Pharmaceutical composition for preventing and treating viral respiratory diseases of poultry and preparation method of pharmaceutical composition

Abstract

The invention belongs to the technical field of veterinary drugs, and provides a pharmaceutical composition for preventing and treating viral respiratory diseases of poultry and a preparation method thereof, and the pharmaceutical composition for preventing and treating viral respiratory diseases of poultry is composed of a cleaning and dissolving agent and doxycycline hydrochloride. Through combined application of Chinese and western medicines, all the components have a synergistic effect, the drug effect is enhanced, and the traditional Chinese medicine composition has a remarkable effect on treatment of avian viral respiratory diseases.

Description

Technical Field

[0001] The invention belongs to the technical field of veterinary drugs and relates to a pharmaceutical composition for preventing and treating avian viral respiratory diseases for poultry and a preparation method thereof. Background Art

[0002] Viral respiratory diseases that need to be focused on in the poultry industry include Newcastle disease, infectious bronchitis, infectious laryngotracheitis, avian metapneumovirus, and avian influenza. Even if the pathogens of these diseases are of low virulence, they may cause local epidemics. Pathogens with stronger virulence are prone to sudden outbreaks of diseases. The prevention and control of poultry viral respiratory diseases is affected by many factors. Therefore, it is necessary to comprehensively consider the interaction between genetics, nutrition, management and infectious diseases to better prevent and control such diseases.

[0003] The pathogens of poultry viral respiratory diseases are hidden in many chickens. When stimulated by the external environment, they will cause the disease. Among them, broilers have the highest incidence rate. The main symptoms are: coughing, runny nose, difficulty breathing, loss of appetite, and even facial swelling. The prevention and treatment methods include injecting targeted drugs such as levomycin and controlling the dosage. In addition, poultry can also be fed with Chinese medicines such as Platycodon grandiflorum and Magnolia grandiflora.

[0004] Newcastle disease is an acute and severe infectious disease caused by Newcastle disease virus. Its symptoms include dyspnea, twisted neck, green stool, bleeding of glandular stomach papilla and intestinal mucosa, etc. At present, there is no specific drug for the prevention and treatment of Newcastle disease in chickens. The prevention mainly relies on the use of Newcastle disease vaccine. However, in recent years, due to various factors such as vaccine quality and unreasonable immunization procedures, virus mutation and immunosuppressive diseases, immunization failure often occurs.

[0005] Avian influenza virus is a highly contagious pathogen that can cause severe respiratory diseases in poultry and wild birds. Traditional Chinese medicine has important value and broad application prospects in the prevention and treatment of avian influenza. Whether it is a single herb or a compound medicine, they can play multiple roles such as antiviral, anti-inflammatory, and immunomodulatory, thereby effectively fighting against avian influenza virus. The research and application of traditional Chinese medicine not only helps to reduce the incidence of avian influenza, but also improve the economic benefits of poultry farming. Summary of the invention

[0006] In order to make up for the deficiencies of the prior art, the present invention provides a new pharmaceutical composition for preventing and treating avian viral respiratory diseases with a reasonable formula and safe use.

[0007] The present invention also provides medical use of the pharmaceutical composition for preventing and treating avian viral respiratory diseases.

[0008] Specifically, the technical problem to be solved by the present invention is achieved through the following technical solutions.

[0009] The invention provides a pharmaceutical composition for preventing and treating avian viral respiratory diseases. The pharmaceutical composition for preventing and treating avian viral respiratory diseases consists of a qingjie mixture and doxycycline hydrochloride, wherein the mass ratio of the qingjie mixture to the doxycycline hydrochloride is 12-18:1.

[0010] Preferably, the mass ratio of the Qingjie mixture to doxycycline hydrochloride is 15:1.

[0011] The Qingjie mixture of the present invention is prepared from 670g of gypsum, 140g of honeysuckle, 100g of Scrophularia, 80g of Scutellaria, 80g of Rehmannia root, 70g of Forsythia, 70g of Gardenia, 60g of Gentiana, 60g of Sweet Buddleijas, 60g of Isatis, 60g of Anemarrhena, and 60g of Ophiopogon.

