JP2004091473A

JP2004091473A - Therapeutic agent for improving chromatosis

Info

Publication number: JP2004091473A
Application number: JP2003189581A
Authority: JP
Inventors: Tadayasu Takada; 高田　任康; Tsukasa Takemura; 竹村　司
Original assignee: Individual
Current assignee: Individual
Priority date: 2002-07-12
Filing date: 2003-07-01
Publication date: 2004-03-25
Anticipated expiration: 2023-07-01
Also published as: WO2004006908A1; JP4786127B2; AU2003281179A1

Abstract

<P>PROBLEM TO BE SOLVED: To develop a therapeutic agent for internal use, excellently effective for chloasma, Riehl's melanosis, chromatosis after eczema/dermatitis, ephelis, postinflammatory chromatosis, or the like, which chaps the skin of females. <P>SOLUTION: This therapeutic agent for internal use for improving the chromatosis contains tranexamic acid, vitamin C, a vitamin B2 family or its salts, and a vitamin B6 family or its salts, and further selectively contains licorice, biotin, L-cysteine, glutathione, and tiopronin. Riboflavin, riboflavin phosphate, sodium riboflavin phosphate, riboflavin lactate, or flavin adenine dinucleotide is exemplified as the vitamin B2 family or its salt. Pyridoxine, pyridoxine hydrochloride, pyridoxine phosphate, pyridoxal, pyridoxal phosphate, calcium pyridoxal phosphate, pyridoxal hydrochloride, pyridoxamine, or pyridoxamine dihydrochloride is exemplified as the vitamin B6 family or its salt. <P>COPYRIGHT: (C)2004,JPO

