A traditional Chinese medicine composition for preventing and treating chicken bordetella and a preparation method and application thereof

Abstract

The application discloses a traditional Chinese medicine composition for preventing and treating chicken Bordetella, a preparation method and application thereof. The traditional Chinese medicine composition for preventing and treating chicken Bordetella comprises the following raw medicinal materials in parts by weight: one red 15-20 parts, Tianwen grass 15-20 parts, goldenrod 10-15 parts, Jixiang grass 10-15 parts, white yam 5-12 parts, Buddha's hand 5-12 parts and platycodon 5-10 parts. The traditional Chinese medicine composition adopts one red, Tianwen grass, goldenrod, Jixiang grass, white yam, Buddha's hand and platycodon for reasonable compounding, has the effects of clearing heat and cooling blood, relieving cough and asthma, and can effectively treat chicken Bordetella disease. The seven kinds of medicines are mixed to prepare an oral liquid, the seven kinds of medicines have a synergistic effect in the preparation process, the effects of the medicines are effectively exerted, and the effects of clearing heat and detoxifying, clearing heat and cooling blood, relieving cough and asthma are further enhanced. The composition is scientifically matched, has no obvious toxic side reaction and drug tolerance, and can provide a train of thought for solving the problem of antibiotic resistance.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for preventing and treating chicken Bordetella, and a preparation method and application thereof. BACKGROUND

[0002] Chicken Bordetella disease is a bacterial infectious disease in livestock and poultry breeding, which was first reported in Canada in the 1960s, and then occurred in various countries. As an environmental pathogenic bacterium, Bordetella exists in the in vivo of the ancestors, parent generation and commodity generation in the egg and broiler breeding, and the detection rate is as high as 20% to 60%. The disease can occur in the chicken flock under the condition of reduced resistance or secondary infection with other diseases, which seriously hinders the development of the poultry industry.

[0003] Chicken Bordetella belongs to Alcaligenaceae and Bordetella, and is gram-negative. It is observed as a small spherical rod under a microscope, with blunt ends, and the size is (0.2-0.5) μm x (0.5-2.0) μm. Most of them exist in a single dispersed state, do not produce spores, and have flagella all over the body. The in-vitro culture has low nutritional requirements and can grow on ordinary nutrient agar, and grows faster in serum-containing culture medium. The optimal culture temperature is 35-38℃. The resistance to external adverse factors is poor, and it can be killed by common disinfectants and conventional disinfection methods. It is not resistant to high temperature and can be killed in less than 15 minutes at 60℃, but can survive for a long time in a low-temperature environment.

[0004] The disease has infectivity to chickens at all stages, and the younger the age, the more susceptible. Young chickens and sexually mature chickens are most susceptible to infection. Infected chickens mainly show respiratory symptoms such as frequent coughing, snoring, panting and difficulty breathing, nasal mucus secretion, mouth opening, neck stretching, conjunctival cyanosis, tearing, and purple comb and whiskers. Most chickens eventually die of hypoxia due to insufficient oxygen. The disease is mainly horizontally transmitted through close contact, and can also be vertically transmitted through breeding eggs. After the breeding chickens are infected, the hatching rate of the breeding eggs is significantly reduced, the dead fetus rate is as high as 60% or more, and the weak chicks also increase. Infected chicks often have acute death. In addition to respiratory symptoms and systemic symptoms, many infected chickens also have ophthalmia, and finally suppurate, become blind, and seriously affect feeding and drinking water, with a mortality rate of 10% to 20%.

[0005] The disease can be diagnosed by the clinical signs of the sick birds, and the diagnosis can also be confirmed by laboratory tests. The nasal discharge, tracheal secretion or lung tissue of the sick birds can be collected by sterile cotton swab, and then the sample can be streaked on the modified McConkey agar plate or sheep blood agar plate, and incubated at 37℃ for 48h. The suspicious colonies can be picked up for staining and microscopic examination, and biochemical identification. If the suspicious colonies meet the characteristics of the Bordetella, the disease can be diagnosed. In addition to the microbial isolation method, the disease can also be diagnosed by serotype detection. The chicken Bordetella plate agglutination antigen can be used for serum antibody detection, or the chicken Bordetella positive serum can be used for plate agglutination test of isolated bacteria. If the result is positive, the disease can be diagnosed.

[0006] At present, the prevention and treatment of the disease is mainly to strengthen environmental disinfection and preventive medication. Many antibiotics can be used for the treatment of the disease. The commonly used antibiotics in clinic include compound amoxicillin, florfenicol, tilmicosin, doxycycline, ligomycin, sulfadiazine sodium and compound sulfamethoxazole. However, scholars found that the drug resistance rate of Bordetella isolated from clinic to 22 kinds of antibiotics in 10 categories was 48.57% to 85.71%. Among them, the Bordetella was more sensitive to tigecycline, florfenicol, tobramycin, gentamicin, kanamycin, tetracycline, doxycycline, and had a higher drug resistance rate to cefpirome, cefotaxime, ceftazidime, enrofloxacin, levofloxacin, norfloxacin, penicillin, ampicillin, amoxicillin, lincomycin, clindamycin, erythromycin, medomycin and fosfomycin, with a drug resistance rate of 48.57% to 85.71%. The large use of antibiotics can lead to drug resistance, drug residues and zoonosis, which makes the disease have important public health significance. Chinese herbal medicine and Chinese medicine compound preparation have good prevention and treatment effect on chicken colibacillosis, and have the advantages of low residue, not easy to produce drug resistance, etc. After use, it also will not affect the edible safety and food quality of livestock and poultry products, which meets the green breeding theme advocated by today's society, and has broad development prospects.

