A plant extract compound composition for preventing and treating piglet diarrhea and a preparation method and use thereof

Abstract

This invention belongs to the field of animal feed additive technology, and discloses a plant extract compound composition for preventing and treating diarrhea in piglets, its preparation method, and its uses. The composition comprises water-soluble extracts of purslane, polysaccharide extracts of Poria cocos, oligosaccharide extracts of roasted malt, fat-soluble extracts of Pulsatilla chinensis, fat-soluble extracts of Coptis chinensis, flavonoid extracts of Sanguisorba officinalis, modified soybean lecithin, polyglycerol fatty acid esters, hydroxypropyl methylcellulose phthalate, sodium alginate, sodium citrate, and silica. The water-soluble extracts are solidified to form a continuous matrix, and the fat-soluble extracts are embedded in pH-responsive microcapsules. The preparation method includes graded low-temperature extraction, preparation of wall material mother liquor, emulsification and mixing with the wall material, spray drying and in-situ embedding, and post-treatment sieving. This invention utilizes an alkali-dissolution-acid-precipitation-thermal fusion process to form a continuous and dense shell, allowing the microcapsules to remain intact in the gastric acid of piglets and release in stages in response to intestinal pH conditions, thus preventing and improving diarrhea in piglets.

Description

Technical Field

[0001] This invention relates to the field of animal feed additives, and in particular to a plant extract compound composition for preventing and treating diarrhea in piglets, its preparation method, and its uses. Background Technology

[0002] Piglets, with their underdeveloped gastrointestinal tract and weak intestinal immune barrier, are highly susceptible to diarrhea due to various factors such as weaning, regrouping, environmental stress, and gut microbiota dysbiosis. Diarrhea not only directly leads to decreased growth rate and feed conversion ratio in piglets, but can also cause mass mortality in severe cases, resulting in significant economic losses for large-scale pig farming. Currently, with the continued implementation of policies banning antibiotics in feed and strict restrictions on the use of traditional antibiotic additives, natural feed additives, represented by plant extracts, have become an important alternative for controlling piglet diarrhea.

[0003] However, existing plant-based feed additives generally do not incorporate the physiological pH gradient characteristics of piglets' digestive tract into their formulation design. The pH in a piglet's stomach is typically 2.0–3.5, while the pH in the jejunum and ileum is 6.0–7.2, the latter being a high-risk area for colonization of diarrhea-causing bacteria and intestinal inflammation. Conventional plant extract products are mostly used in simple physical compound powder form, where the active ingredients are largely degraded and inactivated in the acidic environment of the stomach, failing to effectively deliver to the intestinal lesions. Even when using ordinary microcapsules, their wall materials are mostly inert carriers, lacking the ability to release in stages according to changes in intestinal pH, making it difficult to achieve concentrated release of antibacterial and anti-inflammatory components in the jejunum and ileum, areas prone to diarrhea. Summary of the Invention

[0004] The present invention aims to provide a plant extract compound composition for preventing and treating diarrhea in piglets, its preparation method and uses, in order to solve the problems mentioned in the background art.

[0005] To achieve the above objectives, the present invention provides the following technical solution: A compound plant extract for preventing and treating diarrhea in piglets, comprising the following raw materials in parts by weight: 22-28 parts of water-soluble purslane extract, 11-17 parts of poria cocos polysaccharide extract, 13-19 parts of roasted malt oligosaccharide extract, 16-22 parts of fat-soluble extract of Pulsatilla chinensis, 9-14 parts of fat-soluble extract of Coptis chinensis, 11-17 parts of Sanguisorba officinalis flavonoid extract, 6-10 parts of modified soybean lecithin, 1-3 parts of polyglycerol fatty acid ester with an HLB value of 9-11, 8-12 parts of hydroxypropyl methylcellulose phthalate, 4-6 parts of sodium alginate, 0.3-0.5 parts of sodium citrate, and 3-6 parts of silicon dioxide; The compound composition is a composite powder with a particle size of 80-160 mesh; the composite powder contains a solid continuous matrix formed by solidifying a water-soluble extract of purslane, a polysaccharide extract of Poria cocos, and an oligosaccharide extract of roasted malt, as well as microcapsules uniformly embedded in the solid continuous matrix. The microcapsules use fat-soluble extracts of Pulsatilla chinensis, Coptis chinensis, and Sanguisorba officinalis as core materials, and a complex of hydroxypropyl methylcellulose phthalate and sodium alginate as wall material. The wall material maintains a dense and intact structure in an environment with a pH less than 5.0, gradually swells in an environment with a pH of 5.0 to 6.0, and degrades and ruptures in an environment with a pH not lower than 6.0.

[0006] Preferably, the weight ratio of hydroxypropyl methylcellulose phthalate to sodium alginate is 8:4 to 12:6, and the composite wall material formed by the two is a continuous and dense shell layer formed by an alkali dissolution-acid precipitation-thermal fusion process.

[0007] Preferably, the use of a plant extract compound composition for preventing and treating diarrhea in piglets in the preparation of a feed additive for preventing and improving diarrhea in piglets.

