WO2010118489A1

WO2010118489A1 - Cosmetic and/or pharmaceutical formulations comprising an extract of ilex paraguariensis

Info

Publication number: WO2010118489A1
Application number: PCT/BR2010/000123
Authority: WO
Inventors: Silvia Berlanga De Moraes Barros; Cristina Dislich Ropke; Paulo Chanel Deodato De Freitas; Tânia Cristina Higashi SAWADA; Diogo Pineda Rivelli; Rebeca Leite De Almeida; Carlos Alberto Haroutiounian Filho
Original assignee: Universidade De São Paulo; Ybios S/A
Priority date: 2009-04-14
Filing date: 2010-04-13
Publication date: 2010-10-21
Also published as: BRPI0903382A2

Abstract

The invention concerns cosmetic and/or pharmaceutical formulations containing an extract of Ilex paraguariensis (yerba mate), particularly photoprotectors (sun filters) with wide spectrum (UVA and UVB protection) sun protection factor (SPF) and, optionally, a synthetic stabilizer and/or organic and/or inorganic synthetic sun filters.

Description

COSMETIC AND/OR PHARMACEUTICAL FORMULATIONS COMPRISING AN

EXTRACT OF ILEX PARAGUARIENSIS The present invention concerns cosmetic and/or pharmaceutical formulations comprising an extract of JJex paraguariensis (yerba mate) , particularly photoprotectors (sun filters) with wide spectrum (UVA and UVB protection) sun protection factor (SPF) and, optionally, a synthetic stabilizer and/or organic and/or inorganic synthetic sun filters. PRIOR ART

The rational use of products of vegetal origin in cosmetic and pharmaceutical formulations or food supplements constitutes a challenge to science and technology. The value added presupposes a production chain of the vegetal, conditions to prepare the drug, obtaining standardized and reproducible extracts, and finally the demonstration of the intended biological activity.

The definition of photoprotection is wide, comprising several mechanisms to avoid or lessen the deleterious effects of UV rays. A second protection barrier against damage caused by ultraviolet radiation come from products that impede the damage resulting from the UV action within the skin, i.e. generation of free radicals, damage to the DNA and to elements of the matrix, such as elastin and collagen. Among the products with that kind of action one can mention formulations comprising antioxidants, inhibitors of metalloproteinases and substances that protect and/or regenerate DNA.

Sun filters are the state of the art in the protection against solar radiation. Sun filters are classified as organic (absorbing radiation and convert it into heat) and inorganic (reflecting radiation) (VERSCHOOTEN, L., CLAERHOUT, S., VAN LAETHEM, A., AGOSTINIS, P., GARMYN, M. New Strategies of Photoprotection. Photochemistry and Photobiology 2006, Jul-Aug, v. 82, n.4, 1016-23) and (YAAR, M.; GILCHREST, B. A. Photoageing: mechanism, prevention and therapy. British Journal of Dermatology, 2007, v.157, p 874- 887) .

Most molecules used as sun filters are represented by an aromatic compound conjugated with a carbonyl group and a radical in the "ortho" or "para" positions, for instance the organic sun filters Meroxyl SX® (terephthalylidene dicamphor sulfonic acid) and avobenzone. That configuration is supposed to absorb photons with wavelength near UV. In that portion of the light spectrum, preferential wavelength is about 308 run. Such molecules absorb radiation in that wavelength and convert it to other wavelengths with less photobiological damaging potential to the organism (KRURY, E. Filtros Solares e Fotoprotetores, em Maio, M. Tratado de Medicina Estetica. Roca Editor, 2004, v.l, p. 371) .

The sun protection factor (SPF) is defined as the ratio between the minimum erythemal dose (MED) of radiation determined with the protection product (2mg/cm² application) and the minimum erythemal dose without the protection product. A SPF 15 sun filter can filter 94% of the UVB radiation, and a SPF 30 protects against 97% of that radiation (KULLAVANIJAYA, P.; LIM, H. W. Photoprotection. Journal of the American Academy of Dermatology, v. 52, n. 6, June, 2005, p. 937-958) . In the past years several publications report the potential of natural active principles in the prevention of photo-oxidative damage, the main mechanism of action provided by such substances being the antioxidant activity, inhibiting metalloproteinases and protecting DNA (AFAQ, F., MUKHTAR, H. Botanical antioxidants in the prevention of photocarcinogenesis and photoaging. Exp Dermatol. 2006, Sep, v. 15 n.9, p. 678-84) .

