Rumen bypass choline chloride particle and preparation method thereof

Abstract

The invention discloses rumen bypass choline chloride particles and a preparation method thereof, and belongs to the technical field of feed additives. The rumen bypass choline chloride particle comprises a drug-loading inner core and an outer protective layer coating the drug-loading inner core, the drug-loading inner core is obtained by mixing hydrophobic particles with a melt, extruding and granulating; wherein the hydrophobic particles are obtained by wrapping crystal form choline chloride with a hydrophobic material; the molten liquid is obtained by melting and mixing stearic acid, magnesium stearate and oleophylic cellulose; the oleophylic cellulose adopts ethyl cellulose; the outer protective layer is obtained by mixing fatty acid, hydrogenated grease, a pH sensitive material and a fragrant raw material with fruit fragrance, green grass fragrance or fermentation fragrance; the outer protective layer of the rumen bypass choline chloride particle is good in toughness and fitness, the rumen bypass choline chloride particle is good in rumen bypass effect and good in small intestine release rate, the food intake of dairy cows is not affected, the risk of metabolic diseases is effectively reduced, and the health level of the dairy cows is improved.

Description

Technical Field

[0001] This invention relates to the field of feed additive technology, specifically to a rumen-protected choline chloride granule and its preparation method. Background Technology

[0002] The peripartum period is a crucial stage in dairy cow husbandry, and its management has a vital impact on lactation performance, reproductive performance, and the cow's health throughout the entire lactation period. Furthermore, this period directly affects the health and production performance of calves. Due to the rapid growth and development of the fetus in late pregnancy, the enormous energy expenditure during parturition, and the rapid increase in milk production in early lactation, the cow's energy requirements rise sharply during this time.

[0003] Postpartum, dairy cows experience a lag in feed intake growth compared to milk production growth, leading to insufficient energy supply and a negative energy balance. To maintain high milk production, cows utilize large amounts of body fat for energy through hormonal regulation. However, improper control of this fat mobilization mechanism can result in elevated levels of free fatty acids in the blood. Excessive absorption of free fatty acids by the liver can cause metabolic diseases such as ketosis or fatty liver.

[0004] Choline, as a nutrient, plays a crucial role in promoting the transport of fat out of the liver and preventing fatty liver and ketosis. Choline chloride, due to its high stability, is often used as a feed additive to replace choline. However, given the unique physiological structure of ruminants, most of the choline chloride added directly to the diet is degraded by microorganisms in the rumen, with only a small amount reaching the small intestine for absorption and utilization. Therefore, effectively protecting choline chloride and ensuring its smooth passage through the rumen and release in the abomasum and small intestine is key to improving its bioavailability.

[0005] Currently, although various technologies exist to improve the rumen clearance rate of choline chloride, such as microencapsulation, coating, and granulation-coating technologies, these methods generally have some limitations. For example, while solvent-based coating using polymeric materials can ensure rumen stability, the need for dissolving the material in solvents such as 95% ethanol leads to low production efficiency and solvent recovery issues. This increases the complexity and cost of the production process and fails to effectively address the odor problem specific to acrylic resin IV, severely impacting feed intake in dairy cows. Furthermore, while coating with pure oils avoids the solvent issue, pure oil-based coatings are more brittle and prone to breakage during processing, storage, or rumination, thus affecting the rumen clearance and small intestinal release rate of the product.

[0006] Therefore, there is an urgent need to develop a choline chloride granule that can improve the toughness and fit of the outer protective layer, effectively increase the rumen passage rate and small intestinal release rate, and does not affect the feed intake of dairy cows. Summary of the Invention

[0007] The purpose of this invention is to provide rumen-protected choline chloride granules and a method for preparing the same, in order to solve the technical problems mentioned in the background section.

[0008] The technical solution to achieve the objective of this invention is: In a first aspect, the present invention provides rumen-passed choline chloride granules, comprising a drug-loaded inner core and an outer protective layer covering the drug-loaded inner core; the drug-loaded inner core is obtained by extruding and granulating a mixture of hydrophobic particles and a molten liquid; the hydrophobic particles are obtained by encapsulating crystalline choline chloride with a hydrophobic material; the outer protective layer is obtained by mixing fatty acids, hydrogenated oils, pH-sensitive materials, and fragrance raw materials with fruity, grassy, ​​or fermented aromas.

[0009] Furthermore, the hydrophobic material includes any one or at least two combinations of calcium stearate, magnesium stearate, and hydrophobic silica.

[0010] Furthermore, the fatty acid includes any one or a combination of at least two of stearic acid and palmitic acid.

[0011] Furthermore, the hydrogenated oil includes one or at least two combinations of hydrogenated soybean oil, hydrogenated palm oil, and hydrogenated rapeseed oil.

[0012] Furthermore, the pH-sensitive material is acrylic resin No. IV.

[0013] Furthermore, the melt is obtained by melt mixing stearic acid, magnesium stearate, and lipophilic cellulose.

[0014] Furthermore, the lipophilic cellulose includes ethyl cellulose.

[0015] Furthermore, the drug-loaded core is also equipped with a seven-membered cucurbit ring.

[0016] Furthermore, the fragrance raw materials with fruity, grassy, ​​or fermented aromas include any one or at least two combinations of isoamyl phenylacetate, leaf ester acetate, cinnamyl isovalerate, leaf ester benzoate, leaf ester hexanoate, and furfuryl acetate.

