Astaxanthin solid dispersion and its preparation method

Abstract

This invention provides an astaxanthin solid dispersion and its preparation method, belonging to the field of pharmaceutical preparations. The astaxanthin solid dispersion, by weight percentage, comprises the following components: 10-40% astaxanthin and 60-90% γ-polyglutamic acid. The astaxanthin solid dispersion of this invention uses γ-polyglutamic acid as a carrier matrix, enabling astaxanthin to be uniformly distributed in an aqueous system without precipitation, achieving rapid release of astaxanthin, solving the problem of astaxanthin's poor solubility, and improving its solubility, dissolution rate, and bioavailability.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical preparations, specifically to astaxanthin solid dispersions and their preparation methods. Background Technology

[0002] Astaxanthin (structure as follows) Figure 1 Astaxanthin is the "strongest antioxidant" discovered by humans to date, with an antioxidant activity approximately 4000 times that of vitamin E. It is hailed as a "red miracle" and possesses anti-aging, anti-cancer, anti-inflammatory, immune-boosting, photoprotective, and fruit-quality-improving effects, making it widely used in food, medicine, and agriculture. (Mussagy, Cassamo U. Appl microbiol & biotech. 107, 13(2023): 4199-4215.) The long hydrocarbon chain in the middle of the astaxanthin molecule is hydrophobic, while each end of the molecule has a hydroxyl group with some hydrophilicity. However, due to the long hydrophobic hydrocarbon chain and the strong hydrophobicity of the astaxanthin molecule, the overall molecule is lipophilic. Because of this, its water solubility is very poor, making it difficult for the body to absorb, resulting in low oral bioavailability (Zhang, Congqiang. Appl microbiol & biotech. 104, 13(2020): 5725-5737.).

[0003] To overcome the problem of poor drug water solubility, various solubilization techniques have been developed to improve in vivo bioavailability. These techniques include micronization, nanocrystallization, salt formation, cyclodextrin inclusion, co-crystallization, micellar solubilization, solid dispersions, liposomes, and nanoparticle encapsulation. Among these, solid dispersions (SDs) are currently a well-developed and widely used solubilization technique. SDs disperse drugs in a large amount of carrier excipients, minimizing drug particle size and increasing absorption surface area, thereby improving drug bioavailability. The high energy or metastable state of drugs in SDs makes them inclined to dissolve in the medium, increasing solubility. In addition to improving drug solubility, SDs can also improve the gastrointestinal absorption of poorly soluble drugs by affecting epithelial absorption.

[0004] Solvent evaporation is one method for preparing solid dispersions. The drug and carrier material are dissolved in an organic solvent, and then the organic solvent is removed by rotary evaporation, resulting in a co-precipitated solid mixture of drug and carrier material. This mixture is then cryogenically sieved to obtain the solid dispersion. Solvent evaporation is mainly suitable for heat-sensitive active pharmaceutical ingredients (APIs). Using solvent evaporation to prepare astaxanthin solid dispersions allows for uniform distribution of astaxanthin within the carrier polymer material and effectively inhibits its molecular motion, maintaining its amorphous physical form for a longer period. This significantly improves the solubility, dissolution rate, and bioavailability of the poorly soluble drug astaxanthin.

[0005] CN113288874A discloses a method for preparing an amorphous solid dispersion of astaxanthin using an electrostatic spraying method. Specifically, it discloses using an amphiphilic block copolymer and a hydrophilic polymer as co-spraying carriers, followed by electrostatic spraying to prepare the amorphous solid dispersion of astaxanthin. While this method solves the problem of astaxanthin's poor solubility and can prepare uniformly dispersed amorphous nanoparticles of astaxanthin in an aqueous system, enabling rapid release of astaxanthin, it requires two carriers and is relatively complex to operate. Summary of the Invention

[0006] To address the aforementioned technical problems, this invention provides an astaxanthin solid dispersion and its preparation method. The astaxanthin solid dispersion provided by this invention enables astaxanthin to be uniformly distributed in an aqueous system without precipitation, achieving rapid release of astaxanthin and solving the problem of astaxanthin's poor solubility.

