CN110680848B - Traditional Chinese medicine composition for treating swine fever and preparation method and application thereof - Google Patents
Traditional Chinese medicine composition for treating swine fever and preparation method and application thereof Download PDFInfo
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Abstract
The invention relates to the field of veterinary medicaments, and discloses a traditional Chinese medicine composition for treating swine fever and a preparation method and application thereof. The traditional Chinese medicine composition is prepared from 1-20 parts by weight of rhubarb, 1-15 parts by weight of giant knotweed, 1-30 parts by weight of salvia miltiorrhiza, 1-15 parts by weight of astragalus and 1-10 parts by weight of mirabilite. The preparation method comprises the following steps: (1) 1/2, adding 8-12 times of water into the total weight of radix et rhizoma Rhei, and soaking to obtain radix et rhizoma Rhei warm extractive solution and residue; (2) soaking the rest radix et rhizoma Rhei, rhizoma Polygoni Cuspidati, Saviae Miltiorrhizae radix and radix astragali in 8-12 times of water, mixing with the residue of warm soaking radix et rhizoma Rhei, decocting in water, filtering, and concentrating the filtrate; (3) and (3) mixing the concentrate obtained in the step (2), the rhubarb warm immersion liquid obtained in the step (1) and mirabilite, and stirring and dissolving. The traditional Chinese medicine composition has the effects of promoting intestinal excretion, protecting liver and gallbladder, resisting inflammation, reducing body temperature, resisting toxin and treating swine fever.
Description
Technical Field
The invention relates to the field of veterinary medicaments, in particular to a traditional Chinese medicine composition for treating swine fever and a preparation method and application thereof.
Background
Classical swine fever (Classical swine fever) also known as Classical swine fever or Classical swine fever, commonly known as "gastrointestinal plague", is caused by swine fever viruses of the genus hog cholera of the family flaviviridae.
Hog cholera is an acute, febrile, contact, highly contagious epidemic. The method is characterized in that: can be generated all the year round; acute swine fever is in septicemic change, bleeding of parenchymal organs, necrosis and infarction; chronic swine fever is characterized by cellulolytic necrotic enteritis. Swine fever can cause fever, anorexia, diarrhea and death of sick pigs, and sows infected with swine fever can suffer abortion or produce dead piglets.
At present, swine fever is one of the main infectious diseases threatening the pig industry all over the world, and often causes devastating loss to the pig industry.
Internationally, the prevention and control of swine fever are global problems. During the period from 1 month of 2019 to 10 months of 2019, 26 countries which have outbreak or are outbreaking the epidemic situation of the African swine fever include 13 European countries, 10 Asian countries and 3 African countries, wherein the epidemic situation of several Asian countries is particularly serious. Over the years, a total of 18 countries and regions have reported 5800 outbreaks. According to official data, at the end of 8 months in 2019, 147 non-epidemic situations occur in 31 provinces and urban areas of China, 19355 live pigs are diseased, 13385 dead pigs are dead, and the number of death and killing is 112.76 thousands. However, the actual loss may be more severe. At present, the reason is that from 8 months in the last year to 8 months in the present year, the swine fever epidemic situation can directly and indirectly cause the reduction of the live pig stock of 8000 ten thousand pigs, which is equivalent to two or more times of the total live pig stock. If the average market value of each live pig is 1000-.
In a 9-month 16-month newly-made 8-month national economic operation situation release meeting in 2019, a statistical bureau speaker publishes that the national CPI of 8 months is increased by 2.8% at the same ratio and the ring ratio is increased by 0.7%; wherein the pork price rises by 46.7 percent in the same proportion, and the rising amplitude is increased by 19.7 percent in 7 months, which affects 40 percent of the same rising amplitude of the whole CPI.
Theoretically, the most effective method for preventing swine fever is vaccination of swine fever, but this is a worldwide problem, and no african swine fever vaccine has been approved for marketing in the world so far. Experts in the industry consider that certain characteristics of non-pestiviruses in strain structure and variability make the development of related vaccines difficult, and swine fever still fails to provide efficient vaccines in the international society of hundreds of years.
