Patent Description:
Carotenoids are widely present in nature. Wachenroder firstly crystallized and separated carbohydrate pigments from carrot roots in <NUM>, and named "Carotene". Afterwards Berzelius separated and extracted yellow polar pigments from autumn leaves, and named "Xanthophylls". With the development of biophysical technology, people separated a series of natural pigments through chromatography, and named "Carotenoids". They have common chemical structure characteristics. The center of the molecular structure is polyisoprene long chains with polyene bonds. And many derivatives are produced by means of terminal cyclization, addition of oxygen, rotation and isomerization of bonds. Currently, there are more than <NUM> known members of carotenoids.

Carotenoids belong to terpenoid compounds and are the general name of Carotene and Xantheophylls. Carotenoids of the hydrocarbon family without containing oxygen atoms in their molecule are called carotenoids. Derivatives and their esters containing oxygen functional group (such as hydroxyl, epoxy, ketone, hyderoxyl, etc) in the molecule are called xanthophylls.

There are hundreds of carotenids in nature, but there are six main kinds of carotenoids that are relatively common and relatively large in number such as β-carotene, astaxanthin, canthaxanthin, lutein, zeaxanthin and lycopene. With the development of biotechnology and synthetic technology, many kinds of these six carotenoids come from multiple sources. For example, β-carotene may be obtained by fully synthetic processes, fermentation or breeding salt alga and also may be extracted from natural products such as palm oil; lycopene may be obtained by being extracted or fermented from natural source such as tomato, or fully synthetic processes. Among these carotenoids, lutein is an exception. It may only be extracted from plants and may not be artificially synthesized (except at a high cost) due to the structural asymmetry.

These six types of carotenoids are relatively similar in molecular structure, belong to a class of hydrocarbons and their oxidized derivatives. They consist of eight isoprenoid units, but there are slight differences in the two terminal six-membered rings. The presence of multiple conjugated double bond chromophore groups in the molecular structure of carotenoids not only endows it with a unique absorption region (blue region) in the ultraviolet-visible region. So its crystal or solution has a very brilliant red, orange or yellow under visible light. The displayed color has a certain change due to different concenations. Carotenoids have long been regarded as a kind of pigments. In nature, the autumn leaves and various colorful animals give us an incomparable beauty. At the same time, these conjugated double bonds also make carotenoids become a good free radical quencher with strong antioxidant activity, and can effectively block the chain radical reaction in the cell, and thus have a variety of unique and important physiological function.

The most widespread and important carotenoids is beta-carotene. It is a good source of provitamin A, and according to the amount of vitamin A in the body, beta-carotene may be automatically broken down and supplement the deficiency of vitamin A. Lutein and zeaxanthin are isomers. The only difference between lutein and zeaxanthin is the position of a double bond at the end of one of the six-membered rings. They are the only carotenoid that exists in the retina of human eyes. They are selectively deposited in the macular region and the entire retina, with the highest density around the fovea of the macula, and gradually decreases in the peripheral part of the retina. These macular pigments can effectively prevent from oxidation on the retina and have an important protective effects on the retina. Lycopene has good effects on the prevention and treatment of prostate diseases. Astaxanthin also has important anti-tumor and cancer prevention effects. This is why many epidemiological studies have proved that regular and regular consumption of fruits and vegetables containing carotenoids can reduce risks of chronic diseases, including cardiovascular diseases, and has the beneficial effects of preventing from cancers.

Therefore, nutritionists strongly recommend the addition and preventive intake of antioxidants, vitamins and carotenoids, and the food and drug markets provide consumers with a large number of such "cell protectants".

However, the unique molecular structure characteristic of carotenoids makes it have very poor solubility: it doesn't dissolve in water at all and has very little solubility in oil. It also leads to poor bioavailability of carotenoid crystals in the body, and makes them difficult to absorb and use. Moreover, there are many double bonds in its molecular structure, and thus it is easy to be oxidized and degraded in air, heat and light, and has poor stability. In order to achieve the purpose of improving its stability and bioavailability, a conventional method is to prepare carotenoid crystals into formulations such as water-soluble suspensions, or micro capsule dry powder/particles with good stability, good water solubility and high bioavailability. In these preparations, carotenoid molecules wrapped in water-soluble colloid not only can improve the solubility and dispersion characteristics of carotenoid molecules, but also may be soluble in water, but also can effectively isolate the contact of unfavorable factors such as oxygen and light with the carotenoid molecules, and can enhance its stability. In addition, it is beneficial to the absorption and utilization in the human body and improves its bioavailability because the carotenoid molecule can be dispersed in nano or micron.

