TW202000029A - A pharmaceutical composition for the treatment of European foulbrood disease and sacbrood virus - Google Patents

Abstract

Among these viruses, the sacbrood virus (SBV) infection had resulted in a large amount of honey bee colonies and honey harvest losses. SBV is a single stranded, positive-sense RNA virus and belonging to the Iflaviridae. SBV could be identified by the special symptom of death deformed larvae in the hives, which had fluid-filled sacs and sometimes with slightly sour smell. There are many studies described that A. cerana was susceptible to SBV and had a high virulence. SBV infection usually caused a large amount of A. cerana larvae death and even led to the whole colony losses occurred in China, India, South Korea, Thailand, and Vietnam. However, the infection of SBV is not usually resulting in A. mellifera colony losses, due to its different virulence between A. cerana and A. mellifera. The infected larvae were diagnosed by RT-PCR, partial VP1 was sequenced and analyzed by NCBI BLASTn to confirm the causative pathogen. Total twenty-three partial VP1 sequences were obtained in this study; the results confirmed that the causative pathogen was A. cerana SBV (AcSBV). Comparison of the partial VP1 sequences with those of the known AcSBVs showed the high nucleotide sequence identities (92.4-100%). Besides herb medicine and chemical drug Amantadine, the collection of Taiwan-specific medium sacbrood virus (SBV) as an antigen for the preparation of subsequent immunoglobulin production, is really an efficiency treatment method today. The ultimate goal of this patent is to hope that Taiwan can make exclusive Chinese herbal medicine and globulin nutrient solution.

Description

A method for preventing and curing concomitant disease of middle bee and middle cyst

The present invention relates to a medicinal composition against midcystic disease and European larval disease, in particular to a medicinal composition containing globulin against mesangial disease and European larval disease.

The cystic larval disease that causes extremely high mortality in the middle bees is caused by sacbrood bee virus (SBV). SBV virus is a positive-sense ssRNA virus (positive-sense ssRNA virus). Found on the body of Western bees, but since 1976, it has been found in many Southeast Asian countries that Oriental bees are also infected with this virus. The serotypes of viruses found in Oriental bees and western bees are different, and the two cannot infect each other, so the virus found in Oriental bees is called Oriental bee cystic virus (A. cerara sacbrood bee virus, AcSB or CSBV). AcSBV is extremely active and can live up to 3 months indoors. After one larva is infected and dead, the amount of virus in the body can infect 3000 more larvae. It is currently believed that worker bees are vectors of virus transmission. Viruses can cause the death of larvae and adults, but for worker bees, the virus usually multiplies in the body without obvious symptoms. However, because the virus is easy to be ignored at the initial low volume, but once the virus volume quickly multiplies, it is usually unable to rescue, the bee colony will die in large numbers and escape the bees; the cystic virus (SBV) in Italy makes the larvae unable to pupate, A sac is formed under the skin, but it does not cause particularly serious harm. Therefore, no drug treatment can be used to change the king. The virus can cause a large number of deaths of middle bee larvae, and the mortality rate of infection is as high as 95%. The virus strains of the artificial bee and the middle bee were originally of different serotypes, but at present some virus strains have been found to have the ability to cross-species infection. Therefore, the infection of this virus by the interaction between the two bee colonies is the research direction of scholars today. . Since 1971, there have been the first cases of Chinese mesothelioma in the mainland. The whole concept of rectification is to abandon and improve the environment of the apiary. The epidemic prevention must be carried out at the first time, that is, the use of appropriate Chinese herbal medicines for epidemic prevention and treatment, and then gradually improved. The use of veterinary drugs such as amantadine is added to the apiary environment and the use of Chinese herbal medicine. Amantadine is an enterovirus agent for humans, which was later developed as a veterinary drug. In 2012, there was an epoch-making breakthrough, and protein drugs such as globulin began to appear. The development of protein drugs is extremely difficult and costly, so the willingness of manufacturers to invest in large quantities is low, but once successful, their specificity is high. There are many companies in the world that can increase the immunity and resistance of bees. For example, Advance Science has launched hivealive, which is advertised to improve the immunity of bees, resist bacteria, fungi, microbial diseases, and promote intestinal health. MegaBee Company launched MegaBee Powder formula for Honey protein supplements are advertised to improve the health of bees and stimulate the production of royal jelly. In addition, some special formulas can effectively inhibit the infection rate of microparticles after being eaten by bees, and can also significantly reduce the chronic bee paralysis virus (CBPV) The infection rate has a significant therapeutic effect on larvae infected by Chinese sacbrood virus (CSBV). The mainland has a large territory. In Guangdong and Fujian, cystic disease occurs in March-April and November-December. Jiangxi and Hunan occur in April-May and October-November. In the north, the disease occurs later, generally in 5 ~June, so there are at least 3 or more virus serotypes. It has been reported from Taiwan that Taiwan's cystic disease is caused by smuggling mainland Chinese bees. In this year's announcement by Professor Nai Yuxin, it was also verified that Taiwan virus strains have serotypes Very similar to the Zhejiang type of the mainland. Therefore, Taiwan’s unique mesocystic virus was collected as an antigen for subsequent immunoglobulin preparation. When the Chinese bee was attacked by the mesovirus, it was treated by giving Chinese herbs to improve the self-immunity of the bee or directly given a ball that can fight mesosporosis. Protein therapy is an effective treatment method today. The ultimate goal of this patent is to hope that Taiwan can make exclusive Chinese herbal medicines and globulin nutrient solutions to prevent the bladder virus from raging.

