JP2010275253A - Oral administration composition containing coenzyme q10 - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an oral administration composition containing coenzyme Q10 that can be produced on an industrial scale by a very simple method and has improved absorbability. <P>SOLUTION: The oral administration composition containing coenzyme Q10 includes coenzyme Q10 (A) and a cyclodextrin/coenzyme Q10 complex (B), wherein (B) occupies 15-65 mass% of the sum of (A) and (B). <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to an orally administered composition containing coenzyme Q10.

  Coenzyme Q10 has an in vivo action showing energy production activation ability as an essential component of the mitochondrial electron transport system, and has been conventionally prescribed as a pharmaceutical product effective for improving symptoms of congestive heart failure as a metabolic cardiotonic drug. In recent years, it has been approved as a food, and attention has been given to antioxidant capacity, which is another important in vivo action, and it has become a very important place in the health food market.

  Coenzyme Q10 is already present in all human bodies and is also synthesized in vivo, but it is known that its amount decreases with age. Although foods contain coenzyme Q10, the amount is very small, and it is difficult to make up for the deficiency with only food. For this reason, supplementation with supplements is desirable.

  However, since coenzyme Q10 is fat-soluble, it is known that its absorbability to the living body after oral administration is low. On the other hand, improvement of absorbability of coenzyme Q10 has been attempted by various methods.

  For example, a method of combining coenzyme Q10 with conjugated linoleic acid, linseed oil, ethyl ester marine biological lipids (see Patent Document 1), a method of combining coenzyme Q10 and sesamin (see Patent Document 2), a method of emulsifying coenzyme Q10 ( Patent Document 3), Coenzyme Q10 as a cyclodextrin complex (see Patent Document 4), and Coenzyme Q10 as a reduced form (see Patent Document 5).

  However, for example, the composition described in Patent Document 1 contains oil having a mass 10 times or more that of Coenzyme Q10, and one tablet is very large for a small amount of Coenzyme Q10. In addition, the method described in Patent Document 2 discloses a mixture of sesamin and coenzyme Q10. In the patent, it is described that the mixing method of this mixture is effective even if manufactured by any manufacturing method easily conceived by those skilled in the art, but only the one dissolved in oil is being implemented. It is. Further, the mixing method requires a process of dissolving sesamin at a high temperature and a subsequent process of dissolving Q10, so that it is imagined that the process becomes complicated and an increase in cost cannot be avoided. The method described in Patent Document 3 is an attempt to disperse and emulsify coenzyme Q10 to solve the problem of absorbability in oral administration. To achieve this, polyglycerin monomyristate and polyglycerin condensed ricinoleate There is a problem in safety. The method described in Patent Document 4 contains 4 times as much cyclodextrin as Coenzyme Q10 in the complex, and when the tablet is used, one tablet is enlarged. The method described in Patent Document 5 requires a step for converting oxidized coenzyme Q10 to a reduced form, and furthermore, the reduced form is easily oxidized to return to an oxidized form with low absorbability, so that it can be manufactured and handled. It's not easy.

JP 2007-297395 A JP 2007-70312 A JP 2007-131619 A JP 2002-104922 A International Publication No. 2003/006408 Pamphlet

  The present invention provides a coenzyme Q10-containing composition for oral administration which can be produced by a very simple method even on an industrial scale and has improved absorbability to a living body.

As a result of intensive studies to solve the above problems, the present inventors have obtained a coenzyme Q10-containing oral administration composition having improved absorbability by mixing coenzyme Q10 and cyclodextrin / coenzyme Q10 complex at a specific ratio. The inventors have found that the present invention can be obtained and have completed the present invention.
That is, the present invention is as follows.
(1) Coenzyme Q10-containing oral administration comprising coenzyme Q10 (A) and cyclodextrin / coenzyme Q10 complex (B), wherein (B) is 15 to 65% by mass of the total of the above (A) and (B) Composition.
(2) Coenzyme Q10 according to (1), wherein reduced coenzyme Q10 is 10% by mass or less of the total of coenzyme Q10 (A) and coenzyme Q10 contained in cyclodextrin / coenzyme Q10 complex (B) Orally administered composition.
(3) The oral administration composition containing coenzyme Q10 according to (1) or (2), wherein the cyclodextrin is γ-cyclodextrin.
(4) A food comprising the coenzyme Q10-containing composition for oral administration according to any one of (1) to (3).
(5) The food according to (4), which is a functional food.
(6) A pharmaceutical comprising the coenzyme Q10-containing composition for oral administration according to any one of (1) to (3).
(7) A feed comprising the composition for oral administration containing coenzyme Q10 according to any one of (1) to (3).
(8) A veterinary pharmaceutical comprising the coenzyme Q10-containing composition for oral administration according to any one of (1) to (3).

