Compound Jinqi injection and application thereof

Abstract

The invention discloses a compound radix astragali and radix astragali injection and application thereof, the compound radix astragali and radix astragali injection comprises extracts of radix astragali, honeysuckle, radix isatidis, herba houttuyniae, herba andrographitis, acalypha australis, folium ilicis purpurea and the like, and further comprises a stabilizer. The compound Jinqi injection provided by the invention has a relatively good inhibition effect on TGEV, PEDV and PoRV; a toxicity test proves that the injection is actually non-toxic; a stability test shows that the period of validity is 12 months; through treatment tests, the effective rate of the compound Jinqi injection for treating porcine viral diarrhea reaches 97%, and the cure rate also reaches 90% or above.

Description

Technical Field

[0001] The invention relates to the technical field of biopharmaceuticals, and in particular to a compound Jinqi injection and an application thereof. Background Art

[0002] Porcine epidemic diarrhea (PED), porcine transmissible gastroenteritis (TGE) and porcine rotavirus (PoRV) infections are infectious diseases caused by porcine epidemic diarrhea virus (PEDV), porcine transmissible gastroenteritis virus (TGEV) and porcine group A rotavirus (PoRV-A), characterized by vomiting, diarrhea and dehydration in pigs. They have a high mortality rate and bring significant economic losses to pig farming. The clinical manifestations of pigs infected with the above viruses are very similar. Once a pig becomes ill in a herd, it will soon spread to the entire herd, especially the high incidence and mortality of infected piglets, which brings a devastating blow to pig farms. At the same time, there are also mixed infections of multiple pathogens, which has become a new and eye-catching global problem. Porcine viral diarrhea has been widely prevalent since the 1990s, causing major damage and serious economic losses to the pig farming industry in countries and regions where the epidemic occurred. In recent years, there have been many outbreaks of this disease in my country, causing huge losses.

[0003] Porcine epidemic diarrhea virus, porcine transmissible gastroenteritis virus and porcine rotavirus are the main pathogens that cause porcine viral diarrhea, and now pigs are often mixedly infected. Therefore, a single vaccination against porcine epidemic diarrhea virus can no longer meet the needs of the actual situation, and multi-vaccine vaccination is required. The cost of multi-vaccine vaccination is high and the vaccination procedure is cumbersome. Therefore, in addition to vaccine prevention, it is necessary to develop specific drugs for the treatment of porcine viral diarrhea to meet market demand. Therefore, it is imperative to find and develop new safe, efficient and low-toxic drugs that kill and inhibit porcine viral diarrhea viruses. As a superior and characteristic resource in my country, Chinese herbal medicine has become a hot spot for the development of drugs for the treatment of viral diseases due to its strong activity, safety and lack of drug resistance. Summary of the invention

[0004] The present invention aims at the characteristics of porcine viral diarrhea and intends to use Chinese herbal medicines with antibacterial, antiviral and disease resistance-enhancing properties to develop a compound Chinese medicine preparation for treatment. The purpose of the present invention is to provide a compound Jinqi injection and its application, which is used to provide a Chinese herbal medicine with antibacterial, antiviral and disease resistance-enhancing properties to solve the problem of porcine viral diarrhea.

[0005] In order to achieve the above object, the present invention adopts the following technical solutions: Provided is a compound golden astragalus composition, which comprises traditional Chinese medicine extracts, wherein the traditional Chinese medicine extracts include honeysuckle extract, houttuynia cordata extract and amaranth extract, and any three or four of andrographis paniculata extract, iris extract, isatis indigotica extract and astragalus extract.

[0006] Furthermore, the present invention provides the compound golden astragalus composition as described above, wherein the mass ratio of the components is honeysuckle extract: 0.8-2; Houttuynia cordata extract: 1; Amaranthus tricolor extract: 0.8-1.2; Andrographis paniculata extract: 0-2.4; Ipomoea batatas extract: 0-2.4; Isatis indigotica extract: 0-2.4; and Astragalus membranaceus extract: 0-2.4.

