Pharmaceutical composition and food composition for inhibiting xanthine oxidase

Abstract

To provide a pharmaceutical composition for inhibiting xanthine oxidase and a food composition for inhibiting xanthine oxidase.SOLUTION: The present invention relates to a pharmaceutical composition for inhibiting xanthine oxidase and a food composition for inhibiting xanthine oxidase, each comprising pyroglutamic acid as an active ingredient.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to pharmaceutical and food compositions for inhibiting xanthine oxidase. [Background technology]

[0002] Pyroglutamic acid, which is an active ingredient of the pharmaceutical and food compositions of the present invention, is an amino acid formed by intramolecular condensation reaction between the carboxyl group and amino group of glutamic acid to form a lactam.

[0003] As shown in the following Patent Documents 1 and 2, the present inventors have already discovered the estradiol production promoting action and PDE5 inhibitory action of pyroglutamic acid, but have not discovered its xanthine oxidase inhibitory action.

[0004] In addition, there is no literature that discloses or suggests the xanthine oxidase inhibitory activity of pyroglutamic acid. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Patent No. 6634495 [Patent Document 2] Patent No. 6457687 Summary of the Invention [Problem to be solved by the invention]

[0006] As mentioned above, there is no literature that discloses or suggests that pyroglutamic acid has the effect of inhibiting xanthine oxidase. [Means for solving the problem]

[0007] As a result of extensive research, the present inventors have found that pyroglutamic acid has an inhibitory effect on xanthine oxidase, and have thus completed the present invention.

[0008] That is, the present invention relates to a pharmaceutical composition or a food composition for inhibiting xanthine oxidase, which contains pyroglutamic acid as an active ingredient. Effect of the Invention

[0009] The pharmaceutical composition and food composition for inhibiting xanthine oxidase of the present invention are expected to have effects such as inhibiting uric acid synthesis, inhibiting the generation of reactive oxygen species, and increasing ATP (adenosine triphosphate) or alleviating deficiency by suppressing decomposition involving xanthine oxidase, and can contribute to the prevention, amelioration and treatment of various diseases caused by hyperuricemia, reactive oxygen species or ATP deficiency. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] The present invention relates to a pharmaceutical composition for inhibiting xanthine oxidase, which contains pyroglutamic acid as an active ingredient. The pharmaceutical composition according to the present invention contributes to the prevention and / or treatment of hyperuricemia and various diseases caused by hyperuricemia, various diseases associated with reactive oxygen species, and various diseases caused by ATP deficiency by inhibiting uric acid synthesis, inhibiting the generation of reactive oxygen species, and increasing ATP deficiency based on the inhibition of xanthine oxidase.

[0011] Pyroglutamic acid is an amino acid formed by intramolecular condensation of the carboxyl group and amino group of glutamic acid to form a lactam, and is available in D-, L- and racemic forms.

[0012] [ka]

[0013] Xanthine oxidase is an enzyme that catalyzes the decomposition of hypoxanthine to xanthine and then the decomposition of xanthine to uric acid.

[0014] The pharmaceutical composition of the present invention inhibits the activity of xanthine oxidase, thereby inhibiting uric acid synthesis and reducing blood uric acid levels, thereby contributing to the prevention and / or treatment of hyperuricemia and various diseases caused thereby, such as gouty arthritis and gouty tophi.

[0015] Furthermore, inhibiting the activity of xanthine oxidase leads to suppression of the decomposition of hypoxanthine and the generation of reactive oxygen species such as superoxide that are generated during the decomposition of xanthine, i.e., so-called antioxidant effect, and contributes to the prevention and / or treatment of various diseases involving reactive oxygen species, such as cardiovascular diseases such as arteriosclerosis and heart failure.

[0016] Furthermore, by inhibiting the activity of xanthine oxidase, hypoxanthine is prevented from being decomposed and remains as hypoxanthine. In this way, hypoxanthine is kept in a state where it can be recovered again as nucleotides, and the vicious circle of a large amount of ATP consumption caused by nucleotide shortage in the ATP supply process during an energy crisis can be broken, and it is expected that ATP will be enhanced and the shortage will be alleviated, which will lead to the protection of mitochondria. Therefore, the pharmaceutical composition of the present invention contributes to the prevention and / or treatment of various diseases caused by ATP deficiency, such as circulatory system diseases, cardiovascular diseases, skin diseases, etc., and to the prevention of aging.

