JPS638311A - Drug capable of inhibiting melanization for external use - Google Patents
Drug capable of inhibiting melanization for external useInfo
- Publication number
- JPS638311A JPS638311A JP15201886A JP15201886A JPS638311A JP S638311 A JPS638311 A JP S638311A JP 15201886 A JP15201886 A JP 15201886A JP 15201886 A JP15201886 A JP 15201886A JP S638311 A JPS638311 A JP S638311A
- Authority
- JP
- Japan
- Prior art keywords
- kojic acid
- cyclodextrin
- external
- drug
- external use
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000003814 drug Substances 0.000 title claims abstract description 18
- 229940079593 drug Drugs 0.000 title claims abstract description 17
- 230000002401 inhibitory effect Effects 0.000 title claims abstract description 8
- BEJNERDRQOWKJM-UHFFFAOYSA-N kojic acid Chemical compound OCC1=CC(=O)C(O)=CO1 BEJNERDRQOWKJM-UHFFFAOYSA-N 0.000 claims abstract description 47
- 229960004705 kojic acid Drugs 0.000 claims abstract description 44
- WZNJWVWKTVETCG-UHFFFAOYSA-N kojic acid Natural products OC(=O)C(N)CN1C=CC(=O)C(O)=C1 WZNJWVWKTVETCG-UHFFFAOYSA-N 0.000 claims abstract description 44
- 229920000858 Cyclodextrin Polymers 0.000 claims abstract description 29
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000000203 mixture Substances 0.000 claims abstract description 7
- 230000008099 melanin synthesis Effects 0.000 claims description 11
- 230000000699 topical effect Effects 0.000 claims description 9
- 208000012641 Pigmentation disease Diseases 0.000 abstract description 11
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 abstract description 8
- 239000001116 FEMA 4028 Substances 0.000 abstract description 6
- 235000011175 beta-cyclodextrine Nutrition 0.000 abstract description 6
- 229960004853 betadex Drugs 0.000 abstract description 6
- 206010008570 Chloasma Diseases 0.000 abstract description 3
- 208000003351 Melanosis Diseases 0.000 abstract description 3
- 230000019612 pigmentation Effects 0.000 abstract description 3
- 238000002560 therapeutic procedure Methods 0.000 abstract description 3
- 241000228212 Aspergillus Species 0.000 abstract description 2
- 241000894006 Bacteria Species 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 abstract description 2
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 abstract description 2
- 229940080345 gamma-cyclodextrin Drugs 0.000 abstract description 2
- 241000589236 Gluconobacter Species 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 9
- 238000004519 manufacturing process Methods 0.000 description 7
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000011282 treatment Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 4
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000000839 emulsion Substances 0.000 description 3
- 238000005562 fading Methods 0.000 description 3
- 238000007689 inspection Methods 0.000 description 3
- 210000002752 melanocyte Anatomy 0.000 description 3
- 201000001441 melanoma Diseases 0.000 description 3
- 150000004702 methyl esters Chemical class 0.000 description 3
- 239000008213 purified water Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 description 2
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 2
- XUMBMVFBXHLACL-UHFFFAOYSA-N Melanin Chemical compound O=C1C(=O)C(C2=CNC3=C(C(C(=O)C4=C32)=O)C)=C2C4=CNC2=C1C XUMBMVFBXHLACL-UHFFFAOYSA-N 0.000 description 2
- -1 Polyoxyethylene Polymers 0.000 description 2
- 229930003268 Vitamin C Natural products 0.000 description 2
- 206010047642 Vitiligo Diseases 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 239000007854 depigmenting agent Substances 0.000 description 2
- NOPFSRXAKWQILS-UHFFFAOYSA-N docosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCO NOPFSRXAKWQILS-UHFFFAOYSA-N 0.000 description 2
- 210000002615 epidermis Anatomy 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 229940075507 glyceryl monostearate Drugs 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 208000000069 hyperpigmentation Diseases 0.000 description 2
- 230000003810 hyperpigmentation Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000001788 mono and diglycerides of fatty acids Substances 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- VLPFTAMPNXLGLX-UHFFFAOYSA-N trioctanoin Chemical compound CCCCCCCC(=O)OCC(OC(=O)CCCCCCC)COC(=O)CCCCCCC VLPFTAMPNXLGLX-UHFFFAOYSA-N 0.000 description 2
- 235000019154 vitamin C Nutrition 0.000 description 2
