Anti-hair loss cosmetic complex, cosmetic composition, use of Anti-hair loss cosmetic complex, and method for cosmetic treatment

Abstract

The present invention relates to an anti-hair loss cosmetic complex comprising a combination of the active agents (a) recombinant silk protein, (b) xylitol phosphate ester, and (c) caffeine, as well as to cosmetic compositions containing same, their uses, and a method, the aim being to treat keratinous fibers, such as skin, hair, or scalp, particularly for the prevention of hair loss.

Description

[0001] “ANTI-HAIR LOSS COSMETIC COMPLEX, COSMETIC COMPOSITION, USE OF THE ANTI-HAIR LOSS COSMETIC COMPLEX AND METHOD FOR COSMETIC TREATMENT” FIELD OF THE INVENTION

[0002] [1] The present invention relates to an anti-hair loss cosmetic complex comprising the combination of the active ingredients (a) recombinant silk protein (b) xylitol phosphate ester and (c) caffeine, as well as cosmetic compositions containing the same, their uses and method, aiming at the treatment of keratin fibers, such as skin, hair or scalp, particularly anti-hair loss treatment.

[0003] EARLIER ART

[0004] [2] Within the topic of scalp health, hair loss is a cosmetic issue with multifactorial etiology. Hair loss can occur due to hair breakage, telogen effluvium or temporary hair loss, diffuse alopecia, and even androgenic alopecia.

[0005] [3] Hair loss due to hair breakage is non-pathological and occurs due to external damage to the hair. It usually results from continuous and / or acute physical and / or chemical aggressions that cause substantial mass loss in areas of the cortex and cuticle. The damage generated creates areas of greater fragility to breakage, and thus, with the slightest physical stress, hair breakage is observed in any region along the length of the hair fiber. This condition can be easily recognized by phenomenological observation, in which hair loss resulting from breakage is observed when hands or tools that facilitate detangling and combing pass over it. Diffuse alopecia, also known as diffuse baldness, refers to hair loss of unnatural and cyclical origin and affects both the hair and the scalp.And finally, androgenic alopecia, also called permanent baldness, also refers to unnatural hair loss, but it is not cyclical and affects both the hair and the scalp.

[0006] [4] The classic mechanisms associated with diffuse hair loss have hormonal and inflammatory bases. It is known that the increase in the protein STAT3 and the inflammatory cytokine IL6 reduces the anagen phase, slowing hair growth, which becomes slower. The increase in the hormone DHT miniaturizes the follicle, causing hair thinning. And the increase in the cytokines IL1B, IL6, and IL8 worsens follicle anchoring, reducing blood flow, causing follicular microinflammation, and accelerating hair loss.

[0007] [5] In the case of scalp skin and the impact on the follicle, it is known that high inflammation leads to damage to the dermis where the hair follicles are anchored, degrading the collagen matrix that anchors the follicle and, in a more acute situation, worsening hair loss, affecting the anagen phase and hair growth.

[0008] [6] There are many active ingredients and cosmetic formulations available that suggest direct or indirect action on hair loss. However, there is still a need for new ingredients and formulations capable of targeting all aspects of hair loss.

[0009] [7] Thus, there remains a need for active ingredients with anti-hair loss action, particularly for topical application, which offer proven comprehensive treatment with anti-hair loss action and hair growth, particularly promoting healthy growth, with strong hair and no hair loss.

[0010] BRIEF DESCRIPTION OF THE FIGURES

[0011] [8] Figure 1 illustrates in vivo results, over 150 days, of combating hair loss and improving hair density and thickness after using the anti-hair loss lotion of the present invention.

[0012] [9] Figure 2 shows the heatmap with results on the STAT3, DHT and IL1 b markers of the recombinant silk protein active ingredient and combinations of active ingredients at different concentrations.

[0013]

[0010] Figures 3A and 3B represent comparative results of % hair elongation, in an ex-vivo follicle model, between a market active ingredient and the anti-hair loss cosmetic active ingredient complex of the invention.

