A traditional Chinese medicine preparation for treating enteritis diarrhea in animals and its preparation method

Abstract

The present invention belongs to the technical field of traditional Chinese veterinary medicine preparations, and particularly relates to a traditional Chinese medicine preparation for treating enteritis and diarrhea in animals and a preparation method thereof. The present invention uses the seeds of Sophora alopecuroides L. as raw materials, and adopts a water extraction method to replace the extraction of the main alkaloid components in Sophora alopecuroides L. with organic solvents, avoiding the problem of solvent residues; then selects appropriate excipients and processes, and adopts an inclusion masking technology to mask the bitterness of Sophora alopecuroides L., improving the compliance of animals; a series of production processes from medicinal materials to preparations are formed, the processes are simple, can be industrially produced, the prepared pharmaceutical products are stable, the quality is controllable, the content of active ingredients is high, the bioavailability is high, and it can be used for enteritis and diarrhea related diseases in chickens, pigs and cattle. It is convenient for transportation, storage and use, and can be mixed with drinking water or mixed with feed for feeding. It is particularly suitable for group administration and is used for prevention and treatment in large-scale breeding.

Description

Technical Field

[0001] The invention belongs to the technical field of Chinese veterinary medicine preparations, and specifically relates to a Chinese medicine preparation for treating animal enteritis and diarrhea and a preparation method thereof. Background Art

[0002] Animal enteritis refers to acute or chronic inflammation of the intestinal mucosa, clinically characterized by digestive disorders, abdominal pain, diarrhea, and fever. The most prominent symptom of enteritis is diarrhea. Diarrhea belongs to the category of "diarrhea" in traditional Chinese medicine, and is often caused by spleen and stomach dysfunction and dampness. As one of the common diseases in the breeding process, diarrhea in livestock and poultry is very harmful to animals, with extremely high morbidity and mortality, causing huge economic losses to farmers. There is currently no effective immunization method for diarrhea, and drug treatment is still the main means of prevention and treatment, so the prevention and treatment of diarrhea in livestock and poultry is of great significance. For a long time, veterinary clinics have usually used antibacterial drugs for treatment, but the long-term use of antibiotics has produced resistant strains, which reduces its efficacy; at the same time, the large-scale use of these drugs causes drug residues in livestock and poultry products, which seriously threatens human health.

[0003] At present, the drugs used clinically to treat diarrhea in livestock and poultry are mainly antibiotics, such as amoxicillin, ciprofloxacin, enrofloxacin, chlortetracycline, gentamicin, oxytetracycline, quinolone, etc. Among them, since quinolone drugs such as enrofloxacin and ciprofloxacin are very bitter and have poor palatability, they are generally made into injections or powders using coating technology, but the cost is very high; amoxicillin, gentamicin, oxytetracycline, etc. are prone to drug resistance and are not widely used at present; chlortetracycline is gradually abandoned by breeders due to its high toxicity and impact on growth; although quinolone can be used to prevent and treat bacterial diarrhea, it cannot be used for large livestock weighing more than 35kg, so there are few such products on the market.

[0004] Traditional Chinese medicine has a certain effect on animal enteritis and diarrhea, but the existing traditional Chinese medicine for treating animal enteritis or diarrhea has problems such as slow effect, low efficacy, and large dosage. In addition, since most traditional Chinese medicines taste bitter, animals have poor compliance, which needs further improvement.

[0005] Sophora alopecuroides is a perennial herbaceous plant of the genus Sophora in the Leguminosae family. It is also known as bitter licorice, bitter bean root and grass Sophora alopecuroides. As a traditional medicinal plant, it is mainly distributed in the northwest desert areas of Xinjiang, Inner Mongolia, Ningxia, Shaanxi and Gansu in my country, with large resource reserves. According to the Compendium of Materia Medica, Sophora alopecuroides has pharmacological effects such as clearing away heat and detoxification, antibacterial and anti-inflammatory, and analgesic and sedative, and is often used by the people to treat diseases such as dysentery and stomachache. The main active ingredients of Sophora alopecuroides are alkaloids, including sophoridine, sophorocarpine, alopecurine, sophoramine and matrine. Modern pharmacological studies have shown that the total alkaloids of Sophora alopecuroides have antibacterial and anti-inflammatory, anti-tumor and immunomodulatory effects, especially for the treatment of chronic inflammation of the body. It has a good therapeutic effect on inflammatory damage to the liver, lungs, pancreas and intestines. Therefore, alkaloid components are often extracted from Sophora alopecuroides for medicinal purposes.

