JP2010501551A - Use of rare earth elements for hair improvement - Google Patents
Use of rare earth elements for hair improvement Download PDFInfo
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- JP2010501551A JP2010501551A JP2009525504A JP2009525504A JP2010501551A JP 2010501551 A JP2010501551 A JP 2010501551A JP 2009525504 A JP2009525504 A JP 2009525504A JP 2009525504 A JP2009525504 A JP 2009525504A JP 2010501551 A JP2010501551 A JP 2010501551A
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- Prior art keywords
- hair
- acid
- extract
- rare earth
- tincture
- 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.)
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- 229910052761 rare earth metal Inorganic materials 0.000 title claims abstract description 93
- 230000006872 improvement Effects 0.000 title description 2
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- 230000003779 hair growth Effects 0.000 claims abstract description 82
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- 238000004519 manufacturing process Methods 0.000 claims abstract description 32
- 229910052746 lanthanum Inorganic materials 0.000 claims abstract description 31
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- 150000003839 salts Chemical class 0.000 claims abstract description 28
- 229910052688 Gadolinium Inorganic materials 0.000 claims abstract description 27
- FZLIPJUXYLNCLC-UHFFFAOYSA-N lanthanum atom Chemical compound [La] FZLIPJUXYLNCLC-UHFFFAOYSA-N 0.000 claims abstract description 26
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- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 claims abstract description 22
- OHSVLFRHMCKCQY-UHFFFAOYSA-N lutetium atom Chemical compound [Lu] OHSVLFRHMCKCQY-UHFFFAOYSA-N 0.000 claims abstract description 22
- QEFYFXOXNSNQGX-UHFFFAOYSA-N neodymium atom Chemical compound [Nd] QEFYFXOXNSNQGX-UHFFFAOYSA-N 0.000 claims abstract description 22
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Abstract
セリウム(Ce)、プラセオジミウム(Pr)、プロメチウム(Pm)、ユーロピウム(Eu)、テルビウム(Tb)、ジスプロシウム(Dy)、ホルミウム(Ho)、エルビウム(Er)、ツリウム(Tm)、イッテルビウム(Yb)、スカンジウム(Sc)、イットリウム(Y)、ランタン(La)、ネオジム(Nd)、サマリウム(Sm)、ガドリニウム(Gd)、ルテチウム(Lu)及びこれらの混合物から構成された群から選択される希土類元素、またはその塩若しくは酸化物の脱毛防止、発毛促進、育毛、ふけの除去及び予防、または黒毛生成促進のための用途が開示されている。
【選択図】図5Cerium (Ce), praseodymium (Pr), promethium (Pm), europium (Eu), terbium (Tb), dysprosium (Dy), holmium (Ho), erbium (Er), thulium (Tm), ytterbium (Yb), A rare earth element selected from the group consisting of scandium (Sc), yttrium (Y), lanthanum (La), neodymium (Nd), samarium (Sm), gadolinium (Gd), lutetium (Lu), and mixtures thereof, Or the use for the hair loss prevention of the salt or oxide, hair growth promotion, hair growth, removal and prevention of dandruff, or black hair production promotion is indicated.
[Selection] Figure 5
Description
本発明は、毛髪改善のための希土類元素の用途に関し、より詳細には、セリウム(Ce)、プラセオジミウム(Pr)、プロメチウム(Pm)、ユーロピウム(Eu)、テルビウム(Tb)、ジスプロシウム(Dy)、ホルミウム(Ho)、エルビウム(Er)、ツリウム(Tm)、イッテルビウム(Yb)、スカンジウム(Sc)、イットリウム(Y)、ランタン(La)、ネオジム(Nd)、サマリウム(Sm)、ガドリニウム(Gd)、ルテチウム(Lu)及びこれらの混合物から構成された群から選択される希土類元素、またはその塩若しくは酸化物の脱毛防止、発毛促進、育毛、ふけの除去及び予防、または黒毛生成促進のための用途に関する。 The present invention relates to the use of rare earth elements for hair improvement, more particularly cerium (Ce), praseodymium (Pr), promethium (Pm), europium (Eu), terbium (Tb), dysprosium (Dy), Holmium (Ho), erbium (Er), thulium (Tm), ytterbium (Yb), scandium (Sc), yttrium (Y), lanthanum (La), neodymium (Nd), samarium (Sm), gadolinium (Gd), Use for preventing hair loss, promoting hair growth, hair growth, removing and preventing dandruff, or promoting black hair production of rare earth elements selected from the group consisting of lutetium (Lu) and mixtures thereof, or salts or oxides thereof About.
人体の毛髪は、約10万〜15万個程度であり、それぞれの毛髪は、互いに異なる周期を有して成長期(anagen)、退化期(catagen)、休止期(telogen)を経て成長、脱落する。このような周期は、3〜6年にかけて繰り返されるが、その結果、一日平均50〜100個の毛髪が脱落する。脱毛症は、成長期の毛髪比率が短くなり、退化期または休止期の毛髪比率が長くなって生じる現象である。脱毛の原因としては、毛根、皮脂腺などの器官から男性ホルモンのアンドロゲンが過度に分泌され、毛嚢細胞を強く刺激して毛嚢を萎縮させることにより、毛髪成長が遅延されることが原因として挙げられる。その他にも、局所血流障害による栄養供給の障害、皮脂分泌過剰、過酸化物、細菌などによる頭皮機能の低下、外部の強いストレス、慢性疾患による神経症状の悪化などが主要原因として知られている。しかも、現代社会に入って、過労、環境汚染や中毒性薬物の誤濫用による副作用、パーマ、染色、ムース、スプレーなどの使用による頭皮の血流障害と遺伝などの理由により脱毛の発生がさらに深刻になるにつれて、発毛に対する関心が増加している。最近は、男性型脱毛だけではなく、女性の肥満性脱毛を始めとして、若い層における脱毛が拡散されていく趨勢であって、このような脱毛現象を改善するために、様々な種類の発毛剤または育毛剤が市販されている。市販されている発毛剤または育毛剤としては、塩化カプロニウム(Carpronium chloride)、ミノキシジル(minoxidil)などの血管拡張剤やエストロゲン、エストラジオールなどの男性ホルモン作用を抑制するためのホルモン剤及びペンタデカン酸、フィナステライド(finasteride)などの男性ホルモン活性抑制剤などがある。 The human body has about 100,000 to 150,000 hairs, and each hair grows and drops through a growth period (anagen), a degeneration period (catagen), and a rest period (telogen) with different periods. To do. Such a cycle is repeated over 3 to 6 years. As a result, an average of 50 to 100 hairs per day are lost. Alopecia is a phenomenon that occurs when the hair ratio in the growing period is shortened and the hair ratio in the degenerative or resting period is increased. The reason for hair loss is that male hormone androgen is excessively secreted from organs such as hair roots and sebaceous glands, and hair growth is delayed by strongly stimulating hair follicle cells to atrophy the hair follicles. It is done. Other major causes include impaired nutrient supply due to impaired local blood flow, excessive sebum secretion, peroxide, reduced scalp function due to bacteria, strong external stress, and worsening neurological symptoms due to chronic diseases. Yes. Moreover, after entering the modern society, hair loss is more serious due to overwork, environmental pollution and side effects due to misuse of addictive drugs, blood flow disturbance and inheritance of the scalp due to the use of perms, staining, mousse, spray, etc. As it becomes, interest in hair growth is increasing. Recently, not only male-type hair loss, but also obesity hair loss in women, and the tendency of hair loss in the younger layer to be diffused. Agents or hair restorers are commercially available. Commercially available hair growth agents or hair growth agents include vasodilators such as carpronium chloride and minoxidil, and hormone agents such as estrogen and estradiol that inhibit male hormone action, pentadecanoic acid and finasteride. There are male hormone activity inhibitors such as (finasteride).
脱毛症の治療や予防及び発毛促進用薬物として、現在まで最も広く使用される製剤は、米国特許第4,596,812号に開示されているUpjohn社のミノキシジル含有製剤があって、現在まで米国FDAの承認を受けた二つの発毛剤成分の一つである。ミノキシジルは、血圧降下の目的で開発された高血圧治療剤であるが、使用上の副作用として発毛現象が現れ、今は発毛剤としてもっと有名な薬物となった。ミノキシジルの発毛作用メカニズムについては、正確に明かされていないが、血管拡張効果による血流量の増加により毛根に栄養を供給して、毛髪の成長を促進すると考えられている。このような血流量増加モデルは、ミノキシジルが、毛根を構成する主要細胞である毛乳頭(dermal papilla)において、血管拡張に係わる成長因子の血管上皮成長因子(VEGF; vascular endothelial growth factor)の発現を増加させるとの最近の報告(文献[Br. J. of Dermatol., 1998; 138; 407-411])により間接的に証明される。また、ミノキシジルの発毛効果メカニズムにおいて、血管拡張効果の他にも、体外培養中の毛根の毛乳頭細胞活性化(文献[Skin Pharmacol., 1996; 9; 3-8])及び毛嚢組織培養において毛嚢の成長を促進するとの報告(文献[J. Invest. Dermatol., 1989; 92; 315-320])などは、ミノキシジルが毛根に直接的な成長因子として作用することを示唆している。また、最近発売が始まったMerck社のプロペシア(Propecia)の主成分であるフィナステライドは、男性ホルモンであるテストステロンが、5α-reductaseの作用によりさらに強力な形態の男性ホルモンであるジヒドロテストステロン(DHT: dihydrotestosterone)に転換されることを抑制する。1997年12月、男性型脱毛症の治療剤として、1mgタブレットがFDAから使用承認を受けて、現在市販中であって、臨床結果、有意な効果を示すと判明された(文献[J. Am. Acad. Dermatol., 1998; 39; 578-589])。その他にも、天然物及び生薬成分の抽出物を頭皮に塗るか、服用することにより発毛を促進しようとする試みが数多くなされてきた。 The most widely used preparations to date for the treatment and prevention of alopecia and hair growth promotion are Upjohn's minoxidil-containing preparations disclosed in US Pat. No. 4,596,812. It is one of two hair growth ingredients that have been approved by the US FDA. Minoxidil is a therapeutic agent for hypertension developed for the purpose of lowering blood pressure. However, hair growth occurred as a side effect of use, and it has become a more famous drug as a hair growth agent. Although the mechanism of the hair growth action of minoxidil has not been clarified accurately, it is thought that the growth of hair is promoted by supplying nutrients to the hair root by increasing the blood flow volume due to the vasodilatory effect. In this blood flow increase model, minoxidil expresses the expression of vascular endothelial growth factor (VEGF), a growth factor involved in vasodilation, in the dermal papilla, the main cell that makes up the hair root. It is indirectly proved by a recent report of increasing (ref. [Br. J. of Dermatol., 1998; 138; 407-411]). Moreover, in the hair growth effect mechanism of minoxidil, in addition to the vasodilatory effect, hair follicle papillary cell activation during in vitro culture (reference [Skin Pharmacol., 1996; 9; 3-8]) and hair follicle tissue culture (J. Invest. Dermatol., 1989; 92; 315-320]) suggest that minoxidil acts as a direct growth factor on hair roots . Finasteride, the main component of Merck's recently launched Propecia, is a male hormone, testosterone, which is a more powerful form of the male hormone dihydrotestosterone (DHT: dihydrotestosterone) due to the action of 5α-reductase. ) Is suppressed. In December 1997, a 1 mg tablet was approved for use by the FDA as a treatment for androgenetic alopecia. It is now on the market, and clinical results have shown that it has a significant effect (reference [J. Am Acad. Dermatol., 1998; 39; 578-589]). In addition, many attempts have been made to promote hair growth by applying or taking extracts of natural products and herbal ingredients on the scalp.
脱毛症の予防及び治療に広く使用されているミノキシジルや塩化カプロニウムは、臨床効果に優れていないという問題点を有しており、男性ホルモンの抑制のためのホルモン剤と男性ホルモン活性抑制剤は、臨床効果があまり高くないか、男性機能を抑制する副作用などの問題点があるばかりか、活性成分が合成化合物であって、人体内で安全性に問題があり、発毛、育毛においても十分な効果を得ることが難しい。また、各種抽出物を含有した毛髪改善用組成物は、その作用原理が明確ではなく、効能が十分検証されていないという実情があり、皮膚に塗布時、有効成分の吸収力が低く、頭皮に残ってべたつくなど、皮膚感触がよくないが、皮膚異常を起こす問題点がある。化学薬品の副作用による発毛剤の限界を克服するために、頭皮に髪の毛を移植する手術方法が提案されたが、髪の毛を一々移植する過程でかなりの費用がかかるだけではなく、移植期間が長期化されて、臨時的な処方に過ぎず、根本的な治療方法にはならないという問題点がある。 Minoxidil and capronium chloride, which are widely used for the prevention and treatment of alopecia, have the problem that they are not excellent in clinical effects. Hormonal agents for suppressing male hormones and male hormone activity inhibitors are: Not only the clinical effect is not very high, there are problems such as side effects that suppress male function, but the active ingredient is a synthetic compound, there are safety problems in the human body, and it is sufficient for hair growth and hair growth It is difficult to obtain an effect. In addition, the composition for improving hair containing various extracts has the fact that its principle of action is not clear and its efficacy has not been sufficiently verified. The skin feels bad, such as remaining sticky, but there are problems that cause skin abnormalities. In order to overcome the limitations of hair growth agents due to side effects of chemicals, a surgical method for transplanting hair to the scalp has been proposed, but not only is it costly in the process of transplanting hair one by one, but the transplant period is also long. There is a problem in that it is merely a temporary prescription and does not become a fundamental treatment method.
