JPH07109224A - Therapeutic agent for function disorder of anterior stomach and fatty acid metabolic function disorder of ruminant domestic animal and treating method - Google Patents

Abstract

PURPOSE:To obtain a therapeutic agent for function disorder of anterior stomach of and fatty acid metabolic function disorder of ruminant domestic animal comprising a butyric acid bacterium (Clostridium botulinum) as an active ingredient. CONSTITUTION:This therapeutic agent for function disorder of anterior stomach and fatty acid metabolic function disorder of ruminant domestic animal comprises a butyric acid bacterium such as BP-2789, BP-11868, BP-11,869 and BP-11870 deposited to the National Institute of Bioscience and Human- Technology as an active ingredient. A dose is >=0.05g, preferably 0.10g daily. In administration, a method for suspending the butyric acid bacterium in warm water and orally applying or a method for blending a product (fine granule) with feed and orally administering is used and can be extremely effectively utilized together with a conventional method such as intravenous injection of propylene glycol preparation or caramel-containing preparation.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a therapeutic agent and a method for treating forestomach dysfunction and fatty acid metabolism dysfunction in ruminant livestock.

[0002]

2. Description of the Related Art In recent years, in order to improve the production efficiency of ruminant livestock, especially dairy cows and beef cattle, improvement of high lactation capacity cows and high fattening efficiency cows and intensive feeding technology have been rapidly advanced.
However, along with this, the following problems occur.

At the end of pregnancy in dairy cows and beef cattle, rapid weight gain of the fetus is observed. Therefore, for example, in a dairy cow, a dry period is provided 2 months before calving in order to rest the overwork of the whole body during lactation, particularly udder, and develop the fetus. During this period, a breeding method in which high-quality hay is mainly fed is recommended in order to prevent overfertilization and slimming and increase the next milk production.

However, the production of high quality hay is not sufficient in the climate of Japan. Therefore, when poor quality hay is fed during the dry period, insufficient dry matter intake and lack of necessary nutrients result, and the rumen volume decreases at the time of lactation start after parturition, A decrease in rumen function becomes apparent.

On the other hand, when a concentrated feed or silage is fed for the purpose of nutritional supplementation of bad hay, it becomes hyperfertilized and fat is deposited on various organs in the body, especially the liver. In such fatty liver, the amount of glycogen decreases, the oxidation of fatty acids becomes incomplete, and the production of ketone bodies is accelerated.

Further, in the free stall breeding method adopted from the viewpoint of labor saving in the management of a large number of cattle, a sufficient dry period is not provided, and labor is obese.

[0007] In any of the above cases, by feeding a concentrated feed in the early stage of lactation after parturition, abnormal fermentation due to a decrease in pH of the rumen content liquid in the forestomach mechanism or an imbalance of microflora is caused. As a cause of acidosis due to forestomach dysfunction or fatty acid metabolism dysfunction (ruminal hyperacidity), forestomach relaxation, abolition of appetite associated with forestomach relaxation, rumen bloat, abomasum displacement, and metabolic disease It causes diseases such as ketosis (increase of ketone bodies in the body, ketonemia, ketonuria).

Among the above-mentioned symptoms, for example, abolition of appetite, bloating of the rumen and the like have conventionally been dealt with by treatment with a complex digestive enzyme preparation, metoclopramide hydrochloride, a silicone resin preparation, etc. I couldn't get the effect.

[0009] Further, as drug therapy for ketosis, usually (a) sugar and a sugar source substance are intravenously injected (for example, 20 to 20).
25-% glucose solution 500-1000 ml, xylitol 500-1000 ml) (b) Administration of organic acid salts (for example, oral administration of propylene glycol 200-300 ml, oral administration of sodium propionate 100-500 g,
Intravenous injection of 100-500 ml of 5% sodium propionate solution), (c) intramuscular injection of steroid hormones (eg 10-20 mg dexamethasone, 1.25-2.5 mg flumethasone), (d) at 36-48 hour intervals. Subcutaneous injection of 150 to 200 units of insulin, (e) administration of strong liver and vitamin preparations, etc. have been carried out.