[0006] There are water extraction, ethanol extraction, acid water extraction, resin method, etc. for extracting total alkaloids of Sophora alopecuroides, among which ethanol extraction is the most common. After extracting total alkaloids of Sophora alopecuroides, it is often used to make simple preparations for medicinal use. Chinese Patent 00109238.3 discloses a preparation process of total alkaloids of Sophora alopecuroides, which is complicated, the extraction yield is less than 3%, the benzene and chloroalkane substances used are highly toxic to the human body, and a large amount of sewage is generated during the extraction process. Chinese Patent 201010244222.X discloses an extraction process of total alkaloids of Sophora alopecuroides, using n-butanol instead of chloroalkane or benzene as the extraction solvent, but the steps are also cumbersome, the use of organic solvents cannot be avoided, the cost is expensive, and the yield is low. Chinese Patent No. 201310183692 discloses a perfusion solution for treating endometritis and vaginitis in pigs, its preparation method and application, and Chinese Patent No. 201210073124.3 discloses a compound perfusion solution for treating mastitis in dairy cows and its preparation method. Both of them are to mix the bitter bean extract obtained after a series of extraction steps with injection water to obtain the bitter bean total alkaloid perfusion solution. However, its disadvantage is that in the process of preparing the bitter bean total alkaloid, ether, chloroform and other toxic organic reagents are needed, which inevitably produce solvent residues, and the production process is complicated and the safety is poor. The obtained liquid preparation has the disadvantages of unstable chemical properties, easy decomposition and failure; easy to mildew; large volume, inconvenient to carry, store and transport. It can be seen that there is currently no better process to avoid cumbersome steps to extract alkaloids. Under this condition, water extraction or alcohol extraction can be used to concentrate the extract and directly use it for medicinal purposes, so as to avoid the loss caused by subsequent refining and purification as much as possible.

[0007] Sophora alopecuroides tastes extremely bitter. When the preparation of sophora alopecuroides is taken orally by animals, the animals will refuse to eat significantly, the compliance is extremely poor, and the medication is difficult to use. Therefore, it is not suitable for large-scale production and breeding. The perfusion solution is too bitter, and after perfusion, it will cause livestock to vomit when taking the medicine. Chinese Patent 20150562326 provides a sophora alopecuroides oral liquid and a preparation method thereof, wherein the sophora alopecuroides are fried and boiled with water for extraction. Frying can effectively remove the bitter substances with high polarity and the toxicity of sophora alopecuroides, and the chickens can drink freely. In addition, the toxicity and bitterness of sophora alopecuroides will not affect the drinking water and feed intake of the chicks due to the underdeveloped taste of chickens; however, due to the high frying temperature, the effective ingredient alkaloids will be lost, and the industrial production is difficult, so it can only be used for livestock breeding with underdeveloped taste. Chinese Patent 00136883.4 discloses veterinary drugs prepared from sophora alopecuroides seeds and their production process, and the boiled sophora alopecuroides seeds are fermented to make preparations. The production process is simple and does not require complex equipment. The problem to be solved by this patent is that the fermentation process requires a long time and production cycle, and the quality of the preparation cannot be well controlled.

[0008] Livestock are sensitive to bitterness. When using bitter bean preparations for treatment, the feed intake of livestock, which already have a poor appetite, often decreases again, which greatly reduces the drug effect and the livestock cure rate. Masking technology can be used for bitter beans to improve the poor palatability of total alkaloids of bitter beans. Chinese Patent 108310046A discloses a targeted microcapsule of total alkaloids of bitter beans and a preparation method thereof. The targeted microcapsule is prepared by using total alkaloids of bitter beans, astragalus polysaccharide and attapulgite clay to mask the bitterness of total alkaloids of bitter beans, and achieve the purpose of localized drug release in the large intestine, which can be used as a feed additive. However, its technological level is only reflected in the laboratory stage, and microencapsulation can also lead to unstable drug release, resulting in slow release, and excretion from the body before absorption.

[0009] It can be seen that there is a continuous demand in the current veterinary drug market for Chinese veterinary preparations with total alkaloids of Sophora alopecuroides as the main active ingredient, which are highly effective, low in toxicity, highly palatable and easy to use. Summary of the invention

[0010] The present invention aims at the above-mentioned defects existing in the prior art and provides a Chinese medicine preparation and preparation method for treating enteritis and diarrhea in animals. The present invention extracts the effective ingredients of bitter bean seeds by water, applies the inclusion and taste masking technology to develop a tasteless and non-sense bitter bean granule preparation for animals, and selects appropriate processes and auxiliary materials to prepare a modern Chinese medicine preparation.

