JPS6398359A - Feed additive composition for ruminant - Google Patents

Abstract

PURPOSE:To obtain a feed additive composition for ruminants containing an active substance being effectively digested and absorbed in digestive organs in and after the fourth stomach, by coating a nucleating agent containing a salt of a basic amino acid and a carboxylate with a specific synthetic high polymer. CONSTITUTION:A basic amino acid such as lysine, arginine, histidine, etc., and an alkali metallic salt or an alkaline earth metallic salt of a carboxylic acid such as acetic acid, propionic acid, lactic acid, etc., are used as a nucleating agent to prepare a feed additive composition for ruminants in any shape, containing a physiologically active substance. then 100pts.wt. composition is coated with 10-200pts.wt. covering agent consisting of a synthetic high polymer such as a copolymer of 2-vinylpyridine and styrene, which is dissolved in water or swelled in an acidic range of pH <=5.

Description

Detailed Description of the Invention (Industrial Application Field) The present invention relates to an additive composition for ruminants, and more specifically, when an amino acid is orally administered to a ruminant animal, the amino acid is degraded in the rumen of the animal. The present invention relates to a feed additive composition for ruminants that is protected from the abomasum and is digested or absorbed with high efficiency in the gastrointestinal tract from the abomasum onwards.

In ruminant animals, a large portion of protein amino acids in feed is generally broken down into ammonia and carbon dioxide gas by microbial fermentation in the rumen, and the original biological activity is lost. Bacteria and Protocia within the rumen utilize ammonia for their own growth and multiplication, and the microbial proteins that are formed are transported to the abomasum, which corresponds to the stomach of monogastric animals, and are partially stored in both chambers. This process is completed in the small intestine, where it is absorbed.

(Conventional techniques and their problems) Therefore, in order to increase absorption efficiency in the small intestine and suppress decomposition in the rumen, there is a method of coating the core of basic amino acids such as lysine with various coating agents. have been proposed, but in either case, a mineral salt of a basic amino acid (typically hydrochloride) is used as a nucleating agent (Japanese Patent Application Laid-open No.
ty, -ubg Koko Publication, JP-A-6/-ggg'73
Publication No.).

However, when a mineral acid salt such as a hydrochloride of a basic amino acid is selected as a source of a basic amino acid, there are many problems in the manufacturing process. For example, L-IJ
The use of L-lysine-hydrochloride as a resin source is likely to cause this material to corrode metals during the manufacturing process and wear out mixers when mixing raw materials.

Furthermore, as a coating agent, synthetic polymers such as cellulose propionate morpholinobutyrate or poly(vinylpyridine) are proposed in the above-mentioned publication, for example.

However, especially 1. - IJ resin hydrochloride has extremely high solubility in water (: IO at lS°C).

2 water paste O? The acidity of the solution and its saturation is pH 5,
, S', and pellets containing this material can be coated with a sensitive polymer such as cellulose propionate morpholinobutyrate or poly(vinylpyridine).
It cannot be prevented from eluting in the gastric environment, and the protection rate in buffer solutions corresponding to rumen fluid and the combination with basic substances such as buffered sium or magnesium hydroxide, which correspond to abomasum, are It is necessary (Unexamined Japanese Patent Publication No. 51-11-ttt, gyuφ
Publication No.).

In general, in order for feed to move smoothly through the stomach of ruminants and for efficient digestion and absorption, the specific gravity of particles containing biologically active substances must be lower than the specific gravity of gastric juice, that is, halogen. −
It is desirable that the contents of the rumen float on the surface or settle to the bottom of the rumen, as this will increase the residence time and, if used together with hardware, the specific gravity of the product as feed for ruminants. The problem was that it became too large. That is, in this case, the specific gravity of L-lysine hydrochloride! , 3, and the specific gravity of basic magnesium carbonate and magnesium hydroxide are λ, λ, and 3t, respectively, so they inevitably exceed 3 and remain in the lower part of the stomach. There is a concern that the residence time in the stomach may be longer than necessary.