[0008] The preparation method of the above-mentioned plant extract compound composition for preventing and treating diarrhea in piglets includes the following steps: S1. Purslane, Poria cocos, and roasted malt were extracted at low temperature with ultrasonic assistance using water as a solvent and concentrated to a relative density of 1.18~1.22 at 55℃ to obtain an aqueous concentrate. Pulsatilla chinensis, Coptis chinensis, and Sanguisorba officinalis were extracted at low temperature with ethanol as a solvent and refluxed. After recovering the ethanol, the extract was vacuum de-alcoholized until the ethanol residue was ≤0.5% to obtain an oil extract. The extract was diluted with 10%~15% anhydrous ethanol by weight to obtain a liquid oil phase. S2. Preparation of wall material stock solution: Adjust the pH of pure water to 8.2~9.0 with sodium carbonate, heat to 40~45℃, add hydroxypropyl methylcellulose phthalate and sodium alginate and stir to dissolve, then add sodium citrate and stir to dissolve to obtain wall material aqueous solution; S3. Add modified soybean lecithin and polyglycerol fatty acid ester to the aqueous phase concentrate, stir to dissolve, and then slowly add liquid oil phase. Emulsify at high shear rate of 8000~10000 r / min for 8~12 min to obtain a water-oil composite emulsion with pH 5.0~6.0. Add the wall material aqueous solution slowly to the emulsion over 25~35 min while stirring at 40℃. After mixing, the pH of the system is 4.8~5.5. Continue stirring to obtain the mixture to be sprayed dry. S4. The mixture to be sprayed is subjected to co-flow low-temperature spray drying, with an inlet air temperature of 110~125℃, an outlet air temperature of 60~70℃, and an atomization pressure of 0.20~0.25MPa. The outlet air temperature is higher than the glass transition temperature of hydroxypropyl methylcellulose phthalate, which causes the precipitated wall material particles to soften and fuse upon heating and spread on the surface of the oil phase droplets to form a continuous and dense shell layer; the water-soluble extract is simultaneously solidified to form a solid continuous matrix, in which microcapsules are embedded. S5. Mix the dried powder with silica, pass it through an 80-mesh sieve, then through a 160-mesh sieve, and take the portion retained between the two sieves to obtain a finished product with a particle size of 80-160 mesh.

[0009] Preferably, in step S1, the temperature of the ultrasound-assisted low-temperature extraction is 45~55℃, the material-to-liquid ratio is 1:9~1:11, and the extraction is performed twice, each time for 2 hours; the temperature of the low-temperature reflux extraction is 40~50℃, the material-to-liquid ratio is 1:7~1:9, and the extraction is performed twice, each time for 1.8 hours; the temperature of the vacuum de-alcoholization is 60℃, the vacuum degree is -0.08MPa, and the de-alcoholization time is 30min.

[0010] Preferably, in step S3, the wall material aqueous solution is added for 25-35 minutes, the emulsion temperature is maintained at 40°C during the addition process, and stirring is continued for 15 minutes after the addition is completed.

[0011] Preferably, in step S4, the feed rate of the co-flow low-temperature spray dryer is 15~25 mL / min.

[0012] Preferably, in step S4, the low-temperature spray drying is carried out using a parallel-flow spray drying device.

[0013] Preferably, in step S5, the mixing is carried out using a three-dimensional motion mixer or a V-type mixer, and the mixing time is 15~25 minutes.

[0014] Preferably, in step S2, the weight ratio of the total amount of pure water to hydroxypropyl methylcellulose phthalate and sodium alginate is 3:1 to 5:1; in step S3, the volume ratio of the wall material aqueous solution to the water-oil composite emulsion is 1:3 to 1:5.

[0015] The beneficial effects of this technical solution compared to existing technologies are as follows: (1) This technical solution uses a pH-responsive composite wall material constructed from hydroxypropyl methylcellulose phthalate and sodium alginate, combined with an alkali-dissolution-acid precipitation-thermal fusion process to form a continuous and dense shell, so that the microcapsules can maintain structural integrity in the strong acid environment of the piglet's stomach, effectively isolating the degradation and destruction of fat-soluble antibacterial components by gastric acid; the wall material gradually swells in the front of the duodenum to achieve slow pre-release of active ingredients; the wall material rapidly degrades and breaks in the jejunum and ileum sections where diarrhea is common, releasing the alkaloids and flavonoids of Pulsatilla chinensis, Coptis chinensis and Sanguisorba officinalis in a concentrated manner, which is highly matched with the physiological pH gradient of the piglet's digestive tract, fundamentally solving the technical problem that conventional plant extracts are inactivated in gastric acid in advance and cannot be effectively delivered to the intestinal lesion site.

[0016] (2) A solid continuous matrix is ​​formed by spray drying and solidifying water-soluble extracts (polysaccharides, organic acids, and prebiotic oligosaccharides) from purslane, poria cocos, and roasted malt into powder form. Simultaneously, lipid-soluble antibacterial components are uniformly embedded within this matrix in the form of microcapsules. The water-soluble matrix dissolves first in the intestine, exerting its effects on intestinal mucosal repair, osmotic pressure regulation, and the proliferation of beneficial bacteria. The lipid-soluble core material is subsequently released from the ruptured microcapsules, exerting its antibacterial and anti-inflammatory effects. The two functional components are spatially zoned and act in stages over time, improving the loading of active ingredients and overall bioavailability.