- 239000011718 vitamin C Substances 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- 150000005208 1,4-dihydroxybenzenes Chemical class 0.000 description 1
- RFVNOJDQRGSOEL-UHFFFAOYSA-N 2-hydroxyethyl octadecanoate Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCCO RFVNOJDQRGSOEL-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- DCXXMTOCNZCJGO-UHFFFAOYSA-N Glycerol trioctadecanoate Natural products CCCCCCCCCCCCCCCCCC(=O)OCC(OC(=O)CCCCCCCCCCCCCCCCC)COC(=O)CCCCCCCCCCCCCCCCC DCXXMTOCNZCJGO-UHFFFAOYSA-N 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 206010064127 Solar lentigo Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 102000003425 Tyrosinase Human genes 0.000 description 1
- 108060008724 Tyrosinase Proteins 0.000 description 1
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- 239000012752 auxiliary agent Substances 0.000 description 1
- 235000021302 avocado oil Nutrition 0.000 description 1
- 239000008163 avocado oil Substances 0.000 description 1
- 239000002981 blocking agent Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000004042 decolorization Methods 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- 229960000735 docosanol Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 210000001339 epidermal cell Anatomy 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- VYQNWZOUAUKGHI-UHFFFAOYSA-N monobenzone Chemical compound C1=CC(O)=CC=C1OCC1=CC=CC=C1 VYQNWZOUAUKGHI-UHFFFAOYSA-N 0.000 description 1
- 229960000990 monobenzone Drugs 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000003760 tallow Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- OGIDPMRJRNCKJF-UHFFFAOYSA-N titanium oxide Inorganic materials [Ti]=O OGIDPMRJRNCKJF-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 235000014692 zinc oxide Nutrition 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
- A61Q19/02—Preparations for care of the skin for chemically bleaching or whitening the skin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
- A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/73—Polysaccharides
- A61K8/738—Cyclodextrins
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Birds (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Pyrane Compounds (AREA)
- Cosmetics (AREA)
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野〕
本発明は肝斑などの色素沈着症に対する外用療法に用い
られるメラニン生成抑制外用薬剤に関するものである。DETAILED DESCRIPTION OF THE INVENTION [Industrial Field of Application] The present invention relates to a melanin production inhibiting topical drug used for topical treatment of pigmentation disorders such as melasma.
肝斑点をはじめとする色素沈着症に対する治療法として
は、ビタミンＣの連続内服などによる方法が行われてい
るが、色素沈着の程度が高度になるとビタミンＣの連続
内服では改善されない場合が多い、また外用療法として
色素沈着症がメラノサイトの機能昂進によりひきおこさ
れた表皮細胞のメラノサイトの量の増大と考えられ、こ
のメラニンの過剰生成を抑制させる方法としてのメラノ
サイト機能を昂進させる紫外線の影響を防止する方法と
して、タルク、亜鉛華、酸化チタン等の粉末などの光線
を散乱させる物質、又は紫外線吸収剤例えばパラアミノ
安息香酸などを含む軟膏などを用いる方法が行われてい
た。Continuous oral administration of vitamin C is used as a treatment for pigmentation disorders such as liver spots, but when the degree of pigmentation becomes severe, continuous oral administration of vitamin C often does not improve the condition. In addition, as an external treatment, hyperpigmentation is thought to be caused by an increase in the amount of melanocytes in the epidermal cells caused by the enhancement of melanocyte function, and as a way to suppress the excessive production of melanin, it is possible to prevent the effects of ultraviolet rays, which enhance melanocyte function. Methods to do this include using substances that scatter light such as powders such as talc, zinc white, and titanium oxide, or ointments containing ultraviolet absorbers such as para-aminobenzoic acid.
また、表皮におけるメラニン生成の抑制作用を持つ物質
、パイドロキノン、ハイドロキノン誘導体などの脱色剤
を含有した外用剤として用いることも知られている。It is also known to be used as an external preparation containing a depigmenting agent such as a substance that suppresses melanin production in the epidermis, pydroquinone, or a hydroquinone derivative.
また、コウジ酸、コウジ酸誘導体は表皮におけるメラニ
ン生成の抑制作用を持つものであることより、同物質を
用いた色白化粧料が知られている（例えば特公昭５６−
１８５６９号公報）、またコウジ酸誘導体を用いた色白
化粧料も知られている（例えば特開昭５６−７７１０号
、同５６−７７７６号、同５６−７９６１６号公報）。In addition, since kojic acid and kojic acid derivatives have the effect of suppressing melanin production in the epidermis, skin-whitening cosmetics using the same substance are known (for example,
18569), and fair skin cosmetics using kojic acid derivatives are also known (for example, JP-A-56-7710, JP-A-56-7776, and JP-A-56-79616).