[0007] Furthermore, the present invention provides the compound Jinqi composition as described above, wherein the mass ratio of the components is honeysuckle extract: 0.8-1.2; Houttuynia cordata extract: 1; Amaranthus tricolor extract: 0.8-1.2; Andrographis paniculata extract: 0.8-2.4; Ophiopogon japonicus extract: 0.8-2.4; Isatis indigotica extract: 1.6-2.4; Astragalus membranaceus extract: 0.8-2.4.

[0008] Furthermore, the present invention provides the compound Jinqi composition as described above, wherein the mass ratio of the components is: honeysuckle extract: 1; Houttuynia cordata extract: 1; Amaranthus tricolor extract: 1; Andrographis paniculata extract: 2; Ophiopogon japonicus extract: 1; Astragalus membranaceus extract: 1.

[0009] Furthermore, the present invention provides the compound Jinqi composition as described above, wherein the content of astragalus polysaccharide in the astragalus extract is ≥90%.

[0010] Furthermore, the present invention provides the compound Jinqi composition as described above, wherein the content of astragaloside in the astragalus extract is not less than 10%. The preparation method of the honeysuckle extract, houttuynia cordata extract, amaranth extract, andrographis paniculata extract, andrographis paniculata extract or isatis root comprises: adding 8 to 12 times the mass of 35 to 45% by volume ethanol-water solution to the dried medicinal materials of honeysuckle, houttuynia cordata, amaranth extract, andrographis paniculata, andrographis paniculata or isatis root, extracting for 3 to 5 hours under heating reflux conditions, and filtering; adding the same mass of 35 to 45% by volume ethanol-water solution to the residue again, repeating the extraction twice under the same conditions, and combining the extracts; distilling, concentrating the extract to 40 to 60%, cooling to room temperature, filtering, and concentrating the filtrate to dryness to obtain the corresponding extract.

[0011] Furthermore, the present invention provides a compound Jinqi solution, which comprises the compound Jinqi composition as described above and water.

[0012] Furthermore, the present invention provides a compound Jinqi solution, which comprises the compound Jinqi composition as described above and water in a mass volume ratio of 1 to 10:100 (g / ml), preferably 1 to 8:100 (g / ml), or 1 to 6:100 (g / ml), or 1 to 4:100 (g / ml), or 1 to 2:100 (g / ml).

[0013] Furthermore, the present invention provides a compound Jinqi solution, wherein the compound Jinqi solution further comprises a stabilizer, wherein the stabilizer is selected from a solubilizer and / or an antioxidant; Furthermore, the present invention provides a compound golden qi solution, wherein the solubilizing agent is selected from Tween-80 or sodium deoxycholate; and the antioxidant is selected from one or more of sodium thiosulfate, sodium bisulfite, acetylcysteine, vitamin E, and ascorbic acid.

[0014] Furthermore, the present invention provides a compound Jinqi solution, wherein the solubilizing agent is 0.4-0.6% Tween-80 or 0.08-0.12% sodium deoxycholate; and the antioxidant is 0.08-0.12% sodium thiosulfate or 0.08-0.12% sodium bisulfite.

[0015] Furthermore, the present invention provides a compound Jinqi solution, wherein the solubilizing agent is 0.5% Tween-80, and the antioxidant is 0.1% sodium bisulfite.

[0016] Furthermore, the pH of the injection is 6.5-7.0.

[0017] Furthermore, the present invention provides the use of the compound Jinqi composition or the compound Jinqi solution in the preparation of a medicine for treating porcine viral diarrhea.

