Traditional Chinese veterinary medicine preparation for treating piglet diarrhea as well as preparation method and application of traditional Chinese veterinary medicine preparation

Abstract

The invention relates to a traditional Chinese veterinary medicine preparation for treating piglet diarrhea as well as a preparation method and application of the traditional Chinese veterinary medicine preparation. The traditional Chinese medicine composition is prepared from the following raw materials and auxiliary materials, wherein the raw materials comprise poria cocos, humifuse euphorbia herb, catechu, smoked plum, scorched hawthorn fruit, radix paeoniae alba, liquorice, fructus evodiae, radix aucklandiae, rhizoma atractylodis macrocephalae and hawthorn fruit; the auxiliary materials comprise a disintegrating agent modified starch, a filling agent dextrin, a flavoring agent sucrose and steviosin; the mass ratio of the raw materials to the auxiliary materials is 1: (1-3), starch, mannitol, dilauroyl peroxide and a solvent DMSO react to obtain cross-linked starch, and then the cross-linked starch, water, anhydrous sodium sulfate, sodium chloride, acetic anhydride and a sodium hydroxide solution react to obtain the modified starch. According to the present invention, the piglet diarrhea can be effectively treated, the drinking water administration mode is adopted, the advantages of accurate metering, rapid effect, convenient administration and the like are provided, the clinical medication safety on piglets is high, the growth performance of piglets is not affected, and the method is suitable for mass production and large-scale use.

Description

Technical Field

[0001] The invention relates to the technical field of traditional Chinese veterinary medicines, and in particular to a traditional Chinese veterinary medicine preparation for treating piglet diarrhea, and a preparation method and application thereof. Background Art

[0003] Piglet diarrhea is one of the most common animal diseases in piglets. When piglets have diarrhea, they will have obvious symptoms of diarrhea and vomiting, their growth rate will slow down, their development will stagnate, and their survival rate will decrease, causing serious economic losses to farmers. Because piglets have not yet established a stable micro-ecosystem in their intestines, they have low immunity and are easily affected by external stimuli or invasion by pathogenic microorganisms, which may cause diarrhea. The causes of piglet diarrhea can be divided into pathogenic and non-pathogenic. Factors that cause pathogenic diarrhea include bacteria, viruses, parasites, etc.; factors that cause non-pathogenic diarrhea include the piglet's own physiological factors, improper feeding and management, environmental factors, and weaning stress. In addition to routine feeding and hygiene management, the prevention and control of this disease also requires prevention and control by adjusting the body's angle.

[0004] According to TCM syndrome differentiation, piglet diarrhea includes damp-heat diarrhea, spleen deficiency diarrhea, cold-damp diarrhea, etc. In clinical practice, the incidence of piglet diarrhea is on the rise. Its pathogenic factors are complex, often spleen and stomach weakness plus dampness and heat, which cause spleen deficiency combined with damp-heat diarrhea, which is a syndrome. In the face of piglet diarrhea with complex etiology, conventional prevention and control measures cannot eradicate and control it. Most of the chemical drugs currently used in clinical practice for anti-piglet diarrhea are targeted at a single target. Practice has shown that single-target drugs are difficult to cure multi-factor complex diseases such as piglet diarrhea, and long-term use is prone to drug tolerance, and may also produce toxic side effects such as liver and kidney. Chinese veterinary compound has unique advantages in preventing and treating piglet diarrhea. It often integrates and regulates the imbalanced body through multiple components, multiple targets, and multiple pathways of action. This feature is consistent with the complex etiology of piglet diarrhea. However, the current commercially available products are mostly effective for damp-heat diarrhea. For the more common spleen deficiency combined with damp-heat diarrhea, new preparations are urgently needed. Summary of the invention

[0005] Based on the above problems, this application has determined a one-step granulation method and application of Chinese veterinary medicine granules for treating piglet diarrhea through experimental research and combined with production needs. The extraction process, concentration process and granulation process have been comprehensively explored and optimized, realizing the most efficient, simple and practical preparation method of Chinese veterinary medicine preparations, which can effectively treat piglet spleen and stomach weakness and damp-heat diarrhea. And according to the unique physiological properties and disease characteristics of animals, oral granule dosage forms are selected, which are suitable for breeding industries with a high degree of scale. When preventing and treating animal diseases, the drug can be administered in drinking water or mixed with feed, which has the advantages of accurate measurement, rapid action and convenient administration.

[0006] The first invention of the present invention is: a Chinese veterinary medicine preparation for treating diarrhea in piglets, composed of raw materials and auxiliary materials, characterized in that the raw medicinal materials include: Poria cocos, Herba Euphorbiae, Catechu, Prunus mume, Crataegus pinnatifida, Paeonia lactiflora, Licorice, Evodia rutaecarpa, Aucklandia lappa, Atractylodes macrocephala, Crataegus pinnatifida; the auxiliary materials include: disintegrant modified starch, filler dextrin, flavor corrector sucrose and stevioside; the mass ratio of the raw materials to the auxiliary materials is 1:(1-3);

[0007] Preferably, the modified starch is prepared by reacting starch, mannitol, dilauroyl peroxide and DMSO solution to obtain cross-linked starch, and then reacting cross-linked starch, water, anhydrous sodium sulfate, sodium chloride, acetic anhydride and sodium hydroxide solution to obtain the modified starch.

[0008] Furthermore, the raw medicinal materials are proportioned by weight: 10-300 parts of Poria cocos, 20-300 parts of Euphorbia obesa, 1-100 parts of catechu, 1-200 parts of Prunus mume, 1-200 parts of charred hawthorn, 1-200 parts of white peony root, 20-300 parts of licorice, 1-50 parts of Evodia rutaecarpa, 1-50 parts of costusroot, 1-20 parts of Atractylodes macrocephala, and 1-40 parts of hawthorn.

[0009] Furthermore, the auxiliary materials include 4-8 parts of modified starch, 1-3 parts of sucrose, 1-3 parts of dextrin, and 1-3 parts of stevioside in parts by weight.

[0010] Furthermore, the specific steps for preparing the modified starch are as follows:

[0011] S1: adding starch and mannitol to the solvent DMSO and mixing evenly, adding dilauroyl peroxide, heating reaction, vacuum distillation concentration, filtering and drying to obtain cross-linked starch;

[0012] S2: adding water, anhydrous sodium sulfate and sodium chloride to the cross-linked starch, adding sodium hydroxide solution, adding acetic anhydride, keeping warm for reaction, filtering, washing and drying to obtain modified starch.

[0013] Furthermore, in step S1, the mass ratio of starch, mannitol, dilauroyl peroxide and solvent DMSO is 10:(2-3):(0.1-0.3):(10-20); the heating reaction temperature is 75-90°C and the time is 8-12h.

[0014] Furthermore, in step S2, the mass ratio of cross-linked starch, water, anhydrous sodium sulfate, sodium chloride, acetic anhydride, and sodium hydroxide solution is (37-40):100:(0.1-0.5):(0.1-0.5):(8-12):(10-40); the temperature of the insulation reaction is 60-70°C and the time is 4-7h.

[0015] Furthermore, in step S2, the mass fraction of the sodium hydroxide solution added is 3-6%, and the pH is adjusted to 8.5-9.0.