European larval rot of bees (European larvae) is a disease caused by honeybee cocci. Although the mortality rate is not high, it is generally about 30%. The pests will die before or after the cover is one of the main diseases that harm the bees. . Sometimes Taiwanese bees and Chinese bees are mixed and raised, which not only destroys the middle bee colony due to stolen honey, but also causes a cross-infection of bee diseases to increase the prevalence of middle bees. The larvae of the European bee larvae are more vigorous. Although the mortality rate is lower than that of the cystic larvae of the Chinese bee, the loss is not light if you pay little attention. European larval rot is a bee larvae that is infected with bacteria and died in the nest before sealing. If the spleen of the middle bee raised in the live frame was examined for spleen, it was found that the lid on the spleen was sparse and larval, and the larvae were of different ages. The gray and black dead larvae in the nest were clipped with a camera and had a pungent odor, which is a characteristic of the disease. The disease occurs all year round, and there are also bee colonies in winter. Only by changing boxes and spleens can the bee colonies be saved. In the past, antibiotics and Chinese herbal medicines were commonly used in two ways of treatment. Examples are as follows: 1. Antibiotic (oxytetracycline tablets): 1 tablet/group for the first time (half tablet for veterinary use), 1 vitamin/tablet/group, fed once every 3 days, for total feeding 3 times. Pills are turned into 50% syrup, and each group is fed with 300-500ml of syrup, and then oxytetracycline is halved twice. 2. Chinese herbal medicine: Andrographis paniculata, dandelion 5g each group of bees, honeysuckle 3g, licorice 1g, decoction three times with water for 20 minutes, then mixed with 50% sugar solution, depending on the amount of bees 300~500ml per group, fed once every 3 days . If there is too much honey in the box and the bees are slow to eat or not to eat, boil the medicine liquid and filter the dregs, spray it with 5% sugar liquid (you cannot use honey to avoid sticking the bee wings), spray the king and the bees against the nest spleen Spray until the bee body is full of mist beads, once every 2 days, spray 4 times in total. With increasing health awareness, and avoiding the frequent use of antibiotics to cause drug resistance, Taiwan has been moving towards the goal of not using antibiotics in general, so Chinese herbal medicine is the better choice. Therefore, this patent content attempts to combine Chinese herbal medicine extracts and globulin The prevention and treatment of midcystic disease and European larval disease are novel and available.

The content of the present invention is to provide an extract and globulin mixed nutrient solution for preventing and treating mesocystic virus and European larvae disease. One of the objects of the present invention is to provide a medicinal composition against mesocystic disease and European larvae disease, especially regarding A pharmaceutical composition of protein against midcystic disease and European larval disease. It contains an effective amount of active ingredient and a pharmaceutically acceptable carrier. The active ingredient is at least one selected from the group consisting of compounds of formula (I).

