JPS6188844A - Feed additive composition for ruminant - Google Patents

Abstract

PURPOSE:To provide the titled composition stable in the rumen of a ruminant and enabling the effective absorption of a biologically active substance in the abomasum, by coating the active substance with a coating agent composed of a specific component and a synthetic polymer soluble in water in acidic state. CONSTITUTION:The objective composition can be prepared by coating (A) a nucleus containing a biologically active substance (e.g. amino acid, vitamin, etc.) with (B) a synthetic polymer soluble in water in acidic state of <=5pH (e.g. polyvinyl acetal diethylaminoacetate) and (C) a component selected from fats, waxes, 14-40C (un)saturated aliphatic hydrocarbons, 14-32C (un)saturated aliphatic alcohols and 14-37C (un)saturated fatty acids.

Description

[Detailed description of the invention] Industrial applications The present invention relates to feed additive compositions for ruminants.

More specifically, the present invention relates to a feed additive composition for ruminants in which a biologically active substance is coated with a pH-dependent synthetic polymeric fat, a wax, a higher fat group 117J hydrocarbon, a higher aliphatic alcohol, or a higher fatty acid.

BACKGROUND OF THE INVENTION Conventionally, when biologically active substances, such as amino acids, are directly orally administered to ruminants, they are degraded by rumen fermentation by microorganisms present in the rumen of the ruminants, and their original biological activity is lost. Therefore, in order to increase absorption efficiency in the abomasum, many feed additive compositions that suppress decomposition in the rumen are being investigated.

For example, JP-A-48-12785 discloses a biologically active substance coated with a coating agent such as fat or wax and made into particles, and JP-A-58-175449 discloses a long-chain monocarboxylic acid. Alternatively, it has been shown that coating with a coating agent containing hydrogenated fat and chitosan, etc.
No. 46824 discloses that cellulose propionate is coated with morpholinobutyrate or the like.

However, in these inventions, those that have a strong protective effect in the rumen have a slow disintegration (elution) in the abomasum;
Those that disintegrate (dissolve) quickly in the abomasum tend to have a weak protective effect in the rumen, and it is thought that the gastrointestinal absorption of biologically active substances is insufficient.

Problems to be Solved by the Invention The present invention provides a feed additive composition for ruminants that is stable in the rumen and effectively absorbed from the digestive tract in the abomasum when a biologically active substance is orally administered to ruminants. It provides:

Means for Solving the Problems The present invention provides at least If of a synthetic polymer (hereinafter referred to as an acidic pH-dependent synthetic polymer) in which a core containing a biologically active substance is dissolved in water in an acidic range of pH 5 or less. ! and fats, waxes, saturated or unsaturated aliphatic hydrocarbons having 14-40 carbon atoms, saturated or unsaturated aliphatic alcohols having 14-32 carbon atoms, and saturated or unsaturated fatty acids having 14-37 carbon atoms. The present invention relates to a feed additive composition for ruminants, which is coated with a coating agent containing at least one component (hereinafter referred to as a second component).

As a p+ dependent synthetic polymer in the acidic range, it is water resistant in the neutral range.
Moisture-proofing materials, such as polyvinyl acecool diethylamino acetate, a copolymer consisting of dimethylaminoethyl methacrylate and at least one of an alkyl methacrylate and an alkyl acrylate;
A copolymer of 2-methyl-5-vinylpyridine and at least one of alkyl acrylate, alkyl methacrylate, methacrylic acid, and acrylic acid is used. Polyvinyl acetal diethylaminoacetate has a molecular fn of 3-150,000 and a nitrogen content of 1.
Those containing 0-5.5% (W/W), such as AEA, l(
A [trade name of both Sankyo Qsai] is preferably used.

The copolymer consisting of dimethylaminoethyl methacrylate and at least one of methacrylic acid alkyl ester and acrylic acid alkyl ester has a molecular weight of 15-50.
Eudragit E 100.12.5 containing 3-8% (W/W) nitrogen, e.g. copolymers of dimethylaminoethyl methacrylate, methyl methacrylate and butyl methacrylate.
CR5hm, a trade name of Pharma (West Germany)] is preferably used. 2-methyl-5-vinylpyridine and at least l f of an acrylic acid alkyl ester, a methacrylic acid alkyl ester, methacrylic acid and acrylic acid
An example of a copolymer consisting of ffl is MPM, which is a copolymer of 2-methyl-5-vinylpyridine, methyl acrylate, and methacrylic acid, with a molecular weight of 5,000 to 400,000 and a nitrogen content of 2 to 15% (W/W). -47〔
Tanabe tMx@ trade name] is preferably used.

