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Citation: Kang, S.-Y.; Um, J.-Y.;
Chung, B.-Y.; Lee, S.-Y.; Park, J.-S.;
Kim, J.-C.; Park, C.-W.; Kim, H.-O.
Moisturizer in Patients with
Inflammatory Skin Diseases.
Medicina 2022,58, 888.
https://doi.org/10.3390/
medicina58070888
Academic Editor: Cataldo Patruno
Received: 6 June 2022
Accepted: 30 June 2022
Published: 1 July 2022
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medicina
Review
Moisturizer in Patients with Inflammatory Skin Diseases
Seok-Young Kang †, Ji-Young Um †, Bo-Young Chung , So-Yeon Lee, Jin-Seo Park, Jin-Cheol Kim ,
Chun-Wook Park and Hye-One Kim *
Department of Dermatology, Kangnam Sacred Heart Hospital, Hallym University, Seoul 24252, Korea;
tjdjrdud@naver.com (S.-Y.K.); ujy0402@hanmail.net (J.-Y.U.); victoryby@naver.com (B.-Y.C.);
minggijeook@gmail.com (S.-Y.L.); pahajs@gmail.com (J.-S.P.); aiekfne@naver.com (J.-C.K.);
dermap@hanmail.net (C.-W.P.)
*Correspondence: hyeonekim@gmail.com
† These authors contributed equally to this work.
Abstract:
As interest in skin increases, the cosmetic market is also growing. It is difficult to choose
between the numerous types of basic cosmetics on the market. This article aims to provide advice
and guidance on which products to recommend according to a patient’s skin condition. Appropriate
application of a moisturizer attempts not only to improve the dryness, but also improve the skin’s
natural barrier function to protect the skin from internal and external irritants to keep the skin healthy.
Moisturizers consist of various ingredients, including occlusive agents, emollients, humectants,
lipid mixture, emulsifiers, and preservatives. Pathophysiology of dry skin is also discussed to
provide readers with the background they need to choose the right moisturizer for themselves. As
moisturizers play an important role as adjuvant in the treatment of common skin diseases, such
as atopic dermatitis, contact dermatitis, psoriasis, acne and rosacea, which type of moisturizer is
appropriate for each disease was also dealt with. Basic cosmetics, especially moisturizers, should be
recommended in consideration of the ingredients, effectiveness and safety of each product, and the
skin condition of each patient.
Keywords: cosmetics; moisturizer; cosmeceutical
1. Introduction
Cosmetics and pharmaceuticals are strictly separated in many countries, but many
consumers expect physiological effects from their cosmetics similar to those of pharmaceu-
ticals. The term that was born out of an attempt to express this idea is “cosmeceuticals”
proposed by Dr. Albert Kligman [
1
]. The term “cosmeceutical” is a compound word of
“cosmetic” and “pharmaceuticals,” and it considers cosmetic products with a certain degree
of physiological activity as hybrid or intermediate between the two poles of cosmetics
and drugs [
2
]. Even now, although cosmeceuticals are not recognized as a category by the
Food and Drug Administration in almost all countries, including the US FDA, the term
cosmeceutical is commonly used in various international symposiums and seminars, and
is a term that is actually recognized by consumers in the global market [
3
]. According
to Dr. Albert Kligman, to become a cosmeceutical, all of three conditions must be met:
1. Can the active ingredient penetrate the stratum corneum and can it be provided in
a sufficient concentration to the skin through a process consistent with the mechanism
of action? 2. Does the active ingredient have special biochemical and pharmacological
mechanisms in the cells and tissues of human skin? 3. Is there a statistically significant
double-blind placebo-controlled clinical study to substantiate the efficacy claim, and has it
been published in a medical journal?
In this article, among cosmeceuticals, it is believed that moisturizing agents can serve
as adjuvant treatments for atopic dermatitis, contact dermatitis, and psoriasis. Therefore, it
is thought that doctors and medical experts can help in the treatment and research of skin
Medicina 2022,58, 888. https://doi.org/10.3390/medicina58070888 https://www.mdpi.com/journal/medicina
Medicina 2022,58, 888 2 of 17
diseases through a comprehensive review of moisturizers. The investigated role of moistur-
izers and the effects, safety, and types of the main ingredients included in moisturizers are
reported. This was conducted to inform the proper selection of a moisturizer that performs
a preventive and therapeutic role in various skin diseases accompanied by damage to the
skin barrier or inflammation. The term basic cosmetic is a concept that includes detergents
and moisturizers distributed in various forms such as lotions, creams, and gels. In this
article, the selection criteria and proper use of basic cosmetics will be the focus, especially
for patients with skin diseases.
2. The Role of Moisturizers in the Skin Barrier
The primary function of a moisturizer is to suppress moisture loss. When the skin
barrier is damaged, it is necessary to first suppress the loss of water to restore the normal
barrier [
4
]. A moisturizer supplies moisture to dry skin that is rough and flaky, which may
be caused by dry environment and external stimuli [
5
]. In addition, a moisturizer helps to
maintain and restore skin flexibility by blocking the evaporation of moisture, and induces
uniform exfoliation of old dead skin cells to maintain a smooth skin surface [
6
]. When the
moisturizer functions properly in the skin, the skin maintains homeostasis despite changes
in the external environment, so that the stratum corneum can maintain proper hydration [
7
].
After applying a moisturizer to damaged skin, the skin barrier is restored through the
four-step process that follows [
8
]. (1) The oily component of the moisturizer creates a thin
film on the skin, and barrier repair begins; (2) The skin moisture distribution coefficient
changes; (3) Moisture diffuses from the dermis to the epidermis; (4) Water distribution to
the epidermis is controlled by the synthesis of skin lipids and intercellular lipid secretion.
That is, the oily component of the moisturizer forms a film on the skin to prevent
the evaporation of moisture, the humectant component directly supplies moisture to the
epidermis and dermis, and the emollient component controls the exfoliation of dead skin
cells to make the skin barrier restored. In addition, when components similar to lipids in
the stratum corneum of the skin are included in the moisturizer, the lipid component is
supplied to the keratinocytes of the epidermis to rearrange the intercellular lipids [
9
,
10
],
thereby maintaining the moisture content in the epidermis and improving the function of
the skin barrier [11].
Appropriate application of a moisturizer not only improves the dryness, but also
improves the skin’s natural barrier function to protect the skin from internal and external
irritants to keep the skin healthy [
12
]. In addition, because various skin diseases accompany
abnormalities in the skin barrier function, excellent moisturizing agents serve as adjuvants
to treat and prevent diseases, and also to relieve skin disease symptoms such as itching
and stinging [13].
3. Ingredients of Moisturizers
Moisturizers consist of occlusive agents that form an airtight film on the skin surface
to suppress moisture loss, emollients that give a soft and smooth feeling, humectants that
help the stratum corneum of the skin to contain moisture, lipid components (ceramides and
other barrier lipids), and many other base components [
14
]. Occlusive agents, softeners,
and lipid components are often oil-soluble, and humectants are often water-soluble. Most
moisturizers are made by appropriately mixing these components. In addition to these
base ingredients, emulsifying ingredients, preservatives, fragrances, and cosmetic drugs
(active ingredients) with various functions may be included [15].
Many moisturizer ingredients serve more than one function. For example, if a sub-
stance with the properties of a sealant or softener has structurally hydrophilic and lipophilic
functional groups, it also functions as an emulsifier. In October 2008, the entire ingredi-
ent labeling system was implemented in Korea, allowing consumers to check ingredient
labels when purchasing cosmetics. Because all cosmetic ingredients are marked in the
order of concentration contained in the product, it is possible to determine to some extent
whether the ingredients and order of the moisturizer are centered on the sealant or the
Medicina 2022,58, 888 3 of 17
humectant [
16
]. Therefore, it is necessary to have a clear understanding of the classification
and characteristics of these ingredients of moisturizers.
3.1. Occlusive Agents
Occlusive agents are usually oily substances that coat the stratum corneum (SC)
rendering an emollient effect as well as the ability to decrease transepidermal water loss
(TEWL) [
17
]. In general, the higher the oil component, the greater the softening action. The
sealing and softening action is larger in the order of ointment, oil-based cream, water-based
cream, and lotion.
The advantage of the occlusive agent is that it blocks moisture loss most effectively
when applied immediately after washing or bathing. The disadvantage is that most are
effective only when applied to the skin, and when removed from the skin through washing,
the effect of inhibiting moisture loss disappears. If it is too strong, there is a possibility of
bacterial growth in the stratum corneum (SC). Therefore, when using an occlusive agent as
moisturizer, the degree of sealing should not lower the rate of moisture loss through the
epidermis by 40% or less; thus, it is often mixed with a humectant [18].