[0011] In order to achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0012] In the first aspect, the present invention provides a traditional Chinese medicine preparation for treating enteritis and diarrhea in animals, wherein the traditional Chinese medicine preparation is a granule or powder prepared from a water extract of Sophora alopecuroides seeds as an active ingredient and excipients commonly used in pharmacy.

[0013] As an optional manner, in the above-mentioned traditional Chinese medicine preparation, the auxiliary materials include masking agents, fillers and sweeteners, and in the traditional Chinese medicine preparation, the mass ratio of water extract, masking agent, filler and sweetener is 2-20:5-80:30-100:0.01-10.

[0014] As an optional manner, in the above-mentioned traditional Chinese medicine preparation, the taste masking agent is one or more of chitosan, β-cyclodextrin, hydroxypropyl-β-cyclodextrin or sulfobutyl ether-β-cyclodextrin.

[0015] As an optional manner, in the above-mentioned traditional Chinese medicine preparation, the sweetener is one or more of sucrose, mannitol, xylitol, sucralose, aspartame, glycyrrhizin, stevioside, acesulfame potassium, saccharin or sodium cyclamate.

[0016] As an optional manner, in the above-mentioned traditional Chinese medicine preparation, the filler is one or more of starch, lactose, dextrin, maltodextrin, sucrose, mannitol, microcrystalline cellulose or glucose.

[0017] In a second aspect, the present invention provides a method for preparing the Chinese medicine preparation described in the first aspect, the preparation method comprising the following steps:

[0018] Step 1: Place the bitter bean seeds or seed powder in an extraction tank, add a certain amount of water, soak for 5-24 hours, and heat to reflux;

[0019] Step 2: Heat and boil the bitter bean extract obtained in step 1 and concentrate it to a relative density of 1.0-1.3 g / cm 3 of clear ointment;

[0020] Step 3: Add masking agent, filler and sweetener to the clear paste obtained in step 2, stir for 10-20 minutes to obtain a soft material, sieve the soft material through a 10-14 mesh sieve to granulate, dry the wet granules in an oven at 60-85°C for 3-8 hours to obtain dry granules with a moisture content of ≤8%, which are granules for treating enteritis and diarrhea in animals.

[0021] As an optional manner, in the above preparation method, the mass ratio of sophora alopecuroides seeds to water is 10-40:50-500.

[0022] Preferably, in the above preparation method, the mass ratio of sophora alopecuroides seeds to water is 15-20:120-160.

[0023] As an optional manner, in the above preparation method, the mass ratio of the clear paste, the masking agent, the filler and the sweetener is 2-20:5-80:30-100:0.01-10.

[0024] Preferably, in the above preparation method, the mass ratio of the clear paste, the masking agent, the filler and the sweetener is 6-10:15-30:50-80:0.1-1.

[0025] In a third aspect, the present invention provides a method for preparing the Chinese medicine preparation described in the first aspect, the preparation method comprising the following steps:

[0026] Step 1: Place the bitter bean seeds or seed powder in an extraction tank, add a certain amount of water, soak for 5-24 hours, and heat to reflux.

[0027] Step 2: Heat and boil the bitter bean extract obtained in step 1 and concentrate it to a relative density of 1.0-1.3 g / cm 3 of clear ointment;

[0028] Step 3: Add a taste masking agent and water to the clear paste obtained in step 2 to prepare a solution, stir evenly, and then spray dry to obtain a spray-dried powder;

[0029] Step 4: Take the spray-dried powder, add filler, sweetener and wetting agent, stir for 10-40 minutes to obtain a soft material, sieve the soft material through a 10-14 mesh sieve to granulate, dry the wet granules in an oven at 60-85°C for 3-8 hours to obtain dry granules with a moisture content of ≤8%, which are granules for treating animal enteritis and diarrhea.

[0030] As an optional manner, in the above preparation method, the mass ratio of sophora alopecuroides seeds to water is 10-40:50-500.

[0031] Preferably, in the above preparation method, the mass ratio of sophora alopecuroides seeds to water is 15-20:120-160.

[0032] As an optional manner, in the above preparation method, the mass ratio of the clear paste, the masking agent and water is 2-10:5-80:10-200.

