KR102023380B1 - Composition comprising bee venom for treating or preventing Coccidiosis - Google Patents

Abstract

The present invention relates to a composition for preventing or treating coccidiosis comprising bee venom as an active ingredient. When the composition containing the purified bee venom as an active ingredient to feed broilers or various livestock, it is possible to inhibit the spread of E. parasites in the small intestine as well as the large intestine, as a result can prevent, improve and treat coccidiosis. Therefore, by using the composition of the present invention can reduce the onset of coccidiosis can also reduce the economic loss of the farm through the health of the poultry.

Description

Composition for preventing or treating coccidiosis comprising bee venom as an active ingredient {Composition comprising bee venom for treating or preventing Coccidiosis}

The present invention relates to a composition for preventing or treating coccidiosis comprising bee venom as an active ingredient.

Kinds of bees are generally seoyangjong bees (Apis mellifera), the paper has four known species of bees, such as Eastern (Apis cerana), the maximum longitudinal India (Apis dorsata), minimum longitudinal India (Apis florea). Among them, western bees and oriental bees live in Korea. In particular, oriental honeybees have been bred since the Goryeo Dynasty, and have been used as bee needle therapy in private and oriental medicine. However, western bee is an Italian worker bee which was introduced to Korea around 1892 by German missionary during the period of Emperor Gojong in Joseon Dynasty.

Bee venom, contained in a bee venom, consists of about 40 substances and has been used to treat human diseases since BC. Bee venom differs in its constituents depending on the type of bee, and even the same bee causes differences in constituents according to age. Currently, studies on the effects and mechanisms of bee venom components, hypersensitivity and toxicity of bee venom, immunotherapy and arthritis, herpes simplex, multiple sclerosis, treatment of tumors, etc. have been reported. Known.

Antibiotics are being banned worldwide, and anticoccidium is also expected to be banned in formulated feed. At present, there are eight anticoccidial agents that can be used in domestic feed. Anticoccidial agents act on the coccidial protozoa in chickens, but anticoccidial agents such as salinomycin have antimicrobial effects on bacteria, and therefore have similar gains.

Unlike broiler chickens in broilers, broilers are easily exposed to coccidium because they are raised on litter plains. Antibiotics in formulated feeds are prohibited worldwide, but anticoccidial drugs can be added to formulated feeds and are used alternately with anticoccidial and antimicrobial agents.

However, with the rapid development of drug resistance, the anticoccidial agent has increased interest in anticoccidial substitutes worldwide because of increasing consumer's rejection of drug use and preference for environment-friendly livestock products. Some companies have developed and marketed coccidial vaccines, but they are known to be completely incompatible with anticoccidial agents because they are less effective than anticoccidial agents. This is related to the complex immune avoidance mechanism of coccidium, and the use of the vaccine is limited.

Like antibiotic replacements, research is underway on the development of eco-friendly anticoccidial preparations. In Korea, even coccidium research and anti-coccidium products are not evaluated.

Under these backgrounds, the present inventors studied various physiological activities of purified bee venom, and the purified bee venom isolated from worker bees of 15 days or older of the Western bee ( Apis mellifera L.) was an insect of coccidiosis in poultry such as chicken. Confirmed that the inhibitory effect on the genus parasites is excellent to complete the present invention.

Republic of Korea Patent No. 10-1288380 (Name of the invention: poultry feed composition containing bee venom as an active ingredient, Applicant: Korea, registered date: July 16, 2013) Republic of Korea Patent No. 10-1061257 (Invention: Natural antibiotics using bee venom and herbal extracts and its manufacturing method, Applicant: Republic of Korea, registered date: August 25, 2011) Republic of Korea Patent No. 10-1491775 (Invention name: Composition for inhibiting the growth of antibiotic-resistant harmful bacteria, Applicant: Korea, Registered Date: February 03, 2015)

Johnson J. and Reid W. M., 1970. Anticoccidial drugs: lesion scoring techniques in battery and floor-pen experiments with chickens. Experimental Parasitology 28: 30-36.

An object of the present invention to provide a composition for the prevention or treatment of coccidiosis comprising bee venom as an active ingredient.