[0017] The pharmaceutical composition according to the present invention can be used as a drug or quasi-drug and can be in various forms. These drugs or quasi-drugs can be in dosage forms suitable for oral administration, such as powders, pills, tablets (e.g., coated tablets, sugar-coated tablets, chewable tablets, etc.), capsules (e.g., hard or soft gelatin capsules, etc.), granules, and oral liquids (e.g., emulsions, suspensions, syrups, etc.).

[0018] In addition, the compound may be in a dosage form suitable for rectal administration such as a suppository; a dosage form suitable for intravascular administration such as an injection or infusion, intramuscular administration, subcutaneous administration or intradermal administration such as an ointment, cream, gel, or liquid (including eye drops, eyewash, etc.); i.e., a dosage form suitable for parenteral administration, but oral administration is preferred.

[0019] When the pharmaceutical composition of the present invention is used in the form of tablets, granules, capsules, or chewable tablets, known carriers such as tableting aids, granule processing aids, capsule processing aids, etc. can be used.

[0020] Examples of tableting aids include granulated sugar, white sugar, powdered sugar, reduced maltose syrup powder, lactose, glucose, pullulan, erythritol, starch, dextrin, and other sugars, crystalline cellulose, gum arabic, soybean curd, and other dietary fibers, corn protein, calcium phosphate, and other food calcium, food extracts, dried food powders, natural fruit juice powders, surfactants such as sucrose fatty acid esters, powdered oils and fats, glycerin, fatty acid esters, and other oils and fats, and various sweeteners, various acidulants, and various flavors used in chewable tablets, and shellac, corn protein, yeast cell walls, starch, reduced maltose syrup, sugarless sugar coating, maltitol, glycerin, sorbitol, HPMC, HPC, and the like, as coating materials. However, there are no particular limitations as long as the effects of the present invention are not impaired.

[0021] Furthermore, there are no particular limitations on the granule processing aid as long as it does not impair the effects of the present invention, and examples include all sugars such as granulated sugar, white sugar, powdered sugar, reduced maltose syrup powder, lactose, glucose, pullulan, erythritol, starch, dextrin, and the like, dietary fibers such as crystalline cellulose and gum arabic, corn protein, food calcium such as calcium phosphate, food extracts, dried food powders, natural fruit juice powders, and the like.

[0022] Furthermore, there are no particular limitations on the capsule processing aids as long as they do not impair the effects of the present invention. Examples of such aids include all sugars, such as granulated sugar, white sugar, powdered sugar, reduced maltose syrup powder, lactose, glucose, pullulan, erythritol, starch, dextrin, and other sugars, dietary fibers, such as crystalline cellulose and gum arabic, corn protein, food calcium, such as calcium phosphate, food extracts, dried food powders, and natural fruit juice powders, for preparing hard capsules, and content viscosity adjusters, such as edible oils and fats, beeswax, and glycerin fatty acid esters, for preparing soft capsules.

[0023] Tablets can usually be prepared using a tablet press, but they can also be made into chewable tablets by blending flavoring materials into the tablets, or the tablet surface can be coated using an automatic coating machine, a spray granulator, or a hand pan. Granules can be formed using various granulators, such as spray granulator type, kneading (extrusion) type, or high-speed agitator granulator type. Capsules can be prepared using capsule filling machines (hard and soft types) by mixing capsule assistants.

[0024] The present invention also relates to a food composition for inhibiting xanthine oxidase, which contains pyroglutamic acid as an active ingredient. The food composition of the present invention contributes to the prevention and / or improvement of hyperuricemia and various diseases caused by hyperuricemia, various diseases associated with reactive oxygen species, and various diseases caused by ATP deficiency by inhibiting uric acid synthesis, inhibiting the generation of reactive oxygen species, and increasing ATP deficiency and alleviating ATP deficiency based on the inhibition of xanthine oxidase. Furthermore, alleviating ATP deficiency can contribute to the protection of mitochondria, and thus to the prevention of aging.