毛髪は、大きく毛表皮、毛皮質、毛髄質の三つの部分から構成されており、毛髄質を包んでいる毛皮質は、毛髪において最も厚い部分(80〜90%)であって、メラノソームというメラニン色素と脂質膜とTRP(Tyrosinase Related Protein)−1、TRP−2及びその他のタンパク質から構成された顆粒を含んでいる。メラニン色素は、メラノサイト内の小器官であるメラノソームで合成されて、メラノサイトの樹状突起を通じて、周囲のケラチノサイトに移行する。メラニンの合成経路をみると、まず、アミノ酸のチロシンが酸化されてドパに、さらに酸化されてドパキノンが生成される段階でチロシナーゼが関与して、その後の反応は、自動酸化的に進行されるが、TRP−1及びTRP−2のような酵素が関与して反応を加速化させると知られている。チロシンを原料として形成されるユーメラニン(eumelanin)及びフェオメラニン(pheomelanin)の類型と分布量などの要因により、毛髪の明るさが決定されて、人毎に独特の毛髪色が表れる。ユーメラニンは、最も有り触れて最も濃い色素であって、褐色と黒色の髪を形成して、フェオメラニンは、より薄い色の色調であって、金髪を形成する。白毛は、ドパキノンでその作用が止まって、毛髪がケラチン化されて形成された白髪であって、チロシナーゼを作れないため、酸化作用がなされなかった状態である。白毛は、特に黒褐色系の毛髪を有する人種においてさらに明確に現れて、メラノサイトでメラニン生成が止まったから起こる現象であって、一種の老化現象である。このような老人性白髪の他にも、壮年性白髪、遺伝性白毛、尋常性白斑、円形脱毛症などによる後天性白毛、薬物及び化学物質による白髪、ストレスによる白毛、自己免疫性疾患による白髪、栄養失調及び栄養不均衡による白毛、腎臓機能低下による白毛などがある。 The hair is mainly composed of three parts: the epidermis, fur, and medulla, and the fur that wraps the medulla is the thickest part (80-90%) of the hair, and the melanin called melanosomes It contains granules composed of pigment, lipid membrane, TRP (Tyrosinase Related Protein) -1, TRP-2 and other proteins. Melanin pigments are synthesized in melanosomes, which are organelles in melanocytes, and migrate to the surrounding keratinocytes through the dendrites of melanocytes. Looking at the synthetic pathway of melanin, first, the amino acid tyrosine is oxidized to dopa, and tyrosinase is involved in the further oxidation to produce dopaquinone, and the subsequent reaction proceeds autoxidatively. However, it is known that enzymes such as TRP-1 and TRP-2 are involved to accelerate the reaction. The brightness of hair is determined by factors such as the type and distribution amount of eumelanin and pheomelanin formed from tyrosine, and a unique hair color appears for each person. Eumelanin is the most common and darkest pigment, forming brown and black hair, and pheomelanin is a lighter shade of color, forming a blonde. White hair is white hair formed by dopaquinone that stops its action and is keratinized, and cannot produce tyrosinase, and thus is not oxidized. White hair appears more clearly in races with dark brown hair, and is a phenomenon that occurs because melanin production stops in melanocytes, and is a kind of aging phenomenon. In addition to such senile gray hair, senile gray hair, hereditary white hair, vulgaris vulgaris, acquired white hair due to alopecia areata, white hair due to drugs and chemicals, white hair due to stress, autoimmune diseases White hair due to malnutrition, white hair due to malnutrition and nutritional imbalance, and white hair due to decreased kidney function.
遺伝子により発生する白毛は、遺伝子治療に期待するか、疾患による白毛は、その疾患を治療することにより解決できる。その他の場合は、民間療法として、何首烏やひねショウガ、ひじき、乾地黄、熟地黄、桑の実、プランチーノオイル、竹油、熊脂などを使用する方法が知られているが、大きい効果を期待することは難しい実情である。 The white hair generated by a gene can be expected by gene therapy, or the white hair caused by a disease can be solved by treating the disease. In other cases, as a folk remedy, it is known how to use garlic, kinkweed, hijiki, dry yellow, maturity yellow, mulberry, plancino oil, bamboo oil, bear fat, etc. It is a difficult situation to expect.
一方、希土類元素は、地殻中に約0.016%が含有されている微量の金属元素であって、元素周期律表の原子番号57から71まで15個(La, Ce, Pr, Nd, Pm, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Lu)と第3A族の2個(Sc,Y)とを合わせて、17個の元素が含有された鉱物を意味する。希土類元素は、対イオンと共にイオン結合した塩(salt)の形態、例えば、硫酸塩、硝酸塩、炭酸塩、アセト酸塩、燐酸塩、塩化物などの形態や、水酸化物(hydroxides)を始めとした酸化物(oxides)形態として存在することができる。希土類元素は、発見されてから200余年しか過ぎておらず、一般人にはよく知られていないが、その利用価値は非常に大きくて、希土類元素が有している特異な電子構造により、独特の物理的、化学的性能を示すため、永久磁石、超伝導体、蛍光材料のように、機械、石油化学、光化学などに利用されており、最近は、農業、林業、畜産業などの様々な分野でも応用が試みられている。ひいては、生物学的効果として、希土類元素は、高等植物の光合成作用と葉緑素形成を促進して、芽の発芽促進、根の活力、呼吸作用の活性化、体内養分移動の促進、水分調節、細胞分裂の促進、ホルモン転移移送の促進、栄養元素の吸収と体内移動の促進、物質代謝の活性化、葉内のRNAとタンパク質合成増加などの機能を示して、葉の老化過程を遅延させて、緑藻類のタンパク質含量を高めて、光合成と酸素放出活性を促進させて、タンパク質と葉緑素形成を促進させる。La3+は、ヒトの赤血球細胞膜の(Na+、K+)−ATP酵素と、Mg2+−ATP酵素の活性を増加させて、体内Ca2+イオンの機能を強化することが知られており(文献[The Journal of Biological Chemistry; 1986; 261(20); 9552-9557])、一部の希土類元素は、抗細菌効果を有し(文献[Chem. Pharm. Bull.; 2003; 51(5); 494-498]、活性酸素の生成を抑制し、抗酸化作用を示し(文献[Biochemical and Biophysical Research Communication; 2006. 2; 342; 86-91])、いくつかの希土類元素は、アルカリ性イオンを帯びて、遠赤外線との作用により、体内の細胞活性、血液循環促進、新陳代謝強化、組織再生の能力増加により、疲労と老化現象を抑制する効果があることが公知であり、成長肥育豚において、体重増加と飼料転換率を増進(文献[J. Anim. Physiol. a. Anim. Nutr.; 2001; 85; 263-270])させることが知られている。また、希土類元素は、低毒性物質に属して、消化器官を通じての吸収はごく少なく、特別な体内蓄積現象がなく、奇形を招来するか、突然変異を起こすか、癌を誘発する作用もないことが明かされた(文献[Environmental Health Perspectives; 1996; 104; 85-95])。 On the other hand, rare earth elements are trace amounts of metal elements containing about 0.016% in the earth's crust, and 15 elements (La, Ce, Pr, Nd, Pm) from atomic numbers 57 to 71 in the periodic table of elements. , Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Lu) and two members of Group 3A (Sc, Y), mean a mineral containing 17 elements. Rare earth elements are in the form of salts that are ion-bonded with counterions, such as sulfate, nitrate, carbonate, acetoate, phosphate, chloride, and hydroxides. It can exist in the form of oxidized oxides. Rare earth elements have only been over 200 years since they were discovered and are not well known to the general public, but their utility value is so great that the unique electronic structure of rare earth elements makes them unique. In order to show physical and chemical performance, it is used in machinery, petrochemistry, photochemistry, etc. like permanent magnets, superconductors and fluorescent materials. Recently, it is used in various fields such as agriculture, forestry, and livestock industry. But application is being tried. As a biological effect, rare earth elements promote photosynthetic action and chlorophyll formation in higher plants, promote bud germination, root vitality, activation of respiratory action, promote nutrient transfer, water regulation, cells Delaying the senescence process of the leaf, showing functions such as promoting division, promoting transfer of hormone transfer, promoting absorption of nutrient elements and transport, activation of substance metabolism, increased RNA and protein synthesis in the leaf, Increases protein content of green algae, promotes photosynthesis and oxygen release activity, promotes protein and chlorophyll formation. La 3+ is known to enhance the function of Ca 2+ ions in the body by increasing the activity of (Na + , K + ) -ATP enzyme and Mg 2+ -ATP enzyme in human erythrocyte cell membrane (References) [The Journal of Biological Chemistry; 1986; 261 (20); 9552-9557]), some rare earth elements have an antibacterial effect (Chem. Pharm. Bull .; 2003; 51 (5); 494-498], which suppresses the production of active oxygen and exhibits antioxidant activity (Literature [Biochemical and Biophysical Research Communication; 2006. 2; 342; 86-91]), and some rare earth elements carry alkaline ions. It is known that it has the effect of suppressing fatigue and aging phenomenon by the action of far infrared rays, the cell activity in the body, the promotion of blood circulation, the enhancement of metabolism, the increase of tissue regeneration ability, Increase and feed conversion rate (reference [J. Anim. Physiol. A. Anim. Nutr .; 2001; 85; 263-270]) In addition, rare earth elements belong to low-toxic substances and are hardly absorbed through the digestive tract and have no special internal accumulation phenomenon, leading to malformations, mutations, or cancer. It was revealed that there was no inducing effect (Reference [Environmental Health Perspectives; 1996; 104; 85-95]).
大韓民国特許第569,083号は、酸化セリウムに、4価のセリウムイオンより大きいイオン半径を有する金属イオン及び/または4価のセリウムイオンより低原子価の金属イオンを固溶させてなされる金属酸化物固溶酸化セリウムを含む紫外線遮断剤と、これを含有する化粧料を開示して、これが頭髪化粧料としても使用可能であることを記載している。しかしながら、これは、酸化セリウムの金属イオン固溶体に関するもので、希土類元素やその塩または混合希土を使用することとは全く相異なるものである。米国特許第5,112,360号は、5,6−ジヒドロキシインドール及び/またはインドール誘導体及び少なくとも一つの希土類元素塩を含有する染毛剤を開示している。しかしながら、これは、インドール化合物と希土類元素塩からなる組成物の染毛効果に関するもので、毛根や毛髪に適用時、希土類元素が単独で直接的な黒毛生成促進効果を有することについては、教示や暗示が全くない。また、日本特開2003−137749号(2003.5.14.公開)は、ランタン(La)、ネオジミウム(Nd)、サマリウム(Sm)、ガドリニウム(Gd)またはルテチウム(Lu)のような天然放射性希土類元素を含む天然鉱石を粒径5μm以下に微分化して、これを着色剤と共に、アルコール系溶媒及びこれに可溶の溶質からなる粘液状バインダー中に混合した混合材料をスプレー容器に入れてなされることを特徴とする、スプレー容器に入っている増毛剤を開示している。前記公開特許は、毛髪の欠損部分に処置して、視覚的に増毛したように見せかけながら、頭皮付近の環境を改善し、自毛の再生乃至育毛を促進するための増毛乃至偽増毛剤に関するもので、スプレー後、頭皮に付着された放射性希土類元素が放出するβ線がマイナスイオンを形成し血行促進作用をして、自毛の再生または育毛を促進する効果を示すと記述している。しかしながら、前記公開特許は、天然放射性希土元素単独のβ線放出による血行促進作用及びそれにより期待される増毛乃至育毛効果に関するもので、希土元素による細胞増殖の促進、TGF−β発現の抑制、VEGF発現の促進、チロシナーゼ活性及び発現の促進、メラニン生成の促進については、全く触れていない。 Korean Patent No. 569,083 is a metal oxide formed by dissolving cerium oxide with a metal ion having an ionic radius larger than a tetravalent cerium ion and / or a metal ion having a lower valence than the tetravalent cerium ion. An ultraviolet blocking agent containing solid solution cerium oxide and a cosmetic containing the same are disclosed, and it is described that this can also be used as a hair cosmetic. However, this relates to a metal ion solid solution of cerium oxide, which is completely different from the use of rare earth elements, their salts or mixed rare earth. US Pat. No. 5,112,360 discloses hair dyes containing 5,6-dihydroxyindole and / or indole derivatives and at least one rare earth element salt. However, this is related to the hair dyeing effect of a composition comprising an indole compound and a rare earth element salt. When applied to hair roots and hair, the rare earth element alone has a direct black hair production promoting effect. There is no suggestion. Japanese Unexamined Patent Publication No. 2003-137749 (2003.14.14) discloses a natural radioactive rare earth such as lanthanum (La), neodymium (Nd), samarium (Sm), gadolinium (Gd) or lutetium (Lu). Natural ore containing elements is differentiated to a particle size of 5 μm or less, and this is mixed with a coloring agent and mixed material mixed in an alcoholic solvent and a viscous binder made of a solute soluble in this into a spray container. A hair thickener contained in a spray container is disclosed. The published patent relates to a hair thickening or false hair thickening agent for treating hair defects and improving the environment near the scalp while making it appear as if the hair has been visually increased, and promoting the regeneration or growth of the own hair. Thus, after spraying, it is described that β-rays released by radioactive rare earth elements attached to the scalp form negative ions and promote blood circulation, thereby showing the effect of promoting self-renewal or hair growth. However, the above-mentioned published patent relates to the blood circulation promoting action by β-ray emission of natural radioactive rare earth element alone and the expected hair growth or hair growth effect. The promotion of cell growth and the suppression of TGF-β expression by the rare earth element. No mention is made of promotion of VEGF expression, tyrosinase activity and expression, or promotion of melanin production.