[0012] The preparation method of Qingjie mixture is as follows: the above 12 ingredients, except honeysuckle and scutellaria, are soaked in warm water for 1 hour, and then decocted twice, the first time for 1 hour, and honeysuckle and scutellaria are added after decocting for half an hour; the second time is decocted for 40 minutes, filtered, and the filtrate is combined. The filtrate is concentrated to a relative density of about 1.17 at 90°C, and ethanol is added to make the alcohol content reach 65%-70%. The mixture is refrigerated and allowed to stand for 48 hours, filtered, ethanol is recovered from the filtrate, water is added to 1000mL, filled, and sterilized.

[0013] The pharmaceutical composition of the present invention also includes pharmaceutically acceptable excipients; the pharmaceutically acceptable excipients are selected from one or more of diluents, excipients, fillers, binders, wetting agents, disintegrants, emulsifiers, cosolvents, solubilizers, osmotic pressure regulators, lubricants, surfactants, coating materials, colorants, pH regulators, antioxidants or antibacterial agents.

[0014] The pharmaceutical composition of the present invention is a single compound preparation or a combination of two separate single preparations.

[0015] Preferably, the dosage form of the single compound preparation or the combination of two separate single preparations includes solutions, drops, tablets, capsules, granules, films, gels, powders, emulsions, suspensions, pills, suppositories, aerosols, sprays, powder mists, patches, ointments or creams.

[0016] The present invention also provides application of the pharmaceutical composition for preventing and treating avian viral respiratory diseases in preparing drugs for treating avian viral respiratory diseases.

[0017] The present invention also provides application of the pharmaceutical composition for preventing and treating avian viral respiratory diseases in preparing drugs for treating Newcastle disease.

[0018] The present invention also provides application of the pharmaceutical composition for preventing and treating avian viral respiratory diseases in preparing drugs for treating avian influenza.

[0019] Qingjie mixture is composed of gypsum, honeysuckle, Scrophularia, Scutellaria, Rehmannia, Forsythia, Gardenia, Gentiana, Sweet Peony, Isatis, Anemarrhena, and Ophiopogon. It has good effects of clearing heat and detoxifying, cooling blood and removing blood stasis, reducing fever and relieving pain. It is mainly used to treat various heat toxic diseases caused by Escherichia coli, especially infectious diseases accompanied by high fever, loss of appetite, mental depression, and even death.

[0020] Doxycycline hydrochloride belongs to the tetracycline antibiotics and is a broad-spectrum antibacterial agent. It shows strong antibacterial effects against both Gram-positive cocci and Gram-negative bacilli. It is also sensitive to Rickettsia, Mycoplasma, Chlamydia, atypical mycobacteria, and spirochetes.

[0021] The inventors unexpectedly discovered that when the above two drugs are used in combination, they have a significant synergistic effect in treating avian viral respiratory diseases.

[0022] Compared with the prior art, the present invention has the following beneficial effects: Animal experiments show that the pharmaceutical composition of the present invention has a significant therapeutic effect on Newcastle disease in chickens and has a significant therapeutic effect on avian influenza.

[0023] The invention uses Chinese and Western medicines in combination to produce synergistic effects among the components, thereby reducing the side effects of Western medicine alone and improving the problem of unstable efficacy of Chinese medicine alone. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] Figure 1 It is the number of deaths in each group after Newcastle disease infection and treatment.

[0025] Figure 2 is the number of deaths in each group after avian influenza virus treatment. DETAILED DESCRIPTION

[0026] The content of the present invention is further described in detail below through specific implementation methods, but this should not be understood as the scope of the above subject matter of the present invention is limited to the following examples. The following examples are used to illustrate the technical solution of the present invention rather than to limit the scope of protection of the present invention. If a person of ordinary skill in the art modifies or replaces the technical solution of the present invention with an equivalent without departing from the essence and scope of the technical solution of the present invention, it still belongs to the scope of protection of the present invention.

