JP2019062886A - Composition and use therefor - Google Patents

Abstract

To provide a composition that stably contains docosahexaenoic acid and lutein, and shows excellent usability when made into an oral preparation such as a soft capsule agent.SOLUTION: A composition contains (A) component: docosahexaenoic acid, (B) component: lutein, or, lutein and zeaxanthin, and (C) component: free body capsanthin. The composition is useful as an oral preparation such as a soft capsule agent.SELECTED DRAWING: None

Description

  The present invention relates to compositions and their uses, such as soft capsules.

  Docosahexaenoic acid (DHA) is a type of polyunsaturated fatty acid and is known to have an improving effect on brain function. In order to exert such effects, it is desirable to increase the content of DHA in the preparation. However, since DHA is easily oxidized and lacks stability, there is a problem that the content in the preparation decreases.

  It is known to use antioxidants such as carotenoids (patent document 1) and vitamin E (patent document 2) for improving the stability of unsaturated fatty acids including DHA. Among carotenoids, combinations of carotenoids such as lutein and capsanthin with DHA are also known to have a good improving effect on brain function (Non-Patent Document 1, Patent Document 3).

Patent No. 4768391 JP 2017-61466 A WO 2015/5443

Johnson EJ. et al. (2008) The American Journal of Clinical Nutrition 87, 1521-9

  However, carotenoids such as lutein are easily oxidized, and there is a problem that the content of both of the preparation containing DHA and lutein after storage decreases. Similar to lutein, zeaxanthin, which is an isomer of lutein, has the problem of being easily oxidized.

  Also, when vitamin E is used to improve the stability of DHA, a large amount of vitamin E is usually required. Therefore, when vitamin E is added to a soft capsule containing DHA, the capsule size becomes large and there is a problem that the usability (easiness of taking a drink, ease of intake) decreases.

  An object of the present invention is to provide a composition containing DHA and lutein stably and having good usability when made into an oral preparation such as a soft capsule.

The present invention provides the following.
[1] (A) component: docosahexaenoic acid,
Component (B): Lutein, or a composition containing lutein and zeaxanthin, and (C) component: free form capsanthin.
[2] The composition according to [1], wherein the content of the component (A) is 30 to 70% by mass with respect to the total amount of the composition.
[3] The ratio of the total amount of the content of the component (B) and the content of the component (C) to the content of the component (A) is 0.2 to 12% by mass, [1] or [2] The composition as described in.
[4] The composition according to any one of [1] to [3], which has a viscosity of 150 mPa · s or more at 25 ° C.
[5] Component (D): The composition according to any one of [1] to [4], which further comprises a waxy compound.
[6] The composition according to [5], wherein the component (D) contains at least one or more fatty acid esters.
[7] The composition according to [5] or [6], wherein the content of the component (D) is 1% by mass or more based on the total amount of the composition.
[8] The composition according to any one of [1] to [7], which is a food, a medicine, a quasi-drug or a component thereof.
[9] The composition according to any one of [1] to [8], which is a content liquid of a soft capsule preparation.
[10] An oral preparation containing the composition according to any one of [1] to [9].
[11] The oral preparation according to [10], which is a food, a medicine or a quasi-drug.
[12] The oral preparation as described in [10] or [11], which is a soft capsule.
[13] A method for producing a soft capsule, which comprises coating the composition according to any one of [1] to [9] with a film.
[14] Component (A): Docosahexaenoic acid, and (B) Component: Lutein or a composition containing lutein and zeaxanthin
(C) Component: A method of stabilizing a composition, which comprises adding free body capsanthin.
[15] Component (D): The stabilization method according to [14], which further comprises adding a waxy compound.

  By containing the components (A) to (C), each component of the composition of the present invention exhibits good stability, and when used as an oral preparation such as a soft capsule, its usability is good.

  The composition of the present invention contains the components (A) to (C), and may further contain the component (D) as required. Each component will be described below.

