A vitamin A capsule and a method for preparing the same

Abstract

This invention relates to the field of vitamin microcapsule preparation technology, specifically to a vitamin A capsule and its preparation method. By using kojic acid and lysine together as crosslinking aids, the crosslinking temperature and time can be effectively reduced, thereby minimizing vitamin A ester loss during the crosslinking process. The participation of kojic acid and lysine in the crosslinking process increases the crosslinking network density, resulting in a dense capsule wall, further improving the product's storage and processing stability, and exhibiting good bioavailability. By adding lysine and / or its salts to the kojic acid aqueous solution in different steps—specifically, adding lysine and / or its salts during aqueous phase preparation and mixing the kojic acid aqueous solution with the crude emulsion before homogenization—premature crosslinking between the two or with the wall material can be avoided, thus preventing impact on the emulsion's stability.

Description

Technical Field

[0001] This invention relates to the field of vitamin microcapsule preparation technology, specifically to a vitamin A capsule and its preparation method. Background Technology

[0002] Vitamin A is one of the essential fat-soluble vitamins for the human body, playing an irreplaceable physiological role in maintaining normal visual function, promoting growth and development, enhancing immune function, and acting as an antioxidant. However, the chemical structure of vitamin A contains multiple conjugated double bonds, making it extremely sensitive to environmental factors such as light, heat, oxygen, metal ions, and acids and alkalis. During processing, storage, and transportation, it is highly susceptible to oxidative degradation, isomerization, or polymerization reactions, thereby losing its biological activity.

[0003] To overcome the aforementioned problems, microencapsulation technology is considered an effective means to protect vitamin A and improve its stability and bioavailability. Currently, commonly used methods for preparing vitamin A microcapsules include spray drying, composite coagulation, fluidized bed coating, and emulsion polymerization. Among these, spray granulation is widely used due to its advantages such as simple process flow, continuous operation, and ease of industrial scale-up.

[0004] The preparation of water-repellent microcapsules using spray granulation typically requires a cross-linking process, which has long been a key bottleneck restricting the efficiency and quality improvement of microcapsule preparation. Cross-linking of vitamin A microcapsules is crucial for the water resistance, mechanical strength, and protection of active ingredients in the microcapsule wall material. Insufficient cross-linking results in insufficient mechanical strength and significant vitamin A loss during the high temperatures of feed pelleting and storage; excessive cross-linking prevents product release in animals, severely impairing bioavailability. Traditional cross-linking of vitamin A microcapsules usually relies on high temperatures and prolonged processing.

[0005] Existing technology describes a continuous fluidized bed crosslinking method for microcapsules, achieving continuous crosslinking reaction through a vibrating fluidized bed and a tubular crosslinker. In the tubular crosslinker, materials are transported via airflow, while temperature and humidity are controlled for the crosslinking reaction. The operating temperature of the hot air is controlled at 65–145 °C, and the temperature of the water vapor at 100–160 °C. At 70 °C, the crosslinking time is as long as 5 hours; at 140 °C, the reaction time is shortened, but nearly 5% of vitamin A is lost.

[0006] Other patent documents disclose the addition of metallic inorganic salts (sulfates or hydrochlorides of iron / calcium / magnesium / copper) to the formulation of vitamin A microcapsules to promote cross-linking. However, the cross-linking temperature still needs to be 80-90 °C, and the addition of metal ions may affect the storage stability of vitamin A.

[0007] The above processes all have certain drawbacks. For example, the cross-linking temperature and time are high during the cross-linking process of vitamin A microcapsules. A new process needs to be developed to achieve rapid cross-linking under mild conditions in order to reduce the loss of vitamin A during the cross-linking process. Summary of the Invention

[0008] This invention provides a vitamin A capsule and its preparation method to solve the problem of excessive vitamin A loss caused by high cross-linking temperature and long cross-linking time in the prior art.

[0009] Therefore, this application provides a method for preparing vitamin A capsules, comprising the following steps: S1. Preparation of oil phase and aqueous phase: Vitamin A ester is mixed with a fat-soluble antioxidant and heated to dissolve under inert gas protection to obtain the oil phase; wall material, lysine and / or its salt, water-soluble antioxidant and water are mixed to obtain the aqueous phase; S2. Add the oil phase to the aqueous phase and shear it to obtain a crude emulsion; S3. Mix the crude emulsion with an aqueous solution of kojic acid and homogenize it to obtain a vitamin A emulsion. S4. The vitamin A emulsion is spray-dried in the presence of starch, and then cross-linked to obtain vitamin A capsules.

[0010] In some embodiments, the mass ratio of lysine and / or its salt to kojic acid is 0.5 to 3:1, preferably 1.0 to 2.1:1.

[0011] In some embodiments, the total amount of lysine and / or its salts and kojic acid added is 10wt% to 70wt% of the mass of vitamin A ester, preferably 20wt% to 60wt%.

[0012] In some embodiments, the vitamin A ester is one or more of vitamin A acetate, vitamin A palmitate or vitamin A propionate, preferably vitamin A acetate; And / or, the fat-soluble antioxidant is one or more of propyl gallate, tert-butylhydroquinone, 2,6-di-tert-butyl-4-methylphenol, butyl hydroxyanisole, ethoxyquinoline, tocopherol, and ascorbate palmitate, preferably tert-butylhydroquinone; And / or, the water-soluble antioxidant includes one or more of ascorbic acid, ascorbate, isoascorbic acid, isoascorbate, tea polyphenols, and rosemary extract; And / or, the wall material is one or more of gelatin, casein, whey protein, soy protein, gum arabic, xanthan gum, and carbohydrates; optionally, the carbohydrates are selected from one or more of glucose, sucrose, fructose, lactose, maltodextrin, hydroxypropyl starch, galactose, high-fructose corn syrup, glucose syrup, and dry glucose syrup, preferably sucrose; optionally, the gelatin is one of pigskin glue, pig bone glue, cowhide glue, and cow bone glue; preferably pigskin glue; And / or, the lysine and / or its salts are selected from one or both of lysine and lysine hydrochloride.

