Compositions containing extracts of Jasmin Sambac and their use
The extract of Jasminum sambac leaves, rich in sambacosides and moriphosides, addresses skin and hair care needs by improving skin health and inhibiting hair growth, providing a stable and effective solution for cosmetic and pharmaceutical applications.
Patent Information
- Application Number
- JP2025500829
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2022-07-11
- Filing Date
- 2023-06-13
- Publication Date
- 2025-07-17
AI Technical Summary
There is a need for further extracts of Jasminum sambac with specific components for use in cosmetic and pharmaceutical fields, particularly for skin care, scalp care, and hair care, and existing uses of Jasminum sambac extracts do not effectively address issues such as skin dysbiosis, skin barrier function, and hair growth inhibition.
An extract of Jasminum sambac leaves containing at least two sambacosides, including sambacoside A, and at least two moriphosides, obtained through a solid/liquid extraction method using water or a hydroalcoholic solvent, which has been found to improve skin defense against microbial pathogens, enhance skin barrier function, and inhibit hair growth.
The extract effectively improves skin health by enhancing skin defense, barrier function, and elasticity, while also preventing hair growth, offering a stable and effective solution for skin care and hair management.
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Abstract
Description
Technical Field
[0001] The present invention relates to an extract of Jasminum sambac leaves containing iridoid glycosides including at least sambacoside A and morifolioside, a composition containing such an extract, and their use. Further, the present invention relates to a cosmetic composition or a pharmaceutical composition containing such an extract as an active ingredient for skin care and for inhibiting hair growth.
Background Art
[0002] As the first protective barrier against the human body, the skin barrier function prevents the penetration of harmful substances into the deeper viable layers of the skin and also prevents the loss of water from the skin. Furthermore, the skin harbors a microbiota, usually non-pathogenic and a microbial flora of pathogens, composed of resident symbiotic organisms. The resident symbiotic microbiota is known to prevent pathogenic organisms from colonizing the skin surface by secreting chemical substances, either by themselves or by stimulating the immune system of the skin.
[0003] Skin dysbiosis has been associated with several skin diseases, including atopic dermatitis, acne, rosacea, cellulitis, impetigo, boils, folliculitis, and seborrhea. For example, in atopic dermatitis, dysbiosis is due to the growth of Staphylococus aureus strains, while in acne vulgaris, it is Cutibacterium acnes. The skin expresses various antimicrobial peptides (AMPs), which are constitutively expressed and induced in response to pathogenic microbial stimuli. These AMPs are effective in different forms against a range of microbial skin colonizers, including the bacterial and fungal skin commensals. Among these antimicrobial mechanisms against pathogenic bacteria, defensins are peptides known for their antimicrobial activity. Defensins are an important element of the innate immune system of many organisms, which is the first line of defense against invading pathogens. Indeed, defensins have broad antimicrobial activity against Gram-negative and Gram-positive bacteria, yeasts, and some enveloped viruses. For example, the skin can stimulate the release of human beta-defensins-2 and 3 (hBD2 and hBD3) to enhance antimicrobial defense against pathogenic infectious agents. It has been demonstrated that the expression of hBD2 and hBD3 in keratinocytes increases in response to inoculation with live S. aureus. The skin also expresses psoriasin, also known as S100A7, a well-known antimicrobial peptide, mainly on the face and head.
[0004] Therefore, controlling the formation of microbial colonies such as S. aureus or C. acnes is a major means to maintain skin symbiosis in healthy skin, or to restore skin symbiosis after its alteration, or to restore skin health.
[0005] Unfortunately, the skin barrier function easily deteriorates under various harmful conditions such as aging, genetic diseases (e.g., atopic dermatitis, xerosis), immune dysregulation, skin dysbiosis, and environmental stress (e.g., UV rays, pollutants, etc.).
[0006] Therefore, ensuring the maintenance of skin health typically involves maintaining the skin barrier function. Furthermore, the skin's health status mainly depends on the maintenance of its microbiome symbiosis, which is characterized by good water retention. Skin water retention can be maintained through the production of natural moisturizing factors (NMF) from filaggrin proteolysis by bleomycin hydrolase (BLMH), and the skin retains water thanks to fairly highly hydrophilic molecules such as hyaluronic acid and proteoglycans.
[0007] Another biological mechanism that may be of interest for skin health is the autophagy process. Indeed, autophagy can be involved in the epidermal regeneration and differentiation processes.
[0008] Atopic dermatitis (AD), a multifactorial chronic inflammatory skin disease, typically has clinical symptoms consisting of dry and itchy skin. AD is often caused mainly by filaggrin deficiency, S. aureus colonization, and chronic inflammation due to innate immune deficiency and S. aureus proliferation. A deficiency in the skin barrier function is typically observed in the onset of this disease. Indeed, changes in the skin barrier function can allow deep penetration of S. aureus, making its colonization more likely to occur. Furthermore, lower levels of AMPs are often associated with innate immune deficiency. Indeed, increased expression of interleukin-1 (IL-1), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) has been observed in atopic dermatitis skin.
[0009] Acne vulgaris typically involves the pilosebaceous unit, is characterized by pustules and papules, and is caused by inflamed and infected skin. Acne is typically a multifactorial skin disease: skin inflammation, C. acnes proliferation, increased sebum production, hyperkeratosis, and poor skin barrier function. C. acnes promotes inflammation through activation in keratinocytes and immune cells of the toll-like receptor pathway, thus in turn inducing the synthesis of pro-inflammatory cytokines such as IL-1, IL-6, IL-8, and TNF.
[0010] Topical retinoids and antibiotics are well-known in the treatment of atopic dermatitis. However, these drugs have many drawbacks, mainly antibiotics, which also exacerbate skin and intestinal microbiota dysbiosis, as well as antibiotic resistance.
[0011] Furthermore, skin diseases such as leprosy, seborrheic dermatitis, atopic dermatitis, psoriasis, as well as dandruff, are known to be caused by microorganisms such as Malassezia yeasts.
[0012] Hypertrophic scars and keloids, known as fibrotic skin diseases, are characterized by excessive scarring due to excessive production and deposition of collagen and extracellular matrix (ECM) molecules, representing a dysregulated response to skin wounds. Keloids, typically much more difficult to heal, are so itchy and uncomfortable that they can affect the patient's physical function and appearance and cause psychological disorders.
[0013] One of the key regulators involved in the initiation of the wound healing cascade is transforming growth factor beta (TGF-β). In human skin fibroblasts, TGF-β induces the activation of β-catenin, and abnormal activation of the Wnt / β-catenin signaling is often involved in keloids and hypertrophic pathogenic scars. TGF-β can stimulate the expression of connective tissue growth factor (CTGF), which can act as a downstream mediator of TGF-β, promoting fibroblast proliferation, ECM production, mainly collagen and granulation tissue formation. The overexpression of CTGF in keloids and hypertrophic scars can enhance the pro-fibrotic response to TGF-β, so it is considered that blocking CTGF expression and Wnt signaling may reduce the fibrotic proliferative response of pathological scarring by preventing connective tissue cell proliferation and matrix deposition. Furthermore, in scleroderma, another skin fibrosis disease, upregulation of intracellular adhesion molecule-1 (ICAM1) expression in skin fibroblasts confers the ability of the cells to bind to mast cells, thus leading to a cascade of events that promote fibrosis.
[0014] Currently, there is no currently effective treatment for keloids or hypertrophic scars.
[0015] Hair follicles undergo three cycles consisting of anagen, catagen, and telogen over a lifetime. Cyclic hair growth depends on epithelial stem cells present in the permanent bulge region of the outer root sheath of the hair follicle.
[0016] For certain cosmetic reasons, hair growth may be undesirable. There are various techniques for removing unwanted hair, such as shaving, waxing, chemical depilatory creams, and pulsed light. All of these techniques have drawbacks. Shaving causes rashes, razor bumps, cuts, and irritates the skin. Waxing causes pain and discomfort and only removes some short hairs limitedly. Depilatory creams affect the part of the hair above the skin surface and can induce irritation. Pulsed light makes it possible to remove the part under the skin and thus lasts longer.
[0017] Dickkopf / Wnt signaling pathway inhibitor 1, a human gene encoding a secreted protein called Dickkopf 1 (DKK1), is involved in embryonic development through its inhibition of the Wnt signaling pathway. Thus, if it is interesting to inhibit hair growth, it would be achieved through the inhibition of the Wnt signaling pathway.
[0018] Jasminum sambac (Oleaceae), also known as Arabian jasmine (also called jasmine), is native to the Middle East and Asia. The flowers of Jasminum sambac are used in the perfume industry for thousands of years and are characterized by a very pleasant fragrance used as a perfume in jasmine tea and aromatherapy. In fact, Jasminum sambac is a perennial plant cultivated by farmers essentially for their flowers for the needs of the tea and perfume industries. In this regard, the leaves are regularly cut to promote flowering. As a result, a large amount of leaves are generated which are typically disposed of and discarded.
[0019] The use of extracts of Jasminum sambac is known in the cosmetic field and typically focuses on its flowers.
