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R & D report
Skin lightening ingredient
「Kojic Acid」

For over 60 years since the foundation, Sansho Pharmaceutical has been committed to the research and development of skin care ingredients. In this report, we present you one of the well-received ingredients we developed.

Skin lightening ingredient　Kojic Acid

R & D report　Skin lightening ingredient　Kojic Acid
For over 60 years since the foundation, Sansho Pharmaceutical has been committed to the research and development of skin care ingredients. In this report, we present you one of the well-received ingredients we developed.

Evidence: Skin lightening effect of Kojic Acid

Sansho Pharmaceutical developed Kojic Acid, which brought on the concept of “skin lightening” in Japan.
It has been said that the hands of Japanese sake brewers are bright and beautiful. Based on the saying, we conducted research on Japanese Koji used for brewing Japanese sake, miso and soy sauce. And we found out that Kojic Acid, a secondary metabolite produced during fermentation, effectively inhibits the activity of an enzyme that promotes melanin production. It took 13 years to develop Kojic Acid as an ingredient that can be formulated into cosmetics. After the revision of the Pharmaceutical Affairs Act in 1980, Kojic Acid became the first one to be approved as a skin lightening active ingredient for quasi-drugs with proven effects and safety on human skin. This was the start of the concept, “skin lightening”, in the field of quasi-drugs.
Kojic Acid is also used to treat dark spots at dermatology clinics for its highly effective skin lightening activity.
Kojic Acid being approved as the first skin lightening ingredient was a breakthrough. Following the approval, many other skin lightening ingredients and cosmetics were launched in the early 1990s, which led to a skin lightening cosmetics boom in Japan. For its high efficacy, Kojic Acid is used to treat melasma and solar lentigines. At dermatology clinics, Kojic Acid cream is prescribed for pigmentation disorders. And darkened yellowish skin (yellowish discoloration) turned brighter and dark spots faded.
Since the first approval in 1988, Kojic Acid was and still is considered as a standard skin lightening ingredient and its efficacy is recognized worldwide. We provide Kojic Acid to major cosmetics companies in Japan and overseas as well.

Mechanism of action: Treatment of spots and yellowish discoloration

  • Skin lightening effect of Kojic Acid

    1　Prevent spots
    Kojic Acid prevents damage before the actual melanin production.
    Melanin is a pigment that gives skin and hair their color. It protects skin cells from UV damage, but it is also the cause of dark spots. Normally, excess melanin is excreted through cellular metabolism. But because of UV damage or hormonal imbalance, overproduced melanin is accumulated and it appears as dark spots.
    The most distinctive feature of Kojic Acid is that it prevents damage before the melanin production as well as inhibiting an enzyme that enhances melanin production. It is especially effective on inhibiting “production of transmitters”, “reactive oxygen species” and “inflammation”, thus prevents melanin production. With these mechanisms, Kojic Acid brings back your natural skin tone.

From the laboratory　Little-known power of Kojic Acid

From the laboratory
Little-known power of Kojic Acid

Ingredient development department　Saya Yokota

Kojic Acid is also effective for wrinkles and sagging.
As the word “photoaging” signifies, UV damage is the cause of not only spots but also wrinkles and sagging. And one of the triggers for those aging signs is reactive oxygen species (ROS) generated by UV-induced inflammation. ROS, a major determinant of aging, degrades collagen.
Kojic Acid prevents inflammation and inhibits ROS generation. In other words, Kojic Acid lightens skin and at the same time it protects firmness and suppleness of skin, and it is clinically proved.
2　Prevent yellowish discoloration
Kojic Acid prevents AGEs production with its powerful anti-glycation effect.

As you age, skin tone changes to brownish yellow. This is because of AGEs (Advanced Glycation End Products) produced in glycation, a reaction of bonding proteins such as collagen and carbohydrate, which can happen in anyone’s body. AGEs, brownish yellow substance, tend to accumulate more and change skin tone to brownish yellow as you age.
Clinical studies showed that Kojic Acid effectively lightened skin tone. Therefore we conducted studies once again and found out that it also inhibits AGEs production significantly.

