JPH0214326B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention is an antibacterial product for livestock and poultry containing a macrotetrolide antibiotic and a nonionic surfactant.
This invention relates to antiprotozoal agents and growth promoters. In recent years, macrotetrolide antibiotics have been used in livestock and
It has been found to be effective in promoting the growth of poultry, improving feed efficiency, and preventing and treating diseases, and its practical application is expected. However, the in-
There is a problem that the effect in vivo and the effect in in-vivo do not necessarily match, and the in-vivo effect has not been sufficiently discovered, and therefore the dosage must be increased. Therefore, the present inventors conducted various studies in order to ensure that the effects of macrotetrolide antibiotics can be fully demonstrated in-vivo.
By orally administering a composition containing a macrotetrolide antibiotic and a nonionic surfactant to livestock and poultry, its effects are fully exhibited,
It has been found that even if the dose is reduced, the growth promoting effect etc. can be sufficiently expressed. The present invention was completed based on the above findings. Examples of macrotetrolide antibiotics used in the present invention include nonactin, monactin, dinactin, trinactin, and tetranactin. These may be used in combination. Examples of nonionic surfactants include glycerin fatty acid ester, sucrose fatty acid ester, propylene glycol fatty acid ester, polyoxyethylene fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil derivative, etc. However, polyoxyethylene-based nonionic surfactants such as polyoxyethylene fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene sorbitan fatty acid ester, and polyoxyethylene hydrogenated castor oil derivatives are preferred. These may be used in combination. The ratio of the macrotetrolide antibiotic to the nonionic surfactant is 1 part by weight of the former to 1 part by weight or more of the latter, preferably 1 to 1000 parts by weight, and more preferably 1 to 100 parts by weight. The preparation of the present invention is not particularly limited as long as it contains a macrotetrolide antibiotic and a nonionic surfactant; Examples include preparations in which the above-mentioned agents are mixed together, and feeds containing the above-mentioned two agents. Examples of excipients include coarse wheat flour, wheat soot flour,
Examples include coarse soybean powder, soybean oil cake, cornstarch, cornmeal, defatted rice bran, wheat bran, sweet potato starch, lactose, yeast, fats and oils, calcium carbonate, talc, wood powder, carillon, chalk diatomaceous earth, water, physiological saline, etc. . The feed may be any commercially available feed for livestock and poultry, such as grains such as corn and milo, edible oil meal such as soybean meal, bran such as bran and rice bran, corn gluten meal, starch meal, soybean oil meal, etc. Manufactured lees such as molasses, meat and bone meal,
It is made by mixing feed ingredients such as fish meal, whey, skim milk powder, blood meal, feather meal, animal substances such as animal fats and oils in appropriate proportions, or by adding feed additives such as minerals, vitamins, and amino acids. It can also be feed. To produce the formulation of the present invention, a macrotetrolide antibiotic is dissolved in a volatile organic solvent such as methanol, ethanol, acetone, chloroform, benzene, etc., and a nonionic surfactant is mixed therein. Just remove it. When the nonionic surfactant is solid, it may be heated and melted, then mixed with the macrotetrolide antibiotic dissolved in the above-mentioned organic solvent, and then the solvent may be removed to form a powder. In addition, when using an excipient, the macrotetrolide antibiotic and the nonionic surfactant may be mixed separately with the excipient, but the excipient may be added to the above mixture to ensure uniformity. Mixing is preferable because the amount of nonionic surfactant used can be reduced. The concentration of the macrotetrolide antibiotic in the preparation of the present invention varies depending on its composition, so it cannot be stated unconditionally, but it is 0.0001% (hereinafter, % indicates weight % unless otherwise specified) or more based on the entire preparation, It is preferably 0.0005 to 50%, for example, in the case of a formulation consisting of a macrotetrolide antibiotic, a nonionic surfactant, and an excipient, 0.1 to 40% is preferable; 0.0001% for feed compositions containing surfactants
~0.1%, preferably 0.0005-0.05%. A preferred composition containing the preparation of the present invention includes 0.0005 to 40% macrotetrolide antibiotic, 0.0005 to 95% nonionic surfactant, and 0.001% economically.
~60% and the remainder consists of excipients and/or feed, and the nonionic surfactant is in the range of 1 to 1000 parts by weight, preferably 1 to 200 parts by weight, per 1 part by weight of the macrotetrolide antibiotic. It is a certain composition. This composition may further contain commonly used formulation auxiliaries and feed additives, if necessary. By continuously orally administering the preparation of the present invention produced as described above to livestock and poultry, the macrotetrolide antibiotic acts more effectively than when administered alone, promoting growth. , the effects of improving feed efficiency, preventing and treating diseases, etc. are fully demonstrated. There are no particular restrictions on the livestock/poultry to which the preparation of the present invention is administered, but from a practical standpoint, cows, pigs, chickens, etc. are preferred. In addition, the dosage is 0.025 mg/Kg/day or more as the active ingredient macrotetrolide antibiotic,
Preferably 0.125 to 12.5 mg/Kg/day. or,
The dosage form is the preparation as it is, or in the case of a preparation consisting of a macrotetrolide antibiotic and a nonionic surfactant, or a preparation consisting of it and an excipient, it can be administered as a powder, tablet, or granule in feed or drinking water. It may also be administered by mixing with Next, examples show that the formulation of the present invention has excellent effects. Experimental example 1 Infection prevention test for swine dysentery (1) Sample preparation Dissolve 1 part by weight of polynactin (component ratio: dinactin: trinactin: tetranactin = 1:2:7) in 20 parts by weight of acetone, and then add nonionic to the solution. Add 10 parts by weight of surfactant, mix and dissolve uniformly, then add defatted rice bran to this solution.
The composition of the present invention obtained by adding 89 parts by weight, uniformly mixing, and volatilizing the acetone to form a powder mixture was added to the basal feed shown in Table 1 so that the polynactin concentration was 0.003% ( C~
Seven points of I) were used as samples. In addition, feed alone (A) and feed containing only 0.003% polynactin (B) were used as control feeds.

