Specification
FIELD OF THE INVENTION
The present invention relates to skin lightening agent and compositions obtained thereof and, in particular, to a skin lightening agent isolated from the source Artocarpus heterophyllus Lam and tike compound/ compounds which show benefit attributes as skin care compositions such as cosmetic and/or dermopharmaceutical compositions for topical use. The invention is also directed to simple and cost-effective manner of extraction of the active skin lightening agent from the selective Artocarpus heterophyllus Lam. The invention would thus provide for skin lightening benefit in cosmetic/derrrtopharmacuetical compositions for topical application to skin including leave -on and wash-off products. The invention also provides for processes for producing the said active compound either by isolation from natural sources, as a single entity or in a semi-pure mixture of compounds to the said compositions comprising the said active compound, and to processes for producing and using the said compositions involving such compound to achieve skin lightening effects.
BACKGROUND OF THE INVENTION
There is an increasing demand nowadays for cosmetic preparations which represent active ingredients which impart skin lightening effects.
The degree of pigmentation of the skin is a cause of concern for many people. Skin lightening is an important skin care need, whether among darker- or lighter-skinned people. Such a need includes a lightening of basal skin tone and diminishing spots, freckles or lesions which are hyperpigmented. Others may desire to reduce their natural skin colour or the skin darkening caused by exposure to sunlight. To meet this need different attempts have been made to develop compounds and products that reduce the pigment production in the melanocytes. It is generally known that conditions which result in defective or missing tyrosinase may likely lead to skin lightening via inhibition of melanogenesis. Conversely, it is known that inhibition of tyrosinase, mostly through downregulation of microphthalmia-associated transcription factor (MITF), may likely lead to skin lightening via inhibition of melanogenesis. For a more complete description of how tyrosinase acts within
melanosomes, and how tyrosine inhibitors contribute to decreased melanin formation one can refer to United States Patent No.6537527 (March 25, 2003), to the updated review on hypopigmenting agents and their biological, chemical and clinical aspects (F. Solano et al., Pigment Cell Res (2006), 19, 550-571) and to the review on tyrosinase inhibitors from natural and synthetic sources (Y.-J. Kim and H. Uyama, Cell.Mol.Life Sci. (2005) 62, 1707-1723) as examples of the many literature documents on the subject of tyrosinase inhibition, tyrosinase inhibitors and their role in skin lightening.
Currently there are several tyrosinase inhibitors in the market place including 1,4-dihydroquinone, arbutin, aloesin, kojic acid. However there are disadvantages to each of these products. For example, 1,4-dihydroquinone can be considered to be a potent melanocyte cytotoxic agent and is also reported to induce mutations. Today the human use of hydroquinone has important legal restrictions. The compound was banned in Europe in December 2000, Eur. Com. 6 for general cosmetics purposes, and formulations with this compound are available only by prescription of physicians and dermatologists. Commercially available products, kojic acid and arbutin are marginal tyrosinase inhibitors, marginal efficacy and also are not very bioavailable, and some undesirable side effects. To diminish the adverse side effects of arbutin and aloesin, the use of reduced doses of each of them in synergistically-acting mixtures for depigmentation purposes ;s said to be beneficial (Y.-j. Kim and H. Uyama, Cell.Mol.Life Sci. (2005) 62, 1707 - 1723). Therefore, there is a need to provide a more effective skin lightening agent which is more efficacious than those currently available in the market.