There are several steps involved in the preparation of carrot microcapsules: <NUM>. to dissolve water-soluble colloids such as gelatin, modified starch and fillers such as sucrose, maltodextrin, etc. in water to obtain an aqueous phase; <NUM>. to make carotenoid crystals and antioxidants dissolved, melted, or dispersed to form an oil phase by a certain way; <NUM>. to fully mix the aqueous phase and the oil phase to form an oil-in-water dispersive emulsion. According to needs, the dispersible emulsion can be granulated to obtain carotenoid microcapsule dry powder or particles. Among these steps, the most difficult is to prepare the oil phase. Mainly reasons are poor solubility of carotenoid crystal, high melting point, easy degradation and isomerization denaturation under high temperature caused by the characteristics. Nevertheless, there are three conventional methods for preparing carotenoid oil phase: <NUM>. to dissolve carotenoids in an organic solvent to form an oil phase, and then mix with the aqueous phase to emulsify, and then remove the organic solvent. But the removal of organic solvents will not be complete. Especially, it is more difficult to remove organic solvents cleanly due to the presence of emulsifiers in the emulsion. In addition, some of the all-trans carotenoids may be isomerized into cis-isomers, thereby reducing their biological activity during the process of carotenoid dissolution. to dissolve carotenoid crystals at a high temperature of <NUM> to obtain an oil phase. A significant disadvantage of the method is that a large proportion of carotenoid molecules will degrade or undergo isomerization from all-trans to cis at such a high temperature, thereby greatly reducing its biological activity, and finally resulting in color change of carotenoid solution. to mix carotenoid crystals with vegetable oil and then grind. The advantage of the method is that no organic solvents are used in the process, and thus there are no associated safety concerns. As the carotenoid molecules are not subjected to the high temperature process, a high content of the product is the trans isomer. However, an obvious disadvantage of the approach is that it is difficult to grind carotenoid crystals to a sufficient fineness by conventional methods, thereby resulting in low bioavailability of the final product.

<CIT>, <CIT>, <CIT> use organic solvents to dissolve carotenoids to obtain an oil phase, and then mix with water to emulsify, and remove or not remove the organic solvent to obtain a carotenoid microcapsule preparation.

<CIT> introduces the preparation of carotenoid microcapsule preparations by the melting method. This would result in the final product becoming yellowish in color due to some carotenoids degrading and isomerizing in the high temperature process, thereby reducing the biological activity.

<CIT> discloses a water-soluble suspension comprising carotenoids, wherein in addition to using the solvent method, a grinding machine is also used to prepare an oil phase. However, the oil phase passes through many long cycles in order to achieve the desired fineness. This is detrimental to energy consumption and the stability of carotenoid molecules in the production process.

<CIT> discloses a method for producing a water-soluble carotenoid microcapsule solution by grinding method. In the process, a large amount of alcoholic solvent such as glycerin, propylene glycol, etc. have to be added to the formula to reduce the viscosity of the oil phase during grinding in order to grind the carotenoid to corresponding fineness. This is detrimental to the improvement of active ingredient content and stability of the final product.

<CIT> describes a method for preparing red carotene preparations, in particular, using a nano grinding machine to grind a carotenoid colloidal solution. In order to make carotenoid crystals achieve nano-dispersion in this process, on the one hand, it needs cyclical grinding, but the grinding time is very long and the pressure is very high; on the other hand, the viscosity of the solution requires minimization during grinding. Thus a large amount of water must be added before grinding (usually controlling the solid content to be less than <NUM>% during grinding). This is detrimental to the subsequent spray drying granulation process.

