JPH0499708A - Melanogenetic cell-proliferative and pigment-productive promoter - Google Patents
Melanogenetic cell-proliferative and pigment-productive promoterInfo
- Publication number
- JPH0499708A JPH0499708A JP21418390A JP21418390A JPH0499708A JP H0499708 A JPH0499708 A JP H0499708A JP 21418390 A JP21418390 A JP 21418390A JP 21418390 A JP21418390 A JP 21418390A JP H0499708 A JPH0499708 A JP H0499708A
- Authority
- JP
- Japan
- Prior art keywords
- melanin
- endothelin
- promoter
- pigment
- hair
- 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.)
- Granted
Links
- 239000004480 active ingredient Substances 0.000 claims abstract description 7
- 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 claims description 41
- 108050009340 Endothelin Proteins 0.000 claims description 24
- 102000002045 Endothelin Human genes 0.000 claims description 24
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 claims description 23
- 239000000049 pigment Substances 0.000 claims description 16
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 230000004663 cell proliferation Effects 0.000 claims description 10
- 230000000694 effects Effects 0.000 abstract description 16
- 239000002537 cosmetic Substances 0.000 abstract description 4
- 150000001413 amino acids Chemical class 0.000 abstract description 2
- 239000000203 mixture Substances 0.000 abstract description 2
- 210000003556 vascular endothelial cell Anatomy 0.000 abstract description 2
- 230000002500 effect on skin Effects 0.000 abstract 1
- 231100000957 no side effect Toxicity 0.000 abstract 1
- 230000008099 melanin synthesis Effects 0.000 description 24
- 210000004027 cell Anatomy 0.000 description 14
- 210000003491 skin Anatomy 0.000 description 13
- 230000035755 proliferation Effects 0.000 description 9
- 230000001737 promoting effect Effects 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
- 208000012641 Pigmentation disease Diseases 0.000 description 8
- 230000019612 pigmentation Effects 0.000 description 8
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 239000003814 drug Substances 0.000 description 6
- 230000002285 radioactive effect Effects 0.000 description 6
- 238000010998 test method Methods 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- DWRXFEITVBNRMK-UHFFFAOYSA-N Beta-D-1-Arabinofuranosylthymine Natural products O=C1NC(=O)C(C)=CN1C1C(O)C(O)C(CO)O1 DWRXFEITVBNRMK-UHFFFAOYSA-N 0.000 description 3
- 241000700198 Cavia Species 0.000 description 3
- IQFYYKKMVGJFEH-UHFFFAOYSA-N beta-L-thymidine Natural products O=C1NC(=O)C(C)=CN1C1OC(CO)C(O)C1 IQFYYKKMVGJFEH-UHFFFAOYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000011156 evaluation Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- ZEMGGZBWXRYJHK-UHFFFAOYSA-N thiouracil Chemical compound O=C1C=CNC(=S)N1 ZEMGGZBWXRYJHK-UHFFFAOYSA-N 0.000 description 3
- 229950000329 thiouracil Drugs 0.000 description 3
- 229940104230 thymidine Drugs 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 230000037308 hair color Effects 0.000 description 2
- 210000002510 keratinocyte Anatomy 0.000 description 2
- 210000002752 melanocyte Anatomy 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 1
- 230000006820 DNA synthesis Effects 0.000 description 1
- 101800004490 Endothelin-1 Proteins 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102400000740 Melanocyte-stimulating hormone alpha Human genes 0.000 description 1
- 101710200814 Melanotropin alpha Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010042496 Sunburn Diseases 0.000 description 1
- 206010047642 Vitiligo Diseases 0.000 description 1
- 229940124532 absorption promoter Drugs 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- -1 and in particular Chemical compound 0.000 description 1
