A lactation enhancing functional feed for lactating sows containing a high efficiency plant lactogenic factor

Abstract

The present application relates to the technical field of feed additive, and discloses a lactation-promoting functional feed for lactating sows containing high-efficiency plant lactogenic factors, which is made of the following raw materials: sodium-based montmorillonite, fenugreek extract, motherwort extract, ion intensity regulator, lysophosphatidylcholine, tributyl citrate and high-purity silicon dioxide, and is prepared through the following steps: mixing and drying sodium-based montmorillonite with the ion intensity regulator to prepare a regulation carrier; adding fenugreek and motherwort extract and mixing them by strong shearing to form an active core; atomizing and spraying a mixture of lysophosphatidylcholine and tributyl citrate on the surface of the core to form a functional layer; and finally adding high-purity silicon dioxide and mixing uniformly to obtain the feed. Through the construction of the structure with ion-pretreated montmorillonite as the core and the functional layer as the shell, the present application realizes the protection, sustained release and efficient absorption of the active ingredients, and improves the bioavailability.

Description

Technical Field

[0001] This invention relates to the field of feed additive technology, specifically to a functional feed for lactating sows containing highly efficient plant lactation-promoting factors to enhance lactation. Background Technology

[0002] In modern sow farming, improving the lactation performance of lactating sows is a key link in ensuring the healthy growth of piglets and improving production efficiency. To this end, the industry makes extensive use of natural plant extracts, such as fenugreek extract and motherwort extract. These plant extracts have attracted attention because of their natural origin and diverse composition.

[0003] However, when these plant extracts are applied directly to feed production, their effectiveness is often limited by a variety of factors. First, many of the active ingredients in the extracts are sensitive to the environment. Under the high temperature, high humidity and mechanical shear force that feed processing usually involves, their chemical structure will be damaged, leading to reduced or even lost activity.

[0004] In addition, many plant extracts have a distinctive bitter or pungent odor, and their direct addition can affect the palatability of feed. This can lead to a decrease in feed intake in lactating sows that are sensitive to odors, which not only fails to achieve the expected lactation-promoting effect, but also has a negative impact on their overall nutritional intake.

[0005] More importantly, even if the active ingredients are preserved during processing and consumption, their bioavailability in the animal's digestive tract is still challenged. After the active substances are added directly into the digestive system, they are often released rapidly and uncontrolled, and are then quickly metabolized or excreted by the body. It is difficult to maintain an effective concentration at the target site for a sufficiently long time, thus limiting the full realization of their physiological functions. Summary of the Invention

[0006] To address the shortcomings of existing technologies, this invention provides a functional feed for lactating sows containing highly efficient plant lactation-promoting factors, which solves the problems of poor stability of active ingredients, poor palatability, and low bioavailability that exist when plant lactation-promoting extracts are directly added in existing technologies.

[0007] To achieve the above objectives, the present invention provides the following technical solution: In a first aspect, the present invention provides a functional feed for lactating sows containing highly effective plant-based lactation-promoting factors to enhance lactation, the feed being made from raw materials comprising the following parts by weight: Sodium montmorillonite: 30-50 parts; Fenugreek extract: 10-20 parts; Motherwort extract: 5-10 parts; Ionic strength modifier: 2-8 parts; Lysophosphatidylcholine: 5-15 parts; Tributyl citrate: 1-5 parts; High-purity silica: 0.5-2 parts; The fenugreek extract and motherwort extract are loaded onto sodium montmorillonite pretreated with the ionic strength modifier to form an active core; the lysophosphatidylcholine and the tributyl citrate coat the active core to form a functional layer.

[0008] This technical solution constructs a functional particle with a specific core-shell structure. The technical principle of the preparation process is as follows: Pretreatment of sodium montmorillonite is crucial because, as a silicate mineral with a layered structure and cation exchange capacity, the ionic environment on the surface and between the layers of sodium montmorillonite directly affects its adsorption and loading capacity for other molecules. Introducing ionic strength modifiers can pre-regulate the ion exchange sites on the surface of montmorillonite, thus establishing physicochemical conditions for the orderly loading of active molecules in subsequent plant extracts.

[0009] Fenugreek extract and Leonurus japonicus extract were loaded onto pretreated sodium montmorillonite to form a physically stable active core. This structure immobilizes the plant active ingredients within or on the surface of the layered structure of montmorillonite. The physical barrier effect of montmorillonite isolates the active ingredients from the influence of external environmental factors such as light, heat, humidity, and oxygen, thereby improving their stability during storage and feed processing.

[0010] The active core is coated with a functional layer composed of lysophosphatidylcholine and tributyl citrate. Lysophosphatidylcholine is a phospholipid surfactant that can improve particle dispersibility in the aqueous environment of the animal digestive tract and promote the absorption of phytolaccosin released by the active core by intestinal epithelial cells. Tributyl citrate, as a film-forming aid, works synergistically with lysophosphatidylcholine to ensure the uniformity, integrity and flexibility of the functional layer.

