WO2020155318A1 - 一种治疗家畜细菌性呼吸道疫病的中药制剂及其生产工艺 - Google Patents

一种治疗家畜细菌性呼吸道疫病的中药制剂及其生产工艺 Download PDF

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WO2020155318A1
WO2020155318A1 PCT/CN2019/078073 CN2019078073W WO2020155318A1 WO 2020155318 A1 WO2020155318 A1 WO 2020155318A1 CN 2019078073 W CN2019078073 W CN 2019078073W WO 2020155318 A1 WO2020155318 A1 WO 2020155318A1
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chinese medicine
respiratory diseases
livestock
parts
treatment
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PCT/CN2019/078073
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English (en)
French (fr)
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余波
张涛
姜玲玲
吴位珩
唐远江
杨莉
徐景峨
杨粤黔
孙启跃
刘镜
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贵州省畜牧兽医研究所
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Publication of WO2020155318A1 publication Critical patent/WO2020155318A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/904—Stemonaceae (Stemona family), e.g. croomia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents

Definitions

  • the invention belongs to the technical field of Chinese veterinary medicine, and particularly relates to a Chinese medicine preparation for treating bacterial respiratory diseases of livestock and its production process.
  • Bacterial respiratory diseases in pig farms are mainly caused by Haemophilus parasuis, Actinobacillus pleuropneumoniae and Mycoplasma.
  • Bacterial respiratory diseases in pig farms are mainly caused by Haemophilus parasuis, Actinobacillus pleuropneumoniae and Mycoplasma.
  • antibiotics such as cephalosporins, florfenicol powder, tilmicosin, and tylosin.
  • the excessive abuse of these antibiotics not only causes the production of drug-resistant strains and affects the efficacy, but also easily causes antibiotic residues and affects the safety of animal-derived foods.
  • Traditional Chinese medicine is a pure natural substance, containing a variety of active ingredients. It not only has antibacterial, bactericidal and antiviral effects, but also regulates and promotes the body’s immune function. It has non-specific anti-pathogenic microorganisms and is resistant to bacterial resistance. It has the characteristics of low toxicity, no residue or low residue, and it has dual functions of medicine and nutrient. Appropriate addition and use can prevent and treat animal diseases, increase feed utilization, improve animal product performance and improve the quality of livestock products, and reduce the use of chemicals, drugs and hormones in the breeding process, which is of great significance for ensuring the quality and safety of livestock products.
  • patent application CN201710827782.X discloses a traditional Chinese medicine composition for the treatment of respiratory diseases in chickens, including the following materials: Prunella vulgaris, loquat leaves, artemisia annua, Five skin wind; the preparation method of the present invention has a good therapeutic effect on chickens infected with respiratory diseases, the cure rate of bacterial respiratory diseases is as high as 91.5%, and has a good control effect on the disease, and no deaths have been found; The cure rate of viral respiratory diseases is as high as 78.0%, which effectively prevents the loss and food safety process caused by respiratory diseases during chicken breeding.
  • Patent application CN201210005117.X discloses a traditional Chinese medicine composition for the prevention and treatment of chicken kidney type infectious bronchitis, which includes: Daqingye, Anemarrhena, Scutellaria, Arctium lappa, Scrophulariaceae, Asarum, Ephedra, Peucedanum , Polygonum cuspidatum, Baibu, Asters, Astragalus, Licorice, Lycium barbarum, Cornus and Adenophora.
  • Patent application CN201811356225.5 discloses a pharmaceutical composition for improving human body resistance.
  • the raw material components of the pharmaceutical composition include iron-clad gold, Imperata cylindrica root, Ophiopogon japonicus, Lysimachia and ginger.
  • the invention also discloses a preparation method of the pharmaceutical composition for improving human body resistance, which is prepared by water extraction.
  • the pharmaceutical composition of the present invention can adjust the human body's antiviral and antibacterial ability, improve upper respiratory tract infection, inflammation, fever and other states, thereby improving human body resistance.
  • the pharmaceutical composition of the present invention has exact raw material components, exact curative effect, simple preparation method, and large-scale production.
  • the pharmaceutical composition of the present invention can be prepared in various dosage forms according to clinical needs.
  • Patent application CN201310447699.1 discloses a preparation method of Chinese patent medicine for oral decoction of traditional Chinese medicine for treating upper respiratory tract infection.
  • the raw material components of the traditional Chinese medicine of the oral decoction cassia twig, peony, ginger, jujube, raw licorice, Chuan Fritillaria, loquat leaves, moxibustion mulberry white bark, moxibustion Stemona, honeysuckle, reed root, Bupleurum, Huang Cen , Astragalus, parsnip, gypsum, Ophiopogon japonicus, wild chrysanthemum, perilla, big green leaves, nepeta panicles, mint, dandelion, houttuynia cordata, andrographis paniculata, violet dianthus, oldenlandia diffusa, Qianghuo, cohosh, Xinyi, Angelica dahurica, shegan, burdock
  • Patent application CN201510562379.X discloses a Chinese herbal medicine composition for preventing and treating chicken bronchitis and a preparation method thereof, and belongs to the technical field of livestock disease prevention and control and livestock feed additives.
  • the Chinese herbal medicine composition is prepared from 28 Chinese herbal medicines, such as Didancao, honeysuckle, menthol, chicken feces, solanum, araceae, houttuynia cordata, etc., and is scientifically compounded.
  • composition of the present invention not only has heat-clearing and detoxification , Removal of phlegm and dampness, relieving cough and asthma, nourishing yin, nourishing body fluid, nourishing lung and heart, nourishing yin and lowering fire, moisturizing dryness and smoothing the intestines, etc., through functional complementation and synergy, and whether it is used as drug treatment or feed
  • the application of additives can enhance the immunity of chickens, with energetic, bright feathers, significantly increased feed intake, and fast growth, which shows that it has a good effect on chicken bronchitis.
  • the Chinese medicinal preparations disclosed in the above-mentioned patent documents have a large number of Chinese medicinal flavors, but the curative effect is not high in the treatment of livestock respiratory diseases.
  • it is necessary to use antibiotics for treatment.
  • it is used to treat livestock bacterial respiratory tract.
  • the control effect is not ideal.
  • the taste of Chinese medicine is increased, and the processing technology is also complicated, which makes the cost of Chinese medicine higher.
  • the present invention provides a traditional Chinese medicine preparation for treating bacterial respiratory diseases of livestock and its production process.
  • the Chinese medicinal preparations in this application can effectively solve the problem of respiratory diseases caused by bacteria in livestock, and have little toxic and side effects on livestock, reduce the morbidity and mortality of respiratory diseases caused by bacteria in livestock, and reduce the use of antibiotics, thereby ensuring the quality of livestock products Safety.
  • a Chinese medicinal preparation for the treatment of bacterial respiratory diseases of livestock which is made of the following raw materials in parts by weight: 160-200 parts of Daqingye, 55-85 parts of Stemona, 160-200 parts of Scutellaria baicalensis Georgi, 50-75 parts of Guangzhi Gougecha .
  • the described Chinese medicinal preparation for the treatment of bacterial respiratory diseases of livestock is made from the following raw materials in parts by weight: 165-195 parts of Daqingye, 60-80 parts of Stemona, 165-195 parts of Scutellariae 55 to 70 servings of catechu.
  • the described traditional Chinese medicine preparation for treating bacterial respiratory disease of livestock is made from the following raw materials in parts by weight: 185 parts of Daqingye, 68 parts of Stomata, 185 parts of Scutellaria baicalensis Georgi, and 62 parts of Guangzhi Gou'ercha.
  • the production process of a traditional Chinese medicine preparation for the treatment of bacterial respiratory diseases of livestock includes the following steps: cleaning the large green leaves, scutellaria, scutellaria baicalensis, and glabra scutellariae, draining the surface water and mixing it evenly, Add water 28 to 33 times the weight of the raw material, reflux and extract for 1 to 3 hours at 85-100°C, collect the filtrate by filtration, concentrate the filtrate and spray dry, pass through a 70-100 mesh sieve, microwave sterilize, and cool to room temperature naturally
  • the traditional Chinese medicine preparation is prepared by packaging; the microwave sterilization process is that the microwave frequency is 2000-2400MHz, the power is 500-700W, the temperature is 55-70°C, and the material transmission speed is 0.8-1.5m/min.
  • the traditional Chinese medicine preparation prepared by the method is mainly used for the treatment of respiratory diseases of newborn livestock, and is particularly suitable for the treatment of respiratory diseases of piglets aged 10 to 30 days and calves aged 1 to 3 months.
