JP4248030B2 - Ruminant feed additive - Google Patents

Description

【００４７】
【表２】

【００４８】
【発明の効果】
第１表に示した様に、本発明の実施例１〜９のルーメンバイパス製剤はいずれも模擬第一胃液溶出率が低く、バイパス性が良好であり、第四胃と小腸の模擬液での溶出率の合計が大きく良好な消化性を示している。
一方、第２表では、脂肪族モノカルボン酸の塩のみを保護物質とした比較例１、本発明の範囲外の保護剤組成を使用した比較例２〜４は模擬第一胃液での溶出率が大きく、ルーメンバイパス性が劣り、これらはいずれも実用性が低いことが示されている。
【００４９】
このように特定の組成比の脂肪酸塩と特定の脂肪族カルボン酸または一価の脂肪アルコールからなる保護物質により５０重量％以上の高濃度の生物学的活性物質を含み良好なルーメンバイパス性を示すマトリックス型ルーメンバイパス製剤を得ることができた。[0001]
[Technical field to which the invention belongs]
The present invention relates to a feed additive, and more particularly to a matrix-type lumen (first stomach) bypass preparation in which a biologically active substance suitable for ruminants is dispersed and protected in a protective substance.
[0002]
[Prior art]
Rumen bypass formulation for ruminants is a formulation containing one or more of various amino acids, various vitamins, and other biologically active substances. While limiting the degradation, it has the function of enabling the elution and absorption of biologically active substances in the digestive tract after the fourth stomach.
[0003]
In the breeding of ruminants, the administration of rumen bypass preparations with feed has become widespread due to nutritional and clinical benefits. In a lumen bypass formulation, it is practically economically advantageous and desirable to include a high concentration of biologically active substance. In addition, the formulation hardness is also important in terms of durability against feed mixing and chewing. However, increasing the concentration of biologically active substances tends to make it difficult to maintain lumen bypassability and hardness due to a decrease in the ratio of protective substances in the formulation. Is required. For this reason, the concentration of the biologically active substance in the conventional matrix-type lumen bypass preparation was a low concentration of 50% or less.
[0004]
Many concepts and examples of rumen bypass preparations are already known, but there is no practical example of a preparation containing a biologically active substance at a high concentration of 50% or more (high preparation) in a matrix type preparation. . Although an example of using a salt (fatty acid salt) of an aliphatic monocarboxylic acid (fatty acid) as a protective agent is also disclosed, a composition containing a biologically active substance with a high concentration of 50% or more shows a good rumen bypass property. Examples are not disclosed.
[0005]
Japanese Patent Laid-Open No. 2-163043 discloses the concept of a matrix-type preparation using a fatty acid salt and an oil-based compound compatible therewith as a protective substance, but the concentration of the biologically active substance is 50% or less. There is no specific description about% or more examples.
International Publication WO / 12731 describes an example in which fatty acid calcium and stearyl alcohol are used as protective substances in a ratio of 58: 2 (97: 3), but the concentration of the biologically active substance is 50% or less. It is.
[0006]
Japanese Patent Application Laid-Open No. 56-154958 has an example of a matrix type preparation using an oil-based protective substance, but the composition ratio of the biologically active substance is 50% or less, and the composition of the protective substance is also different. There is no illustration of the scope of the present invention.
[0007]
US Pat. No. 5,425,963 discloses a high-purity fatty acid calcium salt as a feed additive and a method for producing the same, but the object is different from the present invention, and the composition of the protective substance and the content of the biologically active substance are also significantly different. Yes.
[0008]
[Problems to be solved by the invention]
The present invention has been made in view of the above-mentioned problems of the prior art, and contains a biologically active substance at a high concentration using a natural product-derived substance that is safe for ecosystems such as fats and oils as a protective substance. The objective is to obtain an economically advantageous lumen bypass formulation.
[0009]
[Means for Solving the Problems]
The present inventors have already disclosed a lumen bypass preparation using a protective substance composed of a biologically active substance as a fatty acid salt and an oil-based compound compatible therewith (WO91 / 12731). As a result, the composition of the protective substance that protects the biologically active substance at a high concentration and passes through the lumen is in a very limited range, unlike the case of the low concentration, and has an aliphatic composition with a specific composition ratio. The present inventors have found that an excellent rumen bypass preparation can be obtained at a high concentration of 50% or more by a protective matrix comprising a salt of monocarboxylic acid and an aliphatic carboxylic acid or fatty alcohol.