[0007] Although traditional Chinese veterinary medicine has a long history, it has limited expertise in diagnosing chicken diseases. This is because chickens in ancient times were primarily free-range, with small numbers, small-scale operations, and fewer diseases, making diagnosis and treatment more challenging. A comprehensive approach, combining clinical symptoms with visual inspection and questioning, and gathering information from various sources, forms the basis for accurate diagnosis and treatment. Bordetella infection in chickens primarily manifests as respiratory symptoms, such as frequent coughing, wheezing, shortness of breath, and difficulty breathing; nasal discharge; open-mouth breathing with neck extension; cyanosis and tearing of the conjunctiva; and purple discoloration of the comb and wattles. Most chickens eventually die from hypoxemia due to insufficient oxygen. In traditional Chinese veterinary medicine, this disease falls under the category of plague. According to traditional Chinese veterinary theory, when chickens are stressed, have insufficient feed nutrition, or are infected with other diseases, their vital energy (qi) is weakened, and their defensive qi (nutritive and defensive qi) is compromised, making them susceptible to external pathogens. This leads to fever, decreased appetite, depression, and ruffled feathers. External factors such as environmental changes, feed variations, and immunization can further promote the occurrence of this disease. In the early stages, the patient experiences paroxysmal coughing, which is frequent and worse at night, with bubbles in the nasal discharge. The disease progresses rapidly, quickly affecting the entire flock. Coughing, head shaking, and nasal shaking occur, especially during feeding. There is mucus in the mouth, difficulty breathing, rattling sounds in the throat, and cyanosis of the beard. Death often results from suffocation. The lungs govern qi and respiration, opening to the nose. They also govern the skin and hair, and are internally and externally related to the large intestine. When lung qi flows smoothly, it distributes the essence of food and water to the skin and hair, making the skin surface firm, the feathers glossy, and resistant to external pathogens. Weak lung qi weakens the body's defenses, making it susceptible to external pathogens, leading to colds, which in turn affect the lungs, causing symptoms such as a drowsy appearance with a retracted neck and ruffled feathers. When external pathogens invade the lung meridian, lung qi is damaged, the qi mechanism is disrupted, the dispersing and descending functions are impaired, and the water passages are not properly regulated. This leads to fluid retention and the accumulation of phlegm, resulting in symptoms such as shortness of breath, cough, and wheezing. Once infected with this disease, the mortality rate can reach 10% to 20%. Therefore, there is an urgent need to develop a traditional Chinese medicine composition for the prevention and treatment of Bordetella fowleri. Summary of the Invention

[0008] The purpose of this invention is to provide a traditional Chinese medicine composition for the prevention and treatment of Bordetella fowleri, its preparation method, and its application.

[0009] To achieve the above-mentioned objectives, the present invention adopts the following technical solution:

[0010] In a first aspect, the present invention provides a traditional Chinese medicine composition for preventing and treating Bordetella fowleri, comprising the following raw materials:

[0011] One-pointed red, Astronomical grass, Goldenrod, White peony, Lucky grass, Buddha's hand, Platycodon grandiflorus.

[0012] Furthermore, it includes the following active pharmaceutical ingredient in parts by weight:

[0013] 15-20 parts of *Symplocos rubra*, 15-20 parts of *Symplocos rubra*, 10-15 parts of *Solidago canadensis*, 5-12 parts of *Ampelopsis japonica*, 10-15 parts of *Hedyotis diffusa*, 5-12 parts of *Citrus medica*, and 5-10 parts of *Platycodon grandiflorus*.

[0014] Preferably, the raw medicinal materials include the following weight parts: one red 20 parts, astronomical grass 20 parts, goldenrod 15 parts, white 12 parts, leonurus 15 parts, Buddha's hand 12 parts, 6 parts of platycodon.

[0015] In a second aspect, the present application provides the use of the traditional Chinese medicine composition of the first aspect in the preparation of a medicine for preventing and / or treating chicken Bordetella.

[0016] In a third aspect, the present application provides a medicine for preventing and treating chicken Bordetella, comprising the traditional Chinese medicine composition of the first aspect and a medically acceptable excipient; the dosage form of the medicine is oral liquid, pill, powder, ointment, tablet, granule, lozenge, capsule, liquor or tincture.

[0017] In a fourth aspect, the present application provides a preparation method of the medicine for preventing and treating chicken Bordetella of the third aspect, and the dosage form of the medicine is oral liquid, comprising the following steps:

[0018] ① First, use water with a quality of 8-14 times the medicinal materials to soak the medicinal materials;

[0019] ② After heating to boiling at 100℃ constant temperature heater, extract for 1-3 hours, until the oil content in the detector no longer increases, collect the volatile oil after standing and layering, add 20%-40% of anhydrous sulfuric acid of the quality of essential oil to remove water, and reserve;

[0020] ③ Add water with a quality of 10-12 times the medicinal materials to the medicinal residues, decoct 1-3 times, each time for 1-2 hours;

[0021] ④ After filtration, concentrate the mixed medicinal liquid to a density of 0.8-1.5 g / mL, and a relative density of 0.8-1.5 g / cm 3 Add ethanol to make the alcohol content reach 60-90%, then store at 4℃ for 8-12 hours, centrifuge at 4 000 r / min for 15 minutes; the clarity is best; filter the precipitate and then rotary evaporate to recover ethanol;

[0022] ⑤ Add 1-2% Tween-80 by volume fraction to emulsify the volatile oil first, and then mix with the medicinal liquid to make the volatile oil completely dissolved;

[0023] ⑥ After adding a certain amount of purified water, adjust the pH to obtain a brown and clear oral liquid with a crude drug concentration of 0.8-1.5 g / mL.

[0024] Preferably, the preparation method comprises the following steps:

[0025] ① First, use water with a quality of 12 times the medicinal materials to soak the medicinal materials;

[0026] ② 100℃ constant temperature heater heating boiling extraction 1.5h, until the oil in the measuring device does not increase, after standing and separating, collecting the volatile oil, adding 20% of the mass of the essential oil of anhydrous sulfuric acid to remove water, and then standby;

[0027] ③ The residue is added with 12 times of water of the mass of the residue, and decocted twice, each time for 1h;

[0028] ④ After filtering, the mixed medicinal liquid is concentrated to a density of 1g / mL, and a relative density of 1.05g / cm 3 When the alcohol content reaches 60%, the ethanol is refrigerated and placed for 8-12h, centrifuged at 4 000r / min for 15min,

[0029] ⑤ Adding 1.5% of Tween-80 with a volume fraction to the volatile oil to emulsify first, and then mixing with the medicinal liquid, so that the volatile oil is completely dissolved;

[0030] ⑥ After adjusting the pH, a brown and clear oral liquid with a concentration of 1g / mL is obtained.

[0031] Further, the step ⑥ further comprises a filtering step, which adopts a G2 vertical filter funnel to filter, and after filtering, a clear oral liquid solution is obtained.

[0032] Further, the step ⑥ adopts sodium citrate to adjust the pH value to 5.5-7.0.

[0033] Further, the step ⑦ comprises: bottling, taking out after sterilization for 15min, and cooling to obtain the oral liquid with a crude drug concentration of 1g / mL.