- HZZGDPLAJHVHSP-GKHTVLBPSA-N big endothelin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@@H]2CSSC[C@@H](C(N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CSSC1)C1=CN=CN1 HZZGDPLAJHVHSP-GKHTVLBPSA-N 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 238000004113 cell culture Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000002354 daily effect Effects 0.000 description 1
- 230000035614 depigmentation Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 230000002900 effect on cell Effects 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 230000003779 hair growth Effects 0.000 description 1
- 239000003676 hair preparation Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 230000003020 moisturizing effect Effects 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- PHEDXBVPIONUQT-RGYGYFBISA-N phorbol 13-acetate 12-myristate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCCCCCCCCCCCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(C)=O)C1(C)C PHEDXBVPIONUQT-RGYGYFBISA-N 0.000 description 1
- 239000002644 phorbol ester Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000002087 whitening effect Effects 0.000 description 1
- WHNFPRLDDSXQCL-UAZQEYIDSA-N α-msh Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(N)=O)NC(=O)[C@H](CO)NC(C)=O)C1=CC=C(O)C=C1 WHNFPRLDDSXQCL-UAZQEYIDSA-N 0.000 description 1
Abstract
Description
【発明の詳細な説明】
〔産業上の利用分野］
本発明は、メラニン細胞の増殖・色素産生促進剤、詳し
くは、メラニン産生細胞の増殖及び色素産生促進効果を
有するエンドセリンを有効成分として含有する、メラニ
ン産生細胞の増殖・色素産生促進剤に関するもので、本
発明のメラニン産生細胞の増殖・色素産生促進剤は、皮
膚及び毛髪の色調改善や黒化等に利用される。[Detailed Description of the Invention] [Industrial Application Field] The present invention is a melanocyte proliferation/pigment production promoting agent, specifically, a melanin cell proliferation/pigment production promoting agent containing endothelin as an active ingredient. , relates to a melanin-producing cell proliferation/pigment production promoter, and the melanin-producing cell proliferation/pigment production promoter of the present invention is used for improving skin and hair color tone, darkening, etc.
〔従来の技術］
皮膚組織（表皮あるいは毛髪）に存在するメラニン産生
細胞より産生されたメラニンは、角化細胞に移行され、
角化細胞の増殖・分化に伴い組織に供給分散される。そ
して、この際に組織に供給分散されるメラニンの量的及
び質的差異により、組織の色調が決定される。このよう
なメラニン色素産生機構は、内因性及び外因性因子によ
り巧みに制御されていることが明らかになってきた。こ
れらの現象は、日常的には紫外線照射による日焼けとし
て認知することができる。[Prior art] Melanin produced by melanin-producing cells present in skin tissue (epidermis or hair) is transferred to keratinocytes,
It is supplied and distributed to tissues as keratinocytes proliferate and differentiate. The color tone of the tissue is determined by the quantitative and qualitative differences in melanin supplied and dispersed to the tissue at this time. It has become clear that such melanin pigment production mechanism is skillfully controlled by endogenous and exogenous factors. These phenomena can be recognized as sunburn caused by ultraviolet irradiation on a daily basis.
一方、メラニン産生の欠落の結果、加歳に伴い毛髪の白
色化（白髪）や皮膚の白斑が起こる。また、薬物による
アレルギー反応や炎症反応により、可逆的あるいは不可
逆的な色素沈着や色素脱失が生じることもある。On the other hand, as a result of lack of melanin production, whitening of hair (grey hair) and vitiligo on the skin occur as people age. In addition, reversible or irreversible pigmentation or depigmentation may occur due to allergic or inflammatory reactions caused by drugs.
従来より、これらメラニン産生の欠落を予防又は回復せ
しめる目的でメラニン細胞のメラニン産生能や増殖を促
進する活性物質の探索が試みられ、培養細胞系では、α
−ＭＳＨ、プロスタグランジンＥｚ１テオフィリン、ホ
ルボルエステル等の薬剤にその効果が認められており、
さらには臨床評価系では、ＩＩＭＯＰによるＰＵＶＡＵ
Ｖ中α−ＭＳＨによる薬剤療法等が試みられている。In the past, attempts have been made to search for active substances that promote the melanin production ability and proliferation of melanocytes in order to prevent or restore the lack of melanin production, and in cultured cell systems, α
-The effect has been recognized in drugs such as MSH, prostaglandin Ez1 theophylline, and phorbol ester.
Furthermore, in the clinical evaluation system, PUVAU by IIMOP
Drug therapy using α-MSH in V is being attempted.
