A solid dispersion composition formula and its preparation process for anti-diarrhea and anti-stress of pigs

Abstract

The present application relates to the technical field of livestock breeding, and discloses a solid dispersion composition formula for pigs and an anti-diarrhea and anti-stress preparation process thereof, which is composed of the following components in percentage by weight: 10-20% of butyric acid triglyceride, 3-8% of basic zinc chloride, 1-4% of L-theanine, 0.2-1.5% of sodium alginate, 0.2-1.5% of light calcium carbonate, 8-10% of guava extract and 55-77.6% of porous magnesium silico-aluminate; the porous magnesium silico-aluminate is a powder material with micro-mesoporous pores in the interior. The composition reduces the weaning diarrhea rate of piglets by reducing the mucosal permeability; in combination with a specific animal intervention cultivation method, the composition effectively relieves the comprehensive stress response of pigs in a specific physiological stage and improves the growth index. The composition releases L-theanine in the later part of the intestinal tract, participates in the regulation of neurotransmitter metabolism after being absorbed, inhibits the over-activation of the hypothalamus-pituitary-adrenal axis during weaning and replacement, and maintains the serum cortisol at a stable level.

Description

[0001] This invention relates to the field of animal husbandry technology, specifically to a solid dispersion composition formulation for antidiarrheal and anti-stress purposes in pigs and its preparation process. Background Technology

[0002] In the production of high-quality pork, piglets often experience a high incidence of weaning diarrhea due to incomplete digestive system development and feed change stress, leading to damage to the intestinal mucosa and increased permeability. To address this issue, existing feed formulations typically include butyrate derivatives (such as triglycerides) and zinc sources (such as basic zinc chloride) to repair damaged intestines and alleviate diarrhea by providing energy to intestinal mucosal epithelial cells and supplementing zinc, respectively.

[0003] However, conventional direct mixing and addition methods often fail to achieve the desired repair effects in practical applications. Basic zinc chloride, a weakly alkaline substance, has extremely low solubility in the slightly neutral or weakly alkaline physiological environment of the posterior segment of the piglet intestine, making it difficult to spontaneously dissociate into a sufficient concentration of effective zinc ions. Simultaneously, the hydrolysis of conventionally mixed triglycerides in the intestine to produce free butyric acid is independent of the metabolic process of basic zinc chloride. Lacking a specific carrier or structure to combine the reaction conditions of both, it is difficult to utilize the local acidic microenvironment generated by triglyceride hydrolysis to promote the dissociation of the weakly alkaline zinc source. This results in the damaged intestinal mucosa being unable to simultaneously obtain high concentrations of both free butyric acid and free zinc ions, preventing them from effectively synergizing to promote the expression of intestinal tight junction proteins. Consequently, intestinal barrier repair is slow, ultimately failing to fundamentally reduce the weaning diarrhea rate in piglets. Summary of the Invention

[0004] To address the shortcomings of existing technologies, this invention provides a solid dispersion composition formulation for anti-diarrheal and anti-stress in pigs and its preparation process, which solves the problem that conventionally added triglycerides of butyrate and basic zinc chloride are insufficient to repair damaged intestinal mucosa and effectively control weaning diarrhea in piglets.

[0005] To achieve the above objectives, the present invention is implemented through the following technical solution: a solid dispersion composition for antidiarrheal and anti-stress in pigs, the composition comprising the following components in weight percentage: 10%~20% triglyceride butyrate, 3%~8% basic zinc chloride, 1%~4% L-theanine, 0.2%~1.5% sodium alginate, 0.2%~1.5% light calcium carbonate, 8%~12% guava functional ingredient extract, and 53%~77.6% porous magnesium aluminosilicate.

[0006] Preferably, the porous magnesium aluminosilicate is a powder material with micropores inside.

[0007] A method for preparing a solid dispersion composition for treating diarrhea and stress in pigs, comprising the following steps: S1. Porous magnesium aluminosilicate is put into a heating mixer to stabilize the powder bed at 50℃~60℃. Triglycerides of butyrate, heated to the same temperature, are uniformly sprayed into the powder bed through an atomizing nozzle to obtain a primary oil-containing carrier. S2. After cooling the material to 25℃~35℃, add the basic zinc chloride, L-theanine, light calcium carbonate powder and guava functional ingredient extract in the formula amount in sequence, and mix evenly. S3. Disperse the sodium alginate in deionized water according to the formula and stir until completely dissolved to form a hydrosol. Spray the hydrosol into the mixer through an atomizing nozzle to coat the material and obtain wet material. S4. Transfer the wet material to a fluidized bed dryer for drying. Stop drying when the exhaust temperature is close to the material bed temperature and the free moisture content of the material is less than 1.0%, and the target solid dispersion composition is obtained.

[0008] Preferably, in step S1, the atomization pressure of the triglyceride butyrate is 0.2MPa~0.4MPa, and the high-shear blade speed of the mixer is set to 1500r / min~3000r / min.