[0025] The xanthine oxidase inhibiting food composition of the present invention can be used as a food, beverage, or animal feed, for example, as a health food, functional food, food for specified health uses, beauty food, or nutritional supplement (supplement). These foods and animal feeds may be in the form of, for example, drinking water such as tea and juice; ice cream, jelly, candy, chocolate, chewing gum, etc. They may also be in the form of a liquid, powder, granules, capsule, or tablet.

[0026] The amount of intake of the pharmaceutical composition for inhibiting xanthine oxidase and the food composition for inhibiting xanthine oxidase according to the present invention is not particularly limited, and can be appropriately selected depending on the dosage form, and the age, weight, and symptoms of the person or animal that takes the composition, such as a user or a patient. The intake period can be determined arbitrarily depending on the age and symptoms of the person or animal that takes the composition. EXAMPLES

[0027] Next, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to the following examples as long as it does not depart from the gist of the present invention.

[0028] <Xanthine oxidase inhibitory effect test> Xanthine oxidase activity was evaluated by measuring the absorbance at 290 nm of the amount of uric acid finally produced by adding xanthine oxidase using hypoxanthine or xanthine as a substrate. The control without pyroglutamic acid was set at 100%, and the rate of inhibition of the increase in absorbance in the presence of pyroglutamic acid was calculated to confirm whether pyroglutamic acid has an inhibitory effect on xanthine oxidase.

[0029] <method> 1) Sample preparation Pyroglutamic acid was prepared by dissolving it in 450 mM disodium hydrogen phosphate solution. The solution was then serially diluted with 450 mM disodium hydrogen phosphate solution to prepare a series of sample solutions of test concentrations (129.11 mg / mL to 180.75 mg / mL). 2)-1 Measurement of xanthine oxidase inhibitory activity using hypoxanthine as a substrate 50 μL of each test substance at each concentration, 35 μL of 450 mM phosphate buffer, and 30 μL of 0.1 units / mL xanthine oxidase (Xanthine Oxidase from bovine milk: Sigma-Aldrich) were mixed and incubated for 15 minutes at 37° C. 60 μL of 0.75 mM hypoxanthine was then added, and the mixture was allowed to react at 37° C. for 30 minutes. Then, 25 μL of 1N hydrochloric acid was added to stop the reaction. The absorbance of the uric acid produced at this time was measured at 290 nm using a plate reader. 2)-2 Measurement of xanthine oxidase inhibitory activity using xanthine as a substrate 50 μL of each test substance at each concentration, 35 μL of 450 mM phosphate buffer, and 30 μL of 0.1 units / mL xanthine oxidase (Xanthine Oxidase from bovine milk: Sigma-Aldrich) were mixed and incubated for 15 minutes at 25° C. 60 μL of 1.5 mM xanthine was then added and reacted at 25° C. for 30 minutes. Then, 25 μL of 1N hydrochloric acid was added to stop the reaction. The absorbance of the uric acid produced at this time was measured at 290 nm using a plate reader. 3) Analysis Using the measured absorbance at 290 nm in the reaction solution, the xanthine oxidase inhibition rate (%) was calculated according to the following formula, and the concentration corresponding to 50% inhibition rate (IC50) was obtained. Inhibition rate (%) = 100 - {(D absorbance - C absorbance) / (B absorbance - A absorbance) x 100} A: Absorbance at 290 nm without adding test substance and with adding enzyme B: Absorbance at 290 nm without test substance or enzyme. C: Absorbance at 290 nm after addition of test substance and enzyme D: Absorbance at 290 nm with and without the addition of test substance and enzyme

[0030] <result> The IC50 of pyroglutamic acid was 41.3 mg / mL when hypoxanthine was used as a substrate, and 43.6 mg / mL when xanthine was used as a substrate. From these results, it was confirmed that pyroglutamic acid has a xanthine oxidase inhibitory effect.

Claims

1. A pharmaceutical composition for inhibiting xanthine oxidase, comprising pyroglutamic acid as an active ingredient.

2. A food composition for inhibiting xanthine oxidase, comprising pyroglutamic acid as an active ingredient.

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