[0034] The present application has the advantages and beneficial effects that:

[0035] The chicken infected by Bordetella avium mainly shows respiratory symptoms, such as frequent cough, snore, asthma and breathing difficulty, mucus secretion in the nasal cavity, open-mouth and neck breathing, conjunctival cyanosis and lacrimation, and purple comb and wattle. Most chickens eventually die of hypoxia due to oxygen deficiency. The disease belongs to the category of pestilence in traditional Chinese veterinary medicine. According to the theory of traditional Chinese veterinary medicine, when the chicken population is stressed, the feed is insufficient in nutrition or infected with other diseases, the body's own qi is insufficient, the nutrient and defensive qi is not fixed, the external pathogenic factor can take advantage of the situation, the epidemic toxin invades, and the chicken body temperature rises, the appetite decreases, the spirit is depressed, and the feathers are loose. The external factors such as environmental change, feed change and immunization can promote the occurrence of the disease. At the beginning of the disease, the cough is paroxysmal, and the cough is continuous. The nasal fluid has bubbles. The disease develops rapidly, and soon spreads to the whole population. Coughing, shaking head, and shaking nose, especially coughing during feeding, mucus in the oral cavity, breathing difficulty, and phlegm sound in the throat. The comb and wattle are cyanotic, and often die of asphyxia. The lung governs qi and is in charge of respiration, and opens the orifice in the nose. It governs the skin and hair, and is related to the large intestine. If the lung qi is unobstructed, the fine water and food can be distributed to the skin and hair, so that the muscle surface is fixed and the feathers are shiny, and the external pathogenic factor is not easy to invade. If the lung qi is weak, the external defense is not fixed, and it is easy to be invaded by the external pathogenic factor and cause cold, and then attack the lung, cause the neck to shrink and sleep, and the feathers to be loose. The external pathogenic factor invades the lung meridian, the lung qi is injured, the qi movement is disordered, the promotion and descent are not in place, the water channel cannot be regulated, the body fluid is not regulated, the water and liquid are condensed to form phlegm and drink, and thus lead to shortness of breath, cough and asthma and other water and liquid distribution disorders. The composition of the present application plays a role in clearing heat and cooling blood, relieving cough and asthma from the two aspects of clearing heat and cooling blood, and thus has good curative effect in the treatment test.

[0036] In the traditional Chinese medicine composition of the present application, one-point red, Tianwencao, one branch of yellow flower, white vine, jixiangcao, Buddha's hand and jiegeng are reasonably matched. One-point red is matched with Tianwencao, one branch of yellow flower and white vine to strengthen the effects of clearing heat and resolving toxins and cooling blood. Jixiangcao, Buddha's hand and jiegeng are matched to strengthen the effects of relieving cough and asthma and resolving phlegm and regulating qi. Experimental results show that the composition of the present application can effectively treat chicken Bordetella avium disease, and the effective rate is more than 90%.

[0037] The composition of the present application is reasonable. After the seven kinds of medicines are mixed, the preparation of the oral liquid is carried out. The seven kinds of medicines have a synergistic effect during the preparation process, which further enhances the effects of clearing heat and resolving toxins, clearing heat and cooling blood, relieving cough and asthma. The oral liquid prepared by the method of the present application preserves the volatile oil components. At the same time, the oral liquid is convenient for the chicken to drink water, avoids the inconvenience of other dosage forms, the drug effect is faster, can effectively treat chicken Bordetella avium disease, the effective rate is more than 90%, there is no drug resistance, and can provide a train of thought for solving the problem of antibiotic resistance. DETAILED DESCRIPTION

[0038] In a first aspect, the present application provides a traditional Chinese medicine composition for preventing and treating chicken Bordetella avium, which comprises the following raw medicinal materials:

[0039] Rhododendron simsii, Spilanthes acmella, Herba Epilobii, Morinda officinalis, Ophiopogon japonicus, Citrus medica, Platycodon grandiflorum.

[0040] Preferably, the following raw medicinal materials are included by weight:

[0041] Rhododendron simsii 15-20 parts, Spilanthes acmella 15-20 parts, Herba Epilobii 10-15 parts, Morinda officinalis 5-12 parts, Ophiopogon japonicus 10-15 parts, Citrus medica 5-12 parts, Platycodon grandiflorum 5-10 parts.

[0042] Preferably, the following raw medicinal materials are included by weight: Rhododendron simsii 20 parts, Spilanthes acmella 20 parts, Herba Epilobii 15 parts, Morinda officinalis 12 parts, Ophiopogon japonicus 15 parts, Citrus medica 12 parts, Platycodon grandiflorum 6 parts.

[0043] In a preferred embodiment, the medicine of the present application uses effective Chinese herbal medicine (Rhododendron simsii 20 grams, Spilanthes acmella 20 grams, Herba Epilobii 15 grams, Morinda officinalis 12 grams, Ophiopogon japonicus 15 grams, Citrus medica 12 grams, Platycodon grandiflorum 6 grams) per dose.

[0044] I. Raw materials (components)

[0045] (1) Rhododendron simsii, bitter, cool. Liver, lung, bladder meridian. Has the function of clearing heat and resolving toxins, removing blood stasis and swelling. It is suitable for upper respiratory tract infection, oral ulcer, pneumonia, mastitis, enteritis, bacillary dysentery, urinary tract infection, sore abscess, eczema, sprains and injuries. Rhododendron simsii contains chemical substances such as clarkes senecio alkaloid, hyperoside, quercetin, β-sitosterol, stigmasterol and palmitic acid. Pharmacological studies show that it has certain inhibitory effect on Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi. Modern clinical treatment is used for upper respiratory tract infection, pneumonia, mastitis, enteritis, bacterial dysentery, urinary tract infection, sore abscess and eczema. The amount of Rhododendron simsii can be 15-20 parts, preferably 20 parts.

[0046] (2) Spilanthes acmella, a plant of the Asteraceae family, Spilanthes acmella (L.) Murr., is used as a whole grass. It can be harvested all year round, fresh or dried. Nature and taste: pungent, warm. Function and treatment: detoxification and dampness, relieving cough and asthma, swelling and pain. It can be used for cold, cough, asthma, whooping cough, tuberculosis, and can also be used for digestive diseases, can treat dysentery, enteritis, and also for furuncle and abscess. In addition, rheumatoid arthritis, toothache, sprains and injuries can also be treated. Anti-tumor effect: the chloroform-soluble components and chloroform-insoluble components of the ethanol extract of the whole plant of Spilanthes acmella have certain cytotoxicity on colon cancer Colo-205 cells, nasopharyngeal carcinoma KB cells, cervical cancer HeLa cells, hepatoma HA22T cells, laryngeal epidermoid carcinoma Hep-2 cells, glioma GBM8401 / TSGH cells and melanoma H1477 cells. Spilanthes acmella extract also has obvious analgesic effect. The amount of Spilanthes acmella can be 15-20 parts, preferably 20 parts.