[0014] DESCRIPTION OF THE INVENTION

[0015]

[0011] In a first aspect, the present invention relates to an anti-hair loss cosmetic complex comprising the combination of the active ingredients (a) recombinant silk protein, (b) xylitol phosphate ester and (c) caffeine.

[0016]

[0012] The present invention also relates to a cosmetic composition for treating keratin fibers comprising said anti-hair loss cosmetic complex, together with cosmetically acceptable excipients.

[0017]

[0013] Keratin fibers mean skin, hair and / or scalp, particularly hair.

[0018]

[0014] A healthy scalp has certain characteristics such as hair without hair loss, natural hair growth cycle (on average 1 cm every 28 days), absence of signs of inflammation, regular microcirculation of the scalp feeding the hair follicle.

[0019]

[0015] On the other hand, a diseased scalp presents temporary hair loss, with thinning of the strands and reduction in hair density that increases hair loss, an excessive inflammatory process and impaired microcirculation.

[0020]

[0016] It is known that biological factors have an effect on the growth, strength, density and porosity in the quality and integrity of the hairs produced by the hair follicle in the scalp.

[0021]

[0017] Hair growth: inhibition of STAT3 synthesis prolongs the existing anagen phase and accelerates re-entry into the anagen phase after completion of the hair cycle.

[0022]

[0018] Follicle miniaturization: inhibition of DHT synthesis inhibits hair thinning and follicle miniaturization, reducing hair loss (reduction in hair loss).

[0023]

[0019] Reduction of inflammation: inhibition of IL1 b synthesis reduces stimuli triggered by the inflammatory process, such as degradation of the extracellular matrix that affects follicle anchoring and local microcirculation.

[0024]

[0020] Additionally, it is worth noting that in the skin, particularly scalp skin, there are several types of growth factors produced by keratinocytes in the epidermis, fibroblasts in the dermis, by endothelial cells in the inner lining of blood vessels, by platelets and by cells of the immune system.

[0025]

[0021] The invention's anti-hair loss cosmetic complex surprisingly promotes a synergistic effect in controlling biological markers related to hair health. Thus, the invention's anti-hair loss cosmetic complex enables anti-hair loss treatment due to the combined action of specific active ingredients on biological markers related to the hair loss process, considering the biological pathways related to growth, hair loss, inflammation reduction, and microcirculation. Thus, the main markers tested are STAT3, DHT, and IL1b.

[0026]

[0022] The cosmetic complex comprising the combination of the active ingredients (a) recombinant silk protein, (b) xylitol phosphate ester and (c) caffeine presents anti-hair loss activity with proven efficacy in vitro.

[0027]

[0023] In particular, the anti-hair loss cosmetic complex of the present invention acts in at least the following ways:

[0028] - Prolongs hair growth by keeping the anagen phase active;

[0029] - Inhibits hair thinning by reducing DHT while maintaining the hair's natural thickness; and

[0030] - Reduces inflammation by improving anchoring and microcirculation.

[0031]

[0024] In particular, the recombinant silk protein is used in a concentration of 0.001 to 0.5%, particularly approximately 0.33%, relative to the total weight of the composition.

[0032]

[0025] According to one embodiment, the recombinant silk protein may be the recombinant ADF-4 protein which is known by the name Silkgel®.

[0033]

[0026] In particular, the xylitol phosphate ester is used in a concentration of 1 to 4%, particularly around 3%, relative to the total weight of the composition.

[0034]

[0027] According to the present invention, the xylitol phosphate ester used may be the ingredient Hygeaphos®, obtained from the supplier Chemyunion.

[0028] In particular, caffeine is used in a concentration of 0.2 to 1%, particularly about 0.5%, relative to the total weight of the composition.

[0035]

[0029] According to the present invention, caffeine can be obtained from the supplier Brenntag.

