Coenzyme Q10-containing composition

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 containing coenzyme Q10. Specifically, it relates to a coenzyme Q10-containing composition that uses a coenzyme Q10-containing preparation excellent in the stability and absorbability of coenzyme Q10, contains a large amount of coenzyme Q10, and is excellent in disintegration properties and absorbability when formulated. The present invention also relates to tablets and hard capsule preparations containing the coenzyme Q10-containing composition and excellent in disintegration properties and absorbability. In particular, the tablets of the present invention contain a large amount of coenzyme Q10 and are excellent in moldability, and are also excellent in that problems such as tableting failure and sticking do not occur.

Background Art

[0002] Coenzyme Q10, also called ubiquinone or coenzyme Q10, is one of the coenzymes present in higher animals. Coenzyme Q10 is known not only as a coenzyme with biological activity but also as a vitamin-like substance having an action of improving oxygen utilization efficiency, has actions such as energy production and antioxidant action, and is said to be involved in various health functions. 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 for hypertension, arteriosclerosis, heart disease, diabetes, cancer, etc., and is also reported to be effective for fatigue recovery and exercise function recovery.

[0003] Thus, coenzyme Q10 has high physiological activity and is originally present in the living body, so it is a substance with high safety. For this reason, various coenzyme Q10-containing preparations such as tablets and hard capsule preparations are commercially available for the purpose of ingesting coenzyme Q10.

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

[0005] On the other hand, when taking coenzyme Q10 in tablet form, if the coenzyme Q10 content is low, it becomes necessary to take large tablets or many tablets to obtain an effective amount of coenzyme Q10, making efficient intake difficult. For efficient intake of coenzyme Q10, it is desirable to make the tablets as small as possible while maintaining a stable and high coenzyme Q10 content.

[0006] Patent Documents 1 and 2 disclose a method for producing a coenzyme Q10-containing composition in which coenzyme Q10 is pre-mixed with starch or pregelatinized starch, and then other pharmaceutical ingredients are mixed, in order to address tableting problems such as sticking. In this method, by mixing agar and / or gum arabic in the step after pre-mixing, even if a high content of coenzyme Q10 is included, problems such as tableting problems and sticking do not occur, and a coenzyme Q10-containing tablet with good absorption can be obtained.

[0007] Patent Document 3 shows that a coenzyme Q10-containing composition emulsified in an aqueous liquid containing coenzyme Q10, a water-soluble substance consisting of octenyl succinate starch and dextrin, and glycerin can contain a high amount of coenzyme Q10, exhibits 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 a high amount of coenzyme Q10 using a coenzyme Q10-containing composition emulsified with octenyl succinate starch, etc., as described in Patent Document 3, in order to allow for more efficient intake of coenzyme Q10, they found that the disintegration and absorption were insufficient, and in particular, when made into tablets, the tableting properties were poor, and furthermore, the disintegration properties worsened over time as the hardness increased after formulation (after tableting). [Prior art documents] [Patent Documents]

[0009] [Patent Document 1] Japanese Patent Publication No. 2006-117626 [Patent Document 2] Japanese Patent Publication No. 2007-181441 [Patent Document 3] Patent No. 4842824 [Overview of the project] [Problems that the invention aims to solve]

[0010] The object of the present invention is to provide a coenzyme Q10-containing composition that contains a large amount of coenzyme Q10, has good disintegration properties for tablets and hard capsule formulations, and excellent absorption. Furthermore, the object is to provide a coenzyme Q10-containing tablet that has good moldability without problems such as tableting defects when made into tablets. [Means for solving the problem]