本発明者らは、既存の発毛剤の様々な問題点を考慮し、人体に安全で且つ副作用を起こすことなく、優れた脱毛防止、発毛促進、育毛、ふけの除去及び予防、黒毛生成促進剤を開発するために、持続的な研究を行ってきた。その結果、驚くことに、一つ以上の希土類元素が前記用途に効果的に使用できることを確認し、本発明を完成した。 In consideration of various problems of existing hair growth agents, the present inventors are excellent in hair loss prevention, hair growth promotion, hair growth, dandruff removal and prevention, black hair generation, which is safe to the human body and causes no side effects. Sustained research has been conducted to develop accelerators. As a result, it was surprisingly confirmed that one or more rare earth elements can be effectively used for the above-mentioned purposes, and the present invention has been completed.
したがって、本発明の第1目的は、一つ以上の希土類元素を含有する脱毛防止、発毛促進、育毛、ふけの除去及び予防、または黒毛生成促進用の組成物を提供することである。 Accordingly, a first object of the present invention is to provide a composition for preventing hair loss, promoting hair growth, hair growth, removing and preventing dandruff, or promoting black hair generation, which contains one or more rare earth elements.
本発明の第2目的は、一つ以上の希土類元素の脱毛防止、発毛促進、育毛、ふけの除去及び予防、または黒毛生成促進のための用途を提供することである。 The second object of the present invention is to provide a use for preventing hair loss of one or more rare earth elements, promoting hair growth, hair growth, removing and preventing dandruff, or promoting black hair production.
本発明の第3目的は、一つ以上の希土類元素を利用する脱毛防止、発毛促進、育毛、ふけの除去及び予防、または黒毛生成促進方法を提供することである。 The third object of the present invention is to provide a method for preventing hair loss, promoting hair growth, growing hair, removing and preventing dandruff, or promoting black hair generation using one or more rare earth elements.
本発明の第4目的は、一つ以上の希土類元素を利用して、脱毛防止、発毛促進、育毛、ふけの除去及び予防、または黒毛生成促進剤を製造する方法を提供することである。 The fourth object of the present invention is to provide a method for preventing hair loss, promoting hair growth, hair growth, removing and preventing dandruff, or producing a black hair production promoter using one or more rare earth elements.
本発明の第1面は、 有効成分として、セリウム(Ce)、プラセオジミウム(Pr)、プロメチウム(Pm)、ユーロピウム(Eu)、テルビウム(Tb)、ジスプロシウム(Dy)、ホルミウム(Ho)、エルビウム(Er)、ツリウム(Tm)、イッテルビウム(Yb)、スカンジウム(Sc)、イットリウム(Y)、ランタン(La)、ネオジム(Nd)、サマリウム(Sm)、ガドリニウム(Gd)、ルテチウム(Lu)及びこれらの混合物から構成された群から選択される希土類元素、またはその塩若しくは酸化物を含有する、脱毛防止、発毛促進、育毛、ふけの除去及び予防、または黒毛生成促進用組成物に関する。 According to the first aspect of the present invention, as an active ingredient, cerium (Ce), praseodymium (Pr), promethium (Pm), europium (Eu), terbium (Tb), dysprosium (Dy), holmium (Ho), erbium (Er) ), Thulium (Tm), ytterbium (Yb), scandium (Sc), yttrium (Y), lanthanum (La), neodymium (Nd), samarium (Sm), gadolinium (Gd), lutetium (Lu) and mixtures thereof The present invention relates to a composition for preventing hair loss, promoting hair growth, hair growth, removing and preventing dandruff, or promoting black hair production, comprising a rare earth element selected from the group consisting of: or a salt or oxide thereof.
本発明の第2面は、セリウム(Ce)、プラセオジミウム(Pr)、プロメチウム(Pm)、ユーロピウム(Eu)、テルビウム(Tb)、ジスプロシウム(Dy)、ホルミウム(Ho)、エルビウム(Er)、ツリウム(Tm)、イッテルビウム(Yb)、スカンジウム(Sc)、イットリウム(Y)、ランタン(La)、ネオジム(Nd)、サマリウム(Sm)、ガドリニウム(Gd)、ルテチウム(Lu)及びこれらの混合物から構成された群から選択される希土類元素、またはその塩若しくは酸化物の脱毛防止、発毛促進、育毛、ふけの除去及び予防、または黒毛生成促進のための用途に関する。 The second aspect of the present invention includes cerium (Ce), praseodymium (Pr), promethium (Pm), europium (Eu), terbium (Tb), dysprosium (Dy), holmium (Ho), erbium (Er), thulium ( Tm), ytterbium (Yb), scandium (Sc), yttrium (Y), lanthanum (La), neodymium (Nd), samarium (Sm), gadolinium (Gd), lutetium (Lu) and mixtures thereof The present invention relates to a use of a rare earth element selected from the group, or a salt or oxide thereof for preventing hair loss, promoting hair growth, growing hair, removing and preventing dandruff, or promoting black hair production.
本発明の第3面は、脱毛防止、発毛促進、育毛、ふけの除去及び予防、または黒毛生成促進を必要とする対象に、セリウム(Ce)、プラセオジミウム(Pr)、プロメチウム(Pm)、ユーロピウム(Eu)、テルビウム(Tb)、ジスプロシウム(Dy)、ホルミウム(Ho)、エルビウム(Er)、ツリウム(Tm)、イッテルビウム(Yb)、スカンジウム(Sc)、イットリウム(Y)、ランタン(La)、ネオジム(Nd)、サマリウム(Sm)、ガドリニウム(Gd)、ルテチウム(Lu)及びこれらの混合物から構成された群から選択される希土類元素、またはその塩若しくは酸化物を適用する段階を含む、脱毛防止、発毛促進、育毛、ふけの除去及び予防、または黒毛生成促進方法に関する。 The third aspect of the present invention provides cerium (Ce), praseodymium (Pr), promethium (Pm), and europium for subjects that require hair loss prevention, hair growth promotion, hair growth, dandruff removal and prevention, or black hair generation promotion. (Eu), terbium (Tb), dysprosium (Dy), holmium (Ho), erbium (Er), thulium (Tm), ytterbium (Yb), scandium (Sc), yttrium (Y), lanthanum (La), neodymium Hair loss prevention comprising applying a rare earth element selected from the group consisting of (Nd), samarium (Sm), gadolinium (Gd), lutetium (Lu) and mixtures thereof, or a salt or oxide thereof, The present invention relates to a method for promoting hair growth, hair growth, removing and preventing dandruff, or promoting black hair generation.
本発明の第4面は、セリウム(Ce)、プラセオジミウム(Pr)、プロメチウム(Pm)、ユーロピウム(Eu)、テルビウム(Tb)、ジスプロシウム(Dy)、ホルミウム(Ho)、エルビウム(Er)、ツリウム(Tm)、イッテルビウム(Yb)、スカンジウム(Sc)、イットリウム(Y)、ランタン(La)、ネオジム(Nd)、サマリウム(Sm)、ガドリニウム(Gd)、ルテチウム(Lu)及びこれらの混合物から構成された群から選択される希土類元素、またはその塩若しくは酸化物を利用して、脱毛防止、発毛促進、育毛、ふけの除去及び予防、または黒毛生成促進剤を製造する方法に関する。 The fourth aspect of the present invention includes cerium (Ce), praseodymium (Pr), promethium (Pm), europium (Eu), terbium (Tb), dysprosium (Dy), holmium (Ho), erbium (Er), thulium ( Tm), ytterbium (Yb), scandium (Sc), yttrium (Y), lanthanum (La), neodymium (Nd), samarium (Sm), gadolinium (Gd), lutetium (Lu) and mixtures thereof The present invention relates to a method for preventing hair loss, promoting hair growth, hair growth, removing and preventing dandruff, or producing a black hair production promoter using a rare earth element selected from the group, or a salt or oxide thereof.
以下、本発明を詳細に説明する。 Hereinafter, the present invention will be described in detail.
本発明で使用された用語‘脱毛防止’は、部分的または完全脱毛の防止、抑制、阻止及び減少を意味する。 As used herein, the term 'anti-hair loss' refers to the prevention, inhibition, inhibition and reduction of partial or complete hair loss.
本発明で使用された用語‘発毛促進’は、毛髪発生の維持、誘導、刺激、促進及び再生、欠損毛髪の成長、または毛髪周期において成長期の延長を包括する意味として定義する。 The term 'promoting hair growth' as used in the present invention is defined as the meaning encompassing the maintenance, induction, stimulation, promotion and regeneration of hair development, the growth of defective hair, or the extension of the growth phase in the hair cycle.
本発明で使用された用語‘育毛’は、柔毛の脱落防止、発育/成長促進、または 柔毛を末端毛に転換させることを包括する意味として定義する。 The term 'hair growth' used in the present invention is defined as a comprehensive meaning that prevents fur from falling off, promotes growth / growth, or converts fur into terminal hair.
本発明において、‘脱毛’または‘脱毛症’は、毛髪成長の欠損及び部分的あるいは全体的な毛髪の喪失を意味し、男性ホルモン性脱毛症または男性型脱毛症、毒性脱毛症、円形脱毛症、休止期脱毛症、内分泌異常、代謝障害、栄養障害による脱毛、薬剤性脱毛症、機械的脱毛症、皮膚疾患に伴われる脱毛症、瘢痕性脱毛症、先天性脱毛症、トリコチロマニアなどを全て含むが、これらに制限されるものではない。 In the present invention, 'hair loss' or 'hair loss' means loss of hair growth and partial or total hair loss, androgenic alopecia or androgenetic alopecia, toxic alopecia, alopecia areata , Resting alopecia, endocrine abnormalities, metabolic disorders, nutritional disorders, drug-induced alopecia, mechanical alopecia, alopecia associated with skin diseases, scarring alopecia, congenital alopecia, tricotyromania, etc. Including but not limited to all.
希土類元素は、互いに類似した物理化学的性質を共有するため、本発明で使用可能な希土類元素の種類に特に制限はなく、希土類元素のいずれか一つを単独またはその他の希土類元素との混合物として使用することができ、セリウム(Ce)を使用することがより好ましい。希土類元素の塩も同様に、薬剤学的または化粧学的に許容される無毒性のものである限り、使用可能であって、その例としては、硫酸塩、硝酸塩、炭酸塩、アセト酸塩、リン酸塩、塩化物などが挙げられるが、これらに限定されるものではない。希土類元素の酸化物(例えば、Ce2O3、La2O3など)も同様に、薬剤学的または化粧学的に許容される無毒性のものである限り、制限なく使用可能である。本発明において、希土類元素の酸化物は、希土類元素の水酸化物(例えば、Ce(OH)3、La(OH)3など)を含む概念である。 Since rare earth elements share similar physicochemical properties, there is no particular limitation on the type of rare earth elements that can be used in the present invention, and any one of the rare earth elements can be used alone or as a mixture with other rare earth elements. It is more preferable to use cerium (Ce). Rare earth element salts can be used as long as they are non-toxic, pharmaceutically or cosmetically acceptable, and examples thereof include sulfates, nitrates, carbonates, acetoates, Examples thereof include, but are not limited to, phosphates and chlorides. Similarly, oxides of rare earth elements (for example, Ce 2 O 3 , La 2 O 3 and the like) can be used without limitation as long as they are non-toxic pharmaceutically or cosmetically acceptable. In the present invention, the rare earth element oxide is a concept including a rare earth element hydroxide (eg, Ce (OH) 3 , La (OH) 3, etc.).