[0018] The present invention has at least the following beneficial effects: The present invention adopts 7 kinds of Chinese medicinal extracts, namely, astragalus, honeysuckle, isatis root, houttuynia, andrographis paniculata, amaranth and iris, to form 4 formulas of Chinese medicinal extract compound injections, which can be effectively used as therapeutic drugs for porcine viral diarrhea. The effective rate for porcine viral diarrhea is 97%, and the cure rate is also over 90%. DETAILED DESCRIPTION

[0019] In order to make the purpose, technical solution and advantages of the present invention more clearly understood, the present invention is further described in detail below in combination with embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0020] Materials and Methods 1.1 Traditional Chinese Medicine and Chinese Herbal Medicine Extracts 1.1.1 Astragalus extract (purchased from Xi'an Hengruikang Biotechnology Co., Ltd., Shaanxi Province), of which the astragalus polysaccharide content is not less than 90%, UV-visible spectrophotometry; astragaloside content is not less than 10%, HPLC-external standard method.

[0021] 1.1.2 Preparation of honeysuckle extract: Take commercially available dried honeysuckle, add 10 times the mass of 40% volume ratio ethanol-water solution, extract under heating reflux conditions for 4 hours, filter; add the same mass of 40% volume ratio ethanol-water solution to the residue again, repeat extraction twice under the same conditions, combine the extracts, distill, concentrate the extract to 50%, cool to room temperature, filter, and concentrate the filtrate to dryness to obtain honeysuckle extract.

[0022] 1.1.3 Preparation of Houttuynia cordata extract, Andrographis paniculata extract, Amaranthus tricolor extract, Ipomoea aquatica extract, and Radix Isatidis extract: Get the corresponding commercially available Chinese medicine products and refer to the method in Section 1.1.2 to obtain the corresponding Chinese medicine extracts.

[0023] 1.2 Experimental animals Kunming mice were purchased from the Lanzhou Veterinary Research Institute of the Chinese Academy of Agricultural Sciences; rabbits were purchased from a rabbit farm in Kongtong District, Pingliang City; and experimental pigs were provided by a pig farm in Pingliang City.

[0024] 1.3 Experimental Drugs Jingen injection (5 mL, equivalent to 11.25 g of the original drug), ciprofloxacin lactate injection (10 mL: 0.2 g), and oral rehydration salts were purchased from a veterinary drug store in Pingliang City.

[0025] 1.3 Viruses and cells Porcine epidemic diarrhea virus (PEDV), porcine transmissible gastroenteritis virus (TGEV) and porcine group A rotavirus (PoRV-A) were provided by the Virus Laboratory of Gansu Institute of Animal Husbandry and Veterinary Medicine, and ST cells (pig testicular cells), Vero cells (African green monkey kidney cells) and MA104 cells (rhesus monkey kidney cells) were cultured, propagated and preserved by the Cell Laboratory of Gansu Institute of Animal Husbandry and Veterinary Medicine.

[0026] Prescription screening of traditional Chinese medicine preparations 2.1 The compatibility formula of Chinese herbal medicine extract injection is shown in Table 1.

[0027] Table 1: Composition of Chinese herbal medicine extract preparations

[0028] Prepare according to the above formula, add water for injection to 100mL, sterilize at 110℃ for 20min, and set aside.

[0029] 2.2 Study on the inhibitory and killing effects of different routes of administration and duration of action of the preparations on viruses Within the range of safe dosage of Chinese herbal compound injection for cells, different ways of adding drugs and viruses were used to virus-sensitive cells (drugs and viruses were exposed to the virus at the same time at 37°C for 2 hours; drugs were given first, incubated in a CO2 incubator at 37°C and 5% by volume for 2 hours before adding viruses; viruses were added first, and then drugs were added after an interval of 2 hours) to study the direct inactivation effect of drugs on viruses, the blocking effect of drugs on viruses, the effect of drugs on virus replication, and the comprehensive inhibitory effect of drugs on viruses.

[0030] 2.3 Experimental Results The TCID values ​​of TGEV, PDEV and PoRV on cells were calculated by the Reed-Muench method. 50 10 respectively -4.88 , 10 -4.88 , 10 -4.89 Therefore, the experiment used 100 TCID 50 Virus attack volume.

