KR20220134191A - Composition for prevention or treatment of coccidiosis on chickens including berberine - Google Patents

Abstract

The present invention provides a poultry feed composition comprising berberine as an active ingredient at a concentration of 0.1 to 0.5 % by weight, preferably 0.2 to 0.3 % by weight which is a composition for preventing and treating coccidiosis caused by Eimeria species in poultry. The composition of the present invention shows effective efficacy as a natural antibiotic for replacing an anticoccidial agent and reduces an oocyst discharge, intestinal lesion score and cytokine expression in poultry with coccidiosis. In addition, the composition does not affect weight gain during poultry growth.

Description

A composition for preventing or treating coccidiosis, including berberine, {Composition for prevention or treatment of coccidiosis on chickens including berberine}

The present invention relates to a composition for preventing or treating coccidium in poultry comprising berberine as an active ingredient.

Coccidium is a disease caused by several species of protozoan parasites belonging to the genus Eimeria and is an economically important disease in the poultry industry. Seven species of Eimeira infecting poultry have been identified: Eimeria (E.) acervulina, E. brunetti, E. maxima, E. mitis, E. necatrix, E. praecox and E. tenella . Among them, E. tenella is a species with high pathogenicity and prevalence in birds.

In chickens infected with coccidium, weight loss, diarrhea, and bleeding occur, leading to death. In order to reduce the mortality caused by coccidium, in most poultry breeding, antibiotics or antiprotozoal antibiotics are added to the feed. However, antibiotics used indiscriminately in the livestock breeding process have problems such as the emergence of antibiotic-resistant bacteria, human ingestion of antibiotics through meat, and environmental pollution. Accordingly, there is a trend in each country to ban the use of anticoccidial agents in the breeding of poultry. In particular, with the emergence of Eimeria strains resistant to anticoccidial agents, the need for alternative methods for coccidial control is increasing.

Among the alternative methods, the administration of live vaccines has limitations in efficacy and practicality.

Therefore, interest in natural antibiotics as an alternative method has increased, but in the case of natural antibiotics, their antibacterial or antigenic properties are somewhat inferior to those of conventional antibiotics. Therefore, for the practical use of natural antibiotics, it is necessary to develop substances that exhibit satisfactory effects.

Berberine (BBR) is a benzyl isoquinoline alkaloid extracted from plants of the genus Berberis, Coptidis and Mahonia as a material having the structural formula shown in FIG. 1 . It is known to have antibacterial effects against bacteria, viruses, fungi and protozoa.

Accordingly, efforts to use berberine for prevention or treatment of coccidium in poultry have been continued, and efforts to show efficacy against specific pathogens and to be easily used in actual poultry breeding have resulted in the present invention.

An object of the present invention is to provide a composition comprising berberine as an active ingredient as a natural antibiotic for the prevention or treatment of coccidium in poultry.

The composition exhibits a level of efficacy that can replace anticoccidial agents with natural antibiotics, and aims to facilitate use in poultry breeding.

The present invention provides a poultry feed composition comprising berberine as an active ingredient in a concentration of 0.1 to 0.5% by weight.

Preferably, the composition comprises 0.2 to 0.3% by weight of berberine.

Preferably, the composition comprises 0.2% by weight of berberine.

Preferably, the composition consists of E. acervulina, E. brunetti, E. maxima, E. mitis, E. necatrix, E. praecox and E. tenella . It is a composition for preventing or treating poultry diseases caused by one or more selected from the group.

Preferably, the composition comprises 0.2 to 0.3% by weight of berberine and is a composition that exhibits a reduction in oocyst excretion in poultry infected with E. tenella .

Preferably, the composition comprises 0.5% by weight of berberine and is a composition that exhibits a reduction in oocyst excretion in poultry infected with E. maxima .

Preferably, the composition contains 0.2% by weight of berberine and consists of E. acervulina, E. mitis and E. praecox . A composition showing a reduction in oocyst excretion in poultry infected with one or more species selected from the group.

Preferably, the composition comprises 0.2% by weight of berberine, and is a composition for lowering a lesion score in poultry with coccidium.

