A compound preparation for treating chicken infectious bronchitis, its preparation method and application

Abstract

This invention provides a compound preparation for treating infectious bronchitis in chickens, its preparation method, and its application. The compound preparation is made from the following components: ephedra, gypsum, licorice, phellodendron bark, fritillaria thunbergii, ginseng, hawthorn, poria cocos, tangerine peel, and dandelion. The product provided by this invention can treat infectious bronchitis in chickens with good therapeutic effect, is non-toxic, has few side effects, has high clinical safety for chicks, does not affect the growth performance of chickens, and has a high protection and cure rate for the prevention and treatment of infectious bronchitis in chickens, making it suitable for production use.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese veterinary medicine, and in particular to a compound preparation for treating infectious bronchitis in chickens, its preparation method, and its application. Background Technology

[0002] Infectious bronchitis (IBC) is an acute, highly contagious disease of chickens caused by the infectious bronchitis virus (IBV), a virus belonging to the Coronaviridae family and the Coronavirus genus. It primarily affects the respiratory, digestive, and urogenital systems, causing symptoms such as coughing, sneezing, tracheal rales, difficulty breathing, enteritis, and decreased egg production and quality. Chickens of all ages and sexes are susceptible, but it primarily affects chicks aged 1-4 weeks. Infection in young chicks often results in permanent oviduct degeneration, and mortality rates due to respiratory or kidney lesions can reach 40%-90%. Infection with IBC typically leads to decreased feed conversion ratios and increased mortality; the resulting decrease in production efficiency far outweighs the losses from mortality, severely impacting poultry farming.

[0003] Currently, infectious bronchitis in chickens is prevented and treated using the following two methods depending on whether the chicken is in the early or late stage of rearing.

[0004] Vaccination against infectious bronchitis in the early stages of raising chickens is the fundamental measure to prevent the disease. For chicks without maternal antibodies or with very low levels of maternal antibodies, infectious bronchitis vaccination should be carried out within 5 days of age.

[0005] When chickens contract infectious bronchitis (IBB) during the later stages of rearing, it is necessary to administer medication specifically for IBB. Currently available medications for preventing and treating IBB fall into two main categories: Western medicine and traditional Chinese medicine, in addition to vaccines. Commercially available Western medicines lack specific treatments and generally employ symptomatic therapy, such as using antiviral drugs like ribavirin, ciprofloxacin, penicillin, and streptomycin. While these can alleviate symptoms and reduce mortality, their efficacy is poor, and they carry the potential risks of drug resistance and residues. Other commercially available traditional Chinese veterinary drugs, while not having the drawbacks of Western medicines, have certain defects in their formulation and application methods. Inaccurate formulations may affect efficacy, or the application method often involves directly mixing traditional Chinese medicine powders with feed according to instructions, delaying the absorption of the active ingredients by the sick chickens, resulting in unsatisfactory prevention and treatment effects.

[0006] Currently, the most commonly used commercially available traditional Chinese medicine for treating infectious bronchitis in chickens is Baima Oral Liquid. The main ingredients of Baima Oral Liquid are ephedra, bitter almond, gypsum, licorice, and phellodendron bark. It has the functions of clearing heat and detoxifying, effectively relieving fever caused by respiratory diseases, and effectively protecting the body's natural protective ability; while effectively relieving respiratory symptoms (clearing the lungs, relieving asthma, and resolving phlegm), it assists the body in fighting pathogens and ensures the body's own immune function. Among them, the main component of bitter almond is amygdalin, which can be hydrolyzed into glucose, benzaldehyde, and highly toxic hydrocyanic acid under the action of enzymes and acids. Hydrocyanic acid is a potent toxin; long-term or excessive consumption of bitter almond may cause hypoxia, weakness, nausea, abdominal pain, diarrhea, vomiting, and confusion; in severe cases, it can even lead to death due to respiratory center paralysis. If chickens are fed large amounts of cypress-containing oral liquid containing bitter almonds due to improper handling by the breeder or prolonged treatment, it may cause rapid or difficult breathing, convulsions, weakness, coma, death, and weight loss, resulting in economic losses for chicken farmers.