Furthermore, in the conventional beef cattle fattening management, the combined feeding of rice straw and hay is indispensable for the prevention of chronic laminitis caused by rumen acidosis, so that the prolongation of the fattening month is inevitable. was there.

[0011]

SUMMARY OF THE INVENTION It is an object of the present invention to provide an effective therapeutic agent and a therapeutic method for acidosis and the like which could not be obtained by the above conventional therapeutic methods.

[0012]

[Means for Solving the Problems] The present inventor has found that, in response to forestomach dysfunction such as acidosis and fatty acid metabolism dysfunction, Clostridium butyricum
Found that is effective.

Clostridium butyric acid bacterium
Yricum) is a gram-positive bacillus that forms spores in obligate anaerobes. Due to the formation of spores, it has heat resistance and acid resistance, and is highly stable as a live bacterium.

Clostridium butyricum miyairi (Clostridium butyricum MI), which is a strain of butyric acid bacterium used in the examples of the present invention, is used.
The characteristic of YAIRI) is that it promotes the growth of unique useful bacteria (bifidobacteria, lactic acid bacteria) and the like that live in the intestines of animals, while
It has an antagonistic effect against intestinal harmful bacteria. this is,
In the rumen, which is anaerobic to the strength of ruminant livestock, the anaerobic bacterium becomes a vegetative type, and the production of monosaccharides and oligosaccharides by the digestive enzymes of the carbohydrates (starch, fiber) produced by the bacterium The production of effective substances by proteolytic enzymes promotes the growth of useful bacteria (lactic acid bacteria, etc.) peculiar to the intestine, while the production of organic acids such as butyric acid, acetic acid, propionic acid, etc. suppresses the growth of harmful Escherichia coli and the like. This is because The bacterium also produces digestive enzymes such as vitamins and amylase.

In human clinical practice, antagonism against intestinal pathogens and development of lactic acid bacteria have been reported, and safety by long-term administration has been confirmed. In addition, there are many advantages such as a low nutrient requirement of the culture medium and a low cost production.

[0016] Therefore, it is widely used as a probiotic preparation which causes abnormalities of bowel movements such as diarrhea or constipation caused by antibiotics during chemotherapy and normalization of postoperative digestive dysfunction. It is also widely used as an intestinal regulating agent for humans and livestock, and as a therapeutic aid for human atopic dermatitis.

The present inventor has found that Clostridium butyri, which has not been used in the past, for forestomach dysfunction such as acidosis and fatty acid metabolism dysfunction.
It was found to be extremely effective when used for treating the above disorders.

The butyric acid bacterium which can be used in the present invention is, for example, butyric acid bacterium (Clostridium butyricum: C) deposited at the Institute of Life Science and Technology, Institute of Industrial Science and Technology.
Lostridium butyricum), and the microorganism accession number is Micromachine Research Institute No. 2789 (BP).
-2789), Micro Engineering Research Institute of Microbiology No. 11868 (P-118)
68), No. 11869 (P-11869), No. 1
No. 1870 (P-11870).

The dosage is 1 for 1 kg of ruminant body weight.
It is more than 0.05g a day. Preferably, it is about 0.10 g / kg body weight per day. Administration is performed once a day or by dividing the above-mentioned dose into two divided doses. It may be administered every other day or every few days depending on the severity of symptoms.

Upon administration, butyric acid bacteria (Clostri)
For example, a method of suspending the aluminum butterinium in hot water and orally administering it, a method of mixing the product (fine granules) with the feed and orally administering the same are used. In addition, the method of administering the butyric acid bacterium preparation and the conventional therapy as described above are also very effective. Examples of conventional therapies that can be used in combination include, for example, in the case of ketosis treatment, intravenous injection of a propylene glycol preparation or a caramel-containing preparation. Among these, the combination with a propylene glycol preparation is particularly effective.

Below, butyric acid bacteria (Clostridium)
Butyricum MIYAIRI 588) (Microbial accession number at the Institute of Bioengineering and Industrial Science: Microtechnology Research Institute No. 2789) is shown to show an example of improvement of forestomach dysfunction and fatty acid metabolism dysfunction.

