JP2020011927A - Astaxanthin-containing powder - Google Patents

Abstract

To provide an astaxanthin-containing powder that is substantially free of oily components, except astaxanthin, and a method of producing the same.SOLUTION: A liquid oil containing astaxanthin and porous fine particles is mixed, the mixture is subjected to extraction operation by supercritical extraction, extraction residues are recovered therefrom, and an astaxanthin-containing powder composed of astaxanthin and porous fine particles are obtained.SELECTED DRAWING: Figure 5

Description

  The present invention relates to an astaxanthin-containing powder.

  Astaxanthin is a pigment substance that is contained in some algae, krill, shrimp, bream, salmon and the like, and is widely distributed in nature. It is a kind of carotenoid like β-carotene and lycopene, and is classified into xanthophylls. The IUPAC name is 3,3'-dihydroxy-β, β-carotene-4,4'-dione. It is found in shells in crustaceans, and is found on the body surface in red sea bream, which feeds on them, and in the red part of muscles in salmonids. It is considered that astaxanthin has a high antioxidant activity and acts as a factor that protects the living body from ultraviolet rays and lipid peroxidation. For this reason, supplements containing astaxanthin, health foods, skin care products (basic cosmetics), and the like have been released.

  Astaxanthin has three optical isomers and four geometric isomers. In the living body, three forms of free type, monoester type and diester type are possible, but most exist as fatty acid ester type. Usually, these isomers are referred to as astaxanthin without distinction.

  Astaxanthin may be derived from natural products or obtained by chemical synthesis. As those derived from natural products, for example, shrimp, krill, crustacean shells such as crabs, eggs and organs, skins and eggs of various seafood, algae such as green alga Hematococcus, yeasts such as red yeast Phaffia, There are those obtained from seed plants such as marine bacteria, Fussou grass and Kimbong flower. Astaxanthin derived from a natural product and a chemically synthesized product of astaxanthin are commercially available or manufactured by a known method, so that they are easily available.

  Astaxanthin derived from natural products can be obtained, for example, by culturing the red yeast Phaffia rhodozyma (Patent Literature 1) or culturing the green alga Hematococcus bulubialis (Patent Literature 2). Green alga Haematococcus is most often used as a natural product because of its ease of culture and extraction, the highest concentration of astaxanthin, and high productivity.

  Various methods are known for extracting and purifying astaxanthin. For example, since astaxanthin and its ester are oil-soluble substances, astaxanthin can be extracted from the above-mentioned natural product with an oil-soluble organic solvent such as acetone, alcohol, ethyl acetate, benzene, and chloroform. Supercritical extraction can also be performed using carbon dioxide, water, or the like. After the extraction, the solvent is removed according to a conventional method to obtain a mixed concentrate of monoester-type astaxanthin and diester-type astaxanthin. Further, it is known that this concentrate can be purified by a separation column or lipase decomposition.

Chemical synthesis of astaxanthin has also been developed.
Patent Document 3 discloses that a canthaxanthin dimetal enolate prepared from canthaxanthin and metal bistrimethylsilylamide in an ether solvent is added at low temperature to a solution of an aprotic polar solvent of an oxaziridine compound, or A method for producing astaxanthin, which comprises adding the aprotic polar solvent, adding the oxaziridine compound at a low temperature, then adding an acidic substance, and separating unreacted canthaxanthin from the resulting reaction solution at a low temperature, is described. .
In addition, astaxanthin has a high oil solubility like other carotenoids such as beta-carotene, and it is difficult to crystallize or make astaxanthin alone in powder form. For this reason, astaxanthin is used by dissolving it in an astaxanthin-soluble organic solvent or fat or oil. When used for foods and pharmaceuticals, the extract containing triglyceride derived from Haematococcus is usually used as an astaxanthin-containing liquid oil further dissolved and dispersed in edible oil. This commercially available astaxanthin-containing liquid oil contains 1 to 20% by mass of astaxanthin (Non-Patent Document 1).

