Traditional Chinese medicine oral liquid for preventing and treating porcine viral diarrhea disease, preparation method and application thereof

Abstract

The application discloses a traditional Chinese medicine oral liquid for preventing and treating pig viral diarrhea disease and a preparation method and application thereof. The traditional Chinese medicine oral liquid comprises the following active components: honeysuckle, radix scutellariae, capillaris, viticis trifolia, gardenia, gentiana, salvia miltiorrhiza, dried tangerine or orange peel, radix notoginseng, ligustrum lucidum and liquorice. The traditional Chinese medicine oral liquid has the effects of clearing heat and resolving toxins, drying dampness and purging fire, invigorating the spleen and stomach, nourishing yin and generating fluid, and can be effectively used for preventing and treating pig viral diarrhea disease and bacterial diarrhea disease. The traditional Chinese medicine oral liquid has the characteristics of scientific prescription compatibility, wide raw material sources, simple preparation process, safe and wide application, and is suitable for industrialized breeding, and has clear efficacy, stable quality and strong market competitiveness.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of veterinary traditional Chinese medicine, in particular to a traditional Chinese medicine oral liquid for treating porcine viral diarrhea disease and a preparation method and application thereof. BACKGROUND

[0002] Porcine viral diarrhea mainly refers to a porcine gastrointestinal disease caused by infection of one or more of porcine epidemic diarrhea virus (PEDV), porcine transmissible gastroenteritis virus (TGEV) and porcine rotavirus (PoRV), which has the characteristics of more occurrence in winter and spring, and susceptible piglets, and presents clinical symptoms such as vomiting, watery diarrhea, dehydration and emaciation, and often appears mixed infection with pathogenic Escherichia coli, and can cause death in severe cases. The pathogenic mechanisms of the three viruses are similar, and the diarrhea caused by porcine transmissible gastroenteritis is the most serious, which can cause gastric fundus hemorrhage, thinning of intestinal wall and intestinal villus shedding; porcine epidemic diarrhea is the second, which can cause catarrhal gastritis of gastric fundus; and porcine rotavirus diarrhea is relatively mild, which can cause small intestinal villus atrophy.

[0003] Porcine viral diarrhea occurs in most provinces, cities and regions in China, and the serological survey for porcine rotavirus shows that the positive rate is 83%, and the positive pig farm is 100%. Therefore, porcine viral diarrhea has caused great hindrance to the development of China's breeding industry, and the incidence rate far exceeds that of respiratory diseases, which has caused important economic losses to the breeding industry.

[0004] Porcine viral diarrhea is generally prevented by immunization with vaccines, but immunization failure often occurs due to many reasons, such as vaccine quality, transportation and storage, pig farm conditions, pathogen type, whether the vaccine is matched, whether the whole group is immunized, whether the operation is standardized, etc. Immune failure will lead to the return of the virus, and even more, variation or secondary mixed infection, which is difficult to immunize again by vaccine, thereby causing greater economic losses.

[0005] Compared with the uncertainty and relatively high cost of vaccine immunization, the use of traditional Chinese medicine for prevention and treatment has good natural advantages. Traditional Chinese medicine contains numerous complex natural organic chemical components, which have good antiviral, antibacterial, antipyretic and anti-inflammatory, and immunoregulatory effects, etc. After being composed into a compound, it can treat and adjust the body from multiple targets, and achieve the effect of carrying and synergistic effect.

[0006] According to research, most heat-clearing Chinese medicines have good antiviral effect, and have good treatment effect on viral diseases. According to the basic theory of traditional Chinese veterinary medicine, the main reason for the occurrence of viral diarrhea in pigs is that the spleen and stomach of pigs are not in charge, the ascending and descending functions are out of order, leading to invasion of dampness, food stagnation, accumulation of heat and diarrhea. Therefore, the prevention and treatment of viral diarrhea should be mainly based on the principles of drying dampness, detoxifying, regulating the stomach and spleen, astringing the intestines and stopping diarrhea. Therefore, the development of Chinese veterinary medicine preparations with the functions of drying dampness, detoxifying, regulating the stomach and spleen, astringing the intestines and stopping diarrhea, and strengthening the spleen and tonifying qi can effectively inhibit the reproduction of viruses, enhance the appetite of piglets, significantly improve the immunity and resistance to viruses of the body, enhance the constitution, reduce the harm of diarrhea, and promote growth. SUMMARY

[0007] The purpose of the present application is to provide a kind of oral liquid of traditional Chinese medicine for preventing and treating pig viral diarrhea disease, fundamentally adjusting the state of pig population, solving the problem of disease occurrence, the oral liquid of traditional Chinese medicine is dialectically treated, and the new idea for preventing and treating pig viral diarrhea disease is provided.

[0008] Another purpose of the present application is to provide a preparation method and application of the oral liquid of traditional Chinese medicine for preventing and treating pig viral diarrhea disease.

[0009] The present application also provides a powder, granules or soluble powder containing the prescription and preparation method of the oral liquid of traditional Chinese medicine.

