JPH0257903B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention provides 2-(N-2'-hydroxyethyl carbamoyl)-3-methyl-quinoxaline-1,
The present invention relates to a non-dusting animal feed additive composition containing 4-dioxide as a medicinal ingredient. 2-(N-2'-Hydroxyethyl-carbamoyl)-3-methyl-quinoxaline-1,4-dioxide is commonly known as "Olaquindox".
It is a compound with excellent antibacterial properties called olaquindox, and is widely used in the field of veterinary medicine to prevent and treat bacterial infections in livestock and poultry, and to promote growth and/or improve feed efficiency. There is. When Oraquindox is used as an animal medicinal composition for these purposes, Oraquindox is usually supplied to the user in the form of a feed premix, and the user usually mixes this premix with animal feed and feeds it to livestock and poultry. It is. Premixes are generally prepared by mixing ground Oraquindocus powder with a particulate edible excipient (or carrier) material such as rice bran, corn jam meal, soybean meal, or wheat flour in a suitable mixing device such as a mixer or blender. However, since premixes prepared in this way are in powder form, dust is easily scattered during their manufacture, handling, or addition to feed. In particular, since Orakindox is finer than a commonly used excipient, most of the scattered dust is Orakindox. Therefore, to avoid inhalation during handling by manufacturers and users of such premixes,
Premixes are desired to be non-dusting. For example, in response to such requests,
Japanese Patent Publication No. 57-53056 discloses that (a) a non-toxic oil is pre-blended with an edible carrier, (b) this blend is mixed with antibacterial quinoxaline-1,4-dioxide,
Furthermore, (c) by adding non-toxic oil to the mixture obtained in step (b), antibacterial quinoxaline-1,4-
A method for producing a non-dusting animal feed additive premix containing dioxide is disclosed.
However, this method is complicated because it requires a three-step manufacturing process, and the cost of the product is high, and the dust-free properties of the manufactured premixes are not fully satisfactory. Therefore, the present inventors have conducted extensive research in order to provide an Oraquindox-containing composition for animal feed additives that has extremely low dust and can be produced relatively easily using readily available and inexpensive excipients. As a result of this research, they discovered that by employing rice bran oil cake as the excipient and using it in combination with liquid paraffin, an Oraquindox composition with extremely low dust content could be obtained, leading to the completion of the present invention. . According to the invention, therefore, (a) 2-(N-2'-hydroxyethyl-carbamoyl)-3-methyl-quinoxaline-1,4-
Dioxide 5-80% by weight (b) Rice bran oil cake 12-94.5% by weight, and (c) Fluid paraffin 0.5-8% by weight [However, the above weight% is (a), (b) and (c) 3 Based on the total amount of the components] A non-dusty feed additive composition containing Oraquindox is provided. Orakindox, which is used as a medicinal ingredient in the present invention, has the following formula: It is a compound that has excellent antibacterial properties as shown in the following, and is effective in promoting animal growth and/or improving feed efficiency. Therefore, in order to improve absorption into the animal body and uniform dispersibility in the composition, it is desirable that Orakindox be incorporated into the fiber in a finely pulverized form. It is convenient to preferably pass through a 100 mesh sieve. One feature of the present invention is that rice bran oil cake is used as the excipient (or carrier) material in preparing the feed additive composition (hereinafter also referred to as premix) containing Oraquindox. It is in. Conventionally, rice bran, corn jam meal,
Various edible powdery and granular plant congeners such as soybean meal and coarse wheat flour have been used (for example, see the above-mentioned Japanese Patent Publication No. 57-53056), but in the present invention,
It has surprisingly been found that the use of rice bran oil cake as excipient material results in a much less dusty premix than when using other excipient materials, such as bran. The "rice bran oil cake" used in the present invention is a component obtained by removing oil to a desired degree by compression, organic solvent extraction, etc. from raw rice bran containing the seed coat and germ obtained in the process of milling brown rice. included,
Generally, it is convenient to use it in the form of a powder having a particle size that passes through a 20-mesh sieve, preferably a 60-mesh sieve. Another feature of the present invention is the use of fluid paraffin as a dust-preventing agent component to reduce the dustiness of the blend of Oraquindox and rice bran oil cake as an excipient. In the above-mentioned Japanese Patent Publication No. 57-53056, soybean oil, corn oil, mineral oil, etc. are exemplified as dust preventive ingredients for premixes containing quinoxaline-1,4-dioxide, and soybean oil is used in the examples. In the present invention, fluid paraffin is used as a dust prevention agent component, and when it is blended into premixes, it exhibits a dust suppression effect far superior to that of soybean oil, etc., even though it is used in a relatively small amount. was discovered. In addition, compared to soybean oil, corn oil, and other vegetable oils that easily oxidize and deteriorate, liquid paraffin shows no or little change during storage and is much more stable in premixes. Excellent. The feed additive composition of the present invention can be prepared by uniformly mixing the above-mentioned Oraquindox, rice bran oil cake, and liquid paraffin. In that case, the mixing ratio of each component can be within the range shown in the table below.

