JPS588012A - Composition for pig - Google Patents

Abstract

PURPOSE:A composition for pig exhibiting excellent preventing and remedying effect on swine dysentery, promoting the growth of pig, accelerating the feed utility, and raising swine productivity, comprising a compound like lankacidin A or lankacidinol. CONSTITUTION:A composition for preventing and remedying swine dysentery or raising swine productivity, comprising one or plural kinds of lankacidins shown by the formula (R<1> is =O, or =(H)OH; R<2> and R<3> are each H or acyl group derived from carboxylic acid). the lankacidins shown by the formulaI are antibiotics or their derivatives which are separated from the culture of Streptomyces rochei var. volubilis. EFFECT:Having extremly high safety.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention provides 1. Preventive treatment of red-* mt or ilO fertility improvement M
Regarding IIL magistrates. More specifically, the present invention is based on the general formula: H, V and R each represent hydrogen or a S/μ group derived from μ-bonic acid. It is a relative.

swine dysentery)
Ponem hyodys@nt@riae) It is a contagious O-intestinal infection mainly caused by transfusion-induced diarrhea caused by PC, and its occurrence is recognized in most pigs raised (Ilomaalli, R
Muu4'Lmymy4. W, IL Th: Mute
atr, 4th C@31JF, Xmtmrh
Pigma*%8oh, Xow*jJBmu (197・)]
Once a single shrimp emerges, it becomes permanent, and cleaning becomes extremely difficult.For this reason, in the case of low-quality breeding, there is a large economic loss due to death of affected pigs, reduced growth, etc. It is refreshing to be invited.

Conventionally, various drugs have been used to prevent and treat swine dysentery, but they have not always been satisfactory, such as insufficient efficacy or safety issues. Although research into vaccines and the like is progressing, sufficient results have not been obtained, and nothing that is satisfactory for practical use has yet to be completed.

The present inventors have carried out intensive research based on this technical background, and as a result have discovered the new finding that chemical compound (1) has remarkable preventive and therapeutic effects against swine dysentery that cannot be achieved with conventional drugs. In addition, it was found that the chemical compound (1) promotes growth O, improves feed O utilization O, increases pig O productivity, and is extremely beneficial for livestock management.

That is, the present invention is characterized by containing the metal compound (I).
The present invention provides a composition for preventing and treating swine dysentery, which is highly effective against swine dysentery, and is extremely safe, as well as improving pig productivity by promoting population growth and improving feed efficiency.

Chemical compound (I) is funkaoidin (1ankaoidin).
) group, collectively known as Streptomyces lechei ba μ
・Bobilis (streptom70@a rooh*
i var.

Antibiotics (antibiotics? - 2636) isolated from cultures of A.
It is a cast conductor.
H, R”: C0CH,), funkacidin c(n”
knee.

, R": H, R': H), F/its/N/
-*A (R”:<oHe l”: H, R3: C
ocH,), Tsunka V Shino! (11:<.!rR1
: H, R3: H)! Which producing bacteria, manufacturing method, and physicochemical/biological properties (K)%/m are known, for example, from The Journal Antibiotics (J, Jultlb).
iotlos) Vol. 24, pages 1-41 (111)
: COCl! , C1l, , Rs: coaH,)
, ? Ykura Vji/Ca1-7? -to (R unit -
o, t': cocyti.

,R":!ri51g18-pw'o*-)(1'knee0
゜1": cocii, C1j, R': I),
Oka 14-rvx Hio *-) (R": -0, R":
H, R3: C0CH,CH,), 8.14-Sia' to 'P-) (R": -0, R", R":C
0CH, ), 1! Ill, 14-dipropionate (11: 0, R", R": C0CH, CI
I, ), 8-benzony) (R1: -0, R
”: C0Ph, R”: H), Oka 14-penzoate (R1: vaginal 0, R”: H, R”: C0
Ph).

14-Feniμpropione) (R1:60, 1:
H, R”: COCl[, CII, Ph), Oka1
4-nicotine) (ni: a-Q, R”: I
I, R”: Nicotine 4v)tkEOS production method and physicochemical/biological properties, for example, in Journa l&/- Op Antibiotitas, Vol. 26, 647-
657 pages (1973) K, Hunmi V Shin C14-Hoμ
(R1 knee 0, l”: H, II: Co1t
) C) The production method and physicochemical properties are described, for example, in Tokukai Publication No. 4@-74.

Streptomyces tscheiba bilis, which is the producing bacterium of NasifuntI￥Vunmu, C, Tsunka V Ginorum, and Lankashisinomu, has been donated to the Fermentation Research Institute and the American Type Culture Collection. Microbial accession numbers XFO12507 and ATCC212
59, respectively.