[0016] The second invention of the present invention is: a method for preparing a Chinese veterinary medicine preparation for treating piglet diarrhea, characterized in that the specific steps are as follows:

[0017] Step 1) weighing the raw medicinal materials according to the ratio;

[0018] Step 2) decoct with water to extract the raw medicinal materials: mix black plum, charred hawthorn, white peony root, evodia rutaecarpa, costusroot, atractylodes macrocephala, and hawthorn according to the above weight proportions, decoct with water, filter, add herb residue to Herba Euphorbiae Herba, decoct with water again, filter, and combine the above filtrates to obtain extract 1; decoct catechu with water, filter, and obtain the filtrate to obtain extract 2; decoct Poria cocos and licorice with water, extract, filter, and obtain the filtrate to obtain extract 3;

[0019] Step 3) extract 1 is concentrated under reduced pressure to obtain concentrated solution 1, extract 3 is concentrated under reduced pressure to obtain concentrated solution 3, and concentrated solution 1, extract 2, and concentrated solution 3 are combined;

[0020] Step 4) fluidized bed one-step granulation: the auxiliary materials sucrose, dextrin and stevioside are placed in the fluidized bed of the fluidized spray granulation equipment, the modified starch slurry is sprayed into the preheated material, and filtered heated air is introduced with an inlet air temperature of 70-90° C. to preheat and dry the auxiliary materials and bring them to a boiling state; the combined concentrated liquid is sprayed in a mist form, and the fluidized drying is continued, mixed, and packaged to obtain the product.

[0021] Further, in step 2), black plum, charred hawthorn, white peony, evodia rutaecarpa, costus root, atractylodes macrocephala, and hawthorn are mixed according to the above weight ratio, 10-14 times the weight of water of the mixed medicinal materials are added, and the mixture is decocted for 0.5-3 hours, filtered, and the residue is added to herba euphorbiae, and 10-14 times the weight of water is added, and the mixture is decocted continuously for 1-3 times, each time for 0.5-3 hours, and the filtrates are combined to obtain extract 1; catechu is decocted for 1-3 times with 8-12 times the weight of water, each time for 0.5-3 hours, the decoction is filtered, and the filtrates are combined to obtain extract 2; Poria cocos and licorice are decocted for 1-3 times with 10-14 times the weight of water, each time for 1-4 hours, the decoction is filtered, and the filtrates are combined to obtain extract 3.

[0022] Furthermore, the extract 1 in step 3) is concentrated under reduced pressure to a relative density of 1.07-1.09 at a temperature of 50°C, ethanol is added to make the alcohol content reach 60%-70%, and the extract is allowed to stand for 10-14 hours. The supernatant is taken, and the ethanol recovery temperature is 60-80°C. At a temperature of 50°C, the extract is concentrated under reduced pressure to a relative density of 1.10-1.15; the extract 3 is concentrated under reduced pressure to a relative density of 1.07-1.09 at a temperature of 50°C.

[0023] Furthermore, in step 4), the fluidized drying is performed until the moisture content in the particles is less than 2%, the feed rate is 5-20 r / min, and the temperature is 40-60°C.

[0024] The third invention point of the present invention is: use of the above-mentioned Chinese veterinary medicine preparation or the above-prepared Chinese veterinary medicine preparation in the preparation of medicine for treating and / or preventing swine diarrhea.

[0025] Compared with the prior art, the present invention has the following advantages:

[0026] 1) The raw materials of the present invention are low in price, have no side effects and no drug resistance; modified starch is added to the auxiliary materials so that the particles can be quickly dissolved in cold water, the particles have high disintegration performance, and the particles are uniform, which is more conducive to piglet absorption;

[0027] 2) The fluidized bed one-step granulation method adds the raw materials and auxiliary materials in one step and mixes them fully, which greatly improves the production efficiency and reduces the production energy consumption. It is simple and easy to implement and is suitable for industrial production;

[0028] 3) The present invention can effectively treat diarrhea in piglets with an effective rate of 100%. It is administered by drinking water and has the advantages of accurate measurement, rapid effect, and convenient administration. It has high clinical drug safety for piglets, does not affect the growth performance of piglets, and is suitable for mass production and large-scale use.

[0029] Specific implementation method

[0030] In order to make the purpose, technical solution and advantages of the present application more clear, the present application is further described in detail below. However, it should be understood that the description here is only used to explain the present application and is not used to limit the scope of the present application.

[0031] Unless otherwise defined, all technical terms and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art of the present application, and the terms used herein in the specification of the present application are only for the purpose of describing specific embodiments and are not intended to limit the present application. The reagents and instruments used herein are all commercially available, and the characterization means involved can refer to the relevant descriptions in the prior art, which will not be repeated herein.

[0032] In order to further understand the present application, the present application is further described in detail below in conjunction with the best embodiment.

[0033] Example 1

[0034] The present embodiment provides a Chinese veterinary medicine preparation for treating diarrhea in piglets, which is composed of raw materials and auxiliary materials. The raw materials include: Poria cocos, Herba Euphorbiae, Catechu, Prunus mume, Crataegus pinnatifida, Paeonia lactiflora, Licorice, Evodia rutaecarpa, Aucklandia lappa, Atractylodes macrocephala, Crataegus pinnatifida; the auxiliary materials include: disintegrant modified starch, filler dextrin, flavor corrector sucrose and stevioside;

[0035] The mass ratio of the raw material to the auxiliary material is 1:(1-3);

[0036] The modified starch is prepared by reacting starch, mannitol, dilauroyl peroxide and solvent DMSO to obtain cross-linked starch, and then reacting cross-linked starch, water, anhydrous sodium sulfate, sodium chloride, acetic anhydride and sodium hydroxide solution to obtain modified starch.

[0037] Diarrhea in piglets is mostly caused by the mixture of dampness and heat, which are not transformed. The evil qi blocks the defensive qi, and the body heat is not raised, and the limbs are tired. Then the evil qi spreads from the surface to the inside, injuring the spleen and stomach, resulting in abnormal water and moisture transportation and accumulation in the middle jiao, and the appearance of thick and greasy tongue coating, decreased appetite and other qi symptoms. According to the three-jiao dialectical analysis, the evil qi obscures the upper part, and the light orifices are blocked, and the phenomenon of dizziness and unsteady walking occurs; dampness and heat are deposited in the small intestine, and the accumulation in the bladder causes urination difficulties, and the deposition in the large intestine is prone to loose stools. Dampness and heat stagnate in the middle jiao for a long time, consuming the middle qi. At this time, the rise and fall of the middle qi determines the transformation of dampness and heat, and there are two different outcomes: dampness and heat turning into dryness and injuring yin and dampness and yang weakness. Therefore, the treatment should focus on clearing heat and dampness, strengthening the spleen and stopping diarrhea, and relieving pain. The preparation of the present invention uses Poria, Herba Euphorbiae, Catechu, Prunus Mume, Crataegus Pinelliae, White Peony Root, Licorice, Evodia Fructus, Aucklandia Rhizoma, Atractylodes Macrocephalae, Crataegus Pinelliae. Poria can invigorate the spleen and eliminate dampness, Herba Euphorbiae is good at clearing away heat and dampness and stopping diarrhea, Catechu and Prunus Mume are sour and astringent to stop diarrhea, Crataegus Pinelliae can help digestion and relieve stagnation, White Peony Root and Licorice have the effect of relieving urgency and relieving pain, Evodia Fructus warms the interior and stops pain, Aucklandia Rhizoma can invigorate the spleen and relieve food. All the medicines are used together to play the functions of clearing heat and dampness, invigorating the spleen and stopping diarrhea, relieving urgency and relieving pain, and have a good therapeutic effect on treating diarrhea.