[0010]
That is, the present invention relates to a rumen bypass formulation for ruminants characterized in that 50 to 90% by weight of the biologically active substance of the preparation is dispersed in 10 to 50% by weight of the following protective substance [I]. is there.
[I] a protective substance comprising the following 1) and 2), wherein the weight ratio of 1) and 2) is in the range of 30:70 to 10:90;
1) At least one selected from the following a) b) c) a) a linear or branched saturated or unsaturated aliphatic monocarboxylic acid having 8 to 24 carbon atoms b) a linear chain having 8 to 24 carbon atoms Or a fatty alcohol having a branched saturated or unsaturated hydroxyl group c) a straight chain having 2 to 8 carbon atoms or a branched saturated or unsaturated aliphatic di- or tricarboxylic acid 2) a straight chain having 12 to 24 carbon atoms Or a salt of a branched saturated or unsaturated aliphatic monocarboxylic acid. However, the weight% in the present invention means dry weight%, and excludes moisture (adsorbed moisture) removed by normal drying at 80 to 120 ° C. Based on.
[0011]
DETAILED DESCRIPTION OF THE INVENTION
The present invention is described in further detail below.
The biologically active substance used in the present invention is a substance that shows biological activity when administered to ruminants, and a substance that is decomposed by rumen and is not easily digested and absorbed by oral administration, for example, methionine. , Amino acids such as lysine hydrochloride, amino acid derivatives such as 2-hydroxy-4-methylmercaptobutyric acid and its salts, nicotinic acid, nicotinic acid amide, vitamins such as vitamin A and vitamin E, sugars such as glucose and fructose, antibiotics Various veterinary medicines such as substances and anthelmintics.
These active substances may be used alone or in combination of two or more.
[0012]
The total amount of these biologically active substances is 50-90% by weight of the formulation, preferably a high concentration of 60-85% by weight. If the range is less than this range, it is economically disadvantageous, and if the range is large, the lumen bypass property is lowered and the production is difficult.
[0013]
The protective substance used in the present invention consists essentially of a fatty acid salt and an aliphatic (mono, di, tri) carboxylic acid or fatty alcohol. The amount of protective substance used depends on the amount of biologically active substance and the modifier added as required and is selected in the range of 10-50% by weight. Fatty acid salts are also called bypass fats and oils, have the property of being digested from the rumen without being broken down by rumen, and are the main component of the protective substance in the present invention. This fatty acid salt is used in an amount ranging from 70 to 90% by weight of the protective substance. Outside this range, a preparation having a high concentration of biologically active substance and excellent rumen bypass property cannot be obtained.
[0014]
The fatty acid salt used in the present invention is a salt of a linear or branched saturated or unsaturated fatty acid monocarboxylic acid, and the aliphatic monocarboxylic acid of the salt has 12 to 24 carbon atoms, which is less than this. In the range, the rumen bypass property is lowered, and a range larger than this is not preferable because digestibility after the fourth stomach is lowered. Examples of aliphatic monocarboxylic acids include lauric acid, palmitic acid, myristic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, and the like. One or more of these may be used. it can. In particular, a mixture of acids derived from animals and plants such as palm fatty acid and beef tallow fatty acid can be preferably used because of its availability.
[0015]
Examples of fatty acid salts include calcium, magnesium, aluminum, and zinc salts of aliphatic monocarboxylic acids having carbon numbers in the above range, with calcium salts being preferred.
[0016]
The fatty acid salt used in the present invention preferably has a high purity, and in particular, the fatty acid salt purity (hereinafter referred to as purity) in the solid content is preferably 90% or more. The purity of the fatty acid salt here means an insoluble residue when the fatty acid salt is extracted with a solvent such as ethers and ketones, which is a conventional method for analyzing fats and oils, and is calculated by excluding adsorbed moisture. % By weight. However, the solvent used for this extraction treatment is selected so as not to dissolve the fatty acid salt but to dissolve the mixed fats and oils.
