Patent Grant
11911350
The present application enjoys the benefit of priority to Japanese Patent Application No. 2018-34461 (filed on Feb. 28, 2018), the entire disclosure of which is herein incorporated by reference.
The present invention relates to a reduced coenzyme Q10-containing composition and a method of producing the same, particularly to a water-dispersible reduced coenzyme Q10-containing powder composition and a method of producing the same.
Coenzyme Q10, a lipid-soluble component of the respiratory chain and the electron transport chain of photosynthesis, plays a mediating role for the electron transfer between redox proteins in biological membranes. Especially in mammals including human, coenzyme Q10 localizes in organelles such as mitochondria, lysosomes, and Golgi bodies, and is involved, as a component of the electron transport chain, in ATP production-activating and biological antioxidative actions and in membrane stabilization. That is, coenzyme Q10 is a coenzyme that is closely involved in biological energy production, and is also considered as a substance essential for the maintenance of biological functions. Thus, coenzyme Q10 has been widely used as an ingredient for various applications, including pharmaceutical products, dietary supplements, cosmetics, and the like.
Coenzyme Q10 is present in the oxidized and reduced forms and coenzyme Q10 in biological bodies is mostly present in the form of reduced coenzyme Q10. Reduced coenzyme Q10 has antioxidant properties and is recently reported to be more effective in various applications than oxidized coenzyme Q10.
However, enhancing the solubility of coenzyme Q10 in water has been a challenge related to the practical use of coenzyme Q10 in pharmaceutical products, food products, cosmetics, and the like because coenzyme Q10 is poorly soluble in water. A water-soluble inclusion compound of coenzyme Q10 obtained by treatment with cyclodextrin has been previously reported (Patent Documents 1 and 2).
A reduced coenzyme Q10-cyclodextrin inclusion complex prepared according to Patent Document 1 led to only unsatisfactory results in terms of water solubility and storage stability (data not shown). That is, there remains a need for a reduced coenzyme Q10-containing powder composition with high water solubility and excellent storage stability.
An object of the present invention is to provide a reduced coenzyme Q10-containing composition with high water solubility and excellent storage stability and a method of producing the same.
The present invention provides the following inventions.
The composition according to the present invention can allow reduced coenzyme Q10, which is poorly soluble in water, to disperse easily in water, and further exhibits excellent dissolution stability. Thus, an advantage of the present invention is that the present invention can facilitate the usage of reduced coenzyme Q10 in pharmaceutical products, food products, cosmetics, and the like. Additionally, because starch octenylsuccinate or a salt thereof and gum arabic are approved for use in food products and are not allergenic, the composition of the present invention and food products or the like including the same can be consumed without safety concerns, which is another advantage of the present invention.
The composition according to the present invention is a powder composition comprising (A) reduced coenzyme Q10, (B) starch octenylsuccinate or a salt thereof, and (C) gum arabic.
(A) Reduced Coenzyme Q10
Reduced coenzyme Q10 incorporated in the composition of the present invention can be prepared by any known technique, such as chemical synthesis, isolation from a microorganism culture (fermentation), or extraction from natural products, and preferably by reducing oxidized coenzyme Q10, such as existing high-purity coenzyme Q10 products, or a mixture of oxidized coenzyme Q10 and reduced coenzyme Q10 with a commonly used reducing agent, such as sodium hyposulfite, sodium borohydride, or ascorbic acid.
The content of reduced coenzyme Q10 in the composition of the present invention is, for example, from 1.0 to 50% by mass (in terms of solid content), preferably from 5.0 to 40% by mass (in terms of solid content).
(B) Starch Octenylsuccinate
Starch octenylsuccinate incorporated in the composition of the present invention is an excipient or emulsifier which is approved for use in pharmaceutical products, food products, cosmetics, and the like, and any commercially available starch octenylsuccinate may be used. Starch octenylsuccinate incorporated in the composition of the present invention may be in the form of a salt (preferably a salt acceptable for pharmaceutical products, food products, cosmetics, and the like). The salt of starch octenylsuccinate includes sodium starch octenylsuccinate.
