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Skin-Lightening Active Ingredients in Japan
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Japanese pharmaceutical cosmetics, often referred to as quasi-drugs, contain skin-lightening active ingredients formulated to prevent sun-induced pigment spots and freckles. Their mechanisms of action include suppressing melanin production in melanocytes and promoting epidermal growth to eliminate melanin more rapidly. For example, arbutin and rucinol are representative skin-lightening active ingredients that inhibit melanin production, and disodium adenosine monophosphate and dexpanthenol are skin-lightening active ingredients that inhibit melanin accumulation in the epidermis. In contrast, oral administration of vitamin C and tranexamic acid in pharmaceutical products can lighten freckles and melasma, and these products are more effective than quasi-drugs. On the basis of their clinical effectiveness, skin-lightening active ingredients can be divided into four categories according to their effectiveness and adverse effects.

  • skin-lightening
  • pharmaceutical cosmetics
  • quasi-drug
  • ingredient
  • melasma: pigment spots
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1. Development of Skin-Lightening Active Ingredients

Japanese pharmaceutical cosmetics are required to have one of the following purposes of use: (1) cleansing, (2) beautifying, (3) increasing attractiveness, (4) changing appearance, and (5) maintaining healthy skin or hair. Whether or not the product has the above purpose of use should be clarified by the efficacy or effectiveness, usage, and dosage of the product. If a product is determined not to meet the specified purpose of use on these bases of its efficacy or effectiveness, usage, and dosage, it is considered a “drug.” Examples of indications include “spots, freckles, pigmentation due to sunburn, etc.” (internal use), “spots, freckles, pigmentation due to sunburn/rash” (internal use), “skin pigmentation, senile pigmentation” (external use), “spots” (internal use), “Riehl melanosis, post-inflammatory hyperpigmentation” (for injection), and “melasma, freckles, post-inflammatory hyperpigmentation” (for internal use and injection). If the product has only the above efficacy or effectiveness, usage, and dosage, it cannot be considered a pharmaceutical cosmetic (quasi-drug).
In Japan, the efficacy for pharmaceutical cosmetics was changed in 2019 from “prevents sun spots and freckles” to “prevents sun spots and freckles by suppressing melanin production.” In 2004, the action of the ingredients in the formulation was changed to “prevents spots and freckles,” and, on the basis of the mechanism of action of the ingredients in the formula, the indication of “suppressing the accumulation of melanin and preventing spots and freckles” was approved. Thus, it is possible to apply for approval of pharmaceutical cosmetics for new efficacy within the scope of quasi-drug efficacy, on the basis of a clear scientific rationale.
The Japanese skincare market can be divided into the following functional categories: moisturizing, skin-lightening, anti-aging, sensitive skin, and pore and acne care. Lightening of the skin accounts for approximately 30% of the market and is the category with the most rapid growth over the past 35 years, particularly in terms of research and development [1]. Approximately twenty active ingredients have been developed for lightening-related quasi-drugs, including chemical substances and plant extracts with excellent inhibitory effects on tyrosinase activity and melanin production. A chronology of the development of skin-lightening active ingredients is presented in Table 1. The chemical structures of skin-lightening active ingredients in Japan are presented in Figure 1. Recent research on anti-aging skin-lightening has revealed new mechanisms and methods for the treatment of skin lightening. This section introduces the history of the skin-lightening ingredients developed in Japan.
Figure 1. Chemical structure of skin-lightening active ingredients in Japan.
Table 1. List of skin-lightening active ingredients approved in Japan.
Approved Year Generic Name Development Company Chemical Name/Substance Name Main Mechanism of Action
  placenta extract      
1983 magnesium ascorbyl phosphate (APM) Takeda Pharmaceutical Co., Ltd. magnesium L-ascorbyl-2-phosphate tyrosinase inhibition
1988 kojic acid Sansho Seiyaku Co., Ltd. kojic acid tyrosinase inhibition
1989 arbutin Shiseido Co., Ltd. hydroquinone-β-D-glucopyranoside tyrosinase inhibition
1994 ascorbyl glucoside (AA-2G) Hayashibara Co., Ltd., Kaminomoto Co., Ltd., Shiseido Co., Ltd. L- ascorbic acid 2-O-α-glucoside tyrosinase inhibition
1997 ellagic acid Lion Corporation ellagic acid tyrosinase inhibition
1998 Rucinol® Kurarey Co., Ltd.
POLA Chemical industries, Inc.