[0007] Therefore, developing a traditional Chinese medicine compound preparation that does not use bitter almonds, can effectively treat infectious bronchitis in chickens, has a high cure rate, and has no obvious toxic side effects is of great clinical significance for infectious bronchitis in chickens. Summary of the Invention

[0008] Purpose of the invention: The purpose of this invention is to provide a compound traditional Chinese medicine preparation for the prevention and treatment of infectious bronchitis in chickens that does not contain bitter almonds, has a definite curative effect, a high cure rate, and no obvious toxic side effects, as well as its preparation method and application.

[0009] The technical solution of the present invention:

[0010] In one aspect, the present invention provides a compound preparation for treating infectious bronchitis in chickens, comprising the following components:

[0011] Ephedra, gypsum, licorice, phellodendron bark, fritillaria thunbergii, ginseng, hawthorn, poria cocos, tangerine peel, and dandelion.

[0012] In some embodiments, the compound formulation is made from the following components:

[0013] Ephedra alcohol extract, gypsum water extract, licorice alcohol extract, phellodendron alcohol extract, fritillaria thunbergii alcohol extract, ginseng water extract, hawthorn water extract, poria cocos alcohol extract, tangerine peel water extract, and dandelion water extract.

[0014] In some embodiments, the compound formulation comprises the following components in parts by weight:

[0015] Ephedra 20-150 parts, Gypsum 40-150 parts, Licorice 15-120 parts, Phellodendron 20-130 parts, Fritillaria thunbergii 30-120 parts, Ginseng 10-100 parts, Hawthorn 10-70 parts, Poria cocos 20-130 parts, Tangerine peel 20-150 parts, and Dandelion 50-130 parts.

[0016] In some embodiments, the compound formulation comprises the following components in parts by weight:

[0017] Ephedra 20-110 parts, Gypsum 40-60 parts, Licorice 50-70 parts, Phellodendron 60-110 parts, Fritillaria thunbergii 30-120 parts, Ginseng 10-100 parts, Hawthorn 10-30 parts, Poria cocos 30-60 parts, Tangerine peel 20-70 parts, and Dandelion 70-100 parts.

[0018] In some embodiments, the weight ratio of ephedra to poria cocos is 11:5-6.

[0019] In some embodiments, the compound preparation is one of a premix, powder, granule, tablet, granule, oral liquid or injection.

[0020] In another aspect, the present invention also provides a method for preparing the aforementioned compound formulation, specifically comprising,

[0021] S1. Weigh out ephedra, gypsum, licorice, phellodendron bark, fritillaria thunbergii, ginseng, hawthorn, poria cocos, tangerine peel, and dandelion, clean them, and then grind them into coarse powder for later use;

[0022] S2. Take ephedra, licorice, phellodendron bark, fritillaria thunbergii, and poria cocos, add ethanol and reflux to extract, filter, collect the filtrate and residue, and set aside for later use;

[0023] S3. Weigh the remaining raw materials, add water and cook, filter, collect the filtrate and dregs for later use;

[0024] S4. Combine the filtrates obtained from S2 and S3, add ethanol, and concentrate to obtain an extract with a relative density of 1-1.3 at 60°C, thus preparing the desired dosage form.

[0025] In some embodiments, the particle size of the coarse powder is 60-200 mesh.

[0026] In some embodiments, in step S2, the amount of ethanol added is 5-10 times the volume of the solid, and the reflux time is 1-5 hours.

[0027] In some embodiments, in step S3, the amount of water added is 5-10 times the volume of the solid, and the cooking time is 1-5 hours.

[0028] In some embodiments, pharmaceutically acceptable excipients may be added to step S4; these pharmaceutically acceptable excipients include, but are not limited to, lactose, starch, dextrin, powdered sugar, magnesium stearate, maltose, lemon juice, tartaric acid, sodium hydroxide, aspartame, steviol glycoside, cyclamate, protein sugar, acesulfame potassium, aspartame, sucralose, α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, etc.

[0029] In another aspect, the present invention also provides the use of the compound preparation in the treatment of infectious bronchitis in chickens.