Attempts have also been made to powder astaxanthin, which is in the form of a liquid oil. This is due to a combination of commonly employed emulsification techniques and drying techniques such as spray drying.
Patent Literature 4 describes a method for obtaining a powder containing astaxanthin by drying a suspension comprising a crushed astaxanthin-containing Haematococcus alga body, a surfactant, an antioxidant, an excipient, and water.
Patent Document 5 discloses a technique for spray-drying an emulsion solution comprising a liquid oil containing astaxanthin, an emulsifier, and an aqueous phase containing excipients such as dextrin and lactose.
In Patent Document 6, a mixture of a hematococcus alga pigment-containing liquid oil containing astaxanthin and tocopherol, and a solution consisting of sucrose laurate ester, polyglyceryl-10 laurate, lecithin, inulin, and water are mixed to form an emulsion. A technique for preparing and spray-drying this to prepare an astaxanthin-containing powder is disclosed.
These powders contain an edible oil component, an emulsifier, and an excipient, and further contain a liquid oil component in which astaxanthin is dissolved. For this reason, it was not always easy to handle as astaxanthin-containing powder. In particular, when a tablet containing a high concentration of astaxanthin is produced, there is a problem in tableting suitability.

JP 03-206880 A JP 07-039389 A JP-A-07-118227 International Publication No. 02/077105 JP 2011-241176 A JP 2009-062331 A

Catalog Ver. 2.2 SJ "astaxanthin" https://www.oryza.co.jp/pdf/japanese/astaxanthin_e%202.2SJ.pdf

Astaxanthin is provided as a drug or food raw material in a state of being dissolved and dispersed in edible liquid oil. Separating only astaxanthin from this astaxanthin-containing liquid oil requires a complicated separation operation. In order to powder astaxanthin, as described above, an excipient and an emulsifier and water are added to the astaxanthin-containing liquid oil to prepare an emulsified composition, which is dried and powdered by a drying means such as spray drying. I was For this reason, the astaxanthin-containing powder contains a high concentration of an oily component.
The present inventor has been studying to prepare a powder composition having a high content of astaxanthin. Through repeated trials and errors, the inventors have studied and found a technique for obtaining an astaxanthin powder containing substantially no oily substance other than astaxanthin.
That is, an object of the present invention is to provide an astaxanthin-containing powder substantially containing no oily component other than astaxanthin, and a method for producing the same.

The main configuration of the present invention is as follows.
(1) Astaxanthin-containing powder comprising astaxanthin and porous fine particles.
(2) Astaxanthin-containing powder comprising particles in which astaxanthin is carried in pores formed in porous fine particles.
(3) The astaxanthin-containing powder according to (1) or (2), wherein the porous fine particles are at least one substance selected from silicon dioxide, calcium silicate, and porous starch.
(4) The astaxanthin-containing powder according to any one of (1) to (3), which contains 8 to 30% by mass of astaxanthin per powder.
(5) A method for producing an astaxanthin-containing powder, comprising mixing a liquid oil containing astaxanthin and porous fine particles, performing a supercritical extraction operation under a pressure condition of 15 MPa or more, and collecting an extraction residue.
(6) The method for producing an astaxanthin-containing powder according to (5), wherein the porous fine particles are a powder composed of at least one substance selected from silicon dioxide, calcium silicate, and porous starch.

  According to the present invention, there is provided an astaxanthin-containing powder containing substantially no oily component other than astaxanthin. Also provided is a method for producing astaxanthin powder containing substantially no oily component other than astaxanthin. Since the powder of the present invention hardly contains an oily component, it has excellent water dispersibility and excellent absorbability when taken orally. In addition, the powder becomes excellent in tableting aptitude.