In the present invention, starch octenylsuccinate or a salt thereof may be incorporated as an excipient or an emulsifier. Any excipient or emulsifier other than starch octenylsuccinate may further be incorporated in the composition of the present invention, provided that no reduction in water solubility and storage stability occurs in the resulting composition. Any excipient acceptable for pharmaceutical products, food products, cosmetics, and the like can be used as an excipient that may be incorporated in the composition of the present invention, and examples of the excipient include starch, modified starch, saccharides, and cellulose. Among those, starch includes corn starch, wheat starch, and potato starch; and modified starch includes dextrin, maltodextrin, powdered corn syrup, and solubilized starch. Moreover, saccharides include monosaccharides and disaccharides (for example, lactose, xylose) and also include sugar alcohols (for example, xylitol, maltitol, inositol). Additionally, any emulsifier acceptable for pharmaceutical products, food products, cosmetics, and the like can be used as an emulsifier that may be incorporated in the composition of the present invention, and examples of the emulsifier include various saponins, lecithins, enzymatically treated lecithins, enzymatically degraded lecithins, glycerol esters, phytosterols, and sucrose fatty acid esters, and the emulsifier can be added in an amount that will not prevent emulsification and/or dehydration of the composition of the present invention.
The minimum content of starch octenylsuccinate or a salt thereof in the composition of the present invention may be at a ratio of 0.5 (preferably 0.8) with respect to the content of reduced coenzyme Q10 (1) (mass ratio in terms of solid content). The maximum content of starch octenylsuccinate or a salt thereof in the composition of the present invention is not specifically limited but can be at a ratio of, for example, 5, 2, or 1.5 with respect to the content of reduced coenzyme Q10 (1) (mass ratio in terms of solid content). The minimum contents may arbitrarily be combined with the maximum contents, and the above ratio may range, for example, from 0.5 to 5 or from 0.8 to 5.
(C) Gum Arabic
Gum arabic incorporated in the composition of the present invention is a thickener which is approved for use in pharmaceutical products, food products, cosmetics, and the like, and any commercially available gum arabic may be used. Gum arabic includes demineralized and unmodified types of gum arabic, both of which may be incorporated in the composition of the present invention.
In the present invention, gum arabic may be incorporated as a thickener. Any thickener other than gum arabic may further be incorporated in the composition of the present invention, provided that no reduction in water solubility and storage stability occurs in the resulting composition. Any thickener acceptable for pharmaceutical products, food products, cosmetics, and the like may be used, and examples of such a thickener include arabinogalactan, alginate, welan gum, elemi resin, Artemisia sphaerocephala seed gum, curdlan, cassia gum, sodium caseinate, carrageenan, karaya gum, carob bean gum, xanthan gum, chitin, chitosan, guar gum, glucosamine, psyllium seed gum, gellan gum, tamarind gum, Abelmoschus manihot, tragacanth gum, Bacillus natto gum, furcellaran, pullulan, pectin, macrophomopsis gum, methylcellulose, and Gloiopeltis furcata extract.
The minimum and maximum contents of gum arabic in the composition of the present invention may be at a ratio of 0.125 (preferably 0.2) and at a ratio of 1 (preferably 0.5) with respect to the content of reduced coenzyme Q10 (1) (mass ratio in terms of solid content), respectively. The minimum contents may arbitrarily be combined with the maximum contents, and the above ratio may range, for example, from 0.125 to 1 or from 0.2 to 0.5.
(D) Antioxidant
In the present invention, one, two, or more types of antioxidants can be used to prevent, for example, degradation of reduced coenzyme Q10 included in the composition of the present invention. Any antioxidant acceptable for pharmaceutical products, food products, cosmetics, and the like can be used in the present invention, and examples of such an antioxidant include ascorbic acid and esters and salts thereof, sodium sulfite, calcium disodium ethylenediaminetetraacetate, disodium ethylenediaminetetraacetate, L-cysteine chloride, dibutylhydroxytoluene, d-α-tocopherol acetate, d-tocopherols, tocotrienol, mixed tocopherols, catechin, quercetin, rutin, ferulic acid, gallic acid, rice bran oil extract, sage extract, green coffee bean extract, sunflower seed extract, grape seed extract, sesame oil unsaponifiable matter, tea extract, propolis extract, Morella rubra extract, hego-gingko leaf extract, and Styphnolobium japonicum extract. Among those, ascorbic acid and esters and salts thereof include L-ascorbic acid, L-ascorbic acid esters, sodium L-ascorbate, and L-ascorbyl palmitate. In the present invention, ascorbic acid and/or a salt thereof can be suitably used as an antioxidant.
