Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1995-05-24
1998-02-17
Tsang, Cecilia J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
530350, 530412, 530416, A61K 3800
Patent
active
057191263
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to a melanogenic inhibitor, and methods of producing and using the same. More specifically, this melanogenic inhibitor comprises a naturally derived protein, or effective segments thereof, which reduces tyrosinase activity, inhibits pigmentary cell proliferation, and is cytotoxic to melanoma cells.
BACKGROUND ART
Hyperpigmentary disorders affect many people worldwide, and are often the cause of much embarrassment or worse. These disorders include such things as: freckles, solar lentigines (livers spots), the visible darkening that often occurs in skin grafted onto bum victims, and, most serious of all, melanoma. Additionally, many also desire to lighten their basal skin tone merely for cosmetic reasons.
Various means have been utilized in the past for either reducing pigmentation in hyperpigmented areas or for lightening basal skin tone. While mixed results have been obtained with these treatments, most can result in undesirable side-effects. Compounds that have been used for bleaching, or depigmenting, skin include: hydroquinone, derivatives of hydroquinone, ammoniated mercury, ascorbic acid, mercaptoamines, 4-isopropylcatechol, and peroxides. None, however, have proven to be completely reliable and without side effects.
European Patent Application 389,950 discloses a melanocyte-stimulating hormone (MSH) inhibitor that is reported to be useful for such things as preventing or relieving the symptoms of chloasmata or freckles. This inhibitor contains an amino acid sequence represented by the following formulas: -His-Ser-Arg-Trp-; Trp-Arg-Ser-His-; or -Leu-Ala-Cys-Ala-Arg-. The peptides represented by the first two of these sequences have an affinity for the MSH receptor contained on the surface of melanocytes, and thereby antagonize MSH. Peptides represented by the third sequence have an affinity for MSH itself, and thereby inhibit the effect of MSH.
Subsequent to their invention, Applicants have become aware of a recent publication which discloses a protein that may be related to that which they have produced (Madsen, P. et al., I. Invest Dermatol 99:299-305 (1992)), and in fact may be identical. This protein is reported to be highly up-regulated in psoriatic keratinocytes, however no relationship to melanogenesis is mentioned.
A more serious skin hyperpigmentary disorder that effects millions worldwide is melanoma. While it can sometimes be treated if detected early, melanoma is often fatal. Currently available treatments, such as chemotherapy, often cause serious side effects, and are never completely effective in all instances.
Heretofore, however, there has not been an available naturally derived composition that can reliably inhibit melanogenesis and thereby reduce skin pigmentation, is selectively cytotoxic to melanoma cells, and has no known side effects.
SUMMARY OF THE INVENTION
While not exclusive, the following describes some of the important features and objects of the present invention.
It is an object of the present invention to provide a naturally derived melanogenic inhibitor useful for reducing pigmentation in skin and selectively destroying melanoma cells.
It is also an object of the present invention to provide a naturally derived melanogenic inhibitor comprising a naturally derived melanogenic inhibitor protein, or active segments thereof.
It is a further object of the present invention to provide a method for producing a melanogenic inhibitor protein.
It is yet another object of the present invention to provide a method for controlling pigmentation in skin and/or hair utilizing a naturally derived melanogenic inhibitor protein, or active segments thereof.
It is another object of the present invention to provide a method for destroying melanoma cells, without affecting normal, nonpigmentary cells, utilizing a naturally derived melanogenic inhibitor protein, or active segments thereof.
As used herein, "melanogenesis" means the formation of melanin by living cells, and "inhibiting melanogenesis" includes inhibiting the ability of individual cel
REFERENCES:
patent: 5331091 (1994-07-01), Fukuda et al.
Farooqui et al., "The Isolation of a Unique Melanogenic Inhibitor . . . ", Pigment Cell Research, vol. 6, No. 4, pp. 299-300, Aug. (1993), abstract.
Madsen et al., The Journal of Investigative Dermatology, vol. 99, No. 3, pp. 299-305, Sep. 1992.
Rasmussen et al., Elcetrophoresis 13: 960-969 (1992).
"Regulation of Melanin Pigmentation by Tyrosinase, TRP1, TRP2, and a Melanogenic Inhibitor," Koichiro Kameyama, Jun. 18-20, 1992.
"Skin Bleaching Preparations," S.S. Bleehen, 28 J. Soc. Cosmet. Chem. 407-412 (1977) .COPYRGT. 1977 Society of Cosmetic Chemists of Great Britian.
"Evaluation of Skin Bleach Creams," K.V. Curry, 25 J. Soc. Cosmet. Chem 339-354 (1974) Society of Cosmetic Chemists of Great Britian.
Abstract: "Hyperpigmentation of Human Xenografts on Albino Nude Mice," Billye W. Auclair, PanAmerican Society for Pigment Cell Research, Apr. 23-26, 1989.
"Molecular Cloning And Expression Of A Novel Keratinocyte Protein (Psoriasis-Associated Fatty Acid-Binding Protein (PA-FABP) That Is Highly Up-Regulated In Psoriatic Skin And That Shares Similarity To Fatty Acid-Binding Proteins," Madsen, et al., The Journal of Investigative Dermatology, vol. 99, No. 3, pp. 299-305, Sep. (1992).
Abstract of Article: "Immune And Nonimmune Effector Functions Of IgG3 Mouse Monoclonal Antibody R24 Detecting The Disialoganglioside GD3 On The Surface Of Melanoma Cells," Welt, et al., File Server STN Karlsruhe, File Medline Abstract No. 88028034, Clin. Immunol. Immunopathol., Nov. (1987).
Abstract of Japanese Patent: "Preparation Inhibits Melanogenesis And Activates Fibroblasts Proliferation-containing protein or glyco: protein hydrolysate of cuttlefish ink as active cmponent"; JP-A 3 255 016 (Sancho Pharm KK), Nov. 13, 1991, Database WPI, Section CH, Week 9201. Derwent Publications Ltd., Lond, GB; Class B04, AN 92-002611.
Abstract of Article: "Human Skin Xenografts Express A Potent Epidermal Melanogenic Inhibitor," Farrooqui et al., Clinical Research, vol. 41, No. 3, Oct. (1993).
Abstract of Article: "The Isolation Of A Unique Melanogenic Inhibitor From Human Skin Xenografts," Farrooqui et al., Pigment Cell Research, vol. 6, No. 4, pp. 299-300, Aug. (1993).
Farooqui Jamal Z.
Nordlund James J.
Delacroix-Muirheid C.
Tsang Cecilia J.
University of Cincinnati
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