[0009] A formula and preparation process for a solid dispersion composition for antidiarrheal and anti-stress in pigs includes the steps of mixing the solid dispersion composition as a functional additive into the basal diet at a set amount and intervening in the feeding at specific physiological stages of the pigs.

[0010] Preferably, the intervention feeding step includes feeding the sow during gestation: From the 75th day of gestation to the day of farrowing, the solid dispersion composition is mixed evenly with the sow's late gestation basal diet at an addition rate of 1.5 kg / ton to 3.0 kg / ton and fed continuously in a fixed quantity.

[0011] Preferably, the intervention feeding step includes feeding the sow during lactation: During the lactation period of sows, the solid dispersion composition is mixed evenly with the basal diet of lactating sows at an addition rate of 2.0 kg / ton to 2.5 kg / ton and continuously fed until the piglets are weaned.

[0012] Preferably, the intervention feeding step includes feeding piglets during the creep period: Starting from the 5th to the 7th day after the piglets are born, the solid dispersion composition is mixed evenly with the piglet creep feed at an addition rate of 2.5 kg / ton to 4.0 kg / ton for the piglets to consume.

[0013] Preferably, the intervention feeding step includes feeding piglets during the weaning stress period: During the period from the day of weaning to the 10th to the 21st day after weaning, the solid dispersion composition is mixed evenly with the piglet nursery transition feed at an addition rate of 1.0 kg / ton to 3.5 kg / ton for weaned piglets to consume.

[0014] Application of solid dispersion compositions in the preparation of anti-diarrheal and anti-stress functional feeds or feed additives for pigs.

[0015] This invention provides a formulation and preparation process for a solid dispersion composition for treating diarrhea and stress in pigs. It offers the following advantages: 1. This formulation utilizes the intestinal physiological environment to establish a cascade release mechanism of enzymatic hydrolysis and microenvironment acidification, enhancing the synergistic effect in controlling diarrhea. After the composition enters the intestine, triglycerides of butyrate are hydrolyzed by lipase to generate free butyrate, causing a decrease in the local microenvironment pH, which in turn triggers the dissociation of weakly basic zinc chloride. The generated free butyrate directly provides energy to intestinal epithelial cells, and together with the released zinc ions, promotes the expression of intestinal tight junction proteins. Both work synergistically to repair damaged intestinal mucosa, reduce mucosal permeability, and thus reduce the weaning diarrhea rate in piglets.

[0016] 2. This invention, through a combination of specific animal intervention and breeding methods, effectively alleviates the comprehensive stress response of black pigs at a specific physiological stage and improves growth indicators. The composition releases L-theanine in the posterior segment of the intestine, which, after absorption, participates in regulating neurotransmitter metabolism, inhibiting excessive activation of the hypothalamic-pituitary-adrenal axis during weaning and feed change, and maintaining serum cortisol at a stable level. This method of targeted release of anti-stress factors through the intestine alleviates the physiological stress response of piglets, ensures normal feed intake, and ultimately improves the weaning survival rate and daily weight gain of piglets.

[0017] 3. The solid dispersion composition of the present invention achieves targeted sustained release of active ingredients in the digestive tract by constructing a multi-layered spatial encapsulation structure. In the acidic gastric juice environment, the light calcium carbonate in the composition dissociates and releases calcium ions, prompting the surface sodium alginate to undergo in-situ cross-linking to form a calcium alginate gel barrier. This structure effectively blocks the penetration of gastric acid into the pores of the internal carrier, reducing the premature dissolution and loss of components such as triglycerides butyrate and basic zinc chloride in the stomach, and increasing the concentration of active ingredients reaching the intestinal tract. Attached Figure Description

[0018] Figure 1 This is a schematic diagram of the method steps of the present invention. Detailed Implementation

[0019] The technical solution of the present invention will now be clearly and completely described with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0020] The main raw materials and reagents used in the following examples and comparative examples have the following sources and specifications. Reagents not specifically mentioned are all commercially available analytical grade or higher grade products.

[0021] Triglyceride butyrate, CAS number 60-01-5, with a purity greater than or equal to 95% and a dynamic viscosity of less than 25 mPa·s at room temperature, is a commercially available common raw material.

[0022] Basic zinc chloride, CAS number 1332-07-6, with a purity greater than or equal to 98% and a powder particle size D50 of 20 to 50 μm, is a commercially available conventional raw material.

[0023] L-Theanine, CAS number 3081-61-6, with a purity greater than or equal to 98%, is a commercially available, conventional raw material.

[0024] Sodium alginate, CAS number 9005-38-3, has a dynamic viscosity of 100 to 300 mPa·s in a 1% aqueous solution at 20 degrees Celsius. It is a commercially available, conventional raw material.

[0025] Light calcium carbonate, CAS number 471-34-1, purity greater than or equal to 98%, powder particle size D50 of 1 to 5 μm, is a commercially available conventional raw material.

