Oral composition for skin depigmentation

Abstract

The present invention relates to a nutritional and health care composition for oral administration, comprising an extract of Glycyrrhiza glabra L. and an extract of Olea eupaea L.. The nutritional and health care composition is characterized in that the nutritional and health care composition comprises an extract of Glycyrrhiza glabra L. and an extract of Olea eupaea L.. The formulations are suitable for use as skin decolorizing and bleaching agents and for controlling skin protein saccharification.

Description

Invention Field

[0001] This invention relates to an oral composition based on plant extracts suitable for skin depigmentation. Specifically, the subject of this invention is an oral composition comprising extracts of licorice root (Glycyrrhiza glabra L.) and olive (Oleaeuropaea L.) and its use for bleaching dark spots on the skin. Background of the Invention

[0003] Hyperpigmentation refers to darkening of the skin, usually caused by the abnormal production of excessive melanin. Under sunlight, specialized skin cells called melanocytes produce more melanin. In some individuals, especially those with lighter skin tones, certain types of melanocytes produce more melanin than other cells under sunlight. This irregular melanin production leads to dark spots on the skin. Besides sunlight exposure, other factors such as aging and inflammation can also cause increased melanin production in localized or large areas of the skin.

[0004] Licorice is one of the most widely used medicinal plants in food and herbal medicine. It is known to have therapeutic potential in treating a variety of diseases, including lung diseases, heart diseases, gastric ulcers, hypotension, and some microbial infections. Licorice extract contains a variety of bioactive compounds that have been isolated, particularly from the genus *Glycyrrhiza glabra*, among which triterpenoid saponins and flavonoids are the main components exhibiting broad biological activity (Mamedov NA, Egamberdieva D. Phytochemical Constituents and Pharmacological Effects of Licorice: A Review. Plant and Human Health, Vol. 3. Feb. 12, 2019: 1–21. doi: 10.1007 / 978-3-030-04408-4_1. PMCID: PMC7123875).

[0005] Licorice extract possesses bleaching and decolorizing properties due to the presence of bioactive compounds such as glycyrrhizic acid, glycyrrhizin, and liquiritin, making it a potential nutritional supplement for reducing dark spots on the skin at a localized level (Searle T, Al-Niaimi F, Ali FR. The top 10 cosmeceuticals for facial hyperpigmentation. Dermatol Ther. 2020;33(6):e14095. doi:10.1111 / dth.14095).

[0006] The bioactive compounds present in the extract appear to inhibit tyrosinase, which is responsible for the production of melanin in the skin and the appearance of dark spots or pigmentation (Searle T, Al-Niaimi F, Ali FR. The top 10 cosmeceuticals for facial hyperpigmentation. Dermatol Ther. 2020;33(6):e14095. doi:10.1111 / dth.14095).

[0007] Another plant known in the fields of therapeutics, nutritional supplements, and cosmetics is the olive and its derivatives. Olive extracts derived from the European olive (Olea europaea L.) contain high levels of hydroxytyrosol, which is known to have antioxidant properties. Furthermore, due to its bioavailability and biochemical properties, hydroxytyrosol can be used in dietary supplements. Hydroxytyrosol can also improve endothelial dysfunction and has neuroprotective and cardioprotective properties.

[0008] Similar to licorice, when applied topically, hydroxytyrosol combats melanin production by inhibiting tyrosinase, thus reducing the appearance of dark spots on the skin (Bagatin, Julia & Ma, Patrícia & Bagatin, Ediléia. (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.17.1.227).

[0009] The following issues remain: the search for new supplements for the treatment of hyperpigmentation or skin bleaching, especially oral dietary supplements suitable for treating skin and dark spots to achieve whitening.

[0010] Current state of technology

[0011] Indian patent application IN02688MU2013A discloses an edible cosmetic composition and a method for manufacturing the same. The composition can be used as a moisturizer, emollient, soothing agent, skin whitening agent, anti-acne agent, anti-aging agent, and antioxidant. It may contain licorice as an optional active whitening ingredient and olive oil as an emollient.

[0012] Chinese patent application CN107095282A discloses a formulation that can be used for skin bleaching and hair loss inhibition. The formulation contains the fungus Ganoderma lucidum as an active ingredient, as well as other edible compounds, including olive oil and licorice powder. Invention Overview

[0014] The subject of this application is an oral composition comprising extracts of licorice root (Glycyrrhiza glabra L.) and European olive (Olea europaea L.).

[0015] Another subject of this application is the use of the compositions according to the invention for promoting the reduction or elimination of skin blemishes caused by hyperpigmentation and glycation of skin proteins.

[0016] Invention Description

[0017] The authors of this invention unexpectedly discovered that the combination of licorice and olive extracts has a synergistic whitening effect on skin dark spots and overall skin, even when applied to the skin as a dietary supplement rather than topically. Furthermore, it has been found that the composition of the extracts reduces AGEs (advanced glycation end products), which are known precursors of free radicals (e.g., due to the effects of UV radiation on the skin).