The present invention relates to a composition for preventing or treating coccidiosis comprising bee venom as an active ingredient.

The bee venom can be purified bee venom obtained by removing sugars and volatiles from the bee venom isolated from the bee venom of worker bees over 15 days of age of Apis mellifera L ..

The coccidiosis is this Almeria ah Sergio called (Eimeria acervuline), this Almeria Te Canela (Eimeria tenella), this Almeria Maxima (Eimeria maxima), this Almeria your cart Riggs (Eimeria necatrix), this Almeria Brewer Connecticut (Eimeria brunetti), this Almeria and going (Eimeria hagani), this Almeria Framingham Cox (Eimeria praecox) and this in Almeria US Bhatia is characterized in that a multitude 1 a Almeria spp or more species selected from the consisting of (Eimeria mivati) as causative agents.

The coccidiosis is a disease in animals, and the composition of the present invention is preferably characterized in that it has a more therapeutic effect on coccidiosis in poultry.

The present invention also provides a pharmaceutical preparation for preventing or treating coccidiosis of a formulation selected from the group consisting of powders, granules, tablets, capsules, liquid capsules, aqueous solutions, suspensions, emulsions, syrups and aerosols containing the composition. .

The present invention can provide an animal feed for improving coccidiosis containing the composition.

EMBODIMENT OF THE INVENTION Hereinafter, this invention is demonstrated in detail.

The present invention relates to a composition for preventing or treating coccidiosis comprising bee venom as an active ingredient. The bee venom is a purified bee venom, and the collecting process may be used in a conventional sheep farming farm. In particular, the bee venom is a bee venom collecting device in a bee sac of a worker bee 15 days or older of Western species Honeybee ( Apis mellifera L.). The bee venom separated by using may be obtained by removing saccharides and volatile substances, foreign substances other than bee venom. The imaginary composition can be targeted to a variety of animals that develop coccidiosis but is particularly suitable for livestock that are poultry.

Carriers, excipients and diluents that may be included in the pharmaceutical compositions of the present invention include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate , Cellulose, methyl cellulose, microcrystalline cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil. When formulated, diluents or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, and surfactants are usually used. Solid form preparations for oral administration include tablets, pills, powders, granules, capsules, and the like, and such solid form preparations may contain at least one excipient such as starch, calcium carbonate, sucrose or It is prepared by mixing lactose and gelatin. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Oral liquid preparations include suspensions, solvents, emulsions, and syrups, and may include various excipients, such as wetting agents, sweeteners, fragrances, and preservatives, in addition to commonly used simple diluents such as water and liquid paraffin. . Formulations for parenteral administration include sterile aqueous solutions, non-aqueous solvents, suspensions, emulsions, lyophilized preparations, suppositories. As the non-aqueous solvent and suspending agent, propylene glycol, polyethylene glycol, vegetable oil such as olive oil, injectable ester such as ethyl oleate and the like can be used. As the base of the suppository, witepsol, macrogol, tween 61, cacao butter, laurin butter, glycerogelatin and the like can be used.

The dosage of the pharmaceutical composition of the present invention will vary depending on the age, sex, weight of the subject to be treated (animal), the specific disease or pathology to be treated, the severity of the disease or pathology, the route of administration and the judgment of the prescriber. Dosage determination based on these factors is within the level of skill in the art and generally dosages range from 0.01 mg / kg / day to approximately 2000 mg / kg / day. More preferred dosage is 1 mg / kg / day to 500 mg / kg / day. Administration may be administered once a day or may be divided several times. The dosage does not limit the scope of the invention in any aspect.

The pharmaceutical composition of the present invention can be administered by various routes. All modes of administration can be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intrauterine dural or cerebrovascular injections.

The present invention relates to a composition for preventing or treating coccidiosis comprising bee venom as an active ingredient. When the composition containing the purified bee venom as an active ingredient to feed broilers or various livestock, it is possible to inhibit the spread of E. parasites in the small intestine as well as the large intestine, as a result can prevent, improve and treat coccidiosis. Therefore, by using the composition of the present invention can reduce the onset of coccidiosis can also reduce the economic loss of the farm through the health of the poultry.

