JP6523971B2 - Composition containing reduced coenzyme Q10 - Google Patents

Description

  The present invention relates to a composition containing reduced coenzyme Q10. Reduced coenzyme Q10 shows higher oral absorbability than oxidized coenzyme Q10, and has excellent food, health food, nutritional function food, food for specified health use, supplement, nutritional supplement, nutrient solution, beverage, feed Are useful compounds as animal drugs, cosmetics, medicines, therapeutic agents, preventive agents and the like.

Reduced coenzyme Q10 exhibits high oral absorbability as compared to oxidized coenzyme Q10, and is a compound very useful as an antioxidant, and, for example, conventional compounds such as synthesis, fermentation, extraction from natural products, etc. It can also be obtained by reducing oxidized coenzyme Q10 obtained by a known method.
As a composition containing reduced coenzyme Q10, a composition containing, for example, reduced coenzyme Q, minerals, and vitamins has been reported (Patent Document 1). In Patent Document 1 above, an aqueous solution is prepared using reduced coenzyme Q10 and a surfactant, and, specifically, iron salts as minerals and ascorbic acid as vitamins are specifically added thereto in specific proportions. It is disclosed that the emulsion stability of the aqueous solution is improved by blending.

  Besides this, for example, as a composition containing reduced coenzyme Q10 excellent in oral absorbability, a composition in which the ratio of reduced coenzyme Q10 in coenzyme Q10 exceeds 20% by weight has been reported Patent Document 2). In Patent Document 2 above, the absorbability test is performed using a mixture of reduced coenzyme Q10 and oxidized coenzyme Q10 in different weight ratios, and the absorbability is improved when reduced coenzyme Q10 has a specific content or more. I have found something to do. In addition, various preparations using reduced coenzyme Q10 are described.

  By the way, reduced coenzyme Q10 is generally known as a compound susceptible to oxidation, and therefore, various studies have been made on methods and compositions for suppressing oxidation. For example, as a composition containing reduced coenzyme Q10 which is stable against oxidation, a composition in which reduced coenzyme Q10 is allowed to coexist with ascorbic acids and / or citric acids has been reported (Patent Document 3). Patent Document 3 discloses a method for preparing a solution containing reduced coenzyme Q10 and ascorbic acids or citric acids and the oxidation stability thereof.

  Furthermore, recently, it has been found that crystalline polymorph exists in reduced coenzyme Q10, and the newly discovered crystalline form (hereinafter referred to as Form II crystal) is a conventional crystalline form (hereinafter referred to as Form II crystal). Hereinafter, it is reported that the oxidation stability is better than that of the Form I crystal) (Patent Document 4).

  On the other hand, as a composition containing coenzyme Q10 and containing a carbonate and an organic acid, a foamable composition containing coenzyme Q10 (Patent Document 5), ubidecarenone and a vitamin B1 derivative are blended. There is a report of a medicine (patent document 6) etc.

Unexamined-Japanese-Patent No. 2009-0573202 JP 10-109933 A Japanese Patent Application Publication No. 2003-032967 WO 2012/176842 CN 101966165 gazette Japanese Patent Application Laid-Open No. 10-287560

  Although Patent Document 2 reveals that reduced coenzyme Q10 is very excellent in oral absorbability, when it is allowed to stand in the air, oxidation proceeds rapidly, and oxidized coenzyme Q10 is oxidized. There is a problem with respect to the oxidation stability because it has the property of changing to the enzyme Q10.

  As described above, the conventional method for improving the stability of reduced coenzyme Q10 is a state in which the component that mainly improves oxidative stability and reduced coenzyme Q10 are brought into contact in a highly compatible state, that is, the stability in solution The purpose was to improve the stability, and the oxidative stability was not sufficient. For long-term storage, it was necessary to make the preparation in a state of being blocked from the outside, such as a soft capsule. Furthermore, in the soft capsule, there are problems such as high cost in formulation and that high technology is required to manufacture the soft capsule. Therefore, the development of a cheaper and simpler preparation of a reduced coenzyme Q10-containing composition (for example, a dosage form such as a tablet, a powder, a hard capsule, etc.) has been desired from the market. In the solid state such as powder, it was found that a sufficient stabilization effect can not be obtained particularly.

  In addition, Form II crystals of reduced coenzyme Q10 obtained by the process of Patent Document 4 have good oxidation stability compared to Form I crystals of conventional reduced coenzyme Q10, but completely against oxidation. It is not necessarily stable, but for a specific purpose, further improvement in oxidative stability is required. Accordingly, an object of the present invention is to provide a reduced coenzyme Q10 composition in a solid state at room temperature, such as powder, which is suitable for inexpensive and simple formulation that can meet market needs, and which is excellent in oxidation stability.