4-n-butylresorcinol tyrosinase inhibition
1999 Chamomile ET Kao Corporation Matricaria chamomilla L Extract endothelin blocker
2001 linoleic acid S Sunstar Inc. linoleic acid tyrosinase degradation, stimulation of epidermal turn over
2002 tranexamic acid
(t-AMCHA)
Shiseido Co., Ltd. trans-4-aminocyclohexane carboxylic acid inhibition of prostaglandin E2 production by anti-plasmin
2003 4MSK Shiseido Co., Ltd. potassium 4-methoxysalicylate tyrosinase inhibition
2004 Vitamin C ethyl Nippon Hypox Laboratories, Inc. 3-O-ethyl ascorbic acid tyrosinase inhibition
2004 Energy signal AMP® Otsuka Pharmaceutical Co., Ltd. adenosine mono phosphate stimulation of epidermal turnover
2005 Magnolignan® Kanebo Cosmetics Inc. 5,5-dipropyl-biphenyl-2,2-diol inhibition of tyrosinase maturation, cytotoxicity to melanocytes
2007 D-Melano (niacinamide W) P&G Maxfactor niacinamide suppression of melanosome transfer
2008 Rhododenol® Kanebo Cosmetics Inc. 4-(4-hydroxyphenyl)-2-butanol, Rhododendrol tyrosinase inhibition, cytotoxicity of melanocytes
2008 TXC CHANEL tranexamic acid cetyl ester hydrochloride inhibition of prostaglandin E2 production
2009 ascorbyl tetraisopalmitate Nikko Chemicals Co., Ltd. ascorbyl tetra-2-hexyldecanoate tyrosinase inhibition
2018 dexpanthenol W (PCE–DP) POLA ORBIS Holdings Inc. dexpanthenol enhance energy production of epidermal cells

2. Report on the Effectiveness of a Formulation Containing a Lightening Agent and a Spot Remedy for Senile Pigmented Lesions

References

  1. General chapter. Functional Cosmetics Marketing Handbook 2019–2020; Fuji Keizai Group Co., Ltd.: Tokyo, Japan, 2019; pp. 7–32. (In Japanese)
  2. Olsen, E.A.; Katz, H.I.; Levine, N.; Shupack, J.; Billys, M.M.; Prawer, S.; Gold, J.; Stiller, M.; Lufrano, L.; Thorne, E.G. Tretinoin emollient cream: A new therapy for photodamaged skin. J. Am. Acad. Dermatol. 1992, 26, 215–224.
  3. Griffiths, C.E.; Finkel, L.J.; Ditre, C.M.; Hamilton, T.A.; Ellis, C.N.; Voorhees, J.J. Topical tretinoin (retinoic acid) improves melasma. A vehicle-controlled, clinical trial. Br. J. Dermatol. 1993, 129, 415–421.
  4. Griffiths, C.E.; Goldfarb, M.T.; Finkel, L.J.; Roulia, V.; Bonawitz, M.; Hamilton, T.A.; Ellis, C.N.; Voorhees, J.J. Topical tretinoin (retinoic acid) treatment of hyperpigmented lesions associated with photoaging in Chinese and Japanese patients: A vehicle-controlled trial. J. Am. Acad. Dermatol. 1994, 30, 76–84.
  5. Jarratt, M. Mequinol 2%/tretinoin 0.01% solution: An effective and safe alternative to hydroquinone 3% in the treatment of solar lentigines. Cutis 2004, 74, 319–322.
  6. Fleischer, A.B., Jr.; Schwartzel, E.H.; Colby, S.I.; Altman, D.J. The combination of 2% 4-hydroxyanisole (Mequinol) and 0.01% tretinoin is effective in improving the appearance of solar lentigines and related hyperpigmented lesions in two double-blind multicenter clinical studies. J. Am. Acad. Dermatol. 2000, 42, 459–467.
  7. Kameyama, K.; Sakai, C.; Kondoh, S.; Yonemoto, K.; Nishiyama, S.; Tagawa, M.; Murata, T.; Ohnuma, T.; Quigley, J.; Dorsky, A.; et al. Inhibitory effect of magnesium L-ascorbyl-2-phosphate (VC-PMG) on melanogenesis in vitro and in vivo. J. Am. Acad. Dermatol. 1996, 34, 29–33.