1 is a photograph showing a process of collecting bee venom using a bee venom collecting device.
Figure 2 is a chromatogram result confirming the distribution of bee venom components by liquid chromatography analysis of venom sac by the age of bees.
Figure 3 is a graph showing the bee venom content in the venom sac by liquid chromatography analysis according to the age of the honeybee.
FIG. 4 is a picture of the bee venom bee venom collected from worker bees older than 15 days old (before FIG. 4) and after purification (right side of FIG. 4) (top of FIG. 4) and observed with an electron microscope (FIG. 4). Bottom).
Figure 5 is a chromatogram showing the results of confirming whether the standard bee venom apamin, phospholipase A2, adolafine, hyaluronidase and melittin in purified bee venom using ultra-high performance liquid chromatography (UPLC).

Hereinafter, a preferred embodiment of the present invention will be described in detail. However, the present invention is not limited to the embodiments described herein and may be embodied in other forms. Rather, it is provided to fully convey the spirit of the present invention to those skilled in the art so that the contents introduced herein are thoroughly and completely.

Example 1 Preparation of Tablet Bee Venom

Collect bee venom by using the bee venom collection device for Apis meliffera L., worker bee within 1 hour of adult, worker bee of 3 ~ 8 days old, worker bee of 9 ~ 14 days old, worker bee more than 15 days old The bee venom was collected separately from, and the purified bee venom dried product having pure water solubility was removed by removing sugars and volatile substances through the simple refining method of bee venom. Figure 1 discloses a bee venom collection process using such a bee venom collecting device.

On the other hand, the bee venom content in the bee sac of the bees for each day was confirmed, as shown in FIGS. 2 and 3, the content of pure bee venom was highest in the bee sac of the bee 15 years or older. Therefore, in the present invention, the purified bee venom collected from worker bees over 15 days old was to be used in the experiment.

<Example 2. UPLC analysis for identifying the components of purified bee venom>

40 mg of purified bee venom collected from worker bees over 15 days old was dissolved in 10 ml of tertiary distilled water and filtered through a PTFE 0.2 μm filter, and the same standards for ammamine, melittin, phospholipase A2, adolafine, and hyaluronidase were applied Dissolved in tea distilled water to make 2 mg / ㎖ was prepared by filtration using the same filter as the test bee venom. Bee venom analysis was confirmed by ultra-high performance liquid chromatography (UPLC), and the analyzer used I class model of Waters Co., Ltd., Halo peptide ES-C18 (particle size: 2.7 μm, inner diameter: 4.6 mm, Length: 10 cm). As the mobile phase, a mixed solution obtained by mixing A solution: 20 mM trifluoroacetic acid (TFA) with acetonitrile (MeCN) and B solution: 20 mM trifluoroacetic acid (TFA) was used. The mixed solution is a solution A more than 10% by volume less than 31% by volume when the transfer time is less than 3 minutes, A solution is more than 31% by volume less than 40% by volume when the transfer time is less than 5 minutes in more than 3 minutes, the transfer time is 5 When more than 10 minutes or less in minutes, the solution A was used in combination with the solution B so that from 40 to 45% by volume or less. The flow rate of the mobile phase was 1.5 ml / min, the sample injection amount was 4 µl, the ultraviolet absorbance wavelength was set to 220 nm, and the column temperature was adjusted to 50 ° C. during the analysis. Detection limits were calculated according to the International Conference on Harmonisation guideline. The conditions are again shown in detail in Table 1 below.

device Waters i class column Halo ES-18 (4.6 x 100 mm, 2.7 μm) Column temperature 50 ℃ Flow rate 1.5 ml / min Main quantity 4 μl Detection wavelength 220 nm This statue (A) 20 mM TFA / MeCN, (B) 20 mM TFA / H ₂ O
(A) 0-3 min: 10-31 volume% / 3-5 min: 31-40 volume% / 5-10 min: 40-45 volume%

The analysis results of the aqueous solution of purified bee venom are shown in FIG. 5 through a peak comparison with the standard solution, and the apamin, melittin, phospholipase A2, adolafine, and hyaluronidase content in the aqueous solution of purified bee venom are shown in the following table. 2 is shown.