従来技術において、色素沈着症の外用療法における外用
薬剤に用いられる光線遮断剤は色素沈着が日光光線によ
り増大するのを防止するために用いるものであるから、
他の療法と共に使用するものであり、この薬剤の単独使
用によっては色素沈着症の外用薬剤としての効果は期待
できない。In the prior art, light blocking agents used in external drugs for topical treatment of pigmentation disorders are used to prevent pigmentation from increasing due to sunlight;
It is used in conjunction with other therapies, and if used alone, it cannot be expected to be effective as a topical drug for pigmentation disorders.
脱色剤として用いられるハイドロキノン、ハイドロキノ
ンｔ”Ｚｊｔ体′（ハイドロキノンモノベンジルエーテ
ル等）の外用剤は斑状ないし網状の白斑を副作用として
生ずるおそれがあり、色素沈着症などの外用治療剤とし
ては好ましくない。また、コウジ酸、コウジ酸誘導体な
どのメラニン生成抑制物質を含んだ外用剤はチロシナー
ゼ゛活性阻害物質であるため、ハイドロキノンなどに見
られる白斑などの副作用を伴うことのないメラニン生成
抑制作用があり、色素沈着症などの治療用外用剤として
優れたものであるが、未だ充分とはいえない。External preparations of hydroquinone and hydroquinone t"Zjt" (hydroquinone monobenzyl ether, etc.) used as depigmenting agents may cause patchy or reticular vitiligo as a side effect, and are not preferred as external treatments for pigmentation disorders and the like. In addition, external preparations containing melanin production inhibitors such as kojic acid and kojic acid derivatives are tyrosinase activity inhibitors, so they have a melanin production inhibiting effect without the side effects such as vitiligo that are seen with hydroquinone. Although it is excellent as an external preparation for treating pigmentation disorders, it is still not sufficient.
本発明は、色素沈着症などの外用療法に用いる外用薬剤
においてメラニン生成を充分に抑制する薬剤を提供する
ことを目的とするものである。An object of the present invention is to provide an external drug that sufficiently suppresses melanin production for use in external therapy for pigmentation disorders and the like.
本発明者らは、上記目的を達成すべく鋭意研究を重ねた
ところ、コウジ酸とサイクロデキストリンの配合物を外
用薬剤として製剤化し、マウス黒色腫由来の８１６細胞
による試験及び臨床試験によるヰ★討の結果、色素沈着
症等の皮膚疾２色に対し顕著な効果を奏することを見出
し本発明を完成した。The present inventors have conducted extensive research to achieve the above objective, and have formulated a combination of kojic acid and cyclodextrin as a topical drug, and have demonstrated results through tests using 816 cells derived from mouse melanoma and clinical trials. As a result, the present invention was completed by discovering that the present invention has a remarkable effect on two skin diseases such as hyperpigmentation.
本発明はサイクロデキストリンとコウジ酸の配合物を含
存することを特徴とするメラニン生成抑制外用薬剤であ
る。The present invention is an external melanin production suppressing drug characterized by containing a combination of cyclodextrin and kojic acid.
本発明に使用するコウジ酸はアスペルギルス属、ダルコ
ノバクター属などの菌により得られる公知の化合物であ
る。Kojic acid used in the present invention is a known compound obtained from bacteria such as Aspergillus and Dalconobacter.
コウジ酸と配合するサイクロデキストリンはα。Cyclodextrin combined with kojic acid is α.
β、γ−サイクロデキストリン及びメチルサイクロデキ
ストリンが用いられるが、特にβ−サイクロデキストリ
ンが好適である。β, γ-cyclodextrin and methylcyclodextrin are used, with β-cyclodextrin being particularly preferred.
本発明に用いるサイクロデキストリンはコウジ酸と共に
コウジ酸１重量部に対して約１０〜０．５重量部、好適
には４〜５重量部使用する。The cyclodextrin used in the present invention is used together with kojic acid in an amount of about 10 to 0.5 parts by weight, preferably 4 to 5 parts by weight, per 1 part by weight of kojic acid.