The structure of the porous fine particles used for preparing the powder of the present invention will be exemplified. The left figure is a schematic cross-sectional view of the structure of the porous fine particles. The right figure is a scanning electron microscope image of calcium silicate. It is a schematic diagram which shows the operation process for preparing the astaxanthin containing powder of this invention. 5 is an image of the porous fine particles used in Examples 1 to 3 (upper row), and a scanning electron microscope observation image of the particles of the astaxanthin-containing powder of Examples 1 to 3 (lower row). It is a graph which shows the result of the dissolution test based on the Japanese Pharmacopoeia of a porous starch / astaxanthin powder, a calcium silicate / astaxanthin powder, a silicon dioxide / astaxanthin powder, and purified astaxanthin (control). It is a graph which compares the Cmax of the blood astaxanthin concentration of the rat which administered the astaxanthin containing powder of this invention, and the rat which administered the astaxanthin containing liquid oil (Astaryl 50FC). It is a graph which compares the AUC value based on the blood astaxanthin density | concentration change of the rat which administered the astaxanthin containing powder of this invention, and the rat which administered the astaxanthin containing liquid oil (Astaryl 50FC). It is a graph of the astaxanthin-containing powder of the present invention, the liquid oil containing astaxanthin (Astaryl 50FC), a commercial astaxanthin-containing preparation, and a graph of the transition of the astaxanthin concentration in the blood of a rat to which a self-emulsifying astaxanthin preparation was administered. It is a graph which makes the astaxanthin-containing powder of this invention and the commercially available astaxanthin powder raw material into a tablet, and compares tableting characteristics.

The present invention relates to an astaxanthin-containing powder comprising astaxanthin and porous fine particles, and a method for producing the same.
Astaxanthin is generally provided in a state of being dissolved and dispersed in a liquid oil, but it is difficult to separate only astaxanthin from this astaxanthin-containing liquid oil.

  The powder of the present invention contains substantially no oil component such as edible oil other than astaxanthin. The powder of the present invention is a powder composed of astaxanthin and porous fine particles, and can be obtained for the first time by the production method disclosed in the present application.

  In the specification of the present application, astaxanthin is at least one selected from the group consisting of a free form of astaxanthin, astaxanthin fatty acid monoester, and astaxanthin fatty acid diester. The fatty acid ester is composed of at least one selected from the group consisting of saturated fatty acids or unsaturated fatty acids having 2 or more carbon atoms.

  Astaxanthin may be any of a synthetic product and / or a natural product, but in consideration of the safety of a living body, a naturally-derived product, for example, astaxanthin extracted from haematococcus alga, Phaffia yeast, krill, or the like is preferable. Astaxanthin extracted from Haematococcus alga bodies, which can be obtained in large quantities and stably, is particularly suitable. Examples of such astaxanthin include Astaryl Oil 50F (containing 5% by mass of astaxanthin: manufactured by Fuji Chemical Industry Co., Ltd.) and Astaxanthin 20 (containing 20% by mass of astaxanthin: manufactured by Oriza Yuka Co., Ltd.). The concentration of astaxanthin is preferably high.

  When using astaxanthin-derived astaxanthin oil as astaxanthin, the use of porous fine particles based on the content of astaxanthin in the oil and the weight of other contaminants (main components are mono, di, triglyceride) The quantity can be set. Specifically, the amount is 0.1 to 20 parts by mass, preferably 1 to 10 parts by mass, more preferably 1 to 6 parts by mass for 1 part by mass of astaxanthin.

  In the present invention, the porous fine particles are fine powders having an average particle diameter of 2 to 5 μm, having voids having an average pore diameter of 2 to 30 nm, and are water-insoluble organic or inorganic powders. Therefore, those having water wettability are preferable. Examples of such porous fine particles include viscous minerals such as zeolite, kaolinite and montmorillonite, silicate compounds such as calcium silicate and silicon dioxide, porous cellulose and porous starch. Among them, examples of the porous fine particles suitable for the present invention include calcium silicate, silicon dioxide, and porous starch. In addition, a commercial item can be used for these porous fine particles. "Flolite" (Tomita Pharmaceutical Co., Ltd.) is used as calcium silicate, fine silicon dioxide ("Sylopage 720": Fuji Silysia Chemical Ltd.) is used as silicon dioxide, and "Fmelt F1" (Fuji Chemical Co., Ltd.) is used as porous starch. Industrial Co., Ltd.) can be used.