[0047] (3) Solidago decurrens Lour., a plant of the Asteraceae family. It is cool in nature and has a pungent and bitter taste. It enters the Lung and Liver meridians. The whole plant contains rutin, kaemferol-3-3rutinoside, leiocarposide, benzyl-2,6-dimethoxybenzoate, 3,5-dimethoxy-4-acetoxycinnamylangelate, and 2-cis,8-cis-matricariaester. It dispels wind and clears heat, and has antibacterial and anti-inflammatory effects. It is used for wind-heat colds; headaches; sore throats; coughs due to lung heat; jaundice; diarrhea; urinary tract infections; carbuncles and boils; and snake bites. The amount of goldenrod can be 10-15 parts, preferably 15 parts.

[0048] (4) *Heliotropium indicum*, an evergreen perennial herb with creeping rhizomes both underground and above ground, green in color, and leaves clustered at the top or nodes of the rhizome. It can be harvested year-round. The effects and uses of *Heliotropium indicum* include: clearing the lungs, relieving cough, regulating blood, tonifying the kidneys, detoxifying, and promoting bone healing. *Heliotropium indicum* has anti-inflammatory, antioxidant, antitussive, antiasthmatic, and expectorant pharmacological effects, and can be used in expectorant, antitussive, and antiasthmatic drugs, as well as drugs for clearing liver and gallbladder damp-heat, such as cough syrup, cough-clearing capsules, cough syrup capsules, liver-restoring granules, and liver-enhancing granules. The amount of *Heliotropium indicum* can be 10-15 parts, preferably 15 parts.

[0049] (5) *Ampelopsis japonica* (Thunb.) Makino, a plant belonging to the genus *Ampelopsis* of the Vitaceae family. It has a bitter and pungent taste, and is slightly cold in nature; it enters the heart and stomach meridians. It has the effects of clearing heat and detoxifying, reducing swelling and dissipating nodules, and promoting tissue regeneration. It is mainly used to treat carbuncles, boils, scrofula, burns, and chapped hands and feet. *Ampelopsis japonica* has a strong antibacterial effect and a strong antifungal effect. The various polyphenolic compounds it contains have strong anti-hepatotoxic effects and strong anti-lipid peroxidation activity. The amount of *Ampelopsis japonica* can be 5-12 parts, preferably 12 parts.

[0050] (6) Buddha's hand, for Rutaceae Citrus medica L. var. sarcodactylis Swingle dry fruit. The medicine taste is bitter, bitter, sour, warm; return to the liver. Have Shugan Jieyu, Liqi and middle, dry wet phlegm effect. Mainly for liver stagnation and liver stomach disharmony of chest and stomach distending pain, abdominal fullness, spleen and stomach qi stagnation of abdominal distension, vomiting, little food, cough for a long time, phlegm, chest pain. The influence of central nervous system: Buddha's hand alcohol extract was injected into the abdominal cavity of mice, the spontaneous activity was significantly reduced, and the sleep time of mice was significantly prolonged. In addition, Buddha's hand also has certain anti-inflammatory, antiviral, anticoagulant and hemostatic effect. The amount of Buddha's hand can be 5-12 parts, preferably 12 parts.

[0051] (7) Jiegeng, for the dry root of Platycodon grandiflorum (Jacq.) A. DC. of the family Platycodon grandiflorum. Bitter, pungent, flat; return to the lung. It has the effect of promoting lung, eliminating phlegm, benefiting the throat and pus. It is used for cough and phlegm, chest tightness, sore throat, hoarseness, lung abscess and pus. The direct stimulation of jiegeng saponin to the oral cavity, throat and gastric mucosa reflexively increases the secretion of bronchial mucosa, thereby diluting the sputum and making it easier to expel. Jiegeng has antitussive effect, enhances anti-inflammatory and immune function, and its anti-inflammatory intensity is similar to that of aspirin. Water extract can enhance the phagocytic function of macrophages, enhance the bactericidal ability of neutrophils, and improve the activity of lysozyme. It has a preventive effect on stress ulcers. Jiegeng crude saponin has sedative, analgesic and antipyretic effects, and can also lower blood sugar and cholesterol, and relax smooth muscle. Jiegeng saponin has strong hemolytic effect, but oral administration can be broken down in the digestive tract and lose hemolytic effect. The amount of jiegeng is 5-10 parts, preferably 6 parts.

[0052] II. Application

[0053] In a second aspect, the present application provides the use of the traditional Chinese medicine composition described in the first aspect above in the preparation of a medicine for preventing and / or treating chicken Bordetella.

[0054] III. Form and dosage form

[0055] In a third aspect, the present application provides a medicine for preventing and treating chicken Bordetella, comprising the traditional Chinese medicine composition described in the first aspect above and a medically acceptable excipient; the above-mentioned raw materials can be commercially available or prepared according to conventional methods in the art.

[0056] In one embodiment, the traditional Chinese medicine composition of the present application can be made into the form of Chinese patent medicine. The dosage form of Chinese patent medicine includes but is not limited to oral liquid, pill, powder, ointment, tablet, granule (congee), lozenge, capsule, wine, tincture. Preferably, the dosage form is oral liquid.

[0057] IV. Preparation method

[0058] In a fourth aspect, the present application provides a preparation method of the medicine for preventing and treating chicken Bordetella described in the third aspect, wherein the medicine is in the form of oral liquid, and the preparation method comprises the following steps:

[0059] ① The medicinal materials and water with a mass ratio of 8-14 are put into a volatile oil extractor to soak the medicinal materials for 1 hour;

[0060] ② After the water is heated to boiling by a constant temperature heater at 100 ℃, the extraction is carried out for 1-3 hours until the oil amount in the measuring device no longer increases, and then the volatile oil is collected after the static stratification, 20%-40% of anhydrous sulfuric acid of the mass of the essential oil is added to remove the water, and the mixture is used as a reserve;

[0061] ③ The medicinal residues are decocted with 10-12 times of water for 1-3 times, and each time is for 1-2 hours;

[0062] ④ The mixed medicinal liquid is concentrated to a density of 0.8-1.5 g / mL and a relative density of 0.8-1.5 g / cm 3 , and then ethanol is added to make the alcohol content reach 60-90%, and then the mixture is stored at 4 ℃ for 8-12 hours, centrifuged at 4 000 r / min for 15 minutes, and the best clarity is obtained; the precipitate is filtered and then rotary evaporated to recover the ethanol;

[0063] ⑤ The volatile oil is completely dissolved by adding 1-2% of Tween-80 with a volume fraction to emulsify the volatile oil and then mixing the emulsified volatile oil with the medicinal liquid;

[0064] ⑥ After a certain amount of purified water is added, the pH is adjusted, and the brown and clear oral liquid with a concentration of 0.8-1.5 g / mL is obtained.

