A choline chloride microencapsulated formulation and a method of making the same

Abstract

The application discloses a choline chloride microcapsule preparation and a preparation method thereof, and relates to the field of feed additives. The choline chloride microcapsule preparation is prepared from the following raw materials in percentage by weight: 5-28% of choline chloride, 2-12% of fumed silica, 3-15% of vegetable oil, 5-20% of a binder, and the rest of glycerin monostearate and hydrogenated oil. The choline chloride microcapsule preparation has a low moisture absorption weight gain rate, is stable in long-term storage, and is suitable for application in young birds, and can promote the growth and development of broiler chickens and reduce feed consumption.

Description

TECHNICAL FIELD

[0001] The present application relates to the field of feed additives, in particular to a choline chloride microcapsule preparation and a preparation method thereof. BACKGROUND

[0002] Choline is a nitrogen-containing compound isolated from pig bile by Strecker in 1849, and is an essential nutrient for the growth and development of humans and animals. In the feed industry, choline is usually added to feed in the form of choline chloride. Choline chloride molecules have a polar tendency, and are very stable in nature, but their anhydrous substances are extremely hygroscopic and can easily absorb moisture from the air and deliquesce. Whether in solid or liquid form, feed-grade choline chloride has varying degrees of hygroscopicity.

[0003] Choline chloride is a common feed additive in the daily diet. Adding choline chloride to the daily diet can improve the body weight and feed conversion rate of livestock and poultry. The rate of choline synthesis in chickens increases with age, and adult chickens are generally not deficient in choline, but chicks are quite sensitive to choline deficiency, as the rate of choline synthesis in chicks cannot meet their needs. Therefore, adding choline chloride to the daily diet can significantly improve the growth rate and feed conversion rate of chickens.

[0004] Currently, choline products on the market are mainly divided into choline aqueous solution and choline chloride solid, and the water content of choline chloride solid products is generally less than 2%, which is extremely hygroscopic and deliquescent in the daily environment, and must be stored in a dry environment, which leads to a shorter storage time and more stringent requirements for the storage environment.

[0005] In addition, the choline chloride particles disclosed in the current patent documents are basically only suitable for ruminants, but not for poultry. Ruminants have a long digestion time, so the existing choline chloride microcapsule products release slowly in an acidic environment, and the digestion time of poultry is faster than that of ruminants, and because the digestive systems of ruminants and poultry are different, the existing choline chloride microcapsule products are often excreted by poultry before being fully released, resulting in low absorption of choline chloride. In premix feed, commercially available choline chloride can also cause a decrease in the content of vitamin A. According to relevant reports, the average loss rate of vitamin A in commercially available choline chloride premix can reach 12.36%.

[0006] It can be seen that the prior art still needs to be improved and improved. SUMMARY

[0007] In view of the shortcomings of the prior art described above, the purpose of the present application is to provide a choline chloride microcapsule preparation and a preparation method thereof, which aims to solve the technical problems of easy moisture absorption of choline chloride solid products and slow release of choline chloride microcapsule products in the digestive tract of poultry.

[0008] In order to achieve the above object, the present invention adopts the following technical solutions:

[0009] The first aspect of the present invention provides a choline chloride microcapsule preparation, wherein the raw materials for its preparation include the following components, calculated by weight percentage: 5% to 28% of choline chloride, 2% to 12% of fumed silica, 3% to 15% of vegetable oil, 5% to 20% of binder, and the balance being glyceryl monostearate and hydrogenated oil.

[0010] The choline chloride microcapsule preparation comprises glyceryl monostearate and hydrogenated oil in a mass ratio of (2-0.5):1.

[0011] In the choline chloride microcapsule preparation, the mass ratio of the glyceryl monostearate to the hydrogenated oil is 1:1.

[0012] The choline chloride microcapsule preparation, wherein the particle size of the fumed silica is less than 2.6 μm and the specific surface area is greater than 240 m 2 / g.

[0013] In the choline chloride microcapsule preparation, the binder comprises one or more of corn starch and light calcium carbonate.

[0014] In the choline chloride microcapsule preparation, the vegetable oil comprises one or more of soybean oil, sunflower oil, and castor oil.

[0015] The choline chloride microcapsule preparation, wherein the mass ratio of the fumed silica to choline chloride is greater than 3:7.

[0016] The choline chloride microcapsule preparation has a particle size of 200 to 900 μm.

[0017] A second aspect of the present invention provides a method for preparing a choline chloride preparation, which is used to prepare the choline chloride microcapsule preparation described above, comprising the following steps: weighing choline chloride and fumed silica according to a formula, and mixing them uniformly to obtain a mixed material; weighing glyceryl monostearate, hydrogenated oil, and vegetable oil according to a formula, heating and melting them, and mixing them uniformly to obtain a mixed liquid; adding the mixed material to the mixed liquid, and homogenizing and dispersing it for 10 to 30 minutes; then adding a binder, and homogenizing and dispersing it for 10 to 30 minutes; and spray granulating the homogenously dispersed material to obtain the choline chloride microcapsule preparation.

[0018] The method for preparing the choline chloride preparation, wherein the temperature during the spray granulation is 80-90°C.