  8. Naganuma, M. Whitening cosmetics and its effectiveness in Japan. Ski. Surg. 1999, 8, 2–7. (In Japanese)
  9. Yokoyama, M. Clinical evaluation of the use of whitening cream containing ellagic acid for the treatment of skin pigmentation conditions. Ski. Res. 2001, 43, 286–291. (In Japanese)
  10. Harada, T. Clinical evaluation of whitening cream containing kojic acid and oil-soluble licorice extract for senile pigment fleckle on the face. Ski. Res. 2000, 42, 270–275. (In Japanese)
  11. Koide, C.; Suzuki, T.; Mizutani, Y.; Hori, K.; Nakajima, A.; Uchiwa, H.; Sasaki, M.; Ifuku, O.; Maeda, K.; Iwabuchi, H.; et al. A questionnaire on pigmented disorders and use of whitening cosmetics in Japanese women. J. Jpn. Cosmet. Sci. Soc. 2006, 30, 306–310. (In Japanese)
  12. Kondo, S.; Okada, Y.; Tomita, Y. Clinical study of effect of tranexamic acid emulsion on melasma and freckles. Ski. Res. 2007, 6, 309–315. (In Japanese)
  13. Sugai, T. Clinical effects of arbutin in patients with chloasma. Ski. Res. 1992, 34, 522–529. (In Japanese)
  14. Miki, S.; Nishikawa, H. Effectiveness of vitamin C ethyl, Anti-Aging Series 2; N.T.S.: Tokyo, Japan, 2006; pp. 265–278. (In Japanese)
  15. Ichikawa, H.; Kawase, H.; Aso, K.; Takeuchi, K. Topical treatment f pigmented dermatoses by modified ascorbic acid. Jpn. J. Clin. Dermatol. 1969, 23, 327–331. (In Japanese)
  16. Mishima, Y.; Ohyama, Y.; Shibata, T.; Seto, H.; Hatae, S. Inhibitory action of kojic acid on melanogenesis and its therapeutic effect for various human hyper-pigmentation disorders. Ski. Res. 1994, 36, 134–150. (In Japanese)
  17. Nakayama, H.; Sakurai, M.; Kume, A.; Hanada, S.; Iwanaga, A. The effect of kojic acid application on various facial pigmentary disorders. Nishinihon J. Dermatol. 1994, 56, 1172–1181. (In Japanese)
  18. Clinical trial group for linoleic acid-containing gel. Clinical trial for liver spots using a linoleic acid-containing gel. Nishinihon J. Dermatol. 1998, 60, 537–542. (In Japanese)
  19. Harada, S.; Matsushima, T.; Toda, K.; Takemura, T.; Kawashima, M.; Sugawara, M.; Mizuno, J.; Iijima, M.; Miyakawa, S. Efficacy of rusinol (4-n-butylresorcinol) on chloasma. Nishinihon J. Dermatol. 1999, 61, 813–819. (In Japanese)
  20. Kawashima, M.; Imokawa, G. Mechanism of pigment enhancement in UVB-induced melanosis and lentigo senilis, and anti-spot effect of Chamomile ET. Mon. Book Derma 2005, 98, 43–61. (In Japanese)
  21. Kawashima, M.; Mizuno, A.; Murata, Y. Improvement of hyperpigmentation based on accelerated epidermal turnover: Clinical effects of disodium adenosine monophosphate in patients with melasma. Jpn. J. Clin. Dermatol. 2008, 62, 250–257. (In Japanese)
  22. Haramoto, I.; Mizoguchi, M. Clinical evaluation of oil-soluble licorice extracts cream on chloasma. Nishinihon J. Dermatol. 1995, 57, 601–608. (In Japanese)
  23. Hakozaki, T.; Minwalla, L.; Zhuang, J.; Chhoa, M.; Matsubara, A.; Miyamoto, K.; Greatens, A.; Hillebrand, G.G.; Bissett, D.L.; Boissy, R.E. The effect of niacinamide on reducing cutaneous pigmentation and suppression of melanosome transfer. Br. J. Dermatol. 2002, 147, 20–31.
