Oral composition useful for skin depigmentation

Abstract

The present invention relates to a nutraceutical composition for oral administration comprising a Glycyrrhiza glabra L. extract and an Olea europaea L. extract. Said formulation is suitable for use as a skin depigmenting and bleaching agent and to control skin protein glycation.

Description

[0001] ORAL COMPOSITION USEFUL FOR SKIN DEPIGMENTATION

[0002] FIELD OF INVENTION

[0003] The present invention relates to an oral composition based on plant extracts suitable for skin depigmentation. In particular, the subject of the invention is an oral composition comprising a Glycyrrhiza glabra L. extract and an Olea europaea L. extract, and the use thereof to bleach dark skin patches.

[0004] BACKGROUND TO THE INVENTION

[0005] Hyperpigmentation means darkening of the skin, generally caused by abnormal production of a large amount of melanin.

[0006] During exposure to sunlight, specialised skin cells called melanocytes produce larger amounts of melanin. In some individuals, especially those with pale skin, certain types of melanocytes produce more melanin than others in response to sunlight. This irregular production leads to the appearance of dark patches on the skin. Other factors in addition to sunlight, such as aging and inflammation, can cause increased melanin at some localised points or on widespread areas of the skin.

[0007] Liquorice is one of the medicinal plants most widely used in foods and herbal medicine. The therapeutic potential of liquorice is already known in the treatment of various disorders, including lung disease, heart disease, gastric ulcers, hypotension and some microbial infections. Liquorice extract contains numerous active biological compounds which have been isolated, in particular, from Glycyrrhiza glabra L. species, wherein triterpene saponins and flavonoids are the main constituents that exhibit extensive biological activity (Mamedov NA, Egamberdieva D. Phytochemical Constituents and Pharmacological Effects of Licorice: A Review. Plant and Human Health, Volume 3. 2019 Feb 12: 1-21. doi: 10.1007 / 978-3-030-04408-4_l. PMCID: PMC7123875).

[0008] Due to the presence of bioactive compounds such as glycyrrhizin, glabridin and liquiritin, liquorice extract possesses bleaching and depigmenting properties that make it a useful nutraceutical ingredient to reduce dark skin patches at topical level (Searle T, Al-Niaimi F, Ali FR. The top 10 cosmeceuticals for facial hyperpigmentation. Dermatol Ther. 2020;33(6):el4095. doi: 10.1111 / dth.14095).

[0009] The bioactive compounds present in the extract seem able to inhibit the enzyme tyrosinase, which is responsible for melanin production in the skin and the appearance of dark patches or hyperpigmentation patches (Searle T, Al-Niaimi F, Ali FR. The top 10 cosmeceuticals for facial hyperpigmentation. Dermatol Ther. 2020;33(6):el4095. doiilO.l 111 / dth.14095).

[0010] Another plant known in the therapeutic, nutraceutical and cosmetic field is the olive, and derivatives thereof. Olive extract, deriving from the plant Olea europaea L., contains large amounts of hydroxytyrosol, known for its antioxidant properties. Moreover, due to its bioavailability and biochemical properties, hydroxytyrosol is useful for application in dietary supplements. Hydroxytyrosol also improves endothelial dysfunction and possesses neuro- and cardioprotective properties.

[0011] Like liquorice, hydroxytyrosol inhibits tyrosinase by counteracting melanin production, and therefore the appearance of dark patches on the skin, when applied topically (Bagatin, Julia & Ma, Patricia & Bagatin, Edileia. (2020). A pilot clinical study to evaluate the effectiveness of olive extract containing hydroxytyrosol for oral and topical treatment of melasma. Biomedical and Biopharmaceutical Research Journal. 17. 1-15. 10.19277 / bbr.l7.1.227).

[0012] The problem of finding new supplements for skin hyperpigmentation or skin bleaching treatment, in particular dietary supplements for oral administration suitable for treating the skin and dark skin patches with the aim of lightening them, still exists today.

[0013] STATE OF THE ART

[0014] Indian patent application IN02688MU2013A discloses an edible cosmetic composition and its manufacturing process. Said composition is useful as a moisturising, emollient, soothing, skin bleaching, antiacne, anti-aging and antioxidant agent. It can include liquorice as optional active bleaching substance, and olive oil as emollient.

[0015] Chinese patent application CN107095282A discloses a formulation useful for skin bleaching and inhibiting hair loss, which contains the fungus Ganoderma lucidum as active substance and a list of other edible compounds, including olive oil and liquorice powder.

[0016] SUMMARY OF THE INVENTION

[0017] The subject of the present application is an oral composition comprising a Glycyrrhiza glabra L. extract and an Olea europaea L. extract.

[0018] A further subject of the present application is the use of the composition according to the invention to promote attenuation or elimination of skin blemishes caused by skin hyperpigmentation and skin protein glycation.

[0019] DESCRIPTION OF THE INVENTION

[0020] The authors of the present invention have surprisingly found that the combination of liquorice and olive extracts has a synergistic bleaching effect on dark skin patches and the skin in general, even if administered as dietary supplements rather than by topical administration to the skin. Moreover, the composition of extracts has also been found to reduce AGEs (advanced glycation end-products), known to be precursors of free radicals, for example due to the effect of UV radiation on the skin.

