DR.EA SKIN
WHITENING CREAM

Dr. EA Skin Whitening Cream is safe to use with its all natural contents. Provides melanin balance with the extracts inside, and helps to lighten dark spots.

Dr. EA Skin Whitening Cream/

Dr. EA Skin Whitening Cream is safe to use with its all natural contents.

 

Provides melanin balance with the extracts inside, and helps to lighten dark spots.

 

Evens skin tone.
Lightens sun spots, age spots, acne scars, freckles, and moles. If you are complainant about any of them, you should use this cream on the a ected area rst. Once they become lightened (which takes about a month), you can apply the cream to rest of your skin.
Is an e ective moisturizer with shea butter inside. Keeps the skin moisturized for a long time and protects the skin from getting dry.

How It Works? Understanding Melanin/

A person’s skin color is determined by the pigment ‘melanin’. It is produced by specialized skin cells, the melanocytes, and is the natural UV protector for the skin. The different skin types all have the same melanin pigment, but also the same number of melanocytes.

 

Skin color is determined purely by the activity of the melanocytes. This activity is pre- determined by genetic factors and can be additionally stimulated by external factors (e.g.sunlight).

Skin color in the course of time/

In Asia, an immaculate white skin has been the quin-tessence of beauty and femininity for centuries. An old Chinese proverb says: “White skin conceals three blemishes in the face”. The ladies of the Chinese court therefore ground pearls and powdered their face with it to appear more dignified and aristocratic. Anyone who had white skin was and is considered to be wealthy, because he or she did not have to work out in the eld exposed to the sun. In Europe, fashion changed. Noble paleness was the latest thing during the Baroque period.

The trendsetters of the day attached great importance to an immaculately clear and white skin. Powder and white lead were used as make-up, and even blood-letting ensured a re ned paleness.

Coco Chanel turned the tide in 1923 when she became the rst to promote the suntan as the beauty ideal. In the Western world, tanned skin was long considered
a symbol of beauty, health and success. Today we know about the harmful effects of UV radiation and its influence on skin ageing. Sun bed tanning is out, because we know: The tanned Venus of today is the baked apple of tomorrow.

Synthesis and transport of melanin/

The melanocytes are located in the basal cell layer of the epidermis. They produce the pigment melanin in specialized organelles, the melanosomes. Melanocytes have finger-like branches via which the melanosomes are passed on to neighboring kerati-nocytes.

We distinguish between two melanin variants: The brownish-black eumelanin and the reddish-yellow phaeomelanin. Both are produced in the melanocytes.

One melanocyte supplies around 36 neighboring keratinocytes with melanosomes. One speaks of an “epidermal melanocyte unit”. The contact points between melanocytes and keratinocytes are produced by cell adhesion proteins. This is where the melano-somes are transferred to the keratinocytes. Keratinocytes can also exchange melanin between one another. This ensures that melanin is quickly transported to the ‘corneum’ or horny layer of the skin where it can best develop its protective e ect.

Inside the keratinocytes, the melanin is concentrated protectively around the cell nucleus, because the DNA is particularly sensitive to UV radiation. By contrast with the differentiating keratinocytes, melanocytes do not migrate further to the corneum. They remain anchored in the basal layer.

Biochemistry of melanin/

UV radiation accelerates the production of melanin by activating the tyrosinase, the key enzyme for the production of melanin. It catalyses the oxidation of the tyrosine amino acid to l-dopa and further to dopachinon. All the further synthesis steps in the production of melanin then take place spontaneously.

Skin compatibility with chemical skin lighteners/

Active substances for lightening the skin have different functional mechanisms: Generally they inhibit the activity of the tyrosinase enzyme. Furthermore, they can have acytotoxic effect on the melanocytes or may belong to the group of retinoids, peeling or sun protection products.

Their compatibility with the skin is not undisputed, as the aggressiveness of the preparations towards the skin increases with increasing effectiveness.

Skin irritation is a frequent consequence of their use.

Treatment with hydroquinone, for example, can result in a localized bluish-black discoloration of the skin. Amutagenic effect can also not be completely ruled out. A further example is kojic acid, a very effective skin lightener. It is considered to be a contact allergen and can lead to dermatitis. Similar side effects are known from the use of acelaic acid. It kills o melanocytes and can result in irregular pigmentation.