【represent

[Table] Fins However, the weight percentage is based on the total weight of the three components (a), (b), and (c).
Mixing of the above components is carried out by simultaneously charging the three components of Orakin Dox, rice bran cake, and liquid paraffin into a suitable mixing device such as a high-speed mixer, vertical and horizontal blenders, air mixers, and roll mixers. Alternatively, for example, rice bran oil cake and liquid paraffin may be mixed in advance and Orakindox may be added to the mixture, or rice bran oil cake and Orakindox may be mixed while stirring. It is also possible to add liquid paraffin by spraying. In addition, when preparing the feed additive composition of the present invention, a part of the rice bran oil cake as an excipient substance may be substituted with other ordinary excipient substances, such as mineral substances such as calcium carbonate; animal substances such as fish meal; soybean meal. It is also possible to substitute with plant matter such as. However, if other excipients are used in too large a quantity, the effect of the present invention obtained by using the rice bran oil cake described above will be diluted, so if other excipients are used together, It is desirable to limit the amount to 40% by weight or less, preferably 20% by weight or less of the total amount. In addition, in this specification, it should be understood that "rice bran oil cake" includes rice bran oil cake in which a portion of rice bran oil cake is replaced with other excipient substances. Furthermore, the composition of the invention may optionally contain other conventional additives, such as vitamins, minerals,
Amino acids, sugars, antioxidants, antibiotics, synthetic antibacterial agents, pigments, organic acids, enzymes, etc. can also be blended in commonly used amounts. As is clear from the examples below, the feed additive composition of the present invention described above emits extremely little dust, and is useful for health and hygiene for manufacturers and users who handle the composition. Moreover, rice bran oil cake is easily available and inexpensive, and the composition of the present invention can be produced simply by mixing the components, making it economical. Therefore, the composition of the present invention can be used as an animal feed additive for livestock such as cows, pigs, goats, rabbits, dogs, cats, etc.
It can be widely used to prevent or treat bacterial infections in poultry such as chickens, ducks, and turkeys, promote growth, and improve feed efficiency. Next, the present invention will be explained in more detail with reference to Examples. In the Examples, "parts" and "%" are "parts by weight" and "% by weight", respectively. In addition, the dust resistance test of the compositions (premixes) prepared in the examples was conducted using Stauber as specified in the Council Directive on Feed Additives of the European Community.
Heubach method [Fresenius Z.Anal.Chem.318:522
-524, Springer Verlag, 1984] using 50 g of Premix. An outline of the dust test method is given below. (1) Equipment Consists of a rotating drum with internal partitions (dust generator), a glass bottle for removing coarse particles, and a dust collector. The rotating drum is connected to a motor that rotates at low speed. The collection device is connected to a vacuum pump to draw in a certain amount of air. (2) Operation method Accurately weigh 50g of sample, put it into a rotating drum,
Rotate at 30 rpm. A filter with a pore size of 0.45 μm is attached to the collection device, and air is sucked at 4/min for 5 minutes using a vacuum pump. After stopping,
Carefully remove the filter, extract with a solvent, and analyze the collected components. (3) Quantification method of Oraquindox in dust test
Add 50 ml of water mixture (8:2), apply ultrasonic waves for 30 minutes, and then remove the filter. Wash the filter with acetone and combine the washing solution with the extract solution.
Distill the solvent under reduced pressure below 40° and dissolve the residue in water to make exactly 10 ml. This liquid is filtered and used as a sample solution. Separately, dry Orakindox standard product, accurately weigh out approximately 0.02g, add water and dissolve to make exactly 200ml.
Measure 2ml of this liquid accurately, add water to make exactly 200ml.
ml. Furthermore, accurately measure 2 ml of this liquid,
Add water to make exactly 200ml and use it as the standard solution.
Test 800μ of the sample solution and standard solution using liquid chromatography under the following conditions. Measure the peak area or height of olaquindox of each solution and calculate _AT (H _T ) and A _S (H _S ).
seek. Amount of Orakindox (C ₁₂ H ₁₃ N ₃ O ₄ ) (μg) = Amount of Oraquindox standard product (mg) × A _T (H _T ) / A _S (H _S ) × 1
/200 Operating conditions: Detector: Ultraviolet absorption photometer (measurement wavelength: 373 nm) Column: A stainless steel tube with an inner diameter of 4 mm and a length of 200 to 250 nm, filled with octadecyl silylation as a packing material.
Fill with 5 μm silica gel. Column temperature: Constant temperature around 40°C Mobile phase: Add 15 ml of methanol to 85 ml of water. Flow rate: constant flow rate of 1.0 to 1.5 ml per minute Example 1 10 parts of crushed Oraquindocus (particle size: passed through a 60 mesh sieve), 89 parts or 86 parts of excipient material, and 1 part or 4 parts of fluid paraffin were mixed in a high-speed mixer. A premix was prepared by mixing, and the type of excipient material and dust content were investigated. The results are shown in Table 1 below.
Shown below. The excipient materials used were soybean meal, wheat flour, bran, and rice bran oil meal, all of which had a particle size that would pass through a 60-mesh sieve.