[1. (A) Component: docosahexaenoic acid]
The component (A) is docosahexaenoic acid (DHA). DHA is often derived from natural products such as animals (for example, fish), microorganisms (for example, Schizochytrium microbes), but is not limited thereto, and may be obtained by organic synthesis or genetic recombination.

  DHA may be any of free form DHA (DHA as free fatty acid), derivatives, and pharmacologically acceptable salts thereof. As a derivative, for example, DHA ester (eg, DHA methyl ester, DHA ethyl ester), DHA-containing glyceride (eg, monoglyceride, diglyceride, or compound in which DHA is bound to triglyceride), DHA-containing phospholipid (eg, phosphatidylcholine, phosphatidylcholine) And compounds in which DHA is bound to a phospholipid such as serine. The component (A) may be used alone or in combination of two or more.

  Although content with respect to the composition of (A) component is not specifically limited, 25.0 mass% or more is preferable, 30.0 mass% or more is more preferable, 32.0 mass% or more is still more preferable for a lower limit. Thereby, when the composition is administered to a living body, the physiological function of the component (A) can be expected. 70.0 mass% or less is preferable, and 50.0 mass% or less of an upper limit is more preferable. 25.0-70.0 or 30.0-70.0 weight% is preferable, and, as for content of (A) component, 32.0-50.0 mass% is more preferable. Thereby, the stability of the composition is improved, and each component can be dispersed uniformly. When the composition is a soft capsule content liquid, it is more preferable to satisfy the above numerical range.

  Although the daily dose of the component (A) is not particularly limited, 630.0 mg / day or more is preferable, and 672.0 mg / day or more is more preferable. The upper limit is preferably 1470.0 mg / day or less, more preferably 1050.0 mg / day or less. The content of the component (A) per soft capsule when the composition is a content solution of a soft capsule (mass of 525.0 mg of one tablet) is preferably 105.0 mg / particle or more, and 112.0 mg / particle. The above is preferable. The upper limit is preferably 245.0 mg / particle or less, more preferably 175.0 mg / particle or less.

[2. (B) Component: Lutein, or Lutein and Zeaxanthin]
The component (B) is lutein, or lutein and zeaxanthin.

  Lutein (β, ε-carotene-3,3′-diol) is often contained in natural products such as chloroplasts of higher plants (spinach, keel, komatsuna etc.), but is not limited thereto It may be obtained by synthesis or genetic recombination. Lutein may be in the form of a free form (a lutein which is not esterified with a fatty acid), a derivative, or a pharmacologically acceptable salt, and may be a trans form or a cis form. The derivatives include esters of lutein (eg, monoesters and diesters). Lutein as the component (B) may be used alone or in combination of two or more.

  Zeaxanthin (4- [18- (4-hydroxy-2,6,6-trimethyl-1-cyclohexenyl) -3,7,12,16-tetramethyl-octadeca-1,3,5,7,9,11 , 13,15,17-nonaenyl] -3,5,5-trimethyl-3-cyclohexen-1-ol) is often found in natural products such as plants (corn etc.), egg yolks, animal fats etc. However, the present invention is not limited thereto, and may be obtained by organic synthesis or genetic recombination. Zeaxanthin may be in the form of free form (zeaxanthin which is not esterified with fatty acid), a derivative, or a pharmacologically acceptable salt, and may be in trans form or cis form. The derivatives include esters of zeaxanthin (eg, monoesters and diesters). When the component (B) contains zeaxanthin, one of these may be used alone, or two or more may be used.

  Although content with respect to the composition of (B) component is not specifically limited, 0.09 mass% or more is preferable, and, as for a lower limit, 0.14 mass% or more is more preferable. Thereby, when the composition is administered to a living body, physiological function of the component (B) can be expected. The upper limit is preferably 1.7% by mass or less and more preferably 0.57% by mass or less. When the composition is a soft capsule content liquid, it is more preferable to satisfy the above numerical range.