  As a result of intensive studies, the present inventors have surprisingly found that, by combining reduced coenzyme Q10 with an organic acid and a certain type of carbonate to form a solid state composition at 25 ° C., for example, the reduced form It has been found that the oxidation stability of reduced coenzyme Q10 is remarkably improved by adding and mixing an organic acid and a specific type of carbonate in the solid state to coenzyme Q10 in the solid state respectively, and to complete the present invention. It reached.

That is, the present invention relates to a composition in a solid state at 25 ° C. containing reduced coenzyme Q10, an organic acid, and a carbonate containing sodium cation and / or calcium cation. That is, the present invention is as follows.
[1] A composition in a solid state at 25 ° C. containing a reduced coenzyme Q10, an organic acid, and a carbonate containing sodium cation and / or calcium cation.
[2] The composition according to [1], wherein the reduced coenzyme Q10, an organic acid, and a carbonate containing sodium cation and / or calcium cation are solid.
[3] The composition according to [1] or [2], wherein the content of reduced coenzyme Q10 in the composition is 30% by weight or more and 95% by weight or less.
[4] The composition according to any one of [1] to [3], wherein reduced coenzyme Q10 is a Form II crystal of reduced coenzyme Q10.
[5] The organic acid according to any one of [1] to [4], which is one or more selected from the group consisting of itaconic acid, L-ascorbic acid, tartaric acid, citric acid and erythorbic acid Composition.
[6] The composition according to any one of [1] to [5], wherein the carbonate containing a sodium cation is sodium carbonate or a hydrate thereof, or sodium hydrogen carbonate.
[7] The composition according to any one of [1] to [5], wherein the carbonate containing a calcium cation is calcium carbonate or a hydrate thereof.
[8] The composition according to any one of [1] to [7], which is for oral use.
[9] The composition according to any one of [1] to [8], which is in the form of a tablet, a powder, a granule, a chewable, a pill, or a capsule.
[10] A solid composition produced by mixing solid reduced coenzyme Q10, an organic acid, and a carbonate containing sodium cation and / or calcium cation. "

  As reduced coenzyme Q10, Form II crystals of reduced coenzyme Q10 are preferred, and as the organic acid, itaconic acid, L-ascorbic acid, tartaric acid, citric acid or erythorbic acid is preferred, and as a carbonate containing sodium cation Is preferably sodium carbonate or a hydrate thereof or sodium hydrogen carbonate, and as a carbonate containing a calcium cation, calcium carbonate or a hydrate thereof is preferable.

  According to the present invention, by mixing an organic acid and a specific carbonate in the solid state with reduced coenzyme Q10, a reduced coenzyme Q10 composition having good oxidation stability can be easily obtained. It becomes possible to inexpensively manufacture preparations such as tablets, powders and hard capsules which could not be prepared with the reduced coenzyme Q10.

Hereinafter, the present invention will be described in detail.
The composition of the present invention is a composition containing reduced coenzyme Q10, an organic acid, and a carbonate containing sodium cation and / or calcium cation, which is solid at room temperature and solid at 25 ° C. It is a composition.
In the present invention, “solid” is an object in a solid state which is generally one of three forms of substances, and is distinguished from gas or liquid by exhibiting elasticity or plasticity. The "solid state" includes powders, granules, lumps, etc., as well as liquid crystals, plastic crystals, semi-solid states such as incoherent structures and gels, etc. In the present invention, they are in powder or granules. Preferably there. The composition of the present invention and the components thereof may be in a crystalline or amorphous state.

