Administration of lycopene for combating skin/mucous...

Drug – bio-affecting and body treating compositions – Plant material or plant extract of undetermined constitution... – Containing or obtained from a fruit – including berry

Reexamination Certificate

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C424S725000, C514S456000, C514S458000, C514S725000, C514S764000, C514S886000

Reexamination Certificate

active

06623769

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Technical Field of the Invention
The present invention relates to the administration of lycopene or compositions comprised thereof, for treating, preventively and/or curatively, cutaneous signs of aging.
This invention especially relates to the administration of lycopene or compositions comprised thereof to inhibit damage to the skin and/or mucous membranes by the inhibition of collagenases. Too, this invention relates to a cosmetic regime/regimen for the skin and/or mucous membranes.
2. Description of the Prior Art
It is of course known that human skin is composed of two compartments or strata, namely, a surface compartment or layer, the epidermis, and a deep compartment or layer, the dermis.
The natural human epidermis is composed principally of three types of cells which are keratinocytes, melanocytes and Langerhans' cells, the vast majority being keratinocytes. Each of these cell types contributes by its specific functions to the essential role played by the skin in the body.
The dermis provides the epidermis with a solid support. It is also its source of nutrients. It is principally composed of fibroblasts and of an extracellular matrix, itself composed principally of collagen, of elastin and of a substance referred to as “ground” substance, which components are synthesized by the fibroblast. It also comprises leucocytes, mastocytes or tissue macrophages. It is also traversed by blood vessels and nerve fibers. In normal skin, namely, nonpathological and noncicatricial, the fibroblast is in the quiescent state, i.e., nonproliferative, not very active from a metabolic viewpoint and nonmobile.
It is the collagen fibers which provide the dermis with strength. The collagen fibers are composed of fibrils firmly attached to one another, thus forming more than ten types of different structures. The strength of the dermis is largely due to the entanglement of the collagen fibers, which are packed tight against one another in all directions. The collagen fibers contribute to the elasticity and to the tonicity of the skin and/or mucous membranes.
The collagen fibers are constantly replaced but this replacement decreases with age, which results in a thinning of the dermis. This thinning of the dermis is also due to pathological causes, such as, for example, the hypersecretion of corticoid hormones, certain pathologies or vitamin deficiencies (the case of vitamin C in scurvy). It is also accepted that extrinsic factors, such as ultraviolet radiation, tobacco or certain treatments (glucocorticoids, vitamin D and derivatives, for example), also have an effect on the skin and on its level of collagen.
However, various factors damage the collagen, with all the consequences which can be envisaged with regard to the structure and/or the firmness of the skin and/or mucous membranes.
Although highly resistant, collagen fibers are sensitive to certain enzymes known as collagenases. Damage to the collagen fibers results in the appearance of flabby and wrinkled skin which human subjects, preferring the appearance of a smooth and taut skin, have historically sought to combat.
Collagenases belong to a family of enzymes known as metalloproteinases (MMPs) which are themselves members of a family of proteolytic enzymes (endoproteases) which have a zinc atom coordinated to three (3) cysteine residues and a methionine in their active site and which decompose the macromolecular components of the extracellular matrix and of the basal laminae at neutral pH (collagen, elastin, and the like). Very widely distributed in the living world, these enzymes are present, but weakly expressed, in normal physiological situations, such as organ growth and tissue replacement.
Their overexpression in man and their activation are related, however, to numerous processes, sometimes pathological processes, which involve the destruction and the remodelling of the matrix. This results in either an uncontrolled resorption of the extracellular matrix or, conversely, in attaining a state of fibrosis.
The metalloproteinase family is composed of several well defined groups based on their similarities in terms of structure and of substrate specificity (see Woessner J.F.,
Faseb Journal
, Vol. 5, 2145 (1991)). Among these groups, exemplary are collagenases intended to decompose fibrillar collagens (MMP-1 or interstitial collagenase, MMP-8 or neutrophil collagenase, or MMP-13 or collagenase 3), gelatinases which decompose collagen of type IV or any form of denatured collagen (MMP-2 or gelatinase A (72 kDa), or MMP-9 or gelatinase B (92 kDa)), stromelysins (MMP-3), the broad spectrum of activity of which is applicable to proteins of the extracellular matrix, such as glycoproteins (fibronectin, laminin), proteoglycans, and the like, or membrane metalloproteinases.
Prolonged exposure to ultraviolet radiation, particularly to type UV-A and/or UV-B ultraviolet radiation, has the effect of stimulating the expression of collagenases, particularly of MMP-1. This is one of the components of photoinduced cutaneous aging.
Furthermore, at menopause, the principal modifications relating to the dermis are a decrease in the level of collagen and in the dermal thickness. This results in thinning of the skin and/or of the mucous membranes in menopausal women. Women then experience a “dry skin” or tight skin feeling and a marked increase in surface fine wrinkles and fine lines is observed. The skin has a rough appearance on palpation. Finally, the skin exhibits reduced suppleness.
From the foregoing description of the importance of collagen in the structure of tissues, in particular of the skin and/or of the mucous membranes, need continues to exist in combating damage thereto in order to thus control aging, whether chronobiological or photoinduced aging, and the consequences thereof, such as the thinning of the dermis and/or the damage to collagen fibers which result in the appearance of flabby and wrinkled skin.
SUMMARY OF THE INVENTION
Accordingly, a major object of the present invention is the provision of unique treatment for exerting an inhibiting effect with regard to collagenases and which, to the extent possible, does not elicit any significant side effects.
Briefly, it has now surprisingly and unexpectedly been determined that lycopene exhibits an inhibitory activity with respect to the activity of collagenases.
DETAILED DESCRIPTION OF BEST MODE AND SPECIFIC/PREFERRED EMBODIMENTS OF THE INVENTION
More particularly according to the present invention, lycopene is a natural pigment which is present in ripe fruit, particularly in tomatoes. It belongs to the carotenoid family and its structure is similar to that of &bgr;-carotene.
The role of lycopene in the ripening of fruit is known to the prior art.
Lycopene is formulated into compositions with a tanning activity for its role with regard to the synthesis of melanin (WO-97/47278), in compositions suited for the treatment of the scalp and/or of acne, for its activity with regard to 5&agr;-reductases (JP-2940964), or as an agent for combating free radicals (JP-A-8-283136).
To date, however, it is believed that the inhibitory activity of lycopene with regard to the activity of collagenases was unknown.
Thus, the present invention features the administration of lycopene or compositions comprised of lycopene, for treating, preventively and/or curatively, cutaneous signs of aging.
By the term “cutaneous signs of aging” is intended any modification in the external appearance of the skin due to aging, whether chronobiological and/or photoinduced, such as, for example, wrinkles and fine lines, withered skin, flabby skin, thinned skin, or lack of elasticity and/or of tone of the skin, but also any internal modification of the skin which is not reflected systematically by a modified external appearance, such as, for example, any internal damage to the skin, particularly to the collagen, resulting from exposure to ultraviolet radiation.
This invention thus also features the administration of lycopene or compositions comprised of lycopene for inhibiting the expression of

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