(Means for Solving the Problems) The present inventors have made extensive studies to solve these problems, and have used a salt of at least one nonbasic amino acid and an alkali metal salt or an alkali carboxylic acid as a nuclear material. It has been found that it is extremely effective to use at least one earth metal salt. In other words, by using an alkali metal salt or an alkaline earth metal salt of carboxylic acid in combination, it is possible not only to prevent the elution of basic amino acid salts in the rumen environment, but also to prevent the elution of basic amino acid salts in the rumen environment. It is easier to adjust the specific gravity compared to .

Furthermore, when a salt of a long-chain carboxylic acid having 117 or more carbon atoms is used, it can also be expected to have an effect as a lubricant during molding.

The amount of carboxylic acid salts used in combination with basic amino acids is
The usual weight ratio to the basic amino acid salt is 0.0.2 to 2.
It is used in the range of 0 times, preferably in the range of o, or to cθ times.

If the amount used is too small, the protective effect in the abomasum will be small, and if the amount is too large, not only will the content of biologically active substances decrease, but also the biological effect in the abomasum will be reduced. It takes too much time to elute the active substance, which is undesirable.

Basic amino acids used in the present invention include amino acids such as lysine, arginine, histidine, ornithine, and hydroxylysine. Two or more of these basic amino acids may be used in combination.

Acids constituting basic amino acid salts include inorganic acids and organic acids, and examples of the inorganic acids include hydrochlorides and sulfates. Various carboxylic acids can be used as the organic acid.

There are many possible combinations of carboxylic acids used to form carboxylic acid salts of basic amino acids, alkali metals, and alkaline earth metals, but one carboxylic acid component that constitutes carboxylic acid salts is usually Carboxylic acids having about 2 to 2 carbon atoms are suitable. The carboxylic acid may be either saturated or unsaturated.

Further, the carbon chain of the carboxylic acid is not limited to a linear type, but may be a branched type, and may further have a substituent such as a hydroxyl group. Note that the carboxylic acid is not necessarily limited to monobasic acids, and polycarboxylic acids such as dibasic acids can be used.

Examples of carboxylic acids include acetic acid, glopionic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid, caproic acid, enanthic acid, caprylic acid, pelargonic acid, capric acid, lauric acid, tridecanoic acid, -monomethyltetradecanoic acid. , 5
-Methyltetradecane, 2-dimethyltetradecanoic acid.

Methyltetradecanoic acid, myristic acid, palmitic acid,
Aliphatic monocarboxylic acids such as stearic acid, aliphatic unsaturated monocarboxylic acids such as oleic acid, linoleic acid, and lylunic acid 7, malonic acid, succinic acid, fumaric acid, adipic acid, glutaric acid, azelaic acid, and sebacic acid. ,/,2
Aliphatic saturated and unsaturated dicarboxylic acids such as 0-eicosamethyl dicarboxylic acid, 2-hydroxy-gumethylmercaptobutyric acid, oxyacids such as lactic acid, citric acid, incitric acid, glycolic acid, malic acid, tartaric acid and the like. Further examples include aromatic carboxylic acids such as cinnamic acid and mandelic acid. Other examples include carboxylic acids such as alginic acid and pantothenic acid. Aspartic acid and glutamic acid are used as acidic amino acids.

Note that the above-mentioned carboxylic acid salts do not necessarily have to be used alone; a mixture of two or more carboxylic acid salts having different carboxylic acid components and counter-cation components constituting the carboxylic acid salts can also be used.

Carboxylic acid salts can also be used even if they have water of crystallization.

These basic amino acids and inorganic acids, carboxylic acids and/or
Alternatively, salts with acidic amino acids can be used as a nucleating agent and as a source of amino acids.

Specific examples include L-IJ resin hydrochloride, sulfuric acid/com-lysine salt, L-lysine-L-aspartate, L-lysine-L-glutamate, L-lysine acetate, L-lysine propionate, L-lysine lactate, L-lysine tartrate, L-lysine butyrate, fumaric acid comb-lysine salt.

Succinic acid 2L-lysine salt, L-lysine valerate, r,
-IJ resin uhydroxy-gu methyl mercaptobutyrate, L-lysine citrate, L-lysine caproate, L-lysine caprylate, L-lysine cinnamate, L-
Lysine caprate, L-lysine laurate, L-lysine palmitate, L-lysine stearate, L-
Examples include arginine hydrochloride, L-arginine-L-glutamate, and L-histidine hydrochloride.