[0010] The purpose of the present application is realized by the following technical scheme:

[0011] The present application provides an oral liquid of traditional Chinese medicine for preventing and treating pig viral diarrhea disease, which contains active ingredients, and the active ingredients are made of honeysuckle, radix scutellariae, capillaris, lonicera japonica thunb, gardenia, gentiana, salvia miltiorrhiza, pericarpium citri reticulatae, adenosma glutinosum, ligustrum lucidum ait, and licorice.

[0012] Further, the active ingredients are made of honeysuckle 25-40 parts, radix scutellariae 20-35 parts, capillaris 15-25 parts, lonicera japonica thunb 15-25 parts, gardenia 10-20 parts, gentiana 10-18 parts, salvia miltiorrhiza 8-15 parts, pericarpium citri reticulatae 7-12 parts, adenosma glutinosum 7-12 parts, ligustrum lucidum ait 8-12 parts, and licorice 4-9 parts.

[0013] Further, the active ingredients are made of honeysuckle 30-35 parts, radix scutellariae 25-30 parts, capillaris 18-22 parts, lonicera japonica thunb 15-20 parts, gardenia 14-18 parts, gentiana 10-15 parts, salvia miltiorrhiza 10-12 parts, pericarpium citri reticulatae 8-10 parts, adenosma glutinosum 8-10 parts, ligustrum lucidum ait 8-10 parts, and licorice 5-8 parts.

[0014] Further, the active ingredients are made of honeysuckle 32 parts, Huangqi 28 parts, Yincheng 20 parts, Wu Tai 18 parts, Zhizi 16 parts, Longdan 13 parts, Danshen 11 parts, Chenpi 9 parts, Nansha 9 parts, Nuzhizi 9 parts, Gancao 6 parts.

[0015] The application also provides a preparation method of the Chinese medicine oral liquid for preventing and treating porcine viral diarrhea disease, comprising the following steps:

[0016] (1) According to the weight ratio, honeysuckle, Huangqi, Yincheng, Zhizi, Wu Tai, Longdan, Danshen, Chenpi, Nuzhizi and Gancao are weighed and prepared;

[0017] (2) The various medicinal materials weighed in step (1) are crushed respectively, the honeysuckle powder and the Huangqi powder are mixed uniformly to obtain a mixture 1; the Longdan powder, the Nansha powder and the Gancao powder are mixed uniformly to obtain a mixture 2; the Yincheng powder, the Wu Tai powder, the Zhizi powder, the Danshen powder, the Chenpi powder and the Nuzhizi powder are mixed uniformly to obtain a mixture 3, which are prepared for use;

[0018] (3) The concentrated liquid 1 is prepared by the following method: the mixture 2 is soaked in 8-10 times of water by using decoction method, heated, and when the temperature reaches 80-90 DEG C, the mixture 1 is added and stirred uniformly, extracted for 3 times, 60 min each time, filtered, and the filtrates are combined, concentrated under reduced pressure to the relative density of 1.03-1.08 (60 DEG C) under the conditions of 60 DEG C and 0.08-0.12 MPa, to obtain the concentrated liquid 1, which is prepared for use;

[0019] (4) The concentrated liquid 2 is prepared by using the mixture 3 by the following method: the mixture 3 is added to 8-10 times of 70% ethanol and mixed uniformly, extracted for 1.5-2 min at the temperature of 40-50 DEG C, the residue is separated, and the extraction is repeated twice, the extraction liquids are combined, and concentrated under reduced pressure to the relative density of 1.15-1.20 (60 DEG C) under the conditions of 60 DEG C and 0.08-0.12 MPa, to obtain the concentrated liquid 2, which is prepared for use;

[0020] (5) The concentrated liquid 1 is taken for alcohol precipitation, after alcohol precipitation, the precipitate is separated, and the supernatant is concentrated under reduced pressure to recover ethanol to no alcohol taste under the conditions of 60 DEG C and 0.08-0.12 MPa, to obtain the concentrated liquid 3;

[0021] (6) The concentrated liquid 2 and the concentrated liquid 3 are combined, and polysorbate-80, 20% benzoic acid ethanol solution, 10% nipagin ethanol solution, anhydrous sodium sulfite and propylene glycol are added in sequence, mixed uniformly, adjusted to pH 4.5-6.5, added with water to 100 volume parts, filtered, bottled, sealed, sterilized, and obtained.

[0022] In order to better prepare the Chinese medicine oral liquid for preventing and treating the pig viral diarrhea disease, the particle size of each Chinese medicine powder in step (1) is 10-25 mu m after ultrafine grinding.

[0023] In order to better prepare the Chinese medicine oral liquid for preventing and treating the pig viral diarrhea disease, the specific operation of alcohol precipitation extraction in step (5) should be that ethanol is slowly added into the concentrated solution 1 at 60 DEG C, and the alcohol content is 60%-70% while stirring quickly, and then standing for 24 hours.

[0024] In order to better prepare the Chinese medicine oral liquid for preventing and treating the pig viral diarrhea disease, the adjusting agent for adjusting pH in step (6) is 40% sodium hydroxide solution and dilute hydrochloric acid.

[0025] In order to better prepare the Chinese medicine oral liquid for preventing and treating the pig viral diarrhea disease, the filtration in step (6) is carried out by using a microporous filter membrane with a pore size of 0.45 mu m.

