JP2599156B2 - Preventive and therapeutic agent for Corynebacterium renale infection in livestock - Google Patents

Description

The present invention relates to an agent for preventing and treating Corynebacterium renale infection in livestock and a method for preventing and treating the disease.

More specifically, the present invention relates to the bacterium Corynebacterium re
The present invention relates to a prophylactic and therapeutic agent containing a crude drug for pyelonephritis and cystitis, which are infectious diseases of livestock caused by nales, and a method for preventing and treating comprising administering a crude drug.

[Prior art] Pyelonephritis and cystitis in cattle and other domestic animals are one of the bacterial infectious diseases of domestic animals, and the pathogen is Corynebacterium rena.
It is often le. For example, a cow with a disease will have a large amount of this bacterium in its urine and will continue to excrete it for a long time, contaminating the barn. It is.

Sick cows urinate frequently and have clouding of urine and hematuria. As the disease progresses further, fever, anorexia, and a decrease in milk yield are observed, and the skin becomes thin and eventually ends in death or disuse.
Therefore, the economic impact of this disease on the dairy industry etc. is great. The disease is found not only on cattle but also on horses, pigs, goats and sheep.

Despite these serious infectious diseases, there are few effective countermeasures, and measures such as appropriate breeding management have been taken, but in many cases they cannot be prevented in practice.

In addition, in order to prevent and treat this disease so far,
For example, it has been practiced to administer antibiotics and other antibacterial agents together with feed. However, in recent years, there is a growing problem that it is not appropriate to administer antibiotics and the like to animals such as livestock due to the occurrence of resistant bacteria and the problem of persistence of antibiotics and the like in animals. Therefore, development of a method for preventing and treating this disease without using an antibiotic or the like and an agent for preventing and treating the disease are desired.

[Means for Solving the Problems] The present inventors have conducted studies to solve the above problems, and as a result, have found that certain crude drugs have an effect of suppressing the disease, and completed the present invention. Was.

That is, an object of the present invention is to provide Corynebacterium for livestock.
It is an object of the present invention to provide an agent for preventing and treating Renal infection and a method for preventing and treating the same.

The present invention relates to Corynebacterium of livestock containing one or two or more crude drugs selected from the group consisting of oak, gautan, squirrel, squid, and gossip.
It is intended to provide an agent for preventing and treating Renale infection.

The present invention also relates to a Corynebacterium renal infection of the above-mentioned livestock containing a crude drug in a bulk form, an organic solvent, a mixture of an organic solvent and water or a crude drug extract obtained by extraction with water, or a crude drug active ingredient. And a prophylactic and therapeutic agent.

The present invention also provides a preventive and therapeutic agent for Corynebacterium renal infection in livestock, comprising a crude drug blended in feed.

The livestock in the present invention means, for example, companion animals such as dogs, and cows, horses, pigs, goats and sheep.

Further, the present invention provides a method for preventing and treating Corynebacterium renal infection in domestic animals, which comprises administering an effective amount of one or more crude drugs selected from the group consisting of oak, gautan, squirrel, squid, and scotch. It provides a method.

The present invention also provides a crude drug in the form of a raw powder, an organic solvent, a crude drug extract obtained by extraction with water or a mixture of an organic solvent and water, or a livestock Corynebacterium which is administered in the form of a crude drug active ingredient. It is intended to provide a method for preventing and treating Renale infection.

The present invention also provides a method for preventing and treating Corynebacterium renale infection in livestock, which comprises administering a crude drug in feed.

Yellowtail (Phellodendronamurens)
e Ruprecht) or other congeners or other species of bark without the cork layer. It contains berberine, palmatin and the like as components, and is used as a stomachic, intestinal astringent, astringent and anti-inflammatory drug for humans.

Gyutan (cow bile) is a cow (Bostaurusdomesticus)
Gmelin) can be obtained by hanging the gall bladder in the shade or by incising the bile duct and storing the bile in a sealed container. It contains, as an ingredient, sodium cholate, mucoprotein, fatty acids and the like, and has been used for a long time for the treatment of human jaundice, constipation, diabetes, hemorrhoids and the like.

Ubai (Prunus Mume Siebold et Z)
The fruit is peeled from the immature fruit of uccarini), buried in soot and dried. It contains succinic acid, citric acid, malic acid, tartaric acid, etc. as components and is used as a refreshing astringent for humans, antidiarrheal, ascaris, exterminating, antipyretic, and the like.

Enmeiso (extended lifegrass) is a cypress (Isodon jap)
anica Hara) or Kurobana Hikikoshi (Isodon trich)
ocarpus Kudo). This is an ingredient
It contains Plectrantin and Emmain, and is used as a stomach bitter medicine in humans for the treatment of indigestion, anorexia, abdominal pain and the like.