  • inlet temperature is 140-145°C
  • outlet temperature is 80-85°C
  • liquid inlet speed is 55-65 mL ⁇ min-1
  • relative density of extract is 1.10-1.15.
  • the concentration is concentration under reduced pressure
  • the concentration temperature is 60-70°C
  • the vacuum degree is 0.07-0.09Mpa.
  • the concentration is to concentrate the filtrate to an extract with a relative density of 1.10 to 1.15 at 60°C.
  • the production process of a traditional Chinese medicine preparation for the treatment of bacterial respiratory diseases of livestock includes the following steps: cleaning the large green leaves, stalks, scutellaria baicalensis and glabra scutellariae, draining the surface water and mixing uniformly, Send to a pulverizer for pulverization, pass through a 10-30 mesh sieve, microwave sterilize, cool naturally to 25-30°C and package to prepare the traditional Chinese medicine preparation; the microwave sterilization process is that the microwave frequency is 2000-2400MHz, and the power 500 ⁇ 700W, temperature is 55 ⁇ 70°C, material conveying speed is 0.8 ⁇ 1.5m/min.
  • the traditional Chinese medicine preparation prepared by the method is mainly used for the treatment of the respiratory diseases of fattening livestock, and is particularly suitable for the treatment of the respiratory diseases of fattening cattle and pigs.
  • Daqingye The name of Chinese medicine. Bitter taste, cold in nature; return to the liver, heart, stomach and spleen channels. Indications: fever, erysipelas, sore throat, sore mouth and tongue, carbuncle swelling and poison. In recent years, this drug has been widely used in clinical practice. In addition to treating the above-mentioned symptoms, it can also be used for phlegm-heat depression of the lung, and yellowish phlegm; it is especially commonly used for Japanese encephalitis. It can be used for prevention and It can be used with Bupleurum, Yinhua, Forsythia, Ban GmbH, Scrophulariaceae, Habitat, etc.
  • Baibu (Latin scientific name: Stemonajaponica) is also known as Viburnum, a medicine for lice. It grows in areas between 300 meters and 400 meters above sea level. The root tuber can be used as medicine and is toxic. External use can repel mosquitoes, and internal use can relieve cough. It has high medicinal value. Sweet, bitter, lukewarm; return to the lung meridian. 1. Relieve cough and resolve phlegm. The ancients often used Stemona to treat chronic cough and excessive phlegm. Because of chronic cough, the lung Qi is deficient, and Baibu can regulate cough and resolve phlegm separately according to cold and heat. For wind-cold cough, use ginger; for lung-heat cough, use honey.
  • Baibu kills insects without depleting blood and energy, which is the most beneficial to people. However, a larger amount of insects is required to be effective. At the same time, compatibility with ginseng, tuckahoe, atractylodes, etc. can reduce the damage to the stomach and intestines caused by the bitter taste of Baibu. Externally used for head lice, body lice, pinworm, genital itching, ascariasis and other diseases.
  • Scutellaria (Latin scientific name: ScutellariabaicalensisGeorgi), also known as camellia root, earth gold tea root, is a perennial herb of the genus Scutellaria in the Lamiaceae. Bitter taste, cold in nature.
  • the root of Scutellaria baicalensis Georgi is used as medicine. It has a bitter taste and cold nature. It has the effects of clearing heat and dampness, purging fire and detoxification, hemostasis, and anti-fetus. Indications include febrile fever, upper respiratory tract infection, lung-heat cough, damp-heat yellow bile, pneumonia, dysentery, hemoptysis, red eyes, fetal movement, high blood pressure, carbuncle and boils.
  • the clinical antibacterial properties of Scutellaria baicalensis Georgi are better than Coptidis Rhizoma, and it does not produce drug resistance.
  • Guangzhi Gou'er Tea The name of Chinese medicine. It is the ground stem and root of BerchemiapolyphyllaWall.var.leiocladaHand.–Mazz. Born on hillsides, valley shrubs or forests between 600-1000 meters above sea level. Distributed in the Bashan area, the southern slope of the western section of the Qinling Mountains. Shrubs, up to 3 meters high. Old branches are grayish brown or yellowish brown, smooth, young branches alternate, densely covered with light brown pubescent.
  • the leaves are nearly leathery, ovate, ovate-elliptic or ovate-oblong, 2-3cm long, 1-2cm wide, round apex, short tip, round base, whole, top green, shiny,
  • the bottom is gray-green, both sides are glabrous; the pinnate veins are yellowish brown after drying, 7-9 pairs, bulging on the bottom; the petiole is 5mm long, and the top is brown pubescent, the flower is yellow-green, solitary, or 2-3 bunches Born in leaf axils, or arranged in racemes, the inflorescence axis is densely covered with brown pubescent.
  • the drupe is nearly cylindrical, up to 7mm long, about 3mm in diameter, reddish-brown, with persistent disc and calyx. Flowering from June to July, fruiting from August to September; the fruit matures the following year. Collected in summer and autumn and dried. Bitter taste, calm in nature, return to the lung meridian; it has the effects of relieving cough, expectorating, relieving asthma and calming nerves. Used for acute and chronic bronchitis, schizophrenia. "Xinhua Materia Medica Compendium”: "Roots, leaves, seeds. It has the functions of relieving cough, relieving asthma, calming nerves, regulating menstruation and promoting blood circulation. It is used for tuberculosis, chronic bronchitis, schizophrenia, etc.”.
  • Daqingye is used as the monarch medicine, which is the main medicine for clearing heat and detoxification
  • Scutellaria baicalensis is used as the minister medicine, which can assist in clearing heat and removing dampness
  • using Stemone as an adjuvant has the effect of promoting lungs and relieving cough
  • the medicine has the effect of relieving cough and relieving asthma, as well as clearing and detoxifying.
  • Daqingye and Scutellaria have antibacterial and antibacterial effects.
  • the four medicines are used in combination to clear away heat and detoxify, and relieve lung and cough.
  • the Chinese medicinal preparations in this application can effectively solve the problem of respiratory diseases caused by bacteria in livestock, and have little toxic and side effects on livestock, reduce the morbidity and mortality of respiratory diseases caused by bacteria in livestock, and reduce the use of antibiotics, thereby guaranteeing The quality and safety of livestock products.
  • This application provides two different preparation methods of traditional Chinese medicine preparations, and adopts different methods to prepare traditional Chinese medicine preparations for livestock of different ages, so that the prepared traditional Chinese medicine preparations are beneficial to the treatment of livestock diseases.
  • the function of the gastrointestinal tract of newly born livestock has not been fully developed, and it cannot absorb the directly crushed Chinese medicine plants.
  • the Chinese medicines on the market are not suitable for feeding. Especially for piglets aged 10 to 30 days, the gastrointestinal function is not fully developed and cannot absorb Chinese medicine preparations, and feeding may cause discomfort.
  • the traditional Chinese medicine is prepared by spray drying after water extraction, and the extract is more easily absorbed by piglets 10-30 days old.
  • the traditional Chinese medicine preparation prepared by the application has a good effect in treating respiratory diseases of livestock, with a cure rate of up to 94.5% and an effective rate of up to 96.5%.
  • a Chinese medicinal preparation for treating bacterial respiratory diseases of livestock is made from the following raw materials in parts by weight: 160 parts of Daqingye, 55 parts of Stomata, 160 parts of Scutellaria baicalensis Georgi, and 50 parts of Guangzhi Gougecha.
  • the traditional Chinese medicine preparation is applied to the treatment of respiratory diseases in fattening livestock.
  • a Chinese medicinal preparation for treating bacterial respiratory diseases of livestock is made of the following raw materials in parts by weight: 200 parts of Daqingye, 85 parts of Stomata, 200 parts of Scutellaria baicalensis Georgi, and 75 parts of Guangzhi Gou'ercha.
  • the microwave sterilization process is microwave
  • the frequency is 2000MHz, the power is 500W, the temperature is 55°C, and the material transfer speed is 0.8m/min;
  • the spray drying process is: the inlet temperature is 140°C, the outlet temperature is 80°C, and the liquid inlet speed is 55mL ⁇ min -1
  • the extract has a relative density of 1.10; the reflux extraction temperature is 85°C; the concentration is reduced pressure concentration, the concentration temperature is 60°C, the vacuum degree is 0.07Mpa
  • a Chinese medicinal preparation for treating bacterial respiratory diseases of livestock is made from the following raw materials in parts by weight: 165 parts of Daqingye, 60 parts of Stemona, 165 parts of Scutellaria baicalensis Georgi, and 55 parts of Guangzhi Gou'ercha.