[0019] Beneficial effects:

[0020] A first aspect of the present invention provides a choline chloride microcapsule preparation. The choline chloride microcapsule preparation adopts a microencapsulation process, which can effectively block the contact of choline chloride with air, thereby improving the problem that choline chloride is easily hygroscopic and deliquescent. The choline chloride microcapsule preparation is more convenient in later processing and application, and can directly add choline chloride to premixes and compound feeds, thereby reducing the damage to vitamins in the mixture.

[0021] The choline chloride microcapsule formulation of the present invention also has the advantage of being suitable for poultry. In the environment of the poultry digestive tract, it is slowly released within 30 minutes and completely released within 60 minutes. Choline chloride is released as soon as it reaches the poultry small intestine, which facilitates digestion and absorption in poultry and improves the bioavailability of choline chloride. In animal experiments, the choline chloride microcapsule formulation of the present invention can effectively promote the growth and development of poultry chicks and reduce feed consumption.

[0022] The second aspect of the present invention provides a method for preparing a choline chloride preparation, which is used to prepare the choline chloride microcapsule preparation described above. The preparation method has simple process, convenient operation, and is easy to realize industrial production. DETAILED DESCRIPTION

[0023] The present invention provides a choline chloride microcapsule preparation and a preparation method thereof. To make the objectives, technical solutions, and effects of the present invention more clear and explicit, the present invention is further described in detail with reference to the following examples. It should be understood that the specific examples described herein are merely illustrative of the present invention and are not intended to limit the present invention.

[0024] The first aspect of the present invention provides a choline chloride microcapsule preparation, wherein the raw materials for its preparation include the following components, calculated by weight percentage: 5% to 28% of choline chloride, 2% to 12% of fumed silica, 3% to 15% of vegetable oil, 5% to 20% of binder, and the balance being glyceryl monostearate and hydrogenated oil.

[0025] The amount of choline chloride added to the system cannot be too high, otherwise it will cause the viscosity of the system to be too high and the components will be difficult to disperse during preparation.

[0026] The choline chloride microcapsule preparation of the present invention uses safe and environmentally friendly excipients instead of organic solvents and coating materials, thereby greatly improving the addition safety of the choline chloride product.

[0027] The choline chloride microcapsule preparation of the present invention also has good flow and dispersibility, does not aggregate, does not agglomerate, does not raise dust, and has good adsorption performance.

[0028] Among the above-mentioned raw materials, fumed silica mainly plays the role of adsorption and moisture-proofing.

[0029] The addition of vegetable oil can accelerate the melting rate, shorten the material melting time, and reduce the viscosity of the dispersion system, which is beneficial for material dispersion and spray preparation. However, excessive addition will soften the particles and make granulation difficult. When the vegetable oil content is greater than 15%, the microcapsules will have an oily texture and the microcapsule particles will be soft.

[0030] The binder can construct a bridge in the choline chloride microcapsule preparation and aggregate the drug powders together through the bonding effect.

[0031] The combination of glyceryl monostearate and hydrogenated oil can improve the encapsulation rate of choline chloride, and during the encapsulation process, the dispersion speed of each component is the fastest.

[0032] Preferably, the mass ratio of the glyceryl monostearate to the hydrogenated oil is (2-0.5): 1. Within this mass ratio range, the dispersion speed of each component during embedding is the fastest.

[0033] In a further preferred embodiment, the mass ratio of glyceryl monostearate to hydrogenated oil is 1: 1. At this mass ratio, the dispersion speed of each component during encapsulation is the fastest, and the encapsulation rate is the highest.

[0034] Preferably, the particle size of the fumed silica is less than 2.6 μm and the specific surface area is greater than 240 m 2 / g.

[0035] Preferably, the binder includes one or more of corn starch and light calcium carbonate. Light calcium carbonate and corn starch can shorten the solidification time of the material, increase the hardness of the particles, and improve the granulation rate.

[0036] Preferably, the vegetable oil includes one or more of soybean oil, sunflower oil, and castor oil.

[0037] Preferably, the mass ratio of the fumed silica to choline chloride is greater than 3: 7. If the mass ratio of the fumed silica to choline chloride is too small, the fluidity of the components after mixing is poor or becomes watery.

[0038] The choline chloride microcapsule preparation has a particle size of 200 to 900 μm.

[0039] A second aspect of the present invention provides a method for preparing a choline chloride preparation, which is used to prepare the choline chloride microcapsule preparation described above, comprising the following steps:

[0040] Choline chloride and fumed silica are weighed according to the formula and mixed evenly to obtain a mixed material. Fumed silica has a large specific surface area, a multi-mesoporous surface structure, and a strong adsorption capacity. After the fumed silica and choline chloride are evenly mixed, further crushed and dried, it is more conducive to the dispersion of the material.

[0041] Weigh glyceryl monostearate, hydrogenated oil, and vegetable oil according to the formula, heat to melt, and mix evenly to obtain a mixed solution;

[0042] Add the mixed material into the mixed liquid and homogenize and disperse for 10 to 30 minutes; then add the adhesive and homogenize and disperse for 10 to 30 minutes;

[0043] The homogeneously dispersed material is spray granulated to obtain the choline chloride microcapsule preparation.