Description

【０００１】
【発明の属する技術分野】
本発明は色素沈着改善治療薬に関し、詳しくは、人間の顔に出現する肝斑（シミ）、リール黒皮症（女子顔面黒皮症）、雀卵斑（そばかす）、炎症後色素沈着などに対して医師が患者に投与する内用治療薬（飲み薬）に関する。
【０００２】
【従来の技術】
炎症後色素沈着や肝斑、いわゆる３０代以降の妊娠可能な女性にできはじめるシミの治療法としては、トラネキサム酸の内服投与が有効であることが知られている。
トラネキサム酸を化粧品中に微量配合することでアレルギー性皮膚炎等を有効に予防、抑制することが知られている（特公昭４７−１４７９号）。
又トラネキサム酸自体を主成分とする肝斑等への外用治療薬には特許第２６１８６５７号（特開平１−９３５１９号）がある。
【０００３】
トラネキサム酸とビタミンＣ、タチオンの内用、またハイドロキノンやコウジ酸の外用に効果があるとされている。
更に、本願発明者の一人による特開平６−８０５６４号の抗色素沈着治療薬が内用薬として知られている。この治療薬の組成物はトラネキサム酸と、ビタミンＣと、ビタミンＢ２群と、ビタミンＢ６群もしくはそれらの塩類とからなり、肝斑（シミ）の治療に関しては特に有効である。
従って、これらの事例からトラネキサム酸を外用の化粧品又は内用の抗色素沈着治療薬として使用することが非常に安全性が高く、長期使用に耐えるものであることが理解できる。
【０００４】
リール黒皮症は、素因のある成人女子に外来性、化粧品等の物質が皮膚に作用して惹起され、日光照射により悪化する。治療法としては副腎皮質ホルモン含有軟膏や抗ヒスタミン剤を塗布し、ビタミンＣやＳＨ製剤を飲用する。
雀卵斑（そばかす）は、主に５、６歳ごろ発症し、思春期に顕著となり、高齢になると漸次不明瞭となる。そばかす膏、そばかす乳剤、マクラニン、三塩化酢酸などを貼付する。
【０００５】
【特許文献１】
特公昭４７−１４７９号
【特許文献２】
特許第２６１８６５７号
【特許文献３】
特開平６−８０５６４号
【０００６】
【発明が解決しようとする課題】
前記特開平６−８０５６４号の抗色素沈着治療薬は明らかに肝斑に効果が認められた。共に医師である本願の両発明者には、肝斑に対し更に一層有効であり、且つリール黒皮症又は女子顔面黒皮症又は苔癬様水泡性中毒性黒色皮膚炎又は戦争黒皮症又は代謝障害に伴う色素沈着症又は老人性色素斑（老人のしみ）又は網状肢端色素沈着症又は雀卵斑（そばかす）又は夏目斑又は慢性色素性紫斑又は光線性花弁状色素斑又は光線性白斑黒皮症又は炎症後色素沈着症又は湿疹・皮膚炎後の色素沈着症などに対しても効果のある治療薬が求められていた。また体質により異なる人体に副作用発生を極度に最小限度に押さえるために、有効成分数を少なくした治療薬も求められていた。
【０００７】
【課題を解決するための手段】
本願発明は、トラネキサム酸とビタミンＣとに加えて、カンゾウ（甘草）、ビオチン、Ｌシステイン、グルタチオン、チオプロニンを選択的にまたは併用する。他の発明は、トラネキサム酸とビタミンＣとビタミンＢ２群もしくはそれらの塩類やビタミンＢ６群もしくはそれらの塩類とに加えて、カンゾウ（甘草）、ビオチン、Ｌシステイン、グルタチオン、チオプロニンを選択的にまたは併用すると、肝斑又はリール黒皮症又は女子顔面黒皮症又は苔癬様水泡性中毒性黒色皮膚炎又は戦争黒皮症又は代謝障害に伴う色素沈着症又は老人性色素斑（老人のしみ）又は網状肢端色素沈着症又は雀卵斑（そばかす）又は夏目斑又は慢性色素性紫斑又は光線性花弁状色素斑又は光線性白斑黒皮症又は炎症後色素沈着症又は湿疹・皮膚炎後の色素沈着症に対し治療効果が時間的に早期に発現し、極めて効果が高い。
更に他の発明は、トラネキサム酸、ビタミンＣ、ビタミンＢ２群もしくはそれらの塩、ビタミンＢ６群もしくはそれらの塩に加えて、Ｌシステイン、Ｌシステインと甘草、又はＬシステインとチオプロニンを有効成分として含有する内服用の色素沈着改善治療薬とすると、肝斑（シミ）に対して極めて有効であるとの効果が出た。
【０００８】
トラネキサム酸、ビタミンＣ、ビタミンＢ２群もしくはそれらの塩、ビタミンＢ６群もしくはそれらの塩に加えて、Ｌシステイン、Ｌシステインと甘草、又はＬシステインとチオプロニンを有効成分として含有する内服用の色素沈着改善治療薬が、有効に作用する疾患としては、リール黒皮症、女子顔面黒皮症、苔癬様水泡性中毒性黒色皮膚炎、戦争黒皮症、代謝障害に伴う色素沈着症、老人性色素斑（老人のしみ）、網状肢端色素沈着症、雀卵斑（そばかす）、夏目斑、慢性色素性紫斑、光線性花弁状色素斑、光線性白斑黒皮症、炎症後色素沈着症、湿疹・皮膚炎後の色素沈着症、肝斑（しみ）がある。
【０００９】
ビタミンＢ２群もしくはその塩類としては、リボフラビン、リン酸リボフラビン、リン酸リボフラビンナトリウム、酪酸リボフラビン、フラビンアデニンジヌクレオチド（ＦＡＤ）、フラビンアデニンジヌクレオチドナトリウムなどが挙げられる。
又ビタミンＢ６群もしくはその塩類としては、ピリドキシン、塩酸ピリドキシン、リン酸ピリドキシン、ピリドキサール、リン酸ピリドキサール、リン酸ピリドキサールカルシウム、塩酸ピリドキサール、ピリドキサミン、二塩酸ピリドキサミン、リン酸ピリドキサミンなどが挙げられる。
肝斑等に対し治療効果は時間的に緩やかであるが、単純な一つトラネキサム酸を有効成分とすると、体質により異なる人体での副作用発生は限りなくゼロになった。
【００１０】
【発明の実施の形態】
以下本発明について説明する。本発明の色素沈着改善治療薬は使用量としては、
遊離酸又は遊離塩基として成人１日量、トラネキサム酸：５０〜３０００ｍｇ、ビタミンＣ：１０〜３０００ｍｇ、ビタミンＢ２群：０．５〜９０ｍｇ、ビタミンＢ６群：０．５〜２００ｍｇ、及びカンゾウ（甘草）：１日量生薬として５０〜２０００ｍｇ、ビオチン：０．１〜１０ｍｇ、Ｌシステイン：５〜４００ｍｇ、グルタチオン：５〜５００ｍｇ、及びチオプロニン：１０〜１０００ｍｇを使用する。その量を１回又は数回に分けて使用する。
これらの１日の各服用量は、平均的な日本人の成人が、充分に吸収し消化できて、治療効果が最大になるように、治療経験により決定されたものである。
例えば、トラネキサム酸が５０ｍｇ以下だと効果が少なめとなり、トラネキサム酸が３０００ｍｇ以上投与してもそれ以上の治療効果がなく、徒にトラネキサム酸を摂取したことになるからである。
トラネキサム酸、ビタミンＣ、ビタミンＢ２群、ビタミンＢ６群の４成分に追加するカンゾウ（甘草）とビオチンとＬシステインとグルタチオンとチオプロニンは併用することが好ましい。
これらの中でカンゾウ（甘草）、Ｌシステイン及びチオプロニンが更に好ましくＬシステインが最も好ましい。
【００１１】
次に、剤型としては錠剤、カプセル、粒剤、液剤などの内服剤として使用する。その場合、必要に応じて賦形剤、結合剤、崩壊剤などの医薬品添加物又は他の活性剤を含めることができる。
賦形剤には例えば、乳糖、精製白糖、軽質無水ケイ酸、微結晶セルロースなど、また結合剤には例えば、メチルセルロース、カルボキシメチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、ポリビピニルピロリドン、結晶セルロースなど、更にまた崩壊剤には例えば、カルボキシメチルセルロースカルシウム、カルボキシメチルセルロースナトリウム、低置換度ヒドロキシプロピルセルロース、コーンスターチなどが用いられる。
その他の活性剤の１例として、パントテン酸又はその塩、パンテノール、ビオチン、ニコチン酸、ニコチン酸アミド、ビタミンＥ群などが挙げられる。これらを上記有効成分とともに含めることにより、本発明の効果がより増す場合がある。