[0017] In a second aspect, the present invention provides a method for preparing rumen-passed choline chloride granules as described in the first aspect, the steps of which include: (1) Mix crystalline choline chloride with a hydrophobic material to obtain hydrophobic particles; (2) Melt stearic acid into a liquid, control the temperature at 115~125℃, then add magnesium stearate and lipophilic cellulose, stir to homogenize and melt into a molten liquid; mix the molten liquid with hydrophobic particles at 90~100℃, then extrude and granulate to obtain a drug-loaded core of 16~30 mesh. (3) Heat the fatty acids to melt them, control the temperature at 110~120℃, add pH-sensitive materials under stirring and homogenization conditions, add hydrogenated oil after the system becomes clear and transparent, continue stirring evenly, keep warm for later use, add fragrance raw materials with fruity, grassy or fermented aroma 2~4 minutes before coating liquid, stir evenly to obtain coating liquid. (4) The coating solution is atomized into droplets with a diameter of <5 μm and sprayed evenly onto the surface of the drug-loaded core to obtain rumen-exposed choline chloride particles.

[0018] Furthermore, the mass ratio of the crystalline choline chloride to the hydrophobic material is (95~99):(1~5).

[0019] Furthermore, the core material comprises 60-80% of a first hydrophobic layer and 20-40% of molten liquid by mass percentage; the mass ratio of stearic acid, magnesium stearate and oleophilic cellulose in the molten liquid is (50-80):(10-30):(10-20).

[0020] Furthermore, the rumen-passed choline chloride granules comprise 75-80% of a drug-loaded inner core and 15-30% of an outer protective layer by mass percentage; the mass ratio of hydrogenated oil, fatty acid, pH-sensitive material, and flavoring raw material in the outer protective layer is (69-91.9):(3-18):(5-18):(0.1-1).

[0021] Further, in step (2), a seven-membered cucurbitacin is added during the process of mixing the melt with the hydrophobic particles, and then extruded and granulated to obtain the product; the amount of the seven-membered cucurbitacin added is 4 to 6% of the mass of the melt.

[0022] By adopting the above technical solution, the present invention has the following beneficial effects: (1) The rumen-passing choline chloride granules of the present invention include a drug-loaded inner core and an outer protective layer covering the drug-loaded inner core; wherein, the drug-loaded inner core is obtained by mixing and extruding hydrophobic particles with molten liquid; the hydrophobic particles are obtained by encapsulating crystalline choline chloride with hydrophobic material; the outer protective layer is obtained by mixing fatty acids, hydrogenated oils, pH-sensitive materials, and fragrance raw materials with fruity, grassy, ​​or fermented aromas. The outer protective layer of the rumen-passing choline chloride granules has good toughness and adhesion, and can effectively improve the rumen-passing rate and small intestinal release rate. At the same time, the masking effect of the fragrance raw materials effectively avoids the adverse effects of the special odor of the pH-sensitive material acrylic resin No. IV on the feed intake of dairy cows.

[0023] (2) Crystalline choline chloride is prone to deliquescence when the ambient humidity is higher than 40%, which leads to caking. This invention uses hydrophobic materials to encapsulate crystalline choline chloride, effectively giving it hydrophobic properties, thereby preventing it from absorbing moisture and deliquescence and caking in high humidity environments.

[0024] (3) The drug-loaded core of the present invention is obtained by mixing and extruding hydrophobic particles with molten liquid; wherein, the molten liquid is obtained by melting and mixing stearic acid, magnesium stearate and lipophilic cellulose; the lipophilic cellulose is ethyl cellulose; these materials all have the characteristics of being highly stable in the rumen environment and not easily degraded by microorganisms; even if the particles are partially damaged by chewing during the rumination of dairy cows, the drug-loaded core can still effectively resist the erosion of rumen fluid, significantly reduce the risk of premature release and degradation of choline chloride in the rumen, thereby ensuring that it can pass through the rumen smoothly into the small intestine to exert its effect; as a preferred drug-loaded core, when a seven-membered cucurbit ring is added, the seven-membered cucurbit ring has a hydrophobic and lipophilic cavity structure, which can effectively anchor and fix the active ingredients in the drug-loaded core, enhance the stability of the overall structure of the particles, and further improve the rumen passage rate and small intestine release rate.

[0025] (4) The outer protective layer of the present invention is made by mixing fatty acids, hydrogenated oils, pH-sensitive materials, and fragrance raw materials with fruity, grassy, ​​or fermented aromas; wherein, the pH-sensitive material is acrylic resin No. IV. Traditional processes usually require it to be prepared into an organic solvent solution with a solid content of 10%, such as 95% ethanol, for coating. However, the present invention innovatively premixes fatty acids and acrylic resin No. IV at a mass ratio of (3~18):(5~18), making it easier to dissolve in the main coating material, hydrogenated oils, thereby replacing organic solvents with fatty acids, effectively solving the problems of low efficiency and complex solvent recovery in traditional solvent-based coatings; and each component of the outer protective layer has hydrophobic properties, remains stable in the rumen environment, does not react, and ensures that the particles are smooth. The formula allows the product to pass through the rumen without being degraded. Simultaneously, the acrylic resin IV and flavoring ingredients in the formulation are selected from materials that are unstable at pH=2, ensuring rapid release of the product in the abomasum after passing through the rumen. Given that acrylic resin IV has a distinctive odor that can affect dairy cows' feed intake, fruity, grassy, ​​or fermented flavoring ingredients preferred by dairy cows are introduced to effectively mask its unpleasant odor. Furthermore, these flavoring ingredients are stable under neutral conditions and can be destroyed in acidic environments, thus also possessing auxiliary pH-sensitive properties. Finally, pure hydrogenated palm oil is prone to cracking at low temperatures, affecting its rumen-passing protective effect and moisture-proof performance. By combining fatty acids, pH-sensitive materials, and flavoring ingredients with hydrogenated palm oil, the flexibility and adhesion of the outer protective layer are significantly enhanced. Attached Figure Description