The minimum and maximum contents of the antioxidant in the composition of the present invention may be at a ratio of 0.125 (preferably 0.25) and at a ratio of 1 (preferably 0.75) with respect to the content of reduced coenzyme Q10 (1) (mass ratio in terms of solid content), respectively. The minimum contents may arbitrarily be combined with the maximum contents, and the above ratio may range, for example, from 0.125 to 1 or from 0.25 to 0.75.
The composition of the present invention may comprise the above component (D), in addition to the above components (A), (B), and (C), and may further comprise any component acceptable for pharmaceutical products, food products, cosmetics, and the like, other than the above components (A), (B), (C), and (D), and examples of such components include flavoring agents, preservatives, sweetening agents, and coloring agents.
The composition of the present invention can be produced by homogenizing the ingredients, as described below. Thus, the composition of the present invention can contain the above components (A), (B), and (C), and optionally the above component (D) and any other components in a homogenized form.
The composition of the present invention is also a dried emulsion composition that is obtained by drying a reduced coenzyme Q10-containing emulsion composition and is dispersible in water. In this respect, whether or not the composition is “dispersible in water” can be evaluated by introducing 0.2 g (in terms of solid content) of the composition into 100 mL of water at room temperature, stirring the mixture, and visually observing the appearance of the resulting solution. Specifically, full dissolution of the introduced composition in water without suspended and/or precipitated matters makes the composition considered as “water-dispersible.” As used herein, the phrases “dissolution in water” and “water solubility” mean “dispersion in water” and “water dispersibility.”
The composition of the present invention is a water-dispersible reduced coenzyme Q10-containing composition and can thus be added as an ingredient to foods, to produce food products with homogeneously incorporated reduced coenzyme Q10. Besides being added to foods, the composition of the present invention can also be added as an ingredient to feeds or pet foods, to produce feed and pet food products with homogeneously incorporated reduced coenzyme Q10. That is, food, feed, and pet food products each comprising the composition of the present invention are provided by the present invention.
The foods that can include the composition of the present invention are not specifically limited but include water (for example, drinking water, hydrogen water, mineral water, flavored water), soft drinks (for example, fruit juices, vegetable juices, mixed fruit and vegetable juices, carbonated drinks, functional beverages, sports drinks, non-alcoholic drinks), tea drinks (for example, green tea, black tea, Chinese tea, barley tea, buckwheat tea, mate, blended tea drinks), coffee drinks (for example, canned coffee, instant coffee), cocoa drinks, fermented milk drinks, green vegetable juices, soy milk drinks, milk products (for example, cow milk, milk drinks, processed milk, yogurt), nutritional supplement drinks, jelly beverages, soups, alcoholic drinks (for example, beer, low-malt beer, whisky, bourbon whiskey, spirits, liqueur, wine, fruit wine, sake, shochu, other liquors), carbohydrate-containing foods (for example, cooked rice, noodles, bread, pasta), western cakes (for example, biscuit, cracker, cookie, waffle, pie), Japanese cakes (for example, rice cracker, sweet bun, sweet bean jelly), chewing gum, candy, and frozen sweets (for example, ice cream and sherbet).
Additionally, the foods to which the composition of the present invention can be incorporated may be in the form of liquid, such as the form of beverage and/or liquid diet, or in the form of paste, semi-solid, or gel, or in the form of solid or powder. Because the composition of the present invention is excellent not only in water solubility but also in dissolution stability in water, any foods or cosmetics including the composition of the present invention can be advantageously provided in the form of beverages or water-based cosmetics despite of the presence of reduced coenzyme Q10, which is poorly soluble in water. Moreover, because the composition of the present invention is stable even if the composition is compressed into tablets on a tablet press, any pharmaceutical products and/or dietary supplements including the composition of the present invention can advantageously be provided in the form of solid preparations, such as tablets, capsules, and powders.
The amount of the composition of the present invention incorporated into food products according to the present invention can be determined based on the daily intake of reduced coenzyme Q10. That is, the composition of the present invention can be incorporated into any food product according to the present invention in such a manner that the effective daily intake of reduced coenzyme Q10 for human can be consumed from the food product, where the effective daily intake for human is from 3 to 300 mg (preferably 10 to 100 mg). In this case, the food product according to the present invention may be packaged in such a manner that the effective daily intake of reduced coenzyme Q10 can be consumed from the food product, where the packaging format may be a single-dose packaging or multi-dose packaging format as long as the effective daily intake can be consumed. In cases where the food product is provided in a packaged form, it is desirable that a description of the intake be printed on the package or a document describing the intake be provided as a package insert, to facilitate consumption of the effective daily intake. Moreover, in cases where the effective daily intake is provided in a multi-dose packaging format, a set of multiple packages each containing the effective daily intake can also be provided for ease of consumption.
