Skin Whitening


Skin whitening products have become increasingly popular in the past few years. The main purpose for skin lightening products is to lighten or whiten the skin as well as even out skin tone or to treat pigmentation disorders such as freckles, pregnancy marks and age spots.


The most successful recent and natural skin whitening agents are part of Doctor Twaian New Patent Pending Skin Whitening System.


Arbutin, Vitamin C, Kojic Acid, Licorice Extract, Scutellaria Extract, Mulberry Extract, Burner Root Extract, Melanostat in addition to peeling actions of Glycolic Acid, Alpha/Beta Hydroxy Acids, Retinol,


These agents are all Tyrosinase inhibitors, Kojic Acid, Arbutin (Bearberry Extract), Licorice Extract, Mulberry Extract, Scutellaria, Burner Root Extract inactivate Tyrosinase ( the enzyme responsible for skin darkening) by chelating with its vital copper ion and suppressing the tautomerization from Dopachrome to DHICA, L- Ascorbic Acid and its derivatives which include L- Ascorbic Acid ( Vitamin C), act as reducing agents on melanin intermediates, thus blocking the oxidation chain reaction at various points from tyrosine /DOPA to melanin. Melanostat act as the above skin bleaching agents AND on the melanin itself.


Kojic Acid, Arbutin, Mulberry, L- Ascorbic Acid ( Vitamin C) and Bearberry Extract have excellent safety and efficiency and are non toxic, have minimal irritation.


Kojic Acid has been used in Japan since 1988 and has extended into other parts of the world, Arbutin (Bearberry Extract) have been used since 1994 as well as Vitamin C.


The human patch test of Arbutin ( Bearberry Extract), Kojic Acid, Vitamin C, showed that they are completely non-irritating. Vitamin C has an excellent safety record.


In conclusion, Arbutin ( Bearberry Extract, Mulberry ), Kojic Acid, Vitamin C, are all of natural origin, very high quality and considered the most effective skin lightening agents in the world to date.


Skin Whitening Ingredients



Melanostat


Melanostat is a peptide obtained by amino acid synthesis with a technique of Merryfield


A new skin bleaching agent that act on the Tyrosinase Enzyme AND directly on the melanin cell receptors (the only skin bleaching agent that acts directly on melanin cells) and that deactivates those cells. This process is called melanogenesis, which is an important part in skin tanning, once its deactivated, it will help the skin to get lighter.

Melanostat demonstrates an outstanding anti MSH activity experimentally investigated for skin lightening. The target of Melanostat - the membrane receptor of alpha-MSH on the melanocytes and the B- MICR receptor. It’s mode of action is a competitive inhibition of alpha-MSH – thus, the membrane receptors are blocked in a natural way.


The anti-MSH is a molecule naturally present in the skin. It belongs to the system of regulation of pigmentation. Melanostat counterbalances the formation of melanin and especially the synthesis of tyrosinase, the key enzyme involved in the process of pigmentation. In the skin, alpha-MSH plays an essential role in the stimulation of the synthesis of melanin. This process is under the control of an anti—MSH, also naturally present in the skin.


Recently, researches performed on alpha- MSH enabled a detailed study of the structure and function of this molecule, so as the exact determination of its receptor. This receptor is the B receptor, its scientific determination is the MICR receptor. The study of these molecules enabled researchers to synthesize peptides with a similar (MSH-like), or antagonist (anti-MSH) activity. The structure of Melanostat antagonist peptide of the alpha-MSH, is relatively similar to the structure of alpa-MSH. Because of this similarity, Melanostat acts while completing the receptors of alpha-MSH on the melanocytes.


The action of Melanostat occurs before the action of the well-known inhibitors. This acts on the intracellular enzyme system. Melanostat does not penetrate the cell because its competitive activity initiates on membrane receptors. Its action enables a natural and reversible blockage of the membrane receptors, without disturbing the physiological functioning of the cutaneous cells. Thus, Melanostat counteracts the formation of melanin and notably the synthesis of tyrosinase; the key enzyme of the pigmentation process of the skin. The anti-MSH molecule naturally exist in the organism, and is involved in a system that regulates melanogenesis. It is activated in season changes.