[0027] Test Example 1 Study on the effect of the pharmaceutical composition of the present invention on Newcastle disease infection in chickens 1. Materials and Methods 200 25-day-old three-yellow chickens were randomly divided into 5 groups, 40 in each group. 40 chickens were randomly selected as the blank control group, which was not challenged with poison or given medication, and the remaining chickens were randomly divided into the challenge control group, the combination group, the Qingjie mixture group, and the doxycycline hydrochloride group. In addition to the blank control group, the chickens in the combination group, the Qingjie mixture group, and the doxycycline hydrochloride group were challenged with poison and orally administered once a day for a medication period of 10 days. The challenge control group was only challenged with poison and no medication was given.

[0028] Before the challenge, 20 chickens were randomly selected for blood sampling and the ELISA method was used to determine the Newcastle disease HI antibody in chickens. The result was negative. The challenge dose was based on the TCID 50 10 -4.6 ) and clinical pilot test results for 10 5 Dilute and inject Newcastle disease virus strain into the muscle.

[0029] Qingjie mixture group: daily, 3.0g of Qingjie mixture was mixed with 1L of water, and the patients were allowed to drink water freely.

[0030] Doxycycline hydrochloride group: 0.25 g of doxycycline hydrochloride was mixed with 1 L of water daily, and the patients were allowed to drink water freely.

[0031] Combined group: daily, add 1.5g Qingjie mixture + 0.125g doxycycline hydrochloride to 1L of water, mix well, and drink water freely.

[0032] 2. Efficacy evaluation Disease: During the trial period, patients with obvious clinical symptoms of Newcastle disease or with characteristic lesions of Newcastle disease in autopsy were considered to be onset; Death: Death during the trial with obvious clinical symptoms of Newcastle disease or characteristic lesions of Newcastle disease during autopsy was considered as infection death.

[0033] Incidence rate = number of cases / number of test chickens in the group 100%.

[0034] Mortality rate = number of deaths / number of test chickens in this group 100%.

[0035] Cure rate = number of sick chickens that have not died / total number of sick chickens in the group 100%.

[0036] 3. Experimental results Table 1 Cure rate and mortality rate of each group The results are as follows Figure 1As shown in Table 1, the pharmaceutical composition of the present invention has a significant therapeutic effect on Newcastle disease infection in chickens, reduces mortality, and improves cure rate. The therapeutic effect of the combined group is significantly better than that of the Qingjie mixture group and the doxycycline hydrochloride group. The combination of Qingjie mixture and doxycycline hydrochloride achieves a synergistic effect in treating Newcastle disease infection in chickens.

[0037] Test Example 2 Study on the effect of the pharmaceutical composition of the present invention on H9N2 subtype avian influenza virus 1. Materials and Methods 150 30-day-old three-yellow chickens were randomly divided into 5 groups, each with 30 chickens. 30 chickens were randomly selected as the blank control group without drug challenge and medication, and the remaining chickens were randomly divided into the drug challenge control group, the combined group, the Qingjie mixture group, and the doxycycline hydrochloride group.

[0038] Except for the blank control group, the chickens of the other groups were injected with avian influenza H9N2 virus for 10 -4 0.2mL / bird, and 12h after virus inoculation, the chickens in each experimental group were given oral administration, once a day, for 14 days. The challenge control group was only challenged with virus, without drug administration.

[0039] Qingjie mixture group: daily, 3.0g of Qingjie mixture was mixed with 1L of water, and the patients were allowed to drink water freely.

[0040] Doxycycline hydrochloride group: 0.25 g of doxycycline hydrochloride was mixed with 1 L of water daily, and the patients were allowed to drink water freely.

[0041] Combined group: daily, add 1.5g Qingjie mixture + 0.125g doxycycline hydrochloride to 1L of water, mix well, and drink water freely.

[0042] 2. Efficacy evaluation After 14 days, the incidence and mortality of chickens in each group were observed.

[0043] If any chicken dies, an autopsy will be performed and diseased samples will be collected for virus isolation and identification; the preventive and therapeutic effects of each group of drugs on avian influenza will be statistically analyzed.

