KR101231938B1 - Composition comprising the extract of Galla Rhois for preventing and treating the disease caused by Coccidium - Google Patents

Abstract

The present invention relates to a composition having an antiprotozoal activity against coccidium, and in particular, the composition of the present invention containing the gall bladder extract as an active ingredient exhibits excellent anticoccidial and increasing effects on coccidial. It can be usefully used for the prevention and treatment of diseases caused by the medium.

Description

Composition comprising the extract of Galla Rhois for preventing and treating the disease caused by Coccidium}

The present invention relates to a composition and a feed additive for the prevention and treatment of diseases caused by coccidium containing a gall extract as an active ingredient.

1 Hahm et al., Korean J. Gastroenterol . , 37 , pp. 399-405, 2001.

2, Marshall et al., Lancet , 1 , pp. 131-1315, 1984.

3, Ho et al., J. Clin . Microbiol . , 29 , pp. 2543-2549, 1991.

[4] Kim et al., Kor. J. Lab . Anim . Sci . , 20 , pp. 316-320, 2004.

5 Velazquez et al., Int. J. Microbiol . , 53 , pp. 95-1 04, 1999.

Priestnall et al., J. Clin . Microbiol . , 42 , pp. 2214-2151, 2004.

[7] Watanabe et al., Gastroenterology , 115 , pp. 642-648, 1998.

8 Ahn et al., J. Kor . Med . Sci . , 6 , pp. 7-14, 1991.

[9] Jung et al., J. Korean Soc . Microbiol . , 35 , pp. 97-108, 2000.

[Document 10] Jung-Sup et al., Hyang-Yaksa Dictionary, pp.380-384, Younglimsa , 1998.

[11] Narayan et al., Phytother Res . 21 , pp. 190-193, 2007.

12 Daugschies et al. Vet. Parasitol . 103 , pp. 299-308, 2002.

Coccidiosis is a common infectious disease that causes damage to public health and industrial animals (cows, pigs, chickens, etc.) and causes problems throughout the livestock industry. In particular, the economic losses due to reduction of weight gain, decrease in feed efficiency, and mortality when infecting industrial animals are significant. In particular, the poultry industry generates more than $ 1.5 billion in annual economic losses worldwide.

Coxiumium (Eimeriaspp., Toxoplasmagondii) causes disease in animals and humans and leads to death, but antibiotics, which are microbial treatments, have been used because there is no obvious treatment, but the treatment efficiency is known to be extremely low despite the high treatment cost. Coccidium infection occurs through eating blood products, tissue transplants, unpasteurized milk, and raw pork. In addition, coccidial is one of the important causes of congenital infections caused by pregnancy, and coccidium causes coccidial encephalitis and decreases survival rate in patients with AIDS.

      Coccidium infectious agents in the poultry industry include Eimeria, Leucocytozoon, Haemoproeus Toxopla sma, Sarcocystis and Cryptosporidium, and Cryptosporidium. However, the damage caused by Eimeria is the most serious of these. In the swine industry, the main causes of coccidial infection are reported as Eimeria, Isospora, Cryptosporidia and Toxoplasma. Population and dense breeding, a hallmark of the poultry industry, has led to the explosive development of coccidium worldwide, which has resulted in the widespread use of chemotherapeutic agents such as sulfa and ampoulium. By continuously adding various anticoccidial drugs to feed, it was possible to suppress coccidial development somewhat, but prolonged and long-term administration of these antibiotics led to the emergence of antibiotic-resistant protozoa. The life of antibiotics already developed is shortened. In the domestic livestock industry, the damage caused by coccidiosis is enormous, and the sales volume of various imported anticoccidial drugs used for the prevention and treatment of the disease exceeds annually 10 billion won. Coccidium, Cryptosporidium, thermophilic insects, and coccidium are the common spores, and most of them are infectious diseases, causing human and animal diseases and causing damage to humans, as well as to many livestock farming and meat processing businesses.