The carboxylic acid-derived OaV~ group as Ra> and Rs in the above-mentioned nine general formulas (I)
Homi L, Acechi μ, Propioni Voice, Guchiri μ, Inbutiril, Barre 9! , hexaμ, etc. preferably have 1 carbon number
~ T) in the aromatic force μ bonic acid residue (@, pence μ
Preferred are aromatic carboxylic acid residues such as amer μ carboxylic acid residues and nicotinoid μ μ carboxylic acid residues, and this lower fatty acid residue may be substituted at its terminal with a phenyl group (e.g., Fueni μa Kagochi β, Fueni μ de Gekibioni μ Ken and).

Of the metal compounds (1) used in the present invention, bkeR", R"casolesottt hydrogen is Cx-Ca
Those that are OII fatty acid residues are preferred, especially those that are OII fatty acid residues, especially those that are OII fatty acid residues.
c14-p! bionate, a8-acetate, -3-
It is better to use a mixture of these: deta bionate, hunka\vnorm, hunriki vfnormae.

In particular, Ranka V Jinmu 9 (Oyohi) Wonka V Jin C can be used advantageously.

For pigs according to the invention! The chemical substance may contain one type of compound represented by compound (1), and may contain several types of chemical substances (1).
may be contained at the same time. Further, the above-mentioned fermentation medium of Streptomyces rochei pa.

The product for the prevention and treatment of swine dysentery of the present invention is prepared by diluting the chemical compound (1) with a solid diluent, and without diluting it. (by coating etc.),
For example, powder, powder, 111 granule, tablet, liquid, paste, turnip tablet, injection, etc., or feed,
It is produced by dispersing it in a diluent and adding whole pieces directly to drinking water. As a diluent,
Any material may be used as long as it is physiologically harmless in itself, and it is more desirable that it can be used as feed or a component of feed. Solid carriers include barley flour, wheat flour,
Naked wheat flour, corn flour, soybean flour, soybean meal, rapeseed meal, fir gaff, rice mecha, skimmed mecha, KanFit flour, barley stain flour, Tou 7 lees, starch, lactose, sucrose, glucose, fructose,
#Mother, waste yeast.

Examples of the carrier include fish meal, lily, acid clay, and clay. Examples of liquid carriers include water, physiological saline, and physiologically harmless organic solvents. O adjuvant as appropriate for its saturation,
For example, emulsifier 1 dispersant, suspending agent, wetting agent, concentration agent, gel μ
There is no problem in adding an appropriate amount of a curing agent or a solubilizing agent. Furthermore, preservatives *Soda.

Antibiotics, enzyme agents, and lactic acid agents may be combined.
These O compositions may also be blended with vitamins, 1, 1, 1, 1, 2, 1, 2, 3, 3, 3, 3, 3, 4, 5, 6, 7, 8, 1, 2, 3, 3, 3, 3, 4, 4, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , .

For prevention and treatment of swine dysentery according to the present invention! The dosage of the composition for internal use can be selected depending on the pig's symptoms (age), administration method, etc., but for example, during the prevention of swine dysentery, compound (1) should be administered to the pig. It is preferable to administer once 0005-25IIlk47, and when the ζO concentration is about 1-S
@ Opp Otori) It is best to add it to the feed so that the amount is 2 to 200 PPMK. In addition, for the purpose of treating swine dysentery, compound (1) is used at approximately 1 to 25 da/k.
Preferably, the dose is about 2-500 g/8.
It is preferable to add it to the feed at a concentration of about 2.5 to 200 ppm. On the other hand, for the purpose of improving pig productivity, approximately 0.025 to 10QF/
It is preferable to administer about 0.5 kg/day.
It is preferable to add it to the feed in an amount of about 1 to 10,100 ppm (200 ppm).

The toxicity of chemical compound (1) to animals is extremely low, and in an acute toxicity test using mice, it was found that oral administration of L
D, 0 is Ranka FspyC, W414-propionate and Funka V Jim and more than %1 turtle OOO da/kg,
LD, by intraperitoneal administration. ga tsun*vynh II,
000-10,000q/k1. , Funkacidin C14
-10.00011F/kg or more for propionate,
In Tunka V Jin C, it was 4.5001F/-.

This does not mean that it is highly safe for humans during production and distribution, but that Xu Chunjing to target animals is widely rounded. It has been shown that there is heterogeneity in the number of animals tested and that safety can be guaranteed.

Next, the present invention will be explained in more detail with reference to experimental examples and examples, but it is not to be said that these do not limit the %O of the present invention.

Experimental example / In vitro antibacterial activity test against Trebonema hyodei senteriae, the causative bacterium of swine dysentery. : 1978) K
Measure according to the same method, and the result will be shown in the first prize〉, Wonka F
VnC showed strong antibacterial activity, but nine other antibiotics were used for comparison, all of which were ineffective.