[0036]

[0030] The cosmetic compositions according to the present invention may be in the form of emulsions, solutions, gels, powders, pastes, elixirs, among others, also comprising cosmetically appropriate vehicles for the chosen cosmetic form.

[0037]

[0031] The cosmetic compositions according to the present invention are intended for topical application.

[0038]

[0032] Surprisingly, it was found that the anti-hair loss effect provided by the cosmetic complex according to the present invention is not only efficient in reducing hair loss but also improves the density and thickness of the strands.

[0039]

[0033] Due to the other effects found, the topical cosmetic compositions according to the present invention can be used as cleansing and / or moisturizing products with skin-friendly formulas.

[0040]

[0034] The topical anti-hair loss cosmetic compositions according to the present invention may be made available in any cosmetic forms known to the person skilled in the art, suitable for application to the face, body, hair or scalp, for treatment or cleaning, including, without limitation, soaps, shampoos, elixirs, conditioners, sticks, tonics and lotions, among other forms.

[0041]

[0035] Cosmetically acceptable excipients may be selected from compounds known in the prior art. Without limitation, the excipients may be selected from the group comprising emollients, antioxidants, humectants, emulsifiers, surfactants, sensory or viscosity modifiers, preservatives, chelators, stabilizers, lubricants, thickeners, dispersants, solubilizers and their combinations, among other cosmetically acceptable vehicles.

[0036] The present invention also contemplates the use of the anti-hair loss cosmetic complex for the preparation of a cosmetic composition for the treatment of keratinic fibers, such as skin, hair or scalp, particularly anti-hair loss treatment.

[0042]

[0037] An additional aspect of the present invention is a method of cosmetic treatment of keratin fibers which consists of applying to the skin, hair and / or scalp the anti-hair loss cosmetic complex or the anti-hair loss cosmetic composition of the present invention.

[0043]

[0038] The following examples, without imposing any limitation, illustrate the present invention.

[0044] EXAMPLE - Formulations

[0045]

[0039] Below is an example of an anti-hair loss lotion composition (anti-hair loss night treatment elixir) useful in accordance with the present invention:

[0046] Table 1 - Anti-hair loss lotion

[0047]

[0040] Below is an example of an anti-hair loss shampoo composition useful in accordance with the present invention:

[0048] Table 2 - Anti-hair loss shampoo

[0049] EXAMPLE 2 - Anti-hair loss treatment evaluation

[0050]

[0041] To assess the cosmetic effect attributed to the research objective of this descriptive study, a methodology was applied to evaluate the effectiveness of the products in stimulating new hair growth after 30, 60, 90, and 150 days of treatment with the experimental product. Forty research subjects who used the experimental product for up to 150 days were considered. The average age of the subjects was 37 ± 12 years. After recruitment, the subjects were instructed to discontinue use of any cosmetic product on their hair and scalp 48 hours before the start of the study. On the day of the study, the recruited subjects who came to the laboratory received clarification from the researcher regarding the study procedures, ethical and legal aspects, risks and benefits, medical support, and forms of reimbursement for participation costs. The subjects were also asked to sign two copies of the Informed Consent Form.Hair growth kinetics and density were assessed by obtaining scalp microimages using a microcamera (i-Scope USB, Moritex, JP) with a 30x objective and polarized light at baseline and after 30, 60, 90, and 150 days of treatment. Laser Doppler ultrasound was used to assess improvements in blood microcirculation at baseline and after 30, 60, 90, and 150 days of home use of the experimental product.

[0051]

[0042] The method used to evaluate the scalp microbiota was metagenomics, which consists of analyzing fragments of the genome of microorganisms, where a preserved region is evaluated, in bacteria called 16S rRNA and in fungi ITS as a universal marker. It is used in phylogenetic reconstruction to define its taxa, thus allowing the identification of each population in a given community with the aid of the lonChef System and Ion S5 following the NGS (Next-Generation Sequencing) protocols. The samples came from a swab rubbed on the scalp of individuals who used the product and were analyzed at baseline and after 30, 60, 90, and 150 days of treatment.