      Recently, due to the grouping and dense breeding of industrial animals, there has been an explosion of coccidium around the world. Accordingly, the treatment of chemotherapeutic agents such as sulfa drugs and ampoulium has been widely used. It has been possible to suppress coccidium production by continuously adding various anticoccidium drugs to the feed and continuously dosing. However, the sustained and long-term administration of these antibiotics over the decades led to the emergence of antibiotic-resistant protozoa, resulting in shortened shelf life for antibiotics already developed. Accordingly, the continuous development of new drugs is needed, but the development cost of new drugs due to the strengthening of safety regulation of livestock foods and the legal regulation on new development drugs are recently increased by Motivation for drug development is being lost.

Recently, the pathogenic protozoan or attenuated attenuated vaccine against coccidium has been commercialized, but the live poison vaccine can be lowered after a long time in a diluted state in the case of negative administration of live venom vaccine. Furthermore, in the oocyst of koksi Stadium surrounded by a double wall typical disinfectant agent it is a situation that almost no disinfection effect (Daugschies et al .. Vet. Parasitol . 103, pp 299-308).

Rhus is a Rhus tree belonging to the family Anacardiaceae. avanica L. astragalus aphid ( Aphis ) on leaf chinensis J. Bell) is a worm house caused by stab, distributed throughout the country. In the form of gall, the outer surface is greyish brown with light hairs, 3-7 cm long, 2-5 cm wide, and 2 mm thick, hard and easily broken. The genus is usually empty or gray-white dead worms and secretions remain, and there is a disgusting smell. The collected dwarf is dried, boiled or steamed in the sun. Its main ingredient is 50 ~ 70% of pyrogalloltannin, and it includes malated assets and gallic acid. It is used as astringent, branch, and hemostatic agent for diarrhea, sputum, diabetes, bleeding, and anemia (Information et al., Hyangjesa Dictionary, pp.380-384, Younglimsa , 1998).

This project is to develop and commercialize the prevention and treatment of bacteria and parasites, which are common causes of infectious diseases that cause diseases in animals including humans.In the case of human body, development of prevention and treatment of diseases is possible. It is possible to develop alternatives to cope with the regulation of antibiotic use, which is causing social problems recently. In addition, in terms of industrial animals, it is possible to solve the disease transmission and environmental pollution problems caused by the investment and leakage of leachate from infectious diseases, reduce the indiscriminate use of antibiotics used for feed addition, and cause social and public problems caused by antibiotic misuse. Reduce health costs. In addition, by minimizing the problems of antibiotic resistance protozoa and the safety of livestock products due to antibiotic residue, it contributes to the people's safe food culture, and contributes to the public health by preventing the spread of these diseases to people.

Accordingly, the present inventors have developed a natural product that exhibits an excellent antiprotozoal effect against coccidium, and completed the present invention by confirming the antiprotozoal effect and proliferation effect against coccidium (Eimeia tenella) in broiler experiments.

In order to carry out the above object, the present invention provides a veterinary composition for the prevention and treatment of diseases caused by coccidium containing a gall bladder extract as an active ingredient.

In addition, the present invention provides a feed comprising the animal feed additives for the prevention and improvement of diseases caused by coccidium containing the gall bladder extract as an active ingredient.

The present invention provides a pharmaceutical composition for the prevention and treatment of diseases caused by coccidium containing a gall bladder extract as an active ingredient.

In addition, it provides a health functional food for the prevention and improvement of diseases caused by coccidium containing the gall bladder extract as an active ingredient.

The extract as defined herein includes water, including purified water, lower alcohols of C1 to C4 or mixed solvents thereof, preferably extracts soluble in water.

Animals of the coccidium bacterial infection include mammals such as humans, pigs, cows and goats; Fish such as carp and goldfish; And poultry such as pheasants, chickens, ducks, turkeys and the like.

Hereinafter, the present invention will be described in detail.

The gall bladder extract of the present invention is water, including about 1 to 20 times, preferably about 2 to 6 times (v / w), purified water of a dried gall bladder, lower alcohols of C1 to C4 or their Mixed solvent, preferably water, cold extraction, hot water extraction, ultrasonic extraction, for about 1 hour to 10 days, preferably about 2 hours to 5 hours at an extraction temperature of 20 to 150 ℃, preferably 70 to 120 ℃, Extraction method, such as reflux cooling extraction, preferably by reflux cooling extraction and then concentrated under reduced pressure to obtain the extract of the present invention.

