May 28, 2021
Revised June 8, 2021

Mandom Discovers that the Refreshing Ingredient “L-Menthyl Glyceryl Ether”
has the Effect of Suppressing TRPV1 Activity- Reducing the stress of wearing masks in everyday life during the coronavirus pandemic & realizing a refreshingfeeling that lasts with little discomfort -Mandom Corporation (Head Office: Osaka City; President Executive Officer & Director: Ken Nishimura;hereinafter referred to as “Mandom”) is conducting research that focuses on sensory stimulation in theskin in an aim to improve the function and usability of cosmetics (including quasi-drugs).
Due to high external temperatures and the effects of ingredients contained in cosmetics, there arecases when unpleasant irritations such as pain and burning sensations occur on the skin. On thisoccasion, Mandom confirmed that l-menthyl glyceryl ether (cosmetic ingredient label name:Menthoxypropanediol) has the effect of suppressing unpleasant irritation and is capable ofmaintaining a refreshing sensation. In the current situation of the coronavirus pandemic, Mandom
believes that this result will help the company provide consumers with a comfortable refreshingfeeling that can help relieve the frustration they feel from wearing a mask during daily activities.
These findings are scheduled to be presented at the 86th SCCJ Research Symposium (online) to beheld on July 15, 2021.
Background Information on this Research
Items that can achieve a refreshing sensation are being used in a wider range of scenarios that include
not only hot summers when words like “intense heat” and “extreme heat” are exchanged and broadcasted
every year, but also when consumers want to feel refreshed. Therefore, the things required of the term“refreshing sensation” differs depending on the item and usage scenario, such as strength and duration.
At Mandom, we strive to conduct research to provide a comfortable and refreshing sensation in varioussituations.
L-menthol, a commonly used refreshing ingredient, has several advantages such as providing a strong
refreshing feeling and has the effect of suppressing unpleasant stimuli caused by high external
temperatures. On the other hand, it also has several disadvantages such as having difficulty sustainingthat refreshing feeling since it is an ingredient that easily volatilizes.
This research aimed to realize a sustainable refreshing sensation with little unpleasant irritation as oneof the pleasant refreshing sensations that Mandom provides.
1 . Mandom discovers that l-menthyl glyceryl ether suppresses TRP (trip) V1 activity
It is known that high temperatures and some ingredients used in cosmetics cause unpleasant stimuli
such as pain and burning sensations. These unpleasant stimuli involve TRPV1 (a receptor of capsicum
ingredients), which is a type of TRP (trip) channel*1 that is a sensory sensor of cells.
Suppressing TRPV1 activity is effective at reducing these unpleasant stimuli. Until now, Mandom’s
research has shown*2 that the refreshing ingredient l-menthol has the effect of suppressing TRPV1
activity. L-menthyl glyceryl ether, whose structure is similar to that of l-menthol (see Figure 1), wasdiscovered to have an even greater effect of suppressing TRPV1 (see Figure 2).