[0017]
In addition, the base such as calcium contained in the fatty acid salt is preferably substantially equivalent or excessive in terms of physical properties such as hardness, and in the case of a calcium salt, 7 to 12% by weight, preferably 8 to 10% by weight as calcium. Is preferred. A known analytical method can be used for quantification of calcium. Usually, after fatty acid salt is incinerated, calcium contained in the ash is quantified.
[0018]
The beef tallow fatty acid and palm oil fatty acid used as the raw material for the fatty acid salt usually contain about 5 to 40% of triglyceride and the like, and in addition, various compounds such as a reaction control agent and a stabilizer may be added. These are mixed into the fatty acid salt as a reaction product as an unreacted component and become impurities. Some commercially available fatty acid salts contain about 20% impurities. In high-content preparations, it is preferable that the purity of the fatty acid salt is high because such impurities reduce the lumen bypass property and hardness of the preparation.
[0019]
The aliphatic carboxylic acid or fatty alcohol used together with the fatty acid salt as the protective substance of the present invention is considered to be a component that reduces the crystallinity of the fatty acid salt and improves the affinity between the biologically active substance and the protective matrix, It is preferably used in an amount in a range compatible with the fatty acid salt. These melting points tend to be preferably closer to the body temperature of ruminants. The range of the amount used is 10 to 30% by weight of the protective substance, and good lumen bypass properties cannot be obtained outside this range.
[0020]
The aliphatic monocarboxylic acid used in the present invention has 8 to 24, preferably 12 to 18 carbon atoms, and if it is less than this, the preparation softens and the rumen bypass property is lowered. Digestibility after the four stomachs decreases, and none of the results are good.
[0021]
Aliphatic monocarboxylic acids include aliphatics such as caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, linolenic acid, behenic acid, hydrogenated castor oil fatty acid, etc. Monocarboxylic acids and mixtures thereof can be exemplified, and many of the commercial products are saponified refined products of animal and vegetable oils.
[0022]
The carbon number of the (monovalent) fatty alcohol having 1 hydroxyl group used in the present invention is 8 to 24, preferably 12 to 18. If it is less than this, the preparation is softened and the rumen bypass property is lowered. In a larger range, digestibility after the fourth stomach is lowered, and none of the results is good.
[0023]
Examples of fatty alcohols used in the present invention include octanol, nonanol, decanol, undecanol, lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, eicosanol, docosanol, dodecenol, fiseteryl alcohol, somalryl alcohol, oleyl alcohol, Gadrel alcohol and isomers thereof are mentioned.
[0024]
The aliphatic di- or tricarboxylic acid used in the present invention has 2 to 8 carbon atoms, preferably 2 to 6 carbon atoms, and good lumen bypass properties cannot be obtained outside this range.
Examples of the aliphatic di- or tricarboxylic acid include oxalic acid, malonic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, malic acid, citric acid and the like.
[0025]
In the present invention, a wax such as rice wax, carnauba wax, beeswax, waxes, ethyl cellulose, propyl cellulose, polyethylene, chitosan and derivatives thereof, pH sensitive polymer for moldability, mechanical strength and other modifications. Various additives such as organic polymers, inorganic powders, stabilizers, fragrances, and the like can be added as a modifier as necessary. Moreover, it can also be modified by coating the surface with these modifiers.
[0026]
The production method of the lumen bypass preparation of the present invention can be performed by various known granulation methods, but the extrusion granulation method is preferable, and in order to obtain a preparation having a low porosity and a low water content, a vacuum in the kneading step is used. It is preferable to quench the preparation with water, cold air or the like immediately after deaeration and granulation.
[0027]
The shape of the preparation is not particularly limited, but a shape having a small angle such as a spherical shape, a spheroid shape, a bullet shape, or a cylindrical shape is preferable. The size of the preparation may be appropriate as long as it is a feed ingredient, but it can be arbitrarily selected from the range of 0.5 mm to 10 mm in terms of particle size, length, etc., so-called granule to pellet size.
[0028]
【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 in any way by the following examples.