[0013] Among them, isoascorbate can be, but is not limited to, conventional salts such as sodium isoascorbate and potassium isoascorbate.

[0014] In some embodiments, the amount of the fat-soluble antioxidant added is 0.5 wt% to 15 wt% of the mass of vitamin A ester, preferably 1 wt% to 10 wt%. And / or, the amount of the water-soluble antioxidant added is 0.5wt% to 40wt% of the mass of vitamin A ester, preferably 2wt% to 35wt%; And / or, based on the dry matter mass of the vitamin A capsules, the amount of the wall material added is 20wt%-60wt%.

[0015] In some embodiments, the vitamin A emulsion contains 30-70% water by mass.

[0016] In some embodiments, during the preparation of the oil phase, the heating and dissolution temperature is 40–90 °C, preferably 55–70 °C; and the heating and dissolution time is 30–180 min, preferably 60–120 min. And / or, during the preparation of the aqueous phase, a pH adjuster is added to adjust the pH value of the aqueous phase to 4.0–9.0, preferably 6.0–8.0; And / or, the shearing rotation speed is 3000–20000 r / min, preferably 6000–15000 r / min; the shearing time is 5–60 min, preferably 20–50 min; and the system temperature is maintained at 40–75°C during the shearing process. And / or, the homogenization pressure is 15-80 MPa, preferably 20-60 MPa, and the homogenization is performed 1-5 times, preferably 2-3 times; And / or, the crosslinking treatment is carried out by heating and humidification, maintaining the material temperature at 30-50 °C, preferably 40-50 °C; the system humidity at 30%-80%, preferably 40%-70%; and the crosslinking time at 30-240 min, preferably 60-120 min. And / or, the particle size D90 of vitamin A emulsion is 0.2–3.0 μm.

[0017] In some embodiments, the temperature inside the tower is maintained at 5~50°C, preferably 5~20°C, during feeding; after feeding, the temperature inside the tower is raised to 30~90°C, preferably 40~70°C, and dried until the moisture content is less than 10wt%.

[0018] And / or, during the spray drying process, the feed mass ratio of the vitamin A emulsion to starch is 1~30:1, preferably 5~26:1; And / or, during the spray drying process, the starch flow rate is 50-200 g / min, preferably 50-85 g / min.

[0019] In some implementations, during the crosslinking process, the chord length distribution data of the microcapsule particles are collected online using an FBRM probe, and real-time microscopic images of the microcapsule particles are collected online using a PVM probe. The particle size change rate ΔD50 / Δt measured by the FBRM is used as a physical indicator of the crosslinking process. When the change rate of ΔD50 / Δt is less than 5% for three or more consecutive sampling cycles, the crosslinking reaction is determined to have reached its endpoint, and the control system automatically terminates the crosslinking and switches to the cooling and drying program. Optionally, if the PVM image shows abnormal particle aggregation or particle breakage, the system can automatically trigger an alarm and adjust the fluidizing gas rate.

[0020] On the other hand, this application also provides a vitamin A capsule prepared by any of the above-described preparation methods.

[0021] In some embodiments, the encapsulation rate of vitamin A capsules is ≥95%; And / or, under accelerated storage conditions at 40°C for 90 days, the retention rate of vitamin A esters in vitamin A capsules is ≥95%; And / or, in the feed pelleting process, the retention rate of vitamin A esters in vitamin A capsules is ≥90%.

[0022] The mechanism of this invention is based on a tandem reaction of "kojic acid oxidation to quinone - lysine amino group capturing quinone - bridging crosslinking," forming a preliminary three-dimensional network that provides the basic framework for Maillard crosslinking reactions. Under oxygen-containing and appropriate humidity conditions, kojic acid is oxidized to kojic acid quinone. The electron-deficient conjugated ring in kojic acid quinone rapidly undergoes a Michael addition reaction with the α-primary amine on the lysine side chain, forming a stable CN bond. The ε-primary amine or carboxyl group of lysine can further condense with active carbonyl groups (such as aldehyde groups generated by oxidation) or amino groups on the protein molecular chain, thereby forming a "kojic acid-lysine-protein" covalent bridge between kojic acid, lysine, and protein. Because the activation energy of the addition reaction between quinone and primary amine is much lower than that of the traditional glycoamine Maillard condensation reaction, the system completes the main bridging in only 0.5 to 1.5 hours under mild conditions of 40–60°C, much faster than the traditional Maillard reaction. Simultaneously, the bis-primary amine structure of lysine effectively captures kojic acid quinone, inhibiting the self-polymerization and browning of quinone, thus making the product color controllable. Based on the aforementioned synergistic mechanism, this invention enables rapid and complete cross-linking under mild conditions, breaking the existing technical convention that "low-temperature cross-linking must take a long time."

[0023] During the cross-linking process, the morphology of vitamin A microcapsule particles evolves from a loose, porous state to a dense, spherical state. The particle size change exhibits a three-stage characteristic of "fast-slow-flat," providing a quantifiable physical signal for online determination of the cross-linking endpoint. The FBRM online monitoring module: The FBRM probe is vertically inserted into the middle of the fluidized bed material layer, with the laser beam focus located in the central region of the material layer. It continuously collects chord length distribution data of the microcapsule particles at 1-5 minute intervals, calculates and records D10, D50, and D90 values ​​in real time, and calculates the particle size change rate ΔD50 / Δt to monitor the cross-linking process in real time. When the change rate of ΔD50 / Δt is less than 5% for three consecutive sampling cycles, the cross-linking reaction is considered to have reached its endpoint. The PVM online monitoring module: The PVM probe works synchronously with the FBRM probe, acquiring high-resolution microscopic images of the microcapsule particles in real time at the same sampling frequency (resolution up to 2 μm / pixel). This identifies the particle aggregation state and surface morphology changes, providing cross-validation for the accuracy of the FBRM particle size readings. If the PVM image shows abnormal particle aggregation or particle breakage, the system can automatically trigger an alarm and adjust the fluidizing gas velocity.