[0011] The above problems can be solved by the following coenzyme Q10-containing compositions, hard capsule formulations, and tablets. (1) A coenzyme Q10-containing composition comprising a coenzyme Q10 emulsion containing octenyl succinate starch, 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), 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 (1) or (2), wherein the mass ratio of coenzyme Q10 to agar is 1:0.5 to 2. (4) A 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 to 1. (5) A coenzyme Q10-containing composition according to any one of (1) to (3), wherein the mass ratio of coenzyme Q10 to agar is 1:1 to 2. (6) The composition according to any one of (1) to (5), further containing 5 to 25% by mass of maltose and 5 to 70% by mass of cellulose. (7) A tablet containing the coenzyme Q10-containing composition described in any of (1) to (6). (8) A hard capsule formulation containing the coenzyme Q10-containing composition described in any 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 exhibits good disintegration properties when formed into tablets or hard capsules, thus providing a formulation with excellent bioavailability. Furthermore, it exhibits excellent formability in terms of tablet formation, with fewer tableting problems such as sticking during manufacturing. [Modes for carrying out the invention]

[0013] (Coenzyme Q10) The coenzyme Q10 used in the present invention can be obtained by known means, such as extraction from living organisms, synthesis, or fermentation, without any particular limitations. 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, the moldability and disintegration properties deteriorate. On the other hand, if the amount of coenzyme Q10 is reduced, the desired effect becomes difficult to obtain.

[0014] In this invention, coenzyme Q10 is incorporated as a coenzyme Q10 emulsion, which is obtained by mixing and emulsifying octenyl succinate starch, dextrin, and glycerin.

[0015] Coenzyme Q10 emulsion is prepared by mixing coenzyme Q10, octenyl succinate starch, dextrin, and glycerin, and then performing high-speed stirring or shearing to prepare an emulsion of fine particles. In this case, since coenzyme Q10 is crystalline at room temperature, it is preferable to heat it to dissolve it before emulsifying. For example, coenzyme Q10 may be dissolved at a temperature higher than its melting point, such as 45-90°C, and mixed with a water-soluble substance containing octenyl succinate starch, dextrin, and glycerin, and then the emulsion may be prepared using known means, such as a high-pressure homogenizer. Alternatively, the above water-soluble substance may be prepared as an aqueous solution at 45-90°C, and the emulsion may be prepared by gradually adding coenzyme Q10 to it. Immediately after emulsification, it is in the state of an emulsion liquid, but it is preferable to dry it into a powder and use it as coenzyme Q10 emulsion powder in subsequent composition production.

[0016] Examples of coenzyme Q10 emulsified powders particularly suitable in the present invention include, for example, the powder obtained by dispersing and emulsifying coenzyme Q10 in an aqueous liquid containing a water-soluble substance composed of octenyl succinic anhydride starch and dextrin and glycerin as described in Patent Document 3, and drying to obtain a 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 obtained by bleaching seaweeds of the genus Gracilaria such as red algae seaweeds with sunlight and then extracting, filtering, concentrating, and drying them with warm water. Its main components are polysaccharides such as agarose and agaropectin. Agar is a tasteless and odorless powder, insoluble in cold water and alcohol, gradually dissolves in warm water to become a liquid, and is used as an additive such as a thickener and a disintegrant in foods.

[0018] The inventors of the present invention have found that when agar is blended in an appropriate amount and ratio with coenzyme Q10 emulsified powder, the disintegration property of the preparation produced using the coenzyme Q10-containing composition is improved, the absorbability is further improved, and a coenzyme Q10-containing composition with good disintegration property and absorbability can be produced. Furthermore, it has been found that the coenzyme Q10-containing composition in which agar is blended in an appropriate amount and ratio with coenzyme Q10 emulsified powder has an unexpected advantage in that it can suppress the deterioration of disintegration property over time after formulation.