[Table] As is clear from the results shown in Table 1, for both 1% and 4% of liquid paraffin, when rice bran oil cake was used as an excipient, the ratio was higher than when using any other excipient. It can be seen that rice bran oil cake is an excellent excipient material for premixes as it has less dust. Example 2 10 parts of crushed Oraquindocus (particle size: passed through a 60 mesh sieve), 85-90 parts of rice bran oil cake (particle size: passed through a 60 mesh sieve), and 0-90 parts of fluid paraffin
Five parts were taken and blended in a high speed mixer to produce premixes containing 0, 2, 3 and 5% of fluid paraffin. Take 50g of each premix,
A dust test was conducted. As a result, as shown in Table 2 below, when fluid paraffin was present, there was less dustiness and stable results were obtained.

[Table] Example 3 Orakindox (Particle size: Passed through 60 mesh sieve)
Take 10 to 80 parts, 4 parts of liquid paraffin, and rice bran oil cake or bran (particle size of each: passed through a 60-mesh sieve) and the remainder (total amount of 100 parts).
Prepare the premix by mixing in a high-speed mixer,
A dust test was conducted. As a result, as shown in Table 3 below, when rice bran oil cake was used as the excipient material, the amount of dust was stably maintained at a low level regardless of the concentration of Orakindox.

[Table] Example 4 After sieving the rice bran oil cake and adjusting the particle size within a certain range, 16 to 86 parts of the rice bran oil cake, 4 parts of liquid paraffin, and 10 to 80 parts of Orakindox were taken and mixed with a high-speed mixer. Premixes were prepared containing 10, 25, 50 and 80% Oraquindox, respectively. A dust test was conducted on 50 g of each premix. The results are shown in Table 4 below.

[Table] Example 5 86 parts of rice bran oil cake and 4 parts of liquid paraffin were mixed in advance using a high-speed mixer.Next, 10 parts of Orakin Dox was added and further mixed to prepare a premix. On the other hand, 86 parts of rice bran oil cake and 2 parts of liquid paraffin were mixed in advance with a high-speed mixer, then 10 parts of Orakin Dox were added and mixed, and 2 parts of liquid paraffin were added and mixed again to prepare a premix. A dust property test was conducted using 50 g of each premix and. The results are shown in Table 5 below.

[Table] Example 6 Take 87 parts of rice bran oil cake and 10 parts of Orakindox, add liquid paraffin, 3 parts of soybean oil or castor oil, and mix with a high-speed mixer to prepare premixes. Take 50g of each premix. , a dust test was conducted. The results are shown in Table 6 below. As shown in Table 6, the suppression of dustiness was the best when fluid paraffin was used, and the fluidity of the premix was also good.

【table】

Claims (1)

[Claims] 1 (a) 2-(N-2'-hydroxyethyl-carbamoyl)-3-methyl-quinoxaline-1,
4-dioxide 5-80% by weight (b) rice bran oil cake 12-94.5% by weight, and (c) fluid paraffin 0.5-8% by weight [However, the above weight% is based on (a), (b) and (c) ) based on the total amount of the three components] Quinoxaline-1,
A non-dusty feed additive composition containing 4-dioxide.