〔発明が解決しようとする課題］
しかしながら、上記薬剤は、メラニン産生細胞の増殖及
びそれに伴うメラニン産生の増加に対する効果が認めら
れる有効活性濃度が、生理的な濃度より非常に高濃度で
あったり、他の薬理的効能が著しく強い等の問題点があ
るばかりか、その生化学的な作用メカニズムについても
殆ど明らかにされていないのが現状であった。また、従
来、メラニン色素形成を促進するような薬剤は商品化さ
れておらず、皮膚や毛髪の色素形成をコントロールする
薬剤の開発が期待されている。[Problems to be Solved by the Invention] However, the effective activity concentration of the above-mentioned drugs at which the effect on the proliferation of melanin-producing cells and the accompanying increase in melanin production is observed is much higher than the physiological concentration, Not only do they have problems such as their extremely strong pharmacological efficacy, but their biochemical mechanism of action is also largely unknown. Furthermore, there have been no commercially available drugs that promote melanin pigment formation, and there are high expectations for the development of drugs that control pigment formation in the skin and hair.
従って、本発明の目的は、メラニン産生細胞の増殖及び
色素産生促進効果に優れ、且つ長期間使用しても副作用
を生じない安全なメラニン産生細胞の増殖・色素産生促
進剤を提供することにある。Therefore, an object of the present invention is to provide a safe melanin-producing cell proliferation/pigment production promoting agent that is excellent in promoting melanin-producing cell proliferation and pigment production and does not cause any side effects even when used for a long period of time. .
〔課題を解決するための手段］
本発明者らは、上記目的を達成すべく鋭意研究した結果
、血管内皮細胞の産生するエンドセリンがメラニン産生
細胞の増殖を促進し、メラニン産生を亢進することを発
見し、本発明に到達した。[Means for Solving the Problem] As a result of intensive research to achieve the above object, the present inventors have found that endothelin produced by vascular endothelial cells promotes the proliferation of melanin-producing cells and enhances melanin production. discovered and arrived at the present invention.
即ち、本発明は、エンドセリンを有効成分として含有す
る、メラニン産生細胞の増殖・色素産生促進剤を提供す
るものである。That is, the present invention provides a melanin-producing cell proliferation/pigment production promoter containing endothelin as an active ingredient.
以下、本発明のメラニン産生細胞の増殖・色素産生促進
剤（以下、メラニン産生促進剤という場合もある）につ
いて詳述する。Hereinafter, the melanin-producing cell proliferation/pigment production promoter (hereinafter sometimes referred to as a melanin production promoter) of the present invention will be described in detail.
本発明のメラニン産生促進剤の有効成分であるエンドセ
リンには、そのアミノ酸組成の異なる４種の類縁体（タ
イプ１５タイプ■、タイプ■及びビッグエンドセリン）
の存在が明らかにされているが、本発明においては、何
れの類縁体も用いることができ、それらの内でも、タイ
プＩ及びタイプ■のエンドセリンが好ましい。Endothelin, which is the active ingredient of the melanin production promoter of the present invention, has four types of analogues with different amino acid compositions (type 15 type ■, type ■, and big endothelin).
However, in the present invention, any analogue can be used, and among them, type I and type II endothelin are preferred.
上記エンドセリンを含有する本発明のメラニン産生促進
剤は、種々の形態にすることができるが、一般には、乳
液状、軟膏状、ローション状、クリーム状、溶剤による
溶液状等の形態にするのが望ましい。この際、本発明の
メラニン産生促進剤には、他の任意成分を配合すること
ができ、かかる任意成分としては、化粧料に通常配合さ
れている成分、例えば、油性成分、香料、乳化安定剤、
保湿側等を挙げることができる。The melanin production promoter of the present invention containing endothelin can be in various forms, but generally it is in the form of an emulsion, an ointment, a lotion, a cream, a solution in a solvent, etc. desirable. At this time, the melanin production promoter of the present invention may contain other optional ingredients, such as ingredients usually included in cosmetics, such as oily ingredients, fragrances, and emulsion stabilizers. ,
Examples include the moisturizing side.