[0033] Preferably, in the above preparation method, the mass ratio of the clear paste, the taste masking agent and water is 6-10:15-30:30-70.

[0034] As an optional manner, in the above preparation method, the mass ratio of the spray-dried powder, the filler, the sweetener and the wetting agent is 5-90:35-70:0.01-10:20-80.

[0035] Preferably, in the above preparation method, the mass ratio of the spray-dried powder, the filler, the sweetener and the wetting agent is 18-35:42-45:0.1-0.5:30-40.

[0036] As an optional manner, in the above preparation method, the spray drying parameters are: air inlet temperature of 120-160°C, liquid inlet speed of 40-60mL / min, and spray pressure of 200-400kPa.

[0037] As an optional manner, in the above preparation method, step two and step three are modified by adding the taste masking agent to the bitter bean extract, heating and concentrating them together until 20-150 parts of water remain, stirring the obtained concentrated solution evenly, and then spray drying it to obtain a spray-dried powder.

[0038] As an optional manner, in the above preparation method, the wetting agent is water or an ethanol solution with a mass percentage concentration of 0-95%.

[0039] Preferably, in the above preparation method, the wetting agent is water or an ethanol solution with a mass percentage concentration of 60-80%.

[0040] Compared with the prior art, the advantages and beneficial effects of the present invention are:

[0041] (1) Sophora alopecuroides alkaloids have multiple pharmacological activities, but Sophora alopecuroides alkaloids are not easy to extract. The present invention innovatively uses a water extraction method to replace an organic solvent to extract the main alkaloid components in Sophora alopecuroides, greatly reducing costs and avoiding the problem of solvent residues. The optimal water extraction process for Sophora alopecuroides alkaloids is optimized, and the process is simple and easy to produce. After all components are extracted, only post-processing such as filtration and spray drying is performed to reduce the loss of effective ingredients in the subsequent processing process, and the effective ingredients are retained to the maximum extent in the final product to maximize their effect.

[0042] (2) When the total alkaloid content of bitter bean is high, it is more likely to decompose under light and has poor palatability, which will affect and limit the development and bioavailability of drug preparations. The present invention uses a masking agent and a sweetness enhancer to mask the bitterness of bitter bean itself, greatly improves the palatability of the drug, and reduces the photodecomposition of the drug, which is beneficial to the preparation of drug preparations. The obtained extract preparation with a single Chinese medicine improves the absorption and bioavailability of the medicinal material, and is beneficial to the stability and quality controllability of the product.

[0043] (3) The bitter bean granules prepared by the present invention can be used not only as feed, but also as drinking water for sick animals, which is particularly suitable for animals with poor appetite and strong drinking desire, thereby improving the medication compliance of animals. Granules are convenient for transportation, storage and use. They are particularly suitable for group administration and are suitable for preventive and therapeutic medication in large-scale breeding.

[0044] (4) The medicament prepared by the present invention has a high content of effective ingredients, improves the utilization rate of Chinese medicinal materials, has an accurate dosage, can be mixed with drinking water, dissolves quickly, takes effect quickly, and has a small dosage. It improves the defects of bitter taste and high toxicity of bitter beans, and can be used for animal enteritis and diarrhea caused by bacteria (Salmonella galli, Escherichia coli, Salmonella suis, Escherichia coli, Escherichia coli, etc.), viruses (such as porcine transmissible gastroenteritis, porcine viral diarrhea, etc.), and molds.

[0045] (5) The present invention has the advantages of significant effects on the prevention and treatment of enteritis and diarrhea in livestock, no residue or little residue in animal food, avoiding the drug resistance problem caused by long-term use of Western medicine in breeding production, and the problem of Western medicine residue, reducing the harm to human health, and green and healthy breeding. The theoretical guidance of traditional Chinese veterinary medicine, combined with the application of new technologies, will be of great significance to strengthening the stability of veterinary epidemic prevention. DETAILED DESCRIPTION

[0046] If no specific techniques or conditions are specified in the examples, the techniques or conditions described in the literature in the field or the product instructions are used. If no manufacturer is specified for the reagents or instruments used, they are all conventional products that can be purchased through regular channels.

[0047] The experimental methods in the following examples are conventional methods unless otherwise specified. The experimental materials used in the following examples are commercially available products unless otherwise specified.

[0048] Unless otherwise specified, all percentages and parts in the present invention are percentages and parts by weight.

