Composition containing coenzyme q10

Abstract

To provide a composition containing coenzyme Q10 which has good collapsibility of tablet or capsule formulation, and excellent absorbency while containing a large volume of coenzyme Q10.SOLUTION: A composition containing coenzyme Q10 contains: coenzyme Q10 emulsion containing octenylsuccinate starch, a water-soluble substance consisting of dextrin, and glycerol; and agar, where the composition contains coenzyme Q10 by 5 to 50 mass%, and agar by 10 to 50 mass%, and a mass ratio between coenzyme Q10 and agar is 1:0.5 to 3.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a coenzyme Q10-containing composition. Specifically, the present invention relates to a coenzyme Q10-containing composition that contains a large amount of coenzyme Q10 and has excellent disintegration properties and good absorbability when formulated using a coenzyme Q10-containing preparation that exhibits excellent stability and absorbability of coenzyme Q10. The present invention also relates to tablets and hard capsules containing the coenzyme Q10-containing composition, which have excellent disintegration properties and absorbability. In particular, the tablets of the present invention are excellent in compactibility despite their high coenzyme Q10 content, and are free from problems such as tableting failure and sticking. [Background technology]

[0002] Coenzyme Q10, also known as ubidecarenone or coenzyme Q10, is a type of coenzyme present in higher animals. Coenzyme Q10 is not only biologically active as a coenzyme, but is also known as a vitamin-like substance that improves oxygen utilization efficiency, and is thought to play a role in various health functions, including energy production and antioxidant properties. Coenzyme Q10 is clinically used to improve the symptoms of angina pectoris, heart failure, ischemic heart disease, and muscular dystrophy, and is said to be effective against high blood pressure, arteriosclerosis, heart disease, diabetes, cancer, etc., and has also been reported to be effective in recovering from fatigue and restoring motor function.

[0003] Coenzyme Q10 is highly physiologically active and, because it is naturally present in the body, is a highly safe substance. For this reason, various coenzyme Q10-containing preparations, such as tablets and hard capsules, are commercially available for the purpose of coenzyme Q10 intake.

[0004] However, coenzyme Q10 is a lipophilic solid with a low melting point, poorly soluble in water, unstable to light and heat, and highly crystalline, making its formulation difficult. For example, when tablets containing high concentrations of coenzyme Q10 are produced, problems arise in formulation, such as sticking during tableting. Furthermore, because coenzyme Q10 is lipophilic, tablets and hard capsules containing high concentrations of coenzyme Q10 have poor disintegration properties, resulting in poor absorption in the body.

[0005] On the other hand, when taking coenzyme Q10 from tablets, etc., if the coenzyme Q10 content is low, a large tablet or multiple tablets must be taken to ingest an effective amount of coenzyme Q10, making efficient ingestion difficult. For efficient ingestion of coenzyme Q10, it is desirable to make the coenzyme Q10 content in the tablet as high and stable as possible and to make the tablet, etc., smaller.

[0006] Patent Documents 1 and 2 disclose a method for producing a coenzyme Q10 compounded composition in which coenzyme Q10 is premixed with starch or pregelatinized starch and then other formulation raw materials are mixed to address problems with tableting such as sticking. By mixing agar and / or gum arabic in the process after premixing, problems such as tableting problems and sticking do not occur even when a high content of coenzyme Q10 is compounded, and a coenzyme Q10 compounded tablet with good absorbability can be obtained.

[0007] Patent Document 3 discloses that a coenzyme Q10-containing composition emulsified in an aqueous liquid containing coenzyme Q10, a water-soluble substance consisting of starch octenyl succinate and dextrin, and glycerin can contain a high content of coenzyme Q10, has excellent stability and bioavailability of coenzyme Q10, and can be used in coenzyme Q10-containing tablet or hard capsule formulations.