The present invention provides a veterinary composition for the prophylaxis and treatment of diseases caused by coccidial containing an organza extract obtained by the above manufacturing process as an active ingredient.

In another aspect, the present invention provides a pharmaceutical composition for the prevention and treatment of diseases caused by coccidium containing the gall bladder extract obtained by the manufacturing process as an active ingredient.

Veterinary and pharmaceutical compositions containing extracts of the present invention comprise from 0.1 to 50% by weight of said extract, relative to the total weight of the composition.

However, the composition is not limited thereto, and may vary depending on the condition of the patient, the type of disease, and the progress of the disease.

Since the extract of the present invention has little toxicity and side effects, it can be used with confidence even when taken for a long time for the purpose of prevention.

      Veterinary dosage forms of the extracts of the present invention may be used in the form of their veterinary acceptable salts and may also be used alone or in combination with other veterinary active compounds, as well as in any suitable collection.

Veterinary compositions and pharmaceutical compositions comprising the extract of the present invention may further comprise suitable excipients and diluents commonly used in the preparation of the veterinary composition and the pharmaceutical composition.

Excipients and diluents that may be included in the veterinary compositions and pharmaceutical compositions comprising the extract 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.

Veterinary compositions and pharmaceutical compositions comprising extracts of the present invention may further comprise fillers, anti-coagulants, lubricants, wetting agents, spices, emulsifiers, preservatives, etc., which are active after administration of the veterinary composition according to the present invention to animals. Formulations can be formulated using methods well known in the art to provide rapid, sustained or delayed release of the components, the formulations being powders, granules, tablets, capsules, suspensions, emulsions, solutions, syrups, aerosols, soft Or hard gelatin capsules, suppositories, sterile injectable solutions, sterile external preparations, and the like.

Veterinary compositions and pharmaceutical compositions according to the present invention may vary depending on the age, sex, and weight of the animal / human, but may be administered once to several times in an amount of 0.1 to 100 mg / kg. In addition, the dosage of the gall bladder powder may be increased or decreased depending on the route of administration, the severity of the disease, sex, weight, age and the like. Accordingly, the dosage is not limited in any way to the scope of the present invention.

The composition of the present invention may be administered to mammals such as rats, mice, livestock, humans, and the like in various routes. All modes of administration may be expected, for example, by oral, rectal or intravenous, intramuscular, subcutaneous, intra-uterine or intracerebroventricular injections.

      In addition, the present invention provides a feed comprising the animal feed additives for the prevention and improvement of diseases caused by coccidium containing the gall bladder extract obtained in the process as an active ingredient.

The gall bladder extract for animal feed additives may be 20 to 90% high concentrate or powder or granule form.

Extracts for animal feed additives of the present invention are organic acids such as citric acid, fumaric acid, adipic acid, lactic acid, malic acid, phosphates such as sodium phosphate, potassium phosphate, acid pyrophosphate, polyphosphate (polyphosphate), polyphenols, catechins (catechin ), Alpha-tocopherol, rosemary extract (rosemary extract), vitamin C, green tea extract, licorice extract, chitosan, tannic acid, phytic acid and the like may further include any one or more than one.

Animal feed additives containing the extract of the present invention and feed containing them are various supplements such as amino acids, inorganic salts, vitamins, antibiotics, antibacterial substances, antioxidants, antifungal enzymes, live microbial preparations, and the like as grains, for example. Milled or crushed wheat, oats, barley, corn and rice; Vegetable protein feed, such as rape, soybeans and sunflower; Animal protein feeds such as blood meal, meat meal, bone meal and fish meal; Sugars and dairy products, for example, a dry ingredient consisting of various powdered milk and whey powder, and a drying additive, all mixed together with a liquid component, and a component which becomes a liquid after heating, that is, a lipid, for example, an animal liquefied by heating. In addition to the main components such as fats and vegetable fats can be used with substances such as nutritional supplements, digestion and absorption enhancers, growth promoters, disease prevention agents and the like.