【table】

[Table] (2) Test method Five piglets (LWD breed) weighing approximately 12 kg were tested per group.
Using a castrated male head, each animal was allowed to take in each sample ad libitum, and on the 3rd day after the start of ingestion of the sample, 10 pieces of pure culture agar of Treponema hyodeisenteriae were added to each animal.
Artificial infection was caused by oral administration. The state of feces was observed for 21 days after artificial infection. (3) Test results The results are shown in Table 2.

【table】

[Table] Note 2) Treponema hyodeisenteriae was detected in all mucus and bloody stools, confirming that the mucus and bloody stools were caused by swine dysentery. As is clear from Table 2, samples C to I of the present invention had fewer instances of mucus and bloody stool than control samples A and B, and the occurrence time was delayed, and furthermore, all cases had disappeared by the end of the test. In particular, samples C to F in which polyoxyethylene surfactants were used did not have mucus and bloody stools, indicating that the preventive effect on swine dysentery was sufficiently achieved. Experimental Example 2 Coccidia Infection Prevention Test by Chickens (1) Sample Preparation 1 part by weight of polynactin (component ratio: dinactin: trinactin: tetranactin = 1:4:5) was dissolved in 20 parts by weight of acetone, and then the solution was 20 parts by weight of ionic surfactant was added and mixed and dissolved uniformly, then 79 parts by weight of cornstarch was added to this solution, and after uniformly mixing, acetone was volatilized to form a powder mixture, which is shown in Table 3. Polynactin concentration in basal feed
Composition C of the present invention added to 0.002%
Six points from ~H were used as samples. In addition, feed alone (A) and feed containing only 0.002% polynactin (B) were used as control samples.