<CIT> describes the preparation of a water-soluble carotenoid microcapsule solution, in particular using a grinding machine for grinding after mixing part of the aqueous phase with carotenoid crystals, and then adding part of the embedding wall material, filler, antioxidants, etc. under stirring of a reactor to form a secondary embedding. In this process, the carotenoid particle size of the final product is relatively coarse, reaching <NUM> because it only goes through one grinding. This is not enough to improve its bioavailability in humans.

In a word, in the previous production of carotenoid microcapsule preparations by grinding method, a key point is how to effectively reduce the particle size of the product to improve its bioavailability. Especially the particle size of the product is more difficult to reduce, if the viscosity of the solution is higher during grinding. In order to reduce the particle size, one method is to grind circularly for a long time. This will not only greatly increase the production energy consumption, but also has a bad effect on the stability of carotenoids. The other method is to add a large amount of water or water-soluble solvents such as isopropanol and propylene glycol to the formulation to reduce the viscosity during grinding. The effect of this method is not very obvious, and it is detrimental to the subsequent spray drying process. Therefore, it is necessary to find a method of carotenoid water-dispersible microcapsule preparation that can effectively reduce the particle size of the ground product and improve its bioavailability and stability.

The present invention provides a preparation method of a carotenoid water-dispersible microcapsule preparation with high bioavailability and high stability, the preparation method comprising the following steps: a) dissolving part of a water-soluble colloid and a filling substance in water to form an aqueous phase; b) adding a carotenoid crystal to the aqueous phase and stirring for dispersion so as to form a dispersion liquid; c) loading the dispersion liquid into a first-stage grinding machine for first grinding to form a first-stage grinding liquid; d) adding the remaining water-soluble colloid and the filling substance to the first-stage grinding liquid, loading same into a second grinding machine for secondary grinding to obtain a second-stage grinding liquid; and e) drying the moisture in the second-stage grinding liquid to obtain carotenoid dry powder or particles. Wherein, according to needs, a carotenoid microcapsule powder or particle is obtained by drying the water content of the grinding nano-level carotenoid dispersion. Conventional drying methods include spray drying process, spray condensation-starch bed fluidized drying process and so on.

In the preferred technical solution of the preparation method of the present invention, preferably, the carotenoid is β-carotene, lutein, lycopene, canthaxanthin, zeaxanthin or astaxanthin; the water-soluble colloid is selected from the group consist of modified starch, gelatin, casein, Arabic gum and soy isolate protein; the filling substance is selected from the group consist of sucrose, maltodextrin and syrup.

In the preferred technical solution of the preparation method of the present invention, preferably, a grinding medium in the first-stage grinding machine and the second-stage grinding machine is a food-grade sanitary material, including <NUM> stainless steel, tungsten carbide, zirconia, and yttrium stabilized zirconia beads. More preferably, the bead size of the grinding medium in the first-stage grinding machine is <NUM>-<NUM>; the bead size of the grinding medium in the second-stage grinding machine is <NUM>-<NUM>.

In the preferred technical solution of the preparation method of the present invention, preferably, in step a), an amount of the water-soluble colloid added is <NUM>-95wt. % of the total amount of water-soluble colloid, and an amount of the filling substance added is <NUM>-95wt. % of the total filling substance.

In the preferred technical solution of the preparation method of the present invention, preferably, in step b), the solid content of the dispersion is <NUM>-<NUM> wt.

In the preferred technical solution of the preparation method of the present invention, preferably, in step c), performing the first grinding until the particle size of the carotenoid crystal is <NUM>-<NUM>, and then stop grinding to obtain a first grade grinding liquid.

In the preferred technical solution of the preparation method of the present invention, preferably, in step d), the amount of water-soluble colloid added for the second time is <NUM>-5wt. % of the total amount of water-soluble colloid.

In the preferred technical solution of the preparation method of the present invention, preferably, in step d), the amount of the filling substance added for the second time is <NUM>-5wt. % of the total filling substance in the formula.

In the preferred technical solution of the preparation method of the present invention, preferably, in step d), performing the second grinding until the particle size of the carotenoid crystal is <NUM>-<NUM>, and then stop grinding to obtain a second grade grinding liquid.