[0019] The blending ratio of agar in the coenzyme Q10-containing composition of the present invention is 10 to 50% by mass, preferably 10 to 30% by mass, in 100% by mass of the coenzyme Q10-containing composition. If the blending amount is too small, the effect of improving disintegration property cannot be observed. If it is too much, the moldability is poor, stable production becomes difficult, and damage to tablets is likely to occur. In addition, in the coenzyme Q10-containing composition of the present invention, the mass ratio of coenzyme Q10 to agar is 1:0.5 to 3, preferably 1:0.5 to 2, and those in the range of 1:0.5 to 1 or 1 to 2 can be particularly preferably used. When the coenzyme Q10-containing composition of the present invention is in the form of a hard capsule, those having a mass ratio of coenzyme Q10 to agar in the range of 1:0.5 to 1 are particularly preferable.

[0020] It is preferable to blend excipients such as maltose and cellulose in the coenzyme Q10-containing composition of the present invention in which agar is blended in an appropriate amount and ratio. Among them, those blended with maltose were found to be advantageous in terms of improving the formability, particularly in suppressing the deterioration of disintegration over time. (Maltose) The maltose used in the present invention can be used without particular limitation as a commercially available powder. It is preferably blended in the range of 5 to 25% by mass, more preferably 15 to 20% by mass. (Cellulose) The cellulose used in the present invention can be used without particular limitation as commercially available powders such as powdered cellulose and crystalline cellulose. It is preferably blended in the range of 5 to 70% by mass, more preferably 20 to 3% by mass.

[0021] (Production method) The method for preparing the coenzyme Q10-containing composition of the present invention is not particularly limited. For example, the above coenzyme Q10 emulsified powder, agar, maltose, cellulose, etc. can be mixed to prepare a powdery composition. When the mixing step is carried out at a temperature not exceeding the melting point of coenzyme Q10, preferably at a product temperature of 50°C or lower, more preferably 40°C or lower, the stability of coenzyme Q10 can be further enhanced. The above production method does not require a preliminary mixing step of coenzyme Q10 with starch or pregelatinized starch as in the methods of Patent Document 1 and Patent Document 2, so the production process can be made more efficient.

[0022] When preparing a powdered composition, any ingredients commonly used in food and beverages may be added, provided that the effect is not impaired. Examples include excipients, binders, fluidizers, lubricants, glazing agents, stabilizers, thickeners, emulsifiers, antioxidants, pH adjusters, colorants, flavorings, additives, sweeteners, acidulants, and other active ingredients (bioactive ingredients).

[0023] Among the various components, examples of excipients include 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, dicalcium phosphate, and tricalcium phosphate; binders such as gum arabic, alginic acid, povidone, guar gum, starch, and modified starch; fluidizers such as silicon dioxide and talc; and lubricants such as calcium stearate and magnesium stearate, with no particular limit on the list. These excipients may be used individually or in combination.

[0024] (Formulation) The coenzyme Q10-containing composition of the present invention can be formulated in various forms, but is generally preferred in the form of a 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 to be made into tablets, the powdered composition obtained as described above can be manufactured by compressing it into tablets according to a conventional method.

[0026] When the coenzyme Q10-containing composition of the present invention is in the form of a hard capsule, the powdered or granular composition obtained as described above can be filled into hard capsules according to a conventional method. The hard capsule base material is not limited to any particular material, and commonly used animal-derived raw material coatings such as alkali-treated gelatin and acid-treated gelatin, or plant-derived raw material 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. [Examples]

[0028] (Examples 1-6, Comparative Examples 1-3) (Sample preparation method) The powdered raw materials other than the fluidity improvers and lubricants (such as lubricants) listed in Table 1 were sieved through a 30-mesh sieve and mixed. Then, the fluidity improvers and lubricants were added, and tablets weighing 300 mg per tablet were manufactured using a tabletop 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] Table 1 shows the components contained in the tablets of the coenzyme Q10-containing compositions used in Examples 1-6 and Comparative Examples 1-3, as well as the results of the Examples and Comparative Examples. The raw materials used as components of the coenzyme Q10-containing compositions in the Examples and Comparative Examples are as follows.