  In the composition of the present invention, the reduced coenzyme Q10 to be contained in the composition and to be stabilized is, for example, a synthesis, fermentation, extraction from a natural product, reduction of oxidized coenzyme Q10, etc. It can be obtained by known methods. In addition, it is known that the reduced coenzyme Q10 has two crystal polymorphs, FormI, which is conventionally known, and FormII, which is newly discovered recently. Specifically, in powder X-ray (Cu-Kα) diffraction, the melting point is around 48 ° C., and the diffraction angle (2θ ± 0.2 °) is 3.1 °, 18.7 °, 19.0 °, 20 The crystal form of reduced coenzyme Q10 exhibiting a characteristic peak at 2 ° and 23.0 ° is Form I, the melting point is around 52 ° C., and the diffraction angle (X) in powder X-ray (Cu-Kα) diffraction 2θ ± 0.2 °) Crystal of reduced coenzyme Q10 showing characteristic peaks at 11.5 °, 18.2 °, 19.3 °, 22.3 °, 23.0 ° and 33.3 ° The form is Form II. In the present invention, any polymorphic reduced coenzyme Q10 crystal or non-crystal reduced reduced coenzyme Q10 solid may be used, but reduced coenzyme Q10 Form II crystal or reduced coenzyme It is preferable to use a reduced coenzyme Q10 crystal or a crystalline solid mainly composed of Form II crystal of Q10 from the viewpoint of its oxidation stability. The term "main component" as used herein means that 60% by weight or more, preferably 80% by weight or more, more preferably 90% by weight or more of Form II crystals of reduced coenzyme Q10 is based on the total amount of reduced coenzyme Q10. Preferably, it means that 95% by weight or more is contained.

  The reduced coenzyme Q10 used in the composition of the present invention may be reduced coenzyme Q10 alone, or may be a mixture with oxidized coenzyme Q10. When the reduced coenzyme Q10 is a mixture with oxidized coenzyme Q10, the reduced coenzyme Q10 accounts for the total amount of coenzyme Q10 (that is, the total amount of reduced coenzyme Q10 and oxidized coenzyme Q10). The proportion is not particularly limited, but usually about 65 wt% or more, preferably about 70 wt% or more, more preferably 85 wt% or more, particularly preferably 90 wt% or more, especially 95 wt% or more, especially 98 wt% or more It is. Needless to say, the upper limit is 100% by weight.

  The carbonate used in the composition of the present invention is not particularly limited as long as it is a carbonate containing a sodium cation and / or a calcium cation. Examples of the carbonate containing sodium cation include sodium carbonate and its hydrate (eg, monohydrate, heptahydrate, decahydrate etc.) and sodium hydrogen carbonate. Moreover, calcium carbonate and its hydrate (for example, 0.65 hydrate, monohydrate, 1.5 hydrate, hexahydrate etc.) etc. are mentioned as a carbonate containing calcium cation. These carbonates can be used alone or in combination of two or more. Furthermore, it may be a double salt containing both sodium cation and calcium cation.

  The organic acid used in the composition of the present invention is not particularly limited, and examples thereof include glycolic acid, lactic acid, talthronic acid, hydroxybutyric acid, malic acid, tartaric acid, citricamic acid, citric acid, isocitric acid, leucine acid, pantoic acid, Ricinerejinic acid, cerebronic acid, quinic acid, shikimic acid, gallic acid, ferulic acid, caffeic acid, caffeic acid, chlorogenic acid, adipic acid, benzoic acid, gluconic acid, cinnamic acid, succinic acid, sorbic acid, nicotinic acid, parahydroxybenzoic acid, Phenylacetic acid, pantothenic acid, fumaric acid, maleic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, isostearic acid, behenic acid, eicosapentaenoic acid, docosahexaenoic acid, docosapentaenoic acid, L-aspartic acid, 5'-adenylate, alginic acid, itaconic acid, Rigogalacturonic acid, 5'-cytidylic acid, hyaluronic acid, L-ascorbic acid, erythorbic acid, oxalic acid, folic acid and their hydrates are preferred, and in particular, L-aspartic acid, 5'-adenylate, alginic acid , Itaconic acid, oligogalacturonic acid, 5'-cytidylic acid, hyaluronic acid, ferulic acid, gallic acid, adipic acid, L-ascorbic acid, benzoic acid, gluconic acid, erythorbic acid, citric acid, cinnamic acid, succinic acid , Tartaric acid, sorbic acid, nicotinic acid, lactic acid, fumaric acid, folic acid, malic acid and hydrates thereof, and more preferably L-aspartic acid, itaconic acid, adipic acid, L-ascorbic acid, erythorbic acid, citric acid Acids, cinnamic acids, succinic acids, tartaric acids, nicotinic acids, fumaric acids and their hydrates are preferred, in particular Colvin acid, erythorbic acid, citric acid, tartaric acid, preferably itaconic acid and their hydrates, L- ascorbic acid, erythorbic acid, are particularly preferred tartaric acid and their hydrates, tartrate being most preferred. These organic acids can be used alone or in combination of two or more.