When sunshine is high, the amount of alpha MSH exceed the amount of anti-MSH. The receptors for alpha-MSH multiply at the surface of the cells. The result, is an increase of the synthesis of the melanin and the rise of the pigmentation of the skin. When the sunshine is low, anti-MSH exceed alpha-MSH. The receptors at the surface of the melanocytes decrease. The synthesis of melanin is not stimulated anymore, pigmentation of the skin decreases. Thus, alpha-MSH and anti-MSH play the role of accelerator or brake for the synthesis of melanin. Depending on the predominance of anti-MSH or alpha-MSH, the color of the skin evolves in one way or another.



The incorporation of Melanostat in skin lightening creams will place the skin in a physiological dominant anti-MSH situation. Its action is based on the reinforcement of the natural ability of the skin to counteract the activity of alpha-MSH. Melanostat has been investigated in vivo against alpha MSH (the darkening of the skin induced by alpha-MSH) and is assessed and expressed in percentage of change by comparison with the normal situation.


Investigations are performed on the skin biopsies. Melanogenesis is induced by alpha-MSH. The activity of the Melanostat is evaluated for a ratio Melanstat/MSH of 25, 100 and 1.


Melanostat at 2 nmoles/g inhibits pigmentation induced by alpha-MSH at concentration of 0.08 nmoles/g. In these experimental conditions, the maximal inhibition observed is 100%.


Melanostat at 0.2 nmoles/g, inhibits pigmentation induced by alpha MSH at a concentration of 2 pmoles/g. In these experimental conditions, the maximal inhibition observed is 105%.


Melanostat, at 0.2 nmoles/g, inhibits pigmentation induced by alpha-MSH at a concentration of 0.2 nmoles/g.


With equivalent concentration, maximal inhibition observed is 600%. Melanostat demonstrates a remarkable lightening action.


Study of the activity of Melanostatine-DM on the inhibition of melanogenesis:


Melanostat induces an inhibition of synthesis of melanin synthesis by 21% which means that Melanostat inhibit of 21% of the melanin induced by alpha-MSH analogue. Melanostat displays an antagonist of the process of activation of the Tyrosinase.


Alpha Hydroxy Acid, Retinol (Vitamin A) are skin exfoliators, that help in renewing of the skin and gives a new lighter skin.



Arbutin


Natural Double Action Whitening Agent


A new type of skin de-pigmentation and whitening agents, an extract of the Bearberry plant which is produced by a solid /liquid extraction and an environmentally friendly process.


Cosmetic Uses of Arbutin


Arbutin protects the skin against damage caused by free radicals, Arbutin is a skin whitening agent which is very popular in Japan and Asian countries for skin de-pigmentation, Arbutin inhibits the formation of melanin pigment by inhibiting Tyrosinase activity.


Arbutin in medical Use


Back in the 18th century Arbutin was first used in medical areas as an anti-inflammatory and antibacterial agent. It was used particularly for cystitis, urethritis and pyelitis. These natural ingredients still today are used in natural medicine to treat diseases.


It may be used to repress the virulence of bacterial pathogens and to prevent contaminating bacteria, it is also used for treating allergic inflammation of the skin. More recently, Arbutin has been used to prevent pigmentation and to whiten the skin beautifully. It can be used to whiten the skin, to prevent liver spots and freckles, to treat sunburn marks and to regulate melanogenesis.


Arbutin is a very safe skin agent for external use which does not have toxicity, stimulation, unpleasant odor or side effects such as Hydroqinone. The encapsulation of Arbutin constitutes a delivery system to potentialize the effect in time. It is a way to incorporate the hydrophilic Arbutin in lipophilic media. Arbutin gives three main properties; Whitening effects, anti- age effect and UVB/ UVC filter.