To deal with damage caused by UV radiation the vegetable species developed defense mechanisms that, among other strategies, include accumulating phenolic compounds capable of absorbing radiation in the epidermis of the leaves; nevertheless, there is nearly no reports on the action of natural substances in the role of natural sun filters. The main drawback in replacing synthetic sun filters by natural ones is the high cost of that substitution.

Natural origin sun filters, when incorporated in cosmetic formulations in economically feasible concentrations hardly ever attain an SPF above 4, always requiring the incorporation of another synthetic filter to reach higher SPF values .

Inorganic sun filters, such as titanium dioxide and zinc oxide are particularly prone to a whitening effect. The US 5,028,417 patent describes a solution to the whitening problem through the use of ultrafine titanium dioxide, below 10 nm.

The EP 433,086 European patent document describes a combination of titanium dioxide and zinc oxide with a particle sizes respectively below 25nm and 50nm.

The Brazilian patent application PI 9702056-7 discloses a method of obtaining a resin isolated from the leaves of Ilex paragυariensis, as well as a cosmetic formulation and its use in skin and hair treatment, preferentially hair. Also disclosed is an extract for the use of semi-polar or non-polar liquids, exempt from water, employing high temperature .

Patent US 5,470,579 discloses a method of treatment with a xanthic derivative for promoting pigmentation of skin and/or hair. Such xanthinic derivatives may optionally be originated from the extract of Ilex paraguariensis .

US patent application US 2008/0226570 describes a cosmetic method for body shaping by means of an extract of Ilex paraguariensis in the range of 0.3-0.8% only in a sub- product, that is, the final product contains a single compound from the original extract (caffeine) .

International patent publication WO 2007/010478 concerns cosmetic and/or dermatological compositions containing a dermatological acceptable carrier in association with at least one cholesterol-like molecule, at least a xanthinic base and at least one triglyceride synthesis inhibitor. According to the preceding facts, the inventors developed cosmetic formulations containing extracts of Ilex paraguariensis as active ingredient, that is, 100% natural, in photoprotective compositions with protection factors with wide spectrum UVA and/or UVB. DESCRIPTION OF FIGURES

Figure 1 shows the absorption spectrum for a formulation comprising an extract of Ilex paraguariensis incorporated in an oil-in-water emulsion, in a 10% concentration. Figure 2 is a graph with a correlation between extract concentration, of the present invention extract, and in vivo SPF (UVA and UVB protection), where y = 7,606x - 2,35 and R2 = 0,9964, ♦ representing the sequence and — the linear sequence. Figure 3 reports the synergistic effect of the extract upon the in vivo photoprotection parameters of the commercial product, where (—) is a 10% extract, (...) is SPF 30 Sundown ™ and (—) is the combination of a 10% extract and SPF 30 Sundown ™ . Figure 4 reports the synergistic effect of the extract upon the in vivo photoprotection parameters of the commercial product, where (—) is a 10% extract, (...) is SPF 30 Anthelios Fluide Extreme ™ and (—) is a combination of a 10% extract and SPF 30 Anthelios Fluide Extreme ™.

Figure 5 discloses the percentage of the in vivo

SPF decrease of the Ilex paraguariensis extract incorporated in a 10% emulsion after UV irradiation from an artificial source, where ♦ represents the exposed and B represents control.

Figure 6 shows a percentage of in vivo SPF decrease of a 10% Ilex paraguariensis extract incorporated in an emulsion with the presence of 6% octocrylene after UV irradiation from an artificial source, where ♦ represents exposition and 9 represents control.

Figure 7 demonstrates the in vivo SPF decrease of a 10% Ilex paraguariensis extract incorporated in an emulsion with presence of 5% polysilicone-15 after UV irradiation from an artificial source, where ♦ represents exposition and ■ represents control. DETAILED DESCRIPTION OF THE INVENTION

The present invention aims at cosmetic and/or pharmaceutical formulations comprising Ilex paraguariensis (yerba mate) extract, particularly photoprotectors (sun filters) with wide spectrum (UVA and UVB) sun protection factor (SPF) , and optionally a synthetic stabilizer and/or inorganic and/or organic sun filters.

The Ilex paraguariensis extracts of the present invention may be aqueous, alcoholic as methanolic, ethanolic, isopropanolic, and/or hydroalcoholic, or non-polar for instance with chloroform, dichloromethane, ethyl acetate, hexane, ether and/or combination of those, preferentially hydroalcoholic . The formulations of the present invention may be in the form of emulsions, such as lotions and creams, gels, cream-gels, mousse, stick, body oils, lipstick, makeup as base and facial powder, spray, aerosol, pomades, hair products, among others.