[0008] However, when the present inventors attempted to manufacture small tablets or hard capsule formulations containing high amounts of coenzyme Q10 using a coenzyme Q10-containing composition emulsified with starch octenyl succinate, etc., as described in Patent Document 3, in order to enable more efficient intake of coenzyme Q10, they found that the disintegration and absorption properties were insufficient, and that, particularly when made into tablets, the tableting properties were poor.Furthermore, the hardness increased over time after formulation (after tableting), resulting in further deterioration of disintegration properties over time. [Prior art documents] [Patent documents]

[0009] [Patent Document 1] Japanese Patent Application Laid-Open No. 2006-117626 [Patent Document 2] Japanese Patent Application Laid-Open No. 2007-181441 [Patent Document 3] Patent No. 4842824 Summary of the Invention [Problem to be solved by the invention]

[0010] The present invention aims to provide a coenzyme Q10-containing composition that contains a large amount of coenzyme Q10 and yet has good disintegration properties and excellent absorbability when formed into tablets or hard capsules. It also aims to provide a coenzyme Q10-containing tablet that is easy to mold and does not cause problems such as tableting problems when formed into tablets. [Means for solving the problem]

[0011] The above problems can be solved by the following coenzyme Q10-containing composition, hard capsule formulation, and tablet. (1) A coenzyme Q10-containing composition comprising a coenzyme Q10 emulsion containing starch octenyl succinate, dextrin, and glycerin, and agar, wherein the coenzyme Q10-containing composition contains 5 to 50% by mass of coenzyme Q10 and 10 to 50% by mass of agar, and the mass ratio of coenzyme Q10 to agar is 1:0.5 to 3. (2) The coenzyme Q10-containing composition according to (1), which contains 5 to 35% by mass of coenzyme Q10 and 10 to 30% by mass of agar. (3) The Coenzyme Q10-containing composition according to (1) or (2), wherein the mass ratio of Coenzyme Q10 to agar is 1:0.5-2. (4) The Coenzyme Q10-containing composition according to any one of (1) to (3), wherein the mass ratio of Coenzyme Q10 to agar is 1:0.5-1. (5) The Coenzyme Q10-containing composition according to any one of (1) to (3), wherein the mass ratio of Coenzyme Q10 to agar is 1:1-2. (6) The composition according to any one of (1) to (5), further comprising 5 to 25% by mass of maltose and 5 to 70% by mass of cellulose. (7) A tablet containing the coenzyme Q10-containing composition according to any one of (1) to (6). (8) A hard capsule preparation containing the coenzyme Q10-containing composition according to any one of (1) to (6). [Effects of the Invention]

[0012] The coenzyme Q10-containing composition of the present invention contains a large amount of coenzyme Q10 and has good disintegration properties when made into tablets or hard capsules, making it possible to provide a formulation with excellent bioabsorbability.In addition, there is little tableting trouble such as sticking during tableting production, and the formulation is also excellent in terms of moldability. DETAILED DESCRIPTION OF THE INVENTION

[0013] (Coenzyme Q10) The coenzyme Q10 used in the present invention can be obtained by known means, such as extraction from a living organism, synthesis, or fermentation, and can be used without particular limitation. The amount of coenzyme Q10 in the coenzyme Q10-containing composition of the present invention is 5 to 50% by mass, preferably 5 to 35% by mass, and more preferably 5 to 20% by mass. If the amount of coenzyme Q10 exceeds 50% by mass, moldability and disintegration properties will be impaired. On the other hand, if the amount of coenzyme Q10 is reduced, it will be difficult to achieve the intended effects.

[0014] In the present invention, coenzyme Q10 is formulated as a coenzyme Q10 emulsion, which is prepared by mixing and emulsifying coenzyme Q10 with starch octenyl succinate, dextrin, and glycerin.

