FIELD OF THE INVENTION

The present invention is directed to the development of a dermocosmetic formulation for use against skin blemishes, especially melasma. The present invention minimizes or avoids the formation of melasma through performance in various stages of melanogenesis, a process responsible for melanin synthesis, especially the dermocosmetic formulation of the present invention performs its function influencing transcription and/or activation of enzymes that favor the stages of melanogenesis.

BACKGROUND OF THE INVENTION

The skin is, in essence, a protective organ and the function that stands out is the protection against the physical damage caused by the sun. The physiological role of melanin consists fundamentally of providing skin color and chromophore absorption, generating natural photo-protection. As sunscreen, melanin differs or reflects UV radiation. After irradiation, the melanosome regroup around the nucleus and thus protect the genetic material of the cell.

Many are the pathological changes in skin color, which are called dyschromias. Melanins are heterogeneous biopolymers produced by specialized cells called melanocytes, which are found in the basal layer of the epidermis, follicular bulb and eyes. They are synthesized by melanogenesis and responsible for skin, hair and eye pigmentation.

The path of melanin production is the melanogenesis process, and can be modulated by regulating the expression and activity of enzymes. This regulation is determined by different biochemical agents, which are considered fundamental elements for the phenomenon of pigmentation.

Although melanin plays an important role for protection against UV radiation injury, its disordered production can lead to the formation of lentigo or senile purpura. In response to skin exposure to UV radiation, melanogenesis is increased by the activation of tyrosinase, a key enzyme in this process.

Tyrosinase is a metalloprotein located in the membrane of melanosome and catalyzes the first steps of melanin production: hydroxylation of L-tyrosine and L-dihydroxyphenylalanine (L-DOPA) and subsequent oxidation of o-diphenols by the corresponding quinone, L-dopaquinone.

Tyrosinase is initially synthesized on the surface of the rough endoplasmic reticulum, where it is then transferred to the Golgi complex, associated with lysosome and thus activated by the addition of a sugar chain before being secreted into a vesicle.

A pre-melanosome released from the Golgi complex joins with the vesicle to form the functional unit called melanosome. In the melanosome, tyrosinase converts tyrosine into (black) eumelanin or (yellowish or reddish) pheomelanin.

In addition, skin hyperpigmentation occurs due to several factors, including aging, pregnancy, endocrine disorders, treatment with sex hormones and sun exposure to different degrees. Many studies prove that sunlight radiation is the main cause for most dyschromias, followed by hormones and/or external factors. Thus, products capable of reducing melanin production present the potential to act as depigmenting agents.

Among the main ways of promoting skin whitening, the inhibition of enzymes that play an important role in melanin biosynthesis, inhibition of melanosome transport to keratinocytes and the reduction of the production of reactive oxygen species (ROS). Due to the central role of tyrosinase in the pigmentation process, most available depigmenting active ingredients perform their function by influencing transcription or activation of this enzyme, as well as other enzymes of melanogenesis TYRP-1 and TYRP-2. Here reference is made to articles by Kobayashi et al (1994)—Ref. 1, and from Tsukamoto et al (1992)—Ref. 2.

Endothelin-1 (ET-1), besides favoring the initial stages of melanosome formation, stimulates the growth of melanocytes, increases transcription and activity of tyrosinase and, consequently, melanin synthesis.

From this stage of the melanogenesis cascade, the presence or absence of cysteine determines the course of the reaction for the synthesis of eumelanin and pheomelanin. In the absence of cysteine, dopaquione is converted into cyclo-dopa and this, into dopachrome.

There are two ways to modify dopachrome: one that forms DHI (dopa, 5.6 dihydro indol) and another that forms DHICA (5.6 dihydroxyindole-2-carboxylic acid) in smaller quantity. The latter is generated by dopachrome tautomerization, a reaction catalyzed by TYRP-2. In this context, the TYRP-1 enzyme seems to be involved in the process of catalyzing eumelanin oxidation in DHICA.

In order to solve the problem of combating skin blemishes, especially melasma, various techniques and forms of non-therapeutic treatment are suggested in the literature and by another important segment, the cosmetic industry, which promotes treatments that use active ingredients incorporated into creams, cosmetic compositions, gels, elixirs, among others.

For example, the document PI0804089-3 reveals a topical composition for skin whitening. However, in that document, there are no teachings or data on the effect of composition on enzymes involved in melanogenesis.

Thus, the development of a dermocosmetic formulation that has whitening and depigmenting function through the action for this dermocosmetic formulation in enzymes that act on melanin production in the skin.

SUMMARY OF THE INVENTION

The present invention refers to dermocosmetic formulations for use against skin blemishes, especially melasma. The present invention minimizes or avoids the formation of melasma by acting in several stages of melanogenesis.

A preferred embodiment of invention refers to dermocosmetic formulations that act in several stages of melanogenesis, preferably, in the gene expression of tyrosinase-related proteins (TYRP-1 and TYRP-2) and Endothelin-1 (ET-1).

Another embodiment of the invention refers to the cosmetic composition containing a combination of active ingredients that act on the gene expression of tyrosinase-related proteins (TYRP-1 and TYRP-2) and Endothelin-1 (ET-1).

In another preferred embodiment of the invention, the use of the mentioned cosmetic composition to combat melasma is described.

Surprisingly, the inventors of the present invention identified an excellent performance of the formulations herein described in relation to the less traditional mechanisms in the formation of blemishes. In particular, these formulations present excellent activity in the expression of important enzymes in melanogenesis, in addition to the already known activity on tyrosinase.

These characteristics of the invention will be described in more details in the detailed description of the invention.