【００１２】
実施例１
主に肝斑（シミ）と少数の雀卵斑（そばかす）の患者に対して、発明者の両医師が次の処方量１日３回に分けて投与した場合の結果を表１に示す。又この処方により薬剤を投与した患者に副作用はまったく認められなかった。
基本処方　（ビタミンＢ２、Ｂ６抜き）
単一成分　　　　　　　　　　１回量　　　　　　　　　　　　１日量
トラネキサム酸　　　　　　　５００ｍｇ　　　　　　　　　　１５００ｍｇ
ビタミンＣ　　　　　　　　　２００ｍｇ　　　　　　　　　　　６００ｍｇ
カンゾウ（甘草）　　　　　　３００ｍｇ　　　　　　　　　　　９００ｍｇ
ビオチン　　　　　　　　　　　　２ｍｇ　　　　　　　　　　　　　６ｍｇ
Ｌシステイン　　　　　　　　　２０ｍｇ　　　　　　　　　　　　６０ｍｇ
グルタチオン　　　　　　　　　３０ｍｇ　　　　　　　　　　　　９０ｍｇ
チオプロニン　　　　　　　　１００ｍｇ　　　　　　　　　　　３００ｍｇ
【００１３】
【表１】
氏名　　性　年齢　病名　　程度　効果発現時期　効果（判定時期）　備考
Ａ．Ｍ　女　２０　　雀卵斑　軽　　６週間　　　　有効（７ケ月）　　継続
Ｋ．Ｏ　女　２９　　肝斑　　中　　２週間　　　　有効（３ケ月）　　継続
Ｙ．Ｔ　女　３３　　肝斑　　中　　２週間　　　　不明（来医院無）　継続
Ｓ．Ｐ　女　６０　　肝斑　　中　　４週間　　　　有効（３ケ月）　　継続
Ｄ．Ｙ　女　４７　　肝斑　　重　　４週間　　　　有効（３ケ月）　　継続
Ｆ．Ｈ　女　６６　　肝斑　　中　　４週間　　　　有効（５ケ月）　　継続
Ｕ．Ｎ　女　５２　　肝斑　　中　　２週間　　　　有効（７ケ月）　　継続
Ｉ．Ｇ　女　４４　　肝斑　　中　　４週間　　　　有効（３ケ月）　　継続
Ｋ．Ｒ　女　５２　　肝斑　　中　　４週間　　　　有効（５ケ月）　　継続
Ｗ．Ｉ　女　３９　　肝斑　　重　　２週間　　　　著効（６ケ月）　　継続
Ｆ．Ｋ　女　４２　　肝斑　　中　　２週間　　　　有効（４ケ月）　　継続
Ｋ．Ｔ　女　５７　　肝斑　　中　　２週間　　　　有効（３ケ月）　　継続
Ｕ．Ｋ　女　３１　　肝斑　　中　　４週間　　　　有効（６ケ月）　　継続
Ｊ．Ｍ　女　６５　　肝斑　　中　　２週間　　　　有効（５ケ月）　　継続
Ｆ．Ｊ　女　５５　　肝斑　　中　　２週間　　　　有効（６ケ月）　　継続
Ｅ．Ｉ　女　６０　　肝斑　　重　　４週間　　　　有効（４ケ月）　　継続
【００１４】
肝斑等に対し治療効果は長くて弱半年近く掛かっているが、トラネキサム酸とビタミンＣとカンゾウ（甘草）とビオチンとＬシステインとグルタチオンとチオプロニンを有効成分とすると、体質により異なる人体での副作用発生は限りなくゼロになり、まったく認められなかった。
【００１５】
実施例２
主に肝斑（シミ）と少数の雀卵斑（そばかす）とリール黒皮症と炎症後色素沈着症の患者に対して、次の処方量１日３回に分けて投与した場合の結果を表２に示す。又この処方により薬剤を投与した患者に副作用はまったく認められなかった。
基本処方　（ビタミンＢ２、Ｂ６入り）
成分　　　　　　　　　　　　１回量　　　　　　　　　　　　１日量
トラネキサム酸　　　　　　　５００ｍｇ　　　　　　　　　１５００ｍｇ
ビタミンＣ　　　　　　　　　２００ｍｇ　　　　　　　　　　６００ｍｇ
ビタミンＢ２（ＦＡＤ）　１０〜１５ｍｇ　　　　　　　　３０〜４５ｍｇ
ビタミンＢ６（リン酸ピリドキサール）２０〜３０ｍｇ　　６０〜９０ｍｇ
カンゾウ（甘草）　　　　　　３００ｍｇ　　　　　　　　　　９００ｍｇ
ビオチン　　　　　　　　　　　　２ｍｇ　　　　　　　　　　　　６ｍｇ
Ｌシステイン　　　　　　　　　２０ｍｇ　　　　　　　　　　　６０ｍｇ
グルタチオン　　　　　　　　　３０ｍｇ　　　　　　　　　　　９０ｍｇ
チオプロニン　　　　　　　　１００ｍｇ　　　　　　　　　　３００ｍｇ
【００１６】
【表２】
氏名　　性　年齢　病名　　　程度　効果発現時期　効果（判定時期）　備考
Ｏ．Ｋ　女　４７　　肝斑　　　中　　４週間　　　　有効（２ヶ月）　　継続
Ｏ．Ｍ　女　１９　　雀卵斑　　軽　１２週間　　　　有効（４ヶ月）　　継続
Ｋ．Ｍ　女　３２　　肝斑　　　中　　４週間　　　　有効（１．５ヶ月）　　継続
Ｋ．Ｔ　女　２７　　肝斑　　　中　　　不明　　　　不明（来院不明）　継続
Ｓ．Ｔ　女　５７　　肝斑　　　中　　４週間　　　　有効（２ヶ月）　　継続
Ｓ．Ｙ　女　５２　　肝斑　　　重　　４週間　　　　有効（２ヶ月）　　継続
Ｔ．Ｅ　女　５８　　肝斑　　　中　　４週間　　　　有効（２ヶ月）　　継続
Ｆ．Ｓ　女　５７　　肝斑　　　中　　４週間　　　　有効（２ヶ月）　　継続
Ｈ．Ｒ　女　５７　　肝斑　　　中　　４週間　　　　有効（２ヶ月）　　継続
Ｙ．Ｍ　女　５０　　肝斑　　　中　　４週間　　　　有効（２ヶ月）　　継続
Ｙ．Ｎ　女　５０　　肝斑　　　中　　４週間　　　　有効（２ヶ月）　　継続
Ｎ．Ｈ　女　５７　　肝斑　　　中　　８週間　　　　有効（２ヶ月）　　継続
Ｎ．Ｙ　女　４４　　肝斑　　　重　　８週間　　　　有効（２ヶ月）　　継続
Ｉ．Ｋ　女　４６　　肝斑　　　中　　４週間　　　　有効（２ヶ月）　　継続
Ｏ．Ｒ　女　５４　　肝斑　　　中　　４週間　　　　有効（２ヶ月）　　継続
Ｗ．Ｋ　女　４６　　肝斑　　　重　　４週間　　　　著効（２ヶ月）　　継続
Ｔ．Ｋ　女　４８　　肝斑　　　中　　４週間　　　　有効（２ヶ月）　　継続
Ｋ．Ｋ　女　５５　　肝斑　　　中　　４週間　　　　有効（２ヶ月）　　継続
Ｔ．Ｈ　女　６１　　肝斑　　　中　　４週間　　　　不明（２ヶ月）　　継続
Ｓ．Ｋ　女　４８　　肝斑　　　中　　４週間　　　　有効（２ヶ月）　　継続
Ｊ．Ｋ　女　７０　　肝斑　　　中　　４週間　　　　有効（２ヶ月）　　継続
Ｓ．Ｊ　女　５９　　肝斑　　　中　　４週間　　　　有効（２ヶ月）　　継続
Ｒ．Ｙ　女　５１　　肝斑　　　中　　４週間　　　　有効（２ヶ月）　　継続
Ｅ．Ｗ　女　５５　　肝斑　　　重　　４週間　　　　有効（２ヶ月）　　継続
Ｔ．Ａ　女　５２　リール黒皮　中　　４週間　　　　有効（２ヶ月）　　継続
Ｔ．Ｙ　女　６１　　肝斑　　　中　　４週間　　　　有効（２ヶ月）　　継続
Ｍ．Ｍ　女　６４　リール黒皮　中　　４週間　　　　有効（２ヶ月）　　継続
Ｎ．Ｍ　女　４５　　肝斑　　　中　　４週間　　　　有効（２ヶ月）　　継続
Ｍ．Ｃ　女　３９　炎症後色素沈着　中　８〜１２週間　著効（２ヶ月）　継続
Ｇ．Ｓ　女　５０　　肝斑　　　重　　２週間　　　　有効（２ヶ月）　　継続
Ｆ．Ｓ　女　５６　　肝斑　　　中　　４週間　　　　著効（２ヶ月）　　継続
Ｏ．Ｓ　女　５３　　肝斑　　　中　　４週間　　　　有効（２ヶ月）　　継続
Ｋ．Ｙ　女　４９　　肝斑　　　中　　４週間　　　　著効（２ヶ月）　　継続
【００１７】
表１と表２中で、「程度」は治療前患者の肝斑又はそばかすの色素沈着度を示し、「重」は厚化粧でも隠し得ない色素沈着である。
「中」は厚化粧では隠せるが、普通の化粧では隠し得ない色素沈着、「軽」は普通の化粧では隠せるが、薄化粧では隠し得ない色素沈着である。
また「有効」は色素沈着が、「重」→「中」、「重」→「軽」、「重」→消滅や「中」→「軽」、「中」→消滅や「軽」→消滅等にそれぞれ治療されたことを示している。
【００１８】
比較のため表３に本願発明者の一人による特開平６−８０５６４号の効果を示す。
表３の最終効果判定は出願人の一人が投与期間終了後に行った。
【表３】