The gall bladder extract for animal feed additives may be administered to animals alone in combination with other feed additives in an edible carrier.

In addition, the extract for animal feed additives can be easily administered as a top dressing or directly mixed with the animal feed or separately from the feed, in a separate oral formulation, by injection or transdermal or in combination with other ingredients. Typically, a single daily dose or divided daily doses can be used, as is well known in the art.

When the extract for animal feed additives is administered separately from the animal feed, they may be prepared in an immediate release or sustained release formulation in combination with a non-toxic pharmaceutically acceptable edible carrier, as is well known in the art. Such edible carriers may be solid or liquid, for example corn starch, lactose, sucrose, soy flakes, peanut oil, olive oil, sesame oil and propylene glycol. When a solid carrier is used, the dosage form of the extract may be tablets, capsules, powders, torokies or sugar-containing tablets or top dressings in microdisperse form. If a liquid carrier is used, it may be in the form of soft gelatin capsules or syrups or liquid suspensions, emulsions or solutions. In addition, the dosage form may contain auxiliaries such as preservatives, stabilizers, wetting or emulsifying agents, solution promoters and the like. They may also contain other substances useful for the improvement and prevention of diseases caused by viruses.

      In addition, the animal feed, in which the gall bladder extract is included as an animal feed additive, may be any protein-containing organic cereal meal commonly used to meet the dietary needs of the animal. Such protein-containing flours typically consist mainly of corn, soy flour, or corn / bean flour mixtures.

The animal feed additive may be used by adding to the animal feed by dipping, spraying or mixing.

The invention is applicable to a number of animal diets, including mammals, poultry and fish. More specifically, the diet is commercially important mammals such as pigs, cows, sheep, goats, laboratory rodents (rats, mice, hamsters and gerbils), furry animals (eg mink and fox). ), And zoo animals (eg monkeys and tailless monkeys), as well as livestock (eg cats and dogs). Commercially important poultry typically include chickens, turkeys, ducks, geese, pheasants and quails. Commercially raised fish, such as trout, may also be included.

      In the animal feed compounding method including the extract according to the present invention, the gall bladder extract is incorporated into the animal feed in an amount of about 1 g to 100 g per kg of feed on a dry weight basis.

Also, after the feed mixture is thoroughly mixed, lightly viscous granulation or granulation material is obtained depending on the degree of crushing of the components. It is fed as a mash or formed into the desired discrete shape for further processing and packaging. At this time, it is preferable to add water to the animal feed and then go through the usual pelletization, expansion, or extrusion process to prevent separation during storage. Excess water can be dried off.

      In addition, the present invention provides a health functional food for the prevention and improvement of diseases caused by coccidial containing the gall bladder extract obtained in the process as an active ingredient.

The composition comprising the extract of the present invention may be used in various ways, such as drugs, foods and beverages for the prevention and improvement of diseases caused by coccidium. Examples of the foods to which the extract of the present invention can be added include various foods, beverages, gums, tea, vitamin complexes, health supplements and the like, and they can be used as powders, granules, tablets, capsules or beverages have.

The amount of the extract in the food or beverage of the present invention can generally be added to 0.01-15% by weight of the total food weight of the health food composition of the present invention, the health beverage composition is 0.02 to 5 g, preferably based on 100 ml Can be added in a ratio of 0.3 to 1 g.

In addition to containing the extract as an essential ingredient in the indicated ratio, the health functional beverage composition of the present invention is not particularly limited in the liquid component, and may contain various flavors or natural carbohydrates as additional ingredients, such as ordinary drinks. Examples of the above-mentioned natural carbohydrates include monosaccharides such as glucose, fructose and the like; Disaccharides such as maltose, sucrose and the like; And polysaccharides, for example, conventional sugars such as dextrin, cyclodextrin and the like, and sugar alcohols such as xylitol, sorbitol and erythritol. As flavoring agents other than those mentioned above, natural flavoring agents (tauumatin, stevia extract (e.g., Rebaudioside A, glycyrginine, etc.) and synthetic flavoring agents (saccharin, aspartame, etc.) can be advantageously used. The proportion of natural carbohydrates is generally about 1-20 g, preferably about 5-12 g per 100 ml of the composition of the present invention.