[0030] In some embodiments, the dosage and administration of the compound formulation are as follows:

[0031] Usage: Weigh out the compound preparation according to the number of chickens and their condition, mix it with feed or drinking water, and feed for 1-15 days.

[0032] Dosage: 0.5-5g / piece, daily.

[0033] Based on traditional Chinese veterinary medicine theory and combined with the characteristics of infectious bronchitis in chickens, the above-mentioned formula was designed through dialectical analysis. Infectious laryngotracheitis in chickens can occur in all seasons, with an infection rate of up to 90% and a mortality rate of 5%-70%. Chickens of all ages and sexes are susceptible to infection, but it mainly affects chicks under 30 days old. Clinically, it is characterized by sneezing, coughing, increased nasal secretions, tracheal rales, decreased egg production, and the laying of soft-shelled or deformed eggs. In severe cases, it can lead to systemic symptoms such as depression, decreased appetite, and weight loss. Traditional Chinese veterinary medicine believes that external pathogens can invade the body, causing the lungs and defensive qi to become disordered. External invasion of wind, cold, and dampness can lead to stagnation of lung qi, resulting in airway obstruction and symptoms such as cough and wheezing. Spleen and stomach dysfunction can also lead to food stagnation and phlegm production, obstructing lung qi. Internal damage from food or a damp environment can also cause phlegm and dampness to accumulate, obstructing the airways and affecting the lungs' function of dispersing and descending qi. This can result in abnormal gas exchange and impaired fluid metabolism, leading to symptoms such as difficulty breathing and runny nose. Furthermore, a deficiency of vital energy and weakened defensive qi can make the body more susceptible to external pathogens, leading to impaired lung qi and airway disorders. Therefore, from the perspective of traditional Chinese veterinary medicine, the treatment principles should be clearing heat and detoxifying, clearing the lungs and resolving phlegm, relieving cough and wheezing, and clearing the nasal passages. Therefore, the formula establishes ephedra, licorice, and phellodendron as the main active ingredients to ensure that the composition of this invention can clear heat and detoxify, relieve lung congestion and asthma, and dispel wind-cold pathogens. Then, phlegm-resolving drugs such as fritillaria thunbergii, tangerine peel, and poria cocos are selected to clear heat and phlegm, relieve cough and asthma, and moisten dryness to stop coughing. Additionally, gypsum (for clearing heat and nourishing yin), ginseng (for invigorating qi and strengthening the spleen), hawthorn (for promoting qi circulation, strengthening the stomach and aiding digestion), and dandelion (for clearing heat, detoxifying, and promoting urination) are added as adjuvant drugs to work in conjunction with the main ingredients to clear the infectious bronchitis virus in chickens and expel residual toxins from the body through the feces and urinary tract. Therefore, this invention has a higher clinical cure rate than other related drugs in other existing technologies.

[0034] Beneficial effects:

[0035] The product provided by this invention can treat infectious bronchitis in chickens with good therapeutic effect. It has good anti-inflammatory, antitussive, expectorant and antiviral effects. The compound of this invention has no adverse effects on the chicken's mental state, movement and drinking water. It is non-toxic and has few side effects. It has high clinical drug safety for chicks and does not affect the growth performance of chickens. It has a high protection rate and cure rate when used to prevent and treat infectious bronchitis in chickens and is suitable for mass production. Detailed Implementation

[0036] The present invention will be described below with reference to specific embodiments. It should be noted that the following embodiments are examples of the present invention and are used only to illustrate the invention, not to limit it. Other combinations and various modifications within the scope of the present invention can be made without departing from its spirit or scope.

[0037] Unless otherwise specified, all chemical reagents used in this invention are commercially available analytical grade reagents.

[0038] The sources of the Chinese medicinal herbs used in this invention are as follows:

[0039] Ephedra: Sourced from Renxintang Pharmacy;

[0040] Raw gypsum: Sourced from Yuanshengtang Pharmaceutical, a reputable supplier. Brand: Yuanshengtang. Gypsum 01.

[0041] Licorice: Sourced from Anhui Xinyuan Traditional Chinese Medicine Technology Co., Ltd., brand name Huixinyuan, naturally sun-dried.

