JP2004091473A - Therapeutic agent for improving chromatosis - Google Patents
Therapeutic agent for improving chromatosis Download PDFInfo
- Publication number
- JP2004091473A JP2004091473A JP2003189581A JP2003189581A JP2004091473A JP 2004091473 A JP2004091473 A JP 2004091473A JP 2003189581 A JP2003189581 A JP 2003189581A JP 2003189581 A JP2003189581 A JP 2003189581A JP 2004091473 A JP2004091473 A JP 2004091473A
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- Prior art keywords
- pigmentation
- vitamin
- spots
- melasma
- melanosis
- Prior art date
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
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Abstract
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 (30)
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
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JP2003189581A JP4786127B2 (en) | 2002-07-12 | 2003-07-01 | Antipigmentation treatment |
AU2003281179A AU2003281179A1 (en) | 2002-07-12 | 2003-07-10 | Remedies for pigmentation |
PCT/JP2003/008764 WO2004006908A1 (en) | 2002-07-12 | 2003-07-10 | Remedies for pigmentation |
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JP2002204431 | 2002-07-12 | ||
JP2002204431 | 2002-07-12 | ||
JP2003189581A JP4786127B2 (en) | 2002-07-12 | 2003-07-01 | Antipigmentation treatment |
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JP2004091473A true JP2004091473A (en) | 2004-03-25 |
JP4786127B2 JP4786127B2 (en) | 2011-10-05 |
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JP2003189581A Expired - Lifetime JP4786127B2 (en) | 2002-07-12 | 2003-07-01 | Antipigmentation treatment |
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AU (1) | AU2003281179A1 (en) |
WO (1) | WO2004006908A1 (en) |
Cited By (8)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2005314403A (en) * | 2004-03-31 | 2005-11-10 | Dai Ichi Seiyaku Co Ltd | Novel bleach composition |
WO2006003965A1 (en) * | 2004-06-30 | 2006-01-12 | Daiichi Sankyo Healthcare Co., Ltd. | Skin-whitening compositions |
JPWO2004060364A1 (en) * | 2002-12-27 | 2006-05-11 | 第一製薬株式会社 | Whitening composition |
WO2007029345A1 (en) * | 2005-09-01 | 2007-03-15 | Kobayashi Pharmaceutical Co., Ltd. | Tyrosinase activity inhibitor |
WO2010016509A1 (en) * | 2008-08-06 | 2010-02-11 | 第一三共ヘルスケア株式会社 | Stable pharmaceutical composition containing tranexamic acid and ascorbic acid |
WO2010027010A1 (en) * | 2008-09-05 | 2010-03-11 | 第一三共ヘルスケア株式会社 | Pharmaceutical solid preparation having active ingredients separated by boundary therein |
JP2011219402A (en) * | 2010-04-08 | 2011-11-04 | Pola Chemical Industries Inc | Pomc production inhibitor |
JP2014215286A (en) * | 2013-04-30 | 2014-11-17 | 株式会社シャネル化粧品技術開発研究所 | Screening method of candidate compound for controlling melanin formation or pigmentation |
Families Citing this family (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20050048012A1 (en) * | 2003-08-26 | 2005-03-03 | Roland Jermann | Use of biotin or a biotin derivative for skin lightening purposes and for the treatment of senile lentigines |
JP2007063223A (en) * | 2005-09-01 | 2007-03-15 | Kobayashi Pharmaceut Co Ltd | Oral composition and food for prevention or treatment of spot or freckle |
Citations (4)
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JPS56154409A (en) * | 1980-04-30 | 1981-11-30 | Pola Chem Ind Inc | Skin-bleaching cosmetic |
