JP3361364B2 - Ruminant feed additives and manufacturing method - Google Patents

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a feed additive for ruminants, which is prepared by protecting the active substance in the rumen of ruminants and treating it for digestion and absorption in the digestive organs of the fourth stomach and beyond. It is about.

[0002]

2. Description of the Related Art In ruminants, several kinds of microorganisms survive in the rumen, and various nutrients in the feed, including fibers such as cellulose, which cannot be originally used in higher animals, are fermented and decomposed by the action of these microorganisms. It absorbs and utilizes several types of volatile lower fatty acids that are produced, and uses it as an energy source for the living body. Further, the properties of these rumen-gastric juices, especially the pH, are varied within the range of pH 5 to 8 depending on the fermentation state, age and physical condition due to the difference in ingested feed. However, even biologically active substances (hereinafter referred to as effective substances) in the body that are desired to be absorbed and used in the form as they are for the living body are decomposed by these microorganisms or denatured due to changes in the pH of rumen gastric juice. Limited in terms of efficiency of use of the substance. In order to deal with this, at present, as an anti-ruminant preparation, the active substance is dispersed in a matrix of an inactive substance in the rumen (hereinafter, protective substance),
A granular or spherical molded product, or a preparation in which an active substance as a core is coated with a protective substance and the like is used. For example, a matrix composed of a mixture of a saturated linear or branched aliphatic monocarboxylic acid having at least 14 carbon atoms or more, or a salt thereof, with the active substance dispersed and coated, or the active substance having a carbon number of 14 to 22 aliphatic monocarboxylic acid, or a salt of a mixture of the above fatty acids, a hardened plant or animal fat, and a hydrophobic substance containing chitosan and coating treatment.

[0003]

However, in these preparations, since the coating substance is disintegrated in the duodenum and thereafter, there is a limitation in the time required for its digestion and absorption, and there is a drawback that absorption and utilization are not sufficiently performed. . Further, the covering substance that should be disintegrated after the abomasum is not sufficiently disintegrating, and the absorption and utilization effect is not always stable. Furthermore, when the stability of the active substance in the rumen is emphasized in these preparations, the proportion of these substances inevitably increases to make the coating substance stronger, and the content rate of the active substance is 40%. %, Which results in high cost cost of the drug product.
That is, in a preparation in which the active substance is dispersed in a matrix of the protective substance and granulated or spheroidized, or a granule or spherical particles of the active substance coated with the protective substance, changes in the pH of rumen gastric juice (pH 5 to According to 8), a part of the coating material is disintegrated and its protective property is deteriorated. In addition, when importance is attached to stability in the rumen, the proportion of the coating substance is high, and the content rate of the active substance is generally 40%.
It is limited to about%. Most of the aliphatic monocarboxylic acids having 14 to 22 carbon atoms used as the coating substance are hardened vegetable or animal fats, so that the fatty acid composition is stearic acid-based. Therefore,
Since these fatty acids have a high melting point (68 ° C.), the emulsifying action of the bile is suppressed, and as a result, the absorption availability is reduced. The present invention has been made in view of the above circumstances, the content of the active substance is increased as much as possible, in order to solve the above problems, the active substance is stable even against pH fluctuating in the rumen. It is an object of the present invention to provide a feed additive for ruminants that is protected and rapidly disintegrates in the digestive organs after the abomasum and has excellent digestive absorbability, and a method for producing the same.

[0004]

In accordance with the above object, the present invention provides at least one or more kinds of effective substances in an amount of 55 to 65%, a sparingly soluble or insoluble salt in a weakly acidic to weakly alkaline aqueous solution, or an aqueous solution thereof. Stable excipient 20-25
%, And further 2-3% sodium alginate aqueous solution 10
A method for producing a ruminant feed additive, which comprises forming a core with a mixture containing 20% to 20% of a binder, and forming a first to third triple-layered coating structure on the core with a stable substance in an intraruminal solution; By trying to solve the above problems
It is a thing . In the present invention, the effective substance is 55 to 65%.
And a first coating of calcium alginate formed on the surface of the core, and a second coating of fine calcium carbonate having an average particle size of 1 μm or less formed on the first coating.
The above-mentioned problems were solved by using a ruminant feed additive comprising a coating and a third coating made of calcium alginate formed on the second coating.