* IgY蛋黃體免疫球蛋白圖式為式(1)

* IgY yolk body immunoglobulin scheme is formula (1)

The extract of the present invention for the prevention and treatment of mesocystic virus and European larva disease and globulin comprehensive nutrient solution (hereinafter referred to as mesocapsule nutrient solution) is formulated with 1ml of honeysuckle extract and 1ml of angelica extract per 100ml of sterile water. Huangqi extract 1ml, wolfberry extract 0.5ml, jujube extract 0.5ml, garlic extract powder 1g, royal jelly 6g, comprehensive vitamin 6g, IgY yolk body immunoglobulin 12g, the preparation method of the above Chinese herbal preparation is: in proportion Take the above components, put all the above extracts and powder together in sterile water, stir and fully dissolve, and add edible emulsifier and stir it until it appears as a thick paste. .

The use method of the invention for preventing and treating bee diseases is to feed the affected bee colony with 50 ml of nutrient solution once every 2 days, and feeding 3 times as a course of treatment. When feeding, you can add nutrient solution to the feeder of the bee colony, and then add 200mL of syrup to feed together. 1 spleen and 25ml of nutrient solution is enough; if the bee colony has poor appetite, add nutrient solution to 100mL of syrup bee Spray the bee directly, spray the bee and the nest spleen and nest frame with about 2-4ml of nutrient solution every 2 days, 3 consecutive times is a course of treatment.

Compared with the prior art, the present invention has the following benefits:

1. The comprehensive nutrient solution of the present invention can effectively inhibit the pathogens of mesocystic virus and European larvae disease. The comprehensive nutrient solution is more effective than the use of a single component to inhibit viruses and bacteria.

2. The integrated nutrient solution of the present invention is safer than the use of antibiotics to prevent and control the mesosporium virus and European larval disease, and does not cause antibiotic residue problems on bee products.

3. The comprehensive nutrient solution will not cause the resistance of similar pathogens to antibiotics.

4. The comprehensive nutrient solution is easily soluble in water, and it is added to the syrup feeding the bees in an appropriate proportion when feeding the medicine, and the comprehensive nutrient solution is fed together when feeding the sugar to the bees, which is convenient and convenient, and is convenient for popularization and application.

5. The Chinese herbal medicine used in the present invention is a common variety of Chinese herbal medicine, and can be cultivated artificially with abundant resources, so the product is inexpensive and suitable for industrial promotion.

6. The Chinese herbal medicine extract used in the present invention is gentle and friendly to the environment, does not pollute the environment, and is an extract of natural organic products, which has important promotion and application value for the production of green and organic bee products.

7. The IgY yolk body immunoglobulin used in the comprehensive nutrient solution is a commercially available food, which has been approved for use by the Department of Health. It is an SPF egg extract and will not have harmful residues.

detailed description

The following examples further illustrate the present invention.

Confirmation of the pathogen of Chinese bee midcystic disease:

(1) During the bee breeding and production season, the disease mainly infects 2 to 3 days old worms, and the incubation period is 5 to 6 days. About 80% of the diseased larvae die in the large larval stage after capping. The head of the dead and dead insect is upturned, white, and has no odor. It is easily pulled out of the nest with tweezers. The internal tissue is liquefied, the outer skin is tough, and the tip is shaped like a water-filled sac. After the pests died, the nest cover became dark black, concave, and perforated. After the dead insects dried up, they detached from the wall of the nest and shrunk and twisted into a "dragon boat shape". There are two types of bee colonies: some diseases are more serious, a large number of larvae are sick and die, the adult bees are uneasy, the collection activities are reduced, and the bees are easy to fly, which is a "serious disease type". Some disease groups have mild disease, several larvae appear dead in the spleen, and bee colony reproduction and collection activities are normal.

