A pharmaceutical composition for preventing and treating avian viral respiratory disease in poultry and a preparation method thereof

Abstract

The present application belongs to the technical field of veterinary medicine, and provides a poultry medicine composition for preventing and treating avian viral respiratory disease and a preparation method thereof. The poultry medicine composition for preventing and treating avian viral respiratory disease is composed of a Qingjie mixture and doxycycline hydrochloride. The present application produces a synergistic effect between components through the combined application of traditional Chinese medicine and western medicine, enhances the drug efficacy, and has a remarkable effect in treating avian viral respiratory disease.

Description

Technical Field

[0001] This invention belongs to the field of veterinary drug technology and relates to a pharmaceutical composition for the prevention and treatment of avian viral respiratory diseases and its preparation method. Background Technology

[0002] In poultry farming, key viral respiratory diseases requiring prevention and control include Newcastle disease, infectious bronchitis, infectious laryngotracheitis, avian metapneumovirus disease, and avian influenza. Even low-virulence pathogens of these diseases can cause local outbreaks. Highly virulent pathogens are more likely to trigger sudden outbreaks. The effectiveness of controlling viral respiratory diseases in poultry is influenced by multiple factors; therefore, a comprehensive consideration of the interactions between genetics, nutrition, management, and infectious diseases is necessary for better disease control.

[0003] The pathogens of avian viral respiratory diseases lurk in many chickens and can be triggered by external environmental stimuli, with broilers having the highest incidence rate. The main symptoms include coughing, wheezing, runny nose, difficulty breathing, decreased appetite, and even facial swelling. Prevention and treatment methods include injections of targeted drugs such as cyproconazole, with careful dosage control. Additionally, feeding poultry with traditional Chinese medicines such as Platycodon grandiflorus and Magnolia biondii can also be helpful.

[0004] Newcastle disease (ND) in chickens is an acute and highly contagious disease caused by the Newcastle disease virus. Symptoms include difficulty breathing, torticollis, green droppings, and hemorrhage in the proventricular papillae and intestinal mucosa. Currently, there are no specific drugs for the prevention and treatment of ND; prevention primarily relies on Newcastle disease vaccination. However, in recent years, due to factors such as vaccine quality, inappropriate immunization programs, viral mutations, and immunosuppressive diseases, immunization failure is common.

[0005] Avian influenza virus is a highly contagious pathogen that can cause severe respiratory diseases in poultry and wild birds. Traditional Chinese medicine (TCM) has significant value and broad application prospects in the prevention and treatment of avian influenza. Whether single herbs or compound formulas, TCM can exert multiple effects, including antiviral, anti-inflammatory, and immunomodulatory properties, thus effectively combating the avian influenza virus. The research and application of TCM not only help reduce the incidence of avian influenza but also improve the economic benefits of poultry farming. Summary of the Invention

[0006] To overcome the shortcomings of existing technologies, this invention provides a novel, rationally formulated, and safe pharmaceutical composition for the prevention and treatment of avian viral respiratory diseases.

[0007] The present invention also provides the pharmaceutical use of the above-mentioned 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] This invention provides a pharmaceutical composition for preventing and treating avian viral respiratory diseases, the pharmaceutical composition for preventing and treating avian viral respiratory diseases is composed of a clearing and detoxifying agent and doxycycline hydrochloride, wherein the mass ratio of the clearing and detoxifying agent and doxycycline hydrochloride is 12-18:1.

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

[0011] The clearing and detoxifying compound of the present invention is made from 670g of gypsum, 140g of honeysuckle, 100g of scrophularia, 80g of scutellaria, 80g of rehmannia, 70g of forsythia, 70g of gardenia, 60g of gentian, 60g of violet, 60g of isatis root, 60g of anemarrhena, and 60g of ophiopogon.

[0012] The preparation method of Qingjie Mixture is as follows: 12 ingredients, except for honeysuckle and scutellaria, the other 10 ingredients are soaked in water for 1 hour, then decocted twice. The first decoction is for 1 hour, and honeysuckle and scutellaria are added after half an hour of decoction. The second decoction is for 40 minutes. Filter, combine the filtrates, concentrate the filtrate to a relative density of about 1.17 at 90℃, add ethanol to make the alcohol content reach 65%-70%, refrigerate and stand for 48 hours, filter, recover the ethanol from the filtrate, add water to 1000mL, fill, sterilize, and the product is obtained.

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

[0014] The pharmaceutical composition described in this 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, pellets, suppositories, aerosols, sprays, powder mists, patches, ointments, or creams.