[0018] Therefore, the subject of this invention is an oral composition comprising extracts of licorice root (Glycyrrhiza glabra L.) and European olive (Olea europaea L.).

[0019] In a preferred embodiment, the composition comprises the following components, which are independent of each other:

[0020] a. Aqueous extract of Glycyrrhiza glabra L. root, optionally dried;

[0021] b. Aqueous extracts and / or filtrates of leaves and / or fruits of the European olive (Olea europaea L.), optionally dried, having a content of at least 4% by weight of hydroxytyrosol.

[0022] In this article, "water extract" refers to an extract in which water is used as the extraction solvent to prepare a specific extract.

[0023] Licorice extract is obtained from the roots of *Glycyrrhiza glabra* L. by water extraction, followed by solvent evaporation and subsequent grinding. In one embodiment, European olive (*Olea europaea* L.) extract is derived from plant water produced during olive processing in olive oil manufacturing. The extract is then obtained through filtration and foam drying and / or drying processes.

[0024] In this paper, plant water (VW) refers to the wastewater generated from olive pressing, mainly composed of olive washing water, processing water, and the aqueous portion of the juice. Therefore, it also has the added advantage of utilizing byproducts that would otherwise be wasted during the production process.

[0025] In other embodiments, the extract of European olive (Olea europaea L.) leaves and / or fruits is obtained as follows: by extracting European olive (Olea europaea L.) leaves and / or fruits in water using an immersion and subsequent filtration and drying process, or using advanced extraction technologies such as the Naviglio extractor.

[0026] In a preferred embodiment, the European olive (Olea europaea L.) extract used in the composition according to the invention has a hydroxytyrosol content of 4% to 9% by weight. In a further preferred embodiment, the composition also comprises maltodextrin and / or gum arabic as excipients, which are typically added to the European olive (Olea europaea L.) extract. Maltodextrin can be used as a carrier, while gum arabic can be used as a thickener.

[0027] 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 a percentage of the total weight of the composition.

[0028] In a particularly preferred embodiment, licorice root extract (Glycyrrhiza glabra L.) and European olive extract (Olea europaea L.) are the only biologically active or nutritionally active components present in the compositions of the present invention (i.e., excluding inert additives and excipients).

[0029] In one aspect of the invention, the composition can be in a form suitable for oral administration, the form being selected from capsules, tablets, effervescent tablets, powders, granules, sticks, effervescent sticks, single-dose liquid vials and syrups, preferably capsules or sustained-release capsules.

[0030] In one embodiment, the composition of the present invention comprises one or more pharmaceutically acceptable excipients.

[0031] The excipients are preferably selected from diluents, dispersants, thickeners, flow aids, solubilizers, flavoring agents, and sweeteners.

[0032] Capsules are the preferred form of administration and may contain hydroxypropyl methylcellulose (HPMC), hydroxypropyl methylcellulose and gellan gum, gelatin, plant polysaccharides, and optional plasticizers such as glycerin and sorbitol, colorings, disintegrants and lubricants.

[0033] Examples of fillers include maltodextrin, corn starch, pregelatinized corn starch, microcrystalline cellulose, calcium carbonate, gum arabic, FOS, inulin, and GOS, with maltodextrin being preferred.

[0034] Examples of anti-caking agents include silica, sodium aluminum phosphate, calcium silicate, magnesium silicate, talc, sodium aluminum silicate, and potassium aluminum silicate.

[0035] Examples of gliding agents include magnesium stearate, croscarmellose sodium, croscarmellose gum, enzymatically hydrolyzed carboxymethyl cellulose, enzymatically hydrolyzed cellulose gum, sodium fatty acid, potassium fatty acid and calcium fatty acid, magnesium fatty acid salts and fatty acid diglycerides, acetates of fatty acid monoglycerides and diglycerides; lactates of fatty acid monoglycerides and diglycerides, citrates of fatty acid monoglycerides and diglycerides, tartrates of fatty acid monoglycerides and diglycerides, monoacetyl tartrates and diacetyl tartrates of fatty acid monoglycerides and diglycerides; mixed acetates and tartrates of fatty acid monoglycerides and diglycerides, sucrose glycerides, polyglycerol fatty acid esters, polyglycerol polyricinoleate, propane-1,2-diol fatty acid esters, sodium stearoyl-2-lactic acid, calcium stearoyl-2-lactic acid, stearyl alcohol tartrate, sorbitan monostearate, sorbitan tripearate, sorbitan monolaurate, sorbitan monooleate, and sorbitan monopalmitate, preferably magnesium stearate.

