JPH0136810B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention provides a mycinamicin antibiotic selected from the group consisting of the antibiotic mycinamicin, the antibiotic mycinamicin, the antibiotic mycinamicin, the antibiotic mycinamicin, the antibiotic mycinamicin, and the antibiotic mycinamicin or a non-toxic salt thereof. The present invention relates to a growth-promoting carrier containing a substance as an active ingredient and having a body-increasing effect. The antibiotic mycinamicin has the following general formula [] This is a compound expressed in page 16, and is included in the category of ring macrolide antibiotics. In this general formula [], X is an epoxy group or a bonding group, R ₁ is a hydrogen atom or a hydroxyl group, R ₂ is a hydrogen atom or the following general formula [] In the hexose ring represented by, R ₃ represents a hydrogen atom or a lower alkyl group, and R ₄ represents a hydrogen atom or a lower alkyl group. Examples of the antibiotic mycinamicin include antibiotic mycinamicin, antibiotic mycinamicin, antibiotic mycinamicin, antibiotic mycinamicin, antibiotic mycinamicin, antibiotic mycinamicin, antibiotic mycinamicin, and the like. This antibiotic mycinamicin is a compound represented by the general formula [] (hereinafter referred to as compound []), where X = epoxy group, R ₁ = hydrogen atom, R ₂ = hexose ring, R ₃ = methyl group, R ₄ = A compound represented by a methyl group. In addition, the antibiotic mycinamicin has a compound [] in which X = epoxy group, R ₁ = hydroxyl group,
This is a compound represented by R ₂ = hexose ring, R ₃ = methyl group, and R ₄ = methyl group. The antibiotic mycinamicin is a compound represented by X = bonding group, R ₁ = hydrogen atom, R ₂ = hexose ring, R ₃ = hydrogen atom, and R ₄ = methyl group. The antibiotic mycinamicin is a compound []
A compound represented by X = bonding group, R ₁ = hydrogen atom, R ₂ = hexose ring, R ₃ = methyl group, and R ₄ = methyl group. The antibiotic mycinamicin is a compound [] in which X=binding group, R ₁
= hydroxyl group, R ₂ = hexose ring, R ₃ = methyl group,
A compound represented by R ₄ =methyl group. The antibiotic mycinamicin is a compound represented by X = bonding group, R ₁ = hydrogen atom, R ₂ = hexose ring, R ₃ = hydrogen atom, and R ₄ = hydrogen atom. The antibiotic mycinamicin is a compound (demycinosyl-mycinamicin) represented by X = bonding group, R ₁ = hydrogen atom, and R ₂ = hydrogen atom in the compound [], and for example, the antibiotic mycinamicin can be administered orally to mice (male). The acute toxicity of the antibiotic mycinamicin is 2319mg/Kg, the antibiotic mycinamicin is over 2500mg/kg, and the other mycinamicin antibiotics have similar acute toxicity.
These compounds can be used, for example, in Micromonospora sp. A11725 (Micro-monospora sp.
sp.A11725:FERM-PNo.4488, NRRL11452)
It may also be obtained by culturing a bacterial strain, collecting it from this culture, and converting the group X=epoxy group at positions 12-13 into a binding group if necessary (as disclosed in US Patent No.
No. 4291021, JCSChem.Comm., 1980, 120. Japanese Patent Application Publication No. 1982-14801, Japanese Patent Application Publication No. 115900-1980,
(See Japanese Patent Application Laid-Open No. 55-122799, Japanese Patent Application No. 195141-1982, and Japanese Patent Application No. 36602-1982). Furthermore, in U.S. Patent No. 429121, the detailed properties of the aforementioned Micromonospora sp. A11725 strain are listed in the specification, and the antibiotic
A11725 falls under the antibiotic mycinamicin; A11725 falls under the antibiotic mycinamicin; A11725a falls under the antibiotic mycinamicin; A11725a falls under the antibiotic mycinamicin; Added. In addition, as an example of the production of mycinamicin antibiotics, Micromonospora polytrota (Micromonospora polytrota) NRRL12066
(ATCC31584) can also be obtained by culturing a bacterial strain and collecting it from the culture.
Publication No. 83497). Furthermore, as a salt of the antibiotic mycinamicin,
Non-toxic inorganic or organic acid salts may be mentioned. Examples of inorganic acid salts include phosphates and hydrochlorides. Examples of organic acid salts include tartrate,
Hydroxy-carboxylate salts such as lactate, malate, citrate, gluconate, polycarboxylate salts such as malonate, succinate, maleate, fumarate, glutarate, aspartic acid Examples include amino acid salts such as salts and glutamate. The present inventors have proposed a mycinamicin antibiotic selected from the group consisting of the antibiotic mycinamicin, the antibiotic mycinamicin, the antibiotic mycinamicin, the antibiotic mycinamicin, the antibiotic mycinamicin, the antibiotic mycinamicin, and the antibiotic mycinamicin or a non-toxic salt thereof. By adding one or more of these to livestock, poultry feed, fish feed, or drinking water, the growth rate can be significantly increased, the feed efficiency can be improved, and an excellent weight gain effect can be achieved. I learned that it was meant to be played. The present invention was completed based on the above findings, and is a growth promoter for livestock, poultry, and fish containing a mycinamicin antibiotic as an active ingredient. First, as the mycinamicin antibiotic of the present invention, the above-mentioned compounds [], such as the antibiotic mycinamicin, the antibiotic mycinamicin, the antibiotic