In the preferred technical solution of the preparation method of the present invention, preferably an antioxidant is added before the first grinding, and the antioxidant is selected from a group consisting of synthetic tocopherol, natural vitamin E, ascorbic acid and ascorbic palmitate. More preferably, the amount of the antioxidant added is <NUM>%-<NUM>. % of the mass of the final product.

In the preferred technical solution of the preparation method of the present invention, preferably, the content of carotenoids in the water-dispersible microcapsule preparation is <NUM>-30wt.

In short, the preparation method of the present invention is to dissolve part of the water-soluble colloid and the filling substance in water to form an aqueous phase, to disperse the carotenoid crystals in the aqueous phase through the first grinding, and then add the remaining water-soluble colloid and filling substance, go through the second grinding, to obtain a carotenoid nano-dispersed water-soluble suspension. According to needs, the water-soluble suspension can be spray drying process or spray condensation to obtain carotenoid microcapsule dry powder or particles. According to needs, a carotenoid microcapsule powder or particle is obtained by spray drying or spray condensation for water-soluble suspension.

In the process, using two-stages grinding machine for grinding can effectively complete the nanoscale dispersion of carotenoids in a short time. Ball diameter of grinding medium in two-stages grinding machine is different. , The grinding media ball in the first-stage grinding machine has a coarse particle size (the particle size of the ball is <NUM>-<NUM>) to achieve the initial grinding effect, and after the first stage grinding, the particle diameter reaches about <NUM>. The grinding media ball in the second-stage grinding machine has a fine particle size (the particle size of the ball is <NUM>-<NUM>) to carry on the fine grinding, and finally achieve nanoscale dispersion, The particle size is generally less than <NUM>, more preferably <NUM>-<NUM>. The combination of two stage ball mill can make the carotenoid in the final product reach the effect of nano dispersion in a short time, and make the grinding time greatly reduced. The conventional single-stage circular grinding is up to more than <NUM> hours, shortened to <NUM>-<NUM> hours.

Coated water-soluble colloid, filling substances and other substances in the aqueous phase should be separately added before two grinding, considering that the grinding effect is closely related to the viscosity of the solution during grinding. The lower the viscosity is, the better the grinding is. On the contrary, the higher the viscosity is, the more difficult it is to crush particles during grinding, the longer it takes, the more energy it consumes. In other words, during the preparation of aqueous phase before the first grinding, only part of water-soluble colloid and filling substance is added and mixed and dispersed with carotenoid crystals. The solution viscosity is low during grinding because the solid content is relatively low. When grinding, it is easier to achieve rough grinding effect (the particle size is about <NUM>). Afterwards, enter the second stage of grinding, the remaining water-soluble colloid and filling substance are added before entering the second stage of grinding. At this time, the particle size in the solution has been small, reaching micron level. At this time, adding solid matter has little effect on the viscosity of the grinding solution. Moreover, when the particles in the solution are small, the viscosity has little effect on the grinding effect, and it is easy to further disperse the particle size in nanometer scale in a short time.

Of course, for different carotenoid crystals and the same carotenoid crystals, but in different concentrations, the solids content (or viscosity) required for grinding is different. When the concentration of carotenoids in the final product is low (the amount of carotenoid crystals is small), the solid concentration can be higher in one grinding. On the contrary, when the amount of carotenoid crystal is large, in order to achieve the ideal grinding effect, the solid content in the grinding solution should be lower. For example, it is found that the carotenoid content in the final product is about <NUM>% after extensive experiments. <NUM>% of the total amount of water-soluble colloid and filling substance can be put into one grinding, and the solid content can reach <NUM>%. When the final product contains <NUM>% carotenoids, the solids content in a single grinding is only about <NUM>%. In the case of the lower solid content, it can ensure a lower viscosity during one grinding, so as to achieve better grinding effect.