[0020] For example, EP-B 2275113 (Patent Document 1) describes a cosmetic preparation containing 3-methyloctan-4-lactone and an extract of the whole part of Jasminum sambac (typically including the flower part) for use in improving blood circulation in the skin and increasing skin temperature. JP-A2008031089 (Patent Document 2) relates to a plant extract containing the whole part of Jasminum sambac for skin whitening. JP-S6452709 (Patent Document 3) discloses an extract of the whole part of Jasminum sambac for moisturizing and skin softening. KR-B1-101762314 (Patent Document 4) discloses a mixture of plant extracts containing the whole part of Jasminum sambac, preferably an extract of the flower, for moisturizing the skin. However, none of these documents disclose an extract containing specific iridoid glycosides in the extract of Jasminum sambac, nor the specific cosmetic or therapeutic use of the extract of Jasminum sambac.
[0021] The chemical content of the Jasminum sambac flower extract containing iridoid glycosides and its vasodilatory activity have been described (Yin et al., Hindawi Publishing Corp., Evidence-Based Complementary and Alternative Medicine, 2014: Article ID 707908 (Non-Patent Document 1)). However, this is derived from a flower extract and the specific cosmetic or therapeutic use in the skin is not described.
[0022] It has been reported that the hydroethanol extract of the leaves of Jasminum sambac contains sambacoside A and morifficoside A (El-Hawary et al., International Journal of Applied Pharmaceutics, Vol. 11, Issue 6, 154-164, 2019 (Non-Patent Document 2)). This document also does not suggest the presence of any other morifficosides or the specific cosmetic or therapeutic use of the extract of Jasminum sambac.
[0023] Although it has been reported that the composition of the extract of Jasminum sambac contains sambacosides A, E, and F, the specific extraction method used has not been shown (Tanahashi T. et al., Tetrahedron Letters, Vol. 29, N°15, pp 1793-1796, 1988 (Non-Patent Document 3)). This document does not suggest the specific cosmetic or therapeutic use of the extract of Jasminum sambac. Methanolic and ethanolic leaf extracts of Jasminum sambac have been generally reported (Sultana et al., European Journal of Biomedical and Pharmaceutical Sciences, Vol. 6, Issue 5, 350-358, 2019 (Non-Patent Document 4)). However, it has not been taught whether these were prepared in a manner containing iridoid glycosides, such as specific morrhuacins and / or sambacosides. (Yin et al., Hindawi Publishing Corp., Evidence-Based Complementary and Alternative Medicine, 2014: Article ID 707908 (Non-Patent Document 1)). The methanolic leaf extract of Jasminum sambac is known to contain sambacoside A and morrhuacins A-E (Zhang Ying-Jun et al., Phytochemistry, 38(4), 899-903, 1995 (Non-Patent Document 5)). It has also been reported that the methanol extract of the leaves of Jasminum sambac exhibits direct anti-Malassezia activity, represented by the diameter of the inhibition zone due to its tannin and sambasin components. The iridoid glycoside component has not been mentioned (Jacinta et al., Journal of mycology, Vol. 2014; P1-7; 2014 (Non-Patent Document 5)). Tannins are not present in the hydroethanolic leaf extract of Jasminum sambac (Khan et al., Molecules, 26, 5664, 2021 (Non-Patent Document 6)).In phytochemical studies conducted on the leaf extract of Jasminum sambac, only the presence of sambacosides A, E, and F was shown. There is no further information regarding the presence of tannins or sambacin. (Jain et al., “Jasminum species: an overview”, International Journal of Institutional: Pharmacy and life sciences, Vol.1, 1, 251-266, 2011 (Non-Patent Document 7)).
[0024] It is agreed that the concentration of active ingredients in plants (here Jasminum sambac) can vary depending on the season. Furthermore, such concentrations also vary depending on the plant organ. As a result, it may be important to freely obtain an extract of Jasminum sambac that shows a stable amount of specific iridoid glycoside content regardless of the season.
Prior Art Documents
Patent Documents
[0025]
Patent Document 1
Patent Document 2
Patent Document 3
Patent Document 4
Non-Patent Documents
[0026]
Non-Patent Document 1
Non-Patent Document 2
Non-Patent Document 3
Non-Patent Document 4
Non-Patent Document 5
Non-Patent Document 6
Non-Patent Document 7
Summary of the Invention
Problems to be Solved by the Invention
[0027] Therefore, there is still an unmet need for further extracts of Jasminum sambac having specific components and usable in the cosmetic and / or pharmaceutical fields, particularly in skin care, scalp care, and hair care.
Means for Solving the Problems
[0028] Surprisingly, an extract of the leaves of Jasminum sambac containing at least two sambacosides including sambacoside A and at least two molihuasides has been found to have unexpectedly beneficial properties for skin care, particularly for improving skin defense against microbial pathogens, improving skin barrier function, improving skin elasticity, improving skin soothing, and preventing hair growth.
[0029] By using the leaf extract for this purpose, surprisingly, it is possible to use the leaves that are typically disposed of in the production of jasmine flowers. This makes it possible to maintain the price stability of the by-products derived from the plant Jasminum sambac to satisfy the cosmetics industry.
[0030] Indeed, the leaf extract of Jasminum sambac of the present invention may be characterized by having a specific biomarker content and has been found to meet expectations in cosmetic and / or pharmaceutical uses.
[0031] Summary of the Invention The present invention relates to: (A) at least two sambacosides including sambacoside A, and (B) at least two molihuasides, and relates to a water or hydroalcoholic extract of the leaves of Jasminum sambac containing iridoid glycosides.
[0032] A further aspect relates to a method for producing an extract according to the present invention, comprising the following steps: i) a step of pulverizing the leaves, optionally dried, ii) a step of subjecting the ground leaves to solid / liquid extraction with at least one solvent selected from water or a mixture of water and alcohol, wherein the alcohol is selected from the group consisting of glycerol, propanediol, methanol, ethanol, propanol, butanol, butylene glycol, and propylene glycol, and preferably, the solvent is a mixture of ethanol / water, glycerol / water, or propanediol / water in a ratio of 95:5 to 5:95, preferably 90:10 to 20:80, more preferably 70:30 to 50:50, a) the solid / liquid extraction is carried out at room temperature for 30 minutes to 10 hours, preferably 45 minutes to 8 hours, more preferably 1 hour to 5 hours, b) the solid / liquid ratio is 1:5 to 1:20, preferably 1:7 to 1:15, said step, iii) a step of separating the solid phase and the liquid phase to recover the liquid portion, iv) optionally, a step of concentrating the liquid portion containing the solvent-based extract by at least partially removing the extraction solvent.
[0033] Another aspect of the present invention is as follows: - an extract of the leaves of Jasminum sambac according to the present invention as an active ingredient; and - at least one further different cosmetically and / or pharmaceutically acceptable ingredient other than said extract of the leaves of Jasminum sambac, a cosmetic or pharmaceutical composition comprising the same, which is a composition for external use selected from the group consisting of solutions, suspensions, emulsions, creams, pastes, gels, lotions, powders, soaps, surfactant-containing water, oils, shampoos, and sprays; and / or a nutraceutical composition for oral administration, said cosmetic or pharmaceutical composition.
[0034] Another aspect of the present invention relates to the use of a composition comprising or consisting of an extract according to the present invention, or a cosmetic composition, in skin care.
[0035] Accordingly, the present invention relates to the cosmetic use of a composition comprising or consisting of an extract of Jasminum sambac leaves in skin care.
[0036] Another aspect of the present invention relates to the use of a composition according to the present invention, comprising or consisting of an extract, or a cosmetic composition, for inhibiting hair growth.
[0037] The present invention further relates to the cosmetic use of a composition comprising or consisting of an extract of Jasminum sambac leaves in hair care.
[0038] Another aspect of the present invention relates to a composition comprising or consisting of an aqueous extract or a hydroalcoholic extract (preferably the extract of the present invention) of Jasminum sambac leaves as an active ingredient for use in a method for treating or preventing skin disorders selected from the group consisting of atopic dermatitis, acne, dandruff, sebum secretion, oily skin, fibrotic injury, scar, pathological skin redness, pathological skin inflammation, and combinations of two or more thereof.
[0039] In other words, the present invention further relates to the treatment and / or limitation of fibrotic disorders, the treatment and / or limitation of scars, the treatment and / or prevention of skin redness and skin inflammation, or for two or more of them, for the management of skin prone to atopic dermatitis and skin with a tendency to acne (skin prone to acne), as an active ingredient for use in a non-therapeutic method, a composition comprising or consisting of an aqueous extract or a hydroalcoholic extract (preferably the extract of the present invention) of Jasminum sambac leaves. BRIEF DESCRIPTION OF THE DRAWINGS
[0040] FIG. 1 shows the UV chromatogram of the extract of Jasminum sambac leaves according to the present invention scanned at 236 nm.
[0041] Figure 2 shows the evaluation of lucifer yellow passage at the top of the reconstructed human epidermis (RHE) after 6 hours of contact, in reconstructed human epidermis (RHE) that has or has not been treated with the extract according to the invention and that has or has not been infected with Malassezia furfur.