[0044] Preferably, during the spray granulation, the temperature of the homogenized and dispersed material is first lowered to 75-90° C., and then granulated by a low-speed spray granulator. The preparation method can produce choline chloride microcapsules with a particle size of 300-650 μm.

[0045] Preferably, the temperature during the spray granulation is 80-90°C.

[0046] The following examples and comparative examples are given for further explanation.

[0047] Example 1

[0048] A mixture of choline chloride and fumed silicon dioxide is prepared from raw materials comprising the following components by weight: 70% choline chloride and 30% fumed silicon dioxide.

[0049] Example 2

[0050] A mixture of choline chloride and fumed silicon dioxide is prepared from raw materials comprising the following components by weight: 60% choline chloride and 40% fumed silicon dioxide.

[0051] Example 3

[0052] A mixture of choline chloride and fumed silicon dioxide is prepared from raw materials comprising the following components by weight: 50% choline chloride and 50% fumed silicon dioxide.

[0053] Comparative Example 1

[0054] A mixture of choline chloride and fumed silicon dioxide is prepared from raw materials comprising the following components by weight: 90% choline chloride and 10% fumed silicon dioxide.

[0055] Comparative Example 2

[0056] A mixture of choline chloride and fumed silicon dioxide is prepared from raw materials comprising the following components by weight: 80% choline chloride and 20% fumed silicon dioxide.

[0057] Comparative Example 3

[0058] A choline chloride and corn starch mixture comprises the following raw materials by weight: 50% choline chloride and 50% corn starch.

[0059] Comparative Example 4

[0060] A mixture of choline chloride and light calcium carbonate comprises the following components in terms of weight percentage: 50% choline chloride and 50% light calcium carbonate.

[0061] Comparative Example 5

[0062] A mixture of choline chloride and corn cob powder comprises the following components in percentage by weight: 50% choline chloride and 50% corn cob powder.

[0063] Comparative Example 6

[0064] A mixture of choline chloride and talcum powder comprises the following raw materials in percentage by weight: 50% choline chloride and 50% talcum powder.

[0065] Comparative Example 7

[0066] A choline chloride and magnesium stearate mixture comprises the following components in percentage by weight: 50% choline chloride and 50% magnesium stearate.

[0067] Comparative Example 8

[0068] A choline chloride and rice bran mixture comprises the following raw materials in percentage by weight: 50% choline chloride and 50% rice bran.

[0069] Determine the moisture gain of the mixtures of Examples 1-3 and Comparative Examples 1-8, and record their appearance and flowability;

[0070] The test method for the moisture-induced weight gain rate of microcapsules is as follows:

[0071] 1.1 Take a dry, stoppered glass weighing bottle (outer diameter 50 mm, height 15 mm) and place it in an artificial climate chamber set at a temperature of 25°C ± 1°C and a relative humidity of 80% ± 2% the day before the test. Accurately weigh the bottle (m1);

[0072] 1.2 Take an appropriate amount of the test sample and spread it flat in the above weighing bottle. The thickness of the test sample is generally about 1mm. Accurately weigh the weight (m2);

[0073] 1.3 Open the weighing bottle and place it with the bottle cap under the above constant temperature and humidity conditions for 24 hours;

[0074] 1.4 Cover the weighing bottle and accurately weigh the weight (m3);

[0075] 1.5Weight gain due to moisture (%) = (m3-m2) / (m2-m1)×100%.

[0076] The corresponding test results are as follows:

[0077]

[0078]

[0079] From the above results, it can be seen that the mixtures of choline chloride and fumed silica in Examples 1-3 have the best fluidity and are in a loose state, and the moisture gain rate decreases with increasing the amount of fumed silica used.

[0080] The amounts of fumed silica used in Comparative Examples 1-2 are lower than the protection scope of the present invention, namely 10% and 20%, respectively. From the results, the appearance and fluidity of the mixture do not meet the use requirements, and the moisture-induced weight gain rate is obviously too high.

[0081] Comparative Examples 3-8 respectively use corn starch, light calcium carbonate, corn cob powder, talcum powder, magnesium stearate and rice bran to replace the fumed silica in Example 1. From the results, the effects of the above replacement components are far inferior to those of fumed silica.

[0082] The mixture of choline chloride and fumed silica in Examples 1-3 can be further mixed with other excipients to prepare choline chloride microcapsule preparations.

[0083] Example 4

[0084] A choline chloride microcapsule preparation, wherein the raw materials for its preparation comprise the following components, calculated by weight percentage: 25% choline chloride, 10.7% fumed silica, 22.15% glyceryl monostearate, 22.15% hydrogenated oil, 10% soybean oil, 5% corn starch, and 5% light calcium carbonate;

[0085] The fineness of the fumed silica is 2.6 μm and the specific surface area is 240 m 2 / g;

[0086] The preparation method of the choline chloride microcapsule preparation comprises the following steps:

[0087] S001. According to the formula, choline chloride and fumed silica were weighed and mixed to obtain a mixed material;

[0088] S002 weighed according to the formula glyceryl monostearate, hydrogenated oil and vegetable oil, 80 ~ 100 ℃ heating to melt, mix well to obtain a mixture;

[0089] S003. The mixed material is added to the mixture and homogenized for 15 minutes; then the binder is added and homogenized for 20 minutes;

[0090] S004. Cooling the homogeneously dispersed material to 90° C., and then granulating it using a low-speed spray granulator to obtain the choline chloride microcapsule preparation.