  • the traditional Chinese medicine preparation is applied to the treatment of respiratory diseases in fattening livestock.
  • a Chinese medicinal preparation for treating bacterial respiratory diseases of domestic animals is made from the following raw materials in parts by weight: 195 parts of Daqingye, 80 parts of Stemona, 195 parts of Scutellaria baicalensis Georgi, and 70 parts of Guangzhi Gougecha.
  • the microwave sterilization process is microwave
  • the frequency is 2400MHz, the power is 700W, the temperature is 70°C, and the material transfer speed is 1.5m/min;
  • the spray drying process is: the inlet temperature is 145°C, the outlet temperature is 85°C, and the liquid inlet speed is 65mL ⁇ min -1
  • the relative density of the extract is 1.15;
  • the reflux extraction temperature is 100°C;
  • the concentration is reduced pressure concentration, the concentration temperature is 70°C, the vacuum degree is 0.
  • a Chinese medicinal preparation for treating bacterial respiratory diseases of livestock is made from the following raw materials in parts by weight: 185 parts of Daqingye, 68 parts of Stomata, 185 parts of Scutellaria baicalensis Georgi, and 62 parts of Guangzhi Gou'ercha.
  • the microwave sterilization process is microwave The frequency is 2200MHz, the power is 600W, the temperature is 62°C, and the material transfer speed is 1.1m/min;
  • the spray drying process is: the inlet temperature is 143°C, the outlet temperature is 83°C, and the liquid inlet speed is 60mL ⁇ min -1
  • the extract has a relative density of 1.12; the reflux extraction temperature is 92°C; the concentration is reduced pressure concentration, the concentration temperature is 65°C, the vacuum degree is 0.08M
  • Example 1 The difference from Example 1 is that the raw materials of the traditional Chinese medicine preparation for the treatment of bacterial respiratory diseases of livestock are Daqingye, Stemona and Scutellaria, and other conditions remain unchanged.
  • Example 1 The difference from Example 1 lies in that the raw material of the Chinese medicinal preparation for treating bacterial respiratory diseases of domestic animals is Guangzhi Goucate, and other conditions remain unchanged.
  • Experimental groups 1 to 5 were prepared according to Examples 1 to 5 of this application.
  • the traditional Chinese medicine preparations obtained were used for treatment.
  • Experimental groups 6-10 used the traditional Chinese medicines prepared in Comparative Examples 1 to 5, and experimental group 11 was fed with boiled water as the control group.
  • the medicine was fed 3 times a day, with a distance between each experimental group. Do not transmit diseases to each other, and the feeding and management methods are the same. After 7 days of feeding, the recovery of each group of experimental piglets was counted.
  • Table 1 The experimental results are shown in Table 1 below.
  • Example 1 186 head 189 head 11 heads 3% 93.5% 94.5%
  • Example 2 185 head 187 head 13 heads 4% 92.0% 93.5%
  • Example 3 187 head 190 head 10 heads 2% 93.0% 95.0%
  • Example 4 186 head 191 head 9 heads 3% 93.5% 95.5%
  • Example 5 189 head 193 head 7 heads 1% 94.5% 96.5% Comparative example 1 157 head 162 heads 38 heads 33% 80.5% 81.0% Comparative example 2 163 head 169 head 31 heads 28% 82.0% 84.5% Comparative example 3 156 heads 163 head 37 heads 33% 77.0% 81.5% Comparative example 4 157 head 161 head 39 heads 34% 75.5% 80.5% Comparative example 5 159 heads 170 head 30 heads 27% 83.0% 85.0% Control group 2 heads 3 heads 197 head 188% 1.0% 1.5%
  • Comparative Example 1 The raw materials of Comparative Example 1 were not added with Guangzhi Gou'er tea, and the Daqingye, Stemone and Scutellaria baicalensis did not have the Guangzhi Gou'er tea to enhance antibacterial and antibacterial effects, and its efficacy was significantly worse than that of the examples of the application; Comparative Example 2 Guangzhi Gou'er Tea is not supplemented by Daqingye, Stemone and Scutellaria, and its medicinal effect is obviously worse than that of the examples of this application; Comparative Examples 3 and 4 Chinese medicines are made by mixing Daqingye, Stemone, Scutellaria and other medicinal flavors, lacking bright branches.
  • Catechu has enhanced antibacterial and antibacterial effects, and its efficacy is obviously worse than that of the examples of this application;
  • Comparative Example 5 uses iron-coated gold and other traditional Chinese medicines to be mixed into traditional Chinese medicine. Although its efficacy is better than other comparative examples, it still has no effect. The effect is better than the embodiment of this application. It can be seen that only by adopting the formula and preparation method of the present application, the efficacy of the prepared traditional Chinese medicine will be better in the treatment of bacterial respiratory diseases.
  • Florfenicol and Ceftiofur are products of Shandong Enkang Pharmaceutical.
  • Each 500 grams of traditional Chinese medicine preparations contains 185 grams of Daqingye, 68 grams of Stemona, 185 grams of Scutellaria baicalensis Georgi, and 62 grams of Guangzhi Gougecha.
  • mice with a body weight of 20 ⁇ 2g, and randomly divide them into a treatment group and a blank control group. Each group has 20 mice, half male and half.
  • the drug group is given the Chinese medicine prepared by this application once at 5g/kg.
  • the blank control group was given normal saline at a time of 5g/kg, and observed for 14 days, and recorded the reaction of the mice (such as: the time of symptom onset, aggravation, reduction or death, the number of animals that reacted, calculation of animal mortality, etc.) , Count the death of mice. The surviving mice were sacrificed on the 14th day, and the organs of the mice were visually observed after dissection.
  • mice During the entire observation period, none of the mice died, and none of the mice in each group showed abnormal performance. They were in good mental state, active and flexible, their fur was shiny, their eyes and mucous membranes were unchanged, breathing was not abnormal, and there were no abnormalities in the central nervous system. The dissection showed no obvious visual changes, indicating that the traditional Chinese medicine preparation prepared in this application has no obvious toxic and side effects on mice, and the traditional Chinese medicine preparation belongs to the non-toxic level.
  • a Chinese medicinal preparation for treating bacterial respiratory diseases of livestock is prepared to a concentration of 1 g/mL based on the crude drug amount.
  • the concentration of ceftiofur was 20ug/mL and the concentration of florfenicol was 20ug/mL.
  • Dilution of strains take the hatched strains and dilute 10 7 of each strain.
  • a traditional Chinese medicine preparation, ceftiofur, and florfenicol for the treatment of bacterial respiratory diseases of livestock, is subjected to a double dilution method.
  • MIC value is the minimum inhibitory concentration, the smaller the MIC value is It shows that the fewer drugs needed to inhibit bacteria, the better the drug effect).
  • Table 2 The results of the in vitro antibacterial test are shown in Table 2 below.
  • High-dose group Chinese medicine preparations are diluted and administered (equivalent to 400 mg/ml crude drug content, and the dosage is equivalent to 4000 mg/kg body weight of crude drug).
  • Middle-dose group the high-dose group of traditional Chinese medicine preparations, add physiological saline, dilute 1:2, and administer after dilution (equivalent to crude drug content 200mg/ml, administration dose equivalent to crude drug 2000mg/kg body weight).
  • Low-dose group high-dose anti-diarrheal veterinary group, added with physiological saline, diluted 1:4, and administered after dilution (equivalent to crude drug content of 100mg/ml, administration dose equivalent to crude drug of 1000mg/kg body weight).
  • Positive control group florfenicol was used as the positive material, and the dosage was 20 mg/kg.
  • the florfenicol was produced by Shandong Enkang Pharmaceutical, and the batch number was 20180915.
  • the mycoplasma group except for the blank control group without treatment, the mycoplasma group, Haemophilus parasuis group, Actinobacillus pleuropneumoniae group, saline group, positive control group, high-dose Chinese medicine group, middle-dose Chinese medicine group, low-dose Chinese medicine group
  • the bacteria were inoculated by nasal drops for 3 consecutive days; the mixed bacteria group was inoculated by intranasal drops and abdominal injection with a concentration of 3 ⁇ 108 bacteria/mL, and the bacteria were inoculated by nasal drops and injections for 3 consecutive days; SPF Kunming mice On the 3rd day after the inoculation of the bacteria liquid, the gastric administration was started, and the gastric administration was continued for 7 days to observe the therapeutic effect.