  In order to obtain an astaxanthin-containing powder comprising astaxanthin and porous fine particles of the present invention, a liquid oil containing astaxanthin and porous fine particles are mixed at a desired ratio, and this is mixed using a supercritical extraction device to remove carbon dioxide. Is used as a supercritical extraction solvent at a temperature of 20 to 50 ° C., preferably 30 to 40 ° C., and a flow rate of carbon dioxide of 10 to 100 g / min is set for 30 minutes to 1.5 hours for supercritical extraction. Perform the operation. The supercritical extraction pressure is preferably from 15 MPa to 50 MPa. Liquid oil and oily substances other than astaxanthin are extracted from the liquid oil containing astaxanthin by supercritical extraction. In the supercritical extraction method, the porous fine particles remain unchanged, and during the extraction process, the oily component and astaxanthin together with the extraction solvent penetrate into the voids (porosity) formed in the particles of the porous fine particles. Thus, the oily component is extracted together with the supercritical solvent, but astaxanthin is carried as it is. This gap has a gap structure as shown in FIG. The voids are distributed throughout the particles and may penetrate the particles. FIG. 2 is a schematic diagram showing a process of preparing the powder of the present invention in the supercritical extraction device. That is, in the astaxanthin-containing liquid oil that has penetrated into the voids of the particles, fats and oils and oil components are selectively extracted by a supercritical extraction operation, and the astaxanthin is supported on the particles.

When the supercritical extraction is completed, the astaxanthin supported on the porous fine particles remains in the extraction tank of the supercritical extraction device together with the porous fine particles. In this residue, only astaxanthin is carried and remains in the porosity existing in the fine powder particles and on the particle surface. The obtained residue becomes a powder containing astaxanthin as it is. This powder contains astaxanthin in an amount of 8 to 30% by mass per powder. Further, since this powder does not substantially contain an oil component, it is a powder having good fluidity. For this reason, it can be used as a tablet raw material by tableting, which is difficult with conventional astaxanthin-containing powder. By tableting this powder, it can be made into a medicine or health food as a tablet containing high concentration of astaxanthin.
The powder containing astaxanthin has dispersibility in water.

The present invention will be specifically described below with reference to Examples, Comparative Examples and Test Examples using the same.
1. Preparation example of powder by supercritical extraction device (1)
(1) Production Method An astaxanthin-containing powder was prepared using astaxanthin-containing liquid oil "Astaryl Oil 50FC (containing 5% by mass of astaxanthin; Fuji Chemical Industry Co., Ltd.)" and porous fine particles. Powders containing finely divided silicon dioxide (Silopage 720: Fuji Silysia Chemical Ltd.), calcium silicate (Flolite: Tomita Pharmaceutical Co., Ltd.), and porous starch (Efmelt F1: Fuji Chemical Co., Ltd.) as porous fine particles are shown in Table 1. And the mixture was homogenized in the ratio described in (1).
Next, the mixture was transferred to a pressure-resistant container (extraction tank, 0.5 L container) of a supercritical extraction device (Mitsubishi Kakoki Co., Ltd.), and heated and pressurized using carbon dioxide as an extraction solvent, and subjected to 25 MPa and 40 ° C. Under the condition, carbon dioxide was used as an extraction solvent for 1 hour, and a supercritical extraction operation was performed at a CO ₂ flow rate of 65 g / min.

  As Comparative Examples, Comparative Example 1 was not added, Comparative Example 2 was similarly added using γ-cyclodextrin powder (Wacker chemical corporation) and Comparative Example 3 using scallop powder (NC Corporation) at the ratios shown in Table 1. To perform supercritical extraction.

(2) Characteristic evaluation of powder 1) State of residue The state of the residue remaining in the extraction tank was visually evaluated.

2) Concentration of astaxanthin in the residue About 10 mg of a sample is precisely weighed, suspended in about 30 mL of hexane, sonicated at about 30 to 40 ° C. for 10 minutes, and made up to 50 mL with hexane.
The solution is further diluted with hexane so that the absorbance at a wavelength of 470 nm falls within the range of about 0.1 to 2. It is preferable that the solution be filtered through a syringe filter having a pore size of 0.45 μm before the absorbance measurement. Using a sample solution, hexane is used as a control, and a test is performed by an absorbance measurement method, and absorbance A at a wavelength of 470 nm is measured.
Astaxanthin content (%) = (A × dilution ratio) / (2100 × S)
A: Absorbance of sample solution at 470 nm, S: Sampling material (mg), 2100; Coefficient in hexane

3) Water dispersibility About 100 mg of each sample was put into 100 mL of water, mixed with a spoonful for 30 seconds, and the state of the aqueous solution was evaluated by visual observation.
The powder or paste was uniformly dispersed: Δ, not dispersed: evaluated as ×.