[0065] In a preferred embodiment, the preparation method of the oral liquid for preventing and treating chicken Bordetella comprises the following steps:

[0066] ① The medicinal materials and water with a mass ratio of 12 are put into a volatile oil extractor to soak the medicinal materials for 1 hour;

[0067] ② After the water is heated to boiling by a constant temperature heater at 100 ℃, the extraction is carried out for 1.5 hours until the oil amount in the measuring device no longer increases, and then the volatile oil is collected after the static stratification, 20% of anhydrous sulfuric acid of the mass of the essential oil is added to remove the water, and the mixture is used as a reserve;

[0068] ③ The medicinal residues are decocted with 12 times of water for 2 times, and each time is for 1 hour;

[0069] ④ The mixed medicinal liquid is concentrated to a density of 1 g / mL and a relative density of 1.05 g / cm 3 , and then ethanol is added to make the alcohol content reach 60%, and then the mixture is stored at 4 ℃ for 8-12 hours, centrifuged at 4 000 r / min for 15 minutes;

[0070] 5. The volatile oil is completely dissolved by adding 1.5% Tween-80 and volatile oil to emulsify, and then mixing with the medicine solution;

[0071] 6. The pH is adjusted to obtain a brown and clear oral solution with a concentration of 1 g / mL.

[0072] Preferably, the step 6 further comprises a filtering step, which is filtered by a G2 vertical filter funnel, and a clear oral solution is obtained after filtering.

[0073] Preferably, the step 6 adjusts the pH value to 5.5-7.0 by sodium citrate.

[0074] Preferably, the step 7 is bottled, and then sterilized by a wet heat sterilization cabinet with a flow of saturated steam at a temperature of 100°C and a pressure of 0.8 MP for 15 minutes, and the oral solution with a concentration of 1 g / mL is obtained after cooling.

[0075] The technical solutions in the embodiments of the present application are described below. Obviously, the described embodiments are some of the embodiments of the present application, but not all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art belong to the scope of protection of the present application.

[0076] The experimental methods in the following embodiments are conventional methods, and are performed according to the techniques or conditions described in the literature in the art or according to the product instructions, unless otherwise specified. The materials, reagents and the like used in the following embodiments can be obtained from commercial channels, unless otherwise specified.

[0077] Experimental Example 1

[0078] Prescription process screening of traditional Chinese medicine composition

[0079] 1. Screening of the amount of distilled water:

[0080] One point red 20 g, Tianwengao 20 g, one branch yellow flower 15 g, Baiyin 12 g, Jixiangcao 15 g, Foche 12 g, and Jiegeng 6 g were selected, and 8 times, 10 times, 12 times, and 14 times of water of the mass of the medicinal materials were used for distillation, respectively.

[0081] The medicinal materials were loaded into a volatile oil extractor, 8-14 times of distilled water was added, and the constant temperature heater was heated to boiling for 1 h, and the results were that the volatile oils obtained by 8 times, 10 times, 12 times, and 14 times of water were 103.5 mL, 106.3 mL, 121.4 mL, and 123.1 mL, respectively. Therefore, from the perspective of energy saving, 12 times of water of the mass of the medicinal materials is the most suitable.

[0082] 2. Screening of the extraction time:

[0083] The amount of distilled water is fixed at 12 times the mass of the medicinal material, and the volatile oil is obtained by distillation after boiling at 100°C for 1 h, 1.5 h, 2 h, 2.5 h, and 3 h. The amounts of volatile oil obtained are 122.3 ml, 124.5 ml, 124.1 ml, 124.2 ml, and 123.9 ml, respectively. The amount of volatile oil does not increase significantly with the increase of time, and the optimal extraction time is 1.5 h.

[0084] 3. Screening of the amount of anhydrous sodium sulfate:

[0085] Anhydrous sodium sulfate in an amount of 20%, 30%, and 40% of the mass of the volatile oil is added to remove water, and the water content of the volatile oil is 7.03%, 7.06%, and 7.07% of the original volume, respectively. Therefore, the optimal amount of anhydrous sodium sulfate is 20%.

[0086] 4. Screening of the alcohol content:

[0087] The mixed medicinal liquid is concentrated to a density of 1 g / mL and a relative density of 1.05 g / cm 3 Ethanol is added to make the alcohol content reach 60%, 70%, 80%, and 90%, and then the mixture is stored at 4°C for 12 h, centrifuged at 4 000 r / min for 15 min, and the precipitate is filtered and then rotary evaporated to recover ethanol. The total flavonoid content is determined, and it is found that the flavonoid contents of the ethanol with alcohol contents of 60%, 70%, 80%, and 90% are 60%, 55%, 43%, and 40%, respectively. Therefore, the optimal alcohol content is 60%.

[0088] 5. Screening of the amount of Tween-80:

[0089] The volatile oil is emulsified with Tween-80 in a volume fraction of 1%, 1.5%, and 2%, and it is found that the clarity of the volatile oil solution is best when the volume fraction of Tween-80 is 1.5%. Therefore, the optimal concentration of Tween-80 is 1.5%.

[0090] Example 1 (powder)

[0091] The present example provides a traditional Chinese medicine composition for preventing and treating chicken Bordetella, which comprises the following raw medicinal materials in the following amounts:

[0092] One red 15 g, Tianwencao 15 g, One branch of yellow flower 10 g, Jixiangcao 10 g, Baiyan 5 g, Foche 5 g, Nai 10 g.

[0093] The preparation method of the present example is as follows: the above raw medicinal materials are mixed, crushed, and sieved through a 80-mesh sieve to obtain the traditional Chinese medicine composition for preventing and treating chicken Bordetella in the form of powder.

[0094] Example 2 (powder)

[0095] The present example provides a traditional Chinese medicine composition for preventing and treating chicken Bordetella, which comprises the following raw medicinal materials in the following amounts:

[0096] Yi-dianhong 20g, Tian-wengao 20g, Yi-zhenghuang 15g, Bai-yang 12g, Jixiangcao 15g, Fo-shou 12g, Jiegeng 6g.