[0024] The technical solution of this invention has the following advantages: 1. The method for preparing vitamin A capsules provided by the present invention includes the following steps: S1, preparation of oil phase and preparation of aqueous phase: vitamin A ester is mixed with a fat-soluble antioxidant and heated to dissolve under inert gas protection to obtain an oil phase; wall material, lysine and / or its salt, water-soluble antioxidant and water are mixed to obtain an aqueous phase; S2, the oil phase is added to the aqueous phase and sheared to obtain a crude emulsion; S3, the crude emulsion is mixed with kojic acid aqueous solution and homogenized to obtain a vitamin A emulsion; S4, the vitamin A emulsion is spray-dried in the presence of starch and then cross-linked to obtain vitamin A capsules. Using kojic acid and lysine together as crosslinking aids can effectively reduce crosslinking temperature and time, thereby reducing vitamin A loss during the crosslinking process. The participation of kojic acid and lysine in the crosslinking process increases the crosslinking network density, resulting in a dense capsule wall, further improving product storage and processing stability, and exhibiting good bioavailability. By adding lysine and / or its salts to the kojic acid aqueous solution in different steps—with lysine and / or its salts added during aqueous phase preparation and the kojic acid aqueous solution mixed with the crude emulsion before homogenization—premature crosslinking between the two or with the wall material can be avoided, thus preventing impact on emulsion stability and ensuring effective mixing. In summary, adding kojic acid and lysine in the above specific steps significantly reduces the crosslinking temperature and shortens the crosslinking time, effectively achieving mild and rapid crosslinking. The resulting product exhibits excellent storage and processing stability, significantly reduces vitamin A ester loss during feed processing, and demonstrates excellent bioavailability.

[0025] 2. The method for preparing vitamin A capsules provided by this invention involves online acquisition of chord length distribution data of microcapsule particles during the crosslinking process using an FBRM probe and real-time microscopic images of the microcapsule particles using a PVM probe. The particle size change rate ΔD50 / Δt measured by the FBRM is used as a physical indicator of the crosslinking process. When the change rate of ΔD50 / Δt is less than 5% for three consecutive sampling cycles, the crosslinking reaction is considered to have reached its endpoint, and the control system automatically terminates the crosslinking and switches to the cooling and drying program. Adding an FBRM / PVM dual probe to the crosslinking equipment enables quantitative judgment of the crosslinking endpoint and continuous dynamic monitoring of particle morphology changes during the crosslinking process, providing a basis for gas velocity control and ensuring round particle morphology.

[0026] 3. The method for preparing vitamin A capsules provided by the present invention, wherein the mass ratio of lysine and / or its salt to kojic acid is 0.5–3:1, preferably 1.0–2.1:1. By limiting the mass ratio of lysine and / or its salt to kojic acid within the above range, and especially within the preferred range, the loss of vitamin A esters during the cross-linking process can be further reduced, thereby improving the cross-linking yield and encapsulation rate.

[0027] The total amount of lysine and / or its salts and kojic acid added is 10wt% to 70wt% of the mass of vitamin A ester, preferably 20wt% to 60wt%. By limiting the total amount of lysine and / or its salts and kojic acid added to the above range, especially the preferred range, the loss of vitamin A ester during the cross-linking process can be further reduced, and the cross-linking yield can be improved.

[0028] 4. The method for preparing vitamin A capsules provided by the present invention, wherein the crosslinking treatment is carried out by heating and humidification, maintaining the material temperature at 30-50 °C, preferably 40-50 °C; the system humidity at 30%-80%, preferably 40%-70%; and the crosslinking time at 30-240 min, preferably 60-120 min; by limiting the crosslinking temperature, humidity, and time within the above-mentioned ranges, especially the preferred ranges, the loss of vitamin A esters during the crosslinking process can be further reduced, and the crosslinking yield can be improved. Detailed Implementation

[0029] The following embodiments are provided to better understand the present invention, but the following embodiments do not constitute a limitation on the content and scope of protection of the present invention. Any product that is the same as or similar to the present invention, derived by any person under the guidance of the present invention or by combining the features of the present invention with other prior art, falls within the scope of protection of the present invention.

[0030] Unless otherwise specified, all experimental steps or conditions in the examples were performed according to conventional experimental procedures and conditions in the art. Reagents or instruments whose manufacturers are not specified are all commercially available products.

[0031] The particle size testing instrument was a Bettersize2600E laser force meter from Dandong Bettersize. Moisture content was measured using a WKT-A8 Karl Fischer moisture analyzer.

[0032] Example 1 This embodiment provides a method for preparing vitamin A capsules, including the following steps: (1) Weigh 4.56g of antioxidant tert-butylhydroquinone (TBHQ) and 86.64g of vitamin A acetate crystals, heat to 60°C under a nitrogen atmosphere, stir for 60min to obtain the oil phase; (2) Weigh 36.48 g of gelatin (100 bloom g pigskin glue), 132.24 g of sucrose, 22.8 g of sodium isoascorbate, and 27.36 g of lysine hydrochloride. Add 304 g of pure water at 60 °C and stir for 30 min to obtain the aqueous phase. Keep the system temperature at about 60 °C and use a high-speed shearing machine to shear the aqueous phase at 7000 rpm for 20 min. Then adjust the pH of the aqueous phase to about 7.0 with an acetic acid / sodium acetate buffer solution. Increase the shearing speed to 10000 rpm and slowly add the oil phase. After the addition is complete, continue shearing for 10 min. The particle size D90 of the crude emulsion after shearing is 1.4 μm.