[0026] To make the content of this invention easier to understand, the invention will be further described in detail below with reference to specific embodiments and accompanying drawings, wherein... Figure 1 This is a flowchart of the preparation method of the rumen-protected choline chloride granules of the present invention.

[0027] Figure 2 This is a schematic diagram illustrating the application principle of rumen-protected choline chloride granules according to an embodiment of the present invention.

[0028] Figure 3 The triglyceride (TG) levels of dairy cows fed in the experimental and control groups of this invention are shown in the graph.

[0029] Figure 4 The β-hydroxybutyrate (BHBA) levels in dairy cows fed in the experimental and control groups of this invention are shown in the graph.

[0030] Figure 5 Immunoglobulin IgG levels in dairy cows fed in the experimental and control groups of this invention.

[0031] Figure 6 C-reactive protein (CRP) levels in dairy cows fed in the experimental and control groups of this invention.

[0032] Figure 7 In one embodiment of the present invention, rumen-protected choline chloride granules were placed in a friability tester, and the rotation speed was set to 25 rpm. The state graphs were processed for 1 min, 4 min (100 rpm), 7 min and 10 min respectively.

[0033] Figure 8 In another embodiment of the present invention, rumen-protected choline chloride granules were placed in a friability tester, and the rotation speed was set to 25 rpm. The state graphs were processed for 1 min, 4 min (100 rpm), 7 min and 10 min respectively.

[0034] Figure 9 For Comparative Example 2 of this invention, the rumen-protected choline chloride particles were placed in a friability tester, and the rotation speed was set to 25 rpm. The state graphs were processed for 1 min, 4 min (100 rpm), 7 min and 10 min respectively.

[0035] The labels in the attached diagram are: 1. Calcium stearate; 2. Crystalline choline chloride; 3. Molten liquid containing stearic acid, magnesium stearate, and lipophilic cellulose; 4. Homogeneous molten liquid containing fatty acids, hydrogenated oils, and pH-sensitive materials; 5. Fragrance raw materials with fruity, grassy, ​​or fermented aromas. Detailed Implementation

[0036] To better understand the above technical solution, the following will provide a detailed explanation of the technical solution in conjunction with specific implementation methods.

[0037] Based on the embodiments of this invention, all other embodiments obtained by those skilled in the art without inventive effort are within the scope of protection of this invention.

[0038] The following embodiments are only used to illustrate the technical solutions of the present invention more clearly, and should not be used to limit the scope of protection of the present invention.

[0039] Example A method for preparing rumen-protected choline chloride granules, comprising the following steps: (1) Mix crystalline choline chloride with a hydrophobic material to obtain hydrophobic particles; (2) Melt stearic acid into a liquid, control the temperature at 115~125℃, then add magnesium stearate and lipophilic cellulose, stir to homogenize and melt into a molten liquid; mix the molten liquid with hydrophobic particles at 90~100℃, then extrude and granulate to obtain a drug-loaded core of 16~30 mesh. (3) Heat the fatty acids to melt them, control the temperature at 110~120℃, add pH-sensitive materials under stirring and homogenization conditions, add hydrogenated oil after the system becomes clear and transparent, continue stirring evenly, keep warm for later use, add fragrance raw materials with fruity, grassy or fermented aroma 2~4 minutes before coating liquid, stir evenly to obtain coating liquid. (4) The coating solution is atomized into droplets with a diameter of <5 μm and sprayed evenly onto the surface of the drug-loaded core to obtain rumen-exposed choline chloride particles.

[0040] The mass ratio of the crystalline choline chloride to the hydrophobic material is (95~99):(1~5).

[0041] The core material comprises 60-80% of a first hydrophobic layer and 20-40% of molten liquid by mass percentage; the mass ratio of stearic acid, magnesium stearate and oleophilic cellulose in the molten liquid is (50-80):(10-30):(10-20).

[0042] The rumen-passed choline chloride granules comprise, by mass percentage, 75-80% of a drug-loaded inner core and 15-30% of an outer protective layer; the mass ratio of hydrogenated oil, fatty acid, pH-sensitive material, and flavoring raw material in the outer protective layer is (69-91.9):(3-18):(5-18):(0.1-1).

[0043] The hydrophobic material includes any one or at least two combinations of calcium stearate, magnesium stearate, and hydrophobic silica.

[0044] The fatty acids include any one or at least two of stearic acid and palmitic acid.

[0045] The hydrogenated oils include one or at least two combinations of hydrogenated soybean oil, hydrogenated palm oil, and hydrogenated rapeseed oil.

[0046] The pH-sensitive material is acrylic resin No. IV.

[0047] The melt is obtained by melting and mixing stearic acid, magnesium stearate, and lipophilic cellulose.