[0042] Phellodendron bark: Sourced from Anhui Xinyuan Traditional Chinese Medicine Technology Co., Ltd., brand name Huixinyuan, prototype form.

[0043] Fritillaria thunbergii: Sourced from Anhui Xinyuan Traditional Chinese Medicine Technology Co., Ltd., brand name Huixinyuan, original form.

[0044] Ginseng: Sourced from Anhui Xinyuan Traditional Chinese Medicine Technology Co., Ltd., brand name Huixinyuan, Yuanshen.

[0045] Hawthorn: Sourced from Anhui Xinyuan Traditional Chinese Medicine Technology Co., Ltd., brand name Huixinyuan, naturally sun-dried.

[0046] Poria cocos: Sourced from Anhui Xinyuan Traditional Chinese Medicine Technology Co., Ltd., brand name Huixinyuan, Poria cocos cubes, naturally sun-dried.

[0047] Dried tangerine peel: Sourced from Anhui Xinyuan Traditional Chinese Medicine Technology Co., Ltd., brand name Huixinyuan, tangerine peel shreds.

[0048] Dandelion: Sourced from Anhui Xinyuan Traditional Chinese Medicine Technology Co., Ltd., brand name Huixinyuan.

[0049] Example

[0050] S1. Weigh out ephedra, gypsum, licorice, phellodendron bark, fritillaria thunbergii, ginseng, hawthorn, poria cocos, tangerine peel and dandelion according to the raw material ratio in Table 1, clean them and grind them into coarse powder, pass them through a 150-mesh sieve, and set them aside.

[0051] S2. Take ephedra, licorice, phellodendron bark, fritillaria thunbergii and poria cocos, add 10 times the volume of 85% ethanol and reflux in a water bath at 75℃ for 3 times, 2 hours each time, filter, combine the filtrates and set aside.

[0052] S3. Weigh the remaining raw materials, add 10 times the volume of deionized water and decoct 3 times, 2 hours each time, filter, combine the filtrates and set aside;

[0053] S4. Combine the filtrates obtained from S2 and S3, add ethanol to make the alcohol content reach 50%, heat and concentrate to an extract with a relative density of 1.2 at 60℃ to obtain a compound preparation; dry the compound preparation and then pulverize it into a 60-mesh fine powder to obtain a powder for treating infectious bronchitis in chickens.

[0054] Table 1. Formulation of Examples (Unit: Parts by Weight)

[0055]

[0056]

[0057] Comparative Example

[0058] The preparation methods of Comparative Examples 1-6 are the same as those in the Examples, except that the raw material ratios are shown in Table 2.

[0059] Table 2. Formulation table for the comparative examples (unit: parts by weight)

[0060] Ephedra 180 170 210 110 110 240 Gypsum 60 60 60 60 60 60 licorice 70 70 70 70 70 70 Huangbai 110 110 110 110 110 110 Fritillaria thunbergii 120 120 120 120 120 120 Ginseng 100 100 100 100 100 100 hawthorn 30 30 30 30 30 30 Poria 60 0 60 60 0 0 Dried tangerine peel 0 70 70 70 70 0 Dandelion 100 100 0 0 100 0 honeysuckle 0 0 0 100 0 0 Scutellaria baicalensis 0 0 0 0 60 0

[0061] Comparative Example

[0062] The preparation methods of Comparative Examples 7-8 are the same as those in Example 2, except that the raw materials added in S2 are shown in Table 3.

[0063] Table 3. Types of Chinese medicinal herbs used in step S2 (unit: parts by weight)

[0064] Comparative Example 7 Ephedra, Licorice, Phellodendron bark, Fritillaria thunbergii, Comparative Example 8 Ephedra, Licorice, Phellodendron bark, Fritillaria thunbergii, Poria cocos, Tangerine peel, Dandelion

[0065] The obtained compound formulation was subjected to the following tests:

[0066] 1. Safety test

[0067] Experimental animals: 1-day-old chicks, male and female, purchased from the Poultry Research Institute of the Chinese Academy of Agricultural Sciences. Before the experiment, they were fed conventional chick feed without any drugs, with free access to food and water; they were raised to 10 days old for the experiment.