  The composition of the present invention may be a composition comprising only reduced coenzyme Q10 and the above-mentioned carbonate and organic acid, or may further contain another third component. As a third component other than carbonates and organic acids, for example, surfactants, oils and fats, excipients, disintegrants, lubricants, binders, dyes, aggregation inhibitors, absorption accelerators, stabilizers, reduction type There is an active ingredient other than coenzyme Q10 and the like, and the third ingredient is not particularly limited as long as it can keep the composition of the present invention in a solid state in its content.

  The surfactant is not particularly limited, and examples thereof include glycerin fatty acid ester, sucrose fatty acid ester, organic acid monoglyceride, sorbitan fatty acid ester, propylene glycol fatty acid ester, polyglycerin condensed ricinoleate ester, saponin, phospholipid and the like. be able to.

  The glycerin fatty acid ester is not particularly limited, and for example, one having a polymerization degree of glycerin of 1 to 10 can be mentioned. Glycerin fatty acid ester etc. whose carbon number of a fatty acid is 6-22 each can be mentioned. The fatty acid residue constituting the glycerin fatty acid ester is not particularly limited, but one having a carbon number of 6 to 18 for each of the fatty acids can be preferably used, and for example, caproic acid, caprylic acid, capric acid, lauric acid, myristin Acids, palmitic acid, stearic acid, isostearic acid, oleic acid, linoleic acid, linolenic acid and the like can be mentioned.

  The sucrose fatty acid ester is not particularly limited, and examples thereof include one in which a fatty acid having 6 to 22 carbon atoms is ester-bonded to one or more of sucrose hydroxyl groups, for example, sucrose laurate ester, sucrose myristin Examples thereof include acid esters, sucrose palmitic acid esters, sucrose stearic acid esters, sucrose oleic acid esters, sucrose behenic acid esters, and sucrose erucic acid esters.

  The organic acid monoglyceride is not particularly limited, but monoglycerin caprylic acid succinic acid ester, monoglycerin stearic acid citric acid ester, monoglycerin stearic acid acetic acid ester, monoglycerin stearic acid succinic acid ester, monoglycerin stearic acid lactic acid ester, monoglycerin Examples thereof include stearic acid diacetyl tartrate ester and the like.

  Examples of sorbitan fatty acid esters include, but are not limited to, those in which fatty acids each having 6 to 18 carbon atoms are ester-bonded to one or more of sorbitan hydroxyl groups, such as sorbitan monopalmitate and sorbitan monostearate Etc.

  As a propylene glycol fatty acid ester, any monoester or diester can be used. The fatty acid residue constituting the propylene glycol fatty acid ester is not particularly limited, but one having 6 to 18 carbon atoms of the fatty acid can be preferably used, for example, myristic acid, palmitic acid, stearic acid, isostearic acid etc. It can be mentioned. The polyglycerin condensed ricinoleic acid ester is not particularly limited. For example, those having an average degree of polymerization of polyglycerin of 2 to 10 and an average degree of condensation of polyricinoleic acid (average of the condensation number of ricinoleic acid) of 2 to 4 For example, tetraglycerin condensed ricinoleate, pentaglycerin condensed ricinoleate, hexaglycerin condensed ricinoleate and the like can be mentioned.

The saponin is not particularly limited, and enju saponin, quillaja saponin, refined soybean saponin, yucca saponin and the like can be mentioned.
The phospholipid is not particularly limited. For example, egg yolk lecithin, purified soy lecithin, purified soybean lecithin, phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine, sphingomyelin, dicetyl phosphate, stearyl amine, phosphatidyl glycerol, phosphatidic acid, phosphatidyl inositol amine, cardiolipin, ceramide A phosphoryl ethanolamine, ceramide phosphoryl glycerol, and these mixtures etc. can be mentioned. Needless to say, phospholipids which have been subjected to processing such as hydrogenation and enzymatic decomposition can also be used. From the viewpoint of improving the absorbability of reduced coenzyme Q10, it is preferable to use an enzymatically degraded phospholipid.

  The fats and oils may be natural fats and oils from animals and plants, or synthetic fats and oils and processed fats and oils, but in order to maintain the composition in the present invention in a solid state, solid fats and oils may be contained among the fats and oils. It is preferable to use relatively high melting point fats and oils. Examples of such vegetable fats and oils include palm oil, guaiac fat, shea fat, monkey fat, cacao butter, jojoba fat, peanut butter and the like, and as animal fats and oils, for example, pork fat, milk fat, beef fat Chicken oils and the like can be mentioned, and further, fats and oils (for example, hardened oils) obtained by processing vegetable fats and oils and animal fats and oils by fractionation, hydrogenation, transesterification etc. can also be mentioned. Moreover, you may use these mixtures.