[0026] Guava functional component extract is prepared through the following steps, specifically including: (1) Take fresh guava leaves, wash them, dry them under vacuum at 50°C, and then crush them into particles with a particle size of 0.3 mm using a pulverizer; (2) Add 60% ethanol-water mixed solvent at a material-liquid ratio of 1:15, and extract at 52°C for 48 minutes under ultrasonic power of 350W and frequency of 30kHz. (3) The extract was filtered through a 300-mesh filter, and the supernatant was concentrated under reduced pressure to 1 / 5 of the original volume. Then it was freeze-dried at -45℃ and 8Pa vacuum to obtain guava leaf extract.

[0027] Porous magnesium aluminosilicate, CAS number 12511-31-8, has a specific surface area of ​​200 to 500 m² / g and a pore volume of 0.5 to 1.2 cm³ / g. It is a commercially available conventional raw material.

[0028] Preparation Example 1: This preparation example provides a method for preparing a solid dispersion for swine to combat stress and diarrhea, comprising the following steps: Weigh out 15 kg of triglyceride butyrate, 5 kg of basic zinc chloride, 2 kg of L-theanine, 0.8 kg of sodium alginate, 0.8 kg of light calcium carbonate, 10 kg of guava functional ingredient extract, and 66.4 kg of porous magnesium aluminosilicate.

[0029] Porous magnesium aluminosilicate was placed in a plow mixer equipped with a jacketed heating system. The jacket heating was activated to raise and stabilize the powder bed temperature at 55°C, with the spindle speed set to 90 r / min. Triglyceride butyrate was placed in a preheating tank and heated to 55°C. A high-shear fly knife was activated at a speed of 2000 r / min, and the heated triglyceride butyrate was uniformly sprayed into the powder bed through an atomizing nozzle at an atomization pressure of 0.3 MPa. After spraying, mixing was maintained for 15 minutes to obtain the primary oil-containing carrier.

[0030] Cooling water was introduced into the mixer jacket to lower the temperature of the primary oil-containing carrier bed to 30°C. Basic zinc chloride, L-theanine, light calcium carbonate powder, and guava functional ingredient extract were added sequentially, and mixing was maintained for 8 minutes. Sodium alginate was dispersed in 20 kg of deionized water and stirred at room temperature until completely dissolved to form a hydrosol. This hydrosol was sprayed into the mixer through an atomizing nozzle, with the spindle speed maintained at 90 r / min for 10 minutes to obtain a wet material.

[0031] The wet material is quickly transferred to a top-spray fluidized bed dryer. The induced draft fan and heating system are turned on, the inlet air temperature is set to 80°C, and the fluidization temperature of the material bed is controlled at 45°C. When the exhaust air temperature rises and approaches the material temperature, and the free moisture content of the material is less than 1.0% as measured by sampling, the drying is stopped, and the material is discharged to obtain the target solid dispersion.

[0032] Preparation Example 2: This preparation example provides a method for preparing a solid dispersion for swine anti-stress and anti-diarrheal use, comprising the following steps: Weigh out 10 kg of triglyceride butyrate, 3 kg of basic zinc chloride, 1 kg of L-theanine, 0.2 kg of sodium alginate, 0.2 kg of light calcium carbonate, 8 kg of guava functional ingredient extract, and 77.6 kg of porous magnesium aluminosilicate.

[0033] Porous magnesium aluminosilicate was placed in a plow mixer equipped with a jacketed heating system. The jacket heating was activated to raise and stabilize the powder bed temperature at 50°C, with the spindle speed set to 60 r / min. Triglyceride butyrate was placed in a preheating tank and heated to 50°C. A high-shear fly knife was activated at a speed of 1500 r / min, and the heated triglyceride butyrate was uniformly sprayed into the powder bed through an atomizing nozzle at an atomization pressure of 0.2 MPa. After spraying, mixing was maintained for 10 minutes to obtain the primary oil-containing carrier.

[0034] Cooling water was introduced into the mixer jacket to lower the temperature of the primary oil-containing carrier bed to 25°C. Basic zinc chloride, L-theanine, light calcium carbonate powder, and guava functional ingredient extract were added sequentially, and mixing was maintained for 5 minutes. Sodium alginate was dispersed in 15 kg of deionized water and stirred at room temperature until completely dissolved to form a hydrosol. This hydrosol was sprayed into the mixer through an atomizing nozzle, with the spindle speed maintained at 60 r / min for 5 minutes to obtain a wet material.

[0035] The wet material is quickly transferred to a top-spray fluidized bed dryer. The induced draft fan and heating system are turned on, the inlet air temperature is set to 70°C, and the fluidization temperature of the material bed is controlled at 40°C. Drying is stopped when the exhaust air temperature rises and approaches the material temperature, and the free moisture content of the material is less than 1.0% as measured by sampling. The material is then discharged to obtain the target solid dispersion.

[0036] Preparation Example 3: This preparation example provides a method for preparing an anti-stress solid dispersion for pigs, including the following steps: Weigh out 20 kg of triglyceride butyrate, 8 kg of basic zinc chloride, 4 kg of L-theanine, 1.5 kg of sodium alginate, 1.5 kg of light calcium carbonate, 12 kg of guava functional ingredient extract, and 53 kg of porous magnesium aluminosilicate.