[0007] The technical solution of the present invention is as follows:

[0008] The present invention provides an astaxanthin solid dispersion, which is composed of the following components by weight percentage: 10-40% astaxanthin and 60-90% γ-polyglutamic acid.

[0009] In one specific embodiment, the mass ratio of astaxanthin to γ-polyglutamic acid is 4:6.

[0010] In one specific embodiment, the weight-average molecular weight of γ-polyglutamic acid is 2,000 to 100,000; preferably, the weight-average molecular weight of γ-polyglutamic acid is 30,000.

[0011] This invention also provides a method for preparing astaxanthin solid dispersion, comprising the following steps:

[0012] (1) Dissolve astaxanthin in organic solvent I to obtain solution A; dissolve γ-polyglutamic acid in solvent II to obtain solution B;

[0013] (2) Disperse solution A into solution B to obtain a total organic phase solution;

[0014] (3) The total organic phase solution is subjected to rotary evaporation. After the mixture becomes viscous, it is cooled and solidified. Then it is frozen at -78℃ to -20℃ for 12 to 24 hours, vacuum dried, pulverized, and sieved to obtain a solid dispersion.

[0015] In one specific embodiment, in step (1), the mass-to-volume ratio of astaxanthin to organic solvent I is (1-4) g:(1-5) L; and the mass-to-volume ratio of γ-polyglutamic acid to solvent II is (6-9) g:(1-2) L.

[0016] In one embodiment, organic solvent I includes at least one of dichloromethane, chloroform, acetone, toluene, and pyridine; solvent II includes at least one of methanol, ethanol, isopropanol, and water.

[0017] Preferably, organic solvent I is dichloromethane; solvent II is methanol.

[0018] In one specific implementation, the dissolution process in step (1) requires sonication for 5 to 20 minutes.

[0019] In one specific embodiment, the rotary evaporation temperature in step (3) is 25℃~55℃; the sieving is through a 100~400 mesh sieve.

[0020] In this invention, excessively high rotary evaporation temperatures will affect the stability of the prepared astaxanthin solid dispersion.

[0021] The present invention also provides an astaxanthin product, characterized in that it comprises the above-mentioned astaxanthin solid dispersion.

[0022] In one specific embodiment, the astaxanthin product is prepared by filling the astaxanthin solid dispersion into capsules to form capsules or compressing them into tablets.

[0023] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0024] (1) The present invention provides a promising method for preparing astaxanthin solid dispersions. Using γ-polyglutamic acid as a carrier matrix, the prepared astaxanthin solid dispersions are orange-red powders that are evenly distributed and spherical in water.

[0025] (2) The present invention solves the problem of poor solubility of astaxanthin, enabling it to be evenly distributed in the water system without precipitation, and enabling rapid release of astaxanthin.

[0026] (3) This invention improves the solubility, dissolution rate and bioavailability of astaxanthin. Attached Figure Description

[0027] Figure 1 The structural formula for astaxanthin;

[0028] Figure 2 This is a graph showing the blood concentration curve of astaxanthin in rats. Detailed Implementation

[0029] The reagents and instruments used in this embodiment of the invention are as follows:

[0030] Astaxanthin (Yunnan Aierkang Biotechnology Co., Ltd.), γ-polyglutamic acid (Sichuan Jisheng Biomedical Co., Ltd.), dichloromethane (Chengdu Kelong Chemical Co., Ltd.), methanol (Chengdu Kelong Chemical Co., Ltd.), acetone (Chengdu Kelong Chemical Co., Ltd.), n-hexane (Chengdu Kelong Chemical Co., Ltd.).