Table 1 (1) 11 strains: All of them were isolated from the mucus-blood stool of pigs with swine dysentery in Japan* Trepome + aa hyod
Bacterial strain belonging to Ygemteria* (2) Antibacterial activity measurement method: Agar DilutiOl
l Method (agar plate dilution method) (3) Amount of inoculated bacteria: 10'CFIJ/m solution 1 white pot ear (4) Culture conditions: Ga5Pak (BBL) method, 31
゜2-day culture experiment example λ An in vitro antibacterial activity test was carried out on a representative example of chemical compound (1) 0 in the same manner as in experiment example 1. 70@71 Kaisho 58-
8012 (4) The fruit is shown in Table 142), and although there is a slight difference in the minimum inhibitory concentration, all of them show remarkable antibacterial activity against Trebonema hyodysenteriae.

Note) Experimental conditions are Experimental Example/, (Table 1) KM Experimental Example 3 In vitro resistance test was conducted on chemical compound (1) K in the same manner as in Experimental Example/. 9 shown in mS table
All of them showed remarkable antibacterial activity in Trebocarma.

Table 3: Experimental Examples of Experimental Swine Dysentery Infection Using Vemous Mouse: Funka V Jinmu, Funka V Jin C, Wonka S/Sin Cs-Acetate, Funka Shigin Cl4-Propionate, Funka IIV Synome μ and Funka V Shino fi10 anti-swine dysentery efficacy test was conducted in the dormitory.

Tatoehainhueta VM'n and Inmunity 2nd
5, pp. 757-764) (1975).

Amedakan Jana μ op Vetetsu Nataz Search Vol. 41 pp. 1225-1226 (1980) and Veterinary Record Vol. 107 pp. 527-529 (1980)
Using a mouse experimental swine dysentery infection model μ similar to that described by Ziens et al. i.e. 5%
Tryp
ticaa soyagar; BBLjl) was cultured anaerobically on a plate.
ri'i'! 'jjF isolates were ground together with the medium, and the
The infected material was diluted 2 times with soy brot (JBB Lllll) and inoculated into the stomach of mice. The drug was suspended in a 5x gum avia solution and administered orally by force from 1 day to 4 days after infection. After the infection, the lesions in the cecum were observed and the cecum was ground up with an inner surface. repem@m hyo
dys@nt@ria* Measure 11 numbers.

The results are summarized in Table 114) All of the products in Hanazyakuya Yodo showed excellent efficacy.

Experimental example: We conducted an anti-swine dysentery efficacy test of Wonka V Jin C under experimental infection conditions. Namely, 6-year-old Landrace sow 1
Six pigs (4 pigs per group) were tested, and a test drug for home-housed piglet formula BK containing no antibacterial substances was added and mixed to a concentration of 100 ppHl, and each piglet was given ad libitum. To infect pigs, infect pigs by culturing them anaerobically on a 5X horse blood agar plate in advance.
smteria* 79/mu strain was ground together with the medium, and 5X
This was done by administering Kl [JI] mixed with mucin-containing phosphate buffer to APR pigs. Next, the colon contents and mucous membranes of the pigs were collected from a good friend when the onset of typical swine dysentery was observed, diluted 2 times with 5X mucin-containing phosphate buffer, and 940 was used as the final infection material. At the time of pilgrimage, 100 d of each was injected directly into the stomach (eating, fasting 24 hours before infection), causing infection! I21 Hinoseki was bred. The results are summarized in Table 5. Although 9domycin was ineffective, Tsunkayjin C has shown excellent efficacy against swine dysentery.

Go to next page. Note: Results are 11 [our average] for the 21 days from infection to autopsy.

There is a significant difference between row alphabets with opposite signs) (P<0.0
5).

For example, there is no significant difference between a and bfilK. Experimental example & Ranka S/Jin C, the concentration in the feed is 1100pp
It has since been further lowered and is now commonly used as an anti-swine dysentery agent.
The test was conducted in the same manner as in the experimental example, including the comparison with the force μ pads. The results are summarized in Table 6.Lanca VynC was found to be an excellent anti-swine dysentery agent in terms of breeding results.

Table 6 Note) Results are averages for 21 days from infection to necropsy per animal.

There is a significant difference in the row alphabet ^ sign 11) (P<0.
05) For example, there is no significant difference between abo, (IIIK is significant 116) 1abc and aa. Experimental Example 71 In the same manner as Experimental Example t, an anti-swine red blight effect test was conducted when administering Juncasidinmu and Juncasidin Cl4-propionate IOppm. carried out. The results are summarized in Table 7).
Both 4-propionate showed clear efficacy against swine dysentery.

Table 7 Note: Results are average per animal for 21 days from infection to necropsy.