[0038] As a further preferred embodiment, the raw medicinal materials are proportioned by weight: 10-300 parts of Poria cocos, 20-300 parts of Euphorbia obesa, 1-100 parts of catechu, 1-200 parts of black plum, 1-200 parts of charred hawthorn, 1-200 parts of white peony, 20-300 parts of licorice, 1-50 parts of Evodia rutaecarpa, 1-50 parts of costusroot, 1-20 parts of Atractylodes macrocephala, and 1-40 parts of hawthorn.

[0039] Preferably, the raw medicinal materials are matched by weight: 24-120 parts of Poria cocos, 30-180 parts of Euphorbia obesa, 5-40 parts of catechu, 5-50 parts of Prunus mume, 10-40 parts of charred hawthorn, 10-50 parts of white peony root, 40-120 parts of licorice, 1-20 parts of Evodia rutaecarpa, 1-15 parts of costusroot, 5-15 parts of Atractylodes macrocephala, and 1-20 parts of hawthorn.

[0040] Preferably, the raw medicinal materials are proportioned by weight: 30 parts of Poria cocos, 60 parts of Euphorbia obesa, 9 parts of catechu, 10 parts of Prunus mume, 15 parts of charred hawthorn, 15 parts of white peony root, 60 parts of licorice, 1-3 parts of Evodia rutaecarpa, 1-3 parts of costusroot, 5 parts of Atractylodes macrocephala, and 5 parts of hawthorn.

[0041] The following further descriptions can be made for each of the above raw medicinal materials and their weight proportions:

[0042] Poria: sweet, light, and neutral. It has the effects of promoting water and removing dampness, strengthening the spleen, and calming the mind. It is mainly used to treat edema, oliguria, spleen deficiency, poor appetite, loose stools, diarrhea, and restlessness. Preferably, the proportion of Poria by weight can be: for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300 parts or any value between any two values.

[0043] Herba Euphorbiae: spicy, flat in nature; has the effects of clearing away heat and toxic substances, cooling blood and stopping bleeding, and removing dampness and jaundice. It is mainly used for dysentery, jaundice of intestines, blood in stool, hematuria, hemoptysis, traumatic injury, carbuncle, malignant ulcer, and jaundice caused by damp heat. Preferably, Herba Euphorbiae can be taken as follows by weight: for example, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300 parts or any value between any two values.

[0044] Catechu: bitter, astringent, slightly cold, enters the lung and heart meridians. It has the effects of promoting blood circulation and relieving pain, stopping bleeding and promoting tissue regeneration, absorbing dampness and healing sores, clearing the lungs and resolving phlegm. It is used for pain caused by falls, traumatic bleeding, vomiting blood, epistaxis, sores that do not heal, eczema, wet sores, and coughs caused by lung heat. Preferably, the weight ratio of catechu can be: for example, 1, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100 parts or any value between any two values.

[0045] Plum: sour, astringent, neutral. Functions: astringent to the lungs, astringent to the intestines, and promoting the production of body fluids. Used to treat chronic diarrhea, dysentery, milk diarrhea in young animals, ascariasis, etc. Preferably, the weight ratio of Plum can be: for example, 1, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200 parts or any value between any two values.

[0046] Scorched hawthorn: sour, sweet, slightly warm in nature. Functions: digestion, elimination of stagnation, promoting qi and dispersing blood stasis. Indications: abdominal distension due to indigestion, indigestion or postpartum lochia. Preferably, the scorched hawthorn can be prepared in a weight ratio of, for example, 1, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200 parts or any value between any two values.

[0047] White peony root: bitter, sour, slightly cold. Functions: soothing the liver and relieving pain, nourishing blood and consolidating yin. Indications: liver yin deficiency, deficiency heat, diarrhea, abdominal pain, cramps in the limbs. Preferably, the white peony root can be prepared in a weight ratio of, for example, 1, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200 parts or any value between any two values.

[0048] Licorice: sweet, neutral. Functions: tonifying spleen and replenishing qi, removing phlegm and relieving cough, harmonizing the middle and relieving urgency, detoxifying, and harmonizing various medicines. Indications: spleen and stomach weakness, fatigue and weakness, cough and asthma, sore throat, poisoning, sores, etc. Preferably, the licorice can be prepared in a weight ratio of, for example, 20, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300 parts or any value between any two values.

[0049] Evodia rutaecarpa: pungent, bitter, hot; slightly toxic. Functions: dispelling cold and relieving pain, descending adverse qi and stopping vomiting, and assisting yang and stopping diarrhea. Indications: headache due to jueyin meridian, abdominal pain due to cold hernia, beriberi due to cold and dampness, abdominal pain during menstruation, abdominal distension and pain, vomiting and acid swallowing, and diarrhea at dawn. Preferably, the proportion of Evodia rutaecarpa in parts by weight can be: for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50 parts or any value between any two values.

[0050] Aucklandia: pungent, bitter, warm. Return to the spleen, stomach, large intestine, triple burner, gallbladder meridian. Functions: promoting qi and relieving pain, strengthening the spleen and digesting food. Indications: chest and flank, abdominal distension and pain, heaviness after diarrhea, indigestion, and loss of appetite. Stewed Aucklandia strengthens the intestines and stops diarrhea. Used for diarrhea and abdominal pain. Preferably, the Aucklandia can be prepared by weight: for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50 parts or any value between any two values.

[0051] Atractylodes macrocephala: bitter, sweet, warm. It enters the spleen and stomach meridians. Sweet tonic, infiltration, bitter, warm and dry, enters the spleen and stomach meridians, mainly warms and strengthens the body, and can also remove dampness. It is good at replenishing qi and strengthening the spleen, removing dampness and promoting diuresis, stopping sweating, and calming the fetus. It treats spleen and stomach qi deficiency, spleen deficiency edema, phlegm and fluid, spontaneous sweating due to superficial deficiency, and fetal movement disorder. There is a slight difference in performance between raw and fried. The fried one has a strong spleen-tonifying effect, and the raw one has a strong dampness-removing effect. Preferably, the Atractylodes macrocephala can be taken as follows by weight: for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 parts or any value between any two values.

[0052] Hawthorn: sour, sweet, slightly warm. Return to the spleen, stomach, liver meridians. Digestion and stomach, promote qi and dissipate blood stasis, remove turbidity and reduce fat. Indications: meat stagnation, stomach fullness, diarrhea and abdominal pain, blood stasis amenorrhea, postpartum stasis, heart and abdomen stabbing pain, chest pain, hernia pain, hyperlipidemia. Used for meat stagnation, diarrhea. Preferably, the ratio of costus root by weight can be: for example 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40 parts or any value between any two values.

[0053] As a further preferred embodiment, the auxiliary materials are mixed by weight in the following ratios: 4-8 parts of modified starch, 1-3 parts of sucrose, 1-3 parts of dextrin, and 1-3 parts of stevioside.

[0054] As a further preferred embodiment, the method for preparing the modified starch comprises:

[0055] S1: Add starch and mannitol to the solvent DMSO (the solvent is dimethyl sulfoxide with a purity higher than 99% and is liquid at room temperature) and mix well. After adding dilauroyl peroxide, heat and react, reduce pressure,

[0056] After distillation and concentration, filtering and drying are performed to obtain cross-linked starch;

[0057] S2: Add water, anhydrous sodium sulfate and sodium chloride to the cross-linked starch, add sodium hydroxide solution, add acetic anhydride, filter, wash and dry to obtain modified starch.