A convenient method for preparing carboxylic acid salts of basic amino acids is to carry out a neutralization reaction in the presence of water or an organic solvent at room temperature or under heating conditions. It is also possible to carry out the reaction without a solvent. The salts obtained by these reactions may be used alone, but may also be used as other antibiotics or nutritional agents.

Of course, it is also possible to use it in combination with biologically active substances such as veterinary drugs. The biologically active substance that can be used in combination with basic amino acids in the present invention can be administered to animals, especially ruminants, to increase body weight, increase milk production, prevent disease, or be degraded by microorganisms present in the therapeutic solution. Targets substances that are easily deactivated. As a biologically active substance,
Amino acids such as methionine, threonine, and tryptophan; N-acyl amino acids such as N-stearoylmethionine and N-oleylmethionine; calcium salts of N-hydroxymethylmethionine; amino acid derivatives such as lysine hydrochloride; Hydroxy homologues of amino acids such as butyric acid and its calcium salts, proteins such as feather powder, fishmeal bed, casein, potato protein, vitamin A1, vitamin A-acetate, vitamin palmitate, vitamin D
3. Vitamins such as vitamin E, nicotinic acid, nicotinic acid amide, calcium pantothenate, and β-carotene, enzymes such as acid protease, carbohydrates such as glucose, antibiotics such as penicillin and tetracycline, and anthelmintics such as levamisole. , Negufuon, and other veterinary medicines. These may be used alone or in combination.

These nucleating agents are usually substances that are biologically acceptable to ruminants as feed additives, such as binders for granulation, excipients, disintegrants, and various additives for adjusting specific gravity. For example, it is convenient to use them in combination.

For example, binders include polyvinylpyrrolidone, hydroxypropylcellulose, polyvinyl alcohol, gum arabic, guar gum, sodium alginate, sodium cellulose glycolate, sodium polyacrylate, and excipients include lactose, mannitol, and crystalline cellulose. Disintegrants include potato starch, cornstarch, carboxymethyl cellulose calcium,
It may contain carboxymethyl cellulose, crystalline cellulose, various additives for adjusting specific gravity, etc.

In addition, there are binders, excipients, disintegrants, and lubricants described in Pharmaceutical Manufacturing Methods (Part 1) Pharmaceutical Development Basic Course X1 (pp133-/1 da) K published by Jirokushokan.

Known additives such as coloring agents, flavoring agents, and flavoring agents can be used as necessary.

The rate of use of coating agents on the core containing salts of basic amino acids and inorganic acids, carboxylic acids or/and acidic amino acids is such that the substance remains stable during extended residence times in the rumen of ruminants. It is necessary to protect and elute the nuclear material quickly within a relatively short residence time in the abomasum, and the size of the particles to be coated and the type of coating used are important. The amount required varies depending on the
Usually, it is used in a range of 10 to 100 vrt%, preferably 15 to 15 gowt% of the particles before coating.

The coated particles used in the present invention must be suitable for oral administration to ruminants.

Therefore, the diameter of the coated particles is 0.02 - 10 mm, preferably 0.5 mm. The proportion of particles that are crushed during this process increases, which is undesirable.

In addition, the coated particles are designed to shorten their residence time in the rumen.1. It is preferable to adjust it between θ and firmness. The specific gravity varies depending on the type of nuclear material.

In order to adjust the specific gravity, to make it lighter, K can be made of glass balloons or microscopic hollow glass spheres, and to make it heavier, metal oxides and carbonates, which are accepted by ruminants as inert inorganic substances, can be used. used.

To produce the composition of the present invention, a salt of a basic amino acid, a carboxylic acid salt, and additives such as an excipient and a disintegrant are added as necessary, and the mixture is first dry mixed. Water or ethyl alcohol in which a binder is dissolved is added to this, and particles of an appropriate size are formed using a centrifugal flow coating device. Next.

Drying is usually carried out at a temperature range of 30 to 2 hours.