[0031] High-performance liquid chromatography (Agilent 1260), 1 / 100,000 balance (XP205), ultrapure water system (Milli-Q, Millipore, USA), RCZ-5A intelligent drug dissolution apparatus (Tianjin University Chemical Instrument Factory), differential calorimeter (Jade DSC, Perkin Elmer, USA), scanning electron microscope (JSM-7500F, Hitachi, Japan), rotary evaporator (Buchi R-100), CNC ultrasonic cleaner (Kunshan Ultrasonic Instrument Co., Ltd.), magnetic stirrer (Dalong RC2000).

[0032] The present invention will be further described below with specific embodiments, but the implementation of the invention is not limited thereto.

[0033] Example 1: Preparation of astaxanthin solid dispersion:

[0034] (1) Accurately weigh 4 mg of astaxanthin and dissolve it in 5 ml of dichloromethane. Sonicate for 5 min to ensure homogeneity. Accurately weigh 300006 mg of γ-polyglutamic acid and dissolve it in 2 ml of methanol. Sonicate for 10 min to ensure homogeneity. Disperse the astaxanthin solution evenly into the γ-polyglutamic acid solution and sonicate for 20 min to ensure homogeneity.

[0035] (2) Place this mixed solution on a rotary evaporator and continuously stir and evaporate the organic phase in a 25°C water bath at 80 rpm for 10 minutes until the solution becomes viscous. Quickly place it in an ice bath to cool and then freeze it at -50°C for 24 hours to obtain a solid. After vacuum drying the solid, pulverize it and pass it through a 200-mesh sieve to make it uniform, thus obtaining a solid astaxanthin dispersion.

[0036] Example 2: Preparation of astaxanthin solid dispersion:

[0037] (1) Accurately weigh 1 mg of astaxanthin and dissolve it in 1.5 ml of dichloromethane. Sonicate for 5 min to ensure homogeneity. Accurately weigh 2000 9 mg of γ-polyglutamic acid and dissolve it in 1.5 ml of methanol. Sonicate for 10 min to ensure homogeneity. Disperse the astaxanthin solution evenly into the γ-polyglutamic acid solution and sonicate for 20 min to ensure homogeneity.

[0038] (2) Place this mixed solution on a rotary evaporator and continuously stir and evaporate the organic phase in a 45°C water bath at 80 rpm for 10 minutes until the solution becomes viscous. Quickly place it in an ice bath to cool and then freeze it at -40°C for 16 hours to obtain a solid. After vacuum drying the solid, pulverize it and pass it through a 300-mesh sieve to make it uniform, thus obtaining a solid astaxanthin dispersion.

[0039] Example 3: Preparation of astaxanthin solid dispersion:

[0040] (1) Accurately weigh 4 mg of astaxanthin and dissolve it in 5 ml of dichloromethane. Sonicate for 5 min to ensure homogeneity. Accurately weigh 2400006 mg of γ-polyglutamic acid and dissolve it in 2 ml of methanol. Sonicate for 10 min to ensure homogeneity. Disperse the astaxanthin solution evenly into the γ-polyglutamic acid solution and sonicate for 20 min to ensure homogeneity.

[0041] (2) Place this mixed solution on a rotary evaporator and continuously stir and evaporate the organic phase in a 25°C water bath at 80 rpm for 10 minutes until the solution becomes viscous. Quickly place it in an ice bath to cool and then freeze it at -50°C for 24 hours to obtain a solid. After vacuum drying the solid, pulverize it and pass it through a 200-mesh sieve to make it uniform, thus obtaining a solid astaxanthin dispersion.

[0042] Example 4: Preparation of astaxanthin solid dispersion:

[0043] (1) Accurately weigh 4 mg of astaxanthin and dissolve it in 5 ml of dichloromethane. Sonicate for 5 min to ensure homogeneity. Accurately weigh 1000006 mg of γ-polyglutamic acid and dissolve it in 2 ml of methanol. Sonicate for 10 min to ensure homogeneity. Disperse the astaxanthin solution evenly into the γ-polyglutamic acid solution and sonicate for 20 min to ensure homogeneity.