[0042] Detailed Description of the Invention One aspect of the present invention is as follows: (A) at least two sambacosides including sambacoside A, and (B) at least two moriphosides, relates to a water or hydroalcoholic extract of the leaves of Jasminum sambac containing iridoid glycosides comprising.
[0043] When used in the context of the present invention, iridoid glycosides (including sambacosides and moriphosides) can be understood in the broadest sense understood in the art. As used herein, the term "iridoid" can be understood in the broadest sense generally understood in the art. Preferably, it can include any iridoid-based component including iridoid glycosides.
[0044] Examples of such iridoid glycosides are described in El-Hawary et al. (International Journal of Applied Pharmaceutics, Vol. 11, Issue 6, 154-164, 2019) and Tanahashi T. et al. (Tetrahedron Letters, Vol. 29, N°15, pp 1793-1796, 1988). Further examples, and sambacosides such as sambacoside A-G, and moriphosides such as moriphosides A-E are known in the art. The core structure (also referred to as the basic skeleton) of the iridoid glycosides used in the context of the present invention can often be as follows:
[0045]
Chemical formula
[0046] According to one embodiment, the iridoid glycoside content corresponds to at least 5% by weight, based on the total weight of the dry matter of the extract. Preferably, the iridoid glycoside content may correspond to between 5 and 30% by weight, more preferably between 7 and 28% by weight, particularly between 8 and 25% by weight, based on the total weight of the dry matter of the extract. In a preferred embodiment, the extract further comprises at least two sambacosides selected from sambacoside E or F, or mixtures thereof, and moriphenolide is selected from moriphenolide A, B, C, D and E, or mixtures of two or more thereof.
[0047] In a preferred embodiment, the sambacoside may be a mixture of sambacoside A, E and F, and the moriphenolide may be a mixture of moriphenolide A-E. Thus, in a preferred embodiment, the extract comprises sambacoside A, E and F, and the moriphenolide is moriphenolide A-E.
[0048] According to a preferred embodiment, sambacoside A may correspond to 30-70% by weight, preferably 35-65% by weight, even more preferably 40-60% by weight, based on the total weight of all iridoid glycosides.
[0049] In a preferred embodiment, the extract comprises 1-70% by weight, preferably 10-60% by weight, of moriphenolide, based on the total weight of the dry matter of the extract.
[0050] According to a preferred embodiment, the total iridoid glycoside content may correspond to at least 5% by weight, based on the total weight of the dry matter of the extract.
[0051] The total iridoid content in the leaf extract of Jasminum sambac according to the present invention may correspond to 1000 - 3000 ppm, preferably 1500 - 2500 ppm, more preferably 1800 - 2200 ppm, expressed in oleuropein equivalents. Advantageously, the leaf extract of Jasminum sambac according to the present invention may contain less than 0.001% by weight, preferably less than 0.0001% by weight, of tannins and sambacin, based on the total weight of the dry matter of the extract. In particular, the leaf extract of Jasminum sambac according to the present invention may contain neither tannins nor sambacin.
[0052] The leaves of Jasminum sambac contain a pool of active molecules, especially polyphenols and iridoid glycosides. Iridoids are a type of monoterpenoid found in a wide variety of plants. Iridoid glycosides (also called oligomeric iridodial glycosides), namely sambacosides and morifosides, have been reported to be present in the leaves of Jasminum sambac.
[0053] As used herein, the term "extract" can be any substance created by extracting the leaves of Jasminum sambac. According to the present disclosure, the extract of Jasminum sambac may generally be a solvent-based extract obtained by a solid / liquid extraction method called maceration extraction or lixiviation extraction. As used herein, extraction can be achieved by using at least one solvent, preferably a polar solvent. In one embodiment, the extract can be obtained from water, alcohol or hydroalcohol extraction methods, including cold extraction or hot extraction, ultrasonic extraction, reflux cooling, and microwave extraction, which can later be carried out by using water as the extraction solvent.
[0054] As used throughout the disclosure of this specification, the term "extract" means an extract of the leaves of Jasminum sambac.
[0055] Accordingly, the extract can be (or is) obtained by solid / liquid extraction of the leaves of Jasminum sambac in a solvent selected from water or a mixture of water and alcohol, wherein the alcohol is methanol, ethanol, propanol, butanol, glycerol, butylene glycol, propylene glycol, propanediol, preferably ethanol / water, glycerol / water or propanediol / water.
[0056] In a preferred embodiment, the extract can be (or is) obtained by solid / liquid extraction of the leaves of Jasminum sambac in a solvent selected from water or a mixture of water and alcohol, wherein the alcohol is selected from the group consisting of glycerol, propanediol, methanol, ethanol, propanol, butanol, butylene glycol, propylene glycol and combinations of two or more thereof, and preferably the solvent is a mixture of ethanol / water, glycerol / water or propanediol / water.
[0057] As used herein, the term "hydroalcohol(ic / ic system)" can be understood in the broadest sense generally understood in the art. It can be any composition containing one or more alcohols and water. The hydroalcohol extraction solvent can be any alcohol / water mixture. Preferably, the hydroalcohol extraction solvent can be ethanol / water, glycerol / water or propanediol / water. In a particularly preferred embodiment, the extract of the present invention is obtained by extracting the leaves of Jasminum sambac with ethanol / water, glycerol / water or propanediol / water.
[0058] In a preferred embodiment, the leaf extract according to the present invention can be a hydroalcoholic extract in which the water / alcohol ratio is 5:95 (v / v), preferably 10:90 (v / v), more preferably 20 / 80 (v / v), particularly 30:70 (v / v).
[0059] In one embodiment, the dry matter content of the extract corresponds to 5 g / L to 15 g / L, preferably 7 g / L to 13 g / L, more preferably 8.5 g / L to 12 g / L (weight / volume of solvent), and is 0.5 wt% to 1.5 wt%, preferably 0.7 wt% to 1.3 wt%, more preferably 0.85 wt% to 1.2 wt% with respect to the total weight of the extract, respectively.
[0060] The extract according to the present invention can be in liquid, paste or solid form under standard conditions (room temperature of about 20 °C, standard pressure of about 1013 hPa). In this context, the terms "liquid" and "fluid" can be understood interchangeably. Preferably, the extract is initially obtained in liquid form. Then, one or more solvents can be optionally removed to obtain the solid form of the extract. The liquid extract (i.e., the solvent-based extract) can also be concentrated, for example, under reduced pressure. Further, after concentration, the extract may be dried. Preferably, then, a part of one or more solvents is removed. Optionally, a liquid or paste-like extract may be obtained. Optionally, the extract may also be rediluted with one or more solvents to obtain a solvent-based extract. Optionally, the extract may also be purified by any means (e.g., crystallization, chromatography, etc.).
[0061] The extract may optionally be referred to as a "tincture" or an "absolute". The solvent used for the production of the solvent-based extract may be an aqueous solvent (water or buffer), or it may be a combination of an aqueous solvent and a liquid organic solvent. Thus, the extract of Jasminum sambac leaves according to the present invention is a solvent-based extract in which the diluting solvent can be selected from water, aqueous buffer, alcohol, glycol, or a mixture thereof. The alcohol is preferably selected from methanol, ethanol, propanol, butanol, glycerol, butylene glycol, propylene glycol, propanediol, or a mixture of two or more thereof.
[0062] In a preferred embodiment, the extract of Jasminum sambac leaves according to the present invention may be an aqueous extract.
[0063] In another preferred embodiment, the extract of Jasminum sambac leaves according to the present invention can be obtained by extracting with a mixture of glycerol / water in a volume ratio of 95 / 5 to 5 / 95, preferably 90 / 10 to 70 / 30 or 80 / 20 to 20 / 80.
[0064] In another preferred embodiment, the extract of Jasminum sambac leaves according to the present invention can be obtained by extracting with a mixture of ethanol / water or propanediol / water in a volume ratio of 95 / 5 to 5 / 95, preferably 40 / 60 to 60 / 40 or 70 / 30 to 50 / 50.
[0065] Advantageously, when used as a carrier solvent for the extract of Jasminum sambac, the mixtures of glycerol / water and propanediol / water can stabilize the product against changes due to microbial growth, and as a result, no additional preservatives are required.
[0066] The extract of jasmine sambac leaves may optionally be obtained from a fraction produced by separation through an ultrafiltration membrane having a certain molecular weight cut-off value, or by separation using various chromatographic methods, or by other known purification methods including liquid-liquid separation or crystallization or precipitation.
[0067] As used herein, the term "dry matter" can be understood in the broadest sense as the extract according to the present invention in the form of dry matter, i.e., without solvent. In calculations, the mass of the solvent is mathematically subtracted from the total mass.
[0068] The dry matter (in physical form) can be obtained by an appropriate extraction method and a subsequent step of drying the obtained extract. Drying can be carried out by any method suitable for this purpose known in the art. Drying means removing one or more solvents used for extraction.