本発明において、希土類元素は、微細粉末に粉砕して使用でき、0.0001〜10重量%、好ましくは、0.001〜10重量%、より好ましくは0.001〜0.1重量%として含有される。 In the present invention, the rare earth element can be used by being pulverized into a fine powder, and is contained as 0.0001 to 10% by weight, preferably 0.001 to 10% by weight, more preferably 0.001 to 0.1% by weight. Is done.
本発明の組成物は、薬剤学的または化粧学的に許容される担体をさらに含有することができる。本発明の組成物は、製薬または化粧品製造分野で通常的に使用されるか、よく知られている装置及び方法のいずれかを使用して製造することができる(文献[Remington's Pharmaceutical Science, 15th Edition, 1975, Mack Publishing Company, Easton, Pennsylvania 18042 (Chapter 87: Balug, Seymour)])。本発明の組成物は、通常基剤を含有して、必要に応じて、一般に薬品または化粧品原料として使用される成分を適宜配合することができる。本発明の組成物の基剤は、通常的に使用されるいかなるものでも使用可能であって、その例は、精製水、ミネラルウォーター、エタノール、グリセリン、スクアレン、1,3−プロピレングリコール、1,3−ブチレングリコール、蓖麻子油、ツバキ油、liquid petrolatumを含む。本発明の組成物に配合されるその他の成分の例は、界面活性剤、乳化剤、増粘剤、防腐剤、酸化防止剤、香料を含み、これらに限定されるものではない。 The composition of the present invention may further contain a pharmaceutically or cosmetically acceptable carrier. The compositions of the present invention are commonly used in the pharmaceutical or cosmetic manufacturing field or can be prepared using any of the well-known devices and methods (see [Remington's Pharmaceutical Science, 15th Edition). , 1975, Mack Publishing Company, Easton, Pennsylvania 18042 (Chapter 87: Balug, Seymour)]). The composition of the present invention usually contains a base, and if necessary, components generally used as chemicals or cosmetic raw materials can be appropriately blended. As the base of the composition of the present invention, any commonly used one can be used, and examples thereof include purified water, mineral water, ethanol, glycerin, squalene, 1,3-propylene glycol, 1, Contains 3-butylene glycol, coconut oil, camellia oil, and liquid petrolatum. Examples of other components blended in the composition of the present invention include, but are not limited to, surfactants, emulsifiers, thickeners, preservatives, antioxidants, and perfumes.
界面活性剤は、カチオン界面活性剤、アニオン界面活性剤または非イオン界面活性剤である。カチオン界面活性剤の例は、ラウリン酸、ミリスチン酸、パルミチン酸、ステアリン酸、及びオレイン酸などの高級脂肪酸のアルカリ塩類(例えば、ナトリウム塩、カリウム塩、アンモニウム塩、トリエタノールアミン塩);ラウリル硫酸ナトリウム及びラウリル硫酸トリエタノールアミンなどのアルキル硫酸エステル塩類;及びポリオキシエチレンラウリルエーテル硫酸ナトリウム及びポリオキシエチレンラウリルエーテル硫酸トリエタノールアミンなどのアルキルエーテル硫酸エステル塩類を含む。非イオン界面活性剤の例は、ポリオキシエチレンラウリルエーテル及びポリオキシエチレンオレイルエーテルなどのポリオキシエチレンアルキルエーテル類;及びヤシ油脂肪酸ジエタノールアミド及びラウリン酸ジエタノールアミドなどのアルカノールアミドを含む。アニオン界面活性剤の例は、塩化ステアリルトリメチルアンモニウム、塩化セチルトリメチルアンモニウム及び塩化ステアリルビス(ジエチルアルコール)ヒドロキシエチルアンモニウムを含む。 The surfactant is a cationic surfactant, an anionic surfactant or a nonionic surfactant. Examples of cationic surfactants are alkali salts of higher fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, and oleic acid (eg sodium salt, potassium salt, ammonium salt, triethanolamine salt); lauryl sulfate Alkyl sulfate salts such as sodium and lauryl sulfate triethanolamine; and alkyl ether sulfate salts such as polyoxyethylene lauryl ether sodium sulfate and polyoxyethylene lauryl ether sulfate triethanolamine. Examples of nonionic surfactants include polyoxyethylene alkyl ethers such as polyoxyethylene lauryl ether and polyoxyethylene oleyl ether; and alkanolamides such as coconut oil fatty acid diethanolamide and lauric acid diethanolamide. Examples of anionic surfactants include stearyl trimethyl ammonium chloride, cetyl trimethyl ammonium chloride and stearyl bis (diethyl alcohol) hydroxyethyl ammonium chloride.
乳化剤の例は、セタノール、ステアリルアルコール及びベヘニルアルコールを含む。 Examples of emulsifiers include cetanol, stearyl alcohol and behenyl alcohol.
増粘剤の例は、アルギン酸ナトリウム、メチルセルロース、カルボキシメチルセルロース、ポリビニルアルコール及びポリビニルピロリドンを含む。 Examples of thickeners include sodium alginate, methyl cellulose, carboxymethyl cellulose, polyvinyl alcohol and polyvinyl pyrrolidone.
防腐剤の例は、パラヒドロキシ安息香酸エチル、パラヒドロキシ安息香酸ブチル及び塩化ベンズアルコニウムを含む。 Examples of preservatives include ethyl parahydroxybenzoate, butyl parahydroxybenzoate and benzalkonium chloride.
酸化防止剤の例は、ブチルヒドロキシトルエン、プロピルガレート及びブチルヒドロキシアニソールを含む。 Examples of antioxidants include butylhydroxytoluene, propyl gallate and butylhydroxyanisole.
香料は、一般的な目的で主に使用されるパーヒュームであって、その例は、シトラス、ラベンダー、フローラルを含む。 Perfumes are perfumes that are mainly used for general purposes, examples of which include citrus, lavender and floral.
本発明の組成物には、上記成分の他にも、毛嚢に栄養素を供給する役割をするグルコース、キシロース、マンノース、アラビノースなどの単糖類及びマルトース、スクロース、セロビオース、トレハロースなどの二糖類などの糖類から1種以上をさらに含むことができ、これらの量は、全体組成物の0.01〜1重量%が好ましい。また、本発明の組成物は、通常的に使用される毛髪成長促進補助成分を含むことができるが、例えば、人参、苦参、みかん陳皮、緑茶、ニンジン、桔梗、桑椹子、タンキリマメ、石榴皮、松葉、月見子、コノテガシワの葉、何首烏、旱蓮草、トリビュラス抽出物、ベタイン、ハッカ抽出物、イラクサ抽出物、トクサ抽出物、ラベンダー抽出物、ホップ抽出物、アロエ、エゾウコギ、冬蟲夏草、トックリイチゴ、桑の実、木酢液、竹塩、黄花黄蓍、オニノタケ、枸杞子、胡桃、ブドウ、サフラワー、ゴマ、エゴマ、ニンニク、昆布、ワカメ、梅、緑豆、黒米、ペンタデカン酸グリセリド、ヒノキチオール、トウガラシチンキ、ショウガチンキ、カンタリスチンキ、フォルスコリン、トランス−3,4’−ジメチル−3−ヒドロキシフラバノン、アセト酸トコフェロールなどのトコフェロール類、ニコチン酸、ニコチン酸アミド、パルミチン酸レチノール、β−カロチン、 カルシフェロール、 葉酸、ビオチン、D−パントテニルアルコール、アセチルパントテニルエチルエーテル、パントテン酸カルシウム、パントテニルエチルエーテル、アスコルビン酸、グレープフルーツの種抽出物、セファランチン、ニコチン酸ベンジルエステル、ビタミンA、B1、B2、B6及びその誘導体、パントテン酸及びその誘導体、ミノキシジル、ムラサキセンブリ抽出液、アルギニン、アスパラギン酸、メチオニン、セリン、グリシン、グルタミン酸、シスチン、アミノ酸エキス、β−グリシレチン酸、 グリチルリチン酸類、塩酸ピリドキシン、サリチル酸、アラントイン、感光素301、イソプロピルメチルフェノール、ピロクトンオラミン、グリセリン、ピロリドンカーボン酸、エストラジオール、エチニルエストラジオール、及び1−メントールから構成された群から選択される一つ以上の成分をさらに含有することができる。これらの量は、全体組成物の0.0001〜10重量%が好ましい。 In addition to the above components, the composition of the present invention includes monosaccharides such as glucose, xylose, mannose, and arabinose that serve to supply nutrients to the hair follicles, and disaccharides such as maltose, sucrose, cellobiose, and trehalose. One or more saccharides can be further included, and these amounts are preferably 0.01 to 1% by weight of the total composition. In addition, the composition of the present invention can contain commonly used hair growth promoting auxiliary components, such as carrots, bitter ginsengs, mandarin oranges, green tea, carrots, bellflowers, mulberry coconuts, tanuki beans, stone husks. , Matsuba, Tsukimiko, Konotegasiwa leaves, what neck moth, moth lotus grass, tribulus extract, betaine, mint extract, nettle extract, horsetail extract, lavender extract, hop extract, aloe, elegans, winter moth summer grass, tokkuri Strawberry, Mulberry, Wood vinegar, Bamboo salt, Yellow flowers, Yellowtail, Eggplant, Walnut, Grape, Saflower, Sesame, Sesame, Garlic, Kelp, Wakame, Plum, Mung bean, Black rice, Pentadecanoic acid glyceride, Hinokitiol, Pepper tincture, ginger tincture, cantharis tincture, forskolin, trans-3,4'-dimethyl-3-hydroxyflavanone, a Tocopherols such as tocopherol cetate, nicotinic acid, nicotinamide, retinol palmitate, β-carotene, calciferol, folic acid, biotin, D-pantothenyl alcohol, acetyl pantothenyl ethyl ether, calcium pantothenate, pantothenyl ethyl ether , Ascorbic acid, grapefruit seed extract, cephalanthin, nicotinic acid benzyl ester, vitamins A, B 1 , B 2 , B 6 and derivatives thereof, pantothenic acid and derivatives thereof, minoxidil, purple oil extract, arginine, aspartic acid, Methionine, serine, glycine, glutamic acid, cystine, amino acid extract, β-glycyrrhetinic acid, glycyrrhizic acid, pyridoxine hydrochloride, salicylic acid, allantoin, photosensitizer 301, isop Pills methylphenol, piroctone olamine, glycerin, pyrrolidone carbon acid, estradiol, ethinyl estradiol, and 1 one or more components selected from a group consisting of menthol may further contain. These amounts are preferably 0.0001 to 10% by weight of the total composition.
一方、ランタン(La)、ネオジミウム(Nd)、サマリウム(Sm)、ガドリニウム(Gd)またはルテチウム(Lu)の希土類元素とトウガラシチンキの配合時、二つの成分間の相乗作用により、優れたTGF−β発現減少及びVEGF発現促進による脱毛防止、発毛促進、育毛、ふけの除去及び予防効果はもちろん、チロシナーゼ活性及び発現促進及びメラニン生成促進による黒毛生成促進効果を奏することができる。目的とする相乗作用を奏する限り、二つの成分の配合比に特に制限はないが、例えば、前記希土元素とトウガラシチンキは、1:0.0001〜1、好ましくは1:0.01〜1、より好ましくは、1:0.1〜1の重量比で含有することが好ましい。これは、前記範囲内で目的する相乗作用が最大化できるからであるが、本発明の範囲が前記特定範囲に制限されるものではない。さらに、本組成物は、ショウガチンキ及び/またはカンタリスチンキをさらに含有することができる。ショウガチンキは、ショウガ(Zingiber officinate roscoe)の根茎をエタノールで浸出して得たチンキ剤であって、刺激成分であるジンゲロン(zingerone)、ショガオール(shogaol)などが毛根を刺激して発毛を促進すると知られている。カンタリス(cantharis)は、ツチハンミョウ科の昆虫を称するもので、カンタリスチンキは、前記昆虫からエタノール抽出により得られる成分である。 On the other hand, an excellent TGF-β due to the synergistic action between the two components when the rare earth element of lanthanum (La), neodymium (Nd), samarium (Sm), gadolinium (Gd) or lutetium (Lu) and chili tincture are combined. Not only hair loss prevention, hair growth promotion, hair growth, dandruff removal and prevention effect by expression reduction and VEGF expression promotion, but also black hair production promotion effect by tyrosinase activity and expression promotion and melanin production promotion can be achieved. The blending ratio of the two components is not particularly limited as long as the desired synergistic effect is achieved. For example, the rare earth element and chili pepper tincture are in the range of 1: 0.0001 to 1, preferably 1: 0.01 to 1. More preferably, it is contained in a weight ratio of 1: 0.1-1. This is because the desired synergistic effect can be maximized within the above range, but the scope of the present invention is not limited to the specific range. Furthermore, the composition can further contain ginger tincture and / or cantharis tincture. Ginger tincture is a tincture obtained by leaching the rhizome of ginger (Zingiber officinate roscoe) with ethanol, and stimulating ingredients such as zingerone and shogaol stimulate hair roots to promote hair growth. It is known. Cantharis refers to the insects belonging to the family Nymphalidae, and cantalis tincture is a component obtained by ethanol extraction from the insects.
