Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Cosmetic – antiperspirant – dentifrice
Reexamination Certificate
1999-12-29
2003-11-11
Low, Christopher S. F. (Department: 1653)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Cosmetic, antiperspirant, dentifrice
C424S401000, C424S409000, C424S481000, C424S059000, C424S060000, C424S094630, C424S094640, C424S094650, C424S094660, C424S094670, C514S506000, C514S529000, C514S553000, C514S844000, C514S011400, C514S943000, C435S226000, C435S252300, C435S320100, C435S069100, C435S091500, C435S023000, C435S091500, C435S350000
Reexamination Certificate
active
06645509
ABSTRACT:
The subject of the invention is a cosmetic or pharmaceutical composition comprising, in a physiologically acceptable medium, at least one purified natural or synthetic polypeptide, specific to the epidermis, having a role in intercorneocyte cohesion. The subject of the invention is also a cosmetic or pharmaceutical composition comprising a mixture of polypeptides derived from the proteolysis of the purified polypeptide, a method of cosmetic treatment for strengthening intercorneocyte cohesion and a method of cosmetic treatment for reducing intercorneocyte cohesion, and therefore for promoting desquamation.
Human skin consists of two compartments, namely a deep compartment, the dermis, and a superficial compartment, the epidermis.
The dermis provides the epidermis with a solid support. It is also its feeder component. It consists mainly of fibroblasts and an extracellular matrix itself mainly composed of collagen, elastin and a substance called ground substance, these components being synthesized by the fibroblast. Leukocytes, mastocytes or tissue macrophages are also found therein. It also consists of blood vessels and of nerve fibers.
Natural human epidermis is composed mainly of three types of cells which are the keratinocytes, which are highly predominant, the melanocytes and the Langerhans' cells. Each of these cell types contributes, through its specific functions, to the essential role played by the skin in the organism.
The epidermis is conventionally divided into a basal layer of keratinocytes which constitutes the germinative layer of the epidermis, a so-called prickle cell layer consisting of several layers of polyhedral cells arranged on the germinative cells, a so-called granular layer consisting of flattened cells containing distinct cytoplasmic inclusions, the keratohyalin granules, and finally a top layer called horny layer (or stratum corneum), consisting of keratinocytes at the final stage of their differentiation, called corneocytes. These are anucleated, mummified cells which are derived from the keratinocytes.
The corneocytes are mainly composed of a fibrous matrix containing cytokeratins, surrounded by a very resistant structure 15 nm thick, called horny or hornified envelope. The stacking of these corneocytes constitutes the horny layer which is responsible for the barrier function of the epidermis. During the normal desquamation process, the most superficial corneocytes become detached from the surface of the epidermis.
Intercellular structures derived from the desmosomes, called corneosomes or corneodesmosomes, have been described in the horny layer. Recent studies have shown their key importance in intercorneocyte cohesion as well as in the desquamation process. In particular, a close correlation exists between cell dissociation and proteolysis of certain corneodesmosomal components such as desmoglein I.
Several serine proteases of the trypsin or chymotrypsin type appear to be involved in the proteolysis of the corneodesmosomes, in particular the chymotryptic enzyme of the horny layer (stratum corneum chymotryptic enzyme).
Numerous pathological conditions of the skin are characterized by the production of a thick horny layer and by an abnormal desquamation, that is to say by hyperkeratosis. The latter may occur on any anatomical skin area and in a wide variety of clinical contexts. Its physiopathological substratum and its cause are varied.
By way of example, there may be mentioned:
xerosis (or dryness of the skin),
ichthyoses,
psoriasis,
certain benign or malignant tumour lesions,
reactive hyperkeratoses.
Other pathological conditions are characterized by transdifferentiation or metaplasia, at the level of the mucosae, Malpighian or otherwise, but normally nonhornified, which become hornified, that is to say which become covered with an abnormal epithelium, producing a horny layer at its surface. Although the genital mucosae and those of the upper aerodigestive tracts are most often involved, these metaplasias may be seated in various anatomical areas.
By way of examples, there may be mentioned
leukokeratosis of the uterine neck during prolapsus,
buccal leukokeratoses,
keratotic benign tumour lesions of the Malpighian mucosae
By contrast, some pathological manifestations cause thinning of the epidermis and in particular of the horny layer, resulting in excessive fragility of the skin covering. It may be seated in various anatomical areas, its cause is variable and it may be constitutional or acquired.
By way of examples, there may be mentioned:
trophic skin disorders of the lower limbs in patients carrying vascular pathological conditions: varicose veins, arteriopathies (diabetes, arteriosclerosis and the like),
trophic skin disorders in the context of an algodystrophic syndrome,
trophic disorders following abnormal cicatrization.
The purification and knowledge of the polypeptides involved in intercorneocyte cohesion is one of the routes which could allow the production of products for combating the effects of an excess or a deficiency of polypeptides of this type, in particular at the surface of the skin.
One of the objects of the invention is to provide a composition comprising a polypeptide involved in intercorneocyte cohesion in purified form.
After long and laborious studies because of its low representation among the proteins of the epidermis, and its high instability and its high sensitivity to proteases, the applicant has identified, isolated and purified by biochemical techniques, from a human epidermis, a polypeptide specific to the hornified epithelia. This polypeptide, which will also be called elsewhere in the text “corneodesmosine” is expressed in the horny layer of the epidermis and is involved in intercorneocyte cohesion. The applicant has determined the primary amino acid sequence thereof.
The subject of the invention is therefore a cosmetic or pharmaceutical composition comprising, in a physiologically acceptable medium, at least one purified natural or synthetic polypeptide, the said polypeptide being characterized in that it corresponds to the following amino acid sequence SEQ ID NO: 1:
Met Gly Ser Ser Arg Ala Pro Trp Met Gly Arg Val Gly Gly His Gly
1 5 10 15
Met Met Ala Leu Leu Leu Ala Gly Leu Leu Leu Pro Gly Thr Leu Ala
20 25 30
Lys Ser Ile Gly Thr Phe Ser Asp Pro Cys Lys Asp Pro Thr Arg Ile
35 40 45
Thr Ser Pro Asn Asp Pro Cys Leu Thr Gly Lys Gly Asp Ser Ser Gly
50 55 60
Phe Ser Ser Tyr Ser Gly Ser Ser Ser Ser Gly Ser Ser Ile Ser Ser
65 70 75 80
Ala Arg Ser Ser Gly Gly Gly Ser Ser Gly Ser Ser Ser Gly Ser Ser
85 &e
Serre Guy Bruno Rene
Simon Michel
Weber-Vivat Marina
Low Christopher S. F.
Robinson Hope A.
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