The composition of the present invention can be produced by homogenizing the ingredients and drying a resulting emulsion composition.
Homogenization of the ingredients can be performed by first adding ingredients including reduced coenzyme Q10, starch octenylsuccinate or a salt thereof, and gum arabic to water and stirring the resulting mixture, optionally further adding an antioxidant(s) and any other components to the mixture and stirring the resulting mixture, and then homogenizing the resulting mixture.
The homogenization is a process to reduce and homogenize the sizes of ingredient particles contained in the mixture solution. The homogenization can be performed on a homogenizer (for example, Milder (manufactured by Pacific Machinery & Engineering Co., Ltd.), Silverson homogenizer (manufactured by Silverson Japan)), high-pressure homogenizer (for example, homogenizer (manufactured by Sanwa Engineering Ltd.), high-pressure homogenizer (manufactured by Sanmaru Machinery Co., Ltd.)), or the like. When a homogenizer is used, a condition of 25 to 40 m/s can be used for homogenization. In addition, when a high-pressure homogenizer is used, a condition of 50 to 150 MPa can be used for homogenization, or a higher pressure may be applied in homogenization. A reduced coenzyme Q10-containing emulsion composition can be obtained after homogenization, in which reduced coenzyme Q10 is in a homogenized form, namely a dispersed form in water.
Drying of the emulsion composition can be performed by any known method, such as spray drying or lyophilization. A reduced coenzyme Q10-containing powder composition can be obtained after drying, in which reduced coenzyme Q10 and the other components are contained in a homogenized form.
The present invention will be described in more specific detail with reference to the following examples, but the present invention is not limited by these examples.
Emulsifiers were assessed for the production of water-dispersible reduced coenzyme Q10-containing powder compositions. Specifically, 10 g of each of the following emulsifiers (A1 to A15) was individually added to 100 mL of water together with 2.5 g of gum arabic (Inagel, manufactured by Ina Food Industry Co., Ltd.), and the resulting mixtures were then heated to 80° C. To each mixture, 20 g of reduced coenzyme Q10 (manufactured by Kaneka Corporation) was added and then mixed. Subsequently, the mixtures were emulsified using an ultrasonic oscillator (manufactured by SONICS & MATERIALS Inc.; at 20 kHz for 15 min twice). The emulsions were dried using a freeze dryer (FDU-2200, manufactured by EYELA Co., Ltd.) according to a routine procedure, and the resulting dry matters were finely ground with a compact and powerful mill (ForceMill, manufactured by Osaka Chemical Co., Ltd.) to prepare reduced coenzyme Q10-containing dry powder formulations.
<Emulsifiers>
Each obtained reduced coenzyme Q10-containing dry powder formulation was evaluated for the powder appearance, the water solubility, and the stability after dissolution in water and subsequent 8-hour standing. The powder appearance, the water solubility, and the stability after dissolution in water and subsequent 8-hour standing were classified into three grades (A: excellent, B: normal, C: bad) by visual observation. For the water solubility, a powder formulation observed to produce a solution with some suspended matters was graded B, and a powder formulation observed to produce a solution with a ring of oil was graded C. For the stability after dissolution in water and subsequent 8-hour standing, a powder formulation observed to produce a solution retaining the properties at the time of dissolution was graded A, and a powder formulation observed to produce a solution with some suspended matters was graded B, and a powder formulation observed to produce a solution with a ring of oil was graded C. Moreover, the water solubility and the stability after dissolution in water and subsequent 8-hour standing were examined by adding 0.2 g of each reduced coenzyme Q10-containing powder formulation to 100 mL of water at room temperature, stirring the mixture, and then observing the resulting mixture.
The results were as shown in Table 1.
As seen above, only the reduced coenzyme Q10-containing powder compositions comprising sodium starch octenylsuccinate, among those emulsifiers A1 to 15, were excellent not only in powder appearance and water solubility but also in dissolution stability.