[0011] This invention constructs functional particles with this core-shell structure, which synergistically achieves physical protection of plant active ingredients and enhanced targeted delivery and absorption in the digestive tract, thereby improving bioavailability and ultimately lactation enhancement in lactating sows.

[0012] Preferably, the ionic strength regulator is prepared by mixing potassium chloride and sodium chloride, wherein the molar ratio of potassium chloride to sodium chloride is 1.5-2.5:1. Potassium chloride and sodium chloride, as strong electrolytes, provide sufficient potassium and sodium ions to regulate the ionic environment on the surface of montmorillonite, and their specific molar ratio can achieve optimized site preset effects.

[0013] Preferably, the sodium-based montmorillonite has a cation exchange capacity of 90-100 mmol / 100g and a montmorillonite content of not less than 95%. The high cation exchange capacity and montmorillonite content ensure that the carrier has sufficient active sites and loading capacity, which is the basis for the efficient carrying of plant extracts.

[0014] Preferably, the lysophosphatidylcholine contains 1-acyl-lysophosphatidylcholine at a content of not less than 90% w / w. A high content of 1-acyl-lysophosphatidylcholine has strong surface activity and the ability to promote absorption.

[0015] This invention also provides a method for preparing a functional feed for lactating sows containing highly efficient plant-based lactation-promoting factors, comprising the following steps: S1. Mix sodium-based montmorillonite with an ionic strength modifier and dry. S2. The dried materials are dry-mixed to prepare a control carrier with preset ion exchange sites; S3. Fenugreek extract and Leonurus japonicus extract were added to the regulatory carrier and subjected to strong shear mixing to prepare an active core loaded complex. S4. Lysophosphatidylcholine and tributyl citrate are mixed to form a homogeneous liquid phase, and then sprayed onto the active core loading complex to prepare functional layer modified particles. S5. High-purity silica is added to the functional layer modified granules and mixed to obtain feed.

[0016] Preferably, in S1, the step of mixing and drying sodium montmorillonite with the ionic strength modifier includes: placing sodium montmorillonite and the ionic strength modifier in a forced-air drying oven and drying at a temperature of 85-105°C for 2-4 hours.

[0017] Preferably, in step S2, the step of dry mixing the dried material to prepare a controlled carrier with preset ion exchange sites includes: putting the dried sodium montmorillonite and ion strength modifier into a high-speed shear mixer with a jacket, and dry mixing at an ambient temperature of 20-30°C and a rotation speed of 300-500 rpm for 20-30 minutes to obtain a controlled carrier with preset ion exchange sites.

[0018] Preferably, in step S3, the step of adding fenugreek extract and motherwort extract to the regulating carrier for strong shear mixing to prepare the active core loaded complex includes: adding fenugreek extract and motherwort extract to the regulating carrier, increasing the speed of the mixer to 1500-2000 rpm for strong shear mixing for 15-20 minutes, and during the mixing, circulating cooling water at 10-20℃ into the equipment jacket to ensure that the maximum temperature of the material does not exceed 60℃, thereby obtaining the active core loaded complex.

[0019] Preferably, in step S4, the step of mixing lysophosphatidylcholine and tributyl citrate to form a homogeneous liquid phase and spraying it onto the active core loading complex to prepare functionally modified particles includes: mixing lysophosphatidylcholine and tributyl citrate in a mixing tank at 40-50°C to form a homogeneous liquid phase; transferring the active core loading complex to a plow-type mixer, starting the spindle to turn the material at 40-60 rpm, starting the high-speed blade to shear at 2500-3000 rpm, and spraying the homogeneous liquid phase into the powder through a pressure atomizing nozzle at a pressure of 2.0-3.5 bar. The spraying process lasts for 10-15 minutes, and after completion, mixing continues for 5-10 minutes to obtain functionally modified particles.

[0020] Preferably, in step S5, the step of adding high-purity silica to the functional layer modified particles and mixing to obtain feed includes: adding high-purity silica to the functional layer modified particles, reducing the speed of the mixer to 30-50 rpm, stopping the high-speed flying knife, continuing to mix for 5-10 minutes, and discharging and sieving to obtain feed.

[0021] This invention provides a functional feed for lactating sows containing highly effective plant-based lactation-promoting factors to enhance lactation. It has the following beneficial effects: 1. This invention pretreats sodium montmorillonite with an ionic strength modifier, in which potassium ions pre-occupy some cation exchange sites, altering the exchange kinetics of the active ingredient in the intestinal environment. This structure-activity relationship enables the loaded plant extract to change from burst release to sustained and gradual release, prolonging the duration of action of the active ingredient in the animal and improving its utilization efficiency.

[0022] 2. The present invention coats the active core with a functional layer composed of lysophosphatidylcholine and tributyl citrate. Lysophosphatidylcholine, as a highly efficient surfactant, can improve the dispersibility of particles in the intestine and promote the absorption of active ingredients by intestinal epithelial cells, thereby enhancing the bioavailability of plant lactation factors and producing more significant physiological effects when added in equal amounts.