[0037] Porous magnesium aluminosilicate was placed in a plow mixer equipped with a jacketed heating system. The jacket heating was activated to raise and stabilize the powder bed temperature at 60°C, with the spindle speed set to 120 r / min. Triglyceride butyrate was placed in a preheating tank and heated to 60°C. A high-shear fly knife was activated at a speed of 3000 r / min, and the heated triglyceride butyrate was uniformly sprayed into the powder bed through an atomizing nozzle at an atomization pressure of 0.4 MPa. After spraying, mixing was maintained for 20 minutes to obtain the primary oil-containing carrier.

[0038] Cooling water was introduced into the mixer jacket to lower the temperature of the primary oil-containing carrier bed to 35°C. Basic zinc chloride, L-theanine, light calcium carbonate powder, and guava functional ingredient extract were added sequentially, and mixing was maintained for 10 minutes. Sodium alginate was dispersed in 25 kg of deionized water and stirred at a constant temperature of 45°C to 50°C until completely dissolved to form a hydrosol. This hydrosol was sprayed hot into the mixer through an atomizing nozzle, with the spindle speed maintained at 120 r / min for 15 minutes to obtain a wet material.

[0039] The wet material is quickly transferred to a top-spray fluidized bed dryer. The induced draft fan and heating system are turned on, the inlet air temperature is set to 90°C, and the fluidization temperature of the material bed is controlled at 50°C. Drying is stopped when the exhaust air temperature rises and approaches the material temperature, and the free moisture content of the material is less than 1.0% as measured by sampling. The material is then discharged to obtain the target solid dispersion.

[0040] Preparation Example 4: This preparation example provides a method for preparing an anti-stress solid dispersion for pigs, including the following steps: Weigh out 12 kg of triglyceride butyrate, 7 kg of basic zinc chloride, 3 kg of L-theanine, 1.2 kg of sodium alginate, 0.5 kg of light calcium carbonate, 11 kg of guava functional ingredient extract, and 65.3 kg of porous magnesium aluminosilicate.

[0041] Porous magnesium aluminosilicate was placed in a plow mixer equipped with a jacketed heating system. The jacket heating was activated to raise and stabilize the powder bed temperature at 58°C, with the spindle speed set to 100 rpm. Triglyceride butyrate was placed in a preheating tank and heated to 58°C. A high-shear fly knife was activated at a speed of 2500 rpm, and the heated triglyceride butyrate was uniformly sprayed into the powder bed through an atomizing nozzle at an atomization pressure of 0.35 MPa. After spraying, mixing was maintained for 18 minutes to obtain the primary oil-containing carrier.

[0042] Cooling water was introduced into the mixer jacket to lower the temperature of the primary oil-containing carrier bed to 28°C. Basic zinc chloride, L-theanine, light calcium carbonate powder, and guava functional ingredient extract were added sequentially, and mixing was maintained for 7 minutes. Sodium alginate was dispersed in 18 kg of deionized water and stirred at room temperature until completely dissolved to form a hydrosol. This hydrosol was sprayed into the mixer through an atomizing nozzle, with the spindle speed maintained at 100 rpm for 12 minutes to obtain a wet material.

[0043] The wet material is quickly transferred to a top-spray fluidized bed dryer. The induced draft fan and heating system are turned on, the inlet air temperature is set to 85°C, and the fluidization temperature of the material bed is controlled at 48°C. Drying is stopped when the exhaust air temperature rises and approaches the material temperature, and the free moisture content of the material is less than 1.0% as measured by sampling. The material is then discharged to obtain the target solid dispersion.

[0044] Example 1: This example provides a formulation and preparation process for a solid dispersion composition for treating diarrhea and stress in pigs. Please refer to the appendix. Figure 1 This includes the following steps: The solid dispersion obtained in Preparation Example 1 was used as a functional additive. It was mixed evenly with the basal diet of sows in late pregnancy at an addition rate of 1.5 kg per ton and fed continuously and quantitatively from the 85th day of gestation to the day of farrowing. During the lactation period of sows, the solid dispersion obtained in Preparation Example 1 was mixed evenly with the basal diet of lactating sows at an addition rate of 2.0 kg per ton and fed continuously until the piglets were weaned. Starting on the 7th day after the piglets are born, the solid dispersion obtained in Preparation Example 1 is mixed evenly with the piglet creep feed at an addition rate of 2.5 kg per ton, and the piglets are allowed to eat freely. After weaning, the piglet nursery feed is continued to be fed in the same proportion until the 14th day after weaning.

[0045] Example 2: This example provides a method for producing high-quality pigs with anti-diarrheal and anti-stress characteristics that focuses on intervention at the sow end, including the following steps: The solid dispersion obtained in Preparation Example 2 was used as a functional additive. It was mixed evenly with the basal diet of sows in the mid-to-late stages of pregnancy at an addition rate of 3.0 kg per ton. It was continuously and quantitatively fed to sows from the 75th day of pregnancy to the day of farrowing, with the daily feed amount per sow controlled at 2.5 to 3.0 kg. After farrowing, sows resumed regular lactation diets. During the high-stress window from the day of weaning to the 10th day after weaning, the solid dispersion obtained in Preparation Example 2 was mixed evenly with the piglet nursery transition feed at an addition rate of 1.0 kg per ton and allowed to be freely consumed by the piglets.

