Use of low dose glutathione as skin brightness improver

Abstract

[Problem] The present invention addresses the problem of improving, by the use of glutathione, skin brightness or disorders in the skin caused by ultraviolet rays. [Solution] The present inventors have arrived at the present invention as a result of discovering a method with which skin brightness is improved through the use of a glutathione-containing composition containing a dipeptide derived particularly from a yeast extract or the like, even at a low dose where the glutathione content intake is 100 mg / day or less.

Description

Low-dose glutathione as a skin brightener

[0001] The present invention relates to a glutathione-containing composition suitable for use in whitening and beautifying the skin and improving skin brightness, and to a method for whitening and beautifying the skin and improving skin brightness.

[0002] Although the mechanisms of skin pigmentation, age spots, and freckles are still unclear, it is believed that hormonal abnormalities and ultraviolet light stimulation cause the formation of melanin pigment, which then deposits in the skin. Tyrosinase is an enzyme that catalyzes the oxidation of tyrosine or dopa, and by inhibiting the activity of tyrosinase, the production of melanin pigment is suppressed. Tyrosinase inhibitors are used as whitening agents for cosmetics and as browning inhibitors for foods.

[0003] Glutathione is a tripeptide composed of the amino acids cysteine, glutamic acid, and glycine, and is known to improve the liver's detoxification function. Glutathione intake is known to improve non-alcoholic fatty liver disease. It also functions as a rich flavor substance, and is used in food ingredients and pharmaceuticals.

[0004] Furthermore, when glutathione is orally ingested, the typical dosage is 100 mg / day to 300 mg / day, and Non-Patent Document 1 reports that taking 250 mg or more increased blood glutathione levels by 17% after six months. Non-Patent Document 2 examines the effect of taking 500 mg / day for four weeks on melanin in the skin.

[0005] Furthermore, methods have been reported in which glutathione is combined with other materials to improve skin conditions. Patent Document 1 reports that tyrosinase activity is inhibited by α-lipoic acid and reduced glutathione.

[0006] Patent Publication No. 2009-51768

[0007] Richie JP Jr, Nichenametla S, Neidig W, et al. Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Eur J Nutr. 2015;54(2):251-263.Arjinpathana, Nutthavuth, Glutathione as an oral whitening agent: A randomized, double-blind, placebo-controlled study. Journal of Dermatological Treatment 2012;23(2): 97-102

[0008] An object of the present invention is to improve skin damage caused by ultraviolet rays or skin brightness by using glutathione.

[0009] The present inventors have discovered a method for improving skin brightness even with low doses of glutathione, and have completed the present invention.

[0010] The present invention provides the following: (1) an oral preparation for improving skin brightness, containing glutathione as an active ingredient, (2) the oral preparation for improving skin brightness of (1) above, containing less than 100 mg of glutathione, (3) the oral preparation for improving skin brightness of (1) above or (2) above, in which the glutathione is glutathione contained in yeast extract, (4) a method for improving skin brightness, comprising orally ingesting less than 100 mg / day of glutathione, and (5) the method for improving skin brightness of (4) above, in which the glutathione is glutathione contained in yeast extract.

[0011] According to the present invention, skin brightness can be improved even with an intake of less than 100 mg / day of glutathione.

[0012] Arm brightness measurement results

[0013] The improvement in skin brightness in the present invention refers to an increase in skin brightness, and is generally indicated as bright skin, whitening effect, prevention of melanin pigmentation, improvement of melanin pigmentation, etc. The improvement in skin brightness can be confirmed by the difference between before and after ingestion.

[0014] Glutathione in the present invention refers to reduced glutathione, oxidized glutathione, or a mixture thereof. Reduced glutathione refers to a tripeptide having the structure γ-L-Glu-L-Cys-Gly, and oxidized glutathione is formed by two molecules of reduced glutathione bound together via an S—S bond. The form of glutathione may be any as long as it contains glutathione as an active ingredient.

[0015] The glutathione of the present invention is not particularly limited as long as it is obtained by a method that allows it to be used as a pharmaceutical or food. Typically, it can be obtained from microorganisms such as yeast (JP 59-151894 A), produced by synthesis using enzymes (JP 2020-72 A), or produced by chemical synthesis (Bull. Chem., Soc. Jpn., 1980, Vol. 53, p. 2529). The glutathione used in the present invention is not limited. Glutathione and oxidized glutathione can also be purchased, and purchased products may be used as long as they are usable as foods, pharmaceuticals, etc.

[0016] The glutathione content in the composition of the present invention is arbitrary, but it is preferable that the content in the composition is also less than 100 mg so that the daily intake is less than 100 mg. Furthermore, when the composition of the present invention is in the form of a tablet, for example, the content per tablet may be less than 100 mg, or, for example, the content per tablet may be 20 mg, and five tablets may be used as the composition of the present invention. The same applies to granules, liquids, etc.

[0017] The glutathione used in the glutathione-containing composition of the present invention is not particularly limited as long as it is in a form containing glutathione, such as a purified product, a crude product, or a mixture. The mixture may be an extract containing glutathione, such as yeast extract. In the present invention, the use of yeast extract is preferable for achieving effects at low doses. While there are no particular limitations on the yeast extract containing glutathione, it is preferable to use a yeast extract containing a dipeptide. It is particularly preferable to use a yeast extract containing γ-glutamylcysteine ​​(γ-Gly-Cys: γ-GC) or cystenylglycine (Cys-Gly: CG) as the dipeptide.