[0036] In a particularly preferred embodiment, the composition of the present invention is in the form of a capsule, the capsule containing the following dosage:

[0037]

[0038] Another subject of this application is the use of the compositions of the present invention for promoting the reduction or elimination of skin blemishes caused by hyperpigmentation. The compositions of the present invention have been found to reduce AGEs (advanced glycation end products), also known as glycotoxins. AGEs originate from the reaction of glucose and proteins, and their formation is attributed to both endogenous processes (cellular senescence) and exogenous factors such as diet; they are also precursors to free radicals (formed due to the effects of ultraviolet radiation on the skin).

[0039] Based on a variety of factors, such as the patient's weight and age, any concurrent administration of other supplements or medications, the severity of the skin blemish to be treated, the patient's response to the treatment, and the patient's intolerance to the active ingredient, the patient may take a nutritional supplement composition at least once a day, such as one, two, or more capsules daily.

[0040] The following embodiments illustrate the present invention in detail. Example

[0041] Compound extraction process

[0042] Glycyrrhiza glabra L. extract was obtained through the following sequential steps:

[0043] - Extraction of Glycyrrhiza glabra L. roots using water as a solvent

[0044] - Evaporate the solvent by drying.

[0045] - Grinding

[0046] - To obtain the desired final product in powder form.

[0047] European olive (Olea europaea L.) extract was obtained using olive oil manufacturing processes. After pressing the olives and extracting the oil, the plant water was recovered and the following steps were performed:

[0048] -filter

[0049] -Concentrate the filtrate to obtain a liquid product

[0050] - Foam drying

[0051] - To obtain the desired final product in powder form.

[0052] Dosage Examples of Selected Formulations

[0053] Powdered rods

[0054]

[0055] 30ml small bottle

[0056]

[0057] tablet

[0058]

[0059] clinical trials

[0060] The synergistic effect of two extracts was tested in a double-blind, placebo-controlled clinical trial to determine their skin-lightening efficacy, particularly in reducing dark spots. The trial recruited 60 healthy volunteers of different ethnicities (Caucasians, Chinese, and Asians, with skin types IV-V) and sexes, aged 25 to 65 years; all participants had dark spots due to aging, sun exposure, or post-inflammatory hyperpigmentation. Thirty volunteers used the active product, and 30 used the placebo. The total study duration was 56 days, with volunteers examined at the start of treatment (T0), 28 days after treatment (T28), and at the end of treatment (T56). Throughout the treatment period, both products (the active product and the placebo) were taken in capsule form (one capsule daily with a glass of still water).

[0061] The following parameters were evaluated to determine the efficacy of the combination of licorice and olive extracts: pigmentation intensity of spots (expressed as ITA° (Individual Typology Angle) values) and area of ​​dark spots (expressed as a percentage). AGE formation was also evaluated as an indicator of skin aging.

[0062] Overall, in the active ingredient group, a statistically significant increase in ITA° values ​​was recorded (corresponding to lighter skin tones), with an increase of 11.8% at T28 and 18.9% at T56; while the placebo group showed only an 8.1% increase at T56. Regarding the area of ​​dark spots, a statistically significant reduction in spot area was observed only in the active ingredient treatment group, with a reduction of 4.18% at T28 and 8.45% at T56; at T56, intergroup analysis also confirmed that the reduction was statistically significant, supporting the active product group.

[0063] Finally, a statistically significant reduction in AGE formation was observed, decreasing by 10.6% after 56 days of treatment with the active product. Intergroup analysis also confirmed that this change was significant.

[0064] These results demonstrate the effectiveness of the combination of these two extracts in reducing dark spots and thus improving skin tone evenness and radiance. The extracts also showed significant efficacy in combating skin aging, thus proving their anti-aging properties.

Claims

1. A nutritional health composition containing Glycyrrhiza glabra L. extract and Olea europaea L. extract as the only biologically active or nutritionally active ingredients present in the composition.

2. The composition according to claim 1, comprising the following components, which are independent of each other: a. Aqueous extract of Glycyrrhiza glabra L. root, optionally dried; b. Aqueous extracts of leaves and / or fruits of the European olive (Olea europaea L.) and / or filtrates of plant water, optionally dried, having a content of at least 4% by weight of hydroxytyrosol.

3. The composition according to claims 1 and 2, wherein the European olive extract has a hydroxytyrosol content of 4% to 9% by weight.

4. The composition according to claims 1-3 further comprises maltodextrin and / or gum arabic.

5. The 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 a percentage of the total weight of the composition.

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

7. The composition according to claims 1-6, comprising one or more nutritionally and health-adapted excipients.

8. The composition of claim 7, wherein the excipient is selected from diluents, dispersants, thickeners, flow aids, solubilizers, flavoring agents, and sweeteners.

9. Use of the composition according to claims 1-8 for promoting the reduction or elimination of blemishes caused by hyperpigmentation or glycation of skin proteins.

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