Among the currently available occlusive agents, the components with the best sealing
performance are Petrolatum, which is a semi-solid form of petroleum refined products, and
mineral oil, which is a liquid form. Here we will examine components of occlusive agents
such as hydrocarbons which include petroleum, silicone, vegetable oils and vegetable fat,
waxes, and fatty acids and fatty alcohols.
3.1.1. Hydrocarbons (Petrolatum and Mineral Oil)
Hydrocarbons are compounds made of carbon and hydrogen. They are chemically
inert substances that do not have polar groups.
Petrolatum
Petrolatum is a hydrocarbon extracted from petroleum that was patented and brought
into use in the United States in 1872 by Robert A. Chesebrough. Its brand name was
“Vaseline,”; a combination of the Saxon word wassor (water) and the Greek word oleon
(oil) [
19
]. Other names include petroleum jelly, white petrolatum, and soft paraffin. It
is known to exhibit no rancidity and induce no comedones as it is tasteless, odorless,
and neutral, does not cause allergy, and provokes little skin irritation because, except for
carbon and hydrogen, other aromatic and unsaturated structures are removed during the
purification process. Since the 1880s, it has been one of the most used raw materials in
cosmetics and is an excellent ointment base used to formulate most drugs. Petrolatum is
an excellent occlusive agent that reduces moisture loss through the epidermis by 99% [
20
]
and is 170 times more effective in inhibiting moisture loss than olive oil, a vegetable oil.
However, when applied to the skin, the feeling of stickiness is severe [
21
]. Thus, its feeling
in use is not good and it is shiny. For these reasons, it is generally used for such as lip
protectant (lip balm) or a diaper rash ointment, rather than for facial uses.
Mineral Oil
Similar to Petrolatum, mineral oil is extracted from crude oil and is called mineral oil
to contrast with vegetable oil. Other names include white oil, liquid paraffin, paraffinum
liquidum, and liquid petroleum. Mineral oil is colorless and odorless, and is a component
commonly used as an occlusive agent to the extent that a product with added fragrance
has been commercialized as baby oil. Compared to petrolatum, the degree of reduction
in transdermal moisture loss is less when applied, but it has less stickiness and better
spreadability. Mineral oil is controversial in terms of induction of comedones, but one
study concluded that well-refined mineral oil did not induce comedones [22].
Medicina 2022,58, 888 4 of 17
3.1.2. Silicone
Silicone is a compound of the silicon present in sand or quartz. A very strong bond
called a siloxane bond (-Si-O-Si-) is formed between silicon and oxygen, resulting in stability
to heat, ultraviolet light, acid, alkali, electrical stimulation, and oxidation reaction. Silicone
does not dissolve in water, but it can emit water vapor, so it can be used in cosmetics with
a waterproof function without worrying about miliaria. Because it does not mix with the
sebum of the skin as well as water, the cosmetics are not easily erased by the sebum. Silicone
has good spreadability, is not sticky, induces fewer comedones and allergies, and has no
irritating scent. Silicones are commonly used ingredients in products labeled as “oil-free.”
Dimethicone and cyclomethicone are commonly used. Dimethicone has a moisturizing
effect as well as a softening effect, so it softens the dead skin cells of the skin and can vary
the viscosity, increasing the stability of emulsified cosmetics such as creams and lotions [
23
].
Dimethicone is the second most common active agent in moisturizers today, following
petrolatum, due to its hypoallergenic, noncomedogenic and nonacnegenic properties [24].
Toxicity due to topical application of silicone components has not been reported yet.
3.1.3. Vegetable Oils and Vegetable Fat
Oils and fats obtained by pressing various plants or extracting solvents are called
vegetable oils, which are liquid at room temperature, and vegetable fats, which are solid.
Vegetable oils include castor oil, olive oil, camellia oil, macadamia nut oil, and grape seed
oil, and vegetable fats include cocoa butter and shea butter. They are mainly composed of
triglycerides consisting of fatty acids and glycerin in their chemical structure. However,
they also contain unsaturated essential fatty acids of 18 carbons, such as oleic acid and
linoleic acid. These unsaturated fatty acids also play a good role in the barrier function, such
as acting as a PPAR alpha agonist [
25
], but when used as a cosmetic, they oxidize readily
and cause a smell, so antioxidants must be added. According to the recent consumer
preference for natural raw materials, each brand claims that various vegetable oils are
added to enhance the moisturizing function [26].
3.1.4. Waxes
Wax is an ester composed of a fatty acid and an alcohol in terms of chemical structure,
and generally has a high melting point [27].
Beeswax
Beeswax is secreted by bees when they make a honeycomb, and it has a very chemically
stable structure [
28
]. It is mainly composed of free cerotic acid and myricyl palmitate. It is
used in moisturizers used on the lips such as lip balms, lipsticks, and lip glosses, as well as
hair waxes and sunscreens.
Lanolin
Lanolin is an oil produced by the sebaceous glands of sheep and which coats their
wool [
29
]. Lanolin, also called wool fat, is a wax without glycerides. The main component
of lanolin is a long-chain wax ester. Refined lanolin used in pharmaceuticals and cosmetics
is a pale-yellow ointment-like substance and is an odorless substance containing fatty acids
and alcohols in a one-to-one ratio [
29
]. Lanolin is water-soluble and becomes a useful
emulsifying agent when mixed with other lipids. Since lanolin is a common allergen,
lanolin extracts or derivatives should be used instead of natural lanolin when used as
occlusive agents [29].
3.1.5. Fatty Acids and Fatty Alcohols
Fatty acids are esters (R-COOH), the main component of animal oils and fats, and
most of them are distilled by hydrolyzing triglycerides [
30
]. Long-chain fatty acids, such as
palmitic acid and stearic acid, are commonly used. In particular, stearic acids are widely
used in cosmetics as emollients and emulsifiers because they are saturated fatty acids,
Medicina 2022,58, 888 5 of 17
liquid, and chemically or microbially stable [
31
]. Alcohols used in cosmetics include cetyl
alcohol and stearyl alcohol, which are also used in creams or emulsions as emulsifiers, as
well as softening agents.
3.2. Emollients
Emollient refers to an ingredient that fills the gaps in the stratum corneum and gives
a soft feeling. On dry skin, the keratin mass is removed leading to a rough feeling, so
an emollient component is added in addition to the moisturizing component. Although
many emollient ingredients have moisturizing functions, there are also emollients that
do not reduce transepidermal moisture loss; that is, they have little moisturizing func-
tion. Emollients can be classified as protective, fatting, astringent, or dry according to
their inherent properties [
32
]. Emollients include a variety of high-grade alcohols and
esters. Among them, high-grade alcohols such as cetyl alcohol and stearyl alcohol used
as emollients do not dry the skin (unlike isopropyl alcohol and ethyl alcohol, which act
as astringents) and give a soft feeling when applied to the skin [
33
]. Ester type emollients
include octyl stearate, isopropyl myristate, oleyl oleate, cetearyl isononanoate, and PEG-7
glyceryl cocoate. In addition, lanolin, mineral oil, and petrolatum are substances that act as
an emollient and occlusive agent at the same time [
8
]. Substances that act as emollients are
listed in Table 1[8].
Table 1. Emollient substances.
Alcohols Esters
Octyldodecanol Oleyl oleate
Hexyldecanol Octyl stearate
Oleylalcohol
PEG-7 glyceryl cocoate
Coco caprylate/caprate
Myristyl myriate
Cetyaryl isononanoate
Isopropyl myriate
3.3. Humectants
Humectant refers to substances which, when applied to the skin surface, pull both
moisture in the atmosphere and moisture below the stratum corneum toward the stratum
corneum. When the humidity in the atmosphere is less than 80%, it mainly functions
to attract moisture below the stratum corneum [
34
]. Most humectants have a molecular
size of 200–500 kDa and can be absorbed into the stratum corneum. If the humectant
is of small size (MW = 200–300 Da), such as glycerol or urea, deeper layers of SC are
reached where they restore water content and barrier function, and replicate NMF func-
tion. Larger molecules (e.g., hyaluronic acid) do not penetrate the skin but increase the
hydration of the outermost corneocytes [
10
]. They are substances that contain many
hydroxyl (-OH) or amine (-NH) groups that can hydrogen bond with water molecules.
Among the humectants mainly used in cosmetics, water-soluble polyalcohols (glycerin,
-glycol) are the most common, and urea, lactate, pyrrolidine carboxylic acid (PCA), alpha
hydroxy acid (AHA), polypeptide, hyaluronic acid, sorbitol, collagen, and elastin are also
used. Among them, the main humectants are listed in Table 2[
8
]. Because transepidermal
moisture loss can increase when a humectant is applied alone, humectants are usually used
together with an occlusive agent.