[0026] The dosage form of the Chinese medicine oral liquid for preventing and treating the pig viral diarrhea disease prepared by the present application includes but is not limited to oral liquid, powder, granules or soluble powder.

[0027] The Chinese medicine oral liquid for preventing and treating the pig viral diarrhea disease has the advantages and beneficial effects that:

[0028] The prescription principle of the present application is that honeysuckle and scutellaria have good antiviral effects on clearing heat and detoxifying, purging fire and dampness, and stopping dysentery, and are used as monarch drugs; liquorice and lycianthes have good antiviral effects on inhibiting gastrointestinal smooth muscle spasm and clearing heat and dampness, and can enhance the antiviral effects of scutellaria and honeysuckle, and are used as ministerial drugs; gardenia, gentian and salvia can clear damp-heat of triple energizer, and assist honeysuckle and scutellaria in clearing heat and detoxifying, and are used as auxiliary drugs; pericarpium citri reticulatae, notoginseng and ligusticum can tonify yin and invigorate the stomach, and can relieve intestinal disorder and dehydration caused by diarrhea, and are used as ministerial drugs.

[0029] The Chinese medicine oral liquid for preventing and treating the pig viral diarrhea disease has the advantages and beneficial effects that:

[0030] The Chinese medicine oral liquid for preventing and treating the pig viral diarrhea disease has the advantages and beneficial effects that:

[0031] The Chinese medicine oral liquid for preventing and treating pig viral diarrhea disease has good treatment effect on viral diarrhea of livestock and poultry, and has good inhibition and killing effect on pathogenic bacteria causing viral diarrhea.

[0032] The Chinese medicine oral liquid for preventing and treating pig viral diarrhea disease has good treatment effect on viral diarrhea of livestock and poultry, and has good inhibition and killing effect on pathogenic bacteria causing viral diarrhea.

[0033] The Chinese medicine oral liquid for preventing and treating pig viral diarrhea disease can effectively relieve gastrointestinal lesions caused by viral diarrhea, such as intestinal wall transparency, intestinal mucosa shedding, gastric fundus bleeding and the like, can effectively relieve diarrhea symptoms, kill viruses while protecting the gastrointestinal tract, reduce gastrointestinal damage, and promote good recovery of sick livestock.

[0034] The Chinese medicine oral liquid for preventing and treating pig viral diarrhea disease can regulate the immune system of the body to some extent, increase the immune capacity of the body, and improve the disease resistance of the body.

[0035] The Chinese medicine oral liquid for preventing and treating pig viral diarrhea disease adopts ultrafine grinding technology and flash extraction technology, can maximize the retention of effective components of traditional Chinese medicine and biological activity, and has wide raw material sources, simple production process, stable and controllable product quality, low energy consumption, low production cost, and can effectively improve economic benefits.

[0036] The Chinese medicine oral liquid for preventing and treating pig viral diarrhea disease is convenient and fast to use, is suitable for veterinary clinical application, is adapted to large-scale breeding, can make up for the loss caused by vaccine immunization failure, reduces the application of antiviral drugs, ensures food safety, has no residue, and has strong market competitiveness. BRIEF DESCRIPTION OF DRAWINGS

[0037] Figure 1 The figure is a treatment effect diagram of the Chinese medicine oral liquid on pig epidemic diarrhea. DETAILED DESCRIPTION

[0038] The present application will be further described in detail below in combination with examples, but the implementation of the present application is not limited thereto, various substitutions and changes can be made according to ordinary technical knowledge and means in the art without departing from the above technical idea of the present application, and all should be included in the scope of the present application.

[0039] In order to make the purpose, process conditions and advantages of the present application more clear and obvious, the present application will be further described in detail in combination with the following implementation examples, and the specific implementation examples described herein are only used to illustrate the present application, but not to limit the scope of the present application.

[0040] Preparation of the oral liquid in Example 1

[0041] (1) According to the weight ratio, 20 parts of honeysuckle, 15 parts of scutellaria, 10 parts of yinchen, 10 parts of smilax, 8 parts of gardenia, 7 parts of gentian, 6 parts of salvia, 5 parts of dried tangerine or orange peel, 5 parts of south adenosma, 5 parts of ligustrum lucidum, and 3 parts of licorice were weighed and prepared for use;

[0042] (2) The various medicinal materials weighed in step (1) were crushed respectively, the honeysuckle powder and the scutellaria powder were mixed uniformly to obtain mixture 1; the gentian powder, the south adenosma powder, and the licorice powder were mixed uniformly to obtain mixture 2; the yinchen powder, the smilax powder, the gardenia powder, the salvia powder, the dried tangerine or orange peel powder, and the ligustrum lucidum powder were mixed uniformly to obtain mixture 3, which was prepared for use;

[0043] (3) The concentrated liquid 1 was prepared by the following method: the mixture 2 was soaked in 8-10 times the amount of water by using decoction method, heated, and when the temperature reached 80-90℃, the mixture 1 was added and stirred uniformly, extracted for 3 times, 60 min each time, filtered, and the filtrates were combined. The concentrated liquid 1 was obtained by concentrating under reduced pressure to a relative density of 1.03-1.08 (60℃) at 60℃ and 0.08-0.12 MPa, which was prepared for use;

