Active synergetic complex and cosmetic and/or pharmaceutical...

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai

Reexamination Certificate

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C514S457000, C514S460000, C514S773000

Reexamination Certificate

active

06184199

ABSTRACT:

The present invention relates to the fields of cosmetology and pharmacology, particularly preventive and reparative, and has for its object an anti-stress active synergetic complex, as well as a cosmetic and/or pharmaceutical product including this latter.
In the cells of an organism, in particular human, stress can be produced either by external aggressions: heat, zenobiotic attack (cadmium, sodium arsenite), solar irradiation, or by glucose deficiency, oxygen deficiency (anoxia) or by endogenous origin: cellular division, cellular differentiation.
All living organisms, from the most simple (archeobacteria) to the most highly evolved (mammals), have the capacity to respond to stress by synthesis of a set of proteins known as HSP (Heat Shock Proteins) belonging to different families as a function of their molecular weight.
The mentioned aggressions give rise to a denaturizing of the cellular proteins (“proteotoxins”) and the stress proteins (HSP) take place in “renaturing” of these proteins or in their elimination. They thus permit the cells to resist stress.
During stress, the activity of the proteins of the HSP type is also changed to protect the genetic patrimony (ADN) as well as its mode of expression (nucleol, ribosome, messenger ARN).
In the skin, there is found in the normal physiologic condition the expression of most of the stress proteins with in particular a strong expression of the proteins of the family HSP70, but also HSP27.
HSP72 is preferentially localized in the base layer and HSC70 (HSP constituent) in the suprabasal layers.
In the course of different cutaneous stresses, the expression of HSP in the cells increases significantly and these proteins can be considered as true cellular markers of stress.
It has thus been shown that for keratinocytes in culture, a hot thermal shock (1 hour at 42° C. or 15 minutes at 47° C.) induces the expression of HSP72, HSP78, HSP90 and HSP 119 and that a thermal shock (1 hour at 45° C.) induces the expression of HSP72 and HSP27 in human skin in organolyptic culture.
Similarly, in in vivo human skin, there is induction of HSP72 after a hot shock in the epidermal and dermal cells and the cutaneous stress arising from UV-B irradiation induces the appearance of HSP72 in organolyptic cultures of human skin and HSP27 in the skin of mice, in vivo.
Similarly, it has also been verified that a UV-A treatment (5 J/cm
2
at to 80 J/cm
2
) induces the expression of HSP72 in cellular cultures (cellular line of fibrosarcome HT1080).
Thus, it is particularly well established that in the course of physical aggression such as heat or UV irradiation, the proteins of the HSP type are strongly induced at the level of the cutaneous epidermis. They thus represent an excellent marker of the degree of stress of the skin under these conditions: ultraviolet irradiation accompanied or not by temperature rise.
These markers (HSP) can therefore be perfectly used to study active agents and/or cosmetic products and particularly products for solar protection (solar products or against premature aging of the skin).
There exist at present a certain number of methods to evaluate the protective effect on the skin against damage from sunlight, solar preparations, measurement of SPF (“Sun Protecting Factor”), counting SBCs (“Sunburn Cells” in the epidermis, measurement of the anti-free radical effect.
The evaluation of HSP, and particularly HSP27 and 72, is an original method to measure the photoprotective effect of cosmetic products, anti-sun protectors or anti-premature aging of the skin, photo-induced.
It is known moreover that glutathione, a tripeptide composed of three amino acids of which cystine confers on this tripeptide a thiol (—SH) function, exists in the reduced form (GSH) or oxidized form (GS—SG disulfide bridge) in the cell thanks to an enzymatic system for conversion permitting passing from one form to the other and that the glutathione is present in a large quantity in the skin.
In comparison relative to the dermis, it is present in a quantity twice as great in the epidermis, in the layer of the living cells and in the layer of dead cells or corneal layer.
It is well known that in the skin, glutathione plays the role of detoxifier of free radicals and peroxides, and also for protection of the membranes of the living cells and the structural proteins of the corneal layer (keratin).
This detoxification and protective power is exerted under different conditions and natures of stress such as oxidative stress, thermal stress or irradiation stress.
Thus, as indicated above, ultraviolet radiation UV-B and also UV-A gives rise to a depletion of the quantity of glutathione, in the cells undergoing in vitro culture or in vivo culture on mice and it is has been demonstrated that this depletion potentializes the formation of cells of the type of sunburn cells in the skin.
It is also known that UV-R radiation increases the presence of the disulfide bridges (S—S) shown by histochemistry in the epidermis, in particularly in the sunburn cells that appear after irradiation.
These difulside bridges are moreover as a step preceding aptosis or UV-induced programmed cellular death.
The content in the skin of thiol groups, of which glutathione, and of disulfide bridges, are hence good indicators of development toward aging and accelerated cellular death, and it appears that the enrichment of the epidermis in thiol groups, and particularly glutathione, constitutes a good anti-solar protection and anti-photo-accelerated aging protection.
So as to combat the effects of solar radiation, different cosmetic products called “sunscreens” and “anti-sun aging” have been developed and distributed, their development from the beginning until now can be divided in several steps of which each corresponds substantially to the addition of a supplementary active compound.
It has been first of all proposed to introduce into these known products UV-B filters (to avoid sunburn), then to introduce UV-A filters (to act on chronic photo-aging and carcinogenesis).
A third step has consisted in adding anti-oxidant and anti-free radical substances (to combat the formation of sunburn cells), followed by the incorporation of pre-melanogenic substances (acceleration of bronzing by the production of auto-melanin) and, finally, more recently, by the introduction of cytophotoimmunoprotectors (preservation of the cutaneous immunological capital constituted by the Langerhaus cells in the epidermis).
Independently of the above development, which has led to products having a number of ingredients that increase without real synergesis between them, the inventors of the present application have sought and developed a new way consisting in the reinforcement of the natural autodefense of the skin, which is to say by acting on a biomolecular scale on the protection and repair of a sun-damaged skin, by the synergetic and simultaneous actions, on the one hand, of stimulation of autobiosynthesis of reduced glutathione and, on the other hand, by inhibition of the appearance of stress proteins, which are molecular markers of epidermal aggressions.
This research has permitted arriving at a synergetic complex having in particular photoprotective activities from biomolecular deleterious effects and adapted particularly to be integrated into a cosmetic and/or pharmaceutical preparation for topical use for the skin and/or the hair, nails and eyelashes, comprising at least one extract of seeds of
Pisum Sativum
rich in peptides, a plant extract of the family of meliaceae, rich in tannins and/or cumarin derivatives (and, as the case may be, in triterpenoids and/or in saponosids), and, at the case may be, at least one amino acid in the form of complex salt or salts.
This active synergetic complex is present preferably in concentrated form and easily usable by cosmetic formulators.
According to a first characteristic of the invention, the synergetic complex comprises between 0.05% and 40% by weight, preferably between 1% and 40% by weight, of an extract of
Pisum Sativum
rich in peptides, in the dehydrated form or not.
The

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