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"Dendrite Elongation Inhibitor From Piper Longum Linn'

Abstract: Dendrite elongation inhibitor for melanocyte and their cosmetic compositions for lightening the colour of the skin wherein the active ingredient comprises an alkamide derivative of Formula 1 or preferably piperin or isopiperlongumine of Formula 2 in an effective amount along with cosmetically acceptable vehicles with or without skin benefit agents. The active ingredient may be selectively isolated from the plant parts of Piper longum Linn.

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Notices, Deadlines & Correspondence

Patent Information

Application #
Filing Date
14 September 2009
Publication Number
11/2011
Publication Type
INA
Invention Field
BIOTECHNOLOGY
Status
Email
Parent Application

Applicants

CAVINKARE PVT. LTD.
CAVIN VILLE, NO.12,CENOTAPH ROAD, CHENNAI -600 018

Inventors

1. RAO, DR.GOTTUMUKKALA VENKATESWARA
M/S.CAVINKARE RESEARCH CENTER, 12, POONAMALLE ROAD, EKKATTUTHANGAL, CHENNAI 600 032
2. RAO, DR.KOLISETTY SAMBASIVA
M/S.CAVINKARE RESEARCH CENTER, 12, POONAMALLE ROAD, EKKATTUTHANGAL, CHENNAI 600 032
3. MADHAVI,DR.MACHAVOLU SOUBHAGYA LAKSHMI
M/S.CAVINKARE RESEARCH CENTER, 12, POONAMALLE ROAD, EKKATTUTHANGAL, CHENNAI 600 032
4. MUKHOPADHYAY, DR. TRIPTIKUMAR
M/S.CAVINKARE RESEARCH CENTER, 12, POONAMALLE ROAD, EKKATTUTHANGAL, CHENNAI 600 032