ingredient content(%) Apamin 2.3 Melittin 63.6 Phospholipase A2 11.5 Hyaluronidase 1.9 Adopine 0.9

Example 3 Setting of Coccidiosis Animal Model

Specimen experiments were conducted to investigate the effects of bee venom on corn-soybean-based experimental feeds on coccidium (Table 3). A total of 210 1-day-old Ross 308 broilers were completely randomly placed in 5 treatments, 7 replicates and 10 broilers per repetition. Similarly, broilers of comparable weights were placed per pen, and experimental feed was provided from Cheonje Feed. During the first week of the experiment, all treatments were fed pre-starter feed, and experimental feed was given for each treatment for three weeks from the eighth day of age.

Treatment Coccidium Infection (Challenge) additive CON NO NONE Infect YES NONE Infect + BV YES Bee venom (100 ppb)

To induce the coccidium challenge model, all treatments were orally inoculated with 25x of the recommended level of coccidium vaccine at 14 days of age except for the coccidium uninoculated control (treatment 1). After the inoculation of Coccivac D vaccine (Coccivac D), a single number was selected for each repetition on day 6 (20 days of age) to measure the coccidium lesion, and the required sample was taken. Coccidiosis vaccine used in the present invention is Eimeria acervuline, Eimeria tenella, Eimeria maxima , Eimeria necatrix, Eimeria brunetti, Eimeria hagani, Eimeria praecox, Eimeria mivati 8 jong protozoa in the vaccine to be used in young chickens for the purpose of prevention of coccidiosis in the breeders and laying hens It contains. The number of protozoa included in the single-dose vaccine contains about 2,000 oocysts.

<Example 4. Confirmation of coccidiosis symptoms following bee venom administration>

Example 4-1. Feed intake, productivity and mortality

Feed intake was calculated at weekly intervals between the amount of feed and the remaining amount, and the amount of intake per week was calculated. Weight gain (BW gain-body weight gain) was measured by pen week at the same interval as feed intake, and FCR (feed conversion ratio) was calculated using feed intake and live + dead. The dead chickens were weighed every day and used to calibrate the FCR.

In Table 4, the effect of 100 ppb of bee venom on broiler feed was improved by 3.8% in weight gain compared to the coccidium control (Infect treatment) and suppressed FCR (feed rate) (healthy chickens). Has lower FCR than diseased chickens).

The anticoccidial effect is generally measured by three items (weight gain, intestinal lesions, and the number of coccidium in feces). Thus, the results of bee venom intake improved the symptoms of coccidiosis.

Effects of bee venom on growth performance in coccidiosis vaccine-challenged broiler chickens ¹ Item ² Treatmant ³ SEM ⁴ P -value CON Infect Infect + BV Post-challenge (14 to 20 d) BW gain, g / b 335.3 312.3 324.3 41.472 0.593 FCR 1.767 ^a 1.793 ^a 1.546 ^b 0.070 0.043 ¹ n, 7 / treatment.
² BW gain, body weight gain; FCR, feed conversion ratio.
³ CON, control; Infect, infected control; Infect + BV, infected, bee venom at 100 ppb.
⁴ SEM, standard error of the means.
^{a- b} Means within a row with different superscript are significantly different ( p <0.05).

Example  4-2. Determination of Antioxidant Enzyme Activity

At the end of the experiment, the average weight of each pen was selected for each repetition group, sacrificed using CO ₂ , blood was collected directly from the heart with a disposable syringe and centrifuged (1000rpm x 5min) to separate serum. One serum sample was analyzed for Superoxide dismutase (SOD) and Glutathione. Superoxide dismutase (SOD) was analyzed using SOD Assay Kit-WST (Sigma-Aldrich, St. Louis, MO, USA). Glutathione was analyzed using the Glutathione Assay Kit (BioAssay Systems Hayward, CA, USA).

Effects of bee venom on antioxidant activity in coccidiosis vaccine-challenged broiler chickens ¹ Item Treatmant ² SEM ³ P -value CON Infect Infect + BV SOD activity 97.01 94.90 97.49 2.962 0.454 Glutathione, μM 139.7 136.5 139.8 2.114 0.406 ¹ n, 7 / treatment.
² CON, control; Infect, infected control; Infect + BV, infected, bee venom at 100 ppb.
³ SEM, standard error of the means.
^{a- b} Means within a row with different superscript are significantly different ( p <0.05).

