Traditional Chinese medicine composition for preventing and treating respiratory diseases of poultry as well as preparation method and application of traditional Chinese medicine composition

Abstract

The invention belongs to the technical field of poultry medicines, discloses a traditional Chinese medicine composition for preventing and treating poultry respiratory diseases as well as a preparation method and application thereof, and particularly discloses a traditional Chinese medicine composition which is prepared from the following raw materials: ephedra, fritillaria, vitex, almond, gypsum, liquorice, houttuynia cordata, a scutellaria baicalensis extract and olive oil. According to the traditional Chinese medicine composition provided by the invention, a traditional formula is referenced and optimized, and heartleaf houttuynia herb, bulbus fritillariae ussuriensis, hempleaf negundo chastetree leaf and baical skullcap root extracts with the effects of clearing away heat and toxic materials, eliminating carbuncle, expelling pus, resisting bacteria, diminishing inflammation and enhancing immunity are added, so that medicines such as ephedra herb and apricot kernels can be assisted, the effects of relieving cough and eliminating phlegm are enhanced, and the rehabilitation of respiratory diseases is promoted.

Description

Technical Field

[0001] The present invention belongs to the technical field of poultry medicines, and particularly relates to a traditional Chinese medicine composition for preventing and treating poultry respiratory diseases, and a preparation method and application thereof. Background Art

[0002] Poultry respiratory diseases are among the most common ailments in poultry production. These diseases are typically caused by a variety of pathogens, including viruses, bacteria, and mycoplasmas. Symptoms include coughing, wheezing, and difficulty breathing, severely impacting feed intake, clinical mental state, and vital activities. This can lead to growth impairment, reduced feed conversion, and even widespread mortality, resulting in significant economic losses for the poultry industry. Clinical respiratory diseases have complex etiologies, and antibiotic treatment not only requires accurate diagnosis but can also lead to drug residues, drug resistance, and imbalances in the body's microbiome. Traditional Chinese veterinary medicine effectively alleviates respiratory symptoms in the early stages of the disease, significantly reducing mortality, restoring production performance, and minimizing economic losses. In particular, my country has completely banned the addition of antibiotics to feed since 2020, curbing antibiotic abuse at the source of poultry production. Faced with the urgent need to ban antibiotics in feed and reduce antibiotic use in poultry production, Traditional Chinese veterinary medicine, with its advantages of widespread use, preventive and health benefits, low residue levels, low toxicity, and low resistance, is increasingly being used to treat poultry respiratory diseases.

[0003] Poultry respiratory diseases present with diverse clinical manifestations, such as cough, wheezing, and difficulty breathing, and fall under the categories of "cough" and "wheezing" in Traditional Chinese Medicine. Their pathogenesis is often related to exogenous wind-heat and phlegm-heat congesting the lungs. Treatment often focuses on clearing heat, promoting lung function, and resolving phlegm to relieve cough. According to the Treatise on Febrile Diseases, the traditional Chinese medicine formula Ma Xing Shi Gan Tang (Ma Xing Shi Gan Tang) contains four herbs: ephedra (Ephedra sinica Stapf), apricot kernel (Amygdalus communis Vas), gypsum (Gypsum), and licorice (Glycyrrhiza uralensis Fisch.). Ephedra dispels wind-cold, promoting lung function, and relieving asthma; gypsum clears heat and purges fire, relieving restlessness and quenching thirst; apricot kernel relieves cough and asthma, and moistens the intestines and promotes bowel movements; and licorice harmonizes the various herbs, moistening the lungs and detoxifying. Together, these four herbs exert a pungent and cooling effect, clearing the lungs and relieving asthma, effectively alleviating symptoms associated with respiratory diseases in poultry. Poultry respiratory diseases are often accompanied by a decline in the body's immunity. Although the classic Chinese medicine prescription Ma Xing Shi Gan Tang has a certain effect in alleviating clinical respiratory symptoms, it has limited effect on body repair and immunity enhancement. Therefore, based on this theory, further optimizing the formula and function is extremely important to adapt to the current respiratory problems in breeding.

[0004] Currently, a search reveals that there has been some research on traditional Chinese medicine treatments for poultry respiratory diseases. However, existing technologies still have significant deficiencies in terms of in-depth exploration of classic prescriptions, optimization of preparation processes, and improvement of clinical efficacy. Specifically, existing technologies have the following major problems:

[0005] 1) The formula function is not comprehensive enough and the efficacy needs to be improved

[0006] Although some existing patents have demonstrated good therapeutic effects in practical applications, they still face deficiencies in formula efficacy and efficacy that need to be enhanced. For example, a Chinese invention patent discloses a traditional Chinese medicine composition for treating animal cough, which is prepared from the following raw materials in parts by weight: 150-250 parts of ephedra, 130-230 parts of cassia twig, 100-200 parts of bitter almond, 100-200 parts of lily, 50-150 parts of prepared rehmannia, 50-150 parts of ginger, 50-150 parts of jujube, and 0-40 parts of brown sugar. In Experiment 2, which was used to treat sick chickens, the mortality rate remained at 5%-6%. Although this rate decreased compared to the control group, it was still significantly high, indicating room for improvement.

[0007] 2) The traditional extraction process has limited efficiency and low dissolution rate of active ingredients

[0008] In the existing technology, the preparation process of most traditional Chinese medicine compositions is relatively traditional, mainly using simple crushing and stirring or water decoction processes, without combining modern extraction technology to efficiently extract the active ingredients of traditional Chinese medicines. As a result, the active ingredients are not fully extracted and utilized, and the clinical efficacy of the products is limited. For example, the preparation process of traditional Chinese medicine compositions for treating poultry respiratory diseases disclosed in certain Chinese invention patents still remains in the traditional decoction or crushing stage. The preparation process is backward and fails to fully extract the active ingredients in the Chinese herbal medicines, resulting in low extraction efficiency and utilization rate of the active ingredients, making it difficult to meet the current therapeutic needs of poultry breeding for the prevention and control of poultry respiratory diseases.

[0009] 3) The selection of innovative medicinal materials is not universal and the cost is high

[0010] During the search process, it was found that a certain Chinese invention patent disclosed a traditional Chinese medicine composition for preventing and treating poultry respiratory diseases, which contains the following traditional Chinese medicines in parts by weight: 10-45 parts of artificial bezoar, 5-15 parts of toad, 90-125 parts of forsythia, 85-110 parts of isatis root, 30-65 parts of codonopsis, 200-255 parts of houttuynia, 70-120 parts of momordica, 95-120 parts of dandelion, 50-85 parts of sophora flavescens, 5-25 parts of almond, 25-75 parts of siler and 130-165 parts of liquorice. Although the composition shows a certain effect in the prevention and control of clinical respiratory diseases, the artificial bezoar and toad involved are relatively expensive, and the application cost is often not acceptable to the terminal.

[0011] Therefore, there is an urgent need to develop a drug combination that has good therapeutic effect on avian respiratory diseases and low preparation cost. Summary of the Invention

[0012] The present invention aims to develop a traditional Chinese medicine composition for preventing and treating poultry respiratory diseases, as well as its preparation method and application. This traditional Chinese medicine composition has a significant preventive effect on poultry respiratory diseases, with rapid onset of action, high cure rate, no significant side effects on production, and can also enhance the animal's immune capacity.

[0013] The first aspect of the present invention aims to provide a Chinese medicine composition.

[0014] The purpose of the second aspect of the present invention is to provide a method for preparing the Chinese medicine composition of the first aspect of the present invention.

[0015] The third aspect of the present invention aims to provide a medicine.

[0016] The fourth aspect of the present invention aims to provide the use of the Chinese medicine composition of the first aspect of the present invention or the medicine of the third aspect of the present invention.

[0017] The fifth aspect of the present invention aims to provide a product.

[0018] In order to achieve the above object, the technical solution adopted by the present invention is:

[0019] The first aspect of the present invention provides a traditional Chinese medicine composition, which is prepared from the following raw materials: ephedra, fritillaria, vitex, apricot kernel, gypsum, liquorice, houttuynia cordata, scutellaria baicalensis extract and olive oil.

[0020] In some embodiments of the present invention, the traditional Chinese medicine composition is made from raw materials including the following components in parts by weight: 10-50 parts of ephedra, 5-25 parts of fritillaria, 5-20 parts of vitex, 5-40 parts of apricot kernel, 10-30 parts of gypsum, 5-20 parts of houttuynia cordata, 10-35 parts of licorice, 2-20 parts of scutellaria baicalensis extract, and 8-250 parts of olive oil.