Medicina 2022,58, 888 6 of 17
Table 2. Component of skin and moisturizer—hydrophilic humectant.
SC Component Biomimetic Moisturizer Ingredient
Natural moisturizing factors
Amino acid Amino acid
Pyrrolidone carboxylic acid
PCA & salts
Lactate AHA & salts
Urea Urea
Others Polyhydric alcohols:
Glycerin, propylene glycol, sorbitol
3.3.1. Glycerin
Glycerin is a powerful humectant and has similar hygroscopicity to natural moisturiz-
ing factors. After topical application, it increases the moisture content inside and outside
the keratinocytes, and prevents the lamellar structure of intercellular lipids from being
transformed from plate to crystal [
35
]. It also helps to protect the skin barrier by regulating
the expression of aquaporin-3, which is the primary aquaporin in the epidermis [
24
]. This
effect is maintained to some extent even after the glycerin is removed from the skin surface.
In addition, glycerin normalizes the enzyme activity that induces the decomposition of the
keratinocyte complex so that the keratin is removed normally.
3.3.2. Pyrrolidine Carboxylic Acid (PCA)
PCA, as a component of natural moisturizing factor (12%), in cosmetics, has an optimal
moisturizing effect at a concentration of 4% [36,37].
3.3.3. Urea
Urea is a component of a natural moisturizing factor (7%) and is mainly used as a
hand cream. When the concentration is less than 10%, it has a moisturizing effect, and
when it is higher than 10%, it shows a keratolytic effect. Urea is used as a 10% cream for the
treatment of ichthyosis and hyperkeratotic skin disorders, and in lower concentrations for
the treatment of less severe dryness [
38
–
40
]. However, it may sting even at a concentration
of less than 10%, so the face and sensitive areas should be avoided, and it is not a suitable
moisturizer for children.
3.3.4. Hydroxy Acids
Alpha-hydroxy acids (AHAs) are a kind of natural organic acid that not only wets the
stratum corneum of the skin but also decomposes the keratinocytes to exfoliate the dead
skin cells [
41
]. As a result, the keratin becomes thinner, increasing the flexibility of the skin,
and reducing the scales on the skin surface to give a smooth feeling. Glycolic acid and lactic
acid are the most commonly used. Lactic acid is an AHA and a component of a natural
moisturizing factor. It induces the formation of ceramides in keratinocytes as well as the
exfoliation of dead skin cells. The concentrations used for treatment of dry skin disorders
have ranged up to 12% [42], and the permitted use concentration for cosmetics is 5–10%.
3.3.5. Propylene Glycol
Propylene glycol has both a hydrating function (at concentration 10% or less) and
keratolytic function (at concentrations 40% or more) [43].
3.4. Other Ingredients
3.4.1. Emulsifiers
Moisturizers are a mixture of oil and water, which do not mix well with each other.
An emulsion is a two-phase system made up of two immiscible components in which
the dispersed phase is contained in the form of droplets within a continuous phase [
44
].
At this time, one phase is oil (oil phase) and the other phase is water (water phase). The
water-in-oil (w/o) system disperses the aqueous phase in the oil phase to make oily cream
Medicina 2022,58, 888 7 of 17
or cold cream. The oil-in-water (o/w) system disperses the oil phase in the aqueous phase,
so it makes a water-based cream or a vanishing cream that feels as though it disappears
quickly when applied to the skin. Sometimes it is possible to create an emulsion with both
forms in one system, which is called “ambiphilic cream” [45].
To make a stable emulsion by mixing the two components, a surfactant, that is, an
emulsifying component, must be added. The emulsifier has a polar group with strong
hydrophilicity and a non-polar group with strong lipophilicity at the same time, so it is
a material with high molecular weight that connects across the gap between polar and
non-polar substances. Surfactants can be classified into cationic, anionic, zwitterionic,
and nonionic surfactants according to their ionization when dissolved in water. Among
them, amphoteric surfactants or nonionic surfactants are mainly used for the purpose of
emulsifying moisturizers in the form of lotions and creams. Amphoteric surfactants include
amino acids, betaine-type, synthetic raw materials for imidazoline derivatives, and natural
products such as lecithin [
46
]. Nonionic surfactants include a wide variety of substances,
among which are hydroxyl groups (-OH), ether bonds (-O-), (-CONH-), and ester bonds
(-COOR). Among nonionic surfactants, stearate, PEG (polyethylene glycol), and cetearyl
alcohol are commonly used as moisturizing agents.
3.4.2. Preservatives
Moisturizers are stored at room temperature for a considerable period of time after
opening, and people frequently touch the opening of the container with hands so there is
a high probability of contamination. In general, moisturizers with low moisture such as
ointments and oil-based creams do not require preservatives, but lotions, o/w creams, and
gels contain a large amount of moisture so if they are contaminated by bacteria or fungi,
there is a high probability of microbial growth, so it is necessary to use preservatives [
47
].
To prevent the growth of these microbes, various preservatives or substances that discharge
preservative components are added to the moisturizer. Parabens, phenoxyethanol, sorbic
acid, propylene glycol, thimerosal, ethylene diamine-tetraacetate (among others) are used
as preservatives [
48
]. Antioxidants such as gallate, butylhydroxyanisole (BHA), and butyl-
hydroxytoluene (BHT) are used to prevent the rancidity of unsaturated fats in oil-based
moisturizers and lipsticks [49].
4. Moisturizers for Repairing the Barrier Function
Two of the functions of the lipid matrix in the stratum corneum are (1) to prevent
excessive water loss through the epidermis and (2) to avoid that compounds from the
environment permeate into the viable epidermal and dermal alyers and thereby provoke
an immune response [
50
]. Ceramide, cholesterol, and fatty acids, which are the main
components of keratinocyte interstitial lipids, have been found to be required for perme-
ability barrier homeostasis [
51
]. In this context, moisturizers containing these components
are being developed. In particular, the concept of a physiological lipid mixture in which
ceramide or pseudoceramide, cholesterol, and free fatty acids are mixed in an ideal ratio
(1:1:1 or 3:1:1) of stratum corneum lipids is applied to moisturizers. When applied to
the skin, normal lipids act as sealants or softeners in the stratum corneum, whereas the
physiological lipid mixture passes through the stratum corneum. Physiological lipids are
also used for lipid synthesis in granular keratinocytes, are stored in the keratinocytes, and
are transported between keratinocytes, directly participating in restoration of the skin bar-
rier. Therefore, when the physiological lipid mixture and the occlusive agents are applied
together, the occlusive agent prevents moisture loss within a short period of time, and
the lipid mixture gradually restores the skin barrier function, thereby recovering dry skin.
Based on this concept, several products have been developed as moisturizing agents for
atopic dermatitis with impaired barrier function. Although there is controversy over the
ability of the epidermis to synthesize lipids when the application is stopped after applying
a moisturizer containing this physiological lipid mixture for a long time, it is known that
most moisturizers do not reduce the synthesis of epidermal lipids [52,53].
Medicina 2022,58, 888 8 of 17
5. Classification of Moisturizers
Many cosmetic companies are selling not only moisturizers distributed through hospi-
tals and pharmacies, but also a variety of moisturizers through diverse other distribution
channels. In addition to products that claim to increase the moisture content of the skin,
almost all basic cosmetics, including lotions, creams, gels, and ointments, contain base
ingredients that have a moisturizing function. Thus, in fact, almost all basic cosmetics
can be said to be included in the moisturizer category. These basic cosmetics that act as
moisturizers are divided according to their popularly sold formulations [
54
], as shown in
Table 3.
Table 3. Classification of moisturizers.
Type Characteristics Functions Ingredient
Beauty
wash
Flexible lotion,
convergence lotion,
cleansing lotion
Solubilizing the insoluble
material in water soluble or
micro-emulsion techniques
make liquid cosmetic to show
a state that is transparent
ornon-transparent.
Used after cosmetic
washing and restoring
the skin surface pH to
slightly acidic and
supplying water.
Purified water (30 to 95%),
alcohol (0.40), wetting agents (to
20%), the emollient agent, an
emulsifier, detergent, solubilizing
agent (surfactant, thickening
agents), pH adjusting agents,
perfumes, preservatives,
pigments, discoloration inhibitors,
biologically active substance
Lotion o/w, w/o, w/o/w
Suitable for normal and oily
skin during the summer
because the feeling is neat due
to the high proportion of
water compared with oil.
Skin moisturizing and
improving flexibility.
Similar to the ratio of the cream
but the oil or wax components are
low. Nonionic, anionic, amino
acid-based surfactants are used
for easier dissolving.
Cream
High/Low/Mid oil
cream
(o/w, w/o)
Multiple cream
(o/w/o, w/o/w)
Types of emulsions which
disperse the two insoluble
materials in a stable state
Typically, higher proportion
of such as humectants and oil
than lotion.