[0031] The compound injection of traditional Chinese medicine extract was diluted and inoculated into cells at 1 mg / mL. After 96 hours, the cell survival rate was 100%, indicating that the compound injection was non-toxic to cells and was safe within the safety range of 1 mg / mL.

[0032] Table 2 Protective effect of Chinese herbal compound injection (administered simultaneously) on cells

[0033] Note: Dosage method: The drug and virus are simultaneously exposed to 37°C for 2 hours; Test drug concentration: The original drug concentration is diluted to 1 mg / mL using the nutrient solution of different cells.

[0034] Table 3 Protective effect of Chinese herbal compound injection (preventive administration) on cells

[0035] Note: Administration method: first give the drug, incubate in a CO2 incubator at 37°C and 5% by volume for 2 hours, then add the virus; Test drug concentration: dilute the original formula drug concentration to 1 mg / mL with the nutrient solution of different cells.

[0036] Table 4 Protective effect of Chinese herbal compound injection (therapeutic administration method) on cells

[0037] Note: Dosing method: add the virus first, then add the drug after an interval of 2 hours; Test drug concentration: dilute the original formula drug concentration to 1 mg / mL using the nutrient solution of different cells.

[0038] As shown in Table 2-4, compared with the normal control group, the cells in the virus control group all showed pathological changes, and the cell pathological death rate was 100%; within the safe concentration range, the Chinese medicine compound injection had a protective effect on ST cells, VERO cells and MA104 cells, among which the cell survival rate of the Chinese medicine compound injection of formula 4 in three administration methods was more than 62.5%, which was significantly different from the virus control group, formula group 1, formula group 2 and formula group 3; the cell survival rate of the Chinese medicine compound injection of formula 4 in simultaneous administration, preventive administration and therapeutic administration was higher than that of the Chinese medicine compound injection of other formulas. The test results showed that the drug had an inhibitory effect on viral proliferation, and the three administration methods of formula 4 group had a significant inhibitory effect on the three viruses of TGEV, PEDV and PoRV, and the therapeutic administration was stronger than simultaneous administration and preventive administration.

[0039] Preparation of Chinese herbal medicine extract injection preparation: 3.1 Preparation of the compound Jinqi composition (composition preparation example 1): Take 50 g of honeysuckle extract, 25 g of Houttuynia cordata extract, 25 g of Amaranthus tricolor extract, 50 g of Andrographis paniculata extract, 25 g of Ipomoea batatas extract, and 25 g of Astragalus membranaceus extract, mix well, add water for injection, heat to 60°C, dissolve by ultrasonic vibration, adjust the pH to 7.0 with 10% sodium hydroxide solution, add 5 g of activated carbon for decolorization, heat to boiling for 10 minutes, cool and filter; transfer the filtrate to a freeze dryer, cool it to -30°C within 30 minutes, and freeze-dry it to constant weight at a vacuum degree below 600 Pa to obtain a loose powder for later use.

[0040] 3.2 Preparation of Compound Jinqi Injection (Injection Preparation Example 1): Weigh 1 g of the powder of the compound Jinqi composition obtained in Preparation Example 1 of Part 3.1, add 80 ml of purified water, 0.5 g of Tween-80 and 0.1 g of sodium thiosulfate, dissolve it by ultrasonic vibration at 25°C, filter it through a PES polyethersulfone microporous filter membrane with a pore size of 0.22 μm, wash the filter membrane with 2 ml of purified water after filtration, combine the filtrate, add sterilized purified water to 100 ml, and sterilize it in a pressure cooker at 125°C for 30 minutes.