[0030] (raw materials) • Coenzyme Q10 emulsified powder (Aqua Q10 P40, CoQ10 content 40%, manufactured by Nissin Pharma): A powder containing coenzyme Q10 emulsified with octenyl succinate starch, dextrin, and glycerin. • Agar (purified agar for disintegration, manufactured by Ina Food Industry Co., Ltd.) • Cellulose for orally disintegrating tablets (Ceolus OD-20, manufactured by Asahi Kasei) ·Partially pregelatinized starch (PCS FC-50, manufactured by Asahi Kasei) • Reduced maltose syrup (Amalti MR-100, manufactured by Mitsubishi Corporation Life Sciences) • Maltose (Sanmaruto Midori, Sanmaruto S, manufactured by Hayashibara) • Cellulose (KC Floc W-100, manufactured by Nippon Paper Industries; Ceolus UF-F702, Ceolus ST-100, manufactured by Asahi Kasei Corporation) • Lubricant: Calcium stearate (manufactured by Taihei Chemical Industry Co., Ltd.) • Fluidity improver: Silicon dioxide (Silopage 720, manufactured by Fuji Silicia Chemical Co., Ltd.)

[0031] (Evaluation method) ·Moldability The moldability during tablet compression was evaluated according to the following criteria. ◎: Appropriate compression pressure, no compression pressure fluctuations (±1000N or less), no tableting defects (capping, sticking). ○: One of the following occurs: low compression pressure (3000N or less), compression pressure fluctuation, or tableting failure (capping, sticking). △: Two or more of the following occur: low compression pressure (3000N or less), compression pressure fluctuation, or tableting failure (capping, sticking).

[0032] • Collapse After tableting, the disintegration of the tablets after storage at room temperature for one day was measured according to "6.09 Disintegration Test Method" in the "General Test Methods" of the "18th Edition of the Japanese Pharmacopoeia". In addition, the tablets produced in Examples 1-4 and Comparative Examples 1 and 3 were sealed in aluminum bags and stored at room temperature for the period indicated in the table, and then their disintegration was evaluated. For tablets, a disintegration time of 30 minutes or less is considered good.

[0033] [Table 1]

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

[0035] (Example 7, Comparative Examples 4, 5) Table 2 shows the results of measuring the disintegration time of hard capsule formulations prepared by enclosing a coenzyme Q10-containing composition containing the components shown in Table 2 within No. 3 pullulan hard capsules (made of capsugel). The composition was encased in the components listed in Table 2. The disintegration time was measured according to the "6.09 Disintegration Test Method" of the "General Test Methods" in the "18th Edition of the Japanese Pharmacopoeia." The erythritol crystals used as components were manufactured by Mitsubishi Chemical, and the other components were the same as those used for the tablets. In the case of hard capsules, a disintegration time of 15 minutes or less can be considered good.

[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 exhibited excellent disintegration properties.

[0038] Based on the above, the coenzyme Q10-containing composition of the present invention, even when using a coenzyme Q10 emulsion containing a high content of coenzyme Q10 and excellent bioavailability and stability of octenyl succinate starch, dextrin, and glycerin, exhibits good disintegration and excellent absorption in tablet and hard capsule formulations, thus enabling efficient intake of coenzyme Q10.

Claims

1. A coenzyme Q10-containing composition comprising a coenzyme Q10 emulsion containing a water-soluble substance consisting of octenyl succinate starch and dextrin, and glycerin, agar, and maltose, wherein the coenzyme Q10-containing composition contains 5 to 50% by mass of coenzyme Q10, 10 to 50% by mass of agar, and 5 to 25% by mass of maltose, and the mass ratio of coenzyme Q10 to agar is 1:0.5 to 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 to 2.

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

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

6. Furthermore, the coenzyme Q10-containing composition according to claim 1 or 2 further contains 5 to 70% by mass of cellulose.

7. A tablet containing the coenzyme Q10-containing composition described in claim 1 or 2.

8. A hard capsule formulation containing the coenzyme Q10-containing composition described in claim 1 or 2.

Images