In addition to the above-mentioned composition, the composition of the present invention can be used as a flavoring agent such as various nutrients, vitamins, minerals (electrolytes), synthetic flavors and natural flavors, coloring agents and intermediates (cheese, chocolate etc.), pectic acid and its salts, Salts, organic acids, protective colloid thickening agents, pH adjusting agents, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in carbonated beverages and the like. In addition, the composition of the present invention may contain a natural fruit juice and a pulp for the production of fruit juice drinks and vegetable drinks. These components may be used independently or in combination. The proportion of such additives is not so critical, but is generally selected in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition of the present invention.

Since the gall bladder extract of the present invention exhibits an excellent antiprotozoal effect on coccidium, it can be usefully used as a composition and feed additive for the prevention and treatment of diseases caused by coccidium.

1 is a diagram showing the increase effect of Flavo SK on broilers,
2 is a view of the increase effect according to the concentration of Flavo SK,
Figure 3 is a diagram showing the increase effect according to administration of Flavo SK breeding section,
4 is a diagram showing the effect of Flavo SK on broiler gain after coccidial infection,
Figure 5 is a diagram of the in vivo protective effect of the coccidium infection.

Hereinafter, the present invention will be described in detail by the following reference examples, examples and experimental examples.

      However, the following reference examples, examples and experimental examples are merely to illustrate the invention, the content of the present invention is not limited by the following reference examples, examples and experimental examples.

Example  1. Preparation of Gall bladder water extract

Crushed dried gallnuts obtained from the University of Iksan to obtain gallnut powder, and then distilled water corresponding to three times (v / w) of the dried gallnut powder (1 kg) obtained above was added at 3O < 0 > C. The mixture was cooled to reflux for a period of time, filtered and concentrated under reduced pressure, and then lyophilized to obtain 620 g of powdered gallnut extract (hereinafter referred to as "GM-1" and "Flavo SK". Extraction rate: 62%). It used as the sample of an experiment example. On the other hand, except for using ethanol, methanol, 30% ethanol and 70% ethanol as the extraction solvent, the same method as the above extraction method was applied to extract the extract at 52%, 56%, 58% and 54%, respectively Obtained.

Reference Example 1. Experiment Preparation

1-1. Laboratory Animal Preparation

Six weeks-old SD rats supplied by Orient Co., Ltd. and chicks maintained in line at the Animal Resource Development Research Center of Wonkwang University were fed at 8 weeks of age and then purified for one week at the experimental animal breeding room of the Animal Resource Development Research Center of Wonkwang University. It was used for later experiments. During the breeding period, the temperature was raised at 23 ± 1 ℃, humidity 50 ± 5%, noise below 60 phone, lighting time 08: 00-20: 00 (12 hours per day), 10-12 times per ventilation hour. Feeding laboratory animals feed (PicoLab Rodent DIET 20 5053, LabDiet Co., Ltd.) provided by Orient was free, and the negative water was freely supplied with sterile water. All experimental procedures and procedures related to the experimental animals used in this study were performed in compliance with the regulations of the Institutional Animal Care & Use Committee (IACUC).

1-2. Coxium ( Eimeria tenella , 297-1) Eggs  Ready

Coccidium oocytes (College of Veterinary Medicine, Gyeongsang National University) are stored in Potassium Diclomate (Sigma) stock solution at 8.5 × 104 / ml, and the stock solution is toxic. Discard the stock solution and add sterile distilled water (DW) as much as the stock solution to centrifuge three times at 4,000 rpm for 25 minutes. Each time centrifugation, discard the supernatant, add the same amount of distilled water (DW), and after washing, count the eggs to determine the concentration. Dilution containing eggs is first diluted 20 times with distilled water (DW), diluted 5 times with saturated NaCl (Sigma) (usually 5-10 times) and counted using a chamber (Difco) at × 100 magnification. The final concentration of egg was 4.3 × 10 4 / ml was used for the experiment.