[0017] (3) By adopting a polarized low-temperature extraction process, water-soluble components are extracted with ultrasonic-assisted water extraction at 45-55℃, and fat-soluble components are extracted with ethanol at 40-50℃ under low-temperature reflux. This avoids the problems of inactivation of heat-sensitive substances and low extraction rate of fat-soluble components caused by conventional single high-temperature water extraction. At the same time, through the compound emulsification system of modified soybean lecithin and polyglycerol fatty acid esters with specific HLB values, and the process design of alkaline dissolution-acid precipitation-thermal fusion film formation of wall material, uniform dispersion of water and oil phases and integrity and density of microcapsule shell are achieved. The product does not separate into oil and water or agglomerate during storage and feed mixing, which is suitable for the industrial application needs of large-scale breeding. Attached Figure Description

[0018] Figure 1 This is a flowchart of the preparation method of the present invention; Detailed Implementation The present invention will now be described in further detail with reference to the accompanying drawings and embodiments: This invention provides a plant extract compound composition for preventing and treating diarrhea in piglets, comprising the following raw materials in parts by weight: 22-28 parts of water-soluble purslane extract, 11-17 parts of poria cocos polysaccharide extract, 13-19 parts of roasted malt oligosaccharide extract, 16-22 parts of fat-soluble extract of Pulsatilla chinensis, 9-14 parts of fat-soluble extract of Coptis chinensis, 11-17 parts of Sanguisorba officinalis flavonoid extract, 6-10 parts of modified soybean lecithin, 1-3 parts of polyglycerol fatty acid ester with an HLB value of 9-11, 8-12 parts of hydroxypropyl methylcellulose phthalate, 4-6 parts of sodium alginate, 0.3-0.5 parts of sodium citrate, and 3-6 parts of silicon dioxide.

[0019] The composition is a composite powder with a particle size of 80-160 mesh. The composite powder comprises a solid continuous matrix formed by solidifying water-soluble extracts of purslane, polysaccharide extracts of Poria cocos, and oligosaccharide extracts of roasted malt, and microcapsules uniformly embedded within the solid continuous matrix. The microcapsules use fat-soluble extracts of Pulsatilla chinensis, fat-soluble extracts of Coptis chinensis, and flavonoid extracts of Sanguisorba officinalis as core materials, and a composite of hydroxypropyl methylcellulose phthalate and sodium alginate as wall material. The wall material maintains a dense and intact structure in an environment with a pH less than 5.0, gradually swells in an environment with a pH of 5.0-6.0, and degrades and ruptures in an environment with a pH not lower than 6.0.

[0020] The solid continuous matrix is ​​formed by solidifying water-soluble plant extracts, which dissolve first in the intestines, playing a role in intestinal mucosal repair, osmotic pressure regulation, and the proliferation of beneficial bacteria. The lipid-soluble antibacterial and anti-inflammatory components in the microcapsule core are protected by the wall material, remaining unreleased in the highly acidic environment of the stomach, pre-released in small amounts in the weakly acidic environment of the duodenum, and concentratedly released in the jejunum and ileum, where diarrhea is common, achieving a segmented response precisely matched to the pH gradient of the piglet's digestive tract. The microcapsule shell and the external solid continuous matrix form a dual physical barrier, inhibiting the diffusion, migration, and recrystallization of the oil-phase active ingredients during storage and processing, ensuring the long-term stability of the system.

[0021] In this embodiment of the invention, all raw materials can be purchased through publicly available commercial channels. The water-soluble extract of purslane, the polysaccharide extract of Poria cocos, the oligosaccharide extract of roasted malt, the fat-soluble extract of Pulsatilla chinensis, the fat-soluble extract of Coptis chinensis, and the flavonoid extract of Sanguisorba officinalis are plant extracts prepared according to the extraction process described in this invention, or they can be customized and processed by a qualified plant extraction manufacturer. Modified soybean lecithin is a food-grade or feed-grade product. Hydroxypropyl methylcellulose phthalate conforms to the relevant standards of the Chinese Pharmacopoeia. The viscosity of sodium alginate is 200~400 mPa·s, which is suitable for film formation in this system; too high a viscosity leads to gelation, while too low a viscosity results in insufficient shell strength. Polyglycerol fatty acid esters are food-grade products with HLB values ​​in the range of 9~11. Sodium citrate is food-grade trisodium citrate dihydrate. Silica is a food-grade gas-phase product. Sodium carbonate is food-grade anhydrous sodium carbonate. Anhydrous ethanol is food-grade.

[0022] Example 1 The following describes the preferred formulation of Example 1 in detail, in sequence. Figure 1 The specific operation and principle of each step in the preparation method of a plant extract compound composition for preventing and treating diarrhea in piglets are shown.

[0023] S1. Extraction and Concentration Raw material pretreatment: The six dried plant materials—Pulsatilla chinensis, Coptis chinensis, Sanguisorba officinalis, Portulaca oleracea, Poria cocos, and roasted malt—were quickly rinsed with clean water to remove surface dust. After draining, they were separately pulverized in a high-speed universal pulverizer, passed through 30-mesh and 40-mesh standard sieves, and the powder between 30 and 40 mesh was collected and stored separately in sealed containers for later use. During pulverization, the pulverization temperature was controlled to not exceed 40℃ to avoid loss of heat-sensitive components. The particle size was selected based on a balance between extraction efficiency and filtration operability; 30-40 mesh (approximately 425-600 μm) ensured sufficient solvent penetration without causing difficulties in subsequent filtration due to excessively fine particle size.