[0044] (2) Place this mixed solution on a rotary evaporator and continuously stir and evaporate the organic phase in a 25°C water bath at 80 rpm for 10 minutes until the solution becomes viscous. Quickly place it in an ice bath to cool and then freeze it at -50°C for 24 hours to obtain a solid. After vacuum drying the solid, pulverize it and pass it through a 200-mesh sieve to make it uniform, thus obtaining a solid astaxanthin dispersion.

[0045] Comparative Example 1: Preparation of Astaxanthin Solid Dispersion

[0046] (1) Accurately weigh 5 mg of astaxanthin and dissolve it in 1.5 ml of dichloromethane. Sonicate for 5 min to ensure homogeneity. Accurately weigh 15 mg of polyethylene glycol 6000 and dissolve it in 0.5 ml of methanol. Sonicate for 10 min to ensure homogeneity. Disperse the astaxanthin solution evenly into the polyethylene glycol solution and sonicate for 20 min to ensure homogeneity.

[0047] (2) Place this mixed solution on a rotary evaporator and continuously stir and evaporate the organic phase in a 50°C water bath at 80 rpm for 10 minutes until the solution becomes viscous. Quickly place it in an ice bath to cool and then freeze it at -20°C for 12 hours to obtain a solid. After vacuum drying the solid, pulverize it and pass it through a 100-mesh sieve to make it uniform, thus obtaining a solid astaxanthin dispersion.

[0048] Comparative Example 2: Preparation of Astaxanthin Solid Dispersion

[0049] (1) Accurately weigh 10 mg of astaxanthin and dissolve it in 3 ml of dichloromethane. Sonicate for 10 min to ensure homogeneity. Accurately weigh 40 mg of Pronnic F68 and dissolve it in 3 ml of methanol. Sonicate for 20 min to ensure homogeneity. Disperse the astaxanthin solution evenly into the Pronnic F68 solution and sonicate for 20 min to ensure homogeneity.

[0050] (2) Place this mixed solution on a rotary evaporator and continuously stir and evaporate the organic phase in a 30°C water bath at 80 rpm for 15 minutes until the solution becomes viscous. Quickly place it in an ice bath to cool and then freeze it at -78°C for 24 hours to obtain a solid. After vacuum drying the solid, pulverize it and pass it through a 400-mesh sieve to make it uniform, thus obtaining a solid astaxanthin dispersion.

[0051] Comparative Example 3: Preparation of Astaxanthin Solid Dispersion:

[0052] (1) Accurately weigh 5 mg of astaxanthin and dissolve it in 1.5 ml of dichloromethane. Sonicate for 5 min to ensure homogeneity. Accurately weigh 15 mg of hyaluronic acid and dissolve it in 0.5 ml of methanol. Sonicate for 10 min to ensure homogeneity. Disperse the astaxanthin solution evenly into the hyaluronic acid solution and sonicate for 20 min to ensure homogeneity.

[0053] (2) Place this mixed solution on a rotary evaporator and continuously stir and evaporate the organic phase in a 50°C water bath at 80 rpm for 10 minutes until the solution becomes viscous. Quickly place it in an ice bath to cool and then freeze it at -20°C for 12 hours to obtain a solid. After vacuum drying the solid, pulverize it and pass it through a 100-mesh sieve to make it uniform, thus obtaining a solid astaxanthin dispersion.

[0054] Comparative Example 4: Preparation of Astaxanthin Solid Dispersion

[0055] (1) Accurately weigh 5 mg of astaxanthin and dissolve it in 1.5 ml of dichloromethane. Sonicate for 5 min to ensure homogeneity. Accurately weigh 15 mg of polyglucuronic acid and dissolve it in 0.5 ml of methanol. Sonicate for 10 min to ensure homogeneity. Disperse the astaxanthin solution evenly into the polyglucuronic acid solution and sonicate for 20 min to ensure homogeneity.