[0046] Example 3: This example provides a method for producing high-quality pigs with anti-diarrheal and anti-stress characteristics that focuses on direct intervention in the terminal tract of piglets, including the following steps: Sows were fed a regular basal diet throughout the entire pregnancy and lactation period without any intervention. The solid dispersion obtained in Example 3 was used as a functional additive. Starting from the 5th day after the piglets were born, it was added at a rate of 4.0 kg per ton and thoroughly mixed with the piglet creep feed. Small amounts were added frequently each day to encourage feeding and allow free access to feed. After weaning, the solid dispersion obtained in Preparation Example 3 was mixed evenly with the piglet nursery feed at an addition rate of 3.5 kg per ton and fed continuously until the 21st day after weaning.

[0047] Example 4: This example provides an application scheme for a solid dispersion composition for treating diarrhea and stress in pigs, comprising the following steps: The solid dispersion obtained in Preparation Example 4 was used as a functional additive. It was mixed evenly with the basal diet of sows in late pregnancy at an addition rate of 2.0 kg per ton and fed continuously and quantitatively from the 90th day of gestation to the day of farrowing. From farrowing to weaning, the solid dispersion obtained in Preparation Example 4 was mixed evenly with the basal diet of lactating sows at an addition rate of 2.5 kg per ton and fed. During the weaning period, no intervention is required. From the day of weaning to the 14th day after weaning, the solid dispersion obtained in Preparation Example 4 is mixed evenly with the piglet nursery feed at an addition rate of 3.0 kg per ton, and the weaned piglets are allowed to eat freely to smoothly pass through the weaning stress period.

[0048] Comparative Example 1: Compared with Example 1, the difference is that light calcium carbonate is not added to the formulation when preparing the solid dispersion. The missing mass is made up by replacing it with an equal amount of porous magnesium aluminosilicate. All other aspects are the same.

[0049] Comparative Example 2: Compared with Example 1, the difference is that sodium alginate is not added to the formulation when preparing the solid dispersion, and the steps of preparing hydrosol and atomization coating are omitted in the preparation process, while the rest are the same.

[0050] Comparative Example 3: Compared with Example 1, the difference is that sodium butyrate was used in place of triglyceride butyrate in the preparation of the solid dispersion, while all other aspects were the same.

[0051] Comparative Example 4: Compared with Example 1, the difference is that L-theanine was not added to the formulation when preparing the solid dispersion. The missing mass was made up by replacing it with an equal amount of porous magnesium aluminosilicate. All other aspects are the same.

[0052] Comparative Example 5: Compared with Example 1, the difference is that the preparation process of the solid dispersion was changed. Instead of the mesoporous impregnation and fluidized bed attachment crystallization coating steps, all the solid powders and liquid raw materials in the formulation were directly and simply physically mixed at room temperature to make the additive. All other aspects were the same.

[0053] Comparative Example 6: Compared with Example 1, the difference is that the solid dispersion of the present invention was not fed, but commercially available conventional zinc oxide (2 kg / ton) and ordinary physically coated sodium butyrate (1 kg / ton) were directly added to the basal diet at each stage, and the rest were the same.

[0054] Test Example 1: This test example performs in vitro biomimetic digestive tract dissolution kinetics tests on the samples obtained in Preparation Example 1 and Comparative Examples 1 to 3, specifically including the following steps: In vitro simulated digestive fluids were prepared based on the physiological parameters of the pig digestive tract. The simulated gastric fluid was adjusted to pH 2.0 with hydrochloric acid and without the addition of protease. The simulated intestinal fluid was adjusted to pH 6.8 with phosphate buffer and with the addition of standard-activity porcine pancreatic lipase.

[0055] Accurately weigh equal amounts of the solid dispersion samples from Preparation Example 1 and Comparative Examples 1 to 3, and put them into dissolution cups containing 500 ml of simulated gastric fluid. Set the water bath temperature to 39 degrees Celsius and the stirring speed to 100 revolutions per minute to start the first stage of gastric fluid dissolution simulation.

[0056] During the first stage of continuous operation, at the 0.5-hour, 1-hour, and 2-hour milestones, 5 ml of release solution was extracted from each dissolution vessel. At the same time, an equal amount of fresh simulated gastric fluid at the same temperature was immediately added to the vessel. The extracted release solution was filtered through a microporous membrane and then sealed for later use.

[0057] After the gastric juice simulation program has run for 2 hours, an equal volume of simulated intestinal juice containing porcine pancreatic lipase is slowly added to each dissolution vessel. Sodium hydroxide solution is added dropwise to adjust the pH of the mixture to 6.8, and the second stage of the intestinal juice dissolution simulation program begins.