Skin moisturizing,
improving flexibility,
supplying
pharmaceutical
ingredients for
cosmetics.
Stearic acid, alcohol, water,
stearic acid monoglyceride, etc.
Gel Water type
Oil type
Feeling very neat and possible
to use a water-soluble drug.
Providing a cooling
sensation on the skin.
nWater type
Water-soluble polymer in gel
(carboxyvinyl polymer, methyl
cellulose), and other moisturizing
agents, surfactants, a large
amount of water and alcohol, etc.
nOil type
Complex of oil and surfactants in
gel.
Essence Wrinkles
The concentration of
unparalleled beauty
ingredient for skin.
Anti-wrinkles,
moisturizing, softening
effect, whitening,
anti-acne effect
Water, lotion, cream, gel, etc.
Pack
Wiping Type
Detaching type
Attaching type
Improving blood circulation
to seal the skin for a period of
time. Making cosmetic
ingredients that are contained
in cosmetics to be well
absorbed and hydrate the
stratum corneum.
Moisturizing, flexibility,
occlusive effect,
cleansing effect,
promotion of skin
blood circulation
Gels, pastes, purified water,
alcohol, humectants, thickeners,
emollient agent, surfactant, etc.
6. Pathophysiology of Dry Skin
Healthy stratum corneum (SC) contains from 15% to 25% water at the skin surface, and
to about 40% at the SC/stratum granulosum border [
55
]. When the skin barrier structure
Medicina 2022,58, 888 9 of 17
is damaged, dry skin occurs in which the water-holding capacity of the stratum corneum
is reduced. When dry skin is subdivided according to the Baumann Skin Typing System,
dry skin is divided into three stages: dry, slightly dry, and extremely dry [
56
]. Dry skin
conditions can be further classified as combination skin and sensitive skin. Considering
that dry skin increases with age, the role of a moisturizer is likely to play the most basic
skin care role. Healthy skin should generally be able to store 10–15% water [
57
]. Too high
stratum corneum moisture, such as when your hands are soaked in water for a long time,
or too little moisture impairs the barrier function.
Dry skin is a very common condition that most people experience at some point in
their lives. The use of moisturizing products, popularly called emollients or moisturizers,
is the key to treating dry skin. Because the causes, symptoms, and severity of dry skin are
very diverse, the choice of moisturizer varies from person to person. Dry skin may not
have any symptoms to complain about, depending on the degree of subjective dryness, but
many may complain of a feeling of pulling or tightening, stinging, or cutting, especially
if it is accompanied by other diseases. Depending on the degree of dry skin, various
clinical findings are shown, including such as roughness, dull skin tone, scaling, redness,
cracks, and fissures. Several factors are involved, including both exogenous (e.g., climate,
environment, lifestyle) and endogenous (e.g., medication, hormone fluctuations, organ
diseases) factors [
57
]. There are also endogenous factors such as loss of barrier lipids, lack
of natural moisturizing factors (NMF), abnormal moisture delivery, and abnormality of the
keratin exfoliation cycle.
6.1. Abnormalities of Intercellular Lipids of Stratum Corneum
The stratum corneum lipids surround the keratinocytes, which contain adequate
moisture through natural moisturizing factors, and prevent the moisture of the skin from
easily evaporating. The stratum corneum lipids account for about 15% of the dry weight
of the stratum corneum, among which ceramides (50%), cholesterol (25%), and fatty
acids (20%) are particularly related to the barrier function [
58
]. The stratum corneum
lipids are well arranged in multiple layers around the lipid envelope bound to the cornified
cell envelope, and serve as an epidermal barrier. That is, stratum corneum lipids play a
role in preventing water loss through the epidermis, and conversely, prevent water-soluble
substances from passing through the epidermis and entering the human body. In truly dry
skin, the multilayer structure of the lipid membrane is damaged, and the fatty acid content
is increased while the ceramide content is lowered [
59
]. This damage to the lipid membrane
results in an increase in transepidermal water loss. A pH that is too high promotes the
degradation of the stratum corneum lipid membrane. Damage to the lipid membrane
can be caused by various causes, such as ultraviolet rays, use of detergents including
surfactants, acetone, chlorine bleach, friction, and excessive hydration.
6.2. Lack of Natural Moisturizing Factors (NMF)
A natural moisturizing factor is a kind of humectant that exists inside keratinocytes
and plays a role in adequately hydrating the stratum corneum [
60
]. Many researchers
have found a link between a reduction in the levels of NMF and dry skin [
61
]. The
NMF is found within corneocytes and is a mix of hygroscopic molecules which keep the
SC hydrated, helping maintain hydration in the corneocyte [
62
]. When a protein called
filaggrin, which plays a role in arranging and bonding keratinocytes in keratinocytes is
decomposed, urocanic acid, pyrrolidone carboxylic acid (PCA), and several amino acids
are produced. These osmotic amino acids and other natural moisturizing factors exist in
keratinocytes and have a moisturizing function, so they act as a factor to maintain moisture
in the skin. Genetic alterations in filaggrin metabolism are associated with impaired barrier
function and reduced water binding capacity and are the etiology of certain pruritus and
atopic dermatitis cases [
63
]. Other natural moisturizing factors include lactic acid, urea,
and inorganic ions such as sodium, potassium, calcium, and chloride, all of which help to
maintain the epidermis’ moisture content.
Medicina 2022,58, 888 10 of 17
6.3. Abnormal Desquamation of the Stratum Corneum
A normal desquamation process occurs in very small units of keratinocytes and is
invisible to our eyes. Clinically dry skin appears to be covered with scales, which is caused
by abnormal keratinocyte exfoliation. An important factor controlling the exfoliation of
the stratum corneum is the degree of activation of various proteolytic enzymes, which are
controlled by the pH and hydration level of the skin [
64
]. In dry skin caused by winter or
excessive use of soap, the corneodesmosome of the upper stratum corneum is increased
compared to normal skin and desmoglein 1 is increased in the surface stratum corneum.
When the moisture content is low, the function of the enzyme that removes them is reduced,
making skin look rough [
65
]. The aggregated dry keratinocytes are visible. Conversely,
when the stratum corneum is hydrated, a lacuna is formed in a hydrophilic keratinocyte
site due to the action of a proteolytic enzyme, and keratin exfoliation occurs. As this series
of unnatural processes occurs, the phenomenon of keratin aggregation in the form of visible
scales happens, after which they fall off at once.
7. Basic Principles for Using Moisturizers on Dry Skin
Basic skincare for the treatment of dry skin is intended to improve skin moisturization,
supplement barrier lipid deficiency, and improve skin barrier function. Therefore, it is basic
to use moisturizers with a good combination of hydrophilic and hydrophobic ingredients,
and products with low fragrance and allergens are recommended. The lower the lipid
content of the stratum corneum, the better the local fat-rich agents can penetrate, and in
extreme dry cases, moisturizers containing more lipids in the base can quickly relieve dry
symptoms by suppressing moisture loss [66].
It is recommended that dry skin be cleansed and showered with lukewarm water and
a synthetic cleanser (Syndet) made of mild surfactant be used that does less damage to skin
lipids and natural moisturizers and that users refrain from using regular soaps [
67
]. The
ratio of surfactants that can irritate the skin is reduced in the order of cationic > anionic
> amphoteric > non-ionic surfactants. In addition, the larger the size of the micelle of the
surfactant, the less it penetrates the stratum corneum, so it is recommended to refer to the
selection of cleaning agents for dry skin. It is recommended to avoid using alkaline soap
because dry skin has impaired barrier function and degraded pH recovery.
8. Selection of Basic Cosmetics for Individual Skin Diseases
Moisturizers are used not only for the purpose of normal skin care, but also for the
treatment of skin diseases with reduced skin barrier function or for clinically dry skin. In
particular, moisturizers play an important role as adjuvant in the treatment of common
skin diseases such as atopic dermatitis, contact dermatitis, psoriasis, acne, and rosacea.
8.1. Atopic Dermatitis
Moisturizers that can restore the damaged barrier function, the main pathophysiology
of atopic dermatitis, are not just cosmetics, but also act as therapeutic agents. As research on
the skin barrier progresses, moisturizers containing natural moisturizing factors, ceramides,
and pseudoceramides have been released under the concept of a therapeutic moisturizer,
and are widely used by patients with atopic dermatitis.
Prof. Pester Elias’s team investigated the effects of the external application of three
types of lipids (ceramide, cholesterol, and free fatty acids) that constitute intercellular
lipids [
45
]. When applied alone or in a mixture of two, the treatment did not help to
restore the barrier function but rather weakened it due to the direct toxic effect of the
lipid. However, when the three types were mixed in an appropriate ratio and applied, the
restoration of the barrier function was accelerated. Based on the results of these studies, the
concept of a physiological lipid mixture showing optimal synergistic effect was proposed.