[0021] In some embodiments of the present invention, the traditional Chinese medicine composition is made from raw materials including the following components in parts by weight: 15-45 parts of ephedra, 5-20 parts of fritillaria, 5-15 parts of vitex, 10-35 parts of apricot kernel, 15-30 parts of gypsum, 5-15 parts of houttuynia cordata, 10-35 parts of licorice, 2-15 parts of scutellaria baicalensis extract, and 8-20 parts of olive oil.

[0022] In some embodiments of the present invention, the traditional Chinese medicine composition is made from raw materials including the following components in parts by weight: 30-45 parts of ephedra, 8-15 parts of fritillaria, 5-15 parts of vitex, 10-20 parts of apricot kernel, 15-20 parts of gypsum, 8-10 parts of houttuynia cordata, 20-25 parts of licorice, 5-10 parts of scutellaria baicalensis extract, and 10-15 parts of olive oil.

[0023] In some embodiments of the present invention, the traditional Chinese medicine composition further comprises Tween.

[0024] In some embodiments of the present invention, the Tween comprises at least one of Tween-20, Tween-40, Tween-60, and Tween-80.

[0025] In some embodiments of the present invention, the traditional Chinese medicine composition further comprises 2 to 6 parts of Tween; further 2 to 5 parts; further 2 to 3 parts.

[0026] In some embodiments of the present invention, the scutellaria baicalensis extract is a water extract of scutellaria baicalensis.

[0027] In some embodiments of the present invention, the scutellaria baicalensis extract is prepared by the following preparation method: mixing scutellaria baicalensis with a solvent, extracting, collecting the extract, concentrating, adjusting the pH value to 2.0-3.0, solid-liquid separation, and obtaining a precipitate; dissolving the precipitate with a solvent, adjusting the pH value to neutral, adding ethanol, adjusting the pH value to 2.0-3.0, solid-liquid separation, obtaining a precipitate, and washing the precipitate to obtain the scutellaria baicalensis extract.

[0028] In some embodiments of the present invention, the extraction method comprises decoction.

[0029] In some embodiments of the present invention, the solvent comprises water.

[0030] In some embodiments of the present invention, before the radix scutellariae is mixed with the solvent, the radix scutellariae is pulverized and passed through a 20-30 mesh sieve.

[0031] In some embodiments of the present invention, the Fritillaria includes Fritillaria thunbergii.

[0032] In some embodiments of the present invention, the vitex is vitex leaves.

[0033] The Chinese medicine composition of the present invention comprises the following: Ephedra sinica Stapf, which is pungent, slightly bitter and warm in nature, has the effects of diaphoresis, relieving exterior symptoms, promoting lung function and relieving asthma, promoting diuresis and reducing swelling, and is mainly used to treat symptoms such as exogenous wind-cold, cough and asthma; Fritillaria ussuriensis Maxim., which is bitter, sweet and slightly cold in nature, has the effects of moistening the lungs and resolving phlegm, relieving cough and relieving asthma, clearing away heat and dispersing stagnation, and is mainly used to treat cough with excessive phlegm and chronic cough due to yin deficiency; Vitex sampsoni Hance leaves, which are pungent, bitter and neutral in nature, have the effects of promoting lung function and removing phlegm, relieving throat and discharging pus, and is mainly used to treat cough with excessive phlegm and sore throat; Amygdalus CommunisVas), bitter and slightly warm in nature, has the effects of relieving cough and asthma, moistening the intestines and promoting bowel movements, and is mainly used to treat cough, asthma, and dry intestinal constipation; Gypsum (Gypsum), pungent and sweet in nature, and very cold in nature, has the effects of clearing heat and purging fire, relieving restlessness and thirst, and is mainly used to treat high fever, irritability, and lung heat cough; Licorice (Glycyrrhiza uralensis Fisch.), sweet and neutral in nature, has the effects of tonifying the spleen and replenishing qi, relieving urgency, and detoxifying, and is mainly used to treat symptoms such as spleen and stomach deficiency and poisoning; Houttuynia cordata Thunb, slightly cold and pungent in nature, clears heat and detoxifies, eliminates carbuncles and discharges pus, promotes diuresis and relieves stranguria, promotes the discharge of phlegm, unclogs the airways, helps the body eliminate dampness and heat, and harmonizes the internal environment; Scutellaria baicalensis Georgi extract is bitter and cold in nature, and has the effects of clearing away heat and dampness, purging fire and detoxifying, and stopping bleeding. It is mainly used to treat lung heat cough and damp-heat jaundice; olive oil is sweet and flat in nature, and has the effects of moistening the intestines and promoting bowel movements, moistening the lungs and relieving coughs. It is mainly used to treat dry intestinal constipation and dry cough without phlegm.

[0034] In the Chinese medicine composition of the present invention, Ephedra, Apricot Kernel and Gypsum are all monarch drugs, which have the effects of diaphoresis, dispersing the lung and relieving asthma, can open and disperse the lung qi, and play a major therapeutic role for main symptoms (such as exogenous wind pathogens, pathogenic heat obstructing the lungs, etc.). Houttuynia cordata, Fritillaria dahurica and Vitex foetida are ministerial drugs, which can lower and promote the flow of lung qi. Together with Ephedra, one promotes and the other lowers, to restore the flow of lung qi. Ministerial drugs assist the monarch drug in strengthening the therapeutic effect and play a therapeutic role for concurrent symptoms (such as lung heat, asthma, etc.). Scutellaria baicalensis extract and olive oil serve as adjuvant drugs, with the effects of clearing away heat and detoxicating, moistening the lung and relieving cough. Licorice is a guiding drug, which plays a role of harmonizing the medicinal properties and guiding the drug to the meridians in the prescription, ensuring that the prescription can be steadily and effectively played a role. All drugs are used together, and for avian respiratory diseases, such as symptoms such as cough, asthma, pneumonia, there is a significant effect of clearing away heat and dispersing the lung qi, relieving cough and relieving asthma, and enhancing immunity, accelerating the recovery of poultry and improving breeding efficiency.

[0035] Based on the classic prescriptions such as Maxing Shigan Decoction, the present invention combines modern pharmacological research to scientifically optimize the compound compatibility, and adds medicinal materials such as Houttuynia cordata, Fritillaria dahurica, Vitex foetida, and Scutellaria baicalensis extracts that have the effects of clearing heat and detoxifying, eliminating carbuncles and draining pus, and having antibacterial and anti-inflammatory effects and enhancing immunity, thereby further enhancing the clinical efficacy of the prescription in relieving cough and asthma, anti-inflammatory and antipyretic, antibacterial and antiviral effects, and immune regulation.

[0036] The second aspect of the present invention provides a method for preparing the Chinese medicine composition of the first aspect of the present invention. In order to obtain a higher content of active ingredients of Chinese medicine and significantly improve the extraction rate of effective medicinal ingredients in Chinese medicinal materials, the raw materials are prepared by semi-bionic enzymatic hydrolysis technology in the present invention. The preparation method comprises the following steps:

[0037] The gypsum is mixed with a solvent, soaked, heated, extracted, and the medicinal solution A and gypsum residue are collected; the gypsum residue is mixed with the solvent and extracted again to obtain the medicinal solution B;

[0038] Mixing ephedra, houttuynia cordata, liquorice, fritillaria and vitex with a solvent, adding a composite enzyme, and performing enzymolysis to obtain a medicinal solution C and a composite medicinal residue;

[0039] The medicinal solution C, the composite medicinal residue, the medicinal solution A and the solvent are mixed, heated, and almonds are added for extraction to collect the medicinal solution D; the medicinal residue is mixed with the solvent and the medicinal solution B and extracted again to obtain the medicinal solution E; the medicinal solution D and the medicinal solution E are combined and concentrated to obtain the medicinal solution F;

[0040] olive oil, scutellaria baicalensis extract and Tween are mixed and emulsified to obtain an emulsified system;

[0041] The emulsified system is mixed with the medicinal solution F to obtain a Chinese medicine composition.

[0042] This invention utilizes a semi-bionic enzymatic hydrolysis process to hydrolyze Chinese herbal medicines using a composite enzyme preparation, significantly improving the extraction efficiency of active ingredients from these herbs. This allows for the full release of active ingredients from herbs like ephedra and houttuynia cordata, thereby significantly enhancing the overall efficacy of the formula. Because almonds differ from other herbs in that they must be added at high temperatures, the temperature must be raised after the other herbs have been extracted to ensure that the active ingredients are not destroyed by enzymatic hydrolysis.