[0097] The preparation method of this example is the same as that of Example 1.

[0098] Example 3 (oral liquid)

[0099] This example provides an oral liquid for preventing and treating chicken Bordetella, which comprises the following raw medicinal materials by mass:

[0100] Yi-dianhong 20g, Tian-wengao 20g, Yi-zhenghuang 15g, Bai-yang 12g, Jixiangcao 15g, Fo-shou 12g, Jiegeng 6g.

[0101] The preparation method of this example of an oral liquid for preventing and treating chicken Bordetella comprises the following steps:

[0102] ① The above medicinal materials and water in an amount of 12 times the mass of the medicinal materials are loaded into a volatile oil extractor to soak the above medicinal materials for 1 h;

[0103] ② After heating and boiling by a 100℃ constant temperature heater for 1.5 h, until the oil amount in the detector no longer increases, the volatile oil is collected after static stratification, 20% of anhydrous sulfuric acid by mass of the volatile oil is added to remove water, and the mixture is used as a reserve;

[0104] ③ The residue is decocted twice with water in an amount of 12 times the mass of the residue, each time for 1 h;

[0105] ④ The mixed medicinal liquid is concentrated to a density of 1 g / mL and a relative density of 1.05 g / cm 3 , ethanol is added to make the alcohol content reach 60%, and then the mixture is stored at 4℃ for 12 h, centrifuged at 4 000 r / min for 15 min, and the precipitate is filtered and then rotary evaporated to recover ethanol;

[0106] ⑤ 1.5% Tween-80 by volume fraction is added to emulsify the volatile oil, and then the mixture is mixed with the medicinal liquid to completely dissolve the volatile oil;

[0107] ⑥ The mixture is filtered by a G2 vertical funnel to obtain a clear oral liquid solution, the pH value of which is adjusted to 7.0 by sodium citrate to obtain a brown and clear oral liquid, and the concentration of the oral liquid is 1 g / mL;

[0108] ⑦ The oral liquid is bottled and sterilized in a wet heat sterilization cabinet at a flow saturation steam temperature of 100℃ and a pressure of 0.8 MP for 15 min, and then taken out and cooled to obtain an oral liquid with a crude drug concentration of 1 g / mL.

[0109] Example 4 (oral liquid)

[0110] The embodiment provides an oral liquid for preventing and treating chicken Bordetella, which comprises the following raw medicinal materials:

[0111] One red 20 grams, Tianwencao 20 grams, Lonicera japonica 15 grams, Jixiangcao 15 grams, Baiyan 12 grams, Buddha's hand 12 grams, and Platycodon 6 grams.

[0112] The embodiment provides a preparation method of the oral liquid for preventing and treating chicken Bordetella, which comprises the following steps:

[0113] ①The above medicinal materials and water with a mass ratio of 8:1 are put into a volatile oil extractor to soak the medicinal materials for 1 hour;

[0114] ②After being heated to boil by a 100 ℃ constant temperature heater, the volatile oil is extracted for 1.5 hours until the oil amount in the detector no longer increases, and then the volatile oil is collected after being separated by layering; 40% of anhydrous sulfuric acid of the mass of the volatile oil is added to remove water, and the obtained product is used as a reserve;

[0115] ③The medicinal residues are decocted with 8 times of water for two times, each time for 1 hour;

[0116] ④The mixed medicinal liquid is concentrated to a density of 1 g / mL and a relative density of 1.05 g / cm 3 , and then ethanol is added to make the alcohol content reach 90%; then the obtained product is stored at 4 ℃ for 12 hours, centrifuged at 4 000 r / min for 15 minutes, and then the precipitate is filtered and the ethanol is recovered by rotary evaporation;

[0117] ⑤1.5% of Tween-80 with a volume fraction is added to emulsify the volatile oil, and then the volatile oil is completely dissolved in the medicinal liquid;

[0118] ⑥The clear oral liquid solution is obtained by filtering through a G2 vertical fusion funnel, the pH value of the solution is adjusted to 7.0 by sodium citrate, and then the brown and clear oral liquid with a concentration of 1 g / mL is obtained;

[0119] ⑦The oral liquid with a crude drug concentration of 1 g / mL is obtained by storing the bottled product in a wet heat sterilization cabinet, sterilizing the product under the conditions of a flow saturated steam temperature of 100 ℃ and a pressure of 0.8 MP for 15 minutes, and then taking out and cooling the product.

[0120] Comparative example 1 (powder)

[0121] The comparative example provides a traditional Chinese medicine composition for preventing and treating chicken Bordetella, and the difference between the comparative example and the embodiment 2 is that the dosage of one red is 10 grams and the dosage of Tianwencao is 10 grams, and the rest is the same as the embodiment 2.

[0122] Comparative example 2 (powder)

[0123] The comparative example provides a traditional Chinese medicine composition for preventing and treating chicken Bordetella, and the difference between the comparative example and the embodiment 2 is that the dosage of one red is 30 grams and the dosage of Tianwencao is 30 grams, and the rest is the same as the embodiment 2.

[0124] Comparative Example 3 (powder)

[0125] The present comparative example provides a Chinese medicine composition for preventing and treating chicken Bordetella, which is different from Example 2 only in that the amount of Rudbeckia hirta is 150 g, the amount of Tetracera asiatica is 120 g, the amount of Reineckea carnea is 150 g, the amount of Citrus medica is 120 g, and the amount of Platycodon grandiflorum is 60 g.

[0126] Comparative Example 4 (powder)

[0127] The present comparative example provides a Chinese medicine composition for preventing and treating chicken Bordetella, which is different from Example 2 only in that Scutellaria baicalensis is used instead of Rudbeckia hirta, and Lonicera japonica is used instead of Tetracera asiatica, and the rest is the same as Example 2.

[0128] Comparative Example 5 (powder)

[0129] The present comparative example provides a Chinese medicine composition for preventing and treating chicken Bordetella, which is different from Example 2 only in that Isatis indigotica is used instead of Rudbeckia hirta, and Houttuynia cordata is used instead of Tetracera asiatica, and the rest is the same as Example 2.

[0130] Experimental Example 2 Inhibition of chicken Bordetella in vitro

[0131] 1. Experimental reagents:

[0132] Trypticase soy agar (TSA) is a raw material for preparing a culture medium for culturing chicken Bordetella;

[0133] Trypticase soy broth (TSB) is a broth for culturing chicken Bordetella, which is prepared according to the instructions.