本発明の組成物の適用対象に特に制限はなく、本発明の組成物は、人間だけではなく、飼育動物やペットを含む全ての動物に適用できる。 There is no restriction | limiting in particular in the application object of the composition of this invention, The composition of this invention is applicable not only to a human but all animals including a domestic animal and a pet.
本組成物は、経皮(transdermally)または経口(orally)で投与でき、そのために、ローション、軟膏、ジェル、クリーム、パッチ、噴霧剤、錠剤、丸剤、粉末、サシェ(sachet)、エリキシル(elixir)、懸濁液、エマルジョン、溶液、シロップまたは軟質または硬質カプセルに剤形化することができる。 The composition can be administered transdermally or orally, for this purpose lotions, ointments, gels, creams, patches, sprays, tablets, pills, powders, sachets, elixirs ), Suspensions, emulsions, solutions, syrups or soft or hard capsules.
特に、本発明の組成物は、毛髪または頭皮に直接塗布または散布するなどの方法により使用できる。本発明の組成物が適用される毛髪とは、頭の毛根及び毛嚢、髪の毛及び眉毛と睫毛、ひげ、腋毛、陰毛、身体全般の毛根及び毛嚢のある全ての部位を含む。したがって、本発明は、ヘアートニック、ヘアーローション、ヘアークリーム、ヘアースプレー、ヘアームース、ヘアージェル、ヘアーコンディショナー、ヘアーシャンプー、ヘアーリンス、ヘアーパック、ヘアートリートメント、眉毛発毛剤、睫毛発毛剤または睫毛栄養剤、またはペット用シャンプー及びペット用リンスに使用できる。 In particular, the composition of the present invention can be used by a method such as direct application or application to the hair or scalp. The hair to which the composition of the present invention is applied includes all parts of the hair roots and hair follicles, hair and eyebrows and eyelashes, whiskers, eyelashes, pubic hair, hair roots and hair follicles of the entire body. Therefore, the present invention includes hair nick, hair lotion, hair cream, hair spray, hair mousse, hair gel, hair conditioner, hair shampoo, hair rinse, hair pack, hair treatment, eyebrow hair growth agent, eyelash hair growth agent or eyelashes Can be used in nutrients or pet shampoos and pet rinses.
本発明による希土類元素の容量は、性別、年齢、脱毛症状、毛髪状態などを考慮し適宜決定することができる。通常成人を対象にした一日容量は、約0.1〜5mg/cm2で、一日1〜5回適用することができる。 The capacity of the rare earth element according to the present invention can be appropriately determined in consideration of sex, age, hair loss symptoms, hair condition and the like. Usually, the daily dose for adults is about 0.1-5 mg / cm 2 and can be applied 1-5 times a day.
以下、実施例を通じて本発明をさらに詳細に説明するが、本発明の範囲がこれらの実施例に限定されるものではない。 EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, the scope of the present invention is not limited to these Examples.
<実施例1:毛髪改善用組成物の製造>
表1に示した成分及び含量を利用して、混合希土粉末及びその他の成分を均一に混合した後、ろ過して毛髪改善用組成物を製造した。製造された毛髪改善用組成物は、薄い褐色であり、不透明で、pHが5.0〜8.5であった。
<Example 1: Production of composition for improving hair>
Using the components and contents shown in Table 1, the mixed rare earth powder and other components were uniformly mixed, and then filtered to produce a hair improving composition. The produced hair improving composition was light brown, opaque, and had a pH of 5.0 to 8.5.
<実施例2〜18:毛髪改善用組成物の製造>
前記実施例1において、混合希土の代わりに、Ce(実施例2)、Pr(実施例3)、Pm(実施例4)、Eu(実施例5)、Tb(実施例6)、Dy(実施例7)、Ho(実施例8)、Er(実施例9)、Tm(実施例10)、Yb(実施例11)、Sc(実施例12)、Y(実施例13)、La(実施例14)、Nd(実施例15)、Sm(実施例16)、Gd(実施例17)及びLu(実施例18)の個々の希土類元素をそれぞれ使用したことを除いては、実質的に同一な過程により毛髪改善用組成物を製造した。
<Examples 2 to 18: Production of hair improving composition>
In Example 1, instead of mixed rare earth, Ce (Example 2), Pr (Example 3), Pm (Example 4), Eu (Example 5), Tb (Example 6), Dy ( Example 7), Ho (Example 8), Er (Example 9), Tm (Example 10), Yb (Example 11), Sc (Example 12), Y (Example 13), La (Example) Example 14), substantially the same except that individual rare earth elements of Nd (Example 15), Sm (Example 16), Gd (Example 17) and Lu (Example 18) were used respectively. The composition for improving hair was prepared through various processes.
<実施例19:毛髪処理用組成物の製造>
前記実施例1において、混合希土粉末の代わりに、La、Nd、Sm、Gd及びLuの混合粉末を0.1重量%使用して、トウガラシチンキ0.01重量%をさらに使用したことを除いては、実質的に同一な過程により毛髪改善用組成物を製造した。製造された毛髪処理用組成物は、薄い褐色であり、不透明で、pHが5.0〜8.5であった。
<Example 19: Production of hair treatment composition>
In Example 1, except that 0.1% by weight of mixed powder of La, Nd, Sm, Gd and Lu was used instead of mixed rare earth powder, and 0.01% by weight of chili pepper tincture was further used. In this way, a hair improving composition was produced by substantially the same process. The prepared hair treatment composition was light brown, opaque and had a pH of 5.0 to 8.5.
<実施例20〜24:毛髪処理用組成物の製造>
前記実施例19において、La、Nd、Sm、Gd及びLuの混合粉末の代わりに、La(実施例20)、Nd(実施例21)、Sm(実施例22)、Gd(実施例23)及びLu(実施例24)の個々の希土元素をそれぞれ使用したことを除いては、実質的に同一な過程により毛髪処理用組成物を製造した
<Examples 20 to 24: Production of hair treatment composition>
In Example 19, instead of the mixed powder of La, Nd, Sm, Gd and Lu, La (Example 20), Nd (Example 21), Sm (Example 22), Gd (Example 23) and A hair treatment composition was prepared by substantially the same process except that each of the rare earth elements of Lu (Example 24) was used.
<比較例>
実施例1の組成から希土粉末を除いて組成物を製造した。
<Comparative example>
A composition was prepared by removing the rare earth powder from the composition of Example 1.
<実験例1:希土類元素による細胞増殖促進効果の測定>
マウス胚芽線維芽細胞であるNIH 3T3細胞を、10%牛胎児血清(FBS)と1%ペニシリン−ストレプトマイシンが添加されたDMEM(Dulbeceo's Modified Eagle's Medium)で2×106 または4×106 細胞/mlの密度を維持しながら、37℃(95% O2, 5% CO2, 60%湿度)恒温・恒湿培養器で培養した。細胞の増殖促進実験のために、MTT(3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazoliumbromide)アッセイ方法を使用した。MTT実験のために、96ウェルプレートにウェル当たり2×103細胞/mlの各細胞を分株して、10% FBSが含まれた培養液を処理した。培養器で24 時間細胞を安定化させた後、FBSが含まれた培養液を、FBSのないDMEMで入れ換えて、それぞれ10μg、1μg、100ng、10ng、1ng、100pg、10pg及び1pgの混合希土、及び10ngの個々の希土類元素を処理した。一定時間培養後、ウェル当たり50μlのMTT(2mg/1ml滅菌蒸留水)を添加して4時間反応させ、DMSO(dimethyl sulfoxide)を処理して30分間振った後、ELISAリーダー(550, Bio−rad)を利用して540nmで吸光度を測定した。
<Experimental Example 1: Measurement of Cell Growth Promotion Effect by Rare Earth Elements>
NIH 3T3 cells, which are mouse embryo fibroblasts, were 2 × 10 6 or 4 × 10 6 cells / ml in DMEM (Dulbeceo's Modified Eagle's Medium) supplemented with 10% fetal bovine serum (FBS) and 1% penicillin-streptomycin. Was maintained in a constant temperature / humidity incubator at 37 ° C. (95% O 2, 5% CO 2, 60% humidity). The MTT (3- (4,5-dimethyl-thiazol-2-yl) -2,5-diphenyltetrazoliumbromide) assay method was used for cell growth promotion experiments. For the MTT experiment, 2 × 10 3 cells / ml of each cell were sorted into a 96-well plate and a culture solution containing 10% FBS was treated. After stabilizing the cells for 24 hours in an incubator, the culture medium containing FBS is replaced with DMEM without FBS, and mixed rare earth of 10 μg, 1 μg, 100 ng, 10 ng, 1 ng, 100 pg, 10 pg and 1 pg, respectively. , And 10 ng of individual rare earth elements. After incubation for a certain period of time, 50 μl of MTT (2 mg / 1 ml sterilized distilled water) was added per well, reacted for 4 hours, treated with DMSO (dimethyl sulfoxide), shaken for 30 minutes, and then an ELISA reader (550, Bio-rad). ) Was measured at 540 nm.
各元素(混合希土、Ce、Eu、La、Gd)の濃度による細胞増殖結果を図1に、一定な濃度の各元素の処理結果を図2にそれぞれ示した。図1に示したように、10μgから1pgまで各元素を処理した実験群は、何も処理しなかった無処理群より細胞の増殖が活発になることを確認することができた。特に、無処理群に比べ、セリウム添加後は、細胞増殖が1.69倍に増加した。したがって、各元素が細胞の増殖に影響を及ぼすことを確認することができた。また、図2に示したように、それぞれの元素を10ngずつ処理した場合も、細胞増殖が無処理群に比べて増加し、セリウム(Ce)、プラセオジミウム(Pr)、プロメチウム(Pm)、ユーロピウム(Eu)、テルビウム(Tb)、ジスプロシウム(Dy)、ホルミウム(Ho)、エルビウム(Er)、ツリウム(Tm)、イッテルビウム(Yb)、スカンジウム(Sc)、イットリウム(Y)などは、互いにほぼ等しい程度の効果を示すことが確認された。特に、セリウム(Ce)で処理した場合、細胞増殖が最も大きく増加されることが確認できた。これに比べ、ランタン(La)、ネオジム(Nd)、サマリウム(Sm)、ガドリニウム(Gd)、ルテチウム(Lu)などは、相対的に多少劣る効果を有することが確認された。 FIG. 1 shows the result of cell growth depending on the concentration of each element (mixed rare earth, Ce, Eu, La, Gd), and FIG. 2 shows the result of treatment of each element at a constant concentration. As shown in FIG. 1, the experimental group treated with each element from 10 μg to 1 pg could confirm that the cell proliferation was more active than the untreated group where nothing was treated. In particular, cell growth increased 1.69 times after addition of cerium compared to the untreated group. Therefore, it was confirmed that each element has an effect on cell proliferation. In addition, as shown in FIG. 2, when each element was treated with 10 ng, cell proliferation increased compared to the untreated group, and cerium (Ce), praseodymium (Pr), promethium (Pm), europium ( Eu), terbium (Tb), dysprosium (Dy), holmium (Ho), erbium (Er), thulium (Tm), ytterbium (Yb), scandium (Sc), yttrium (Y), etc. are approximately equal to each other. It was confirmed to show an effect. In particular, when treated with cerium (Ce), it was confirmed that the cell proliferation was greatly increased. Compared to this, it was confirmed that lanthanum (La), neodymium (Nd), samarium (Sm), gadolinium (Gd), lutetium (Lu) and the like have a relatively inferior effect.