また、本発明のメラニン産生促進剤は、必要に応して、
血行促進剤や経皮吸収促進剤等の他種薬剤を併用する薬
用外用剤等の形態で用いることにより、養毛前厄効果と
毛色コントロールの効果を兼ね備えたメラニン産生促進
剤とすることも可能である。Further, the melanin production promoter of the present invention may optionally include:
By using it in the form of a medicated topical preparation in combination with other drugs such as blood circulation promoters and transdermal absorption promoters, it is possible to create a melanin production promoter that has both the effect of promoting hair growth and the effect of controlling hair color. be.
本発明のメラニン産生促進剤における上記エンドセリン
の含有量は、特に制限されないが、例えば、乳化皮膚化
粧料及び毛髪化粧料とする場合には、通常、０． ＯＯ
２〜１．０重量％が好ましい。The content of endothelin in the melanin production promoter of the present invention is not particularly limited, but for example, when used in emulsified skin cosmetics and hair cosmetics, it is usually 0. OO
2 to 1.0% by weight is preferred.
上述した本発明のメラニン産生促進剤は、皮膚及び毛髪
の患部に局所的に適用される。The melanin production promoter of the present invention described above is applied topically to affected areas of the skin and hair.
本発明のメラニン産生促進剤は、皮膚及び毛髪に適用さ
れると、有効成分として含有するエンドセリンの作用に
より、適用部位におけるメラニン産生細胞の増殖及び色
素産生を促進する。When applied to the skin and hair, the melanin production promoter of the present invention promotes the proliferation of melanin-producing cells and pigment production at the application site due to the action of endothelin contained as an active ingredient.
〔実施例］
以下、本発明のメラニン産生促進剤の効果を示す実施例
を挙げ、本発明を更に詳しく説明するが、本発明はこれ
らの実施例に限定されるものではない。[Examples] Hereinafter, the present invention will be described in more detail with reference to Examples showing the effects of the melanin production promoter of the present invention, but the present invention is not limited to these Examples.
実施例１
本発明のメラニン産生促進剤について、培養ヒトメラニ
ン産生細胞の増殖及びメラニン産生に対する効果を下記
試験方法により検討した。その結果を下記の第１表及び
第２表に示す。Example 1 The effect of the melanin production promoter of the present invention on proliferation of cultured human melanin-producing cells and melanin production was investigated using the following test method. The results are shown in Tables 1 and 2 below.
〔試験方法］
クラポウ社より市販されている正常ヒトメラニン産生細
胞（商品名メラノバック）を常法に従って継代培養し、
本試験に供した。この細胞培養プレートに、最終濃度が
０．１〜ｌｏｏｎＭとなるように各種エンドセリンを添
加した後、一定期間経過後の細胞の増殖及びメラニン産
生に対する効果を調べた。また、比較のために、エンド
セリン未添加の場合（対照）についても、同様に試験し
た。[Test method] Normal human melanin-producing cells (trade name Melanovac) commercially available from Klapow were subcultured according to a conventional method.
It was used in this test. Various endothelins were added to this cell culture plate at a final concentration of 0.1 to 1000 m, and the effects on cell proliferation and melanin production after a certain period of time were examined. For comparison, the same test was also conducted in the case where endothelin was not added (control).
尚、細胞増殖に対する効果は、ＤＮＡ合成を定量する方
法、即ち、放射性チミジンの細胞内への取り込み量を測
定することにより評価した。また、メラニン産生に対す
る効果は、放射性チオウラシルの細胞内への取り込み量
を測定することにより評価した。The effect on cell proliferation was evaluated by a method of quantifying DNA synthesis, that is, by measuring the amount of radioactive thymidine taken into cells. Furthermore, the effect on melanin production was evaluated by measuring the amount of radioactive thiouracil taken into cells.
下記第１表に、エンドセリンを２．０ ｎ Ｍ、４．０
ｎＭ及び２０．０ ｎ Ｍ添加した場合における放射性
チミジンの細胞内への取り込み量の測定結果を示す。ま
た、下記第２表に、エンドセリンを２．ＯｎＭ、４．０
ｎ Ｍ及び２０．０ ｎ Ｍ添加した場合における放
射性チオウラシルの細胞内への取り込み量の測定結果を
示す。Table 1 below shows endothelin at 2.0 nM and 4.0 nM.