[0024] Extraction of water-soluble components: Take purslane powder, Poria cocos powder, and roasted malt powder by weight, and add them to the extraction tank at a material-to-liquid ratio of 1:10 (i.e., 10L of deionized water per 1kg of mixed powder). The extraction tank is equipped with a jacketed temperature control device and an ultrasonic generator with an ultrasonic power of 200~300W / L and an ultrasonic frequency of 20~40kHz. Turn on the jacketed circulating water bath and control the extraction temperature at 50℃ (the extraction temperature can be selected within the range of 45~55℃). Simultaneously, turn on the ultrasonic generator for ultrasonic-assisted extraction. After 2 hours, release the extract. Add an equal amount of deionized water to the filter residue and perform a second extraction under the same conditions for 2 hours. Combine the two extracts and filter them through a plate and frame filter press with a filter cloth pore size of 200 mesh to remove the residue and insoluble impurities. The filtrate is transferred to an external circulation vacuum concentrator and concentrated under reduced pressure at low temperature under vacuum conditions of -0.08 MPa and water bath temperature of 55°C. During the concentration process, samples are taken periodically, and the relative density is measured at 55°C using a hydrometer or densitometer (with pure water as a reference). Concentration is stopped when the relative density reaches 1.18~1.22, and the aqueous concentrate is obtained. The concentrate is then cooled to 40°C for later use.

[0025] The polysaccharides and organic acids in purslane, the β-glucan polysaccharides in Poria cocos, and the maltodextrin in roasted malt are all water-soluble substances, which can be efficiently extracted using water as a solvent. A temperature of 45-55℃ is chosen because below 45℃, the molecular diffusion rate is slow and the extraction efficiency is low, while above 55℃, large polysaccharide molecules are prone to degradation and chain breakage, and the dissolution of starch impurities increases. The cavitation effect of ultrasound can instantly destroy plant cell walls, accelerating the dissolution of active ingredients. Two extractions ensure thorough extraction. Reduced-pressure, low-temperature concentration utilizes vacuum to lower the boiling point of water (approximately 60℃), avoiding the thermal degradation of polysaccharides and oligosaccharides caused by atmospheric pressure concentration at approximately 100℃. A relative density of 1.18-1.22 for the concentrate is suitable for subsequent emulsification and spray drying; too high a density results in high emulsion viscosity and difficulty in atomization, while too low a density leads to high drying energy consumption and low powder yield.

[0026] Extraction of lipid-soluble components: Take Pulsatilla chinensis powder, Coptis chinensis powder, and Sanguisorba officinalis powder, and add them to a jacketed stainless steel reflux extraction tank at a material-to-liquid ratio of 1:8 (i.e., 8 L of food-grade anhydrous ethanol per 1 kg of mixed powder). Turn on the jacketed circulating water bath and control the extraction temperature at 45℃ (the extraction temperature can be selected within the range of 40~50℃). Extract for 1.8 hours under normal pressure reflux conditions, then release the extract. Add an equal amount of anhydrous ethanol to the filter residue and perform a second reflux extraction under the same conditions for 1.8 hours. Combine the two ethanol extracts and filter through a 200-mesh stainless steel filter. Transfer the filtrate to a rotary evaporator and recover the ethanol solvent under a 60℃ water bath and a vacuum of -0.08 MPa. After recovering ethanol until no distillate drips out, continue vacuum de-ethanolification for 30 minutes. Sample and detect by gas chromatography to ensure that the residual ethanol in the extract does not exceed 0.5%, obtaining the oil phase extract.

[0027] Saponins in Pulsatilla chinensis, alkaloids in Coptis chinensis, and flavonoid aglycones in Sanguisorba officinalis are all fat-soluble or slightly fat-soluble components with low solubility in water, requiring extraction with ethanol as the solvent. Ethanol has a boiling point of 78℃, and stable reflux can be maintained at 40-50℃. Low-temperature conditions also prevent the oxidative degradation of heat-sensitive flavonoids. After conventional ethanol recovery processes, a small amount of ethanol remains in the extract, which not only irritates the digestive tract of piglets but also affects the interfacial tension of the oil phase in subsequent emulsification steps. De-alcoholization at 60℃ and -0.08MPa for 30 minutes can control the ethanol residue to below 0.5%, a parameter that can be achieved in a rotary evaporator or an external circulation concentrator.

[0028] Pretreatment of the oil phase extract: The oil phase extract is a viscous semi-solid at room temperature, which is difficult to pump and disperse directly. Add 12% (by weight of the extract) of food-grade anhydrous ethanol to the obtained oil phase extract (this proportion can be selected within the range of 10% to 15% by weight of the extract). Stir at 100 to 200 r / min for 15 to 20 minutes at room temperature to fully dilute the extract until a homogeneous, flowable liquid oil phase is formed. The liquid oil phase should be able to flow continuously along a glass rod without stringing or clinging to the wall, as observed by visual inspection. Seal and store temporarily for later use.

[0029] The viscosity of alcohol-extracted extracts is typically in the tens to hundreds of thousands of mPa·s, making precise metering and delivery by peristaltic pumps impossible, and they cannot be emulsified and broken down into micron-sized droplets by high shear. Adding a small amount of anhydrous ethanol can reduce the viscosity to a pumpable range (usually below 1000 mPa·s). The reason for choosing anhydrous ethanol over water for dilution is that the fat-soluble components in the extract are immiscible with water; dilution with water would cause the components to precipitate or the two phases to separate. Too little ethanol will result in insufficient viscosity reduction, while too much will increase the drying burden; 10%–15% is the optimal balance between flowability and process cost.