[0033] (3) Weigh 18.24g of kojic acid, dissolve it in 10g of pure water to obtain an aqueous solution of kojic acid, and add it to the crude emulsion. Use a high-pressure homogenizer to adjust the homogenization pressure to 30 MPa, and homogenize the crude emulsion three times to obtain a uniform and stable emulsion with a particle size D90 of 0.95 μm; (4) The prepared emulsion is transported to a spray drying tower for spray drying. The emulsion enters a rotary atomizer and forms rotating droplets through the centrifugal action of the atomizer. At the same time, 123.1g of starch is introduced from the side pipe next to the rotary atomizer by wind force, and the direction of entry is opposite to the rotation direction of the rotary atomizer. The atomizer speed is 4000 rpm, the emulsion feed rate is 15 g / min, the starch flow rate is 50 g / min, the tower temperature is maintained at 15℃ during feeding, and the tower temperature is raised to 40℃ after feeding is completed. The emulsion droplets are embedded in the starch to obtain a crude product of microcapsule particles with a water content of less than 10%. (5) The crude product was cross-linked in a fluidized bed with a temperature of 40 °C and a humidity of 50%. After 60 min of cross-linking, the change rates of ΔD50 / Δt in three consecutive sampling periods were 3.8%, 3.2% and 2.9%, respectively, all <5%. After the cross-linking was completed, vitamin A acetate microcapsules were obtained.

[0034] Example 2 This embodiment provides a method for preparing vitamin A capsules, which is basically the same as in Example 1, except that the types and / or amounts of each substance are different, as detailed below: Adjust the amount of TBHQ in step (1) to 1.78g and the amount of vitamin A acetate crystals to 134.55g.

[0035] In step (2), adjust the amount of pigskin glue to 39.05 g, the amount of sucrose to 124.25 g, replace 22.8 g of sodium isoascorbate with 3.6 g of ascorbic acid, adjust the amount of lysine hydrochloride to 10.65 g, and adjust the amount of pure water to 236.7 g.

[0036] In step (3), the amount of kojic acid is adjusted to 10.65 g.

[0037] In step (4), the amount of starch used is adjusted to 28.4g.

[0038] Example 3 This embodiment provides a method for preparing vitamin A capsules, including the following steps: (1) Weigh 1.6g of antioxidant tocopherol and 119.39g of vitamin A acetate crystals, heat to 60°C under a nitrogen atmosphere, stir for 100min to obtain the oil phase; (2) Weigh 47.3g of bovine bone glue (150 bloom g), 63g of glucose, 25.2g of potassium ascorbate, and 18.9g of lysine hydrochloride, add 210g of pure water at 60℃, and stir for 30min. Keep the system temperature at about 60℃, and use a high-speed shearing machine to shear the aqueous phase at 6000 rpm for 20min. Then adjust the pH of the aqueous phase to about 6.0 with an acetic acid / sodium acetate buffer solution. Increase the shearing speed to 8000 rpm and slowly add the oil phase. After the addition is complete, continue shearing for 20min. The D90 of the crude emulsion after shearing is 1.5 μm.

[0039] (3) Weigh 12.6g of kojic acid, dissolve it in 10g of pure water to obtain an aqueous solution of kojic acid, and add it to the crude emulsion. Use a high-pressure homogenizer to adjust the homogenization pressure to 50MPa, and homogenize the crude emulsion 4 times to obtain a uniform and stable emulsion with a D90 of 0.85 μm; (4) The prepared emulsion is transported to the spray drying tower for spray drying. The emulsion enters the rotary atomizer and forms rotating droplets through the centrifugal action of the atomizer. At the same time, 22.0g of starch is introduced from the side pipe next to the rotary atomizer by the action of wind, and the direction of entry is opposite to the rotation direction of the rotary atomizer. The atomizer speed is 6000 rpm, the emulsion feed rate is 25 g / min, the starch flow rate is 50 g / min, the tower temperature is maintained at 10℃ during feeding, and the tower temperature is raised to 45℃ after feeding is completed, so that the emulsion droplets are embedded in the starch to obtain a crude product of microcapsule particles with a water content of less than 10%. (5) The crude product was cross-linked in a fluidized bed with a temperature of 30 °C and a humidity of 60%. After cross-linking for 90 min, the change rates of ΔD50 / Δt in three consecutive sampling periods were 3.0%, 2.8%, and 2.2%, respectively, all <5%, and vitamin A acetate microcapsules were obtained.

[0040] Example 4 This embodiment provides a method for preparing vitamin A capsules, including the following steps: (1) Weigh 2.6g of antioxidant palmitic acid ascorbate and 153.4g of vitamin A palmitic acid crystals, heat to 60°C under a nitrogen atmosphere, stir for 60min, and obtain the oil phase; (2) Weigh 31.2 g of gum arabic, 114.4 g of fructose, 33.8 g of tea polyphenols, and 26 g of lysine hydrochloride, add 346.7 g of pure water at 60°C, and stir for 30 min. Keep the system temperature at around 60°C, and use a high-speed shearing machine to shear the aqueous phase at 6000 rpm for 15 min. Then adjust the pH of the aqueous phase to around 6.8 with an acetic acid / sodium acetate buffer solution. Increase the shearing speed to 8000 rpm and slowly add the oil phase. After the addition is complete, continue shearing for 10 min. The D90 of the crude emulsion after shearing is 1.25 μm.