[0052] Results

[0053]

[0043] The application of the composition of the present invention provides a double-action treatment, combating breakage and stimulating hair growth, as shown in the results illustrated in Figure 1 and summarized in the Table below:

[0054] Table 3 - Clinical efficacy results versus baseline time

[0055]

[0044] Therefore, based on the results, it can be seen that treatment with the anti-hair loss lotion of the present invention combats hair loss, improves hair density and contributes to improving the nutritional supply of the follicular units of the scalp.

[0056] EXAMPLE 3 - Variation in marker concentration

[0057]

[0045] The preclinical efficacy of the evaluated products in the synthesis of STAT3 in cultured human fibroblasts and keratinocytes was evaluated. Human fibroblasts and keratinocytes were incubated with 3 non-cytotoxic concentrations of the evaluated products for subsequent quantification of STAT3. The cell cultures were incubated with the evaluated products for 48 hours, as shown in Table 4. After this period, the lysates were collected for quantification of STAT3.

[0058] Table 4

[0059]

[0046] STAT3 quantification was performed on cell culture lysate by enzyme-linked immunosorbent assay (ELISA) using a commercially available kit (Rheabiotech, Campinas, SP, Brazil). Absorbance was read on a Multiskan GO monochromator (Thermo Fisher Scientific).

[0060]

[0047] For the statistical evaluation, the ANOVA test was used to measure the variation in results, comparing the data between the groups. Then, the Bonferroni post-test was applied, which strengthened and made the result presented in the ANOVA more accurate. The significance level was 5% (GraphPad Prism v6).

[0061]

[0048] Figure 2A represents the effect of the evaluated products on STAT3 production in human fibroblasts. The evaluated products 7306PT, COMBINATION 1 and COMBINATION 2 demonstrated a decrease of 28.48%, 31.18% and 50.12% in STAT3 production, compared to the basal control, respectively, (P<0.01; P<0.001).

[0049] Figure 2B represents the effect of the evaluated products on STAT3 production in human keratinocytes. The evaluated products 7306PT, COMBINATION 1 and COMBINATION 2 demonstrated a decrease of 38.00%, 47.99% and 56.03% in STAT3 production, compared to the basal control, respectively, (P<0.01; P<0.001).

[0062]

[0050] According to the results presented, it was possible to conclude that the evaluated recombinant protein products (this one and another active) COMBINATION 1 and COMBINATION 2 promoted a decrease in the synthesis of STAT3.

[0063] EXAMPLE 4 - Variation in marker concentration

[0064]

[0051] It is known that recombinant silk protein is capable of acting alone in reducing the STAT3 marker, which is responsible for prolonging the anagen (growth) phase. The present invention surprisingly enables an improvement in the reduction of the STAT3 marker, in addition to adding other desired effects. FIG. 2 shows the results of the concentration of the STAT3, DHT, and IL1b markers. In this sense, it is observed that the desired effect is the reduction of the STAT3, DHT, and IL1b markers, and the redder the color, the better the result.

[0065]

[0052] The concentrations of the ingredients are represented in the table below. They deal with concentrations used to compare in vitro results and understand whether we have a dose versus response effect on the total weight of the composition.

[0066] Table 5 - Percentage

[0067]

[0053] The results are also shown in the table below (Table 6) and demonstrate the results considering the active ingredient, recombinant silk protein, alone versus the anti-hair loss cosmetic complex of the invention (Pro-web + Caffeine + Hygeaphos), for the main hair loss markers, showing that the combination of active ingredients has a greater (synergistic) result in relation to the recombinant silk protein ingredient alone.

[0068]

[0054] The table below contains the raw data used to construct the heatmap of FIG. 2, so the same conclusions are drawn. The markers are expressed as an average protein value (ug / mg).