[0030] S2, Preparation of wall material masterbatch In a separate mixing tank, add pure water and adjust the pH to 8.5 (selectable within the range of 8.2 to 9.0) with food-grade sodium carbonate. Heat to 42°C (selectable within the range of 40 to 45°C). While stirring, add 10 parts of hydroxypropyl methylcellulose phthalate and 5 parts of sodium alginate sequentially. The weight ratio of pure water to the total amount of hydroxypropyl methylcellulose phthalate and sodium alginate is 4:1 (this ratio can be selected within the range of 3:1 to 5:1). Stir for 30 minutes until both are completely dissolved, forming a transparent or translucent viscous liquid. Then add 0.4 parts of sodium citrate and continue stirring for 10 minutes until completely dissolved, obtaining a homogeneous wall material aqueous solution.

[0031] Hydroxypropyl methylcellulose phthalate molecules contain phthalate groups. Under alkaline conditions (pH 8.2~9.0), its free carboxyl groups ionize into carboxylate anions. The molecular chains fully extend due to electrostatic repulsion, allowing the material to dissolve in water to form a transparent solution. However, it will not dissolve completely if added directly to water under neutral or acidic conditions. Sodium carbonate is used to adjust the pH because it is a food-grade alkalinity regulator, with mild alkalinity that is easy to control and does not introduce harmful residues. Heating to 40~45℃ can accelerate dissolution. The total weight ratio of pure water to wall material is 3:1~5:1. If the water volume is too small, the wall material will not dissolve completely, resulting in a very high solution viscosity, making it difficult to transport and add dropwise. If the water volume is too large, the wall material concentration will be too low, requiring a large amount of water to evaporate during subsequent spray drying, and the wall material particles will be too sparse, which is not conducive to forming a continuous and dense shell. Sodium alginate is dissolved together with hydroxypropyl methylcellulose phthalate in this step. The two molecular chains begin to intertwine and entangle in the liquid phase, laying the molecular foundation for the subsequent thermal fusion to form a composite shell. Sodium citrate must be added after the hydroxypropyl methylcellulose phthalate and sodium alginate are completely dissolved. Its role is to complex trace amounts of calcium and magnesium ions introduced by the raw materials and water into the system, preventing sodium alginate from cross-linking with calcium and magnesium ions in the liquid phase to form insoluble gel clumps, thus ensuring the stability of the wall material aqueous solution and the subsequent mixing system.

[0032] S3, Emulsion and Wall Material Mixing Two-phase composite emulsification: The aqueous phase concentrate obtained from S1 was transferred to an emulsification tank equipped with a jacketed insulation device, and the temperature was controlled at 40℃. Under low-speed stirring (200~300 r / min), 8 parts of modified soybean lecithin and 2 parts of polyglycerol fatty acid ester with an HLB value of 10 were added to the aqueous phase concentrate, and stirred for 15 minutes until completely dissolved. Stirring was continued, and the liquid oil phase obtained from S1 was slowly added dropwise at a rate of 5~10 mL / min using a peristaltic pump. After the addition was complete, the stirrer was replaced with a high-shear emulsification head, and high-shear emulsification was performed at 9000 r / min for 10 minutes (speed range 8000~10000 r / min, emulsification time 8~12 minutes) to obtain a milky white homogeneous water-oil composite emulsion. The pH of the emulsion should be controlled within the range of 5.0~6.0, as measured by a pH meter. The emulsion showed no oil-water separation after being stored in a sealed container at room temperature for 72 hours.

[0033] The aqueous concentrate contains a large amount of water-soluble polysaccharides and organic acids, while the oil extract contains fat-soluble alkaloids and flavonoids. These two components have drastically different polarities, dispersing the fat-soluble components as tiny oil droplets in the aqueous phase. Modified soybean lecithin (HLB value approximately 4-8, strong lipophilicity) can firmly adsorb at the oil-water interface to form an interfacial film, while polyglycerol fatty acid esters (HLB value 9-11, strong hydrophilicity) provide steric stabilization. When these two are compounded at a mass ratio of 8:2, the overall HLB value, calculated based on the HLB additivity principle, is approximately 8.5-11.5, falling precisely within the optimal HLB value range (8-18) required for oil-in-water emulsion systems. The strong mechanical shear force provided by high-shear emulsification (9000 r / min) breaks the oil phase into tiny droplets with a diameter of approximately 1-10 μm, and the emulsifier rapidly adsorbs onto the newly formed interface to form a protective film. Maintaining the pH of the emulsion within the acidic range of 5.0 to 6.0 prepares for the next step of acid precipitation film formation of the wall material.

[0034] Controlled-speed mixing of the wall material solution: Maintain the temperature of the water-oil composite emulsion at 40℃. Under medium-speed stirring at 200~300r / min, slowly add the wall material aqueous solution obtained in S2 to the emulsion at a uniform rate using a peristaltic pump. The addition time should be controlled within 30 minutes (selectable within the range of 25~35 minutes). The volume ratio of the wall material aqueous solution to the water-oil composite emulsion is 1:4 (this ratio can be selected within the range of 1:3~1:5). During the addition process, when the wall material aqueous solution encounters the acidic emulsion, hydroxypropyl methylcellulose phthalate precipitates uniformly in the form of tiny solid particles due to the sudden drop in pH, dispersing throughout the system. After the addition is complete, continue stirring for 15 minutes and use a pH meter to check the mixed system. The pH should be maintained within the range of 4.8~5.5. The resulting mixture is ready for spraying.