Therefore, the research of antiviral drugs is very important and urgent while developing vaccines.
In recent decades, various antiviral drugs such as tamiflu, ribavirin, acyclovir, ribavirin and adamantane have been studied at home and abroad, but the treatment effect is not nearly satisfactory. For example, duffy has certain effect on the influenza A virus H1N1 in the early infection stage or latent stage, but is ineffective in the late stage, and the pharmacological action of the duffy mainly inhibits the replication of the virus and does not help the functional recovery of the human body. In addition, it has been reported that "duffy" has begun to develop resistance to seasonal influenza. Other medicines, such as ribavirin and adamantane, have large toxic and side effects when being used in large dose, and as a result, the diseases are not cured, but the leucocytes are rapidly reduced, hepatotoxicity is caused, and even death is caused.
In the early stage of viral infection, the influence on the body is only a factor, and the pathological process causing the body reaction after infection is the key to influencing the disease development. Severe infectious viral diseases (plague) such as SARS, avian influenza, influenza A, etc. have distinct characteristics of exogenous febrile disease, acute onset, epidemic toxin exuberance and rapid transmission. When epidemic toxin is exuberant, viscera dysfunction and even Multiple Organ Dysfunction Syndrome (MODS) appear immediately, thus endangering life. Therefore, for critically ill patients, the focus of the research on the prevention and treatment of viral diseases is on the pathological process causing the body reaction after infection, rather than on the etiology. The treatment of viral diseases must be comprehensive and integrated.
Modern researches show that the traditional Chinese medicine has the functions of broad-spectrum antibiosis, antivirus, immunity regulation, interferon induction, allergy resistance, hemagglutination resistance, fibrosis resistance, virus replication inhibition, fever relief, pain relief and the like, can play the overall comprehensive regulation role, and can play the corresponding role in different pathological links of viral diseases. Therefore, the antiviral effect of the traditional Chinese medicine and the compound is deeply and systematically researched, and the antiviral composition has unique advantages and wide development prospect.
Disclosure of Invention
The invention aims to provide a traditional Chinese medicine composition for treating swine fever and a preparation method and application thereof.
Theoretically, viral diseases (plagues) and endotoxemia belong to the category of epidemic febrile diseases in traditional Chinese medicine, and the viral diseases and endotoxemia have great similarity on clinical symptoms. Therefore, on the basis of a large number of experimental studies, in combination with the warm disease theory of traditional Chinese medicine, the inventor creatively uses a traditional Chinese medicine preparation with high-efficiency prevention and treatment effects on endotoxemia for prevention and treatment of viral diseases (plague) after improvement and optimization, and develops a traditional Chinese medicine composition capable of effectively preventing and treating swine fever, thereby completing the invention.
The invention provides a traditional Chinese medicine composition for treating swine fever, which is prepared from 1-20 parts by weight of rhubarb, 1-15 parts by weight of giant knotweed rhizome, 1-30 parts by weight of salvia miltiorrhiza, 1-15 parts by weight of astragalus and 1-10 parts by weight of mirabilite.
Preferably, the traditional Chinese medicine composition is prepared from 5-20 parts by weight of rheum officinale, 5-15 parts by weight of polygonum cuspidatum, 5-20 parts by weight of salvia miltiorrhiza, 3-12 parts by weight of astragalus membranaceus and 2-8 parts by weight of mirabilite.
More preferably, the traditional Chinese medicine composition is prepared from 10-20 parts by weight of rheum officinale, 10-15 parts by weight of polygonum cuspidatum, 10-20 parts by weight of salvia miltiorrhiza, 8-12 parts by weight of astragalus membranaceus and 4-8 parts by weight of mirabilite.