[0043] In some embodiments of the present invention, the complex enzyme comprises cellulase, hemicellulase and pectinase.

[0044] In some embodiments of the present invention, the mass ratio of the cellulase, hemicellulase and pectinase is 1:(1-3):(1-4); further 1:(1-2):(2-4); further 1:1:2.

[0045] In some embodiments of the present invention, the added amount of the complex enzyme is 1% to 5% of the total mass of ephedra, houttuynia cordata, liquorice, fritillaria and vitex; further 1% to 3%; further 2% to 3%.

[0046] In some embodiments of the present invention, the enzymatic hydrolysis conditions are: pH value of 4-6, temperature of 45-60° C., and enzymatic hydrolysis time of 0.5-2 h.

[0047] In some embodiments of the present invention, the enzymatic hydrolysis conditions are: pH 5-6, temperature 45-55° C., and enzymatic hydrolysis time 1-2 h.

[0048] In some embodiments of the present invention, the enzyme activity of the complex enzyme is 50,000 to 100,000 U / g.

[0049] In some embodiments of the present invention, the solvent comprises water.

[0050] In some embodiments of the present invention, the material-liquid ratio of gypsum to solvent is 1:(8-12); further 1:(8-10).

[0051] In some embodiments of the present invention, during the gypsum extraction process, the soaking time is 20 to 40 minutes; further 20 to 30 minutes.

[0052] In some embodiments of the present invention, during the gypsum extraction process, the temperature is raised to 90-100°C.

[0053] In some embodiments of the present invention, during the gypsum extraction process, the extraction time is 1 to 2 hours; further 1.5 to 2 hours.

[0054] In some embodiments of the present invention, the material-liquid ratio of the gypsum slag to the solvent is 1:(5-10); further 1:(7-8).

[0055] In some embodiments of the present invention, during the gypsum extraction process, the re-extraction conditions are: extraction at 90-100° C. for 0.5-1.5 h; further extraction at 90-100° C. for 1-1.5 h.

[0056] In some embodiments of the present invention, the solid-liquid ratio of the ephedra, houttuynia cordata, licorice, fritillaria and vitex (the total mass of ephedra, houttuynia cordata, licorice, fritillaria and vitex) to the solvent is 1:(8-12); further 1:(8-10).

[0057] In some embodiments of the present invention, during the preparation of the medicinal solution D, the amount of the solvent is calculated based on the mass of the almonds, and the solid-liquid ratio is 1:(9-10); the temperature is raised to 92-98° C.; and the extraction time is 1-2 h.

[0058] In some embodiments of the present invention, during the preparation of the medicinal solution E, the material-liquid ratio of the medicinal residue to the solvent is 1:(7-9), and the re-extraction condition is 90-100° C. for 0.5-1.5 h.

[0059] In some embodiments of the present invention, the preparation method further includes a sterilization step.

[0060] The present invention reduces the cost of finished products and improves the economy and practicality of products by selecting conventional medicinal materials and optimizing the preparation process and formula ratio, thereby meeting the urgent demand of the breeding end for efficient and economical Chinese medicine products. Through the above innovations, the present invention not only draws on the formula of traditional classical prescriptions, but also improves the content and bioavailability of active ingredients and reduces production costs through innovative extraction processes, and ensures the stability and safety of Chinese medicine preparations through scientific compatibility and innovation of preparation processes, thus meeting the breeding end's demand for all-round, high-efficiency, economical and practical Chinese medicine prevention and control products. The various Chinese medicine ingredients of the present invention work together to clear away heat and detoxify, relieve cough and asthma, and have antibacterial and anti-inflammatory effects, as well as to strengthen the body's resistance and promote the recovery of poultry, providing a better solution for the prevention and control of poultry respiratory diseases.

[0061] The third aspect of the present invention provides a medicine comprising the Chinese medicine composition of the first aspect of the present invention.

[0062] In some embodiments of the present invention, the drug further comprises a pharmaceutically acceptable excipient.

[0063] In some embodiments of the present invention, the excipient is at least one of a filler, a disintegrant, a diluent, a lubricant, a binder, a wetting agent, a flavoring agent, a suspending agent, a solvent, a sustained-release agent, an emulsifier, an absorption enhancer, a surfactant, a preservative, a pigment, a flavor, and a solvent.

[0064] In some embodiments of the present invention, the filler is selected from starch, sucrose, lactose, mannitol, sorbitol, xylitol, microcrystalline cellulose or glucose; the binder is selected from cellulose derivatives, alginate, starch, water, dextrin, gelatin or polyvinyl pyrrolidone; the disintegrant is selected from microcrystalline cellulose, sodium hydroxymethyl starch, cross-linked polyvinyl pyrrolidone, low-substituted hydroxypropyl cellulose or cross-linked sodium hydroxymethyl cellulose; the lubricant is selected from stearic acid, polyethylene glycol, calcium carbonate, sodium bicarbonate, micropowder silica gel, talc or magnesium stearate; the suspending agent is selected from micropowder silica gel, beeswax, cellulose, solid polyethylene glycol : The wetting agent is selected from glycerol, Tween-80, hydrogenated castor oil or lecithin; the solvent is selected from ethanol, liquid polyethylene glycol, isopropyl alcohol, Tween-80, glycerol, propylene glycol or vegetable oil, and the vegetable oil is selected from soybean oil, castor oil, peanut oil, blending oil, etc.; the surfactant is selected from sodium dodecylbenzenesulfonate, stearic acid, polyoxyethylene-polyoxypropylene copolymer, fatty acid sorbitan or polysorbate (Tween), etc.; the flavoring agent is selected from aspartame, sucralose, essence, stevia, acesulfame potassium, citric acid or saccharin sodium; the preservative is selected from at least one of methyl paraben or propyl paraben.

[0065] In some embodiments of the present invention, the dosage form of the drug is selected from tablets (such as ordinary tablets, double-layer tablets, multi-layer tablets, sustained-release tablets, single-chamber controlled-release tablets, double-chamber controlled-release tablets, microporous controlled-release tablets, sublingual tablets, orally rapidly disintegrating tablets, dispersible tablets, enteric-coated tablets), pills, powders, suspensions, gels, emulsions, creams, granules, nanoparticles, capsules (such as ordinary capsules, sustained-release capsules, controlled-release capsules, capsules containing micropellets or small tablets, pH-dependent capsules containing micropellets or small tablets, gastrointestinal composite capsules), suppositories, injections, sprays, injections, granules, drops, pills, solutions, creams, patches, lozenges or any combination thereof.

[0066] The fourth aspect of the present invention provides the use of the Chinese medicine composition of the first aspect of the present invention or the drug of the third aspect of the present invention in at least one of (1) to (4):

[0067] (1) Preparation of products for preventing and / or treating respiratory diseases in livestock and poultry;

[0068] (2) preparing anti-inflammatory products;

[0069] (3) Preparation of products that enhance the body / intestinal immunity of livestock and poultry;

[0070] (4) Preparation of livestock and poultry farming products.

[0071] In some embodiments of the present invention, the livestock and poultry respiratory diseases include at least one of swine asthma, porcine contagious pleuropneumonia, porcine infectious atrophic rhinitis, porcine reproductive and respiratory syndrome, swine streptococcosis, swine plague, swine influenza, and infectious bronchitis, infectious laryngotracheitis, and avian influenza.

[0072] In some embodiments of the present invention, the livestock and poultry respiratory diseases include clinical symptoms such as coughing, wheezing, rales, and runny nose.

[0073] In some embodiments of the present invention, the product includes medicines (such as antitussive drugs, expectorants, and anti-inflammatory drugs for livestock and poultry) and / or feed.

[0074] The fifth aspect of the present invention provides a product comprising the Chinese medicine composition of the first aspect of the present invention or the medicine of the third aspect of the present invention.

[0075] In some embodiments of the present invention, the product comprises medicine and / or feed.

[0076] In some embodiments of the present invention, the product can be used to prevent and / or treat respiratory diseases in livestock and poultry (such as anti-inflammatory, antitussive, and expectorant) and improve the body / intestinal immunity of livestock and poultry.

