, which corresponds to the ruminal fluid of ruminants, and is easily disintegrated in the Clark Lubs buffer, which corresponds to the abomasal fluid. They found this and completed the present invention.

The present invention provides molded granules of biologically active substances that are sparingly soluble in neutral or alkaline water and easily soluble in acidic water (PH dependent), consisting of the following (a) and (b). A feed additive for ruminants characterized by being coated with a protective film of.

(a) The following (a), (b), (c), (d), (e), (f) and (
G) At least one film-forming component selected from the group consisting of (b) Hydrogenated vegetable oils (c) Hardened animal oils (d) Waxes (e) Beeswax (f) Ester gum (g) Water-insoluble binder (b) The following (a), (b), (c), (ni) ), (E), and (F), at least one component that imparts pH dependence to the film-forming component in item (a) above. (a) Aminocelluloses (b) Aminoacetates ( c) Vinylamines (d) Chitosan (e) Metal hydroxides (f) Alkaline earth metal salts In the present invention, the biologically active substance can be orally administered to livestock to increase body weight, milk production, and ovulation. Any substance may be used as long as it exhibits biological activity such as increasing volume or curing diseases, and in particular for ruminants, those that are easily degraded and lose their activity in the rumen juice are used.

For example, amino acids such as methionine and lysine, N-acyl amino acids, amino acid derivatives such as N-hydroxymethylmethionine calcium salt, lysine hydrochloride, and hydroxyl amino acids such as 2-hydroxy-4-methylmercaptobutyric acid and its salts. Homologous compounds, feather powder, fishmeal, casein,
Proteins such as potato protein, vitamins such as vitamin A, vitamin A acetate, vitamin A palmitate, vitamin _D3 , vitamin E, nicotinic acid, nicotinamide, calcium pantothenate, β-carotene, glucose , carbohydrates such as glucose, antibiotics, veterinary medicines such as anthelmintics, etc., or a mixture of two or more thereof.

In addition, a coating that is poorly soluble in neutral or alkaline water and easily soluble in acidic water is stable against the ruminal fluid of neutral or weakly alkaline ruminants, and is stable in the ruminal fluid of normal animals that are acidic. A combination of (a) and (b) above is used, which is easily dissolved or disintegrated in the gastric juice of a ruminant or the abomasal juice of a ruminant.

Examples of (a) and (b) are as follows.

Aminocelluloses benzylaminomethylcellulose, diethylaminomethylcellulose, etc.

Aminoacetates Diethylaminoacetate, polyvinyl acetal diethylaminoacetate (AEA), etc.

Vinylamines polyvinyldiethylaminoacetoacetal,
Vinyl piperidyl acetoacetal, vinyl acetate, copolymer, etc.

Metal hydroxides Aluminum hydroxide, calcium hydroxide, magnesium hydroxide, copper hydroxide, etc.

Alkaline earth metal salts: calcium carbonate, barium carbonate, calcium metasilicate, calcium sulfate, calcium sulfate hydrate, calcium hydrogen phosphate dihydrate, calcium pyrophosphate, etc.

Water-insoluble binder: ethyl cellulose, silica, polyvinyl alcohol, etc.

The feed additive of the present invention coats the biologically active substance, which is granulated into approximately spherical particles with a particle size of 0.2 to 2 mm, with a defect-free coating that is sparingly soluble in neutral to alkaline water and easily soluble in acidic water. Manufactured by coating. The biologically active substance may be produced by any method as long as it is in the form of approximately spherical granules with a particle size of 0.2 to 2 mm. For example, using a rolling granulator, a centrifugal granulator, a stirring granulator, a marmerizer, etc., fine powders of biologically active substances and core substances that form the core of granules, such as salt, calcium carbonate, Inorganic substances such as calcium sulfate, sodium or calcium salts of phosphate, iron sulfate, copper sulfate, sodium sulfate, oyster shell powder, kaolin, diatomaceous earth, vermiculite, etc. and/or starch, corn flour, soybean flour, sugar, etc. one or two organic substances
When a mixture of seeds or more fine powder is used to form the film, it is granulated using a water and/or organic solvent solution of the same kind of binder to form a solid and almost spherical granulated organism suitable for coating with a film. Chemically active substances can be produced. In the case of an organic coating, the granulated biologically active substance is coated with the above-mentioned film using a conventional method such as a rolling coating device, a fluidized bed, etc., using a solution of the above-mentioned film-forming components in an organic solvent such as ethyl alcohol or a heated melt. This is carried out by coating the granulated biologically active substance by a method using a coating device, a pan coating device, etc., a dipping method, etc. On the other hand, when coating with an inorganic film, the same equipment as used for granulating the biologically active substance is used, and following the granulation of the biologically active substance, the above-mentioned inorganic film-forming components and binder water and/or By supplying an organic solvent solution, the granulated biologically active substance is coated with a coating consisting of an inorganic substance and a binder. Since the film is required to have low solubility in neutral to alkaline water, it is preferable to use a water-insoluble binder such as ethyl cellulose, silica, polyvinyl alcohol, or the like. Since the film composed of an inorganic substance and a binder obtained by this method is likely to cause defects, the above-mentioned organic film-forming components, wax, beeswax, ester gum,
It is preferable to impregnate and/or coat with a water-insoluble binder or the like by a method using a fluidized bed coating device, a pan coating device, etc., a dipping method, or the like.