[0029]
Example 1
28 parts by weight (hereinafter referred to as “parts”) of beef tallow fatty acid calcium salt (purity 97.3%), 7 parts of palmitic acid and 65 parts of methionine were mixed. The mixture is put into a hopper of a twin screw granulator, melt extruded from a die with a hole diameter of 2 mm while being vacuum deaerated, cut with a water-cooled cutter, blown and dried at room temperature after centrifugal dehydration, and an average diameter of 2 mm. An approximately cylindrical lumen bypass formulation with an average length of 2 mm was obtained.
[0030]
Example 2
25 parts of palm oil fatty acid calcium salt (purity 94.0%), 5 parts of lauric acid, and 70 parts of methionine were mixed. The mixture is put into a hopper of a twin-screw extrusion granulator, melt extruded from a die having a hole diameter of 1.2 mm while being vacuum degassed, and cut with a water-cooled cutter, with an average maximum diameter of 1.2 mm and an average length of 1.2 mm. A bullet-shaped preparation was obtained. After the centrifugal dehydration treatment, 100 parts of this preparation and 1 part of talc powder were mixed, put in an oven at 60 ° C. and dried for 16 hours to obtain the desired lumen bypass preparation.
[0031]
Example 3
23 parts of beef tallow fatty acid calcium salt (purity 97.3%), 4 parts of palmitic acid, 71 parts of methionine, and 1 part of ethyl cellulose were mixed. The mixture is put into a hopper of a twin screw granulator, melt extruded from a die having a hole diameter of 1.6 mm while being vacuum deaerated, and cut with a water-cooled cutter, and has an average diameter of 1.6 mm and an average length of 1.6 mm. A cylindrical formulation was obtained. After the centrifugal dehydration treatment, the desired lumen bypass preparation was obtained by drying at 40 ° C. for 16 hours.
[0032]
Example 4
Palm oil fatty acid calcium salt (purity 97.1%) 32 parts, myristic acid 5 parts, methionine 62.5 parts, vitamin E acetate 0.5 parts were mixed. The mixture is put into a hopper of a twin screw granulator, melt-extruded from a die having a hole diameter of 1.2 mm while being vacuum deaerated, and cut by a water-cooled cutter, and has an average diameter of 1.2 mm and an average length of 1.2 mm. A nearly cylindrical formulation was obtained. Next, 100 parts of this preparation was mixed with 1 part of bone powder, placed in a kiln heated to 50 ° C., passed slowly over 40 minutes, cooled to room temperature by applying cold air, and the desired lumen bypass preparation was obtained. .
[0033]
Example 5
20 parts of palm oil fatty acid calcium salt (purity 94.0%), 4 parts of lauric acid, 1 part of glyceryl monostearate, 65 parts of methionine and 10 parts of lysine hydrochloride were mixed. The mixture is put into a hopper of a twin screw granulator, melt-extruded from a die having a hole diameter of 1.2 mm while being vacuum deaerated, and cut by a water-cooled cutter, and has an average diameter of 1.2 mm and an average length of 1.2 mm. A nearly cylindrical formulation was obtained. Next, this preparation was put in a kiln heated to 50 ° C. and allowed to pass over 50 minutes while rotating slowly, and cooled to room temperature by applying cold air to obtain the desired lumen bypass preparation.
[0034]
Example 6
22 parts of beef tallow fatty acid calcium salt (purity 97.3%), 6 parts of stearyl alcohol, 1 part of carnauba wax and 73 parts of methionine were mixed. The mixture is put into a hopper of a twin screw granulator, melt-extruded from a die having a hole diameter of 1.2 mm while being vacuum deaerated, and cut by a water-cooled cutter, and has an average diameter of 1.2 mm and an average length of 1.2 mm. A nearly cylindrical formulation was obtained. Next, this preparation was subjected to centrifugal dehydration treatment and then dried in an oven heated to 40 ° C. for 16 hours to obtain a target lumen bypass preparation.