[0058] When the second-stage program reaches the 3rd, 4th, and 6th hour nodes, the release fluid at each node is extracted for later use according to the sampling method set in step 3.

[0059] The concentration of free butyric acid in the release liquid samples at each time point was determined using high performance liquid chromatography, and the concentration of zinc ions in the corresponding samples was determined using atomic absorption spectrophotometry. Finally, the cumulative drug dissolution rate at each time point was calculated and summarized.

[0060] Table 1. Test data on the dynamic cumulative dissolution rate of zinc ions and free butyric acid in each test group under simulated digestive tract environment. According to the data in Table 1, the cumulative dissolution rates of zinc ions and free butyric acid in the solid dispersion of Preparation Example 1 were only 8.4% and 4.6% respectively after 2 hours in the simulated gastric fluid stage (pH 2.0). However, the dissolution rates of both increased after entering the simulated intestinal fluid stage containing lipase, reaching 88.3% and 86.9% respectively by the 6th hour. Combined with the analysis of the formulation characteristics, in the acidic simulated gastric fluid, the calcium ions released by the dissociation of light calcium carbonate promote the cross-linking of sodium alginate, forming a calcium alginate gel layer on the material surface. This gel layer reduces the penetration of acidic fluid into the internal carrier pores, thereby reducing the premature dissolution of the internal active ingredients in the gastric fluid stage.

[0061] Comparative test data show that Comparative Example 1, without the addition of light calcium carbonate, lacked the calcium ion source required for cross-linking, resulting in a cumulative dissolution rate of 62.1% for zinc ions at 2 hours in the simulated gastric fluid stage. Comparative Example 2, without the addition of sodium alginate, failed to form a film on the particle surface, directly exposing internal pores to the fluid, leading to premature dissolution of both zinc ions and free butyric acid at the gastric fluid stage. Comparative Example 3, using conventional sodium butyrate instead of triglycerides, exhibited a high dissolution rate of 92.4% for free butyric acid at the gastric fluid stage, demonstrating conventional non-targeted release characteristics. Simultaneously, due to the lack of microenvironmental acidification from the degradation of triglycerides by intestinal lipases, the dissociation of basic zinc chloride in the slightly neutral simulated intestinal fluid was limited, resulting in a decrease in the cumulative dissolution rate of zinc ions to 55.4% at 6 hours.

[0062] The test results reflect the synergistic mechanism among the components of the composition of this invention. Triglyceride butyrate is hydrolyzed by lipase in the simulated intestinal fluid stage to produce free butyrate, causing a decrease in the local microenvironment pH. This slightly acidic condition promotes the dissociation of basic zinc chloride. The released zinc ions not only form a coordination complex with L-theanine but also induce secondary gelation of partially dissolved alginic acid, thereby retaining the released components in the local intestinal region. This design achieves the release of components at a specific stage of the intestine through a tandem reaction of digestive enzyme hydrolysis and microenvironment pH change, reducing fluid flushing losses in the early digestive tract.

[0063] Test Example 2: This test example examines the antidiarrheal and antistress phenotypes of the feeding methods used in Example 1 and Comparative Examples 1, 2, 4, 5, and 6. The specific steps include: Sixty healthy pregnant sows with similar genetic backgrounds, parity, and expected delivery dates were selected and randomly divided into six test groups, with ten sows in each group.

[0064] According to the feeding stages and dosages set in Example 1 and the various comparative examples, the corresponding solid dispersions or commercially available additives were mixed with the basal diet for sows in late pregnancy, the basal diet for lactation, and the creep feed and nursery feed for piglets.

[0065] Record the initial weight of piglets after farrowing in each group of sows, and calculate the average birth weight of piglets in each group.

[0066] During the piglet training stage, the effective feed intake of each group of piglets is recorded daily, and the average daily feed intake is calculated.

[0067] Record the survival status of piglets in each group from birth to the day of weaning, and calculate the survival rate of weaned piglets in each group.

[0068] During the high-stress window of 14 consecutive days after weaning, the fecal condition of piglets was recorded daily, and the average diarrhea rate and diarrhea index of piglets during this period were calculated.

[0069] On the day of weaning and on the fourteenth day after weaning, the surviving piglets in each group were weighed. Based on the total feed consumption at the corresponding stage, the average daily weight gain and feed conversion ratio of the piglets were calculated.

[0070] Table 2. Macroeconomic breeding indicators of black pigs and test data on anti-diarrheal phenotypes of piglets at weaning period for each test group. According to the data in Table 2, the feeding method of Example 1 showed the best performance in multiple indicators of pig reproduction and piglet growth, with a weaning survival rate of 96.5%, a post-weaning diarrhea rate of only 4.2%, and a stage feed conversion ratio reduced to 1.35. This data indicates that the solid dispersion of the present invention achieves the expected sustained-release intervention mechanism in animals. After the solid dispersion enters the animal's stomach with the feed, the calcium alginate gel formed on the outer layer reduces the erosion of acidic gastric juice.