The results of measuring the amount of radioactive thymidine taken into cells when added at nM and 20.0 nM are shown. In addition, Table 2 below shows endothelin in 2. OnM, 4.0
The results of measuring the amount of radioactive thiouracil taken into cells when nM and 20.0 nM were added are shown.
下記第１表に示す結果から判るように、エンドセリンを
４〜２０ｎＭ添加した場合、特にエンドセリンとしてタ
イプＩ及びタイプ■のエンドセリンを添加した場合に、
放射性チミジンの細胞内への取り込みの亢進が顕著に認
められた。As can be seen from the results shown in Table 1 below, when 4 to 20 nM of endothelin was added, especially when type I and type II endothelin were added as endothelin,
Significant enhancement of radioactive thymidine uptake into cells was observed.
また、下記第２表に示す結果から判るように、放射性チ
オウラシルの細胞内への取り込みについても、特にタイ
プ１及びタイプ■のエンドセリン（４〜２０ｎＭ）を添
加した場合に、上記取り込みの亢進が顕著に認められた
。Furthermore, as can be seen from the results shown in Table 2 below, regarding the uptake of radioactive thiouracil into cells, the uptake is significantly enhanced, especially when type 1 and type II endothelin (4 to 20 nM) is added. was recognized.
以上の結果から、エンドセリンを含有する本発明のメラ
ニン産生促進剤は、培養ヒトメラニン産生細胞の増殖及
びメラニン産生に対する促進効果が認められ、特に、エ
ンドセリンとしてタイプＩ及びタイプ■のエンドセリン
を含有する場合に、上記効果が顕著であることが判る。From the above results, the melanin production promoter of the present invention containing endothelin is recognized to have a promoting effect on the proliferation and melanin production of cultured human melanin-producing cells, especially when containing type I and type II endothelin as endothelin. It can be seen that the above effect is remarkable.
第１表 （Ｘ１０’ｄｐｍ士標準誤差／プレート）第２
表 （Ｘ ｌ Ｏ’ ｄｐｍ＝標’ｌ誤差／プレート）
実施例２
本発明のメラニン産生促進剤について、モルモットの紫
外線色素斑に対する色素沈着促進効果を下記試験方法に
より調べた。その結果を下記第３表に示す。Table 1 (X10'dpm standard error/plate) 2nd
Table (X l O' dpm=standard error/plate)
Example 2 The pigmentation promoting effect of the melanin production promoter of the present invention on ultraviolet pigment spots in guinea pigs was investigated using the following test method. The results are shown in Table 3 below.
［試験方法］
後天的な色素斑形成能を有する黄褐色モルモット（皮膚
色が黄色人種のものと酷イ以し、人間と同様に紫外線照
射により皮膚が１化するモルモ。[Test method] Yellow-brown guinea pigs with an acquired ability to form pigmented spots (guinea pigs whose skin color is very similar to those of the yellow race, and whose skin becomes monochromatic when exposed to ultraviolet rays, similar to humans.
ト）１群２０匹の背部皮膚を用いて評価した。即ち、モ
ルモットの背部毛を剃ｔし、刺毛した背部を、１．５
Ｘ １．５ ｃ＋ａの正方形の開口部を６ケ所設けたア
ルミ箔で覆った後、Ｉｊ Ｖ Ｂ （３ｓ＋Ｗ／ｃ４）
で−回、５分間、照射した。照射直後から紫外線照射部
位に、４種のエンドセリンＯ，１％含をエタノール溶液
（本発明のメラニン産生促進剤）を−日一回３０日間連
続塗布した。また、対照群には、溶媒のエタノールのみ
を塗布した。皮膚色調の黒化度を以下に示す判定基準に
より肉眼判定することにより、色素沈着促進効果を評価
した。g) Evaluation was performed using the back skin of 20 animals per group. That is, the hair on the back of the guinea pig was shaved, and the hair on the back with pricked hair was 1.5
After covering the square openings of X 1.5 c+a with 6 aluminum foils, Ij V B (3s+W/c4)
It was irradiated twice for 5 minutes. Immediately after irradiation, an ethanol solution containing 1% of four types of endothelin O (melanin production promoter of the present invention) was continuously applied once every day for 30 days. In addition, only the solvent ethanol was applied to the control group. The pigmentation promoting effect was evaluated by visual judgment of the degree of darkening of the skin tone according to the criteria shown below.