In Table 5, it can be seen that the superoxide dismutase (SOD) and Glutathione, which are reduced due to coccidial protozoan infection, are restored to a normal state due to bee venom treatment.

Example 4-3. Identification of Acute Base Protein (alpha-1-acid Glycoprotein)

At the 3rd week of the experiment, the average weight of each pen was selected by repeating group, sacrificed using CO ₂ , blood was collected directly from the heart with a disposable syringe, and centrifuged (1000 rpm x 5 min) to separate serum. The serum was used to measure acute base protein (Alpha-1-Acid Glycoprotein). Acute base protein (Alpha-1-Acid Glycoprotein) was measured using Chicken Alpha-1-acid Glycoprotein Assay Kit (Life Diagnostics, Inc, West Chester, PA, USA).

Effects of bee venom on serum acute phase protein in coccidiosis vaccine-challenged broiler chickens ¹ Item ² Treatmant ³ SEM ⁴ P -value CON Infect Infect + BV α1-AGP, μg / ml 265 ^b 637 ^ab 408 ^a 127.320 0.047 ¹ n, 7 / treatment.
² α1-AGP, alpha-1-acid glycoprotein.
³ CON, control; Infect, infected control; Infect + BV, infected, bee venom at 100 ppb.
⁴ SEM, standard error of the means.
^{a- b} Means within a row with different superscript are significantly different ( p <0.05).

Checking Table 6, it can be seen that Alpha-1-Acid Glycoprotein is reduced by bee venom treatment in coccidium protozoa infected group. Acute phase protein, such as Alpha-1-Acid Glycoprotein, increases in response to external stimuli, stress, and pathogens, indicating that coccidiosis has improved due to bee venom treatment.

Example  4-4. Microbial composition in the cecum

At the 3rd week of the experiment, the average weight of each pen was selected for each pen and sacrificed using CO _{2. The} cecum was collected and the total aerobes, Lactobacilli and Escherichia coli counts were measured. 1 g of cecum powder was diluted in 9 ml of sterile distilled water. The dilutions were diluted 10-fold and then applied to specific media and incubated in a 37 ° C. incubator for 24 hours. Specific colonies were counted and expressed as colony forming units (gfu) per gram.

Effects of bee venom on different bacterial populations in cecal digesta in coccidiosis vaccine-challenged broiler chickens ¹ Item Treatmant ² SEM ³ P -value CON Infect Infect + BV log10 cfu / ml Total aerobes 7.82 ^b 8.24 ^a 8.30 ^a 0.115 0.032 Lactobacilli 8.35 8.64 8.67 0.142 0.276 Esherichia Coli 7.06 7.77 7.59 0.254 0.288 ¹ n, 7 / treatment.
² CON, control; Infect, infected control; Infect + BV, infected, bee venom at 100 ppb.
³ SEM, standard error of the means.
^{a- b} Means within a row with different superscript are significantly different ( p <0.05).

From Table 7, it is confirmed that the number of lactic acid bacteria among the microorganisms in the cecum is similar before and after bee venom treatment, but the number of Escherichia coli is significantly reduced. Therefore, it can be seen that bee venom has an effect of selectively inhibiting only E. coli, which can further increase inflammation that can occur through coccidial infection without inhibiting the growth of beneficial bacteria.

Example 4-6. Oocyst count and intestinal lesions

The number of coccidium protozoa oocysts was measured by taking three litters around the nipple and two around the feed container for each repetition group. In the third week of the experiment, 1 number of cells were selected for each repetition, and coccidial lesions were measured in the duodenum, jejunum, and ileum. Coccidium-specific lesions are evaluated with a score of 0-4 through the naked eye, referring to [Johnson J. and Reid WM, 1970]. If there is no lesion, it is '0' (normal), and if the redness is very severe, it is '4'. Evaluate.