JPH04243825A (en) * | 1991-01-25 | 1992-08-31 | Ss Pharmaceut Co Ltd | Remedy for pigmentation |
JPH0680564A (en) * | 1992-09-03 | 1994-03-22 | Meiji Seika Kaisha Ltd | Anti-pigmentation agent |
JP2002193796A (en) * | 2000-12-27 | 2002-07-10 | Ajinomoto Co Inc | Inhibitor to activation of inflammatory factor, usage thereof and new polysulfide derivative usable for the same |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
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JPH1192326A (en) * | 1997-09-22 | 1999-04-06 | Shiseido Co Ltd | Skin preparation for external use |
JP4115656B2 (en) * | 2000-10-11 | 2008-07-09 | 株式会社坂本バイオ | Melanin production inhibitor and whitening agent comprising ergosterol derivative |
-
2003
- 2003-07-01 JP JP2003189581A patent/JP4786127B2/en not_active Expired - Lifetime
- 2003-07-10 WO PCT/JP2003/008764 patent/WO2004006908A1/en active Application Filing
- 2003-07-10 AU AU2003281179A patent/AU2003281179A1/en not_active Abandoned
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS56154409A (en) * | 1980-04-30 | 1981-11-30 | Pola Chem Ind Inc | Skin-bleaching cosmetic |
JPH04243825A (en) * | 1991-01-25 | 1992-08-31 | Ss Pharmaceut Co Ltd | Remedy for pigmentation |
JPH0680564A (en) * | 1992-09-03 | 1994-03-22 | Meiji Seika Kaisha Ltd | Anti-pigmentation agent |
JP2002193796A (en) * | 2000-12-27 | 2002-07-10 | Ajinomoto Co Inc | Inhibitor to activation of inflammatory factor, usage thereof and new polysulfide derivative usable for the same |
Cited By (13)
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JP4667875B2 (en) * | 2002-12-27 | 2011-04-13 | 第一三共ヘルスケア株式会社 | Whitening composition |
JPWO2004060364A1 (en) * | 2002-12-27 | 2006-05-11 | 第一製薬株式会社 | Whitening composition |
JP2005314403A (en) * | 2004-03-31 | 2005-11-10 | Dai Ichi Seiyaku Co Ltd | Novel bleach composition |
WO2006003965A1 (en) * | 2004-06-30 | 2006-01-12 | Daiichi Sankyo Healthcare Co., Ltd. | Skin-whitening compositions |
JPWO2006003965A1 (en) * | 2004-06-30 | 2008-04-17 | 第一三共ヘルスケア株式会社 | Whitening composition |
WO2007029345A1 (en) * | 2005-09-01 | 2007-03-15 | Kobayashi Pharmaceutical Co., Ltd. | Tyrosinase activity inhibitor |
JP5517938B2 (en) * | 2008-08-06 | 2014-06-11 | 第一三共ヘルスケア株式会社 | Stable tranexamic acid and ascorbic acid-containing pharmaceutical composition |
WO2010016509A1 (en) * | 2008-08-06 | 2010-02-11 | 第一三共ヘルスケア株式会社 | Stable pharmaceutical composition containing tranexamic acid and ascorbic acid |
KR101602000B1 (en) | 2008-08-06 | 2016-03-17 | 다이이찌 산쿄 헬스케어 가부시키가이샤 | Stable pharmaceutical composition containing tranexamic acid and ascorbic acid |
WO2010027010A1 (en) * | 2008-09-05 | 2010-03-11 | 第一三共ヘルスケア株式会社 | Pharmaceutical solid preparation having active ingredients separated by boundary therein |
JP5579066B2 (en) * | 2008-09-05 | 2014-08-27 | 第一三共ヘルスケア株式会社 | Pharmaceutical solid preparation with active ingredient having boundary |
JP2011219402A (en) * | 2010-04-08 | 2011-11-04 | Pola Chemical Industries Inc | Pomc production inhibitor |
JP2014215286A (en) * | 2013-04-30 | 2014-11-17 | 株式会社シャネル化粧品技術開発研究所 | Screening method of candidate compound for controlling melanin formation or pigmentation |
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WO2004006908A1 (en) | 2004-01-22 |
JP4786127B2 (en) | 2011-10-05 |
AU2003281179A1 (en) | 2004-02-02 |
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