The present invention may also comprise other components, such as ingredients and additives, for instance water, preservatives, colorants, co-actives, pigments, thickeners, fragrances, alcohols, polyols, esters, electrolytes, gelling agents, mineral and vegetal oils, polymers and copolymers, emulsifying agents, wax, stabilizers, surfactants, humectants, propellants, pH controllers, emollients, antioxidants, among others. In an optional manner, the photostabilizer components (stabilizers) present in the invention formulations concern octocrylene and polysilicone-15.

Furthermore, the present invention also encompasses the optional use of synthetic photoprotectors such as physical (or inorganic) filters for instance titanium dioxide and/or zinc oxide, and chemical (or organic) filters, for instance anisotriazine, benzophenone-3, bis- ethylhexyloxyphenolmethoxyphenyl triazine, octylmethoxycinnamate and octyl salicylate. Particularly, the present invention utilizes photoprotectors of natural origin - extract of Ilex paraguariensis leaves - with an in-vivo SPF from 2 to 15. The invention formulation may optionally incorporate organic and/or inorganic photoprotector agents, and/or stabilizer agents, resulting in SPF values from 15 to 60.

The cosmetic and/or pharmaceutical formulations of the present invention may comprise 1-20 % concentration of active extracts. EXAMPLES PREPARATION AN EXTRACTS FROM ILEX PARAGUARIENSIS

Ilex paraguariensis leaves were ground and sieved in 40 mesh (to standardize size, ensuring uniformity of contact surface) , put in a percolator and extracted with a 50% in volume water/ethanol mixture. The ethanol was then removed from the extract by rotoevaporation at temperatures of about 45-50⁰C and 600 mmHg vacuum. The remaining aqueous material was lyophilized and the resulting dry extract was used in the following tests. ASSAYS

2 mg/cm² of a cosmetic formulation according to the present invention was applied upon about 25 cm of a skin- mimicking substrate (Vitro-Skin®, commercialized by IMS Inc., Portland, USA) .

The analyses were run using a transmittance analyzer Labsphere® UVlOO-S, measuring diffuse transmittance in the 250-400 nm region. A double spectrophotometer with a xenon lamp that emits flashes (optimized for the UV region) and an integration sphere provided instantaneous spectral acquisitions. The geometry of diffuse illumination of the sphere allows measurement of absorption from all angles and directions through the sample, and employs the total energy of the xenon lamp for an optimal signal/noise ratio (SPRINGSTEEN, A.; Ywer, R.; Frazier, M.; Carr, K. F. In vitro measurement of sun protection factor of sunscreens by diffuse transmittance. Analytica Chimica Acta, v.380, 1999, p. 155- 164) .

To evaluate UVA protection, one employed the verification of absorption along all spectrum of this region

(320-400nm) and the Boots Stars methodology, based on the calculation of the UVA/UVB ratio, and the level of UVA protection of the product is expressed in terms of punctuation stars. The critical wavelength evaluates the uniformity of the protection spectrum UVA/UVB of the product

(SPRINGSTEEN, A.; Ywer, R.; Frazier, M.; Carr, K. F. In vitro measurement of sun protection factor of sunscreens by diffuse transmittance. Analytica Chimica Acta, v.380, 1999, p. 155- 164) .

The calculation of the UVA/UVB ratio and the critical wavelength are independent from the absorbance obtained for the spectral reading interval, thus independent from the product concentration in the substrate. The critical wavelength (c) is expressed in nm and values above 370nm present wide absorption spectrum (UVA/UVB) and a strong co- relation to adequate UVA in vivo protection.

In the Boots Stars methodology, the UVA/UVB ratio is expressed in the form of punctuation stars, as shown in table 1 below:

TABLE 1

The in vivo SPF measurement consists of evaluating the transmittance obtained from a VitroSkin ® substrate with and without the application of the invention product, taken into account the solar radiance and the erythematogenic efficacy of each wavelength, according to harmonized standard for in vivo SPF evaluation (COLIPA, JCIA, CTFA, CTFASA) .