【００１９】
表３のＧ−４が表２の「重」に相当し、厚化粧でも隠し得ない色素沈着である。同様にＧ−３が「中」に相当し厚化粧では隠せるが、普通の化粧では隠し得ない色素沈着、同様にＧ−２が「軽」で普通の化粧では隠せるが、薄化粧では隠し得ない色素沈着である。
さて表３中では症状が「重」の患者では、

である。これらの患者が治るまでに１０週から３２週即ち２．５ヶ月から７．５ヶ月要している。
【００２０】
一方本願の実施例２では症状が「重」の患者は、
Ｓ．Ｙ　　　女　　　５２　　　肝斑　　　重　　　有効１ヶ月
Ｎ．Ｙ　　　女　　　４４　　　肝斑　　　重　　　有効２ヶ月
Ｗ．Ｋ　　　女　　　４６　　　肝斑　　　重　　　著効
Ｅ．Ｗ　　　女　　　５５　　　肝斑　　　重　　　有効１ヶ月
Ｇ．Ｓ　　　女　　　５０　　　肝斑　　　重　　　有効２週間
である。これらの患者が治るまでに最短で２週間、最長でも２ヶ月しか要していない。更に表２から明らかのように症状が「中」の患者については殆ど顕著な効果が現れている。
【００２１】
実施例３
次の基本成分からなる服用薬である。
成分　　　　　　　　　１日量
トラネキサム酸　　　　１５００ｍｇ
ビタミンＢ２　　　　　　　６０ｍｇ
ビタミンＢ６　　　　　　　６０ｍｇ
ビタミンＣ　　　　　　　６００ｍｇ
Ｌシステイン　　　　　　２４０ｍｇ
主に肝斑（シミ）の患者に対して、次の処方量１日３回に分けて投与した場合の結果を表４に示す。又この処方により薬剤を投与した患者に副作用はまったく認められなかった。
【００２２】
【表４】
氏名　　性　年齢　程度　効果発現時期　効果（判定時期）　　　備考
Ｓ．Ｏ　女　４７　　中　　　４週間　　　有効（４週間）　　　　継続
Ｍ．Ｋ　女　１９　　軽　　　　不明　　　不明　　　　　　　　　継続
Ｍ．Ｙ　女　４４　　重　　　８週間　　　著効（８週間）　　　　継続
Ｓ．Ｏ　女　５４　　中　　　４週間　　　有効（４週間）　　　　継続
Ｈ．Ｍ　女　４６　　重　　　６週間　　　著効（６週間）　　　　継続
Ｙ．Ｎ　女　４８　　中　　　４週間　　　有効（４週間）　　　　継続
Ｆ　　　女　５５　　中　　　４週間　　　有効（４週間）　　　　継続
Ｋ．Ｗ　女　４８　　中　　　４週間　　　有効（４週間）　　　　継続
Ｋ．Ｓ　女　５５　　重　　　４週間　　　有効（４週間）　　　　継続
Ｋ．Ｉ　女　５３　　中　　　８週間　　やや有効（８週間）　　　継続
Ａ．Ｔ　女　５２　　中　　　４週間　　　有効（４週間）　　　　継続
Ｙ．Ｔ　女　６１　　中　　　４週間　　　著効（４週間）　　　　継続
Ｋ．Ｉ　女　４９　　中　　　４週間　　　有効（４週間）　　　　継続
Ｔ．Ｍ　女　３９　　中　　８〜１２週間　有効（８〜１２週間）　継続
Ｓ．Ｆ　女　５６　　中　　　４週間　　　著効（４週間）　　　　継続
Ｓ．Ｏ　女　５３　　中　　　４週間　　　有効（４週間）　　　　継続
【００２３】
表４から明らかのようにこれらの患者で目に見える効果が始まるまでに最短で４週間、最長でも１２週間しか要していない、更に症状が「中」の患者については殆ど４週間以内に顕著に効果が現れている。
実施例４
次の基本成分からなる内服薬である。
成分　　　　　　　　　１日量
トラネキサム酸　　　　１５００ｍｇ
ビタミンＢ２　　　　　　　６０ｍｇ
ビタミンＢ６　　　　　　　６０ｍｇ
Ｌシステイン　　　　　　２４０ｍｇ
ビタミンＣ　　　　　　　６００ｍｇ
甘草　　　　　　　　　　９００ｍｇ
主に肝斑（シミ）の患者に対して、発明者の医師が患者に処方した例を説明する。
処方量１日３回に分けて服用投与した場合の結果を表５に示す。又この処方により薬剤を投与した患者に副作用はまったく認められなかった。
【００２４】
【表５】
氏名　　性　年齢　程度　　効果発現時期　効果（判定時期）　　備考
Ｔ．Ｍ　女　４６　　中の上　　１週間　　　著効（６週間）　　　継続
Ｋ．Ｙ　女　６７　　中　　　　３週間　　　有効（８週間）　　　継続
Ｋ．Ｍ　女　４７　　中　　　　２週間　　　著効（８週間）　　　継続
Ｏ．Ａ　女　４７　　重　　　　３週間　　　有効（６週間）　　　継続
Ｍ．Ｔ　女　４１　　中　　　　４週間　　　有効（８週間）　　　継続
表５から明らかのようにこれらの患者に有効が見られるまでに最長でも４週間しか要していない、更に症状が「中」の患者については著効が見られるまで殆ど２週間以内に効果が現れている。
【００２５】
実施例５
次の基本成分からなる内服薬である。
成分　　　　　　　　　１日量
トラネキサム酸　　　　１５００ｍｇ
ビタミンＢ２　　　　　　　６０ｍｇ
ビタミンＢ６　　　　　　　６０ｍｇ
Ｌシステイン　　　　　　２４０ｍｇ
ビタミンＣ　　　　　　　６００ｍｇ
チオプロニン　　　　　　３００ｍｇ
主に肝斑（シミ）の患者に対して、発明者の医師が患者に処方した他の例を説明する。
処方量１日３回に分けて服用投与した場合の結果を表６に示す。又この処方により薬剤を投与した患者に副作用はまったく認められなかった。
【００２６】
【表６】
氏名　　性　年齢　程度　　効果発現時期　効果（判定時期）　　備考
Ｆ．Ｙ　女　３９　　中　　　　４週間　　　有効（８週間）　　　継続
Ｋ．Ｙ　女　３５　　中　　　　３週間　　　有効（８週間）　　　継続
Ｎ．Ｍ　女　４９　　中　　　　２週間　　　有効（６週間）　　　継続
Ｍ．Ｍ　女　５４　　軽　　　　３週間　　　著効（６週間）　　　継続
表６から明らかのようにこれらの患者に有効が現れるまでに最長でも４週間しか要していない、更に症状が「軽」の患者については３週間以内に著効効果が現れている。
【００２７】
実施例６
トラネキサム酸、アスコルビピン酸、リボフラビン、塩酸ピリドキシン、Ｌシステイン、乳糖、低置換度ヒドロキシプロピルセルロース及びヒドロキシプロピルセルロースを混合し、７５％エタノールを加えて常法により造粒し、乾燥した後、製粒した。
この粒に結晶セルロース及びステアリン酸マグネシウムを加えて打錠して、９錠中に以下の成分・含量を有する錠剤を得た。
成分　　　　　　　　　　　　　　分量（ｍｇ／９錠）
トラネキサム酸　　　　　　　　　　　　１５００
アスコルビン酸　　　　　　　　　　　　　６００
リボフラビン　　　　　　　　　　　　　　６０
塩酸ピリドキシン　　　　　　　　　　　　６０
Ｌシステイン　　　　　　　　　　　　　　２４０
乳糖　　　　　　　　　　　　　　　　　　８６
低置換度ヒドロキシプロピルセルロース　　２７０
ヒドロキシプロピルセルロース　　　　　　３２
結晶セルロース　　　　　　　　　　　　　３１５
ステアリン酸マグネシウム　　　　　　　　３２
合計　　　　　　　　　　　　　　　　　３１５０（３５０ｍｇ／錠）
【００２８】
実施例７
トラネキサム酸、アスコルビン酸、リボフラビン、塩酸ピリドキシン、Ｌシステイン、精製白糖、コーンスターチ及びヒドロキシプロピルセルロースを混合し、７５％エタノールを加えて常法により造粒し、乾燥した後、整粒、分級して、３包中に以下の成分・含量を有する顆粒剤を得た。
成分　　　　　　　　　　　　　　分量（ｍｇ／３包）
トラネキサム酸　　　　　　　　　　　　１５００
アスコルビン酸　　　　　　　　　　　　　６００
リボフラビン　　　　　　　　　　　　　　６０
塩酸ピリドキシン　　　　　　　　　　　　６０
Ｌシステイン　　　　　　　　　　　　　　２４０
精製白糖　　　　　　　　　　　　　　　１５４５
コーンスターチ　　　　　　　　　　　　　４５０
ヒドロキシプロピルセルロース　　　　　　４５
合計　　　　　　　　　　　　　　　　　４５００（１５００ｍｇ／包）
【００２９】
【発明の効果】
トラネキサム酸とビタミンＣとビタミンＢ２群とＢ６群に加えカンゾウ及び／又はビオチン及び／又はＬシステイン及び／又はグルタチオン及び／又はチオプロニンを併用した場合は、効果が短期間に現れ、肝斑、リール黒皮症又は女子顔面黒皮症又は苔癬様水泡性中毒性黒色皮膚炎又は戦争黒皮症又は代謝障害に伴う色素沈着症又は老人性色素斑（老人のしみ）又は網状肢端色素沈着症又は雀卵斑（そばかす）又は夏目斑又は慢性色素性紫斑又は光線性花弁状色素斑又は光線性白斑黒皮症又は炎症後色素沈着症又は湿疹・皮膚炎後の色素沈着症に対して、より効果的な優れた医薬となった。
また、トラネキサム酸とビタミンＣとビタミンＢ２群とＢ６群に加え、Ｌシステインを併用するか、Ｌシステインと甘草又はＬシステインとチオプロニンを併用した場合は、特に肝斑に対して早期に有効な医薬となった。[0001]
TECHNICAL FIELD OF THE INVENTION
TECHNICAL FIELD The present invention relates to a therapeutic agent for improving pigmentation, and more specifically, for treating melasma (stain) appearing on the human face, melanosis of the skin (female melanosis), sperm egg spot (freckles), and post-inflammatory pigmentation. On the other hand, the present invention relates to an internal medicine (drink) which is administered to a patient by a doctor.
[0002]
[Prior art]
It is known that oral administration of tranexamic acid is effective as a method for treating post-inflammatory pigmentation and melasma, a so-called spot that begins to occur in women who can be pregnant after 30s.
It has been known that a small amount of tranexamic acid is incorporated into cosmetics to effectively prevent and suppress allergic dermatitis and the like (Japanese Patent Publication No. 47-1479).
Japanese Patent No. 2618657 (Japanese Unexamined Patent Publication No. 1-93519) discloses a topical remedy for melasma and the like containing tranexamic acid itself as a main component.
[0003]
It is said to be effective for internal use of tranexamic acid, vitamin C and tathione, and for external use of hydroquinone and kojic acid.
Further, an anti-pigmentation therapeutic drug disclosed in Japanese Patent Application Laid-Open No. 6-80564 by one of the present inventors is known as an internal medicine. The composition of this remedy comprises tranexamic acid, vitamin C, vitamin B2 group, vitamin B6 group or salts thereof, and is particularly effective for treating melasma (stain).
Therefore, it can be understood from these cases that the use of tranexamic acid as a cosmetic for external use or as an anti-pigmentation therapeutic agent for internal use is extremely high in safety and endures long-term use.
[0004]
Melanosis of the reel is induced by foreign and cosmetic substances acting on the skin in predisposed adult girls and is exacerbated by sunlight irradiation. As a treatment method, an ointment containing a corticosteroid or an antihistamine is applied, and a vitamin C or SH preparation is taken.
Speckle spots (freckles) mainly develop around the age of 5 or 6 years, become remarkable during puberty, and gradually become unclear as the age increases. Apply freckle plaster, freckle emulsion, macranin, acetic acid trichloride, etc.
[0005]
[Patent Document 1]
JP-B-47-1479 [Patent Document 2]
Patent No. 2618657 [Patent Document 3]
JP-A-6-80564
[Problems to be solved by the invention]
The anti-pigmentation therapeutic agent described in JP-A-6-80564 was clearly effective for liver spots. Both inventors of the present application, both doctors, are even more effective against melasma and are melanosis dermatosis or melasma acne or female lichenoid vesicular toxic melanosis or war melasma or Pigmentation or senile pigmentation associated with metabolic disorders (stain of the elderly) or reticulata pigmentation or sparrow egg spot (freckles) or summer spots or chronic pigmented purpura or actinic petal pigmented spots or actinic vitiligo There is a need for a therapeutic agent that is also effective against melasma or post-inflammatory pigmentation or pigmentation after eczema / dermatitis. Further, in order to minimize the occurrence of side effects in the human body which differs depending on the constitution, a therapeutic drug having a reduced number of active ingredients has been required.
[0007]
[Means for Solving the Problems]
In the present invention, in addition to tranexamic acid and vitamin C, licorice (licorice), biotin, L-cysteine, glutathione, and thiopronin are selectively used or used in combination. Another invention selectively or jointly uses licorice (licorice), biotin, L-cysteine, glutathione, and thiopronin in addition to tranexamic acid, vitamin C, vitamin B2 group or salts thereof, and vitamin B6 group or salts thereof. Then, melasma or melasma or rosacea melanosis or lichenoid vesicular toxic dermatitis or war melasma or hyperpigmentation associated with metabolic disorders or senile pigment spots (stains of the elderly) or Reticular extremity pigmentation or Sparrow egg spots (freckles) or Natsume spots or chronic pigmented purpura or actinic petal pigmented spots or actinic leukoplakia or pigmentation after inflammation or eczema or dermatitis Therapeutic effect is manifested earlier in the disease, and is extremely high.
Still another invention contains L-cysteine, L-cysteine and licorice, or L-cysteine and thiopronin as active ingredients in addition to tranexamic acid, vitamin C, vitamin B2 group or a salt thereof, vitamin B6 group or a salt thereof. When used as an internal treatment for improving pigmentation, it was found to be extremely effective against melasma (stain).
[0008]
Improved pigmentation for internal use containing L-cysteine, L-cysteine and licorice, or L-cysteine and thiopronin as active ingredients in addition to tranexamic acid, vitamin C, vitamin B2 group or salt thereof, vitamin B6 group or salt thereof Diseases for which the therapeutic drug works effectively include melanosis melanosis, melasma aurisum, lichen-like vesicular toxic black dermatitis, melanosis war, pigmentation associated with metabolic disorders, senile pigments Spots (stains of the elderly), reticulata pigmentation, sparrow egg spots (freckles), summer spots, chronic pigmented purpura, actinic petal pigmented spots, actinic vitiligo melanosis, post-inflammatory pigmentation, eczema・ Pigmentation after dermatitis and liver spots.