[0041] (3) Weigh 15.6g of kojic acid, dissolve it in 10g of pure water to obtain an aqueous solution of kojic acid, and add it to the crude emulsion. Use a high-pressure homogenizer to adjust the homogenization pressure to 30 MPa, homogenize the crude emulsion once to obtain a homogeneous and stable emulsion with a D90 of 0.92 μm; (4) The prepared emulsion is transported to the spray drying tower for spray drying. The emulsion enters the rotary atomizer and forms rotating droplets through the centrifugal action of the atomizer. At the same time, 130.0g of starch is introduced from the side pipe next to the rotary atomizer by the action of wind, and the direction of entry is opposite to the rotation direction of the rotary atomizer. The atomizer speed is 4000 rpm, the emulsion feed rate is 15 g / min, the starch flow rate is 50 g / min, the tower temperature is kept at 15℃ during feeding, and the tower temperature is raised to 50℃ after feeding is completed. The emulsion droplets are embedded in the starch to obtain a crude product of microcapsule particles with a water content of less than 10%. (5) The crude product is cross-linked in a fluidized bed. The cross-linking temperature in the fluidized bed is 40℃ and the humidity is 55%. After 60 min of cross-linking, the change rates of ΔD50 / Δt in three consecutive sampling periods are 3.1%, 2.5% and 1.9%, respectively, all <5%, and vitamin A palmitate microcapsules can be obtained.

[0042] Example 5 This embodiment provides a method for preparing vitamin A capsules, including the following steps: (1) Weigh 4.12g of antioxidant tocopherol and 92.7g of vitamin A acetate crystals, heat to 60°C under a nitrogen atmosphere, stir for 60min to obtain the oil phase; (2) Weigh 49.4 g of 150 bloom g pigskin glue, 94.76 g of fructose, 28.84 g of sodium isoascorbate, and 34.2 g of lysine hydrochloride, add 274.7 g of pure water at 60℃, and stir for 30 min. Keep the system temperature at about 60℃, and use a high-speed shearing machine to shear the aqueous phase at 5000 rpm for 20 min. Then adjust the pH of the aqueous phase to about 6.0 with an acetic acid / sodium acetate buffer solution. Increase the shearing speed to 8000 rpm and slowly add the oil phase. After the addition is complete, continue shearing for 20 min. The D90 of the crude emulsion after shearing is 1.5 μm.

[0043] (3) Weigh 16.48g of kojic acid, dissolve it in 10g of pure water to obtain an aqueous solution of kojic acid, and add it to the crude emulsion. Use a high-pressure homogenizer to adjust the homogenization pressure to 50MPa, and homogenize the crude emulsion 4 times to obtain a uniform and stable emulsion with a particle size D90 of 0.85 μm; (4) The prepared emulsion is transported to the spray drying tower for spray drying. The emulsion enters the rotary atomizer and forms rotating droplets through the centrifugal action of the atomizer. At the same time, 103.0g of starch is introduced from the side pipe next to the rotary atomizer by the action of wind. The direction of entry is opposite to the rotation direction of the rotary atomizer. The atomizer speed is 6000 rpm, the emulsion feed rate is 25 g / min, the starch flow rate is 50 g / min, the tower temperature is maintained at 10℃ during feeding, and the tower temperature is raised to 60℃ after feeding is completed. The emulsion droplets are embedded in the starch to obtain a crude product of microcapsule particles with a water content of less than 10%. (5) The crude product is cross-linked in a fluidized bed. The cross-linking temperature in the fluidized bed is 30℃ and the humidity is 40%. After cross-linking for 90 min, the change rates of ΔD50 / Δt in three consecutive sampling periods are 3.3%, 2.9% and 2.3%, respectively, all <5%, and vitamin A acetate microcapsules can be obtained.

[0044] Example 6 The only difference from Example 1 is the amount of lysine hydrochloride and kojic acid used. In this example, the amounts of lysine hydrochloride and kojic acid are adjusted to 34.2g and 11.4g, respectively.

[0045] Example 7 The only difference from Example 1 is the amount of lysine hydrochloride and kojic acid used. In this example, the amounts of lysine hydrochloride and kojic acid are adjusted to 15.2g and 30.4g, respectively.

[0046] Example 8 This embodiment provides a method for preparing vitamin A capsules, including the following steps: (1) Weigh 0.9g of antioxidant tert-butylhydroquinone (TBHQ) and 88g of vitamin A acetate crystals, heat to 70°C under a nitrogen atmosphere, stir and dissolve for 60min to obtain the oil phase; (2) Weigh 136.8g of gelatin (100 bloom g pigskin glue), 136.8g of sucrose, 29.6g of sodium isoascorbate, and 4.6g of lysine hydrochloride. Add 300g of pure water at 50℃ and stir for 20min. Keep the system temperature at around 50℃ and use a high-speed shearing machine to shear the aqueous phase at 10000 rpm for 30min. Then adjust the pH of the aqueous phase to around 7.0 with an acetic acid / sodium acetate buffer solution. Increase the shearing speed to 15000 rpm and slowly add the oil phase. After the addition is complete, continue shearing for 5min. The D90 of the crude emulsion after shearing is 1.49μm.

[0047] (3) Weigh 4.6g of kojic acid, dissolve it in 10g of pure water to obtain an aqueous solution of kojic acid, and add it to the crude emulsion. Use a high-pressure homogenizer to adjust the homogenization pressure to 20 MPa, and homogenize the crude emulsion twice to obtain a uniform and stable emulsion with a D90 of 0.88μm; (4) The prepared emulsion is transported to the spray drying tower for spray drying. The emulsion enters the rotary atomizer and forms rotating droplets through the centrifugal action of the atomizer. At the same time, 45.6g of starch is introduced from the side pipe next to the rotary atomizer by the wind force. The direction of entry is opposite to the rotation direction of the rotary atomizer. The atomizer speed is 4000 rpm, the emulsion feed rate is 35 g / min, the starch flow rate is 85 g / min, the tower temperature is maintained at 10℃ during feeding, and the tower temperature is raised to 40℃ after feeding is completed. The emulsion droplets are embedded in the starch to obtain a crude product of microcapsule particles with a water content of less than 10%. (5) The crude product was cross-linked in a fluidized bed. The cross-linking temperature in the fluidized bed was 50 °C and the humidity was 40%. The change rates of ΔD50 / Δt in three consecutive sampling cycles after 60 min of cross-linking were 3.2%, 2.6% and 2.0%, respectively, all <5%. After the cross-linking was completed, vitamin A acetate microcapsules were obtained.