[0048] The fragrance raw materials with fruity, grassy, ​​or fermented aromas include any one or at least two combinations of isoamyl phenylacetate, leaf ester acetate, cinnamon ester isovalerate, leaf ester benzoate, leaf ester hexanoate, and furfuryl acetate.

[0049] The lipophilic cellulose includes ethyl cellulose; The drug-loaded core also contains a seven-membered cucurbit ring; in step (2), the seven-membered cucurbit ring is added during the process of mixing the melt with the hydrophobic particles, and then extruded and granulated; the amount of the seven-membered cucurbit ring added is 4 to 6% of the mass of the melt.

[0050] Example 1 like Figure 1 As shown, a method for preparing rumen-passed choline chloride granules includes the following steps: (1) Mix 93 kg of crystalline choline chloride and 4 kg of calcium stearate in a biaxial mixer until uniform, and control the mixing uniformity to within 5% to obtain hydrophobic particles. (2) Set the temperature of the 100L melting kettle to 120℃, add 37kg of stearic acid to melt into liquid, control the liquid temperature at about 120℃, then add 10kg of magnesium stearate and 6kg of ethyl cellulose, and melt into a uniform and transparent molten liquid under stirring and homogenization; set the jacket temperature of the high-speed shear granulator to 95℃, control the jacket temperature at 90~100℃, add the hydrophobic particles to the high-speed shear granulator, then add the molten liquid and mix evenly, then extrude and granulate through a screw extruder, the pore size of the extruded membrane is 1.2~1.5mm, the extruded particles are cooled and solidified into shape, and then screened (upper layer 16 mesh, lower layer 30 mesh) to obtain the drug-loaded inner core; (3) Heat 1.5 kg of stearic acid in a beaker to melt it, and control the temperature at 110~120℃. Add 1.7 kg of acrylic resin IV under stirring and homogenization conditions. Wait until the system is clear and transparent and set aside. Add 14 kg of solid hydrogenated palm oil to a 50 L melting kettle, set the temperature to 115℃, control the temperature of the coating solution at 110~120℃, and add it to the beaker to melt the system under stirring conditions. Mix it into a homogeneous and transparent solution and keep it warm for later use. Add 85 g of furfuryl acetate about 3 minutes before the coating solution is applied and stir evenly to obtain the coating solution. (4) Add 83kg of drug-loaded inner core into the coating machine, keep it in a fluidized state, keep the air inlet temperature at 50~55℃, feed at a speed of 1.5L / min, keep the atomization temperature at 120~130℃ under an atomization pressure of 0.25MPa, and spray the coating liquid evenly onto the surface of the drug-loaded inner core to form an outer protective layer, and obtain rumen-protected choline chloride granules.

[0051] Example 2 A method for preparing rumen-protected choline chloride granules, comprising the following steps: (1) Mix 93 kg of crystalline choline chloride and 4 kg of calcium stearate in a biaxial mixer until uniform, and control the mixing uniformity to within 5% to obtain hydrophobic particles. (2) Set the temperature of the 100L melting kettle to 120℃, add 37kg of stearic acid to melt into liquid, control the liquid temperature at about 120℃, then add 10kg of magnesium stearate and 6kg of ethyl cellulose, and melt into a uniform and transparent molten liquid under stirring and homogenization; set the jacket temperature of the high-speed shear granulator to 95℃, control the jacket temperature at 90~100℃, add the hydrophobic particles to the high-speed shear granulator, then add the molten liquid and mix evenly, then extrude and granulate through a screw extruder, the pore size of the extruded membrane is 1.2~1.5mm, the extruded particles are cooled and solidified into shape, and then screened (upper layer 16 mesh, lower layer 30 mesh) to obtain the drug-loaded inner core; (3) Heat 1.5 kg of stearic acid in a beaker to melt it, and control the temperature at 110~120℃. Add 1.7 kg of acrylic resin IV under stirring and homogenization conditions. Wait until the system is clear and transparent and set aside. Add 14 kg of solid hydrogenated palm oil to a 50 L melting kettle, set the temperature to 115℃, control the temperature of the coating solution at 110~120℃, and add it to the beaker to melt the system under stirring conditions. Mix it into a homogeneous and transparent solution and keep it warm for later use. Add 170 g of furfuryl acetate about 3 minutes before the coating solution is applied and stir evenly to obtain the coating solution. (4) Add 83kg of drug-loaded inner core into the coating machine, keep it in a fluidized state, keep the air inlet temperature at 50~55℃, feed at a speed of 1.5L / min, keep the atomization temperature at 120~130℃ under an atomization pressure of 0.25MPa, and spray the coating liquid evenly onto the surface of the drug-loaded inner core to form an outer protective layer, and obtain rumen-protected choline chloride granules.

