JP2024020094A - Use of low-dose glutathione as a skin brightening agent - Google Patents
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- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 title claims abstract description 134
- 108010024636 Glutathione Proteins 0.000 title claims abstract description 68
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- 238000005282 brightening Methods 0.000 title 1
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- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
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- AGBQKNBQESQNJD-UHFFFAOYSA-N alpha-Lipoic acid Natural products OC(=O)CCCCC1CCSS1 AGBQKNBQESQNJD-UHFFFAOYSA-N 0.000 description 1
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Abstract
【課題】本発明は、グルタチオンにより、肌の明度を改善することを課題とする。【解決手段】本発明者は、グルタチオンを低用量においても、肌明度を改善する方法を見出し、本発明を完成させた。【選択図】なしAn object of the present invention is to improve skin brightness using glutathione. SOLUTION: The present inventors have discovered a method of improving skin brightness even with low doses of glutathione, and have completed the present invention. [Selection diagram] None
Description
本発明は、美白・美肌用、肌明度向上に好適に用いられるグルタチオン含有組成物、及び、美白・美肌用、肌明度向上方法に関する。 The present invention relates to a glutathione-containing composition suitably used for whitening and beautifying the skin and improving skin brightness, and a method for whitening and beautifying the skin and improving skin brightness.
皮膚の色素沈着、シミ・ソバカスなど発生機序については不明な点もあるが、ホルモンの異常や紫外線の刺激が原因となってメラニン色素が形成され、これが皮膚内に沈着するのが一因と考えられている。チロシナーゼは、チロシンあるいはドーパ等の酸化を触媒する酵素であり、チロシナーゼの活性を阻害することによりメラニン色素の生成を抑えることを利用して、チロシナーゼ活性の阻害剤が、化粧品などの美白剤あるいは食品の褐変防止剤として使用されている。 Although the mechanisms behind the development of skin pigmentation, age spots, and freckles are still unclear, one reason is that melanin pigments are formed due to hormonal abnormalities and stimulation from ultraviolet rays, and this is deposited within the skin. It is considered. Tyrosinase is an enzyme that catalyzes the oxidation of tyrosine or dopa, etc., and inhibiting tyrosinase activity suppresses the production of melanin pigment. It is used as an anti-browning agent.
グルタチオンは、システイン、グルタミン酸、グリシンといったアミノ酸からなるトリペプチドであり、肝臓の解毒作用改善薬として知られている。グルタチオンの摂取により、非アルコール性脂肪肝の改善機能が知られており、また、コク味物質としての機能もあり、食品素材、医薬品等に利用されている。 Glutathione is a tripeptide consisting of amino acids such as cysteine, glutamic acid, and glycine, and is known as a drug that improves liver detoxification. Ingestion of glutathione is known to improve non-alcoholic fatty liver disease, and also functions as a kokumi substance, and is used in food materials, medicines, etc.
また、グルタチオンを経口摂取する場合、一般的に、100mg/日から300mg/日の摂取をすることが多く、非特許文献1では、250mg以上摂取することで、6カ月経過後に血中グルタチオン量が17%増加したとの報告がある。非特許文献2では、500mg/日を4週間摂取し、皮膚のメラニンへの影響を見ている。 In addition, when glutathione is orally ingested, the intake is generally 100 mg/day to 300 mg/day, and Non-Patent Document 1 states that by taking 250 mg or more, the amount of glutathione in the blood increases after 6 months. It is reported that the number has increased by 17%. In Non-Patent Document 2, 500 mg/day was taken for 4 weeks and the effect on skin melanin was observed.
さらに、グルタチオンでは、他の素材と組み合わせで、肌の状態を改善する方法が報告されている。特許文献1では、α - リポ酸と還元型グルタチオンでチロシナーゼの活性を阻害することが報告されている。 Furthermore, it has been reported that glutathione can be used in combination with other materials to improve skin conditions. Patent Document 1 reports that α-lipoic acid and reduced glutathione inhibit tyrosinase activity.
本発明は、グルタチオンにより、肌の明度を改善することを課題とする。 An object of the present invention is to improve skin brightness using glutathione.
本発明者は、グルタチオンを低用量においても、肌明度を改善する方法を見出し、本発明を完成させた。 The present inventors have discovered a method for improving skin brightness even at low doses of glutathione, and have completed the present invention.
本発明は以下のような発明である。
(1)有効成分としてグルタチオンを含む肌の明度向上用経口剤、
(2)グルタチオン含量が100mg以下である、前記(1)の肌の明度向上用経口剤、
(3)グルタチオンが酵母エキスに含まれるグルタチオンである前記(1)又は(2)の肌の明度向上用経口剤、
(4)グルタチオンを100mg/日以下を経口摂取する、肌明度の向上方法、
(5)グルタチオンが酵母エキスに含まれるグルタチオンである前記(4)の肌明度の向上方法。
The present invention is as follows.