[0048] Example 9 It is basically the same as Example 1, except that the crosslinking time in step (5) is extended to 240 min.

[0049] Example 10 It is basically the same as Example 2, except that the crosslinking time in step (5) is extended to 240 min.

[0050] Comparative Example 1 The process is basically the same as in Example 9, except that: lysine hydrochloride is not added to the aqueous phase in step (2); and kojic acid aqueous solution is not added to the crude emulsion in step (3). Accordingly, the amount of sucrose used in step (2) is increased to 177.84g.

[0051] Comparative Example 2 The procedure is basically the same as in Example 1, except that: in step (2), lysine hydrochloride is not added to the aqueous phase; in step (3), kojic acid aqueous solution is not added to the crude emulsion. In step (5), the crosslinking temperature is increased to 70°C and the crosslinking time is extended to 240 min.

[0052] Comparative Example 3 It is basically the same as Example 9, except that: lysine hydrochloride is not added to the aqueous phase in step (2), and the amount of sucrose in step (2) is increased to 159.6g accordingly.

[0053] Comparative Example 4 The process is basically the same as in Example 9, except that kojic acid aqueous solution is not added to the crude emulsion in step (3). Correspondingly, the amount of sucrose used in step (2) is increased to 150.48g.

[0054] Experimental Example 1 (1) Test method for crosslinking yield: Vitamin A capsules were prepared according to the methods of each embodiment and comparative example. The crude product before crosslinking and the vitamin A capsules (hereinafter referred to as "microcapsules") obtained after crosslinking were taken as test samples. The content of vitamin A acetate was determined according to GB / T7292-1999 "Vitamin A Acetate Microparticles for Feed Additives" (for microcapsules encapsulating palmitate, the content of vitamin A palmitate was determined according to national standard GB 23386-2017 "Vitamin A Palmitate (Powder) for Feed Additives"). The crosslinking yield was then calculated as follows: Crosslinking yield = Vitamin A ester content in microcapsules / Vitamin A ester content in crude product.

[0055] (2) Appearance and water repellency test: Observe the appearance of the final product and conduct a water repellency test as follows: Take about 1g of microcapsules in a beaker, add 100mL of boiling water, stir for 1min, and observe whether the water is clear after the particles settle. If the water is clear, it indicates that the test has been passed; if the water is cloudy, it indicates that the test has not been passed.

[0056] (3) Encapsulation efficiency test: The content of vitamin A acetate in the vitamin A capsules prepared in each example and comparative example was tested according to the national standard GB / T 7292-1999 "Vitamin A Acetate Microparticles for Feed Additives" (for microcapsules encapsulating palmitate, the content of vitamin A palmitate was determined according to the national standard GB23386-2017 "Vitamin A Palmitate (Powder) for Feed Additives"), and recorded as Q1; Weigh approximately 1.0g of vitamin A capsules into a 50mL volumetric flask, add hexane to dilute to volume, shake well by inverting for 1 minute, filter, and take the filtrate for high performance liquid chromatography (HPLC). Determine the content of unencapsulated vitamin A acetate in the microcapsules under the HPLC conditions specified in GB / T 7292-1999 (for microcapsules encapsulated with palmitate, refer to the national standard GB 23386-2017 "Vitamin A Palmitate (Powder) Feed Additives" to determine the content of vitamin A palmitate), and record it as Q2; then calculate the encapsulation rate according to the following formula: Encapsulation rate = 1 - Q2 / Q1.

[0057] The results are shown in Table 1.

[0058] Table 1

[0059] The results showed that, compared with the comparative examples, the vitamin A capsules obtained in each embodiment of this application had significantly improved encapsulation efficiency and cross-linking yield, and the loss of vitamin A esters during the cross-linking process was significantly reduced. Furthermore, the product of Comparative Example 1 failed the hydrophobicity test and was therefore unqualified.

[0060] Experiment Example 2 Retention rate test after 90 days: After being placed in a constant temperature and humidity chamber (40 ℃, 65%RH) for 90 days, the content of vitamin A acetate in vitamin A capsules before and after placement was tested according to the national standard GB / T 7292-1999 "Vitamin A Acetate Microparticles for Feed Additives" (for microcapsules encapsulated with palmitate, the content of vitamin A palmitate was determined according to the national standard GB 23386-2017 "Vitamin A Palmitate (Powder) for Feed Additives"). Then, the retention rate was calculated as follows: Retention rate = Vitamin A ester content after 90 days / Vitamin A ester content in microcapsules before placement.

[0061] The results are shown in Table 2.

[0062] Table 2

[0063] The results showed that, compared with the comparative examples, the vitamin A capsules obtained in each embodiment of this application had a significantly improved retention rate after 90 days of storage.

[0064] Experimental Example 3 In vitro release rate experiments were conducted on samples from each of the embodiments and comparative examples: (1) Simulated gastric digestion stage: Accurately weigh 0.5g of vitamin A capsules and 20mL of simulated gastric digestion liquid into a brown conical flask. After sealing the conical flask, place it in a constant temperature water bath shaker and fix it in place. Maintain a constant temperature of 41ºC in the water bath and stir at a speed of 60r / min for 2 hours of static digestion.

[0065] (2) Simulated intestinal digestion stage: The pH of the gastric digestion system was adjusted to 6.8 with 1 mol / L NaOH solution, and then 30 mL of simulated intestinal digestion solution and 7.5 mL of bile salt solution were added. The system was then quickly kept at a constant temperature of 41℃ in a water bath, with a stirring speed of 60 r / min, and static digestion was carried out for 4 hours.