  The oral administration composition containing coenzyme Q10 of the present invention is excellent in the absorbability of coenzyme Q10 in vivo. Therefore, the coenzyme Q10-containing oral administration composition of the present invention is useful for foods, pharmaceuticals and the like.

Coenzyme Q10 absorption results by rats

  The oral administration composition containing coenzyme Q10 of the present invention comprises coenzyme Q10 (A) and a cyclodextrin / coenzyme Q10 complex (B), and (B) is 15 to 65 mass in total of the above (A) and (B). % Orally administered composition containing coenzyme Q10. When (B) is less than 15% by mass, the absorbability is inferior. Moreover, when (B) exceeds 65 mass%, when the composition of the present invention is made into a tablet containing a certain amount of coenzyme Q10, its size increases, which is not preferable. Furthermore, it is preferable that (B) is 25 to 55% by mass of the total of the above (A) and (B).

  In the coenzyme Q10-containing composition for oral administration of the present invention, the content of reduced coenzyme Q10 in the total coenzyme Q10 in the composition is preferably 10% by mass or less, and preferably 0.1 to 10% by mass. It is more preferable. Here, the total coenzyme Q10 in the composition refers to the sum of coenzyme Q10 (A) and coenzyme Q10 contained in the cyclodextrin / coenzyme Q10 complex (B). If the content of reduced coenzyme Q10 is 10% by mass, the absorbency is not inferior to a composition exceeding 10% by mass, which is advantageous in terms of ease of production and cost. In addition, if the reduced coenzyme Q10 is 0.1% by mass or more, the absorption can be increased as compared with a composition not containing the reduced coenzyme Q10.

  In the oral administration composition containing coenzyme Q10 containing reduced coenzyme Q10, the ratio of the reduced coenzyme Q10 that is a cyclodextrin / coenzyme Q10 complex (hereinafter referred to as reduced complex ratio) is 10% or more. It is preferable that Further, it is more preferable that the reduced composite ratio is 30% or more. The present inventors have found that the above complex is more stable against oxidation by molecular oxygen than reduced coenzyme Q10 which is not complexed, and the oral administration containing coenzyme Q10 of the present invention is performed. By increasing the reduced complex ratio of the composition, a composition containing reduced coenzyme Q10 and easy to handle can be obtained.

  Next, the raw materials for producing the coenzyme Q10-containing oral administration composition of the present invention will be described.

  Coenzyme Q10 has an oxidized form and a reduced form. Oxidized coenzyme Q10 can be produced by a synthesis method using solanesol and benzoquinone, or a fermentation method using microorganisms such as yeast and bacteria. Reduced coenzyme Q10 can be easily synthesized by reducing oxidized coenzyme Q10 with a suitable reducing agent such as sodium sulfite hydrosulfite. For both oxidized and reduced coenzyme Q10, crystals obtained by crystallization and recrystallization in the final production step can be used as the raw material of the present invention.

  Cyclodextrins are cyclic oligosaccharides in which glucose is α-1,4-linked, and α, β, γ-cyclodextrins with 6,7,8 glucose units are currently industrialized among natural cyclodextrins It is a cyclodextrin being produced. As described above, there are three types of available cyclodextrins, and the cyclodextrin used in the present invention is particularly preferably γ-cyclodextrin.

  The cyclodextrin / coenzyme Q10 complex used in the present invention refers to a compound in which coenzyme Q10 is included in a so-called cyclodextrin. The production method of the complex is an emulsification method in which an aqueous suspension of cyclodextrin is homogenized in the presence of coenzyme Q10, a saturated solution method in which coenzyme Q10 is added to a saturated aqueous solution of cyclodextrin and mixed with stirring, and a small amount of water is added to cyclodextrin and pasted There are known kneading methods in which coenzyme Q10 is added and kneaded in the form of a mixture, and mixed pulverization methods in which cyclodextrin and coenzyme Q10 are mixed and pulverized. The ratio of coenzyme Q10 in the complex is 19 to 25% by mass when γ-cyclodextrin is used as the cyclodextrin.

  A method for producing an orally administered composition containing coenzyme Q10 with an increased reduced complex ratio will be described below.

  The production process includes a process of mixing (A) and (B) and a process of reducing a part of oxidized coenzyme Q10 to reduced coenzyme Q10 using a reducing agent. As the raw material coenzyme Q10 (A) and cyclodextrin / coenzyme Q10 complex (B), those in which coenzyme Q10 is oxidized may be used. As the reducing agent, a reducing agent capable of reducing the oxidized coenzyme Q10 may be used, but vitamin C is preferably used as a reducing agent that does not need to be removed in applications such as foods and pharmaceuticals. Vitamin C is produced in large quantities on an industrial scale using glucose as a raw material by a semisynthetic method or a fermentation method. In the present invention, these products can be used as they are. The amount of vitamin C is preferably 0.5 to 2 times the mass ratio of the raw material other than vitamin C to be used in the reduction step.

