JP6842998B2 - Coenzyme Q10 film formulation - Google Patents

Description

The present invention relates to a coenzyme Q10 film preparation having excellent handleability.

Coenzyme Q10 (coenzyme Q10) is a vitamin-like fat-soluble substance present in mitochondria throughout the body. Coenzyme Q10 protects cells from oxidative stress because it functions as a coenzyme in electron transfer in the oxidative phosphorylation reaction, is involved in systemic energy production, and also has an antioxidant function. Coenzyme Q10 is widely used not only as a therapeutic agent for cardiovascular diseases such as congestive heart failure, but also as a supplement and food. However, coenzyme Q10 is a fat-soluble substance having a low melting point, and has a problem that it is unstable and decomposes by heat or the like to produce ubichromenol or the like.

Therefore, coenzyme Q10 is used in the form of tablets or the like, which is prepared by dissolving it in oil and filling it in capsules, or by powdering it together with an excipient. However, capsules and tablets need to be taken together with water when ingested, which is somewhat inferior in convenience and has a problem that they cannot be ingested except by mouth.

The film preparation is a preparation in the form of a thin film, and can be contained in the mouth as it is, dissolved in the mouth, and ingested. The film form is very useful because it is a form that is easy to ingest even for elderly people with impaired swallowing function. In addition, the film form can be attached to the skin and absorbed transdermally, and is a highly convenient form of preparation. On the other hand, since it is a thin film, it may be cracked or chipped and is inferior in destructibility, and even if the film is too soft or too hard, it is necessary to pay attention to operations such as taking it out of the packaging.

Patent Document 1 describes a film-like food in which a supplement component encapsulated in cyclodextrin is retained in an edible film. Patent Document 2 describes a composition in which an unstable component is incorporated into a water-soluble polymer film. However, in those of these inventions, when coenzyme Q10 is blended, only ones that are easily broken and inferior in handleability can be obtained when trying to form a film, and if the thickness is increased to avoid this, the film becomes too hard and handleability is also obtained. It had become inferior to.

Japanese Unexamined Patent Publication No. 2008-72915 Japanese Unexamined Patent Publication No. 2008-503580

An object of the present invention is to provide a coenzyme Q10 film preparation which is excellent in handleability while containing coenzyme Q10 and a method for producing the same.

The present invention mixes a coenzyme Q10 film preparation containing coenzyme Q10 and alginic acid emulsified with a water-soluble polymer or emulsifier, alginic acids selected from salts thereof or esters thereof, and coenzyme Q10 with a water-soluble polymer or emulsifier. The present invention relates to a method for producing a coenzyme Q10 film preparation, which comprises adding alginic acid, a salt thereof or an alginic acid selected from an ester thereof to the produced coenzyme Q10 emulsion and mixing them to form a film.

The present invention includes the following aspects.
(1) A coenzyme Q10 film preparation containing coenzyme Q10 emulsified with a water-soluble polymer or emulsifier, alginic acid, alginic acids selected from salts thereof or esters thereof. (2) The preparation of (1), wherein the water-soluble polymer is a modified starch having a molecular weight of 2000 or more.
(3) The preparation according to any one of (1) or (2), wherein the emulsifier contains one or more emulsifiers selected from sucrose fatty acid ester and glycerin fatty acid ester.
(4) The preparations of (1) to (3), wherein the blending amount of the alginic acids is 10 to 94% by mass in the preparation.
(5) A water-soluble polymer or emulsifier and coenzyme Q10 are mixed and emulsified, and alginic acid, a salt thereof or alginic acids selected from esters thereof are added to the produced coenzyme Q10 emulsion and mixed to form a film. A method for producing a coenzyme Q10 film preparation.
(6) The production method of (5), wherein the water-soluble polymer is a modified starch having a molecular weight of 2000 or more.
(7) The production method according to any one of (5) or (6), wherein the emulsifier contains one or more emulsifiers selected from sucrose fatty acid ester and glycerin fatty acid ester.
(8) The production methods of (5) to (7), wherein the blending amount of the alginic acids is 10 to 94% by mass in the preparation.

The coenzyme Q10 film preparation of the present invention can be produced by forming a coenzyme Q10 emulsion obtained by emulsifying a fat-soluble coenzyme Q10 with a water-soluble polymer or an emulsifier in advance using alginic acids.

As the coenzyme Q10 used in the present invention, those obtained by known means such as those extracted from a living body, those produced by a synthetic method, and those produced by a fermentation method can be used. The amount of coenzyme Q10 blended in the film preparation of the present invention can be blended up to about 72% by mass. If the amount of coenzyme Q10 blended exceeds 72% by mass, it becomes difficult to form a film. Further, if the amount of coenzyme Q10 is increased, the components for emulsification and film formation are relatively reduced, which may reduce the handleability of the film preparation. On the other hand, if the amount of coenzyme Q10 is decreased, the effect is difficult to obtain. Become. Therefore, the blending amount of coenzyme Q10 is preferably about 10 to 60% by mass, and more preferably about 20 to 55% by mass.