[0058] Preferably, in step S1, the mass ratio of starch, mannitol, dilauroyl peroxide and solvent DMSO is 10:(2-3):(0.1-0.3):(10-20); the heating reaction temperature is 75-90° C. and the time is 8-12 h.

[0059] Preferably, in step S2, the mass ratio of cross-linked starch, water, anhydrous sodium sulfate, sodium chloride, acetic anhydride and sodium hydroxide solution is (37-40):100:(0.1-0.5):(0.1-0.5):(8-12):(10-40); the temperature of the insulation reaction is 60-70°C and the time is 4-7h.

[0060] Preferably, the volume fraction of the sodium hydroxide solution added in step S2 is 3-6%, and the pH is adjusted to 8.5-9.0.

[0061] In Chinese veterinary medicine preparations, starch is added to the raw materials and auxiliary materials as a disintegrant, which enables the solid preparation to disintegrate through capillary action. However, when ordinary starch is used as a disintegrant, the disintegration speed in cold water still cannot meet the requirements, and there is also the problem of drug taste fusion. The present invention utilizes acetic anhydride to esterify starch, improves its gelatinization properties, and cross-links mannitol with starch chains through step S1, further improves the distribution of starch in the capillaries, and then accelerates the process of water molecules entering the particles through the capillaries to disintegrate the particles, thereby achieving the gelatinization requirements in cold water.

[0062] In practical applications, modified starch can increase viscosity, that is, modified starch can quickly dissolve in cold water and form a high-viscosity solution, improve solubility, and effectively improve taste; improve stability, that is, the acid resistance, alkali resistance, and high temperature resistance of modified starch are significantly enhanced, and it is suitable for a variety of processing environments. In addition, the hygroscopicity of modified starch is reduced, which helps to extend the shelf life and reduce quality changes caused by moisture changes.

[0063] Example 2

[0064] A use of the above-mentioned pharmaceutical preparation or the above-mentioned pharmaceutical preparation prepared in the preparation of a drug for treating and / or preventing swine diarrhea.

[0065] Example 3

[0066] This embodiment provides a method for preparing a Chinese veterinary medicine preparation for treating piglet diarrhea, and the specific steps are as follows:

[0067] 1) Weigh the auxiliary materials and raw materials respectively according to the mass ratio;

[0068] 2) Decoction to extract raw materials: Mix black plum, charred hawthorn, white peony root, evodia rutaecarpa, costusroot, atractylodes macrocephala, and hawthorn according to the above weight proportions, decoct with water, filter, add herb residue to herb rutinae, decoct with water again, filter, and the filtrate is extract 1; decoct catechu with water, filter, and the filtrate is extract 2; decoct Poria cocos and licorice with water, decoct, filter, and the filtrate is extract 3;

[0069] 3) extract 1 is concentrated under reduced pressure to obtain concentrated solution 1, extract 3 is concentrated under reduced pressure to obtain concentrated solution 3, and concentrated solution 1, extract 2, and concentrated solution 3 are combined;

[0070] 4) Fluidized bed one-step granulation: Place the auxiliary materials sucrose, dextrin and stevioside in the fluidized bed of the fluidized spray granulation equipment, spray the modified starch slurry into the preheated material, and pass the filtered heated air with an inlet temperature of 70-90°C to preheat and dry the auxiliary materials and make them in a boiling state. Spray the combined concentrated liquid in a mist form, continue fluidized drying, mix well, and package to obtain the product.

[0071] As a further preferred embodiment, in step 2), black plum, charred hawthorn, white peony, evodia rutaecarpa, costus root, atractylodes macrocephala, and hawthorn are mixed in the above weight proportions, 10-14 times the weight of water of the mixed medicinal materials are added, and the mixture is decocted for 0.5-3 hours, filtered, and the residues are added to herba euphorbiae, and 10-14 times the weight of water are added, and the mixture is decocted continuously for 1-3 times, each time for 0.5-3 hours, and the filtrates are combined to obtain extract 1; catechu is decocted for 1-3 times with 8-12 times the weight of water, each time for 0.5-3 hours, the decoction is filtered, and the filtrates are combined to obtain extract 2; Poria cocos and licorice are decocted for 1-3 times with 10-14 times the weight of water, each time for 1-4 hours, the decoction is filtered, and the filtrates are combined to obtain extract 3.

[0072] As a further preferred embodiment, the extract 1 in step 3) is concentrated under reduced pressure to a relative density of 1.07-1.09 at a temperature of 50°C, ethanol is added to make the alcohol content reach 50-70%, and the extract is allowed to stand for 10-14 hours. The supernatant is taken, and the ethanol recovery temperature is 60-80°C. At a temperature of 50°C, the extract is concentrated under reduced pressure to a relative density of 1.10-1.15; the extract 3 is concentrated under reduced pressure to a relative density of 1.07-1.09 at a temperature of 50°C).

[0073] As a further preferred embodiment, in step 4), the fluidized drying is performed until the moisture content in the particles is appropriately less than 2%, the feed rate is 5-20 r / min, and the temperature is 40-60°C.

[0074] The present invention prepares granules by a fluidized bed process. Specifically, the modified starch is sprayed into granules to form granules during the spraying stage of fluidized bed granulation, which enables the modified starch to function better than other wet granulation methods such as extrusion wet granulation.

[0075] The clinical application of the present invention is mainly used to treat diarrhea in piglets, with symptoms of increased defecation frequency, thin or watery feces, abdominal pain, poor appetite, etc. The present invention is used to administer 0.5-1g / kg·bw drinking water for 3-5 consecutive days to effectively treat diarrhea in piglets.

[0076] Example 4

[0077] According to the content of this application, the modified starch in Example 1 was prepared, and the specific description is as follows:

[0078] Modified starch: The specific steps are as follows:

[0079] S1: Add 100 g of starch and 20 g of mannitol to 150 ml of DMSO solvent and mix well. Add 2 g of dilauroyl peroxide, heat at 75° C. for 12 h, concentrate by vacuum distillation, filter and dry to obtain 50 g of cross-linked starch.

[0080] S2: Take 40g of cross-linked starch, add 100ml of water, 0.1g of anhydrous sodium sulfate and 0.1g of sodium chloride, then add 10g of 5% sodium hydroxide solution to adjust the pH to 8.7, add 12g of acetic anhydride, keep stirring at 60℃ for 6h, filter, wash and dry to obtain 50g of modified starch.

[0081] Example 5

[0082] According to the content of this application, the Chinese veterinary medicine preparation in Example 1 was prepared, and the specific description is as follows:

[0083] Test Example 1

[0084] Chinese veterinary medicine preparation 1 for treating diarrhea in piglets: its raw material ratio: 180g of Poria cocos, 360g of Herba Euphorbiae Ichthyophthirius, 54g of Catechu, 60g of Prunus mume, 90g of Charred Hawthorn, 90g of White Peony Root, 360g of Licorice, 18g of Evodia rutaecarpa, 18g of Aucklandia lappa, 30g of Atractylodes macrocephala, and 30g of Hawthorn. Its auxiliary material ratio: 1075g of modified starch, 645g of sucrose, 645g of dextrin, and 215g of stevioside. It is made of raw materials and auxiliary materials in a mass ratio of 1:2.