The mixing ratio of ceramide, cholesterol and free fatty acids is known to be most effective at
a molar ratio of 3:1:1, and each concentration of 1–2% or more is appropriate. Moisturizers
based on these research results went through clinical trials directly applied to patients and
Medicina 2022,58, 888 11 of 17
were approved by the US FDA as a therapeutic material for improving the symptoms of
atopic dermatitis.
In addition, moisturizers for atopic dermatitis often contain natural moisturizing
factors, such as urea, lactate, sodium PCA, and hyaluronate. Anti-inflammatory ingredients
such as glycyrrhetinic acid and palmitoylethanolamide (PEA), along with various plant
extracts with anti-inflammatory and antibacterial effects (such as Peony extract) are widely
used [
68
]. However, although anti-inflammatory and antibacterial effects of individual
ingredients are confirmed, because each ingredient is added in a small amount, there is a
lack of evidence to prove the beneficial effects of cosmetic formulations in atopic dermatitis.
The results of clinical studies on the use of cosmetics that claim to be effective for atopic
dermatitis vary, ranging from just a slight relief of dry skin to an effect corresponding
to that with steroid ointment, as well as increased antimicrobial peptides in the lesions.
Because atopic dermatitis is a chronic disease, the selection of a moisturizer is important,
but it is more important for patients to regularly use an appropriate amount of moisturizer
through identification of the patient’s characteristics and the education of patients and
caregivers.
In addition to moisturizers, cleaning agents are important skin care products that can
help patients with atopic dermatitis. Two effects can be expected through proper bathing in
atopic dermatitis patients: the action of cleaning away harmful irritants or allergy-causing
substances and various pathogens (bacteria/viruses) present on the skin surface, and
temporary promotion of skin hydration. Despite these positive effects, excessive bathing
and use of strong detergents can destroy the skin’s natural moisturizing factor and lipid
membrane, so the skin barrier function may be impaired. There are cases where patients
and caregivers think only of these effects and do not bathe often, or even only with water.
Alternatively, there is the opposite case of excessively washing with a detergent such as
solid soap, which is strongly irritating to the skin. In order to enhance the effectiveness
of the bath, it is necessary to use an appropriate cleaning agent. Although any type of
cleaning agent used for bathing can be used as long as it does not significantly affect the
stratum corneum acidity, a mild surfactant should be used if possible, and a mildly acidic,
hypoallergenic detergent is recommended. Most synthetic detergents that come in the
form of liquid, gel, or foam rather than solid soap, reflect these characteristics well. It is
appropriate to shower or bathe once a day or every two days.
Meanwhile, there is controversy about the claim that applying a moisturizer prevents
the occurrence of atopic dermatitis. Several studies showed that when emollient was
applied daily to infants starting within 3 weeks of age, the relative risk of developing atopic
dermatitis was reduced at 6 to 24 months of age [
69
,
70
]. On the other hand, other studies
claimed that applying emollients showed reduction in AD incidence up to 12 months of
age no benefit at 24 months of age, hypothesizing that the emollients delay the onset of AD
rather than prevent it [71].
However, in other studies of similar design, moisturizer application did not reduce
the incidence of AD [
72
]. A large randomized controlled trial conducted in 2020 reported
that daily emollient application had no effect in preventing eczema in high-risk children,
but could increase the risk of skin infection or disturb the natural protective skin micro-
biome [73].
Various factors can affect the effectiveness of the emollient, such as the type of emol-
lient, the number of times of application, and the start time, so it is difficult to conclude yet.
A new large randomized controlled trial, Prevention of Eczema by a Barrier Lipid Equilib-
rium Strategy (PEBBLES), which controlled for these factors, is currently underway [
7
,
74
].
8.2. Contact Dermatitis
Irritant contact dermatitis is dermatitis caused by acute or chronic damage to the
stratum corneum of the skin due to exposure of the skin to an irritant substance, thereby
damaging the barrier function. Although irritant contact dermatitis patients use moistur-
izers empirically, some moisturizers do not play a role in improving the barrier function
Medicina 2022,58, 888 12 of 17
other than a temporary softening effect on the skin, so the selection of a moisturizer with
an appropriate proportion of occlusive agent and humectant is important. Regular use of
a moisturizing agent with a high lipid content is effective in preventing irritant contact
dermatitis caused by surfactants in normal skin and in treating existing irritant contact
dermatitis [13,75].
The non-lesional skin of patients with allergic contact dermatitis has a slow barrier
recovery rate and a significant decrease in ceramide content, showing a barrier defect as in
atopic dermatitis [
76
]. The principle of using a moisturizer or cleaning agent for allergic
contact dermatitis is similar to that of atopic dermatitis patients.
8.3. Psoriasis
Psoriatic lesions show a higher TEWL value compared to that of uninvolved sites [
77
].
The use of moisturizers for psoriasis is effective when supplemented with other treatments,
such as steroids and vitamin D preparations. Moreover, the use of moisturizers such as
mineral oil before UV treatment can reduce the reflectivity of dead cells in thick skin. In a
randomized controlled trial in palmoplantar psoriatic patients, the degree of desquamation,
surface area, and subjective symptom improvement was significantly greater when emol-
lient was used together compared to when only steroids were used [
41
]. In another study,
it is claimed that applying a moisturizer in a stable state while applying a steroid ointment
intermittently for mild psoriasis prevents recurrence [
78
]. To relieve hyperkeratosis of
psoriasis, one can use a moisturizer containing such as AHA, salicylic acid (BHA), urea,
and glycolic acid, which have keratolytic action.
9. Moisturizer Selection Criteria, Usage, and Side Effects
9.1. Moisturizer Selection Criteria
A good moisturizer should be applied gently to the skin, retain moisture for a long
time, and be able to restore the skin’s normal barrier function. The choice of moisturizer
depends on the user’s skin type (i.e., dry, oily, or combination), the season, and the area
to be treated. Moisturizer formulations are divided into lotions and cream ointments in
the order of high moisture content. When choosing a formulation, skin type is the most
important factor (dry, oily, normal, and combination are the selection criteria). For dry
skin, select an ointment or oily cream formulation, and for oily skin, select a lotion and
water-based cream formulation. The body part to be used is also a consideration. For hands,
feet, shins, and lips, which are prone to dry skin due to their small amount of sebaceous
glands, an ointment or cream formulation containing a large amount of occlusive agents
should be selected. In addition, it is preferable to use a moisturizer-oriented product in
summer and an oil-based cream formulation containing large amounts of occlusive agents
in winter.
In skin diseases with accompanying dryness, the importance of moisturizers as an
adjuvant therapy beyond simply moisturizing is being emphasized. In the past, moistur-
izers gave the skin the wetting function of natural moisturizing factors and the sealing
function of sebum. Recently, in terms of restoration and strengthening of the skin bar-
rier function, it is known that inter-keratinocyte lipid components such as ceramide and
lamellar structure play a very important role in maintaining the skin barrier function and
maintaining skin homeostasis. The ideal moisturizer should have the wetting function
of natural moisturizing factors, the sealing function of the skin lipid membrane, and the
barrier function of lipid between keratinocytes. This will be a product that can effectively
restore the lamellar structure. Several domestic and foreign companies are highlighting
the advantage of having their own lipid layered structure be well-fused to the stratum
corneum lipid membrane. Many moisturizers use synthetic ceramides or similar pseudoce-
ramides, or some have ceramide precursors or enhancers that can increase synthesis [
79
].
Moisturizers in the form of physiological lipid compounds are known to reduce damage
to the skin barrier function caused by external steroids, so their use can be expected to
increase as a therapeutic adjuvant.
Medicina 2022,58, 888 13 of 17
9.2. How to Use Moisturizer
Moisturizer should be applied gently after wiping away the moisture on the skin after
washing the face or bathing. Apply several times for dry skin, and reduce the number of
times for oily skin. Moisturizers centered on humectants can evaporate epidermal moisture
when exposed to cold, dry air after being applied to the skin, so it is recommended to apply
the product 30 min before exposure to cold, dry air. If the skin will be exposed to dry air
immediately after application, select a product that contains an occlusive agent. It is good
to suppress water loss immediately.
9.3. Side Effects of Moisturizers
Side effects may occur when using cosmetics containing moisturizers. The stability
of cosmetic ingredients is being treated as more and more important, and the cumulative
amount of cosmetics that are frequently applied to the whole body, such as moisturizers, is
considerable. It is especially important to choose products with safe ingredients and at safe
concentrations because the absorption of cosmetic ingredients can increase if users have
damaged skin barriers due to something comparable to atopic dermatitis, or because their
skin is immature (infants and children).