なお、コウジ酸はサイクロデキストリンで包接して配合
してもよい。Note that kojic acid may be included and blended with cyclodextrin.
コウジ酸を包接化するにはサイクロデキストリンを水中
に分散せしめ、これにコウジ酸を徐々に添加しながら攪
拌し、両者を完全に溶解し、包接化コウジ酸を得る。本
発明に使用する包接化コウジ酸は、かくして得られたも
のを凍結乾燥したものでもよい。To clathrate kojic acid, cyclodextrin is dispersed in water, and kojic acid is gradually added thereto while stirring to completely dissolve the two to obtain clathrated kojic acid. The clathrated kojic acid used in the present invention may be obtained by freeze-drying the clathrated kojic acid thus obtained.
この場合サイクロデキストリンに対するコウジ酸の量は
サイクロデキストリン１０重量部に対しコウジ酸０．１
〜２０重量部、好適には、２．５重量部である。本発明
はコウジ酸とサイクロデキストリンを別々に又は包接し
て通常の外用薬剤の基剤に配合し、通常の方法で製剤化
して外用剤とする。これらの外用薬剤に配合するコウジ
酸とサイクロデキストリンの配合物の量は、コウジ酸と
して０．０１〜２％（重量）程度で充分その効果を奏す
ることができる。In this case, the amount of kojic acid relative to cyclodextrin is 0.1 parts by weight of kojic acid per 10 parts by weight of cyclodextrin.
~20 parts by weight, preferably 2.5 parts by weight. In the present invention, kojic acid and cyclodextrin are blended separately or together in a base of a conventional external drug, and then formulated by a conventional method to obtain a topical drug. The amount of the mixture of kojic acid and cyclodextrin added to these external medicines is about 0.01 to 2% (by weight) of kojic acid to achieve sufficient effects.
本発明の外用薬剤は主として乳剤、ローション剤３軟膏
などの外用薬剤である。これらの各製剤は上記有効成分
を各製剤に通常使用される基剤、助剤などと通常用いら
れる方法により製剤化する。The external medicines of the present invention are mainly emulsions, lotions, ointments, and the like. Each of these preparations is prepared by combining the above-mentioned active ingredients with a base, an auxiliary agent, etc. commonly used in each preparation, and a method commonly used.
次に本発明のを効成分である包接化コウジ酸の製剤例を
示す。Next, examples of formulations of clathrated kojic acid, which is the active ingredient of the present invention, will be shown.
製造例
β−サイクロデキストリン４重量部に精製水１２重量部
を加え、ゆるやかに撹拌する。次にコウジ酸０．８Ｍ１
部を加え均一になるまで充分攪拌し包接化コウジ酸を得
る。Production Example 12 parts by weight of purified water are added to 4 parts by weight of β-cyclodextrin and gently stirred. Next, kojic acid 0.8M1
1 part and stir thoroughly until homogeneous to obtain clathrated kojic acid.
かくして得られた包接化コウジ酸を凍結乾燥する。The clathrated kojic acid thus obtained is freeze-dried.
次に、本発明のメラニン生成抑制外用薬剤の有効成分の
マウスメラノーマＢ１６細胞による脱色試験を述べる。Next, a decolorization test using mouse melanoma B16 cells of the active ingredient of the melanin production-inhibiting topical drug of the present invention will be described.