The invention also provides a preparation method of the traditional Chinese medicine composition for treating swine fever, which comprises the following steps:
(1) 1/2, adding 8-12 times of water into the total weight of radix et rhizoma Rhei, and soaking to obtain radix et rhizoma Rhei warm extractive solution and residue;
(2) soaking the rest radix et rhizoma Rhei, rhizoma Polygoni Cuspidati, Saviae Miltiorrhizae radix and radix astragali in 8-12 times of water, mixing with the residue of warm soaking radix et rhizoma Rhei, decocting in water, filtering, and concentrating the filtrate;
(3) mixing the concentrate obtained in the step (2), the rhubarb warm immersion liquid obtained in the step (1) and mirabilite, and stirring and dissolving;
wherein, the total dosage of rhubarb is 1 to 20 weight portions, the dosage of giant knotweed is 1 to 15 weight portions, the dosage of salvia miltiorrhiza is 1 to 30 weight portions, the dosage of astragalus is 1 to 15 weight portions, and the dosage of mirabilite is 1 to 10 weight portions.
Preferably, the total dosage of rhubarb is 5 to 20 weight portions, the dosage of giant knotweed is 5 to 15 weight portions, the dosage of salvia miltiorrhiza is 5 to 20 weight portions, the dosage of astragalus is 3 to 12 weight portions, and the dosage of mirabilite is 2 to 8 weight portions.
Preferably, the method further comprises: stirring and dissolving in the step (3) until the final concentration is 1.8-2.2g crude drug/mL, adding sodium benzoate, filling and sealing, and sterilizing.
Preferably, in the step (1), the soaking is carried out for 1 time and 15-30min at the temperature of 80-100 ℃.
Preferably, in step (1), soaking time is 0.5-2h, and decocting for 2 times, each time for 1-3 h.
In a specific embodiment, the preparation method of the traditional Chinese medicine composition for treating swine fever comprises the following steps:
adding 10 times of water into 1/2 of radix et rhizoma Rhei total weight, and soaking at 80-100 deg.C for 1 time for 20min to obtain radix et rhizoma Rhei warm soaking solution and residue;
soaking the rest radix et rhizoma Rhei, Saviae Miltiorrhizae radix and radix astragali in 10 times of water for 1h, mixing with the residue of warm soaking radix et rhizoma Rhei, decocting in water for 2 times (each time for 1.5 h), mixing filtrates, and concentrating;
mixing the obtained concentrate, the radix et rhizoma Rhei warm extractive solution and Natrii sulfas, stirring to dissolve until the final concentration is 2g crude drug/mL, adding 0.2 wt% sodium benzoate, bottling, and sterilizing.
The invention also provides a traditional Chinese medicine composition prepared by the method.
The invention also provides application of the traditional Chinese medicine composition in preparing a medicine for preventing or treating swine fever.
The invention has the beneficial effects that: the components in the invention are all selected from natural traditional Chinese medicines, the composition is simple, the cost is low, the sources are rich, the hog cholera virus can be effectively inhibited or killed, toxic substances in a body are discharged out of the body, the immunity of the hog is improved, the infection risk is reduced, the effect of preventing the hog cholera is obvious, the safety and the non-toxic side effect are realized, and the production requirement of green and pollution-free pork is met.
The invention has important significance for improving the production performance of the pigs, reducing the economic loss and promoting the continuous and healthy development of the pig breeding industry.
Drawings
FIG. 1 is a graph showing the change in rabbit body temperature measured in the experimental examples.
Detailed Description
The following detailed description of embodiments of the invention refers to the accompanying drawings. It should be understood that the detailed description and specific examples, while indicating the present invention, are given by way of illustration and explanation only, not limitation.
Example 1
The raw material formula used in the present example: 15g of rheum officinale, 10g of polygonum cuspidatum, 20g of salvia miltiorrhiza, 10g of astragalus membranaceus and 5g of mirabilite.