[0009]
Examples of the vitamin B2 group or salts thereof include riboflavin, riboflavin phosphate, sodium riboflavin phosphate, riboflavin butyrate, flavin adenine dinucleotide (FAD), and sodium flavin adenine dinucleotide.
Examples of the vitamin B6 group or salts thereof include pyridoxine, pyridoxine hydrochloride, pyridoxine phosphate, pyridoxal, pyridoxal phosphate, pyridoxal calcium phosphate, pyridoxal hydrochloride, pyridoxamine, pyridoxamine dihydrochloride, pyridoxamine phosphate, and the like.
Although the therapeutic effect on liver spots and the like is moderate in time, the use of simple tranexamic acid as the active ingredient has resulted in zero occurrence of side effects in the human body that differ depending on the constitution.
[0010]
BEST MODE FOR CARRYING OUT THE INVENTION
Hereinafter, the present invention will be described. The amount of the pigmentation improving therapeutic agent of the present invention is as follows.
Daily adult dose as free acid or free base, tranexamic acid: 50-3000 mg, vitamin C: 10-3000 mg, vitamin B2 group: 0.5-90 mg, vitamin B6 group: 0.5-200 mg, and licorice (licorice) : 50-2000 mg of daily crude drug, 0.1-10 mg of biotin, 5-400 mg of L-cysteine, 5-500 mg of glutathione, and 10-1000 mg of thiopronin. The amount is used once or in several portions.
Each of these daily doses has been determined by therapeutic experience so that the average Japanese adult can absorb and digest well and maximize therapeutic efficacy.
For example, if the tranexamic acid content is 50 mg or less, the effect is lower, and even if tranexamic acid is administered at 3000 mg or more, there is no further therapeutic effect, and the tranexamic acid is taken without notice.
It is preferable to use licorice (licorice), biotin, L-cysteine, glutathione, and thiopronin in addition to the four components of tranexamic acid, vitamin C, vitamin B2 group, and vitamin B6 group.
Of these, licorice (licorice), L-cysteine and thiopronin are more preferred, and L-cysteine is most preferred.
[0011]
Next, as a dosage form, it is used as an internal preparation such as a tablet, a capsule, a granule, and a liquid. In that case, if necessary, excipients, binders, pharmaceutical additives such as disintegrants, or other active agents can be included.
For excipients, for example, lactose, purified sucrose, light anhydrous silicic acid, microcrystalline cellulose, etc., and for binders, for example, methyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, polybipinyl pyrrolidone, crystalline cellulose Further, as disintegrants, for example, carboxymethylcellulose calcium, carboxymethylcellulose sodium, low-substituted hydroxypropylcellulose, corn starch and the like are used.
Examples of other activators include pantothenic acid or salts thereof, panthenol, biotin, nicotinic acid, nicotinamide, vitamin E group, and the like. By including these together with the above-mentioned active ingredients, the effects of the present invention may be further increased.
[0012]
Example 1
Table 1 shows the results obtained when both the inventor's physicians administer the following prescribed amount three times a day to patients with liver spots (spots) and a few sparrow eggs (freckles). No side effects were observed in patients who received the drug according to this prescription.
Basic prescription (without vitamin B2 and B6)
Single component Single dose Daily dose Tranexamic acid 500mg 1500mg
Vitamin C 200mg 600mg
Licorice (licorice) 300mg 900mg
Biotin 2mg 6mg
L cysteine 20mg 60mg
Glutathione 30mg 90mg
Thiopronin 100mg 300mg
[0013]
[Table 1]
Name Age Age Disease level Effect onset Effect (judgment) Remarks A. M Female 20 Sparrow egg spot Light 6 weeks Effective (7 months) Continued O Female 29 Melasma Medium 2 weeks Effective (3 months) Continued T Female 33 Melasma Medium 2 weeks Unknown (no visit) Continued P female 60 Melasma Medium 4 weeks Effective (3 months) Continued Y Woman 47 Melasma Weight 4 weeks Effective (3 months) Continued H Woman 66 Melasma Effective for 4 weeks (5 months) Continued N Female 52 Melasma Effective for 2 weeks (7 months) Continued G Female 44 Melasma Medium 4 weeks Effective (3 months) Continued R Woman 52 Melasma Medium 4 weeks Effective (5 months) Continued I female 39 Melasma weight 2 weeks Excellent effect (6 months) Continued K Woman 42 Melasma Medium 2 weeks Effective (4 months) Continued T Woman 57 Melasma Medium 2 weeks Effective (3 months) Continued K Woman 31 Melasma Medium 4 weeks Effective (6 months) Continued M Woman 65 Melasma Medium 2 weeks Effective (5 months) Continued J Female 55 Melasma Medium 2 weeks Effective (6 months) Continued I Woman 60 Melasma Weight 4 weeks Effective (4 months) Continued
The treatment effect for melasma etc. is long and takes almost half a year, but when tranexamic acid, vitamin C, licorice, biotin, L-cysteine, glutathione, and thiopronin are the active ingredients, side effects differ depending on the constitution. Occurrence was infinitely zero and was not recognized at all.
[0015]
Example 2
For patients with melasma (spots), few spots of freckles (freckles), melanosis of the reel, and post-inflammatory pigmentation, the results of the following prescribed doses three times a day are given. It is shown in Table 2. No side effects were observed in patients who received the drug according to this prescription.
Basic prescription (with vitamin B2, B6)
Ingredients 1 dose daily dose tranexamic acid 500mg 1500mg
Vitamin C 200mg 600mg
Vitamin B2 (FAD) 10-15mg 30-45mg
Vitamin B6 (pyridoxal phosphate) 20-30mg 60-90mg
Licorice (licorice) 300mg 900mg
Biotin 2mg 6mg
L cysteine 20mg 60mg
Glutathione 30mg 90mg
Thiopronin 100mg 300mg
[0016]
[Table 2]
Name Gender Age Disease level Effect onset Effect (judgment) Remarks K Woman 47 Melasma Medium 4 weeks Effective (2 months) Continued M Female 19 Sparrow egg spot Light 12 weeks Effective (4 months) Continued M female 32 melasma medicated 4 weeks effective (1.5 months) continuous T Female 27 Melasma Medium Unknown Unknown (Visit unknown) Continued T Woman 57 Melasma Medium 4 weeks Effective (2 months) Continued Y Female 52 Melasma Weight 4 weeks Effective (2 months) Continued E Female 58 Melasma Medium 4 weeks Effective (2 months) Continued S Female 57 Melasma Medium 4 weeks Effective (2 months) Continued R Woman 57 Melasma Medium 4 weeks Effective (2 months) Continued M Female 50 Melasma Effective for 4 weeks (2 months) Continued N Female 50 Melasthema Medium 4 weeks Effective (2 months) Continued H Woman 57 Melasma Medium 8 weeks Effective (2 months) Continued Y Female 44 Melasma Weight 8 weeks Effective (2 months) Continued I. K woman 46 Melasma Medium 4 weeks Effective (2 months) Continued R Woman 54 Melasma Medium 4 weeks Effective (2 months) W. K woman 46 Melasma weight 4 weeks Excellent effect (2 months) Continued K Woman 48 Melasma Medium 4 weeks Effective (2 months) Continued K Woman 55 Melasma Medium 4 weeks Effective (2 months) Continued H Woman 61 Melasma Medium 4 weeks Unknown (2 months) Continued K Woman 48 Melasma Medium 4 weeks Effective (2 months) Continued K Female 70 Melasma Medium 4 weeks Effective (2 months) Continued J Female 59 Melasma Medium 4 weeks Effective (2 months) Continued Y Female 51 Melasma Active for 4 weeks (2 months) Continued W Female 55 Melasma Weight 4 weeks Effective (2 months) Continued A Woman 52 Reel Blackscale Medium 4 weeks Valid (2 months) Continued Y Female 61 Melasma Medium 4 weeks Effective (2 months) Continued M Woman 64 reel black scale Medium 4 weeks Valid (2 months) Continued M Woman 45 Melasma Effective for 4 weeks Medium (2 months) Continued C Female 39 During pigmentation after inflammation 8 to 12 weeks Excellent effect (2 months) Continued S Female 50 Melasma Weight 2 weeks Effective (2 months) Continued S Female 56 Melasma Medium 4 weeks Excellent effect (2 months) Continued S Female 53 Melasma Medium 4 weeks Effective (2 months) Continued Y Woman 49 Melasma Medium 4 weeks Excellent effect (2 months) Continued
In Tables 1 and 2, "Degree" indicates the degree of pigmentation of the melasma or freckle of the patient before treatment, and "Heavy" indicates pigmentation that cannot be hidden even with heavy makeup.
“Medium” is pigmentation that can be hidden with heavy makeup but cannot be hidden with ordinary makeup, and “Light” is pigmentation that can be hidden with normal makeup but cannot be hidden with light makeup.
"Effective" means that pigmentation is "heavy" → "medium", "heavy" → "light", "heavy" → disappearance or "medium" → "light", "medium" → disappearance or "light" → disappearance And so on, respectively.
[0018]
For comparison, Table 3 shows the effect of JP-A-6-80564 by one of the present inventors.
The final effect determination in Table 3 was performed by one of the applicants after the end of the administration period.
[Table 3]