It is stable under weakly acidic to weakly alkaline conditions corresponding to the gastric juice in the rumen of ruminants, but disintegrates and swells under strongly acidic conditions corresponding to the gastric juice in the abomasum (swelling here refers to This means that during the time that the particles remain in the abomasum, they swell to such an extent that they can pass through the synthetic polymer membrane that covers most of the basic amino acid salts and elute. Examples of substances having this include benzylaminomethylcellulose, dimethylaminomethylcellulose,
piperidylethyl hydroxyethyl cellulose, cellulose acetate diethylamino acetate, cellulose acetate dibutylamino hydroxyglobyl ether, ethylcellulose-N,N-shetylaminohydroxyglobyl ether, ethylcellulose viridino hydroxyglobyl ether, diethylaminomethylcellulose, piperidylethylhydroxyethylcellulose,
Cellulose derivatives such as.

N,N-diethylvinylamine rubinyl acetate copolymer, vinylpiperidine rubinyl acetate copolymer,
Vinyldiethylamine rubinyl acetate copolymer, vinylbenzylamine-vinyl acetate copolymer, polyvinyldiethylaminoacetoacetal, polyvinylbenrivinyl acetal diethylamine acetate.

Acetate conductor such as.

Polydiethylaminomethylstyrene, polyjetanolaminomethylstyrene, polydimethylaminoethyl (meth)acrylate, dimethylaminoethyl acrylate tolmethyl (meth)acrylate copolymer, dimethylaminoethyl methacrylate tolmethyl (meth)acrylate copolymer , polyalkylvinylpyridine such as poly2methyl-S-vinylpyridine, polycoethyl-5-vinylpyridine, polygovinylpyridine, polygovinylpyridine, and polyvinylpyridine.

Vinylpyridine-styrene copolymers such as vinylpyridine-styrene copolymer, Hiro-vinylpyridine-styrene copolymer, two-ethyl-5-vinylpyridine-styrene copolymer,
: Vinyl alkylpyridine-styrene copolymers such as 1-methyl-5-vinylpyridine-styrene copolymers; vinylpyridine-acrylonitrile copolymers such as two-vinylpyridine-acrylonitrile copolymers.

Vinylethylpyridine-acrylonitrile copolymer, methylvinylpyridine-acrylonitrile copolymer, vinylpyridine-methylmethacrylate copolymer, Hiro-
vinyl pyridine-methyl methacrylate copolymers, such as vinyl pyridine-methyl methacrylate copolymers, -
of vinylpyridine or alkylvinylpyridine such as monovinylpyridine-butadiene copolymer, vinylpyridine-butadiene-styrene copolymer, vinylpyridine-styrene copolymer, 2-vinylpyridine-styrene-methyl methacrylate copolymer, etc. Polymers or copolymers with other vinyl compounds, N,N-dimethylaminopropyl(meth)acrylamide middle acrylonitrile copolymer, N,N-dimethylaminepropyl(meth)acrylamide middle styrene copolymer, N,N - Polyvinyl derivatives such as dialkylaminoalkyl methacrylamide middle acrylonitrile copolymer, vinylpyridine-acrylonitrile copolymer, methylvinylpyridine-acrylonitrile copolymer, and methylvinylpyridine-styrene copolymer.

Styrene - N,N-diethylethylenediamine derivative of dimethyl fumarate or styrene-maleimide copolymer, reaction mesh of terephthalic acid or maleic acid and N-n-butyljetanolamine, globylene glycol -
Examples include benzylamine adducts of maleic acid polyesters.

The coating material is a synthetic polymer that dissolves in water in an acidic region below pHjt, but it also contains anti-fusing agents such as talc, aluminum, mica, silica, stearic acid, aluminum stearate, and magnesium stearate. There is no harm in doing so.

The synthesis molecules for coating are usually used in a state dissolved in a solvent, but they may also be used in the form of an emulsion using an emulsifier.

Suitable solvents for coating include methylene chloride, chloroform, isopropanol, ethyl alcohol, methyl alcohol, ethyl acetate, acetone, methyl ethyl ketone, toluene or mixtures thereof.

At the time of coating, the raw materials for coating may be supplied in a state in which anti-fusing agents and the like are suspended, or they may be supplied separately in a shredded form.

Various methods are known for coating granules, and for example, any of the general coating methods such as centrifugal granulation coating, fluid coating, and pan-coating may be used. In addition, chemical modification methods,
Microencapsulation methods are also conceivable.