[0041] 3.3 Preparation of Compound Jinqi Injection, Preparation Example 2-9, Weigh 1 g of the powder of the compound Jinqi composition obtained in Preparation Example 1 of Part 3.1, and prepare the compound Jinqi injection according to the method of Preparation Example 1, taking the combination of solubilizers / antioxidants of Groups 2-9 in Table 5. Table 5 Stabilizer / Antioxidant Selection Test

[0042] 4. Quality inspection of compound Jinqi injection: According to the requirements of the 2010 edition of the "Chinese Pharmacopoeia of Veterinary Medicine", the "Technical Guidelines for Stability Testing of Chinese and Natural Veterinary Medicines", the "Technical Guidelines for Local Irritation and Hemolysis Studies of Chinese and Natural Medicines", the "Technical Guidelines for Acute Toxicity Studies of Chinese and Natural Medicines", and the "General Rules for Veterinary Preparations" regarding mixtures and injections, and the "Guidelines for the Application of Safety Inspection Methods for Chinese Veterinary Injections", they are subject to quality inspection.

[0043] 4.1 Determination of pH pH value has a crucial impact on the stability and clarity of Chinese herbal medicine injections. Drug solutions generally have a most stable pH value.

[0044] 4.2 Clarity inspection There should be no visible turbidity or insoluble matter in the injection. The clarity test method shall be carried out in accordance with the provisions of the Chinese Pharmacopoeia.

[0045] 4.3 Impurity inspection Quality inspection: Take 1 ml of injection solution, add 5 ml of freshly prepared 1% egg white saline solution, and let it stand for 10 minutes. No turbidity or precipitation should appear.

[0046] Protein test: Take 1 ml of injection solution and add 1 to 3 drops of freshly prepared tannic acid test solution. No turbidity should be observed.

[0047] 4.4 Sterility test After sterilization or aseptic packaging, samples should be taken for sterility testing. The test should be carried out in accordance with the provisions of the "Sterility Test Method" in the Appendix of the "Chinese Veterinary Pharmacopoeia" (2010 Edition), with Escherichia coli [CVCC1570] as the control bacteria. When the positive control tube is turbid and bacteria grow, and the negative control tube has no bacteria growth, it can be judged that the sterility test is qualified.

[0048] 4.5 Stability test of injection preparations The injection stability test is to examine the quality changes of injection drugs under different environmental conditions through accelerated tests and long-term tests, providing a scientific basis for the production, packaging, storage, transportation conditions of injection preparations and the final determination of the shelf life of injection drugs.

[0049] Test sample: the compound Jinqi injection prepared in section 3.2 of the present invention.

[0050] In the accelerated test, the finished injection is placed at 40℃ for 6 months, and samples are taken at 30d, 60d, 90d, and 180d to test the properties, clarity, pH value, insoluble particles, and sterility of the injection. In the long-term test, the finished injection is placed at room temperature and 4℃ for 360d, and samples are taken every 90d. The properties, clarity, pH value, insoluble particles, and sterility of the injection are tested at 0d, 90d, 180d, 270d, and 360d.

[0051] Table 6-1 Stability test of injection (Part 3.2, injection preparation example 1, group 1)

[0052] Table 6-1 Stability test of injection (Part 3.2 Group 5)

[0053] Note: “-” means the injection is clear, the pH value meets the requirements, no insoluble particles are found, and it is sterile; “+” means the injection is not clear, the pH value does not meet the requirements, insoluble particles are found, and it is contaminated with foreign bacteria. As shown in Table 6-1, the results of the accelerated test and long-term test show that the properties, clarity and pH value of the injection remain unchanged after being placed at 40℃±2℃, 20-25℃ and 4℃ for 0d, 30d, 60d, 90d, 180d, 270d and 360d, respectively. The insoluble particles and sterility tests meet the general requirements for injection preparations. The test results also confirm that the quality of the injection has not changed within 360 days, so the injection is tentatively valid for 12 months.

[0054] It can be seen from Table 6-2 that the type of antioxidant also has a great influence on the stability of the injection of the present invention, and the accelerated stability protection effect of ascorbic acid on the injection of the present invention is weaker than that of sodium thiosulfate.