Reduced coenzyme Q10-containing powder compositions comprising the components as indicated in Table 2 below were produced. That is, all the components for each test sample were added to and dissolved with stirring in 500 mL of water heated at 80° C. After the dissolution, the mixtures were emulsified using an ultrasonic oscillator (manufactured by SONICS & MATERIALS Inc.; at 20 kHz for 15 min twice). The emulsions were dried using a freeze dryer (FDU-2200, manufactured by EYELA Co., Ltd.) according to a routine procedure, and the resulting dry matters were finely ground with a compact and powerful mill (ForceMill, manufactured by Osaka Chemical Co., Ltd.) to prepare reduced coenzyme Q10-containing dry powder formulations.
Each obtained reduced coenzyme Q10-containing dry powder formulation was evaluated for the powder appearance (characteristics), the water solubility, and the stability after dissolution in water and subsequent 8-hour standing. The powder appearance, the water solubility, and the stability after dissolution in water and subsequent 8-hour standing were classified into three grades (A: excellent, B: normal, C: bad) by visual observation. For the water solubility, a powder formulation observed to produce a solution with some suspended matters was graded B, and a powder formulation observed to produce a solution with a ring of oil was graded C. For the stability after dissolution in water and subsequent 8-hour standing, a powder formulation observed to produce a solution retaining the properties at the time of dissolution was graded A, and a powder formulation observed to produce a solution with some suspended matters was graded B, and a powder formulation observed to produce a solution with a ring of oil was graded C. Moreover, the water solubility and the stability after dissolution in water and subsequent 8-hour standing were examined by adding 0.2 g of each reduced coenzyme Q10-containing dry powder formulation to 100 mL of water at room temperature, stirring the mixture, and then observing the resulting mixture.
The results were as shown in Table 3.
As seen above, the powder compositions comprising a given amount of sodium starch octenylsuccinate with respect to reduced coenzyme Q10 were excellent not only in powder appearance and water solubility but also in dissolution stability. Additionally, the powder compositions comprising given amounts of sodium starch octenylsuccinate and also of gum arabic with respect to reduced coenzyme Q10 were excellent not only in powder appearance and water solubility but also in dissolution stability.
Moreover, each obtained reduced coenzyme Q10-containing dry powder formulation with a weight of 5 g was placed in a glass vial with a volume of 50 mL and stored at 45° C. for evaluation of storage stability. The powder appearance (characteristics), the water solubility, the stability after dissolution in water and subsequent 8-hour standing, and the residual amount of reduced coenzyme Q10 were evaluated on Day 14. The powder appearance, the water solubility, and the stability after dissolution in water and subsequent 8-hour standing were classified into three grades (A: excellent, B: normal, C: bad) by visual observation. For the water solubility, a powder formulation observed to produce a solution with some suspended matters was graded B, and a powder formulation observed to produce a solution with a ring of oil was graded C. For the stability after dissolution in water and subsequent 8-hour standing, a powder formulation observed to produce a solution retaining the properties at the time of dissolution was graded A, and a powder formulation observed to produce a solution with some suspended matters was graded B, and a powder formulation observed to produce a solution with a ring of oil was graded C. Moreover, the water solubility and the stability after dissolution in water and subsequent 8-hour standing were examined by adding 0.2 g of each reduced coenzyme Q10-containing dry powder formulation to 100 mL of water at room temperature, stirring the mixture, and then observing the resulting mixture. The storage stability of the active ingredient was evaluated based on the content ratio of reduced coenzyme Q10 (the content ratio (%) between before and after the storage stability test). The content of reduced coenzyme Q10 was measured by high-performance liquid chromatography (HPLC). The conditions for HPLC were as follows.
<HPLC Conditions>
The results were as shown in Table 4.
As seen above, the powder compositions comprising a given amount of sodium starch octenylsuccinate with respect to reduced coenzyme Q10 were excellent not only in powder appearance and water solubility after storage, but also in dissolution stability after storage. Additionally, the powder compositions comprising given amounts of sodium starch octenylsuccinate and also of gum arabic with respect to reduced coenzyme Q10 were excellent not only in powder appearance and water solubility after storage, but also in dissolution stability after storage. Furthermore, the powder compositions comprising an antioxidant at a given percentage (%) by mass with respect to reduced coenzyme Q10 were excellent in storage stability of reduced coenzyme Q10.