[0019]
G-4 in Table 3 corresponds to “heavy” in Table 2, and is pigmentation that cannot be hidden even with heavy makeup. Similarly, G-3 is equivalent to "medium" and can be hidden with heavy makeup, but cannot be hidden with ordinary makeup. Similarly, G-2 is "light" and can be hidden with normal makeup, but cannot be hidden with light makeup. Pigmentation.
By the way, in Table 3, in the patients whose symptoms are "severe",

It is. It takes 10 to 32 weeks, or 2.5 to 7.5 months, for these patients to heal.
[0020]
On the other hand, in Example 2 of the present application, the patient whose symptoms are "severe"
S. Y Female 52 Melasma Weight Effective 1 month N. Y Female 44 Melasma Weight Effectiveness 2 months W. K woman 46 Liver spots severely effective W Woman 55 Melasma Weight Effective 1 month G. S Female 50 Melasma Weight Effective 2 weeks. It takes at least two weeks and at most two months for these patients to heal. Furthermore, as is apparent from Table 2, almost remarkable effects are exhibited in patients with "medium" symptoms.
[0021]
Example 3
It is a medicine consisting of the following basic components.
Ingredients Daily dose tranexamic acid 1500mg
Vitamin B2 60mg
Vitamin B6 60mg
Vitamin C 600mg
L cysteine 240mg
Table 4 shows the results when the following prescribed amount was mainly administered to patients with melasma (spots) three times a day. No side effects were observed in patients who received the drug according to this prescription.
[0022]
[Table 4]
Name Sex Age Degree Effect onset Effect (judgment) Remarks O Female 47 out of 47 valid for 4 weeks (4 weeks) Continued K Woman 19 Minor Unknown Unknown Continued Y Female 44 Weight 8 Weeks Effective (8 weeks) Continued O Female 54 out of 54 Effective for 4 weeks (4 weeks) Continued M woman 46 weight 6 weeks Remarkably effective (6 weeks) Continued Valid for 4 weeks out of 48 N women (4 weeks) Continued Valid for 4 weeks out of 55 F women (4 weeks) Continued Valid for 4 weeks out of 48 W women (4 weeks) Continued S woman 55 weight 4 weeks Effective (4 weeks) Continue K. 8 weeks out of 53 females Effective slightly (8 weeks) Continued Valid for 4 weeks out of 52 T women (4 weeks) Continued Y. T woman 61 out of 4 weeks Excellent effect (4 weeks) Continued Valid for 4 weeks out of 49 women (4 weeks) Valid for 8 to 12 weeks (8 to 12 weeks) out of 39 M women 4 weeks out of 56 females Effective significantly (4 weeks) Continued O Female 53 out of 4 valid for 4 weeks (4 weeks) Continued [0023]
As is evident from Table 4, these patients require a minimum of 4 weeks and a maximum of 12 weeks for the visible effect to begin, and are more pronounced within 4 weeks for patients with "medium" symptoms The effect has appeared.
Example 4
It is an oral medicine consisting of the following basic components.
Ingredients Daily dose tranexamic acid 1500mg
Vitamin B2 60mg
Vitamin B6 60mg
L cysteine 240mg
Vitamin C 600mg
Licorice 900mg
An example in which a doctor of the inventor prescribes a patient mainly for a melasma (stain) will be described.
Table 5 shows the results when the prescribed dose was administered three times a day. No side effects were observed in patients who received the drug according to this prescription.
[0024]
[Table 5]
Name Sex Age About Effect onset Effect (judgment) Remarks 1 week in M woman 46 Excellent (6 weeks) Continued Valid for 3 weeks out of 67 women (8 weeks) 2 weeks out of 47 females Effective significantly (8 weeks) Continued A woman 47 weight 3 weeks Effective (6 weeks) Continued T women 41 out of 4 weeks effective (8 weeks) As is clear from continuation table 5, it takes only 4 weeks at most for these patients to be effective. The effect appears almost within two weeks until the effect is seen.
[0025]
Example 5
It is an oral medicine consisting of the following basic components.
Ingredients Daily dose tranexamic acid 1500mg
Vitamin B2 60mg
Vitamin B6 60mg
L cysteine 240mg
Vitamin C 600mg
Thiopronin 300mg
Another example mainly prescribed by a doctor of the inventor for a patient with melasma (stain) will be described.
Table 6 shows the results in the case where the prescribed amount was administered three times a day. No side effects were observed in patients who received the drug according to this prescription.
[0026]
[Table 6]
Name Name Age Level Effect onset Effect (judgment) Remarks Valid for 4 weeks out of 39 Y women (8 weeks) Continued Valid for 3 weeks out of 35 Y women (8 weeks) Continued Valid for 2 weeks out of 49 women (6 weeks) M Woman 54 Minor 3 weeks Excellent effect (6 weeks) As is clear from continuation table 6, it takes only up to 4 weeks for the effect to appear in these patients. Significant effects appear within a week.
[0027]
Example 6
Tranexamic acid, ascorbicin acid, riboflavin, pyridoxine hydrochloride, L-cysteine, lactose, low-substituted hydroxypropylcellulose and hydroxypropylcellulose were mixed, added with 75% ethanol, granulated by a conventional method, dried, and granulated. .
The granules were added with crystalline cellulose and magnesium stearate and tableted to obtain tablets having the following components and contents in 9 tablets.
Ingredient quantity (mg / 9 tablets)
Tranexamic acid 1500
Ascorbic acid 600
Riboflavin 60
Pyridoxine hydrochloride 60
L cysteine 240
Lactose 86
Low substituted hydroxypropylcellulose 270
Hydroxypropyl cellulose 32
Microcrystalline cellulose 315
Magnesium stearate 32
Total 3150 (350mg / tablet)
[0028]
Example 7
Mix tranexamic acid, ascorbic acid, riboflavin, pyridoxine hydrochloride, L-cysteine, purified sucrose, corn starch and hydroxypropylcellulose, add 75% ethanol, granulate by a conventional method, dry, then granulate and classify. Granules having the following components and contents in three packets were obtained.
Ingredient quantity (mg / 3 packets)
Tranexamic acid 1500
Ascorbic acid 600
Riboflavin 60
Pyridoxine hydrochloride 60
L cysteine 240
Purified white sugar 1545
Cornstarch 450
Hydroxypropyl cellulose 45
Total 4500 (1500mg / package)
[0029]
【The invention's effect】
When tranexamic acid, vitamin C, vitamins B2 and B6 and licorice and / or biotin and / or L-cysteine and / or glutathione and / or thiopronin are used in combination, the effect appears in a short time, Dermatosis or melasma acne or lichenoid bullous toxic dermatitis or war melasma or hyperpigmentation associated with metabolic disorders or senile pigment spots (stains of the elderly) or reticulopigmenta It is more effective against freckles or summer spots or chronic pigmented purpura or actinic petal pigmented spots or actinic melanosis or post-inflammatory pigmentation or pigmentation after eczema or dermatitis. Became an excellent medicine.
In addition, in addition to tranexamic acid, vitamin C, and vitamins B2 and B6, if L-cysteine is used in combination or L-cysteine and licorice or L-cysteine and thiopronin are used in combination, a medicament that is effective at an early stage especially for melasma It became.