Arctostaphylos uva-ursi ( Bearberry )


This plant is from the botanical family of the ericacae, which grows in many areas of the world; Europe, Northern Temperate Asia and North America. The bush is green of 15-20 centimeters high with leaves dark green on the upper surface, paler beneath, leathery, obovate, spatulate, about 2 cm long and 0.5-1 cm broad, margins entire, slightly revolute.


Vitamin C (L- Ascorbyl Acid)


There is an increasing awareness that Vitamin C has a wide variety of roles in human health. New therapeutic uses are being investigated daily, among recent discoveries is that Vitamin C can play important role in the health and beauty of your skin. Vitamin C as Ascorbyl form has been tested extensively and reported in the journal of American Academy of Dermatology to inhibit the production of the melanin (Melanin is the pigment which gives the skin it's dark color), and when Vitamin C inhibits the production of the melanin, a lighter and brighter skin will reveal in just few weeks.


Vitamin -C is required for collagen synthesis, which declines markedly in aging skin. As we grow older, we suffer diminished micro capillary circulation within our skin, which deprives our skin cells of the supply of Vitamin -C it needs for youthful collagen synthesis. The topical application of Vitamin -C in a skin-penetrating medium can dramatically enhance the availability of Vitamin -C for collagen production.


Vitamin -C regenerates vitamin E in the skin. An antioxidant like vitamin E can only suppress a limited number of free radicals before it runs out of electrons to donate. Vitamin -C regenerates vitamin E and enables vitamin E to provide sustained antioxidant protection in the skin's elastin fibers.


Vitamin -C plays a vital role in skin repair. When your skin is injured, its Vitamin -C content is used up rapidly in the scavenging of free radicals, and in synthesizing collagen to speed healing.


Licorice


Glycyrrhetinic acid, isolated from Glycyrrihiza glabra (licorice) is widely used in the cosmetic industry. Licorice inhibit tyrosinase activity of melanocytes without any cytotoxicity, it also showed that UV-B–induced pigmentation and erythema can be inhibited by topical application of 0.5% Licorice. The anti-inflammatory properties of Licorice were attributed to inhibition of superoxide anion production and cyclooxygenase activity.


Kojic acid


Kojic Acid is one of the most successful recent and natural skin whitening agents. It acts as Tyrosinase inhibitors, similar to Arbutin which inactivate Tyrosinase by chelating with its vital copper ion and suppressing the tautomerization from dopachrome to DHICA, it also acts as reducing agents on melanin intermediates, thus blocking the oxidation chain reaction at various points from tyrosine/DOPA to melanin. The result is skin Lightening.


The technology for the production of Kojic acid is based on aerobic fermentation using a strain of Aspergillus sp. and has been developed and optimized for bulk manufacture. Kojic acid is a UV absorber and is reported to inhibit Tyrosinase in the melanin pathway. This property of Kojic acid has led to its use in cosmetics formulation for helping de-pigmentation of the skin including whitening age spots and hyper pigmentation (brown spotting). Kojic acid also has mild antibiotic properties.


A fungal metabolic product, kojic acid inhibits the catecholase activity of tyrosinase, which is the rate-limiting, and the essential enzyme in the biosynthesis of the skin pigment melanin. Kojic acid also is consumed widely in the Japanese diet, with the belief that that it will benefit good health. Indeed, it has been shown to significantly enhance neutrophil phagocytosis and lymphocyte proliferation, stimulated by phytohemagglutinin. Melanocytes treated with kojic acid becomes nondendritic with a decreased melanin content. Additionally, it scavenges reactive oxygen species that are excessively released from cells or generated in tissue or blood.


Mulberry


This tyrosinase inhibitor was isolated from a plant herbal extract. The plant roots from which paper mulberry was isolated were collected in Korea. The tyrosinase inhibition of paper mulberry was compared to kojic acid and HQ. The IC50, the concentration causing 50% inhibition of the activity of tyrosinase, was reported to be 0.396% compared to 5.5% for hydroquinone and 10.0% for kojic acid.