[0044] (4) The concentrated liquid 2 was prepared by using the mixture 3 by the following method: the mixture 3 was added to 8-10 times the amount of 70% ethanol and mixed uniformly, and extracted for 1.5-2 min at a temperature of 40-50℃. The residue was separated, and the extraction was repeated twice. The concentrated liquid 2 was obtained by concentrating under reduced pressure to a relative density of 1.15-1.20 (60℃) at 60℃ and 0.08-0.12 MPa, which was prepared for use;

[0045] (5) The concentrated liquid 1 was taken for alcohol precipitation by the following method: ethanol was slowly added to the concentrated liquid 1 at 60℃, and stirred quickly while adding, so that the alcohol content reached 60%-70%. After standing for 24 h, the precipitate was separated, and the supernatant was concentrated under reduced pressure at 60℃ and 0.08-0.12 MPa to recover ethanol until there was no alcohol smell, to obtain the concentrated liquid 3;

[0046] (6) The concentrated liquid 2 and the concentrated liquid 3 were combined, and polysorbate-80, 20% benzoic acid ethanol solution, 10% nipagin ethanol solution, anhydrous sodium sulfite, and propylene glycol were added in sequence, mixed uniformly, adjusted to pH 4.5-6.5, and diluted to 100 volumes with water. After filtration, the product was bottled, sealed, sterilized, and obtained.

[0047] The specific research process of step (3) and step (4) is as follows:

[0048] According to the required effective components, the prescription was divided into two parts of water extraction and alcohol extraction.

[0049] Water extraction part of process screening: according to the weight ratio of 20 parts of honeysuckle, 15 parts of scutellaria, 7 parts of gentian, 5 parts of south-salvia, 3 parts of licorice, according to the horizontal factors (see Table 1) and orthogonal test L9 (34) (see Table 2), the solid-liquid ratio is 1:10, the extraction liquid is concentrated to the relative density of 1.03-1.08 (60℃), the contents of baicalin and chlorogenic acid and the extraction rate of polysaccharide are determined, and the variance analysis of the determination data is carried out. The results are shown in Tables 3 and 4.

[0050] Table 1 Factor level table

[0051]

[0052] Table 2 Water extraction L9 (34) orthogonal test scheme and results

[0053]

[0054]

[0055] Table 3 Variance analysis table

[0056]

[0057] *F0.05 (2,2) = 19, **F0.01 (2,2) = 99

[0058] From Table 3, it can be seen that the extraction temperature of factor C has a very significant effect on the contents of baicalin and chlorogenic acid and the extraction rate of polysaccharide, the extraction times of factor A has a significant effect on the contents of baicalin and chlorogenic acid and the extraction rate of polysaccharide, and the extraction time of factor B has no significant effect on the contents of baicalin and chlorogenic acid and the extraction rate of polysaccharide.

[0059] From Table 2, it can be seen that the optimal combination for baicalin is A3B1C3, the optimal combination for chlorogenic acid content is A3B2C3, and the optimal combination for polysaccharide extraction rate is A3B1C3. In summary, the optimal combination is A3B1C3.

[0060] Alcohol extraction part of process screening: according to the weight of 10 parts of yinchen, 10 parts of smilax, 8 parts of gardenia, 6 parts of danshen, 5 parts of dried tangerine or orange peel, and 5 parts of female privet, 70% ethanol is added and extracted twice according to different extraction methods, the extraction liquid is combined and concentrated under reduced pressure to the relative density of 1.15-1.20 (60℃), and the total content of iridoid glycosides is determined. The results are shown in Table 4.

[0061] Table 4 Extraction method

[0062]

[0063] According to Table 4, it can be seen that the extraction using the flash extraction method has obvious advantages, so the flash extraction method is used to screen the optimal extraction process. See Tables 5 and 6.

[0064] Table 5 Factor level table

[0065]

[0066] Table 6 Alcohol extraction L9(34) orthogonal test scheme and results

[0067]

[0068]

[0069] Table 7 Variance analysis table

[0070]

[0071] F0.05(2,2) = 19, F0.01(2,2) = 99

[0072] From Table 7, it can be seen that the extraction times of the A factor have a significant effect on the total iridoid glycoside content and a very significant effect on the total flavone content; the solvent concentration of the B factor has a significant effect on the total flavone content and no significant effect on the total iridoid glycoside; and the solid-liquid ratio of the C factor has no significant effect on the total iridoid glycoside and the total flavone content.

[0073] From Table 6, it can be seen that from the total iridoid glycoside content, the optimal combination is A3B2C2; and from the total flavone content, the optimal combination is A2B2C3. Because the A factor has a very significant effect on the total flavone glycoside, and A2 and A3 have little difference from the total iridoid glycoside, A2 is selected here; the C factor has no significant effect on both, so C2 is selected by comprehensive consideration; and the optimal combination is A2B2C2 by comprehensive consideration.