[0023] 3. This invention forms an active core by loading fenugreek and motherwort extracts onto sodium montmorillonite, which protects the active ingredients and prevents them from degrading and becoming ineffective due to high temperature and high humidity during feed processing and storage. At the same time, the external functional layer also masks the unpleasant flavor of the plant extracts, improves the palatability of the feed, and ensures stable feed intake for sows. Attached Figure Description

[0024] Figure 1 The results of the stepwise enzymatic hydrolysis-pH response mechanism verification test of the sample in Example 2 of the present invention are shown in the figure. (a) is the change curve of pH value of suspension in experimental group and control group over time; (b) is the change curve of cumulative dissolution rate of total saponins of fenugreek in the two groups of samples over time. Figure 2 This is a comparison of the in vitro cumulative release curves of leonurine in simulated intestinal fluid in Example 2 and Comparative Example 4 of the present invention. Figure 3 This is a comparative bar chart showing the effect of LPC on the apparent solubility of total saponins from fenugreek and leonurine in Test Example 3 of the present invention. Figure 4 This is a comparison of the apparent permeability coefficients of the active ingredients in a human colon adenocarcinoma cell monolayer model in Example 2 of the present invention, compared with those in each comparative example and control group; Figure 5 This is a graph showing the Karl Fischer index change of the powders in Example 2 and Comparative Example 6 of the present invention under accelerated storage conditions. Detailed Implementation

[0025] The technical solutions in the embodiments of the present invention will be clearly and completely described below 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.

[0026] 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.

[0027] Fenugreek extract is a pale yellow powder obtained by ethanol extraction, purification, and drying of fenugreek seeds. The total saponin content (calculated as diosgenin) is 50-55% (w / w) as determined by high performance liquid chromatography. The loss on drying is not more than 5.0% as determined by constant weight method at 105℃.

[0028] Leonurus japonicus extract is a brownish-brown dry powder obtained by extraction and purification of the whole Leonurus japonicus plant. The content of leonurine was determined to be 1.5-2.0% (w / w) by high performance liquid chromatography.

[0029] Sodium-based montmorillonite is a naturally purified layered aluminosilicate mineral. Its cation exchange capacity is 90-100 mmol / 100g, as determined by the ammonium acetate method. The montmorillonite content is not less than 95%, as determined by X-ray diffraction analysis. The proportion of particles passing through a 200-mesh sieve is not less than 90%, as determined by laser particle size analyzer.

[0030] Lysophosphatidylcholine is a pale yellow waxy solid obtained by enzymatic hydrolysis of soybean phospholipids with immobilized phospholipase A2 and purification. The content of 1-acyl-lysophosphatidylcholine is not less than 90% (w / w) as determined by high performance liquid chromatography-evaporative light scattering detector, and the acid value is not more than 30 mg KOH / g.

[0031] Tributyl citrate, chemical name: tri-n-butyl citrate, CAS No.: 77-94-1, is a food-grade product with a purity of not less than 99.0%.

[0032] High-purity silica, fumed silica, with a specific surface area of ​​180-220 m². 2 / g.

[0033] In this invention, the units of measurement for all materials and solvents are uniformly referred to as parts by weight.

[0034] Preparation Examples 1-3: Preparation Example 1: This preparation example provides a method for preparing an ionic strength modifier, including the following steps: Weigh out 111.83 parts of potassium chloride and 58.44 parts of sodium chloride. Place the two powders together in a ball mill. Set the ball mill speed to 400 rpm and run it for 2 hours at an ambient temperature of 20℃ to 25℃ to ensure thorough mixing and pulverization. After ball milling, remove the material and sieve it through a 200-mesh standard sieve. Collect the sieve-underfill material to obtain the sealed ionic strength regulator, hereinafter referred to as ionic strength regulator A.

[0035] Preparation Example 2: This preparation example provides a method for preparing an ionic strength modifier, including the following steps: Weigh out 149.10 parts of potassium chloride and 58.44 parts of sodium chloride. Place the two powders together in a ball mill. Set the ball mill speed to 400 rpm and run it for 2 hours at an ambient temperature of 20℃ to 25℃ to ensure thorough mixing and pulverization. After ball milling, remove the material and sieve it through a 200-mesh standard sieve. Collect the sieve-underfill material to obtain the sealed ionic strength regulator, hereinafter referred to as ionic strength regulator B.

[0036] Preparation Example 3: This preparation example provides a method for preparing an ionic strength modifier, including the following steps: Weigh out 186.38 parts of potassium chloride and 58.44 parts of sodium chloride. Place the two powders together in a ball mill. Set the ball mill speed to 400 rpm and run it for 2 hours at an ambient temperature of 20℃ to 25℃ to ensure thorough mixing and pulverization. After ball milling, remove the material and sieve it through a 200-mesh standard sieve. Collect the sieve-underfill material to obtain the sealed ionic strength regulator, hereinafter referred to as ionic strength regulator C.