[0049] Example 1: Preparation process research, only some representative experimental results are listed

[0050] 1.1 Alkaloid content and transfer rate of different extraction processes

[0051] Table 1: Alkaloid content transfer rate of different processes

[0052]

[0053] 1.2 Comparison of different formulations on particle formability and taste

[0054] 1.2.1 Taste masking agent (taking β-cyclodextrin as an example)

[0055] Sophora alopecuroides extract and β-cyclodextrin were mixed in a ratio of 1:1, 1:2, 1:3, and 1:4, and other factors were kept unchanged to prepare granules. One gram of granules was weighed, brewed with 50 mL of hot water, and the taste was tasted to select the optimal addition amount.

[0056] Table 2: Effect of taste masking agent dosage on bitter taste masking

[0057]

[0058]

[0059] The bitterness level of the taste is divided into extremely bitter (+++), bitter (++), slightly bitter (+), and almost no bitterness (-).

[0060] 1.2.2 Flavoring agents (taking sucralose as an example)

[0061] Table 3: Bitterness masking results of different flavoring agent dosages

[0062]

[0063] 1.2.3 Wetting agent

[0064] Table 4: Effect of different wetting agents on particle forming properties

[0065]

[0066] Table 5: Effect of different wetting agent dosages on the granulation properties

[0067]

[0068] Example 2: Animal Compliance Test Study

[0069] Under free feeding conditions, 10 piglets were investigated for feeding times of bitter bean powder mixed with feed, bitter bean extract mixed with feed, bitter bean spray-dried powder mixed with feed, bitter bean granule powder mixed with feed, and bitter bean granule aqueous solution. The results are shown in Table 6 below.

[0070] Table 6: Animal compliance test results of different preparations of Sophora alopecuroides

[0071]

[0072] The results showed that the animals' acceptance of the spray-dried powder and granules after inclusion was significantly improved.

[0073] Example 3: Preparation Example of the Chinese Medicine Preparation for Treating Animal Enteritis and Diarrhea of ​​the Present Invention

[0074] Example 1: A method for preparing a Chinese medicine preparation for treating enteritis and diarrhea in animals comprises the following steps:

[0075] Step 1: Take 10 parts of 10-mesh coarse powder of Sophora alopecuroides seeds and place it in an extraction tank, add 40 parts of water, soak for 5 hours, heat and reflux for extraction for 4 hours, filter to obtain a filtrate, repeat the extraction with an equal amount of water for 2 times, combine the filtrates, and obtain a Sophora alopecuroides extract;

[0076] Step 2: Heat and boil the bitter bean extract obtained in step 1 and concentrate it to a relative density of 1.00 g / cm 3 of clear ointment;

[0077] Step 3: Take 2 parts of clear paste, add 5 parts of β-cyclodextrin, 33 parts of lactose, and 0.2 parts of cyclamate in sequence, stir for 20 minutes to obtain a soft material, granulate the soft material through a 14-mesh sieve, and dry the wet granules in an oven at 60°C for 8 hours to obtain granules for treating animal enteritis and diarrhea.

[0078] Example 2: A method for preparing a Chinese medicine preparation for treating enteritis and diarrhea in animals comprises the following steps:

[0079] Step 1: Take 40 parts of 10-mesh coarse powder of Sophora alopecuroides seeds and place it in an extraction tank, add 500 parts of water, soak for 24 hours, heat and reflux for extraction for 1 hour, filter to obtain a filtrate, repeat the extraction with an equal amount of water for 5 times, combine the filtrates, and obtain a Sophora alopecuroides extract;

[0080] Step 2: Heat and boil the bitter bean extract obtained in step 1 and concentrate it to a relative density of 1.30 g / cm 3 of clear ointment;

[0081] Step 3: Take 20 parts of clear paste, add 80 parts of hydroxypropyl-β-cyclodextrin, 39 parts of sucrose, 20 parts of maltodextrin and 1 part of aspartame in sequence, stir for 30 minutes to obtain a soft material, granulate the soft material through a 14-mesh sieve, and dry the wet granules in an oven at 80°C for 3 hours to obtain granules for treating animal enteritis and diarrhea.