Adding water-soluble colloid in batches has another unexpected effect. That is, it can make the carotenoid in the final product form a secondary embedding, thereby greatly enhances the stability of the carotenoid content in the final product. The main reason is that the carotenoid crystals continue to form micro powders under the action of grinding medium ball bearings and dispersed in the water-soluble colloidal solution to form micron droplets when the water-soluble colloid and carotenoid crystals are grinded together for the first time. This is the first embedding. Adding water-soluble colloid before the second grinding, the micron dispersed droplets are continuously broken and recombined during grinding to form new nanoscale droplets. In this process, the water-soluble colloids added are re-coated on the surface of the nanodroplets, to form a second embedding. The second embedding has a positive effect on the stability and pressure resistance of the final product.

The grinding machine can be purchased on the market - such as a ball mill, or a sand mill. The main structure is a horizontal placed, rotating around the horizontal axis of the hollow cylinder. The cylinder body is equipped with grinding medium and grinding material. When the cylinder rotates, the medium and the material are lifted and fall down by gravity after reaching a certain height. The movement of the grinding medium causes the material to be crushed by extrusion, friction, impact, grinding stripping, shearing and other effects. The grinding medium in the grinding machine used in the present application process is food-grade sanitary materials, including <NUM> type stainless steel, or tungsten carbide, or zirconia, etc., preferably yttrium-stabilized zirconia beads.

The water-soluble colloids can be purchased on the market, with emulsifying stability of conventional colloid substances, including one or more of modified starch, gelatin, casein, acacia, and soy protein isolate.

The filling substances include one or more of sucrose, malt dextrin and syrup.

Before the first grinding, only part of the water-soluble colloid and filling substance are added to the aqueous phase in order to reduce the solid content in the solution during grinding and reduce the viscosity. The first addition of the water-soluble colloids and the filling substances account for <NUM>%-<NUM>% of the total water-soluble colloids and filling substances in the formula respectively.

The solid content is <NUM>-<NUM>% before the first grinding.

The particle size of the grinding medium in the grinding machine is <NUM>-<NUM> during the first grinding.

After taking out the micron dispersion obtained from the first grinding, the remaining water-soluble colloids and filling substances are added. The remaining water-soluble colloids and filling substances account for <NUM>%-<NUM>% of the total water-soluble colloids and filling substances in the formula respectively, and enter the second stage grinding machine.

During the second grinding, the particle size of the grinding medium balls in the grinding machine is <NUM>-<NUM>.

According to needs, a certain amount of antioxidants such as synthetic tocopherol, natural vitamin E, ascorbic acid, ascorbyl palmitate, BHT, etc. can be added to the formula.

The preparation process for preparing for carotenoid preparation by the process of "second grinding and second embedding" is easy to operate, has a short grinding time, low energy consumption, the droplets in the final product reach a nanoscale dispersion, and have homogeneous dispersion and small particle size spans. Moreover the carotenoid preparation has good stability and is easy to compress into tablets because the carotenoid molecules are embedded twice. Compared with the previous process of the prior art, this process of the present invention has significant advantages.

The following examples are used to further specifically illustrate the present invention, but not limited to the following examples and the range of process parameters in the examples.

Add <NUM> of modified starch (PG <NUM>, purchased from Ingredion) and <NUM> of sucrose completely dissolve in <NUM> of hot water at <NUM> to form a water-soluble colloid solution. Add <NUM> of beta-carotene crystals and <NUM> of synthetic tocopherols to the water-soluble colloid solution (solid content <NUM>%), and then carry out a first grinding in a Sunller Machine, the particle size of the yttrium stabilized zirconia beads of the grinding medium is <NUM>-<NUM>, and afterwards carry out sampling and testing after grinding for <NUM>. 3hr, the particle size of beta-carotene particles is <NUM>, and then stop grinding to obtain a first stage grinding liquid.

Add <NUM> of modified starch (PG <NUM>, Ingredion) and <NUM> of sucrose to the first stage grinding liquid, and then stir and disperse, afterwards enter a second Sunller Machine for the second grinding. Here the particle size of the yttrium stabilized zirconia beads of the grinding medium is <NUM>-<NUM>. Carry on sampling and testing after grinding for <NUM>. 2hr, the particle size of the beta-carotene particles is <NUM>, and then stop grinding to obtain a second stage grinding liquid. The grinding liquid has very good water dispersibility. It is transparent red after dispersing in water, wherein the content of the beta-carotene is <NUM>%.