1-2. Military composition

In the reference example 1-1, the healthy young chicks of 7-weeks-old purified for one week were divided into two groups, as shown in Table 1 below. The chicks used in the experiment were disease-free and apparently healthy chicks. 301-5 farm (13,14,15 dong) was used as a test and 301-6 farm (16,17,18,19 dong) was used as a control and applied to 20,000 chicks. In addition, the test group did not use any dosing or additives, and the experiment was administered 'flavo SK' to the feed by administering 0.29% of the feed amount. As a control group, antibiotics (product number 49071202, manufacturer CTC bio, brand name Amoshot) and nutrients (gold Vitawon / ampicoli / ylcosine-S liquid / vegetable alpha) (product number 720541, manufacturer handong, product name) Mia-S) was administered. Commonly, both groups received ND at 10 days and IBD at 14 days of age.

Group n Existing feed Flavo - SK Separate management Test group 0 X X Flavo - SK
No addition Control group 0 0 X Flavo - SK
Addition

Experimental Example 1 Increased effect of FlavoSK on broilers

Flavor SK powder is added to the diets for 2 days of 0.5% and 1% in the meat jujube adapted to the basic feed (modern feed) for 5 days, and treated for 21 days, and the control group supplies only the basic feed. The weight of each group is measured at 0, 2, 4, 12, 16 and 21 days after feeding.

As a result, as shown in Figure 1 Flavo SK powder 0.5% treated group was treated from the 16th day after treatment, 1% treated group showed a clear increase effect compared to the control group from 12 days after treatment.

Experimental Example 2 Plasma SK Concentration in Broiler Chickens and Weight Gain

2-1. Flavo SK  According to concentration Gain effect

Flavor SK powder was added to the diet for four days, 0.20, 0.25, 0.30 and 0.35%, and treated for 22 days. The weight of each group is measured every 18, 25 and 30 days after feeding.

     As a result, as shown in Figure 2 Flavo SK powder concentration of 0.20, 0.25, 0.30 and 0.35% of the control group showed a high weight gain overall, especially at a concentration of 0.35% compared to the control group in about 10 A gain of about% was recognized (see Figures 2A, B and C).

2-2. Flavo SK  Following administration Gain effect

Flavor SK powder was added to the feed at 0.5% concentration in the meat jujube adapted to the basic feed for 8 days, divided into two sections for 10 days, and the control group supplied only the basic feed. In the first section, the feed is supplied from the 1st to 8th day, the feed containing 0.5% Flavo SK from 8th to 18th, and the basic feed from 18th to 30th. Feed basic feed by day, feed containing 0.5% Flavo SK from 18th to 28th, and feed from 28th to 30th. The weight of each group is measured every 18 days and 25 days and 30 days after feeding.

As a result, as shown in FIG. 3, the first section administration group of 0.5% Flavo SK powder concentration showed an increase of about 10% or more in the body weight of 18 days compared to the control group and the second section administration group (see FIG. 3A). In the body weight of the first section and the second section of the group was increased by about 10% or more compared to the control group (see Fig. 3B), and at the 30-day-old body weight of the first section and the second section group was about 8% or more compared to the control group It was shown to have a gain effect (see Figure 3C).

Experimental Example  3. Flavo SK of Anticoccidium  effect

3-1. Coxium  Oral Infection and Drug Administration

The test was divided into 10 groups in each group: 4 groups, vaccinated in the coccidium group after administration of two doses (0.5% and 0.1%) of Flavo SK powder in the non-vaccinated negative control group, the coccidium inoculation positive control group (non-treated group), respectively. Use the meat. Flavo SK powder was divided into two concentrations, 0.5% and 1%, and added to the feed, pretreated for 5 days, and the untreated positive control group fed only the basic feed, and then fed orally at a concentration of 104 / ml for each meat. Inoculate challenge by administration.

3-2. After coccidium infection Flavo SK Autumn broiler To increase  Impact

For 12 days after coccidial vaccination, the untreated group supplied only the basic feed, and the treated group added the Flavo SK powder in the feed in two concentrations of 0.5% and 1%, and continued supplying drugs while maintaining 0, 2, 4 Body weight is measured every 8, 12 days. The control group only fed the basic feed without coccidium challenge.