Among the above-mentioned monomers 7-, the alkyl of the alkyl ester is straight or branched alkyl having carbon Vi1-8, such as methyl, ethyl, 1-propyl, n-butyl, and the like.

Next, in the second component, the fat used is beef tallow, hardened beef tuna, beef bone finger, hardened soybean oil, wood wax, etc., and the wax used is beeswax, carnauba wax, wax, etc.

Saturated or unsaturated aliphatic hydrocarbons having 1410 carbon atoms may be single components, but are usually mixtures such as paraffin wax, osikerite, ceresin, etc.
Examples of the saturated or unsaturated aliphatic alcohol of 4-32 include ceryl alcohol, mylinyl alcohol, etc.
Valmitic acid, stearic acid, montanic acid, melisic acid, valinaric acid, eleostearic acid, etc. are used as the saturated or unsaturated fatty acids for f1R14-37. These second components may also be used in combination.

The ratio of the acidic pH-dependent synthetic polymer to the second component in the coating material is preferably I:0.5-1:10 (weight ratio), particularly 1:1-1. When the latter (second component) is smaller than 1:0.5, biologically active substances such as amino acids are significantly eluted in the rumen and degraded by rumen fermentation. 1: If each person becomes aloof after 1O, the first
Although it is not eluted in the stomach, even if it enters the abomasum, the active substance is not eluted sufficiently and cannot achieve its purpose.

The coating material has a solid content, and contains the above-mentioned acidic pH-dependent synthetic polymer, a plasticizer such as polyethylene glycol, triacetin, mybacet, etc., an anti-aggregation agent,
For example, it may contain talc, magnesium stearate, etc. However, it is preferable that the total amount of these other components is 30% (1'l/W) unbottled.

Biologically active substances are not particularly limited, but include amino acids or derivatives thereof, such as methionine, 9-terminus, tryptophan, threonine, glutamic acid, N-amino acids such as glutamine, asparagine, vitamins such as vitamin A, enzymes such as acid propase, Antibiotics such as dextrose, veterinary antibiotics such as peninrin, anthelmintics such as levamisole, etc. are used alone or in combination. The core containing the biologically active substance is solid and, in addition to the active substance, binders such as hydroxypropylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, excipients such as lactose, mannitol, crystalline cellulose, etc., disintegrants such as e.g. It may contain valaine starch, corn starch, carboxymethyl cellulose sodium calcium chloride, crystalline cellulose sodium, and the like.

The ratio of coating to the core containing the biologically active substance also has a significant influence on the utilization rate of the active substance. That is, 100 j. [50-50% coating material for part ii]
It is appropriate to use 300 weights.

If the amount is less than 50 parts, the coating amount is insufficient and a significant amount will be eluted and degraded in the rumen. If it is more than 300 parts, the amount of coating is too large, and a significant amount will not be sufficiently eluted in the abomasum.

Ruminants are also not particularly limited, but are usually cows or sheep.

For the preparation of the composition of the present invention, the biologically active substance is usually mixed with water or ethanol at a suitable solids concentration, e.g. 3-15% (W/W), along with binders, excipients and disintegrants as required. Dissolve in alcohol and knead, then granulate with a cylindrical granulator, or knead and granulate with an egg pelleter, and then use a marmerizer to make granules of appropriate particle size. Then, for example, 6
Dry with hot air at 0°C for 1 hour. The particle size after drying is 0.
5-2. Approximately 5 ml is appropriate.

Next, the granules are given a suitable solids concentration, for example 1-10% (
The coating granules are coated with a suitable spray coating solution of W/vj). The amount of the IW agent to be used is as described above, but as a result, the particle size of the granules is usually 0. 8
=1. It will be about 5 mm. Solvent used for preparing the coating solution: one that dissolves the highly acidic pH-dependent synthetic polymer and the second component, such as chloromethane, ethanol,
Isopropatool and the like are suitable alone or in combination.

The feed additive composition for ruminants of the present invention has its TXIi
The structure is water-resistant and moisture-proof in the neutral range, and disintegrates or swells in the low and II ranges, so it is stable in the rumen (pH 6-7) and its contents are not eluted in the abomasum (pH around 3). Ru.

Next, examples of the present invention will be shown.

Example 1.