Gentle and natural preparations for skin lightening are therefore the skin compatible alternative to aggressive chemical active ingredients.

Active ingredients/

Tyrosinase – motor of the melanin synthesis

Tyrosinase is the key enzyme for the melanin synthesis. It is activated by UV-B radiation. The tyrosinase catalyzes the first two steps of the pigment production, the oxidation of tyrosine to l-dopa and further to dopachinon. All the subsequent steps of the melanin production then take place spontaneously. To function eficiently, tyrosinase requires the co-factor, copper. Copper exists as a bivalent ion in the active nucleus of the enzyme (see Fig. 3). Without the co-factor copper, the tyrosinase cannot function.

The active ingredient inhibits the tyrosinase in two ways:
(a) by depriving the tyrosinase of copper and

(b) by spatial inhibition.

 

Watercress extract

The tyrosinase is deprived of the essential co-factor, copper. Watercress extract, naturally rich in hydro- sulphide compounds, is able to complex copper.

The formation of this copper-hydrosulphide chelate deactivates the tyrosinase.

Bio-available zinc

Bio-available zinc, known as a ligand of the tyrosinase, changes the 3-dimensional structure of the enzyme. This conformational change screens the active nucleus from its substrate. The oxidation of tyrosine is thus prevented.

 

Vitamin B3 inhibitor of the melanosome transfer
The melanocytes are the skin’s pigment producers. They produce the melanin and pack it in melanosomes. The pigments formed are then exported to neighboring keratinocytes.

The contact between a melanocyte and keratinocytes is made via dendritic branches. Under normal circumstances, one melanocyte supplies some 36 keratinocytes.

Vitamin B3 is essential for our health. As an important component of various co-enzymes (NAD, NADH), Vitamin B3 is of central importance for the metabolism of proteins, carbohydrates and fats.

The daily requirement of an adult person is around 250mg.

New studies have shown that Vitamin B3 inhibits the melanosome transfer from the melanocytes to the keratinocytes.

Essential Cell Boost-Factor – for a uniform pigment distribution
The melanosome transfer takes place at the contact point between melanocyte and keratinocyte. This con- tact point is referred to as the pigmentation synapse. Cell adhesion proteins play an important role in the formation of the pigmentation synapse.

The Essential Cell Boost-Factor stimulates the production of cell adhesion proteins. The function of cell adhesion proteins is to connect cells.

A pigmentation synapse can only be established when solid and intact links exist between melanocyte and keratinocyte. The stimulation of the production of cell adhesion proteins by the Essential Cell Boost-Factor has been proved in a cDNA screening test on human keratinocytes.

 

A total of more than 600 genes were tested. The production of the cell adhesion proteins cadherin (+ 374%) and catenin (+154 %) was measured.

More adhesion proteins on the cell surface increase the number of pigmentation synapses. The melanin can be distributed more homogeneously in the skin. This results in a generally more uniform complexion.

Treatment concept and efficacy studies/

Concept

Dr. EA Whitening Cream has been specially developed for gentle skin lightening. The balanced combination of its special active ingredient, Vitamin B3, sulphurous extract of watercress and bioavailable zinc provides a naturally lighter complexion. The Essential Cell Boost Factor pro- motes the homogeneous pigment distribution in the skin for a generally more uniform and lighter appearance.

Mode of action

Dr. EA Whitening Cream’s special active ingredient functions on two levels. Extracts of watercress and complexed zinc with high bio-availability inhibit the tyrosinase, the key enzyme for melanin production.

 

Vitamin B3 and the Essential Cell Boost-Factor influence the melanin transport. Vitamin B3 thereby inhibits the melanosome transfer from the melanocytes to the keratinocytes. The Essential Cell Boost-Factor supports the formation of cell adhesion proteins that contribute to the uniform pigment distribution in the skin.

Inhibition of Melanin Synthesis/

(in-vitro study)

Aim

The aim of the study was to investigate the in uence of the active ingredient, Natural Komplex, on the melanin production of the skin.