(1) Oral agent for improving skin brightness containing glutathione as an active ingredient;
(2) The oral preparation for improving skin brightness according to (1) above, which has a glutathione content of 100 mg or less;
(3) the oral preparation for improving skin brightness according to (1) or (2) above, wherein the glutathione is glutathione contained in yeast extract;
(4) A method for improving skin brightness by orally ingesting 100 mg/day or less of glutathione;
(5) The method for improving skin brightness according to (4) above, wherein the glutathione is glutathione contained in yeast extract.
本発明によると、グルタチオンの摂取量100mg/日以下であっても、肌明度を改善することができる。 According to the present invention, skin brightness can be improved even if the intake of glutathione is 100 mg/day or less.
本発明の肌明度向上とは、肌の明度が高くなることを示し、一般的には、明るい肌、美白効果、メラニン色素沈着予防、メラニン色素沈着改善などと示される。 Improving skin brightness in the present invention refers to increasing the brightness of the skin, and generally refers to bright skin, whitening effect, prevention of melanin pigmentation, improvement of melanin pigmentation, etc.
本発明でいうグルタチオンは、還元型グルタチオン若しくは酸化型グルタチオン又はこれらの混合物をいう。還元型グルタチオンとはγ - L - G l u - L - C y s - G l y の構造を有するトリペプチドを表し、酸化型グルタチオンとは還元型グルタチオン2 分子がS-S 結合により結合したものである。グルタチオンの形態は、グルタチオンが有効成分として含有するものであれば何でもよい。 Glutathione as used in the present invention refers to reduced glutathione, oxidized glutathione, or a mixture thereof. Reduced glutathione is a tripeptide with the structure γ-L-Glu-L-Cys-Gly, and oxidized glutathione is two molecules of reduced glutathione bound together through an S-S bond. It is. The form of glutathione may be any form as long as it contains glutathione as an active ingredient.
本発明のグルタチオンは、医薬品又は食品として使用できる方法で取得されれば、特に制限はない。通常は、酵母等の微生物(特開昭59-151894)から得る方法、酵素を用いた合成等により製造される方法(特開2020-72)、化学的合成法により製造される方法(Bull.Chem.,Soc.Jpn.,1980年、第53巻、p.2529)などがあり、本発明で使用するグルタチオンに制限はない。また、グルタチオン及び酸化型グルタチオンは、購入もでき、食品、医薬品等として利用できるものであれば、購入したものでも良い。 The glutathione of the present invention is not particularly limited as long as it can be obtained by a method that can be used as a medicine or food. Usually, methods are obtained from microorganisms such as yeast (JP 59-151894), methods produced by synthesis using enzymes (JP 2020-72), and methods produced by chemical synthesis (Bull. Chem., Soc. Jpn., 1980, Vol. 53, p. 2529), and there are no limitations on the glutathione used in the present invention. Moreover, glutathione and oxidized glutathione can be purchased, and any purchased products may be used as long as they can be used as foods, medicines, etc.
本発明の組成物中のグルタチオン含量は、任意であるが、1日あたりの摂取量を100mg以下とするため、組成物中の含量も100mg以下となることが好ましい。また、本発明の組成物は、例えば錠剤の形状の場合、1錠剤あたりの含量を100mgとしても良いし、例えば、1錠剤あたりの含量を20mgとして、5錠分を本願の組成物としても良い。顆粒や液剤等でも同様に考える。 The glutathione content in the composition of the present invention is arbitrary, but since the daily intake is 100 mg or less, the content in the composition is preferably 100 mg or less. Furthermore, when the composition of the present invention is in the form of a tablet, for example, the content per tablet may be 100 mg, or, for example, the content per tablet may be 20 mg, and the composition of the present invention may be used for 5 tablets. . The same applies to granules, liquids, etc.
本発明のグルタチオンを含む組成物に使用されるグルタチオンは、精製物、粗精製物、混合物など、グルタチオンを含む形態であれば特に制限はない。混合物としては、酵母エキスのような、グルタチオンを含む抽出物であっても良い。グルタチオンを含有する酵母としては「ハイチオンコーボMG」(三菱商事ライフサイエンス社)、グルタチオンを含有する酵母エキスとしては「ハイチオンエキスYH」(三菱商事ライフサイエンス社)などがある。 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 crudely purified product, or a mixture. The mixture may be an extract containing glutathione, such as yeast extract. Examples of yeast containing glutathione include "Haithion Cobo MG" (Mitsubishi Corporation Life Sciences), and yeast extracts containing glutathione include "Haithion Extract YH" (Mitsubishi Corporation Life Sciences).