  The daily dose of the component (B) is not particularly limited, but is preferably 2.0 mg / day or more, and more preferably 3.0 mg / day or more. The upper limit is preferably 36.0 mg / day or less, more preferably 12.0 mg / day or less. The content of the component (B) per soft capsule when the composition is a content solution of a soft capsule (mass of 525.0 mg of one tablet) is preferably 0.33 mg / particle or more, and 0.5 mg / particle. The above is preferable. The upper limit is preferably 6.0 mg / particle or less, more preferably 2.0 mg / particle or less.

[3. (C) ingredient: free body capsanthin]
Component (C) is free-form capsanthin (capsanthin not esterified with fatty acid). Capsanthin ((3R, 3'S, 5'R) -3,3'-dihydroxy-.beta.,. Kappa.-carotene-6'-one, (3R, 3'S) -3,3'-dihydroxy-.beta.,. Kappa. -Carotene-6'-one) is often contained in natural products such as paprika and pepper, but is not limited thereto, and may be obtained by organic synthesis or genetic recombination. Capsanthin may be in trans form or cis form, and may be in the form of a pharmacologically acceptable salt.

  Although content with respect to the composition whole quantity of (C) component is not specifically limited, 0.09 mass% or more is preferable, and, as for a lower limit, 0.14 mass% or more is more preferable. The upper limit is preferably 1.7% by mass or less and more preferably 0.57% by mass or less. Thereby, when the composition is administered to a living body, the physiological function of the component (C) can be expected.

  The daily dose of the component (C) is not particularly limited, but is preferably 2.0 mg / day or more, and more preferably 3.0 mg / day or more. The upper limit is preferably 36.0 mg / day or less, more preferably 12.0 mg / day or less. The content of the component (C) per soft capsule when the composition is a content liquid of soft capsule (mass of 525.0 mg of one tablet) is preferably 0.33 mg / particle or more, and 0.5 mg / particle The above is preferable. The upper limit is preferably 6.0 mg / particle or less, more preferably 2.0 mg / particle or less.

[4. Component ratio]
The ratio ({(B + C) / A} × 100) of the total of the content of the component (B) and the content of the component (C) to the content of the component (A) is preferably 12.0 mass% or less, 8 The content is more preferably not more than 0, 7.0, 6.0, or 4.0% by mass, and still more preferably 3.0% by mass or less. Thereby, separation of each component can be suppressed. 0.2 mass% or more is preferable, 1.0, 1.1, 1.3, or 1.5 mass% or more is more preferable, and 1.9 mass% or more is still more preferable for a minimum. 0.2-12.0 mass% is preferable, and {(B + C) / A} x100 is 1.0-8.0, 1.1-7.0, 1.3-6.0, or 1.. 5-4.0 mass% is more preferable, and 1.9-3.0 mass% is further more preferable. Thereby, the stability of the composition can be improved without excessively increasing the amount of each component, so that the capsule size up of the soft capsule can be suppressed.

  2000 mass% or less is preferable, as for the ratio ({B / C} x 100) to content of (C) component of content of (B) component, 700 or 400 mass% or less is more preferable, and 300 mass% or less Is more preferred. 5.0 mass% or more is preferable, 10 or 30 mass% or more is more preferable, and 100 mass% or more is still more preferable for a minimum. 5.0 to 2000 mass% is preferable, 10 to 700, or 30 to 400 mass% is more preferable, and 100 to 300 mass% is more preferable. By being in the range of the above upper limit or the lower limit, the stability of the composition may be good. In addition, brain function improvement effect can be confirmed.