[0056] (2) Place this mixed solution on a rotary evaporator and continuously stir and evaporate the organic phase in a 50°C water bath at 80 rpm for 10 minutes until the solution becomes viscous. Quickly place it in an ice bath to cool and then freeze it at -20°C for 12 hours to obtain a solid. After vacuum drying the solid, pulverize it and pass it through a 100-mesh sieve to make it uniform, thus obtaining a solid astaxanthin dispersion.

[0057] Comparative Example 5: Preparation of Astaxanthin Solid Dispersion

[0058] (1) Accurately weigh 5 mg of astaxanthin and dissolve it in 1.5 ml of dichloromethane. Sonicate for 5 min to ensure homogeneity. Accurately weigh 15 mg of povidone and dissolve it in 0.5 ml of methanol. Sonicate for 10 min to ensure homogeneity. Disperse the astaxanthin solution evenly in the povidone and sonicate for 20 min to ensure homogeneity.

[0059] (2) Place this mixed solution on a rotary evaporator and continuously stir and evaporate the organic phase in a 50°C water bath at 80 rpm for 10 minutes until the solution becomes viscous. Quickly place it in an ice bath to cool and then freeze it at -20°C for 12 hours to obtain a solid. After vacuum drying the solid, pulverize it and pass it through a 100-mesh sieve to make it uniform, thus obtaining a solid astaxanthin dispersion.

[0060] Comparative Example 6: Preparation of Astaxanthin Solid Dispersion

[0061] (1) Accurately weigh 1 mg of astaxanthin and dissolve it in 1.5 ml of dichloromethane. Sonicate for 5 min to ensure homogeneity. Accurately weigh 9 mg of cyclic γ-polyglutamic acid and dissolve it in 1.5 ml of methanol. Sonicate for 10 min to ensure homogeneity. Disperse the astaxanthin solution evenly into the cyclic γ-polyglutamic acid solution and sonicate for 20 min to ensure homogeneity.

[0062] (2) Place this mixed solution on a rotary evaporator and continuously stir and evaporate the organic phase in a 45°C water bath at 80 rpm for 10 minutes until the solution becomes viscous. Quickly place it in an ice bath to cool and then freeze it at -40°C for 16 hours to obtain a solid. After vacuum drying the solid, pulverize it and pass it through a 300-mesh sieve to make it uniform, thus obtaining a solid astaxanthin dispersion.

[0063] Preparation of astaxanthin solid dispersion in Comparative Example 7:

[0064] (1) Accurately weigh 10 mg of astaxanthin and dissolve it in 3 ml of dichloromethane. Sonicate for 10 min to ensure homogeneity. Accurately weigh 40 mg of α-polyglutamic acid and dissolve it in 3 ml of methanol. Sonicate for 20 min to ensure homogeneity. Disperse the astaxanthin solution evenly into the α-polyglutamic acid solution and sonicate for 20 min to ensure homogeneity.

[0065] (2) Place this mixed solution on a rotary evaporator and continuously stir and evaporate the organic phase in a 30°C water bath at 80 rpm for 15 minutes until the solution becomes viscous. Quickly place it in an ice bath to cool and then freeze it at -78°C for 24 hours to obtain a solid. After vacuum drying the solid, pulverize it and pass it through a 400-mesh sieve to make it uniform, thus obtaining a solid astaxanthin dispersion.

[0066] Preparation of astaxanthin solid dispersion in Comparative Example 8:

[0067] (1) Accurately weigh 10 mg of astaxanthin and dissolve it in 3 ml of dichloromethane. Sonicate for 10 min to ensure homogeneity. Accurately weigh 40 mg of pectinic acid and dissolve it in 3 ml of methanol. Sonicate for 20 min to ensure homogeneity. Disperse the astaxanthin solution evenly into the pectinic acid solution and sonicate for 20 min to ensure homogeneity.

[0068] (2) Place this mixed solution on a rotary evaporator and continuously stir and evaporate the organic phase in a 30°C water bath at 80 rpm for 15 minutes until the solution becomes viscous. Quickly place it in an ice bath to cool and then freeze it at -78°C for 24 hours to obtain a solid. After vacuum drying the solid, pulverize it and pass it through a 400-mesh sieve to make it uniform, thus obtaining a solid astaxanthin dispersion.