Retinol


The most important natural form of vitamin A. Vitamin A is the first vitamin to be used topically for the treatment of damaged human skin. Today, the term vitamin A is applied to retinol (Vitamin A alcohol), retinal (Vitamin A aldehyde) and tretinoin (Vitamin A acid). Vitamin A stimulates mitotic activity and the production of collagen - the stuff skin is made of. It is now known that the clinical effect obtained with high doses of vitamin A is necessary for normal differentiate and maintenance of epithelial tissues. Retinol, is held out as the new great hope for reduction of photo aging skin. Retinol or Vitamin A helps to renew and exfoliate the skin, giving a new lighter, and more beautiful look to the skin.


More on Skin Pigmentation

The Reason Behind Skin Color


Skin color is a function of the size, number and the distribution of melanin cells (not their density )


In fact, the number of melanin cells is the same in all races, however melanin cells of darker pigmented skin have thicker, longer and branched dendrites. The differences in racial skin pigmentation depend on the quantity of melanin pigments produced and on the distribution and the deposition of these pigments throughout the epidermis.


Tyrosinase is a rate-limiting enzyme for melanin synthesis, and defects in the enzymes activity lead to the albinism in humans. It also seems likely that racial differences in human color may primarily be due to differences in the tyrosinase activity in the melanin cells from varying skin types. Melanin cells derived from black skin have up to ten times more tyrosinase activity and produce up to ten times more melanin than do melanin cells in white skin.


Melanin The Skin Pigments


Visible pigmentation in humans result from the synthesis and distribution of melanin in the skin, hair bulbs and eyes. Melanin plays a crucial role in the absorption of free radicals generated within the cytoplasm and in shielding the host from various types of ionizing radiation, including the UV light. Thus, melanin protects the skin against sun burn.


The essential enzyme in melanin biosynthetic pathway is tyrosinase, the only enzyme absolutely required for melanin production.


Tyrosinase, The Enzyme Behind The Dark Skin


Tyrosinase is multifunctional, glycosylated, copper-containing oxidase with a molecular weight of approximately 60 to70 kDa. In mammals, it is exclusively found in melanin cells. It is therefore, a good specific marker for these cells. Tyrosinase is synthesized in melanosomal ribosome's found on the rough endoplasmic reticulum. After synthesis, tyrosinase is glycosylated within Golgi, then delivered to melanosomes via coated vesicles.


Tyrosinase is rate-limiting, the essential enzyme in the biosynthesis of the skin pigment melanin. As such it catalyzes three different reactions in the biosynthetic pathway of melanin.


The rate limiting steps in melanogenesis are the oxidation of tyrosine and DOPA. The quantity of melanin synthesized is thus proportional to the amount of tyrosinase activity present in the cell.


Regulation of Melanogensis


The regulation of pigmentation in mammals is controlled at many different levels and is quite complex at each level. Melanin cells are initially derived from the neural crest and migrate throughout the embryo during development. These migration patterns are under strict genetic control and can lead to some interesting patterns when final melanin distribution in the skin is not uniform, as can be seen in zebras and giraffes.


Pigmentation is also regulated at the cellular level by melanin cells synthesizing melanin within melanosomes, which can be produced in varying sizes, numbers and densities. Lastly, melanogenesis is regulated at the sub cellular level where synthesis and expression of various melanogenic enzymes and inhibitors play a critical role.


Skin pigmentation depends upon the organization and function of epidermal melanin unit and several separate but related events:


• Melanoblast migration from the neural crest.

• Melanoblast differentiation into melanin cells.

• The rate of synthesis and melanization of melanosomes.

• The size of melanosomes.

• Synthesis of melanin.

• The efficacy of melanosome transfer into keratin layer.

• The rate of melanosome degradation within the keratin layer.

• The rate of synthesis and inhibition of the tyrosinase enzyme.

• Activity of tyrosinase in melanosomes.


Melanin cells work in close harmony with their neighboring cells in the epidermis. They are influenced by a variety of biological factors and environmental factors with the most important factor, UV- exposure ( sun exposure) which increases the melanin cells activity up to 100-fold.