[0091] Example 5

[0092] A choline chloride microcapsule preparation, wherein the raw materials for its preparation comprise the following components, calculated by weight percentage: 28% choline chloride, 12% fumed silicon dioxide, 20% glyceryl monostearate, 20% hydrogenated oil, 10% soybean oil, 5% corn starch, and 5% light calcium carbonate;

[0093] In this example, the preparation method of the choline chloride microcapsule preparation is the same as that in Example 4.

[0094] Example 6

[0095] A choline chloride microcapsule preparation, wherein the raw materials for its preparation comprise the following components, calculated by weight percentage: 5% choline chloride, 2.14% fumed silica, 36.43% glyceryl monostearate, 36.43% hydrogenated oil, 10% soybean oil, 5% corn starch, and 5% light calcium carbonate;

[0096] In this example, the preparation method of the choline chloride microcapsule preparation is the same as that in Example 4.

[0097] Example 7

[0098] A choline chloride microcapsule preparation, wherein the raw materials for its preparation comprise the following components, calculated by weight percentage: 25% choline chloride, 10.7% fumed silica, 28.15% glyceryl monostearate, 28.15% hydrogenated oil, 3% soybean oil, 2.5% corn starch, and 2.5% light calcium carbonate;

[0099] In this example, the preparation method of the choline chloride microcapsule preparation is the same as that in Example 4.

[0100] Example 8

[0101] A choline chloride microcapsule preparation, wherein the raw materials for its preparation comprise the following components, calculated by weight percentage: 25% choline chloride, 10.7% fumed silica, 17.15% glyceryl monostearate, 17.15% hydrogenated oil, 15% soybean oil, 5% corn starch, and 10% light calcium carbonate;

[0102] In this example, the preparation method of the choline chloride microcapsule preparation is the same as that in Example 4.

[0103] Example 9

[0104] A choline chloride microcapsule preparation, wherein the raw materials for its preparation include the following components by weight percentage:

[0105] Choline chloride 25%, fumed silica 10.7%, glyceryl monostearate 14.77%, hydrogenated oil 29.53%, soybean oil 10%, corn starch 5%, light calcium carbonate 5%;

[0106] In this embodiment, the preparation method of the choline chloride microcapsule preparation is the same as that of Example 4.

[0107] Example 10

[0108] A choline chloride microcapsule preparation, by weight percentage, its preparation raw materials include the following components:

[0109] Choline chloride 25%, fumed silica 10.7%, glyceryl monostearate 29.53%, hydrogenated oil 14.77%, soybean oil 10%, corn starch 5%, light calcium carbonate 5%;

[0110] In this embodiment, the preparation method of the choline chloride microcapsule preparation is the same as that of Example 4.

[0111] Example 11

[0112] A choline chloride microcapsule preparation, by weight percentage, its preparation raw materials include the following components:

[0113] Choline chloride 25%, fumed silica 10.7%, glyceryl monostearate 22.15%, hydrogenated oil 22.15%, sunflower seed oil 10%, corn starch 5%, light calcium carbonate 5%;

[0114] In this embodiment, the preparation method of the choline chloride microcapsule preparation is the same as that of Example 4.

[0115] Example 12

[0116] A choline chloride microcapsule preparation, by weight percentage, its preparation raw materials include the following components:

[0117] Choline chloride 25%, fumed silica 10.7%, glyceryl monostearate 22.15%, hydrogenated oil 22.15%, castor oil 10%, corn starch 5%, light calcium carbonate 5%;

[0118] In this embodiment, the preparation method of the choline chloride microcapsule preparation is the same as that of Example 4.

[0119] Example 13

[0120] A choline chloride microcapsule preparation, by weight percentage, its preparation raw materials include the following components:

[0121] Choline chloride 25%, fumed silica 10.7%, glyceryl monostearate 17.15%, hydrogenated oil 17.15%, castor oil 5%, sunflower oil 5%, soybean oil 5%, corn starch 5%, light calcium carbonate 10%;

[0122] In this example, the preparation method of the choline chloride microcapsule preparation is the same as that in Example 4.

[0123] Example 14

[0124] A choline chloride microcapsule preparation, wherein the raw materials for its preparation include the following components by weight percentage:

[0125] Choline chloride 25%, fumed silica 10.7%, glyceryl monostearate 22.15%, hydrogenated oil 22.15%, soybean oil 10%, light calcium carbonate 10%;

[0126] In this example, the preparation method of the choline chloride microcapsule preparation is the same as that in Example 4.

[0127] Example 15

[0128] A choline chloride microcapsule preparation, wherein the raw materials for its preparation include the following components by weight percentage:

[0129] Choline chloride 25%, fumed silica 10.7%, glyceryl monostearate 22.15%, hydrogenated oil 22.15%, soybean oil 10%, corn starch 10%;

[0130] In this example, the preparation method of the choline chloride microcapsule preparation is the same as that in Example 4.