(2) Pick three samples with typical symptoms and carry out RNA extraction of bee virus: RNA extraction of bee virus, the steps are briefly described as follows: 1-80 ℃ take samples. 2. Take the organization. 3. Grind in ceramic mortar in liquid nitrogen. When the tissue is powdered, transfer to a pre-weighed 5ml plastic centrifuge tube. The centrifuge tube needs DEPC water treatment and sterilization. Weigh and get 100mg of tissue. 4. Add TRIZOL 1.5ml. 5. Incubate at room temperature for 5 minutes. 6. Add 0.3ml of chloroform, cover tightly and shake for 15s. 7. Room temperature 2-3min. 8.4℃, 12000g for 15min. 9. Take about 0.8ml of the supernatant and transfer it to a 1.5ml centrifuge tube. The treatment of the tube is the same as above. Remove the supernatant's lower and middle liquid for DNA and protein extraction. 10. Add 0.7ml of isopropanol, mix well, and room temperature Next 10min. 11.4℃, 10000g for 10min. 12. Discard the supernatant, add 1.4ml of 75% ethanol (prepared with DEPC treated sterilized water), mix well at 13.4°C, 7000g 5min 14. Discard the supernatant and dry at room temperature for 5min. 15. DEPC treatment sterilized pure water 100ml dissolved at 4 ℃. 12. primer: Refer to the primer sequence of Nai et al. 2017 to design primers. 13.CBPV-F(5_-AGTTGTCATGGTTAACAGGATACGAG-3_)CBPV-R(5_-TCTAATCTTAGCACGAAAGCCGAG-3_) RT-PCR conditions: 95(30sec)==>55(30sec)==>72(1mim)35cycle, finally, then Place at 72°C for 10 min. 14. RT-PCR products are sequenced to determine what serotype the virus is. The results are shown in Table 1.

(3) Example 1 The main steps of feeding nutrient solution to the bee colony: 1. Spleen extraction first, the bee colony that is not long at the time of onset and still has a large number of spleen closures until the spleen is out of the baffle plate is Standard, the less spleen left, the faster the cure, the faster the colony develops. 2. For a colony that does not heal for a long time or is prone to recurrence, it is necessary to change the king for this hypersensitive colony. 3. After dissolving 2 kg of white sugar water, cool and mix in 1 kg of nutrient liquid, each time 25 ml per spleen, pour directly on the frame beam from the front, or you can use a feeder. Once every two days, feed three times for a total of 6 days. Example 1 The invention was developed by a team of experts from Xukang Biotechnology Co., Ltd., and was tested by a bee farm in a deep pit. The test situation is as follows: The test process: using the medium capsule nutrient solution prepared by the invention to feed 10 groups of bees and a total of 45 spleens as the test group, As a control group, a total of 40 spleens of 10 groups of bees without feeding the medium capsule nutrient solution were used as a control group. The experiment was conducted in the autumn of 2017 and the spring of 201 in two consecutive years. The method of quantitatively giving 5 consecutive times every 2 days was used to determine that the bee had eaten. The test method and control of the control group were the same as the test group. The appearance health status of bees and 2-3 day old larvae colonies, the change of virus content (with or without) and the emergence rate, etc. reflect the growth performance and health status of the colony. Figure 1(A)-(D) The appearance of the colony is healthy. Figure 1(A) is the change of the colony after the first (March 10) feeding of the mid-capsule nutrient solution; Figure 1(B) is the second ( (March 13) Changes in the bee colony after feeding the mid-capsule nutrient solution; Figure 1(C) third time (March 16) after feeding the mid-capsule nutrient solution; Figure 1(D) fourth time ( March 19) Change of bee colonies after feeding the mid-capsule nutrient solution; results and analysis: According to statistics, after feeding the mid-capsule nutrient solution with 10 groups of 45 spleens in the experimental group, the group potential reached 50 spleens, and the control group had 10 groups with 40 spleen groups. There were 33 spleens left. At the beginning of the test, 6 of the 45 spleens in the test group had cystic disease, and 8 of the 40 spleens in the control group had cystic disease. After 5 consecutive treatments, no spleens were found in the 45 spleens of the test group. In the case of cystic disease, 3 of the 40 spleens in the control group still had cystic disease, and another 7 spleens were discarded because of serious illness. The test group marked 1,000 bee eggs, and eventually 931 bees emerged, with an emergence rate of 93.1%. The control group marked 1,000 bee eggs, and finally successfully emerged 672 bees, with an emergence rate of 67.2%. The safety of the medium capsule nutrition solution is obviously higher than that of the western medicine-based veterinary drugs, and there is no possibility that drug resistance will occur. There should be an opportunity for the infected bees to rejuvenate smoothly and eat, and increase the purpose of the group.