Oocyst count per gram of litter and lesion scores ¹ Item Treatmant ² SEM ³ P -value CON Infect Infect + BV Oocyte count  log 10 oocyst / g 0 ^b 2.965 ^a 1.015 ^a 0.169 <.0001 Lesion score  Duodenum 0 ^b 1.680 ^a 1.024 ^a 0.062 <.0001  Jejunum 0 ^b 1.505 ^a 1.167 ^a 0.045 <.0001  Ileum 0 1.118 1.069 0.059 0.413 ¹ n, 7 / treatment.
² CON, control; Infect, infected control; Infect + BV, infected, bee venom at 100 ppb.
³ SEM, standard error of the means.
^ab Means within a row with different superscript are significantly different ( p <0.05).

Checking Table 8, the bee venom treated in the coccidium protozoa treatment, compared with the single protozoa treatment can be confirmed that the number of oocyst is suppressed and coccidium-specific lesions are suppressed.

Example 4-7. Check your blood appearance

In the 3rd and 5th experiments, the average weight of each pen was selected by repeating groups and sacrificed using CO _2. Blood was collected directly from the heart with a disposable syringe and centrifuged to separate serum (1000 rpm). x 5 min), isolated serum samples were analyzed for Ca, P and other blood component concentrations.

Effects of bee venom on serum biological profile in coccidiosis vaccine-challenged broiler chickens ¹ Item ² Treatmant ³ SEM ⁴ P -value CON Infect Infect + BV TP, g / dl 3.214 3.400 3.800 0.159 0.117 ALB, g / dl 1.357 1.450 1.580 0.068 0.138 r-GLO, g / dl 13.83 ^a 10.83 ^b 10.80 ^b 0.576 0.006 BUN, mg / dl 2.700 2.733 2.400 0.155 0.329 GLU, mg / dl 248.4 259.0 265.3 13.663 0.700 T-CHO, mg / dl 123.6 ^a 104.2 ^ab 95.0 ^b 6.550 0.033 Ca, mg / dl 11.77 ^a 10.78 ^b 12.17 ^a 0.252 0.021 Mg, mg / dl 2.575 2.600 2.740 0.154 0.797 IP, mg / dl 9.65 8.60 9.28 0.445 0.323 GOT, IU / L 215.4 204.8 222.5 6.287 0.244 r-GTP, IU / L 1.857 2.000 1.983 0.116 0.648 NEFA, uEq / L 457.3 323.2 235.8 66.503 0.126 Nitric oxide , μM 19.75 21.13 18.83 0.926 0.266 ¹ n, 7 / treatment.
² TP, total protein; ALB, albumin; r-GLO, gamma-globulin; BUN, blood urea nitrogen; GLU, glucose; T-CHO, total cholesterol; Ca, calcium; Mg, magnesium; IP, inorganic phosphorous; GOT, glutamic oxaloacetic transaminase; r-GTP, gamma- guanosine triphosphate; NEFA, non-esterified fatty acids.
³ CON, control; Infect, infected control; Infect + BV, infected, bee venom at 100 ppb.
⁴ SEM, standard error of the means.
^{a- b} Means within a row with different superscript are significantly different ( p <0.05).

In Table 9, it was found that the blood nitric oxide content of each blood component was reduced by about 10.9% compared to the coccidium control, indicating that bee venom suppressed the inflammatory response due to coccidial protozoa infection. Can be.

Example 4-8. Determination of Volatile Fatty Acid Content in Caecum Content

At week 3 of the experiment, the average weight of each pen was selected for each of the repetitors and sacrificed using CO ₂ . 1 g of cecum powder was diluted in 9 ml of sterile distilled water. A mixture of 0.05 ml of HgCl ₂ , 1 ml of 25% H ₃ PO ₄ and 0.2 ml of 2% pivalic acid was centrifuged (3,000 rpm x 20 min, 4 ° C.) in 5 ml of sample. Only the supernatant was collected and the volatile fatty acids were measured by gas chromatography (6890 Series GC System, HP, Palo Alto, CA, USA).