[0037] Examples 1-5: Example 1

[0038] This embodiment provides a method for preparing a functional feed for lactating sows containing highly efficient plant-based lactation-promoting factors, comprising the following steps: S1. Place 50 parts of sodium montmorillonite and 8 parts of ionic strength modifier C in a forced-air drying oven and dry at 105°C for 2 hours. S2. The dried sodium montmorillonite and ion strength modifier from step S1 are put into a high-speed shear mixer with a jacket. The mixture is dry-mixed at 500 rpm for 30 minutes at an ambient temperature of 30°C to obtain a modulated carrier with preset ion exchange sites. S3. Add 20 parts of fenugreek extract and 10 parts of motherwort extract to the aforementioned regulating carrier, increase the speed of the mixer to 2000 rpm for strong shear mixing for 20 minutes, and during the mixing, 10°C cooling circulating water is introduced into the equipment jacket to ensure that the maximum temperature of the material does not exceed 60°C, thereby obtaining the active core loaded complex. S4. Mix 15 parts of lysophosphatidylcholine and 5 parts of tributyl citrate in a mixing tank at 50°C to form a homogeneous liquid phase. Transfer the active core loaded complex obtained in step S3 to a plow-type mixer. Start the spindle to turn the material at 60 rpm and start the high-speed flying knife to shear at 3000 rpm. Spray the above homogeneous liquid phase into the powder through a pressure atomizing nozzle at a pressure of 3.5 bar. The spraying process lasts for 15 minutes. After the process is completed, continue mixing for 10 minutes to obtain functional layer modified particles. S5. Add 2 parts of high-purity silica to the aforementioned functional layer modified granules, reduce the mixer speed to 50 rpm, stop the high-speed flying knife, continue mixing for 10 minutes, and discharge and sieve to obtain feed. Example 2

[0039] This embodiment provides a method for preparing a functional feed for lactating sows containing highly efficient plant-based lactation-promoting factors, comprising the following steps: S1. Place 40 parts of sodium montmorillonite and 5 parts of ionic strength modifier B in a forced-air drying oven and dry at 95°C for 3 hours. S2. The dried sodium montmorillonite and ion strength modifier from step S1 are put into a high-speed shear mixer with a jacket. The mixture is dry-mixed for 25 minutes at 400 rpm under an ambient temperature of 20°C to obtain a modulated carrier with preset ion exchange sites. S3. Add 15 parts of fenugreek extract and 7.5 parts of motherwort extract to the aforementioned regulating carrier, increase the speed of the mixer to 1800 rpm for strong shear mixing for 18 minutes, and circulate 15°C cooling water into the equipment jacket during mixing to ensure that the maximum temperature of the material does not exceed 60°C, thereby obtaining the active core loaded complex. S4. Mix 10 parts of lysophosphatidylcholine and 3 parts of tributyl citrate in a mixing tank at 45°C to form a homogeneous liquid phase; transfer the active core loaded complex obtained in step S3 to a plow-type mixer, start the spindle to turn the material at 50 rpm, start the high-speed flying knife to shear at 2800 rpm, and spray the above homogeneous liquid phase into the powder through a pressure atomizing nozzle at a pressure of 2.8 bar. The spraying process lasts for 12 minutes, and after the process is completed, continue mixing for 8 minutes to obtain functional layer modified particles. S5. Add 1.5 parts of high-purity silica to the aforementioned functional layer modified granules, reduce the mixer speed to 40 rpm, stop the high-speed flying knife, continue mixing for 8 minutes, and discharge and sieve to obtain feed. Example 3

[0040] This embodiment provides a method for preparing a functional feed for lactating sows containing highly efficient plant-based lactation-promoting factors, comprising the following steps: S1. Place 30 parts of sodium montmorillonite and 2 parts of ionic strength modifier A in a forced-air drying oven and dry at 85°C for 4 hours. S2. The dried sodium montmorillonite and ion strength modifier from step S1 are put into a high-speed shear mixer with a jacket. The mixture is dry-mixed for 20 minutes at 300 rpm under an ambient temperature of 25°C to obtain a modulated carrier with preset ion exchange sites. S3. Add 10 parts of fenugreek extract and 5 parts of motherwort extract to the aforementioned regulating carrier, increase the speed of the mixer to 1500 rpm for strong shear mixing for 15 minutes, and during the mixing, circulate 20°C cooling water into the equipment jacket to ensure that the maximum temperature of the material does not exceed 60°C, thereby obtaining the active core loaded complex. S4. Mix 5 parts of lysophosphatidylcholine and 1 part of tributyl citrate in a mixing tank at 40°C to form a homogeneous liquid phase. Transfer the active core loaded complex obtained in step S3 to a plow-type mixer. Start the spindle to turn the material at 40 rpm and start the high-speed flying knife to shear at 2500 rpm. Spray the above homogeneous liquid phase into the powder through a pressure atomizing nozzle at a pressure of 2.0 bar. The spraying process lasts for 10 minutes. After the process is completed, continue mixing for 5 minutes to obtain functional layer modified particles. S5. Add 0.5 parts of high-purity silica to the aforementioned functional layer modified granules, reduce the mixer speed to 30 rpm, stop the high-speed flying knife, continue mixing for 5 minutes, and discharge and sieve to obtain feed. Example 4

