JPH0789876B2 - Feed additives for ruminants - Google Patents

Description

Description: FIELD OF THE INVENTION The present invention relates to a ruminant feed additive, and more particularly to protecting a biologically active substance from ruminant rumen fluid of a ruminant, The present invention relates to a feed additive in which a biologically active substance is coated with a protective substance film so as to be released in the digestive organs after the stomach.

The feed additive for ruminants of the present invention can be effectively absorbed into ruminants by being added to concentrated feed or the like and orally administered to ruminants such as cattle and sheep.

[Conventional technology]

As a method of orally administering a biologically active substance such as an amino acid to a ruminant, in order to protect the biologically active substance from fermentation degradation by microorganisms present in the rumen of the ruminant, a biologically active substance is used. The method of administering a granulated preparation in which the above is dispersed in a matrix of a protective substance is used.

For example, a preparation in which a biologically active substance is dispersed and granulated in a matrix such as fat or wax is disclosed in JP-A-56-15.
It is disclosed in Japanese Patent No. 4950.

The inventors of the present invention also disclosed a formulation in which a biologically active substance is dispersed in a matrix of a protective substance consisting of chitosan and an aliphatic monocarboxylic acid and / or a hardened oil and fat, as disclosed in JP-A-58-175449. Proposed and launched.

Furthermore, a preparation prepared by coating a granule of a biologically active substance with a film that is sparingly soluble in neutral to alkaline water and easily soluble in acidic water is disclosed in JP-A-59-198946. Disclosed.

[Problems to be solved by the invention]

Dispersing biologically active substances in a matrix of protective substances,
In granulated preparations, the biologically active substance is distributed on the surface of the drug product. Therefore, if the rumen animal rumen bypassability is emphasized, the biologically active substance content should be 40% or less. It needs to be suppressed. In addition, in a preparation in which granules of a biologically active substance are coated with a protective substance, it is possible to increase the content rate of the biologically active substance. Residence time in the stomach
Since it is as long as 24 to 48 hours, the preparation is softened and crushed by the contents, and the pH of the rumen gastric juice has individual differences, so that the bypass property of the rumen is reduced.

The present invention provides a feed additive for ruminants having a high content of a biologically active substance, and excellent release properties in the digestive organs after rumen bypass and abomasum. To aim.

[Means for solving problems]

The present inventors, as a result of intensive studies to achieve the above-mentioned object, a coating agent consisting of a conventional protective substance, a hydrophobic substance that has been used, and a pH-dependent substance that dissolves in an acidic range of pH 5 or less, The present invention has been completed by finding that a preparation having a multilayer coating of a core containing a biologically active substance as a main component has excellent rumen bypass properties.

The present invention provides a nucleus containing a biologically active substance with 12 carbon atoms.
At least one hydrophobic substance selected from the group consisting of linear or branched saturated or unsaturated aliphatic monocarboxylic acids having -24, hydrogenated vegetable oils, hydrogenated animal oils and waxes And a feed additive for ruminants, which is obtained by multi-layer coating with a coating agent containing at least one pH-dependent substance that dissolves in an acidic region of pH 5 or less at different ratios.

In the present invention, the biologically active substance is not particularly limited as long as it is administered to a ruminant and gives physiological activity, but when orally administered, it is fermented and decomposed by the microorganisms present in the rumen. Easy substances are targeted.

For example, amino acids such as methionine, lysine, tryptophan, N-acyl amino acids such as glutamic acid and aspartic acid, and their derivatives, vitamin A, vitamin A.
Examples include derivatives, vitamins such as vitamin D ₃ and vitamin E, and other animal drugs.

The core containing the biologically active substance is a mixture of the biologically active substance, an excipient, and a binder, and a mixture obtained by further adding and mixing an inorganic substance and the like, if desired, with a particle size of 0.4 to 2.0 mm. Is a solid material formed into a granular shape, preferably a shape close to a sphere.

The method for producing the core of the biologically active substance is not particularly limited, but it can be produced, for example, by pelletizing the mixture using an extrusion device and then spheroidizing using a spheronizing device.

As a binder, a cellulose derivative such as methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, or a vinyl derivative such as polyvinyl alcohol or polyvinylpyrrolidone,
Starch, fatty acid, hydrogenated vegetable oil, hydrogenated animal oil and the like can be used.

Starch, microcrystalline cellulose and the like are used as excipients.

Further, calcium carbonate, calcium phosphate, talc, etc. are used as the inorganic substance.

The coating material that coats the core containing the biologically active substance as a main component is composed of a hydrophobic substance and a pH-dependent substance.