[0066] (3) Test of vitamin A ester content in digestive fluid: Filter the digestive fluid, then transfer the filtrate to a 250 mL volumetric flask, dilute to volume with ethanol, shake well, filter, and take the filtrate for high performance liquid chromatography determination. Determine the amount of vitamin A acetate in the digestive fluid under the high performance liquid chromatography conditions specified in GB / T 7292-1999 (for microcapsules encapsulated with palmitate, refer to the national standard GB 23386-2017 "Vitamin A Palmitate (Powder) Feed Additives" to determine the content of vitamin A palmitate.

[0067] (4) Take another 0.5g of vitamin A capsules and determine the total amount of vitamin A acetate in the microcapsules according to GB / T 7292-1999 "Vitamin A Acetate Microparticles for Feed Additives" (for microcapsules encapsulated with palmitate, determine the content of vitamin A palmitate in them according to national standard GB23386-2017 "Vitamin A Palmitate (Powder) for Feed Additives").

[0068] (5) Calculate the release rate according to the following formula: Release rate = Amount of vitamin A ester in digestive fluid (IU / g) / Amount of vitamin A ester in microcapsules (IU / g) 100%.

[0069] In step (1), the simulated gastric fluid was prepared (pepsin activity 1550 U / mL): Based on the principle of equivalent chicken pepsin activity, 387.5 KU of pepsin was weighed and dissolved in hydrochloric acid solution at pH 2.0 (pH determined at 41ºC), stirred slowly until completely dissolved, and then diluted to 250 mL in a volumetric flask. The solution was prepared fresh for use. In step (2), the simulated small intestinal fluid was prepared (amylase activity 401.46 U / mL, trypsin activity 49.28 U / mL, chymotrypsin activity 11.31 U / mL): Based on the amylase, trypsin, and chymotrypsin activities in chicken intestinal fluid, 13.55 KU of trypsin and 3.11 KU of chymotrypsin were weighed and dissolved in 200 mL of deionized water, stirred slowly until completely dissolved, and then 110.40 KU of amylase was added after stirring for about 10 min. 100 mL of bile salt solution (5 g / L, purchased from Yuanye Biotechnology) was also prepared for later use.

[0070] Table 3

[0071] The results showed that, compared with Comparative Example 2, the in vitro release rate of vitamin A capsules obtained in each embodiment of this application was significantly improved.

[0072] Experiment Example 4 The vitamin A capsules prepared in each example and comparative example were used to prepare fattening pig feed according to the following method: (1) Vitamin A capsules, vitamin E, vitamin K3, vitamin B1, vitamin B2, vitamin B6, vitamin B12, nicotinamide, calcium pantothenate, folic acid, biotin, 0.1% livestock and poultry trace elements (trade name: Calcium Phosphorus Magnesium Zinc Treasure), DL-methionine (purity 98.5%), betaine hydrochloride, choline chloride (purity 60%, purchased from Shandong Aokete), sodium bicarbonate (baking soda), compound enzyme preparation (purchased from Bestgen Biotech, trade name: Baijiemei), compound antioxidant (Jiangsu Zhongdan Group Co., Ltd., trade name: Danquilline), compound probiotics (purchased from Yantai Jinhai Pharmaceutical, billion-level compound Bacillus), phytase (20000 IU / g) ordinary type, sodium chloride (purity 99%), dicalcium phosphate (containing 16.5% phosphorus), stone powder, and rice husk powder are mixed according to the dosages in Table 4 below to obtain a premix.

[0073] Table 4 Composition of premix for fattening pigs

[0074] (2) The premixed feed is mixed with corn, soybean meal, soybean oil, limestone powder, dicalcium phosphate, lysine, methionine, threonine, tryptophan, choline chloride, and rice bran according to the percentages shown in Table 5 below, and then pelleted to obtain feed pellets. The pelleting process is as follows: The uniformly mixed powder is fed into a conditioner at a conditioning temperature of 85-90℃, and humid hot air is introduced. The fully conditioned humid hot material is then fed into a ring die pellet mill, where it forms dense cylindrical strips under a pressure of about 5-10 MPa, and is cut into pellets by the outer cutter. The material is then forced to cool down by air through a cooler until its temperature drops to near room temperature.

[0075] Table 5. Feed Formulation for Fattening Pigs

[0076] (3) To test the retention rate of vitamin A esters during feed pelleting, the specific method is as follows: Take the product obtained before pelleting and the final product obtained after pelleting as the test samples, and determine the content of vitamin A acetate or palmitate in them according to the national standard GB / T 17817-2024 "Determination of Vitamin A in Feed by High Performance Liquid Chromatography". Then calculate the pelleting yield as follows: Pelletizing yield = Vitamin A ester content in the product obtained after pelleting / Vitamin A ester content in the product obtained before pelleting.

[0077] Table 6

[0078] The results showed that, compared with the comparative examples, the granulation retention rate of vitamin A capsules obtained in each embodiment of this application was significantly improved, and the loss of vitamin A esters during the granulation process was significantly reduced.

[0079] In summary, the above results fully demonstrate that using kojic acid and lysine together as cross-linking aids to prepare vitamin A microcapsules significantly reduces the cross-linking temperature and shortens the cross-linking time, effectively achieving mild and rapid cross-linking. The resulting product has excellent storage and processing stability, significantly reduces vitamin A loss during feed processing, and has excellent bioavailability.

[0080] Obviously, the above embodiments are merely illustrative examples for clear explanation and are not intended to limit the implementation. Those skilled in the art will recognize that other variations or modifications can be made based on the above description. It is neither necessary nor possible to exhaustively list all possible implementations. However, obvious variations or modifications derived therefrom are still within the scope of protection of this invention.