[0022]

【Example】

Example 1 Example 1 is a treatment example of anorexia associated with forestomach flaccidity. Control example: A Holstein cow born on January 23, 1991 had an appetite loss on May 16 after the first calving on April 8, 1993, and the milk yield decreased by 15 kg / day. Upon initial medical examination on May 17, an extremely weak rumen motility was observed, and 20 ml of metoclopramide hydrochloride preparation was intravenously injected, and 200 g of complex digestive enzyme preparation.
Was orally administered. The following breakfast was observed, and the mixed feed was 3k.
g, 1 kg of hay. At the home visit, the same treatment as the day before was performed. On the third day, loose feces were excreted. The excretion of normal stools was followed on the 6th day, but the rumen movement was still weak on the 8th day, and the recovery was about 16 kg / day.

Example of administration: A Holstein cow born on January 3, 1991, had an appetite loss on March 20, 1993, after the first calving, and the milk yield decreased by 12 kg / day. Butyric acid bacteria (Clostr
A formulation containing 40 mg of 1 g of idium butyricum MIYAIRI (hereinafter, "CBM formulation")
The abbreviation of is used. ) When 50 g was suspended in warm water and orally administered, it showed appetite in the evening, and 2 kg of compounded feed, 6 kg of dent corn silage, and 2 kg of hay were eaten and rumined. From March 22, when 25 kg of the CBM preparation was mixed and administered to the mixed feed, 4 kg of the mixed feed, 8 kg of dent corn silage, and 2 kg of hay were consumed. When the farmer was instructed to mix and feed 25 g of the CBM preparation in the mixed feed from the evening feed, 6 kg of the mixed feed, 12 kg of dent corn silage, and 3 kg of hay were eaten. CBM formulation 25 for 10 days thereafter
g was mixed with the compounded feed and administered twice a day. During that time, the milk amount returned to 26 kg on the 5th day from the start of administration, and no abnormalities in appetite and milk amount were observed even after the administration of the CBM formulation was stopped, and no visit request was made.

Example 2 Example 2 is a healing example of the first gastric bloat. Control Example: A Holstein cow born on September 18, 1990 had the first calving on January 22, 1993, had an appetite loss on the morning of May 24, and had a left abdominal swelling around 10:00 on the same day. Upon receiving the visit request, he made his first visit at 12:00 and was diagnosed with bloating of the first stomach. Immediately after perforating the stomach to discharge gas, 40 ml of the silicone resin preparation and 200 g of the complex digestive enzyme preparation were orally administered. As a result, the symptom improved, but it recurred on June 26 and 28. The amount of milk changed at 8 kg / day because the dietary feed was stopped and only grass hay was fed.

Administration example: Holstein cows born on September 9, 1990, had their first calving on April 13, 1993,
The milk amount reached 38kg / day on June 20, so 16kg / day of mixed feed and 20k of dent corn silage.
g / day, 4 kg / day of hay was fed. The appetite was abolished from the morning of June 23, and swelling of the left abdomen was observed. I received a home visit request and made my first visit at 9:30. A diagnosis of rumen bloat was made, and gastric emptying was performed after perforation of the stomach. After implementing initial measures for 40 ml of silicone resin formulation and visiting other farmers, 11:03
As a secondary treatment for 0 minutes, 50 g of the CBM preparation was suspended in warm water and orally administered. When the patient was examined again in the evening and examined, the patient had no bloating and showed appetite. Therefore, in addition to 2 kg of the mixed feed, hay was freely taken. When I revisited on July 1st,
No abnormalities were observed, and only 50 g of the CBM formulation was suspended in hot water for oral administration, 8 kg of the compound feed was given, and hay was freely ingested. From July 2, the farmer was instructed to mix 25 g of the CBM preparation with the mixed feed and continuously administer it twice a day for 4 days. As a result, no abnormalities were observed and it was judged that the treatment was cured. Feed supply, intake, and milk production also recovered as before the disease.