[0068] Experimental Methods: 120 healthy 10-day-old chicks were weighed and randomly divided into 4 groups: 0.5g daily, 2g daily, 5g daily, and a blank control group (no medication). The powder prepared in Example 3 was mixed into the feed of each treatment group according to the corresponding weight, and the chicks had free access to feed and water for 15 consecutive days. The chicks' mental state, appetite, water intake, defecation, movement, and adverse reactions were observed daily after administration. At the end of the experiment, the chicks were weighed, and the average daily weight gain of each group was recorded. Blood samples were collected to detect the red blood cell count and total white blood cell count, and the average values ​​were calculated. The test results are shown in Table 4.

[0069] 2. Pharmacological experiments

[0070] Experimental animals: 1-day-old chicks, male and female, purchased from the Poultry Research Institute of the Chinese Academy of Agricultural Sciences. Before the experiment, they were fed conventionally complete chick feed without any drugs, with free access to food and water; they were raised to 30 days old for the experiment.

[0071] Experimental Methods: 360 30-day-old chicks diagnosed with infectious bronchitis were used as clinical trial subjects and randomly divided into 12 groups: Example 1 (D1), Example 2 (D2), Example 3 (D3), Example 4 (D4), Example 5 (D5), Comparative Example 1 (L1), Comparative Example 2 (L2), Comparative Example 3 (L3), Comparative Example 4 (L4), Comparative Example 5 (L5), Comparative Example 6 (L6), Comparative Example 7 (L7), Comparative Example 8 (L8), Ciprofloxacin group, Baima oral solution group, and blank control group (no medication). Each treatment group received 2g / day of the drug mixed into their feed for 15 consecutive days, with free access to feed and water. After administration, the clinical symptoms and recovery status of the affected chickens in each group were observed, and the number of cured chickens, mortality, and duration of symptoms were recorded. The test results are shown in Table 5.

[0072] Table 4. Test results of safety tests

[0073]

[0074]

[0075] Safety tests showed that when the compound formulation of the present invention was administered to each chick at a dosage of 0.5-5g per day, all clinical symptoms of the chickens in each treatment group were normal, and the daily weight gain, red blood cell count, and white blood cell count were the same as those in the blank control group. This indicates that the compound formulation of the present invention, when administered continuously for 15 days at the above dosage, did not cause any toxic side effects to the chicks. The test results suggest that the compound formulation of the present invention has high clinical safety for chicks.

[0076] Table 5. Test results of pharmacological experiments

[0077]

[0078] Note: "Longest time for symptom disappearance" refers to the longest time taken for a single animal in each experimental group to be fully cured from the start of the experiment.

[0079] In terms of mortality, cure rate, and symptom duration, the compound preparation of this invention shows certain advantages in therapeutic effect compared to the Baima oral liquid group and the blank control group. The mortality rate of the example groups was significantly reduced, reaching below 3%, with the efficacy of the administered samples in Examples 2 and 3 being superior, achieving a cure rate of 100% for infectious bronchitis in chicks. Among them, the optimal efficacy was achieved with the following raw material weight ratios: Ephedra 20-110 parts, Gypsum 40-60 parts, Licorice 50-70 parts, Phellodendron 60-110 parts, Fritillaria thunbergii 30-120 parts, Ginseng 10-100 parts, Hawthorn 10-30 parts, Poria cocos 30-60 parts, Tangerine peel 20-70 parts, and Dandelion 70-100 parts.

[0080] Traditional Chinese medicine (TCM), as a complex therapeutic system, exhibits its complexity through its multiple components, multiple targets, synergistic effects, complementary and antagonistic interactions, dynamic balance, and self-regulation. Therefore, the mechanism of action of TCM does not rely solely on the efficacy of a single component, but rather achieves overall therapeutic effects through the synergistic effects of multiple components. The rational combination of TCM herbs can synergistically exert multiple effects. As can be seen from the embodiments of this invention, the addition of tangerine peel, poria cocos, and dandelion has a certain degree of influence on the final therapeutic effect of the compound preparation, i.e., there is a synergistic effect. Furthermore, through multiple experiments, the inventors confirmed that the optimal efficacy is achieved when the weight ratio of ephedra to poria cocos is 11:6.