[0035] When an alkaline wall material solution (pH 8.2~9.0) is added dropwise to an acidic emulsion (pH 5.0~6.0), the carboxylate anions on the hydroxypropyl methylcellulose phthalate molecular chains rapidly combine with hydrogen ions, protonating to form free carboxyl groups. The molecular chains contract and coil, causing a sharp drop in solubility, resulting in uniform precipitation of nano- to micron-sized particles. Slow addition (25~35 minutes) is crucial to ensuring uniform particle dispersion. If the addition is too rapid, excessively strong local alkalinity can lead to large precipitates, affecting the uniformity of subsequent thermal fusion and the continuity of the shell. A wall material solution to emulsion volume ratio of 1:3~1:5 is recommended because too little wall material solution is insufficient to completely cover all oil phase droplets, while too much increases the drying burden and may form independent wall material fragments. The pH of the mixed system is 4.8~5.5, which is a safe window to ensure that the sodium alginate molecular chains remain extended. The critical value for sodium alginate acid coagulation is about pH 4.5. Below this value, sodium alginate will coagulate and precipitate, losing its function of interpenetrating and entangled with the molecular chains of hydroxypropyl methylcellulose phthalate.

[0036] S4. Low-temperature spray drying in-situ embedding The mixture obtained in S3 is transported to a co-current spray dryer via a peristaltic pump. The drying tower is made of stainless steel and equipped with a two-fluid nozzle or a centrifugal atomizer. The inlet air temperature is set to 115℃ (range 110~125℃), the outlet air temperature to 65℃ (range 60~70℃), the atomization pressure to 0.22MPa (range 0.20~0.25MPa), and the feed rate to 20mL / min (range 15~25mL / min). The mixture is atomized into fine droplets through the nozzles and comes into contact with the hot air in a co-current flow.

[0037] Two parallel physical processes occur in the droplets within the drying tower: The wall material microparticles undergo thermal fusion to form a film: The glass transition temperature of hydroxypropyl methylcellulose phthalate is approximately 45-55℃, while the outlet air temperature is 65℃, which is higher than this value. Below the glass transition temperature, the polymer is in a glassy state, and the molecular chain segments are "frozen," making the material hard and brittle; above this temperature, it enters a rubbery state, and the molecular chain segments gain mobility. The hydroxypropyl methylcellulose phthalate / sodium alginate microparticles precipitated in S3 soften under heat at 65℃, and spread and fuse together on the surface of the oil phase droplets under the drive of capillary force and surface tension, forming a continuous and dense shell. The sodium alginate molecular chains and the hydroxypropyl methylcellulose phthalate molecular chains form a physically interpenetrating network structure during fusion. The pure hydroxypropyl methylcellulose phthalate shell is brittle and easily breaks during processing such as feed mixing and extrusion. The introduction of sodium alginate improves the flexibility and impact resistance of the shell through physical blending.

[0038] Water-soluble extracts solidify to form a matrix: Portulaca polysaccharides, Poria cocos polysaccharides, and roasted malt oligosaccharides in the aqueous phase solidify and precipitate after water evaporation, forming a continuous solid matrix encapsulating the microcapsules. The microcapsules are naturally embedded within the matrix during solidification. The entire film formation and matrix solidification process is completed within seconds to tens of seconds of droplet flight, achieving a one-step continuous operation of wall material dissolution, precipitation, film formation, and matrix solidification.

[0039] The principle of co-current spray drying (where the material and hot air flow in the same direction) is as follows: when the droplets with the highest moisture content come into contact with the hottest air, the evaporation rate is fastest. The droplet temperature is maintained at the wet-bulb temperature (usually below 60°C) due to the heat absorbed by moisture evaporation. As the moisture evaporates and the droplets dry, the particle temperature gradually rises to the outlet air temperature. This temperature change process is extremely beneficial for protecting heat-sensitive active ingredients, avoiding localized overheating caused by direct contact between dry particles and high-temperature hot air in counter-current drying. The dried powder is then carried by the airflow into a cyclone separator for collection.

[0040] S5. Post-processing and finished product preparation The dried microcapsule powder obtained in step S4 was added together with 4 parts of silica into a three-dimensional motion mixer. The speed was set to 20 r / min, and the mixture was mixed for 20 minutes (the mixing time can be selected within the range of 15-25 minutes, and a V-type mixer can also be used). During the mixing process, the silica uniformly adhered to the surface of the microcapsule powder particles, playing a role in preventing agglomeration and improving flowability. After mixing, the material was first passed through an 80-mesh sieve to remove coarse agglomerates. The material that passed through the sieve was then passed through a 160-mesh sieve, and the material that passed through the 160-mesh sieve was collected to obtain a finished powder of 80-160 mesh.