[5. Component (D): Waxy Compound]
The component (D) is a waxy compound. The waxy compound may be one having properties equivalent to wax (wax), for example, a compound having the ability to solidify an oil (oil gelling agent). The wax compound may be any component that can be used in food, and is preferably a component that can be used as an emulsifier or thickener for food. Wax compounds include, for example, glycerin fatty acid ester, polyglycerin fatty acid ester, organic acid monoglyceride, propylene glycol fatty acid ester, polyglycerin condensed ricinoleate ester, sorbitan fatty acid ester, sucrose fatty acid ester, calcium stearoyl lactate, sodium stearoyl lactate and the like Fatty acid esters of: Lecithin, Phospholipids such as enzyme-degraded lecithin; Waxes such as beeswax, rice wax, candelilla wax; hydrogenated extremely hardened oil of soybean, extremely hardened oil of rapeseed, extremely hardened oil of palm, extremely hydrogenated oil of hierucine rapeseed Extremely hardened oil; pectin, guar gum, xanthan gum, tamarind gum, carrageenan, propylene glycol, cellulose derivatives (eg, carboxymethyl cellulose, hydroxyethyl cellulose) (Eg, loin, hypromellose, etc.), soybean polysaccharides, fatty acid esters are preferable, mono-diglycerin fatty acid esters, polyglycerin fatty acid esters, glyceryl monostearate are more preferable, and monostearic acid glycerin and polyglycerin fatty acid esters are further preferable . The component (D) may be used singly or in combination of two or more, but it is preferable that the component (D) contains at least a fatty acid ester.

  Although content in particular with respect to the composition of (D) component is not limited, 0.5 mass% or more is preferable, 1.0 mass% or more is more preferable, 3.0 mass% or more is still more preferable. Thereby, the stability of the composition is improved, and each component can be dispersed uniformly. 62.0 mass% or less is preferable, and 17.5 mass% or less is more preferable. When the composition is a soft capsule content liquid, it is more preferable to satisfy the above numerical range.

[6. viscosity]
The composition of the present invention preferably has a viscosity of 150 mPa · s or more at 25 ° C., more preferably 150 mPa · s or more after 12 hours of production, and 150 mPa · s after 24 hours of production. More preferably, it is s or more. Thereby, separation of the components in the composition is suppressed, and stability can be maintained. The measurement of the viscosity can be performed with an E-type viscometer, and may be performed in accordance with the conditions described in the examples.

[7. Optional ingredients]
The composition of the present invention may further contain optional components. The optional component may be a pharmacologically acceptable component, and one example is a component (for example, a storage stabilizer) that mainly ensures stability in storage and distribution. As another example of the optional components, one or more types of components (preferably about 1 to 3 types) selected from various components constituting the desired end product (for example, food and drink, pharmaceutical products, quasi-drugs) Preferably, it may contain one or more.

  The pharmacologically acceptable optional ingredients are not particularly limited as long as the object of the present invention is not impaired. For example, excipients, disintegrants, binders, lubricants, coatings, coloring agents, coloring agents, flavoring agents, flavoring agents, antioxidants, preservatives, taste agents, acidulants, sweeteners, fortification Agents, vitamin agents, expanders, thickeners, and surfactants, which do not impair various properties (for example, formulation stability) necessary for the preparation, and which are end products (for example, medicines, 1 type or 2 or more types according to the dosage form of goods, food-drinks) can be selected. The pharmacologically acceptable optional component may be another component having a nitric oxide production inhibitory effect.