In the production method of the present invention, coenzyme Q10 needs to be emulsified before producing the film. Coenzyme Q10 is fat-soluble and can be emulsified using various water-soluble components and surfactant components. The water-soluble polymer used for emulsification in the present invention generally has a molecular weight of 2000 Da or more among the components that can be used for emulsification in the food and pharmaceutical fields. If it is less than 2000 Da, the flexibility of the obtained film preparation is insufficient, and the preparation becomes fragile. The molecular weight is preferably 4000 to 1 million Da.

The water-soluble polymer used in the present invention has the above molecular weight, and includes gums such as arabic gum and xanthan gum, water-soluble polysaccharides such as pullulan and water-soluble soybean polysaccharide, octenyl succinate starch, and hydroxypropyl starch. Among these, modified starch is preferable, and octenyl succinate starch is most preferable.
Examples of the emulsifier used in the present invention include sucrose fatty acid ester, glycerin fatty acid ester, sorbitan fatty acid ester, propylene glycol fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil, polyglycerin fatty acid ester, and organic acid monoglyceride. Any synthetic or natural emulsifier used as a food emulsifier such as lecithin, saponin, casein, and sodium casein can be used, but among them, sucrose fatty acid ester or glycerin fatty acid ester is particularly preferable from the viewpoint of handleability and the like. ..

The blending amount of coenzyme Q10 and the water-soluble polymer or emulsifier in the coenzyme Q10 emulsion is not particularly limited, but coenzyme Q10 is 10 to 80% by mass and the water-soluble polymer or emulsifier is 10 to 70% by mass. is there. The blending ratio of coenzyme Q10 to the water-soluble polymer or emulsifier is 40:60 to 70:30, preferably 45:55 to 60:40.

In addition to coenzyme Q10 and a water-soluble polymer or emulsifier, an emulsifying aid or an emulsion stabilizer may be added to the coenzyme Q10 emulsion. Such components include polyhydric alcohols such as glycerin and sorbitol, organic acids such as succinic acid and citric acid, and the like. The blending amount of these emulsifying aids and emulsion stabilizers is 30% by mass or less, preferably 20% by mass or less in the coenzyme Q10 emulsion.

The coenzyme Q10 emulsion is prepared by mixing the above components and performing high-speed stirring, shearing treatment, or the like to prepare an emulsion having fine particles. At this time, since coenzyme Q10 is crystalline at room temperature, it is preferable to heat it to make an emulsion in a state in which coenzyme Q10 is dissolved. For example, the coenzyme Q10 may be dissolved at 45-90 ° C., which is a temperature higher than the melting point of the coenzyme Q10, mixed with other components, and then the emulsion may be prepared using a known means, for example, a high pressure homogenizer. , The water-soluble polymer or emulsifier may be prepared in an aqueous solution at 45 to 90 ° C., and coenzyme Q10 may be gradually added thereto to prepare an emulsion. When the aqueous solution is used, it is in the state of an emulsified solution immediately after emulsification, but this may be dried once to be powdered, or it may be directly used in the film forming step of the next step.

The coenzyme Q10 emulsion obtained as described above is then mixed with alginic acids and then molded as a film agent. The content of alginic acids in the film preparation is 10 to 94% by mass. If it is less than 10% by mass, the film agent is easily cracked, and if it exceeds 94% by mass, the film agent becomes hard and the handleability is deteriorated. The blending amount of alginic acids is preferably 30 to 60% by mass.
Even if coenzyme Q10 is emulsified and filmed in the same process to form a film, a desired coenzyme Q10 film preparation cannot be obtained. In order to obtain the coenzyme Q10 film preparation of the present invention, first It is necessary to produce a coenzyme Q10 emulsion, mix it with alginic acids, and then mold it as a film agent.

Examples of alginic acids include alginic acid, alginate, and alginic acid ester, and one of these can be used alone or in combination of two or more. Examples of the alginate include monovalent salts such as sodium alginate and potassium alginate; divalent salts such as calcium alginate; and basic salts such as ammonium alginate. Examples of the alginate ester include propylene glycol alginate. Among these alginates, sodium alginate is particularly preferable.

In addition to the above-mentioned coenzyme Q10 emulsion and alginic acid, the film preparation of the present invention may contain a plasticizer such as glycerin, a sweetener, a fragrance, a coloring agent, an emulsifier, etc., if necessary. The amount is about 20% by mass or less in the film preparation.

The film thickness of the film agent of the present invention can be appropriately set depending on the usage mode of the film agent, but it is not too hard and not too soft, and from the viewpoint of ease of handling, the thickness is set to about 30 to 500 μm. Is preferable.