[0069] A method for producing an extract according to the present invention, comprising the following steps: i) Optionally drying and then pulverizing the leaves, ii) Subjecting the pulverized leaves to solid / liquid extraction with at least one solvent selected from water or a mixture of water and alcohol, wherein the alcohol is selected from the group consisting of glycerol, propanediol, methanol, ethanol, propanol, butanol, butylene glycol, propylene glycol, and preferably, the solvent is a mixture of ethanol / water, glycerol / water or propanediol / water in a ratio of 95:5 to 5:95, preferably 90:10 to 20:80, more preferably 70:30 to 50:50, a) The solid / liquid extraction is carried out at room temperature for 30 minutes to 10 hours, preferably 45 minutes to 8 hours, more preferably 1 hour to 5 hours, b) The solid / liquid ratio is 1:5 to 1:20, preferably 1:7 to 1:15, The above step, iii) Separating the solid phase and the liquid phase to recover the liquid part. iv) Optionally, concentrating the liquid portion containing the solvent-based extract by at least partially removing the extraction solvent.
[0070] It will be understood that the extract obtained after the solid / liquid extraction in step ii) may exhibit biological activity as described in the experimental section of the present application.
[0071] It will be understood that the definitions and preferred embodiments described in the context of the above extract apply to the method of the present invention with the necessary modifications, and vice versa.
[0072] Optionally, the method may include step ii') of repeating step ii). For example, such repetition can be 1 to 3 times, and thus can be 1, 2 or 3 times.
[0073] In one embodiment, the solid / liquid extraction can be carried out at 15 to 120 °C, preferably 15 to 110 °C, more preferably 18 to 100 °C, particularly 20 to 100 °C, for 30 minutes to 72 hours, preferably 45 minutes to 60 hours, more preferably 1 hour to 55 hours, most preferably 2 to 48 hours.
[0074] In one embodiment, the separation of the solid and liquid phases for recovering the liquid portion can be carried out by any means known in the art, such as centrifugation, decantation or filtration.
[0075] In one embodiment, the solvent-based extract may be further dried, for example by spray drying, by any means known in the art after concentration.
[0076] In one embodiment, the concentrated extract may be further solubilized in a suitable cosmetic solvent selected from the group consisting of polyols, glycols, esters, and mixtures of water with one of them. For example, suitable cosmetic solvents can be glycerol, propanediol, butylene glycol, propylene glycol, ethyl acetate.
[0077] The ratio of plant material to extraction solvent may be between 1 / 5 and 1 / 50 by weight, preferably between 1 / 10 and 1 / 20.
[0078] In the context of the present invention, the extract is preferably dried, frozen, lyophilized, or fresh. The plant material can be used in any form, such as powder, crushed or any other form.
[0079] The extract according to the present invention may be obtained from a commercial supplier or may be prepared from the leaves of Jasminum sambac as described above.
[0080] The hydroalcoholic solvent may be a solvent mixture mainly composed of one or more alcohols and water. Preferably, the hydroalcoholic solvent contains alcohol between 1 and 99% (v / v), or between 5 and 95% (v / v), or between 10 and 90% (v / v), or between 15 and 85% (v / v), or between 20 and 80% (v / v), or between 25 and 75% or between 30 and 70% (v / v), or between 40 and 60% (v / v), or about 50% (v / v). Here, when used, water can also include hot water or subcritical water. Also, one or more aqueous buffers may be used.
[0081] Accordingly, one aspect of the present invention relates to an extract of the leaves of Jasminum sambac obtainable (or obtained) by the implementation of the above manufacturing method.
[0082] Furthermore, the present invention relates to the cosmetic use in skin care of a composition comprising or consisting of an extract of Jasminum sambac leaves or of a cosmetic composition comprising such an extract.
[0083] One aspect of the present invention relates to the use in skin care of a composition according to the present invention, comprising or consisting of an extract, or of a cosmetic composition. Preferably, such use is cosmetic (preferably non-therapeutic), but may be therapeutic.
[0084] It will be understood that the definitions and preferred embodiments described in the context of the above extracts and methods apply, mutatis mutandis, to the above uses of such materials, and vice versa.
[0085] In other words, the present invention relates to an extract or a cosmetic composition according to the present invention for use in a method in skin care.
[0086] As used herein, the term "skin care" can be understood in the broadest sense. Preferably, it includes preventing skin dysbiosis, maintaining or restoring skin symbiosis, improving and / or restoring the skin barrier function, preventing the formation of stretch marks, preventing and / or regulating sebum secretion, preventing the oily appearance of hair and / or skin, or for two or more of these, and improving skin defense against microbial pathogens.
[0087] In a preferred embodiment, the extract of the present invention or a cosmetic composition comprising such an extract can be used as an anti-dandruff agent.
[0088] In a preferred embodiment, skin care is for managing skin prone to atopic dermatitis, preventing acne, limiting fibrotic disorders, limiting scarring, preventing inflammation and / or erythema, or for a combination of two or more of these.
[0089] In a preferred embodiment, the skin care is for preventing or reducing skin irritation.
[0090] Advantageously, the extract of the present invention or a cosmetic composition containing such an extract can be used as an antioxidant.
[0091] Advantageously, the extract of the present invention, or a cosmetic composition containing such an extract, can be used as a skin whitening agent.
[0092] In other words, the present invention relates to an extract or a cosmetic composition according to the present invention for use in a method for preventing or reducing skin irritation.
[0093] In a preferred embodiment, the skin care is the prevention or reduction of skin irritation, including at least one of the following: reduction of skin inflammation and / or skin soothing; stimulation of the skin's innate antimicrobial defense mechanism.
[0094] In a preferred embodiment, the skin care includes the following effects: improving and / or restoring skin barrier function and / or skin moisture retention, improving skin elasticity, stimulating the skin's innate antimicrobial defense mechanism, preventing skin dysbiosis, maintaining or restoring skin symbiosis, reducing skin inflammation and / or soothing the skin, reducing fibrosis, especially when associated with scar formation, preventing the formation of stretch marks, preventing and / or regulating sebum secretion, preventing the oily appearance of the skin, or a combination of two or more thereof.
[0095] In a preferred embodiment, the skin care is for reducing the amount and / or degree of reddish skin lesions.
[0096] In one embodiment, the skin care may further be for preventing acne vulgaris, improving or restoring the appearance of the skin, or a combination thereof.
[0097] In one embodiment, the skin care may further be for improving skin hydration, improving skin comfort, improving and / or restoring skin elasticity, preventing the formation of stretch marks, improving and / or restoring skin sagging, or for two or more of these.
[0098] A further aspect relates to the use of a composition comprising or consisting of an extract according to the invention, or a cosmetic composition, for inhibiting hair growth. Preferably, such use is cosmetic (preferably non-therapeutic), but may also be therapeutic.
[0099] In other words, the present invention relates to an extract or a cosmetic composition according to the invention for use in a method for inhibiting hair growth and for preventing an oily appearance of the hair.
[0100] It will be understood that the definitions and preferred embodiments made in the context of the use of the extract of Jasminum sambac leaves of the present invention apply, with the necessary modifications, to compositions comprising such extracts.
[0101] The present invention further relates to a composition comprising or consisting of an extract of Jasminum sambac leaves as an active ingredient for use in a non-therapeutic method for the management of skin prone to atopic dermatitis and skin with acneic tendencies, for the treatment and / or limitation of fibrotic disorders or conditions, for the treatment or limitation of scars, for the treatment and / or prevention of skin redness and skin inflammation, or for two or more of these.
[0102] As used herein, the term "manage" can be understood in the broadest sense as a means to limit, reduce, and improve atopic dermatitis and / or acne-prone skin to reduce the risk of developing atopic dermatitis and / or acne-prone skin and improve atopic dermatitis and acne skin phenotypes (acne).
[0103] As used herein, "skin prone to atopic dermatitis" and "skin likely to develop atopic dermatitis" are types of skin that have a tendency to develop inflammatory and itchy skin lesions. This does not refer to skin that already has a skin disease, but if untreated, it can cause atopic dermatitis.
[0104] As used herein, "skin prone to acne" and "skin likely to develop acne lesions" can be understood in the broadest sense as types of skin that have a tendency to develop pimples and inflammatory lesions. Skin prone to acne does not refer to skin that already has a skin disease, but if untreated, it can cause acne vulgaris.
[0105] Both atopic dermatitis and acne lesions preferably refer to inflamed and inflammatory lesions, preferably associated with atopic dermatitis (redness) and acne vulgaris (redness, pimples, pustules, and papules).
[0106] Since there is no currently effective treatment for keloids or hypertrophic scars, the extract of the present invention can regulate connective tissue abnormalities against their inflammatory origin, and by reducing skin pain and by improving skin elasticity, can improve the itching and discomfort of the skin that are often reported in these diseases. In this regard, experimental results have demonstrated that the extract according to the present invention can reduce CTGF expression and can reduce the associated collagen synthesis. Since CTGF plays a central role in the development and maintenance of the fibrotic response, the extract according to the present invention represents a potential strategy for treating keloids and other fibrotic disorders or conditions. Furthermore, the extract according to the present invention can induce MMP-1 and MMP-3 expression and lead to a decrease in the protein level of collagen, and thus reverse the fibrosis-promoting phenotype of fibrotic fibroblasts found in keloids, hypertrophic scars and scleroderma.