Gobishi is a goal mainly produced on the leaves of nurde (Rhus javanica Linn) due to a stab wound of a nuldenomimibashibushi (Melaphis chinensis J. Bell), and contains tannin, gallic acid, fat, resin and the like as components. . It is used as a raw material for producing quintuple tincture, tannic acid, gallic acid, and pyrogallol.

As described above, each of the crude drugs used in the present invention, i.g., oak, gautan, squid, saccharomyces radiata, and gobishi, have been conventionally used alone or in combination for the prevention and treatment of human diseases. Nevertheless, no attempt has been made to use them for the purpose of preventing and treating livestock diseases, especially for preventing and treating livestock infectious diseases.

The present inventors have conducted various studies focusing on the medicinal effects of the above crude drugs, and as a result, administered one or more of the above crude drugs in combination for the prevention and treatment of Corynebacterium renal infection in livestock by Corynebacterium renale It has been found that it is extremely effective to complete the present invention.

That is, as described below, the above-mentioned specific types of crude drugs and their extracts can
It was revealed that Corynebacterium renale has a specific bacteriostatic and bactericidal action. And this Coryne
As a result of the inhibitory effect on bacterium renale, when the above crude drug was administered to livestock, pyelonephritis and cystitis, which are diseases of livestock derived from Corynebacterium renale, could be prevented and cured.

The fact that the above-mentioned specific crude drug and its extract were effective for this disease peculiar to domestic animals could not be expected, and this was first revealed by the present inventors.

These crude drugs may be directly administered as raw powder or in the form of an extract or crude drug active ingredient, or they may be added to feed or in the form of a solution, dispersion, semi-solid, powder, granule, or molded product. , Leaching preparations, injection preparations and the like.

The extracted extract is used, for example, by solvent extraction using water, an organic solvent or a mixture of water and an organic solvent, and then directly extracting, concentrating, diluting, or removing the solvent.

As the organic solvent, for example, methanol, ethanol,
n-Propanol, n-butanol, acetone, ethyl acetate, ether, methylene chloride, chloroform, benzene, carbon tetrachloride, petroleum ether and the like are used, and methanol and ethanol are particularly desirable. These organic solvents are 1
It can be used as a species or a mixture of two or more species.

This solvent extraction can be performed by cold or hot digestion of the crude drug in these solvents. 15-25 ° C for cold soaking,
In the case of digestion, it can be performed in a temperature range of 35 to 45 ° C. The extraction time depends on the extraction temperature, but is generally about 5 days or until the soluble components are sufficiently dissolved.

Crude drug active ingredient, for example, the extract extract is further shaken using various solvents, a fraction that is transferred to this solvent is extracted, and the solvent is distilled off, and the effective fraction, that is, the active ingredient may be used as the active ingredient. it can.

The solvent used in this case is a non-polar solvent, for example, lower aliphatic ethers (diethyl ether, ethyl methyl ether, etc .; lower halogen alkanes (chloroform,
Examples include dichloroethane, dibromoethane, etc .; benzenes (benzene, toluene, xylene, etc.); and other petroleum solvents (petroleum ether, petroleum benzene, ligroin, etc.).

The remaining aqueous solution obtained by extracting the effective fraction is shake-extracted by using water and a certain organic solvent saturated with water, washed with water, and transferred to an organic solvent layer as a residue. The solvent obtained by distilling off the solvent of the fraction to be used can also be used as an effective fraction, that is, an active ingredient. This effective fraction differs from the above-mentioned effective fraction in the physicochemical properties and the detected components are also different.

The dose is 0.001 mg / kg of body weight in terms of the weight of the crude drug.
/ Day to 100 g / kg body weight / day. This amount is different between the case where it is used as a prophylactic agent and the case where it is used as a therapeutic agent, and generally the latter dose is larger.

The method of administration can be oral or parenteral, and parenteral administration can be intramuscular, intraperitoneal, transdermal, nasal, intravenous, and the like.

[Effects of the Invention] As described above in detail, according to the present invention, an effective agent for preventing and treating Corynebacterium renal infection in livestock and an effective method for preventing and treating the disease are provided.

Since the prophylactic and therapeutic agent of the present invention is mainly composed of a crude drug or an extract obtained therefrom, there is no problem of occurrence of resistant bacteria or side effects in the case of antibiotics and the like, and it can be administered with confidence.

Further, since there is no concern about the effect of the residual drug on the human body, it is suitable as a drug for preventing and treating pyelonephritis and cystitis in dairy cows and the like.

Furthermore, the disease can be prevented and treated at a lower cost than in the case where an antibiotic or the like is used.

Hereinafter, the present invention will be described in more detail with reference to Test Examples and Examples.

Test Example 1 The sensitivity of Corynebacterium renale to various crude drugs was examined.