  Either mixing or conversion to reduced coenzyme Q10 may be performed first. In the first production method, the cyclodextrin / coenzyme Q10 complex (B) and the reducing agent are mixed and heated, then cooled to below the melting point of coenzyme Q10, and mixed with coenzyme Q10 (A). This is a method for obtaining a Q10-containing composition for oral administration. In this method, only oxidized coenzyme Q10 contained in the cyclodextrin / coenzyme Q10 complex (B) is converted to reduced coenzyme Q10, so that all the reduced coenzyme Q10 becomes a cyclodextrin / coenzyme Q10 complex. A composition is obtained.

  The second production method is a method for obtaining the composition by mixing and heating Coenzyme Q10 (A), cyclodextrin / Coenzyme Q10 complex (B) and a reducing agent. Oxidized coenzyme Q10 not in a complex is not easily reduced by a reducing agent, and oxidized coenzyme Q10 contained in the cyclodextrin / coenzyme Q10 complex (B) is preferentially converted to reduced coenzyme Q10. Therefore, a composition having a high ratio of the reduced coenzyme Q10 in the form of a cyclodextrin / coenzyme Q10 complex is obtained.

  The mixing of these components can be carried out with a stirring mixer, which is an ordinary mixer, a container rotating mixer such as a V-type or a W-corn, a ribbon mixer, or a conical mixer.

  Mixing can be performed under normal pressure or reduced pressure in an air atmosphere or an inert gas atmosphere. When the reduced coenzyme Q10 is contained in the raw material, it is preferable to mix in an atmosphere of an inert gas such as nitrogen. Moreover, it can serve as drying by mixing under reduced pressure.

  In the first production method, the heating temperature is preferably 25 ° C to 90 ° C, more preferably 40 ° C to 90 ° C. In the second production method, the temperature is preferably 25 ° C to 70 ° C so that the coenzyme Q10 having a low melting point does not melt and cannot be mixed.

  The heating time is preferably 24 hours or longer, although the optimum time varies depending on the temperature and composition.

  Heating may be performed at the time of mixing, or may be performed by standing after mixing.

  The dosage form of the oral administration composition of coenzyme Q10 obtained in the present invention is not particularly limited and can be appropriately selected depending on the intended use. The composition for oral administration containing CoQ10 according to the present invention can be used as a food for humans, a functional food, a pharmaceutical product or a quasi-drug, and can be used as a pharmaceutical product or feed for animals. The functional food here means foods taken for the purpose of maintaining nutrition or supplementing nutrition, such as health foods, nutritional supplements, functional nutritional foods, and nutrition insurance foods. Specific forms include, but are not limited to, capsules, tablets, chewable tablets, drinks and the like.

  EXAMPLES Hereinafter, although this invention is demonstrated in more detail with an Example and a comparative example, this invention is not limited only to these examples.

Content of Reduced Coenzyme Q10 100 mg of an orally administered composition containing coenzyme Q10 was extracted 5 times with 10 mL of acetone. The extracts were combined and analyzed by HPLC under the following conditions to quantify oxidized coenzyme Q10 and reduced coenzyme Q10. The content of reduced coenzyme Q10 relative to the total coenzyme Q10 was obtained by dividing the quantitative value of reduced coenzyme Q10 by the sum of the quantitative value of reduced coenzyme Q10 and the quantitative value of oxidized coenzyme Q10.

Coenzyme Q10 Absorption Test by Rats 1) Feeding Method For 8-week-old SD rats (male, 3 rats per group, body weight 250-300 g), the oral administration composition containing coenzyme Q10 was 100 mg / kg rat weight as CoQ10 amount. After 3 hours after administration, blood was collected from the tail vein using a heparinized vacuum blood collection tube, and plasma was separated.

2) Measurement of the amount of CoQ10 in blood 1 ml of the obtained plasma is collected, and 2.5 ml of 2% FeCl3-ethanol solution is added and mixed so that the total amount of CoQ10 in the plasma becomes oxidized, and reduced CoQ10 Was converted to oxidized CoQ10. Next, 5 ml of hexane was added and mixed vigorously to extract oxidized CoQ10 in plasma, followed by centrifugation, and the hexane layer was collected in another test tube. 15 ml of the hexane extract obtained by repeating this operation three times was concentrated under reduced pressure (10 to 100 torr) with an evaporator, and then 0.2 ml of isopropanol was added and dissolved. 0.2 ml of the obtained isopropanol solution was analyzed by HPLC under the following conditions, and the Co10 concentration in 1 ml of plasma was calculated.

