JPS6188843A - 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 ethyl cellulose 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) ethyl cellulose. The ratio of the component B to component C is preferably 1:1-7.

Description

[Detailed description of the invention] Industrial applications The present invention relates to a feed additive composition 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 polymer and ethyl cellulose.

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, ethyl cellulose is currently used as a moisture-proof synthetic polymer in the neutral range for coating. However, although R11 granules coated with ethylcellulose are well protected in the rumen, they have difficulty dissolving in the abomasum.

Furthermore, JP-A-48-12785 discloses a biologically active substance coated with a coating agent such as fat or wax and made into particles; It has been shown that coating with a coating agent containing acid or hydrogenated fat and chitosan, etc.
No. 6824 shows coating with cellulose propionate, morpholinobutyrate, etc.

However, in these inventions, those that have a strong protective effect in the rumen have a slow disintegration (elution) in the abomasum, and those that have a fast disintegration (elution) in the abomasum have a strong protective effect in the abomasum. The effects tend to be weak, and it seems 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 to Solve the Problems The present invention provides a synthetic polymer (hereinafter referred to as acidic region p) that dissolves a core containing a biologically active substance in water in an acidic region of pH 5 or less.
The present invention relates to a feed additive composition for ruminants, which is coated with a coating agent containing at least one type of ethyl cellulose (referred to as a synthetic polymer) and ethyl cellulose.

Acidic pH-dependent synthetic polymers include those that have water resistance and moisture resistance in a neutral range, such as polyvinyl acetal diethylaminoacetate; a copolymer consisting of dimethylaminoethyl methacrylate and at least one of methacrylic acid alkyl ester and acrylic acid alkyl ester. : A copolymer of 2-methyl-5-vinylpyridine and at least one of acrylic acid alkyl ester, methacrylic acid alkyl ester, methacrylic acid, and acrylic acid is used. Polyvinyl acetal diethylaminoacetate has a molecular weight of 30,000 to 150,000 and a nitrogen content of 1.0
~5.5% (W/W), such as l'VFΔ,
HΔ [Together, Sankyo! ! [Kado's trade name] 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 5 to 5.
Eudragit E 100, which is a copolymer of dimethylaminoethyl methacrylate, methyl methacrylate and butyl methacrylate, containing 3-8% (W/W) nitrogen at
, l2.5 CR5hmPharma (West Germany) trade name] is preferably used.

2-Methyl-5-vinylpyridine, acrylic acid alkyl ester, methacrylic acid alkyl ester.

A copolymer based on at least one of methacrylic acid and acrylic acid has a molecular weight of 5,000 to 400,000 and a nitrogen content of 2 to 400,000.
15% (11/11), e.g. 2-methyl-5
- MPM-717, a copolymer of vinylpyridine, methyl acrylate and methacrylic acid [Tanabe's "tto"
[trade name] is preferably used. -F2 Among each monomer, the alkyl of the alkyl ester is a straight or branched alkyl having 1 to 8 carbon atoms, such as methyl, ethyl, l-propyl, n-butyl, and the like. Next, as ethylcellulose, 2.0 to 2.0 to 1 ethoxy groups are added to 1 glucose unit.
Those containing 28 are preferably used.

The ratio of the acidic pH-dependent synthetic polymer and ethyl cellulose in the coating material is 1.05 to 1:10 (weight ratio), especially l:
1 to 17 are preferred. l: 0.5 When the latter (ethyl cellulose) becomes small, biologically active substances such as amino acids are significantly eluted in the rumen and degraded by rumen fermentation. If the latter is larger than 1:IO, the active substance will not be eluted in the rumen, but even if it enters the abomasum, the active substance will not be eluted sufficiently and the purpose cannot be achieved.

The coating material has a solid content and contains, in addition to both polymers, plasticizers such as polyethylene gelcol, triacetin, mybacet, etc., and V binders such as talc, magunium stearate, stearic acid, etc. There is no problem. However, the total of these other components is 30% (1'l
/W).

Biologically active substances are not particularly limited, but include amino acids or derivatives thereof such as methionine, lysine, tryptophan, threonine, glutamic acid, N-amino acids such as glutamine, asparagine, vitamins such as vitamin A, enzymes such as acid protease monosaccharide neck. For example, glucose, veterinary antibiotics such as beni/phosphorus, anthelmintics such as levamisole, etc. may be used alone or in combination. The core containing the biologically active substance is a solid and the active substance is bound by a binder such as hydroquinopropyl cellulose, polyvinylpyrrolidone, polyvinyl alcohol, etc., and an excipient such as lactose.