[0041] This embodiment provides a method for preparing a functional feed for lactating sows containing highly efficient plant-based lactation-promoting factors, comprising the following steps: S1. Place 45 parts of sodium montmorillonite and 3 parts of ionic strength modifier B in a forced-air drying oven and dry at 95°C for 3 hours. S2. The dried sodium montmorillonite and ion strength modifier from step S1 are put into a high-speed shear mixer with a jacket. The mixture is dry-mixed for 22 minutes at 450 rpm under an ambient temperature of 25°C to obtain a modulated carrier with preset ion exchange sites. S3. Add 18 parts of fenugreek extract and 6 parts of motherwort extract to the aforementioned regulating carrier, increase the speed of the mixer to 1900 rpm for strong shear mixing for 16 minutes, and circulate 15°C cooling water into the equipment jacket during mixing to ensure that the maximum temperature of the material does not exceed 60°C, thereby obtaining the active core loaded complex. S4. Mix 12 parts of lysophosphatidylcholine and 2 parts of tributyl citrate in a mixing tank at 45°C to form a homogeneous liquid phase. Transfer the active core loaded complex obtained in step S3 to a plow-type mixer. Start the spindle to turn the material at 55 rpm and start the high-speed flying knife to shear at 2900 rpm. Spray the above homogeneous liquid phase into the powder through a pressure atomizing nozzle at a pressure of 3.0 bar. The spraying process lasts for 13 minutes. After the process is completed, continue mixing for 7 minutes to obtain functional layer modified particles. S5. Add 1 part of high-purity silica to the aforementioned functional layer modified granules, reduce the mixer speed to 45 rpm, stop the high-speed flying knife, continue mixing for 7 minutes, and discharge and sieve to obtain feed. Example 5

[0042] This embodiment provides a method for preparing a functional feed for lactating sows containing highly efficient plant-based lactation-promoting factors, comprising the following steps: S1. Place 35 parts of sodium montmorillonite and 6 parts of ionic strength modifier C in a forced-air drying oven and dry at 95°C for 3 hours. S2. The dried sodium montmorillonite and ion strength modifier from step S1 are put into a high-speed shear mixer with a jacket. The mixture is dry-mixed for 28 minutes at 350 rpm under an ambient temperature of 25°C to obtain a modulated carrier with preset ion exchange sites. S3. Add 12 parts of fenugreek extract and 9 parts of motherwort extract to the aforementioned regulating carrier, increase the speed of the mixer to 1600 rpm for strong shear mixing for 19 minutes, and circulate 15°C cooling water into the equipment jacket during mixing to ensure that the maximum temperature of the material does not exceed 60°C, thereby obtaining the active core loaded complex. S4. Mix 8 parts of lysophosphatidylcholine and 4 parts of tributyl citrate in a mixing tank at 45°C to form a homogeneous liquid phase. Transfer the active core loaded complex obtained in step S3 to a plow-type mixer. Start the spindle to turn the material at 45 rpm and start the high-speed flying knife to shear at 2600 rpm. Spray the above homogeneous liquid phase into the powder through a pressure atomizing nozzle at a pressure of 2.5 bar. The spraying process lasts for 14 minutes. After the process is completed, continue mixing for 9 minutes to obtain functional layer modified particles. S5. Add 1.8 parts of high-purity silica to the aforementioned functional layer modified granules, reduce the mixer speed to 35 rpm, stop the high-speed flying knife, continue mixing for 9 minutes, and discharge and sieve to obtain feed.

[0043] Comparative Examples 1-6: Comparative Example 1: Compared with Example 2, the difference is that sodium montmorillonite, ionic strength modifier, lysophosphatidylcholine and tributyl citrate are not used. Instead, 15 parts of fenugreek extract, 7.5 parts of Leonurus japonicus extract and 77.5 parts of high-purity silica are simply physically mixed to obtain a conventional mixture.

[0044] Comparative Example 2: Compared with Example 2, the difference is that no ionic strength modifier, lysophosphatidylcholine and tributyl citrate are used. The preparation method only includes steps S1 (drying sodium montmorillonite only) and S3 in Example 2. The resulting active core-loaded complex is directly mixed with high-purity silica.

[0045] Comparative Example 3: The difference compared to Example 2 is that tributyl citrate is not added to the formulation.

[0046] Comparative Example 4: Compared with Example 2, the difference is that no ionic strength modifier is added in step S2, that is, sodium-based montmorillonite without pre-set ion exchange sites is used directly as a carrier.