mycinamicin, the antibiotic mycinamicin, the antibiotic mycinamicin, the antibiotic mycinamicin, the antibiotic mycinamicin, or their non-toxic One type of salt, purified or crude, or a mixture of two or more types can be used. In addition, as a salt of the antibiotic mycinamicin, based on the properties of the weakly basic antibiotic mycinamicin, which is soluble in acidic water, methanol, acetone, and ethyl acetate, and insoluble in basic water, it can be prepared in an inert medium. , a selected inorganic salt, a hydroxy-carboxylic acid, a polycarboxylic acid, an amino acid, etc. are added to an aqueous solution of an acidic substance to form the desired salt, which is then dried and collected. various acid salts of. Furthermore, the mycinamicin antibiotic may be used as it is, and if necessary, binders, fragrances, surfactants, disintegrants, dispersion aids, etc.
It may be used after being granulated and processed by adding excipients and the like. Next, when preparing a growth promoter containing this mycinamicin antibiotic as an active ingredient, this mycinamicin antibiotic is added to the target feed or aqueous solution to produce a growth promoting effect that can increase the body mass and improve feed efficiency. To obtain a carrier, which is an additive composition for the purpose of the present invention, target feeds include livestock feeds, including those for experimental or pet animals, poultry feeds, and fish feeds, and any appropriate feed can be used. . For example, corn, rice, wheat,
Cereals and brans such as milo, rice bran, and bran; oil meal such as cottonseed meal, soybean meal, and safflower meal; meat; fatty oils such as bone meal, fish meal, soybean meal, cottonseed oil, peanut oil, corn oil, and sesame oil; Yeast, alpha alpha, lactose, sucrose, glucose, methionine, choline chloride, vitamin A, vitamin D, vitamin E,
Vitamins such as vitamin _K1 , vitamin _K2 , vitamin B1, vitamin _B2 , vitamin _B6 , vitamin _B12 , calcium _pantothenate , folic acid, talc acid, acid clay, calcium carbonate, magnesium sulfate, potassium iodide, It may be a mixture of part or all of calcium phosphate, sodium salt, etc.
In addition, antibiotics such as colistin, penicillin antibiotics and amino sugar antibiotics, sulfur drugs, hemostatic agents such as tranexamic acid, anthelmintic agents, enzyme agents, lactic acid bacteria preparations, preservatives, flavoring agents, emulsifiers, wetting agents and solubilizers. The agent may be added as necessary, and may be selected and prepared according to the intended breeding type, animal species, etc. by those skilled in the art.
Morrison Publishing Compang, Clinton;
Iowa, 1959). For example, in animals such as pigs, supplemental vitamins and grains
A feed containing 80% protein, 5-35% animal and vegetable protein, and 2-5% minerals is suitable. In addition, the amount of mycinamicin antibiotic added to such feeds, feedstuffs, or aqueous solutions is generally 0.5
It may be adjusted to contain up to 500 ppm. For more information, see pigs, cows, horses, sheep, goats, rabbits,
For domestic animals, including laboratory animals such as dogs, cats, rats, mink, and mice, do not include the following in their livestock feed:
Generally, 200 ppm or less, preferably 5 to 40 ppm of mycinamicin antibiotics may be contained as an active ingredient. Also egg-laying or meat-producing chickens, ducks, geese, turkeys, quail, pheasants,
For poultry animals such as parakeets and doves, the poultry feed and drinking water may generally contain 200 ppm or less, preferably 0.5 to 20 ppm, of mycinamicin antibiotics as an active ingredient. Furthermore, feeds and aqueous solutions for marine fish such as yellowtail, sea bream, and shrimp, and freshwater fish such as trout, carp, eel, and sweetfish, generally contain 200 ppm or less, preferably 5 to 200 ppm, of mycinamicin antibiotics as an active ingredient. Bye. Furthermore, an aqueous solution of mycinamicin antibiotic may be prepared and used in the above concentration range based on the intended breeding type. In addition, when preparing the desired carrier by adding mycinamicin antibiotics to these feeds or aqueous solutions, it can be done by any appropriate conventional method, and it may be added to the feed or feed materials in advance, or It can be prepared by uniformly adding and mixing by mixing, dipping, spraying, etc., using a mixer if necessary, when formulating food or feed or before administering feed or feed. When the carrier prepared in this way is fed to the target livestock, poultry, and fish, the growth rate is significantly increased, and the feed efficiency is also improved, and it has a growth promoting effect that is an excellent weight gain effect. In addition, the egg production rate and fertilization rate were also improved and were extremely excellent. Next, the effects of the present invention will be explained using test examples, but the present invention is not limited thereto in any way. Test Example 1 [Body Gain Effect on Chickens] Using 10 male and 10 female chickens, the antibiotic mycinamicin phosphate (antibiotic mycinamicin 1000 μg titer/mg) was prepared by adding the antibiotic mycinamicin to salt by adding an aqueous solution of phosphoric acid. (formed product) was added to a test feed having the ingredients shown in Table 1 below, and the feed was thoroughly and uniformly mixed in a V-type mixer to determine its weight gain effect.