[0085] The preparation method thereof comprises the following specific steps:

[0086] Step 1) taking raw medicinal materials according to the proportion in the Chinese veterinary drug preparation 3;

[0087] Step 2) decoction with water: Mix black plum, charred hawthorn, white peony, evodia rutaecarpa, costus root, atractylodes macrocephala, and hawthorn according to the above weight ratio, add 12 times the weight of water of the mixed medicinal materials and decoct for 1 hour, filter, add herbaceous stalks to herbaceous stalks, add 12 times the weight of water and decoct for 2 consecutive times, each time for 1 hour, filter and combine the filtrates to obtain extract 1 for later use; add 10 times the weight of water to catechu and decoct for 2 times, each time for 1 hour, filter the decoction, and combine the filtrates to obtain extract 2 for later use; add 12 times the weight of water to tuckahoe and licorice and decoct for 2 times, each time for 2 hours, filter the decoction, and combine the filtrates to obtain extract 3 for later use.

[0088] 3) Concentration under reduced pressure: Concentrate extract 1 under reduced pressure at 50°C to a relative density of 1.08, add ethanol to make the alcohol content reach 60%, let stand for 12 hours, take the supernatant, and recover ethanol at 70°C. Concentrate under reduced pressure at 50°C to a relative density of 1.13. Concentrate extract 3 under reduced pressure at 50°C to a relative density of 1.08;

[0089] 4) Fluidized bed one-step granulation: Place auxiliary materials sucrose, dextrin, and stevioside in the fluidized bed of the fluidized spray granulation equipment, spray modified starch slurry into the preheated material, and introduce filtered heated air to preheat and dry the auxiliary materials and make them boil. Spray the concentrated liquid in the form of mist to form granules, and continue fluidized drying until the moisture content in the granules is appropriate (<2%), the air inlet temperature is 80°C, the feed speed is 10r / min, the temperature is 50°C, mix well, and package.

[0090] The packaging material that directly contacts the drug is a multi-layer composite food packaging film bag. The subpackaging uses a polyethylene / polypropylene composite bag for food packaging, each bag contains 100g or 500g, sealed and labeled, and packed in a double-layer corrugated box.

[0091] Test Example 2

[0092] Chinese veterinary medicine preparation 2 for treating diarrhea in piglets: The raw material ratio of the medicine is: 180g of Poria cocos, 360g of Herba Euphorbiae Ichthyophthirius, 54g of Catechu, 60g of Prunus mume, 90g of Charred Hawthorn, 90g of White Peony Root, 360g of Licorice, 6g of Evodia rutaecarpa, 6g of Aucklandia lappa, 5g of Atractylodes macrocephala, and 5g of Hawthorn. The auxiliary material ratio is: 1512g of modified starch, 534g of sucrose, 356g of dextrin, and 178g of stevioside. It is made of raw materials and auxiliary materials in a mass ratio of 1:2.

[0093] The preparation method thereof comprises the following specific steps:

[0094] Step 1) taking raw materials and auxiliary materials according to the proportions in the Chinese veterinary drug preparation 2;

[0095] The remaining steps are roughly the same as those in Experimental Example 1.

[0096] Experimental Example 1 Stability Test

[0097] (I) Test methods

[0098] 1. High temperature test

[0099] The Chinese veterinary drug preparation 1 in Test Example 1 was placed in a sealed clean container and placed at 60° C. for 10 days. Samples were taken for testing at 0, 5, and 10 days, and the testing was performed according to the key stability inspection items.

[0100] 2. High humidity test

[0101] The Chinese veterinary preparation 1 in Test Example 1 was placed at 25°C and relative humidity (90±5)% [KNO3 saturated solution (25C, relative humidity 92±5%)] for 10 days, and samples were taken for testing at 0, 5, and 10 days, and the stability key inspection items were tested, and the moisture absorption and weight gain were tested.

[0102] 3. Strong light irradiation test

[0103] Take the Chinese veterinary drug preparation 1 in Test Example 1, put it in commercial packaging, place it in a light cabinet, adjust the illumination to 4500±5001x, leave it for 10 days, take samples for testing at 0, 5, and 10 days, and test it according to the key items of stability inspection.

[0104] 4. Accelerated testing

[0105] Take the Chinese veterinary drug preparation 1 in Test Example 1, commercially available packaging, place it in a constant temperature and humidity chamber, and place it for 6 months (August 2022-February 2023) at a temperature of (40±2)°C and a relative humidity of (75±5)% (set temperature 40°C, relative humidity 75%). During the test period, samples were taken once at the end of the first month, second month, third month and sixth month, and long-term tests were conducted according to the key stability inspection items.

[0106] 5. Long-term trials

[0107] Take the Chinese veterinary preparation 1 in Test Example 1, place it under long-term conditions (temperature of (25±2)°C, relative humidity of (60±10)%) for 36 months (August 2022-August 2025), take samples once at the end of the 3rd month, 6th month, 9th month, 12th month, 18th month, 24th month, and 36th month, and conduct tests according to the key stability inspection items.

[0108] (II) Test conclusion

[0109] After the Chinese veterinary drug preparation 1 in Test Example 1 was placed under high temperature conditions for 10 days according to commercial packaging, there was no significant change in each inspection item (properties, identification, appearance uniformity, loss on drying, loading, solubility, content, etc.) compared with 0 days, and all met the quality standards, indicating that the packaging form used is stable to high temperature. After being placed under high humidity conditions for 10 days according to the above packaging, there was no significant change in each inspection item (properties, identification, appearance uniformity, loss on drying, loading, solubility, content, etc.) compared with 0 days, and all met the quality standards, indicating that the packaging form used is stable to high humidity. After being placed under strong light conditions for 10 days according to the above packaging, there was no significant change in each inspection item (properties, identification, appearance uniformity, loss on drying, loading, solubility, content, etc.) compared with 0 days, and all met the quality standards, indicating that the packaging form used is stable to light. This product is placed for 6 months under the conditions of accelerated heating (temperature 40℃±2℃, humidity 75%±5%) according to the above packaging. There is no obvious change in each inspection item (properties, identification, appearance uniformity, drying loss, filling amount, solubility, content, etc.) compared with 0 month, and all meet the quality standards. This product is placed for 12 months under the conditions of temperature 25℃±2℃ and relative humidity 60%±10% according to the above packaging. There is no obvious change in each inspection item (properties, identification, appearance uniformity, drying loss, filling amount, solubility, content, etc.) compared with 0 month, and all meet the quality standards, and the quality is stable. The above preliminary stability test results show that the quality of the present invention is stable when it is accelerated for 6 months and placed under natural conditions at room temperature for 12 months. In summary, the results of the high temperature, high humidity, strong light test, accelerated test and long-term test of the drug of the present invention show that each of the detection indicators is relatively stable.