[0047] Comparative Example 5: The difference compared to Example 2 is that lysophosphatidylcholine is not added to the formulation.

[0048] Comparative Example 6: Compared with Example 2, the difference is that all the components of the formulation in Example 2 (fenugreek extract, motherwort extract, sodium montmorillonite, ionic strength modifier, lysophosphatidylcholine, tributyl citrate, and high-purity silica) were added to the mixer at one time for simple physical mixing.

[0049] Test Case 1-Test Case 5: Test Example 1: This test measures the enzymatic response of tributyl citrate coating to the release of the active ingredient by performing an in vitro dissolution experiment under conditions with and without lipase.

[0050] The in vitro release test was performed on the functional composition product prepared in Example 2. 2.0 g of the product of Example 2 was weighed and dispersed in 100 mL of simulated intestinal fluid (pH 6.8, without enzymes) preheated to 37 °C. The solution was placed in a constant temperature shaking water bath at 37 °C and 100 rpm. The resulting suspension was divided into two parts, namely Group A and Group B.

[0051] Add 1 mL of lipase solution to group A; add 1 mL of enzyme-free phosphate buffer to group B.

[0052] Both groups continued to oscillate at 37℃ and 100rpm, and the pH value of the suspension was measured and recorded using a micro pH electrode at time points of 0, 5, 15, 30, 60, and 120 min.

[0053] Meanwhile, 2 mL samples were taken at each time point, centrifuged at 10,000 rpm for 5 minutes, the supernatant was collected and filtered, and the concentration of total saponins in fenugreek was determined by high performance liquid chromatography to calculate the cumulative dissolution rate.

[0054] The test results are shown in Table 1.

[0055] Table 1: pH changes and total saponin dissolution rate of the product in Example 2 in simulated intestinal fluid under the action of lipase.

[0056]

[0057] From Table 1 and Figure 1 We can obtain: In group B without added lipase, the system pH was stable, and the cumulative dissolution rate after 120 minutes was only 14.2%. In group A with added lipase, the system pH first decreased and then rose, and the cumulative dissolution rate after 120 minutes reached 88.7%.

[0058] In group A, the decrease in pH value and the increase in the dissolution rate of total saponins from fenugreek occurred synchronously over time. This experimental result indicates that the presence of lipase leads to changes in the pH of the environment in which the composition is located and an increase in the dissolution rate of the active ingredients.

[0059] Test Example 2: This test determined the effect of the ion strength modifier on the release kinetics of leonurine by comparing samples with and without the ion strength modifier.

[0060] In vitro release tests were conducted on the products of Example 2 (using an ionic strength modifier) ​​and Comparative Example 4 (without using an ionic strength modifier). Equal amounts of the products of Example 2 and Comparative Example 4 containing leonurine were weighed and placed in conical flasks. 100 mL of simulated intestinal fluid (containing lipase and bile salts, pH 6.8) preheated to 37°C was added, and the conical flasks were placed in a constant temperature shaking water bath at 37°C and 100 rpm.

[0061] At time points of 0, 5, 10, 20, 30, 60, 120, and 240 min, 2 mL of suspension was taken from each conical flask. The suspension was centrifuged at 10,000 rpm for 5 minutes, and the supernatant was collected and filtered through a 0.22 μm filter membrane. The concentration of leonurine in the filtrate was determined by high performance liquid chromatography, and its cumulative release rate was calculated.

[0062] The test results are shown in Table 2.

[0063] Table 2: Cumulative release rate of leonurine in simulated intestinal fluid in Example 2 and Comparative Example 4.

[0064]

[0065] From Table 2 and Figure 2 We can obtain: The sample of Comparative Example 4 released almost completely within 30 minutes, exhibiting a burst release. The sample of Example 2 released more gradually, showing a continuous release. The difference between the preparation of Example 2 and Comparative Example 4 lies in whether or not an ionic strength modifier was added.

[0066] The potassium ions in this regulator undergo solid-phase ion exchange with montmorillonite, occupying some cation exchange sites. When this product enters the simulated intestinal fluid, the kinetic conditions for sodium ions in the intestinal fluid to replace the interlayer leonurine change.

[0067] Test Example 3: This test compares systems with and without added lysophosphatidylcholine to determine the desorption and solubilization effects of lysophosphatidylcholine on the active ingredient loaded on the carrier.

[0068] An intermediate free of lysophosphatidylcholine was prepared. This intermediate was the active core-loaded complex obtained after performing the formulation and process according to Example 2 up to step S3. Two equal parts of the above intermediate were accurately weighed and placed in two conical flasks, labeled as Group A and Group B, and 100 mL of simulated intestinal fluid (pH 6.8) was added.

[0069] Lysophosphatidylcholine was added to group A, and the amount added was consistent with the mass ratio of the intermediate in Example 2. An equal volume of blank buffer without lysophosphatidylcholine was added to group B.