As shown in FIG. 4, in the coccidium infection control group, the increase in body weight was delayed according to the infection and the treatment group of 0.5% of the Flavo SK powder showed no significant difference from the control group, whereas the treatment of 1% concentration The group showed a definite increase in effect compared to the control group at 12 days after treatment, and as a result, it was judged to have an effect of overcoming the delayed increase rate due to coccidial infection.

3-3. Minute variable  And Feces  genus Ovulation test

All feces in the chicken coop are removed the day after the end of the medication period and the feces are collected daily for five days from the next day. The collected fecal sample counts the number of eggs in the feces through the dilution process. That is, after diluting 1000 times with distilled water (DW) and homogenizing, the first dilution, the second dilution with saturated NaCl and counting using a chamber at × 100 magnification.

Experimental results, as shown in Figure 5 compared to the coccidium infection control group on the seventh day post-infection, the treatment group of 0.5% of the Flavo SK powder concentration of about 40%, the treatment group of 1% concentration of about 60% inhibitory effect On the 7th day after infection, the 1% treatment group showed about 50% inhibitory effect. As a result, 40% and 60% reductions in the number of eggs were reduced according to the concentration gradient. As each appears, it seems to have an anticoccidial effect.

Experimental Example  4. By test substance Toxicity  evaluation

In this experiment, 6-week-old SD rats (Orient Co., Ltd.) were used to comply with the Toxicological Test Standards of the Korea Food and Drug Administration (Toxicity Test Standards of the Korea Food and Drug Administration, Drugs, and KFDA 2005-60, 2005). 2,000 mg / kg was determined as the highest dose and diluted with purified distilled water to prepare 5 mg / kg, 50 mg / kg and 500 mg / kg of test substance. Administration was oral administration, which is the main application route in the clinic, and the administration method was fixed directly by transcutaneous skin fixation and then injected directly into the stomach using a metal oral administration zone. Once daily, 10 ml / kg body weight was administered as a dose, and the feed was restrained for 2 hours after administration of the test substance to the test animals, and the feed and water were continuously supplied during the test period.

     After administration in accordance with the Toxicological Test Standards of the Agency and the Acute Toxicity Testing Guidelines of the International Economic Cooperation Organization (OECD Guideline for the Testing Chemicals revised draft guideline 420, Organization for Economic Cooperation and Development (OECD), 2001). During the first six hours, with special attention, the skin, hair, eyes, mucous membranes, respiratory tract, circulatory system, autonomic nervous system, central nervous system, physical activity, behavioral patterns and tremors, convulsions, Salivation, diarrhoea, lethargy, sleep, coma and the like were observed. General clinical symptoms were observed once a day for 14 days after administration, and the individual body weights of the test animals were measured before and after administration of the test substance and once a day during the test period.

Rats were anesthetized with ethyl ether (DUKSAN pharmaceutical Co., LTD.) 14 days after administration, and all organs were removed after bleeding to death, and the organ weights were measured after visual lesion observation of individual test animals.

In the acute toxicity test by single oral administration of gall extract, no deaths were observed in the test animals used in this study and the highest dose administered at 2,000 mg / kg under the conditions. Toxicity by administration of gall extract was not induced in all the indicators observed according to the toxicity criteria. In conclusion, it was confirmed that the gall extract was safe without toxicity even at the recommended maximum dose of 2,000 mg / kg.

Group Experimental group n Gross lesion Pathological lesion I Mellitus Extract Administration Group 10 0 0 Ⅱ Control group 10 0 0

Hereinafter, the preparation examples of the composition comprising the gall bladder extract of the present invention, the present invention is not intended to limit it, but is intended to explain in detail only.

Formulation Example 1 . Feed composition

Ginseng Extract (GM-1) 240g

Excipient (powder) 760 g

Although the composition ratio of the mixture is a composition suitable for a relatively suitable feed composition in a preferred embodiment, the mixing ratio may be arbitrarily modified, and after mixing the above components according to a conventional feed composition manufacturing method, It can be used for manufacture according to the powder preparation method.