[0021] The subject of the present invention is therefore an oral composition comprising a Glycyrrhiza glabra L. extract and an Olea europaea L. extract.

[0022] In a preferred embodiment, the composition comprises the following, independently of one another: a. an aqueous extract of Glycyrrhiza glabra L. roof optionally dried; b. an aqueous extract of leaves and / or fruit and / or a filtrate of vegetation water of Olea europaea L., optionally dried, having a hydroxytyrosol content of at least 4% by weight.

[0023] “Aqueous extract” here means that the extraction solvent used to produce the specific extract is water.

[0024] The liquorice extract is obtained from the root of Glycyrrhiza glabra L. by extraction with water followed by evaporation of the solvent and subsequent grinding. In one embodiment, the Olea europaea L. extract derives from the vegetation water generated by olive processing during the olive-oil manufacturing process. Said extract is then obtained by a process of filtration and foam-drying and / or drying.

[0025] Vegetation water (VW) here means the waste water produced by olive presses, mainly consisting of olive washing water and process water, together with the aqueous fraction of the fruit juices. It thus has the further advantage of exploiting a by-product of the production process which would otherwise be wasted.

[0026] In other embodiments, the Olea europaea L. leaf and / or fruit extract is obtained by extraction in water of Olea europaea L. leaves and / or fruit, using infusion and subsequent filtration and drying processes or advanced extraction technologies, such as a Naviglio extractor.

[0027] In a preferred embodiment, the Olea europaea L. extract used in the composition according to the invention has a hydroxytyrosol content ranging between 4 and 9% by weight. In a further preferred embodiment, the composition also comprises maltodextrins and / or gum arabic, acting as excipients, which are generally added to the Olea europaea L. extract Maltodextrin can be used as carrier, while gum arabic can be useful as a thickener.

[0028] In a particularly preferred embodiment, the composition according to the invention comprises 70 to 90% of Glycyrrhiza glabra L. extract and 10 to 30% of Olea europaea L. extract, expressed as percentages of the total weight of the composition.

[0029] In a particularly preferred embodiment, the Glycyrrhiza glabra L. extract and the Olea europaea L. extract are the only biologically or nutraceutically active ingredients present in the composition according to the invention (ie. excluding inert additives and excipients).

[0030] In one aspect of the invention, the composition can be used in a form suitable for oral administration selected from capsules, tablets, effervescent tablets, powders, granulates, sticks, effervescent sticks and single-dose vials of liquids and syrups, preferably capsules or modified- release capsules.

[0031] In one embodiment, the composition according to the invention comprises one or more pharmaceutically acceptable excipients.

[0032] Said excipients are preferably selected from diluents, dispersing agents, thickeners, glidants, dissolution promoters, flavour modifiers and sweeteners.

[0033] Capsules are the preferred form of administration, and can contain hydroxypropyl methylcellulose (HPMC), hydroxypropyl methylcellulose and gellan gum, gelatin, plant polysaccharides and optionally plasticisers, such as glycerin and sorbitol, colourings, disintegrating agents and lubricants.

[0034] Examples of filling agents include maltodextrin, corn starch, pre-gelatinised corn starch, microcrystalline cellulose, calcium carbonate, gum arabic, FOS, inulin and GOS, preferably maltodextrin.

[0035] Examples of anti-caking agents include silicon dioxide, acid sodium aluminium phosphate, calcium silicate, magnesium silicate, talc, sodium aluminium silicate and potassium aluminium silicate.

[0036] Examples of glidants include magnesium stearate, crosslinked sodium carboxymethylcellulose, crosslinked cellulose gum, enzymatically hydrolysed carboxymethylcellulose, enzymatically hydrolysed cellulose gum, fatty acid sodium, potassium and calcium salts, fatty acid magnesium salts and fatty acid diglycerides, acetic acid esters of mono- and diglycerides of fatty acids; lactic acid esters of mono- and diglycerides of fatty acids, citric acid esters of mono- and diglycerides of fatty acids, tartaric acid esters of mono- and diglycerides of fatty acids, mono- and diacetyl tartaric acid esters of mono- and diglycerides of fatty acids; mixed acetic and tartaric acid esters of mono- and diglycerides of fatty acids, sucroglycerides, polyglycerol fatty acid esters, poly glycerol polyricinoleate, propane- 1,2-diol esters of fatty acids, sodium stearoyl-2-lactylate, calcium stearoyl-2-lactylate, stearyl tartrate, sorbitan monostearate, sorbitan tristearate, sorbitan monolaurate, sorbitan monooleate and sorbitan monopalmitate, preferably magnesium stearate.

[0037] In a particularly preferred embodiment, the composition according to the invention takes the form of a capsule comprising the following doses:

[0038] A further subject of the present invention is the use of the composition according to the invention to promote attenuation or elimination of skin blemishes due to skin hyperpigmentation. The composition according to the invention has also been found to reduce AGEs (advanced glycation end products), also called glycotoxins. AGEs originate from the reaction between glucose and proteins, and their formation is due to both an endogenous process (cell aging) and exogenous factors such as diet; they are also precursors of free radicals formed due to the effect of UV radiation on the skin.