[0070] Both conical flasks were placed in a constant temperature shaking water bath at 37℃ and 100 rpm for 12 hours. After shaking, samples were taken, centrifuged at 10000 rpm for 10 minutes, and the supernatant was collected and filtered through a 0.22 μm filter membrane. The concentrations of total fenugreek saponins and leonurine in the filtrate were determined by high performance liquid chromatography.

[0071] The test results are shown in Table 3.

[0072] Table 3: Effect of lysophosphatidylcholine on the apparent solubility of the active ingredient.

[0073]

[0074] From Table 3 and Figure 3 We can obtain: Compared with group B without lysophosphatidylcholine, the concentrations of the two active ingredients in the supernatant of group A with lysophosphatidylcholine were increased by approximately 4.5 times and 4.4 times, respectively. This result indicates that the addition of lysophosphatidylcholine alters the distribution balance of the active ingredients between the solid support and the liquid medium. Lysophosphatidylcholine molecules interact with the active ingredients on the surface of montmorillonite, promoting their desorption and increasing their apparent solubility in the aqueous phase by forming micellar structures.

[0075] Test Example 4: This test uses a human colon adenocarcinoma cell monolayer model to determine the effect of the composition of the present invention on the transmembrane transport efficiency of the active ingredient.

[0076] The experiment used samples from Example 2, Comparative Example 1, and Comparative Example 5, and set up a group of pure active ingredient solutions as a control group. The test solution was prepared by releasing the samples from Example 2, Comparative Example 1, and Comparative Example 5 in simulated intestinal fluid for 4 hours, centrifuging, taking the supernatant and filtering for sterilization.

[0077] The control group consisted of equal amounts of total saponins from fenugreek and leonurine dissolved directly in simulated intestinal fluid and filtered to remove bacteria. Human colon adenocarcinoma cells were then seeded onto Transwell culture plates and cultured for 21 days to form a cell monolayer.

[0078] By measuring transepithelial resistance values ​​greater than 400 Ω·cm 2 To confirm the integrity of the cell monolayer, replace the culture medium with Hanks balanced salt solution before the experiment, pre-incubate at 37°C for 30 minutes, discard the top buffer, add 1.5 mL of the corresponding test solution, and add 2.5 mL of blank Hanks balanced salt solution to the bottom.

[0079] After incubation at 37℃ and 50rpm for 2 hours, samples were taken from the bottom side. The concentrations of total saponins and leonurine in the bottom side samples were determined by high performance liquid chromatography, and their apparent permeability coefficients were calculated.

[0080] The test results are shown in Table 4.

[0081] Table 4: Apparent permeability coefficients of active ingredients in each group of samples.

[0082]

[0083] From Table 4 and Figure 4 We can obtain: The apparent permeability coefficients of the two active ingredients in the sample of Example 2 were higher than those of the pure active ingredient solution, the simple physical mixture of Comparative Example 1, and Comparative Example 5 without lysophosphatidylcholine. The only difference in formulation between Example 2 and Comparative Example 5 was the lysophosphatidylcholine, whose apparent permeability coefficients were approximately 4.4 times (total saponins of fenugreek) and 3.0 times (leonurine) of Comparative Example 5.

[0084] The results indicate that the composition of Example 2, which contains lysophosphatidylcholine, can improve the transmembrane transport rate of the active ingredient in a human colon adenocarcinoma cell model.

[0085] Test Example 5: This test, through accelerated storage experiments, determined the impact of the preparation process of this invention on the physical properties and storage stability of the final product.

[0086] The physical properties of the final powder products of Example 2 and Comparative Example 6 were tested. A powder comprehensive characteristic tester was used to measure the angle of repose, loose density and tap density of each sample in the initial state (day 0), and the Karl index was calculated.

[0087] Two samples were placed in open petri dishes and placed in a constant temperature and humidity chamber (40℃, 75% relative humidity) for accelerated storage. The samples were taken out on the 15th and 30th days, and their appearance was observed. Clumping, discoloration and other phenomena were recorded. The samples were gently ground and their angle of repose and Karl index were remeasured.

[0088] The test results are shown in Table 5.

[0089] Table 5: Changes in physical properties of Example 2 and Comparative Example 6 under accelerated storage conditions.

[0090]

[0091] From Table 5 and Figure 5 We can obtain: In the initial state, the Karl Fischer index (14.7%) of the product of Example 2 was lower than that of Comparative Example 6 (28.3%), indicating that it had better flowability. After being stored for 30 days under accelerated conditions of 40°C and 75% relative humidity, the Karl Fischer index of Example 2 increased slightly to 19.8%, while Comparative Example 6 was severely agglomerated, and the Karl Fischer index rose to 48.2%. Example 2 and Comparative Example 6 had the same components but different preparation processes. The multi-step process of Example 2 formed a multi-layer structure with physical protection function, which reduced the hygroscopicity of the powder.