[0015] Coenzyme Q10 emulsion is prepared by mixing coenzyme Q10, starch octenyl succinate, dextrin, and glycerin, followed by high-speed stirring, shearing, or other treatments to prepare a fine-particle emulsion. Because coenzyme Q10 is crystalline at room temperature, it is preferable to emulsify the coenzyme Q10 in a dissolved state by heating. For example, coenzyme Q10 may be dissolved at 45-90°C, which is higher than the melting point of coenzyme Q10, and mixed with a water-soluble substance containing starch octenyl succinate, dextrin, and glycerin. The emulsion may then be prepared by known means, such as a high-pressure homogenizer. Alternatively, the water-soluble substance may be made into an aqueous solution at 45-90°C, to which coenzyme Q10 is gradually added to prepare the emulsion. While the emulsion is in the form of a liquid immediately after emulsification, it is preferable to dry it and turn it into a powder to produce a coenzyme Q10 emulsified powder, which can then be used in subsequent composition preparations.

[0016] An example of a particularly suitable emulsified coenzyme Q10 powder in the present invention is, for example, a powder obtained by dispersing and emulsifying coenzyme Q10 in an aqueous liquid containing glycerin and a water-soluble substance consisting of starch octenyl succinate and dextrin, as described in Patent Document 3, and drying the resulting coenzyme Q10-containing liquid composition containing 1 to 50% by mass of coenzyme Q10, 0.01 to 10% by mass of glycerin, 4 to 30% by mass of the water-soluble substance, and 40 to 94% by mass of water.

[0017] (agar) Agar is a substance made by bleaching red seaweed and other seaweeds of the Gelidium genus in sunlight, then extracting it with hot water, filtering, concentrating, and drying it. Its main components are polysaccharides such as agarose and agaropectin. Agar is a tasteless, odorless powder that is insoluble in cold water and alcohol, but gradually dissolves in hot water to become liquid. It is used in foods as a thickener, disintegrant, and other additives.

[0018] The present inventors have found that blending agar in an appropriate amount and ratio with coenzyme Q10 emulsified powder improves the disintegration and absorbability of preparations made using the coenzyme Q10-containing composition, enabling the production of a coenzyme Q10-containing composition with good disintegration and absorbability. Furthermore, they have found that a coenzyme Q10-containing composition blended with agar in an appropriate amount and ratio with coenzyme Q10 emulsified powder has an unexpected advantage in that it can suppress deterioration of disintegration over time after formulation.

[0019] The proportion of agar in the coenzyme Q10-containing composition of the present invention is 10 to 50% by mass, preferably 10 to 30% by mass, based on 100% by mass of the coenzyme Q10-containing composition. If the amount is too small, the effect of improving disintegration is not observed. If the amount is too large, moldability is poor, making stable production difficult and making tablets more susceptible to damage. Furthermore, the mass ratio of coenzyme Q10 to agar in the coenzyme Q10-containing composition of the present invention is 1:0.5 to 3, more preferably 1:0.5 to 2, and particularly preferably 1:0.5 to 1 or 1:2. When the coenzyme Q10-containing composition of the present invention is in the form of a hard capsule, a mass ratio of coenzyme Q10 to agar in the range of 1:0.5 to 1 is particularly preferred.

[0020] It is preferable to incorporate excipients such as maltose or cellulose into the coenzyme Q10-containing composition of the present invention, which contains an appropriate amount and ratio of agar. In particular, it has been found that incorporating maltose is advantageous in terms of improving moldability, particularly in terms of suppressing deterioration of disintegration over time. (maltose) Maltose used in the present invention may be any commercially available powdered product, and is preferably blended in an amount of 5 to 25% by mass, more preferably 15 to 20% by mass. (cellulose) The cellulose used in the present invention can be any commercially available powdered product such as powdered cellulose, crystalline cellulose, etc. It is preferably blended in an amount of 5 to 70% by mass, more preferably 20 to 30% by mass.

[0021] (Manufacturing method) The method for preparing the Coenzyme Q10-containing composition of the present invention is not particularly limited, and for example, a powdered composition can be prepared by mixing the above-mentioned Coenzyme Q10 emulsified powder with agar, maltose, cellulose, etc. The stability of Coenzyme Q10 can be further enhanced by carrying out the mixing step at a temperature not exceeding the melting point of Coenzyme Q10, preferably at a product temperature of 50°C or less, and more preferably at a product temperature of 40°C or less. The above manufacturing method does not require the pre-mixing step of coenzyme Q10 with starch or pregelatinized starch, which is required in the methods of Patent Documents 1 and 2, and therefore can improve the efficiency of the manufacturing process.