（１）試料
Ａ；コウジ酸
Ｂ；製造例により製造された２０％包接化コウジ酸
Ｃ：コウジ酸±β−サイクロデキストリンＤ：β−サイ
クロデキストリン
（２）試験方法
シャーレ１枚につき４Ｘ１０’個のマウスメラノーマＢ
Ｉ６細胞（以下Ｂ１６細胞と称す）をまき込み、１０％
牛脂児血清を添加したイーグルＭＥＭ培地を用いて、こ
の培地に（１１コウジ酸濃度２．５ ＋＋＋Ｍとなるよ
うに添加（試験区Ａ）、（２１製造例により製造された
包接化コウジ酸をコウジ酸として２．５ｍＭとなるよう
に換算して添加（試験区Ｂ）、＋３１試験区Ｂに使用し
たコウジ酸及びβ−サイクロデキストリン相当量を各々
添加（試験区Ｃ）、（４１β−サイクロデキストリンを
試験区已に使用した包接化コウジ酸のβ−サイクロデキ
ストリン相当量添加（試験区Ｄ）、（５１無添加（試験
区Ｅ）の各培地を５％ｃｏ、 、９５％空気中、３７℃
で６日間培養し、トリプシン処理し、後、遠心＜２００
０ｒｐｒｍ、５分間）を行い、細胞ペレットを作製し、
各試験区の黒色度を肉眼的に比較した。(1) Sample A; Kojic acid B; 20% clathrated kojic acid produced according to the production example C: Kojic acid ± β-cyclodextrin D: β-cyclodextrin (2) Test method 4 x 10' pieces per Petri dish mouse melanoma B
Inoculate I6 cells (hereinafter referred to as B16 cells) and 10%
Using Eagle MEM medium supplemented with tallow baby serum, (11 kojic acid concentration was added to this medium so that the concentration was 2.5 +++ M (Test Area A), (21) clathrated kojic acid produced according to Production Example was added. Added at a concentration of 2.5mM as kojic acid (Test Group B), Added equivalent amounts of kojic acid and β-cyclodextrin used in +31 Test Group B (Test Group C), (41β-Cyclodextrin) Each culture medium containing β-cyclodextrin-equivalent amount of clathrated kojic acid was added (test area D) and (51 was not added (test area E)) in 5% CO, 95% air, 37 ℃
Culture for 6 days, trypsinization, and then centrifugation <200
0 rpm, 5 minutes) to prepare a cell pellet,
The degree of blackness of each test plot was visually compared.
（３）試験結果
試験区Ａは試験区Ｅ（対照）に比し中等度の褪色を示し
た。(3) Test results Test plot A showed moderate fading compared to test plot E (control).
試験区Ｂ及びＣは明らかな褪色を示し、その程度は試験
区Ａよりも強く、ペレットの色は白〜淡黄色であった。Test plots B and C showed obvious discoloration, and the degree of fading was stronger than test plot A, and the color of the pellets was white to pale yellow.
試験区りに褪色は認められなかった。No fading was observed in the test plots.
次に本発明の実施例を挙げる。 Next, examples of the present invention will be given.
モノステアリン酸ポリエチレングリコール（４０Ｅ、Ｏ
，）２．００ ｇ、自己乳化型モノステアリン酸グリセ
リン５．００ ｇ−ステアリン！５．ＯＯｇ、ヘヘニル
アルコール１．００ ｇ 、流動パラフィン１０．００
ｇ、トリオクタン酸グリセリル１０．００ ｇ、パラ
オキシ安息香酸メチルエステル０．２０ｇを加温溶解す
る。これに１．３−ブチレングリコール５．ＯＯｇ及び
ｔ＋ｔｙ水５６．８０ ｇを加温した溶液を加え乳化攪
拌し、冷却する。かくして得られた乳化液に製造例で得
た包接化コウジ酸の５ｇを加え、混合撹拌し、冷却後容
器に充填し、検査後製品とする。Polyethylene glycol monostearate (40E, O
) 2.00 g, self-emulsifying glyceryl monostearate 5.00 g - Stearin! 5. OOg, hehenyl alcohol 1.00 g, liquid paraffin 10.00
g, 10.00 g of glyceryl trioctanoate, and 0.20 g of paraoxybenzoic acid methyl ester were dissolved by heating. Add 1.3-butylene glycol and 5. A heated solution of 56.80 g of OOg and t+ty water is added, stirred to emulsify, and cooled. 5 g of the clathrated kojic acid obtained in the production example is added to the emulsion thus obtained, mixed and stirred, and after cooling, it is filled into a container and used as a product after inspection.
例２
（乳剤）
モノステアリン酸ポリオキシエチレルソルビクン（２０
Ｅ、０．）１．００ ｇ、テトラオレイン酸ポリオキシ
エチレンソルビント（６０Ｅ、Ｏ，）０．５０ ｇ、親
油型モノステアリン酸グリセリン１．ＯＯｇ、ステアリ
ン酸０．５０ｇ、ベヘニルアルコール０．５０ｇ、アボ
ガド油４．００ ｇ 、 トリオクタン酸グリセリル
４．００ ｇ 、パラオキシ安息香酸メチルエステル０
．２０ｇを加温溶解する。それに１．３−ブチレングリ
コール５．００ｇ、キサンタンガム０．１４ ｇ 、製
造例で得た包接化コウジ酸３．０ｇ、精製水８０．１６
ｇを加温した溶液を加え乳化攪拌し、冷却する。この液
に香料を微量加え攪拌・混合する。かくして得られた液
を冷却後、容器に充填し、検査後製品とする。Example 2 (Emulsion) Polyoxyethylene sorbicun monostearate (20
E, 0. ) 1.00 g, polyoxyethylene sorbate tetraoleate (60E, O,) 0.50 g, lipophilic glyceryl monostearate 1. OOg, stearic acid 0.50g, behenyl alcohol 0.50g, avocado oil 4.00g, glyceryl trioctanoate 4.00g, paraoxybenzoic acid methyl ester 0
．． Dissolve 20g by heating. In addition, 5.00 g of 1.3-butylene glycol, 0.14 g of xanthan gum, 3.0 g of clathrated kojic acid obtained in the production example, and 80.16 g of purified water.