Confirmation of the pathogen of European larval disease:

1) During the bee breeding and production season, small day-old larvae in the bee colony were found to have lesions. The main symptoms were yellowish color and tarnish of the diseased larvae, and rot in severe cases, but the rotten larvae did not have an unpleasant sour odor, disease Insects usually die at 4 to 5 days of age, the symptoms of adult bees crawling in severely ill swarms, and the swarm declines rapidly.

2) Pick three samples with typical symptoms, put them into 1.5mL sterilized centrifuge tubes, disinfect the surface with 75% alcohol, rinse three times with sterile water, cut the larval epidermis under sterile conditions and mash it; take homogenate in EFB medium (containing 10g of yeast extract per liter, 10g of glucose, 10g of soluble starch, 10g dry powder of bovine heart extract, 13.6g of dibasic potassium phosphate, 10g of agar, pH 6.6) on the plate; 37'C culture 24h, colonies The diameter is about 1mm, pearl white, translucent water drop-like, neat edges, smooth surface. Observed under light microscope and electron microscope, the bacterial cells are oval, arranged in short chains or scattered in pairs, without flagella, and Gram stain positive. Bacterial DNA is extracted using conventional phenol method (see "Molecular Cloning Experiment Guide" (Third Edition) Beijing: Science Press, 2003, pp. 27-30). PrimerA (5-AAGATTTGATC (CA) TGGCTCAG-3) and PrimerB (5, -TACGGCTCTACCTTGTTACGACTT-3) were used as primers for amplification. PCR amplification conditions: 94°C 3min; 94°C 1min, 53°C 1min, 72°C 1min, 30 cycles; 72'C 10min. The cloning of PCR amplified products refers to the DNA molecular cloning method introduced by Li Yongming, Zhao Yuqi, etc. in "Practical Molecular Biology Method Manual", Beijing: Science Press, 2000, pp. 46-48). After cloning and sequencing, the sequencing results The BLAST software was compared with the database in GenBank (httD: //nCbi.nih.g0V/BLAST) analysis to determine that the pathogen of the bee colony was Enterococcus faecium. Example 2: Unilateral Chinese herbal medicine preparation to inhibit bee larvae rot disease Enterococcus faecium test 5 kinds of unilateral Chinese herbal medicine powder purchased from Hong Kong Pandan Co., Ltd. Unilateral Chinese herbal medicine liquid preparation: according to the ratio of 1 gram of Chinese herbal medicine powder plus 9 mL of sterile water The concentration of the drug solution is 10%, and the control experiment group is a comprehensive nutrient solution. The formula of the comprehensive nutrient solution is 1ml of honeysuckle extract per 100ml of sterile water, 1ml of angelica extract, 1ml of Huangqi extract, and wolfberry extract. 0.5ml, red jujube extract 0.5ml, garlic extract powder 1g, royal jelly 6g, comprehensive vitamin 6g, IgY yolk body immunoglobulin 12g, the preparation method of the above-mentioned Chinese herbal medicine preparation is: take the above components in proportion, combine all the above The extract and the powder are put into sterile water together, stirred and fully dissolved into a nutrient solution method: take Xinhua No. 1 qualitative filter paper, and punch into a small circular paper sheet with a diameter of 6mm using a punching machine. Take 10 round paper sheets into a clean and dry 2mL centrifuge tube. After autoclaving at 121°C for 30 minutes, put it in an oven to dry it completely. Add 0.5 mL of drug solution to the above 2 mL centrifuge tube containing 10 pieces of paper, and flip the pieces of paper to make each piece of paper fully saturated with the drug solution. When turning the pieces of paper, the pieces of paper cannot be smashed. At the same time, record the name and concentration of the drug on the centrifuge tube, and dry in a 37°C incubator. Preparation of bacterial solution: Enterococcus faecium strains isolated and preserved from samples of diseased larvae. Bacteria were cultured in EFB liquid medium at 37°C overnight, so that the growth turbidity reached 1.25X109/mL; when used, the bacterial solution was diluted 1000 times with sterilized EFB liquid medium to make the bacterial concentration reach 1.25X10VmL, and set aside. Determination of the size of the zone of inhibition: 50uL of the prepared bacterial solution was added to the EFB plate and smeared evenly. Use sterilized forceps to carefully attach the drug-sensitive tablets to the EFB plate coated with bacterial solution. After incubating at 37°C for 24 hours, measure and record the size of the zone of inhibition. Make 3 repetitions of each drug-sensitive tablet. Results: The bacteriostatic effects of the five kinds of Chinese herbal medicines and comprehensive nutrient solutions tested are shown in Table 2. It can be seen from Table 2 that the antibacterial effect of honeysuckle and garlic powder is obvious. The antibacterial circles of Angelica, Huangqi, Lycium barbarum, and red dates are all below 10mm, and the inhibitory effect is weak. The antibacterial effect of the comprehensive nutrient solution is the most significant. The test results are shown in Table 3.