[0082] Example 3: A method for preparing a Chinese medicine preparation for treating enteritis and diarrhea in animals comprises the following steps:

[0083] Step 1: Take 20 parts of bitter bean seeds and place them in an extraction tank, add 160 parts of water, soak for 12 hours, heat and reflux for extraction for 1 hour, filter to obtain a filtrate, repeat the extraction with an equal amount of water for 4 times, combine the filtrates, and obtain a bitter bean extract;

[0084] Step 2: Heat and boil the bitter bean extract obtained in step 1 and concentrate it to a relative density of 1.15 g / cm 3 of clear ointment;

[0085] Step 3: Take 10 parts of clear paste, add 30 parts of β-cyclodextrin, 60 parts of mannitol, and 0.5 parts of sucralose in sequence, stir for 20 minutes to obtain a soft material, granulate the soft material through a 14-mesh sieve, and dry the wet granules in an oven at 80°C for 2 hours to obtain granules for treating animal enteritis and diarrhea.

[0086] Example 4: A method for preparing a Chinese medicine preparation for treating enteritis and diarrhea in animals comprises the following steps:

[0087] Step 1: Take 40 parts of 10-mesh coarse powder of Sophora alopecuroides seeds and place it in an extraction tank, add 320 parts of water, soak for 3 hours, heat and reflux for extraction for 1 hour, filter to obtain a filtrate, repeat the extraction with an equal amount of water for 4 times, combine the filtrates, and obtain a Sophora alopecuroides extract;

[0088] Step 2: Heat and boil the bitter bean extract obtained in step 1 and concentrate it to a relative density of 1.15 g / cm 3 of clear ointment;

[0089] Step 3: Take 15 parts of clear paste, add 45 parts of β-cyclodextrin, 30 parts of glucose, 9 parts of maltodextrin, and 1 part of sucralose in sequence, stir for 20 minutes to obtain a soft material, granulate the soft material through a 14-mesh sieve, and dry the wet granules in an oven at 60°C for 8 hours to obtain granules for treating animal enteritis and diarrhea.

[0090] Example 5: A method for preparing a Chinese medicine preparation for treating enteritis and diarrhea in animals comprises the following steps:

[0091] Step 1: Place 40 parts of bitter bean seeds in an extraction tank, add 500 parts of water, soak for 24 hours, heat and boil for 1 hour,

[0092] Step 2: Heat and boil the bitter bean extract obtained in step 1 and concentrate it to a relative density of 1.30 g / cm 3 of clear ointment;

[0093] Step 3: Take 20 parts of the clear paste, take 80 parts of β-cyclodextrin, add 200 parts of water, prepare a solution, stir evenly, and spray dry at an air inlet temperature of 120°C, a liquid inlet speed of 30mL / min, and a spray pressure of 200kPa to obtain a spray-dried powder;

[0094] Step 4: Take 90 parts of spray-dried powder, add 70 parts of glucose, 1 part of sucralose, and 80 parts of 50% ethanol solution to prepare a soft material, sieve the soft material through a 10-mesh sieve to granulate, dry the wet granules in an oven at 60°C for 4 hours to obtain dry granules with a moisture content of ≤8%, which are granules for treating animal enteritis and diarrhea.

[0095] Example 6: A method for preparing a Chinese medicine preparation for treating enteritis and diarrhea in animals comprises the following steps:

[0096] Step 1: Take 10 parts of bitter bean seeds and place them in an extraction tank, add 50 parts of water, soak for 24 hours, heat and boil to extract for 1 hour,

[0097] Step 2: Heat and boil the bitter bean extract obtained in step 1 and concentrate it to a relative density of 1.15 g / cm 3 of clear ointment;

[0098] Step 3: Take 2 parts of the clear paste, take 5 parts of hydroxypropyl-β-cyclodextrin, add 10 parts of water to prepare a solution, stir evenly, and then spray dry at an air inlet temperature of 120°C, a liquid inlet speed of 30mL / min, and a spray pressure of 200kPa to obtain a spray-dried powder;

[0099] Step 4: Take 5 parts of spray-dried powder, add 34 parts of glucose, 1 part of sucralose, and 20 parts of 50% ethanol solution to prepare a soft material, sieve the soft material through a 12-mesh sieve to granulate, and dry the wet granules in an oven at 60°C for 4 hours to obtain dry granules with a moisture content of ≤8%, which are granules for treating animal enteritis and diarrhea.

[0100] Example 7: A method for preparing a Chinese medicine preparation for treating enteritis and diarrhea in animals comprises the following steps:

[0101] Step 1: Place 40 parts of bitter bean seeds in an extraction tank, add 320 parts of water, soak for 24 hours, heat and boil to extract for 1 hour.