(3) Evaluation results The evaluation results are shown in Table 1.

In Examples 1 to 3, all of them became preferable red powders that were easy to handle. The oil component contained in the astaxanthin-containing liquid oil was transferred to the recovery tank by supercritical extraction.
The astaxanthin concentration in the obtained powder was 8 mass% or more, which was difficult with the conventional astaxanthin-containing powder. Further, all of the powders of Examples 1 to 3 had preferable water dispersibility.
In addition, when using porous fine particles, a powder containing astaxanthin can be obtained.However, in the case of a non-porous powder such as cyclodextrin or scallop powder, astaxanthin remains in the extraction tank, but has a paste form. It was considered that the particles of the powder to be added had to be porous for powderization. Further, when the particles of the powders of Examples 1, 2, and 3 were observed with a scanning electron microscope, it was confirmed that astaxanthin was supported on the particle surface and inside of each particle. It was confirmed by comparing and observing the image of the conductive fine particles (FIG. 3).

2. Preparation example of powder by supercritical extraction device (2)
The optimum conditions of supercritical extraction were discussed.
(1) Production method As in Example 1, astaxanthin-containing liquid oil "Astaril oil 50FC (containing 5% by mass of astaxanthin; Fuji Chemical Co., Ltd.)" and calcium silicate (Fluorite: Tomita Pharmaceutical Co., Ltd.) are listed in Table 2. , And a supercritical extraction operation was performed under the supercritical conditions shown in Table 2 for one hour using carbon dioxide as an extraction solvent at a CO ₂ flow rate of 65 g / min.

(2) Characteristic evaluation of powder 1) State of residue The state of the residue remaining in the extraction tank was visually evaluated.

2) Astaxanthin concentration in residue Astaxanthin concentration was analyzed in the same manner as in 1.

3) Water dispersibility About 100 mg of each sample was put into 100 mL of water, mixed with a spoonful for 30 seconds, and the state of the aqueous solution was evaluated by visual observation.
The powder or paste was evaluated as uniformly dispersed: Δ, not dispersed: ×.

(3) Evaluation results The evaluation results are shown in Table 2.

  As shown in Table 2, it was found that high-pressure conditions of 15 MPa or more were necessary as supercritical extraction conditions in order to obtain a powder meeting the object of the present invention.

3. Elution properties due to differences in porous microparticles to be added Elution tests were performed on three types of astaxanthin-containing powders having different porous microparticles prepared in the same manner as in Examples 1, 2, and 3.
(1) Test method The test was performed according to the dissolution test method specified in the Japanese Pharmacopoeia.
Test conditions Test sample:
-Porous starch / astaxanthin powder: contains 10% by mass of astaxanthin (Efmelt)
・ Calcium silicate / astaxanthin powder: contains 15% by mass of astaxanthin (Flolite)
・ Silicon dioxide / astaxanthin powder: contains 16% by mass of astaxanthin (silo page)
・ Purified astaxanthin (control)
The above sample was used for the test so as to have an astaxanthin concentration of 30 mg.
Test solution: Dissolution test solution second solution (pH 6.8) + 0.1% polysorbate 80
Paddle rotation speed: 100 rpm
Detector: UV (A460 nm) The sample was collected with an autosampler and measured with a UV meter attached to a dissolution tester.
Filter: Uses 70μm pores

(2) Test results FIG. 4 shows the results of the dissolution test.
Silicon dioxide / astaxanthin powder (silopage) showed particularly high dissolution.
When prepared using silicon dioxide as the porous fine particles, a powder with good elution of astaxanthin could be prepared.