〔Effect of the invention〕

The feed additive of the present invention has the following features, in which the granulated biologically active substance is coated with a film that is poorly soluble in neutral or alkaline water and easily soluble in acidic water. .

(a) When administered orally to ruminants, biologically active substances are protected from microorganisms, enzymes, etc. present in the ruminal fluid, and the coating dissolves or disintegrates in the ruminal fluid, so it is It is effectively digested and absorbed in the gastrointestinal tract.

(b) Even when given to livestock other than ruminants, biologically active substances are effectively digested and absorbed because the coating dissolves or disintegrates in acidic gastric fluid.

(c) Depending on the granulation and coating conditions of the biologically active substance, the content of the biologically active substance in the feed additive is at a higher level compared to known ruminant feed additives; be able to.

(d) By appropriately selecting film-forming components, it is possible to obtain a film that is not destroyed by heating, so it can be mixed into concentrated feed when it is pelletized.

(e) Since it is in the form of granules of 0.2 to 2 mm, it is easy to handle without dusting, and even if it is mixed in mixed feed, it will not move or move.
It will not separate during transportation, etc.

The present invention provides a granular, easy-to-handle feed additive that contains a high level of biologically active substances and is particularly suitable for ruminants, and has extremely great industrial significance.

Hereinafter, the present invention will be explained in more detail with reference to Examples. However, the scope of the present invention is not limited in any way by the following examples.

〔Example〕

Example 1 Preparation of granules: 800 g of methionine with an average particle size of 5 μ, 100 g of calcium carbonate, 30% of hydroxypropylcellulose
Pour 333g of ethyl alcohol solution into the kneader,
After thorough kneading, hot water was passed through a jacket and heated to evaporate the ethyl alcohol solvent to obtain a dry powder. The obtained powder was continuously sprayed with 100 g of a water:ethyl alcohol solution with a volume ratio of 1:1 while stirring using a Henschel mixer, and further dried to form approximately spherical methionine-based granules (hereinafter referred to as " (referred to as "granulated methionine") was obtained.

Coating: Screened in fluidized bed coating equipment
Weight ratio of 70/to granulated methionine with particle size of 0.2 to 1.5 mm
Ethylcellulose/AEA using an ethyl alcohol solution of 30% ethylcellulose/AEA.
A feed additive was obtained by coating with a composite film.

The methionine concentration in the feed additive was 77.5%, and the coating amount per 100 g of granulated methionine was 14 g.

Dissolution test 1 g of the obtained feed additive was immersed in 200 ml of Mc Dougall's artificial saliva, which corresponds to the rumen juice of cows.
Shake for 24 hours at a temperature of 39°C, and then
Clark Lubs PH2 buffer solution 200 for gastric juices
ml and shaken at a temperature of 39°C for 3 hours. Methionine in Mc Dougall's artificial saliva and Clark Lubs buffer was quantified, and the methionine elution rate in each solution was determined. The results were 0.8% for Mc Dougall's artificial saliva and 72% for Clark Lubs' buffer.
It was %.

Mc Dougall's artificial saliva: Sodium bicarbonate: 9.8g, Potassium chloride:
0.57g, calcium chloride: 0.04g, disodium phosphate dodecahydrate: 9.30g, sodium chloride: 0.47
g and sodium sulfate heptahydrate: 0.12 g to 1 part water
A liquid with a pH of 8.3 dissolved in

Clark Lubs buffer: A pH2 solution containing 50 ml of 0.2N potassium chloride, 10.6 ml of 0.2N hydrochloric acid, and 139.4 ml of water.