Preferably, the composition comprises 0.2% by weight of berberine, and is a composition that inhibits the expression of cytokines in poultry infected with coccidium.

Preferably, the composition contains 0.1 to 0.2% by weight of berberine, and does not affect weight gain during the growth of poultry.

According to the present invention, as a poultry feed composition for preventing or treating coccidium in poultry, a composition showing effective efficacy as a natural antibiotic replacing an anticoccidium agent is provided. The composition of the present invention exhibits the effect of reducing oocyst discharge, lesion score, and cytokine expression in poultry infected with coccidium. Therefore, the present invention is to provide a means to replace the anticoccidial agent in the rearing of poultry.

1 is a structural formula of berberine.
Fig. 2 shows the site where each of the 7 Eimeira species affects the poultry intestine.
3 is a comparison of oocyst emissions in chicks infected with E. tenella .
4 is an evaluation of cytokine expression in E. tenella infected chicks.
5 shows intestinal lesion scores in E. tenella infected chicks.
6 is a comparison of oocyst emissions in chicks infected with E. acervulina .
7 is a comparison of oocyst excretion in E. maxima infected chicks.
8 is a comparison of oocyst excretion in chicks infected with E. mitis .
9 is a comparison of oocyst excretion in E. praecox -infected chicks.

The present invention provides a composition for preventing or treating coccidium as a poultry feed composition comprising berberine as an active ingredient in a concentration of 0.1 to 0.5% by weight.

The poultry feed composition includes all feeds that can be fed each time to poultry, that is, birds raised for food or pets, such as chickens, ducks or turkeys. Therefore, a case in which 0.1 to 0.5% of berberine is mixed and fed in such a feed and the mixed feed are included in the scope of the present invention.

The amount of berberine contained in the feed composition of the present invention is a very important variable in preventing or treating coccidium. Therefore, it is required for the treatment and prevention of coccidium to feed a feed composition containing berberine in an amount adjusted according to the type of poultry, sex, disease and symptoms.

The composition of the present invention consists of E. acervulina, E. brunetti, E. maxima, E. mitis, E. necatrix, E. praecox and E. tenella . It is a composition for preventing or treating poultry diseases caused by one or more selected from the group. These seven species are known to cause coccidium, and each affects several different parts of the poultry intestine, as shown in FIG. 2 . Therefore, in the present invention, the efficacy against diseases of poultry infected by the above species is confirmed, and in particular, although the above species are similar, the composition of the present invention shows slightly different efficacy for each species depending on the amount of berberine contained, so the actual poultry It is desirable to identify the species causing the disease during breeding and feed a suitable feed composition.

The poultry feed composition of the present invention contains 0.2 to 0.5% by weight of berberine, preferably 0.2 to 0.3% by weight of berberine, and more preferably 0.2% by weight of berberine. When a feed composition comprising an amount of more than 0.5% by weight is fed, it shows a significant reduction in weight gain in the growth of poultry. In other words, it can affect the growth of poultry. Therefore, it is not preferable to provide a feed composition containing berberine in an amount exceeding 0.5% by weight, except when the disease is very serious.

Preferably, the composition consists of E. acervulina, E. brunetti, E. maxima, E. mitis, E. necatrix, E. praecox and E. tenella . It is a composition for preventing or treating poultry diseases caused by one or more selected from the group.

For the prevention or treatment of coccidium, the feed composition of the present invention reduces oocyst discharge in poultry infected with one or more of the seven species, lowers intestinal lesion score, and reduces the expression of cytokines. indicates.

One embodiment of the present invention is a poultry feed composition comprising 0.2 to 0.3% by weight of berberine and exhibiting a reduction in oocyst emissions in poultry infected with E. tenella .

In addition, another embodiment of the present invention is a poultry feed composition comprising berberine in an amount of 0.5% by weight and exhibiting the efficacy of reducing oocyst emissions in poultry infected with E. maxima .

In addition, another embodiment of the present invention contains 0.2% by weight of berberine, and consists of E. acervulina, E. mitis and E. praecox . A poultry feed composition showing the efficacy of reducing oocyst emissions in poultry infected with one or more species selected from the group.