<実験例2:動物における発毛効果の測定>
実験動物は、6週齢のC57BL6雄性マウス(29±3g)で、実験開始前、一般固形飼料(Samyang社)と水を自由摂取させ、ポリプロピレンボックス(453×293×247(H)mm, 19l)で1週間(20〜24℃、湿度60〜80%)の予備飼育で適応期間をおいた。その後、実験動物群の背中部位の一定面積(3×5cm2)を刈って、無作為に比較例の組成物処理群(対照群)、及び実施例1の組成物処理群及び実施例2の組成物処理群(実験群)に分けた。各群は、一日24時間を、それぞれ12時間ずつ明、暗状態に分けて維持した。実施例1及び2と比較例によって製造された組成物を、朝と夜の一定な時間を決めて、一日2回ずつ一定量(1ml)を塗布した。全ての実験では、暗状態の時は実験を行わず、実験マウスが安定を取るように配慮して、組織採取時は、実験前24時間の回復期間をおいた。
<Experimental Example 2: Measurement of hair growth effect in animals>
The experimental animals are 6-week-old C57BL6 male mice (29 ± 3 g). Before starting the experiment, the animals were allowed to freely take a general chow (Samyang) and water, and a polypropylene box (453 × 293 × 247 (H) mm, 19 l). ) For 1 week (20 to 24 ° C., humidity 60 to 80%). Thereafter, a fixed area (3 × 5 cm 2 ) of the back part of the experimental animal group was cut, and the composition treatment group of the comparative example (control group) and the composition treatment group of Example 1 and Example 2 were randomly selected. Divided into composition treatment groups (experimental group). Each group was maintained for 24 hours a day, divided into light and dark states for 12 hours each. A fixed amount (1 ml) of the composition prepared according to Examples 1 and 2 and Comparative Example was applied twice a day at a fixed time in the morning and night. In all experiments, the experiment was not performed in the dark state, and consideration was given to the stability of the experimental mice, and a recovery period of 24 hours before the experiment was allowed when collecting the tissues.
その結果を図3に示した。図3に示されたように、実施例1と実施例2の組成物で処理した場合、時間が経つにつれて毛が生えていることを確認した。実施例1及び実施例2の組成物で処理した場合、比較例の組成物で処理した場合より毛が生える速度が著しく速く、毛の数にも大きい差があって、毛の太さ及びつやにおいても勝っていることが確認できた。また、組成物処理20日後からは、発毛速度が非常に速く、実験群と対照群の明らかな差を確認することができた。特に、セリウムが添加された実施例2の組成物は、混合希土が添加された実施例1の組成物とほぼ等しい効果を示した。 The results are shown in FIG. As shown in FIG. 3, when treated with the compositions of Example 1 and Example 2, it was confirmed that hair grew over time. When treated with the compositions of Example 1 and Example 2, the speed of hair growth was significantly faster than when treated with the composition of the comparative example, and there was a large difference in the number of hairs. I was able to confirm that I was winning. Further, after 20 days from the composition treatment, the hair growth rate was very fast, and a clear difference between the experimental group and the control group could be confirmed. In particular, the composition of Example 2 to which cerium was added showed almost the same effect as the composition of Example 1 to which mixed rare earth was added.
<実験例3:動物皮膚組織の観察>
頚椎脱臼法で前記実験例2の実験動物を犠牲させた後、皮膚を分離してPBS(Phosphate buffered saline)で異物を最大限除去し、はさみで実験部位を切り出した後、下記の実験に使用した。分離した皮膚を10%ホルムアルデヒドに入れて、一日間固定させて、10mm3大きさに切って、自動浸透器で12時間自動浸透させた後、パラフィンブロックを作って、薄切り機を使用して4μmの厚さに薄切 した。その後、ヘマトキシリン&エオシン染色条件によって染色した。判読及び写真撮影は、光学顕微鏡を使用して100倍で行った。
<Experimental Example 3: Observation of animal skin tissue>
After sacrificing the experimental animal of Experimental Example 2 by cervical dislocation, the skin was separated, foreign matter was removed to the maximum with PBS (Phosphate buffered saline), the experimental site was cut out with scissors, and used for the following experiment did. The separated skin is placed in 10% formaldehyde, fixed for one day, cut into 10 mm 3 size, and automatically infiltrated with an automatic permeator for 12 hours. Then, a paraffin block is made and 4 μm is used using a slicer. Sliced to a thickness of. Then, it dye | stained by hematoxylin & eosin staining conditions. Interpretation and photography were performed at 100x using an optical microscope.
その結果を図4に示した。図4に示されたように、実施例1及び実施例2の組成物を処理した実験群と比較例の組成物を処理した対照群は、毛髪成長において大きい差があることが分かった。実験群の場合は、毛嚢(Hair follicle)が皮膚及び脂肪組織と真皮(dermis)から生じて、表皮(epidermis)側に多く成長して生えているが、対照群の場合は、成長の始まり段階であることが分かった。毛嚢の数においても、対照群に比べ、実験群でさらに多いことを確認した。特に、セリウムが添加された実施例2の組成物は、混合希土が添加された実施例1の組成物とほぼ等しい効果を示した。参考に、実験動物は、人間のようにそれぞれ異なる毛周期を有するモザイクタイプではなく、毛髪全体の毛周期が一致するシンクロニスティック(synchronistic)タイプである。 The results are shown in FIG. As shown in FIG. 4, it was found that the experimental group treated with the compositions of Example 1 and Example 2 and the control group treated with the comparative composition had a large difference in hair growth. In the experimental group, hair follicles originate from the skin and adipose tissue and the dermis and grow and grow on the epidermis side, whereas in the control group, the growth starts. It turned out to be a stage. It was confirmed that the number of hair follicles was higher in the experimental group than in the control group. In particular, the composition of Example 2 to which cerium was added showed almost the same effect as the composition of Example 1 to which mixed rare earth was added. For reference, the experimental animal is not a mosaic type having a different hair cycle like a human being, but a synchronous type in which the hair cycle of the whole hair matches.
<実験例4:TGF−β2及びVEGF発現の測定>
TGF−βは、同種異形質体であって、種々の細胞と組織において、初期発生の調節、細胞周期の調節、細胞増殖及び分化、移動、生存、細胞外基質の生産、免疫体系、血管生成と血球細胞の生産、細胞死誘導、骨格形成、傷の治癒などを調節する多機能性サイトカインであって、毛周期の退化期には、TGF−βが発現されつつ毛髪細胞の枯死(apoptosis)を誘導すると知られている。血管上皮成長因子(VEGF)は、同種異形質の糖タンパク質で、傷部位で血管新生を刺激すると知られた最も一般的且つ効果的な成長因子であって、多い血管組織で発現されて、上皮細胞に特異的なマイトジェン(mitogen)で上皮細胞の移動と増殖を誘導し、血管の透過性を増加させる役割をすると知られている。VEGFは、既に販売されているミノキシジルの発毛作用メカニズムで、毛根を構成する主要細胞である毛乳頭で血管拡張効果による血流量増加により毛根に影響を供給し、毛髪成長を促進すると考えられている。
<Experimental Example 4: Measurement of TGF-β2 and VEGF expression>
TGF-β is an allogeneic and regulates early development, cell cycle regulation, cell proliferation and differentiation, migration, survival, extracellular matrix production, immune system, blood vessel generation in various cells and tissues Is a multifunctional cytokine that regulates the production of blood cells, cell death induction, skeletal formation, wound healing, etc., and TGF-β is expressed and hair cell death occurs during the degeneration phase of the hair cycle It is known to induce. Vascular epidermal growth factor (VEGF) is an allogeneic glycoprotein, the most common and effective growth factor known to stimulate angiogenesis at the wound site, expressed in many vascular tissues, and epithelial It is known that mitogen specific to cells induces migration and proliferation of epithelial cells and increases vascular permeability. VEGF is a hair growth mechanism of minoxidil that is already on the market. It is thought that hair follicles, which are the main cells that make up the hair roots, supply hair roots by increasing blood flow due to vasodilatory effects and promote hair growth. Yes.
上記のタンパク質の発現程度をウェスタンブロッティング(western blotting)により確認するために、実験例3の実験動物組織から得たタンパク質を12% SDS−PAGEで分離した後、NC(nitrocellulose membrane)に移した。この際、実験例2及び3において、ランタンが添加された実施例14の組成物で処理した群を含ませた。その後、NCを、5%脱脂乳を含有したトリス緩衝塩水(TBS)でブロッキングして、1:1,000に希釈した一次抗体(抗−TGF−β2及び抗−VEGFラビットIgG)と1:1,000に希釈した二次抗体(ペルオキシダーゼ−抱接された抗−ラビットIgG)にそれぞれ反応させた後、0.05%ツイン−20が含有されたTBSで洗浄し、ECL検出キットを利用してX−線フィルムに感光させた。その後、LabWork(商標)(version 4.5.00.0)のイメージ分析プログラムを使用して、OD値をグラフで示した。 In order to confirm the expression level of the above protein by Western blotting, the protein obtained from the experimental animal tissue of Experimental Example 3 was separated by 12% SDS-PAGE and then transferred to NC (nitrocellulose membrane). At this time, in Examples 2 and 3, a group treated with the composition of Example 14 to which lanthanum was added was included. NCs were then blocked with Tris-buffered saline (TBS) containing 5% skimmed milk and 1: 1 with primary antibodies (anti-TGF-β2 and anti-VEGF rabbit IgG) diluted 1: 1,000. Each was reacted with a secondary antibody diluted to 1,000,000 (peroxidase-conjugated anti-rabbit IgG), then washed with TBS containing 0.05% twin-20, and using an ECL detection kit. X-ray film was exposed. Thereafter, the OD values were displayed graphically using an image analysis program of LabWork ™ (version 4.5.00.0).
その結果を図5に示した。図5に示されたように、実施例1、2及び14の組成物処理群(実験群)において、TGF−β2の発現量は、比較例の組成物処理群(対照群)に比べ、大きく減少することが分かる。また、VEGFは、対照群より実験群でさらに多く発現されることを確認することができた。即ち、本発明の毛髪改善用組成物は、TGF−βの活性を減少させて、VEGFの活性を促進させることにより、TGF−βによる毛嚢細胞死滅を抑制して、血管拡張効果による血流量増加により毛根に栄養を供給し毛髪成長を促進して、脱毛の防止及び育毛の効果を奏することができる。特に、セリウムが含まれた実施例2の組成物処理群において、混合希土が含まれた実施例1の組成物処理群より優れた効果が現れた。その反面、ランタンが含まれた実施例14の組成物処理群では、無処理群よりは優れた効果が現れたが、実施例1や実施例2の組成物処理群よりは相対的に劣る効果が現れた。 The results are shown in FIG. As shown in FIG. 5, in the composition-treated group (experimental group) of Examples 1, 2, and 14, the expression level of TGF-β2 was larger than that in the comparative composition-treated group (control group). It turns out that it decreases. It was also confirmed that VEGF was expressed more in the experimental group than in the control group. That is, the composition for improving hair of the present invention decreases the activity of TGF-β and promotes the activity of VEGF, thereby suppressing the death of hair follicle cells by TGF-β and the blood flow volume due to the vasodilation effect. By increasing the nutrients to the hair roots and promoting hair growth, hair loss can be prevented and hair growth can be achieved. In particular, in the composition treatment group of Example 2 containing cerium, an effect superior to that of the composition treatment group of Example 1 containing mixed rare earth appeared. On the other hand, in the composition-treated group of Example 14 containing lanthanum, an effect superior to that of the untreated group appeared, but the effect relatively inferior to the composition-treated groups of Example 1 and Example 2. Appeared.
<実験例5:ヒトにおける発毛及び黒毛効果の測定>
男性及び女性の各種脱毛症患者30名を、10名ずつ、実施例1の組成物、実施例2の組成物、比較例の組成物で処置した後、その有効性を評価した。頭皮への投与は、1日2回、毎日2ヶ月間行って、育毛状態を1ヶ月後と2ヶ月後に評価した。判定基準は、
1.高い効果がある−新生毛が観察される(硬毛)
2.中間程度の効果がある−新生毛が観察される(柔毛)
3.少し効果がある−脱毛の数が減少する
4.ふけが減少する
で評価して、その結果を表2に示した。
<Experimental Example 5: Measurement of hair growth and black hair effect in human>
Thirty male and female patients with various alopecia were treated with the composition of Example 1, the composition of Example 2, and the composition of Comparative Example, respectively, and then their effectiveness was evaluated. The scalp was administered twice a day for 2 months every day, and the hair growth state was evaluated after 1 month and 2 months. Judgment criteria are
1. Highly effective-new hair is observed (hard hair)
2. Intermediate effect-new hair is observed (soft hair)
3. 3. Has a little effect-reduces the number of hair loss The results are shown in Table 2.