酵母エキス中などの混合物中のグルタチオン含量の測定方法は、本発明では、高速液体クロマトグラフィー(HPLC)を用いて行う。測定条件は以下の通りである。
・カラム:マイティシルRP-18GP(関東化学製)4.6mm-150cm
・移動相:5%リン酸水素二アンモニウム(pH3.2にリン酸で調整)
・測定波長:210nm
更にGSH及びGSSGを合わせたトータルのグルタチオンの定量は、Tietzeの方法(「アナリティカル バイオケミストリー」 第27巻、502ページ、1969年)に従って測定する。なお、本発明のグルタチオン含量は、還元型、酸化型を合わせた、トータルグルタチオン含量を意味している。
In the present invention, the glutathione content in a mixture such as yeast extract is measured using high performance liquid chromatography (HPLC). The measurement conditions are as follows.
・Column: Mighty Sil RP-18GP (Kanto Chemical) 4.6mm-150cm
・Mobile phase: 5% diammonium hydrogen phosphate (adjusted to pH 3.2 with phosphoric acid)
・Measurement wavelength: 210nm
Furthermore, the total amount of glutathione including GSH and GSSG is determined according to the method of Tietze ("Analytical Biochemistry" Vol. 27, p. 502, 1969). Note that the glutathione content in the present invention refers to the total glutathione content including reduced and oxidized forms.
本発明では、グルタチオンは、精製品であっても低用量摂取であれば、効果を有するが、グルタチオン含有酵母エキスであれば、なお良い。酵母エキスは、グルタチオンを高含有する酵母エキスを用いるのが特に好ましい。特に好ましいのは、グルタチオンを8重量%以上含む酵母エキスであり、さらに好ましくは、10重量%以上含む酵母エキスである。特に好ましくは15重量%以上含む酵素エキスである。 In the present invention, glutathione has an effect even if it is a purified product if taken in low doses, but it is even better if it is a glutathione-containing yeast extract. As the yeast extract, it is particularly preferable to use a yeast extract with a high content of glutathione. Particularly preferred is a yeast extract containing 8% by weight or more of glutathione, and more preferably a yeast extract containing 10% by weight or more. Particularly preferred is an enzyme extract containing 15% by weight or more.
本発明の組成物は、本発明の効果を阻害ない範囲で、他の物質を添加することができる。添加できるものは、通常のサプリメント、飼料、医薬品に添加される賦形剤、各種ビタミン剤、カルシウム、マグネシウム、鉄、亜鉛などの無機物、乳酸、クエン酸、リンゴ酸などの有機酸、タンパク質、乳酸菌抽出物、ポリフェノール、植物抽出物などの有機物などを適宜添加しても良い。また、一般食品に添加される、酸味料、甘味料、香料、安定化剤なども添加することができる。 Other substances may be added to the composition of the present invention as long as the effects of the present invention are not impaired. Things that can be added include regular supplements, feed, excipients added to medicines, various vitamins, inorganic substances such as calcium, magnesium, iron, and zinc, organic acids such as lactic acid, citric acid, and malic acid, proteins, and lactic acid bacteria. Organic substances such as extracts, polyphenols, and plant extracts may be added as appropriate. In addition, acidulants, sweeteners, flavoring agents, stabilizers, and the like that are added to general foods can also be added.
本発明品を投与する方法は、特に限定されず、経口投与、静脈内、腹膜内もしくは皮下投与等の非経口投与をあげることができる。具体的には、錠剤、散剤、顆粒剤、丸剤、懸濁剤、乳剤、浸剤・煎剤、カプセル剤、シロップ剤、液剤、エリキシル剤、エキス剤、チンキ剤、流エキス剤等の経口剤、又は注射剤、点滴剤、クリーム剤、坐剤等の非経口剤のいずれでもよい。これらの錠剤等の調整方法は、常法を採用でき、本発明での制限はない。 The method of administering the product of the present invention is not particularly limited, and can include oral administration, parenteral administration such as intravenous, intraperitoneal, or subcutaneous administration. Specifically, oral preparations such as tablets, powders, granules, pills, suspensions, emulsions, infusions/decoctions, capsules, syrups, solutions, elixirs, extracts, tinctures, and liquid extracts; Or parenteral preparations such as injections, drops, creams, and suppositories may be used. Conventional methods can be used to prepare these tablets, etc., and there are no limitations in the present invention.