Ruminants are typically, but not limited to, cows, sheep, or goats.

(Example) Below are five representative examples of the method of the present invention,
This will be explained more specifically. Note that these are merely examples, and the present invention is not limited in any way by these examples.

In order to be useful and practical as a feed additive for ruminants, it is believed that the amino acids or amino acid salts in the coated particles of the present invention must be released upon shaking. Therefore, the following examples were evaluated according to the above-mentioned criteria.

[Example 1] [Granulation] L-lysine-hydrochloride 3y-, calcium stearate? , /7. A substantially homogeneous mixture was obtained by mixing polyvinylpyrrolidone (K--20=qo)s,of in a mortar. Add 139% of water to this powder mixture.
was added little by little and kneaded well to form a putty.

Extrude this using an extruder with a hole diameter of 2 mm,
By cutting, cylindrical pellets with a diameter of about 1,000 kg were obtained. The pellets were rolled into marmerizer balls, dried at room temperature for 3 hours, and then placed in a hot air circulation constant temperature bath for t.
Dry in OC for 5 hours. Sift the dried pellets.

g-9 mesh (:1. o o -s, 3t rtmφ
) were obtained.

[Preparation of coating liquid and coating of particles] Copolymer of govinylpyridine and styrene in a weight ratio of 70 to 30 (
0 in ethanol. ! Reduced viscosity at ff/di: ηsp/
c = 0. 5) aoy-, aluminum powder 32.
Ethyl alcohol boy was added to a mixture of 3 F-, 3 U of talc powder, and 5 S's stearic acid ty, and the mixture was stirred at room temperature for 3 hours to prepare a coating liquid. Example 1
Coating was performed in the same manner as above until the weight of the coating layer became JO,/wt% of the entire coated particles.

[Elution test]

The coating of particles with L IJ resin hydrochloride as a nucleating agent was retained after shaking for 2'1 hour at 39 C in a Madougall buffer solution corresponding to the rumen juice of a ruminant.
J resin hydrochloride was q s, o %.

Further, when the mixture was shaken at 39° C. for 2 hours in a C1ark Lubs buffer solution corresponding to abomasal juice, too much of the L-IJ resin hydrochloride was eluted. This indicates that this pellet is useful as feed for ruminants.

[Example]

L-lysine-hydrochloride 3? , sodium stearate?
,/? , polyvinylpyrrolidone (K-qo)s, oy,
A nearly homogeneous mixture was obtained by mixing 9 ml of microcrystalline cellulose in a mortar. Add water to this powder mixture/<Z? was added little by little and kneaded well to form a putty. This was granulated in the same manner as in Example/, and g-9 mesh (YU, 00-U, 3
gmφ) were obtained.

Copolymer with rylate, Rohm Pharma (West Germany)] 30y-, aluminum powder, ? 5? , talc powder 3S? Ethyl alcohol t and oy-q were added to the mixture and stirred at room temperature for 3 hours to prepare a coating liquid.

Using this coating liquid, the weight of the coating layer was 30% of the total coated particles. Coating was carried out until 1 wt%.

The thus obtained particle coating using L-lysine hydrochloride as a nucleating agent was subjected to JqC in McDougall buffer solution.
The L-lysine-hydrochloride retained after shaking for = q hours was 9 to 1I%. Further, when the mixture was shaken in C1ark Lubs buffer solution at 39°C for 1 hour, L-lysine-hydrochloride was eluted at 0.00%.

This indicates that the pellets are useful as feed for ruminants.

[Example 3] L-lysine acetate 50? , calcium laurate 10
f, silica powder 20y-, polyvinylpyrrolidone (K-
qo)2. A nearly homogeneous mixture was obtained by mixing the sl in a mortar. To this powdery mixture, 9.51 g of water was added little by little and kneaded well to form a putty. This was granulated in the same manner as in Example 1 to obtain pellets in the range of 1 g-9 mesh (2, OO-U, 3 gM 11φ).

Coating was carried out using the same solution as in Example/1 until the weight of the coating layer was 1 wt % J O of the entire coated particles.

1, - The coating of particles with IJ lysine acetate nucleating agent as M
The amount of L-lysine acetate retained after shaking for an hour with jqc in cdougall buffer was 90%.