[0069] Table 6

[0070]

[0071] EXAMPLE 5 - Comparative growth assessment

[0072]

[0055] A growth evaluation in an ex-vivo follicle model of the invention's anti-hair loss blend versus a market active (Redensyl) was performed.

[0073]

[0056] The results are shown in the graphs represented by FIG. 3A and FIG. 3B, where it is demonstrated that the treatment with a market product Redensyl showed no difference when compared to the basal control (= culture medium), while the treatment with the anti-hair loss cosmetic complex blend of the invention (Pro-web + Caffeine + Hygeaphos) showed growth of + 5pp.

[0074] EXAMPLE 6 - Evaluation of hair growth in a preclinical hair follicle model (this is the same as before)

[0075]

[0057] To evaluate hair growth, the following experiment was conducted:

[0076]

[0058] To perform the Ex Vivo follicle culture and evaluate growth, the growth cycle stage of each batch of follicles (e.g. anagen, catagen or telogen) was first identified by image analysis, evaluating the follicles under a magnifying glass (inside the clean room) in a bright field.

[0077]

[0059] Culture medium data:

[0078] - William E medium or medium (RPMI + 10% DMEM)

[0079] - L-Glutamine 2 mM.

[0080] - Antibiotics 1% mixture of penilicin and streptomycin.

[0081] - The culture medium must be kept in a refrigerator at +4°C and transportation must be carried out at a similar temperature.

[0082]

[0060] Each culture batch consists of 5 follicles, in general, which are placed in the apparatus in the following positions:

[0083] - Positions 1 and 2: follicles stimulated only with culture medium

[0084] - Positions 1, 2 and 3: follicles stimulated with the active ingredient every 2 days for a period of 10 days.

[0061] Images of the follicles were captured using a magnifying glass: a) on day zero (after 24 hours of incubation with culture medium) and b) on day 10.

[0085]

[0062] The images were analyzed to obtain measurements of follicle length over a period of 10 days, comparing the growth of follicles incubated in culture medium and follicles incubated with culture medium.

[0086]

[0063] Table 7 below contains a summary of the test, with a description of the days of stimulation with culture medium and with the active ingredient under investigation, and image capture to assess hair growth in ex-vivo culture:

[0087] Table 7

[0088]

[0064] The measured length values ​​(mm or pm) were compared to understand the growth profile of each follicle batch.

[0089]

[0065] The person skilled in the art will readily know how to evaluate, through the teachings contained in the text and in the examples presented, the advantages of the invention and propose variations and equivalent alternatives for implementation, without departing from the scope of the invention, as defined in the attached claims.

Claims

CLAIMS 1. ANTI-HAIR LOSS COSMETIC COMPLEX, characterized by comprising the combination of the active ingredients (a) recombinant silk protein, (b) xylitol phosphate ester and (c) caffeine.

2. COSMETIC COMPLEX, according to claim 1, characterized by comprising: (a) from 0.001 to 0.5% recombinant silk protein; (b) from 1 to 4% xylitol phosphate ester; and (b) from 0.2 to 1% caffeine, all percentages in relation to the total weight of the cosmetic composition.

3. COSMETIC COMPLEX, according to claim 2, characterized by comprising: (a) 0.33% recombinant silk protein; (b) 3% xylitol phosphate ester; and (b) 0.5% caffeine, all percentages in relation to the total weight of the cosmetic composition.

4. COSMETIC COMPOSITION, characterized by comprising the prebiotic cosmetic complex defined in any one of claims 1 to 3 together with cosmetically acceptable excipients.

5. USE OF THE ANTI-HAIR LOSS COSMETIC COMPLEX, as defined in any one of claims 1 to 3, characterized in that it is in the preparation of a cosmetic composition.

6. METHOD FOR COSMETIC TREATMENT, characterized by consisting of applying to the skin, hair and / or scalp a complex as defined in any one of claims 1 to 3.

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