  • the in vivo therapeutic effects of the low, medium, and high-dose Chinese medicine groups of this application are statistically significant (P ⁇ 0.05 or 0.01), indicating that the Chinese medicine preparation group has certain antibacterial effects in vivo.
  • the in vivo bacteriostatic pharmacodynamic study results of the Chinese medicinal preparation of this application on SPF Kunming mice infected with Mycoplasma are shown in Table 3 below.
  • the in vivo bacteriostatic effect on SPF Kunming mice infected with Haemophilus parasuis The results of the pharmacodynamic study are shown in Table 4 below.
  • Chinese medicine low-dose group 10 Chinese medicine preparation 100mg/mL 7
  • Chinese medicine dose group 10 Chinese medicine preparation 200mg/mL 2 only Chinese medicine high-dose group 10
  • Group Number of experiments Gavage drugs Number of deaths Blank control group 10 / 0 only Haemophilus parasuis group 10 / 8 Saline group 10 To 8 Positive control group 10 Florfenicol 2 only Chinese medicine low-dose group 10 Chinese medicine preparation 100mg/mL 6 Chinese medicine dose group 10 Chinese medicine preparation 200mg/mL 3 Chinese medicine high-dose group 10 Chinese medicine preparation 400mg/mL 3
  • Group Number of experiments Gavage drugs Number of deaths Blank control group 10 / 0 only Actinobacillus pleuropneumoniae group 10 / 9 Saline group 10 To 9 Positive control group 10 Florfenicol 1 Chinese medicine low-dose group 10 Chinese medicine preparation 100mg/mL 8 Chinese medicine dose group 10 Chinese medicine preparation 200mg/mL 3 Chinese medicine high-dose group 10 Chinese medicine preparation 400mg/mL 4
  • Group Number of experiments Gavage drugs Number of deaths Blank control group 10 / 10 Mixed bacteria group 10 / 10 Saline group 10 To 10 Positive control group 10 Florfenicol 0 only Chinese medicine low-dose group 10 Chinese medicine preparation 100mg/mL 8 Chinese medicine dose group 10 Chinese medicine preparation 200mg/mL 2 only Chinese medicine high-dose group 10 Chinese medicine preparation 400mg/mL 2 only
  • Multi-dose levels of administration were used for the study, and 32 piglets were selected, half of which were male and female, and randomly divided into 4 groups with 8 pigs in each group.
  • the experiment has the following experimental groups and doses:
  • 1 times the maximum recommended dose is 0.5 g/mL per piglet per kilogram body weight of the traditional Chinese medicine preparation prepared in this application.
  • Results The test piglets were alive and healthy, with normal clinical manifestations; necropsy showed that no obvious gross lesions were seen in the test pigs in each group, and there were no abnormal microscopic pathological changes in the animal organs from the 5-fold dose group; In terms of blood physiological and biochemical indicators, there were no significant differences in the indicators in the 1-fold recommended dose group, 3-fold recommended dose group, and 5-fold recommended dose group compared with the blank control group. The results show that the traditional Chinese medicine preparation prepared in this application has good safety and tolerance to piglets when used at the recommended dosage.
  • Case 1 A bovine respiratory disease occurred during the introduction of cattle in Bijie City, Guizhouzhou Province, which was diagnosed as mycoplasma infection by the laboratory, with a total of 110.
  • the Chinese medicine preparation prepared in this application was used for treatment at 0.5g per kilogram of body weight.
  • the treatment was The medicine was mixed in the feed, and after 7 days of continuous treatment, the condition of 17 cattle improved, 99 cattle were cured, and the effective rate was 92.9%.