[0052] Example 3 A method for preparing rumen-protected choline chloride granules, comprising the following steps: (1) Mix 93 kg of crystalline choline chloride and 4 kg of calcium stearate in a biaxial mixer until uniform, and control the mixing uniformity to within 5% to obtain hydrophobic particles. (2) Set the temperature of the 100L melting kettle to 120℃, add 37kg of stearic acid to melt into liquid, control the liquid temperature at about 120℃, then add 10kg of magnesium stearate and 6kg of ethyl cellulose, and melt into a uniform and transparent molten liquid under stirring and homogenization; set the jacket temperature of the high-speed shear granulator to 95℃, control the jacket temperature at 90~100℃, add hydrophobic particles and 2.5kg of seven-membered cucurbit rings to the high-speed shear granulator, then add the molten liquid and mix evenly, then extrude and granulate through a screw extruder, the pore size of the extruded membrane is 1.2~1.5mm, the extruded particles are cooled and solidified into shape, and then screened (upper layer 16 mesh, lower layer 30 mesh) to obtain the drug-loaded inner core; (3) Heat 1.5 kg of stearic acid in a beaker to melt it, and control the temperature at 110~120℃. Add 1.7 kg of acrylic resin IV under stirring and homogenization conditions. Wait until the system is clear and transparent and set aside. Add 14 kg of solid hydrogenated palm oil to a 50 L melting kettle, set the temperature to 115℃, control the temperature of the coating solution at 110~120℃, and add it to the beaker to melt the system under stirring conditions. Mix it into a homogeneous and transparent solution and keep it warm for later use. Add 85 g of furfuryl acetate about 3 minutes before the coating solution is applied and stir evenly to obtain the coating solution. (4) Add 83kg of drug-loaded inner core into the coating machine, keep it in a fluidized state, keep the air inlet temperature at 50~55℃, feed at a speed of 1.5L / min, keep the atomization temperature at 120~130℃ under an atomization pressure of 0.25MPa, and spray the coating liquid evenly onto the surface of the drug-loaded inner core to form an outer protective layer, and obtain rumen-protected choline chloride granules.

[0053] Comparative Example 1 A method for preparing rumen-protected choline chloride granules, comprising the following steps: (1) Mix 93 kg of crystalline choline chloride and 4 kg of calcium stearate in a biaxial mixer until uniform, and control the mixing uniformity to within 5% to obtain hydrophobic particles. (2) Set the temperature of the 100L melting kettle to 120℃, add 37kg of stearic acid to melt into liquid, control the liquid temperature at about 120℃, then add 10kg of magnesium stearate and 6kg of ethyl cellulose, and melt into a uniform and transparent molten liquid under stirring and homogenization; set the jacket temperature of the high-speed shear granulator to 95℃, control the jacket temperature at 90~100℃, add the hydrophobic particles to the high-speed shear granulator, then add the molten liquid and mix evenly, then extrude and granulate through a screw extruder, the pore size of the extruded membrane is 1.2~1.5mm, the extruded particles are cooled and solidified into shape, and then screened (upper layer 16 mesh, lower layer 30 mesh) to obtain the drug-loaded inner core; (3) Heat 1.5 kg of stearic acid in a beaker to melt it, and control the temperature at 110~120℃. Add 1.7 kg of acrylic resin IV under stirring and homogenization conditions. Wait until the system is clear and transparent and set aside. Add 14 kg of solid hydrogenated palm oil to a 50 L melting kettle, set the temperature to 115℃, control the temperature of the coating solution at 110~120℃, and add the system to the beaker under stirring conditions to melt it. Mix it into a homogeneous and transparent solution, keep it warm and set aside to obtain the coating solution. (4) Add 83kg of drug-loaded inner core into the coating machine, keep it in a fluidized state, keep the air inlet temperature at 50~55℃, feed at a speed of 1.5L / min, keep the atomization temperature at 120~130℃ under an atomization pressure of 0.25MPa, and spray the coating liquid evenly onto the surface of the drug-loaded inner core to form an outer protective layer, and obtain rumen-protected choline chloride granules.

[0054] Comparative Example 2 A method for preparing rumen-protected choline chloride granules, comprising the following steps: (1) Mix 93 kg of crystalline choline chloride and 4 kg of calcium stearate in a biaxial mixer until uniform, and control the mixing uniformity to within 5% to obtain hydrophobic particles. (2) Set the temperature of the 100L melting kettle to 120℃, add 37kg of stearic acid to melt into liquid, control the liquid temperature at about 120℃, then add 11kg of magnesium stearate and 5kg of ethyl cellulose, and melt into a uniform and transparent molten liquid under stirring and homogenization; set the jacket temperature of the high-speed shear granulator to 95℃, control the jacket temperature at 90~100℃, add the hydrophobic particles to the high-speed shear granulator, then add the molten liquid and mix evenly, then extrude and granulate through a screw extruder, the pore size of the extruded membrane is 1.2~1.5mm, the extruded particles are cooled and solidified into shape, and then screened (upper layer 16 mesh, lower layer 30 mesh) to obtain the drug-loaded inner core; (3) Add 17 kg of solid hydrogenated palm oil to a 50 L melting kettle, set the temperature to 115 °C, control the temperature of the coating solution to 110~120 °C, and mix under stirring to form a uniform coating solution; (4) Add 83kg of drug-loaded inner core into the coating machine, keep it in a fluidized state, keep the air inlet temperature at 50~55℃, feed at a speed of 1.5L / min, keep the atomization temperature at 120~130℃ under an atomization pressure of 0.25MPa, and spray the coating liquid evenly onto the surface of the drug-loaded inner core to form an outer protective layer, and obtain rumen-protected choline chloride granules.

[0055] Example of effect Test Example 1 1.1 Test Materials Five groups of samples from Examples 1, 2, 3, Comparative Example 1, and Comparative Example 2. 1.2 Experimental diet and feeding management Each experimental group consisted of three healthy Holstein cows with permanent rumen fistulas. The cows were fed three times a day in equal amounts, tethered, and had free access to water.