[0107] As used in the context of the present invention, the terms "subject" and "individual" can be understood in the broadest sense as any living organism. The subject is preferably a human or (non-human) animal, more preferably a human or (non-human) mammal, particularly a human. In the context of treatment and prevention, the subject can also be referred to as a "patient".
[0108] Advantageously, the subject can have or be suffering from a wound that can cause scarring, such as keloids and hypertrophic scars, and / or a fibrotic disorder or condition, for example via a surgical procedure, or has had a wound that has caused scarring, such as keloids and hypertrophic scars, and / or a fibrotic disorder or condition.
[0109] As used herein, the term "wound" can be understood in the broadest sense as an injury to the skin and subcutaneous tissue. Such wounds can include lacerations, burns, punctures, trauma, bites, fistulas, ulcers, lesions caused by infections, surgical wounds, incisional wounds, post-burn contractures, and wounds resulting from cosmetic surgical procedures.
[0110] As used herein, the term "keloid" can be understood in the broadest sense as a scar that results in overgrowth of tissue at the site of a healed skin injury. Keloids are usually accompanied by intense itching, pain, and changes in texture. In severe cases, it can affect the movement of the skin.
[0111] As used herein, "reduction of scarring" and "management of scarring" can be understood in the broadest sense. Preferably, it is, for example, with respect to keloids or hypertrophic scarring, by reducing the size and / or depth of a keloid or hypertrophic scar, or by reducing the size of an existing keloid or hypertrophic scar in a subject, any reduction or condition in keloid or hypertrophic scarring that provides a therapeutic or cosmetic benefit.
[0112] In one embodiment, the fibrotic disorder or condition may be related to TGF-β-induced CTGF expression, including but not limited to tissue fibrosis.
[0113] In one embodiment, the fibrotic disorder or condition and / or scar can be a keloid, and hypertrophic scars are those accompanied by an increase in the level of one or more of the following biomarkers: CTGF expression, type I collagen (COL1A1), fibulin-5 (FBLN5), fibromodulin (FMOD).
[0114] As used herein, the terms "treating" and "managing" can be understood in the broadest sense as means for achieving one or more of the following: (a) reducing the severity of a disorder or condition; (b) limiting or preventing the onset of symptoms characteristic of the disorder or condition being treated; (c) inhibiting the worsening of symptoms characteristic of the disorder or condition being treated; (d) limiting or preventing recurrence of the disorder or condition in a patient who has previously had the disorder or condition; and (e) limiting or preventing recurrence of symptoms in a subject who has previously had symptoms of the disorder(s) or condition(s).
[0115] As used herein, the terms "limiting" and "reducing" can be understood in the broadest sense as means for limiting a disorder or condition in a subject at risk of developing the disorder or condition.
[0116] Another aspect of the present invention is as follows: - an extract of Jasminum sambac leaves as an active ingredient (preferably according to the present invention), and - at least one other cosmetically and / or pharmaceutically acceptable ingredient other than the extract of Jasminum sambac, a cosmetic or pharmaceutical composition comprising wherein the composition is a composition for external use selected from the group consisting of solutions, suspensions, emulsions, creams, pastes, gels, lotions, serums, powders, soaps, surfactant-containing waters, oils, shampoos and sprays, or wherein the composition is a nutraceutical composition for oral administration, relating to the cosmetic or pharmaceutical composition.
[0117] It will be understood that the definitions and preferred embodiments described in the context of the above extract, method and use apply to the above pharmaceutical composition with the necessary modifications, and vice versa.
[0118] Here, the extract according to the present invention may optionally be regarded as an active ingredient (or even as the only active ingredient). As used herein, the term "active ingredient" can be understood in the broadest sense as a component that can exhibit the desired intended activity, either alone or together with one or more other components, such as one or more carriers that are themselves inactive or other active ingredients that may act synergistically.
[0119] The cosmetic or pharmaceutical composition can be used for any purpose and in any form. In a preferred embodiment, the composition is a composition for external use selected from the group consisting of solutions, suspensions, emulsions, creams, pastes, gels, lotions, serums, powders, soaps, surfactant-containing waters, oils, shampoos, and sprays, or the composition is a nutraceutical composition for oral administration.
[0120] The composition may be a product selected from the group consisting of emulsions, gels, ointments, tonics, liquid soaps, solid soaps, bath oils, shower oils, massage oils, makeup, scalp treatments, aftershaves, shaving products, deodorants, shower gels, shampoos, and combinations of two or more thereof, or may be contained in such products.
[0121] Optionally, the cosmetic or pharmaceutical composition may be a nutraceutical composition that can be orally administered to a subject. And the cosmetic or pharmaceutical composition may optionally be contained in foods, such as food supplements. And the composition can typically have a systemic effect. The nutraceutical composition according to the present invention can be formulated into any form suitable for oral administration, such as tablets, capsules, granules, powders, solutions, emulsions, or suspensions, together with an acceptable carrier.
[0122] The cosmetic or pharmaceutical composition can contain the extract of the present invention in any content. In a preferred embodiment, the composition contains less than 15% by weight of the extract according to the present invention based on the total weight of the composition. In a preferred embodiment, the composition contains 0.0001 to 10% by weight, more preferably 0.001 to 8% by weight, and even more preferably 0.01 to 5% by weight of the extract according to the present invention based on the total weight of the composition.
[0123] At least one further different cosmetic and / or pharmaceutically acceptable component other than the extract of the present invention can be any cosmetic and / or pharmaceutically acceptable component. In a preferred embodiment, the cosmetic and / or pharmaceutically acceptable component is or includes at least one cosmetic and / or pharmaceutically acceptable carrier.
[0124] As used herein, the terms "pharmaceutically acceptable carrier", "pharmaceutically acceptable excipient", "cosmetically acceptable carrier", "cosmetically acceptable excipient", "carrier" and "excipient" can be understood interchangeably in the broadest sense as any substance that can support the cosmetic and / or pharmacological acceptability or usability of the composition of the present invention containing the extract of Jasminum sambac. Preferably, neither the extract of Jasminum sambac according to the present invention nor the composition containing at least one such extract is toxic when administered to tissues.
[0125] The ready-to-use composition can preferably be a liquid formulation, particularly a composition suitable for topical and oral administration. The storage form of the composition can also be liquid (i.e., a solvent-based extract), but can also be a dry form (e.g., a powder, e.g., a powder containing or consisting of the extract of Jasminum sambac), or a paste or syrup, etc. Optionally, the dry form, paste or syrup can be dissolved or emulsified before being administered to the skin of interest.
[0126] Cosmetically and / or pharmaceutically acceptable carriers can typically be selected from a list consisting of aqueous buffers, physiological saline, water, alcohol, vegetable oil, mineral oil, polymers, or combinations of two or more thereof. Optionally, the cosmetically or pharmaceutically acceptable carrier may contain one or more cosmetically or pharmaceutically acceptable additives.
[0127] In a preferred embodiment, such cosmetically and / or pharmaceutically acceptable additives can be selected from the group consisting of fragrances / aromatics, dyes, pigments, emulsifiers, lubricants, chelating agents, acidity regulators, antimicrobial agents, preservatives, antioxidants, and combinations of two or more thereof.
[0128] Furthermore, the composition of the present invention may contain one or more other active ingredients in addition to the extract of Jasminum sambac.
[0129] The composition according to the present invention may be a cosmetic or may be included in a cosmetic. The composition may be for any use. Any route of administration that provides the desired purpose described in the claims is appropriate. Administration can be local or systemic. Administration can be topical, transdermal, oral, or by injection.
[0130] In a preferred embodiment, the composition is a composition for topical use. In a preferred embodiment, the composition is a composition for topical use to be topically administered to a subject. In a preferred embodiment, the composition is a composition for topical use to be topically administered to a part of the skin, such as the face, scalp, or any part of the body.
[0131] The present invention may also be used in vitro, ex vivo or in vivo for the following purposes: reducing inflammation; stimulating the endogenous antimicrobial defense mechanism; reducing fibrosis; inhibiting hair growth; skin barrier function; skin soothing; skin water retention; and / or improving skin elasticity.
[0132] The present invention may also be used in in vitro cell culture or tissue models for the following purposes: reducing inflammation; stimulating the endogenous antimicrobial defense mechanism; and / or reducing fibrosis.