A number of plant polyphenol compounds are known to display tyrosinase
inhibitory activity (cf. F. Solano et al., Pigment Cell Res (2006), 19, 550-571 and Y.-
J. Kim and H. Uyama, Cell.Mol.Life Sci. (2005) 62, 1707 - 1723). To the class of
plant polyphenols which include the families of flavanoid-like agents such as
flavanols conjugated to gallic acid, flavanones, hydroxycoumarins and prenylated
flavonoids belong the sub-group of hydroxystilbene derivatives, one of the most
efficient because of its high affinity for tyrosinase. The sub-group includes
compounds like resveratrol (3,4', 5-tri hydroxystilbene) and the isomers
oxyresveratrol (2', 3,4', 5-tetra hydroxystilbene and gnetol (2',3,5,6'-
tetrahydroxystilbene)(Y.M. Kim et al, J. Biol. Chem. (2002) 277, 16340 -16344; K. Shimuzu et al, Planta Med., (2000) 66, 11 - 15; Lee et al., J.Cosmet. Sci., (2003)
54, 133-142;). The presence of an isoprenyl chain in the 4-position of the hydroxystilbenes is claimed to increase their tyrosinase inhibitory activity (E. T. Arung et al., Planta Med., (2006) 72, 847-850). Components from Artocarpus incisus such as 4-prenyloxyresveratrol and 4-geranyloxyresveratrol (also known as chiorophorin) are described in K. Shimuzu et al., Planta Med., (1998) 64, 408 -412 and the utility of extracts of Artocarpus incisus and their components as skin lightening actives in cosmetic compositions is disclosed in different Japanese patents JP 08 277,225 (1996), JP 10 17,455 (1998), JP 10 101,665 and JP 10 072330 (1998).
The genus Artocarpus comprises a family of many species, the extensively studied among which, besides A. incisus, are A. integer, A. communis, A. aitis, A. heterophyllus, A. rigidus, A. integrifolia, A. gomezianus, A, rotunda, A. landefolia, A, lakoocha, A. tonkiinensis, A, nobilis and A. dadah. In particular, A. heterophyllus has been extensively investigated and has provided different polyphenols compounds with diverse activities ( cf. The Wealth of India, supplement series, vol. no.2, (2000) 96-98 ; JP 03 68,580 (1991); JP 08 73,368 (1996); F. N. Ko et al., Free Radical Biol. Med., (1998) 25,160-168), including hypoglycaemic activity, antiplaque for prevention of dental caries, antihypertensive and antibacterial activities, antimicrobial cosmetic composition, and scavenger and antioxidant properties. Besides A. incisus mentioned above, the only other Artocarpus species reported to provide tyrosinase inhibitory compounds, including a dimeric stilbene, has been the plant A. gomezianus.
OBJECTS OF THE INVENTION
It has thus been the basic object of the present invention to identify selective sources including natural sources of tyrosinase inhibitiors which function as skin lightening agent and which would show benefit attributes in skin care compositions such as cosmetic and/or dermopharmaceutical compositions for topical use.
Another object of the present invention is directed to simple and cost-effective manner of extraction of the active skin lightening agent from natural sources which would serve as a single entity or in a semi-pure mixture of compounds and to provide compositions comprising the said skin lightening agent and compound/s, and
to processes for producing and using the said compositions to achieve skin lightening effects.
Another object of the invention is to provide compounds and compositions based on selective skin lightening agent which would be potent tyrosinase-inhibiting, melanogenesis-influencing agents and favour providing variety of cosmetic compositions particularly suited for topical application to achieve skin lightening effects.
A further object of the invention is directed to providing isolation procedures of the skin lightening agent from renewable natural resources such as plants to benefit the cosmetic and /or dermopharmaceutical compositions for topical use involving the same.
Yet further object of the present invention is directed to provide for cosmetic/dermopharmacuetical compositions for skin lightening benefit for topical application to skin including leave-on and wash-off products.
A further object of the invention is directed to simple and cost-effective and importantly also safe and user friendly process for producing skin lightening actives by isolation from natural sources, as a single entity or in a semi-pure mixture of compounds to the said compositions comprising the said active compound and to processes for producing and using the said compositions involving such compounds to achieve skin lightening effects.