[0069] In vitro dissolution determination of astaxanthin solid dispersion

[0070] Weigh 50.0 mg of the astaxanthin solid dispersion prepared in the above examples and comparative examples, and determine its in vitro dissolution rate according to the basket method of the 2020 edition of the Pharmacopoeia of the People's Republic of China. The dissolution media were 900 mL of artificial intestinal fluid (pH 6.8) and 900 mL of artificial gastric fluid (pH 1.2), the temperature was 37.0 ± 0.5℃, and the rotation speed was 100 rpm. Place the enteric-coated capsules prepared in the examples and comparative examples (the astaxanthin solid dispersion was simply filled into commercially available enteric-coated capsules) in a rotating basket. Start timing when the basket contacts the medium, and take 10 mL samples at regular intervals, while simultaneously adding 10 mL of isothermal medium. Filter the sampled liquid through a 0.22 μm microfiltration membrane, and analyze the filtrate by HPLC. The release rate (Wt / W0*100%, where Wt is the cumulative drug release mass at the corresponding time point, and W0 is the initial total added drug mass) of the astaxanthin solid dispersions prepared in each example and comparative example is shown in Table 1. The results showed that the dissolution rate of the astaxanthin solid dispersion prepared by carrier γ-polyglutamic acid 30000 was significantly improved in artificial gastric fluid, with 84.4% dissolving in 30 minutes and a total of 88.7% dissolving in 2 hours. This solved the problem of poor solubility of astaxanthin raw material and indicated that the astaxanthin solid dispersion prepared by solvent method met the purpose of the formulation design.

[0071] The chromatographic conditions are as follows:

[0072] UV-HPLC: Agilent 1260 chromatograph

[0073] Chromatographic column: XBridge C18 3.5μm 4.6*50mm

[0074] Liquidity: Methanol: 0.05% formic acid water = 85:15;

[0075] Flow rate: 1 ml / min; run for 10 min

[0076] Wavelength: 480nm

[0077] Injection volume: 5 μl for determination

[0078] Accurately pipette 5 μl of the reference solution and the test solution into the liquid chromatograph. Calculate the retention time of astaxanthin by peak area using the external standard method. The retention time is 14.797 min.

[0079] Table 1. Release rate of astaxanthin solid dispersions prepared in the examples and comparative examples

[0080]

[0081]

[0082] Preliminary evaluation of the in vivo bioavailability of the astaxanthin solid dispersion prepared in Example 1

[0083] (1) Animal administration

[0084] Six healthy male SD rats (200±20g) were fasted for 12 hours but allowed free access to water, and then randomly divided into an astaxanthin standard group and an astaxanthin solid dispersion administration group, with three rats in each group and clearly labeled. Since astaxanthin raw material is insoluble in water, 0.5% sodium carboxymethyl cellulose was added and dissolved in ultrapure water to ensure oral absorption in rats. The solid dispersion group consisted of astaxanthin solid dispersion prepared in Example 1. Samples from both groups were accurately weighed according to a dosage of 50 mg / kg BW, dissolved in ultrapure water, and administered to rats by gavage at a dose of 3.0 mL. Blood samples of 0.5 mL were collected at 0.5, 1, and 2 time points after gavage.

[0085] (2) Sample processing

[0086] 0.5 mL of blood sample from rats was collected via the orbital cavity and added to a 1.5 mL EP tube containing 20 μL of heparin sodium. After standing for 30 min, the sample was centrifuged at 3700 rpm for 10 min, and the supernatant was obtained as the plasma sample. The plasma sample was then processed by adding 1.6 mL of acetone to a 10 mL EP tube, vortexing thoroughly, and then shaking in a rotary incubator for 40 min. Next, 1.6 mL of n-hexane was added, and after vortexing to mix thoroughly, the sample was allowed to stand in the dark for 1 h. The supernatant was then transferred to a 10 mL EP tube and heated in a 37°C water bath, followed by nitrogen drying. Finally, 100 μL of 50% dichloromethane-methanol mixed solvent was added to the dried 10 mL EP tube to reconstitute the astaxanthin. After centrifugation at 12000 rpm for 10 min, the supernatant was analyzed by HPLC, and a blood drug concentration curve was plotted. The results are shown below. Figure 2 As shown.