[0035]
Example 7
29 parts by weight of palm oil fatty acid calcium salt (purity 97.1%), 6 parts of cetyl alcohol, and 65 parts of methionine were mixed. The mixture is put into a hopper of a twin screw granulator, melt extruded from a die with a hole diameter of 2 mm while being vacuum deaerated, cut with a water-cooled cutter, blown and dried at room temperature after centrifugal dehydration, and an average diameter of 2 mm. The desired lumen bypass formulation of the desired bullet shape with an average length of 2 mm was obtained.
[0036]
Example 8
29 parts by weight of beef tallow fatty acid calcium salt (purity 97.3%), 3 parts of lauric acid, 3 parts of palmitic acid and 65 parts of methionine were mixed. The mixture is put into a hopper of a twin screw granulator, melt extruded from a die with a hole diameter of 2 mm while being vacuum deaerated, cut with a water-cooled cutter, blown and dried at room temperature after centrifugal dehydration, and an average diameter of 2 mm. The target lumen bypass preparation with an average length of 2 mm was obtained.
[0037]
Example 9
29 parts by weight of palm oil fatty acid calcium salt (purity 97.1%), 4 parts of myristic acid, 2 parts of succinic acid and 65 parts of methionine were mixed. The mixture is put into a hopper of a twin screw granulator, melt extruded from a die with a hole diameter of 2 mm while being vacuum deaerated, cut with a water-cooled cutter, blown and dried at room temperature after centrifugal dehydration, and an average diameter of 2 mm. The desired lumen bypass formulation of the desired bullet shape with an average length of 2 mm was obtained.
[0038]
Comparative Example 1
35 parts of beef tallow fatty acid calcium salt (purity 97.3%) and 65 parts of methionine were mixed. The mixture is put into a hopper of a twin screw granulator, melt extruded from a die with a hole diameter of 2 mm while being vacuum deaerated, cut with a water-cooled cutter, blown and dried at room temperature after centrifugal dehydration, and an average diameter of 2 mm. A substantially cylindrical preparation with an average length of 2 mm was obtained.
[0039]
Comparative Example 2
20 parts of beef tallow fatty acid calcium salt (purity 97.3%), 15 parts of stearic acid and 65 parts of methionine were mixed. The mixture is put into a hopper of a twin screw granulator, melt extruded from a die with a hole diameter of 2 mm while being vacuum deaerated, cut with a water-cooled cutter, blown and dried at room temperature after centrifugal dehydration, and an average diameter of 2 mm. A substantially cylindrical preparation with an average length of 2 mm was obtained.
[0040]
Comparative Example 3
Palm oil fatty acid calcium salt (purity 94.0%) 20 parts, glyceryl monostearate 5 parts, methionine 65 parts, lysine hydrochloride 10 parts were mixed. The mixture is put into a hopper of a twin screw granulator, melt-extruded from a die having a pore diameter of 1.2 mm while being vacuum deaerated, cut with a water-cooled cutter, centrifuged and dehydrated at room temperature, and air-dried at an average diameter. An approximately cylindrical preparation having a diameter of 1.2 mm and an average length of 1.2 mm was obtained.
[0041]
Comparative Example 4
28 parts of palm oil fatty acid calcium salt (purity 94.0%), 2 parts of stearyl alcohol, and 70 parts of methionine were mixed. The mixture is put into a hopper of a twin screw granulator, melt-extruded from a die with a hole diameter of 1.2 mm while vacuum degassing, cut with a water-cooled cutter, centrifuged and dehydrated, and then blown and dried at room temperature to obtain an average maximum diameter. A bullet-shaped preparation of 1.2 mm and an average length of 1.2 mm was obtained.
[0042]
Evaluation Purity of Fatty Acid Salt: Reflux extraction was performed with acetone for 8 hours using a Soxhlet extractor. The purity of the fatty acid salt was calculated from the difference in dry weight before and after the reflux extraction operation.
Calcium concentration of fatty acid salt: 1 g of fatty acid salt was incinerated at 550 ° C., dissolved in hydrochloric acid, diluted, and quantitatively analyzed with an emission spectrophotometer (ICP) to calculate the calcium concentration relative to the dry weight of the fatty acid salt.
Hardness: A tablet hardness meter is used. The weight was applied to the preparation and the breakage was started, and the hardness was measured.