Table 3 Results of bacteriostatic ring analysis

The content of the present invention is to provide an extract and globulin mixed nutrient solution for preventing and treating mesocystic virus and European larvae disease. One of the objects of the present invention is to provide a medicinal composition against mesocystic disease and European larvae disease, especially regarding A pharmaceutical composition of protein against midcystic disease and European larval disease. It contains an effective amount of active ingredient and a pharmaceutically acceptable carrier. The active ingredient is at least one selected from the group consisting of compounds of formula (I).

* IgY蛋黃體免疫球蛋白圖式為式(1)

* IgY yolk body immunoglobulin scheme is formula (1)

The compound of formula (I) is IgY yolk body immunoglobulin. Like chickens and mammals, in order to fight against externally invaded antigens, antibodies that specifically bind to the antigens will also be produced in the blood. Different antibodies can be transferred to the mature yolk, and because of these antibody transfer mechanisms, the chicks obtain antibodies from the mother to survive the difficulty of the immune system that is not enough to resist the invasion of the disease. In biotechnology, in order to obtain the antibody of a specific antigen, the specific antigen can be injected into the animal body (such as a rabbit), after the rabbit's blood produces an antibody that specifically binds to the specific antigen, and then blood can be purified to obtain This specific antibody. In addition, if the antigen is injected into the body of a mature hen, the specific antibodies produced by the hen's blood can also be transferred to the egg yolk produced. Because the main antibody in yolk has the same function as the mammalian IgG, it is named after IgY only because it comes from yolk (YolK). Due to the easy breeding of chickens, the stable egg production of hens, and the high IgY antibody content in the eggs, the establishment of a large amount of specific antibody technology against specific antigens has been established, so that the limited use of immune proteins can be widely used so far. The preparation of IgY immune protein antibodies for general special purposes must be carried out on a strictly quality-controlled and well-equipped breeding farm. The refined target antigen is first injected into the hen to produce antibodies, and the eggs produced by the hen contain specific antibodies. After being sterilized by high temperature instantaneously, the egg yolk can be made into egg yolk powder, and finally refined into IgY immune yolk body. Studies have shown that IgY antibodies can effectively inhibit H. pylori and prevent rotavirus-induced diarrhea (Rotaviral Diarrhea). Rotavirus (Rotavirus) is the most important pathogenic cause of infectious gastroenteritis in infants, and is currently the cause of severe diarrhea in infants and young children. The main reason is that in developing countries, about 2,000 newborns die every day, and no effective vaccine has been developed yet. The prevention of rotavirus infections by the administration of oral active antibodies (passive immunotherapy) may be a promising application of anti-rotavirus antibodies. Many researchers have demonstrated that oral anti-rotavirus IgG or IgY Can effectively control diarrhea caused by rotavirus infection.