4. Animal test (1)
The absorption of astaxanthin by oral administration was tested.
(1) Test method 1) Test sample • Silicon dioxide / astaxanthin powder: containing 16% by mass of astaxanthin (AXSC)
・ Astaryl oil 50FC (containing 5% by mass of astaxanthin; Fuji Chemical Co., Ltd.) (control)
2) Animals used
Species: rat Strain: SD Gender: male
Age at the time of experimental treatment: 8 weeks old 3) Number of administrations: single oral administration 4) Administration volume and administration route
Gavage is orally administered as 50 mg / kg astaxanthin.
5) Rearing conditions ・ After the animals are brought in, acclimatize them for 7 days.
-On the 7th day, the body weight is measured, the animals are divided into 6 groups per group by the weight stratification method, and fasted in the evening.
・ Fasting is performed for 16 hours or more from the day before the administration of the test substance, and feeding is started after blood collection 8 hours later.
-The next morning, the drug solution is orally administered intragastrically using a sonde.
-Make the animal non-awake by isoflurane inhalation anesthesia, and collect about 200 µL of blood using a heparin-treated syringe. Blood sampling points were eight points before administration, 0.5 hour after administration, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, and 48 hours.
-Free water after administration.

6) Plasma analysis method-Pretreatment 100 µL of plasma is collected and deproteinized. For protein removal, 300 μL of methanol containing 0.5 mg / mL of antioxidant BHT is added, stirred for 20 minutes, cooled with ice for 5 minutes, and then centrifuged at 12,000 rpm for 10 minutes to collect 200 μL of supernatant.

-Analysis The amount of plasma astaxanthin is measured by LC / MS (liquid chromatography / mass spectrum) analysis.
LC conditions Column: Capcellpak CORE C18 2.1 × 75 mm 2.7 μm
Column temperature: 35 ° C
Mobile phase liquid A: water
Liquid B: acetonitrile: methanol = 1: 1
Gradient B liquid
0 minutes (90%) → 2-3 minutes (100%) → 3.1-4.7 minutes (90%)
Flow rate: 0.5 mL / min

(2) Results Cmax and AUC were calculated from changes in astaxanthin concentration in plasma.
FIG. 5 shows the result of Cmax, and FIG. 6 shows the result of AUC. Outliers were excluded from the results by a Smirnov-Grubbs test, and a significance test was performed.

  As a result of an absorption test using rats, Cmax and AUC showed that the astaxanthin powder of the present invention significantly improved the bioabsorbability of astaxanthin.

5. Animal test (2)
Self-emulsifying composition (SEDDS) having improved absorption properties of astaxanthin-containing powder and astaxanthin for oral administration according to the present invention, a pharmaceutical composition (current product) marketed by FANCL CORPORATION, Astalil 50FC which is a raw material of astaxanthin (control) )), The absorbability of astaxanthin was tested under the same conditions as in the animal test (1).
(1) Test method 1) Test sample-Silicon dioxide astaxanthin powder: containing 16% by mass of astaxanthin (the present invention)
-Self-emulsifying composition with improved absorbency (SEDDS)
・ Composition for current formulation (current product)
・ Asteril oil 50FC (containing 5% by mass of astaxanthin; Fuji Chemical Co., Ltd.) (control)
2) Animals used
Species: rat Strain: SD Gender: male
Age at the time of experimental treatment: 8 weeks of age 3) Number of administrations: single oral administration 4) Administration volume and administration route
Gavage is orally administered as 50 mg / kg astaxanthin.
5) Rearing conditions ・ After carrying the animals, rear them for 7 days.
・ Measure the body weight on the 7th day, divide the animals into groups of 6 animals by the weight stratification method, and fast from the evening.
-Fasting is performed for 16 hours or more from the day before the administration of the test substance, and feeding is started after blood collection 8 hours later.
-The next morning, the drug solution is orally administered intragastrically using a sonde.
-Make the animal non-awake by isoflurane inhalation anesthesia, and collect about 200 µL of blood using a heparin-treated syringe. Blood collection points were eight points before administration, 0.5 hour after administration, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, and 48 hours.
-Free water after administration.

6) Plasma analysis method-Pretreatment 100 µL of plasma is collected and deproteinized. For protein removal, 300 μL of methanol containing 0.5 mg / mL of antioxidant BHT is added, stirred for 20 minutes, cooled with ice for 5 minutes, and then centrifuged at 12,000 rpm for 10 minutes to collect 200 μL of supernatant.