  Examples of the excipient include, but not limited to, sucrose, lactose, glucose, starch, mannitol, crystalline cellulose, calcium phosphate, calcium sulfate and the like.

  Examples of the disintegrator include, but not limited to, starch, agar, calcium citrate, calcium carbonate, crystalline cellulose, carboxymethylcellulose, tragacanth and the like.

  The lubricant is not particularly limited, and examples thereof include talc, magnesium stearate, polyethylene glycol, silica, hydrogenated oil and the like.

  The binder is not particularly limited, and examples thereof include ethyl cellulose, methyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, tragacanth, shellac, gelatin, pullulan, gum arabic, polyvinyl pyrrolidone, polyvinyl alcohol, polyacrylic acid, polymethacrylic acid, Sorbitol etc. can be mentioned.

Although it does not restrict | limit especially as said pigment | dye, For example, pigment | dyes, such as a titanium oxide, a synthetic pigment, Bengala pigment, a tar pigment, can be mentioned.
The above-mentioned anticoagulation agent is not particularly limited, and examples thereof include stearic acid, talc, light anhydrous silicic acid, hydrous silicic acid silicic acid and the like.

  The absorption promoter is not particularly limited, and examples thereof include higher alcohols and higher fatty acids.

The stabilizer is not particularly limited, and examples thereof include beeswax, hydroxypropyl methylcellulose, methylcellulose and the like.
The active ingredient other than the above-mentioned reduced coenzyme Q10 is not particularly limited, but, for example, amino acids, vitamins such as vitamin C and vitamin E and derivatives thereof, carotenoids such as β-carotene and astaxanthin, minerals, polyphenols, Organic acids, saccharides, peptides, proteins and the like can be mentioned.

  The above-described substances may play multiple roles. For example, starch may serve as an excipient and a disintegrant.

  In the composition of the present invention, the content of reduced coenzyme Q10 with respect to the total weight of the composition is not particularly limited, but in view of producing a composition containing as much as possible of reduced coenzyme Q10, it is usually about It is 10% by weight or more, preferably about 20% by weight or more, more preferably about 23% by weight or more, still more preferably 25% by weight or more, and particularly preferably 30% by weight or more. In addition, from the viewpoint of improving oxidation stability, it is necessary to add an organic acid and a specific carbonate at a content of a certain level or more, and the content of reduced coenzyme Q10 is usually about 99% by weight or less, preferably about It is at most 98 wt%, more preferably at most about 95 wt%, still more preferably at most 90 wt%, even more preferably at most 80 wt%, particularly preferably at most 70 wt%.

  The use amount of the carbonate containing sodium cation and / or calcium cation in the composition of the present invention is not particularly limited, but from the viewpoint of obtaining a sufficient oxidation stabilization effect, relative to reduced coenzyme Q10 in the composition The molar ratio is preferably 0.5 times or more, preferably 1 time or more, and more preferably 2 times or more. The upper limit is not particularly limited, but is usually 10 times or less, and an effect can be sufficiently obtained with 5 times or less. Further, the content of the carbonate containing sodium cation and / or calcium cation with respect to the total weight of the composition of the present invention is not particularly limited, although it depends on the type thereof, usually at least about 1% by weight, preferably about 2% by weight or more, more preferably about 3% by weight or more, still more preferably 5% by weight or more, usually about 60% by weight or less, preferably about 50% by weight or less, more preferably about 45% by weight or less, more preferably Is 40% by weight or less.

  The amount of the organic acid used in the composition of the present invention is not particularly limited, but from the viewpoint of obtaining a sufficient oxidation stabilization effect, the molar amount ratio to reduced coenzyme Q10 in the composition is 1 or more It is preferred to use it, preferably 2 times or more, and more preferably 4 times or more. The upper limit is not particularly limited, but is usually 20 times or less, and a sufficient effect can be obtained with 10 times or less. Further, the content of the organic acid relative to the total weight of the composition of the present invention is not particularly limited, and depending on the type thereof, usually about 1% by weight or more, preferably about 3% by weight or more, more preferably about It is 7 wt% or more, more preferably 15 wt% or more, usually about 80 wt% or less, preferably about 70 wt% or less, more preferably about 65 wt% or less, more preferably 60 wt% or less.