Adding water 10 times the weight of radix et rhizoma Rhei into 1/2 of radix et rhizoma Rhei total weight, and soaking at 90 deg.C for 1 time for 20min to obtain radix et rhizoma Rhei warm soaking solution and residue;
soaking the rest radix et rhizoma Rhei, rhizoma Polygoni Cuspidati, Saviae Miltiorrhizae radix and radix astragali in 10 times of water for 1h, mixing with the residue of warm soaking radix et rhizoma Rhei, decocting in water for 1.5h for 2 times, mixing filtrates and concentrating;
mixing the obtained concentrate, the radix et rhizoma Rhei warm extract and Natrii sulfas, stirring for dissolving to final concentration of 2g crude drug/mL, adding 0.2 wt% sodium benzoate, bottling, and sterilizing to obtain the target Chinese medicinal composition. The Chinese herbal medicines used in the following experimental examples are the Chinese herbal medicine composition prepared in this example.
Examples of the experiments
Pharmacodynamics study of Chinese medicinal composition
1. Influence on intestinal propulsion of mice in vivo
40 mice, randomly divided into 4 groups of 10 mice each. The control group is perfused with 0.2mL of 5% active carbon suspension per 10g of body weight. The oral liquid is prepared into 5 percent active carbon suspension of 0.2mL/10g (the dosage of the traditional Chinese medicine is respectively 5, 10 and 20g/kg) by respectively intragastric administration for mice in the small, middle and high dosage groups. After 20min of administration, the animals were sacrificed by pulling the neck, the entire intestine was quickly taken out and laid on a plate, and the total length of the small intestine and the moving distance of the charcoal powder in the intestine were measured in the mice.
The percentage of carbon powder pushed into the small intestine is the moving distance of the carbon powder/the whole length of the small intestine is multiplied by 100 percent
Table 1: the influence of the oral liquid on the propulsion of small intestine of mouse (
n＝10)
Compared with the saline group, ﹡ P is less than 0.05, ﹡ ﹡ P is less than 0.01.
The result shows that the traditional Chinese medicine composition has the function of promoting intestinal excretion.
2. Study of anti-inflammatory action
40 mice, randomly divided into 4 groups of 10 mice each. The control group is perfused with the normal saline 0.2mL/10g of the body weight; respectively intragastrically irrigating 0.2mL/10g of oral liquid (the dosage of the traditional Chinese medicines is respectively 5, 10 and 20g/kg) with different concentrations for 3d continuously, 1 time every day, 1h after 3 days of administration, smearing 0.1mL of dimethylbenzene on the left ear of each mouse by using an injector, pulling the neck to kill after 20min, respectively cutting off the left ear and the right ear, cutting off the same ear piece with the same position on the left ear and the right ear by using a perforator with the diameter of 9mm, and respectively weighing by using a ten-thousandth analytical balance. The difference between the left and right ear piece weights was used as an index of inflammatory swelling, and the difference between each administration group and the control group was compared to calculate the swelling inhibition rate.
Table 2: the effect of the Chinese medicinal oral liquid on the mouse ear swelling caused by xylene (
n＝10)
Compared with the saline group, ﹡ P is less than 0.01.
The result shows that the traditional Chinese medicine composition has good anti-inflammatory effect.
3. Study of gallbladder Effect
The rats are anesthetized and fixed in the backward facing position, the bile duct is inserted into a sterile tiny plastic tube, and the bile dripping condition is observed. Counting the number of the juice flowing out of the liner for a certain time, after the juice is stable, taking the number of the juice flowing out of the liner 20min before administration as a reference, then injecting 1mL/100g of the Chinese medicinal oral liquid into the duodenum (the dosage of the Chinese medicinal liquid is 10g/kg), after administration, respectively counting the number of bile flowing out within 20-40 min and 40-60 min, and comparing with the counting before administration.
The number of juice drops in the liner 20min before administration is 15.5 + -3.5
The dosage is increased by 4.5 +/-1.5 drops (P is less than 0.05) in a time period of 20-40 min after administration compared with that before administration;
the time period of 40-60 min after administration is increased by 5.5 +/-2.5 drops (P is less than 0.05) compared with the time period before administration.
The result shows that the traditional Chinese medicine composition has the function of promoting bile secretion.