[0071] After entering the small intestine, butyrate triglycerides undergo enzymatic hydrolysis under the action of intestinal lipases. The resulting free butyrate repairs intestinal epithelial cells while lowering the local intestinal fluid pH. This slightly acidic microenvironment promotes the dissociation of basic zinc chloride within the intestine. The released zinc ions then undergo secondary gelation with residual alginic acid in the intestinal fluid, fixing L-theanine on the small intestinal mucosa surface, achieving a synergistic effect of astringing and stopping diarrhea while alleviating weaning stress.

[0072] Comparative analysis showed that the absence of specific components or processes in each control group led to a decline in breeding indicators. Control groups 1 and 2, lacking the addition of light calcium carbonate or sodium alginate, lost their in-situ cross-linking and anti-peeling ability in the gastric juice environment, resulting in premature consumption of the active ingredients in the stomach. This led to insufficient concentrations of zinc ions and free butyric acid in the posterior intestinal tract, causing diarrhea rates to rise to 15.6% and 18.3%, respectively. Control group 4, due to the removal of L-theanine from its formula, failed to effectively alleviate the physiological stress response of piglets during weaning and feed change, manifested as a decrease in daily creep feed intake to 35.1 grams, affecting average daily weight gain.

[0073] Comparative Example 5 used a conventional physical mixing process, where each component dissolved independently in the digestive tract, failing to form an in-situ encapsulation and cascade release mechanism, resulting in a diarrhea rate as high as 19.5%, confirming the necessity of a specific preparation process for achieving this mechanism. Comparative Example 6 used commercially available conventional zinc oxide and ordinary coated sodium butyrate. Although it had some effect, the diarrhea rate and daily weight gain were lower than in Example 1. This reflects that the specific coordination and in-situ gel sustained-release system constructed in this invention is superior to traditional simple high-dose physical addition schemes in improving the local intestinal bioavailability of drugs.

[0074] Test Example 3: This test example involves testing serum stress resistance and intestinal mucosal permeability biochemical indicators in the test animals of Example 1 and Comparative Examples 1, 2, 4, 5, and 6. The specific steps include: 1. On the morning of the day of weaning and the seventh day after weaning, six piglets were randomly selected from the test groups of Example 1 and each comparative example, and blood was collected from the anterior vena cava on an empty stomach. The blood volume collected at one time was five milliliters.

[0075] 2. Let the collected blood sample stand at room temperature for 30 minutes, then place it in a centrifuge at 4 degrees Celsius and centrifuge at 3,000 revolutions per minute for 15 minutes.

[0076] 3. Extract the upper serum layer and aliquot it into sterile centrifuge tubes, then store it in an ultra-low temperature freezer at -80 degrees Celsius for later use.

[0077] 4. The concentration of cortisol in serum samples was detected by enzyme-linked immunosorbent assay (ELISA) to quantitatively assess the physiological stress level of piglets.

[0078] 5. The activity of diamine oxidase in serum was quantitatively determined using a UV spectrophotometer combined with spectrophotometry, and the concentration of dextrorotatory lactate in serum was determined using a biochemical reagent kit. These two indicators were used to assess the degree of damage and leakage of the intestinal physical barrier.

[0079] 6. Record the data of each indicator on the day of weaning and the seventh day after weaning, and make statistical comparisons.

[0080] Table 3. Serum stress and intestinal mucosal permeability biochemical indicators of piglets in each test group during weaning. Table 3 shows that on the seventh day after weaning and feed change, the piglets in Example 1 maintained relatively stable serum cortisol concentration, diamine oxidase activity, and dextrorotatory lactate concentration, at 158.3 nmol / L, 4.9 U / L, and 0.98 mmol / L, respectively. The increase in each indicator was significantly lower than that in the control groups. Based on the technical mechanism analysis of the formulation, the solid dispersion of this invention, after being blocked by the acidic environment of the stomach, achieves the cascade release of butyric acid, zinc ions, and L-theanine under the combined triggering of intestinal lipase and a decrease in local microenvironment pH. L-theanine, after intestinal absorption, participates in regulating the metabolism of neurotransmitters in the central nervous system, reducing the body's sensitivity to drastic changes in the external environment, and effectively inhibiting the overactivation of the hypothalamic-pituitary-adrenal axis, thereby maintaining serum cortisol at a normal basal level.

[0081] Meanwhile, free butyrate provides a direct energy source for intestinal epithelial cells, and dissociated zinc ions promote the expression of tight junction proteins in intestinal epithelium. Under the enrichment of local secondary gel, the two work together to repair the intestinal mucosa, maintain the physical compactness of the epithelial barrier, and prevent large amounts of diamine oxidase and dextrorotatory lactate from leaking into the blood in the intestinal lumen.

[0082] Comparison of the data from each group shows that the above-mentioned regulatory mechanism is disrupted when specific components or structures are missing from the system. Comparative Examples 1 and 2, lacking calcium carbonate or sodium alginate, were unable to construct an in-situ cross-linked anti-peel barrier against gastric juice, resulting in excessive loss of core components at the front of the digestive tract. Consequently, the concentrations of butyrate and zinc ions reaching the rear of the small intestine were insufficient, and the tight junctions of the intestine were damaged. This resulted in significantly abnormal concentrations of diamine oxidase and dextrorotatory lactate on day 7.