[0081] Furthermore, due to the complexity of traditional Chinese medicine ingredients, its active ingredients may contain a variety of chemical substances, and the types of effective ingredients that can be dissolved using different methods may differ, which may affect the efficacy of compound preparations.

[0082] As can be seen from the above embodiments, the present invention provides a compound preparation for infectious bronchitis in chickens, which is safe and efficient to use. It has a high protection rate and cure rate for the prevention and treatment of infectious bronchitis in chickens, and can effectively improve the profitability of poultry farming.

[0083] This invention can also be implemented in various other ways. Without departing from the spirit and essence of this invention, those skilled in the art can make various corresponding changes and modifications according to this invention, but these corresponding changes and modifications should all fall within the protection scope of the appended claims.

Claims

1. A compound preparation for treating infectious bronchitis in chickens, characterized in that, Made from the following components: Ephedra, gypsum, licorice, phellodendron bark, fritillaria thunbergii, ginseng, hawthorn, poria cocos, tangerine peel, and dandelion.

2. The compound formulation according to claim 1, characterized in that, Made from the following components: Ephedra alcohol extract, gypsum water extract, licorice alcohol extract, phellodendron alcohol extract, fritillaria thunbergii alcohol extract, ginseng water extract, hawthorn water extract, poria cocos alcohol extract, tangerine peel water extract, and dandelion water extract.

3. The compound formulation according to claim 1, characterized in that, The components include the following parts by weight: Ephedra 20-150 parts, Gypsum 40-150 parts, Licorice 15-120 parts, Phellodendron 20-130 parts, Fritillaria thunbergii 30-120 parts, Ginseng 10-100 parts, Hawthorn 10-70 parts, Poria cocos 20-130 parts, Tangerine peel 20-150 parts, and Dandelion 50-130 parts.

4. The compound formulation according to claim 1, characterized in that, The components include the following parts by weight: Ephedra 20-110 parts, Gypsum 40-60 parts, Licorice 50-70 parts, Phellodendron 60-110 parts, Fritillaria thunbergii 30-120 parts, Ginseng 10-100 parts, Hawthorn 10-30 parts, Poria cocos 30-60 parts, Tangerine peel 20-70 parts, and Dandelion 70-100 parts.

5. The compound formulation according to claim 1, characterized in that, The weight ratio of ephedra to poria is 11:5-6.

6. The compound formulation according to claim 1, characterized in that, The compound preparation is one of the following: premix, powder, granule, tablet, granule, oral liquid or injection.

7. The method for preparing the compound formulation according to any one of claims 1-6, characterized in that, include, S1. Weigh out ephedra, gypsum, licorice, phellodendron bark, fritillaria thunbergii, ginseng, hawthorn, poria cocos, tangerine peel, and dandelion, clean them, and then grind them into coarse powder for later use; S2. Take ephedra, licorice, phellodendron bark, fritillaria thunbergii, and poria cocos, add ethanol and reflux to extract, filter, collect the filtrate and residue, and set aside for later use; S3. Weigh the remaining raw materials, add water and cook, filter, collect the filtrate and dregs for later use; S4. Combine the filtrates obtained from S2 and S3, add ethanol, and concentrate to obtain an extract with a relative density of 1-1.3 at 60°C, thus preparing the desired dosage form.

8. The method for preparing the compound formulation according to claim 7, characterized in that, In step S2, the amount of ethanol added is 5-10 times the volume of the solid, and the reflux time is 1-5 hours; in step S3, the amount of water added is 5-10 times the volume of the solid, and the cooking time is 1-5 hours; in step S4, pharmaceutically acceptable excipients are also added.

9. The use of the compound preparation according to any one of claims 1-6 in the treatment of infectious bronchitis in chickens.

10. The application of the compound formulation according to claim 9, characterized in that, The usage and dosage of the compound preparation are as follows: Usage: Weigh out the compound preparation according to the number of chickens and their condition, mix it with feed or drinking water, and administer for 1-15 days. Dosage: 0.5-5g / chicken, daily.

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