[0102] Step 2: Take 80 parts of β-cyclodextrin, add it to the sophora alopecuroides extract, heat and concentrate together until there are 150 parts of water remaining, stir the obtained concentrated solution evenly, and then spray dry it. The spray drying parameters are as follows: the inlet air temperature is 160°C, the liquid inlet speed is 60mL / min, and the spray pressure is 400kPa to obtain a spray-dried powder;

[0103] Step 3: Take 90 parts of spray-dried powder, add 70 parts of glucose, 1 part of sucralose, and 20 parts of 50% ethanol solution to prepare a soft material, sieve the soft material through a 14-mesh sieve to granulate, dry the wet granules in an oven at 60°C for 4 hours to obtain dry granules with a moisture content of ≤8%, which are granules for treating enteritis and diarrhea in animals.

[0104] Example 4: Pharmaceutical research on the Chinese medicine preparation for treating enteritis and diarrhea in animals 4.1 Comprehensive evaluation research on the preparation

[0105] Comprehensive prescription evaluation was conducted on Examples 1-7 prepared in Example 3, and the evaluation results are shown in Table 7. The experimental results show that when a large proportion of fillers or taste masking agents are added (Examples 1, 2, 6, and 7), the bitterness is effectively improved, but the alkaloid content is low and it is difficult to ensure the efficacy. The granules obtained in Example 4 have poor solubility, while the bitterness of the granules obtained in Examples 3 and 5 is within an acceptable range, the solubility and solution clarity are good, and the alkaloid content can be guaranteed to be high.

[0106] Table 7: Comprehensive evaluation results of formulations of Examples 1-7

[0107]

[0108] Note: The bitterness level is divided into extremely bitter (+++), bitter (++), slightly bitter (+), and almost no bitterness (-)

[0109] 4.2 Preparation stability study

[0110] The high temperature 60°C stability of Examples 1-7 prepared in Example 3 was studied. The experimental results are shown in Table 8. The experimental results show that the particles prepared in Examples 1-7 are stable under high temperature 60°C, and the alkaloid content and properties do not change significantly, and can be stored for a long time.

[0111] Table 8: Results of 10-day high temperature 60°C stability test of formulations of Examples 1-7

[0112]

[0113]

[0114] Example 5: Pharmacodynamics study of the Chinese medicine preparation for treating enteritis and diarrhea in animals according to the present invention 1. Test drug

[0115] According to the results of pharmaceutical research, the evaluation results of the granules of Examples 3, 4 and 5 were good, so the granules prepared in Examples 3, 4 and 5 were used to treat animal enteritis and diarrhea.

[0116] 2. Experimental Animals

[0117] 60 piglets aged 8-15 days were naturally infected with enteritis and diarrhea without any drug treatment.

[0118] 3. Trial location

[0119] A group pig breeding farm in Fuxin City, Liaoning Province.

[0120] 4. Test methods

[0121] (1) Case selection criteria

[0122] ① Main symptoms: diarrhea, vomiting, weakness in the limbs, thin or watery stools, fishy or even foul odor, significantly increased frequency of defecation, redness and swelling of the anus, and increased body temperature.

[0123] ② Secondary symptoms: depression, decreased or no appetite, thirst, frequent drinking, and short and dark urine.

[0124] Inclusion criteria: Pigs that meet 3-4 main symptoms and 1-2 secondary symptoms are considered experimental pigs.

[0125] (2) Grouping and treatment of experimental animals

[0126] Select 8-15 days old pigs that meet the inclusion criteria and randomly divide them into 3 groups. The experimental animals are randomly divided into 20 groups in each group. Mix the drug with drinking water at a dose of 0.01g / kg, twice a day, for 3-5 consecutive days.

[0127] (3) Trial duration and efficacy evaluation criteria

[0128] The experiment continued to observe for 15 days after stopping the drug administration; the cure rate, total effective rate and ineffective rate were recorded and calculated.

[0129] ① Cured: After treatment, pigs with thin or watery diarrhea or fishy or even foul odor have disappeared, and the main symptoms such as frequency of defecation, redness and swelling of the anus, and elevated body temperature have disappeared. The mental and dietary habits have returned to normal and there is no recurrence during the observation period. The cure rate is calculated based on the ratio of the number of cured pigs to the number of pigs in the group.

[0130] ② Effective: After treatment, the feces of the affected pigs became thicker, the number of defecation decreased, the redness and swelling of the anus improved, and the spirit and appetite improved. The sum of the effective number of pigs and the number of cured pigs is the total effective number of pigs, and the total effective rate is calculated based on the ratio of the total effective number of pigs to the number of pigs in the group.