[0083] Comparative Example 4, which lacked L-theanine, showed a sharp increase in cortisol concentration to 245.2 nmol / L on day 7 post-weaning, demonstrating that L-theanine is a key factor in achieving the anti-stress phenotype in this system. Comparative Example 5, using conventional physical mixing, exhibited excessively rapid dispersion of materials in the intestine, failing to achieve localized sustained release and gel enrichment effects, resulting in inferior serum permeability biochemical indicators.

[0084] Comparative Example 6 used a commercially available conventional zinc oxide and physically coated sodium butyrate scheme. Due to the lack of a site-specific synergistic mechanism of enzymatic degradation and pH triggering, the intestinal bioavailability of the active ingredient was limited. Its effect in controlling cortisol surge and repairing mucosal permeability was still inferior to that of Example 1, which verified the technical advantages of the solid dispersion of the present invention at the physiological and metabolic level.

[0085] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A solid dispersion composition for swine antidiarrheal and anti-stress purposes, characterized in that, The composition comprises the following components in weight percentage: 10%~20% triglyceride butyrate, 3%~8% basic zinc chloride, 1%~4% L-theanine, 0.2%~1.5% sodium alginate, 0.2%~1.5% light calcium carbonate, 8%~12% guava functional ingredient extract, and 53%~77.6% porous magnesium aluminosilicate.

2. The solid dispersion composition for antidiarrheal and anti-stress in pigs according to claim 1, characterized in that: The porous magnesium aluminosilicate is a powder material with microscopic mesopores inside.

3. A method for preparing a solid dispersion composition for swine antidiarrheal and antistress purposes, as described in any one of claims 1-2, characterized in that: Includes the following steps: S1. Porous magnesium aluminosilicate is put into a heating mixer to stabilize the powder bed at 50℃~60℃. Triglycerides of butyrate, heated to the same temperature, are uniformly sprayed into the powder bed through an atomizing nozzle to obtain a primary oil-containing carrier. S2. After cooling the material to 25℃~35℃, add the basic zinc chloride, L-theanine, light calcium carbonate powder and guava functional ingredient extract in the formula amount in sequence, and mix evenly. S3. Disperse the sodium alginate in deionized water according to the formula and stir until completely dissolved to form a hydrosol. Spray the hydrosol into the mixer through an atomizing nozzle to coat the material and obtain wet material. S4. Transfer the wet material to a fluidized bed dryer for drying. Stop drying when the exhaust temperature is close to the material bed temperature and the free moisture content of the material is less than 1.0%, and the target solid dispersion composition is obtained.

4. The method for preparing a solid dispersion composition for swine antidiarrheal and anti-stress purposes according to claim 3, characterized in that: In step S1, the atomization pressure of the triglyceride butyrate is 0.2MPa~0.4MPa, and the high-shear blade speed of the mixer is set to 1500r / min~3000r / min.

5. A formulation and preparation process of a solid dispersion composition for treating diarrhea and stress in pigs, characterized in that, This includes the steps of using solid dispersion compositions as functional additives, mixing them into the basal diet at a set dosage, and intervening in the feeding of pigs at specific physiological stages.

6. The solid dispersion composition for antidiarrheal and anti-stress in pigs according to claim 5, characterized in that: The intervention feeding steps include feeding sows during gestation: From the 75th day of gestation to the day of farrowing, the solid dispersion composition is mixed evenly with the sow's late gestation basal diet at an addition rate of 1.5 kg / ton to 3.0 kg / ton and fed continuously in a fixed quantity.

7. The solid dispersion composition for antidiarrheal and anti-stress in pigs according to claim 5, characterized in that: The intervention feeding steps include feeding during the sow's lactation period: During the lactation period of black pig sows, the solid dispersion composition is mixed evenly with the basal diet of lactating sows at an addition rate of 2.0 kg / ton to 2.5 kg / ton and continuously fed until the piglets are weaned.

8. The solid dispersion composition for antidiarrheal and anti-stress in pigs according to claim 5, characterized in that: The intervention feeding steps include feeding piglets during the starter period: Starting from the 5th to the 7th day after the piglets are born, the solid dispersion composition is mixed evenly with the piglet creep feed at an addition rate of 2.5 kg / ton to 4.0 kg / ton for the piglets to consume.

9. The solid dispersion composition for antidiarrheal and anti-stress in pigs according to claim 5, characterized in that: The intervention feeding steps include feeding piglets during the weaning stress period: During the period from the day of weaning to the 10th to the 21st day after weaning, the solid dispersion composition is mixed evenly with the piglet nursery transition feed at an addition rate of 1.0 kg / ton to 3.5 kg / ton for weaned piglets to consume.

10. The use of the solid dispersion composition according to claim 1 or 2 in the preparation of antidiarrheal and anti-stress functional feed or feed additive for pigs.

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