Various crude drugs were added to a 50% aqueous ethanol solution 7 times the amount of the crude drug and extracted for 16 hours to obtain an alcohol extract.

The extract was infiltrated into an 8 mm diameter disk by 25 μl and dried. The disc was placed on a blood agar medium coated with a Corynebacterium renale strain, cultured at 37 ° C. for 18 hours, and then the diameter of the inhibition circle was measured.

 Next, Table 1 shows the test results.

Example 1 Basic feed Pressed barley 22.2 parts by weight Corn 6.3 parts by weight Beer lees 25.3 parts by weight Vitamin / mineral agent 0.3 parts by weight Italian ryegrass silage 28.5 parts by weight Italian ryegrass dried 17.4 parts by weight % As a test feed. The test feed was fed freely to 40 healthy cows of about 36 to 48 months and bred for 90 days. On the 30, 60 and 90 days after the start of the test, urine was collected from all the heads, Corynebacterium renale in the urine was separated, and whether or not the bacteria were infected was observed. In the control group, a basal feed was given instead of the test feed.

As a result, in the test plot of the present invention, the bacteria were isolated once in the total number of times in one animal, whereas in the control group, the bacteria were isolated 19 times in the total number of times.

Examples 2 to 5 The same procedures were performed as in Example 1 except that crude drugs shown in the following table were used instead of Ubi.

 The following table shows the test results.

Example 6 1 kg of each of oak, gautan, squirrel, squid, and rub stake were placed in 10 pieces of water, respectively, and 100 g of the mixture was added.
Extracted at C for 1 hour. Each water extract was diluted 1000 times to obtain an extract. Healthy cows about 36 to 48 months old
Forty animals were fed the extract in place of water. As the feed, the basic feed used in Example 1 was used. Water was given instead of the extract as a control. Thus 90
After breeding for 30 days, urine was collected from the whole head on days 30, 60 and 90, respectively, and Corynebacterium renale in the urine was isolated.

As a result, in all the test plots, the number of cows from which the bacteria were isolated was smaller than in the control plots, and the total number of isolated cows was also smaller.

Example 7 Basic feed Corn 250 parts by weight Myro 492 parts by weight Bran 35 parts by weight Degreasing rice bran 35 parts by weight Soybean meal 85 parts by weight Bean seed meal 40 parts by weight Cottonseed meal 10 parts by weight Fish meal 5 parts by weight Meat Bone meal 10 parts by weight Sugar dense 20 parts by weight Calcium carbonate 11 parts by weight Food salt 3 parts by weight Premix 4 parts by weight Healthy female pigs of about 12 months to about 24 months old were replaced with cows in Example 6. The procedure was carried out in the same manner as in Example 6, except that 50 animals were used and the above-mentioned basic feed was used. As a result, the number of Corynebacterium renale separated and the total number of separated Corynebacterium renale were smaller in the test plot than in the control plot.

Example 8 Basic feed Corn 430 parts by weight Small wheat flour 250 parts by weight Meat meal 160 parts by weight Soybean meal 90 parts by weight Soybean white squeezed oil 10 parts by weight Vitamin mixture 20 parts by weight Mineral mixture 40 parts by weight Instead of cow in Example 6 The same procedure was performed as in Example 6 except that 50 adult female dogs aged 3 to 5 years were used and pellets having the above composition were used as a basal feed. As a result, both the number of Corynebacterium renale isolated and the total number of isolated Corynebacterium renale were smaller in the test plot than in the control plot.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ Identification code Agency reference number FI Technical display location A61K 35/78 ACV A61K 35/78 ACVC (56) References JP-A-62-259214 (JP, A JP-A-51-61612 (JP, A) JP-A-57-26549 (JP, A) JP-A-57-132847 (JP, A) Kanayoshi Akamatsu, Shinshin Wakanyaku, Medical and Dental Medicine Publishing Co., Ltd., October 15, 1980, 1st edition, 5th edition, see pages 301, 784, 369, 97, 268

Claims (5)

(57) [Claims] 1. Corynebacterium of a domestic animal containing one or more crude drugs selected from the group consisting of oak, gautan, squirrel, squid, and goby
Agent for preventing and treating Renale infection. 2. The prophylactic and therapeutic agent according to claim 1, wherein the crude drug is in bulk form. 3. The prophylactic and therapeutic agent according to claim 1, wherein the crude drug is an organic solvent, a mixture of water and an organic solvent or a crude drug extract extracted with water and / or a crude drug active ingredient obtained therefrom. 4. The preventive and therapeutic agent according to claim 1, wherein the crude drug is incorporated in feed. 5. The preventive and therapeutic agent according to claim 1, wherein the livestock is a cow, horse, pig, goat, sheep, or dog.