As a result of various studies, the present inventors have found that weak acid
A core consisting of a spherically shaped effective substance is formed by using a substance that is stable to a weakly alkaline aqueous solution as a shaping material, and calcium alginate is used as the first coating on this core, and the particle size is 1 μm.
The following fine calcium carbonate or fine calcium carbonate coated with mono-fatty acid glycerin ester as the second coating, and the surface of which is further coated with calcium alginate to form the third coating in the rumen It was found that the present invention has excellent stability and rapidly disintegrates in the digestive organs after the abomasum and thus completed the present invention. The animals to which the feed additive of the present invention is administered are ruminants such as beef cattle, dairy cows, cotton sheep, and goats, and the microorganisms are allowed to survive in the rumen and have a coexisting relationship with them. In addition, the effective substance means a nutrient source for the living body, a substance useful for treating or preventing a disease, specifically, amino acids such as methionine, lysine and tryptophan, and their derivatives, fat-soluble and water-soluble. Examples include vitamins and their derivatives, and nutritional sources such as proteins and carbohydrates. Further, the excipients required for molding the core containing the active substance as a main component shown in the present invention are poorly soluble in weak acid to weak alkaline aqueous solution,
Alternatively, it is an insoluble salt or a stable substance, and examples thereof include calcium salts such as tricalcium phosphate, calcium carbonate, zeolite, and silicic acid compounds such as bentonite. Also, the protective substance used for the film treatment is a substance that is stable to weakly acidic to weakly alkaline aqueous solution as well as the excipient and should be rapidly decomposed in the aqueous solution of strong acid, such as calcium alginate. An insoluble gel substance in which a thickening polysaccharide and calcium are bound, or a calcium compound bound to a weak acid group such as calcium carbonate.

Next, a method for producing the feed additive according to the present invention will be described. First, the molding of the spherical core containing the active substance as the main component is carried out by using 55 to 65% of a mixture of one or two or more of the above-mentioned active substances and calcium salt 18 to 2 as a shaping agent.
0%, zeolite 4-6%, and bentonite 1-2%
And a mixture of which the residual amount is adjusted with 10 to 20% of a sodium alginate solution of 2 to 3% is extruded into granules having a particle diameter of about 1 mmφ and granulated with a plate rolling spherical molding machine to a spherical diameter of 1-2 mm. The core is the transformed one. If the content of the effective substance is 55%, the content does not change much from the conventional content, and if the content exceeds 65%, the amount of the shaping material is small and there is a problem in strength. Weak acid as a shaping material
Use a stable substance that is sparingly soluble or insoluble in a weakly alkaline aqueous solution. In particular, the reason for selecting zeolite and bentonite is that the former granules have excellent disintegration properties against liquids, and the latter is that the addition of a small amount increases the hardness of other granules and has a strong swelling property. The point is to disintegrate the capsule of the nucleus described later from the inside of the nucleus and to contribute to the promotion effect of decomposition in the abomasum and thereafter. In addition, regarding the additives of each excipient, the content of the active substance in the nucleus should be increased as much as possible, and the hardness as a preparation and the stability in the rumen should be maintained. It is optimum when the disintegration property is considered, and the total amount is preferably 20 to 25%. The binder is not particularly limited as long as it is generally used for granulation of feed in order to form only the core, but in forming the first coating of calcium alginate, which is a feature of the present invention, the core is The thixotropy phenomenon that occurs during rolling spheroidization (a phenomenon in which the water-solubility released between the powders in the core becomes easy to flow due to rolling. In this case, the aqueous binder solution leaks to the surface of the core.) In particular, an aqueous solution of sodium alginate is used for the purpose. The concentration of the aqueous solution of sodium alginate used as the binder and the addition rate are 2 to 3 in consideration of the hardness of the core, the film formability described later, and the drying efficiency.
%, The addition rate is 10 to 20%, and 10 to 15% is optimum.

The formation of the first film of calcium alginate in the present invention is carried out by uniformly spraying an aqueous solution of calcium chloride while continuously rolling on the nucleus obtained by the above-mentioned contents, or by the thixotropic phenomenon. In a state where the sodium alginate aqueous solution was sufficiently leaked, calcium ions were mediated in the leaked calcium alginate aqueous solution by immersing it in an aqueous solution of calcium chloride for a short time, and sodium was replaced with calcium ions to form an insoluble calcium alginate gel film. It is formed uniformly. Generally, alginic acid, or sodium alginate and calcium ion are bound in an aqueous solution,
Alternatively, it is well known that an insoluble calcium alginate gel is formed by the substitution reaction, but a gel film of calcium alginate is uniformly formed on the surface of a solid substance such as a nucleus containing the active substance in the present invention as a main component. However, it is extremely difficult to uniformly disperse one aqueous solution on the surface of the solid even if a method such as spraying or dipping is used.Therefore, a gel film of calcium alginate to be formed by such a reaction is formed. It is hard to say that the condition is constant. However, in the present invention, the sodium alginate aqueous solution used as the granulation binder of the nucleus in the thixotropic phenomenon developed by the rolling treatment at the time of spherical molding of the nucleus is used to uniformly leak to the surface of the nucleus, and sprayed on this. Alternatively, a uniform insoluble calcium alginate gel film can be formed on the surface of the nucleus only by the reaction by contact with an aqueous solution containing calcium ions by a method such as immersion. The concentration and the addition rate of the calcium chloride aqueous solution used in this treatment are 20% and the addition rate is 3 to 5 in consideration of the coating strength, the drying efficiency, and the formation of the third coating (calcium alginate).
% Is optimal.