[0074] It has been verified by experiments that the solubility of chlorogenic acid in water at 80-90°C is relatively high, and high-temperature conditions can destroy the activity of endogenous enzymes in Huangqin. Under the above conditions, the extraction of honeysuckle and Huangqin can effectively improve the solubility of chlorogenic acid in honeysuckle, prevent the degradation of baicalin, and thus increase the content of chlorogenic acid and baicalin in the extract. The flash extraction method has the advantages of low extraction temperature, fast extraction speed, wide extraction range, short extraction time, high extraction efficiency, high efficiency, energy and reagent saving, simple operation, and the like, and can maximize the extraction of effective components without damaging the effective components. The flash extraction method can effectively improve the transfer rate of main effective components such as gardenoside, protocatechuic aldehyde, ursolic acid, and oleanolic acid, and increase their content in the extract.

[0075] Example 2

[0076] Lonicera japonica 25 parts, Scutellaria baicalensis 20 parts, Yin Chen 15 parts, Sambucus williamsii 15 parts, Gardenia 10 parts, Gentiana 10 parts, Salvia miltiorrhiza 8 parts, Tangerine peel 6 parts, South Adenosma 6 parts, Ligustrum lucidum 6 parts, and licorice 4 parts were weighed according to the weight ratio. The preparation method of Example 1 was used for preparation.

[0077] Example 3

[0078] Lonicera japonica 28 parts, Scutellaria baicalensis 23 parts, Yin Chen 16 parts, Sambucus williamsii 16 parts, Gardenia 12 parts, Gentiana 11 parts, Salvia miltiorrhiza 9 parts, Tangerine peel 7 parts, South Adenosma 7 parts, Ligustrum lucidum 7 parts, and licorice 5 parts were weighed according to the weight ratio. The preparation method of Example 1 was used for preparation.

[0079] Example 4

[0080] Lonicera japonica 30 parts, Scutellaria baicalensis 25 parts, Yin Chen 18 parts, Sambucus williamsii 18 parts, Gardenia 14 parts, Gentiana 12 parts, Salvia miltiorrhiza 10 parts, Tangerine peel 8 parts, South Adenosma 8 parts, Ligustrum lucidum 8 parts, and licorice 6 parts were weighed according to the weight ratio. The preparation method of Example 1 was used for preparation.

[0081] Example 5

[0082] Lonicera japonica 32 parts, Scutellaria baicalensis 28 parts, Yin Chen 20 parts, Sambucus williamsii 18 parts, Gardenia 16 parts, Gentiana 13 parts, Salvia miltiorrhiza 11 parts, Tangerine peel 9 parts, South Adenosma 9 parts, Ligustrum lucidum 9 parts, and licorice 6 parts were weighed according to the weight ratio. The preparation method of Example 1 was used for preparation.

[0083] To further prove the effect of the Chinese medicine oral liquid for preventing and treating viral diarrhea disease of pigs, the applicant carried out a clinical efficacy observation test on the Chinese medicine oral liquid of the present application. The beneficial effects of the Chinese medicine oral liquid of the present application are further illustrated by the following test examples.

[0084] Test Example 1 The present application is a test of the Chinese medicine oral liquid for treating mice with test diarrhea, and the inhibitory effect of the Chinese medicine oral liquid of the present application on mouse diarrhea is investigated.

[0085] 1 Material

[0086] Test drug: Chinese medicine oral liquid prepared in Examples 1, 2, 3, 4, and 5 of the present application; control drug: Chinese medicine oral liquid I, and physiological saline.

[0087] Test animals: 80 SPF mice, half male and half female, purchased from Beijing Vantoll Life Science and Technology Co., Ltd.

[0088] 2 Method

[0089] The experiment was divided into 8 groups, 10 mice in each group. After 12 hours of fasting, the mice were administered the drugs. The grouping and administration are shown in Table 8. 0.5 hours after the administration, each mouse was orally administered 0.3 ml of senna leaf decoction, except for the blank control group. After the oral administration, the mice were individually placed in cages with filter paper and wire mesh. The diarrhea of the mice was observed. The stool of the mice can be roughly divided into 5 types: normal stool, stool with normal appearance but with more water, soft stool with abnormal appearance, water-like stool, and mucous stool. The first two types are considered normal stool, and the last three types are considered diarrhea stool. The mice were changed with new filter paper every time they had diarrhea. The frequency of diarrhea was calculated every hour, and the observation was continued for 6 hours. The frequency and incidence of diarrhea were used to determine the strength of the anti-diarrhea effect of the Chinese medicine oral liquid.

[0090] Table 8: Grouping and administration of the experiment

[0091]

[0092] The preparation method of the Chinese medicine oral liquid I is according to the prescription and method in patent CN105250449A. The specific process is as follows: take 30 parts of Huanglian, 30 parts of Jinyinhua, 20 parts of Huangqi, 30 parts of Chenpi, 30 parts of Baishu, 30 parts of Huangqi, 30 parts of Matizixian, and 30 parts of Gancao. Grind them to 60-80 mesh. Add 1 part of lactic acid bacteria (104-106 / g) to the ground Chinese medicine powder. Add 10 times the amount of water and incubate at 36°C for 32 hours. Filter, fill, sterilize, and obtain the fermented Chinese medicine oral liquid I.