Claims

1. A method for preparing vitamin A capsules, characterized in that, Includes the following steps: S1. Preparation of oil phase and aqueous phase: Vitamin A ester is mixed with a fat-soluble antioxidant and heated to dissolve under inert gas protection to obtain the oil phase; wall material, lysine and / or its salt, water-soluble antioxidant and water are mixed to obtain the aqueous phase; S2. Add the oil phase to the aqueous phase and shear it to obtain a crude emulsion; S3. Mix the crude emulsion with an aqueous solution of kojic acid and homogenize it to obtain a vitamin A emulsion. S4. The vitamin A emulsion is spray-dried in the presence of starch, and then cross-linked to obtain vitamin A capsules.

2. The method for preparing vitamin A capsules according to claim 1, characterized in that, The mass ratio of lysine and / or its salt to kojic acid is 0.5 to 3:1, preferably 1.0 to 2.1:

1.

3. The method for preparing vitamin A capsules according to claim 1, characterized in that, The total amount of lysine and / or its salts and kojic acid added is 10wt% to 70wt% of the mass of vitamin A ester, preferably 20wt% to 60wt%.

4. The method for preparing vitamin A capsules according to claim 1, characterized in that, The vitamin A ester is one or more of vitamin A acetate, vitamin A palmitate or vitamin A propionate, preferably vitamin A acetate; And / or, the fat-soluble antioxidant is one or more of propyl gallate, tert-butylhydroquinone, 2,6-di-tert-butyl-4-methylphenol, butyl hydroxyanisole, ethoxyquinoline, tocopherol, and ascorbate palmitate, preferably tert-butylhydroquinone; And / or, the water-soluble antioxidant includes one or more of ascorbic acid, ascorbate, isoascorbic acid, isoascorbate, tea polyphenols, and rosemary extract; And / or, the wall material is one or more of gelatin, casein, whey protein, soy protein, gum arabic, xanthan gum, and carbohydrates; optionally, the carbohydrates are selected from one or more of glucose, sucrose, fructose, lactose, maltodextrin, hydroxypropyl starch, galactose, high-fructose corn syrup, glucose syrup, and dry glucose syrup, preferably sucrose; optionally, the gelatin is one of pigskin glue, pig bone glue, cowhide glue, and cow bone glue; preferably pigskin glue; And / or, the lysine and / or its salts are selected from one or both of lysine and lysine hydrochloride.

5. The method for preparing vitamin A capsules according to claim 1, characterized in that, The amount of the fat-soluble antioxidant added is 0.5 wt% to 15 wt% of the mass of vitamin A ester, preferably 1 wt% to 10 wt%. And / or, the amount of the water-soluble antioxidant added is 0.5wt% to 40wt% of the mass of vitamin A ester, preferably 2wt% to 35wt%; And / or, based on the dry matter mass of the vitamin A capsules, the amount of the wall material added is 20wt%-60wt%; And / or, the water content in the vitamin A emulsion is 30-70% by mass.

6. The method for preparing vitamin A capsules according to claim 1, characterized in that, During the preparation of the oil phase, the heating and dissolution temperature is 40–90 °C, preferably 55–70 °C; the heating and dissolution time is 30–180 min, preferably 60–120 min. And / or, during the preparation of the aqueous phase, a pH adjuster is added to adjust the pH value of the aqueous phase to 4.0–9.0, preferably 6.0–8.0; And / or, the shearing rotation speed is 3000–20000 r / min, preferably 6000–15000 r / min; the shearing time is 5–60 min, preferably 20–50 min; and the system temperature is maintained at 40–75°C during the shearing process. And / or, the homogenization pressure is 15-80 MPa, preferably 20-60 MPa, and the homogenization is performed 1-5 times, preferably 2-3 times; And / or, the crosslinking treatment is carried out by heating and humidification, maintaining the material temperature at 30-50 °C, preferably 40-50 °C; the system humidity at 30%-80%, preferably 40%-70%; and the crosslinking time at 30-240 min, preferably 60-120 min. And / or, the particle size D90 of vitamin A emulsion is 0.2–3.0 μm.

7. The method for preparing vitamin A capsules according to claim 1, characterized in that, During the spray drying process, the temperature inside the tower is maintained at 5~50℃, preferably 5~20℃, during feeding; after feeding, the temperature inside the tower is raised to 30~90℃, preferably 40~70℃, until the moisture content is less than 10wt%. And / or, during the spray drying process, the feed mass ratio of the vitamin A emulsion to starch is 1~30:1, preferably 5~26:1; And / or, during the spray drying process, the starch flow rate is 50-200 g / min, preferably 50-85 g / min.

8. The method for preparing vitamin A capsules according to claim 1, characterized in that, During the crosslinking process, the chord length distribution data of microcapsule particles are collected online using the FBRM probe, and real-time microscopic images of microcapsule particles are collected online using the PVM probe. The particle size change rate ΔD50 / Δt measured by FBRM is used as the physical indicator for judging the crosslinking process. When the change rate of ΔD50 / Δt is less than 5% for three or more consecutive sampling cycles, the crosslinking reaction is judged to have reached the endpoint, and the control system automatically terminates the crosslinking and switches to the cooling and drying program. Optionally, if the PVM image shows abnormal particle aggregation or particle breakage, the system can automatically trigger an alarm and adjust the fluidizing gas rate.

9. Vitamin A capsules prepared by any one of the preparation methods according to claims 1-8.

10. The vitamin A capsule according to claim 9, characterized in that, The encapsulation rate of vitamin A capsules is ≥95%; And / or, under accelerated storage conditions at 40°C for 90 days, the retention rate of vitamin A esters in vitamin A capsules is ≥95%; And / or, in the feed pelleting process, the retention rate of vitamin A esters in vitamin A capsules is ≥90%.

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