上記表2に示したように、本発明による組成物は、発毛及び育毛効果が処置1ヶ月で現れ、2ヶ月目にも持続される。また、実施例1及び実施例2の組成物を塗布した後、1〜2週内に脱毛減少効果が現れて、個人的な差はあるが、組成物を塗布した後、5〜7日内にふけ減少効果が現れ、時間が経つほどふけは完全に除去されて、頭のかゆみ症も完全に解消された。また、被験者の中、白毛を有した男性と女性の場合、黒毛が生成されたことを肉眼で確認することができた。前記結果から分かるように、発毛時期や発毛効果において、本発明の組成物は、個体による差は大きくなく、脱毛患者に効果がよくて、全体被験者において毛髪の太さが増加して、黒毛生成を促進した。また、副作用は、全く発見されなかった。比較例の組成物で処置した場合は、綿毛が生えるか、脱毛の減少、ふけの除去などが現れたが、有意性は見えなかった。 As shown in Table 2 above, in the composition according to the present invention, the hair growth and hair growth effects appear in 1 month of treatment and are maintained even in the 2nd month. In addition, after applying the compositions of Example 1 and Example 2, the effect of reducing hair loss appears within 1-2 weeks, and there are individual differences, but after applying the composition, within 5-7 days The effect of reducing dandruff appeared, and as time passed, the dandruff was completely removed and the head itch was completely eliminated. In the case of males and females with white hair among the subjects, it was confirmed with the naked eye that black hair was generated. As can be seen from the above results, in the hair growth time and the hair growth effect, the composition of the present invention is not greatly different among individuals, is effective for hair loss patients, and increases the thickness of the hair in the entire subject, Promoted black hair generation. In addition, no side effects were found. When treated with the composition of the comparative example, fluff grew, hair loss decreased, dandruff removed, etc., but no significance was seen.
前記被験者の中、40〜47歳男性の実施例2組成物の適用前及び適用2ヶ月経過後の様子を写真で撮影して、これを図6に示した。図6に示されたように、被験者は、脱毛が始まって前頭や脳天部分の髪の毛がほとんどなく、はげの兆候が現れ始めた。症状としては、頭のかゆみ症、ふけ、ストレスによる疲労などにより脱毛が深刻に進行されてきた。そこで、実施例2の組成物を一日2回にかけて頭皮に塗布した結果、塗布3日後から頭のかゆみ症とふけがなくなり、脱毛現象が顕著に減って、塗布1ヶ月後から前頭や脳天部分の脱毛部位に綿毛のような髪の毛が生え始め、連続的に髪の毛が生え始めて、塗布2ヶ月ぶりに肉眼で確認できる程度の毛髪状態になった。上記の結果から、本発明による組成物は、優れた毛髪成長効果を有するだけではなく、長期間塗布時にも人体に無害であることを確認することができた。 Among the test subjects, 40- to 47-year-old males were photographed before and 2 months after application of the composition of Example 2 and are shown in FIG. As shown in FIG. 6, the test subject began to lose hair, had almost no hair in the frontal area or the top of the brain, and began to show signs of baldness. Symptoms have been severe hair loss due to head itchiness, dandruff, fatigue due to stress, and the like. Therefore, as a result of applying the composition of Example 2 to the scalp twice a day, itching and dandruff in the head disappeared 3 days after application, and the hair loss phenomenon was remarkably reduced. A hair like a fluff started to grow on the hair removal site of the hair, and the hair started to grow continuously, and it became a hair state that could be confirmed with the naked eye after two months of application. From the above results, it was confirmed that the composition according to the present invention not only has an excellent hair growth effect, but is also harmless to the human body even when applied for a long period of time.
<実験例6:黒毛生成促進効果を評価するためのチロシナーゼ活性測定>
黒毛生成促進効果を評価するために、ヒト由来黒色腫細胞(human melanoma cell)であるSk−mel−31とマウス由来黒色腫細胞(mouse melanoma cell)であるB16F10においてチロシナーゼの活性を調べた。細胞の培養のために、RPMI−1640(1%ペニシリン−ストレプトマイシン、10%牛胎児血清)培地で 、Sk−mel−31は1×106/ml、 B16F10は2×105/mlの密度を維持しながら、37℃(5% CO2, 60%相対湿度)の恒温・恒湿培養器で培養した。培養器で24時間細胞を安定化させた後、FBSが含まれた培養液を、FBSのないRPMI−1640で入れ換えて、それぞれ10μg、1μg、100ng、10ng、1ng、100pg、10pg及び1pgの混合希土、及び10ngの個々の希土類元素を処理した。チロシナーゼ活性を測定するために、一定時間培養した後、細胞を10分間遠心分離(100×g)して収獲した後、0.01Mリン酸ナトリウム緩衝液(1%トリトンX−100, 0.1mM PMSF(phenylmethyl sulfonyl fluoride)、pH 7.4)で細胞を超音波破砕し、1時間氷に放置した後、4℃で40,000×gで20分間遠心分離し、上澄み液のみを取った。100mM リン酸カリウム(pH 7.1)と4% N,N−ジメチルホルムアミド、0.1%(v/v)トリトンX−100を混合した分析用緩衝液250μlに5mM L−DOPA(L−3,4−ジヒドロキシフェニルアラニン)130μl、25mM MBTH(3−メチル−2−ベンゾチアゾリノンヒドラゾン(3-methyl-2-benzothiazolinone hydrazone))120μlを入れて、37℃恒温槽で5分間反応させた後、細胞抽出物100μgを入れて、再び2時間さらに反応した。その後、500μlの1M過塩素酸を加えて、常温で9,000×gで3分間遠心分離した。その後、上澄み液のみを取って、505nm で吸光度を測定した。
<Experimental Example 6: Measurement of tyrosinase activity for evaluating the effect of promoting black hair production>
In order to evaluate the effect of promoting black hair production, the activity of tyrosinase was examined in Sk-mel-31 which is a human melanoma cell and B16F10 which is a mouse melanoma cell. For cell culture, in RPMI-1640 (1% penicillin-streptomycin, 10% fetal bovine serum) medium, Sk-mel-31 had a density of 1 × 10 6 / ml and B16F10 had a density of 2 × 10 5 / ml. While maintaining, the cells were cultured in a constant temperature / humidity incubator at 37 ° C. (5% CO 2, 60% relative humidity). After stabilizing the cells for 24 hours in an incubator, the culture medium containing FBS is replaced with RPMI-1640 without FBS, and mixed with 10 μg, 1 μg, 100 ng, 10 ng, 1 ng, 100 pg, 10 pg and 1 pg, respectively. Rare earth and 10 ng of individual rare earth elements were treated. In order to measure tyrosinase activity, after culturing for a certain period of time, the cells were collected by centrifugation (100 × g) for 10 minutes, and then 0.01 M sodium phosphate buffer (1% Triton X-100, 0.1 mM). Cells were ultrasonically disrupted with PMSF (phenylmethylsulfonyl fluoride), pH 7.4), left on ice for 1 hour, and then centrifuged at 40,000 × g for 20 minutes at 4 ° C., and only the supernatant was collected. 100 mM potassium phosphate (pH 7.1), 4% N, N-dimethylformamide, 0.1% (v / v) Triton X-100 mixed with 250 μl of analytical buffer was mixed with 5 mM L-DOPA (L-3 , 4-dihydroxyphenylalanine) 130 μl, 25 mM MBTH (3-methyl-2-benzothiazolinone hydrazone) 120 μl was added and reacted in a 37 ° C. thermostat for 5 minutes. 100 μg of cell extract was added and reacted again for 2 hours. Thereafter, 500 μl of 1M perchloric acid was added, and centrifuged at 9,000 × g for 3 minutes at room temperature. Thereafter, only the supernatant was taken and the absorbance was measured at 505 nm.
図7及び図8にそれぞれsk−mel−31及びB16F10に混合希土及び個々の希土類元素(Ce, Eu, La, Gd)を処理した場合の結果を示した。図7及び8に示したように、10μgから1pgまで混合希土及び個々の希土類元素を処理した実験群では、混合希土を処理しなかった対照群よりチロシナーゼ活性が増加することを確認することができた。したがって、希土類元素がチロシナーゼ活性に影響を及ぼすことを確認することができた。即ち、混合希土や個々の希土類元素は、チロシナーゼの酵素活性を増加させて、メラニン生成を促進するため、黒毛生成促進効果があることが分かった。一方、個々の希土類元素で処理した場合、セリウム(Ce)、プラセオジミウム(Pr)、プロメチウム(Pm)、ユーロピウム(Eu)、テルビウム(Tb)、ジスプロシウム(Dy)、ホルミウム(Ho)、エルビウム(Er)、ツリウム(Tm)、イッテルビウム(Yb)、スカンジウム(Sc)、イットリウム(Y)などは、混合希土と実質的に同一な効果を奏することができることが確認された。特に、セリウム(Ce)で処理した場合、チロシナーゼの酵素活性が最も大きく増加されることが確認できた。一方、ランタン(La)、ネオジム(Nd)、サマリウム(Sm)、ガドリニウム(Gd)、ルテチウム(Lu)などは、上記の元素より効果が多少低いことが確認された。 FIGS. 7 and 8 show the results when sk-mel-31 and B16F10 were treated with mixed rare earth and individual rare earth elements (Ce, Eu, La, Gd), respectively. As shown in FIGS. 7 and 8, in the experimental group treated with mixed rare earth and individual rare earth elements from 10 μg to 1 pg, it is confirmed that the tyrosinase activity is increased as compared with the control group not treated with the mixed rare earth. I was able to. Therefore, it was confirmed that the rare earth element affects tyrosinase activity. That is, it was found that the mixed rare earth and the individual rare earth elements increase the enzyme activity of tyrosinase and promote melanin production, and thus have a black hair production promoting effect. On the other hand, when treated with individual rare earth elements, cerium (Ce), praseodymium (Pr), promethium (Pm), europium (Eu), terbium (Tb), dysprosium (Dy), holmium (Ho), erbium (Er) It has been confirmed that thulium (Tm), ytterbium (Yb), scandium (Sc), yttrium (Y), and the like can exhibit substantially the same effect as the mixed rare earth. In particular, when treated with cerium (Ce), it was confirmed that the enzyme activity of tyrosinase was greatly increased. On the other hand, it was confirmed that lanthanum (La), neodymium (Nd), samarium (Sm), gadolinium (Gd), lutetium (Lu) and the like are somewhat less effective than the above elements.
<実験例7:黒毛生成促進効果を評価するためのチロシナーゼ発現測定>
実験例6と同様な方法により細胞を培養した後、10分間遠心分離(100×g)して、細胞を収獲した。チロシナーゼの発現程度をウェスタンブロッティングにより確認するために、細胞抽出物100μgを10% SDS−PAGEで分離した後、NCに移して、5%脱脂乳を含有したTBSでブロッキングした後、1:2,500に希釈した一次抗体(monoclonal anti-tyrosine hydroxylase clone Th-2)と、1:5,000に希釈した二次抗体(Anti-mouse IgG)をそれぞれ反応させて、0.2%ツイン−20が含有されたTBSで洗浄し、ECL検出キットを利用してX−線フィルムに感光させた。その後、LabWork(商標)(version 4.5.00.0)のイメージ分析プログラムを使用して、OD値をグラフで示した。
<Experimental example 7: Tyrosinase expression measurement for evaluating the effect of promoting black hair production>
After culturing the cells by the same method as in Experimental Example 6, the cells were collected by centrifugation (100 × g) for 10 minutes. To confirm the expression level of tyrosinase by Western blotting, 100 μg of cell extract was separated by 10% SDS-PAGE, transferred to NC, blocked with TBS containing 5% skim milk, and then 1: 2, A primary antibody diluted to 500 (monoclonal anti-tyrosine hydroxylase clone Th-2) and a secondary antibody diluted to 1: 5,000 (Anti-mouse IgG) were reacted to give 0.2% twin-20. It was washed with the contained TBS and exposed to X-ray film using an ECL detection kit. Thereafter, the OD values were displayed graphically using an image analysis program of LabWork ™ (version 4.5.00.0).