When using cosmetics, the main side effects are irritating reactions such as stinging,
itching, burning, and pulling. Moreover, symptoms of allergic contact dermatitis, photo
contact dermatitis, and contact moles may occur. The main causative substances are preser-
vatives, fragrances, and other additives, and their concentrations are important indicators
as well as types. For example, propylene glycol, which is a moisturizer and serves as a
preservative, is known to irritate frequently if the concentration is higher than 20%, but con-
centrations of 2 to 3% are known to cause little irritation [
80
]. In Korea, from 1 January 2020,
the labeling of allergens in cosmetics and fragrances became mandatory. In addition,
25 types of allergen-inducing ingredients among the ingredients of fragrances determined
by the Ministry of Food and Drug Safety are indicated by their ingredient names [
81
].
There are 25 allergens, including Alpha-isomethylionone, Amylcinnamal, Amylcinnamyl
alcohol, Anisethanol, Benzyl alcohol, Benzylbenzoate, Benzylcinnamate, Benzyl salicylate,
Butylphenylmethylpropional, Cinnamyl, Cinnamyl alcohol, Citral, Citronellol, Coumarin,
Eugenol, Gerani All, Hexylcinnamal, Hydroxycitronellal, Isoeugenol, Limonene, Linalol,
Methyl2-octinoate, Oaktree moss extracts, and Panesol.
When allergic or irritant reactions caused by moisturizing ingredients are suspected, a
single or repeated patch test and open patch test are performed for diagnosis [
64
]. Because
other long-term safety issues regarding the effect on reproductive function or the possibility
of carcinogenesis are emerging in products such as preservatives and fungicides, the
dermatologist should know the exact basis for any issue.
10. Conclusions
As the interest in beauty continues to increase, the use and demand for cosmetics
in women, men, and children are increasing explosively. Numerous cosmetics are being
released by a variety of cosmetic companies today, and in particular, moisturizers are used
not only for patients suffering from skin diseases but also for people with normal skin.
Moreover, it is often difficult to choose from among the numerous moisturizers available.
With the information provided in this paper, it should be possible to compare and select
moisturizers based on accurate scientific information for the effectiveness and safety of the
bases and additives included in these moisturizers.
Author Contributions:
Conceptualization, S.-Y.K. and H.-O.K.; formal analysis, S.-Y.K., J.-S.P., J.-Y.U.
and B.-Y.C.; investigation, S.-Y.K., B.-Y.C. and S.-Y.L. ; resources, C.-W.P., J.-Y.U. and H.-O.K.; data
curation, J.-C.K., J.-S.P. and S.-Y.L.; writing—original draft preparation, S.-Y.K. and H.-O.K.; writing—
review and editing, H.-O.K., C.-W.P. and B.-Y.C.; supervision, H.-O.K.; project administration, H.-O.K.,
J.-S.P. and S.-Y.K.; funding acquisition, H.-O.K. All authors have read and agreed to the published
version of the manuscript.
Medicina 2022,58, 888 14 of 17
Funding:
This study was supported by grants from the Hallym University Research Fund (HURF-
2021-07).
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Not applicable.
Conflicts of Interest: The authors declare no conflict of interest.
Abbreviations
TEWL Trans-epidermal Water Loss
SC Stratum Corneum
PPAR Peroxisome Proliferated-activated Receptor
PEG Polyetyhylene Glycol
PCA Pyrrolidine Carboxylic Acid
AHA Alpha Hydroxy Acid
BHA Butylhydroxyanisole
BHT Butylhydroxytoluene
NMF Natural Moisturizing Factors
SLS Sodium Lauryl Sulfate
References
1.
Kligman, A. The future of cosmeceuticals: An interview with Albert Kligman, MD, Ph.D. Interview by Zoe Diana Draelos.
Dermatol. Surg. 2005,31 Pt 2, 8890–8891.
2.
Assali, M.; Zaid, A.N. Features, applications, and sustainability of lipid nanoparticles in cosmeceuticals. Saudi Pharm. J.
2022
,30,
53–65. [CrossRef] [PubMed]
3. Pandey, A.; Jatana, G.K.; Sonthalia, S. Cosmeceuticals. In StatPearls; StatPearls Publishing: Treasure Island, FL, USA, 2022.
4.
Shindo, S.; Murota, H.; Seki, T.; Mori, K.; Kaizu, K.; Nishizaka, T.; Takagi, Y.; Katayama, I. Effects of a moisturizer containing
pseudo-ceramide and a eucalyptus extract on sweating function in adult atopic dermatitis: A double-blind, randomized,
controlled left-right comparison clinical trial. J. Cosmet. Dermatol. 2022. [CrossRef] [PubMed]
5.
Bhat, B.B.; Kamath, P.P.; Chatterjee, S.; Bhattacherjee, R.; Nayak, U.Y. Recent Updates on Nanocosmeceutical Skin Care and
Anti-Aging Products. Curr. Pharm. Des. 2022. [CrossRef]
6.
Wang, Q.; Lu, J.; Jin, Z.; Chen, K.; Zhao, M.; Sun, Y. Study on the Structure and Skin Moisturizing Properties of Hyaluronic Acid
Viscose Fiber Seamless Knitted Fabric for Autumn and Winter. Materials 2022,15, 1806. [CrossRef]
7.
Danby, S.G.; Andrew, P.V.; Taylor, R.N.; Kay, L.J.; Chittock, J.; Pinnock, A.; Ulhaq, I.; Fasth, A.; Carlander, K.; Holm, T.; et al.
Different types of emollient cream exhibit diverse physiological effects on the skin barrier in adults with atopic dermatitis.
Clin. Exp. Dermatol. 2022,47, 1154–1164. [CrossRef]
8. Lodén, M.; Maibach, H.I. Dry Skin and Moisturizers: Chemistry and Function; CRC Press: Boca Raton, FL, USA, 1999.
9.
Chamlin, S.L.; Kao, J.; Frieden, I.J.; Sheu, M.Y.; Fowler, A.J.; Fluhr, J.W.; Elias, P.M. Ceramide-dominant barrier repair lipids
alleviate childhood atopic dermatitis: Changes in barrier function provide a sensitive indicator of disease activity. J. Am. Acad.
Dermatol. 2002,47, 98–208. [CrossRef]
10.
Proksch, E.; Lachapelle, J.M. The management of dry skin with topical emollients–recent perspectives: Behandlung der trockenen
Haut mit topischen Emulsionen–neue Entwicklungen. JDDG J. Dtsch. Dermatol. Ges. 2005,3, 768–774. [CrossRef]
11.
Kawasaki, A.; Hashimoto, H.; Shimotoyodome, Y.; Ito, S.; Ishikawa, J.; Sugai, Y.; Fujimori, T. Limonoids and unsaturated fatty
acids present in Melia toosendan increase ceramide production in keratinocytes. Fitoterapia 2021,155, 105058. [CrossRef]
12. Rawlings, A.V.; Harding, C.R. Moisturization and skin barrier function. Dermatol. Ther. 2004,17, 43–48. [CrossRef]
13.
Yokota, M.; Maibach, H.I. Moisturizer effect on irritant dermatitis: An overview. Contact Dermat.
2006
,55, 65–72. [CrossRef]
[PubMed]
14.
Rowley, G.G.; MacNeill, S.J.; Ridd, M.J. Emollient satisfaction questionnaire: Validation study in children with eczema. Clin. Exp.
Dermatol. 2022,47, 1337–1345. [CrossRef] [PubMed]
15.
Glaser, D.A.; Mattox, A.R. Cutaneous Barrier Function, Moisturizer Effects and Formulation. In Cosmeceuticals and Cosmetic
Practice; Wiley: Hoboken, NJ, USA, 2013; pp. 55–65.
16.
Lee, J.; Lee, M. Comparative review on Cosmetics Legislation of Korea, Japan, the United States and Europe. Regul. Res. Food
Drug Cosmet. 2008,3, 57–70.
17. Baumann, L.S. Cosmeceuticals and Cosmetic Ingredients; McGraw Hill Professional: New York, NY, USA, 2014.
18.
Gallinger, J.; Kuhn, A.; Wessel, S.; Behm, P.; Heinecke, S.; Filbry, A.; Hillemann, L.; Rippke, F. Depth-dependent hydration
dynamics in human skin: Vehicle-controlled efficacy assessment of a functional 10% urea plus NMF moisturizer by near-infrared
Medicina 2022,58, 888 15 of 17
confocal spectroscopic imaging (KOSIM IR) and capacitance method complemented by volunteer perception. Skin Res. Technol.
2022,28, 342–349. [CrossRef]
19.
Al-Zuhairy, S.A.S.; Kadhum, W.R.; Alhijjaj, M.; Kadhim, M.M.; Al-Janabi, A.S.; Salman, A.W.; Al-Sharifi, H.K.R.; Khadom, A.A.