[0077] The beneficial effects of the present invention are:

[0078] The traditional Chinese medicine composition provided by the present invention draws on and optimizes traditional formulas, and adds extracts of Houttuynia cordata, Fritillaria tiliaceus, Vitex oleifera leaves, and Scutellaria baicalensis, which have the effects of clearing away heat and detoxifying, eliminating carbuncles and draining pus, and having antibacterial and anti-inflammatory effects and enhancing immunity. It can assist drugs such as ephedra and apricot kernel to enhance the effects of relieving cough and expectoration, and promote recovery from respiratory diseases.

[0079] The preparation method provided by the present invention uses a semi-bionic-enzymatic hydrolysis process for extraction, which can promote the dissolution and collection of active ingredients of traditional Chinese medicine to a greater extent, enhance the efficacy of medicinal materials such as ephedra, houttuynia cordata, and flat fritillaria, thereby effectively alleviating and treating respiratory symptoms, and exerting more significant clinical therapeutic effects such as cough and asthma relief, anti-inflammatory and antipyretic, antibacterial and antiviral, and immune regulation. BRIEF DESCRIPTION OF THE DRAWINGS

[0080] Figure 1 This is the result of high performance liquid chromatography (ammonium glycyrrhizate).

[0081] Figure 2 This is the result of high performance liquid chromatography (amygdalin).

[0082] Figure 3 This is the result of high performance liquid chromatography (ephedrine).

[0083] Figure 4 Mice were fed for in vivo validation experiments.

[0084] Figure 5 Phenol red OD value was used for in vivo verification of expectorant effect.

[0085] Figure 6 For antitussive effect - the number of coughs in the ammonia-induced cough test.

[0086] Figure 7 For antitussive effect - cough latency period of ammonia-induced cough test.

[0087] Figure 8 This is Shed #1 of a Magong broiler breeding farm in Meizhou, Guangdong.

[0088] Figure 9 It shows the symptoms of the trachea, air sacs and lungs before and after administration.

[0089] Figure 10 The condition of the air sacs and lungs before and after administration (enlarged image). DETAILED DESCRIPTION

[0090] The present invention is further described in detail below through specific examples.

[0091] It should be understood that these examples are only used to illustrate the present invention and are not used to limit the scope of the present invention.

[0092] To make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention are described clearly and completely below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer are used. Where the manufacturer of the reagents or instruments is not specified, all are conventional products that can be purchased commercially.

[0093] The scutellaria baicalensis extract used in the embodiment was prepared by the following steps:

[0094] (1) Medicinal material grinding: select the medicinal material of Scutellaria baicalensis, grind it and pass it through a 30-mesh sieve to obtain the pulverized Scutellaria baicalensis;

[0095] (2) Extraction and concentration: Add water to the processed scutellaria baicalensis powder at a material-liquid ratio of 1:10, decoct for 1.5 hours, filter and collect the extract, and extract twice continuously. Combine the extracts and concentrate to an appropriate amount to obtain a concentrate. Adjust the pH value to 2.0-3.0 with hydrochloric acid, keep it at 75°C for 2 hours, filter and obtain a precipitate (1);

[0096] (3) Precipitation treatment: Add water to the precipitate (1) and stir evenly. Adjust the pH value to 7.0 with 20% sodium hydroxide solution, add an equal amount of ethanol, stir until dissolved, adjust the pH value to 2.0-3.0 with hydrochloric acid again, keep it at 75°C and let it stand for 2 hours, filter it, and obtain the precipitate (2);

[0097] (4) Washing and drying: The precipitate (2) is washed with anhydrous ethanol to a pH value of 6.0 to 7.0, and then dried under reduced pressure to obtain Scutellaria baicalensis extract powder, i.e., Scutellaria baicalensis extract.

[0098] The features and performance of the present invention are further described in detail below with reference to the embodiments.

[0099] Example 1

[0100] A traditional Chinese medicine composition for preventing and treating respiratory diseases in avian tracts is prepared from the following raw materials in parts by weight: 35 parts of ephedra, 10 parts of fritillaria brevis, 10 parts of vitex quinata leaves, 20 parts of apricot kernel, 20 parts of gypsum, 20 parts of liquorice, 8 parts of houttuynia cordata, 5 parts of scutellaria baicalensis extract, 15 parts of olive oil, and 3 parts of Tween-80.

[0101] In order to obtain the active ingredients in medicinal materials such as ephedra, fritillaria brevis, vitex oleifera, houttuynia cordata, and licorice, enzymatic hydrolysis and water extraction technology are used in this embodiment to ensure that the effective ingredients in the medicinal materials are dissolved to a greater extent and improve the efficacy of the drugs.

[0102] The preparation method of the above-mentioned Chinese medicine composition comprises the following steps:

[0103] (1) Medicinal material crushing: Ephedra, apricot kernel, houttuynia cordata, licorice, Fritillaria thunbergii and Vitex foetida were washed, cut and dried according to the traditional processing technology of Chinese herbal medicine. Then, each medicinal material was crushed separately and passed through a 10-mesh sieve.

[0104] (2) Gypsum Extraction: Take the gypsum in the above combination and extract it with water at a solid-liquid ratio of 1:10 for the first time. Soak it at 45°C for 0.5 h, then raise the temperature to 95±5°C, keep it at a slight boiling point for 1.5 h, and collect liquid A. Extract it for the second time at a solid-liquid ratio of 1:8, raise the temperature to 95±5°C, keep it at a slight boiling point for 1 h, and collect liquid B.

[0105] (3) Enzymatic extraction of ephedra, houttuynia cordata, licorice, balsam pear, and vitex chinensis leaves: Take the five medicinal materials of ephedra, houttuynia cordata, licorice, balsam pear, and vitex chinensis leaves in the above composition, add 10 times the volume of distilled water, adjust the pH value to 4.5-5.5, and then add a total of 2% of the medicinal material weight of the complex enzyme, the mass ratio of cellulase: hemicellulase: pectinase = 1:1:2. After starting the enzymatic hydrolysis program, stir and hydrolyze in the extraction tank for 1 hour. The enzymatic hydrolysis temperature is controlled at 50±5℃. After the enzymatic hydrolysis is completed, a medicinal solution C and a medicinal residue are obtained. Among them, the cellulase activity is 2000U / g; the hemicellulase activity is 50000U / g; and the pectinase activity is 5000U / g.

[0106] (4) Combined extraction of aqueous solution and residue: Combine solution C, residue, and solution A. Add distilled water at a ratio of 1:10 based on the amount of almonds. Heat to 95.0±2.0°C, add almonds, and maintain a slight boiling point for 1.5 h. Collect solution D to complete the first combined extraction. Add water to the remaining residue at a ratio of 1:8, continue to combine with solution B, heat to 95±5°C, maintain a slight boiling point for 1 h, and collect solution E to complete the second combined extraction.

[0107] (5) Combining aqueous phase solutions: Combine solution D and solution E, concentrate under reduced pressure, and centrifuge to a total material-liquid ratio of 1:2, and collect solution F.

[0108] (6) Preparation of emulsified system: Take corresponding amounts of olive oil, scutellaria baicalensis extract and Tween and mix them until they are evenly distributed to obtain emulsified system G.

[0109] (7) Final preparation: After the emulsified system G and the drug solution F are mixed, they are stirred and mixed, sterilized, filtered, and filled.

[0110] Example 2

[0111] A traditional Chinese medicine composition for preventing and treating respiratory diseases in avian tracts is prepared from the following raw materials in parts by weight: 40 parts of ephedra, 15 parts of fritillaria brevis, 5 parts of vitex foetida, 20 parts of apricot kernel, 15 parts of gypsum, 25 parts of liquorice, 8 parts of houttuynia cordata, 5 parts of scutellaria baicalensis extract, 10 parts of olive oil and 3 parts of Tween-80.

[0112] The preparation method of the above-mentioned Chinese medicine composition is the same as that in Example 1.

[0113] Example 3

[0114] A traditional Chinese medicine composition for preventing and treating respiratory diseases in avian tracts is prepared from the following raw materials in parts by weight: 30 parts of ephedra, 8 parts of fritillaria brevis, 15 parts of vitex foetida, 20 parts of apricot kernel, 20 parts of gypsum, 20 parts of liquorice, 10 parts of houttuynia cordata, 5 parts of scutellaria baicalensis extract, 15 parts of olive oil, and 3 parts of Tween-80.