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12. Permeability & residualness of l-menthyl glyceryl ether to the skin
Since general-purpose l-menthol is highly volatile, the challenge lies in the low sustainability of its
refreshing sensation. L-menthyl glyceryl ether, on the other hand, is considered to remain in and on theskin for a long time due to its low volatility.
When this was verified through permeability tests using skin models, it was newly confirmed that lmenthyl glyceryl ether penetrates the skin more than l-menthol and stays there longer (see Figure 3). Thissuggests that l-menthyl glyceryl ether can feel more refreshing for longer than l-menthol.
3. L-menthyl glyceryl ether might be able to achieve a sustained refreshing sensation & less unpleasantirritation even when wearing a mask
Many consumers are unsatisfied*3 with the heat, stuffiness, etc., that comes with the new normal ofwearing a mask throughout their daily routines due to the coronavirus pandemic. In response to this,Mandom thought that the technology it discovered during this research can be utilized to address this issue,
and so the company has conducted a verification.
[Details Regarding Verification]
A comparative verification was conducted on the refreshing sensation and irritating sensation of lmenthyl glyceryl ether and l-menthol by carrying out a test that involved wearing masks that had
been sprayed with a mist containing a 2.5% formulation of each ingredient (l-menthyl glyceryl ether
and l-menthol). This mist was specially designed for these model masks.
[Evaluation Method]
Subjects wore non-woven masks that had dried after being sprayed on the inside with two pushes(approximately 0.2 mL) of the specially designed mist for the model masks. After 60 minutes had passed,
an evaluation was conducted on the refreshing sensation and irritating sensation subjects felt as they
wore the masks.
[Evaluation Results]
・Refreshing Sensation: The decrease in the score for refreshing sensation over time for l-menthyl
glyceryl ether was more gradual and sustained compared to l-menthol (see Figure 4).
・Irritating Sensation: When it comes to eye irritation and skin irritation, l-menthyl glyceryl ether
had a lower irritating sensation than l-menthol (see Figure 5). According to the above results, it canbe said that l-menthyl glyceryl ether is an ingredient that has a less unpleasant irritating sensationand longer-lasting refreshing sensation than l-menthol.
[Considerations]
It has been found that the activation temperature threshold for TRP channels, such as TRPV1, varies
according to pH. The weak acidity of the skin lowers the temperature threshold of TRP, and TRPV1 may
be activated by external temperatures in the summer and temperatures within the mask, which may
cause unpleasant stimuli such as burning sensations. However, it is thought that a comfortablerefreshing sensation was achieved by suppressing TRPV1 activity and reducing unpleasant stimuli, suchas burning sensations, thanks to blending in the refreshing ingredient l-menthyl glyceryl ether. Since
consumers wear masks for long periods of time on a daily basis, and since the face is a part of the bodywhere the skin is thin and particularly feels irritation more easily, l-menthyl glyceryl ether (which provides
a lasting refreshing sensation with little unpleasant stimuli) can be said to be a suitable refreshingingredient.
In addition, l-menthyl glyceryl ether has the characteristic feature of providing a refreshing sensationthat increases when perspiring*4, and together with the aforementioned results, it can be expected tohelp reduce the stress consumers feel, such as the heat within their masks from having to wear theirmasks during daily activities in the summer time.
From these results, Mandom believes that using l-menthyl glyceryl ether with highly effective TRPV1
suppressing capabilities as a key ingredient for achieving a refreshing sensation will allow the company toprovide consumers with a lasting refreshing sensation with little unpleasant stimuli.
Mandom will continue to conduct research on refreshing sensations and release products that can offer
a more comfortable refreshing feeling that is more suited to consumers’ usage scenarios.
*1 TRP = Transient Receptor Potential. A sensor, which belongs to a family of cation channels involved in various sensory
receptor functions, that senses chemical substances, temperatures, etc., and converts them into electrical signals.
*2“Mandom identified menthol-induced analgesic mechanisms.”(December 10, 2015 news release)https://www.mandom.co.jp/en/release/pdf/2015121001_en.pdf*3 June 2020 online survey/Mandom study on males aged 16-24/n=204*4“Research by Mandom and application of “comfortable coolness”: Effect of perspiration on coolingsensation”(April 10, 2009 news release)https://www.mandom.co.jp/en/release/pdf/2009041001_en.pdf[Reference Material]
Figure 2 TRPV1 suppression effect

TRPV1 activity (%)

Figure 1 Structures of l-menthyl glyceryl ether & l-menthol

L-menthyl glyceryl ether

L-menthyl glyceryl ether
L-menthol

L-menthol

Concentration (mM)
Figure 3 Results of skin permeability test

Figure 4 Results of mask wearing test (refreshingsensation)

Refreshing sensation within mask
immediately after putting mask on

L-menthyl glyceryl ether
L-menthol

Refreshing sensation

Amount of each compound in skinL-menthyl glyceryl ether
L-menthol

Elapsed time (minutes)
Time (minutes)

Unpleasantness of irritating sensation in eyes

Unpleasantness of irritating sensation on skin

Unpleasantness

Unpleasantness

Figure 5 Results of mask wearing test (irritating sensation)

More unpleasant

L-menthyl glyceryl ether

L-mentholMore unpleasant

L-menthyl glyceryl etherL-menthol