Method and Implementation

A 3-dimensional reconstituted epidermis from human skin cells was used as the in-vitro skin model. A total of three different skin models were investigated:

1. Keratinocytes without melanocytes
2. Keratinocytes with melanocytes of Caucasian origin
3. Keratinocytes with melanocytes of colored origin

The different tissues were treated with 0.05% Natural Komplex for 16 days. As a reference standard, the cultures were treated with the tyrosinase inhibitor, kojic acid. After 16 days’ treatment, the melanin content of the cultures was evaluated by 3 different methods:

a) Histological evaluation b) Qualitative comparison of the cell pigmentations c) Quantitative evaluation of the melanin content

Result
a) Histological evaluation
Longitudinal sections through the re- constituted epidermis show clearly the lightening e ect of Natural Komplex. This was true for both the Caucasian skin model(Fig.9) and for the colored skin mod- el(Fig.10). The dendritic melanocytes are shown dark in the gure. After treatment with Natural Komplex, the melanin content was signi cantly reduced. The comparison with the known tyrosinase inhibitor, kojic acid (in Fig. c in each case) shows a light- ening e ect of a comparable order.

b) Qualitative comparison

The visual evaluation of the di erent skin models produced complementary data. Fig.11 shows the top view of the cell cultures from the test series. A darker

Melanin content: Cell cultures in top-view after treatment with Natural Komplex or Kojic acid pigmentation of the cultures indicates the stronger production of melanin. The left hand side of Fig.11 shows the Caucasian skin model. The right-hand side of Fig. 11 shows the colored skin model. The comparison of the two figures provides a clear conclusion: In the pres-ence of Natural Komplex, far less melanin is produced

(Fig. 11 d and Fig. 11 h). The lightening effect is even slightly stronger compared with the known tyrosinase inhibitor, kojic acid (Fig.candFig.g).

 

c) Quantitative evaluation

The results of the photometric quanti cation of the melanin produced underline the lightening e ect of Natural Komplex. Depending on the skin type, 52% or 54% less melanin is produced. The reference kojic acid shows a comparable e ect. Inhibition of melanin production by Natural Komplex and Kojic acid.

Safety evaluation of Natural Komplex in-vitro
The in-vitro studies performed confirmed an effective concentration of Natural Komplex of 0.05 % with no cytotoxic effects being observed. Additional studies for the safety evaluation showed that even an application of many time the effective concentration had no cytotoxic effect.

Skin Lightening Effect Caucasian Skin/

(in-vivo study)

Aim

In order to delimit the e ective concentration range of Natural Komplex in advance, an effectiveness test with high concentration (10%) was performed in our own laboratories.

Method and Implementation

The test product was applied to the lower arm twice
a day. The other arm was treated with placebo (0 % Natural Komplex) and used as a reference. The skin color was documented after 28 days’ treatment.

Result

Fig. 13 shows the comparison of the skin lightening effect of test product against placebo.

In order to quantify the lightening effect, an independent study was subsequently performed on 21 female test persons with Asian skin type.

Skin Lightening Effect Asian Skin/

(in-vivo study)

Aim

The aim of the study was to determine the skin lightening e ect of Natural Komplex.

Method and Implementation

The study was performed as a double blind test on 21 female test persons with Asian skin type. The partici- pants were clinically healthy and had no skin ailments. The average age was 32.

The test persons were split into two groups. One group was treated with the test product containing 5% Natu- ral Komplex. The second group was treated with 7.5 % Natural Komplex.

The test product was applied to the inside of the lower arm twice a day. The other arm was treated with a placebo (0 % Natural Komplex) and used as a reference.

The skin color was recorded using the Chroma meter MINOLTA CR300 on days 0, 14, 28 and 56 and statistically evaluated (t-test). The measurement parameter is the ITA value, a measure of the lightness of the skin. (As a general rule: The higher the ITA value, the lighter the skin.)

Result

The results of the study show a lightening effect of Natural Komplex compared with the placebo.

The treatment with 5% Natural Komplex resulted in a lightening of the skin by up to 7%. The treatment with 7.5 % Natural Komplex resulted in a lightening of the skin by up to 11%.

The maximum lightening effect was already achieved after 28 days. An illustrative presentation of the results and detailed information is contained in Fig.14.

 

Safety evaluation of Natural Komplex in-vivo

 

The in-vivo studies performed confirmed an effective skin lightening with 5% Natural Komplex.

No skin irritation was observed. Additional studies for the safety evaluation showed that even the undiluted active ingredient caused no skin irritation.

In summary it can be said that Natural Komplex is a skin lightening agent with high skin compatibility.