[0115] The preparation method of the above-mentioned Chinese medicine composition is the same as that in Example 1.

[0116] Example 4

[0117] A traditional Chinese medicine composition for preventing and treating respiratory diseases in avian tracts is prepared from the following raw materials in parts by weight: 35 parts of ephedra, 10 parts of fritillaria brevis, 5 parts of vitex quinata leaves, 20 parts of apricot kernel, 18 parts of gypsum, 25 parts of liquorice, 10 parts of houttuynia cordata, 10 parts of scutellaria baicalensis extract, 10 parts of olive oil and 3 parts of Tween-80.

[0118] The preparation method of the above-mentioned Chinese medicine composition is the same as that in Example 1.

[0119] Example 5

[0120] A traditional Chinese medicine composition for preventing and treating respiratory diseases in avian tracts is prepared from the following raw materials in parts by weight: 35 parts of ephedra, 10 parts of fritillaria brevis, 10 parts of vitex quinata leaves, 20 parts of apricot kernel, 20 parts of gypsum, 20 parts of liquorice, 8 parts of houttuynia cordata, 5 parts of scutellaria baicalensis extract, 15 parts of olive oil, and 3 parts of Tween-80.

[0121] Compared with Example 1, the preparation method of the above-mentioned traditional Chinese medicine composition is that the mass ratio of the complex enzyme in step (3) is 1:1:3 (cellulase: hemicellulase: pectinase).

[0122] Example 6

[0123] A traditional Chinese medicine composition for preventing and treating respiratory diseases in avian tracts is prepared from the following raw materials in parts by weight: 15 parts of ephedra, 20 parts of fritillaria brevis, 15 parts of vitex quinata leaves, 5 parts of apricot kernel, 20 parts of gypsum, 35 parts of liquorice, 8 parts of houttuynia cordata, 5 parts of scutellaria baicalensis extract, 20 parts of olive oil and 3 parts of Tween-80.

[0124] The preparation method of the above-mentioned Chinese medicine composition is the same as that in Example 1.

[0125] Example 7

[0126] A traditional Chinese medicine composition for preventing and treating respiratory diseases in avian tracts is prepared from the following raw materials in parts by weight: 15 parts of ephedra, 20 parts of fritillaria brevis, 10 parts of vitex chinensis leaves, 35 parts of apricot kernel, 20 parts of gypsum, 5 parts of liquorice, 18 parts of houttuynia cordata, 15 parts of scutellaria baicalensis extract, 5 parts of olive oil, and 3 parts of Tween-80.

[0127] The preparation method of the above-mentioned Chinese medicine composition is the same as that in Example 1.

[0128] Example 8

[0129] A traditional Chinese medicine composition for preventing and treating respiratory diseases in avian tracts is prepared from the following raw materials in parts by weight: 35 parts of ephedra, 10 parts of fritillaria brevis, 10 parts of vitex quinata leaves, 25 parts of apricot kernel, 20 parts of gypsum, 20 parts of liquorice, 8 parts of houttuynia cordata, 5 parts of scutellaria baicalensis extract, 10 parts of olive oil, and 3 parts of Tween-80.

[0130] The preparation method of the above-mentioned Chinese medicine composition is the same as that in Example 1.

[0131] Example 9

[0132] A traditional Chinese medicine composition for preventing and treating respiratory diseases in avian tracts is prepared from the following raw materials in parts by weight: 35 parts of ephedra, 10 parts of fritillaria brevis, 10 parts of vitex quinata leaves, 25 parts of apricot kernel, 20 parts of gypsum, 20 parts of liquorice, 8 parts of houttuynia cordata, 5 parts of scutellaria baicalensis extract, 10 parts of olive oil, and 3 parts of Tween-80.

[0133] The preparation method of the above-mentioned Chinese medicine composition is different from that of Example 1 in that the semi-bionic enzymatic hydrolysis technology is eliminated in the preparation process, that is, the active ingredients of ephedra, houttuynia cordata, licorice, fritillaria brevis and vitex foetida are extracted by conventional water extraction, which specifically comprises the following steps:

[0134] (1) Medicinal material crushing: Ephedra, apricot kernel, houttuynia cordata, licorice, Fritillaria thunbergii and Vitex foetida were washed, cut and dried according to the traditional processing technology of Chinese herbal medicine. Then, each medicinal material was crushed separately and passed through a 10-mesh sieve.

[0135] (2) Gypsum Extraction: The gypsum in the above combination was extracted for the first time at a solid-liquid ratio of 1:10, soaked for 0.5 h, heated to 95±5°C, and maintained at a slight boiling point for 1.5 h, and the medicinal solution A was collected. The second extraction was performed at a solid-liquid ratio of 1:8, heated to 95±5°C, and maintained at a slight boiling point for 1 h, and the medicinal solution B was collected.

[0136] (3) Conventional water extraction of ephedra, houttuynia cordata, liquorice, fritillaria brevis and vitex foetida: Take ephedra, houttuynia cordata, liquorice, fritillaria brevis and vitex foetida in the above composition, add 10 times the volume of distilled water, heat to 95±5℃, maintain slight boiling for 1h, and obtain liquid C and residue.

[0137] (4) Combined extraction of aqueous solution and residue: Combine solution C, residue, and solution A. Add distilled water at a ratio of 1:10 based on the amount of almonds. Heat to 90±2°C, add almonds, and maintain a slight boiling point for 1.5 h. Collect solution D to complete the first combined extraction. Add water to the remaining residue at a ratio of 1:8, continue to combine with solution B, heat to 95±5°C, maintain a slight boiling point for 1 h, and collect solution E to complete the second combined extraction.

[0138] (5) Combining aqueous phase solutions: Combine solution D and solution E, concentrate under reduced pressure, and centrifuge to a total material-liquid ratio of 1:2, and collect solution F.

[0139] (6) Preparation of emulsified system: Take corresponding amounts of olive oil, scutellaria baicalensis extract and Tween and mix them until they are evenly distributed to obtain emulsified system G.

[0140] (7) Final preparation: After the emulsified system G and the drug solution F are mixed, they are stirred and mixed, sterilized, filtered, and filled.

[0141] Comparative Example 1

[0142] A traditional Chinese medicine composition for preventing and treating respiratory diseases in poultry, compared with Example 1, does not contain scutellaria baicalensis extract, and is supplemented with an equal number of apricot kernels. That is, the traditional Chinese medicine composition is prepared by including the following raw materials in parts by weight: 35 parts of ephedra, 10 parts of fritillaria brevis, 10 parts of vitex chinensis leaves, 25 parts of apricot kernels, 20 parts of gypsum, 20 parts of liquorice, 8 parts of houttuynia cordata, 15 parts of olive oil, and 3 parts of Tween-80.

[0143] The preparation method of the above-mentioned Chinese medicine composition is the same as that in Example 1.

[0144] Comparative Example 2

[0145] A traditional Chinese medicine composition for preventing and treating respiratory diseases in poultry, compared with Example 1, does not contain Fritillaria cirrhosa, Vitex foetida, Houttuynia cordata, Scutellaria baicalensis extract and olive oil, that is, the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 35 parts of ephedra, 20 parts of apricot kernel, 20 parts of gypsum, 20 parts of liquorice and 3 parts of Tween-80.

[0146] The preparation method of the above-mentioned Chinese medicine composition is the same as that in Example 1.

[0147] Comparative Example 3

[0148] A traditional Chinese medicine composition for preventing and treating respiratory diseases in poultry. Compared with Example 1, 8 parts of loquat leaves are used instead of 8 parts of houttuynia cordata. That is, the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 35 parts of ephedra, 10 parts of fritillaria brevis, 10 parts of vitex foetida, 20 parts of apricot kernel, 20 parts of gypsum, 20 parts of liquorice, 8 parts of loquat leaves, 5 parts of scutellaria baicalensis extract, 15 parts of olive oil, and 3 parts of Tween-80.

[0149] The preparation method of the above-mentioned Chinese medicine composition is the same as that in Example 1.

[0150] Effect embodiment

[0151] 1. Content of extracted active ingredients in different Chinese medicine compositions

[0152] The Chinese medicine composition of the present invention is reasonably compatible with various drugs, aiming at achieving effective prevention and control of avian respiratory diseases through the synergistic effect of multiple ingredients. Due to the large amount of experimental data, the present invention has made multiple adjustments to the components, dosages and preparation methods of the Chinese medicinal materials in the composition and conducted experimental verification. The comparison results of the effective ingredient content extraction of Examples 1 to 9 and Comparative Examples 1 to 3 are listed here.