[0131] Comparative Example 9

[0132] A choline chloride microcapsule preparation, wherein the raw materials for its preparation comprise the following components, calculated by weight percentage: 30% choline chloride, 12.8% fumed silicon dioxide, 18.6% glyceryl monostearate, 18.6% hydrogenated oil, 10% soybean oil, 5% corn starch, and 5% light calcium carbonate;

[0133] The viscosity is too high during preparation and cannot be dispersed.

[0134] Comparative Example 10

[0135] A choline chloride microcapsule preparation, wherein the raw materials for its preparation comprise the following components, calculated by weight percentage: 25% choline chloride, 10.7% fumed silicon dioxide, 14.65% glyceryl monostearate, 14.65% hydrogenated oil, 10% soybean oil, 12.5% ​​corn starch, and 12.5% ​​light calcium carbonate;

[0136] The viscosity is too high during preparation and it is difficult to disperse.

[0137] Comparative Example 11

[0138] A choline chloride microcapsule preparation, wherein the raw materials for its preparation comprise the following components, calculated by weight percentage: 25% choline chloride, 10.7% fumed silicon dioxide, 17.15% glyceryl monostearate, 17.15% hydrogenated oil, 20% soybean oil, 5% corn starch, and 5% light calcium carbonate;

[0139] In this comparative example, the preparation method of the choline chloride microcapsule preparation is the same as that in Example 4.

[0140] Comparative Example 12

[0141] A choline chloride microcapsule preparation, which differs from Example 1 in that ordinary silicon dioxide is used instead of fumed silicon dioxide;

[0142] The passing rate of the ordinary silicon dioxide through a 180 μm test sieve is greater than 99%.

[0143] Comparative Example 13

[0144] A choline chloride microcapsule preparation, which differs from Example 1 in that precipitated hydrated silicon dioxide is used instead of fumed silicon dioxide;

[0145] The precipitated hydrated silica all passed through a 150 μm test sieve, with a specific surface area of ​​190 m 2 / g.

[0146] The granulation rate, microcapsule embedding rate and microcapsule moisture-inducing weight gain rate of Examples 4-15 and Comparative Examples 9-13 were measured.

[0147] Among them, the test method of granulation rate is as follows:

[0148] Microcapsule particle size requirements: granular, non-agglomerated, good fluidity, and must pass the No. 2 standard pharmacopoeia sieve;

[0149] Microcapsule granulation rate (%) = total amount of microcapsules meeting the particle size requirements / total material input amount × 100%.

[0150] The test method for microcapsule embedding efficiency is as follows:

[0151] Accurately weigh the prescribed amount of choline chloride (accurate to 0.0001 g) and determine the dissolution rate using the basket method according to the 2020 edition of the Veterinary Pharmacopoeia of the People's Republic of China. The basket screen is 200 mesh and purified water is used as the release medium.

[0152] Accurately weigh approximately 2.0000-4.0000 g of sample and place it in a rotating basket. At a release medium temperature of 37±0.5°C, accurately add 1000 ml of release medium to each dissolution cup. Stir at a release medium temperature of 37±0.5°C at a speed of 100 r / min for 2 minutes. Then stop stirring, remove the rotating basket, and accurately pipette 20-100 ml of the sample solution (control the mass of the precipitate to be 0.1-0.2 g) into a tall beaker as the test solution. Determine the choline chloride microcapsule content according to the Reinecke salt gravimetric method to obtain the external drug content (G) of the microcapsule sample.

[0153] Accurately weigh approximately 2.0000 g of sample and place it in a 250 ml stoppered conical flask. Add 70 ml of water and shake well. Heat in a water bath at approximately 70°C for 30 min. Ultrasonic disperse in an ultrasonic cleaner at 65°C for 10 min. After cooling to room temperature, transfer the solution to a 250 ml volumetric flask, dilute to the mark with water, shake well, filter with dry filter paper and a funnel, discard the initial filtrate, and transfer 25.00 ml of the subsequent filtrate to a 250 ml tall beaker. Determine the choline chloride microcapsule content according to the Reinecke salt gravimetric method to obtain the total content of the microcapsule sample (W).

[0154] The microcapsule embedding rate was calculated based on the obtained drug content outside the microcapsule and the total content of the microcapsule sample. The calculation formula of the microcapsule embedding rate was: microcapsule embedding rate = (WG) / W×100%, where W is the total content of the sample and G is the drug content outside the sample.

[0155] The corresponding test results of Examples 4-15 and Comparative Examples 9-13 are as follows:

[0156]

[0157]

[0158] From the above results, it can be seen that the components of the choline chloride microcapsule preparations of Examples 4-8 are well dispersed after mixing, the granulation rate and microcapsule embedding rate are high, and the microcapsule moisture-inducing weight gain rate is low.

[0159] In Comparative Example 9, the amount of choline chloride used was greater than the protection scope of the present invention, and the viscosity was too high and the dispersion could not be achieved during the mixing of the components.