  As an excipient, for example, cellulose such as hydroxypropyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, crystalline cellulose, ethyl cellulose, low substituted hydroxypropyl cellulose and pharmacologically acceptable derivatives thereof, polyvinyl pyrrolidone, partially saponified polyvinyl alcohol Synthetic polymers such as gelatin, gum arabic powder, pullulan, agar, alginic acid, sodium alginate, polysaccharides such as xanthan gum, ethanol, isobutyl alcohol, isopropyl alcohol, butanol, propanol, 2-pentanol, 2-methyl butanol, 3 -Lower alcohols such as methyl-2-butanol, 3-methyl-2-butenol, 1-penten-3-ol; hydrogenated rapeseed oil alcohol, lauryl alcohol Higher alcohols such as stearyl alcohol, cetyl alcohol, cetostearyl alcohol, lanolin alcohol, octyl dodecanol and other aliphatic higher alcohols; corn starch, potato starch, carboxymethyl cellulose, carboxymethyl cellulose calcium, carboxymethyl starch sodium, hydroxypropyl starch Starches such as partially gelatinized starches and gelatinized starches and pharmacologically acceptable derivatives thereof; lactose, fructose, glucose, sucrose, trehalose, palatinose, mannitol, sorbitol, erythritol, xylitol, reduced palatinose, powder reduced maltose starch syrup , Sugars such as maltitol and sugar alcohols; polyhydric alcohols such as propylene glycol and glycerin; light anhydride Lee acid, particulate silicon oxide, particulate silicon dioxide, titanium oxide, and inorganic excipients such as aluminum hydroxide gel.

  The lower limit value of the content of the excipient relative to the total amount of the composition is preferably 0.01% by mass or more. The upper limit is preferably 70% by mass or less.

  As an emulsifier, components other than the component (D) may be used. For example, triethyl citrate, sodium casein, saponin and the like can be mentioned.

  Examples of coloring agents include caramel dyes, turmeric dyes, orange dyes, cocoa dyes, pepper dyes, marigold dyes, iron (III) oxide, titanium dioxide, safflower dyes, gardenia dyes, copper chlorophyll dyes.

[8. Method of preparing composition]
The method of preparing the composition is not particularly limited, and one example is as follows. First, mixing (dispersion or homogenization) may be performed while warming up the component (A), the component (D) optionally used, and the optional component. The heating is usually performed at 40 ° C. or more, preferably 50 ° C. or more, more preferably 55 ° C. or more. The upper limit is usually 100 ° C. or less, preferably 90 ° C. or less, more preferably 80 ° C. or less. Therefore, the heating is usually performed at 40 to 100 ° C., preferably 50 to 90 ° C., more preferably 55 to 80 ° C.

  The mixing is preferably performed mechanically. The apparatus used for mechanical mixing includes, for example, a high-speed stirrer (eg, three-one motor (agitator), homomixer, high-pressure homogenizer, etc.) and a high-pressure grinder. In the case of a three one motor, it is preferable to combine with other devices. The high-pressure homogenizer is preferable in that the crushing effect of each component (in particular, the phospholipid as the component (D)) is high and the residue of the lump is easily eliminated. On the other hand, the homomixer is preferable because there is no concern about the complexity of the manufacturing process and the manufacturing cost such as the power consumption can be suppressed. The mixing using the homomixer can be performed, for example, by charging each component in a stainless steel container and stirring for 5 to 10 minutes at a rotation speed of 3000 to 10000 rpm in a state of being heated at the above temperature .

  Subsequently, the components (B) and (C) are mixed while being heated, completely dissolved, and then cooled. The cooling temperature is usually 70 ° C. or less, preferably 60 ° C. or less, more preferably 40 ° C. or less, although it depends on the heating temperature. The lower limit is usually 20 ° C. or more, preferably 22 ° C. or more, more preferably 25 ° C. or more. Therefore, the cooling temperature is usually 20 to 70 ° C., preferably 22 to 60 ° C., more preferably 25 to 40 ° C. By cooling, the (B) component, the (C) component, and the optionally included (D) component precipitate, and the viscosity of the composition can be increased. In the case of cooling, stirring is performed as needed. Thereby, the component (D) can be precipitated, and the viscosity of the composition can be increased. The composition obtained after cooling may be passed through a 80 mesh (180 μm mesh) sieve, if necessary. This makes it possible to break up aggregates.