SUMMARY OF THE INVENTION
Thus according to the basic aspect of the invention there is provided a skin lightening agent comprising selectively atleast one stilbene derivative sourced from Artocarpus heterophyllus Lam., and displaying substantially the following characteristics on thin layer chromatography using a pre-coated silica gel plate, the isolated substance provides a spot with an Rf value of 0.39 in EtOAc: CHCI3 3:1; the UV(MeOH) spectrum showed an absorbance value at 345 nm; IR. spectrum values are at 3450 (br), 1610 cm"1 and other characteristic signals; Proton NMR values in DMSO-d6 are: 5 1.02 (6H, d, J=6.7Hz), 2.35 (m), 6.22 (dd, J = 2.3, 8.4Hz), 6.31 (d,
3=2.3Hz), 6.44 (2H, s), 6.48
Documents
Orders
| Section |
Controller |
Decision Date |
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Application Documents
| # |
Name |
Date |
| 1 |
1067-che-2007-form 3.pdf |
2011-09-03 |
| 1 |
1067-CHE-2007_EXAMREPORT.pdf |
2016-07-02 |
| 2 |
1067-CHE-2007 CORRESPONDENCE OTHERS 13-02-2014.pdf |
2014-02-13 |
| 2 |
1067-che-2007-form 26.pdf |
2011-09-03 |
| 3 |
1067-che-2007-form 1.pdf |
2011-09-03 |
| 3 |
1067-CHE-2007 AMENDED PAGES OF SPECIFICATION 16-08-2013.pdf |
2013-08-16 |
| 4 |
1067-che-2007-description(provisional).pdf |
2011-09-03 |
| 4 |
1067-CHE-2007 AMENDED CLAIMS 16-08-2013.pdf |
2013-08-16 |
| 5 |
1067-che-2007-correspondnece-others.pdf |
2011-09-03 |
| 5 |
1067-CHE-2007 CORRESPONDENCE OTHERS 16-08-2013.pdf |
2013-08-16 |
| 6 |
1067-che-2007 form-5.pdf |
2011-09-03 |
| 6 |
1067-CHE-2007 FORM-1 16-08-2013.pdf |
2013-08-16 |
| 7 |
1067-che-2007 description (complete).pdf |
2011-09-03 |
| 7 |
1067-CHE-2007 AMENDED CLAIMS 30-07-2012.pdf |
2012-07-30 |
| 8 |
1067-che-2007 claims.pdf |
2011-09-03 |
| 8 |
1067-CHE-2007 EXAMINATION REPORT REPLY RECEIVED 30-07-2012.pdf |
2012-07-30 |
| 9 |
1067-che-2007 abstract.jpg |
2011-09-03 |
| 9 |
1067-che-2007 abstract.pdf |
2011-09-03 |
| 10 |
1067-che-2007 abstract.jpg |
2011-09-03 |
| 10 |
1067-che-2007 abstract.pdf |
2011-09-03 |
| 11 |
1067-CHE-2007 EXAMINATION REPORT REPLY RECEIVED 30-07-2012.pdf |
2012-07-30 |
| 11 |
1067-che-2007 claims.pdf |
2011-09-03 |
| 12 |
1067-CHE-2007 AMENDED CLAIMS 30-07-2012.pdf |
2012-07-30 |
| 12 |
1067-che-2007 description (complete).pdf |
2011-09-03 |
| 13 |
1067-CHE-2007 FORM-1 16-08-2013.pdf |
2013-08-16 |
| 13 |
1067-che-2007 form-5.pdf |
2011-09-03 |
| 14 |
1067-CHE-2007 CORRESPONDENCE OTHERS 16-08-2013.pdf |
2013-08-16 |
| 14 |
1067-che-2007-correspondnece-others.pdf |
2011-09-03 |
| 15 |
1067-CHE-2007 AMENDED CLAIMS 16-08-2013.pdf |
2013-08-16 |
| 15 |
1067-che-2007-description(provisional).pdf |
2011-09-03 |
| 16 |
1067-CHE-2007 AMENDED PAGES OF SPECIFICATION 16-08-2013.pdf |
2013-08-16 |
| 16 |
1067-che-2007-form 1.pdf |
2011-09-03 |
| 17 |
1067-CHE-2007 CORRESPONDENCE OTHERS 13-02-2014.pdf |
2014-02-13 |
| 17 |
1067-che-2007-form 26.pdf |
2011-09-03 |
| 18 |
1067-CHE-2007_EXAMREPORT.pdf |
2016-07-02 |
| 18 |
1067-che-2007-form 3.pdf |
2011-09-03 |