[0153] Samples were prepared according to the preparation methods of Examples 1 to 9 and Comparative Examples 1 to 3 in the specific embodiments, and the effective ingredient contents of ephedra, bitter almonds, and licorice in the traditional Chinese medicine composition of the present invention were described as follows:

[0154] (1) Determination of ephedrine content

[0155] The chromatographic conditions and system suitability test used octadecylsilane bonded silica gel as the filler; acetonitrile-0.1% phosphoric acid solution (containing 0.1% triethylamine) (3:97) as the mobile phase; and the detection wavelength was 207 nm. The theoretical plate number calculated based on the ephedrine hydrochloride peak should be no less than 4000.

[0156] Preparation of reference (i.e., standard) solution: Accurately weigh 1.2 mg of ephedrine hydrochloride reference solution and add 0.1 mol / L hydrochloric acid to a solution containing 24 μg per 1 mL. (Ephedrine hydrochloride, manufactured by China Food and Drug Administration, 100% purity)

[0157] Preparation of the test solution of the traditional Chinese medicine composition: accurately measure 1 mL of the traditional Chinese medicine composition, place it in a 50 mL volumetric flask, add 1 mL of concentrated ammonia test solution, add chloroform to the scale, weigh the weight, ultrasonicate for 20 minutes, cool, add chloroform to make up the lost weight, shake well, and filter; accurately measure 4 mL of the filtrate, recover the chloroform under reduced pressure at 60°C to dryness (rotary evaporation), dissolve the residue in 0.1 mol / L hydrochloric acid, place it in a 25 mL volumetric flask, wash the container with 0.1 mol / L hydrochloric acid solution in batches, combine the washings into the same volumetric flask, add 0.1 mol / L hydrochloric acid solution to the scale, shake well, and obtain.

[0158] Preparation of Chinese herbal medicine test solution: Take about 0.5045 g of ephedra fine powder, accurately weigh it, place it in a stoppered conical flask, accurately add 50 mL of 1.44% phosphoric acid solution, weigh the weight, ultrasonically treat (power 600 W, frequency 50 kHz) for 20 minutes, let cool, weigh it again, make up the lost weight with 1.44% phosphoric acid solution, shake well, filter, and take the filtrate.

[0159] Determination method: Accurately measure 10 μL of each reference solution and test solution, inject into liquid chromatography, and determine. Each 1 mL of this product contains not less than 0.30 mg of ephedra, calculated as ephedrine hydrochloride.

[0160] (2) Determination of amygdalin content

[0161] Determined according to high performance liquid chromatography (General Rule 0512).

[0162] Detection conditions: Acetonitrile-0.1% phosphoric acid solution (8:92) as the mobile phase; detection wavelength at 207 nm. The theoretical plate number calculated based on the amygdalin peak should be less than 7000.

[0163] Preparation of reference (i.e., standard) solution: Accurately weigh 4.2 mg of amygdalin reference solution and add methanol to a solution containing 41.16 μg per 1 mL. (Amygdalin, manufacturer: Chenguang Biological, purity >98%).

[0164] Preparation of test solution: Accurately measure 1 mL of the traditional Chinese medicine composition or accurately weigh about 0.25 g of bitter almond powder (passed through a No. 2 sieve), accurately weigh, and place in a stoppered conical flask. Accurately add 25 mL of methanol, stopper, weigh, and ultrasonically treat (power 250 W, frequency 50 kHz) for 30 minutes. Let cool, weigh again, make up the lost weight with methanol, shake well, filter, accurately measure 5 mL of the filtrate, place in a 50 mL volumetric flask, add 50% methanol to dilute to the scale, shake well, filter, and take the filtrate.

[0165] Determination method: Accurately aspirate 10-20 μL of reference solution and test solution respectively, inject into liquid chromatograph, and determine.

[0166] (3) Determination of ammonium glycyrrhizate content

[0167] Determined according to high performance liquid chromatography (General Rule 0512).

[0168] Detection conditions: Acetonitrile as mobile phase A, 0.05% phosphoric acid solution as mobile phase B; detection wavelength: 237 nm. The theoretical plate number calculated based on the ammonium glycyrrhizate peak should be no less than 5000.

[0169] Preparation of reference (i.e., standard) solution: Accurately weigh 4.0 mg of ammonium glycyrrhizate reference substance and add 70% ethanol to a solution containing 0.196 mg per 1 mL, yielding (weight of glycyrrhizic acid = weight of ammonium glycyrrhizate / 1.0207). (Ammonium glycyrrhizate, manufactured by Chenguang Biological, purity >98%).

[0170] Preparation of the test solution: Accurately measure 1 mL of the traditional Chinese medicine composition or accurately weigh about 0.2244 g of licorice powder (passed through a No. 3 sieve) and place it in a stoppered conical flask. Accurately add 100 mL of 70% ethanol, stopper it tightly, weigh it, and ultrasonically treat it (power 250 W, frequency 40 kHz) for 30 minutes. Let it cool, weigh it again, make up the lost weight with 70% ethanol, filter it, and take the filtrate to obtain the solution.

[0171] Determination method: Accurately aspirate 10-20 μL of reference solution and test solution respectively, inject into liquid chromatograph, and determine.

[0172] The results are shown in Table 1 and Figures 1 to 3As shown, there are differences in the contents of each active ingredient in the traditional Chinese medicine compositions of Examples 1 to 9 and Comparative Examples 1 to 3. From the perspective of formula adjustment, there are differences in the contents of active ingredients in Examples 1 to 8 and Comparative Examples 1 to 3, and the main difference is due to the different amounts of medicinal materials added; from the perspective of process adjustment, the content of active ingredients in Example 9 is significantly lower than that in other groups. Compared with the conventional water extraction process, the semi-bionic-enzymatic extraction process can increase the content of ephedrine hydrochloride by 19.9%, the content of amygdalin by 28.5%, and the content of ammonium glycyrrhizate by 6.7%. This shows that the semi-bionic-enzymatic extraction process adopted in the present invention has the advantage of promoting the dissolution of active ingredients.

[0173] Table 1 Statistics of the content of active ingredients extracted from various Chinese medicine compositions

[0174]

[0175]

[0176] 2. Comparative evaluation of the anti-inflammatory effects of different Chinese medicine compositions

[0177] Samples were prepared according to the preparation methods of Example 1 and Comparative Examples 1 to 3 of Examples 6 to 8 in the specific implementation manner, and the anti-inflammatory effects of the Chinese medicine compositions of different formulations of the present invention were described as follows.

[0178] Experimental design: 48 Kunming mice were randomly selected and divided into 8 experimental groups, corresponding to Example 1 of the present invention, Examples 6 to 8 Comparative Examples 1 to 3, and a modeling group (using normal saline), and administered by gavage (dosage 0.2 mL / 20 g) for 3 consecutive days. One hour after the last administration, xylene was evenly applied to the front and back of the right auricle of the mouse to induce inflammation (dosage 0.02 mL / mouse). After waiting for another 1 hour, the mice were killed by dislocating the neck, and the ears were cut off along the baseline of the auricle. A stainless steel punch with a diameter of 8 mm was used to punch holes symmetrically on the ears. The ear pieces were taken and weighed, and the swelling degree of the auricle of each group of mice was calculated according to the formula. (Auricle swelling degree = left ear mass – right ear mass)

[0179] Anti-inflammatory effect: The xylene-induced ear swelling experiment in mice, the results of ear swelling of each group of mice are shown in Table 2.

[0180] The experimental results showed that the ear swelling of mice in test group 1 (i.e., the Chinese medicine composition of Example 1) was significantly less than that in test groups 2 to 7 (P < 0.05), and extremely significantly less than that in test group 8 (P < 0.001). This shows that the anti-inflammatory activity of the Chinese medicine composition of Example 1 is significantly better than that of Examples 6 to 8, and the optimization of the medicinal material ratio further affects the active ingredient content and anti-inflammatory activity of the Chinese medicine composition; the anti-inflammatory activity of the Chinese medicine composition of Example 1 is better than that of Comparative Example 1 and Comparative Example 2. The anti-inflammatory effect of the prescription is weakened by not adding Chinese herbal medicines such as Scutellaria baicalensis extract and Houttuynia cordata. On the one hand, the lack of Scutellaria baicalensis extract significantly weakens the heat-clearing and detoxifying effect of the prescription. On the other hand, the significant reduction in the types of medicinal materials leads to insufficient synergy between the medicinal materials; the anti-inflammatory activity of the Chinese medicine composition of Example 1 is better than that of Comparative Example 3 (using loquat leaves instead of Houttuynia cordata). Although the effective ingredients in loquat leaves (such as amygdalin, ursolic acid, etc.) have certain anti-inflammatory effects, their anti-inflammatory effects are not as good as those of Houttuynia cordata, and the anti-inflammatory activity does not meet expectations.