[0092] 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 functional feed for lactating sows containing highly effective plant-based lactation-promoting factors, characterized in that, The feed is made from ingredients comprising the following parts by weight: Sodium montmorillonite: 30-50 parts; Fenugreek extract: 10-20 parts; Motherwort extract: 5-10 parts; Ionic strength modifier: 2-8 parts; Lysophosphatidylcholine: 5-15 parts; Tributyl citrate: 1-5 parts; High-purity silica: 0.5-2 parts; The fenugreek extract and motherwort extract are loaded onto sodium montmorillonite pretreated with the ionic strength modifier to form an active core; the lysophosphatidylcholine and the tributyl citrate coat the active core to form a functional layer.

2. The functional feed for lactating sows containing highly efficient plant-based lactation-promoting factors according to claim 1, characterized in that, The ionic strength modifier is prepared by mixing potassium chloride and sodium chloride, wherein the molar ratio of potassium chloride to sodium chloride is 1.5-2.5:

1.

3. The functional feed for lactating sows containing highly efficient plant-based lactation-promoting factors according to claim 2, characterized in that, The sodium-based montmorillonite has a cation exchange capacity of 90-100 mmol / 100g and a montmorillonite content of not less than 95%.

4. The functional feed for lactating sows containing highly efficient plant-based lactation-promoting factors according to claim 3, characterized in that, The content of 1-acyl-lysophosphatidylcholine in the lysophosphatidylcholine is not less than 90% w / w.

5. The functional feed for lactating sows containing highly efficient plant-based lactation-promoting factors according to claim 4, characterized in that, The feed is prepared by the following steps: S1. Mix sodium-based montmorillonite with an ionic strength modifier and dry. S2. The dried materials are dry-mixed to prepare a control carrier with preset ion exchange sites; S3. Fenugreek extract and Leonurus japonicus extract were added to the regulatory carrier and subjected to strong shear mixing to prepare an active core loaded complex. S4. Lysophosphatidylcholine and tributyl citrate are mixed to form a homogeneous liquid phase, and then sprayed onto the active core loading complex to prepare functional layer modified particles. S5. High-purity silica is added to the functional layer modified granules and mixed to obtain feed.

6. The functional feed for lactating sows containing highly efficient plant-based lactation-promoting factors according to claim 5, characterized in that, In S1, the step of mixing and drying sodium-based montmorillonite with the ionic strength modifier includes: Sodium-based montmorillonite and an ionic strength modifier were placed in a forced-air drying oven and dried at 85-105℃ for 2-4 hours.

7. The functional feed for lactating sows containing highly efficient plant-based lactation-promoting factors according to claim 5, characterized in that, In S2, the step of dry mixing the dried materials to prepare a controlled carrier with preset ion exchange sites includes: The dried sodium-based montmorillonite and the ion strength modifier were put into a jacketed high-speed shear mixer and dry-mixed for 20-30 minutes at an ambient temperature of 20-30℃ and a speed of 300-500 rpm to obtain a regulated carrier with preset ion exchange sites.

8. The functional feed for lactating sows containing highly efficient plant-based lactation-promoting factors according to claim 5, characterized in that, In S3, the step of adding fenugreek extract and motherwort extract to the regulating carrier and performing strong shear mixing to prepare the active core-loaded complex includes: Fenugreek extract and Leonurus japonicus extract are added to the control carrier. The speed of the mixer is increased to 1500-2000 rpm for strong shear mixing for 15-20 minutes. During the mixing, cooling circulating water at 10-20℃ is introduced into the jacket of the equipment to ensure that the maximum temperature of the material does not exceed 60℃, thus obtaining the active core loaded complex.

9. The functional feed for lactating sows containing highly efficient plant-based lactation-promoting factors according to claim 5, characterized in that, In S4, the step of mixing lysophosphatidylcholine and tributyl citrate to form a homogeneous liquid phase and spraying it onto the active core-supported complex to prepare functionally modified particles includes: Lysophosphatidylcholine and tributyl citrate were stirred and mixed in a mixing tank at 40-50°C to form a homogeneous liquid phase. The active core-loaded composite is transferred to a plow-type mixer. The main shaft is started to turn the material at a speed of 40-60 rpm, and a high-speed flying knife is started to shear at a speed of 2500-3000 rpm. The homogeneous liquid phase is sprayed into the powder through a pressure atomizing nozzle at a pressure of 2.0-3.5 bar. The spraying process lasts for 10-15 minutes. After the process is completed, mixing continues for 5-10 minutes to obtain functional layer modified particles.

10. The functional feed for lactating sows containing highly efficient plant-based lactation-promoting factors according to claim 5, characterized in that, In step S5, the step of adding high-purity silica to the functional layer-modified particles and mixing them to obtain the final product includes: Add high-purity silica to the functional layer modified granules, reduce the mixer speed to 30-50 rpm, stop the high-speed flying knife, continue mixing for 5-10 minutes, and then discharge and sieve to obtain feed.

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