判定基準 ：０−色素沈着を認めない。Judgment criteria :0 - No pigmentation observed.
±：１＝境界不明瞭なわずかな色素沈着を認める。±: 1 = Slight pigmentation with unclear borders is observed.
十＝２：境界明瞭な中程度の色素沈着を認める。10=2: Moderate pigmentation with clear borders is observed.
＋＋：３：境界明瞭な強度の色素沈着を認める。++: 3: Intense pigmentation with clear boundaries is observed.
［結果］
下記第３表に、肉眼判定の結果及び評価点の平均値を示
す。[Results] Table 3 below shows the results of visual judgment and the average value of the evaluation points.
下記第３表に示す結果から、エンドセリン含有エタノー
ル溶液（本発明のメラニン産生促進剤）は、対照のエタ
ノールに比して、色素沈着効果が認められ、特に、エン
ドセリンとしてタイプＩ及びタイプ■のエンドセリンを
含有する場合に、上〔発明の効果〕
本発明のメラニン産生細胞の増殖・色素産生促進剤は、
メラニン産生細胞の増殖及び色素産生促進効果に優れ、
且つ長期間使用しても副作用を生しない安全なものであ
るため、皮膚及び毛輩の色調改善や黒化等に利用するこ
とができる。From the results shown in Table 3 below, it was found that the endothelin-containing ethanol solution (melanin production promoter of the present invention) has a pigmentation effect compared to the control ethanol, and in particular, endothelin containing type I and type II endothelin. [Effects of the Invention] The melanin-producing cell proliferation/pigment production promoter of the present invention contains the following:
Excellent in promoting the proliferation of melanin-producing cells and pigment production,
In addition, it is safe and does not cause any side effects even when used for a long period of time, so it can be used to improve the color tone of the skin and hair, darken the skin, etc.
Claims (1)
細胞の増殖・色素産生促進剤。A melanin-producing cell proliferation and pigment production promoter containing endothelin as an active ingredient.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21418390A JPH0678224B2 (en) | 1990-08-13 | 1990-08-13 | Proliferation / pigmentation promoter for melanocytes |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP21418390A JPH0678224B2 (en) | 1990-08-13 | 1990-08-13 | Proliferation / pigmentation promoter for melanocytes |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH0499708A true JPH0499708A (en) | 1992-03-31 |
| JPH0678224B2 JPH0678224B2 (en) | 1994-10-05 |
Family
ID=16651613
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP21418390A Expired - Fee Related JPH0678224B2 (en) | 1990-08-13 | 1990-08-13 | Proliferation / pigmentation promoter for melanocytes |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0678224B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001028509A1 (en) * | 1999-10-21 | 2001-04-26 | Kao Corporation | Depilatories and agents for external use |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5858654B2 (en) * | 2010-06-25 | 2016-02-10 | ホーユー株式会社 | White hair prevention / treatment agent, non-therapeutic beauty method, endothelin receptor B gene expression promoter and MITF-M gene expression promoter |
-
1990
- 1990-08-13 JP JP21418390A patent/JPH0678224B2/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001028509A1 (en) * | 1999-10-21 | 2001-04-26 | Kao Corporation | Depilatories and agents for external use |
| JP2001187720A (en) * | 1999-10-21 | 2001-07-10 | Kao Corp | Depiratory and external preparation |
| US6884772B1 (en) | 1999-10-21 | 2005-04-26 | Kao Corporation | Depilatories and agents for external use |
| US7468421B2 (en) | 1999-10-21 | 2008-12-23 | Kao Corporation | Depilatories and agents for external use |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0678224B2 (en) | 1994-10-05 |
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