Another embodiment of the present invention is a poultry feed composition comprising 0.2% by weight of berberine and lowering intestinal lesion scores in poultry with coccidium, in particular, the coccidium may be caused by E. tenella .

Another embodiment of the present invention is a poultry feed composition comprising 0.2% by weight of berberine and reducing the expression of cytokines in poultry with coccidium, in particular, the coccidium may be caused by E. tenella . In addition, the cytokine may be IL-2, IL-4, IFN-γ, IL-17A, iNOS or OCLN.

The composition of the present invention is effective for preventing or treating coccidium, while not hindering the growth of poultry. That is, it does not affect the weight gain during the poultry growth process. Specifically, an embodiment of the present invention is a poultry feed composition containing 0.1 to 0.2% by weight of berberine, and does not affect weight gain in the growth process of poultry.

In the present invention, the berberine to be mixed into the poultry feed composition may be in any form. That is, the solid feed composition may be fed by directly mixing berberine in a solid form such as a powder or tablet, and if it is a liquid feed composition, it may be fed by dispersing the berberine in powder form in the feed composition.

Since the amount of berberine included in the composition of the present invention is 'berberine as an active ingredient', for example, if additives such as excipients are included to prepare berberine in tablet form, the amount of berberine alone is included in the above range. A feed composition should be provided as much as possible. Accordingly, in the present invention, 'berberine as an active ingredient' means an amount of berberine alone in berberine that may exist in various forms.

The feed composition of the present invention may be fed as a feed composition for poultry for 1 to 3 weeks for a preventive or therapeutic effect on coccidium. More preferably, it is fed for 2 to 3 weeks.

The present invention will be described in more detail with reference to the following examples. However, it should not be construed that the present invention is limited thereto.

Example 1

1. Assessment of oocyst production

12-day-old male chicks (ROSS 308) were orally inoculated with 10,000 E. tenella sporulated oocysts. A feed mixed with powdered berberine at 0.05 wt%, 0.1 wt%, 0.2 wt% and 0.3 wt% was fed two days before infection. Excretions were collected 6 to 9 days after infection, and oocyst discharge was counted by light microscopy using a McMaster chamber.

On the other hand, healthy chicks that were not inoculated with E. tenella germinated eggs were fed a feed not mixed with berberine (control), and chicks that were inoculated with E. tenella germinated eggs but fed a feed that were not mixed with berberine (unsupplement). The results are shown in FIG. 3 together with the oocyst discharge in the same tea excreta for Korea.

Data are the mean ± standard error range from 4 replicates. Twelve rats were tested in each replicate, and two experiments were performed to represent one. *** indicates a significant decrease compared to unsupplement, with a P value of <0.001.

Looking at the results, it can be confirmed that the oocyst emission was significantly reduced compared to the unsupplement when the feed mixed with berberine in amounts of 0.2% by weight and 0.3% by weight was fed.

2. Cytokine expression evaluation

For control, untreated chicks inoculated with E. tenella germinated eggs but fed a feed without berberine) and chicks fed a 0.2 wt% berberine mixed feed, the cytokine IL- 2, the expression of IL-4, IFN-γ, IL-17A, iNOS and OCLN was evaluated. Cytokine expression was measured by qRT-PCR technique. The results are shown in FIG. 4 .

Looking at the results, it can be seen that on the 7th day, the expression of cytokines was reduced in chicks fed with berberine 0.2% by weight mixed feed compared to untreated.

3. Intestinal lesion score

For chicks fed control, untreated, and 0.2 wt% berberine mixed feed, the cecum was necropsied on the 7th day after infection to evaluate the intestinal lesion score. Bowel lesion scores were presented using the Jonhson and Reid scoring technique. The results are shown in FIG. 5 .

From the results, it can be confirmed that the intestinal lesion score was reduced in the case of feeding the feed mixed with berberine in an amount of 0.2% by weight compared to the untreated.

Example 2

One week old male chicks (ROSS 308) were orally inoculated with 10,000 E. acervulina sporulated oocysts. A feed in which berberine in powder form was mixed at 0.2% by weight was fed 2 days before infection. Feces were collected 6 to 9 days after infection and oocyst excretion was counted.