Next, regarding the formation of a second coating of fine calcium carbonate, fine calcium carbonate is added to the core coated with calcium alginate by the above-mentioned method while further rolling treatment, and at the same time, An aqueous solution of sodium alginate is sprayed on as a binder. By this treatment, calcium carbonate is spotted on the gel film of calcium alginate, which is highly viscous.
Fine calcium carbonate with a size of μm or less, such as fine ground calcium carbonate produced by physical crushing, or colloidal calcium carbonate produced by a chemical reaction, tends to agglomerate between particles, resulting in poor dispersibility. The disadvantage occurs that it does not evenly deposit on the calcium gel coating. In this regard, the inventors
Fine calcium carbonate surface-treated with fats and oils such as glycerin fatty acid ester has excellent fluidity and dispersibility as a powder, and is suitable for even spot application on the calcium alginate gel film. And applied this. The oils and fats used for the surface treatment are not particularly limited, but considering the stability in the rumen and the fact that they are commercially available at a low price, monostearic acid glycerin ester is particularly preferable. (Stearic acid monoglyceride) is preferred. The addition ratio of oils and fats used for surface treatment is 0.5 to 2.
0% is sufficient to achieve the above purpose. That is, when 0.5% or less, good results cannot be obtained in terms of fluidity and dispersibility, and when 2.0% or more, in terms of spotting of calcium carbonate itself due to hydrophobicity peculiar to fats and oils. The spotted fine calcium carbonate serves to fill the pinholes scattered on the gel film of calcium alginate formed by the above-mentioned primary treatment, and enhances the action as the first film in the rumen. The addition amount necessary for forming the second coating film of the fine calcium carbonate particles is most preferably 10 to 15% with respect to the core weight.

Regarding the binder used at this time, the unreacted calcium ions of the calcium chloride aqueous solution sprayed at the time of the first film forming treatment are utilized again to form calcium alginate as the third film on the outermost layer of the core,
In order to form a second coating having a higher stability with respect to a weak acid to weakly alkaline solution, a 1% sodium alginate aqueous solution is again sprayed onto the surface of the nucleus at an optimal ratio of 3 to 5% with respect to the weight of the nucleus. To do. By the above processing, the first, second,
And a spherical preparation having a third coat formed are obtained, and by drying this, the content of the active substance which is the object of the present invention is high, and the stability is high in the rumen. The feed additive for ruminants, which is excellent in decomposition and absorption in the digestive tract, can be promptly obtained. The composition of the feed additive according to the present invention is shown in FIG. That is, 4 is a core made of an active substance or the like, 1 is a first coat for covering the surface of the nucleus 4, 2 is a second coat, and 3 is a third coat.

The core consisting of the active substance in the present invention is a solid solid insoluble or poorly soluble salt in a rumen solution which is used as a shaping agent to be spherically solidified. Zeolite has excellent adsorptivity to liquids, promotes disintegration of the granules in the liquid, facilitates release of the active substance in the digestive tract after the abomasum, and contributes to digestion and absorption. In addition, the addition of bentonite increases the strength of the nucleus, and when it has a favorable effect on the subsequent formation of a film on the nucleus, the bentonite itself swells in the liquid due to its high swelling property, causing the film to collapse from the inside of the nucleus. It has the action of promoting the degradation of the drug product in the digestive tract. The first coating layer of calcium alginate uniformly leaks to the surface layer due to the thixotropic phenomenon that the sodium alginate solution added as a binder for nucleation as a binder develops by the rolling treatment, and reacts with this and calcium ions in the calcium chloride solution. It is a gel-like film that is insoluble in the produced water. In order to maintain the stability of this first coating in the rumen solution, pinholes scattered on the gel coating of calcium alginate are filled with fine calcium carbonate having an average particle size of 1 μm or less, and calcium carbonate is used by itself. A second coating is formed to enhance stability in rumen solution.
Also, the sodium alginate solution used after forming the second coating reacts with the unreacted calcium ions in the calcium chloride solution leaked by the thixotropic phenomenon in the same manner as above, and again the gel-like coating of calcium alginate is used as the third coating. It becomes a feed additive for ruminants having a triple-layered structure formed on the surface layer of. This formulation protects the nuclei against rumen fluid in all of the first to third coats, maintains stability in the rumen, and is readily degraded in the abomasum and beyond. That is, the fourth
After the stomach, the fourth gastric juice penetrates through the fine pores of the third coat. Then, the strong acid of the gastric juice dissolves the calcium carbonate coating and the calcium carbonate filling the pinholes of the first coating. The bentonite swells due to the permeation of gastric juice into the nucleus, which promotes the disintegration of the preparation.