Add <NUM> of gum arabic and <NUM> of maltodextrin completely dissolve in <NUM> of hot water at <NUM> to form a water-soluble colloid solution, and then cool down to <NUM>. Add <NUM> of lutein crystals (wherein <NUM> of lutein crystals, content of <NUM>%, <NUM> of zeaxanthin, content of <NUM>%) and <NUM> of natural vitamin E to the water-soluble colloid solution (solid content <NUM>%), and then carry out a first grinding in a Sunller Machine, the particle size of the yttrium stabilized zirconia beads of the grinding medium is <NUM>-<NUM>, and afterwards carry out sampling and testing after grinding for <NUM>. 0hr, the particle size of lutein particles is <NUM>, and then stop grinding to obtain a first stage grinding liquid.

Add <NUM> of gum Arabic and <NUM> of syrup to the first stage grinding liquid, and then stir and disperse, afterwards enter a second Sunller Machine for the second grinding. Here the particle size of the yttrium stabilized zirconia beads of the grinding medium is <NUM>-<NUM>. Carry on sampling and testing after grinding for <NUM>. 0hr, the particle size of the beta-carotene particles is <NUM>, and then stop grinding to obtain a second stage grinding liquid. The grinding liquid has very good water dispersibility. It is transparent yellow after dispersing in water.

Remove water from the second stage grinding liquid by spray drying method, to obtain lutein microcapsule dry powder, wherein the content of lutein is <NUM>%. The lutein microcapsule dry powder has very good storage stability, and the data of its stability retention rate is shown in Table <NUM>.

Add <NUM> of gelatin and <NUM> of sucrose completely dissolve in <NUM> of hot water at <NUM> to form a water-soluble colloid solution, and then cool down to <NUM>. Add <NUM> of canthaxanthin crystals (content of <NUM>%) and <NUM> of ascorbyl palmitate to the water-soluble colloid solution (solid content <NUM>%), and then carry out a first grinding in a Sunller Machine, the particle size of the yttrium stabilized zirconia beads of the grinding medium is <NUM>-<NUM>, and afterwards carry out sampling and testing after grinding for <NUM>. 5hr, the particle size of canthaxanthin particles is <NUM>, and then stop grinding to obtain a first stage grinding liquid.

Add <NUM> of gelatin and <NUM> of maltodextrin and <NUM> of ascorbic acid to the first stage grinding liquid, and then stir and disperse, afterwards enter a second Sunller Machine for the second grinding. Here the particle size of the yttrium stabilized zirconia beads of the grinding medium is <NUM>-<NUM>. Carry on sampling and testing after grinding for <NUM>. 5hr, the particle size of the canthaxanthin particles is <NUM>, and then stop grinding to obtain a second stage grinding liquid. The grinding liquid has very good water dispersibility. It is transparent red after dispersing in water.

Remove water from the second stage grinding liquid by spray drying method, to obtain canthaxanthin microcapsule dry powder, wherein the content of canthaxanthin is <NUM>%. The canthaxanthin microcapsule dry powder has very good storage stability, and the data of its stability retention rate is shown in Table <NUM>.

Add <NUM> of soy isolate protein, <NUM> of casein protein, <NUM> of syrup and <NUM> of maltodextrin completely dissolve in <NUM> of hot water at <NUM> to form a water-soluble colloid solution, and then cool down to <NUM>. Add <NUM> of lycopene crystals (content of <NUM>%) and <NUM> of synthetic tocopherols and <NUM> of natural vitamin E to the water-soluble colloid solution (solid content <NUM>%), and then carry out a first grinding in a Sunller Machine, the particle size of the tungsten carbide of the grinding medium is <NUM>-<NUM>, and afterwards carry out sampling and testing after grinding for <NUM>. 5hr, the particle size of canthaxanthin particles is <NUM>, and then stop grinding to obtain a first stage grinding liquid.