[0093] 3. Results and analysis

[0094] The specific results are shown in Table 9. In terms of the total number of diarrhea, compared with the blank control group, the total number of diarrhea in groups 1-5 was significantly reduced, and the drug control group was slightly reduced. In terms of the average number of diarrhea, compared with the negative control group, groups 1-5 had a very significant difference (P<0.01), and the drug control group had a significant difference (P<0.05). Compared with the drug control group, groups 1-5 had a very significant difference (P<0.01), and there was no significant difference between groups 1-5.

[0095] Table 9: Effect of Chinese medicine oral liquid and Baotouweng oral liquid on senna leaf-induced diarrhea in mice

[0096]

[0097]

[0098] Note: 1) Different letters represent significant differences (P <0.01), different lowercase letters represent significant differences (P <0.05), and the same letters represent no significant difference; 2) Compared with the negative control group, the P values of the 1st-6th groups were 0.000, 0.000, 0.000, 0.000, 0.000, and 0.015, respectively; compared with the drug control group, the P values of the 1st-5th groups were 0.000, 0.000, 0.000, 0.000, and 0.000, respectively.

[0099] 4Conclusion

[0100] The traditional Chinese medicine oral liquid of the present application can significantly inhibit diarrhea caused by senna leaves in mice, and is significantly better than the control drug traditional Chinese medicine oral liquid I (prepared according to the prescription and method in patent CN105250449A), wherein the traditional Chinese medicine oral liquid of Example 5 of the present application has the best effect, which is the optimal prescription of the present application. It is proved that the traditional Chinese medicine oral liquid of the present application can reduce the frequency of diarrhea and relieve diarrhea, and the effect is obvious.

[0101] Test Example 2 Influence of the traditional Chinese medicine oral liquid of the present application on small intestine movement of mice

[0102] 1Materials

[0103] Test drugs: the traditional Chinese medicine oral liquids prepared in Examples 1, 2, 3, 4, and 5 of the present application; control drug: traditional Chinese medicine extract II prepared according to the prescription and method in patent CN106039260A, and physiological saline.

[0104] Test animals: 70 SPF mice, purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd.

[0105] 2Methods

[0106] The test is divided into 7 groups, each group of 10 mice. After fasting for 24 hours (free drinking water), each group of mice is orally administered with the corresponding traditional Chinese medicine oral liquid 0.3 mL per mouse according to Table 10, the drug control group is orally administered with traditional Chinese medicine extract II 0.3 mL per mouse, and the blank control group is orally administered with the same amount of physiological saline. After 0.5 hours, each mouse is orally administered with carbon ink 0.1 mL, and 20 minutes later, the mice are executed by cervical dislocation, the abdominal cavity of the mice is opened, the small intestine is cut, the upper end is to the pylorus part, and the lower end is to the ileocecal part, the length from the pylorus to the farthest running end of the ink and the length from the pylorus to the ileocecal end are measured, and recorded.

[0107] Table 10 Grouping of traditional Chinese medicine oral liquid

[0108]

[0109] The traditional Chinese medicine extract II is prepared according to the prescription and method in patent CN106039260A, and specifically as follows: 15 parts of honeysuckle, 10 parts of coptis, 10 parts of radix scrophulariae, 15 parts of dried ginger, 8 parts of angelica, 15 parts of white flower snake tongue, 10 parts of barbata, 10 parts of costus, 15 parts of indigo, 15 parts of radix rehmanniae preparata, 15 parts of Chinese yam, 15 parts of radix angelicae pubescentis, 10 parts of medicated leaven, and 10 parts of licorice are added into 10 times of water for decocting, and the decocting is performed twice, the first time for 45 min and the second time for 30 min, filtration is performed, the filtrates are combined, vacuum concentration is performed to 0.5-0.8 times of the original volume, sealing is performed, sterilization is performed, and the traditional Chinese medicine extract II is obtained.

[0110] 3. Determination index

[0111] Propulsion rate = length from pylorus to the farthest running end of ink / length from pylorus to ileocecal junction

[0112] Inhibition rate of traditional Chinese medicine oral liquid = [(propulsion rate of blank control group - propulsion rate of traditional Chinese medicine oral liquid) / propulsion rate of blank control group] * 100%

[0113] Inhibition rate of control drug = [(propulsion rate of blank control group - propulsion rate of drug group) / propulsion rate of blank control group] * 100%

[0114] 4. Results and analysis

[0115] Specific results are shown in Table 11. In terms of propulsion rate, compared with the blank control group, the first to fifth groups and the drug control group have extremely significant differences (P < 0.01); in terms of inhibition rate, the first to fifth groups are obviously higher than the drug control group, and the inhibition rate of the fifth group is the highest, which is 36.84%.

[0116] Table 11 Influence of traditional Chinese medicine oral liquid on small intestinal movement of mice

[0117]

[0118] Note: Different letters represent extremely significant differences (P < 0.01), and the same letters represent no obvious difference.

[0119] 5. Conclusion

[0120] The traditional Chinese medicine oral liquid of the application can reduce the propulsion distance of ink in the small intestine, effectively inhibit the small intestinal movement, and is significantly better than the control drug traditional Chinese medicine extract II, which indicates that the traditional Chinese medicine oral liquid of the application has a significant inhibitory effect on the small intestinal movement and can effectively relieve the symptoms of diarrhea.