Add a heated solution of g to emulsify, stir, and cool. Add a small amount of fragrance to this liquid and stir to mix. After cooling the liquid obtained in this way, it is filled into a container and used as a product after inspection.
例３
（ローション剤）
製造例で得た包接化コウジ酸２．０ｇとパラオキシ安息
香酸メチルエステル０．１０ ｇ、ヒアルロン酸０．０
１ｇ、香料微量と精製水を加え全量を１００ ｇとして
撹拌・混合し、容器に充填し検査後製品とする。Example 3 (Lotion) 2.0 g of clathrated kojic acid obtained in Production Example, 0.10 g of paraoxybenzoic acid methyl ester, and 0.0 g of hyaluronic acid.
1g, add a small amount of fragrance and purified water to make a total of 100g, stir and mix, fill in a container, and use as a product after inspection.
本発明のメラニン生成抑制外用薬剤は、その症状により
適宜使用されるが、−ａに１日３回洗顔後、患部に塗布
することにより充分その効果が奏せられる。The melanin production inhibiting topical drug of the present invention is used as appropriate depending on the symptoms, but its effects can be fully exerted by applying it to the affected area after washing the face three times a day.
本発明の外用薬剤は、これを、・患部に塗布することに
より肝斑などによる色素沈着症の予防、治療に極めて有
効なものである。The external drug of the present invention is extremely effective in preventing and treating pigmentation disorders caused by melasma and the like by applying it to the affected area.
Claims (1)
ることを特徴とするメラニン生成抑制外用薬剤。 ２、サイクロデキストリンとコウジ酸の配合物がサイク
ロデキストリンで包接されたコウジ酸である特許請求の
範囲第１項記載のメラニン生成抑制外用薬剤。[Scope of Claims] 1. An external medicine for suppressing melanin production, characterized by containing a combination of cyclodextrin and kojic acid. 2. The melanin production inhibiting topical drug according to claim 1, wherein the mixture of cyclodextrin and kojic acid is kojic acid clathrated with cyclodextrin.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15201886A JPS638311A (en) | 1986-06-27 | 1986-06-27 | Drug capable of inhibiting melanization for external use |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP15201886A JPS638311A (en) | 1986-06-27 | 1986-06-27 | Drug capable of inhibiting melanization for external use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS638311A true JPS638311A (en) | 1988-01-14 |
Family
ID=15531259
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP15201886A Pending JPS638311A (en) | 1986-06-27 | 1986-06-27 | Drug capable of inhibiting melanization for external use |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS638311A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU667338B2 (en) * | 1993-02-08 | 1996-03-21 | Kabushiki Kaisha Kobe Seiko Sho | Melanin decomposing method and melanin decomposing substance |
| JP2012153647A (en) * | 2011-01-26 | 2012-08-16 | Stella Pharma Corp | Carborane-modified kojic acid/cyclodextrin inclusion complex and production method of the same |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61109705A (en) * | 1984-11-01 | 1986-05-28 | Sansho Seiyaku Kk | Whitening cosmetics |
-
1986
- 1986-06-27 JP JP15201886A patent/JPS638311A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS61109705A (en) * | 1984-11-01 | 1986-05-28 | Sansho Seiyaku Kk | Whitening cosmetics |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU667338B2 (en) * | 1993-02-08 | 1996-03-21 | Kabushiki Kaisha Kobe Seiko Sho | Melanin decomposing method and melanin decomposing substance |
| JP2012153647A (en) * | 2011-01-26 | 2012-08-16 | Stella Pharma Corp | Carborane-modified kojic acid/cyclodextrin inclusion complex and production method of the same |
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