[0044] 3. Experimental results The H9N2 avian influenza virus was isolated from the diseased materials, confirming that the chickens died from avian influenza infection.

[0045] from Figure 2 As shown in Table 2, each medication group had a certain protective effect on chickens artificially infected with avian influenza, and the survival rate of the combination group was better than that of the Qingjie mixture group and the doxycycline hydrochloride group. The combination of Qingjie mixture and doxycycline hydrochloride achieved a synergistic effect in the treatment of avian influenza in chickens.

[0046] Table 2 Cure rate and mortality rate of each group The above description of the disclosed embodiments enables one skilled in the art to implement or use the present invention. Various modifications to these embodiments will be apparent to one skilled in the art, and the general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the present invention. Therefore, the present invention will not be limited to the embodiments shown herein, but rather to the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A pharmaceutical composition for preventing and treating avian viral respiratory diseases, characterized in that: The pharmaceutical composition for preventing and treating avian viral respiratory diseases consists of Qingjie mixture and doxycycline hydrochloride, wherein the mass ratio of Qingjie mixture to doxycycline hydrochloride is 12-18:

1.

2. A pharmaceutical composition for preventing and treating avian viral respiratory diseases according to claim 1, characterized in that: The mass ratio of the Qingjie mixture to doxycycline hydrochloride is 15:

1.

3. A pharmaceutical composition for preventing and treating avian viral respiratory diseases according to any one of claims 1 or 2, characterized in that: The Qingjie mixture is prepared from 670g of gypsum, 140g of honeysuckle, 100g of Scrophularia, 80g of Scutellaria, 80g of Rehmannia root, 70g of Forsythia, 70g of Gardenia, 60g of Gentiana, 60g of Sweet Peony, 60g of Isatis, 60g of Anemarrhena, and 60g of Ophiopogon.

4. A pharmaceutical composition for preventing and treating avian viral respiratory diseases according to claim 3, characterized in that: The preparation method of the Qingjie mixture is as follows: the above 12 ingredients, except honeysuckle and scutellaria, are soaked in warm water for 1 hour, and then decocted twice, the first time for 1 hour, and honeysuckle and scutellaria are added after decocting for half an hour; the second time is decocted for 40 minutes, filtered, and the filtrate is combined, and the filtrate is concentrated to a relative density of about 1.17 at 90°C, ethanol is added to make the alcohol content reach 65%-70%, refrigerated and allowed to stand for 48 hours, filtered, ethanol is recovered from the filtrate, water is added to 1000mL, filled, sterilized, and the mixture is obtained.

5. A pharmaceutical composition for preventing and treating avian viral respiratory diseases according to any one of claims 1 or 2, characterized in that: The pharmaceutical composition also includes pharmaceutically acceptable excipients; the pharmaceutically acceptable excipients are selected from one or more of diluents, excipients, fillers, binders, wetting agents, disintegrants, emulsifiers, cosolvents, solubilizers, osmotic pressure regulators, lubricants, surfactants, coating materials, colorants, pH regulators, antioxidants or antibacterial agents.

6. A pharmaceutical composition for preventing and treating avian viral respiratory diseases according to claim 5, characterized in that: The pharmaceutical composition is a single compound preparation or a combination of two separate single preparations.

7. A pharmaceutical composition for preventing and treating avian viral respiratory diseases according to claim 6, characterized in that: The dosage form of the single compound preparation or the combination of two separate single preparations includes solutions, drops, tablets, capsules, granules, films, gels, powders, emulsions, suspensions, pills, suppositories, aerosols, sprays, powder mists, patches, ointments or creams.

8. Use of the pharmaceutical composition for preventing and treating avian viral respiratory diseases according to any one of claims 1 or 2 in the preparation of drugs for treating Newcastle disease.

9. Use of the pharmaceutical composition for preventing and treating avian viral respiratory diseases according to any one of claims 1 or 2 in the preparation of drugs for treating avian influenza.

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