  • Case 2 A piglet respiratory disease occurred in a pig farm in Guiyang City, Guizhouzhou Province, and was diagnosed as a mixed infection of Haemophilus parasuis and Actinobacillus pleuropneumoniae in total, 48 in total.
  • the Chinese medicine preparation prepared in this application was used. The treatment was performed at 0.5g per kilogram of body weight. The treatment was to prepare the drug at 0.5g/mL for intragastric administration. After 7 days of continuous treatment, 8 piglets improved in condition and 43 were cured. The effective rate was 91.7%.
  • the raw materials used in this application are scientific and reasonable, and the flavors of traditional Chinese medicines used are small, and the preparation process is simple, which reduces the production cost of traditional Chinese medicines and has obvious clinical treatment effects. It is a powerful substitute for antibiotics and chemicals. Good antibacterial and antibacterial effects, can effectively solve the problem of domestic animal respiratory diseases caused by bacteria, and have little toxic and side effects on domestic animals, reduce the morbidity and mortality of domestic animal respiratory diseases caused by bacteria, and reduce the use of antibiotics, Thereby ensuring the quality and safety of livestock products.

Abstract

一种治疗家畜细菌性呼吸道疫病的中药制剂，其特征在于，由以下重量份的原料制成：大青叶160～200份、百部55～85份、黄芩160～200份、光枝勾儿茶50～75份。该中药制剂具有抗菌、抑菌效果，用于解决家畜因细菌引起的呼吸道疾病问题。

Description

一种治疗家畜细菌性呼吸道疫病的中药制剂及其生产工艺 技术领域
本发明属于中兽药技术领域，尤其涉及一种治疗家畜细菌性呼吸道疫病的中药制剂及其生产工艺。
背景技术
近年来，由于集约化养殖规模的扩大，家畜细菌性呼吸道疫病愈发严重，发病率通常在30％～70％，病死率高达15％～20％。由于养牛场大量引种，在引种时，牛容易产生应激，继而发生支原体病和巴氏杆菌病。而猪场细菌性呼吸道疫病主要由副猪嗜血杆菌、猪传染性胸膜肺炎放线杆菌、支原体引起。现阶段，这些疾病的防治主要依赖抗生素，如头孢、氟苯尼考粉、替米考星、泰乐菌素等。这些抗生素的大量滥用不仅造成耐药菌株的产生，影响疗效，同时易造成抗生素残留，影响动物源食品安全。
中药是纯天然物质，含有多种活性成分，不但具有抑菌、杀菌和抗病毒作用，而且能够调节、促进机体的免疫功能，具有非特异性抗病原微生物作用，具有不易产生细菌耐药性、低毒、无残留或低残留等特点，兼有药物与营养剂双重功能。适当添加使用可预防和治疗动物疾病，提高饲料利用率，提高动物产品性能和改善畜产品质量，减少养殖过程中化学物质、药物和激素的使用，对于保障畜产品质量安全有着重要意义。
目前，专门用于治疗家畜呼吸道疾病的中药有一些文献报道，例如：专利申请CN201710827782.X，公开了一种治疗鸡呼吸道疾病的中药组合物，包括以下原料：夏枯草、枇杷叶、青蒿、五皮风；本发明制备的药剂方法，对于鸡感染呼吸道疾病具有很好的治疗效果对细菌型呼吸道疾病的治愈率高达91.5％，并对病 情有很好的控制作用，没有发现死亡例；对病毒型呼吸道疾病的治愈率高达78.0％，有效地防止了鸡养殖过程中由于感染呼吸道疾病带来的损失和食品安全过程。
专利申请CN201210005117.X，公开了一种用于防治鸡肾型传染性支气管炎的中药组合物，其包括：大青叶、知母、黄芩、牛蒡子、玄参、细辛、麻黄、前胡、虎杖、百部、紫苑、黄芪、甘草、枸杞子、山茱萸和南沙参。采用这种中药组合物对患有鸡肾型传染性支气管炎的鸡的防治具有疗效显著，不易复发，服用方便，无毒副作用，使用安全，细菌难以产生耐药性，避免了兽药残留和社会公害的发生。
专利申请CN201811356225.5，公开了一种提高人体抵抗力的药物组合物，所述药物组合物的原料组份包括铁包金、白茅根、麦冬、金钱草和生姜。本发明还公开了一种提高人体抵抗力的药物组合物的制备方法，所述方法通过水提制备而成。本发明所述的药物组合物能够调节人体抗病毒及抗菌能力，改善上呼吸道感染、发炎及发热等状态，从而提高人体抵抗力。本发明所述的药物组合物的原料组份确切，疗效确切，制备方法简单，可大规模生产。本发明所述的药物组合物可根据临床需要制备多种剂型。
专利申请CN201310447699.1，公开了一种治疗上呼吸道感染的中药口服汤剂中成药的制备方法。所述口服汤剂的中药原料组分：桂枝、芍药、生姜、大枣、生甘草、川贝母、枇杷叶、灸桑白皮、灸百部、金银花、芦根、柴胡、黄岑、黄芪、防风、生石膏、麦冬、野菊花、紫苏、大青叶、荆芥穗、薄荷、蒲公英、鱼腥草、穿心莲、紫花地丁、白花蛇舌草、羌活、升麻、辛夷、白芷、射干、牛蒡子、午香草、桔梗、板蓝根、连翘、天花粉、诃子、灸麻黄、山豆根、灸款冬花，且水煎煮而成中药口服汤剂；而所述中成药制备方法的步骤是，称重，炒药，灸药，萃取黄岑苷，收集蒸馏液，水煮余药，乙醇浓缩，加水过滤，滤液分装。具有配方合理，制备方法科学，疗效显著等特点。
专利申请CN201510562379.X，公开了一种防治鸡支气管炎的中草药组合物及其制备方法，属于家畜疾病防治及家畜饲料添加剂的技术领域。该中草药组合物，由地胆草、忍冬藤、薄荷脑、鸡屎藤、龙葵、天南星、鱼腥草等共28味中草药制备而成，科学复配，本发明的组方不仅具有清热解毒、除痰去湿、止咳平喘的功效，还具有养阴生津、润肺清心、滋阴降火、润燥滑肠等功效，通过功能互补和协同增效，而且无论是作为药物治疗或饲料添加剂的应用，都能增强鸡的免疫能力，且精力充沛、羽毛鲜艳、采食明显加大，生长速度快，可见对鸡支气管炎的病症具有很好的疗效。
上述专利文献公开的中药制剂采用的中药味数较多，但是在用于治疗家畜呼吸道疾病效果上看疗效并不高，为提高疗效还需使用抗生素配合进行治疗，目前用于治疗家畜细菌性呼吸道疫病的中药较少，而且配方不合理、只能针对单一动物或疾病，防治效果并不理想，且为了能够达到更好的效果而增加中药药味，加工工艺也复杂，使得中药成本较高。
发明内容
本发明为解决上述技术问题，提供了一种治疗家畜细菌性呼吸道疫病的中药制剂及其生产工艺。本申请中药制剂能有效地解决家畜因细菌引起的呼吸道疾病问题，而且对家畜的毒副作用小，降低家畜因细菌引起的呼吸道疫病的发病率和死亡率，减少抗生素的使用，从而保障家畜产品质量安全。
为了能够达到上述所述目的，本发明采用以下技术方案：
一种治疗家畜细菌性呼吸道疫病的中药制剂，由以下重量份的原料制成：大青叶160～200份、百部55～85份、黄芩160～200份、光枝勾儿茶50～75份。
进一步地，所述的一种治疗家畜细菌性呼吸道疫病的中药制剂，由以下重量份的原料制成：大青叶165～195份、百部60～80份、黄芩165～195份、光枝勾儿茶55～70份。
进一步地，所述的一种治疗家畜细菌性呼吸道疫病的中药制剂，由以下重量份的原料制成：大青叶185份、百部68份、黄芩185份、光枝勾儿茶62份。