Example 2 After charging 800 g of methionine with an average particle size of 10 μ, 100 g of dibasic calcium phosphate, and 333 g of a 30% carbon tetrachloride solution of ester gum into a kneader and kneading them thoroughly,
Warm water was passed through the jacket and heated to evaporate the solvent carbon tetrachloride to obtain a dry powder. The obtained powder was continuously sprayed with carbon tetrachloride while being stirred using a Henschel mixer to obtain approximately spherical granulated methionine. Granulated methionine with a particle size of 0.2 to 1.5 mm, which has been sieved in a centrifugal coating device, is coated with an ethyl cellulose/monocalcium phosphate film using an ethanol slurry of ethyl cellulose/monocalcium phosphate (80/20 weight ratio). A feed additive was obtained. The methionine content in the obtained feed additive was 71.6%, and the coating amount of ethyl cellulose/monocalcium phosphate was 12 g per 100 g of granulated methionine. Example 1
The methionine elution rates for Mc artificial saliva and CL buffer measured in the same manner as above were 10.7% and 68%.

Example 3 A centrifugal flow type granulator was charged with 400 g of calcium carbonate with an average particle size of 80 μm and activated, and at the same time, an ethyl alcohol solution of hydroxypropyl cellulose was sprayed, and at the same time, methionine with an average particle size of 1 μm was sprayed from a position opposite to the spray nozzle. was continuously supplied.
When hydroxypropyl cellulose: 300g and methionine: 2300g were charged, the particle size was 0.2 to 2.0.
mm spherical granulated methionine was obtained. Subsequently, while spraying an ethyl alcohol solution of hydroxypropylcellulose, calcium carbonate with an average particle size of 2.2μ was continuously charged in place of methionine, and when 30g of hydroxypropylcellulose and 600g of calcium carbonate were charged, the granulation device was operation was stopped to obtain methionine granules coated with calcium carbonate. After drying the obtained granules, chitosan was dispersed in a carbon tetrachloride solution of ester gum, and an ester gum/chitosan film was coated using a centrifugal granulation device, followed by drying to remove carbon tetrachloride. , feed additives were obtained. A slurry of 70/30 weight ratio of ester gum and chitosan was used.
The amount of ester gum/chitosan coated is 15.2 for 110 g of methionine granules coated with calcium carbonate.
It was hot at g.

Methionine content in feed additive is 60.0% by weight
It was hot.

Mc Dougall's artificial saliva and Clark's obtained feed additives were treated and measured in the same manner as in Example 1.
The elution rate of methionine in Lubs buffer is:
They were 18.3% and 52.1%, respectively.

Comparative Example 1 Granulated methionine not coated with the film obtained in Example 1 was treated with Mc Dougall in the same manner as in Example 1.
When treated with artificial saliva, it completely disintegrated.

Comparative Example 2 Methionine: 30 parts by weight, stearic acid: 50 parts by weight, and sodium stearate: 20 parts by weight were uniformly mixed and heated to melt a molten slurry, which was then granulated using a rotating disk granulator to obtain a 0.8 to 1.5 molten slurry. mm feed additive was obtained.

The obtained feed additive was added to Mc in the same manner as in Example 1.
The elution rate of methionine was determined by treating with Dougall's artificial saliva and Clark Lubs' buffer. Mc
The dissolution rates of methionine for Dougall's artificial saliva and Clark Lubs buffer were 36.2% and 35.1%, respectively.

Claims (1)

[Scope of Claims] 1 Molded granules containing a biologically active substance are prepared as follows (a):
A feed additive for ruminants characterized by being coated with a protective film that is sparingly soluble in neutral or alkaline water and easily soluble in acidic water (PH-dependent), comprising: and (b). a) The following (a), (b), (c), (d), (e), (f) and (
G) At least one film-forming component selected from the group consisting of (b) Hydrogenated vegetable oils (c) Hardened animal oils (d) Waxes (e) Beeswax (f) Ester gum (g) Water-insoluble binder (b) The following (a), (b), (c), (ni) ), (E), and (F), at least one component that imparts pH dependence to the film-forming component in item (a) above. (a) Aminocelluloses (b) Aminoacetates ( c) Vinylamines (d) Chitosan (e) Metal hydroxides (f) Alkaline earth metal salts.