[0055] Safety and therapeutic effect testing of compound Jinqi injection: 5.1 Safety testing and LD50 determination of injection preparations 70 Kunming mice weighing 18-22g, half male and half female, were fasted for 12 hours before the experiment, but not water. The LD50 of the compound Chinese herbal extract injection was determined by the modified Koch method.

[0056] Test sample: Preparation of compound Jinqi injection in Part 3.2 of the present invention (injection preparation example 1).

[0057] First, conduct a preliminary experiment to find out the doses that cause 100% and 0% death of animals based on experience or literature, i.e., the upper and lower limit doses (Dm, Dn). Then conduct a formal experiment, randomly divide the mice into 5 groups, 10 mice in each group, half male and half female; inject the drug solution into the mice intraperitoneally according to the designed dose, observe and record the number of mice that died, and calculate the LD50 and 95% confidence limit.

[0058] Preliminary experiments determined that the reference values ​​of the dosage range that causes 0% and 100% animal death are: minimum dose (Dn) 8486 mg / kg, maximum dose (Dm) 15000 mg / kg.

[0059] The experiment was divided into 5 groups, and the common dosage ratio of each group was:

[0060] Calculate the dosage of each group according to the common ratio: D1, D2, D3, D4, D5 D1= 8486 D2=D1×r=9784 D3=D2×r=11281 D4=D3×r=13007 D5=D4×r=15000 The drug solution was injected into the peritoneum of mice according to the designed dose, and the number of mouse deaths was observed and recorded (see Table 10).

[0061] Table 6 LD of injection 50 Measurement result record sheet

[0062] After calculation:

[0063] LD 50 95% mean confidence limit = LD 50 ±4.5LD 50 ×SX 50 ) =11444.58±4.5×11444.58×0.0146 ) =11444.58±751.91 The median lethal dose (LD50) of the injection solution (the dose of the drug component contained) was 100 mg / dL in mice after intraperitoneal injection. 50 ) is 11444.58 mg / kg.bw, and its 95% credible range is 11444.58±751.91 mg / kg.bw. According to the classification standard of drug toxicity, it can be determined that the injection is actually non-toxic.

[0064] 5.2 Therapeutic Trial of Compound Jinqi Injection 5.2.1 Artificial infection treatment experiment 30 piglets aged 7-10 days without maternal antibodies to TGEV, PEDV, and PoRV were introduced from a pig farm and randomly divided into 3 groups, 2 groups as experimental groups and the other group as a control group, each group of 10 piglets, all of which were artificially fed with suckling pig feed. Before the test, the piglets were artificially infected with a mixed virus of porcine viral diarrhea. After the onset of the disease, the first test group was treated with the compound Jinqi injection prepared in Preparation Example 1 of Part 3.2 of the present invention, the second test group was treated with oral rehydration salt + ciprofloxacin injection, and the control group was not treated, and the treatment effect and the survival of the experimental piglets were recorded.

[0065] After artificial infection, cotton swabs were used to collect anal feces from each group of piglets when the disease occurred, and three viruses of porcine viral diarrhea were detected, indicating that the artificial replication infection was successful. At this time, the piglets showed symptoms such as mental depression, poor appetite, vomiting, and diarrhea. After the disease occurred, treatment was carried out in time according to the experimental plan, and the treatment effect is shown in Table 8.