HPLC analysis conditions Column: YMC PACK ODS-A, mobile phase: methanol: hexane = 4: 1 (V: V), detection wavelength: 275 nm, flow rate: 1.0 ml / min, column temperature of 30 ° C., retention of reduced CoQ10 Time: 10 min, retention time of oxidized CoQ10; 16 min.

Raw material Coenzyme Q10 used was oxidized coenzyme Q10 (trade name Bio Q10) manufactured by Mitsubishi Gas Chemical. As the γ-cyclodextrin / coenzyme Q10 complex, an inclusion body of γ-cyclodextrin and oxidized coenzyme Q10 (trade name Bio Q10 CD inclusion body) manufactured by Mitsubishi Gas Chemical Co., Ltd. was used. Vitamin C used was L-ascorbic acid manufactured by Wako Pure Chemical Industries.

Example 1
7 g of coenzyme Q10, 3 g of γ-cyclodextrin / coenzyme Q10 complex and 10 g of vitamin C were mixed in a coffee mill and heat-treated at 60 ° C. for 92 hours to obtain a coenzyme Q10-containing composition for oral administration. .

  In this composition, the amount of (B) relative to the total of coenzyme Q10 (A) and cyclodextrin / coenzyme Q10 complex (B) (hereinafter referred to as (B) / ((A) + (B))) is 30. % By mass. In addition, the reduced content with respect to the total coenzyme Q10 was 5.5%. The absorptivity result of the obtained composition is shown in FIG.

Example 2
5 g of coenzyme Q10, 5 g of γ-cyclodextrin / coenzyme Q10 complex and 10 g of vitamin C were mixed in a coffee mill and heat-treated at 60 ° C. for 92 hours to obtain a coenzyme Q10-containing composition for oral administration. .

  In this composition, (B) / ((A) + (B)) is 50% by mass. Further, the content of reduced form relative to the total coenzyme Q10 was 6.1%. The absorptivity result of the obtained composition is shown in FIG.

Example 3
5 g of γ-cyclodextrin / coenzyme Q10 complex and 10 g of vitamin C were mixed in a beaker while stirring with a stirring blade at 60 ° C. and heat-treated for 72 hours. Subsequently, the obtained mixture and 5 g of coenzyme Q10 were stirred and mixed at room temperature to obtain a coenzyme Q10-containing oral administration composition.

  In this composition, (B) / ((A) + (B)) is 50% by mass. In addition, the content of reduced form relative to the total coenzyme Q10 was 6.5%.

Comparative Example 1
9 g of coenzyme Q10, 1 g of γ-cyclodextrin / coenzyme Q10 complex, and 10 g of vitamin C were mixed in a coffee mill and heat-treated at 60 ° C. for 92 hours to obtain a coenzyme Q10-containing composition for oral administration. .

  In this composition, (B) / ((A) + (B)) is 10% by mass. The absorptivity result of the obtained composition is shown in FIG. In addition, the reduced content with respect to the total coenzyme Q10 was 1.2%.

Comparative Example 2
3 g of coenzyme Q10, 7 g of γ-cyclodextrin / coenzyme Q10 complex and 10 g of vitamin C were mixed in a coffee mill and heat-treated at 60 ° C. for 92 hours to obtain a coenzyme Q10-containing composition for oral administration. .

  In this composition, (B) / ((A) + (B)) is 70% by mass. In addition, the reduced content with respect to the total coenzyme Q10 was 13.2%. The absorptivity result of the obtained composition is shown in FIG.

Reference Example Coenzyme Q10 was tested for absorbability. The results are shown in FIG.

Claims (8)

A coenzyme Q10-containing oral administration composition comprising coenzyme Q10 (A) and cyclodextrin / coenzyme Q10 complex (B), wherein (B) is 15 to 65% by mass of the total of (A) and (B). The coenzyme Q10-containing oral administration composition according to claim 1, wherein the reduced coenzyme Q10 is 10% by mass or less of the total of coenzyme Q10 (A) and coenzyme Q10 contained in the cyclodextrin / coenzyme Q10 complex (B). object. The composition for oral administration containing coenzyme Q10 according to claim 1 or 2, wherein the cyclodextrin is γ-cyclodextrin. The foodstuff containing the coenzyme Q10 containing oral administration composition in any one of Claims 1-3. The food according to claim 4, which is a functional food. A pharmaceutical comprising the coenzyme Q10-containing composition for oral administration according to any one of claims 1 to 3. A feed comprising the coenzyme Q10-containing composition for oral administration according to any one of claims 1 to 3. A veterinary pharmaceutical comprising the coenzyme Q10-containing oral administration composition according to any one of claims 1 to 3.