[0181] Table 2 Comparative evaluation of ear swelling in each group of mice

[0182]

[0183] Note: In the table above, experimental group 1 was administered with the Chinese herbal composition of Example 1, experimental groups 2 to 4 were administered with the Chinese herbal compositions of Examples 6 to 8, experimental groups 5 to 7 were administered with the Chinese herbal compositions of Comparative Examples 1 to 3, and experimental group 8 was a modeling group using normal saline. Data marked with "*" indicate significant differences compared with Example 1, P < 0.05; data marked with "***" indicate extremely significant differences compared with Example 1, P < 0.001.

[0184] 3. In vivo evaluation of expectorant efficacy (mouse tracheal phenol red secretion experiment)

[0185] Under the influence of expectorants, the increase of bronchial secretions is promoted, thereby achieving the effect of diluting sputum and relieving the degree of bronchial obstruction. In this experiment, phenol red was injected as an indicator of bronchial secretions. The higher the concentration of phenol red in the bronchial lavage fluid, the better the expectorant effect of the drug.

[0186] Experimental design: 32 mice were randomly selected ( Figure 4), were divided into 4 groups, namely, Example 1 of the Chinese medicine composition of the present invention, Comparative Example 2, a positive drug group (dosage of ambroxol hydrochloride: 90 mg / kg), and a modeling group (normal saline). The mice were administered by gavage according to the dosage in Table 3, once a day, for 5 consecutive days. 30 minutes after the last administration, each group of mice was intraperitoneally injected with 2.5% phenol red solution at a dosage of 10 mL / kg. 60 minutes later, the mice were killed by spinal dislocation. A section of trachea from the thyroid cartilage to the bronchial branch of each group of mice was cut and placed in 2 mL of normal saline. 0.1 mL of 1 mol / L NaOH solution was added, and the mice were ultrasonically treated for 30 minutes. The OD value was measured at a wavelength of 546 nm using a microplate reader.

[0187] Table 3 In vivo expectorant efficacy evaluation groups and dosages

[0188]

[0189] The results of the in vivo expectorant efficacy evaluation in mice are shown in Tables 4 and Figure 5 The OD values of the groups were as follows: Example 1 group > positive drug group > Comparative Example 2 group > modeling group. Compared with the modeling group, the Chinese medicine composition of Comparative Example 2 can promote phenol red excretion as a whole, and the effect is significant (P < 0.05), but the phenol red excretion of the mice in Example 1 is extremely significantly increased (P < 0.001), which is better than that of the Chinese medicine composition of Comparative Example 2, indicating that the Chinese medicine composition of Example 1 of the present invention has a good expectorant effect.

[0190] Table 4 OD values of each group in the evaluation of expectorant efficacy in vivo

[0191]

[0192] Note: Data marked with "*" indicate significant differences compared with the model group, P < 0.05; data marked with "***" indicate extremely significant differences compared with the model group, P < 0.001.

[0193] 4. Evaluation of antitussive efficacy in vivo (ammonia-induced cough test in mice)

[0194] Model construction: Experimental mice were placed in a 1L beaker. A cotton ball soaked in 0.5mL of concentrated ammonia was placed in the beaker. The number of coughs in the mice was observed and counted within 3 minutes. The time from the start of observation to the first cough was recorded as the cough latency period.

[0195] Screening criteria: Patients with 10 to 80 coughs within 3 minutes, a latent period of 10 to 50 seconds, a good condition after coughing, and mild abdominal distension were selected as models for subsequent formal testing.

[0196] Coughing in mice is defined as an open mouth accompanied by a coughing sound, contraction of the chest and abdominal muscles, and twitching of the front of the body.

[0197] Ammonia-induced cough experiment: 40 Kunming mice were randomly selected and divided into 4 groups, namely, Example 1 group (Chinese medicine composition of the present invention), Comparative Example 2 group, positive drug group (pentoxyverine citrate, which has a selective inhibitory effect on the cough center and has an antitussive effect in clinical application, and its dosage is 30 mg / kg) and modeling group (normal saline). According to the dosage in Table 5, each group of mice were gavage-administered once a day for continuous administration. The model was established one hour after administration on the fourth day. The time of the first cough after modeling was observed and the number of coughs in the mice within 3 minutes was counted.

[0198] Table 5 In vivo antitussive efficacy evaluation groups

[0199]

[0200] The experimental results of the ammonia-induced cough experiment in mice are shown in Table 6 and Figures 6 and 7 As shown, the order of cough frequency is modeling group > positive drug group > comparative example 2 group > embodiment 1 group; the order of cough latency is embodiment 1 group > comparative example 2 group > positive drug group > modeling group. Compared with the modeling group, embodiment 1 can significantly reduce the number of coughs in mice after ammonia-induced cough (P < 0.001) and significantly prolong the latency (P < 0.05). Although comparative example 2 group and the positive drug group can also significantly reduce the number of coughs in mice, the overall effect is weaker than that of embodiment 1 group, and cannot significantly prolong the latency of cough in mice (P > 0.05). This shows that after screening and adding medicinal materials such as Houttuynia cordata and Scutellaria baicalensis extract, the synergistic effect of the components of the Chinese medicine composition of embodiment 1 of the present invention is enhanced, and it can fully regulate the tension of airway smooth muscle and the release of antiasthmatic mediators to achieve better antitussive effects.

[0201] Table 6 Number of coughs induced by ammonia and cough latency in each group

[0202]

[0203]

[0204] Note: Data marked with "***" indicate that the difference is extremely significant compared with the modeling group, P < 0.001. Data marked with "#" indicate that the cough latency period has a significant difference compared with the modeling group, P < 0.05.

[0205] 5. Evaluation of therapeutic efficacy (clinical verification on Meizhou flat-raised broiler chickens)

[0206] Experimental subjects: Shed #1 of a Magong broiler breeding farm in Meizhou, Guangdong ( Figure 8 2000 broiler chickens, 26 days old. Clinical diagnosis revealed obvious signs of panting with extended necks and unusual coughing (clicking sounds). Randomly selected chickens presented with fever. Autopsy revealed yellow sputum and opacified pleural sacs.

[0207] Experimental grouping: The chickens were randomly divided into four pens, each with about 500 birds, corresponding to experimental group 1, using the Chinese medicine composition of Example 1 of the present invention; experimental group 2, using the Chinese medicine composition of Comparative Example 2 of the present invention; experimental group 3, using the Chinese medicine composition of Example 1 in the published Chinese invention patent (patent No. CN106138392A); and a blank control group without any treatment.

[0208] Dosage regimen: The three TCM composition-administered groups were fed with 40 catties of concentrated drinking water twice, with 20 catties of water and 50 mL of the corresponding TCM composition added each time for 3 days. The blank control group was given normal water.

[0209] Test monitoring indicators:

[0210] Feed intake: The daily feed intake of each experimental group and the blank control group before and after administration was counted.

[0211] Number of deaths: The daily number of deaths in each test group and blank control group was counted before and after administration.

[0212] Number of coughs (including strange cries): Count the number of coughs (strange cries) in each test group and the blank control group in a quiet state within 3 minutes. Repeat the operation for three consecutive times; from 1 day before the test to the end of drug administration.

[0213] Number of chickens stretching their necks to breathe: Within 3 minutes, the number of chickens in each experimental group and the blank control group stretching their necks to breathe was counted in a quiet state. The operation was repeated three times in a row; the number of chickens was counted from 1 day before the experiment to the end of the drug administration.

[0214] Dissection evaluation: 1 day before administration and 1 day after the end of administration, 3 chickens were randomly selected from each test group and blank control group for dissection to observe the symptoms of trachea, air sac and lungs.

[0215] Organ disease scoring and efficacy evaluation criteria:

[0216] The chickens in each experimental group and the blank control group were dissected to observe the symptoms of the trachea, air sacs, and lungs. The anatomical symptoms were scored before and after administration. The scoring criteria are shown in Table 7.