Development and Evaluation of Biocompatible Topical Petrolatum-liquid Crystal Formulations with Enhanced Skin Permeation
Properties. J. Oleo Sci. 2022,71, 459–468. [CrossRef]
20. Friberg, S.; Ma, Z.-N.; Curtis, H. Stratum corneum lipids, petrolatum and white oils. Cosmet. Toilet. 1993,108, 55–59.
21.
Sethi, A.; Kaur, T.; Malhotra, S.K.; Gambhir, M.L. Moisturizers: The Slippery Road. Indian J. Dermatol.
2016
,61, 279–287. [CrossRef]
22. DiNardo, J.C. Is mineral oil comedogenic? J. Cosmet. Dermatol. 2005,4, 2–3. [CrossRef]
23.
Yamaguchi, S.; Yasumura, R.; Okamoto, Y.; Okubo, Y.; Miyagi, T.; Kawada, H.; Takahashi, K. Efficacy and safety of a dimethicone
lotion in patients with pyrethroid-resistant head lice in an epidemic area, Okinawa, Japan. J. Dermatol.
2021
,48, 1343–1349.
[CrossRef]
24.
Nair, B. Final report on the safety assessment of stearoxy dimethicone, dimethicone, methicone, amino bispropyl dimethicone,
aminopropyl dimethicone, amodimethicone, amodimethicone hydroxystearate, behenoxy dimethicone, C24-28 alkyl methicone,
C30-45 alkyl methicone, C30-45 alkyl dimethicone, cetearyl methicone, cetyl dimethicone, dimethoxysilyl ethylenediamino-
propyl dimethicone, hexyl methicone, hydroxypropyldimethicone, stearamidopropyl dimethicone, stearyl dimethicone, stearyl
methicone, and vinyldimethicone. Int. J. Toxicol. 2003,22 (Suppl. S2), 11–35.
25.
Levin, J.; Miller, R. A Guide to the Ingredients and Potential Benefits of Over-the-Counter Cleansers and Moisturizers for Rosacea
Patients. J. Clin. Aesthet. Dermatol. 2011,4, 31–49. [PubMed]
26. Draelos, Z.D. Active agents in common skin care products. Plast. Reconstr. Surg. 2010,125, 719–724. [CrossRef] [PubMed]
27.
Domergue, F.; Miklaszewska, M. The production of wax esters in transgenic plants: Towards a sustainable source of bio-lubricants.
J. Exp. Bot. 2022,73, 2817–2834. [CrossRef]
28.
Rojas, J.; Cabrera, S.; Benavides, J.; Lopera, Y.; Yarce, C.J. Lipidic Matrixes Containing Clove Essential Oil: Biological Activity,
Microstructural and Textural Studies. Molecules 2021,26, 2425. [CrossRef] [PubMed]
29.
Uldahl, A.; Engfeldt, M.; Svedman, C. Clinical relevance of positive patch test reactions to lanolin: A ROAT study. Contact Dermat.
2021,84, 41–49. [CrossRef]
30.
Aziz, A.A.; Nordin, F.N.M.; Zakaria, Z.; Abu Bakar, N.K. A systematic literature review on the current detection tools for
authentication analysis of cosmetic ingredients. J. Cosmet. Dermatol. 2022,21, 71–84. [CrossRef] [PubMed]
31.
Zhi, Z.; Liu, R.; Wang, W.; Dewettinck, K.; Van Bockstaele, F. Recent progress in oil-in-water-in-oil (O/W/O) double emulsions.
Crit. Rev. Food Sci. Nutr. 2022, 1–12. [CrossRef] [PubMed]
32.
Draelos, Z.D.; Dover, J.S.; Alam, M. Cosmeceuticals E-Book: Procedures in Cosmetic Dermatology Series; Elsevier: Amsterdam, The
Netherlands, 2014.
33.
Nishioka, K.; Koizumi, A.; Takita, Y. Seven cases of contact dermatitis due to stearyl alcohol contained in topical medications.
J. Dermatol. 2022,49, 515–518. [CrossRef]
34. Idson, B. Dry skin: Moisturizing and emolliency. Cosmet. Toilet. 1992,107, 69.
35.
Froebe, C.L.; Simon, F.A.; Ohlmeyer, H.; Rhein, L.D.; Mattai, J.; Cagan, R.H.; Friberg, S.E. Prevention of stratum corneum lipid
phase transitions in vitro by glycerol-An alternative mechanism for skin moisturization. J. Soc. Cosmet. Chem. 1990,41, 51–65.
36.
Harding, C.R.; Rawlings, A.V. Effects of natural moisturizing factor and lactic acid isomers on skin function. In Dry Skin and
Moisturizers: Chemistry and Function, 2nd ed.; Maibach, H.I., Loden, M., Eds.; CRC Press LLC: Boca Raton, FL, USA, 2006;
pp. 187–209.
37.
Biagi, M.; Giachetti, D.; Miraldi, E.; Figura, N. New non-alcoholic formulation for hand disinfection. J. Chemother.
2004
,26, 86–91.
[CrossRef] [PubMed]
38. Lodén, M. The clinical benefit of moisturizers. J. Eur. Acad. Dermatol. Venereol. 2005,19, 672–688. [CrossRef] [PubMed]
39.
Kibbe, A.W. Handbook of Pharmaceutical Excipients, 3rd ed.; American Pharmaceutical Association, Pharmaceutical Press: Washing-
ton, DC, USA; London, UK, 2000.
40.
Rosten, M. The treatment of ichthyosis and hyperkeratotic conditions with urea. Australas. J. Dermatol.
1970
,11, 142–144.
[CrossRef] [PubMed]
41.
Tang, J.; Yang, J.; Zhang, C.; Zhang, X.; Chen, Q.; Zhang, S.; Chen, L.; Wang, C.; Li, W. The factors influencing the unmet effects of
alpha hydroxy acid peels on acne vulgaris: A single tertiary center experience. Dermatol. Ther. 2021,34, e14956. [CrossRef]
42.
Wehr, R.; Krochmal, L.; Bagatell, F.; Ragsdale, W. A controlled two-center study of lactate 12 percent lotion and a petrolatum-based
creme in patients with xerosis. Cutis 1986,37, 205–207, 209.
43. Baran, R.; Maibach, H.I. Textbook of Cosmetic Dermatology, 4th ed.; CRC Press: London, UK, 2011; pp. 184–185.
44.
Lu, G.W.; Gao, P. CHAPTER 3—Emulsions and Microemulsions for Topical and Transdermal Drug Delivery. In Personal Care &
Cosmetic Technology, Handbook of Non-Invasive Drug Delivery Systems; Kulkarni, V.S., Ed.; William Andrew Publishing: Oxford, UK,
2010; pp. 59–94.
45.
Tepmongkol, P.; Chuthasri, S.; Rodprasert, T.; Rattanapol, P.; Maneenil, W. The use of ambiphilic dermatological cream and
radiation dermatitis in radiation therapy: A clinical study at Siriraj hospital, Bangkok. J. Med. Assoc. Thai 1981,64, 328–332.
46.
Seino, H.; Kawaguchi, N.; Arai, Y.; Ozawa, N.; Hamada, K.; Nagao, N. Investigation of partially myristoylated carboxymethyl
chitosan, an amphoteric-amphiphilic chitosan derivative, as a new material for cosmetic and dermal application. J. Cosmet.
Dermatol. 2021,20, 2332–2340. [CrossRef]
Medicina 2022,58, 888 16 of 17
47. Roden, K. Preservatives in personal care products. Microbiol. Aust. 2010,31, 195–197. [CrossRef]
48.
Jung, S.J.; Hwang, Y.S.; Choi, C.M.; Park, A.S.; Kim, S.U.; Kim, H.J.; Kim, J.H.; Jung, K. Examination and quantification of
preservatives in cosmetics for children. J. Soc. Cosmet. Sci. Korea 2015,41, 219–227. [CrossRef]
49.
García, C.D.; Ortiz, P.I. BHA and TBHQ quantification in cosmetic samples. Electroanal. Int. J. Devoted Fundam. Pract. Asp.
Electroanal. 2000,12, 1074–1076. [CrossRef]
50.
Van Smeden, J.; Bouwstra, J.A. Stratum Corneum Lipids: Their Role for the Skin Barrier Function in Healthy Subjects and Atopic
Dermatitis Patients. Curr. Probl. Dermatol. 2016,49, 8–26.
51.
Man, M.M.; Feingold, K.R.; Thornfeldt, C.R.; Elias, P.M. Optimization of physiological lipid mixtures for barrier repair. J. Investig.
Dermatol. 1996,106, 1096–1101.
52.