[0022] When preparing a powdered composition, any ingredients typically used in foods and beverages can be added as long as the effects are not impaired, such as excipients, binders, flow agents, lubricants, glossing agents, stabilizers, thickeners, emulsifiers, antioxidants, pH adjusters, colorants, flavorings, additives, sweeteners, acidulants, and other active ingredients (biologically active ingredients).

[0023] Examples of optional components that can be used without limitation include excipients such as sugars and sugar alcohols, such as lactose, refined sucrose, mannitol, and sorbitol; starches and modified starches, such as corn starch, potato starch, tapioca starch, starch hydrolysates, and oxidized starch; inorganic salts, such as calcium carbonate, kaolin, dibasic calcium phosphate, and tribasic calcium phosphate; binders such as gum arabic, alginic acid, povidone, guar gum, starch, and modified starch; flow agents such as silicon dioxide and talc; and lubricants such as calcium stearate and magnesium stearate. These auxiliary agents may be used alone or in combination.

[0024] (Formulation) The Coenzyme Q10-containing composition of the present invention can be formulated in various forms, but is usually preferably in the form of powder, granules, tablets, soft capsules or hard capsules, with tablets or hard capsules being particularly preferred.

[0025] When the coenzyme Q10-containing composition of the present invention is in the form of a tablet, it can be produced by compressing the powdered composition obtained as described above into tablets in a conventional manner.

[0026] When the coenzyme Q10-containing composition of the present invention is made into a hard capsule form, the powdered or granular composition obtained as described above can be filled into a hard capsule according to a conventional method to produce it.The base material of the hard capsule is not limited to a specific one, and commonly used animal-derived coatings such as alkali-processed gelatin and acid-processed gelatin, and vegetable-derived coatings such as HPMC, pullulan, and carrageenan can be used as appropriate.

[0027] The present invention will be described in detail below with reference to examples, but the present invention is not limited to these examples. [Example]

[0028] (Examples 1 to 6, Comparative Examples 1 to 3) (Sample preparation method) The powdered raw materials other than the flow improver and lubricant (lubricants, etc.) listed in Table 1 were sieved through a 30-mesh sieve and mixed, and then the flow improver and lubricant were mixed together. Tablets weighing 300 mg each were produced using a benchtop rotary tablet press PIKKOLA-NOVA B-10 (manufactured by Estec) at a rotation speed of 10 rpm and a target tableting pressure of 5000 N.

[0029] The ingredients contained in the tablets of the coenzyme Q10-containing composition used in Examples 1 to 6 and Comparative Examples 1 to 3, and the results of the Examples and Comparative Examples, are shown in Table 1. The raw materials used as ingredients of the coenzyme Q10-containing compositions in the Examples and Comparative Examples are as follows:

[0030] (raw materials) Coenzyme Q10 emulsified powder (Aqua Q10P40, CoQ10 content 40%, manufactured by Nisshin Pharma) - A powder of emulsified coenzyme Q10 containing starch octenyl succinate, dextrin, and glycerin. Agar (refined agar for disintegration, manufactured by Ina Food Industry Co., Ltd.) Cellulose for orally disintegrating tablets (Ceolas OD-20, manufactured by Asahi Kasei) ·Partially pregelatinized starch (PCS FC-50, manufactured by Asahi Kasei) Reduced maltose syrup (Amalty MR-100, manufactured by Mitsubishi Corporation Life Sciences) Maltose (Sunmalto Midori, Sunmalto S, Hayashibara) Cellulose (KC Flock W-100, manufactured by Nippon Paper Industries Co., Ltd., Ceolus UF-F702, Ceolus ST-100, manufactured by Asahi Kasei Co., Ltd.) Lubricant: Calcium stearate (manufactured by Taihei Chemical Industry Co., Ltd.) Flow improver: Silicon dioxide (Silopage 720, manufactured by Fuji Silysia Chemical)

[0031] (Evaluation method) ·Moldability The compactibility during tableting was evaluated according to the following criteria. ◎: Appropriate impact pressure, no impact pressure fluctuation (less than ±1000N), no tableting problems (capping, sticking) ○: Occurrence of one of the following: low hitting force (3000N or less), hitting force fluctuation, or tableting failure (capping, sticking) △: Two or more of the following occurred: low impact pressure (3000N or less), impact pressure fluctuation, and tableting problems (capping, sticking).