[0133] The present invention can also be used for the following in vitro, ex vivo or in vitro, particularly in in vitro cell culture or tissue models: for example: increasing the expression of one or more polypeptides related to antimicrobial defense mechanisms such as human β - defensins (e.g., human β - defensin 1, human β - defensin 2, and human β - defensin 3) and / or psoriasin S100A7, cathelicidin antimicrobial peptide (CAMP), RNase7, etc.; decreasing the expression of one or more polypeptides related to inflammatory processes such as interleukin - 1 (IL - 1), interleukin - 17 (IL - 17), tumor necrosis factor (TNF), bleomycin hydrolase (BLMH), and / or cholesterol 25 - hydroxylase (CH25H); increasing the expression of one or more polypeptides related to skin barrier functions such as corneodesmosin (CDSN), keratin 1 (KRT1), loricrin (LOR), transient receptor potential cation channel subfamily V member 4 (TRPV4), and / or sphingomyelin phosphodiesterase (SMPD1); increasing the expression of one or more polypeptides related to water - retaining properties such as GPAT3 or glycerol - 3 - phosphate acyltransferase 9 (AGPAT9), bleomycin hydrolase (BLMH), histidine ammonia - lyase (HAL), xylosyltransferase 1 (XYLT1), and / or chondroitin sulfate proteoglycan (CSPG4); increasing the expression of one or more matrix metalloproteinases (e.g., matrix metalloproteinase 1 (MMP - 1) and / or matrix metalloproteinase 3 (MMP - 3); increasing the expression of elastin (ELN); decreasing one or more polypeptides related to fibers and / or connective tissues such as collagen 1a1 (COL1A1), connective tissue growth factor (CTGF), fibulin - 5 (FBLN5), and / or intracellular adhesion molecule 1 (ICAM1); decreasing the expression of caspase 9 (CASP9); decreasing the expression of heparin - binding EGF - like growth factor (HBEGF);Reduce the expression of the transient receptor potential cation channel subfamily V member 1 (TRPV1); and / or increase the expression of Dickkopf Wnt signaling pathway inhibitor 1 (DKK1).;
[0134] As described above, the extract or the composition of Jasminum sambac of the present invention can be used for any purpose. Preferably, it is used for cosmetic and / or pharmaceutical purposes.
[0135] A further aspect refers to the use as an active ingredient in a method for the treatment or prevention of skin disorders selected from the group consisting of atopic dermatitis, acne, fibrotic injury, scar, pathological skin redness, pathological skin inflammation, dandruff, and combinations of two or more thereof, of an aqueous extract or a hydroalcoholic extract of the leaves of Jasminum sambac, preferably a composition comprising or consisting of the extract of the present invention.
[0136] It will be understood that the definitions and preferred embodiments described in the context of the above extract, method, use and pharmaceutical composition apply to the above pharmaceutical composition with the necessary modifications, and vice versa.
[0137] In other words, the present invention also relates to a method for the treatment or prevention of skin disorders selected from the group consisting of atopic dermatitis, acne, fibrotic disorders, scars, pathological skin redness, pathological skin inflammation, and combinations of two or more thereof, said method comprising administering, as an active ingredient, a sufficient amount of an extract of the leaves of Jasminum sambac, preferably a composition comprising or consisting of the extract according to the present invention, to a subject in need thereof.
[0138] In the context of treatment, atopic dermatitis can be, for example, classified as L20 in the 10th Revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10).
[0139] In the context of treatment, atopic dermatitis can be classified as L70 in ICD-10.
[0140] In the context of treatment, scarring and fibrosis can be classified as L90.5 in ICD-10.
[0141] In the context of treatment, pathological skin erythema can be erythema classified as L51-L54 in, for example, ICD-10.
[0142] The extract of the present invention or a composition containing such an extract can have local and / or systemic effects. In a preferred embodiment, when administered locally and / or topically, it has (mainly or completely) local effects.
[0143] As used herein, the terms "disorder" or "condition" can be understood in the broadest sense as any pathological condition. In the context of treatment, it can also be referred to as a disease. It may preferably be a congenital disease. As used herein, the term "injury" can be understood in the broadest sense as any perturbation or dysfunction in a tissue, particularly (otherwise) healthy tissue. A skin disorder is a disorder of the skin.
[0144] Throughout this specification and the claims, unless the context otherwise requires, open-ended phrases such as "comprise", "contain", "include", etc., and variations such as "comprises", "contains", "includes", "comprising", "containing", "including", etc., are to be understood to mean including the recited element, component, integer or step, or group of elements, components, integers or steps, but not to exclude any other element.
[0145] As used in the context of describing the present invention (especially in the context of the claims), the terms "a," "an," and "the" and similar references should be construed to cover both the singular and plural forms unless otherwise indicated herein or clearly contradicted by the context. The description of a range of values herein is merely intended to serve as a concise way of referring individually to each separate value within that range. Unless otherwise indicated herein, each separate value is incorporated herein as if it were individually and collectively recited herein. All methods and procedural steps (including product-by-process steps) described herein can be performed in any suitable order unless otherwise indicated herein or clearly contrary to the context. The use of any and all examples, or exemplary language (e.g., "such as," "for example") provided herein is merely intended to better illuminate the present invention and is not intended to limit the scope of the claimed invention. No language in this specification should be construed as indicating any non-claimed element as essential to the practice of the present invention.
[0146] More generally, it will be understood that the foregoing aspects and embodiments can be combined in any manner and in any number to form additional embodiments. Any substitution and combination of all the components described in this application should be considered to be disclosed by the description of this application unless the context dictates otherwise.
[0147] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. The methods and materials described herein are preferred, but other methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention.
[0148] All documents cited or referenced in this specification are incorporated by reference and may be used in the practice of the present invention. More specifically, all referenced documents are incorporated by reference to the same extent as if each individual document was specifically and individually indicated to be incorporated by reference.
[0149] The following examples and drawings are intended to illustrate further embodiments of the present invention without limiting its scope.
Example
[0150] Example 1. Preparation of extract of leaves of Jasminum sambac extracted by glycerol / water The leaves of Jasminum sambac were collected, washed, dried, and ground to a particle size of 1 mm or less. Then, 9.5 g of the powder was immersed in 0.095 L of a 80 / 20 (v / v) glycerol / water mixture. Solid-liquid extraction with glycerol / water was carried out at room temperature (about 20 °C) for 1 hour. The resulting liquid was filtered through filter paper (Advantec n°2).
[0151] Figure 1 shows the UV chromatogram at 236 nm of the leaf extract of Jasminum sambac prepared by the above preparation method.
[0152] Materials and methods The sample was analyzed by a Waters Acquity UPLC chromatography system connected to a Waters Xevo G2 Q-Tof instrument equipped with an electrospray ionization system. Chromatographic separation was performed on a column (Phenomenex Kinetex EVOC18: 2.1 mm x 150 mm, 1.7 μm) maintained at a temperature of 40 °C. A mobile phase system containing acetonitrile (A) with 0.1% formic acid and water (B) with 0.1% formic acid was carried out by gradient elution as follows: 2% (B) from 0 to 2 minutes, 2 - 10% (B) from 2 to 2.10 minutes, 10 - 28% (B) from 2.10 to 19 minutes, 28 - 100% (B) from 19 to 19.5 minutes, 100% (B) from 19.5 to 21.5 minutes, and 2% (B) from 21.6 minutes to 23 minutes. 5 μL of the sample was injected for analysis. The UV spectrum was recorded at 236 nm. The flow rate was set at 0.5 mL / min. ESI-MS spectra were obtained in both negative ion mode and positive ion mode, and the mass range was set at m / z 150 - 1500. The sample cone voltage was set at 30 volts. In MS / MS analysis, the dissociation collision energies were set at 15, 25, and 35 eV.
[0153] As shown in Figure 1, analysis demonstrated that sambacoside A, E, and F, numbered 19, 18, and 20 respectively, as well as moriffic acid A, B, C, D, and E, numbered 14, 17, 16, 15, and 13 respectively, were present in the extract. Tannin and sambacin were not detected.
[0154] The dry matter content of the leaf extract of Jasminum sambac extracted with glycerol / water corresponds to 7 g / L.
[0155] 2. Preparation of hydroalcoholic extract of leaves of Jasminum sambac The leaves of Jasminum sambac were prepared according to Example 1. Solid / liquid extraction was carried out using propanediol / water at 50 / 50 (v / v) or ethanol / water at 70 / 30 (v / v). For later use, the hydroethanol extract was concentrated by evaporating ethanol under reduced pressure. The concentrated extract was redissolved in propanediol / water 80 / 20 (v / v) and further filtered. This filtered extract of Jasminum sambac (hereinafter, JSE) was used in the following experiments.
[0156] The dry matter content of the leaf extract of Jasminum sambac extracted with ethanol / water 70 / 30 (v / v) corresponds to 8 - 11 g / L.
[0157] For all of the above solvents, the same chromatographic profile of the extract of Jasminum sambac was observed.
[0158] The same results were obtained using water as the extraction solvent.
[0159] By other methods as well, the aforementioned solvents were able to extract the leaves of Jasminum sambac having the said characteristics. This means that it contains at least two sambacosides including sambacoside A and at least two moriffic acids (data not shown).