[0041] Silica (gas phase method) has an extremely high specific surface area (200~400m² / g) and abundant surface silanol groups. It adheres to the surface of powder particles through physical adsorption, forming a micro-isolation layer and preventing particle adhesion and agglomeration through steric hindrance. An 80-mesh sieve removes a few large particles and agglomerates, and a 160-mesh sieve removes excessively fine powder. Excessively fine powder with a particle size below 96μm has an excessively large specific surface area, is prone to moisture absorption and agglomeration, has poor flowability, and easily generates dust during feed mixing; particles with a particle size exceeding 180μm have poor mixing uniformity in feed, and their small specific surface area results in a slow intestinal dissolution rate. Controlling the particle size within the range of 80~160 mesh balances flowability, mixing uniformity, and intestinal dissolution rate. The angle of repose is typically 30°~35°, which is within the range of good flowability and suitable for use in industrial automated batching and mixing equipment. After passing inspection, it is sealed in aluminum foil bags or composite plastic bags and stored in a cool, dry place.

[0042] Take 1.0 g of each of the finished powders from Example 1 and place them in 100 mL of simulated gastric fluid (pH 2.5 hydrochloric acid-potassium chloride buffer, containing 0.1% pepsin), simulated duodenal fluid (pH 5.5 phosphate buffer), and simulated jejunal and ileal fluid (pH 6.8 phosphate buffer). Shake at 37°C and 100 r / min. Take samples at 0.5, 1, 2, 3, and 4 hours respectively. Use Pulsatilla saponin B4 and berberine hydrochloride as indicator components and determine the release amount by high performance liquid chromatography.

[0043] In simulated gastric fluid at pH 2.5, the cumulative release rate was approximately 2% at 0.5 hours, 3.5% at 1 hour, 5% at 2 hours, 8% at 3 hours, and 10% at 4 hours, showing an extremely low overall release rate and significant protective effect of the wall material. In simulated duodenal fluid at pH 5.5, the release rate was approximately 8% at 0.5 hours, 19% at 1 hour, 35% at 2 hours, 52% at 3 hours, and 69% at 4 hours, exhibiting a gradual swelling-slow release characteristic. In simulated jejunal and ileal fluid at pH 6.8, the release rate was approximately 16% at 0.5 hours, 42% at 1 hour, 79% at 2 hours, 93% at 3 hours, and 97% at 4 hours, showing rapid and complete release. These results perfectly match the release requirements of different segments of the piglet digestive tract corresponding to different pH levels: almost no release in the gastric acid environment, a small amount of pre-release in the duodenum, and a concentrated and large release in the jejunum and ileum, where diarrhea is common.

[0044] Comparative Example 1 Prepared according to the formulation and process of Example 1, but without sodium alginate in the wall material, only 10 parts of hydroxypropyl methylcellulose phthalate were used. 1.0 g of each of the obtained finished powders were placed in 100 mL of simulated gastric fluid (pH 2.5 hydrochloric acid-potassium chloride buffer, containing 0.1% pepsin), simulated duodenal fluid (pH 5.5 phosphate buffer), and simulated jejunal and ileal fluid (pH 6.8 phosphate buffer), respectively. The mixture was kept at 37°C and 100 r / min with constant temperature shaking. Samples were taken at 0.5, 1, 2, 3, and 4 hours. The release amount was determined by high performance liquid chromatography using Pulsatilla saponin B4 and berberine hydrochloride as indicator components.

[0045] In a simulated gastric fluid environment at pH 2.5, the cumulative release rate of Comparative Example 2 was approximately 8% after 0.5 hours, approximately 15% after 1 hour, approximately 22% after 2 hours, and approximately 35% after 4 hours, which was higher than the release rate of Example 1 under the same conditions (only about 10% after 4 hours). This indicates that the pure hydroxypropyl methylcellulose phthalate shell without sodium alginate is not dense enough in the acidic gastric environment, and has microcracks or pores, leading to premature leakage of the core material.

[0046] In a simulated empty ileum environment at pH 6.8, the 2-hour release rate of Comparative Example 1 was approximately 88%, which was faster than that of Example 1 (approximately 79%) but the difference was not significant, indicating that both could respond to rupture under intestinal pH conditions.

[0047] The above descriptions are merely embodiments of the present invention, and common knowledge such as specific technical solutions and / or characteristics are not described in detail here. It should be noted that those skilled in the art can make various modifications and improvements without departing from the technical solutions of the present invention, and these should also be considered within the scope of protection of the present invention. These modifications and improvements will not affect the effectiveness of the implementation of the present invention or the practicality of the patent. The scope of protection claimed in this application should be determined by the content of its claims, and the specific embodiments described in the specification can be used to interpret the content of the claims.

Claims

1. A plant extract compound composition for preventing and treating diarrhea in piglets, characterized in that, The raw materials contain the following parts by weight: 22-28 parts of water-soluble purslane extract, 11-17 parts of poria cocos polysaccharide extract, 13-19 parts of roasted malt oligosaccharide extract, 16-22 parts of fat-soluble extract of Pulsatilla chinensis, 9-14 parts of fat-soluble extract of Coptis chinensis, 11-17 parts of Sanguisorba officinalis flavonoid extract, 6-10 parts of modified soybean lecithin, 1-3 parts of polyglycerol fatty acid ester with an HLB value of 9-11, 8-12 parts of hydroxypropyl methylcellulose phthalate, 4-6 parts of sodium alginate, 0.3-0.5 parts of sodium citrate, and 3-6 parts of silicon dioxide; The compound composition is a composite powder with a particle size of 80-160 mesh; the composite powder contains a solid continuous matrix formed by solidifying a water-soluble extract of purslane, a polysaccharide extract of Poria cocos, and an oligosaccharide extract of roasted malt, as well as microcapsules uniformly embedded in the solid continuous matrix. The microcapsules use fat-soluble extracts of Pulsatilla chinensis, Coptis chinensis, and Sanguisorba officinalis as core materials, and a complex of hydroxypropyl methylcellulose phthalate and sodium alginate as wall material. The wall material maintains a dense and intact structure in an environment with a pH less than 5.0, gradually swells in an environment with a pH of 5.0 to 6.0, and degrades and ruptures in an environment with a pH not lower than 6.