Formulation example  2. Sanje  Produce

Mellitus Extract (GM-1) 20 mg

Lactose 100 mg

Talc 10 mg

The above components are mixed and filled in airtight bags to prepare powders.

Formulation example  3. Preparation of Tablets

Ginseng Extract (GM-1) 10 mg

Corn starch 100 mg

Lactose 100 mg

2 mg magnesium stearate

After mixing the above components, tablets are prepared by tableting according to the usual preparation method of tablets.

Formulation example  4. Manufacture of capsule

Ginseng Extract (GM-1) 10 mg

3 mg of crystalline cellulose

Lactose 14.8 mg

Magnesium Stearate 0.2 mg

The above components are mixed according to a conventional capsule preparation method and filled in gelatin capsules to prepare capsules.

Formulation example  5. Preparation of Injectables

Ginseng Extract (GM-1) 10 mg

180 mg mannitol

Sterile sterilized water for injection 2974 mg

Na2HPO4,12H2O 26 mg

(2 ml) per 1 ampoule according to the usual injection preparation method.

Formulation example  6. Liquid  Produce

Mellitus Extract (GM-1) 20 mg

10 g of isomerized sugar

5 g of mannitol

Purified water

Each component was added to purified water in accordance with the usual liquid preparation method and dissolved, and the lemon flavor was added in an appropriate amount. Then, the above components were mixed, and purified water was added thereto. The whole was adjusted to 100 ml with purified water, And sterilized to prepare a liquid preparation.

Formulation example  7. Manufacture of Healthy Foods

Ginseng Extract (GM-1) 1000 mg

Vitamin mixture proper amount

70 μg of Vitamin A Acetate

Vitamin E 1.0 mg

Vitamin B1 0.13 mg

Vitamin B2 0.15 mg

Vitamin B6 0.5 mg

0.2 μg of vitamin B12

Vitamin C 10 mg

10 μg biotin

Nicotinic Acid 1.7 mg

50 μg folic acid

Calcium Pantothenate 0.5mg

Mineral mixture

Ferrous Sulfate 1.75 mg

Zinc Oxide 0.82 mg

Magnesium carbonate 25.3 mg

Potassium monophosphate 15 mg

Dibasic calcium phosphate 55 mg

Potassium Citrate 90 mg

Calcium Carbonate 100 mg

Magnesium chloride 24.8 mg

Although the composition ratio of the above-mentioned vitamin and mineral mixture is comparatively mixed with a composition suitable for health food as a preferred embodiment, the compounding ratio may be arbitrarily modified, and the above ingredients are mixed according to a conventional method for producing healthy foods , Granules can be prepared and used in the manufacture of health food compositions according to conventional methods.

Formulation example  8. Manufacture of health drinks

Ginseng Extract (GM-1) 1000 mg

Citric acid 1000 mg

100 g of oligosaccharide

Plum concentrate 2 g

Taurine 1 g

Purified water was added to a total of 900 ml

The above components were mixed according to a conventional health drink manufacturing method, and the mixture was heated at 85 DEG C for about 1 hour with stirring, and the solution thus prepared was filtered to obtain a sterilized 2-liter container, which was sealed and sterilized, ≪ / RTI >

Although the composition ratio is a composition that is relatively suitable for the preferred beverage in a preferred embodiment, the compounding ratio may be arbitrarily modified according to regional and ethnic preferences such as demand hierarchy, demand country, and usage.

Claims (10)

Veterinary composition for the prevention and treatment of infectious diseases of the Eimeria protozoa containing the gall bladder water extract as an active ingredient. delete delete Pharmaceutical composition for the prevention and treatment of infectious diseases of the Eimeria protozoa containing the gall bladder water extract as an active ingredient. delete Animal feed additives for the prevention and improvement of infectious diseases of the Eimeria protozoa containing the gall bladder water extract as an active ingredient. delete Feed comprising the animal feed additive of claim 6. Health functional food for the prevention and improvement of infectious diseases of Eimeria protozoa, which contains gall bladder water extract as an active ingredient. 10. The dietary supplement of claim 9 which is a powder, granule, tablet, capsule or beverage.

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