  As described above, the reduced coenzyme Q10 is made to be a solid composition at 25 ° C. by causing the reduced coenzyme Q10 to coexist with an organic acid and a carbonate containing a sodium cation and / or a calcium cation. It protects against oxidation and can be stored more stably. For example, the composition of the present invention has a residual ratio of reduced coenzyme Q10 of about 90% or more, preferably about 95% or more, more preferably 97% or more, particularly preferably, after storage for 28 days at 25.degree. Preferably, the storage stability can be 98% or more, and the residual ratio of reduced coenzyme Q10 after storage for 7 days at 40 ° C., 75% RH is about 90% or more, preferably about 95%. %, More preferably 97% or more, and particularly preferably 99% or more. The term “remaining ratio” as used herein means the ratio of the absolute amount in the composition of reduced coenzyme Q10 after storage for a predetermined period / the absolute amount in the composition of reduced coenzyme Q10 before storage, or the predetermined period The ratio of reduced coenzyme Q10 to the total amount of coenzyme Q10 after storage / the ratio of reduced coenzyme Q10 to the total amount of coenzyme Q10 before storage is determined.

In the composition of the present invention, the method of preparing a composition containing reduced coenzyme Q10, an organic acid and a specific carbonate is not particularly limited as long as the composition is finally in a solid state. For example, it may be prepared by mixing each in the solid state. That is, a solid composition produced by mixing solid reduced coenzyme Q10, an organic acid, and a carbonate containing sodium cation and / or calcium cation is also included in the present invention. In this case, the reduced coenzyme Q10 may simply be mixed with an organic acid and a specific carbonate, or after mixing these, other components as described above may be further mixed.
Alternatively, the composition of the present invention can be prepared by mixing the reduced coenzyme Q10 in the molten state with an organic acid and a carbonate containing sodium cation and / or calcium cation, followed by cooling and solidification. The reduced coenzyme Q10, an organic acid, a carbonate containing sodium cation and / or a calcium cation or any two or more thereof in a state of being dissolved in an appropriate solvent, mixed with other components, and then the solvent The composition of the present invention can also be prepared by removing Further, oxidized coenzyme Q10 in a molten state or oxidized coenzyme Q10 dissolved in a solvent is mixed with an organic acid and a carbonate containing sodium cation and / or calcium cation in the presence of a reducing agent, and the mixture is in the mixture. The composition of the present invention may be prepared by reducing oxidized coenzyme Q10 to reduced coenzyme Q10.
Among these, it is convenient and preferable to prepare the composition of the present invention by mixing solid reduced coenzyme Q10, an organic acid, and a carbonate containing sodium cation and / or calcium cation.

  In order to make the most of the effects of the present invention, it is preferable to prepare and / or store the composition of the present invention under a deoxygenated atmosphere. Moreover, it is preferable to carry out the processing to the formulation mentioned later and the preservation | save after processing also under deoxidizing atmosphere. The deoxidizing atmosphere can be achieved by substitution with an inert gas, pressure reduction, boiling, or a combination thereof. It is preferred at least to replace with an inert gas, ie to use an inert gas atmosphere. Examples of the inert gas include nitrogen gas, helium gas, argon gas, hydrogen gas, carbon dioxide gas and the like, with preference given to nitrogen gas.

  The composition of the present invention may be in the form of tablets, powders, granules, chewables, pills, or capsules, and generally it is an oral formulation such as capsules (hard capsules, microcapsules), tablets, granules, powders, etc. It can be used as a dosage form. Further, the third component may be added to the composition of the present invention and used as an oral dosage form such as a syrup or a beverage, or a form for a cream, a suppository, a toothpaste or the like. Among them, the above-mentioned oral administration form is preferable, particularly preferably in the form of capsule and tablet, and especially hard capsule form is preferable. At this time, the capsule base material is not particularly limited, and other base materials (eg, carrageenan that can be used as a food additive, including gelatin derived from bovine bone, bovine hide, porcine hide, fish hide, etc.) Materials for manufacturing containing a thickening stabilizer or cellulose, such as seaweed-derived products such as alginic acid and plant seed-derived products such as locust bean gum and guar gum may also be used.

  The base material of the tablet is not particularly limited, and examples thereof include cellulose, maltitol, lactose, dextrin, anhydrous calcium phosphate and the like, and cellulose is particularly preferable. Since the composition of the present invention is protected from oxidation and highly stably maintained as the active ingredient, reduced coenzyme Q10, foods and supplements such as nutritive functional foods and foods for specified health use, medicines, veterinary drugs, It can also be a composition useful as cosmetics, nutritional agents, beverages, therapeutic agents, prophylactic agents, quasi drugs, cosmetics, feeds, pet foods and the like.