进一步地，所述的一种治疗家畜细菌性呼吸道疫病的中药制剂的生产工艺，包括以下步骤：将大青叶、百部、黄芩、光枝勾儿茶清洗干净，沥干表面水分后混合均匀，加入原料重量28～33倍的水，在85～100℃下回流提取1～3h，过滤收集滤液，将滤液浓缩后进行喷雾干燥，过70～100目筛，微波灭菌，自然冷却至室温后包装制得所述中药制剂；所述微波灭菌的工艺为微波频率为2000～2400MHz，功率500～700W，温度为55～70℃，物料传输速度为0.8～1.5m/min。该方法制得的中药制剂主要用于刚出生家畜呼吸道疫病的治疗，特别适合用于10～30日龄的仔猪和1～3月龄的犊牛呼吸道疫病的治疗。
进一步地，所述喷雾干燥的工艺为：进口温度为140～145℃，出口温为80～85℃，进液速度为55～65mL·min-1，浸膏相对密度为1.10～1.15。
进一步地，所述浓缩为减压浓缩，浓缩温度为60～70℃，真空度为0.07～0.09Mpa。
进一步地，所述浓缩是将滤液浓缩至在60℃下相对密度为1.10～1.15的浸膏。
进一步地，所述的一种治疗家畜细菌性呼吸道疫病的中药制剂的生产工艺，包括以下步骤：将大青叶、百部、黄芩和光枝勾儿茶清洗干净，沥干表面水分后混合均匀，送入粉碎机进行粉碎，过10～30目筛，微波灭菌，自然冷却至25～30℃后包装制得所述中药制剂；所述微波灭菌的工艺为微波频率为2000～2400MHz，功率500～700W，温度为55～70℃，物料传输速度为0.8～1.5m/min。该方法制得的中药制剂主要用于育肥家畜呼吸道疫病的治疗，特别适合育肥牛和育肥猪的呼吸道疫病的治疗。
进一步地，一种如上述所述的治疗家畜细菌性呼吸道疫病的中药制剂的应用，所述中药制剂应用于刚出生家畜呼吸道疫病的治疗。
进一步地，一种如上述所述的治疗家畜细菌性呼吸道疫病的中药制剂的应用，所述中药制剂应用于育肥家畜呼吸道疫病的治疗。
本申请所用原料的功效如下：
大青叶：中药名。味苦，性寒；归肝，心，胃，脾经。主治：热毒发斑、丹毒、咽喉肿痛、口舌生疮、疮痈肿毒等症。近年来此药在临床上广泛应用，除可用治上述诸症外，又可用于痰热郁肺、咯痰黄稠；尤常用于流行性乙性脑炎，既可单味应用于预防，又可配合柴胡、银花、连翘、板蓝根、玄参、生地等，能清解气分、营分的热毒，可用治各种乙脑，而以偏热型较为合适。中国各地市售的大青叶品种甚多，植物来源各异，又：爵床科植物马蓝。十字花科植物菘蓝及大青。蓼科植物蓼蓝。豆科植物木蓝。以上植物的叶，都做为大青叶使用，也均能作为制青黛的原料，除木蓝外，其根均作为板蓝根使用。
百部(拉丁学名：Stemonajaponica)亦称婆妇草，药虱药。生长于海拔300米至400米的地区，块根可入药，有毒性。外用可驱除蚊虫，内服有止咳的功能。具有很高的药用价值。甘、苦，微温；归肺经。1、止咳化痰。古人多用百部治疗久咳，痰多，因久咳者肺气素虚，百步可根据寒热分别调理止咳化痰。风寒咳嗽则佐以生姜；肺热咳嗽则和蜜。用于肺结核、长期咳嗽、肺痨咳嗽、百日咳、哮喘等症。2、温润肺气。肺气上逆则气喘咳嗽，百部苦而下泄，善降气，所以能够下气散肺热，主温肺。用于肺寒咳嗽、肺结核等症。3、散热解表。百部润而不燥，能开泄降气，清肺热而解表，用于皮肤疥癣、湿疹、牛皮癣、遍身黄肿、皮炎、湿疹等症。杀虫灭虱。据清代医学典籍《本草新编》记载，百部杀虫而不损耗气血，最有益于人，但是杀虫时需要量大一点，才能有效果。同时与人参、茯苓、白术等配伍可以降低百部味苦对肠胃的损伤。外用于头虱、体虱、蛲虫、阴部瘙痒、蛔虫病等病。
黄芩：(拉丁学名：ScutellariabaicalensisGeorgi)，别名山茶根、土金茶根，是唇形科黄芩属多年生草本植物。味苦，性寒。黄芩的根入药，味苦、性寒，有清热燥湿、泻火解毒、止血、安胎等功效。主治温热病、上呼吸道感染、肺热咳 嗽、湿热黄胆、肺炎、痢疾、咳血、目赤、胎动不安、高血压、痈肿疖疮等症。黄芩的临床抗菌性比黄连好，而且不产生抗药性。
光枝勾儿茶：中药名。为鼠李科植物多叶勾儿茶BerchemiapolyphyllaWall.var.leiocladaHand.–Mazz.的地上茎和根。生于海拔600-1000米间的山坡、山谷灌丛或林下。分布于巴山地区，秦岭西段南坡。灌木，高达3米。老枝灰褐色或黄褐色，平滑，幼枝互生，密被淡褐色短柔毛。叶近革质，卵形，卵状椭圆形或卵状长圆形，长2-3cm，宽1-2cm，先端圆形，有短尖，基部圆形，全缘，上面绿色，有光泽，下面灰绿色，两面均无毛；羽状脉干后黄褐色，7-9对，在下面隆起；叶柄长5mm，上面被褐色短柔毛，花黄绿色，单生，或2-3朵束生于叶腋，或排成总状花序，花序轴密被褐色短柔毛。核果近圆柱形，长达7mm，直径约3mm，红褐色，具宿存花盘和花萼。花期6-7月，果期8-9月；果实翌年成熟。夏、秋季采集，晒干。味苦，性平，归肺经；具有止咳，祛痰，平喘，安神之功效。用于急、慢性支气管炎，精神分裂症。《新华本草纲要》：“根、叶、种子。有止咳、平喘、安神，调经活血的功能。用于肺痨，慢性支气管炎，精神分裂症等。”。
本申请以大青叶为君药，是清热解毒的主药；以黄芩为臣药，具有辅助清热燥湿的作用；以百部为佐药，具有宣肺止咳之作用；以光枝勾儿茶为使药，具有止咳、平喘的作用，同时也有清解解毒之用。大青叶和黄芩具有抗菌、抑菌的作用，四种药合用起到清热解毒，宣肺止咳之用。
由于本发明采用了以上技术方案，具有以下有益效果：
(1)本申请中药制剂能有效地解决家畜因细菌引起的呼吸道疾病问题，而且对家畜的毒副作用小，降低家畜因细菌引起的呼吸道疫病的发病率和死亡率，减少抗生素的使用，从而保障家畜产品质量安全。
(2)本申请中药制剂具有很好的抗菌、抑菌效果，且制备工艺简单，临床治疗效果明显，是抗生素和化学药品有力的替代品。
(3)本申请中药制剂原料搭配科学合理，且所采用的中药味数较少，制备方法简单，降低了中药的生产成本，还能够有效地解决家畜因细菌引起的呼吸道疾病问题。
(4)本申请提供两种不同的中药制剂制备方法，针对不同年龄段的家畜，采用不同的方式制备中药制剂，使制得的中药制剂有益于治疗家畜疾病。刚出生的家畜胃肠道功能还未发育完全，对中药植物直接粉碎物无法吸收，市面上销售的中药均不适用于饲喂。特别是10～30日龄的仔猪，胃肠道功能还未发育完全，对中药制剂无法吸收，饲喂还可能会引起不适。本申请采用水提后进行喷雾干燥制备中药，提取物对10～30日龄的仔猪更易吸收。
(5)本申请制得的中药制剂在治疗家畜呼吸道疾病具有良好的效果，治愈率高达94.5％，有效率高达96.5％。
具体实施方式
下面对本发明的具体实施方式作进一步详细的说明，但本发明并不局限于这些实施方式，任何在本实施例基本精神上的改进或代替，仍属于本发明权利要求所要求保护的范围。
实施例1
一种治疗家畜细菌性呼吸道疫病的中药制剂，由以下重量份的原料制成：大青叶160份、百部55份、黄芩160份、光枝勾儿茶50份。
一种如上述所述的治疗家畜细菌性呼吸道疫病的中药制剂的生产工艺，包括以下步骤：将大青叶、百部、黄芩和光枝勾儿茶清洗干净，沥干表面水分后混合均匀，送入粉碎机进行粉碎，过10目筛，微波灭菌，冷却后包装制得；所述冷却是自然冷却至25℃；所述微波灭菌的工艺为微波频率为2000MHz，功率500W，温度为55℃，物料传输速度为0.8m/min。所述中药制剂应用于育肥家畜呼吸道疫病的治疗。
实施例2
一种治疗家畜细菌性呼吸道疫病的中药制剂，由以下重量份的原料制成：大青叶200份、百部85份、黄芩200份、光枝勾儿茶75份。
一种如上述所述的治疗家畜细菌性呼吸道疫病的中药制剂的生产工艺，包括以下步骤：将大青叶、百部、黄芩、光枝勾儿茶清洗干净，沥干表面水分后混合均匀，加入原料重量28倍的水，回流提取1h，过滤收集滤液，将滤液浓缩后进行喷雾干燥，过70目筛，微波灭菌，自然冷却直室温后包装制得；所述微波灭菌的工艺为微波频率为2000MHz，功率500W，温度为55℃，物料传输速度为0.8m/min；所述喷雾干燥的工艺为：进口温度为140℃，出口温为80℃，进液速度为55mL·min -1，浸膏相对密度为1.10；所述回流提取的温度为85℃；所述浓缩为减压浓缩，浓缩温度为60℃，真空度为0.07Mpa，浓缩至在60℃下相对密度为1.10的浸膏。所述中药制剂应用于刚出生家畜呼吸道疫病的治疗。
实施例3
一种治疗家畜细菌性呼吸道疫病的中药制剂，由以下重量份的原料制成：大青叶165份、百部60份、黄芩165份、光枝勾儿茶55份。
一种如上述所述的治疗家畜细菌性呼吸道疫病的中药制剂的生产工艺，包括以下步骤：将大青叶、百部、黄芩和光枝勾儿茶清洗干净，沥干表面水分后混合均匀，送入粉碎机进行粉碎，过30目筛，微波灭菌，冷却后包装制得；所述冷却是自然冷却至30℃；所述微波灭菌的工艺为微波频率为2400MHz，功率700W，温度为70℃，物料传输速度为1.5m/min。所述中药制剂应用于育肥家畜呼吸道疫病的治疗。