[Table] TDN: (Total digestible nutrient) Calculate the total digestible nutrients by multiplying the feed component content by the digestibility of each component. However, in this case, digestible crude fat has a high amount of heat generated in the body, so it is added by multiplying it by 2.25. The test plot settings are as shown in Table 2.

【table】

【table】

[Body gain effect on chickens]

The antibiotic mycinamicin from Test Example 1 above
The same procedure as in Test Example 1 was conducted using the antibiotic mycinamicin phosphate (antibiotic mycinamicin titer 525 μg/mg) instead of the phosphate. As a result, the average weight of chickens during the test period (average per bird in each group) is shown in Table 5, and the average weight of chickens during the test period (average per bird in each group) is shown in Table 6. The antibiotic mycinamicin had a good weight gain effect when added in amounts of 1 ppm or more.

[Body gain effect on chickens]

Using 25 male and 25 female chickens each, the antibiotic Mycinamicin mixture/phosphoric acid (Antibiotic Mycinamicin 25%, Antibiotic Mycinamicin 70%
% and other 5%, including the antibiotic mycinamicin, etc.: Antibiotic mycinamicin mixture (647 μg titer/mg) was added to the test feed shown in Table 1 of Test Example 1, and the mixer was added to the test feed shown in Table 1 of Test Example 1. The animals were given a feed that had been thoroughly and uniformly mixed in the feed, and the weight gain effect and feed conversion rate were determined. The test plot settings are as shown in Table 7.

【table】

[Body gain effect on pigs]

Using 10 pigs, the antibiotic Mycinamicin
Phosphate was added to a test feed containing the ingredients shown in Table 11 below, and the feed was mixed sufficiently and uniformly in a V-type mixer to determine its weight gain effect.

[Table] DCP: (Digestible crude protein) The test area settings are as shown in Table 12.