The nutrient solution of the present invention can be used in veterinary and human medicine, and can be administered in any form and in any suitable manner. For example, but not limited to this, the pharmaceutical composition can be administered by oral, subcutaneous, spray, intravenous, or intra-articular injection. Depending on the form of use and use, a pharmaceutically acceptable carrier may be included in the pharmaceutical composition of the present invention.

Taking the preparation of a pharmaceutical form suitable for oral administration as an example, the nutrient solution of the present invention may contain a pharmaceutically acceptable carrier that does not adversely affect the activity of IgY yolk body immunoglobulin, such as a solvent, an oily solvent, a diluent, and a stabilizer , Absorption delay agent, disintegrant, emulsifier, antioxidant, binder, lubricant, hygroscopic agent, etc. Any suitable method can be used to prepare the composition in a form suitable for oral administration, such as tablets, capsules, granules, powders, flow extracts, solutions, syrups, suspensions, emulsions, and Tincture and so on.

As for the pharmaceutical form suitable for subcutaneous, intravenous or intra-articular injection, the nutrient solution of the present invention may contain one or more such as isotonic solution, salt buffer solution (such as phosphate buffer or malate buffer), Ingredients such as solvents, emulsifiers, and other carriers to prepare, for example, intravenous infusion, emulsion intravenous infusion, dry powder injection, suspension injection, or dry powder suspension injection.

The nutrient solution of the present invention may contain additives such as flavoring agents, coloring agents, coloring agents, etc. as needed to improve the mouthfeel and visual perception of the obtained medicament; in addition, a reasonable amount of preservatives, preservatives, antibacterial agents, anti-bacterial agents, etc. may be added Fungi, etc., to improve the storage of the resulting medicament.

If necessary, one or more other active ingredients may be included in the nutrient solution of the present invention to further enhance the efficacy of the pharmaceutical composition of the present invention or increase the flexibility and formulation of the formulation. For example, the pharmaceutical composition of the present invention may contain one or more of the following active ingredients: vitamins, whey protein, muscle relaxants, non-steroidal anti-inflammatory drugs, and other active ingredients, as long as the other active ingredients There is no adverse effect on the benefits.

The present invention also provides the use of the compound of the above formula (I), wherein the agent is used for the prevention and treatment of mesosporium virus and European larval disease. In particular, the agent can be used to inhibit the activity of mesocystic virus and the performance of bacteria. In addition, the nutrient solution can be administered once a day, multiple times a day, or once a few days, depending on the needs of the target.

The present invention is further illustrated by the following specific implementation examples. These embodiments are only provided as illustrations, not to limit the scope of the present invention.

[Example] [Example 1] Establishment of mesocystic virus serotype

[Example 2] Results of comprehensive nutrient solution treatment of mid-cystic bee colony

[Example 3] Analysis of the bacteriostatic ring of comprehensive nutritional solution for Enterococcus faecium

* IgY蛋黃體免疫球蛋白圖式為式(1)

* IgY yolk body immunoglobulin scheme is formula (1)

Claims (6)

The content of the present invention is to provide an extract and globulin mixed nutrient solution for preventing and treating mesocystic virus and European larvae disease. One of the objects of the present invention is to provide a medicinal composition against mesocystic disease and European larvae disease, especially regarding A pharmaceutical composition of protein against midcystic disease and European larval disease. It contains an effective amount of active ingredient and a pharmaceutically acceptable carrier. The active ingredient is at least one selected from the group consisting of compounds of formula (I).

* The IgY yolk body immunoglobulin scheme is formula (1) 1. The nutrient solution of claim 1, which is used to control the weakening of bee colonies caused by mesangial disease or European larval disease. The nutrient solution according to claim 1 is used to inhibit the activity of Enterococcus faecium. The nutrient solution according to any one of claims 1 to 3, wherein the active ingredient is a compound of formula (I). The use according to claim 5, wherein the amount of the nutrient solution, based on the compound of formula (I), is about 800 to 2400 mg/kg body weight per day. For use according to claim 5, the amount of the nutrient solution is about 2.4 to 7.2 g/kg body weight per day. The use according to claim 5, wherein the nutrient solution is used to reduce the content of mesocystic virus.