本発明の投与量は、低用量において効果を発揮する。ヒトに投与する場合の摂取量および投与回数は、投与形態、被投与者の年齢、体重等により異なるが、成人一日当り、グルタチオンを100mg以下となるよう摂取する。通常は、10mg~100mg、好ましくは20 m g ~ 80mg、特に好ましくは30 m g~50mg となるように一日一回乃至数回摂取する。グルタチオンを含む酵母エキスを用いる場合、酵母エキス中のグルタチオン含量を測定し、本段落の用量になるよう、摂取量を調整する。 The dosage of the present invention is effective at low doses. When administered to humans, the intake amount and frequency of administration vary depending on the dosage form, age and weight of the recipient, but adults should ingest 100 mg or less of glutathione per day. Usually, the amount is taken once to several times a day in an amount of 10 mg to 100 mg, preferably 20 mg to 80 mg, particularly preferably 30 mg to 50 mg. When using yeast extract containing glutathione, measure the glutathione content in the yeast extract and adjust the intake amount to meet the dosage in this paragraph.
本発明の組成物は、医薬品だけでなく、機能性食品、栄養補助食品としても摂取可能であり、その場合、前段の摂取量になるよう摂取すればよい。本発明の組成物は、メタボリックシンドロームなどの生活習慣病の改善・予防・治療用組成物として利用することができる。 The composition of the present invention can be ingested not only as a medicine but also as a functional food or a nutritional supplement, and in that case, the composition should be ingested to the same amount as the previous intake amount. The composition of the present invention can be used as a composition for improving, preventing, and treating lifestyle-related diseases such as metabolic syndrome.
以下に、本願の発明をより詳細に説明する。しかし、本願発明は、以下の説明によって、限定されるものではない。 The invention of the present application will be explained in more detail below. However, the present invention is not limited by the following explanation.
(試験方法)
20歳以上65歳以下の健常成人を対象に、ランダム化プラセボ対照二重盲検並群間比較介入試験にて、試験食品を12週間摂取させることで、肌の明度に与える影響を検証した。
(Test method)
In a randomized, placebo-controlled, double-blind, parallel-group comparative intervention study, healthy adults aged 20 to 65 years were asked to consume test foods for 12 weeks, and the effect on skin brightness was examined.
(試験食品)
・酵母エキスAは、グルタチオンを含む15重量%含む酵母エキスであり、被験食品A中のグルタチオン含量は、グルタチオン80mgである。
・被験食品Bの酵母エキスA量は被験食品A半量とし、被験食品B中のグルタチオン含量は、グルタチオン40mgである。
・対照食品で使用した酵母エキスBは、グルタチオンを含まない酵母エキスであるため、対照食品中のグルタチオン含量は、0mgである。
(試験期間)
2021年12月から2022年3月
(服用量)
・低用量第1群は、被験食品Aを経口摂取し、1日あたりの各成分の摂取量は、グルタチオン80mgとなる。
・低用量第2群は、被験食品Bを経口摂取し、1日あたりの各成分の摂取量は、グルタチオン40mgとなる。
・プラセボ群は、対照食品を経口摂取し、グルタチオン以外の成分は、試験食1及び2と同様である。
(肌明度測定)
測定は、分光測色計(CM-26d(コニカミノルタジャパン株式会社))を用いて、0、4、8、12週目に、顔の同箇所の明度を経時的に測定した。
(Test food)
- Yeast extract A is a yeast extract containing 15% by weight of glutathione, and the glutathione content in test food A is 80 mg of glutathione.
- The amount of yeast extract A in test food B is half the amount of test food A, and the glutathione content in test food B is 40 mg of glutathione.
- Yeast extract B used in the control food is a yeast extract that does not contain glutathione, so the glutathione content in the control food is 0 mg.
(Test period)
December 2021 to March 2022 (Dosage)
- The first low-dose group will orally ingest test food A, and the daily intake of each ingredient will be 80 mg of glutathione.
-The second low-dose group orally ingested test food B, and the daily intake of each component was 40 mg of glutathione.
- The placebo group orally ingested the control food, and the ingredients other than glutathione were the same as Test Foods 1 and 2.
(Skin brightness measurement)
The brightness of the same spot on the face was measured over time at 0, 4, 8, and 12 weeks using a spectrophotometer (CM-26d (Konica Minolta Japan, Inc.)).
結果は、図1及び表1に示す。腕の明度を測定した結果、低用量第1群及び第2群において、摂取開始時と比較し、優位に明度の改善がみられた。さらに低用量群第2群に関しては、プラセボ群に対しても優位に改善し、低用量のグルタチオンでも肌明度が改善した。
The results are shown in Figure 1 and Table 1. As a result of measuring the brightness of the arm, a significant improvement in brightness was observed in the low-dose groups 1 and 2 compared to the time at the start of intake. Furthermore, regarding the second low-dose group, the skin brightness improved even with a low dose of glutathione, which was significantly improved compared to the placebo group.
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