[Table] As a result, Table 13 shows the average weight gain of piglets during the test period (average per pig in each group), and the average weight gain of piglets during the test period (average weight per pig in each group). ) are shown in Table 14, and the feed intake and feed conversion rate (average per head in each area) are shown in Table 15. As a result, the antibiotic Mycinamicin
A good weight gain effect was achieved at 5ppm or higher.

【table】

[Table] *: Significant difference at 5% risk rate

[Body gain effect on pigs]

The antibiotic mycinamicin from Test Example 4 above
Instead of phosphate, a mixture of antibiotic myinamicin (contains 25% antibiotic mycinamicin, 70% antibiotic mycinamicin, and other 5% antibiotic mycinamicin, etc.)
Phosphate was added to a test feed containing the ingredients shown in Table 11 above, and the feed was thoroughly mixed in a V-type mixer to determine the weight gain effect. The experimental plot settings are as shown in Table 16.

[Table] As a result, Table 17 shows the average weight gain of piglets during the test period (average per pig in each group), and the average weight gain of piglets during the test period (average weight per pig in each group). ) are shown in Table 18, and the feed intake and feed conversion ratio are shown in Table 18.

【table】

[Table] *: Significant difference at 5% risk rate

[Table] (Average per head in each area) is shown in Table 19. The antibiotic mycinamicin mixture had a good weight gain effect at 10 ppm or more. Test Example 6 Using 100 yellowtail (young fish) each, add the antibiotic mycinamicin phosphate to frozen sardines and frozen horse mackerel, and add it to the prepared test feed until it becomes sufficiently uniform. We fed them the mixed feed for 21 days and determined its effect on weight gain. The test plot settings are as shown in Table 20.

[Table] The results are shown in Table 21, and the antibiotic mycinamicin had a good weight gain effect at 5 ppm or more.

【table】

[Table] Test Example 7 Using 10 pigs, the antibiotic mycinamicin mixture (containing the antibiotic mycinamicin 25%, the antibiotic mycinamicin 70%, and the antibiotic mycinamicin as the other 5%), phosphate, and using gentamicin,
The feed was added to a test feed containing the ingredients shown in Table 11 above and thoroughly mixed in a V-type mixer to determine its weight gain effect. The test plot settings are as shown in Table 22.

[Table] As a result, Table 23 shows the average weight gain of piglets during the test period (average per pig in each group), and the average weight gain of piglets during the test period (average weight per pig in each group). ) are shown in Table 24, and the feed intake and feed conversion rate (average per head for each group) are shown in Table 25.
The 1st ward had a better weight gain effect compared to the 4th ward.

【table】

【table】

[Table] Also, instead of the antibiotic mycinamicin, the antibiotic mycinamicin, or the antibiotic mycinamicin mixture containing these as main ingredients, the antibiotic mycinamicin, the antibiotic mycinamicin, the antibiotic mycinamicin, the antibiotic mycinamicin, or the antibiotic mycinamicin may be used. , which also has a body-increasing effect.

Claims (1)

[Scope of Claims] 1. A mycinamicin antibiotic selected from the group consisting of the antibiotic mycinamicin, the antibiotic mycinamicin, the antibiotic mycinamicin, the antibiotic mycinamicin, the antibiotic mycinamicin, and the antibiotic mycinamicin or a non-toxic salt thereof. A growth promoter for livestock, poultry, and fish containing substances as active ingredients. 2 Claim 1 containing 0.5 to 500 ppm of mycinamicin antibiotic as an active ingredient
Growth promoters as described in section. 3. The growth promoter according to claim 1 or 2, which is livestock feed containing 5 to 40 ppm of a mycinamicin antibiotic as an active ingredient. 4. The growth promoter according to claim 1 or 2, which is a poultry feed containing 0.5 to 20 ppm of a mycinamicin antibiotic as an active ingredient. 5. The growth promoter according to claim 1 or 2, which is fish feed or an aqueous solution containing 5 to 200 ppm of a mycinamicin antibiotic as an active ingredient. 6 Non-toxic salts include phosphate, hydrochloride, tartrate,
selected from the group consisting of lactate, malate, citrate, gluconate, malonate, succinate, maleate, fumarate, glutarate, adipate, aspartate and glutamate The growth promoter according to claim 1, which is a non-toxic salt.