[0110] Experimental Example 2 Safety Test

[0111] (I) Oral acute toxicity test of the drug of the present invention on mice

[0112] 20 SD rats were randomly divided into a drug administration group (Chinese veterinary drug preparation 1 in Test Example 1) and a blank control group, with 10 rats in each group (half male and half female). They were fasted for 16 hours before gavage, and feeding was resumed within 3 to 4 hours after poisoning. The animals were free to drink water during the fasting process. Gavage was administered after fasting. The drug prepared in Test Example 1 was gavaged twice a day, with an interval of 2 to 3 hours. The gavage volume was 2mL / 100g, which is equivalent to Chinese veterinary drug preparation 1, 20g / kg·bw. The blank group was orally administered with an equal amount of normal saline. Once before administration, close observation within 12 hours after administration, and then daily observation for 14 consecutive days. The results showed that all rats survived, with good mental state, normal diet, and normal bowel movements until the end of the experiment 14 days after administration. No obvious abnormal clinical symptoms appeared. Animal autopsy showed that there were no obvious lesions visible to the naked eye, and its LD50 was greater than 20g / kg body weight. According to the Appendix 2 "Acute Toxicity Dose Classification Table of Chemicals" in the "Guidelines for Acute Toxicity Testing of Veterinary Drugs (LD50 Determination)" in the Compilation of Technical Guidelines for Veterinary Drug Research (2006-2011), an oral dose greater than 15000 mg / kg bw is non-toxic.

[0113] (II) Safety test of the drug of the present invention on target animal pigs

[0114] Test drug: Chinese veterinary drug preparation 1

[0115] Experimental animals: 32 three-way hybrid pigs, 40-50 days old, weighing 11-18 kg, half male and half female, were adaptively raised for 7 days under a strict disinfection environment and immunization procedures.

[0116] Experimental design: On D0, 32 experimental pigs were weighed and numbered on an empty stomach. The experimental pigs were randomly divided into 4 groups using the Excel random number method with body weight as the core indicator, namely, the blank control group, the test drug 1-fold dose group, the test drug 3-fold dose group and the test drug 5-fold dose group, with 8 pigs in each group, half male and half female. There was no significant difference in body weight among the experimental groups after grouping (P>0.05). On D1-D6, the recommended dose of 1 times (1.0g / kg·bw), 3 times (3.0g / kg·bw), and 5 times (5.0g / kg·bw) determined by the efficacy evaluation test was administered. The specific administration method was to calculate the dosage according to the average body weight of each group of pigs on D0, add 1 / 3 of the average drinking water for the whole day, stir and mix thoroughly, then add to the water tank, and add regular drinking water after the drug-containing water is finished. Clean the water tank before administration on the second day, and then add the newly prepared drinking water containing the test drug. The age of the pigs in this experiment was about 50 days. According to the clinical feeding routine, the average daily water intake of pigs of this age was about 2-3L. In order to ensure that the experimental pigs could drink the drug-containing water, the calculation was based on 2L of water per pig per day. 1 / 3 of the average daily water intake of 8 pigs is 2L×8÷3=5.33L. For the convenience of measurement, the amount of water added was set to 5.00L. According to the average weight of pigs in each dosage group, the dosage of the test drug was calculated according to the dosage in Table 1. The drug was administered once a day for 6 consecutive days, and continued to be observed for 7 days after the drug was stopped. The observation method was to observe and record the clinical manifestations of the experimental pigs one by one in the morning and afternoon every day, including body temperature, respiration, behavior, mental state, etc., and record them according to the facts. If there is any abnormality, the abnormal situation and the number of dead pigs were recorded in detail, and the dead animals or animals with obvious abnormal clinical manifestations were promptly autopsied to determine the cause of death or abnormality. The fasting weight of the experimental pigs in each group was weighed on D0, D7 and D14. The average body weight and average daily weight gain of each group were recorded and calculated. The daily feed amount and residual feed amount of each dose group during the administration period and the observation period after drug withdrawal were recorded, and the daily feed consumption of each group was calculated. On D0 and D7 days, the experimental pigs in each group were weighed on an empty stomach and blood was collected for hematological examination. Routine blood tests included hemoglobin content (HGB), white blood cell count (WBC), red blood cell count (RBC), platelet count (PLT), neutrophil percentage (NEUT), eosinophil percentage (EO), basophil percentage (BASO), lymphocyte percentage (LYMPH), and monocyte percentage (MONO); blood biochemical indicators included serum total protein (TP), serum albumin (ALB), blood glucose (GLU), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total cholesterol (CHOL), creatinine (CREA), urea (UREA), and triglycerides (TG).During the trial, any test pigs that showed drug-related clinical symptoms or obvious abnormalities in physiological and biochemical indicators should be slaughtered and subjected to autopsy; if no abnormalities were found, 4 test pigs were selected from the 5-fold dose group and the blank control group after the end of administration (D7) and the end of the trial (D14), respectively, and the heart, liver, spleen, lung, kidney, thymus, pancreas, stomach, duodenum, ileum, rectum, lymph nodes and other organs were carefully examined for abnormalities.

[0117] Table 1 Experimental dosage and solute dosage

[0118]

[0119] Data processing: SPSS application software was used to perform significance tests on inter-group data, and the weight gain, feed intake and other quantitative data of the experimental animals between groups were compared using the "mean ± standard deviation" Indicates; the differences of data at the same time point between groups were compared. If the data conformed to the normal distribution and the variance was homogeneous, the one-way analysis of variance was used for testing. If the data did not conform to the normal distribution or the variance was homogeneous, the non-parametric Kruskal-Wallis method was used for testing.

[0120] Results and Analysis:

[0121] ① General clinical symptoms: During the trial, there were no abnormalities in the clinical symptoms, behavior, mental state, appearance, and feeding of the test pigs in the test drug 1-fold dose group, test drug 3-fold dose group, and test drug 5-fold dose group. No symptoms of poisoning occurred and no test pigs died. It was preliminarily determined that the test drug was non-toxic to the test pigs when administered at doses of 1, 3, and 5 times the clinically recommended dose.

[0122] ② Body weight: The fasting body weight of each experimental pig was recorded before administration (D0), after administration (D7) and after the observation period (D14). The average body weight and average daily weight gain of the experimental pigs in each group are shown in Table 2.

[0123] Table 2 Statistical results of weight of experimental pigs ( n=8)

[0124]

[0125] Note: In the same column of data, the same shoulder letters or no letters indicate no statistical difference (P>0.05), and different shoulder letters indicate significant difference (P<0.05).

[0126] As shown in Table 2, before administration (D0), there was no significant difference in the body weight of each test pig in each test drug group and the blank control group (P>0.05), which met the grouping criteria; after the end of administration (D7) and the end of the observation period (D14), there was no significant difference in the body weight of each test drug group and the blank control group (P>0.05). During the trial, there was no significant difference in the average daily weight gain of each dose group of the test drug compared with the blank control group (P>0.05).

[0127] The body weight results showed that the test drug had no adverse effects on the body weight of the test pigs when administered at 1, 3, and 5 times the clinically recommended dose.

[0128] ③ Feed intake and feed-to-weight ratio: During the experiment, the feed consumption of each experimental group of pigs was recorded every day, and the feed-to-weight ratio of each group of experimental pigs during the experiment was calculated. See Table 3 for details.

[0129] Table 3 Feed consumption statistics of experimental pigs ( n=8)

[0130]

[0131] As shown in Table 3, the feed-to-weight ratio of each drug administration group during the administration period and the observation period was close to that of the blank control group, indicating that the drug administration at 1, 3, and 5 times the clinically recommended dose had no adverse effects on the feed-to-weight ratio of the test pigs.

[0132] Based on the results of body weight and feed weight ratio, the test drug had no adverse effects on the growth performance of test pigs when administered at 1, 3, and 5 times the clinically recommended dose.