[0011]

[Examples] Using DL-methionine as an active substance, nuclei were molded with 13 kinds of compositions in the groups A to M shown in Table 1, and these nuclei were treated with the first to third coats and dried at the addition rates shown in the table. Formulation recovery rate, strength in the formulation after treatment (water content 3% or less),
The results shown in Table 1 were obtained for the methionine content and the elution rate of methionine in the artificial rumen fluid and rumen fluid. In addition, artificial rumen fluid is CaCl ₂ · 2H
₂ O: 0.01 g, KCl: 0.2 g, NaCl: 2.
6 g, MgSO ₄ .2H ₂ O: 0.1 g, Na ₂ HPO
_{4 · 12H 2 O: 15.0g,} K 2 HPO 4: 2.0g
Was dissolved in 1 liter of pure water, and the pH was adjusted to 7.2 to 7.4. The artificial abdominal fluid was macrovain buffer solution (0.2M NaH ₂ PO ₄ , B as solution A).
A solution prepared with appropriate amount) to pH 2.0 to 2.2 using 0.1M C ₆ H ₈ O ₇ as a liquid. In the dissolution test, artificial rumen fluid and artificial abdominal fluid were placed in an Erlenmeyer flask containing 500 ml each, and 10 g of each of the preparations A to M were placed in a nylon net bag and immersed, and a constant temperature shaker was used to After treating the former for 18 hours and the latter for 5 hours under a constant temperature of 40 ° C., the weight of methionine eluted from the preparation into the liquid was measured to calculate the dissolution rate.

[0012]

[Table 1]

Each item shown on the left end of Table 1 (for convenience,
Nos. 1 to 9) are as follows. No. 1: The ratio of the content of the nuclear component forming the active substance is shown for each section (AM). No. 2, 3, 4: Shows the ratio of each component used when forming the first to third coatings to the weight of the core. No. 5: Formulation recovery rate = formulation weight / (nuclear weight + calcium carbonate weight) x 100 No. 6: Measured with a Fudoh rheometer. No. 8, 9: Elution rate (%) = weight of methionine eluted in each artificial gastric juice ÷ methionine content in preparation x 1
00

According to the results shown in Table 1, the constituent components of the core are within the numerical range of claim 1 of the present invention, and in the subsequent 1st to 3rd coating treatments, the range of claims 3 to 5 is satisfied. Under certain manufacturing conditions, that is, B, C, E, F, G, K, L 7
It was confirmed that a preparation suitable for the purpose of the present invention was obtained in the plot. That is, comparing the groups A to C, when the concentration of the sodium alginate solution used as the binder of the nucleus is 1%, the strength of the preparation and the dissolution rate of the active substance in the artificial rumen fluid are unsuitable. In addition, when the composition ratio of the active substance and the binder is changed by comparing D to I groups, even if the sodium alginate solution concentration of the binder is an appropriate value, it is recovered when the composition ratio is 10% or less (D group). Rate, strength, and dissolution rate in artificial rumen fluid are inappropriate, and when the excipient in the nucleus is deficient (H group) or out of the claimed range (I group), the same applies. It was found that the result would be In addition, in J to M wards, when the amount of each substance used in the primary to tertiary coating formation treatment is less than the range (J ward) with respect to the nuclei defined within the claimed range, artificial rumen fluid is used. A decrease in the dissolution rate was observed, and even when the addition amount was increased beyond the range of the present invention (M group), the improvement results in strength and dissolution rate could not be confirmed. Based on the above results, it was confirmed that the most suitable production conditions for producing the preparations suitable for the purpose of the present invention are within the range of the numerical values limited to each claim.