Reduced coenzyme Q10-containing powder compositions were produced based on the results obtained in Example 2. That is, all the components for each test sample as indicated in Table 5 below were dissolved in 1 L of water with heating to 80° C. The resulting mixtures were then emulsified using a high-pressure homogenizer (manufactured by Sanmaru Machinery Co., Ltd.; at 500 kg/cm2, 3 repeats). After the emulsification, reduced coenzyme Q10-containing dry powder formulations were prepared using a spray dryer (Mini Spray Dryer GB22, manufactured by Yamato Scientific Co., Ltd.).
Each obtained reduced coenzyme Q10-containing dry powder formulation with a weight of 10 g was placed in brown glass vials with a volume of 100 mL, three of which were degassed and purged with nitrogen gas and then sealed, and the vials were stored in a refrigerator at 5° C., a storage container at 18° C., or an incubator at 45° C. for evaluation of storage stability. Each vial was stored for two weeks to evaluate later the powder appearance (characteristics), the water solubility, the stability after dissolution in water and subsequent 8-hour standing, and the residual amount of reduced coenzyme Q10. The powder appearance was examined by visual observation. Additionally, the water solubility and the stability after dissolution in water and subsequent 8-hour standing were classified into three grades (A: excellent, B: normal, C: bad) by visual observation. For the water solubility, a powder formulation observed to produce a solution with some suspended matters was graded B, and a powder formulation observed to produce a solution with a ring of oil was graded C. For the stability after dissolution in water and subsequent 8-hour standing, a powder formulation observed to produce a solution retaining the properties at the time of dissolution was graded A, and a powder formulation observed to produce a solution with some suspended matters was graded B, and a powder formulation observed to produce a solution with a ring of oil was graded C. Moreover, the water solubility and the stability after dissolution in water and subsequent 8-hour standing were examined by adding 0.2 g of each reduced coenzyme Q10-containing dry powder formulation to 100 mL of water at room temperature, stirring the mixture, and then observing the resulting mixture. The storage stability of the active ingredient was evaluated based on the content ratio of reduced coenzyme Q10 (the content ratio (%) between before and after the storage stability test). The content of reduced coenzyme Q10 was measured by HPLC, similarly to Example 2.
The results were as shown in Tables 6 to 8.
As seen above, the powder compositions comprising sodium starch octenylsuccinate and gum arabic at given ratios with respect to reduced coenzyme Q10 were excellent not only in powder appearance and water solubility after storage, but also in dissolution stability after storage. Additionally, the powder compositions comprising an antioxidant at a given ratio with respect to reduced coenzyme Q10 were excellent in storage stability of reduced coenzyme Q10.
The reduced coenzyme Q10-containing dry powder formulations obtained in Example 3 (Test samples 51 to 55) were individually formulated into tablets according to a routine procedure, for evaluation of storage stability. Specifically, 150 mg of reduced malt sugar, 100 mg of each reduced coenzyme Q10-containing dry powder formulation (any one of Test samples 51 to 55), 100 mg of microcrystalline cellulose, 35 mg of corn starch, 2 mg of magnesium stearate, and 2 mg of sucrose fatty acid ester were mixed, and the resulting mixture was compressed into tablets with a diameter of 8 mm and a thickness of 3.8 mm at a pressure of 14 kN. Twenty of the obtained tablets were placed in each of brown glass vials with a volume of 50 mL and were evaluated for the storage stability at the start, 2 weeks, 4 weeks, and 6 weeks of storage at 45° C. The storage stability was evaluated based on the content ratio of reduced coenzyme Q10 (the content ratio (%) between before and after the storage stability test). The content of reduced coenzyme Q10 was measured by HPLC, similarly to Example 2.
The results were as shown in Table 9.
As seen above, the powder compositions comprising sodium starch octenylsuccinate, gum arabic, and an antioxidant at given ratios with respect to reduced coenzyme Q10 were excellent in storage stability of the active ingredient, reduced coenzyme Q10. Additionally, the result from the storage stability test of the tablets containing the dry powder of Test sample 55 indicated that the presence of gum arabic as well as of an antioxidant is effective in improving the storage stability of reduced coenzyme Q10.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2018-034461 | Feb 2018 | JP | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/JP2019/005516 | 2/15/2019 | WO |
| Publishing Document | Publishing Date | Country | Kind |
|---|---|---|---|
| WO2019/167663 | 9/6/2019 | WO | A |
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| 20210046020 A1 | Feb 2021 | US |