实施例4
一种治疗家畜细菌性呼吸道疫病的中药制剂，由以下重量份的原料制成：大青叶195份、百部80份、黄芩195份、光枝勾儿茶70份。
一种如上述所述的治疗家畜细菌性呼吸道疫病的中药制剂的生产工艺，包括以下步骤：将大青叶、百部、黄芩、光枝勾儿茶清洗干净，沥干表面水分后混合 均匀，加入原料重量33倍的水，回流提取3h，过滤收集滤液，将滤液浓缩后进行喷雾干燥，过100目筛，微波灭菌，自然冷却直室温后包装制得；所述微波灭菌的工艺为微波频率为2400MHz，功率700W，温度为70℃，物料传输速度为1.5m/min；所述喷雾干燥的工艺为：进口温度为145℃，出口温为85℃，进液速度为65mL·min -1，浸膏相对密度为1.15；所述回流提取的温度为100℃；所述浓缩为减压浓缩，浓缩温度为70℃，真空度为0.09Mpa，浓缩至在60℃下相对密度为1.15的浸膏。所述中药制剂应用于刚出生家畜呼吸道疫病的治疗。
实施例5
一种治疗家畜细菌性呼吸道疫病的中药制剂，由以下重量份的原料制成：大青叶185份、百部68份、黄芩185份、光枝勾儿茶62份。
一种如上述所述的治疗家畜细菌性呼吸道疫病的中药制剂的生产工艺，包括以下步骤：将大青叶、百部、黄芩、光枝勾儿茶清洗干净，沥干表面水分后混合均匀，加入原料重量30倍的水，回流提取2h，过滤收集滤液，将滤液浓缩后进行喷雾干燥，过80目筛，微波灭菌，自然冷却直室温后包装制得；所述微波灭菌的工艺为微波频率为2200MHz，功率600W，温度为62℃，物料传输速度为1.1m/min；所述喷雾干燥的工艺为：进口温度为143℃，出口温为83℃，进液速度为60mL·min -1，浸膏相对密度为1.12；所述回流提取的温度为92℃；所述浓缩为减压浓缩，浓缩温度为65℃，真空度为0.08Mpa，浓缩至在60℃下相对密度为1.13的浸膏。所述中药制剂应用于刚出生家畜呼吸道疫病的治疗。
对比例1
与实施例1不同之处在于：治疗家畜细菌性呼吸道疫病的中药制剂的原料为大青叶、百部和黄芩，其他条件不变。
对比例2
与实施例1不同之处在于：治疗家畜细菌性呼吸道疫病的中药制剂的原料为光枝勾儿茶，其他条件不变。
对比例3
按照专利申请CN201710827782.X中的实施例进行。
对比例4
按照专利申请CN201210005117.X中的实施例进行。
对比例5
按照专利申请CN201811356225中的实施例进行。
选择选用25～30日龄、体重10～12kg的2200只患有呼吸道疾病的小猪，随机平均分为11组，每组200头，实验组1～5分别使用本申请实施例1～5制得的中药制剂进行治疗，实验组6～10分别使用对比例1～5制得的中药，实验组11喂养白开水作为对照组，每日喂药3次，每个实验组之间拉开距离，不互相传播疾病，喂养和管理方式相同，喂药7d后，分别统计每组实验小猪的恢复情况，实验结果如下表1所示。
表1
组别 显效数 有效数 无效数 死亡率 治愈率 有效率
实施例1 186头 189头 11头 3％ 93.5％ 94.5％
实施例2 185头 187头 13头 4％ 92.0％ 93.5％
实施例3 187头 190头 10头 2％ 93.0％ 95.0％
实施例4 186头 191头 9头 3％ 93.5％ 95.5％
实施例5 189头 193头 7头 1％ 94.5％ 96.5％
对比例1 157头 162头 38头 33％ 80.5％ 81.0％
对比例2 163头 169头 31头 28％ 82.0％ 84.5％
对比例3 156头 163头 37头 33％ 77.0％ 81.5％
对比例4 157头 161头 39头 34％ 75.5％ 80.5％
对比例5 159头 170头 30头 27％ 83.0％ 85.0％
对照组 2头 3头 197头 188％ 1.0％ 1.5％
由表1实验数据可知，本申请制得的中药制剂在治疗家畜呼吸道疾病具有良好的效果，治愈率高达94.5％，有效率高达96.5％，死亡率低至1％。对比例1原料没有加入光枝勾儿茶，大青叶、百部和黄芩没有光枝勾儿茶进行增强抗菌、抑菌作用，其药效明显比本申请实施例差；对比例2中光枝勾儿茶没有大青叶、百部和黄芩作辅助，其药效明显比本申请实施例差；对比例3和4中药采用了大青叶、百部、黄芩及其他药味混合制成，缺少光枝勾儿茶进行增强抗菌、抑菌作用，其药效明显比本申请实施例差；对比例5采用铁包金和其他中药混合制成中药，其药效虽然较其他对比例好一些，但还是没有比本申请实施例效果好。可见，只有采用本申请的配方和制备方法，制得的中药药效在治疗细菌性呼吸道疾病上才会更好。
为了进一步说明本发明能够达到所述技术效果，做以下实验：
1、实验材料与方法
1.1试验材料
菌种：选用由贵州省畜牧兽医研究所畜禽疫病保存的猪源支原体、牛源支原体、牛源巴氏杆菌、副猪嗜血杆菌、猪传染性胸膜肺炎放线杆菌。
中药材：大青叶、百部、黄芩均购于四川成都，光枝勾儿茶为贵州安顺市野生收集药材。
化学药品：氟苯尼考、头孢噻呋为山东恩康药业产品。
1.2中药制剂的生产工艺
1.2.1制剂的处方组成
每500克中药制剂中含有大青叶185克、百部68克、黄芩185克、光枝勾儿茶62克。
1.2.2制剂的制备
将上述大青叶、百部、黄芩、光枝勾儿茶混合均匀后，加入30倍的水，回流提取2h，过滤得滤液，将滤液浓度浓缩至每毫升1.15g进行喷雾干燥，过80目筛子，63℃微波灭菌，自然冷却直室温后包装制得。
1.3中药制剂的急性毒理实验
选取昆明小鼠40只，体重为20±2g，随机分为给药组和空白对照组，每组20只，雌雄各半，给药组按照5g/kg一次灌胃给本申请制得的中药制剂，空白对照组按照5g/kg一次灌胃给生理盐水，观察14d，并记录小鼠反应(如：症状出现、加重、减轻或死亡的时间和出现反应的动物数量，计算动物死亡率等)，统计小鼠死亡情况。第14d处死存活小鼠，解剖后肉眼观察小鼠脏器情况。
结果：在整个观察期间，小鼠无一死亡，各组小鼠均无异常表现，精神状态良好，活动积极灵活，皮毛光泽，眼与黏膜无变化，呼吸无异常，未见中枢神经系统异常，剖解未见明显肉眼变化，表明本申请制得的中药制剂对小鼠无明显毒副反应，该中药制剂属于无毒级别。
1.4体外抑菌试验
将一种治疗家畜细菌性呼吸道疫病的中药制剂制备成以生药量计浓度为1g/mL。头孢噻呋浓度为20ug/mL、氟苯尼考浓度为20ug/mL。
采用体外抗菌法(二倍稀释法)进行实验：取猪源支原体、牛源支原体、牛源巴氏杆菌、副猪嗜血杆菌、猪传染性胸膜肺炎放线杆菌用接种环接种于已灭菌的营养肉汤培养基中，在37℃恒温箱中培养。
菌种的稀释：取孵化后的菌种，将每种菌稀释10 7个。
一种治疗家畜细菌性呼吸道疫病的中药制剂、头孢噻呋、氟苯尼考，进行二倍稀释法。
抗菌实验：各取经过稀释的菌液0.1mL分别接种于0.9mL不同的实验组培养基用肉汤培养基，加入1mL的药液(中药制剂制备成以生药量计浓度为1g/mL，头孢噻呋为0.4ug/mL、氟苯尼考浓度为0.3ug/mL)进行二倍稀释，再置于37℃ 培养箱培养，培养18-36h候后分别从中吸取0.05ml涂布在肉汤培养平皿琼脂培养基上，共作3个平皿，用无菌涂棒，再将平皿置37℃培养基培养18-36小时，计算药物的MIC值(MIC值是最小抑菌浓度，MIC值越小说明抑制细菌需要的药物越少，说明药效果越好)。体外抑菌试验结果如下表2所示。
表2各药物对不同菌的MIC试验结果
菌株 中药制剂 头孢噻呋 氟苯尼考
猪源支原体 125mg/mL 2.5ug/mL 0.62ug/mL
牛源支原体 125mg/mL 2.5ug/mL 0.31ug/mL
副猪嗜血杆菌 62.5mg/mL 1.25ug/mL 2.5ug/mL
猪传染性胸膜肺炎放线杆菌 31.25mg/mL 1.25ug/mL 2.5ug/mL
1.5中药制剂的体内抑菌药效学实验
1.5.1实验动物
选取体征相近的SPF昆明小鼠280只，雌雄兼用，体重为20±2g，由成都达硕实验动物有限公司提供，许可证号：SCXK(川)2015-030，随机平均分成28组，每组10只。设支原体组、副猪嗜血杆菌、猪传染性胸膜肺炎放线杆菌组，以及空白对照组。
1.5.2样品来源与配制
(1)本申请制得的中药制剂：折合生药含量为400mg/mL。
(2)高剂量组：中药制剂稀释给药(相当于生药含量400mg/ml，给药剂量相当于生药4000mg/kg体重)。
(3)中剂量组：中药制剂高剂量组，加生理盐水，按照1:2稀释，稀释后给药(相当于生药含量200mg/ml，给药剂量相当于生药2000mg/kg体重)。
(4)低剂量组：兽用止痢高剂量组，加生理盐水，按照1:4稀释，稀释后给药(相当于生药含量100mg/ml，给药剂量相当于生药1000mg/kg体重)。