[0056] The basal diet and its nutritional composition are shown in Table 1.

[0057] Table 1

[0058] Note: 1. Nutritional components are measured values.

[0059] 2. The premix provides the following per kilogram: VA 300,000 IU, VD 385,000 IU, VE 14,551 U, nicotinic acid 550 mg, Cu 770 mg, Mn 930 mg, Fe 1200 mg, Zn 3600 mg, Se 21 mg, I 50 mg, and Co 12 mg.

[0060] 1.3 Test Procedure (1) Determine the choline chloride content in the sample The choline chloride content in Examples 1, 2, and 3, and Comparative Examples 1 and 2 was determined.

[0061] (2) Detection of choline chloride rumen pass-through rate: Then, using 300-mesh nylon cloth, nylon bags of 8cm×16cm were made. Before use, the bags were pre-balanced in the rumen of cattle for 24 hours, then removed, cleaned, and dried in an oven at 65℃ until constant weight, and the weight was recorded.

[0062] 5.00g of each of the samples from Examples 1, 2, 3 and Comparative Examples 1 and 2 were weighed into the bottom of a nylon bag of known weight (the weighing was repeated 3 times at each sampling time point and placed into the fistula cattle of the corresponding experimental group), fixed on a plastic tube, and sent into the rumen abdominal sac chyme 2 hours after morning feeding. The plastic tube was then fixed to the rumen fistula cap with nylon thread.

[0063] Three replicates were performed for each cow at each time point, with measurement times of 0, 1, 2, 4, 8, 12, 16, and 24 hours. The rumen nylon bags were washed, placed on trays, dried in a 50°C drying oven for 24 hours, weighed, and then placed into sample vials to determine the choline chloride content.

[0064] (3) Detection of choline chloride release rate in the small intestine: 0.500 g of each sample cultured in the rumen for 16 h was placed in a 50 ml culture tube, with each sample repeated three times (the average value was used for calculation). 10 ml of pepsin solution (pH=2) was added, and the mixture was shaken in a shaker at 38 °C for 1 h. Then, 14 ml of trypsin solution (pH=7.8) was added, and the mixture was shaken in a shaker at 38 °C for 12 h. After shaking, the mixture was removed and immediately 3 ml of 00% (w / v) trichloroacetic acid solution was added, shaken to mix, and allowed to stand for 15 min before being collected in a nylon bag and dried in a 50 °C oven for 24 h. The samples were then weighed, and the choline chloride content was measured to calculate the small intestinal release rate.

[0065] 1.4 Sample Index Determination Choline: Determined according to the national standard method GB / T17481-2008.

[0066] 1.5 Calculation Method (1) Rumen pass rate (%) = (M2) X2 / M1 X1) 100% M2: Weight of the sample after rumen drying X2: Choline chloride content after passing through the rumen M1: Weigh the sample before passing it through the rumen. X1: Content of precholine chloride passing through the rumen (2) Small intestinal release rate (%) = (1-A2) B2 / A1 B1) 100% A2: Weight of dried sample after small intestine release B2: Choline chloride content after release from the small intestine A1: Sample weight before small intestine release B1: Choline chloride content before release in the small intestine 1.6 Test Results Table 2 below shows the rumen passage rate (%) of cattle with fistulas: Table 2

[0067] Table 2 shows that Examples 1-3 and Comparative Example 2 have better rumen-passing effects. Among them, the coating of Example 3, which uses lipophilic modified oxidized cellulose instead of ethyl cellulose, has a better rumen-passing effect than Example 1. The amount of furfuryl acetate added in Example 2 is twice that of Example 1, resulting in a better rumen-passing effect than Example 1. Comparative Example 2, which uses pure solid oil as a coating, has the best rumen-passing effect, proving that pure solid oil has the best hydrophobic effect. The rumen-passing effects of Examples 1-3 are close to those of pure solid oil, indicating that the compound system of solid vegetable oil and high-molecular materials in this scheme can achieve a hydrophobic effect close to that of pure solid oil. The difference between Comparative Example 1 and Examples 1-2 is that the absence of furfuryl acetate results in a worse rumen-passing effect compared to Examples 1-2, indicating that small molecule flavoring agents in this coating formula can increase the film spreading effect and improve the rumen-passing protective effect.

[0068] Table 3 below shows the results of the small intestinal release rate test (%). Table 3

[0069] Table 3 shows that Comparative Example 2, coated with pure solid vegetable oil, had a poor small intestinal release rate; Examples 1-3 all had small intestinal release rates above 90%. Among them, the small intestinal release rate of Example 3, which used lipophilic modified oxidized cellulose instead of ethyl cellulose, was better than that of Examples 1-2; and the small intestinal release rates of Examples 1-3 were all better than those of Comparative Example 1. This indicates that the aromatic raw materials selected in this scheme have the physicochemical properties of being stable under neutral conditions but unstable under acidic conditions of pH=2, which can increase the pH sensitivity of the coating material, promote the destruction of the coating film under abomasal conditions, expose the active ingredients, and increase the release of active ingredients in the small intestine.

[0070] Test Example 2 2.1 Test Materials The experimental group used the sample from Example 2, and the control group used the sample from Comparative Example 1.