[0016] The present invention also provides the use of the pharmaceutical composition for preventing and treating avian viral respiratory diseases in the preparation of a drug for treating avian viral respiratory diseases.

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

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

[0019] The Qingjie compound is composed of gypsum, honeysuckle, scrophularia, scutellaria, rehmannia, forsythia, gardenia, gentian, violet, isatis root, anemarrhena, and ophiopogon. It has good effects in clearing heat and detoxifying, cooling blood and removing blood stasis, reducing fever and relieving pain. It is mainly used to treat various heat-toxin syndromes caused by Escherichia coli, especially infectious diseases accompanied by high fever, loss of appetite, lethargy, and even death.

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

[0021] The inventors unexpectedly discovered that the combined use of the two drugs had a significant synergistic effect in treating avian viral respiratory diseases.

[0022] Compared with the prior art, the beneficial effects of the present invention are:

[0023] Animal experiments have shown that the pharmaceutical composition of the present invention has a significant therapeutic effect on Newcastle disease in chickens and a significant therapeutic effect on avian influenza.

[0024] This invention achieves synergistic effects among its components through the combined application of traditional Chinese and Western medicine, reducing the side effects of Western medicine alone and improving the problem of unstable efficacy of traditional Chinese medicine alone. Attached Figure Description

[0025] Figure 1 The number of deaths in each group after treatment for Newcastle disease infection in chickens.

[0026] Figure 2 The number of deaths in each group after treatment with avian influenza virus. Detailed Implementation

[0027] The following detailed description of specific embodiments further illustrates the content of the present invention, but it should not be construed as limiting the scope of the above-mentioned subject matter of the present invention to the following embodiments. The following embodiments are used to illustrate the technical solutions of the present invention and not to limit the scope of protection of the present invention. Modifications or equivalent substitutions made by those skilled in the art to the technical solutions of the present invention without departing from the essence and scope of the technical solutions of the present invention shall still fall within the scope of protection of the present invention.

[0028] Experimental Example 1: Study on the effect of the pharmaceutical composition of the present invention on Newcastle disease infection in chickens

[0029] 1. Materials and Methods

[0030] Two hundred 25-day-old Sanhuang chickens were randomly divided into 5 groups of 40 each. Forty chickens were randomly selected as the blank control group, receiving no viral load or medication. The remaining chickens were randomly divided into a viral load control group, a combined treatment group, a detoxifying and neutralizing agent group, and a doxycycline hydrochloride group. Except for the blank control group, the chickens in the combined treatment group, the detoxifying and neutralizing agent group, and the doxycycline hydrochloride group were challenged with viral load and administered orally once daily for 10 days. The viral load challenge control group received viral load but no medication.

[0031] Before challenge, blood was collected from 20 randomly selected chickens, and Newcastle disease HI antibody was measured using ELISA. The results were negative. The challenge dose was based on the TCID50 (median cellular infectious dose). 50 10 -4.6 ) and clinical trial results 10 5 Dilute and administer the Newcastle disease virus strain intramuscularly.

[0032] Qingjie Mixture Group: Mix 3.0g of Qingjie Mixture with 1L of water daily, drink freely.

[0033] Doxycycline hydrochloride group: 0.25g of doxycycline hydrochloride per 1L of water daily, mix well, and drink freely.

[0034] Combined use group: 1.5g of Qingjie Mixture + 0.125g of Doxycycline Hydrochloride per 1L of water daily, mix well and drink freely.

[0035] 2. Drug efficacy evaluation

[0036] Onset of disease: During the trial period, individuals with obvious clinical symptoms of Newcastle disease or whose autopsies revealed characteristic lesions of Newcastle disease were defined as having developed the disease.

[0037] Death: Those who died during the trial, exhibiting obvious clinical symptoms of Newcastle disease or whose autopsies revealed Newcastle disease-characteristic lesions, were considered to have died from infection.

[0038] Incidence rate = Number of cases / Number of chickens in the experimental group 100%.

[0039] Mortality rate = Number of deaths / Number of chickens in the experimental group 100%.

[0040] Cure rate = Number of surviving sick chickens / Total number of sick chickens in the group 100%.

[0041] 3. Experimental Results

[0042] Table 1. Cure rate and mortality rate for each group

[0043]

[0044] 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, reducing mortality and increasing cure rate. The combined treatment group showed significantly better therapeutic effects than the Qingjie compound group and the doxycycline hydrochloride group, and the combined use of Qingjie compound and doxycycline hydrochloride achieved a synergistic effect in the treatment of Newcastle disease infection in chickens.