4. Research on liver protection effect of traditional Chinese medicine oral liquid
White rats were randomly divided into 2 groups of 8 rats each. Firstly, 1ml of intragastric administration oral liquid per 100g of body weight is continuously added for 5 days; ② the control group is perfused with physiological saline with the same volume as the stomach for 5 days continuously. After 1 hour of the intragastric administration on day 5, the two groups both underwent intragastric administration of CCL4 oil solution (CCL 4: sesame oil of 0.4: 0.6) of 0.4mL/100g of body weight, and after 24 hours, blood was collected by decapitation, and the contents of alanine Aminotransferase (ALT) and aspartate Aminotransferase (AST) in the serum were determined, and the results are shown in Table 3.
Table 3: the traditional Chinese medicine oral liquid has the protective effect on the liver injury of the white rat caused by the CCL4 (U/L,
)
note: ﹡ represents P < 0.01.
The result shows that the traditional Chinese medicine composition has good liver protection effect.
5. Research on antipyretic action
16 rabbits with basal body temperature meeting the requirement of an antipyretic experiment are taken and randomly divided into a normal control group, a modeling control group and an oral liquid group. Before the experiment, the patient is fasted for 15 hours without water. The temperature was measured 2 times the day of the experiment, and the average value was taken as the base body temperature value. Then, the rabbits were drenched with 10mL/kg of oral liquid or physiological saline of the same volume. After 30min, 1 microgram/kg of endotoxin is injected along the vein of each rabbit ear in the oral liquid group and the modeling control group; the normal control group was injected with an equal volume of saline.
After endotoxin injection, the rectal temperature of the rabbits was measured for 1 time at 0.5h, 1h, 1.5h, 2h, 3h, 4h and 5h, the body temperature change condition of each rabbit was calculated with the mean temperature value of the prodrug as the base number, the body temperature change was taken as the ordinate, and the time after endotoxin injection was taken as the abscissa to draw the body temperature change curve, and the result is shown in fig. 1, wherein the series 1 was the model group and the series 2 was the administration group. The body temperature response height (delta t3) of 3h and the body temperature response index (TRI5) of 5h were counted, and the results are shown in Table 4.
Table 4: influence of traditional Chinese medicine oral liquid on model animals delta t3 and TRI5
Note that compared with the normal control group, the delta P is less than 0.05, and the delta P is less than 0.01; ﹡ ﹡ P <0.01 when compared to the molded control.
The result shows that the traditional Chinese medicine composition has good body temperature reducing effect.
6. Study of detoxification Effect
20 rabbits with basal body temperature meeting the requirement of an antipyretic experiment are taken and randomly divided into a normal control group, a modeling control group and an oral liquid group. Before the experiment, fasting was performed for 15 hours, but water was not prohibited. The temperature was measured 2 times the day of the experiment, and the average value was taken as the base body temperature value. Then, the rabbit is irrigated with 10mL/kg of traditional Chinese medicine oral liquid or physiological saline with the same volume. After 30min, 1 microgram/kg of endotoxin is injected along the vein of each rabbit ear in the traditional Chinese medicine oral liquid group and the modeling control group; the normal control group was injected with an equal volume of saline.
After 2h of modeling, the heart blood was collected, plasma was separated, the LPS content was measured by the limulus test using endotoxin, the TNFa content was measured by the ELTSA method, and the results are shown in Table 5. 2h after molding, plasma LPS and TNFa of animals in the two endotoxin injection groups are obviously higher than those in a normal control group. The LPS and TNFa levels of the medicines are obviously reduced compared with the control group.
Table 5: effect on plasma LPS and TNFa levels in model animals
Note that compared with the normal control group, the delta P is less than 0.01; ﹡ P was <0.05 compared to the molded control.
The result shows that the traditional Chinese medicine composition has good detoxification effect.