Example 3 Example 3 is a healing example of abdominal displacement and torsion associated with ketosis. Control Example: A Holstein cow born on September 5, 1990 received the first visit on February 25, 1993, at the time of the first delivery, and on March 2, receiving a call-up request to exhibit anorexia and recumbent pain. A diagnosis of abdominal torsion was made. Immediately after laparotomy, a fourth gastrectomy was performed, but on March 4, she had no appetite and had no feces. Administration of 300 g of the dry yeast preparation twice a day was continued for 10 days. Diarrhea was excreted from the 4th day of administration. A 50-ml intravenous injection of berberine sulfate formulation was used together for 4 days to return to normal stool, but the outcome was improved without appreciable improvement in appetite and milk yield.

Administration Example 1: A Holstein cow born on October 2, 1990 gave birth at its first on February 10, 1993,
Since February 22, he has shown anorexia. Receiving a home visit request, 2
The first visit was made on the 3rd day, 20 ml of metoclopramide hydrochloride preparation was intravenously injected, and 200 g of complex digestive enzyme preparation was orally administered. Although he was appetizing in the evening, he ingested only a small amount of the mixed feed and excreted diarrhea. A metal noise was found when the lower left rib was percussed, and the patient was diagnosed with left abomasum displacement.

Laparotomy was performed on the morning of February 24. In the afternoon, 50 ml of berberine sulfate preparation, 50 pantethine preparation
ml was injected intravenously. On February 25, although he had an appetite, he had excreted mixed diarrhea and feces, and thus 50 ml of berberine sulfate preparation and 50 ml of pantethine were intravenously injected again. In addition, 50 g of the CBM preparation was suspended in warm water and orally administered.
From the next day 26th, 25 g of CBM preparation was mixed with the mixed feed, and 1
I instructed the farmers to pay twice a day. He had no bloody stools on 28th and became normal stools on 4th March, which was confirmed as the outcome.

Administration Example 2: A Holstein cow born on February 25, 1986 delivered a fifth calf on May 21, 1993 and received a complaint that he could not stand up, and then visited the house in the afternoon. Rumen movement is weak, calcium polygluconate preparation 50
0 ml was injected intravenously. Symptoms did not improve even on May 22, and calcium polygluconate preparation 500m again
1 was injected intravenously. On the 23rd, he was able to roll over by himself and showed appetite. Again, 500 ml of calcium polygluconate preparation was intravenously injected. Abolition of appetite was seen on the 24th. Ruminal movement was observed, but a metal noise was observed on percussion of the lower left rib. Elevated ketone bodies in the urine were recognized, and the patient was diagnosed with mild left displacement of the abomasum. 500 ml of propylene glycol preparation and 50 ml of pantethine preparation were intravenously injected. Propylene glycol preparation 500m on 25th
l, pantethine preparation 50ml was intravenously injected, CBM
50 g of the preparation was suspended in warm water and orally administered. From 26th to 2nd June, mix 25g of CBM preparation into the mixed feed and
Recovery of appetite and milk amount was observed just by administration twice a day, and it was confirmed that healed without laparotomy.

Administration Example 3: A Holstein cow born on December 28, 1983, delivered a seventh calf on June 22, 1993. Immediately after delivery, she was called up because she could not stand up. From the test results of blood Ca of 3.1 mg / dl or less and P2.9 of 2.9 mg / dl, it was diagnosed as an orthostatic disease due to milk fever. Intravenous injection of 500 ml of calcium polygluconate preparation and 500 ml of DL methionine-vitamin complex was continued for 3 days. As a result, the skin temperature is cold (body temperature 38.0 ° C)
The rumen movement was weak, and the anorexia continued.
On the 5th day, urinary ketone bodies became strongly positive, and a percussion of the middle and lower part of the left rib produced a metallic sound. The patient was diagnosed with left abomasum displacement accompanied by ketosis. When 50 g of the CBM preparation was suspended in warm water and orally administered, appetite was observed from the second day. Thereafter, the farmer was instructed to mix 25 g of the CBM preparation with the mixed feed and administer it twice a day. From the day of admission, rumination was accepted, 7
The daily dose resulted in an outcome. The patient was considered cured without laparotomy.