[0121] Test example 3 Treatment effect of the traditional Chinese medicine oral liquid of the application on porcine epidemic diarrhea

[0122] A certain pig farm of frequently-occurring porcine epidemic diarrhea in Hebei, 50 piglets of 7-30 days old were selected, wherein the feces were detected by laboratory to have porcine epidemic diarrhea virus, and the piglets were divided into 3 groups according to the litter, and were respectively fed with sample of example 1, sample of example 2 and traditional Chinese medicine oral liquid I (prepared according to the prescription and method in patent CN105250449A, and the specific preparation method is shown in test example 1), and the grouping and administration are specifically shown in table 12. The administration was continuously carried out for one week, and during the administration period, the basic conditions and symptoms of the sick piglets were observed and recorded, and after one week, the sick piglets were examined, the drug efficacy was judged according to the efficacy judgment standard, and the score was given according to the actual situation, and the specific judgment standard is shown in table 13.

[0123] Table 12 Test grouping and drug administration

[0124]

[0125] Table 13 Efficacy judgment standard

[0126]

[0127] Specific results are shown in Figure 1 . From Figure 1 and table 14, it can be seen that the treatment effect of example 1 and example 2 of the present application is obvious compared with the drug control group, and the difference is significant (P≤0.01), and the treatment effect of example 2 is the most obvious.

[0128] Table 14 Treatment effect of traditional Chinese medicine oral liquid on porcine epidemic diarrhea

[0129]

[0130] Note: different letters represent extremely significant difference (P≤0.01), and the same letter represents no obvious difference.

[0131] The traditional Chinese medicine oral liquid of the present application can effectively treat porcine epidemic diarrhea, and relieve the disease condition of the sick piglets, and is significantly better than the control drug traditional Chinese medicine oral liquid I, which shows that the traditional Chinese medicine oral liquid of the present application has a significant treatment effect on porcine epidemic diarrhea of piglets, and can effectively relieve the diarrhea symptoms caused by porcine epidemic diarrhea virus.

[0132] Test example 4 Treatment effect of the present application on porcine infectious gastroenteritis

[0133] In a pig farm in Lijiang, Yunnan, 45 piglets were purchased, and some piglets were found to have symptoms such as shivering, being afraid of cold, being weak, vomiting and diarrhea, and reduced appetite, and then rapidly spread to the whole group. The body temperature of the sick piglets was significantly elevated, all between 40.5-41.5℃, and laboratory diagnosis confirmed that it was porcine transmissible gastroenteritis. The 45 piglets were divided into three groups, and the table 15 was continuously administered for one week, and at the same time, intraperitoneal fluid infusion (1 time / head / day) was performed, and the livestock house was strengthened in feeding management, and potassium persulfate compound powder was used for disinfection. After one week, the sick piglets basically recovered, and during the treatment process, 7 piglets died in total, including 1 piglet in the first group, 14 piglets were cured, and the cure rate was 93.3%, all piglets in the second group were cured, and the cure rate was 100%, and 6 piglets died in the drug control group, and 9 piglets were cured, and the cure rate was 60%.

[0134] Table 15 Test grouping and drug administration

[0135]

[0136] The traditional Chinese medicine oral liquid of the present application can effectively alleviate the symptoms of piglet infectious gastroenteritis, and the treatment effect on piglet infectious gastroenteritis is significantly better than that of the control drug traditional Chinese medicine oral liquid II, which shows that the traditional Chinese medicine oral liquid of the present application has a significant treatment effect on piglet infectious gastroenteritis, can effectively improve the cure rate of piglet infectious gastroenteritis, and can prevent the occurrence of piglet infectious gastroenteritis.

[0137] Test example 5 Treatment effect of the traditional Chinese medicine oral liquid of the present application on mixed infection of pig viral diarrhea

[0138] In a pig farm, 30 newborn weaned piglets had diarrhea, and the sick piglets had symptoms such as depression, decreased appetite, vomiting and diarrhea, and some piglets had high fever symptoms, and severe cases died due to organ failure. The dead piglets were diagnosed by laboratory diagnosis as mixed infection of porcine epidemic diarrhea virus, porcine transmissible gastroenteritis virus and porcine rotavirus. In addition to the dead piglets, the remaining 26 piglets were divided into three groups according to the clinical symptoms, and were respectively given 4ml, 3ml and 2ml of the traditional Chinese medicine oral liquid of example 5 per piglet, and were given twice a day, and after one week, 5 piglets with severe symptoms were cured, 3 piglets with reduced symptoms were cured, and 1 piglet died; 6 piglets with severe symptoms were cured, 3 piglets with reduced symptoms were cured, and no death occurred; 8 piglets with mild symptoms were cured, 1 piglet with reduced symptoms was cured, and no death occurred, and the cure rate was 73%, and the effective rate was 96%. After another week of follow-up, the sick piglets basically recovered.

[0139] The above only describes the preferred embodiments of the present application, and it should be noted that for ordinary skilled persons in the technical field, some improvements and refinements can be made without departing from the technical principles of the present application, and these improvements and refinements should also be considered as the protection scope of the present application.