Next, the following confirmation tests I and II were conducted. [Test I] With respect to the preparation obtained by the production method of the present invention, in order to confirm the stability of the ruminant juice against pH fluctuation, the artificial ruminant juice used in the above Examples was adjusted to pH with citric acid and an aqueous potassium oxide solution. PH 5.0 and pH respectively
A solution adjusted to 8.0 was prepared, and an elution test of the active substance methionine was carried out under these solutions in the same manner as in Examples,
The results shown in Table 2 were obtained. In this test, two types of preparations, E and L, obtained in the examples were used, and the test results were cited.

[0016]

[Table 2]

From Table 2, it can be seen that the elution rate of methionine is stable in the pH range of 5.0 to 8.0.

[Test II] In order to compare the preparations E and L obtained by the production method of the present invention with the preparations (a and b) obtained by the conventional production technique, shown in Table 3. With respect to the intraruminal protective preparation constituted by the contents described above, a dissolution test was conducted on the artificial rumen fluid and the fourth gastric juice in the same manner as in the above-mentioned Examples, and the following results were obtained.

[0019]

[Table 3]

In Table 3, section a is a matrix-dispersed inactive substance in the rumen (hardened oil and fat) matrix, and b is a coated type inactive substance in the rumen (hardened oil and fat). According to the above results, the preparation according to the present invention (E section, L
Group) has a lower elution rate of methionine in artificial rumen fluid than the conventional preparations (groups a and b).
It can be seen that the elution rate of methionine in gastric juice is remarkably large.

[0021]

INDUSTRIAL APPLICABILITY According to the present invention, the content of the active substance is high, the stability in the rumen is high, and it rapidly disintegrates in the digestive organs after the abomasum and is excellent in digestive absorbability. A feed additive for ruminants and a method for producing the same can be provided.

[Brief description of drawings]

FIG. 1 is an enlarged explanatory view showing a right half of a feed additive according to the present invention in section.

[Explanation of symbols]

1 first coating 2 Second coating 3 Third film 4 nuclear

Claims (6)

(57) [Claims] 1. At least one or more active substances 55-6
5%, a poorly soluble or insoluble salt in a weakly acidic to weakly alkaline aqueous solution, or 20 to 25% of a shaping agent stable in these aqueous solutions, and a binder of 10 to 20% of a 2 to 3% aqueous sodium alginate solution. Forming a core with a mixture consisting of and forming a calcium alginate coating on the surface of the core
The first coating is used, and fine particles with an average particle size of 1 μm or less are formed on this coating.
Form a film with different calcium carbonate to make a second film, and
Form a calcium alginate film again on this film
As a third coat, a method for producing a feed additive for ruminants, comprising forming a first to a third triple coat structure in the nucleus with a stable substance in a rumen solution. 2. At least one or more active substances 55-6
5%, a poorly soluble or insoluble salt in a weakly acidic to weakly alkaline aqueous solution, or 20 to 25% of a shaping agent stable in these aqueous solutions, and a binder of 10 to 20% of a 2 to 3% aqueous sodium alginate solution. shaping the nuclear with a mixture consisting of together to form the first to third triple film structure stable substance rumen solution to the nucleic and in forming the first coating, rolling process on the nucleus Give
Alginate present on the surface of the nucleus
Thorium solution with 3,000 to 3,500 mgeq / l
Contact the lucium salt aqueous solution with 3 to 5% of the weight of the nucleus.
Reacts to form a calcium alginate coating
A method for producing a feed additive for ruminants, which comprises: 3. When forming the second coating, rolling treatment is performed to form fine calcium carbonate having an average particle size of 1 μm or less, which is coated with 0.5 to 2.0% of monofatty acid glycerin ester. The ruminant according to claim 1 or 2 , wherein by adding 10 to 15% relative to the weight of the core , calcium carbonate is uniformly spotted on the surface of the calcium alginate film to form a film. For producing feed additives for foods. 4. In forming the third film, subjected to rolling processing <br/>, 1% sodium alginate aqueous solution was sprayed from 3 to 5% with respect to core weight, calcium in the first coating The method for producing a feed additive for ruminants according to claim 2 , which comprises reacting with an aqueous salt solution to form a film of calcium alginate. 5. A calcium salt 18 to 2 is added to the shaping material of the core.
0%, 4-6% of zeolite, and 1-2% of bentonite are used, The manufacturing method of the feed additive for ruminants according to any one of claims 1 to 4 . 6. A first core composed of 55 to 65% of the active substance and a calcium alginate formed on the surface layer of the core.
A coating film, and a second coating film formed on the first coating film, which is made of fine calcium carbonate having an average particle size of 1 μm or less, and the second coating film.
A feed additive for ruminants, comprising a third coating formed of calcium alginate on the coating.