その結果を図9に示した。図9に示されたように、対照群に比べ、混合希土を処理した場合、チロシナーゼの発現が増加したことを確認することができた。したがって、混合希土は、チロシナーゼの発現を増加させて、髪の色を決定するメラニン色素の生成を促進させることが分かった。一方、個々の希土類元素で処理した場合、セリウム(Ce)、プラセオジミウム(Pr)、プロメチウム(Pm)、ユーロピウム(Eu)、テルビウム(Tb)、ジスプロシウム(Dy)、ホルミウム(Ho)、エルビウム(Er)、ツリウム(Tm)、イッテルビウム(Yb)、スカンジウム(Sc)、イットリウム(Y)などは、混合希土と実質的に同一な効果を奏することが確認された。特に、セリウム(Ce)で処理した場合、チロシナーゼの発現が最も大きく増加されることが確認できた。一方、ランタン(La)、ネオジム(Nd)、サマリウム(Sm)、ガドリニウム(Gd)、ルテチウム(Lu)などは、上記の元素より効果が多少劣ることが確認された。 The results are shown in FIG. As shown in FIG. 9, it was confirmed that the expression of tyrosinase increased when the mixed rare earth was treated as compared with the control group. Therefore, it was found that the mixed rare earth increases the expression of tyrosinase and promotes the production of melanin pigment that determines hair color. On the other hand, when treated with individual rare earth elements, cerium (Ce), praseodymium (Pr), promethium (Pm), europium (Eu), terbium (Tb), dysprosium (Dy), holmium (Ho), erbium (Er) It has been confirmed that thulium (Tm), ytterbium (Yb), scandium (Sc), yttrium (Y) and the like have substantially the same effect as the mixed rare earth. In particular, when treated with cerium (Ce), it was confirmed that the expression of tyrosinase was greatly increased. On the other hand, it was confirmed that lanthanum (La), neodymium (Nd), samarium (Sm), gadolinium (Gd), lutetium (Lu) and the like are somewhat inferior to the above elements.
<実験例8:黒毛生成促進効果を評価するためのメラニン生成量測定>
実験例6と同一な方法で細胞を培養した後、10分間遠心分離(100×g)して、細胞を収獲した。メラニン生成量を測定するために、1N NaOHに細胞抽出物200μg(総1ml)を加えて、30分間常温に放置した後、400nmで吸光度を測定した。
<Experimental Example 8: Measurement of melanin production for evaluating the effect of promoting black hair production>
After culturing the cells by the same method as in Experimental Example 6, the cells were harvested by centrifugation (100 × g) for 10 minutes. In order to measure the amount of melanin produced, 200 μg (total 1 ml) of cell extract was added to 1N NaOH, left at room temperature for 30 minutes, and the absorbance was measured at 400 nm.
その結果を図10に示した。図10に示したように、混合希土を処理した場合、メラニンの生成量が、対照群に比べ増加することが分かった。このような結果からチロシナーゼの活性及び発現増加により、メラニンの量が増加して、黒毛生成促進効果を奏することがわかった。一方、個々の希土類元素で処理した場合も、混合希土で処理した場合と実質的に同一な効果が得られることが確認された。一方、個々の希土類元素で処理した場合、セリウム(Ce)、プラセオジミウム(Pr)、プロメチウム(Pm)、ユーロピウム(Eu)、テルビウム(Tb)、ジスプロシウム(Dy)、ホルミウム(Ho)、エルビウム(Er)、ツリウム(Tm)、イッテルビウム(Yb)、スカンジウム(Sc)、イットリウム(Y)などは、上記と実質的に同一な効果が得られることが確認された。特に、セリウム(Ce)で処理した場合、メラニン量が最も大きく増加されることが確認できた。一方、ランタン(La)、ネオジム(Nd)、サマリウム(Sm)、ガドリニウム(Gd)、ルテチウム(Lu)などは、上記の元素より効果が多少劣ることが確認された。 The results are shown in FIG. As shown in FIG. 10, when mixed rare earth was processed, it turned out that the production amount of melanin increases compared with a control group. From these results, it was found that the amount of melanin increased due to increased activity and expression of tyrosinase, and the effect of promoting black hair production was achieved. On the other hand, it was confirmed that substantially the same effect can be obtained when treated with individual rare earth elements as when treated with mixed rare earth. On the other hand, when treated with individual rare earth elements, cerium (Ce), praseodymium (Pr), promethium (Pm), europium (Eu), terbium (Tb), dysprosium (Dy), holmium (Ho), erbium (Er) It was confirmed that thulium (Tm), ytterbium (Yb), scandium (Sc), yttrium (Y), and the like have substantially the same effects as described above. In particular, when treated with cerium (Ce), it was confirmed that the amount of melanin was greatly increased. On the other hand, it was confirmed that lanthanum (La), neodymium (Nd), samarium (Sm), gadolinium (Gd), lutetium (Lu) and the like are somewhat inferior to the above elements.
<実験例9:ランタン(La)、ネオジム(Nd)、サマリウム(Sm)、ガドリニウム(Gd)、ルテチウム(Lu)とトウガラシチンキ配合によるTGF−β及びVEGF発現、及びメラニン生成量の比較>
希土類元素の中、ランタン(La)、ネオジム(Nd)、サマリウム(Sm)、ガドリニウム(Gd)及びルテチウム(Lu)とトウガラシチンキの配合による相乗作用を調べるために、TGF−β及びVEGF発現量、及びメラニン生成量を比較した。
<Experimental Example 9: Comparison of TGF-β and VEGF expression by lanthanum (La), neodymium (Nd), samarium (Sm), gadolinium (Gd), lutetium (Lu) and chili pepper tincture, and melanin production amount>
In order to investigate the synergistic effect of the combination of lanthanum (La), neodymium (Nd), samarium (Sm), gadolinium (Gd) and lutetium (Lu) and chili tincture among rare earth elements, the expression levels of TGF-β and VEGF, And melanin production was compared.
TGF−β2とVEGF発現量を調べるために、前記実験例1と同一な方法により細胞を培養した後、実験例4と同一な方法により発現の程度を確認した。 In order to examine the expression levels of TGF-β2 and VEGF, cells were cultured by the same method as in Experimental Example 1, and then the degree of expression was confirmed by the same method as in Experimental Example 4.
メラニン生成量実験のために、実験例6と同一な方法により細胞を培養及び収獲した後、実験例8と同一な方法によりメラニン生成量を測定した。 For the melanin production amount experiment, cells were cultured and harvested by the same method as in Experimental Example 6, and then the melanin production amount was measured by the same method as in Experimental Example 8.
その結果を図11及び図12に示した。図11に示したように、TGF−β2の場合、ランタンとトウガラシチンキが配合された実施例20の組成物を処理した場合、セリウムが含まれた実施例2の組成物を処理した場合と類似した発現量の減少を示した。VEGFの場合、ランタンとトウガラシチンキが配合された実施例20の組成物を処理した場合、セリウムが含まれた実施例2の組成物を処理した場合と類似した発現量の増加を示した。また、図12に示したように、ランタンとトウガラシチンキが配合された実施例20の組成物を処理した場合、セリウムが含まれた実施例2の組成物を処理した場合と類似したメラニン生成量の増加を示した。一方、ネオジム(Nd)、サマリウム(Sm)、ガドリニウム(Gd)及びルテチウム(Lu)とトウガラシチンキが配合された実施例21乃至24の組成物を処理した場合も、上記のものと実質的に同一な効果が得られることが確認された。 The results are shown in FIG. 11 and FIG. As shown in FIG. 11, in the case of TGF-β2, when the composition of Example 20 containing lanthanum and chili pepper was processed, it was similar to the case of processing the composition of Example 2 containing cerium. Decreased expression level. In the case of VEGF, when the composition of Example 20 containing lanthanum and chili tincture was treated, the increase in the expression level was similar to that when the composition of Example 2 containing cerium was treated. Also, as shown in FIG. 12, when the composition of Example 20 containing lanthanum and chili pepper was processed, the amount of melanin produced was similar to the case of processing the composition of Example 2 containing cerium. Showed an increase. On the other hand, when the compositions of Examples 21 to 24 in which neodymium (Nd), samarium (Sm), gadolinium (Gd), and lutetium (Lu) and chili tincture were mixed were processed, it was substantially the same as the above. It was confirmed that an advantageous effect was obtained.
上述のように、本発明による毛髪改善用組成物は、TGF−βの発現を減少させて、毛嚢細胞の死滅を防止し、VEGFの発現を促進して血管拡張による血流量の増加により、毛根に栄養を供給して毛髪の成長を促進することにより、優れた脱毛防止、発毛促進、育毛、ふけの除去及び予防効果を有するだけではなく、毛根周囲のメラノサイトを活性化させて、メラニン色素の生産を増加させることにより、黒毛生成促進効果を有して、人体に無害で且つ安全であり、皮膚吸収力が高くて、べたつかないため皮膚感触に優れ、頭皮に副作用がない。 As described above, the composition for improving hair according to the present invention reduces the expression of TGF-β, prevents the death of hair follicle cells, promotes the expression of VEGF, and increases blood flow due to vasodilation. By supplying nutrients to the hair root and promoting hair growth, it not only has excellent hair loss prevention, hair growth promotion, hair growth, dandruff removal and prevention effects, but also activates melanocytes around the hair root to promote melanin By increasing the production of pigments, it has the effect of promoting black hair generation, is harmless and safe for the human body, has high skin absorbability, is non-sticky, has excellent skin feel, and has no side effects on the scalp.
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FR2740341B1 (en) * | 1995-10-26 | 1997-12-19 | Oreal | USE OF LANTHANIDE SALT, TIN, ZINC, MANGANESE, YTTRIUM, COBALT, BARIUM, STRONTIUM IN A SKIN COMPOSITION |
FR2740335B1 (en) * | 1995-10-26 | 1997-12-19 | Oreal | USE OF LANTHANIDE, LITHIUM, TIN, ZINC, MANGANESE OR YTTRIUM SALT AS A SUBSTANCE P ANTAGONIST |
EP0903344B1 (en) * | 1997-08-21 | 2011-01-26 | Shiseido Co., Ltd. | Quinazolin-4-one derivatives, their preparation and their use as hair growth promoters or in external compositions for skin |
-
2007
- 2007-08-24 JP JP2009525504A patent/JP2010501551A/en active Pending
- 2007-08-24 EP EP07793681.3A patent/EP2066289A4/en not_active Withdrawn
- 2007-08-24 WO PCT/KR2007/004084 patent/WO2008023960A1/en active Application Filing
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JPH05286837A (en) * | 1992-04-03 | 1993-11-02 | Kanebo Ltd | Hair-raising agent |
JP2001139436A (en) * | 1999-11-16 | 2001-05-22 | Hoyu Co Ltd | Hair tonic and grower |
JP2003119608A (en) * | 2001-10-15 | 2003-04-23 | Yukio Sato | Hair restoration material |
JP2003137749A (en) * | 2001-10-29 | 2003-05-14 | Yukio Sato | Artificial hair restorer contained in spray container |
JP2004035531A (en) * | 2002-07-05 | 2004-02-05 | Nobuyo Azuma | Hair grower and cosmetic containing the same |
JP2005273123A (en) * | 2004-03-24 | 2005-10-06 | Santamonica:Kk | Hat having new hair growth function |
JP2006160652A (en) * | 2004-12-06 | 2006-06-22 | Asahi Kasei Chemicals Corp | Nourishing hair composition |
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JP2011524424A (en) * | 2009-06-05 | 2011-09-01 | ジャエ ホワ チン | Perm composition |
JP2013539792A (en) * | 2010-10-15 | 2013-10-28 | ザ プロクター アンド ギャンブル カンパニー | Use of monoamine oxidase inhibitors to improve epithelial ecology |
JP2013053143A (en) * | 2011-08-09 | 2013-03-21 | Kao Corp | Cosmetic emulsion for eyebrows or eyelashes |
JP2016064992A (en) * | 2014-09-22 | 2016-04-28 | 和伎獅子株式会社 | Powder external preparation for skin for hair growing/restoration, and skin condition improvement |
JP2016074608A (en) * | 2014-10-02 | 2016-05-12 | 株式会社イムダイン | Hair elasticity improving agent that is orally administered |
TWI716751B (en) * | 2018-02-02 | 2021-01-21 | 國立臺灣海洋大學 | Hair growth stimulating dressing |
KR20220099189A (en) * | 2021-01-05 | 2022-07-13 | 엘리펀 주식회사 | Composition for preventing alopecia and activating growth of hair comprising distilled extract of rare earth complexbiomineral |
KR102489107B1 (en) * | 2021-01-05 | 2023-01-18 | 엘리펀 주식회사 | Composition for preventing alopecia and activating growth of hair comprising distilled extract of rare earth complexbiomineral |
Also Published As
Publication number | Publication date |
---|---|
WO2008023960A1 (en) | 2008-02-28 |
EP2066289A1 (en) | 2009-06-10 |
EP2066289A4 (en) | 2013-11-27 |
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