Effects of bee venom on short-chain fatty acid (SCFA) concentration (μM / g) in cecal digesta in coccidiosis vaccine-challenged broiler chickens ¹ Item ² Treatmant ³ SEM ⁴ P -value CON Infect Infect + BV Acetate 44.28 ^ab 36.40 ^b 54.20 ^a 3.393 0.040 Propionate 3.378 ^b 2.979 ^b 5.371 ^a 0.242 0.003 Isobutyrate 0.159 0.147 0.282 0.034 0.088 Butyrate 16.49 12.50 16.65 2.688 0.584 Isovalerate 0.298 0.276 0.697 0.099 0.068 Valerate 0.662 0.607 0.963 0.070 0.066 BCFA 1.119 ^b 1.015 ^b 2.100 ^a 0.118 0.002 Total SCFA 61.19 52.50 83.89 6.110 0.179 ¹ n, 7 / treatment.
² BCFA, branched-chain fatty acids (isobutyrate + valerate + isovalerate; Total SCFA, total short-chain fatty acid (acetate + propionate + butyrate + isobutyrate + valerate + isovalerate).
³ CON, control; Infect, infected control; Infect + BV, infected, bee venom at 100 ppb.
⁴ SEM, standard error of the means.
^{a- b} Means within a row with different superscript are significantly different ( p <0.05).

Checking Table 10, it was confirmed that the volatile fatty acids in the cecum increased overall in the bee venom treated group, especially the content of acetate, propionate, butyrate increased compared to the coccidium control. Volatile fatty acid levels correlate well with the type and metabolism of the cecal microorganisms, and because it is related to the immunity of the host animal, it can be confirmed that increased intestinal immunity.

Preparation Example 1. Pharmaceutical Formulations

Formulation Example 1-1. Manufacture of tablets

200 g of purified bee venom of Example 1 was mixed with 175.9 g of lactose, 180 g of potato starch, and 32 g of colloidal silicic acid. 10% gelatin solution was added to the mixture, which was then ground and passed through a 14 mesh sieve. It was dried and tableted for the treatment of coccidiosis by compression of the mixture obtained by adding 160 g of potato starch, 50 g of talc and 5 g of magnesium stearate.

Formulation Example 1-2. Preparation of Injection

100 mg of purified bee venom of Example 1, 0.6 g of sodium chloride and 0.1 g of ascorbic acid were dissolved in distilled water to make 100 ml. The solution was placed in a bottle, heated and sterilized at 20 ° C. for 30 minutes, and subdivided to prepare an injection solution for treating coccidiosis.

Preparation Example 2 Feed Composition

200 g of purified bee venom of Example 1 was added to prepare 1 ton for the preparation of broiler feed, thereby preparing a feed for improving coccidiosis.

Claims (6)

As a composition containing bee venom as an active ingredient,
The bee venom is a purified bee venom obtained by removing sugars and volatiles from the bee venom isolated from the bee venom of worker bees ( Apis mellifera L.) over 15 days old, and apamin, melittin, phospholipase A2, adolafine and hyaluronic acid. It contains nidase as an active ingredient,
The bee venom, for poultry, gains weight gain; Feed rate inhibitory effect; Activity enhancing function of peroxidase; Potency to reduce acute base protein (Alpha-1-Acid Glycoprotein); Reduced efficacy of the number of E. coli in the cecum; Anti-inflammatory function through reduction of nitric oxide content in blood; And, a composition for the prevention or treatment of coccidiosis, which has an effect of increasing the volatile fatty acid in the cecum. delete The method of claim 1,
The coccidiosis is this Almeria ah Sergio called (Eimeria acervuline), this Almeria Te Canela (Eimeria tenella), this Almeria Maxima (Eimeria maxima), this Almeria your cart Riggs (Eimeria necatrix), this Almeria Brewer Connecticut (Eimeria brunetti), this Prevention of oral coccidiosis characterized by protozoa of at least one Amerian parasite selected from the group consisting of Eimeria hagani , Eimeria praecox and Eimeria mivati . Therapeutic composition. delete Pharmaceuticals for the prevention or treatment of coccidiosis of formulations selected from the group consisting of powders, granules, tablets, capsules, liquid capsules, aqueous solutions, suspensions, emulsions, syrups and aerosols containing the composition according to claim 1 or 3. Formulation. An animal feed for improving coccidiosis, which contains a composition according to claim 1.

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