[0133] ④Hematology-related indices: Before administration (D0) and after administration (D7), venous blood was taken from each group of experimental pigs to test blood routine related indices. The test results of hematology-related indices of each group of experimental pigs are shown in Table 4.

[0134] Table 4 Hematology related index test results ( n=8)

[0135]

[0136]

[0137] Note: In the same column of data, the same shoulder letters or no letters indicate no significant difference (P>0.05), and different shoulder letters indicate significant difference (P<0.05).

[0138] The results of routine blood tests showed that the test drug had no adverse effects on the routine blood indicators of the test pigs when administered at 1, 3, and 5 times the clinically recommended dose.

[0139] ⑤ Blood biochemical related indicators: Before administration (D0) and after administration (D7), venous blood was taken from each group of experimental pigs to test blood biochemical related indicators. The test results of blood biochemical related indicators of experimental pigs are shown in Table 5.

[0140] Table 5 Blood biochemical related index test results ( n=8)

[0141]

[0142]

[0143]

[0144] Note: In the same column of data, the same shoulder letters or no letters indicate no significant difference (P>0.05), and different shoulder letters indicate significant difference (P<0.05).

[0145] Aspartate aminotransferase (AST) can be used as an index for the examination of heart and liver diseases; serum albumin (ALB), total protein (TP), and globulin (GLB) can be used as indexes for the examination of kidney and intestinal diseases; blood glucose (GLU) can be used as an index for the examination of pancreatic diseases; cholesterol (CHOL) and triglycerides (TG) are used to determine fat metabolism and can be used as indexes for the examination of liver and gallbladder diseases; urea (UREA) can reflect the filtration function of the glomerulus and can be used as an index for the examination of kidney diseases; creatinine (CREA) is produced during muscle metabolism and excreted through the kidneys and can be used as an index for the examination of glomerular diseases. The results of blood biochemistry showed that the test drug had no adverse effects on the blood biochemical indexes of the test pigs when administered at 1, 3, and 5 times the clinically recommended dose, that is, it would not cause adverse effects on major organs such as the heart, liver, kidney, pancreas, and intestines.

[0146] ⑥ Autopsy: After the end of the drug administration and the end of the observation period, the blank control group and the test drug 5-fold dose group (half of the test pigs in each group) were taken for autopsy. The results showed that the main internal organs of the test pigs in the test drug administration groups and the blank control group were normal.

[0147] ⑦ Histopathological examination: After the end of the administration and the end of the observation period, the heart, liver, spleen, lung and kidney of the blank control group and the test drug 5-fold dose group (half of the test pigs in each group) were taken for pathological observation, and no significant difference was found compared with the blank control group. The histopathological results combined with the anatomical observation results showed that the test drug 5-fold dose did not produce toxicity to the organs of the test pigs.

[0148] The results of autopsy and histopathological examinations showed that the test drug had no adverse effects on the organs and tissues of the test animals when administered at 1, 3, and 5 times the clinically recommended dose.

[0149] The above conclusions show that feeding 1g, 3g and 5g of the test drug per 1kg of body weight once a day for 6 consecutive days did not cause poisoning or death in the test pigs; no abnormalities were found in the clinical symptoms, diet, hematological indices, blood biochemical indices, organ observations, and tissue sections of the test pigs in each group, indicating that the test drug is clinically safe for the target animal pigs.

[0150] Experimental Example 3 Clinical Application

[0151] Test drug: Chinese veterinary drug preparation 1 of Test Example 1

[0152] Experimental animals: 80 three-way crossbred piglets, aged 21 to 40 days, weighing about 6-13kg, naturally suffered from diarrhea, showing symptoms of piglet diarrhea such as "diarrhea, depression, decreased appetite, and increased drinking water", as shown in Table 6. Sick pigs with at least 3 main symptoms and 2 secondary symptoms, with a main symptom score of ≥6 points and a secondary symptom score of ≥2 points, were included in the experimental pig category for the treatment of piglet diarrhea. Veterinary staff conducted routine examinations and confirmed the diagnosis of all sick pigs, and then included the sick pigs for isolation and breeding.

[0153] Table 6 Criteria for determining clinical symptoms of piglet diarrhea

[0154]

[0155]

[0156] Experimental design: The experimental pigs were randomly divided into 4 groups, namely the high-dose group of the test drug (2.0g / kg·bw, administered in drinking water), the medium-dose group of the test drug (1.0g / kg·bw, administered in drinking water), the low-dose group of the test drug (0.5g / kg·bw, administered in drinking water), and the positive drug control group (Huangqin Jiedusan 5g / kg feed, administered in feed), with 20 pigs in each group. Another 20 healthy piglets of similar age were selected and raised separately as the negative control group. Except for the negative control group, the other groups were administered once a day for 5 consecutive days. After the end of the administration, the pigs were observed for 7 days. The diarrhea and mental state of the experimental pigs and other symptoms were recorded every day. The syndrome points were calculated after the end of the administration period (D5) and the end of the observation period (D12). If a pig died during the experiment, a timely autopsy was performed to determine the cause of death, and a pathological histological examination was performed if necessary. With cure rate and markedly effective rate as the main indicators, and weight change, feed-to-weight ratio and water intake of pigs during the experiment as secondary indicators, the therapeutic effect of the test drugs on piglet diarrhea was comprehensively evaluated.

[0157] Test results: The changes in clinical symptom scores of piglets in each group are shown in Table 7. After the administration period, the scores of the medium and high dose groups of the test drug were significantly lower than those of the low dose group of the test drug and the positive drug control group (P<0.05). The medium dose group of the test drug had the lowest score and the best clinical effect. After the observation period, there was no significant difference in the clinical symptom scores of each group compared with the negative control group. The symptom score of the medium dose group of the test drug was 0, indicating that the clinical symptoms of the piglets had completely disappeared.

[0158] Table 7 Changes in clinical syndrome scores in each group of the experiment

[0159]

[0160] The effective rate, marked effective rate, cure rate and total effective rate of each group are shown in Tables 8-9. After the administration period, the marked effective rate + cure rate of the medium and high dose groups were higher than that of the control drug group; after the observation period, the cure rate, marked effective rate + cure rate and total effective rate of the medium dose group of the test drug all reached 100%, indicating that it has the best clinical efficacy.

[0161] Table 8 Effective rate, marked effective rate, cure rate and total effective rate of the experimental pigs after administration

[0162]

[0163]

[0164] Note: In the same column of data, different shoulder letters indicate significant differences, P<0.05; no shoulder letters or the same shoulder letters indicate no statistical difference, P>0.05.

[0165] Table 9 Effective rate, marked effective rate, cure rate and total effective rate of experimental pigs after the observation period

[0166]

[0167] Note: In the same column of data, different shoulder letters indicate significant differences, P<0.05; no shoulder letters or the same shoulder letters indicate no statistical difference, P>0.05.

[0168] The weight changes, feed-to-weight ratio, and water intake of piglets during the experiment are shown in Tables 10 to 12. As shown in Table 10, diarrhea significantly affects the weight gain of piglets, reduces feed intake, and increases feed-to-weight ratio, but medium-dose drugs can partially restore the weight loss and decreased feed intake caused by diarrhea.

[0169] Table 10 Weight data of experimental pigs during the experiment

[0170]

[0171]

[0172] Note: In the same column of data, different shoulder letters indicate significant differences, P<0.05; no shoulder letters or the same shoulder letters indicate no statistical difference, P>0.05.