[0018] In the present invention, the glutathione content and dipeptide content in a mixture such as yeast extract are measured using high-performance liquid chromatography (HPLC). The measurement conditions are as follows: Column: Mightysil RP-18GP (Kanto Chemical) 4.6 mm-150 cm; Mobile phase: 5% diammonium hydrogen phosphate (adjusted to pH 3.2 with phosphoric acid); Measurement wavelength: 210 nm. Furthermore, the total glutathione, which includes GSH and GSSG, is quantified according to the Tietze method (Analytical Biochemistry, Vol. 27, p. 502, 1969). Note that the glutathione content in the present invention refers to the total glutathione content, including both reduced and oxidized forms.

[0019] In the present invention, glutathione is effective even if it is a purified product when taken in small doses, but glutathione-containing yeast extract is even better. As the yeast extract, it is particularly preferable to use a yeast extract with a high glutathione content. Particularly preferred is a yeast extract containing 8% by weight or more of glutathione, more preferably a yeast extract containing 10% by weight or more. Particularly preferred is an enzyme extract containing 15% by weight or more of glutathione.

[0020] The composition of the present invention can contain other substances as long as they do not impair the effects of the present invention.Additions that can be made include excipients used in common supplements, feeds, and pharmaceuticals, various vitamin preparations, inorganic substances such as calcium, magnesium, iron, and zinc, organic acids such as lactic acid, citric acid, and malic acid, proteins, lactic acid bacteria extracts, polyphenols, and organic substances such as plant extracts.In addition, acidulants, sweeteners, flavorings, stabilizers, and the like that are commonly added to foods can also be added.

[0021] The method of administering the product of the present invention is not particularly limited, and examples thereof include oral administration and parenteral administration such as intravenous, intraperitoneal, or subcutaneous administration. Specifically, the product may be administered in any of oral forms such as tablets, powders, granules, pills, suspensions, emulsions, infusions / decoctions, capsules, syrups, liquids, elixirs, extracts, tinctures, and liquid extracts, or parenteral forms such as injections, drip infusions, creams, and suppositories. Conventional methods can be used to prepare these tablets, and there are no limitations to the present invention.

[0022] The dosage of the present invention is effective even at low doses. When administered to humans, the intake amount and frequency of administration vary depending on the dosage form, the age and weight of the recipient, etc., but an adult should ingest less than 100 mg of glutathione per day. Typically, 10 mg to 100 mg, preferably 20 mg to 80 mg, and particularly preferably 30 mg to 50 mg, is ingested once or several times a day. When using a yeast extract containing glutathione, the glutathione content in the yeast extract is measured, and the intake amount is adjusted to achieve the dose specified in this paragraph.

[0023] The composition of the present invention can be ingested not only as a pharmaceutical product but also as a functional food or nutritional supplement, and in such cases, it is sufficient to ingest it in the amount described above. The composition of the present invention can be used as a composition for improving, preventing, or treating lifestyle-related diseases such as metabolic syndrome.

[0024] The present invention will be described in more detail below, but the present invention is not limited to the following description.

[0025] (Test Method) A randomized, placebo-controlled, double-blind, comparative, group-by-group intervention study was conducted on healthy adults aged 20 to 65 years, in which the test food was ingested for 12 weeks to examine the effect on skin brightness.

[0026] (Test food) - Yeast extract A is a yeast extract containing 15% glutathione by weight, and the glutathione content in test food A is 80 mg. - The amount of yeast extract A in test food B is half that of test food A, and the glutathione content in test food B is 40 mg. - Since yeast extract B used in the control food is a yeast extract that does not contain glutathione, the glutathione content in the control food is 0 mg. (Test period) December 2021 to March 2022 (Dosage) - Low-dose group 1 orally ingested test food A, with a daily intake of 80 mg of glutathione. - Low-dose group 2 orally ingested test food B, with a daily intake of 40 mg of glutathione. - The placebo group orally ingested the control food, with the same ingredients as test foods 1 and 2 except for glutathione. (Skin Brightness Measurement) The brightness of the same area on the face was measured over time at 0, 4, 8 and 12 weeks using a spectrophotometer (CM-26d (Konica Minolta Japan, Inc.)).

[0027] The results are shown in Figure 1 and Table 1. Measurement of arm brightness showed a significant improvement in brightness compared to the start of intake in low-dose Groups 1 and 2. Furthermore, low-dose Group 2 showed a significant improvement compared to the placebo group, demonstrating that skin brightness improved even with low doses of glutathione.

[0028]

Claims

1. An oral agent for improving skin brightness that contains glutathione as an active ingredient.

2. The oral preparation for improving skin lightening according to claim 1, having a glutathione content of less than 100 mg.

3. The oral preparation for improving skin brightness according to claim 1 or 2, wherein the glutathione is glutathione contained in yeast extract.

4. A method for improving skin clarity by orally taking less than 100 mg of glutathione per day.

5. The method for improving skin brightness according to claim 4, wherein the glutathione is that contained in yeast extract.

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