[0087] (3) Results

[0088] The peak time for both astaxanthin standard and astaxanthin solid dispersion was 2 hours. However, the plasma concentration (Cmax) of the astaxanthin standard (45.11 ± 6.22 ng / mL) was significantly lower than that of the astaxanthin solid dispersion (230.78 ± 24.63 ng / mL), only about 20% of that of the solid dispersion. The half-life of the astaxanthin standard was 18.44 hours, and the mean residence time was 27.55 hours; while the half-life of the astaxanthin solid dispersion was only 2.85 hours, and the mean residence time was 6.73 hours, indicating that the solid dispersion was rapidly absorbed after entering the body. Furthermore, the AUC of the astaxanthin standard was only 700.32 h·ng / mL, while the AUC of the astaxanthin solid dispersion was 1842.76 h·ng / mL, with a relative bioavailability (F) of 263.13%, significantly improving the oral bioavailability of astaxanthin and promoting its absorption by the human body.

[0089] The above description discloses only preferred embodiments of the present invention and should not be construed as limiting the scope of the present invention. Therefore, equivalent variations made in accordance with the claims of the present invention are still within the scope of the present invention.

Claims

1. Astaxanthin solid dispersion, characterized in that, It consists of the following components by weight percentage: astaxanthin 10-40%, γ-polyglutamic acid 60-90%.

2. The astaxanthin solid dispersion according to claim 1, characterized in that, The mass ratio of astaxanthin to γ-polyglutamic acid is 4:

6.

3. The astaxanthin solid dispersion according to claim 1, characterized in that, The weight-average molecular weight of γ-polyglutamic acid is 2,000 to 100,000; preferably, the weight-average molecular weight of γ-polyglutamic acid is 30,000.

4. The method for preparing the astaxanthin solid dispersion according to any one of claims 1-3, characterized in that, Includes the following steps: (1) Dissolve astaxanthin in organic solvent I to obtain solution A; dissolve γ-polyglutamic acid in solvent II to obtain solution B; (2) Disperse solution A into solution B to obtain a total organic phase solution; (3) The total organic phase solution is subjected to rotary evaporation. After the mixture becomes viscous, it is cooled and solidified. Then it is frozen at -78℃ to -20℃ for 12 to 24 hours, vacuum dried, pulverized, and sieved to obtain a solid dispersion.

5. The method for preparing astaxanthin solid dispersion according to claim 4, characterized in that, In step (1), the mass-to-volume ratio of astaxanthin to organic solvent I is (1-4) g:(1-5) L; the mass-to-volume ratio of γ-polyglutamic acid to solvent II is (6-9) g:(1-2) L.

6. The method for preparing astaxanthin solid dispersion according to claim 4, characterized in that, Organic solvent I includes at least one of dichloromethane, chloroform, acetone, toluene, and pyridine; solvent II includes at least one of methanol, ethanol, isopropanol, and water.

7. The method for preparing astaxanthin solid dispersion according to claim 4, characterized in that, The dissolution process in step (1) requires sonication for 5 to 20 minutes.

8. The method for preparing astaxanthin solid dispersion according to claim 4, characterized in that, In step (3), the rotary evaporation temperature is 25℃~55℃; the sieving is done through a 100~400 mesh sieve.

9. An astaxanthin product, characterized in that, Includes the astaxanthin solid dispersion according to any one of claims 1-3.

10. An astaxanthin product according to claim 9, characterized in that, The astaxanthin solid dispersion is filled into capsules to form capsules or compressed into tablets.

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