Table 2 below brings the results of in vitro SPF (UVB protection) in a gel-cream formulation:

TABLE 2

N 5% IP 10% IP 15% IP 20% IP

1 36.0 71.5 116.2 146. 7

2 36.9 74.2 111.1 148. 3

3 32.9 71.1 120.7 147. 1

Average 35.2 72.3 116.0 147. 4

Standard deviation 2.1 1.6 4.8 0.9

% Variation

5.9 2.2 4.1 0.6 coefficient

Table 3 below brings the in vitro FPS results (UVA protection) in a gel-cream formulation, where the Variation coefficient is based on a population of 3 analyses per sample These values are acceptable up to 10%, according to the utilized methodology. N= sample number IP=Ilex paraguariensis concentration

The data related to UVA/UVB ratio, Boot Stars classification, and Critical Wavelength do not need calculation of variation coefficient for they derive directly from the data presented herein. TABLE 3

15% IP 88.9 / 0.8 .0.75 *** 370

(good)

20% IP 92 .6 / 0 .2 0. 82 **** 372

(Superior)

Table 4 below shows the effect of incorporating the extract (synergism) in two commercial products. TABLE 4

PHOTOSTABILITY RESULTS To evaluate the photostability of the JJ ex paraguariensis, formulations comprising the extract were irradiated with a 290-400 run radiation-emitting xenon lamp, with different doses of radiation controlled by a radiometer aimed at that end up to maximal accumulated dose of 40 MED, equivalent to maximal exposure of a SPF 30 product, with more than a thousand results related to minimum erythemal doses to cause the first sign of erythema on unprotected skin (1.32 MED) . The samples were applied to a commercially available substrate composed of polymethylmetacrilate in the amount of 0,75mg/cm², and the spectrophotometry was performed both on at least 3 sites exposed to radiation and a control that consists of a site not submitted to exposure to UVA-UVB. The result was expressed as being the mean variation of the SPF of the exposed sites and the control, the accepted variation coefficient among the sites of a same sample was up to 10% according the employed methodology.

TABLE 5

Claims

1. COSMETIC AND/OR PHARMACEUTICAL FORMULATIONS characterized in that they comprise an extract of Ilex paraguariensis (yerba mate) and, optionally, a synthetic stabilizer and/or organic and/or inorganic synthetic sun filters.

2. COSMETIC AND/OR PHARMACEUTICAL FORMULATIONS according to claim 1 characterized by the fact that said formulations comprise, photoprotectors (sun filters) with sun protection factor (SPF) of wide spectrum such as UVA and/or UVB.

3. COSMETIC AND/OR PHARMACEUTICAL FORMULATIONS according to any one of claims 1 or 2, characterized in that said extract is aqueous, alcoholic for instance methanolic, ethanolic, isopropanolic and/or hydroalcoholic, and/or non- polar such as with chloroform, dichloromethane, ethyl acetate, hexane, ether, and/or combinations of those, preferably hydro-alcoholic.

4. COSMETIC AND/OR PHARMACEUTICAL FORMULATIONS according to any one of claims 1 to 3 characterized in that they are emulsions such as lotions and creams, gels, cream- gels, mousse, stick, body oils, lipstick, makeup such as base and facial powder, spray, aerosol, pomades, products for hair, and their derivatives.

5. COSMETIC AND/OR PHARMACEUTICAL FORMULATIONS according to any one of claims 1 to 4, characterized in that they comprise additional components such as excipients and additives, such as water, preservatives , colorants, co- actives, pigments, thickeners, fragrances, alcohols, polyols, esters, electrolytes, gelling agents, mineral and vegetal oils, polymers and copolymers, emulsifying agents, waxes, stabilizers, surfactants, humectants, propellants, pH controllers, emollients, antioxidants, their derivatives and/or combinations thereof

6. COSMETIC AND/OR PHARMACEUTICAL FORMULATIONS according to any one of claims 1 to 5 characterized in that they additionally comprise photostabilizers such as octocrylene and/or polysilicone-15.

7. COSMETIC AND/OR PHARMACEUTICAL FORMULATIONS according to any one of claims 1 to 6 characterized by the fact that they also optionally comprise anisotriazine, benzophenone-3, bis-ethylhexyloxyphenol methoxyphenyl triazine, octylmethoxycinamate and octyl salicylate.

8. COSMETIC AND/OR PHARMACEUTICAL FORMULATIONS according to any one of claims 1 to 7 characterized in that they provide a sun protection factor form 2 to 60.

9. COSMETIC AND/OR PHARMACEUTICAL FORMULATIONS according to one of claims 1 to 8 characterized by the fact that they comprise about 1 to 20% active extracts .