[9. Application and Dosage Form of Composition]
The composition of the present invention can be used as food, medicine, quasi-drug and their constituent materials. Examples of food include beverages (soft drinks, carbonated drinks, nutritional drinks, powdered drinks, fruit drinks, milk drinks, jelly drinks, etc.), confectionery products (cookies, cakes, gums, candies, tablets, gummi, buns, york, Pudding, jelly, ice cream, sherbet etc., processed fishery products (kamaboko, chikuwa, rice etc.), processed livestock products (hamburg, ham, sausage, wine, cheese, butter, yogurt, fresh cream, margarine, fermented milk etc.) , Soup (powdered soup, liquid soup, etc.), staple foods (rice, noodles (dried noodles, fresh noodles), bread, cereals, etc.), seasonings (mayonnaise, shortening, dressing, sauce, soy sauce, etc.) Be The food may be any of health food, functional food, dietary supplement (supplement), food for specified health use, food for medical use, food for sickness, food for infants, food for nursing care, and food for elderly people.

  The mode of administration of the drug or quasi-drug is not particularly limited, but oral administration (eg, buccal administration, sublingual administration) is preferred because of its low invasiveness.

  As a dosage form of food, medicine and quasi-drug, for example, liquid (liquid), syrup (syrup), tablet (tablet, tablet), capsule (capsule), powder (granule, fine particle) Among them, soft capsules (soft capsules), solid forms, semi-liquids, creams and pastes may be mentioned. Among them, dosage forms which can be used for oral preparations are preferable, and soft capsules are more preferable. The composition of the present invention is preferably a component of an oral preparation, more preferably a component of a soft capsule, and still more preferably a liquid of a soft capsule.

[10. Oral preparation]
The oral preparation of the present invention contains the composition of the present invention. The administration target of the oral preparation may be any animal including human, and is usually a human but non-human animals (eg, mouse, rat, hamster, dog, cat, sheep, goat, cow, pig, monkey, etc.) (Mammals) may be

[11. Soft capsule agent]
The dosage form of the oral preparation may be any dosage form that can be used as a food, medicine, quasi drug. Examples of dosage forms are the same as those exemplified above, and among these, soft capsules are preferred. A soft capsule is an agent consisting of a content liquid and a film surrounding the periphery. The film usually contains a base polymer such as gelatin and starch, a plasticizer such as glycerin and sorbitol, and an optional component (eg, a pigment etc.) optionally used.

[12. Method of producing soft capsule agent]
The method for producing the soft capsule preparation is not particularly limited as long as it is a method including covering (encapsulating) the composition of the present invention with a film, and examples thereof include a flat plate method and a rotary die method. Hereinafter, according to the rotary die method, a medicine tank and a gelatin melting tank are provided, and a manufacturing example using a filling machine capable of setting a die roll and a tumble dryer will be described.

  The composition of the invention is placed in a medicine tank and set in place on the filling machine. Before being placed in the medicine tank, pretreatment such as emulsification, suspension, etc. of the composition may be carried out, if necessary. Subsequently, the base polymer, plasticizer and purified water are added to the gelatin melting tank, heated and dissolved (for example, about 80 ° C.), defoaming operation is performed in the same tank, and the viscosity is adjusted to prepare a film stock solution. Get The membrane stock solution is transferred to a dispensing tank (generally, heating (for example, 50 to 55 ° C.)) while filtration is performed, and set in a predetermined position of the filling machine.

  The target die roll is set in the filling machine, and the film stock solution and composition are molded to obtain a soft capsule. The temperature of the filling chamber is usually adjusted to 20 to 30 ° C. The relative humidity of the filling chamber is usually maintained at 30 to 50%. The soft capsule immediately after molding is fed into a tumbler dryer connected to a filling machine, and while rotating, temporary fixing of the shape and temporary drying of moisture in the film are performed with clean air similar to the room conditions (usually about 1 to 4) time). Thereafter, it is transferred to a tumble dryer and dried. The temperature during drying is usually 20 to 30 ° C., and the relative humidity is usually 30 to 50%. The drying time is usually 24 to 48 hours. Drying is performed until it falls to 6 to 8%, for example, in the case of 30 to 40% of moisture content at the time of filling.