20 kg of lysine hydrochloride and 1 liter of water/ethanol mixture (11)
6% hydroxypropylcellulose? kg as a binder and kneaded. Pour the mixture into cylindrical granules with a diameter of 0.
．． It was extruded using an 8 mm screwdriver, spheroidized using a marmerizer, dried with hot air at 60°C for 1 hour, and then smoked.
Sieve through a 0-32mm screen to obtain a particle size of 0. 5-0.
8 mm (7) granules are i). i! ) Retarishin! 1
Spray coating using a fluidized bed device with a coating solution with a concentration of 10% by dissolving the Jff substance in a dichloromethane/ethanol mixture (2 °l) so that each grain has a composition as shown in Table 1. Then, coated granules were obtained.

Table 1 Example 2.

Seven-page grains were prepared in the same manner as in Example 1. Granule] 00
Milinol alcohol as a coating agent to 0g.

A coating solution in which 850 g of Eudragit E100 (5:I) was dissolved in 15 kg of dichloromethane ethanol (5:I) and 150 g of talc was added as an anti-aggregation agent was spray coated using a fluidized bed apparatus. Rf1 granules with a lysine content of 48% were coated with 100 weight fifitL of the coating material per 100 weight granules.

Example 3 200 g of spiramycin, 1000 g of milk fi, 660 g of corn starch, and 80 g of crystalline cellulose were mixed well, and 60 g of polyvinyl alcohol was added as a binder to
Add the solution dissolved in 0 g of water and mix well. The kneaded product was extruded using a cylindrical granulator with a diameter of 0.8 mm, and then spheroidized using a marmerizer and dried with hot air at 60° C. for 1 hour. Carnauba wax using 1000g of humiliated granules as a coating agent: A
900g of EA (221) and plasticizer (Mybase) lon
g to dichloromethane=ethanol (10:1) mixture 18
Flow the coating liquid dissolved in kg! The coated granules containing 5% spiramycin were spray coated in the I1 layer.

Example 4 pH 3 for lysine coated granules obtained in Example 1.2
, 0 (corresponding to the abomasum) and 6.0 (corresponding to the rumen).

(1) Test conditions Test solution; pH 3,0 hydrochloric acid-acetic acid) IJum pH 6,
0 Primary Potassium Citrate NaOH Liquid Volume: 500ml Liquid Temperature: 37°C Sample: 500mg Detection Method, Ninhydrin Color Development OD Method 5650m Test Method 1st Bureau 10 General Test Method 44. Elution test method Paddle method Number of rotations: 100 rpm (2) Results As is clear from the above, the elution of lysine was almost suppressed at pH 6.0, but it was rapidly eluted at pH 3.0. That is, the utilization rate of these granules in the digestive tract of ruminants is expected to be extremely high.

Effects of the Invention The feed additive composition of the present invention is stable in the rumen of ruminants, and is effectively absorbed from the digestive tract in the abomasum, so its utilization rate in the digestive tract is extremely high.

Patent applicant (102) Representative of Kyowa Hakko Kogyo Co., Ltd.
Mikio Kato

Claims (7)

[Claims] (1) At least one synthetic polymer that dissolves a core containing a biologically active substance in water in an acidic range of pH 5 or less (hereinafter referred to as an acidic pH-dependent synthetic polymer), fat, wax,
At least one selected from saturated or unsaturated aliphatic hydrocarbons having 14-40 carbon atoms, saturated or unsaturated aliphatic alcohols having 14-32 carbon atoms, and saturated or unsaturated fatty acids having 14-37 carbon atoms. (hereinafter referred to as a second component). (2) The acidic pH-dependent synthetic polymer is polyvinyl acetal diethylaminoacetate; a copolymer consisting of dimethylaminoethyl methacrylate and at least one of methacrylic acid alkyl ester and acrylic acid alkyl ester; or 2-methyl-5-vinylpyridine and acrylic acid. The feed additive composition for ruminants according to claim 1, which is a copolymer consisting of at least one of acid alkyl ester, methacrylic acid alkyl ester, methacrylic acid, and acrylic acid. (3) The ratio of the acidic range pH-dependent synthetic polymer and the second component in the coating material is 1:0.5 to 1:10 (weight ratio). Feed additive composition for ruminants. (4) The ruminant feed according to claim 1 or 2, wherein the total ratio of the acidic pH-dependent synthetic polymer and the second component in the coating is 70% (W/W) or more. Additive composition. (5) The biologically active substance is an amino acid, an amino acid derivative,
The feed additive composition for ruminants according to claim 1 or 2, which is a vitamin, an enzyme, a saccharide, a veterinary antibiotic, or an anthelmintic. (6) The ruminant feed additive composition according to claim 1 or 2, wherein the coating agent is used in an amount of 50 to 300 parts by weight per 100 parts by weight of the core containing the biologically active substance. . (7) Claim 1 in which the ruminant is a cow or sheep
The feed additive composition for ruminants according to item 1 or 2.