(5)阳性对照组：阳性物采用氟苯尼考，用量为20mg/kg，该氟苯尼考是由山东恩康药业生产，批号为：20180915。
1.5.3中药治疗小鼠细菌性呼吸道疫病动物模型试验
分别设置支原体组、副猪嗜血杆菌组、猪传染性胸膜肺炎放线杆菌组、混合菌组与空白对照组、生理盐水组、阳性对照组、中药高剂量组、中药中剂量组、中药低剂量组，混合菌是将副猪嗜血杆菌、猪传染性胸膜肺炎放线杆菌和支原体三种菌按照质量比＝1:1:1混合制成。除空白对照组不作处理外，支原体组、副猪嗜血杆菌组、猪传染性胸膜肺炎放线杆菌组、生理盐水组、阳性对照组、中药高剂量组、中药中剂量组、中药低剂量组按照预实验方法连续3d通过滴鼻接种菌液；混合菌组采用浓度细菌数为3×108个/mL滴鼻和腹部注射，连续3d通过滴鼻和注射接种菌液进行感染；SPF昆明小鼠第3d接种菌液后开始灌胃药物，连续灌胃7d，观察治疗效果。
1.5.4实验结果
本申请中药低、中、高剂量组的体内治疗效果与对照组比较，差异具有统计学意义(P<0.05或0.01)，说明中药制剂组具有一定的体内抑菌作用。体内抑菌药效学研究中，本申请中药制剂对SPF昆明小鼠感染支原体的体内抑菌药效学研究结果如下表3所示、对SPF昆明小鼠感染副猪嗜血杆菌的体内抑菌药效学研究结果如下表4所示、对SPF昆明小鼠感染猪传染性胸膜肺炎放线杆菌的体内抑菌药效学研究结果如下表5所示、对SPF昆明小鼠感染混合菌的体内抑菌药效学研究结果如下表6所示。
表3
组别 实验数量 灌胃药物 死亡数
空白对照组 10只 / 10只
支原体组 10只 / 10只
生理盐水组 10只   10只
阳性对照组 10只 氟苯尼考 0只
中药低剂量组 10只 中药制剂100mg/mL 7只
中药中剂量组 10只 中药制剂200mg/mL 2只
中药高剂量组 10只 中药制剂400mg/mL 3只
由表3实验数据可知，本申请制得的中药制剂对支原体具有一定的体内抑菌作用。
表4
组别 实验数量 灌胃药物 死亡数
空白对照组 10只 / 0只
副猪嗜血杆菌组 10只 / 8只
生理盐水组 10只   8只
阳性对照组 10只 氟苯尼考 2只
中药低剂量组 10只 中药制剂100mg/mL 6只
中药中剂量组 10只 中药制剂200mg/mL 3只
中药高剂量组 10只 中药制剂400mg/mL 3只
由表4实验数据可知，本申请制得的中药制剂对副猪嗜血杆菌具有一定的体内抑菌作用。
表5
组别 实验数量 灌胃药物 死亡数
空白对照组 10只 / 0只
猪传染性胸膜肺炎放线杆菌组 10只 / 9只
生理盐水组 10只   9只
阳性对照组 10只 氟苯尼考 1只
中药低剂量组 10只 中药制剂100mg/mL 8只
中药中剂量组 10只 中药制剂200mg/mL 3只
中药高剂量组 10只 中药制剂400mg/mL 4只
由表5实验数据可知，本申请制得的中药制剂对猪传染性胸膜肺炎放线杆菌具有一定的体内抑菌作用。
表6
组别 实验数量 灌胃药物 死亡数
空白对照组 10只 / 10只
混合菌组 10只 / 10只
生理盐水组 10只   10只
阳性对照组 10只 氟苯尼考 0只
中药低剂量组 10只 中药制剂100mg/mL 8只
中药中剂量组 10只 中药制剂200mg/mL 2只
中药高剂量组 10只 中药制剂400mg/mL 2只
由表6实验数据可知，本申请制得的中药制剂对混合菌具有一定的体内抑菌作用。由表3-6可知，本申请制得的中药制剂体内抑菌效果明显。
1.6中药制剂靶动物安全实验
采用多剂量水平给药进行研究，选取32头仔猪，公母各占一半，随机平均分为4组，每组8只。设置空白对照组和1倍、3倍、5倍最大推荐剂量组，连续给药14d，观察仔猪反应，实验结束后宰杀，剖检采用肉眼和显微镜观察仔猪脏器情况。
试验设以下的实验组和给药剂量：
(1)不给药对照组；
(2)1倍最大推荐剂量组，一日两次；
(3)3倍最大推荐剂量组，一日两次；
(4)5倍最大推荐剂量组，一日两次。
其中，1倍最大推荐剂量为每只仔猪每公斤体重按照0.5g/mL灌服本申请制得的中药制剂。
结果：试验仔猪均存活且健康状况良好，临床表现正常；剖检表明各组受试猪均未见明显肉眼病变，且来自5倍剂量组中的动物脏器亦未见异常显微病理变化；在血液生理生化指标方面，1倍推荐剂量组、3倍推荐剂量组、5倍推荐剂量组与空白对照组相比，各项指标无显著差异。结果表明，本申请制得的中药制剂在推荐剂量下使用对仔猪具有很好的安全性和耐受性。
1.7应用实例
案例一：贵州省毕节市在引牛过程中，发生牛呼吸道疫病，经实验室诊断为支原体感染，共计110头，采用本申请制得的中药制剂，按每公斤体重0.5g进行治疗，治疗是将药物拌料在饲料中，连续治疗7d后牛病情好转17头，痊愈99头，有效率为92.9％。
案例二：贵州省贵阳市猪场发生仔猪呼吸道疫病，经实验室诊断为副猪嗜血杆菌、猪传染性胸膜肺炎放线杆菌混合感染，共计48头，采用本申请制得的中药制剂，按每公斤体重0.5g进行治疗，治疗是将药物配置成0.5g/mL进行灌胃，连续治疗7d后仔猪病情好转8头，痊愈43头，有效率为91.7％。
综上所述，本申请原料搭配科学合理，且所采用的中药味数较少，且制备工艺简单，降低了中药的生产成本，临床治疗效果明显，是抗生素和化学药品有力的替代品，具有很好的抗菌、抑菌效果，能有效地解决家畜因细菌引起的呼吸道疾病问题，而且对家畜的毒副作用小，降低家畜因细菌引起的呼吸道疫病的发病率和死亡率，减少抗生素的使用，从而保障家畜产品质量安全。
对于本领域技术人员而言，显然本发明不限于上述示范性实施例的细节，而且在没有背离本发明的精神或基本特征的情况下，能够以其他的具体形式实现本发明。因此，无论从哪一点来看，均应将实施例看作是示范性的，而且是非限制性的，本发明的范围由所附权利要求而不是上述说明限定，因此旨在将落在权利要求的等同腰间的含义和范围内的所有变化囊括在本发明的保护范围之内。

Claims (10)

  1. 一种治疗家畜细菌性呼吸道疫病的中药制剂，其特征在于，由以下重量份的原料制成：大青叶160～200份、百部55～85份、黄芩160～200份、光枝勾儿茶50～75份。
  2. 根据权利要求1所述的一种治疗家畜细菌性呼吸道疫病的中药制剂，其特征在于，由以下重量份的原料制成：大青叶165～195份、百部60～80份、黄芩165～195份、光枝勾儿茶55～70份。
  3. 根据权利要求1所述的一种治疗家畜细菌性呼吸道疫病的中药制剂，其特征在于，由以下重量份的原料制成：大青叶185份、百部68份、黄芩185份、光枝勾儿茶62份。
  4. 根据权利要求1～3任一项所述的一种治疗家畜细菌性呼吸道疫病的中药制剂的生产工艺，其特征在于，包括以下步骤：将大青叶、百部、黄芩、光枝勾儿茶清洗干净，沥干表面水分后混合均匀，加入原料重量28～33倍的水，在85～100℃下回流提取1～3h，过滤收集滤液，将滤液浓缩后进行喷雾干燥，过70～100目筛，微波灭菌，自然冷却至室温后包装制得所述中药制剂；所述微波灭菌的工艺为微波频率为2000～2400MHz，功率500～700W，温度为55～70℃，物料传输速度为0.8～1.5m/min。
  5. 根据权利要求4所述的一种治疗家畜细菌性呼吸道疫病的中药制剂的生产工艺，其特征在于：所述喷雾干燥的工艺为：进口温度为140～145℃，出口温为80～85℃，进液速度为55～65mL·min -1，浸膏相对密度为1.10～1.15。
  6. 根据权利要求4所述的一种治疗家畜细菌性呼吸道疫病的中药制剂的生产工艺，其特征在于：所述浓缩为减压浓缩，浓缩温度为60～70℃，真空度为0.07～0.09Mpa。
  7. 根据权利要求4所述的一种治疗家畜细菌性呼吸道疫病的中药制剂的生产工艺，其特征在于：所述浓缩是将滤液浓缩至在60℃下相对密度为1.10～1.15的浸膏。
  8. 根据权利要求1～3任一项所述的一种治疗家畜细菌性呼吸道疫病的中药制剂的生产工艺，其特征在于，包括以下步骤：将大青叶、百部、黄芩和光枝勾儿茶清洗干净，沥干表面水分后混合均匀，送入粉碎机进行粉碎，过10～30目筛，微波灭菌，自然冷却至25～30℃后包装制得所述中药制剂；所述微波灭菌的工艺为微波频率为2000～2400MHz，功率500～700W，温度为55～70℃，物料传输速度为0.8～1.5m/min。
  9. 一种如权利要求4所述的治疗家畜细菌性呼吸道疫病的中药制剂的应用，其特征在于：所述中药制剂应用于刚出生家畜呼吸道疫病的治疗。
  10. 一种如权利要求8所述的治疗家畜细菌性呼吸道疫病的中药制剂的应用，其特征在于：所述中药制剂应用于育肥家畜呼吸道疫病的治疗。
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