In addition, 3% at 39°C in C1ark Lubs buffer solution.
After shaking for hours, 9 g of L-lysine acetate was eluted.

[Example G]

A similar experiment was conducted in Example 3 except that the polymer in the coating slurry was changed from a copolymer of gouvinylpyridine and styrene to a copolymer of vinylpyridine and styrene.

Copolymer of vinylpyridine and styrene in a weight ratio of 0:30 (reduced viscosity at 0.5fldi in ethanol: ηaV'c -0,'l) 3of, aluminum powder 32. ! ethyl alcohol 6θ in a mixture of 9f-talc powder 3Jy-, stearic acid 51? was added and stirred at room temperature for 3 hours to prepare a coating solution. Coating was carried out in the same manner as in Example/1 until the weight of the coating layer became 9.9 wt % of the entire coated particles.

Mc
There was 990 g% of I, -IJ lysine acetate that was retained after shaking for a ladder hour at 39° C. in Dougall's buffer solution. Also, at 39°C in C1ark Luba buffer solution.
After shaking for 3 hours, LIJ lysine acetate gaO was eluted.

[Example S]

L-lysine acetate 100g, talc 20.0? , Microcrystalline Cellulose J Of.

A nearly homogeneous mixture was obtained by mixing the sodium fibrous glycolate 109 in a mortar.

Water to this powder mixture: 1! ;9- was added little by little and kneaded well to form a putty. This was granulated in the same manner as in Example/, and g-9 mesh (s,
Pellets in the range of o o −s, 3 g exφ) were obtained.

Using the same coating solution as in Example 1, coating was carried out until the weight of the coating layer became 9.3 wt% of the entire coated particles.

1. - The coating of particles using IJ resin acetate as a nucleating agent is M
The fcL-IJ resin acetate is kept at 39 °C in cDougall buffer solution after shaking for a cog period.

There were many. In addition, when shaken for 2 hours at J9C in C1ark Luba buffer solution, the L-IJ resin acetate was ioθ-extracted.

[Example 6] L-lysine malate [Lye: malic acid-U: /
(mol/mol) ]56.0? , polyvinylpyrrolidone (K-qo): 1.32 sodium stearate/j,! i. Microcrystalline cellulose/3LiF was mixed in a mortar to obtain a substantially homogeneous mixture. Add water to this powder mixture? was added little by little and kneaded well to form a putty. This was granulated in the same manner as in Example 1 to form a g-9 mesh (=, o o
- J g - φ) were obtained.

Furthermore, the weight of the coating layer was 29,'l vt% of the total coated particles with the same coating liquid as in Example/.
The coating was carried out until it became .

The particle coating using L-lysine malate as a nucleating agent is M
The malate of L-lysine retained after shaking for 2 hours at 39C in Edoug B11 buffer solution was 9. Also, in C1ark Lubs buffer solution?
When shaken for 3 hours at qC, malate of L-lysine is g
g, i% eluted.

-27= [Example] L-lysine glutamate s OP, calcium acetate i'o, o1. Polyvinylpyrrolidone (K-qo)
A substantially homogeneous mixture was obtained by mixing s, 09- in a mortar. Water 107 was added little by little to this powdery mixture and kneaded well to form a putty. Granulation was carried out in the same manner as in Example 1, yielding 95% yield Tel-9 mesh (2,
A pellet having a diameter of 00-:2,31 mm was obtained. It was coated in the same manner as in Example/, and the weight of the coating layer was 2? , 7 wt%.

The glutamate of L-lysine that was retained after shaking the particles with glutamate of L-lysine as a nucleating agent in Madougall buffer solution for a long time with YQC was 97.
．． It was 9%. Also +C1arkLub@ in buffer solution? ? After shaking for hours at 10°C, qq% of L-lysine glutamate was eluted.

[Example g]

L-lysine aspartate 30y-1 calcium acetate/0.01i1-, polyvinylpyrrolidone (K-9
0) 5.Off was mixed in a mortar to obtain a substantially homogeneous mixture. 10 f of water was added little by little to this powdery mixture and kneaded well to form a putty. Example 1
Granulate in the same manner as g-9 mesh:x-(2,0o
-x, 3 g rranφ) were obtained.