[0131] ③ Ineffectiveness: After treatment, the pigs’ feces, defecation frequency, anal swelling, tongue coating, spirit, and appetite still showed no significant improvement, and some even died. The ineffectiveness was calculated based on the ratio of the number of ineffective pigs to the number of pigs in the group.

[0132] 5. Results and Analysis

[0133] Table 9: Effects of the Chinese medicinal preparations for treating enteritis and diarrhea in animals of the present invention on treating enteritis and diarrhea in animals

[0134]

[0135] The results in Table 9 show that the granule preparations of Examples 3, 4 and 5 are clinically effective in treating enteritis diarrhea in pigs, and the granules prepared in Example 5 are the most effective.

[0136] In this experiment, the granule preparations of Examples 3, 4, and 5 were used to treat enteritis diarrhea in pigs, and good results were achieved. Therefore, the clinically recommended dosage of the therapeutic drug is 0.01 g / kg body weight, twice a day, for 3 consecutive days.

[0137] Example 6: Safety study of the Chinese medicine preparation for treating enteritis and diarrhea in animals according to the present invention

[0138] 1. Experimental drug: Granules for treating enteritis and diarrhea in animals prepared in Application Examples 3, 4 and 5.

[0139] 2. Experimental subjects: 15 healthy piglets aged 8-15 days.

[0140] 3. Experimental location: a sow farm in Jixi City, Heilongjiang Province.

[0141] 4. Experimental method: Healthy piglets aged 8-15 days were given 5 times the clinically recommended dose, i.e. 0.05 g / kg, twice a day for three consecutive days, and observed for 14 days after stopping the drug.

[0142] 5. Results: No death occurred during the trial.

[0143] 6. Conclusion: The granules for treating animal enteritis and diarrhea prepared in Examples 3, 4, and 5 have no toxic effects on pigs and are safe for clinical use.

[0144] Obviously, those skilled in the art can make various changes and modifications to the present invention without departing from the spirit and scope of the present invention. Thus, if these modifications and variations of the present invention fall within the scope of the claims of the present invention and their equivalents, the present invention is also intended to include these modifications and variations.

Claims

1. A preparation method of a traditional Chinese medicine preparation for treating enteritis diarrhea in animals, characterized in that, it comprises the following steps: Step 1: Take 20 parts of Sophora alopecuroides seeds and place them in an extraction tank, add 160 parts of water, soak for 12 hours, heat under reflux for 1 hour, filter to obtain a filtrate, repeat the extraction 4 times with the same amount of added water, and combine the filtrates to obtain a Sophora alopecuroides extract; Step 2: Heat and boil the Sophora alopecuroides extract obtained in Step 1 to concentrate it into a clear paste with a relative density of 1.15 g / cm 3 ; Step 3: Take 10 parts of clear paste, successively add 30 parts of β-cyclodextrin, 60 parts of mannitol, and 0.5 part of sucralose, stir for 20 minutes to obtain a soft material, granulate the soft material through a 14-mesh sieve, and dry the wet granules in an oven at 80°C for 2 hours to obtain a granule for treating enteritis diarrhea in animals.

2. A preparation method of a traditional Chinese medicine preparation for treating enteritis diarrhea in animals, characterized in that, it comprises the following steps: Step 1: Take 40 parts of Sophora alopecuroides seeds and place them in an extraction tank, add 500 parts of water, soak for 24 hours, and heat to boiling for extraction for 1 hour. Step 2: Heat and boil the Sophora alopecuroides extract obtained in Step 1 to concentrate it into a clear paste with a relative density of 1.30 g / cm 3 ; Step 3: Take 20 parts of clear paste, take 80 parts of β-cyclodextrin, add 200 parts of water, prepare a solution, stir evenly, and then carry out spray drying. The inlet air temperature is 120°C, the liquid inlet speed is 30 mL / min, and the spray pressure is 200 kPa to obtain a spray-dried powder. Step 4: Take 90 parts of the spray-dried powder, add 70 parts of glucose, 1 part of sucralose, and 80 parts of a 50% ethanol solution to prepare a soft material, granulate the soft material through a 10-mesh sieve, and dry the wet granules in an oven at 60°C for 4 hours to obtain dry granules with a water content ≤ 8% to obtain a granule for treating enteritis diarrhea in animals.

3. A granule for treating enteritis diarrhea in animals prepared by the preparation method of the traditional Chinese medicine preparation for treating enteritis diarrhea in animals according to claim 1 or claim 2.

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