Lee, S.-S.; Kim, S.-Y.; Im, M.; Lee, Y.; Lee, J.-H.; Seo, Y.-J. The influence of physiologic lipid containing moisturizer on the normal
skin barrier. Korean J. Dermatol. 2011,49, 339–344.
53.
Hon, K.L.; Leung, A.K.; Barankin, B. Barrier repair therapy in atopic dermatitis: An overview. Am. J. Clin. Dermatol.
2013
,14,
389–399. [CrossRef] [PubMed]
54. Tagami, H.; Sugibayashi, K.; Nozaki, H.; Shukuzaki, K.; Kanda, Y. Cosmetic Science Guide, 2011.
55.
Caspers, P.J.; Lucassen, G.W.; Carter, E.A.; Bruining, H.A.; Puppels, G.J.
In vivo
confocal Raman microspectroscopy of the skin:
Noninvasive determination of molecular concentration profiles. J. Investig. Dermatol. 2001,116, 434–442. [CrossRef] [PubMed]
56. Baumann, L. The Skin Type Solution: A Revolutionary Guide to Your Best Skin Ever; Bantam Books: New York, NY, USA, 2006.
57.
Pons-Guiraud, A. Dry skin in dermatology: A complex physiopathology. J. Eur. Acad. Dermatol. Venereol.
2007
,21 (Suppl. S2), 1–4.
[CrossRef]
58.
Feingold, K.R. Thematic review series: Skin lipids. The role of epidermal lipids in cutaneous permeability barrier homeostasis.
J. Lipid Res. 2007,48, 2531–2546. [CrossRef]
59.
Danby, S.G.; Andrew, P.V.; Kay, L.J.; Pinnock, A.; Chittock, J.; Brown, K.; Williams, S.F.; Cork, M.J. Enhancement of stratum
corneum lipid structure improves skin barrier function and protects against irritation in adults with dry, eczema-prone, skin. Br.
J. Dermatol. 2021,186, 875–886. [CrossRef]
60.
Sonoki, Y.; Dat Pham, Q.; Sparr, E. Beyond Additivity: A mixture of glucose and NaCl can influence skin hydration more than the
individual compounds. J. Colloid Interface Sci. 2022,613, 554–562. [CrossRef]
61. Nakagawa, N.; Sakai, S.; Matsumoto, M.; Yamada, K.; Nagano, M.; Yuki, T.; Sumida, Y.; Uchiwa, H. Relationship between NMF
(lactate and potassium) content and the physical properties of the stratum corneum in healthy subjects. J. Investig. Dermatol.
2004
,
122, 755–763. [CrossRef]
62.
Verdier-Sévrain, S.; Bonté, F. Skin hydration: A review on its molecular mechanisms. J. Cosmet. Dermatol.
2007
,6, 75–82. [CrossRef]
[PubMed]
63.
Lodén, M. Role of topical emollients and moisturizers in the treatment of dry skin barrier disorders. Am. J. Clin. Dermatol.
2003
,4,
771–788. [CrossRef]
64.
Borgoño, C.A.; Michael, I.P.; Komatsu, N.; Jayakumar, A.; Kapadia, R.; Clayman, G.L.; Sotiropoulou, G.; Diamandis, E.P.
A potential role for multiple tissue kallikrein serine proteases in epidermal desquamation. J. Biol. Chem.
2007
,282, 640–652.
[CrossRef] [PubMed]
65.
Cassano, N.; Mantegazza, R.; Battaglini, S.; Apruzzi, D.; Loconsole, F.; Vena, G.A. Adjuvant role of a new emollient cream in
patients with palmar and/or plantar psoriasis: A pilot randomized open-label study. G Ital. Dermatol. Venereol.
2010
,145, 789–792.
[PubMed]
66.
Spada, F.; Harrison, I.P.; Barnes, T.M.; Greive, K.A.; Daniels, D.; Townley, J.P.; Mostafa, N.; Fong, A.T.; Tong, P.L.; Shumack, S.
A daily regimen of a ceramide-dominant moisturizing cream and cleanser restores the skin permeability barrier in adults with
moderate eczema: A randomized trial. Dermatol. Ther. 2021,34, e14970. [CrossRef]
67. Subramanyan, K. Role of mild cleansing in the management of patient skin. Dermatol. Ther. 2004,17, 26–34. [CrossRef]
68.
Zhang, Y.Q.; Liang, R.; Liu, C.; Yang, C. Improved stability and skin penetration through glycethosomes loaded with glycyrrhetinic
acid. Int. J. Cosmet. Sci. 2022,44, 249–261. [CrossRef]
69.
Simpson, E.L.; Chalmers, J.R.; Hanifin, J.M.; Thomas, K.S.; Cork, M.J.; McLean, W.H.; Brown, S.J.; Chen, Z.; Chen, Y.; Williams,
H.C. Emollient enhancement of the skin barrier from birth offers effective atopic dermatitis prevention. J. Allergy Clin. Immunol.
2014,134, 818–823. [CrossRef]
70.
McClanahan, D.; Wong, A.; Kezic, S.; Samrao, A.; Hajar, T.; Hill, E.; Simpson, E.L. A randomized controlled trial of an emollient
with ceramide and filaggrin-associated amino acids for the primary prevention of atopic dermatitis in high-risk infants. J. Eur.
Acad. Dermatol. Venereol. 2019,33, 2087–2094. [CrossRef]
71.
Zhong, Y.; Samuel, M.; van Bever, H.; Tham, E.H. Emollients in infancy to prevent atopic dermatitis: A systematic review and
meta-analysis. Allergy 2021,77, 1685–1699. [CrossRef]
72.
Skjerven, H.O.; Rehbinder, E.M.; Vettukattil, R.; LeBlanc, M.; Granum, B.; Haugen, G.; Hedlin, G.; Landrø, L.; Marsland, B.J.;
Rudi, K.; et al. Skin emollient and early complementary feeding to prevent infant atopic dermatitis (PreventADALL): A factorial,
multicentre, cluster-randomised trial. Lancet 2020,395, 951–961. [CrossRef]
73.
Chalmers, J.R.; Haines, R.H.; Bradshaw, L.E.; Montgomery, A.A.; Thomas, K.S.; Brown, S.J.; Ridd, M.J.; Lawton, S.; Simpson, E.L.;
Cork, M.J.; et al. Daily emollient during infancy for prevention of eczema: The BEEP randomised controlled trial. Lancet
2020
,
395, 962–972. [CrossRef]
Medicina 2022,58, 888 17 of 17
74. Perrett, K.P.; Peters, R.L. Emollients for prevention of atopic dermatitis in infancy. Lancet 2020,395, 923–924. [CrossRef]
75.
Lodén, M. Barrier recovery and influence of irritant stimuli in skin treated with a moisturizing cream. Contact Dermat.
1997
,36,
256–260. [CrossRef] [PubMed]
76.
Kim, D.; Lee, N.R.; Park, S.Y.; Jun, M.; Lee, K.; Kim, S.; Park, C.S.; Liu, K.H.; Choi, E.H. As in Atopic Dermatitis, Nonlesional Skin
in Allergic Contact Dermatitis Displays Abnormalities in Barrier Function and Ceramide Content. J. Investig. Dermatol.
2017
,137,
748–750. [CrossRef]
77.
Maroto-Morales, D.; Montero-Vilchez, T.; Arias-Santiago, S. Study of Skin Barrier Function in Psoriasis: The Impact of Emollients.
Life 2021,11, 651. [CrossRef]
78.
Seité, S.; Khemis, A.; Rougier, A.; Ortonne, J.P. Emollient for maintenance therapy after topical corticotherapy in mild psoriasis.
Exp. Dermatol. 2009,18, 1076–1078. [CrossRef]
79.
Chung, B.Y.; Kim, H.O.; Kang, S.Y.; Jung, M.J.; Kim, S.W.; Yoo, K.S.; Shin, K.O.; Jeong, S.K.; Park, C.W. Increased 1-
Deoxysphingolipids and Skin Barrier Dysfunction in the Skin of X-ray or Ultraviolet B Irradiation and Atopic Dermatitis Lesion
Could Be Prevented by Moisturizer with Physiological Lipid Mixture. Ann. Dermatol. 2020,32, 306–318. [CrossRef]
80.
Lessmann, H.; Schnuch, A.; Geier, J.; Uter, W. Skin-sensitizing and irritant properties of propylene glycol. Contact Dermat.
2005
,
53, 247–259. [CrossRef]
81.
Korean Cosmetics Act Enforcement Rule No. 1516. 2019. 12. 31 Promulgated, 2020. 1.1 Enforcement. Available online:
https://elaw.klri.re.kr/eng_service/lawView.do?hseq=38682&lang=ENG (accessed on 31 May 2022).