Relation of Yellowish Discoloration and Glycation

Evidence: Safety and Efficacy of Kojic Acid

  • Study 1　Skin lightening effect
    Significant melanogenesis inhibitory effect and safety
    In the scales of black goldfish, the melanin pigment exists just like in human cells. After being kept in water containing Kojic Acid, color tone of the goldfish faded. This is because of the melanogenesis inhibitory effect of Kojic Acid. Later the goldfish was kept in water without Kojic Acid. And it turned back to its original black color. It indicates that Kojic Acid inhibits melanogenesis without damaging cells nor its function. It is a highly effective and safe ingredient.

  • Melanocytes were not damaged, and skin function was not influenced.
    Melanoma B16 cells which produce melanin were cultured in a medium containing Kojic Acid. The cells were depigmented over time. Then the depigmented cells were cultured in a fresh medium without Kojic Acid, which led the color of the cells and cell activity to return to the pre-cultured level. This also indicates that Kojic Acid does not damage melanocytes, never induce incureable depigmentation and effectively lightens skin.
Melanogenesis inhibitory effect of Kojic Acid
Tyrosinase, an enzyme for controlling the production of melanin, is contained in Mushrooms. You can actually see Kojic Acid inhibiting melanin production.

  • Study 2　Anti-glycation effect
    Inhibitory effect of AGEs production, a cause of yellowish discoloration.
    AGEs, brownish yellow substance, are produced by glycation. In a study measuring AGEs production, Kojic Acid showed significant inhibitory effect. It proves that yellowish discoloration cured in clinical studies was the result of Kojic Acid suppressing AGEs production.

Research papers on Kojic Acid

1 肝斑患者に対するコウジ酸配合製剤の使用成績. The Nishinihon Journal of Dermatology Vol. 44(3), 474-478
2 コウジ酸配合製剤の使用経験:—女子の顔面色素増加症にたいする治療効果— The Nishinihon Journal of Dermatology Vol. 44(3), 470-473
3 Kojic Acid外用による肝斑の治療. Japanese Journal of Clinical Dermatology Vol. 36(7), 715-722
4 コウジ酸のmelanin生成抑制作用について. Fragrance Journal No.63, 40-44
5 Pigmentation in aging and melanogenic inhibitors. Fragrance Journal Vol.17(1), 25-33
6 Therapy of chloasma. Practical Dermatology Vol.12(7), 625-640
7 シミの新しい治療法.　Journal of Japan Hair Beauty Association Vol.3
8 特集「コウジ酸クリームのシミ予防効果」　The Pharmacy companion　Vol.16(2)
9 Melanogenesis-inhibitory effect of kojic Acid and its action mechanism. Fragrance Journal Vol.18(6), 53-58
10 Inhibitory Action of Kojic Acid on Melanogenesis and Its Therapeutic Effect for Various Human Hyper-Pigmentation Disorders. Skin Research Vol.36(2), 134-150
11 Clinical Effect of a Kojic Acid Containg Cream on Hyperpigmentaion of the Skin. Skin Research Vol.36(5), 707-714
12 The Effect of Kojic Acid Application on Various Facial Pigmentary Disorders. The Nishinihon Journal of Dermatology Vol.56(6), 1172-1181
13 Further studies on the therapeutic effect of a new composite type of kojic acid cream on human hyper-pigmentary disorders. Fragrance Journal Vol.14, 113-137
14 美白剤の評価‐コウジ酸について　The Journal of Japan Hair Science Association Vol.28 No.4
15 The result of long term use test of kojic acid mixture pharmaceutical.　The Nishinihon Journal of Dermatology Vol.60(6)
16 Cosmeceuticals Drugs vs. Cosmetics　P. Elsner　H. I. Maibach
17 Prevention of the photodamage in the hairless mouse dorsal skin by kojic acid as an iron chelator European J of Pharmacol. 411
18 Review of Liver Function, Tumor Marker and Tumors after Long-term Topical Use of 1% Kojic Acid Cream. The Nishinihon Journal of Dermatology Vol.67(4), 412-415
19 Side effect and utility of a cosmetic. J.JOCD No.47, 38-43
20 コウジ酸の生合成遺伝子,麹菌培養条件に応答した遺伝子発現機構　発酵・醸造食品の最新技術と機能性

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