  24. Navarrete-Solís, J.; Castanedo-Cázares, J.P.; Torres-Álvarez, B.; Oros-Ovalle, C.; Fuentes-Ahumada, C.; González, F.J.; Martínez-Ramírez, J.D.; Moncada, B. A double-blind, randomized clinical trial of niacinamide 4% versus hydroquinone 4% in the treatment of melasma. Derm. Res. Pract. 2011, 2011, 379173.
  25. Shimokawa, Y.; Kamisasanuki, S.; Tashiro, M. Treatment of facial dysmelanosis with cosmetics containing Placen A. Nishinihon J. Dermatol. 1982, 44, 1027–1029. (In Japanese)
  26. Tucker-Samaras, S.; Zedayko, T.; Cole, C.; Miller, D.; Wallo, W.; Leyden, J.J. A stabilized 0.1% retinol facial moisturizer improves the appearance of photodamaged skin in an eight-week, double-blind, vehicle-controlled study. J. Drugs Dermatol. 2009, 8, 932–936.
  27. Taylor, M.B.; Yanaki, J.S.; Draper, D.O.; Shurtz, J.C.; Coglianese, M. Successful short-term and long-term treatment of melasma and postinflammatory hyperpigmentation using vitamin C with a full-face iontophoresis mask and a mandelic/malic acid skin care regimen. J. Drugs Dermatol. 2013, 12, 45–50.
  28. Verallo-Rowell, V.M.; Verallo, V.; Graupe, K.; Lopez-Villafuerte, L.; Garcia-Lopez, M. Double-blind comparison of azelaic acid and hydroquinone in the treatment of melasma. Acta. Derm. Venereol. Suppl. 1989, 143, 58–61.
  29. Gu, L.; Zeng, H.; Takahashi, T.; Maeda, K. In vitro methods for predicting chemical leukoderma caused by quasi-drug cosmetics. Cosmetics 2017, 4, 31.
  30. Swinnen, I.; Goossens, A. Allergic contact dermatitis caused by ascorbyl tetraisopalmitate. Contact Dermat. 2011, 64, 241–242.
  31. Assier, H.; Wolkenstein, P.; Grille, C.; Chosidow, O. Contact dermatitis caused by ascorbyl tetraisopalmitate in a cream used for the management of atopic dermatitis. Contact Dermat. 2014, 71, 60–61.
  32. Scheman, A.; Fournier, E.; Kerchinsky, L. Allergic contact dermatitis to two eye creams containing tetrahexyldecyl ascorbate. Contact Dermat. 2022, 86, 556–557.
  33. Tagawa, M.; Murata, T.; Onuma, T.; Kameyama, K.; Sakai, C.; Kondo, S.; Yonemoto, K.; Quigley, J.; Dorsky, A.; Bucks, D.; et al. Inhibitory effects of magnesium ascorbyl phosphate on melanogenesis. SCCJ J. 1993, 27, 409–414. (In Japanese)
  34. Yamamoto, K.; Ebihara, T.; Nakayama, H.; Okubo, A.; Higa, Y. The result of long term use test of kojic acid mixture pharmaceutical. Nishinihon J. Dermatol. 1998, 60, 849–852. (In Japanese)
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Subjects: Dermatology
Contributor :
View Times: 43
Entry Collection: Biopharmaceuticals Technology
Revisions: 2 times (View History)
Update Time: 08 Aug 2022
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    Maeda, K. Skin-Lightening Active Ingredients in Japan. Encyclopedia. Available online: https://encyclopedia.pub/entry/25917 (accessed on 17 August 2022).
    Maeda K. Skin-Lightening Active Ingredients in Japan. Encyclopedia. Available at: https://encyclopedia.pub/entry/25917. Accessed August 17, 2022.
    Maeda, Kazuhisa. "Skin-Lightening Active Ingredients in Japan," Encyclopedia, https://encyclopedia.pub/entry/25917 (accessed August 17, 2022).
    Maeda, K. (2022, August 06). Skin-Lightening Active Ingredients in Japan. In Encyclopedia. https://encyclopedia.pub/entry/25917
    Maeda, Kazuhisa. ''Skin-Lightening Active Ingredients in Japan.'' Encyclopedia. Web. 06 August, 2022.
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