The results are shown in FIG. 6 . Data are the mean ± standard error range from 2 replicates. Fourteen rats were tested in each replicate. Controls were healthy chicks fed a non-berberine diet that was not inoculated with E. acervulina germinated eggs, and *** indicates a significant decrease compared to untreated chicks fed an inoculated, but not berberine-admixed diet, P. The value is <0.001.

Looking at the results, it can be confirmed that the oocyst emission was significantly reduced in the case of feeding the feed mixed with berberine in an amount of 0.2% by weight compared to the untreated.

Example 3

Experiment in the same manner as in Example 2, except that E. maxima sporulated oocysts were inoculated instead of E. acervulina sporulated oocysts, and a feed mixed with berberine 0.2 wt% and 0.5 wt% was fed. did. The results are shown in FIG. 7 .

Looking at the results, it can be confirmed that the oocyst emission was significantly reduced in the case of feeding the feed mixed with berberine in an amount of 0.5% by weight compared to the untreated.

Example 4

An experiment was conducted in the same manner as in Example 2, except that E. mitis sporulated oocysts were inoculated instead of E. acervulina sporulated oocysts. The results are shown in FIG. 8 .

Looking at the results, it can be confirmed that the oocyst emission was significantly reduced in the case of feeding the feed mixed with berberine in an amount of 0.2% by weight compared to the untreated.

Example 5

An experiment was conducted in the same manner as in Example 2, except that E. praecox sporulated oocysts were inoculated instead of E. acervulina sporulated oocysts. The results are shown in FIG. 9 .

Looking at the results, it can be confirmed that the oocyst emission was significantly reduced in the case of feeding the feed mixed with berberine in an amount of 0.2% by weight compared to the untreated.

Example 6

For 12-day-old male chicks (ROSS 308), a feed mixed with powdered berberine of 0.1 wt%, 0.2 wt% and 0.5 wt% was fed, and body weights were measured on the 2nd and 6th days. Table 1 shows the ratio (%) to the same car body weight of chicks (controls) fed a feed not mixed with berberine. ** P value is <0.01, *** P value is <0.001 when compared to control.

weight measurement day berberine concentration control 0.1% by weight 0.2% by weight 0.5% by weight Day 2 100±9.7 108.4±12.1** 68.5±10.4*** Day 6 100±22.6 103±21.8 98.3±22.2 55±12.2***

In chicks fed a feed mixed with berberine 0.1% by weight and 0.2% by weight for 6 days, the change in body weight was increased compared to the control group, or there was no significant difference. On the other hand, weight loss was observed in chicks fed a feed containing 0.5% by weight of berberine.

Claims (10)

A poultry feed composition comprising berberine as an active ingredient in a concentration of 0.1 to 0.5% by weight.
In claim 1,
A poultry feed composition comprising 0.2 to 0.3% by weight of the berberine.
In claim 1,
A poultry feed composition comprising 0.2% by weight of the berberine.
In claim 1,
The composition consists of E. acervulina, E. brunetti, E. maxima, E. mitis, E. necatrix, E. praecox and E. tenella . A poultry feed composition for preventing or treating diseases of poultry caused by one or more selected from the group.
In claim 1,
A poultry feed composition comprising 0.2 to 0.3% by weight of the berberine and exhibiting a reduction in oocyst emissions in poultry infected with E. tenella .
In claim 1,
A poultry feed composition comprising 0.5% by weight of berberine and exhibiting a reduction in oocyst emissions in poultry infected with E. maxima .
In claim 1,
It contains 0.2% by weight of berberine, and consists of E. acervulina, E. mitis and E. praecox . A poultry feed composition showing a reduction in oocyst emissions in poultry infected with one or more species selected from the group.
In claim 1,
A poultry feed composition comprising 0.2% by weight of the berberine, and lowering the lesion score in poultry suffering from coccidium.
In claim 1,
A poultry feed composition comprising 0.2% by weight of the berberine, and inhibiting the expression of cytokines in poultry affected by coccidium.
In claim 1,
A poultry feed composition comprising 0.1 to 0.2% by weight of the berberine, which does not affect weight gain in the growth process of poultry.

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