[0071] 2.2 Experimental Design The experiment selected healthy early-lactation dairy cows with similar lactation days and divided them into a control group and an experimental group, with 300 cows in each group. The control group was fed a basal diet plus the sample from Example 1, while the experimental group was fed a basal diet plus the sample from Example 2, with an addition amount of 27 grams per cow per day.

[0072] The average daily sample intake for each group of dairy cows was 8.1 kg, with 4.05 kg added in the morning and afternoon respectively. Before the experiment, the sample was premixed with concentrate, then placed in a mixer truck, and roughage was added to prepare a total mixed ration (TMR) for feeding.

[0073] 2.3 Feeding and Management of Experimental Animals All experimental animals were free-range, with free access to water, and were fed three times a day.

[0074] 2.4 Dry matter intake record After grouping, the daily feed amount and remaining amount of the experimental group and the control group were recorded for the first 3 days of the experiment as basic data. During the 7 days of the formal experiment, the feed amount was increased by about 2% to 3%, and the feed amount and remaining amount of the two groups were recorded every day to ensure that the feed tank was continuously filled with material. During the process, the TMR moisture content was measured once a day.

[0075] 2.5 Test Results Based on the collection and analysis of dry matter intake data for the two groups of dairy cows during the first 3 days and the 7-day trial period, the results are shown in Table 4 below: Table 4

[0076] Table 4 shows that the control group's feed intake was 20.39 kg / head / day in the first 3 days of the experiment and 19.93 kg / head / day during the experiment, a decrease of 0.46 kg / head / day. This indicates that the sample in Comparative Example 1 affects the feed intake of dairy cows to some extent. The experimental group's feed intake was 22.31 kg / head / day in the first 3 days of the experiment and 22.41 kg / head / day during the experiment, a slight increase of 0.10 kg / head / day. This indicates that the sample in Example 2 did not affect the feed intake of dairy cows. Therefore, it is evident that the coating solution of Comparative Example 1, prepared using the method of "solid vegetable oil + fatty acid + acrylic resin IV," can affect the feed intake of dairy cows to some extent. Based on the properties of the raw materials in the above system, the reason is that acrylic resin No. IV has a "particular odor" property. As a coating liquid, it is located on the surface of the particles, thus affecting the feed intake of dairy cows. In Example 2 of this solution, a fragrance ingredient is added to the above coating liquid system, which can solve the problem of reduced feed intake caused by the "particular odor" of resin No. IV in the above system.

[0077] Test Example 3 3.1 Test Materials The experimental group used rumen-passed choline chloride granules (choline chloride content 50%) as described in Example 2, while the control group used ordinary silicon-type choline chloride raw material (choline chloride content 50%). According to literature research, 12g of choline can have an effective effect when it reaches the small intestine. Therefore, considering the effective content of the product, the rumen-passing rate, and the small intestine release rate, the designed addition amount was 27g / head / day.

[0078] Table 5 below shows the basic information of the animals in the experimental and control groups: Table 5

[0079] Table 6 below shows the composition and nutrient levels of the basal diet for the experimental and control groups: Table 6

[0080] Note: The premix provides the following per kilogram: Vitamin A 5130 IU; Vitamin D3 1283 IU; Vitamin E 26 mg; Biotin 0.05 mg; β-carotene 0.12 mg; Manganese 12 mg; Phosphorus 12 mg; Sulfur 0.85 mg; Zinc 64 mg; Selenium 0.4 mg; Cobalt 0.19 mg.

[0081] 3.2 Test Environment Both the experimental group and the control group of cattle were kept in normal temperature conditions (average temperature 8℃). 3.3 Sample collection and determination of key biochemical indicators related to liver health in blood Blood samples of 10 mL were collected from the root vein of the calf at 21 days before delivery, 7 days after delivery, and 14 days after delivery. The blood was centrifuged at 1000 g / min for 10 min, and the supernatant was collected. Triglycerides, β-hydroxybutyrate (MM-927208O1, ELISA), C-reactive protein (MM-0021O1, ELISA), and IgG (MM-0694O1, ELISA) were measured using an ELISA kit. Figure 3 This is a graph showing the triglyceride levels in dairy cows in the experimental and control groups. Triglycerides serve as an indicator of hepatic fat accumulation. Figure 3 The experimental group of cattle fed with Example 2 had a liver fat accumulation of 0.54 mmol / L 14 days postpartum, which was 36% lower than the control group's 0.85 mmol / L.

[0082] Figure 4 This is a graph showing the β-hydroxybutyrate levels in dairy cows in the experimental and control groups. β-hydroxybutyrate is a core indicator of ketosis. Figure 4 It was found that 14 days postpartum, the β-hydroxybutyrate level of the experimental group of cattle fed Example 2 was 1122 μmol / L, which was 44 μmol / L lower than that of the control group of cattle (1166 μmol / L), further reducing the risk of subclinical ketosis.

[0083] Figure 5 This is a graph showing the immunoglobulin IgG levels in dairy cows in the experimental and control groups. Figure 5 It was found that 14 days postpartum, the level of ketosis immunoglobulin IgG in the experimental group fed with Example 2 was 1864 μmol / L, which was 2% higher than that in the control group (1828 μmol / L), thus helping dairy cows fight infection.

[0084] Figure 6 This is a graph showing the C-reactive protein (CRP) levels in dairy cows in the experimental and control groups. Figure 6 It was found that 14 days postpartum, the risk of inflammation in the control group surged by 3.25%, while the risk in the experimental group remained almost unchanged, thus reducing the risk of mastitis and other inflammations.