Claims

As an active ingredient, tranexamic acid and licorice (licorice) or biotin or one of L-cysteine or glutathione or thiopronin, as active ingredients, melasma dermatosis or melasmae algae or lichenoid vesicular toxic black dermatitis or war Pigmentation or senile pigmentation associated with melasma or metabolic disorder (stain of the elderly) or reticulum pigmentosa or sphagnum (freckles) or summer spots or chronic pigmented purple spots or light petal pigmented spots Or an internal pigmentation-improving therapeutic agent for one of photomyeloma leukoderma or post-inflammatory pigmentation or eczema / dermatitis-induced pigmentation or melasma (spot).

Tranexamic acid, vitamin C, liquorice (licorice), biotin, L-cysteine, glutathione, or one of thiopronin as active ingredients, as an active ingredient of melasma scleroderma or melasmae albicans or lichenoid vesicular toxic black Pigmentation associated with dermatitis or war melasma or metabolic disorder or senile pigment spot (stain of the elderly) or reticulum pigmentosa or sponge spot (freckles) or Natsume spot or chronic pigmented purpura or actinic rays An internal pigmentation-improving therapeutic agent for one of petal-like pigment spots or actinic leukoderma or post-inflammatory pigmentation or eczema or dermatitis pigmentation or liver spots.

As an active ingredient, tranexamic acid, vitamin C, vitamin B2 group or a salt thereof, and licorice (licorice) or biotin or L cysteine or glutathione or thiopronin as active ingredients, reel melanosis or female melanosis. Or lichenoid bullous toxic black dermatitis or hyperpigmentation associated with melanosis or metabolic disorder or senile pigmentation (stain of the aged) or reticulosa pigmentosa or sphagnum (freckles) or Natsume For internal use on one of the following: spots or chronic pigmented purpura or actinic petal pigmented spots or actinic leukoderma or post-inflammatory pigmentation or eczema or dermatitis pigmentation or liver spots A pigmentation improving therapeutic drug.

As an active ingredient of tranexamic acid, vitamin C, vitamin B2 group or salts thereof, licorice (licorice), and biotin or L-cysteine or glutathione or thiopronin as active ingredients, reel melasma or female black skin Or lichenoid vesicular toxic melanosis or war melasma or hyperpigmentation associated with metabolic disorders or senile pigment spots (stains of the elderly) or reticulata pigmentosa or sperm spots (freckles) or Internal use for one of summer spots, chronic pigmented purpura or actinic petal pigmented spots or actinic melanosis or melanosis after inflammation or pigmentation after inflammation or eczema or dermatitis Therapeutic agent for improving pigmentation.

Tranexamic acid, vitamin C, vitamin B2 group or salts thereof, biotin, and one of L-cysteine or glutathione or thiopronin as active ingredients, for example, melasma striata or melasmae auris or lichenoid Hydrophobic toxic black dermatitis or hyperpigmentation associated with melasma war or metabolic disorder or senile pigment spots (stains of the elderly) or reticulum pigmentosa or sphagnum spots (freckles) or summer spots or chronic pigments Pigmentation improvement treatment for one of the following: Purpura or actinic petal pigment spot or actinic melasma or post-inflammatory pigmentation or pigmentation after eczema or dermatitis or liver spot (spot) medicine.

Tranexamic acid, vitamin C, vitamin B2 group or salts thereof, L-cysteine, and one of glutathione or thiopronin as active ingredients, which are used as melanosis scleroderma or melasmae albicans or lichenoid vesicles Toxic dermatitis or hyperthermia associated with melasma or metabolic disorder or senile pigmentation (stain of the elderly) or reticulum pigmentosa or sphagnum (freckles) or summer spots or chronic pigmented purpura Or an internal pigmentation-improving remedy for one of light petal pigment spots or actinic melasma or post-inflammatory pigmentation or eczema or dermatitis pigmentation or liver spots.

Tranexamic acid, vitamin C, vitamin B2 group or salts thereof, glutathione, and thiopronin as active ingredients, which are used as active ingredients for melasma dermatosis or melasmae algae or rosacea-like vesicular toxic black dermatitis or Hyperpigmentation associated with melanosis or metabolic disorders or senile pigment spots (stains of the elderly) or reticulum pigmentosa or sphagnum spots (freckles) or summer spots or chronic pigmented purpura or light petal pigments An internal pigmentation-improving therapeutic agent for one of the following: macula or actinic leukoderma or post-inflammatory pigmentation or eczema / dermatitis-induced pigmentation or melasma (spot).

As an active ingredient, tranexamic acid, vitamin C, vitamin B2 group or a salt thereof, licorice (licorice), biotin, and one of L-cysteine or glutathione or thiopronin, as active ingredients of melasma striata or female face Melasma or lichenoid vesicular toxic melanosis or war pigmentation associated with melasma or metabolic disorders or senile pigment spots (stains of the elderly) or reticulum pigmentosa or sperm spots (freckles) ) Or for one of the following: Natsume or chronic pigmented purpura or actinic petal pigmentation or actinic melanosis or post-inflammatory pigmentation or pigmentation after eczema or dermatitis or liver spots Pigmentation treatment for internal use.

Tranexamic acid, vitamin C, vitamin B2 group or salts thereof, licorice (licorice), biotin, L-cysteine, and one of glutathione or thiopronin as active ingredients, and Melanosis facial or lichenoid vesicular toxic dermatitis or hyperpigmentation associated with melanosis or metabolic disorders or senile pigmentation (stain of the elderly) or reticulopigmentosis or egg spot ( Freckles) or Natsume or chronic pigmented purpura or actinic petal pigmentation or actinic melanosis or pigmentation after inflammation or pigmentation after eczema or dermatitis or one of the liver spots Pigmentation-improving remedies for internal use.

As an active ingredient of tranexamic acid, vitamin C, vitamin B2 group or salts thereof, licorice (licorice), biotin, L-cysteine, glutathione, and thiopronin as active ingredients, melanoderma hirsuta or female blackhead skin Or lichenoid vesicular toxic melanosis or war melasma or hyperpigmentation associated with metabolic disorders or senile pigment spots (stains of the elderly) or reticulata pigmentosa or sperm spots (freckles) or Internal use for one of summer spots, chronic pigmented purpura or actinic petal pigmented spots or actinic melanosis or melanosis after inflammation or pigmentation after inflammation or eczema or dermatitis Therapeutic agent for improving pigmentation.

As an active ingredient, tranexamic acid, vitamin C, vitamin B6 group or a salt thereof, and licorice (licorice) or biotin or L cysteine or glutathione or thiopronin, as active ingredients, reel melasma or melanosis melanosis. Or lichenoid bullous toxic black dermatitis or hyperpigmentation associated with melanosis or metabolic disorder or senile pigmentation (stain of the aged) or reticulosa pigmentosa or sphagnum (freckles) or Natsume For internal use on one of the following: spots or chronic pigmented purpura or actinic petal pigmented spots or actinic leukoderma or post-inflammatory pigmentation or eczema or dermatitis pigmentation or liver spots A pigmentation improving therapeutic drug.

As an active ingredient, tranexamic acid, vitamin C, vitamin B6 group or salts thereof, licorice (licorice), and one of biotin or L-cysteine or glutathione or thiopronin, as an active ingredient, reel melasma or female blackskin Or lichenoid vesicular toxic melanosis or war melasma or hyperpigmentation associated with metabolic disorders or senile pigment spots (stains of the elderly) or reticulata pigmentosa or sperm spots (freckles) or Internal use for one of summer spots, chronic pigmented purpura or actinic petal pigmented spots or actinic melanosis or melanosis after inflammation or pigmentation after inflammation or eczema or dermatitis Therapeutic agent for improving pigmentation.

Tranexamic acid, vitamin C, vitamin B6 group or salts thereof, biotin, and one of L-cysteine or glutathione or thiopronin as active ingredients, using as active ingredients such as dermatitis melicaris or melasmae auris or lichenoid Hydrophobic toxic black dermatitis or hyperpigmentation associated with melanosis or metabolic disorders or senile pigment spots (stains of the elderly) or reticulum pigmentosa or sphagnum spots (freckles) or summer spots or chronic pigments Pigmentation improvement treatment for internal purpura or actinic petal-like pigment spots or actinic leukoderma or melanosis after inflammation or pigmentation after eczema or dermatitis or liver spot (spot) medicine.

Tranexamic acid, Vitamin C, Vitamin B6 group or salts thereof, L-cysteine, and one of glutathione or thiopronin as active ingredients, using as an active ingredient melasma scleroderma or melasmae albicans or lichenoid vesicles Toxic dermatitis or hyperthermia associated with melasma or metabolic disorder or senile pigmentation (stain of the elderly) or reticulum pigmentosa or sphagnum (freckles) or summer spots or chronic pigmented purpura Or an internal pigmentation-improving remedy for one of light petal pigment spots or actinic melasma or post-inflammatory pigmentation or eczema or dermatitis pigmentation or liver spots.