[0045] Experimental Example 2: Study on the effect of the pharmaceutical composition of the present invention on H9N2 subtype avian influenza virus

[0046] 1. Materials and Methods

[0047] One hundred and fifty 30-day-old Sanhuang chickens were randomly divided into five groups of 30 each. Thirty chickens were randomly selected as the blank control group, which was not challenged with the virus or given any medication. The remaining chickens were randomly divided into the challenge control group, the combined treatment group, the clearing and detoxifying mixture group, and the doxycycline hydrochloride group.

[0048] Except for the blank control group, the meat of the remaining chickens was injected with 10 mg of avian influenza H9N2 virus. -4 0.2 mL / bird was administered orally to chickens in each experimental group 12 hours after virus inoculation, once daily for 14 days. The challenge control group was challenged with the virus but not given any medication.

[0049] Qingjie Mixture Group: Mix 3.0g of Qingjie Mixture with 1L of water daily, drink freely.

[0050] Doxycycline hydrochloride group: 0.25g of doxycycline hydrochloride per 1L of water daily, mix well, and drink freely.

[0051] Combined use group: 1.5g of Qingjie Mixture + 0.125g of Doxycycline Hydrochloride per 1L of water daily, mix well and drink freely.

[0052] 2. Drug efficacy evaluation

[0053] After 14 days, the incidence and mortality of chickens in each group were observed.

[0054] If any chickens die, they will be necropsyd, and the pathological material will be collected for virus isolation and identification; the effectiveness of each group of drugs in preventing and controlling avian influenza will be statistically analyzed.

[0055] 3. Experimental Results

[0056] H9N2 avian influenza virus was isolated from the pathogen, confirming that the chickens died from avian influenza infection.

[0057] from Figure 2 As shown in Table 2, all drug administration groups have a certain protective effect against artificially infected chickens with avian influenza. The survival rate of the combined treatment group is better than that of the Qingjie compound group and the doxycycline hydrochloride group. The combined use of Qingjie compound and doxycycline hydrochloride has a synergistic effect in the treatment of avian influenza in chickens.

[0058] Table 2 Cure rate and mortality rate for each group

[0059]

[0060] The above description of the disclosed embodiments enables those skilled in the art to make or use the invention. Various modifications to these embodiments will be readily apparent to those 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 invention. Therefore, the invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.

Claims

1. A pharmaceutical composition for preventing and treating new castle disease and avian influenza of chicken, characterized in that, The drug composition for preventing and treating Newcastle disease and avian influenza in chickens consists of a clearing and detoxifying agent and doxycycline hydrochloride, wherein the mass ratio of the clearing and detoxifying agent to doxycycline hydrochloride is 12-18:1; the clearing and detoxifying agent is made from 670g of gypsum, 140g of honeysuckle, 100g of scrophularia, 80g of scutellaria, 80g of rehmannia, 70g of forsythia, 70g of gardenia, 60g of gentian, 60g of violet, 60g of isatis root, 60g of anemarrhena, and 60g of ophiopogon. ​ 2. The pharmaceutical composition of claim 1, wherein, The mass ratio of the purging agent to doxycycline hydrochloride is 15:

1.

3. The pharmaceutical composition of claim 1, wherein, The preparation method of the above 12 ingredients, except for honeysuckle and scutellaria, is as follows: soak the remaining 10 ingredients in water for 1 hour, then decoct twice. The first decoction is for 1 hour, and honeysuckle and scutellaria are added after half an hour of decoction. The second decoction is for 40 minutes. Filter, combine the filtrates, concentrate the filtrate to a relative density of 1.17 at 90℃, add ethanol to make the alcohol content reach 65%-70%, refrigerate and stand for 48 hours, filter, recover the ethanol from the filtrate, add water to 1000mL, fill and sterilize to obtain the product.

4. The pharmaceutical composition according to any one of claims 1 or 2, characterized in that, The pharmaceutical composition also includes pharmaceutically acceptable excipients.

5. The pharmaceutical composition according to claim 4, characterized in that, The pharmaceutical composition is a single compound preparation or a combination of two separate single preparations.

6. The pharmaceutical composition according to claim 5, characterized in that, The dosage forms of the single compound preparation or the combination of two separate single preparations include solutions, tablets, capsules, granules, films, gels, powders, emulsions, suspensions, pellets, suppositories, aerosols, sprays, powders, patches, ointments, or creams.

7. Use of the pharmaceutical composition according to claim 1 or 2 in the preparation of a drug for treating Newcastle disease in chickens.

8. Use of the pharmaceutical composition according to claim 1 or 2 in the preparation of a medicament for treating avian influenza.

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