It may contain disintegrants such as mannitol monocrystalline cellulose, potato starch, corn starch, calhoki/methylcellulose cal/rum, carboquine methylcellulose sodium, crystalline cellulose, 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, 20 to 20 parts of the coating material is added to 100 parts by weight of the core granules.
It is appropriate to use 0 parts by weight. If the amount is less than 20 parts, the coating amount is insufficient and a significant amount will be eluted and degraded in the rumen. If it is more than 200 parts, the coating amount 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 compositions of the invention, the biologically active substance is usually mixed with binders, excipients, disintegrants, if necessary, in water or ethanol at a suitable solids concentration, e.g. 3-15% (W/W). After kneading in alcohol such as alcohol, granulate with a cylindrical granulator, or knead and granulate with an egg pelleter, and use quince to make granules of appropriate particle size. Then, it is dried with hot air at, for example, 60° C. for 1 hour. Dry grains (approximately 0.5 to 2.5 ml/l is appropriate).

Next, the granules are given a suitable solid content concentration, for example, 1 to 10% (
11/W) coating agent solution is coated with one appropriate spray to obtain coating agent granules. The amount of coating agent used is as described above, and as a result, the particle size of the coated granules is usually 0.8-1.
It will be about 5mm. The solvent used to prepare the T agent solution is preferably one that dissolves the polymer, such as dichloromethane, ethanol, isopropanol, etc. alone or in combination.

The feed additive composition for ruminants of the present invention has a coating film that is water-resistant and moisture-proof in a neutral range, and disintegrates or swells in a low pH range, so that it is not absorbed in the rumen (pH 6 to 7). It is stable and the contents are eluted in the abomasum (about pH 3).

Next, examples of the present invention will be shown.

Example 1 6% (W/I'l) was added as a binder to 2000 g of lysine hydrochloride.
) 0.7 kg of hydroxypropylcellulose/water/ethanol mixture was added and kneaded. The mixture was extruded using a cylindrical granulator using a screen with a diameter of 0.8 m+n, further spheroidized using a Marmerizer, sieved through a 20 to 32 mesh screen, and then air-dried at 60°C for 1 hour to determine the particle size. 05
~0.8 ml of granules were added.

A polymer solution prepared by dissolving 850 g of ethyl cellulose: Eudragit E100 (5: l) in 18 kg of dichloromethane:ethanol (l: 1) and adding 150 g of talc as a lubricant was fluidized. Spray coated with layer equipment.

Particle size of 100 parts by weight of granules coated with 100 parts by weight of coating agent is 0.8-1. Omm, lysine content 45
~55% (W/W) coated granules were coated.

Example 2゜Particle size 0.8-1.0I obtained by the same operation as Example 1
I1m granules were used to coat with the same device. ′
That is, ethyl cellulose AEA (2: 1) 8
50g dichloromethane:ethanol (1:1) 18
100 parts by weight of the granules were spray-coated with 50 parts by weight of the solid content of the polymer solution prepared by dissolving in Ta.

Example 38 200 g of subiramine, 1000 g of lactose, 660 g of corn starch, and 80 g of crystalline cellulose were mixed well, and a solution of 60 g of polyvinyl alcohol dissolved in 540 g of water was added to the mixture, kneaded well, and extruded using a cylindrical granulator with a diameter of 0.8 mo. , and dried with hot air at 60° C. for 1 hour. Obtained pellet-shaped granules (particle size 0.5-0.8 mm) I 0
00 g, ethyl cellulose: MPM47 (3:
1) 700 g and 100 g of mybaset as a plasticizer were dissolved in dichloromethane:ethanol (1:11) and spray coated in a fluidized bed.This resulted in granules 1
00 weight 1 was coated with 55 to 65 parts by weight of the coating agent.
Particle size 0.8-1. Omm, Subira Mine content 6%
coated granules were obtained.

Example 4. Regarding the lysine granules obtained in dissolution test example 1.2, pH 3,
0 (corresponds to the abomasum), 6.0 (corresponds to the rumen)
A dissolution test was conducted.

(1) Test conditions Test solution; pH 3,0 hydrochloric acid-acetic acid) IJum pH 6
,0 primary potassium citrate-Nal solution Volume: 500m
l Liquid temperature: 37°C Sample: 500 mg Detection method: Ninhydrin color development OD method 565 nm Test method: Diurnal cycle 10. General test method 44. Elution Test Method Paddle Method Number of revolutions: 10 Orpm (2) Results As is clear from the above table, the elution of lysine was almost suppressed at pH 6.0, but it was rapidly eluted at pH 3.0. In other words, it is expected that the utilization rate of these cervical grains in the digestive tract of ruminants is 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.

Claims (7)

[Claims] (1) A coating material containing 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) and ethyl cellulose. A feed additive composition for ruminants, which is coated with. (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 acidic pH-dependent synthetic polymer and ethyl cellulose in the coating material is 1:0.5 to 1:10 (weight ratio)
A feed additive composition for ruminants according to claim 1 or 2. (4) The feed additive composition for ruminants according to claim 1 or 2, wherein the proportion of the total polymer in the coating is 70% (W/W) or more. (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 20 to 200 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.