Example 4 Example 4 relates to the treatment of ketosis. Inadequate feeding management of ruminant livestock during the dry period (2 months before parturition), that is, insufficient dry matter intake and insufficient nutrition due to feeding bad hay caused a decrease in rumen capacity and rumen. In addition, feeding of concentrated feed, dent corn silage, and shortening of the dry period in the free stall feeding method resulted in a decrease in glycogen and incomplete oxidation of fatty acids especially in fatty liver. Causes increased production of ketone bodies.

[0032] For 4 cattle with extremely high postpartum blood ketone bodies, 25 g of the CBM preparation, which is an obligate anaerobic bacterium, was given daily.
The following blood test results were obtained by mixing and feeding 25 g once a day for 7 to 10 days, once a day for 2 days.

[Table 1]

In addition to the above, an effect was observed in the treatment of chronic laminitis (robot disease) derived from rumen acidosis. Rumen acidosis is attributed to abnormal production of D-lactic acid in the rumen. In this regard, butyric acid bacteria (Cl
ostridium butyricum often uses D-type lactic acid to decompose it into butyric acid and acetic acid, while it does not work for L-type lactic acid.
SZYLIT) et al. (Reprod. Nu
tr. Development. , 1988, 28 (6A), 1
455-1464). This rationale supports the efficacy of CBM formulations in the treatment of rumen acidosis.

[0034]

EFFECTS OF THE INVENTION Butyric acid bacterium (Clostridium bu)
administration of tyricum) significantly improves forestomach dysfunction or fatty acid metabolism dysfunction such as forestomach flaccidity, rumen bloat, abomasum displacement, loss of appetite, and ketosis, which frequently occur after calving. There is. Moreover, the effect is remarkably amplified by the combined use with the conventional therapeutic agent.

In addition, due to inadequate feeding management during the dry period, the normal function of the forestomach mechanism was lost, and cows with abnormal metabolism of volatile fatty acids were treated with butyric acid bacteria (Clostridium b).
euricum), the osmotic pressure in the rumen, the pH of the rumen contents (gastric juice), the microflora in the rumen are normalized, and forestomach relaxation, rumen bloat, Abdominal displacement, loss of appetite, and marked improvement in ketosis as a metabolic disease are observed.

Furthermore, in the administration example 1 of Example 3, laparotomy is performed for abomasum displacement in consideration of the debilitating of the cattle by only medical treatment, but in this case, butyric acid bacterium (Clostridium) is also used. Butyricum) administration causes postoperative recovery from bloody stools to normal stools in a short time.

According to the conventional method, laparotomy is easily performed for treatment, and as a result, the useful life of dairy cows is extremely shortened. However, as in Administration Example 2 and Administration Example 3 of Example 3, laparotomy is not performed. If the abomasum displacement is treated only by the medical treatment, the situation in which the dairy business is economically stressed is remarkably improved.

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[Procedure amendment]

[Submission date] November 9, 1993

[Procedure Amendment 1]

[Document name to be amended] Statement

[Correction target item name] 0011

[Correction method] Change

[Correction content]

[0011]

SUMMARY OF THE INVENTION An object of the present invention is to provide an effective therapeutic agent and a therapeutic method for ketosis and the like which could not be obtained by the above conventional therapeutic methods.

[Procedure Amendment 2]

[Document name to be amended] Statement

[Correction target item name] 0012

[Correction method] Change

[Correction content]

[0012]

The present inventors have found that Clostridium butyricum is effective against forestomach dysfunction such as ketosis and fatty acid metabolism dysfunction.

[Procedure 3]

[Document name to be amended] Statement

[Correction target item name] 0017

[Correction method] Change

[Correction content]

The present inventor has found that Clostridium butyri, which has not been used in the past, for forestomach dysfunction such as ketosis and fatty acid metabolism dysfunction.
It was found to be extremely effective when used for treating the above disorders.

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Claims (2)

[Claims] 1. A butyric acid bacterium (Clostridium bu)
tyricum) as an active ingredient, a therapeutic agent for forestomach dysfunction and fatty acid metabolism dysfunction in ruminant livestock. 2. A butyric acid bacterium (Clostridium bu)
tyricum) for the treatment of forestomach dysfunction and fatty acid metabolism dysfunction in ruminant livestock.