[0085] In summary, the rumen-protected choline chloride granules of this invention effectively reduce the risk of metabolic diseases, including a decrease in fatty liver accumulation indicators and a reduction in the risk of ketosis, by precisely regulating lipid metabolism and immune balance in peripartum dairy cows. Furthermore, they enhance the immune defense by increasing IgG antibody levels and stabilizing inflammatory markers, thereby improving the health of dairy cows.

[0086] Test Example 4 0.65 g of the rumen-protected choline chloride granules from Example 1, Example 2, and Comparative Example 2 were placed in a friability tester. The rotation speed was set to 25 rpm, and the samples were processed for 1 min, 4 min (100 rpm), 7 min, and 10 min, respectively. The results are as follows: Figures 7-9 As shown, the rumen-protected choline chloride granules of Example 1 and Example 2 showed no cracks after treatment for 1 min, 4 min (100 rpm), 7 min, and 10 min, and the outer protective layer remained intact, without affecting the protective effect. However, in Comparative Example 2, which used pure solid hydrogenated palm oil as the outer protective layer material, no cracks appeared at 1 min and 4 min, but cracks appeared at 7 min and 10 min, affecting the integrity of the outer protective layer. This proves that the outer protective layer of the present invention is obtained by mixing fatty acids, hydrogenated oils, pH-sensitive materials, and fragrance raw materials with fruity, grassy, ​​or fermented aromas, which can improve the toughness and adhesion of the coating film and solve the brittleness problem of hydrogenated oil materials as coating materials.

[0087] The specific embodiments described above further illustrate the purpose, technical solution, and beneficial effects of the present invention. It should be understood that the above descriptions are merely specific embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A rumen-protected choline chloride granule, characterized in that, It includes a drug-loaded inner core and an outer protective layer covering the drug-loaded inner core; the drug-loaded inner core is obtained by mixing and extruding hydrophobic particles with molten liquid; the hydrophobic particles are obtained by encapsulating crystalline choline chloride with hydrophobic materials; the outer protective layer is obtained by mixing fatty acids, hydrogenated oils, pH-sensitive materials, and fragrance raw materials with fruity, grassy, ​​or fermented aromas.

2. The rumen-protected choline chloride granules according to claim 1, characterized in that, The melt is obtained by melting and mixing stearic acid, magnesium stearate, and lipophilic cellulose.

3. The rumen-protected choline chloride granules according to claim 2, characterized in that, The lipophilic cellulose includes ethyl cellulose.

4. The rumen-protected choline chloride granules according to claim 1, characterized in that, The drug-loaded core also contains a seven-membered cucurbit ring.

5. The rumen-protected choline chloride granules according to claim 1, characterized in that, The fragrance raw materials with fruity, grassy, ​​or fermented aromas include any one or at least two combinations of isoamyl phenylacetate, leaf ester acetate, cinnamon ester isovalerate, leaf ester benzoate, leaf ester hexanoate, and furfuryl acetate.

6. A method for preparing rumen-passed choline chloride granules as described in any one of claims 1 to 5, characterized in that, step... include: (1) Mix crystalline choline chloride with a hydrophobic material to obtain hydrophobic particles; (2) Melt stearic acid into a liquid, control the temperature at 115~125℃, then add magnesium stearate and lipophilic cellulose, stir, homogenize and melt into a molten liquid; The molten liquid and hydrophobic particles are mixed evenly at 90~100℃, and then extruded and granulated to obtain a drug-loaded core of 16~30 mesh. (3) Heat the fatty acids to melt them, control the temperature at 110~120℃, add pH-sensitive materials under stirring and homogenization conditions, add hydrogenated oil after the system becomes clear and transparent, continue stirring evenly, keep warm for later use, add fragrance raw materials with fruity, grassy or fermented aroma 2~4 minutes before coating liquid, stir evenly to obtain coating liquid. (4) The coating solution is atomized into droplets with a diameter of <5 μm and sprayed evenly onto the surface of the drug-loaded core to obtain rumen-exposed choline chloride particles.

7. The method for preparing rumen-passed choline chloride granules according to claim 6, characterized in that, The mass ratio of the crystalline choline chloride to the hydrophobic material is (95~99):(1~5).

8. The method for preparing rumen-passed choline chloride granules according to claim 6, characterized in that, The core material comprises 60-80% of a first hydrophobic layer and 20-40% of molten liquid by mass percentage; the mass ratio of stearic acid, magnesium stearate and oleophilic cellulose in the molten liquid is (50-80):(10-30):(10-20).

9. The method for preparing rumen-passed choline chloride granules according to claim 6, characterized in that, The rumen-passed choline chloride granules comprise, by mass percentage, 75-80% of a drug-loaded inner core and 15-30% of an outer protective layer; the mass ratio of hydrogenated oil, fatty acid, pH-sensitive material, and flavoring raw material in the outer protective layer is (69-91.9):(3-18):(5-18):(0.1-1).

10. The method for preparing rumen-passed choline chloride granules according to claim 6, characterized in that, In step (2), a seven-membered cucurbit ring is added during the process of mixing the melt with the hydrophobic particles, and then extruded and granulated to obtain the product; the amount of the seven-membered cucurbit ring added is 4 to 6% of the mass of the melt.

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