[0032] Collapsibility After tableting, disintegration properties after storage at room temperature for 1 day were measured according to "6.09 Disintegration Test Method" in the "General Test Methods" of the "Japanese Pharmacopoeia, 18th Edition." The tablets produced in Examples 1 to 4 and Comparative Examples 1 and 3 were sealed in aluminum bags and stored at room temperature for the periods shown in the table, after which disintegration properties were evaluated. In the case of tablets, disintegration properties can be evaluated as good if the disintegration time is 30 minutes or less.

[0033] [Table 1]

[0034] The results in Table 1 show that the disintegration properties were poor when cellulose or partially pregelatinized starch was used as a disintegrant, but the examples using agar maintained good moldability while exhibiting excellent disintegration properties. Furthermore, it can be confirmed that the deterioration of disintegration properties over time was suppressed in Examples 1 to 4, which contained maltose.

[0035] (Example 7, Comparative Examples 4 and 5) A hard capsule formulation was produced by encapsulating a coenzyme Q10-containing composition containing the ingredients shown in Table 2 in No. 3 pullulan hard capsules (manufactured by Capsugel). The disintegration time was measured according to "6.09 Disintegration Test Method" in the "General Test Methods" of the "18th Revised Japanese Pharmacopoeia." The results are shown in Table 2. The erythritol crystals used as each ingredient were manufactured by Mitsubishi Chemical, and the other ingredients were the same as those used for the tablets. In the case of hard capsules, disintegration can be evaluated as good if the disintegration time is 15 minutes or less.

[0036] [Table 2]

[0037] The results in Table 2 show that even in the case of hard capsule formulations, the Examples in which agar was used as a disintegrant showed excellent disintegrability.

[0038] From the above, the coenzyme Q10-containing composition of the present invention can be formulated to allow efficient intake of coenzyme Q10, even when using a coenzyme Q10 emulsion containing starch octenyl succinate, dextrin, and glycerin, which contains a high content of coenzyme Q10 and has excellent bioavailability and stability, and even when formulated in the form of tablets or hard capsules, it has good disintegration properties and excellent absorbability.

Claims

1. A coenzyme Q10-containing composition comprising a water-soluble substance consisting of starch octenyl succinate and dextrin, a coenzyme Q10 emulsion containing glycerin, and agar, the coenzyme Q10-containing composition comprising 5-50% by mass of coenzyme Q10 and 10-50% by mass of agar, and the mass ratio of coenzyme Q10 to agar is 1:0.5-3.

2. The coenzyme Q10-containing composition according to claim 1, comprising 5 to 35% by mass of coenzyme Q10 and 10 to 30% by mass of agar.

3. The coenzyme Q10-containing composition according to claim 1 or 2, wherein the mass ratio of coenzyme Q10 to agar is 1:0.5-2.

4. The coenzyme Q10-containing composition according to claim 3, wherein the mass ratio of coenzyme Q10 to agar is 1:0.5-1.

5. The coenzyme Q10-containing composition according to claim 3, wherein the mass ratio of coenzyme Q10 to agar is 1:1-2.

6. The coenzyme Q10-containing composition according to claim 1 or 2, further comprising 5 to 25% by mass of maltose and 5 to 70% by mass of cellulose.

7. A tablet comprising the coenzyme Q10-containing composition according to claim 1 or 2.

8. A hard capsule formulation comprising the coenzyme Q10-containing composition according to claim 1 or 2.