Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Cosmetic – antiperspirant – dentifrice
Patent
1995-03-17
1997-03-04
Venkat, Jyothsna
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Cosmetic, antiperspirant, dentifrice
424701, 514 8, 514863, 514944, A61K 748
Patent
active
056076797
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to the use of lectins for the treatment of skin disorders associated with hyperproliferation of keratinocytes or with hyperkeratosis, particularly, but not exclusively, psoriasis and benign keratoses. Lectins are plant or animal proteins or glycoproteins of non-immune origin with specific affinity for carbohydrates.
2. Description of the Related Art
Lectins have been used widely as probes for locating carbohydrate groups in cell membranes, since they have affinities for certain saccharides.
Certain lectins are known to act as mitogens, i.e. stimulators of cell proliferation. For example, peanut agglutinin (PNA) is a mitogen for human colon epithelial cells [S. D. Ryder et al., J. Nat. Cancer Institute 84, 1410-1416 (1992)]. Conconavalin A (Con-A) and phyto-hemagglutinin have a mitogenic effect on haematopoietic cells.
On the other hand, certain lectins have been reported to have an anti-tumour action. See, for example, Japanese Patent Application Publication (Kokai) No. 61-205218, (Ajinomoto K. K.), published in 1986, which mentions the agglutinins of a) Agaricus bisporus, b) Trichosanthes kinlowii, c) Rhizobium trifolii, d) Salvia horminium, e) Maclura pomifera, f) Sarothamnus scoparius, g) Wistaria floribunda, h) Griffonia (Bandeiraea) simplicifolia and i) Euonymus europeus.
SUMMARY OF THE INVENTION
The TF antigen (galactose .beta.-1,3-N-acetylgalactosamine .alpha.-) is expressed on normal human keratinocytes. It is the receptor for several lectins including Arachis hypogaea (peanut agglutinin), Amarinthus caudatus (amarinthin lectin), Artocarpus integrifolia (jacalin lectin) and Agaricus bisporus lectin. Whereas lectins are well known for their mitogenic properties and whereas previous work by the inventor has shown that peanut agglutinin stimulates proliferation of epithelial cells which express TF antigen, recent studies by the inventor have shown that Agaricus bisporus lectin (ABL) has the unusual property of inhibiting proliferation in keratinocytes without causing significant cytotoxcity. Keratinocytes are the predominant cells (>95%) of the epidermis, which is the upper section of the skin tissue. Keratinocytes are continually dividing in the basal layer to produce fresh cells, which migrate towards the skin surface, eventually dying in the upper levels. Hyperproliferation of the epidermis produces excessive scale, comprising dead cells, which is manifested in psoriasis, for example.
Since ABL differs from PNA in its ability to bind sialylated TF antigen, the inventor believes that lectins which bind to sialylated TF antigen inhibit the proliferation of cells.
According to one aspect of the present invention there is provided the use of a lectin, which is capable of binding a sialylated TF antigen, for the treatment of skin disorders caused by or associated with hyperproliferation of keratinocytes or hyperkeratosis. Thus, where patent law permits, the invention includes (1) a method of treating a patient suffering from a skin disorder caused by or associated with hyperproliferation of keratinocytes or hyperkeratosis, especially psoriasis and benign keratoses, which comprises administering to the patient a therapeutically effective amount of a said lectin, and (2) the use of a said lectin in the manufacture of a medicament for the treatment of such a skin disorder.
The medicament may be formulated as a pharmaceutical composition comprising a lectin which is capable of binding sialylated TF antigen and a pharmaceutically acceptable carrier or diluent appropriate to application to the skin. Preferably the composition is a cream, ointment, gel, cosmetic lotion containing a perfume ingredient or a shampoo.
DESCRIPTION OF THE PREFERRED EMBODIMENTS
Jacalin lectin, which comes from the seeds of the jackfruit, Artocarpus integrifolia, is another example of a lectin which binds to sialylated TF antigen and its use for the purposes of the invention is also within the invention. Another example of a lectin within the
REFERENCES:
patent: 4217341 (1980-08-01), Suddick
patent: 4421746 (1983-12-01), Kojima et al.
patent: 4440761 (1984-04-01), Kojima et al.
patent: 4742046 (1988-05-01), Bliah
British Technology Group Limited
Venkat Jyothsna
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