-Analysis The amount of plasma astaxanthin is measured by LC / MS (liquid chromatography / mass spectrum) analysis.
LC conditions Column: Capcellpak CORE C18 2.1 × 75 mm 2.7 μm
Column temperature: 35 ° C
Mobile phase liquid A: water
Liquid B: acetonitrile: methanol = 1: 1
Gradient B liquid
0 min (90%) → 2-3 min (100%) → 3.1-4.7 min (90%) Flow rate: 0.5 mL / min

(2) Results Changes in the astaxanthin concentration in the plasma of the composition of the present invention and each test sample are shown in FIG.

As a result of the absorption test using rats, as shown in FIG. 7, the composition of the present invention showed Cmax 48 hours after administration. On the other hand, it was confirmed that the control, the SEDDS, and the current product all had a Cmax between 1 and 3 hours.
From the comparison of the time course of the astaxanthin concentration in each test sample over time, the improvement in absorbability by the composition of the present invention is different from the rapid absorption by a general emulsification technique, and it is understood that the absorption is gradually absorbed into the living body. It became clear (see FIG. 7).

6. Powder properties (powder properties)
The compositions of the present invention of Examples 1 to 6 were free-flowing powders, and were easy to handle without adhesion or the like.

7. Tableting aptitude Tablets were prepared using Examples 1, 2, and 3 and a commercially available powdered raw material containing 2% by mass of astaxanthin (Astaryl Powder 20F; Fuji Chemical Industry Co., Ltd.) and compared the tableting characteristics. did.
The evaluation and comparison of tableting properties were evaluated based on the method described in the following literature.
References: Osamura T, Takeuchi Y, Onodera R, et al. . Int Pharm 2016; 510: 195-202.

(1) Preparation of Test Tablet A tableting powder having the formulation shown in Table 5 below was prepared so that 150 mg of tablet contained 6 mg of astaxanthin.

Using a measuring device GTP-2 (manufactured by Gamlen Tableting Ltd.), the tablet is molded at a compression pressure of 200 MPa, and the tablet strength (Tensilefracture stress, hereinafter referred to as TS), the ejection friction (Ejection Stress), and the friction with the punch (Detachment Stress) are measured. did.
Tablet weight: 150mg
Punch size: φ6mm flat punch Compression pressure: 200MPa
Punch speed: 30 mm / min

(2) Evaluation of tableting aptitude Tablet measurement aptitude was evaluated by plotting the measurement results of tablet strength, discharge friction pressure, and friction pressure with a punch in accordance with the description in the above-mentioned literature.
The four plotted areas have the following meanings.
Region I: Good productivity, high tablet strength Region II: Good productivity, low tablet strength Region III: Poor productivity, high tablet strength Region IV: Low productivity, low tablet strength

A high discharge friction means a high risk of capping, and a high friction with a punch means a high risk of sticking. Generally, when molding at 200 MPa, it is most preferable if the discharge friction is 2 MPa or more and TS is 2 MPa or more (bubbles are small and most preferably plotted in a region I in FIG. 8).
In FIG. 8, the tablet strength (TS) is plotted on the horizontal axis, and the ejection friction (Ejection Stress) is plotted on the vertical axis, and the friction with the punch is represented by the size of a bubble (circle in the figure).
The commercially available astaxanthin powder (existing powder product) had low tablet strength and high friction with a punch (Detachment Stress), which is a risk of sticking. Example 3 was evaluated as having the best tableting performance.
That is, it became clear that the astaxanthin powder according to the present invention had preferable tableting aptitude which was clearly different from that of the conventional product.

Claims (6)

  An astaxanthin-containing powder comprising astaxanthin and porous fine particles.   An astaxanthin-containing powder comprising particles in which astaxanthin is carried in pores formed in porous fine particles.   The astaxanthin-containing powder according to claim 1 or 2, wherein the porous fine particles are at least one substance selected from silicon dioxide, calcium silicate, and porous starch.   The astaxanthin-containing powder according to any one of claims 1 to 3, which contains 8 to 30% by mass of astaxanthin per powder.   A method for producing an astaxanthin-containing powder, comprising mixing a liquid oil containing astaxanthin and porous fine particles, performing a supercritical extraction operation under a pressure condition of 15 MPa or more, and collecting an extraction residue. The method for producing an astaxanthin-containing powder according to claim 5, wherein the porous fine particles are a powder composed of at least one substance selected from silicon dioxide, calcium silicate, and porous starch.