[0134] Trypticase soy agar plate is a culture medium for culturing chicken Bordetella, which is prepared according to the instructions.

[0135] The above are all purchased from Hangzhou Tianhe Microbial Reagent Co., Ltd.

[0136] 2. Experimental strain:

[0137] The drug sensitivity test was performed on the clinically isolated chicken Bordetella (isolated from a chicken farm in Sichuan, identified as chicken Bordetella by bacterial 16S rDNA sequence analysis method, and preserved in the laboratory of the Department of Pharmacy, Sichuan Agricultural University).

[0138] 4. Experimental drugs:

[0139] The Chinese medicine compositions prepared in Examples 1-2 and Comparative Examples 1-5, and the Chinese medicine oral liquid prepared in Examples 3-4.

[0140] 5. Test method:

[0141] First, the traditional Chinese medicine composition powder prepared in Example 1-2 and Comparative Example 1-5 was decocted with 12 times the mass of water of the medicinal material, decocted twice for 1 hour each time, and the filtered medicinal liquid was mixed and concentrated to a density of 1 g / mL for standby use.

[0142] The decoction prepared in Example 1-2 and Comparative Example 1-5 and the traditional Chinese medicine oral liquid prepared in Example 3-4 were then diluted with sterilized water to 1000, 500, 250 and 125 mg / mL, respectively.

[0143] Cup and dish method for inhibiting bacteria

[0144] Preparation of bacterial suspension:

[0145] The freeze-preserved tube of chicken Pasteurella multocida in the ultra-low temperature refrigerator was opened, 0.02 mL was taken with a pipette and inoculated into a tube of tryptone soya broth (TSB), and incubated in a 37°C constant temperature incubator for 18-20 hours. After purification, 1 platinum ear was inoculated onto a tryptone soya agar (TSA) slant, and incubated in a 37°C constant temperature incubator for 16-18 hours. After taking out, it was stored in a 4°C refrigerator for standby use.

[0146] Before the antibacterial test, the strain was inoculated with an inoculation loop to inoculate 1 platinum ear into a tube of tryptone soya broth (TSB), and incubated in a 37°C constant temperature incubator for 16-18 hours. After taking out, the bacterial suspension was diluted with sterilized normal saline to 1x10 6 Cfu / mL. 0.1 mL of the Pasteurella multocida suspension with the optimal dilution turbidity determined in the pre-experiment was added to a tryptone soya agar plate, and immediately a L-shaped smearing rod was used to evenly smear the bacterial liquid on the agar surface. After the bacterial liquid was completely absorbed, the Oxford cup was slightly burned on an alcohol lamp, and then stood on the agar surface at equal intervals. Then different dilution multiples of the medicinal liquid were added to the Oxford cup, and the Oxford cup with added sterile normal saline was used as a blank control. The medicinal liquid was just filled and could not overflow. Two parallel repeats were performed, and a ceramic tile was covered, and then placed in a 7°C constant temperature incubator for 20-24 hours. After taking out, the size (diameter mm) of the inhibition zone was measured with a vernier caliper in a bright place. The average value of two repeated tests was taken.

[0147] Determination standard of antibacterial effect According to the Standard of Pharmacology of Traditional Chinese Medicine, the diameter of the inhibition zone ≥20 mm is extremely sensitive, ≥15 mm-<20 mm is highly sensitive, ≥10 mm-<15 mm is moderately sensitive, and <10 mm is not antibacterial. The test results are shown in Table 1.

[0148] Table 1 Inhibition results by the cup and dish method cm

[0149]

[0150] As can be seen from Table 1, both Example 3 and Example 4 have better antibacterial effect, but the antibacterial effect of Example 3 is the best, and it is still moderately sensitive at a concentration of 125 mg / mL. The antibacterial effect of Example 1 and Example 2 is better than that of Comparative Examples 1-5, but there is a gap compared with Example 3 and Example 4, which is due to the small amount of volatile oil component in the powder, so the antibacterial effect is decreased. The antibacterial effect of Comparative Example 1 is not as good as Example 2 because the dosage of radix ardisia japonica and astragalus-basedowii is reduced. The antibacterial effect of Comparative Example 2 is not as good as Example 2 because the dosage of radix ardisia japonica and astragalus-basedowii is increased. The antibacterial effect of Comparative Example 3 is not as good as Example 2 because there is no radix ardisia japonica and astragalus-basedowii. The antibacterial effect of Comparative Example 4 is not as good as Example 2 because scutellaria baicalensis and honeysuckle are used to replace radix ardisia japonica and astragalus-basedowii, and the compatibility is not good. The antibacterial effect of Comparative Example 5 is not as good as Example 2 because radix scophulariae is used to replace lonicera japonica, and radix hedygdis is used to replace radix ampelopsis, and the compatibility is not ideal.

[0151] Observation of the treatment effect of experimental example 3 on chickens with avian pasteurellosis

[0152] Experimental animals:

[0153] 320-day-old cage-bred Sichuan Fengyan Pasture Agricultural Development Co., Ltd. chickens that appeared listless, loss of appetite, constant sneezing, eyes and nose exuding colorless transparent liquid, tracheal collapse, submaxillary gland edema, and a large amount of nasal discharge, even nasal and tracheal obstruction were selected. Through preliminary diagnosis and using a cotton swab to take the chicken nasal mucus to directly smear McConkey culture medium or blood agar plate with 0.1% chloral hydrate, after 37°C culture overnight, 1mm diameter, bead-shaped, smooth and neat edge, and surface sparkling colonies appeared, and through bacterial 16S rDNA sequence determination method of Novo Source Biotechnology Co., Ltd., the disease of the Sichuan Fengyan Pasture Agricultural Development Co., Ltd. cage-bred 320-day-old egg-producing black-bone chickens was identified as avian pasteurellosis.

[0154] 1320 diseased Sichuan Fengyan Pasture Agricultural Development Co., Ltd. cage-bred 320-day-old egg-producing black-bone chickens with a body weight of 2.2±0.3 kg were selected and evenly divided into 11 groups, with 120 chickens in each group. Group 1 was a blank group without drug administration; group 2 was a florfenicol control group, administered with 15 mg / kg·d of florfenicol once; group 3 was Example 1, group 4 was Example 2, group 5 was Example 3, group 6 was Example 4, group 7 was Comparative Example 1, group 8 was Comparative Example 2, group 9 was Comparative Example 3, group 10 was Comparative Example 4, and group 11 was Comparative Example 5. Groups 3-11 were administered with 1 g of drug solution per 1 L of water according to the total water consumption of 120 chickens per day. Each group was administered for 5 consecutive days, and then the treatment was counted. The results are shown in Table 2.