[0066] Table 7 The therapeutic effect of compound Jinqi injection on piglets suffering from porcine viral diarrhea Group drug Route of administration and dosage Quantity (head) Number of deaths (heads) mortality rate(%) Number of cured patients Cure rate (%) Valid number (head) Effectiveness (%) Try 1 group Compound Jinqi Injection 0.2 ml / kg intramuscularly 10 1 10 9 90 10 100 Try 2 groups Oral rehydration salt + ciprofloxacin injection 0.5ml / kg 10 10 100 0 0 0 0 Control group --- ---- 10 10 100 0 0 0 0 From Table 8, we can see that the application of compound Jinqi injection is 100% effective and 90% cure rate for artificially infected pigs with viral diarrhea; it is also known from the table that the application of antibiotics to treat pigs with viral diarrhea cannot achieve the expected therapeutic effect. Therefore, in the treatment of pig viral diarrhea cases, after diagnosis, Chinese medicine, interferon and other drugs can be used for comprehensive treatment; it also shows that the compound Jinqi injection developed by this institute is effective in treating pigs with viral diarrhea and can be used to treat pig viral diarrhea.

[0067] 5.2.2 Clinical treatment trials Piglets of 15-20 days old in a pig farm weighed 3-5kg and were raised conventionally. The sows were fed complete feed without antibiotics. The piglets all had natural disease conditions, depression, decreased appetite, diarrhea, and yellow or yellow-green watery feces. They were diagnosed as acute infectious diseases caused by mixed infection of TGEV, PEDV, and PoRV by RT-CPA detection and gold-labeled kit of TGEV, PEDV, and PoRV. Five piglets died suddenly at the beginning of the disease, and diarrhea symptoms appeared before death. 90 sick piglets were randomly divided into 3 groups, 30 in each group, and divided into 3 test groups. Test group 1 was treated with the compound Jinqi injection + ciprofloxacin injection prepared in Preparation Example 1 of Part 3.2 of the present invention, intramuscular injection; test group 2 was treated with Jingen injection + ciprofloxacin injection intramuscular injection; test group 3 was treated with oral rehydration salt only; the treatment medication was used once a day for 5 consecutive days, and the treatment effect and survival of sick piglets in each group were recorded.

[0068] 90 piglets with porcine viral diarrhea were divided into groups and treated according to different treatment plans. The treatment effects were observed, and the number of cured pigs, survivors, and deaths in each group were counted. The results are shown in Table 8.

[0069] Table 8 Clinical therapeutic effect of compound Jinqi injection Group Quantity (head) Number of deaths (heads) mortality rate(%) Number of cured patients Cure rate (%) Valid number (head) Effectiveness (%) Test Group 1 30 0 0 27 90 29 97 Test Group 2 30 3 10 24 80 27 90 Experiment 3 groups 30 15 50 As can be seen from Table 8, the compound Jinqi injection developed in this study has an efficacy of 97% in the treatment of viral diarrhea in piglets, and a cure rate of over 90%, which is significantly better than the combined treatment of Jingen injection + ciprofloxacin injection.

[0070] summary This study developed a compound injection of Chinese herbal extracts consisting of 4 formulas of 7 Chinese herbal extracts, including Astragalus, Honeysuckle, Radix Isatidis, Houttuynia, Andrographis, Amaranthus, and Sijiqing. The effects of 1 mg / mL on TGEV, PEDV, and PoRV were studied using a cell-based method with 3 administration methods. The results showed that formula 4 was superior to the other 3 formulas and had a good inhibitory effect on TGEV, PEDV, and PoRV. The compound injection of Chinese herbal extracts developed using formula 4 (Compound Jinqi Injection) complies with the general principles of injection preparations in the Pharmacopoeia of Veterinary Medicine, and its LD500 / mL intraperitoneal injection in mice is 1.38 mmol / l. 50 It is 11444.58mg / kg.bw, and its 95% credible range is 11444.58±751.91mg / kg.bw; according to the drug toxicity classification standard, it can be determined that the injection is actually non-toxic; after stability testing, its shelf life is tentatively set at 12 months.

[0071] After treatment experiments, the compound Jinqi injection developed in this study had an efficacy of 97% and a cure rate of over 90% in the treatment of porcine viral diarrhea.