Add <NUM> of soy isolate protein, <NUM> of casein protein, <NUM> of syrup and <NUM> of maltodextrin to the first stage grinding liquid, and then stir and disperse, afterwards enter a second Sunller Machine for the second grinding, here a grind medium is <NUM> stainless steel, the bead size is between <NUM>-<NUM>. Carry on sampling and testing after grinding for <NUM>. 5hr, the particle size of the lycopene particles is <NUM>, and then stop grinding to obtain a second stage grinding liquid. The grinding liquid has very good water dispersibility. It is transparent red after dispersing in water.

Remove water in the second level grinding liquid by spray-starch flow instant molding method to obtain lycopene microcapsule particles, wherein the lycopene content is <NUM>%. The storage stability of cantharidin particles is very good, and its stability retention rate data is shown in Table <NUM>.

Remove water from the second stage grinding liquid by spray-starch flow instant molding method, to obtain lycopene microcapsule particles, wherein the content of lycopene is <NUM>%. The lycopene microcapsule particles has very good storage stability, and the data of its stability retention rate is shown in Table <NUM>.

Add <NUM> of gelatin and <NUM> of sucrose completely dissolve in <NUM> of hot water at <NUM> to form a water-soluble colloid solution, and then cool down to <NUM>. Add <NUM> of canthaxanthin crystals (content of <NUM>%) and <NUM> of ascorbyl palmitate and <NUM> of ascorbic acid to the water-soluble colloid solution (solid content <NUM>%), and then carry out a grinding in a Sunller Machine, the particle size of the yttrium stabilized zirconia beads of the grinding medium is <NUM>-<NUM>, and afterwards carry out sampling and testing particle size of canthaxanthin particles every <NUM> hours after grinding for <NUM>. the particle size of canthaxanthin particles is <NUM>, and then stop grinding when the particle size reaches <NUM> or less to obtain a grinding fluid. Table <NUM> shows the change of canthaxanthin particle size at different sampling points.

This grinding liquid has good water dispersibility and it is pinkish and opaque after dispersion in water. Remove water in the grinding liquid by the spray-starch flow instant molding method to obtain canthaxanthin microcapsule particles. Wherein the content of canthaxanthin is <NUM>%. The storage stability retention rate of the canthaxanthin particle is shown in Table <NUM>.

Add <NUM> of Arabic gum and <NUM> of maltodextrin completely dissolve in <NUM> of hot water at <NUM> to form a water-soluble colloid solution, and then cool down to <NUM>. Add <NUM> of astaxanthin crystals (content of <NUM>%) and <NUM> of natural vitamin E to the water-soluble colloid solution (solid content <NUM>%), and then carry out a grinding in a Sunller Machine, the particle size of the yttrium stabilized zirconia beads of the grinding medium is <NUM>-<NUM>, and afterwards carry out sampling and testing after grinding for <NUM>. The particle size of astaxanthin particles is <NUM>, and then stop grinding to obtain a first stage grinding fluid.

The first stage grinding liquid is directly added to a second Sunller Machine for the second grinding. The particle size of the yttrium stabilized zirconia beads of the grinding medium is <NUM>-<NUM>. Carry out sampling and testing after grinding for <NUM> hr, the astaxanthin particles have a particle size of <NUM>, and then stop grinding to obtain a second stage grinding liquid.

Remove water in the second stage grinding liquid by spray drying method to obtain astaxanthin microcapsule dry powder, wherein the content of astaxanthin is <NUM>%, and the data of its stability retention rate are shown in Table <NUM>.

Claim 1:
A preparation method of a carotenoid water-dispersible microcapsule preparation with high bioavailability and high stability, the preparation method comprising the following steps:
a) dissolving part of a water-soluble colloid and a filling substance in water to form an aqueous phase;
b) adding a carotenoid crystal to the aqueous phase and stirring for dispersion so as to form a dispersion liquid;
c) loading the dispersion liquid into a first-stage grinding machine for first grinding to form a first-stage grinding liquid;
d) adding the remaining water-soluble colloid and filling substance to the first-stage grinding liquid, loading same into a second grinding machine for secondary grinding to obtain a second-stage grinding liquid; and
e) drying the moisture in the second-stage grinding liquid to obtain carotenoid dry powder or particles.