[0173] Table 11 Feed intake and feed-to-weight ratio of experimental pigs during drug administration

[0174]

[0175] Table 12 Total amount of drinking water for experimental pigs during the experiment

[0176]

[0177] In summary, the drug of the present invention is administered in drinking water at a dose of 1 g / kg·bw for 3-5 consecutive days to effectively treat diarrhea in piglets, with symptoms such as increased frequency of defecation, thin or watery feces, abdominal pain, loss of appetite, etc.

[0178] Through the analysis of the above clinical efficacy, it can be confirmed that the veterinary preparation of the present invention is 100% effective in treating piglet diarrhea. It can be seen that the present invention has the characteristics of good efficacy and high cure rate. In addition, the medicinal raw materials used in the veterinary preparation of the present invention are inexpensive and widely available, the drug preparation method is simple, and the production cost is low. At the same time, the drug is easy to administer and has good palatability, so it is suitable for large-scale breeding applications.

[0179] The above description is only a preferred embodiment of the present application and is not intended to limit the present application. Any modifications, equivalent substitutions or improvements made within the spirit and principles of the present application should be included in the protection scope of the present application.

Claims

1. A Chinese veterinary medicine preparation for treating piglet diarrhea, consisting of raw materials and auxiliary materials, characterized in that: The raw medicinal materials include: Poria, Herba Euphorbiae, Catechu, Prunus mume, Crataegus pinnatifida, White Peony Root, Licorice, Evodia rutaecarpa, Aucklandia lappa, Atractylodes macrocephala, Crataegus pinnatifida; The auxiliary materials include: disintegrant modified starch, filler dextrin, flavoring agent sucrose and stevioside; The mass ratio of the raw material to the auxiliary material is 1:(1-3); The modified starch is prepared by reacting starch, mannitol, dilauroyl peroxide and solvent DMSO to obtain cross-linked starch, and then reacting the cross-linked starch, water, anhydrous sodium sulfate, sodium chloride, acetic anhydride and sodium hydroxide solution to obtain the modified starch.

2. The Chinese veterinary medicine preparation according to claim 1, characterized in that: The raw medicinal materials are proportioned by weight: 10-300 parts of Poria cocos, 20-300 parts of Euphorbia cerasifera, 1-100 parts of catechu, 1-200 parts of Prunus mume, 1-200 parts of charred hawthorn, 1-200 parts of white peony root, 20-300 parts of liquorice, 1-50 parts of Evodia rutaecarpa, 1-50 parts of costusroot, 1-20 parts of Atractylodes macrocephala, and 1-40 parts of hawthorn.

3. The Chinese veterinary drug preparation according to claim 1, characterized in that: The auxiliary materials include 4-8 parts of modified starch, 1-3 parts of sucrose, 1-3 parts of dextrin and 1-3 parts of stevioside by weight.

4. The Chinese veterinary medicine preparation according to claim 1, characterized in that: The specific steps of preparing the modified starch are as follows: S1: adding starch and mannitol to the solvent DMSO and mixing evenly, adding dilauroyl peroxide, heating reaction, vacuum distillation concentration, filtering and drying to obtain cross-linked starch; S2: adding water, anhydrous sodium sulfate and sodium chloride to the cross-linked starch, adding sodium hydroxide solution, adding acetic anhydride, keeping warm for reaction, filtering, washing and drying to obtain modified starch.

5. The Chinese veterinary medicine preparation according to claim 4, characterized in that: In step S1, the mass ratio of starch, mannitol, dilauroyl peroxide and solvent DMSO is 10:(2-3):(0.1-0.3):(10-20); the heating reaction temperature is 75-90°C and the time is 8-12h.

6. The Chinese veterinary medicine preparation according to claim 4, characterized in that: The mass ratio of the cross-linked starch, water, anhydrous sodium sulfate, sodium chloride, acetic anhydride and sodium hydroxide solution in step S2 is (37-40):100:(0.1-0.5):(0.1-0.5):(8-12):(10-40); the temperature of the insulation reaction is 60-70°C and the time is 4-7h. The mass fraction of the sodium hydroxide solution added in step S2 is 3-6%, and the pH is adjusted to 8.5-9.

0.

7. A method for preparing a Chinese veterinary drug preparation according to any one of claims 1 to 6, characterized in that: The specific steps are as follows: Step 1) weighing the raw medicinal materials according to the ratio; Step 2) decoct with water to extract the raw medicinal materials: mix black plum, charred hawthorn, white peony root, evodia rutaecarpa, costusroot, atractylodes macrocephala, and hawthorn according to the above weight proportions, decoct with water, filter, add herb residue to Herba Euphorbiae Herba, decoct with water again, filter, and combine the above filtrates to form extract 1; decoct catechu with water, filter, and the filtrate is extract 2; decoct Poria cocos and licorice with water, decoct, filter, and the filtrate is extract 3; Step 3) extract 1 is concentrated under reduced pressure to obtain concentrated solution 1, extract 3 is concentrated under reduced pressure to obtain concentrated solution 3, and concentrated solution 1, extract 2, and concentrated solution 3 are combined; Step 4) fluidized bed one-step granulation: the auxiliary materials sucrose, dextrin and stevioside are placed in the fluidized bed of the fluidized spray granulation equipment, the modified starch slurry is sprayed in, and filtered heated air is introduced, the air inlet temperature is 70-90° C., so that the auxiliary materials are preheated and dried and in a boiling state; the combined concentrate and extract are sprayed in a mist form, and the fluidized drying is continued, mixed, and packaged to obtain.

8. The Chinese veterinary medicine preparation according to claim 7, characterized in that: In step 2), ebony, charred hawthorn, white peony, evodia rutaecarpa, costus root, atractylodes macrocephala, and hawthorn are mixed according to the above weight ratio, 10-14 times the weight of water of the mixed medicinal materials are added, and the mixture is decocted for 0.5-3 hours, filtered, and the residue is added to herba euphorbiae, and 10-14 times the weight of water is added to continuously decoct for 1-3 times, each time for 0.5-3 hours, and the filtrates are combined to obtain extract 1; catechu is decocted for 1-3 times with 8-12 times the weight of water, each time for 0.5-3 hours, the decoction is filtered, and the filtrates are combined to obtain extract 2; Poria cocos and licorice are decocted for 1-3 times with 10-14 times the weight of water, each time for 1-4 hours, the decoction is filtered, and the filtrates are combined to obtain extract 3.

9. The Chinese veterinary medicine preparation according to claim 7, characterized in that: The extract 1 in step 3) is concentrated under reduced pressure to a relative density of 1.07-1.09 at a temperature of 50°C, ethanol is added to make the alcohol content reach 60%-70%, and the extract is allowed to stand for 10-14 hours. The supernatant is taken, and the ethanol recovery temperature is 60-80°C. At a temperature of 50°C, it is concentrated under reduced pressure to a relative density of 1.10-1.15; the extract 3 is concentrated under reduced pressure to a relative density of 1.07-1.09 at a temperature of 50°C. Preferably, in step 4), the fluidized drying is performed until the moisture content in the particles is less than 2%, the feed rate is 5-20 r / min, and the temperature is 40-60°C.

10. Use of the Chinese veterinary preparation according to any one of claims 1 to 6 or the Chinese veterinary preparation prepared according to any one of claims 7 to 9 in the preparation of a drug for treating and / or preventing swine diarrhea.

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