Coating was performed in the same manner as in Example 1 until the weight of the coating layer became 9.6 wt % of the entire coated particles.

After shaking the particles coated with L-lysine aspartate as a nucleating agent at 39° C. in Madougall's buffer solution for 21 hours, the L-lysine aspartate retained was 100%. Further, when the mixture was shaken in a C1ark Lubl buffer solution at 39° C. for several hours, 100% of the aspartate of L-lysine was eluted.

[Example 9] L-lysine-hydrochloride') 3f, sodium acetate 209-
, microcrystalline cellulose/4'2, polyvinylpyrrolid 7 (K-qo)3. A nearly homogeneous mixture was obtained by mixing Of in a mortar. Water was added little by little to this powdery mixture and kneaded well to form a putty.

This was granulated in the same manner as in Example/1 to obtain pellets in the range of 1 g-9 mesh (2,00-2,3 grrrmφ).

Using the same coating solution as in Example %i, coating was carried out in the same manner as in Example/until the weight of the coating layer reached 7 o,avt% of the total coated particles.

Mc
96.9% of the l,-IJ lysine salt was retained after shaking for a cog hour at 39 °C in Dougall's buffer solution.

In addition, 3% at 39°C in C1ark Lubs buffer solution.
After shaking for an hour, I and IJ lysine salts/00.0% were eluted.

[Example IQ-/Y]

L IJ lysine hydrochloride 3oz, carboxylic acid calcium salt 61. A nearly homogeneous mixture was obtained by mixing talc/OA; f, polyvinylpyrrolidone (K-qo)t, and sf/ in a mortar. Add 1 liter of water and O to this powdered mixture.
Add the ingredients little by little and knead well to form a putty. This was granulated in the same manner as in Example 1 to obtain pellets in the range of 1g-9 mesh (YU, 00-YU, 3gMφ).

Using the same coating solution as in Example 1 and using the same method as in Example 1, the weight of the coating layer was 30.0% of the total coated particles. Covering was carried out until it reached Owt level.

[Elution test]

M
L-IJ lysine hydrochloride which was retained after shaking for a cog period at 39'C in cdougall buffer solution and C1ar
The amount of L-lysine-hydrochloride eluted during shaking at 39° C. for 3 hours in the k Lubs buffer solution was as shown in Table 1.

[Example 13] L-lysine-hydrochloride so y, succinic acid disodium salt Sψ, talc 22.3 fP, polyvinylpyrrolidone (
'K -90) 2. A homogeneous mixture was obtained by mixing SP in a mortar. Add water to this powder mixture/
2. Add Of little by little and knead well to form a putty. This was granulated in the same manner as in Example 1, and g-
A pellet with a range of 9 mesh Cx, oθ-1, 31 frMLφ) was obtained.

Using the same coating solution as in Example 1, coating was performed in the same manner as in Example 1 until the weight of the coating layer became 30.3 wt% of the entire coated particles.

Mcd coating of particles using L IJ resinate as a nucleating agent
The L-lysine salt that was kept at 39°C in Ougall's buffer solution for several hours after shaking was flathead. Also, C
When the mixture was shaken in a 1ark Lubs buffer solution at 39° C. for 2 hours, L-lysine salt was eluted in ioo and θ.

[Comparative Example 1] A substantially homogeneous mixture was obtained by mixing L-lysine hydrochloride lθoy-microcrystalline cellulose/05+- and gum arabic Oy- in a mortar. 35 g of water was added little by little to this powdery mixture and kneaded well to form a putty.

This was granulated in the same manner as in Example 1 to obtain particles in the range of g-9 mesh (s, o o -2,3 grmφ).

Copolymer with 9-vinylpyridine and styrene in a 70:30 ratio (reduced viscosity reaction at 0.!/di in ethanol: η
sp/c-θ, ri5) 3θ? , aluminum powder 3.2
．． Ethyl alcohol in a mixture of j 1il-, talc powder, 72J jil-, stearic acid 5Z! -02 was added and stirred at room temperature for 3 hours to prepare a coating liquid. Coating was performed in the same manner as in Example 1, and the weight of the coating layer was 30% of the total particle size. Coating was carried out with 1 which becomes Qwt circulation.