  The dried soft capsule may be finished by brushing with a tumbler for 2 minutes to 1 hour, if necessary.

[13. Use of oral preparation]
The oral preparation of the present invention can be used as food, medicine, quasi drug. The food may be any of health food, functional food, dietary supplement (supplement), food for specified health use, food for medical use, food for sickness, food for infants, food for nursing care, and food for elderly people.

[14. Stabilization method]
By adding the component (C) to the composition containing the components (A) and (B), the stability of the composition can be improved. The contents of the components (A) and (B) in the composition, the daily dose, and the content per tablet when the composition is the content liquid of the soft capsule are each after addition of the component (C). It is sufficient if the amount of is as described above. In addition, the amount of the component (C) added to the composition is the content of the component (C) in the composition after the addition, the daily dose, and one tablet when the composition is the content liquid of the soft capsule. It is sufficient if the content of is as described above.
Further, by further adding the component (D), the stability of the composition can be made better. The addition amount of the component (D) to the composition is the content of the component (D) in the composition after addition, the daily dose, and the content per tablet when the composition is the content liquid of the soft capsule. The amount may be any amount as described above.
The composition containing the components (A) and (B) may contain optional components, and may be any of food, drink, medicine, quasi drug, dosage form (soft capsule is preferred), administration form (oral preparation Is the same as the composition containing the components (A) to (C) described above.

  Hereinafter, the present invention will be described in detail by way of examples. The following examples are intended to illustrate the invention but not to limit it.

Examples 1 to 24 and Comparative Examples 1 to 12
Composition of Tables 2 to 7 (unit of numerical value of each component in Tables 2 to 7 using the components shown in Table 1: mg / particle; each content and blending ratio of Components (A) to (D) are converted The soft capsule formulation of the numerical value as a value; each content and the compounding ratio of "others edible oil and fat" produced the numerical value of the component containing solvents other than component (A)-(D) was produced. The soft capsule formulation was prepared by the following method. First, components (A) and (D) and optional components were placed in a stainless beaker and mixed at 70 ° C. The mixing (stirring and mixing) was performed for 10 minutes under 8000 rpm in a homomixer (homomixer MK2; manufactured by Primix). Subsequently, the components (B) and (C) were mixed while being heated, and the components (B) and (C) were completely dissolved, and then cooling was performed in an environment of 25 ° C. together with a stainless beaker. In the cooling step, the composition was cooled to 25 ° C. under 500 rpm conditions using Three One Motor BL 1200 (manufactured by Shinto Scientific Co., Ltd.) so that the composition containing oil and fat becomes uniform. Thereafter, it was passed through a sieve of 80 mesh (180 μm mesh). At this time, if there is any undissolved matter on the sieve, the aggregate is broken up to form a content solution for a soft capsule (oral preparation). The content liquid was coated with a film component by a conventional method to obtain a soft capsule. The results of the evaluation test are shown in Tables 2-7. The information regarding the component used by each Example and the comparative example is shown in Table 1.

  The storage stability test and the viscosity test were conducted for each soft capsule preparation.

[Storage stability test]
After storing the soft capsule formulation-filled bottles (with desiccant) at 40 ° C, 75% relative humidity, 4 months, and then storing the soft capsule formulations of carotenoids (lutein, zeaxanthin, capsanthin, β-cryptoxanthin, astaxanthin) And the amount of DHA was quantified, compared with each amount (initial value) before storage, and evaluated based on the following criteria.
A: Initial value 99 99%
B: 96% ≦ initial value <99%
C: 94% ≦ initial value <96%
D: Initial value <94%

  The soft capsule formulation of Example 2 was stored at 40 ° C., 75% relative humidity, for 4 months. As a result of quantifying the soft capsule preparation after storage, DHA is relative to the initial value 100.0% (reference A), lutein is relative to the initial value 100.7% (reference A), capsanthin to the initial value 99.8% (reference A )Met. Evaluation was similarly performed about other compositions.