[0155] Mortality = number of deaths ÷ total number * 100%; cure rate = number of cures ÷ number of cases * 100%; efficiency = number of survival ÷ total number * 100%.

[0156] Table 2 Treatment effect observation

[0157]

[0158] As can be seen from Table 2, without treatment, the mortality rate is as high as 35.83%, the mortality rate of Example 1 and Example 2 groups is lower due to the treatment with the inventive medicine powder. The mortality rate of Example 3 and Example 4 groups is far lower than that of other groups due to the treatment with the inventive medicine oral liquid, which preserves the volatile oil component and thus the drug effect is exerted faster. Among them, the treatment effect of Example 3 group is the best, the mortality rate is only 9.17%, and the cure rate and efficiency are the best, which are superior to the fluoroquinolone group, which may be related to the antibacterial and antitoxic effects of Example 3.

[0159] Comparative Example 1 has a lower dosage of Yidianhong and Tianwencao, so the mortality rate is higher than that of Example 2. Comparative Example 2 has a higher dosage of Yidianhong and Tianwencao, so the mortality rate is higher than that of Example 2. Comparative Example 3 has no Yidianhong and Tianwencao, so the mortality rate is higher than that of Example 2. Comparative Example 4 uses Huangqi and Jinyinhua to replace Yidianhong and Tianwencao, and the compatibility is not good, so the mortality rate is higher than that of Example 2. Comparative Example 5 uses Banlangen and Yuxingcao to replace Yizihuanghua and Baizhen, and the compatibility is not good, so the mortality rate is higher than that of Example 2.

[0160] The above describes the embodiments of the present application, but the present application is not limited to the above specific embodiments, which are only illustrative and not restrictive, and those skilled in the art can make many forms under the inspiration of the present application without departing from the scope of the present application and the scope protected by the claims, which are all within the protection of the present application.

Claims

1. A traditional Chinese medicine composition for preventing and treating avian Bordetella infection, characterized in that, Made from the following parts by weight of active pharmaceutical ingredient: 15-20 parts of *Symplocos rubra*, 15-20 parts of *Gynostemma pentaphyllum*, 10-15 parts of *Solidago canadensis*, 10-15 parts of *Gynostemma pentaphyllum*, 5-12 parts of *Ampelopsis japonica*, 5-12 parts of *Citrus medica*, and 5-10 parts of *Platycodon grandiflorus*.

2. The traditional Chinese medicine composition for preventing and treating avian Bordetella infection according to claim 1, characterized in that, Made from the following parts by weight of active pharmaceutical ingredient: 20 parts of *Polygonum multiflorum*, 20 parts of *Gynostemma pentaphyllum*, 15 parts of *Solidago canadensis*, 15 parts of *Hedyotis diffusa*, 12 parts of *Ampelopsis japonica*, 12 parts of *Citrus medica*, and 6 parts of *Platycodon grandiflorus*.

3. The use of the traditional Chinese medicine composition according to any one of claims 1-2 in the preparation of a medicament for the prevention and / or treatment of Bordetella fowleri infection.

4. A drug for preventing and treating avian Bordetella infection, characterized in that, It includes the traditional Chinese medicine composition according to any one of claims 1-3 and medically acceptable excipients; the dosage form of the medicine is oral liquid or powder.

5. A method for preparing a drug for preventing and treating avian bortezomib infection as described in claim 4, characterized in that, The drug is in the form of an oral liquid and includes the following steps: ① First, soak the medicinal materials in water that is 8-14 times their weight in volume; ② After heating to boiling in a 100℃ constant temperature heater, extract for 1-3 hours until the amount of oil in the measuring device no longer increases. After standing and separating into layers, collect the volatile oil, add 20%-40% anhydrous sodium sulfate (by weight of the volatile oil) to remove moisture, and then set aside for later use. ③ Add 10-12 times the weight of the dregs of the medicine to the dregs of the medicine, and decoct 1-3 times, 1-2 hours each time; ④ After filtration, the mixed medicinal solution is concentrated to a density of 0.8-1.5 g / mL and a relative density of 0.8-1.5 g / cm³. 3 Add ethanol to achieve an alcohol content of 60-90%, then refrigerate at 4°C for 8-12 hours, centrifuge at 4000 r / min for 15 min, filter the precipitate, and then rotary evaporate to recover the ethanol. ⑤ Add 1-2% by volume of Tween-80 and emulsify it with the volatile oil first, then mix it with the drug solution to completely dissolve the volatile oil; ⑥ Add purified water and adjust the pH to obtain a clear brown oral solution containing 0.8-1.5 g / mL of crude drug.

6. The preparation method according to claim 5, characterized in that, Includes the following steps: ① First, soak the medicinal materials in water that is 12 times their weight in water; ② After heating to boiling in a constant temperature heater at 100℃, extract for 1.5 hours until the amount of oil in the measuring device no longer increases. After standing and separating into layers, collect the volatile oil, add 20% anhydrous sodium sulfate (by weight of the volatile oil) to remove moisture, and then set aside for later use. ③ Add 12 times the weight of the dregs of the medicine to water and decoct twice, 1 hour each time; ④ After filtration, the mixed medicinal solution is concentrated to a density of 1 g / mL and a relative density of 1.05 g / cm³. 3 Add ethanol to bring the alcohol content to 60%, then refrigerate at 4°C and let stand for 8-12 hours. Centrifuge at 4000 r / min for 15 min. Filter the precipitate and then rotary evaporate to recover the ethanol. ⑤ Add 1.5% Tween-80 by volume and emulsify it with the volatile oil first, then mix it with the drug solution; ⑥ Add purified water and adjust the pH to obtain a clear brown oral solution containing 1 g / mL of crude drug.

7. The preparation method according to claim 5 or 6, characterized in that: Step ⑥ further includes a filtration step, in which a G2 sintered funnel is used for filtration, and a clear oral liquid solution is obtained after filtration.

8. The preparation method according to claim 5 or 6, characterized in that: In step ⑥, sodium citrate is used to adjust the pH value to 5.5-7.

0.

9. The preparation method according to claim 5 or 6, characterized in that, Including step ⑦: Bottle, sterilize for 15 minutes, then remove and cool.

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