[Table] (2) Test method Five female broiler chickens (Arbor Acre species) were used per group. After the chicks were raised on a drug-free basal diet for 5 days from the first day of age, feeding of each sample was started from the 6th day of age. Then, at 8 days old, oocysts of Eimericatenella were added to each bird, 2×
¹⁰⁴ were orally administered to cause artificial infection. On the 8th day after administration of the oocysts, the chicks were necropsied, the degree of lesions in the cecum was observed, and the degree of coccidia infection was determined. Cecal lesions were classified into the following five grades as criteria for evaluation. −……The cecum is completely normal. ＋……The shape of the cecum is normal. The contents are slightly fluid and yellowish in color. The cecal mucosa is slightly swollen and whitish. ...The shape of the cecum is almost normal, and swelling of the mucous membrane is visible all over. There is no bleeding in the contents, and the mucus is yellow and discolored. A small number of white punctate necrotic foci and hemorrhagic spots are seen within the mucosa. ...The atrophic deformity of the cecum is clear and it is slightly longer than the rectum. It is often devoid of any normal contents and filled with blood clots or off-white cheese-like degeneration. The cecal wall becomes noticeably thickened and brittle, and petechiae may still remain. The lesions extend to the base of the cecum but not to the rectum. 〓...The atrophy and deformation of the cecum are noticeable, generally sausage-shaped, and its length may be the same as that of the rectum.
Or it's getting shorter. The lesion extends to 1/3 to 1/4 of the rectum. Others are the same. (3) Test results The test results are shown in Table 4.

[Table] As is clear from Table 4, Samples C to H of the present invention have better anti-coccidial effects than Control Feeds A and B, and especially Samples C to E using polyoxyethylene surfactants have anti-coccidial effects. The effect was excellent. Experimental Example 3 Growth promotion test using ruminant livestock (1) Preparation of feed 1 part by weight of polynactin (component ratio: dinactin: trinactin: tetranactin = 1:4:5) was dissolved in 20 parts by weight of acetone, and then non-ionized was added to the solution. Add 20 parts by weight of surfactant and mix and dissolve uniformly, then add wheat bran 69 to this solution.
Parts by weight were added, uniformly mixed, and then the acetone was volatilized to form a powder mixture, which was added to the basal feed shown in Table 5 so that the polynactin concentration was 0.005%. A point was used as a sample. In addition, feed alone (A) and feed containing only 0.005% polynactin (B) were used as control samples.

【table】

[Table] (2) Test method Four sheep (Suffoak breed) weighing approximately 25 kg were used per group (♀2〓2), and the sheep were given free access to samples, and their body weights were measured at the start of the test and 7 weeks after the start of the test. In addition, feed intake during that period was also measured, and body weight gain and feed conversion ratio were determined. (3) Test results The results are shown in Table 6.

【table】

[Table] As is clear from Table 6, Samples C to F of the present invention were superior to Control Samples A and B in both body weight gain and feed conversion rate, and were found to have a growth promoting effect and an improvement in feed efficiency. Next, the production of the composition of the present invention will be explained with reference to Examples. Example 1 1 part by weight of nonactin was dissolved in 40 parts by weight of acetone, and then 10 parts by weight of polyoxyethylene sorbitan monooleate was added to this solution and mixed with stirring to obtain a uniform solution composition. Example 2 89 parts by weight of defatted rice bran were added to 11 parts by weight of the liquid composition obtained in Example 1 and mixed, and then acetone was evaporated to obtain a powdered composition. Example 3 Add acetone to 1 part by weight of polynactin (dinactin: trinactin: tetranactin = 1:4:5)
This is added to 50 parts by weight of cured polyoxyethylene and castor oil derivative heated and melted at 60°C, and stirred and mixed to form a uniform liquid composition.
Next, after volatilizing the acetone, the mixture was cooled and solidified, and then pulverized to obtain a powdery composition. Example 4 5 parts by weight of the composition obtained in Example 2 was added to commercially available mixed feed.
It was added to 1000 parts by weight and mixed uniformly to obtain a feed composition.

Claims (1)

[Claims] 1. An antibacterial/antiprotozoal agent for livestock and poultry containing a macrotetrolide antibiotic and a nonionic surfactant. 2. A growth promoter for livestock and poultry containing a macrotetrolide antibiotic and a nonionic surfactant.