Shiseido Develops ”4MSK/Fluid Penetration Technology” Penetrating Brightening Effective Ingredient 4MSK into Skin

Shiseido has developed the“4MSK/fluid penetration technology”, which enhances the penetration of the company’s uniquely developed brightening effective ingredient, 4MSK (4-methoxysalicylic acid potassium salt)*1 into the skin. This innovative technology combines 4MSK, which is solid at room temperature, with other ingredients to liquefy it, allowing it to remain in a fluid form even after application
on the skin (Figure 1). It has been confirmed that, with this technology, the amount of 4MSK that penetrates into the skin is increased and brightening effect enhanced. The results of this study were partly presented at the 32nd IFSCC*2 Congress in London (September 19-22, 2022). The paper*3 contributed to the IFSCC Magazine (2023) following the presentation won the Henry Maso Award for 2024, an award given to young researchers. In the future, Shiseido will apply the new penetration enhancement technology developed in this study to offer safe and secure high-performance skin care products with an excellent penetration ability.

*1 An ingredient approved by the then Health, Labour and Welfare Ministry of Japan in 2003 as a quasi-drug effective ingredient for suppressing melanogenesis and preventing dark spots and freckles.
*2 IFSCC: The International Federation of Societies of Cosmetic Chemists
*3 A. Okishima, T. Okamoto et. al., IFSCC Magazine, 26 (1)71-75 (2023) IFSCC


Figure 1: ”4MSK/fluid penetration technology” combined with trimethylglycine increases penetration of 4MSK into the skin

Figure 1

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Research background

In addressing the longing for a ”bright skin” among consumers, Shiseido has been developing effective brightening ingredients one after another since the 1990s, introducing numerous products formulated with these ingredients. In recent years, however, as the means to achieve bright skin diversified with the expanding cosmetic medical market, the company identified the need to strengthen technologies that enhance the penetration of brightening effective ingredients in order to develop safe and highly effective products for skin brightening.

Inspired by ”ionic liquids”

As Shiseido engaged in tasks to accomplish its goal, the company focused on ”ionic liquids” that have drawn attention in the field of chemistry in recent years. An ionic liquid is a new type of liquid composed of an ionic substance having a high melting point (temperature at which a solid melts and turns into a liquid) combined with another ionic substance also having a high melting point, that becomes liquid at temperatures lower than the melting points of the original substances (Figure 2). Shiseido envisioned that, by combining 4MSK, which is solid at room temperature, with other substances to form ionic liquids, it would be possible to maintain its liquid properties even on the skin. To this end, the company set out to search for substances that can, when combined with 4MSK, turn the ingredient into fluid form.

Figure 2: ”Ionic liquid” that inspired this research

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”4MSK/fluid penetration technology” realized by combining 4MSK with trimethylglycine

Shiseido examined over 100 different substances and their compositions to determine the optimal combination with 4MSK. As a result, it found that 4MSK becomes liquid when combined with the moisturizing ingredient trimethylglycine at the optimum blending ratio (Figure 3). The company then confirmed that, when the two ingredients were blended into a formulation in this ratio, almost twice the amount of 4MSK penetrated the skin compared to a formulation containing 4MSK alone (Figure 4). This is considered to be the result of 4MSK in the formulation maintaining its fluid form. Shiseido named this technology that increases the penetration of 4MSK into the skin the ”4MSK/fluid penetration technology.”


Figure 3: 4MSK becomes liquid when it is combined with trimethylglycine at the optimal blending ratio

Figure 4: ”4MSK/fluid penetration technology”allows 4MSK to penetrate into the skin in high amount

Figure 3

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Figure 4

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Highly effective in suppressing melanogenesis

Shiseido then examined the effect of the ”4MSK/fluid penetration technology” using a three-dimensional cultured skin model. The results revealed that the technology is effective in increasing the effect of 4MSK to suppress melanogenesis (Figure 5). Moreover, with respect to the effect of 4MSK to promote exfoliation of the stratum corneum with melanin deposition, it was suggested that the use of this technology may increase this effect as well.

Figure 5: ”4MSK/fluid penetration technology” increases the melanogenesis suppression effect

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