Tranexamic acid, vitamin C, vitamin B6 group or salts thereof, glutathione, and thiopronin as active ingredients, and as a melanosis of the lire or melanosis of the female face or lichen-like vesicular toxic black dermatitis or Hyperpigmentation associated with melanosis or metabolic disorders or senile pigment spots (stains of the elderly) or reticulum pigmentosa or sphagnum spots (freckles) or summer spots or chronic pigmented purpura or light petal pigments An internal pigmentation-improving therapeutic agent for one of the following: macula or actinic leukoderma or post-inflammatory pigmentation or eczema / dermatitis-induced pigmentation or melasma (spot).

As an active ingredient, tranexamic acid, vitamin C, vitamin B6 group or salts thereof, licorice (licorice), biotin, and one of L-cysteine or glutathione or thiopronin, as an active ingredient, reel melasma or black on female face Dermatosis or lichenoid vesicular toxic dermatitis or war melasma or hyperpigmentation associated with metabolic disorders or senile pigmentation (stain of the elderly) or reticulosa pigmentosa or sphagnum (freckles) Or for one of the following: Natsume spot, chronic pigmented purpura or actinic petal pigment spot or actinic melanosis or pigmentation after inflammation or pigmentation after eczema or dermatitis or liver spot (spot) Pigmentation-improving therapeutic agent.

Reel melasma or female face using tranexamic acid, vitamin C, vitamin B6 group or salts thereof, licorice (licorice), biotin, L cysteine, and one of glutathione or thiopronin as active ingredients Melasma or lichenoid vesicular toxic melanosis or war pigmentation associated with melasma or metabolic disorders or senile pigment spots (stains of the elderly) or reticulum pigmentosa or sperm spots (freckles) ) Or for one of the following: Natsume or chronic pigmented purpura or actinic petal pigmentation or actinic melanosis or post-inflammatory pigmentation or pigmentation after eczema or dermatitis or liver spots Pigmentation treatment for internal use.

As an active ingredient, tranexamic acid, vitamin C, vitamin B6 group or salts thereof, licorice (licorice), biotin, L-cysteine, glutathione, and thiopronin, as active ingredients of melasma striata or melanogaster Or lichenoid vesicular toxic melanosis or war melasma or hyperpigmentation associated with metabolic disorders or senile pigment spots (stains of the elderly) or reticulata pigmentosa or sperm spots (freckles) or Internal use for one of summer spots, chronic pigmented purpura or actinic petal pigmented spots or actinic melanosis or melanosis after inflammation or pigmentation after inflammation or eczema or dermatitis Therapeutic agent for improving pigmentation.

Using, as active ingredients, tranexamic acid, vitamin C, a vitamin B2 group or a salt thereof, a vitamin B6 group or a salt thereof, and licorice (licorice) or biotin or L cysteine or glutathione or thiopronin as an active ingredient; Melasma or female melanosis or lichenoid vesicular toxic dermatitis or war melasma or hyperpigmentation associated with metabolic disorders or senile pigment spots (stains of the elderly) or reticulosa pigmentosa Or freckles or freckles or summer spots or chronic pigmented purpura or actinic petal pigments or actinic leukoderma or post-inflammatory pigmentation or eczema or pigmentation after dermatitis or spots (spots) A) an internal pigmentation-improving therapeutic agent for one of the above.

Tranexamic acid, vitamin C, vitamin B2 group or a salt thereof, vitamin B6 group or a salt thereof, licorice (licorice), and one of biotin or L-cysteine or glutathione or thiopronin as active ingredients Melasma leuria or melasma acari alba acini or lichenoid vesicular toxic black dermatitis or war melasma or hyperpigmentation associated with metabolic disorders or senile pigment spots (stains of old people) or reticulum pigment Deposition disease or sparrow egg spot (freckles) or Natsume spot or chronic pigmented purpura or actinic petal pigmentation or actinic leukoderma or post-inflammatory pigmentation or eczema or pigmentation after eczema or dermatitis An internal pigmentation improving drug for one of (stain).

Tranexamic acid, vitamin C, vitamin B2 group or salts thereof, vitamin B6 group or salts thereof, biotin, and one of L-cysteine or glutathione or thiopronin as active ingredients; Female melanosis or lichenoid vesicular toxic melanosis or war pigmentation or hyperpigmentation associated with metabolic disorder or senile pigmentation (stain of the elderly) or reticulosa pigmentosa or sphagnum (Freckles) or Natsume or chronic pigmented purpura or actinic petal-like pigmentation or actinic melanosis or post-inflammatory pigmentation or pigmentation after eczema or dermatitis or one of the liver spots Internal pigmentation-improving remedy for one.

Tranexamic acid, vitamin C, vitamin B2 group or salts thereof, vitamin B6 group or salts thereof, L-cysteine, and one of glutathione or thiopronin as active ingredients, for example, melanosis melanoderma or female Melanosis facial or lichenoid vesicular toxic dermatitis or hyperpigmentation associated with melanosis or metabolic disorders or senile pigmentation (stain of the elderly) or reticulopigmentosis or egg spot ( Freckles) or Natsume or chronic pigmented purpura or actinic petal pigmentation or actinic melanosis or pigmentation after inflammation or pigmentation after eczema or dermatitis or one of the liver spots Pigmentation-improving remedies for internal use.

As an active ingredient, tranexamic acid, vitamin C, vitamin B2 group or their salts, vitamin B6 group or their salts, glutathione, and thiopronin as active ingredients, Rier melasma or female melanosis or lichen Toxoid toxic black dermatitis or hyperpigmentation associated with melanosis or metabolic disorder or senile pigmentation (stain of the elderly) or reticulum pigmentosa or reticulum freckles or summer spots or chronic Improvement of internal pigmentation for one of pigmented purpura or actinic petal pigmentation or actinic melasma or post-inflammatory pigmentation or eczema or dermatitis pigmentation or liver spot (spot) Therapeutic drugs.

Tranexamic acid, vitamin C, vitamin B2 group or salts thereof, vitamin B6 group or salts thereof, licorice (licorice), biotin, and one of L-cysteine or glutathione or thiopronin as active ingredients Melasma leuria or melasma acari alba acini or lichenoid vesicular toxic black dermatitis or war melasma or hyperpigmentation associated with metabolic disorders or senile pigment spots (stains of old people) or reticulum pigments Deposition disease or sparrow egg spot (freckles) or Natsume spot or chronic pigmented purpura or actinic petal pigmentation or actinic leukoderma or post-inflammatory pigmentation or eczema or pigmentation after eczema or dermatitis An internal pigmentation improving drug for one of (stain).

Tranexamic acid, vitamin C, vitamin B2 group or their salts, vitamin B6 group or their salts, licorice (licorice), biotin, L-cysteine, and one of glutathione or thiopronin as active ingredients As dermatosis or female melanosis or lichenoid bullous toxic dermatosis or war melasma or hyperpigmentation associated with metabolic disorders or senile pigment spots (stains of the elderly) or reticulate limbs Hyperpigmentation or Sparrow egg spot (freckles) or Natsume spot or chronic pigmented purpura or actinic petal-like pigmentation or actinic leukoderma or post-inflammatory pigmentation or pigmentation after eczema or dermatitis or liver An internal pigmentation remedy for one of the spots.

Tranexamic acid, vitamin C, vitamin B2 group or their salts, vitamin B6 group or their salts, licorice (licorice), biotin, L cysteine, glutathione, and thiopronin as active ingredients Melasma leesorrhea or female melasma or lichenoid vesicular toxic melanosis or war melasma or hyperpigmentation associated with metabolic disorders or senile pigmentation (stain of the elderly) or reticular pigmentation Disease or sparrow egg spots (freckles) or summer spots or chronic pigmented purpura or actinic petal-like pigmentation or actinic leukoplakia or melanosis after inflammation or pigmentation after eczema or dermatitis or liver spots ( Internal use pigmentation-improving therapeutic agent for one of the following:

An internal pigmentation-improving therapeutic agent containing tranexamic acid, vitamin C, vitamin B2 group or a salt thereof, vitamin B6 group or a salt thereof, and L-cysteine as active ingredients.

An agent for treating melasma (stain) for oral use, comprising tranexamic acid, vitamin C, vitamin B2 group or a salt thereof, vitamin B6 group or a salt thereof, and L-cysteine as active ingredients.

A pigmentation-improving therapeutic agent for internal use, comprising tranexamic acid, vitamin C, vitamin B2 group or a salt thereof, vitamin B6 group or a salt thereof, L-cysteine, and licorice as active ingredients.

An internal pigmentation-improving therapeutic agent containing tranexamic acid, vitamin C, vitamin B2 group or a salt thereof, vitamin B6 group or a salt thereof, L-cysteine, and thiopronin as active ingredients.