Specification

FIELD OF THE INVENTION The present invention relates to skin care agents and cosmetic skin lightening compositions, and, in particular, selective alkamide derivatives as skin care/ lightening agents and cosmetic and/ or dermopharmaceutical compositions containing the same. The invention is further directed to cosmetic compositions comprising alkamide derivatives in effective amounts in the said compositions alongwith cosmetically and/ or dermopharmaceutically accepted vehicles with or without other skin benefit agents. More specifically, the invention is further directed in providing dendrite elongation inhibitory compositions involving the said alkamide derivatives. Importantly, the invention further relates to a simple and cost-effective dermopharmaceutical composition for external application to facilitate lightening of skin colour comprising said skin care agents preferably sourced from appropriate, safe and renewable plant source such as, Piper longum Linn., as extracts/ concentrates used singly or in combination with cosmetically/ dermopharmaceutically acceptable vehicle/ carriers. BACKGROUND ART An increase in skin pigmentation over the basal constitutive level is referred to as facultative pigmentation. A major stimulus of facultative pigmentation in humans is UVR. UVR induced skin pigmentation or tanning as it is commonly known, involves several processes like increased proliferation, enhanced tyrosinase expression, increased dendricity and increased transfer of melanin to ease the transfer of melanin keratinocytes. Skin lightening is an important contributor to skin care attribute of cosmetic formulation/ compositions, especially among darker skinned people including Asian population. Such a need includes a lightening of basal skin tone. Also it is desired by persons having spots, freckles or lesions which are hyper pigmented and thus need to be diminished. In other situations subjects may desire to reduce their natural skin colour or the skin darkening caused by exposure to intense sun rays. The degree of pigmentation of the skin is thus a principal cause of concern for many people. The complexion of the skin is determined by the pigment melanin. Melanocytes are the pigment producing cells that provide photo protection to the skin by synthesizing and distributing the pigment melanin to keratinocytes. These melanocytes are located in the basal layer of keratinocytes. Melanocytes and keratinocytes are resident population of epidermis and the color of skin is only because of the melanin in keratinocytes which is transferred from melanocytes. Melanocytes are derived from neural crest cells, comprise of 1-2 % of epidermal cell population and are solely responsible for the production and transfer of melanin to keratinocytes and pilosebaceous follicle. Melanin is synthesized and packed in cytoplasmic organelles of melanocytes, called melanosomes and are later transferred to keratinocytes through specialized structures in the melanocytes called dendrites. Since melanocytes are the minor population in the epidermis, the presence of the multiple dendrites facilitates transfer of melanosomes to keratinocytes that surround melanocytes. Movement of the mielanosomes along melanocyte dendrites is also necessary for the transfer of melanin pigment from melanocytes to basal and suprabasal keratinocytes to maintain the normal skin color. Melanocyte dendrite formation is regulated by multiple signaling pathways stimulated by paracrine factors released by keratinocytes (Hara et. al., J. Invest. Dermatol. 2000, 114, 438-443). The dendricity of melanocytes is regulated by various intrinsic and extrinsic factors. Addition of agents that increase the intracellular levels of cyclic adenosine monophosphate, dibutyryl cyclic adenosine monophosphate or isobuty I methyl xanthine (IBMX), has strong effects on dendrite formation (Glynis et. al., J. Invest. Dermatol., 2007, 127, 668-675). Each melanocyte makes contact with around 30-40 keratinocytes and this constitutes the epidermal melanin unit. Mammalian melanocytes in the epidermal unit extend their dendrites towards keratinocytes in response to UV rays in addition to proliferation and melanin synthesis leading to tanned skin (Suzuki et al., In Vitro Cell Dev. Biol. Anim., 1993, 29, 419-426). Increased number of dendrites and increase in the length of the dendrites leading to higher levels of transfer of melanin to keratinocytes is a phenomenon already established in the art. Thus colour of the skin can be determined/ regulated by modulating the elongation of dendrites or dendrite numbers (Akihiro, Fragr J, 2005, 33, 30 and Tada et. al.. Bio. Ind., 2005, 22, 12-17). Under normal conditions it is not the number of melanocytes in the skin that determines the degree of pigmentation but their levels of activity and the transfer of melanin in to the neighboring keratinocytes is the sole determining factor. Phospholipse A2 secreted by kertinocytes is also known to mediate melanocyte dendricity. The effective transfer of the synthesized melanin by the melanocytes to the keratinocytes plays a very critical role in the skin colour than the extent of synthesis of melanin by the melanocytes. The most effective mode of transfer of the melanin to the keratinocytes is governed by the dendritic phenomena of the melanocytes. Abrogating the dendriticity of melanocytes is of great importance for controlling skin colour (Yuko et. al., Biochlmica et Biophysica Acta, 2006, 1769, 487). There are several dendrite inhibitors already reported in the literature. Benzoquinone group of chemicals that includes methyl ophiopogonanone B and centaureidin, benzopyranone, xanthanone derivatives were reported to inhibit dendrite formation in melanocytes and effectively affect the skin colour (Yuko et. al., Blochimica et Biophysica Acta, 2006, 1769, 487). Inhibiting the dendrite formation in melanocytes is thought to be more effective in the related prior arts than tyrosinase inhibition for the purpose of skin lightening/ whitening cosmetics (Tada et. al., USP: 7, 141, 601, 2006). US patent 7141601 and Korean patents 20050084088 and 20057009913 by Tada et al., are directed to a method of inhibiting the elongation of melanocytic dendrites through a skin preparation comprising of methylophiopogonanone B (2, 3-dihydro-3[(4-methoxyphenyl) methyl]-5, 7-dihydroxy-6, 8-dimethyl-4H-l-benzopyran-4-one) extracted from the tubers of Ophiopogon japonicus ker-Gawler wherein the activity was studied by invitro and invivo methods. 3P 2004143073 A further illustrates a 1, 3-dioxolane derivative of methyl¬ophiopogonanone B to possess the same property of inhibiting the elongation of melanocytic dendrites. Saito et al. in JP 2001335420 A teaches a skin lotion comprising the essence of rhizomes of Acorus calamus; Saito et al, in JP 2001335421 A is directed to the essence of Sophora subprostata] Saeki et al. in JP 2003081748 A teaches a fruit essence of Forsythia suspensa Thunb. Vahl of Oleaceae; all of which have the same dendrite inhibition property. Howcjver, some of these products are associated with simultaneous disadvantages associated with each of them. For example, Acorus calamus is considered to be cytotoxic as reported by Padmaja et al. in Fitoterapia. 2002, 73, 508-510. While inhibiting the elongation of dendrites that occurs when melanocytes allow melanin granules to migrate is a well known skin lightening mechanism, not so many lightening agents utilizing such a mechanism are known in the art and it can thus be said that there is a strong need in the art for the development of new skin lightening agents utilizing such a mechanism. Therefore, the existing state of the art clearly reveals the need for newer, effective and safe dendrite elongation inhibitors and more importantly the need for possible isolation of the said dendrite elongation inhibitors from renewable resource materials such as plants. OBJECTS OF THE INVENTION It is thus the basic object of the present invention to provide for a new skin care agent for effective protection against darkening/ tanning of the skin involving inhibiting the elongation of dendrites as its mechanism of action that would be effective, safe and compatible to the skin. Another object of the present invention is directed to skin care formulation involving the said skin care agent in effective amounts in cosmetic and/ or dermopharmaceutical compositions whose functional attribute includes dendrite elongation inhibitory property to cater for variety of skin care conditions in association with a dermopharmaceutically acceptable vehicle with or without other skin benefiting agents. Yet another object of the present invention is to provide for a skin care agent for variety of skin care formulations and the like with anti-tanning property involving dendrite inhibitory mechanism that can be sourced simply and cost-effectively via synthesis or from renewable resource materials such as plants. A further object of the present invention is to provide for a process of formulation of the selective extract and/ or active ingredients having dendrite elongation inhibitory property from the plant sources wherein such selective actives act as a skin benefiting agent/ active that would especially favour the lightening of skin colour. Still another object of the present invention is directed to the formulation of the skin care composition using effective amounts of said extracts and/or active ingredients isolated from the plant sources such that the product obtained by incorporating said active ingredients / extracts have good skin compatibility. SUMMARY OF THE INVENTION Thus according to the basic aspect of the invention there is provided a skin lightening agent comprising an effective amount of a dendrite elongation inhibiting agent comprising one or more of alkamide derivative of Formula 1. Wherein R^=H, linear or branched hydrocarbons with 1-6 carbon atoms R^=H, linear or branched hydrocarbons with 1-6 carbon atoms R^-R^= -(CH2)n- where n=4-5 methylene groups as part of heterocyclic ring According to a preferred aspect of the invention there is provided a skin lightening agent wherein the said alkamide derivative is preferably selected from one or more of alkamides such as isopiperlongumine or piperin of Formula 2 6 Importantly, in keeping with tfie requirement for a sl