In producing the film agent of the present invention, the film formation itself after producing the coenzyme Q10 emulsion can be carried out by a known method. For example, the raw material is dispersed in water or alginic acid is added to the emulsion. It can be produced by adding the above, applying this dispersion on a smooth flat surface, and drying. Alternatively, the raw materials can be preferably powdered, mixed uniformly, and rolled with a hammer, a roller, or the like while applying heat of about 40 to 70 ° C. to produce the raw material. Further, it can be continuously produced by applying the above dispersion liquid on a slowly rotating roller and peeling it while rotating the roller and drying it with hot air or the like.

The coenzyme Q10 film preparation of the present invention may be formed into a sheet having an appropriate size, for example, about 1 cm × 2 cm, taken as it is, licked and dissolved, and ingested, or it may be attached to the skin via a tape agent. It may be used as a transdermal preparation. Therefore, the coenzyme Q10 film preparation of the present invention can be used as a pharmaceutical product, a food product, and a cosmetic product.

Next, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to the following Examples.

(Example 1)
100 g of purified water was added to 10 g of sodium octenyl succinate (molecular weight 4500 Da, manufactured by Matsutani Chemical Industry Co., Ltd.), dissolved, and heated to about 60 ° C. To this, 10 g of Coenzyme Q10 (manufactured by Nisshin Pharma) was added and mixed, and a uniform emulsion was produced with a high-pressure homogenizer. 80 g of sodium alginate (manufactured by Kimika) was added to the emulsion and mixed well. This liquid was spread thinly on a stainless steel tray and dried in a constant temperature bath at 60 ° C. to produce a film preparation. A substantially smooth film agent was obtained, and the thickness was about 400 μm.

(Comparative Example 1)
100 g of purified water was added to 10 g of sodium octenyl succinate starch (manufactured by Matsutani Chemical Industry Co., Ltd.), dissolved, and heated to about 60 ° C. To this, 10 g of coenzyme Q10 (manufactured by Nisshin Pharma) and 80 g of sodium alginate (manufactured by Kimika) were added, and the mixture was stirred and mixed at high speed. This liquid was spread thinly on a stainless steel tray and dried in a constant temperature bath at 60 ° C. to produce a film preparation. Although the thickness was slightly uneven, the average thickness was about 400 μm.

(Comparative Example 2)
100 g of purified water was added to 10 g of γ-cyclodextrin (molecular weight 1300 Da, manufactured by Cyclochem), dissolved, and heated to about 60 ° C. To this, 10 g of coenzyme Q10 (manufactured by Nisshin Pharma) was added and mixed to prepare an inclusion solution. To this inclusion solution, 80 g of sodium alginate (manufactured by Kimika) was added and mixed well. This liquid was spread thinly on a stainless steel tray and dried in a constant temperature bath at 60 ° C. to produce a film preparation. It was a film agent with many wrinkles, and the average thickness was about 400 μm.

(Test Example 1)
The film preparations of Examples 1 and Comparative Examples 1 and 2 were cut into a 4 cm × 4 cm sheet, bent at 90 degrees, that is, at a right angle, and then bent in the opposite direction repeatedly to make the sheet easy to bend and crack. Was evaluated. The evaluation was performed 10 times, and each was performed according to the following evaluation criteria. The results are shown in Table 1 as the average value of 10 times.

(Evaluation points)
5: Moderately sticky to bend and does not break even if bent repeatedly 4: Sticky to bend but cracks when bent 5 times 3: Sticky to bend but breaks when bent 3 times 2: Slightly hard and 2 It breaks when bent once 1: It is hard and breaks during one bending or cannot be bent

(Examples 2 to 8)
A film preparation was produced in the same manner as in Example 1 except that the blending amount was changed as shown in Table 2. Each production example was evaluated in the same manner as in Test Example 1. The results are shown in Table 2.

Claims (6)

A coenzyme Q10 film preparation containing coenzyme Q10 emulsified with octenyl succinic starch and alginic acids selected from alginic acid, salts thereof or esters thereof. Octenyl an acid starch molecular weight 2000 on more than, the formulation of claim 1, wherein. The preparation according to claim 1 or 2, wherein the blending amount of the alginic acids is 10 to 94% by mass in the preparation. A coenzyme Q10 film, which comprises mixing and emulsifying octenyl succinic acid starch and coenzyme Q10, adding alginic acid, a salt thereof, or alginic acid selected from an ester thereof to the produced coenzyme Q10 emulsion, and mixing and forming a film. Method of manufacturing the formulation. The octenyl succinate starch is the molecular weight 2000 on more than process according to claim 4, wherein. The production method according to claim 4 or 5 , wherein the blending amount of the alginic acids is 10 to 94% by mass in the preparation.