[0160] In Comparative Example 10, the total amount of starch and light calcium carbonate is greater than the protection scope of the present invention, and the viscosity is too high and the dispersion cannot be achieved when the components are mixed.

[0161] In Comparative Example 11, the amount of soybean oil used was greater than the protection scope of the present invention, and stratification occurred when the components were mixed, indicating that excessive soybean oil should not be used.

[0162] Comparative Examples 12 and 13, respectively, used conventional silica and precipitated hydrated silica instead of fumed silica. Although the choline chloride microcapsule preparations produced in Comparative Examples 12 and 13 had higher granulation rates than some of the examples, their microcapsule embedding efficiency was inferior to that of Examples 4-15. Furthermore, their microcapsule weight gain due to moisture absorption was also much higher than that of Examples 4-15. This demonstrates that the use of fumed silica can effectively increase the microcapsule embedding efficiency and reduce the microcapsule weight gain due to moisture absorption.

[0163] Comparative Example 14

[0164] A choline chloride preparation comprises the following raw materials, calculated by weight percentage: 25% choline chloride, 10.7% fumed silicon dioxide, 32.15% glyceryl monostearate, and 32.15% hydrogenated oil.

[0165] Comparative Example 15

[0166] A choline chloride preparation comprises the following raw materials, calculated by weight percentage: 25% choline chloride, 10.7% fumed silicon dioxide, 42.87% glyceryl monostearate, and 21.43% hydrogenated oil.

[0167] Comparative Example 16

[0168] A choline chloride preparation comprises the following raw materials, calculated by weight percentage: 25% choline chloride, 10.7% fumed silicon dioxide, 21.43% glyceryl monostearate, and 42.87% hydrogenated oil.

[0169] Comparative Example 17

[0170] A choline chloride preparation comprises the following raw materials, calculated by weight percentage: 25% choline chloride, 10.7% fumed silicon dioxide, and 64.3% hydrogenated oil.

[0171] Comparative Example 18

[0172] A choline chloride preparation comprises the following raw materials, calculated by weight percentage: 25% choline chloride, 10.7% fumed silicon dioxide, and 64.3% glyceryl monostearate.

[0173] Comparative Example 19

[0174] A choline chloride preparation comprises the following raw materials, calculated by weight percentage: 25% choline chloride, 10.7% fumed silicon dioxide, and 64.3% stearic acid.

[0175] Comparative Example 20

[0176] A choline chloride preparation comprises the following raw materials, calculated by weight percentage: 25% choline chloride, 10.7% fumed silicon dioxide, and 64.3% PEG4000.

[0177] Comparative Example 21

[0178] A choline chloride preparation comprises the following raw materials, calculated by weight percentage: 25% choline chloride, 10.7% fumed silicon dioxide, and 64.3% paraffin.

[0179] Comparative Example 22

[0180] A choline chloride preparation comprises the following raw materials, calculated by weight percentage: 25% choline chloride, 10.7% fumed silicon dioxide, and 64.3% PEG6000.

[0181] Comparative Example 23

[0182] A choline chloride preparation comprises the following raw materials, calculated by weight percentage: 25% choline chloride, 10.7% fumed silicon dioxide, and 64.3% hydrogenated castor oil.

[0183] Comparative Example 24

[0184] A choline chloride preparation comprises the following raw materials, calculated by weight percentage: 25% choline chloride, 10.7% fumed silicon dioxide, and 64.3% sucrose fatty acid ester.

[0185] Comparative Example 25

[0186] A choline chloride preparation comprises the following raw materials, calculated by weight percentage: 25% choline chloride, 10.7% fumed silicon dioxide, and 64.3% edible balsam ester.

[0187] The choline chloride preparations of Comparative Examples 14-25 were prepared as follows: glyceryl monostearate, hydrogenated oil, paraffin, stearic acid, or a carrier such as PEG4000 were weighed according to the formula, melted in a water bath, and the melting rates were compared. A mixture of choline chloride and fumed silica was then added and homogenized. The dispersion and stratification of the materials after homogenization were observed, and the embedding efficiency and moisture-induced weight gain were measured.

[0188] The dispersion time and embedding efficiency of Comparative Examples 14-25 were measured, and the results were as follows:

[0189]

[0190] Comparisons between Comparative Examples 14-25 revealed that sucrose fatty acid esters, edible balsam, and hydrogenated castor oil as carriers resulted in long melting times (greater than 60 minutes), excessive viscosity, poor choline chloride embedding, and delamination after standing for 30 minutes. Using polyethylene glycol 4000, polyethylene glycol 6000, stearic acid, and paraffin as carriers resulted in a system with a moisture gain greater than 15.0%, indicating high moisture absorption. Therefore, polyethylene glycol 4000, polyethylene glycol 6000, stearic acid, and paraffin were also unsuitable as carriers for choline chloride microcapsule preparations.

[0191] Comparing Comparative Examples 14-18 with Comparative Examples 19-25, it can be found that when glyceryl monostearate and hydrogenated oil are used in combination, the dispersion time of each component in the system is faster and the embedding rate is higher.