  The present invention will next be described in more detail by way of examples, which should not be construed as limiting the invention thereto. The purity of reduced coenzyme Q10 and the weight ratio of reduced coenzyme Q10 to oxidized coenzyme Q10 in the examples were determined by the following HPLC analysis, but the purity of the obtained reduced coenzyme Q10 was It does not specify the limit value of purity in the present invention, and similarly, the weight ratio of reduced coenzyme Q10 and oxidized coenzyme Q10 also does not specify its upper limit value. In the present example, the ratio of reduced coenzyme Q10 in the total amount of coenzyme Q10 (total amount of oxidized coenzyme Q10 and reduced coenzyme Q10) is defined as “QH ratio”. Also, from the QH ratio at the start of sample storage and the QH ratio at the end, “QH ratio residual rate” is calculated by the following equation and used as an evaluation scale of oxidation stability. The higher the QH ratio residual rate, the better the oxidation stability.

  The reduced coenzyme Q10 used in this example is a commercially available reduced coenzyme Q10 (manufactured by Kaneka Co., Ltd., trade name: Kaneka QH) for the conventional Form I crystals, and for the recently found Form II crystals, Those prepared from commercially available reduced coenzyme Q10 (manufactured by Kaneka Co., Ltd., trade name: Kaneka QH) according to the method of Example 5 described in Patent Document 4 were used respectively.

QH ratio residual ratio = (QH ratio at the end of evaluation) / (QH ratio at the start of evaluation) * 100

(HPLC analysis conditions)
Column: YMC-Pack (manufactured by YMC), 150 mm (length), 4.6 mm (inner diameter)
Mobile phase: methanol / hexane = 9/1 (v / v)
Detection wavelength: 290 nm
Flow rate: 1 ml / min

(Example 1, Comparative Example 1)
A predetermined amount of the carbonate described in Table 1 was mixed with 1.0 g of reduced coenzyme Q10 (form II crystals) and 1.0 g of ascorbic acid to prepare a mixed powder. Each obtained powder was put into a sample bottle and stored for 7 days at 40 ° C. and 75% RH in air in an open state. Further, for comparison, one not containing carbonate and ascorbic acid (only reduced coenzyme Q10 (Form II crystal)) was also prepared and similarly stored. After storage, HPLC analysis of the mixed powder was performed to check the remaining ratio of QH ratio of coenzyme Q10 contained in the powder. The results are shown in Table 1.

(Example 2, Comparative Example 2)
A predetermined amount of the carbonate described in Table 2 was mixed with 1.0 g of reduced coenzyme Q10 (form II crystals) and 0.87 g of tartaric acid to prepare a mixed powder. Each obtained powder was put into a sample bottle and stored for 7 days at 40 ° C. and 75% RH in air in an open state. Further, for comparison, the one without addition of carbonate and tartaric acid (only reduced coenzyme Q10 (Form II crystal)) was also prepared and stored in the same manner. After storage, HPLC analysis of the mixed powder was performed to check the remaining ratio of QH ratio of coenzyme Q10 contained in the powder. The results are shown in Table 2.

(Example 3, Comparative Example 3)
A predetermined amount of the carbonate described in Table 3 was mixed with 1.0 g of reduced coenzyme Q10 (form II crystals) and 1.1 g of citric acid to prepare a mixed powder. Each obtained powder was put into a sample bottle and stored for 7 days at 40 ° C. and 75% RH in air in an open state. Further, for comparison, one not containing carbonate and citric acid (only reduced coenzyme Q10 (Form II crystal)) was also prepared and stored similarly. After storage, HPLC analysis of the mixed powder was performed to check the remaining ratio of QH ratio of coenzyme Q10 contained in the powder. The results are shown in Table 3.

(Example 4, Comparative Example 4)
A predetermined amount of the carbonate described in Table 4 was mixed with 1.0 g of reduced coenzyme Q10 (Form II crystal) and 1.0 g of erythorbic acid to prepare a mixed powder. Each obtained powder was put into a sample bottle and stored for 7 days at 40 ° C. and 75% RH in air in an open state. Further, for comparison, one not containing carbonate and erythorbic acid (only reduced coenzyme Q10 (Form II crystal)) was also prepared and stored similarly. After storage, HPLC analysis of the mixed powder was performed to check the remaining ratio of QH ratio of coenzyme Q10 contained in the powder. The results are shown in Table 4.