[0160] 3. Transcriptome study for evaluation of biological activity of JSE against isolated skin cells Experimental studies were carried out in either normal human dermal fibroblasts (NHDF) or normal human epidermal keratinocytes (NHEK) using RT-qPCR technology (Taqman). JSE was demonstrated to have the ability to improve skin defense against microbial pathogens (see Table 1), the ability to prevent skin inflammation (see Table 2), the ability to improve skin barrier function (see Table 3), the ability to improve skin water retention (see Table 4), the ability to improve the appearance of skin scars, thereby improving the state of skin fibrosis, and the ability to improve fibrotic skin and skin comfort (see Table 5). In addition, skin soothing properties were also investigated (see Table 6). Finally, it was demonstrated that JSE exhibits hair growth inhibitory properties (see Table 7).
[0161] Methods: After 24 hours of NHDF or NHEK treatment in test JSE at 0.25% by weight, mRNA expression was quantified. mRNA extraction was performed according to the supplier's recommendations (Qiagen). Briefly, lysis buffer RLT-Plus was added onto the cell pellet, and the homogeneous lysate was transferred to an "RNeasy" column. The column was washed with buffer. Elution was performed with RNase-free water, and RNA quantification was performed with the "Nucleic Acid Quantification" software application by measuring O.D260nm, 280nm, and 320nm (Biotek, Cytation3 & Take3 Plate). The quality of the mRNA was confirmed using a Fragment Analyzer (Advanced Analytical). Subsequently, mRNA reverse transcription enabling the obtaining of cDNA templates was performed in a thermal cycler (Bio-Rad). qPCR was performed using the cDNA templates. For the transcriptome study, pre-designed plates (Bio-Rad) regarding ECM components, skin barrier function, epidermal differentiation, inflammation, water retention, and skin homeostasis were used. Subsequently, the generated data enabled the automatic calculation using Bio-Rad CFX manager of the mRNA expression fold change and p-value compared to the untreated conditions. All data were statistically significant compared to the control conditions (threshold of <0.1 for the p-value).
[0162] Results: The following table summarizes the results obtained after the transcriptome study:
[0163]
Table 1
[0164]
Table 2
[0165]
Table 3
[0166]
Table 4
[0167]
Table 5
[0168]
Table 6
[0169]
Table 7
[0170] Stimulation of the skin's innate antimicrobial defense mechanism Table 1 shows the ability of JSE to protect the skin from pathogenic microorganisms through induction of the expression of endogenous antimicrobial peptides in NHEK. Table 1 is the comparison result of the relative gene expression ratio of antimicrobial peptides between the control group and the JSE-treated group. The set of modulated genes includes DEFB4A, DEFB103B, and S100A7, which encode the antimicrobial peptides hBD2 and hBD3 and psoriasin, respectively. Indeed, it has been demonstrated that JSE significantly modulates the expression of hβD2 and hβD3 and psoriasin, which were statistically significantly upregulated in NHEK treated with JSE for 24 hours. These results demonstrated that JSE can protect the skin from pathogen colonization. Furthermore, stimulation of the expression of these antimicrobial peptides is known to have beneficial effects on both commensal skin, i.e., healthy skin, and dysbiotic skin, i.e., unhealthy skin.
[0171] Anti-inflammatory activity Table 2 demonstrates the anti-inflammatory properties of JSE in NEHK, as it enables significant inhibition of the mRNA expression of several pro-inflammatory markers (IL1, TNF, CH25H). In contrast, BLMH was significantly upregulated, enabling better control of skin inflammation: - IL1 is known to often play a role in health and disease as a master regulator of inflammation through the control of various innate immune processes. - TNF is involved in the regulation of immune cells. TNF is released in response to bacterial products such as lipopolysaccharide, but also in response to IL1. Additionally, TNF promotes the inflammatory response, which in turn causes many diseases, such as psoriasis, atopic dermatitis, and acne.
[0172] - CH25H plays multiple roles in lipid biosynthesis and innate immunity.
[0173] In contrast, JSE induces the upregulation of BLMH. In NHEK, BLMH is known to regulate the secretion of chemokines involved in inflammation and wound healing. Indeed, when BLMH is downregulated, skin inflammation increases.
[0174] These results demonstrate that JSE exhibits an anti-inflammatory effect that may be beneficial for soothing inflammatory skin, such as acneic skin (acne), atopic dermatitis skin, psoriatic skin, or erythematous skin.
[0175] Improvement of skin barrier function Table 3 demonstrates the ability of JSE to improve skin barrier function by upregulating the expression of differentiation genes and an enzyme (SMPD1) involved in ceramide metabolism and the autophagy process in NHEK. Indeed, JSE induces the overexpression of CDSN, KRT1, TRPV4, and SMPD1: - CDSN contributes to the aggregation of keratinocytes - KRT1 (a member of the keratin family) maintains skin integrity and the structure of keratinocytes.
[0176] - LOR contributes to the protective barrier function of the stratum corneum.
[0177] - TRPV4 (a cation channel activated by hypotonicity, moderate heat, or shear stress) is required for the proper establishment of tight junctions and the regulation of the barrier function of both tight junctions.
[0178] - SMPD1 is an enzyme that degrades sphingomyelin into ceramide and phosphorylcholine, and ceramide is an important factor in lysosome biosynthesis. Lysosomes are known to play a role in epidermal homeostasis in many cases.
[0179] These results demonstrated that JSE can maintain and enhance skin barrier function. In fact, JSE induces a statistically significant overexpression of several proteins of interest for the epidermal differentiation process (a major biological process involved in maintaining skin barrier function).
[0180] Improvement of skin water retention Table 4 shows the ability of JSE to improve skin water retention in NHEK. In fact, the expression of the genes AGPAT9, BLMH, HAL, XYLT1, and CSPG4 was statistically significantly upregulated in cells treated with JSE.
[0181] - AGPAT9 is an enzyme involved in glycerolipid and glycerophospholipid metabolism. This functions as a source of free fatty acids that are later known to be often involved in maintaining the epidermal permeability barrier function.
[0182] - BLMH is a protease involved in the degradation of citrullinated filaggrin monomers into free amino acids of interest for skin water retention. The expression and activity of BLMH have been shown to be decreased in patients suffering from atopic dermatitis and psoriasis.
[0183] - HAL catalyzes the histidine degradation in urocanate derived from the catabolism of filaggrin in the skin.
[0184] - XYLT1 is an enzyme that catalyzes the transfer of UDP-xylose to serine residues. The addition of this xylose to the core protein is required for the biosynthesis of glycosaminoglycan chains characteristic of proteoglycans.
[0185] - CSPG4 is a cell surface proteoglycan that binds specifically to another proteoglycan, perlecan.
[0186] These results demonstrated that JSE can maintain skin health by keeping the skin in a well-hydrated state. In fact, JSE induces a statistically significant overexpression of several enzymes and macromolecules, such as CSPG4, which often function in the skin hydration process.
[0187] Anti-scarring properties, anti-fibrotic properties Table 5 shows the ability of JSE to improve fibrotic skin by regulating the expression of genes involved in connective tissue formation and its breakdown in NHDF. These results demonstrated that JSE acts as an anti-fibrotic agent and can improve the healing outcomes of fibrotic scars, such as hypertrophic scars and keloid scars. Furthermore, JSE stimulated the expression of elastin. This allows for better comfort of the skin. In fact, the stimulation of elastin expression in scarred skin makes the skin more supple and thus restores better skin sensation and comfort. In fact, scarred skin suffers from the hardness associated with the loss of skin comfort.
[0188] Skin suctioning properties Table 6 shows the ability of JSE to soothe the skin in NHEK. Indeed, a statistically significant downregulation of TRPV1 mRNA expression was observed in keratinocytes treated with JSE. These results demonstrated that JSE has soothing properties, which can be useful for sensitive and itchy skin. Furthermore, JSE may also be beneficial for dry skin / dry skin, which is known to be quite reactive and painful. Inhibition of TRPV1 can also be interesting for atopic and psoriatic skin.
[0189] Inhibition of hair growth Table 7 shows the ability of JSE to inhibit hair growth in NHEK. Indeed, a statistically significant downregulation of DKK1 mRNA expression was observed in keratinocytes treated with JSE. Since DKK1 is an inhibitor of the Wnt pathway, a major biological pathway involved in the hair growth cycle, it can be considered that JSE can reduce hair growth.
[0190] 4. Transcriptome study for evaluation of biological activity of JSE against reconstituted human epidermis To confirm the results obtained with the skin cells (NHDF, NHEK) isolated in Example 3, gene expression evaluated by RTqPCR assay was further realized on reconstructed human epidermis (RHE) infected or not infected with Malassezia furfur, treated or not treated with JSE at a concentration of 0.25% by weight. RHE is a well-known model that mimics the behavior of the human epidermis. The preparation method (RTqPCR) is the same as described in Example 3.