[0192] Further comparison of Comparative Examples 14-18 shows that when the ratio of glyceryl monostearate to hydrogenated oil is 1:1, the dispersion time of each component is the shortest and the embedding efficiency is the highest.

[0193] Further comparison of Comparative Example 14 with Examples 4-15 demonstrates that when other components are further added to the excipients, the embedding efficiency of the microcapsules can be further significantly improved.

[0194] In order to further verify the performance of the choline chloride microcapsule preparation of the present invention, three batches of choline chloride microcapsule preparation were produced according to the formulation and preparation method of Example 4, and corresponding performance tests were carried out.

[0195] 1. Content uniformity test

[0196] The uniformity test is carried out in accordance with the content uniformity test method in the appendix of the Veterinary Pharmacopoeia of the People's Republic of China (2020 edition). Ten samples are taken from each batch for inspection. The corresponding inspection results are as follows:

[0197]

[0198]

[0199] Note: Conclusion standard: Mixing uniformity should be ≤15.0.

[0200] The above results show that the content uniformity of the choline chloride microcapsule preparation provided by the present invention meets the requirements and has uniform properties.

[0201] 2. Stability Test

[0202] The stability test refers to the long-term test method in Appendix 9001 of the 2020 edition of the Veterinary Pharmacopoeia of the People's Republic of China. The samples are placed at a temperature of 25±2°C and a humidity of 60%±10%. The properties and content of the samples are tested at 0, 3, 6, 9, 12, 18, and 24 months respectively;

[0203] Three batches of samples were tested for stability. These three batches of samples corresponded to the choline chloride microcapsule preparations of Examples 4-6, respectively.

[0204] The results of the stability investigation are as follows:

[0205]

[0206]

[0207] The above results show that the content of the choline chloride microcapsule preparation provided by the present invention remains stable after being stored for 36 months, with little decrease, and the moisture content also meets the requirements, indicating that it is not easy to absorb moisture.

[0208] 3. Dissolution Test

[0209] The dissolution test was conducted in accordance with the dissolution and release method in Appendix 0931 of the 2020 edition of the Veterinary Pharmacopoeia of the People's Republic of China. Appropriate amounts of the test product and reference product were weighed and placed in rotating baskets (200-mesh screen). A hydrochloride solution with a pH of 2.0 was used as the release medium (referring to the pH test results of chicken gizzard). The choline chloride microcapsule content was determined at 10, 20, 30, 40, 50, 60, 90, 120 minutes, and 6 hours. The dissolution rate of the solution at each time point was calculated by calculating the percentage of choline chloride content in the solution to the labeled amount.

[0210] In this test, commercially available choline chloride microcapsules (Shenzhen Biotechnology Co., Ltd., batch number 498Y21) and commercially available silicon-type choline chloride (Liaoning Biotechnology Co., Ltd., batch number 2021032371) were used as control substances, and the choline chloride microcapsule preparation of Example 4 was used as a test substance.

[0211] The corresponding test results are as follows:

[0212]

[0213] Poultry food typically stays in the digestive tract for 5-6 hours and in the gizzard for about 30 minutes. The above results show that currently available silicon-based choline chloride is almost completely released after 20 minutes in a solution of simulated gastric fluid. However, the choline chloride microcapsules provided by the present invention have a solubility of approximately 30% in 20 minutes and 100% in 60 minutes, making them suitable for the poultry digestive system. In contrast, commercially available choline chloride microcapsules have a release rate of only 12.35% in 6 hours, hindering poultry digestion and absorption. The choline chloride microcapsules of the present invention are adapted to the physiological characteristics of poultry, allowing the particles to be slowly released within 30 minutes in a gastric acid environment, thereby improving the absorption and utilization rate of choline chloride.

[0214] 4. Feeding test

[0215] The choline chloride microcapsule preparation prepared according to Example 4, commercially available choline chloride microcapsules (Shenzhen Biotechnology Co., Ltd., batch number 498Y21), and commercially available silicon-type choline chloride (Liaoning Biotechnology Co., Ltd., batch number 2021032371) were used to feed broiler chickens respectively;

[0216] The experimental method is as follows: 600 healthy one-day-old broiler chickens with similar body weight differences were randomly selected through orthogonal experimental design and randomly divided into four treatment groups. Each treatment group had five replicates, with 30 chickens in each group. Of these, 20 were used as regular experimental subjects for dynamic observation and 10 were used for full observation. The experimental period was 28 days.

[0217] According to the Ministry of Agriculture Announcement No. 2625 - Specifications for the safe use of feed additives, choline chloride is added to the feed at a dosage of 1300 mg / kg;

[0218] The experimental groups and treatment methods are shown in the following table

[0219]

[0220] The broilers were weighed in the morning on an empty stomach at 1 day and 28 days of age, and the weight, feed intake, and health status of each group were recorded daily. Finally, the daily weight gain, average daily feed intake, and feed-to-weight ratio of each group were calculated and analyzed.

[0221] The corresponding test results are as follows:

[0222]

[0223] Note: In the above data table, in the same row of data, different lowercase letters in the columns indicate significant differences (P﹤0.05), and the same lowercase letters indicate no significant differences.