(Example 5, Comparative Example 5)
A predetermined amount of the carbonate described in Table 5 was mixed with 1.0 g of reduced coenzyme Q10 (form II crystals) and 0.75 g of itaconic acid to prepare a mixed powder. Each obtained powder was put into a sample bottle, and stored in air at 40 ° C., 75% RH for 28 days in an open state. Moreover, what added the carbonate was produced also for comparison, and it preserve | saved similarly. After storage, HPLC analysis of the mixed powder was performed to check the remaining ratio of QH ratio of coenzyme Q10 contained in the powder. The results are shown in Table 5.

(Example 6, Comparative Example 6)
A predetermined amount of each of the organic acids and carbonates listed in Table 6 was mixed with reduced coenzyme Q10 (Form II crystals) to prepare a mixed powder. Each powder obtained was placed in a sample bottle and stored in an open state at 25 ° C., 60% RH for 28 days in air. Further, for comparison, a product of only reduced coenzyme Q10 (Form II crystal) and a product without addition of carbonate were prepared and stored in the same manner. After storage, HPLC analysis of the mixed powder was performed to check the remaining ratio of QH ratio of coenzyme Q10 contained in the powder. The results are shown in Table 6.

(Example 7, Comparative Example 7)
A predetermined amount of each of the organic acid and carbonate described in Table 7 was mixed with reduced coenzyme Q10 (Form II crystal) to prepare a mixed powder. Each powder obtained was placed in a sample bottle and stored open at 40 ° C., 75% RH for 56 days in air. Further, for comparison, those of only reduced coenzyme Q10 (Form II crystal) were similarly stored. After storage, HPLC analysis of the mixed powder was performed to check the remaining ratio of QH ratio of coenzyme Q10 contained in the powder. The results are shown in Table 7.

(Example 8, Comparative Example 8)
A predetermined amount of each of the organic acids and carbonates listed in Table 8 was mixed with reduced coenzyme Q10 (Form II crystals) to prepare a mixed powder. Each powder obtained was placed in a sample bottle and stored open at 25 ° C., 60% RH for 84 days in air. Further, for comparison, those of only reduced coenzyme Q10 (Form II crystal) were similarly stored. After storage, HPLC analysis of the mixed powder was performed to check the remaining ratio of QH ratio of coenzyme Q10 contained in the powder. The results are shown in Table 8.

(Example 9, Comparative Example 9)
A predetermined amount of each of the organic acids and carbonates listed in Table 9 was mixed with reduced coenzyme Q10 (Form I crystal) to prepare a mixed powder. Each powder obtained was placed in a sample bottle and stored in an open state at 25 ° C., 60% RH for 28 days in air. Further, for comparison, those of only reduced coenzyme Q10 (Form I crystal) were similarly stored. After storage, HPLC analysis of the mixed powder was performed to check the remaining ratio of QH ratio of coenzyme Q10 contained in the powder. The results are shown in Table 9.

The present invention is based on Japanese Patent Application No. 2014-027544 filed in Japan, the contents of which are incorporated in full herein.

Claims (11)

  A composition in the solid state at 25 ° C. containing reduced coenzyme Q10, an organic acid, and a carbonate containing sodium cation and / or calcium cation.   The composition according to claim 1, wherein the reduced coenzyme Q10, the organic acid, and the carbonate containing sodium cation and / or calcium cation are solid.   The composition according to claim 1 or 2, wherein the content of reduced coenzyme Q10 in the composition is 30% by weight or more and 95% by weight or less.   The composition according to any one of claims 1 to 3, wherein the reduced coenzyme Q10 is a Form II crystal of reduced coenzyme Q10.   The composition according to any one of claims 1 to 4, wherein the organic acid is one or more selected from the group consisting of itaconic acid, L-ascorbic acid, tartaric acid, citric acid and erythorbic acid.   The composition according to any one of claims 1 to 5, wherein the carbonate containing sodium cation is sodium carbonate or a hydrate thereof, or sodium hydrogen carbonate.   The composition according to any one of claims 1 to 5, wherein the carbonate containing a calcium cation is calcium carbonate or a hydrate thereof.   The composition according to any one of claims 1 to 7, which is for oral use.   9. A composition according to any one of the preceding claims, which is in the form of a tablet, a powder, a granule, a chewable, a pill or a capsule.   A solid composition produced by mixing solid reduced coenzyme Q10, an organic acid, and a carbonate containing sodium cation and / or calcium cation, respectively. The composition according to any one of claims 1 to 9, wherein the residual ratio of reduced coenzyme Q10 after storage at 25 ° C and 60% RH for 28 days is 97% or more.