7. Acute toxicity test of oral liquid
Animals were observed for toxicity and mortality after 1 or several administrations of the test drug over 24 hours. Because the oral liquid has low toxicity, the intragastric administration of animals is limited by the concentration and the volume of the medicament, the LD50 can not be detected, the maximum administration amount test is carried out, the experimental basis is provided for the clinical safe administration, and the reference is provided for the design of indexes such as the dosage of the long-term toxicity test, the possible target organs, the toxic reaction and the like.
80 Kunming mice with the weight of 18-22 g are taken, fasted and not forbidden for 12 hours, and randomly divided into 4 groups, namely male and female halves. The test solution (2g crude drug/ml) of the traditional Chinese medicine oral liquid is used for 24 hours, the mice with the concentration of 0.3ml/10g are respectively gavaged for 1, 2 and 3 times, the mice with the concentration of 0.3ml/10g are gavaged for 24 hours for 3 times of physiological saline, and the continuous observation is carried out for 14 days. The toxicity response of mice after administration is shown in Table 6, and the acute toxicity results are shown in Table 7.
Table 6: toxic response in mice following administration
Table 7: acute toxicity results
The experimental result shows that the mice in the 3 groups of the traditional Chinese medicine oral liquid are observed immediately after the infection, and no acute poisoning symptom and death are caused. The test was observed for 14 consecutive days, and none of the animals died. After the experiment, the mice are killed, and the main organs of the mice, such as brain, heart, liver, spleen, lung, kidney and the like, are examined by dissection without obvious abnormality.
8. Therapeutic effect on swine fever
5000 kg of the traditional Chinese medicine composition is produced according to the method of the example 1, and the survival rate of 4000 swine fever pigs is about 60 percent after treatment and observation.
The result shows that the traditional Chinese medicine composition has good effect of treating swine fever.
Conclusion
The pharmacodynamic research shows that the traditional Chinese medicine composition has the effects of promoting excretion, protecting liver and gallbladder, resisting inflammation, reducing body temperature, resisting toxin and treating swine fever, and is low in preparation toxicity and safe to use.
The preferred embodiments of the present invention have been described above in detail, but the present invention is not limited thereto. Within the scope of the technical idea of the invention, many simple modifications can be made to the technical solution of the invention, including combinations of various technical features in any other suitable way, and these simple modifications and combinations should also be regarded as the disclosure of the invention, and all fall within the scope of the invention.
Claims (6)
1. A preparation method of a traditional Chinese medicine composition for treating swine fever is characterized by comprising the following steps:
(1) 1/2, adding 8-12 times of water into the total weight of radix et rhizoma Rhei, and soaking to obtain radix et rhizoma Rhei warm extractive solution and residue;
(2) soaking the rest radix et rhizoma Rhei, rhizoma Polygoni Cuspidati, Saviae Miltiorrhizae radix and radix astragali in 8-12 times of water, mixing with the residue of warm soaking radix et rhizoma Rhei, decocting in water, filtering, and concentrating the filtrate;
(3) mixing the concentrate obtained in the step (2), the rhubarb warm immersion liquid obtained in the step (1) and mirabilite, and stirring and dissolving;
wherein, the total dosage of the rhubarb is 15 weight portions, the dosage of the giant knotweed is 10 weight portions, the dosage of the salvia miltiorrhiza is 20 weight portions, the dosage of the astragalus is 10 weight portions, and the dosage of the mirabilite is 5 weight portions.
2. The method of claim 1, further comprising: stirring and dissolving in the step (3) until the final concentration is 1.8-2.2g crude drug/mL, adding sodium benzoate, filling and sealing, and sterilizing.
3. The method according to claim 1, wherein in step (1), the soaking is performed 1 time for 15-30min at a temperature of 80-100 ℃.
4. The method according to claim 1, wherein in step (1), the soaking time is 0.5-2h, and the decoction is carried out 2 times, each time for 1-3 h.
5. A Chinese medicinal composition prepared by the method of any one of claims 1-4.
6. The use of the Chinese medicinal composition of claim 5 in the preparation of a medicament for the treatment of swine fever.
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