Claims

1. A traditional Chinese medicine oral liquid for the prevention and treatment of swine viral diarrhea, characterized in that, The active ingredients are prepared from honeysuckle 25-40 parts, scutellaria 20-35 parts, yinchen 15-25 parts, sambucus williamsii 15-25 parts, gardenia 10-20 parts, gentiana 10-18 parts, salvia miltiorrhiza 8-15 parts, dried tangerine or orange peel 7-12 parts, south notoginseng 7-12 parts, ligustrum 8-12 parts, licorice 4-9 parts; The preparation method of the traditional Chinese medicine oral liquid for preventing and treating viral diarrhea disease of pigs comprises the following steps: (1) According to the weight ratio, the honeysuckle, scutellaria, yinchen, gardenia, sambucus williamsii, gentiana, salvia miltiorrhiza, dried tangerine or orange peel, ligustrum and licorice are weighed and prepared; (2) The various medicinal materials weighed in step (1) are crushed, the honeysuckle powder and the scutellaria powder are mixed uniformly to obtain a mixture 1, the gentiana powder, the south notoginseng powder and the licorice powder are mixed uniformly to obtain a mixture 2, and the yinchen powder, the sambucus williamsii powder, the gardenia powder, the salvia miltiorrhiza powder, the dried tangerine or orange peel powder and the ligustrum powder are mixed uniformly to obtain a mixture 3, which are prepared for use; (3) The concentrated liquid 1 is prepared by the following method: the mixture 2 is soaked in 8-10 times the amount of water, heated, and when the temperature reaches 80-90 DEG C, the mixture 1 is added and stirred uniformly, extracted for 3 times, 60 min each time, filtered, combined, concentrated under reduced pressure to a relative density of 1.03-1.08 at 60 DEG C and 0.08-0.12 MPa, and the concentrated liquid 1 is obtained and prepared for use; (4) The concentrated liquid 2 is prepared by using the mixture 3 by the following method: the mixture 3 is added to 8-10 times the amount of 70% ethanol, mixed uniformly, extracted for 1.5-2 min at 40-50 DEG C, the residue is separated, repeated for two times, combined, concentrated under reduced pressure to a relative density of 1.15-1.20 at 60 DEG C and 0.08-0.12 MPa, and the concentrated liquid 2 is obtained and prepared for use; (5) The concentrated liquid 1 is alcohol precipitated, and after alcohol precipitation, the precipitate is separated, and the supernatant is recovered by ethanol under reduced pressure at 60 DEG C and 0.08-0.12 MPa until there is no alcohol smell, and the concentrated liquid 3 is obtained; (6) The concentrated liquid 2 and the concentrated liquid 3 are combined, and polysorbate-80, 20% benzoic acid ethanol solution, 10% nipagin ethanol solution, anhydrous sodium sulfite and propylene glycol are added in sequence, mixed uniformly, adjusted to pH 4.5-6.5, added with water to 100 volumes, filtered, bottled, sealed, sterilized, and the traditional Chinese medicine oral liquid for preventing and treating viral diarrhea disease of pigs is obtained.

2. The Chinese medicine oral liquid for preventing and treating porcine viral diarrhea disease according to claim 1, characterized in that, The active ingredients are prepared from honeysuckle 30-35 parts, scutellaria 25-30 parts, yinchen 18-22 parts, sambucus williamsii 15-20 parts, gardenia 14-18 parts, gentiana 10-15 parts, salvia miltiorrhiza 10-12 parts, dried tangerine or orange peel 8-10 parts, south notoginseng 8-10 parts, ligustrum 8-10 parts and licorice 5-8 parts.

3. The Chinese medicine oral liquid for preventing and treating viral diarrhea disease of pigs according to claim 2, characterized in that, The active ingredients are prepared from honeysuckle 32 parts, scutellaria 28 parts, yinchen 20 parts, sambucus williamsii 18 parts, gardenia 16 parts, gentiana 13 parts, salvia miltiorrhiza 11 parts, dried tangerine or orange peel 9 parts, south notoginseng 9 parts, ligustrum 9 parts and licorice 6 parts.

4. The Chinese medicine oral liquid for preventing and treating viral diarrhea disease of pigs according to claim 1, characterized in that, In step (1), the particle size of the ultrafine powder of each kind of traditional Chinese medicine is 10-25 μm.

5. The Chinese medicine oral liquid for preventing and treating viral diarrhea disease of pigs according to claim 1, characterized in that, In the step (5), the specific operation of alcohol precipitation should be: at 60°C, ethanol is slowly added into the concentrated solution 1, and the alcohol content is 60%-70% while stirring quickly, and then standing for 24h.

6. The Chinese medicine oral liquid for preventing and treating viral diarrhea disease of pigs according to claim 1, characterized in that, In the step (6), the adjusting agent used in the process of adjusting pH is 40% sodium hydroxide solution and dilute hydrochloric acid.

7. The Chinese medicine oral liquid for preventing and treating porcine viral diarrhea disease according to any one of claims 1-3, characterized in that, The prepared dosage forms include but are not limited to: oral liquid, powder, granules or soluble powder.

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