The hydrophobic substance is the main component of the protective substance that protects the biologically active substance from the fermentation decomposition of the microorganisms present in the rumen of the ruminant, and has a saturated or branched chain having 12 to 24 carbon atoms. Alternatively, it is selected from the group consisting of unsaturated aliphatic monocarboxylic acids, hardened vegetable oils, hardened animal oils and waxes.

As the aliphatic monocarboxylic acid, palmitic acid, stearic acid, oleic acid, lauric acid, etc. can be used. Hardened castor oil, hardened soybean oil, hardened rapeseed oil, etc. are used as hardened vegetable oil, 54 hardened beef tallow, extremely hardened beef tallow, etc. are used as hardened animal oil, and beeswax, carnauba wax, whale wax, etc. are used as wax and wax. It

The pH-dependent substance is selected from substances that are hardly soluble in the rumen gastrointestinal fluid pH 5 to 8 and easily soluble in the digestive fluid of the digestive organs after the abomasum, pH 5 or less, usually 3 or less.

These pH-dependent substances include chitosan and polyvinyl acetal diethylaminoacetate (AEA Sankyo Co., Ltd.).
Commercially available products such as aminoacetates, dimethylaminoethylmethacrylate, copolymers of methylmethacrylate and butylmethacrylate (tradename of Euradid E. Sankyo Co., Ltd.), and the like, and polyacrylic acid derivatives can be used.

In the coating agent, the mixing ratio of the hydrophobic substance and the pH-dependent substance varies depending on the physical properties of the biologically active substance, particularly the water solubility, but usually the hydrophobic substance / pH-dependent substance = 100 / 1- 100/10
It is 0 (weight basis).

As the pH-dependent substance, a solid substance that is not compatible with the hydrophobic substance, for example, when using chitosan or the like dispersed in the hydrophobic substance, the particle size of the pH-dependent substance is preferably smaller, and more preferably, It is about 2 to 3 μm or less.

The feed additive of the present invention is a preparation in which the core containing the biologically active substance as a main component is multi-layer coated with the coating agent.

The content of the pH-dependent substance in the coating layer may be within the above range for each layer, but at the contact portion between the core mainly containing the biologically active substance and the coating layer, the coating layer PH inside
It is preferable that the content of the addictive substance is high, while on the other hand, in the surface layer of the coating agent that comes into contact with the rumen gastric juice, the content of the addictive substance is preferably low. In addition, biologically active substances
When it is water-soluble, it is preferable that the content of the pH-dependent substance in the coating agent is low. Conversely, when the biologically active substance is poorly water-soluble, the content of the pH-dependent substance is Higher is preferable.

In this way, a coating agent having a different content of a pH-dependent substance, which is coated on the core containing a biologically active substance as a main component, is used to form a multilayer coating of the core by using a coating agent having a different content of the pH-dependent substance. It is easily obtained by performing.

The method of coating the core containing a biologically active substance as a main component is not particularly limited, and for example, a method of spray-coating a molten liquid or a molten slurry of the coating agent on the core can be adopted.

The coating amount of the core with the coating agent is 5 to 3 with respect to 100 parts by weight of the core.
It is 0 part by weight, preferably 10 to 30 parts by weight.

[Action]

The present invention, as described above, is a granular preparation in which a core containing a biologically active substance as a main component is coated with a coating agent composed of a hydrophobic substance and a pH-dependent substance in multiple layers. It is a feed additive for ruminants.

In the present invention, the hydrophobic substance in the coating layer acts as a protective substance for preventing the fermentation decomposition of the biologically active substance in the nucleus by the microorganisms present in the rumen of the ruminant, and the pH-dependent substance is , It acts as a release-controlling agent that releases biologically active substances in the nucleus in the digestive organs of the ruminant after the abomasum.

In particular, by coating the core in multiple layers, the coating amount decreases,
Not only does the content of the biologically active substance in the formulation increase, but the ratio of the hydrophobic substance and the pH-dependent substance of the coating agent is changed according to the physical properties of the biologically active substance. It is possible to control the rumen bypass property and the release property in the digestive organs after the abomasum. Furthermore, when performing multi-layer coating of the core, each coating layer having a different ratio of the hydrophobic substance and the pH-dependent substance can be formed, so that the above effect can be further improved.

〔Example〕

The present invention will be described in more detail with reference to Examples and Comparative Examples.

However, the scope of the present invention is not limited to the following examples.