  The amount of carotenoids is HPLC method (pump: liquid transfer unit LC-20AD (Shimadzu Corporation), sample introduction device: autosampler SIL-20AC (Shimadzu Corporation), column oven: CTO-20AC (corporation) Shimadzu Corporation) Detector: Photodiode array detector SPD-M20A (Shimadzu Corporation) Column: A stainless steel tube with an inner diameter of 4.6 nm and a length of 150 mm filled with 5 μm of silica gel for liquid chromatography) It was measured.

  The amount of DHA is GC method (gas chromatograph: GC-2025 (Shimadzu Corporation) or GC-2010 Plus (Shimadzu Corporation), sample introduction device: AOC-20i / AOC-20S (Shimadzu Corporation) Hydrogen generator: Measured with HGE-260 (manufactured by Shimadzu Corporation), detector: hydrogen flame ionization detector, column: (50% -cyanopropyl) -methylpolysiloxane column).

[Viscosity test]
The viscosity at 25 ° C. of the soft capsule formulation was measured over time. The viscosity was measured using an E-type viscometer (rotational speed: 10 rpm, rotor: 1 ° 34 ′ × R24). From the measured values, the viscosity was evaluated based on the following criteria.
A: 150 mPa · s or more after 24 hours of production (no separation of contents)
B: A does not satisfy, but after 12 hours of production, 150 mPa · s or more (no separation of contents)
C: A does not satisfy, and less than 150 mPa · s (with separation of contents liquid) after 12 hours of production
D: A to C are not satisfied, and after 6 hours of production, less than 150 mPa · s (with separation of contents)

  The viscosity at 25 ° C. of the soft capsule formulation of Example 2 was measured over time. As a result, it was 737.3 mPa · s (standard A) 24 hours after production. Evaluation was similarly performed about other compositions.

  The following can be understood from Tables 2 to 7. The soft capsules of Examples 1 to 24 had good viscosity and good stability of each component as compared with Comparative Examples 1 to 12 containing no (B) or (C) component. These results show that the composition of the present invention shows good stability of each component and has good usability as a soft capsule.

Claims (15)

(A) Component: docosahexaenoic acid,
Component (B): Lutein, or a composition containing lutein and zeaxanthin, and (C) component: free form capsanthin.   The composition according to claim 1, wherein the content of the component (A) is 30 to 70% by mass with respect to the total amount of the composition.   The composition according to claim 1 or 2, wherein the ratio of the total amount of the content of component (B) and the content of component (C) to the content of component (A) is 0.2 to 12% by mass. .   The composition according to any one of claims 1 to 3, wherein the viscosity at 25 ° C is 150 mPa · s or more.   Component (D): The composition according to any one of claims 1 to 4, further comprising a waxy compound.   The composition according to claim 5, wherein the component (D) contains at least one or more fatty acid esters.   The composition according to claim 5 or 6, wherein the content of the component (D) is 1% by mass or more based on the total amount of the composition.   The composition according to any one of claims 1 to 7, which is a food, a medicine, a quasi-drug or a component thereof.   The composition according to any one of claims 1 to 8, which is a content liquid of a soft capsule.   An oral formulation comprising the composition according to any one of claims 1-9.   The oral preparation according to claim 10, which is a food, a medicine or a quasi-drug.   The oral preparation according to claim 10, which is a soft capsule.   A method of producing a soft capsule, comprising coating the composition according to any one of claims 1 to 9 with a film. Component (A): docosahexaenoic acid, and (B) component: lutein, or a composition comprising lutein and zeaxanthin,
(C) Component: A method of stabilizing a composition, which comprises adding free body capsanthin. (D) Component: The stabilization method according to claim 14, which further comprises adding a waxy compound.