[0224] From the above results, it can be seen that the average daily feed intake of each test group is close to that of the control group, and the difference is not significant (p>0.05); the average daily gain of the test group three is higher than that of the test group one and the control group, and the difference is not significant (p>0.05), higher than that of the test group two, and the difference is significant (p<0.05); the feed conversion ratio of the test group three is lower than that of the test group one and the control group, and the difference is not significant (p>0.05), lower than that of the test group two, and the difference is significant (p<0.05);

[0225] The above results show that after normal feeding of the chlorocholine microcapsules of the present application, the average daily gain of the broiler chickens increases, the feed conversion ratio significantly decreases, and the feed conversion ratio increases; the average daily gain of the broiler chickens fed with the commercially available chlorocholine microcapsules is lower than that of the control group, and there is no significant difference in the feed conversion ratio.

[0226] Five, the destructive effect of chlorocholine preparations on vitamins

[0227] The commercially available silicon type chlorocholine (Liaoning Biotechnology Co., Ltd., batch number 2021032371) and the chlorocholine microcapsules prepared in Example 4 were mixed with the compound premix feed III (product name: Gannengsufu) produced by the Jingdian Company to prepare compound premixes containing different types of chlorocholine preparations, and then the test was carried out, two replicates were set for each group, the addition amount of chlorocholine in the feed was 1300 mg / kg, and the actual addition amount of the two chlorocholine products was calculated according to the chlorocholine content proportion of the samples (the content of commercially available silicon type chlorocholine was 49.94%, and the content of chlorocholine microcapsules was 23.69%). The compound premixes prepared in each group were stored at 20℃±1℃ and relative humidity of 70%±2% for 0, 1, 2, 4, and 6 months, and the vitamin A content and moisture were measured.

[0228] The explanations of each test group are as follows:

[0229] Control group: compound premix without adding chlorocholine;

[0230] Test group one: compound premix with commercially available silicon type chlorocholine;

[0231] Test group two: compound premix with chlorocholine microcapsules prepared in Example 4;

[0232] The corresponding test results are as follows:

[0233]

[0234]

[0235] Note: The column data with different lowercase letters indicate significant difference (P<0.05), and the same or no letters indicate no significant difference (P>0.05).

[0236] The results in the table above demonstrate that commercially available silicon-based choline chloride significantly impacts the stability of vitamin A in the premix, with a six-month decline of 24.82%. While the vitamin A content of the composite premix prepared with the choline chloride microcapsules of the present invention also decreases with extended storage, the vitamin A loss in Experimental Group 2 was significantly lower than that in the composite premix prepared with commercially available silicon-based choline chloride over the same period. Vitamin A loss is directly related to the hygroscopicity of the product. The microcapsule formulation in Experimental Group 2 significantly reduced the hygroscopicity of the product, thereby minimizing the destructive effects of choline chloride on vitamin A in the composite premix.

[0237] The above results comprehensively prove that the choline chloride microcapsules of the present invention have good effects of promoting the growth and development of broiler chickens, reducing feed consumption, and reducing the destructive effect of choline chloride preparations on vitamins.

[0238] It is understandable that those skilled in the art can make equivalent substitutions or changes based on the technical solution and inventive concept of the present invention, and all these changes or substitutions should fall within the scope of protection of the claims attached to the present invention.

Claims

1. A choline chloride microcapsule preparation, characterized in that: The preparation raw materials include the following components in percentage by weight: 5% to 28% of choline chloride, 2% to 12% of fumed silica, 3% to 15% of vegetable oil, 5% to 20% of binder, and the balance is glyceryl monostearate and hydrogenated oil; the mass ratio of the glyceryl monostearate to the hydrogenated oil is (2 to 0.5):1; the binder includes one or more of corn starch and light calcium carbonate; and the mass ratio of the fumed silica to choline chloride is greater than 3:

7.

2. The choline chloride microcapsule preparation according to claim 1, wherein The mass ratio of the glyceryl monostearate to the hydrogenated oil is 1:

1.

3. The choline chloride microcapsule preparation according to claim 1, characterized in that The particle size of the fumed silica is less than 2.6 μm and the specific surface area is greater than 240 m 2 / g.

4. The choline chloride microcapsule preparation according to claim 1, characterized in that The vegetable oil includes one or more of soybean oil, sunflower oil and castor oil.

5. The choline chloride microcapsule preparation according to claim 1, characterized in that Its particle size is 200 to 900 μm.

6. A method for preparing a choline chloride preparation, characterized in that: The method for preparing the choline chloride microcapsule preparation according to any one of claims 1 to 5 comprises the following steps: Choline chloride and fumed silica were weighed according to the formula, and mixed evenly to obtain a mixed material; Weigh glyceryl monostearate, hydrogenated oil, and vegetable oil according to the formula, heat to melt, and mix evenly to obtain a mixed solution; Add the mixed material into the mixed liquid and homogenize and disperse for 10 to 30 minutes; then add the adhesive and homogenize and disperse for 10 to 30 minutes; The homogeneously dispersed material is spray granulated to obtain the choline chloride microcapsule preparation.

7. The method for preparing the choline chloride preparation according to claim 6, wherein The temperature during the spray granulation is 80-90°C.

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