There is a significant difference between the horizontal alphabets with different signs (P<0.0
5) Experimental Example 1 This experimental example was carried out under the conditions of so-called therapeutic medication, in which medication was administered at the same time as the onset of swine dysentery. The infection method was the same as in the experimental example, and five dogs that developed symptoms on the same day (6th day) after infection were used for the test, and lancasidin C5Q Pp! was administered at the same time as the onset of symptoms. 1 supplementary feed was given. The results are shown in Table 8. On the day after administration, the mucus and bloody stools stopped and the stools changed from soft to normal. On the second day, the number of bacteria in the stools was also detected (10tCF).
U/g) or less. 15th day after onset (9th day of physical medication)
An autopsy was performed and no lesions were found in the large intestine.
4m not detected.

Table 8 Note: Stool properties were divided into four grades (0, normal; ■, soft stool; ■, diarrhea brown; 0, mucus bloody stool).

1 The number is shown in log/g, and (-) is the detection It calculation (l
o”cr rU7g) The following is shown.

The umbrella indicates the feeding date of the feed supplemented with 50 ppm of Funkacidin C.

EXPERIMENTAL EXAMPLE The therapeutic effect of funcasidins under the conditions of therapeutic administration for swine dysentery was tested in the same manner as in the experimental example.

The effect on stool properties was determined according to Experimental Example 8. The results are shown in Table 9. It was found that Junka V-Zim, Junkacidin C, and Junkacidin 14-globionate had therapeutic effects when administered with seppm.

(Margins below) Table 9 Note) Hardness was determined in four stages (○, normal; ■, soft stool; ■, diarrheal stool; O1 mucus-bloody diarrhea stool).

Indicates the feeding port for medium-drug-added feed.

As is clear from the results of Experimental Examples/~9 above, one compound (
I) is extremely effective as a prophylactic and therapeutic agent for swine dysentery, and is superior to similar antibiotics or antigenic dysentery agents that are already commercially available and in frequent use, and is extremely effective in livestock management.

Experimental Example 10 The effect of compound (1) on the growth of O pigs was tested under barking conditions without the involvement of swine dysentery. In other words, 401 litters of 5 Landrace pigs of 1-power age were tested, with 8 pigs per group (4 males).
．． 51F consisting of 4 females was installed and friends.

The concentration of funkacidin and C added to feed is O (Goods 11),
1, 2, 5, 5, and 10pp. From the start to the 3rd month of age, antibacterial-free artificial milk 11 is used, and from the 4th to 6th month of age (end), it is used for pig meat production ability test. We added and mixed each of these ingredients to the feed (also without the addition of antibacterial agents) and fed them to the IIFK Ren.

The results are summarized in No. 1031.
The growth of pigs is promoted in approximately proportion to the increase in the added concentration of
Feed availability is improved and compound (■) is useful for improving pig productivity even under normal breeding conditions.

Note) Results are averages per animal.

Significant difference between horizontal alphabets with different signs (P〈◎, 05)
tomorrow.

For example, there is a significant difference between a and b. There is no significant difference between ab and a, and ab and b.

Experimental example // 48 35-day-old Huntrace seed IIS bellies were tested;
6Il was established, consisting of 8 animals per group (4 salts, 4 females). Table 11 (Note) Performance is the average of 1 group.

Significant difference between horizontal alphabets with different signs (P<0.05)
can be.

Example 1 The composition for preventing and treating swine dysentery and the composition for improving swine productivity of the present invention can be prepared, for example, by incorporating compound (1) at an arbitrary concentration into a part of the following basic feed or its raw materials. Premixes can be produced.

Basal feed composition (%) &)+kg V, A 2.5 million IU, V, Ds 500,000 IU
, V, E O, 75g, 71 ・Nitric acid I 411g,
Y, 15g, VJ, 0.25g, V, kl”F, pantothenic acid power ~ Vum 3.5g, nicotinic acid amide 7.5
g, coria chloride 50g, iron 50g, steel 5g, zinc 25g
, manganese 15g, cobalt 0.25g, iodine 0.1
b) A mixture, B mixture and C mixture containing 9. 15:0. +5:0. A mixture of 1 ml and 1 ml was used.

Mixture: 5% manganese, 5% iron, 1% copper.

Zinc 6%, iodine 0. B mixture containing IX: V, A 10,000 IU, V, D, 20,001 in 1 g
C mixture containing U: IBI/nitrate 1 g in 1 kg, V, 'B
m7g, V, 0.5g + nicotinic acid amide 6g.

Claims (1)

[Claims] General formula ′ [In the formula, V stands for 10. , V and 171m respectively represent a hydrogen group and a Vfi/group derived from Kurabonic acid] 1 for the prevention and treatment of swine dysentery. Eha is a great product for pig productivity.