[0217] In addition, the anatomical score is used as a criterion for judging the effect of drug administration:

[0218] Ineffective: After administration, the average score decreased by less than 10% compared with before administration.

[0219] Effective: After administration, the average score decreased by more than or equal to 10% compared with that before administration.

[0220] Table 7 Respiratory disease scores in chickens

[0221]

[0222] Changes in feed intake and mortality: Feed intake and mortality were monitored 2 days before dosing, 3 days after dosing, and 2 days after drug withdrawal. The results are shown in Table 8. The change ratios of feed intake and mortality relative to pre-dose after drug withdrawal 1 day are shown in Table 9, indicating that the administration of the Chinese medicine composition of Example 1 of the present invention can increase feed intake and reduce mortality in chickens.

[0223] Changes in the number of coughs and neck extensions: The number of coughs and neck extensions were monitored 1 day before administration, 3 days after administration, and 2 days after discontinuation of the drug. The results are shown in Tables 10 and 11: The number of coughs and neck extensions in the three experimental groups administered with the Chinese medicine composition gradually decreased, and there was a very significant decrease relative to the blank control group (P < 0.001). One day after discontinuation of the drug, the number of coughs in each group was in the order of blank control group > experimental group 2 > experimental group 3 > experimental group 1, among which the number of coughs in experimental group 1 decreased by 9.4 times relative to experimental group 3, which was a significant difference (P < 0.05). One day after discontinuation of the drug, the number of neck extensions in each group was in the order of blank control group > experimental group 2 > experimental group 3 > experimental group 1, among which the number of coughs in experimental group 1 decreased by 0.4 relative to experimental group 3, but the difference was not significant (P > 0.05). The above results suggest that the administration of the Chinese medicine composition according to Example 1 of the present invention can significantly alleviate the symptoms of respiratory diseases.

[0224] Comparison of anatomical results: The comparison of organ anatomical score results of the Chinese medicine composition of Example 1 of the present invention and other Chinese medicine compositions for the treatment of respiratory diseases is shown in Table 12. The proportion of symptom score reduction in each group is, test group 1> test group 2> test group 3> blank control group, but relative to the blank control group, after administration of the regimen of test group 1 (the medicine composition of Example 1 of the present invention), the symptom score of the respiratory organs decreased significantly (P < 0.001), and was significantly better than test group 3 (P < 0.05). Test group 2 also had a better decrease effect than test group 3, but it was not significant (P > 0.05). Some anatomical pictures show the results as follows Figure 9 、 Figure 10 The results indicate that the Chinese medicine composition of Example 1 of the present invention can effectively promote the recovery of respiratory organs, and has certain advantages over the published patents.

[0225] Table 8 Comparison of feed intake and mortality of various chicken groups

[0226]

[0227] Table 9 Changes in feed intake and mortality of chickens after drug withdrawal for 1 day relative to that before drug administration

[0228]

[0229] Table 10 Comparison of coughing frequency in each group of chickens

[0230]

[0231] Table 11 Comparison of the number of chickens stretching their necks in each group

[0232]

[0233] Note: In Tables 10-11, data marked with "***" indicate extremely significant differences compared with the blank control group, P < 0.001. Data marked with "#" indicate significant differences relative to experimental group 3, P < 0.05. Data marked with "##" indicate very significant differences relative to experimental group 3, P < 0.01. Data marked with "###" indicate extremely significant differences relative to experimental group 3, P < 0.001.

[0234] Table 12 The proportion of respiratory disease organ symptom scores that decreased in each group

[0235]

[0236] Note: In Table 12, data marked with "***" indicate extremely significant differences compared with the blank control group, P < 0.001. Data marked with "**" indicate very significant differences compared with the blank control group, P < 0.01. Data marked with "#" indicate significant differences compared with experimental group 3, P < 0.05.

[0237] In summary, based on classic prescriptions such as Ma Xing Shi Gan Tang, the traditional Chinese medicine composition of the present invention is obtained by optimizing the traditional formula and combining the semi-bionic-enzymatic hydrolysis technology preparation technology (significantly improving the extraction efficiency of the active ingredients of traditional Chinese medicine). The traditional Chinese medicine composition has a good therapeutic effect on respiratory diseases of livestock and poultry.

[0238] While the embodiments of the present invention have been described in detail above with reference to the accompanying drawings, the present invention is not limited to the embodiments described above. Various modifications may be made within the scope of knowledge possessed by a person skilled in the art without departing from the spirit of the present invention. Furthermore, the embodiments of the present invention and the features thereof may be combined with one another unless there is a conflict.

Claims

1. A Chinese medicine composition, prepared from the following raw materials: ephedra, fritillaria, vitex, apricot kernel, gypsum, liquorice, houttuynia cordata, scutellaria baicalensis extract and olive oil.

2. The Chinese medicine composition according to claim 1, characterized in that The scutellaria baicalensis extract is a water extract of scutellaria baicalensis.

3. The Chinese medicine composition according to claim 1, characterized in that The traditional Chinese medicine composition is prepared from raw materials including the following components in parts by weight: 10-50 parts of ephedra, 5-25 parts of fritillaria, 5-20 parts of vitex chinensis, 5-40 parts of apricot kernel, 10-30 parts of gypsum, 5-20 parts of houttuynia cordata, 10-35 parts of liquorice, 2-20 parts of scutellaria baicalensis extract, and 8-25 parts of olive oil.

4. The Chinese medicine composition according to any one of claims 1 to 3, further comprising Tween.

5. The method for preparing the Chinese medicine composition according to claim 4, comprising the following steps: The gypsum is mixed with a solvent, soaked, heated, extracted, and the medicinal solution A and gypsum residue are collected; the gypsum residue is mixed with the solvent and extracted again to obtain the medicinal solution B; Mixing ephedra, houttuynia cordata, liquorice, fritillaria and vitex with a solvent, adding a composite enzyme, and performing enzymolysis to obtain a medicinal solution C and a composite medicinal residue; The medicinal solution C, the composite medicinal residue, the medicinal solution A and the solvent are mixed, heated, and almonds are added for extraction to collect the medicinal solution D; the medicinal residue is mixed with the solvent and the medicinal solution B and extracted again to obtain the medicinal solution E; the medicinal solution D and the medicinal solution E are combined and concentrated to obtain the medicinal solution F; olive oil, scutellaria baicalensis extract and Tween are mixed and emulsified to obtain an emulsified system; The emulsified system is mixed with the medicinal solution F to obtain a Chinese medicine composition.

6. The preparation method according to claim 5, characterized in that The complex enzyme comprises cellulase, hemicellulase and pectinase; Preferably, the mass ratio of the cellulase, hemicellulase and pectinase is 1:(1-3):(1-4); Preferably, the added amount of the complex enzyme is 1% to 5% of the total mass of ephedra, houttuynia cordata, liquorice, fritillaria and vitex.

7. The preparation method according to claim 5 or 6, characterized in that: The enzymatic hydrolysis conditions are as follows: pH value is 4-6, temperature is 45-60° C., and enzymatic hydrolysis time is 0.5-2 h.

8. A medicine comprising the Chinese medicine composition according to any one of claims 1 to 4; Preferably, the drug further comprises a pharmaceutically acceptable excipient; The auxiliary material is preferably at least one of a filler, a disintegrant, a diluent, a lubricant, a binder, a wetting agent, a flavoring agent, a suspending agent, a solvent, a sustained-release agent, an emulsifier, an absorption promoter, a surfactant, a preservative, a pigment, a flavor and a solvent.

9. Use of the Chinese medicine composition according to any one of claims 1 to 4 or the drug according to claim 8 in at least one of (1) to (4): (1) Preparation of products for preventing and / or treating respiratory diseases in livestock and poultry; (2) preparing anti-inflammatory products; (3) Preparation of products that enhance the body / intestinal immunity of livestock and poultry; (4) Preparation of livestock and poultry farming products; Preferably, the livestock and poultry respiratory diseases include at least one of swine asthma, porcine contagious pleuropneumonia, porcine infectious atrophic rhinitis, porcine reproductive and respiratory syndrome, swine streptococcosis, swine plague, swine influenza, infectious bronchitis, infectious laryngotracheitis, and avian influenza.

10. A product comprising the traditional Chinese medicine composition according to any one of claims 1 to 4 or the medicine according to claim 8.

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