[0191] The results obtained with RHE confirmed the results obtained with the isolated skin cells as discussed in Example 3, Table 1. Indeed, JSE enhances the skin's ability to induce the expression of antimicrobial defense genes after skin infection with Malassezia furfur, as shown below:
[0192] [Table 8]
[0193] Confirmation of the stimulation of the skin's innate antimicrobial defense mechanism As shown in Table 8, in RHE, the ability of JSE to protect the skin from Malassezia furfur through induction of the expression of endogenous antimicrobial peptides is demonstrated and confirmed. Surprisingly, JSE has no direct inhibitory activity against Malassezia furfur. Furthermore, Table 8 emphasizes that JSE is able to induce the synthesis of antimicrobial peptides in RHE as compared to Table 1. Indeed, CAMP, hBD1 and RNase7 are also modulated. CAMP is a peptide cleaved into the active form of LL-37 with broad-spectrum antimicrobial activity. RNase7 has shown strong ribonuclease activity against human skin. RNase7 has broad-spectrum antimicrobial activity.
[0194] Stimulation of the expression of these antimicrobial peptides is known to have beneficial effects, for example, to prevent dandruff formation on the scalp, to soothe the scalp, and more generally, to maintain the health of the skin and scalp.
[0195] Confirmation of the anti-inflammatory properties of JSE in RHE The results obtained in RHE also confirmed the results obtained with isolated skin cells as discussed in Example 3, Table 2. Indeed, JSE enhances the skin's ability to inhibit the expression of inflammatory genes after colonization of the skin by Malassezia furfur, as shown below:
[0196] [Table 9]
[0197] Table 9 demonstrates that JSE exhibits anti-inflammatory properties in RHE, because it enables significant inhibition of the mRNA expression of several pro-inflammatory markers (IL1, TNF, IL-17). Therefore, JSE is able to calm the skin.
[0198] Confirmation of improvement of skin barrier function in RHE The results obtained in RHE are in line with the results obtained for the skin cells isolated in Example 3, Table 3, and confirm the ability of JSE in the recovery and / or maintenance of the epidermal barrier function of the skin.
[0199] To further investigate, a lucifer yellow permeability assay was performed on RHE that had been treated or not treated with JSE and infected or not infected with Malassezia furfur. As shown in Figure 2, in the absence of Malassezia furfur, JSE (0.1% and 0.25%) did not affect the barrier permeability of RHE.
[0200] In the presence of Malassezia furfur in RHE, lucifer yellow managed to pass through the epidermis somehow, which means that the epidermal barrier function was disrupted by yeast colony formation. Surprisingly, when RHE was infected with Malassezia furfur and treated with JSE (0.1% and 0.25%), a recovery of the epidermal barrier function was observed. In fact, JSE was able to restore the epidermal barrier function at the same level as ketoconazole, a known antifungal compound used as a positive control.
[0201] Furthermore, the results obtained by periodic acid-Schiff (PAS) staining, either after Malassezia furfur colony formation in RHE or without Malassezia furfur colony formation, demonstrated the ability of JSE to reduce the amount of Malassezia furfur on the RHE surface (data not shown).
Claims
1. The following (A) and (B): (A) At least two sambacosides including sambacoside A, and (B) At least two morrhuacids, A water extract or hydroalcoholic extract of the leaves of Jasminum sambac containing an iridoid glycoside containing the same.
2. The extract according to claim 1, wherein - The at least two sambacosides are selected from sambacoside E or F, or a mixture thereof, and - The morrhuacids are selected from morrhuacids A, B, C, D and E, or a mixture of two or more thereof, The extract.
3. The extract according to claim 1 or 2, wherein the extract contains sambacosides A, E and F, and the morrhuacids are morrhuacids A to E.
4. The following: (A) Sambacoside A in an amount of 30 to 70% by weight, preferably 35 to 65% by weight, more preferably 40 to 60% by weight, based on the total weight of the iridoid glycoside; and / or (B) Morrhuacids in an amount of 1 to 70% by weight, preferably 10 to 60% by weight, based on the total weight of the dry matter of the extract; and / or (C) One or more phenolic components in an amount of 15 to 60% by weight, preferably 20 to 50% by weight, more preferably 25 to 45% by weight, particularly 30 to 40% by weight, based on the total weight of the dry matter of the extract, The extract according to any one of claims 1 to 3, further characterized by containing the same.
5. The extract according to any one of claims 1 to 4, wherein the total iridoid content corresponds to 1000 to 3000 ppm, preferably 1500 to 2500 ppm, more preferably 1800 to 2200 ppm, expressed in oleuropein equivalents.
6. The extract according to any one of claims 1 to 5, wherein the dry matter content of the extract corresponds to 5 g / L to 15 g / L, preferably 7 g / L to 13 g / L, more preferably 8.5 g / L to 12 g / L (weight / volume of the solvent).
7. An extract according to any one of claims 1 to 6, which can be obtained by solid / liquid extraction of the leaves of Jasminum sambac in a solvent selected from water or a mixture of water and alcohol, wherein the alcohol is selected from the group consisting of glycerol, propanediol, methanol, ethanol, propanol, butanol, butylene glycol, propylene glycol and combinations of two or more thereof, said extract.
8. An extract according to any one of claims 1 to 7, wherein the solvent is a mixture of ethanol / water, a mixture of glycerol / water, or a mixture of propanediol / water.
9. An extract according to any one of claims 1 to 8, which is a hydroalcoholic extract, wherein the water / alcohol ratio is 5:95 (v / v), preferably 10:90 (v / v), more preferably 20 / 80 (v / v), particularly 30:70 (v / v), said extract.
10. A method for producing an extract according to any one of claims 1 to 9, comprising the following steps: i) Optionally dried, the step of pulverizing the leaves, ii) The step of subjecting the pulverized leaves to solid / liquid extraction with at least one solvent selected from water or a mixture of water and alcohol, wherein the alcohol is selected from the group consisting of glycerol, propanediol, methanol, ethanol, propanol, butanol, butylene glycol, propylene glycol, and preferably, the solvent is a mixture of ethanol / water, a mixture of glycerol / water, or a mixture of propanediol / water in a ratio of 95:5 to 5:95, preferably 90:10 to 20:80, more preferably 70:30 to 50:50, a) The solid / liquid extraction is carried out at room temperature for 30 minutes to 10 hours, preferably 45 minutes to 8 hours, more preferably 1 hour to 5 hours, b) The solid / liquid ratio is 1:5 to 1:20, preferably 1:7 to 1:
15. Said step, iii) The step of separating the solid phase and the liquid phase to recover the liquid part, iv) Optionally, the step of concentrating the liquid part containing the solvent-based extract by removing at least part of the extraction solvent.
11. The following: - As an active ingredient, an extract according to any one of claims 1 to 9, or an extract obtained from the method according to claim 10; and - At least one cosmetic and / or pharmaceutically acceptable ingredient other than the extract of the leaves of Jasmin sambac, A cosmetic or pharmaceutical composition comprising: a composition for external use selected from the group consisting of solutions, suspensions, emulsions, creams, pastes, gels, lotions, powders, soaps, surfactant-containing water, oils, shampoos and sprays, or a nutraceutical composition for oral administration.
12. Use of a composition comprising or consisting of the extract according to any one of claims 1 to 9 or the cosmetic composition according to claim 10 in skin care, for the following purposes: - Improving and / or restoring skin barrier function and / or skin hydration, - Improving skin elasticity, - Preventing the formation of stretch marks, - Preventing and / or regulating sebum secretion, - Preventing the oily appearance of the skin, or - A combination of two or more of them.
13. A composition comprising or consisting of the extract according to any one of claims 1 to 9 or the cosmetic composition according to claim 10 for use as an anti-dandruff agent.
14. A composition comprising or consisting of the extract according to any one of claims 1 to 9 or the cosmetic composition according to claim 10 as an antioxidant.
15. A composition comprising or consisting of the extract according to any one of claims 1 to 9 or the cosmetic composition according to claim 10 as a whitening agent.
16. Use of a composition comprising or consisting of the extract according to any one of claims 1 to 9 or the cosmetic composition according to claim 10 in skin care for the following purposes: - Stimulating the skin's innate antimicrobial defense mechanism, - Preventing skin dysbiosis, - Maintaining or restoring skin symbiosis, - Reducing skin inflammation and / or soothing the skin, - Reducing fibrosis, particularly when associated with scar formation, - A combination of two or more of them.
17. A composition for use according to claim 16, wherein the skin care is for reducing the amount and / or degree of reddish skin lesions, preferably the skin care is for managing skin prone to atopic dermatitis, acne lesions, fibrotic lesions, scarring, inflammation, redness or a combination of two or more thereof.
18. Use of a composition comprising or consisting of an extract according to any one of claims 1 to 9 or a cosmetic composition according to claim 11 for inhibiting hair growth.
19. Use of a composition comprising or consisting of an extract according to any one of claims 1 to 9 or a cosmetic composition according to claim 11 for preventing an oily appearance of hair.
20. The water extract or hydroalcoholic extract of the leaves of Jasminum sambac, preferably a composition comprising or consisting of an extract according to any one of claims 1 to 9, as an active ingredient for use in a method for the treatment or prevention of skin disorders selected from the group consisting of atopic dermatitis, acne, dandruff, fibrotic injury, scar, pathological skin redness, pathological skin inflammation, and combinations of two or more thereof.
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