[0039] The nutraceutical composition can be taken by the patient at least once a day, for example one, two or more capsules a day, on the basis of various factors such as the patient’s weight and age, any concomitant treatments with other supplements or medicaments, the extent of the skin blemish to be treated, the patient’s response to the treatment, the patient’s intolerance of the active ingredients, and other factors.

[0040] The present invention is illustrated in detail in the examples below.

[0041] EXAMPLES

[0042] Compound extraction processes

[0043] The Glycyrrhiza glabra L. extract was obtained by the following sequential steps: Extraction from Glycyrrhiza glabra L. roots with water as solvent

[0044] - Evaporation of solvent by drying

[0045] Grinding

[0046] Obtaining desired end product in powder form.

[0047] The Olea europaea L. extract was obtained by the olive-oil manufacturing process. After the olives have been pressed and oil is extracted, the vegetation water is recovered and undergoes the following steps:

[0048] Filtration

[0049] Concentration of filtrate to obtain a liquid product

[0050] Foam-drying

[0051] Obtaining desired end product in powder form. Dosage examples for alternative formulations

[0052] Stick in powder form

[0053] 30 ml vial

[0054] Tablets

[0055] Clinical trial

[0056] The synergy of the two extracts was tested in a double-blind placebo-controlled clinical trial to establish their skin-bleaching efficacy, in particular in reducing dark patches. 60 healthy volunteers of different ethnic origins (Caucasian, Chinese and Asian with phototype IV- V) and different sexes, with ages ranging between 25 and 65 years, were recruited to the trial; all participants had dark skin patches caused by aging, sun exposure or post-inflammatory hyperpigmentation. 30 of the volunteers took the active product, and 30 took the placebo. The total duration of the study was 56 days, and the volunteers were examined at the start of treatment (TO), after 28 days (T28) and at the end of treatment (T56). Both products (active and placebo) were taken in capsule form (1 capsule a day with a glass of still water) throughout the duration of the treatment.

[0057] The following parameters were evaluated to establish the efficacy of the combination of liquorice and olive extracts: the intensity of the pigmentation of the patches, expressed as ITA° (Individual Typology Angle) value, and the area of the dark patch, expressed as a percentage. AGE formation was also evaluated as a parameter indicative of skin aging.

[0058] On the whole, in the active ingredient group a statistically significant increase was recorded for the ITA° value parameter, corresponding to lighter skin, amounting to 11.8% at T28 and 18.9% at T56, whereas the group treated with the placebo only exhibited an increase of 8.1% at T56. As regards the area of the dark skin patches, a statistically significant reduction in patch area, amounting to 4.18% at T28 and 8.45% at T56, was only observed for the group treated with the active product; said reduction also proved statistically significant in the intergroup analysis in favour of the active product group at T56.

[0059] Finally, a statistically significant reduction in AGE formation was observed, amounting to 10.6% after 56 days’ treatment with the active product. Said variation also proved significant in the inter-group analysis.

[0060] These results demonstrate the efficacy of the combination of the two extracts in question in reducing dark skin patches and consequently improving the uniformity and glow of the complexion. The extracts used also exhibited significant efficacy in counteracting skin aging, thus demonstrating that they possess anti-aging efficacy.

Claims

CLAIMS1. Nutraceutical composition comprising an extract of Glycyrrhiza glabra L. and an extract of Olea europaea L. as the sole biologically or nutraceutically-active ingredients present in the composition.

2. Composition according to claim 1 comprising, independently of each other: a. an aqueous extract of Glycyrrhiza glabra L. root, optionally dried; b. an aqueous extract of leaves and / or fruit and / or a filtrate of vegetation water of Olea europaea L., optionally dried, having a hydroxytyrosol content of at least 4% by weight.

3. Composition according to claims 1 and 2 wherein the Olea europaea L. extract has a hydroxytyrosol content ranging between 4 and 9% by weight.

4. Composition according to claims 1-3, further comprising maltodextrins and / or gum arabic.

5. Composition according to claims 1-4 comprising 70 to 90% of Glycyrrhiza glabra L. extract and 10 to 30% of Olea europaea L. extract, expressed as percentages of the total weight of the composition.

6. Composition according to claims 1-5, wherein said composition is in the form of capsules, tablets, effervescent tablets, powders, granulates, sticks, effervescent sticks, single-dose liquid vials and syrups, preferably in the form of capsules or modified-release capsules.

7. Composition according to claims 1-6 comprising one or more nutraceutically acceptable excipients.

8. Composition according to claim 7 wherein said excipients are selected from diluents, dispersing agents, thickeners, glidants, dissolution promoters, flavour modifiers and sweeteners.

9. Use of the composition according to claims 1-8 to promote the attenuation or elimination of blemishes due to skin hyperpigmentation or glycation of skin proteins.

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