The above preparations were sequentially immersed in the following simulated eluents (solution temperature 40 ° C.), and the preparation performance was evaluated from the dissolution properties.
Ruminal dissolution rate: The ratio of the amount of active substance eluted when the preparation is immersed in simulated rumen fluid at pH 6.4 and shaken for 16 hours to the amount of active substance in the preparation, and the rumen dissolution property is evaluated.
Ruminal elution rate: after measuring the rumen elution rate, the solids were separated, and the biological activity eluted into the solution when the solids were immersed in a simulated rumen fluid at pH 2.0 and shaken for 2 hours. It is the ratio of the amount of substance to the amount of active substance in the preparation, and the dissolution of the rumen is evaluated.
Elution rate of the small intestine: After measuring the elution rate of the rumen, the amount of biologically active substance eluted in the solution when the solid was separated and immersed in simulated small intestinal fluid of pH 8.2 and shaken for 4 hours. It is a ratio to the amount of active substance in the preparation, and the small intestine dissolution is evaluated.
[0043]
Simulated rumen fluid: A solution corresponding to rumen gastric juice, which is a solution in which 2.5 g of disodium hydrogen phosphate and 6.7 g of potassium dihydrogen phosphate are dissolved in water to make the total amount 11 and the pH is 6.4. .
[0044]
Simulated rumen gastric fluid: A solution corresponding to rumen gastric juice, a solution in which water is added to 50 ml of 0.2N potassium chloride and 10 ml of 0.2N hydrochloric acid to make the total volume 200 ml, and pH is 2.0.
[0045]
Simulated intestinal fluid: 9.8 g of sodium bicarbonate, 0.57 g of potassium chloride, 9.30 g of disodium phosphate 12-hydrate, 0.47 g of sodium chloride, 0.12 g of magnesium sulfate heptahydrate, 0.12 g of bovine bile powder A solution in which 05 g and 0.05 g of lipase are dissolved in water to bring the total amount to 11, the pH is 8.2.
[0046]
[Table 1]

[0047]
[Table 2]

[0048]
【The invention's effect】
As shown in Table 1, the rumen bypass preparations of Examples 1 to 9 of the present invention all have a low simulated rumen gastric elution rate, good bypass properties, and a simulated solution of the rumen and small intestine. The total dissolution rate is large, indicating good digestibility.
On the other hand, in Table 2, Comparative Example 1 using only a salt of an aliphatic monocarboxylic acid as a protective substance and Comparative Examples 2 to 4 using a protective agent composition outside the scope of the present invention are the dissolution rates in simulated rumen fluid Is large, and the lumen bypass property is inferior, and all of these are shown to have low practicality.
[0049]
As described above, a protective substance comprising a fatty acid salt having a specific composition ratio and a specific aliphatic carboxylic acid or a monovalent fatty alcohol contains a biologically active substance at a high concentration of 50% by weight or more and exhibits a good rumen bypass property. A matrix-type lumen bypass formulation could be obtained.

Claims (6)

A rumen bypass formulation for ruminants, wherein 50 to 90% by weight of the biologically active substance of the preparation is dispersed in 10 to 50% by weight of the following protective substance [I].
[I] A protective substance comprising the following 1) and 2), wherein the weight ratio of 1) and 2) is in the range of 30:70 to 10:90;
1) Palmitic acid, lauric acid, myristic acid, stearyl alcohol or cetyl alcohol 2) Fatty acid calcium salt of beef tallow or palm oil The rumen bypass preparation according to claim 1, wherein the biologically active substance is an amino acid. The rumen bypass preparation according to claim 2, wherein the biologically active substance is at least one selected from methionine and lysine hydrochloride. The rumen bypass preparation according to claim 1, wherein the biologically active substance is at least one selected from 2-hydroxy-4-methylmercaptobutyric acid and a salt of 2-hydroxy-4-methylmercaptobutyric acid. Tallow or lumen bypass formulation according to any one of claims 1 to 4 Ca concentration of fatty acid calcium salt of palm oil is 7 to 12% by weight of the calcium salt by weight. The rumen bypass preparation according to any one of claims 1 to 5, wherein the fatty acid calcium salt of beef tallow or palm oil has a purity of 90% by weight or more.