0.

2. The plant extract compound composition for preventing and treating diarrhea in piglets as described in claim 1, characterized in that, The weight ratio of hydroxypropyl methylcellulose phthalate to sodium alginate is 8:4 to 12:6, and the composite wall material formed by the two is a continuous and dense shell layer formed by an alkali dissolution-acid precipitation-thermal fusion process.

3. The use of the plant extract compound composition for preventing and treating piglet diarrhea as described in claim 1 or 2 in the preparation of feed additives for preventing and improving piglet diarrhea.

4. A method for preparing a plant extract compound composition for preventing and treating piglet diarrhea as described in any one of claims 1-2, characterized in that, Includes the following steps: S1. Purslane, Poria cocos, and roasted malt were extracted at low temperature with ultrasonic assistance using water as a solvent and concentrated to a relative density of 1.18~1.22 at 55℃ to obtain an aqueous concentrate. Pulsatilla chinensis, Coptis chinensis, and Sanguisorba officinalis were extracted at low temperature with ethanol as a solvent and refluxed. After recovering the ethanol, the extract was vacuum de-alcoholized until the ethanol residue was ≤0.5% to obtain an oil extract. The extract was diluted with 10%~15% anhydrous ethanol by weight to obtain a liquid oil phase. S2. Preparation of wall material stock solution: Adjust the pH of pure water to 8.2~9.0 with sodium carbonate, heat to 40~45℃, add hydroxypropyl methylcellulose phthalate and sodium alginate and stir to dissolve, then add sodium citrate and stir to dissolve to obtain wall material aqueous solution; S3. Add modified soybean lecithin and polyglycerol fatty acid ester to the aqueous phase concentrate, stir to dissolve, and then slowly add liquid oil phase. Emulsify at high shear rate of 8000~10000 r / min for 8~12 min to obtain a water-oil composite emulsion with pH 5.0~6.

0. Add the wall material aqueous solution slowly to the emulsion over 25~35 min while stirring at 40℃. After mixing, the pH of the system is 4.8~5.

5. Continue stirring to obtain the mixture to be sprayed dry. S4. The mixture to be sprayed is subjected to co-flow low-temperature spray drying, with an inlet air temperature of 110~125℃, an outlet air temperature of 60~70℃, and an atomization pressure of 0.20~0.25MPa. The outlet air temperature is higher than the glass transition temperature of hydroxypropyl methylcellulose phthalate, which causes the precipitated wall material particles to soften and fuse upon heating and spread on the surface of the oil phase droplets to form a continuous and dense shell layer; the water-soluble extract is simultaneously solidified to form a solid continuous matrix, in which microcapsules are embedded. S5. Mix the dried powder with silica, pass it through an 80-mesh sieve, then through a 160-mesh sieve, and take the portion retained between the two sieves to obtain a finished product with a particle size of 80-160 mesh.

5. The method for preparing a plant extract compound composition for preventing and treating diarrhea in piglets as described in claim 4, characterized in that: In step S1, the ultrasonic-assisted low-temperature extraction is performed at a temperature of 45-55°C, with a material-to-liquid ratio of 1:9-1:11, and is repeated twice for 2 hours each time; the low-temperature reflux extraction is performed at a temperature of 40-50°C, with a material-to-liquid ratio of 1:7-1:9, and is repeated twice for 1.8 hours each time; the vacuum de-alcoholization is performed at a temperature of 60°C, a vacuum degree of -0.08 MPa, and a de-alcoholization time of 30 min.

6. The method for preparing a plant extract compound composition for preventing and treating diarrhea in piglets as described in claim 4, characterized in that: In step S3, the wall material aqueous solution is added for 25-35 minutes, the emulsion temperature is maintained at 40°C during the addition process, and stirring is continued for 15 minutes after the addition is completed.

7. The method for preparing a plant extract compound composition for preventing and treating diarrhea in piglets as described in claim 4, characterized in that: In step S4, the feed rate of the co-flow low-temperature spray dryer is 15~25mL / min.

8. The method for preparing a plant extract compound composition for preventing and treating diarrhea in piglets as described in claim 4, characterized in that: In step S4, the low-temperature spray drying is carried out using a parallel-flow spray drying device.

9. The method for preparing a plant extract compound composition for preventing and treating diarrhea in piglets as described in claim 4, characterized in that: In step S5, the mixing is carried out using a three-dimensional motion mixer or a V-type mixer, and the mixing time is 15~25 minutes.

10. The method for preparing a plant extract compound composition for preventing and treating diarrhea in piglets as described in claim 4, characterized in that: In step S2, the weight ratio of the total amount of pure water to hydroxypropyl methylcellulose phthalate and sodium alginate is 3:1 to 5:1; in step S3, the volume ratio of the wall material aqueous solution to the water-oil composite emulsion is 1:3 to 1:5.

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