[0072] The above shows and describes the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited to the above embodiments, and the above embodiments and descriptions only describe the principles of the present invention. The present invention may be subject to various changes and improvements without departing from the spirit and scope of the present invention, and these changes and improvements fall within the scope of the present invention claimed.

Claims

1. A compound Jinqi composition, comprising Chinese herbal extracts, wherein the Chinese herbal extracts include honeysuckle extract, houttuynia cordata extract and amaranth extract, and any three or four of Andrographis paniculata extract, Sijiqing extract, Isatis indigotica extract and Astragalus membranaceus extract.

2. The compound Jinqi composition according to claim 1, wherein the mass ratio of the components is: honeysuckle extract: 0.8-2; Houttuynia cordata extract: 1; Amaranthus chinensis extract: 0.8-1.2; Andrographis paniculata extract: 0-2.4; Sijiqing extract: 0-2.4; Isatis indigotica extract: 0-2.4; Astragalus membranaceus extract: 0-2.4; Preferably, the mass ratio of the components is: honeysuckle extract: 0.8-1.2; Houttuynia cordata extract: 1; Amaranthus tricolor extract: 0.8-1.2; Andrographis paniculata extract: 0.8-2.4; Sijiqing extract: 0.8-2.4; Isatis indigotica extract: 1.6-2.4; Astragalus membranaceus extract: 0.8-2.4; More preferably, the mass ratio of the components is: honeysuckle extract: 1; Houttuynia cordata extract: 1; Amaranthus tricolor extract: 1; Andrographis paniculata extract: 2; Ophiopogon japonicus extract: 1; Astragalus membranaceus extract:

1.

3. The compound golden astragalus composition according to claim 1, wherein the content of astragalus polysaccharide in the astragalus extract is ≥90%.

4. The compound Jinqi composition according to claim 1, wherein the preparation method of the honeysuckle extract, houttuynia cordata extract, amaranth extract, andrographis paniculata extract, cyperus rotundus extract, or isatis indigotica extract comprises: Add 8 to 12 times the mass of 35 to 45% by volume ethanol-water solution to the dried medicinal materials of honeysuckle, houttuynia cordata, amaranth, andrographis paniculata, evergreen or isatis root, extract for 3 to 5 hours under heating reflux conditions, and filter; add the same mass of 35 to 45% by volume ethanol-water solution to the residue again, repeat the extraction twice under the same conditions, combine the extracts; distill, concentrate the extract to 40 to 60%, cool to room temperature, filter, and concentrate the filtrate to dryness to obtain the corresponding extract.

5. A compound Jinqi solution, comprising the compound Jinqi composition according to any one of claims 1 to 4 and water.

6. The compound Jinqi solution according to claim 5, wherein the mass volume ratio of the compound Jinqi composition to water is 1-10:100 (g / ml), preferably 1-8:100 (g / ml), or 1-6:100 (g / ml), or 1-4:100 (g / ml), 1-2:100 (g / ml).

7. according to the compound golden qi solution described in claim 5 or 6, described compound golden qi solution further comprises a stabilizing agent, and described stabilizing agent is selected from solubilizing agent and / or antioxidant.

8. according to the compound golden qi solution of claim 7, the solubilizing agent is selected from Tween-80 or sodium deoxycholate; the antioxidant is selected from one or more of sodium thiosulfate, sodium bisulfite, acetylcysteine, vitamin E, and ascorbic acid.

9. The compound Jinqi solution according to claim 7, wherein the solubilizing agent is 0.4-0.6% Tween-80 or 0.08-0.12% sodium deoxycholate; the antioxidant is 0.08-0.12% sodium thiosulfate or 0.08-0.12% sodium bisulfite; Preferably, the solubilizer is 0.5% Tween-80, and the antioxidant is 0.1% sodium bisulfite.

10. Use of the compound Jinqi composition according to any one of claims 1 to 4 or the compound Jinqi solution according to any one of claims 5 to 9 in the preparation of a medicament for treating porcine viral diarrhea.

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