[,-IJ The particle coating using lysine hydrochloride as a nucleating agent is
At 39C in Cdougall buffer solution, only 250% of L-IJ lysine hydrochloride was retained after shaking for 1 hours; The salt was eluted at t00%.

[Comparative example U]

L-lysine-hydrochloric acid 1 boy, polyvinylpyrrolid 7 (K
-qo)sy, MercktOf, ethyl alcohol isl
The mixture was added little by little and kneaded well to form a putty. This was granulated in the same manner as in Example 1, and g-9 mesh (
, 2, OO-U, 3 If關φ) were obtained.

The coating suspension was coated with the same coating suspension as used in Example 1, and the weight of the coating layer was 30% of the total coated particles.
．． It was coated with 1 to give 0 wt%.

L-lysine salt in McDougal 1 buffer solution 39
After shaking for 2 hours at °C, only 2g, θ% was retained. 700.0% of the L-lysine salt was leached out by shaking in C1ark-Lubs buffer solution for 1 hour at 39'C.

= 35- [Test method] Add the ruminant nutrient 19- obtained in the example to an Erlenmeyer flask with a content grade of 300-. , C1ark-Lubs artificial gastric juice,
Add 2 oomt each and incubate for -min at tIcrrI in a constant temperature bath at 39±O, SC. It was shaken while applying reciprocating vibration / times.

In Madougall's mild solution, after 2 hours, C1ar
In the kLubs buffer solution, the elution rate of the basic amino acid salt after 3 hours was determined using high performance liquid chromatography.

*I McDaugall buffer solution magnesium hexahydrate o, 1 otl, calcium chloride o
, o, and ty were dissolved in 1/1 water and saturated with carbon dioxide gas to adjust the pH (pHt,,g).

*2 C1ark-Lubs buffer solution 0.2N potassium chloride 50- and 0.2N hydrochloric acid/0. /, - is water /39. '1 m was added and adjusted (pHs, o).

(Effect of the invention) By using a specific substance as a nucleating agent, basic substances such as basic magnesium carbonate and magnesium hydroxide are not required. Therefore, the additive of the present invention has a lower specific gravity than conventional known additives, and the protection in the rumen is improved.

In other words, the specific gravity of a feed additive made by coating an amino acid salt with a coating agent is determined not only by the amino acid salt as a nucleating agent but also by
Although it varies depending on the composition of the drug to be treated, it is possible to reduce the specific gravity of the additive.

This means that the specific gravity of the coated particles can be controlled to be small.

As a result, as described above, the effective utilization rate of the coated particles can be increased.

Claims (6)

[Claims] (1) At least one type of polymer that dissolves or swells in water in an acidic region of pH 5 or less, with a core containing at least one kind of basic amino acid salt and an alkali metal salt or alkaline earth metal salt of a carboxylic acid. A feed additive composition for ruminants coated with a coating agent. (2) The carboxylic acid is a compound selected from the group consisting of acetic acid, propionic acid, lactic acid, succinic acid, fumaric acid, citric acid, lauric acid, palmitic acid, and stearic acid. The animal feed additive composition according to item 1. (3) The coating material is a copolymer of dimethylaminoethyl methacrylate and (meth)acrylic acid alkyl ester, or 2-methyl-5-vinylpyridine, 2-vinylpyridine, 4-vinylpyridine, 2-vinyl-6 - A combination of vinylpyridine selected from the group of methylpyridine and 2-vinyl-5-ethylpyridine and an acrylic compound selected from the group of (meth)acrylic acid alkyl ester, (meth)acrylic acid, and acrylonitrile, or styrene. The animal feed additive composition according to claim 1, which is a polymer. (4) The ratio of coating agent used is 10 to 2 parts by weight per 100 parts by weight of the core.
00 parts by weight of the animal feed additive composition according to claim 1. (5) Claim 1 in which the ruminant is a cow, sheep, or goat
The animal feed additive composition described in Section 1. (6) the basic amino acid salt is an amino acid hydrochloride selected from lysine, arginine, histidine, ornithine;
Claim 1, characterized in that the salt is a carboxylate, aspartate, or glutamate selected from acetate, butyrate, fumarate, valerate, laurate, palmitate. An animal feed additive composition.