(1) Preparation of ruminant feed additive (a) Production of methionine-containing nuclear material (M-1) Methionine crystal powder (1,800 g) and calcium carbonate (200 g) were charged in a kneader and methylcellulose (binder) 0.7 g
Was dissolved in 70 g of water and kneaded. The resulting kneaded product was extruded using a 0.9 mmφ opening screen, then spheroidized using a Marumerizer, and dried with hot air to obtain spherical granules. The granules were sieved with a 12 mesh and a 20 mesh sieve to obtain a methionine-containing nuclear material (M-1).

(B) Production of lysine-containing nuclear material (L-1) 205 g of lysine hydrochloride, 15 g of calcium carbonate and 80 g of hydrogenated rapeseed oil were charged into a Henschel mixer, and the tank wall was heated to 90 ° C. and stirred.

While continuing to stir, 93 g of lysine hydrochloride and 7 g of calcium carbonate
The mixed powder of and was added in several divided portions to give sprinkled spherical granules to the growing granules. The obtained granules were sieved to 12 to 20 mesh to obtain a nuclear material (L-1) having an average lysine hydrochloride content of 70.2% by weight.

(C) Coating of nuclear material The nuclear materials (M-1) and (L) prepared in the above (1).
Using -1) as a hydrophobic substance, hydrogenated rapeseed oil or extremely hardened oil and a coating agent comprising chitosan or polyvinyl acetal diethyl acetate (AEA) as a pH-dependent substance were subjected to multilayer coating by a flow method.

The composition of the coating agent and the number of coating layers are shown in Table 1.

(2) Dissolution test of biologically active substance 2 g of the preparation prepared in the above (1) was immersed in 200 cc of Mc Dougall's artificial gastric juice corresponding to the rumen gastric juice of cattle, and the solution was placed at 37 ° C for 24 hours. After shaking and holding for a period of time, the plate was immersed in 200 cc of Clark Lubs' pH 2 buffer solution corresponding to bovine abomasum gastric juice, and further shaken at a temperature of 37 ° C. for 4 hours.

Then, methionine eluted in Mc Dougall's artificial gastric juice and Clark Lubs buffer was quantified by the iodometric titration method, and lysine was quantified by the ninhydrin coloring method.

The dissolution test results are shown in Table 1 together with the comparative examples.

Mc Dougall's artificial gastric juice: sodium bicarbonate; 9.8g, potassium chloride; 0.57g, calcium chloride; 0.04g, disodium phosphate dodecahydrate; 9.30g, sodium chloride; 0.47g and sodium sulfate heptahydrate; 0.1
A solution of 2 g in water; pH 8.3 in 1 Clark Lubs buffer: 0.2 N potassium chloride; 50 ml, 0.2 N hydrochloric acid; 10.6 ml and water; 139.
4 ml of mixed solution [Effect of the invention] In the ruminant feed additive of the present invention, as shown in the above-mentioned Examples (see Table 1), the nuclear substance containing the biologically active substance was added to the protective substance. By multilayer coating with
In comparison with a monolayer-coated preparation (see Comparative Examples 1 and 3) in which the elution characteristics of the biologically active substance to the rumen-supporting liquid and the abomasum-supporting liquid and the hardness after immersion in the rumen-supporting liquid are almost the same, The amount of the protective substance coated is greatly reduced, and as a result, the content rate of the biologically active substance is improved and the cost is reduced.

On the other hand, in the preparation in which the nuclear substance was coated in a single layer with the same amount of the protective substance as that of the product of the present invention (see Comparative Example 2), the hardness after immersion in the rumen-supporting liquid was remarkably reduced, and The elution rate of biologically active substances is increased. This result suggests that the rumen bypass property of the biologically active substance is not obtained when the formulation is orally administered to ruminants.

The present invention provides a feed additive for ruminant animals, which has a high content of biologically active substances, is excellent in rumen bypass properties, and is low in cost. Is extremely significant.

Claims (3)

[Claims] 1. A nucleus containing a biologically active substance, having a carbon number of
At least one hydrophobic selected from the group consisting of linear or branched saturated or unsaturated aliphatic monocarboxylic acids having 12 to 24, hardened vegetable oils, hardened animal oils and waxes A feed additive for ruminants, which is obtained by coating a substance and at least one pH-dependent substance that dissolves in an acidic range of pH 5 or less in multiple layers with a coating agent containing different ratios. 2. The feed additive for ruminants according to claim 1, wherein the pH-dependent substance is chitosan / polyvinyl acetal diethylaminoacetate and / or a polyacrylic acid derivative. 3. The value of the hydrophobic substance / pH-dependent substance in the coating agent contacting the core containing the biologically active substance is lower than that of the coating agent contacting rumen gastric juice. Feed additive for ruminants according to the range (1) or (2).