Documents

Application Documents

# Name Date
1 2217-che-2009 power of attorney 14-09-2009.pdf 2009-09-14
1 2217-CHE-2009_EXAMREPORT.pdf 2016-07-02
2 2217-che-2009 form-18 24-03-2011.pdf 2011-03-24
2 2217-che-2009 form-3 14-09-2009.pdf 2009-09-14
3 2217-che-2009 form-2 14-09-2009.pdf 2009-09-14
3 2217-che-2009 correspondence others 24-03-2011.pdf 2011-03-24
4 2217-che-2009 form-1 14-09-2009.pdf 2009-09-14
4 2217-che-2009 abstract 14-09-2009.pdf 2009-09-14
5 2217-che-2009 claims 14-09-2009.pdf 2009-09-14
5 2217-che-2009 description(complete) 14-09-2009.pdf 2009-09-14
6 2217-che-2009 correspondence others 14-09-2009.pdf 2009-09-14
7 2217-che-2009 claims 14-09-2009.pdf 2009-09-14
7 2217-che-2009 description(complete) 14-09-2009.pdf 2009-09-14
8 2217-che-2009 abstract 14-09-2009.pdf 2009-09-14
8 2217-che-2009 form-1 14-09-2009.pdf 2009-09-14
9 2217-che-2009 correspondence others 24-03-2011.pdf 2011-03-24
9 2217-che-2009 form-2 14-09-2009.pdf 2009-09-14
10 2217-che-2009 form-3 14-09-2009.pdf 2009-09-14
10 2217-che-2009 form-18 24-03-2011.pdf 2011-03-24
11 2217-CHE-2009_EXAMREPORT.pdf 2016-07-02
11 2217-che-2009 power of attorney 14-09-2009.pdf 2009-09-14