Composition comprising at least one boswellic acid and a hyaluronan for use in the treatment of dermatoporosis

Abstract

A composition for use in the treatment of dermatoporosis, comprising: at least one boswellic acid, optionally in the form of a plant extract in a proportion of 0.1 to 15% by weight relative to the weight of the composition, a hyaluronan in a proportion of 0.1 to 15% by weight relative to the weight of the composition, said composition further having a proportion by weight of boswellic acid to hyaluronan of between 0.5 and 2 and an excipient phase in a proportion of 99.8% to 70% by weight relative to the weight of the composition, the excipient phase being aqueous-based.

Description

[0001] Composition comprising at least one boswellic acid and one hyaluronane for use in the treatment of dermatoporosis

[0002] The present invention relates to a composition for use in the treatment of dermatoporosis.

[0003] Dermatoporosis, sometimes called "osteoporosis of the skin," is a chronic condition associated with skin aging. It manifests as increased skin fragility, making the skin thinner, more delicate, and more prone to injury. This condition primarily affects older adults and is characterized by skin atrophy, loss of elasticity, and a decrease in skin thickness.

[0004] It primarily affects the epidermal and dermal layers, causing a range of visible and functional changes. The skin gradually becomes thinner, a consequence of the atrophy of the epidermal and dermal layers. This atrophy is due to a decrease in the production of collagen, elastin, and hyaluronic acid, which are essential for skin firmness, elasticity, and hydration.

[0005] At the epidermal level, dermatoporosis leads to a reduction in the keratinocytes' ability to regenerate, thus slowing cell renewal. This results in more vulnerable skin, prone to dehydration and microtrauma. The stratum corneum loses cohesion, making the skin more fragile and less resistant to external aggressors, such as UV rays or chemical irritants.

[0006] In the dermis, the decrease in the density and quality of collagen and elastin fibers weakens the overall structure of the skin. Blood vessels become more fragile, which explains the frequent occurrence of bruising (senile purpura) even after minor trauma. This vascular fragility is often accompanied by poor wound healing, as the dermis's capacity to support repair processes is significantly reduced. Alteration of the dermis's extracellular matrix, combined with a decrease in hyaluronic acid, leads to a significant loss of hydration. The skin then becomes dry, less elastic, and more prone to cracking or tearing. These cracks and lesions can develop into chronic wounds, increasing the risk of infection and complications.

[0007] Dermatoporosis also affects the overall appearance of the skin, which becomes translucent, parchment-like, and sometimes marked by hyperpigmented areas or textural irregularities. These aesthetic changes, combined with functional fragility, can have a significant psychological impact on patients, diminishing their quality of life and self-confidence.

[0008] Dermatoporosis is often caused by a combination of factors, including intrinsic aging, chronic UV damage, and sometimes prolonged use of corticosteroids, which impair collagen and elastin production. Affected skin has a translucent appearance, revealing the underlying veins, and is particularly vulnerable to tearing and bruising, even from minor trauma. This, combined with a reduced capacity for wound healing, can lead to complications such as ulcers or infections.

[0009] Possible treatments for dermatoporosis aim to strengthen the skin's structure, improve hydration, and reduce fragility. These treatments include retinoids, which stimulate collagen production and thicken the skin, and hyaluronic acid, which hydrates and improves skin elasticity. There are also treatments containing antioxidants, such as vitamins C and E, which protect the skin from oxidative stress. Some formulations include growth factors and biomimetic peptides to promote cell repair and dermal regeneration. These treatments can be combined to provide a comprehensive approach tailored to each patient.Such compositions are well known from the prior art, see for example document WO2024 / 163456 which describes a topical composition comprising an extract of Centella asiatica encapsulated in liposomes and an alpha-hydroxy acid which can be used for the treatment and reduction of the effects of dermatoporosis.

[0010] Document EP2237775 describes a topical composition including 6-formylindolo[3,2-b]carbazole for the treatment of dermatoporosis.

[0011] Unfortunately, these active ingredients are expensive, sometimes complex to produce or of synthetic origin, and their effectiveness proves to be insufficient for the treatment of dermatoporosis.

[0012] The invention aims to overcome the drawbacks of the prior art by providing an invention that allows dermatoporosis to be treated effectively using more natural, inexpensive active ingredients that do not necessarily require costly or complex production steps.

[0013] To solve this problem, the invention provides a composition as indicated at the beginning comprising: at least one boswellic acid, possibly in the form of a plant extract in a proportion of 0.1 to 15% by weight relative to the weight of the composition, preferably 0.5% to 5% by weight relative to the weight of the composition, a hyaluronan in a proportion of 0.1 to 15% by weight relative to the weight of the composition, preferably 0.5% to 5% by weight relative to the weight of the composition, said composition further having a weight proportion between the boswellic acid and the hyaluronan of between 0.5 and 2 and an excipient phase in a proportion of 99.8% to 70% by weight relative to the weight of the composition, said excipient phase being aqueous-based.

[0014] It has indeed been surprisingly identified that the aforementioned composition provides rapid relief and improved skin elasticity. While not specifically linked to any particular theory, it is believed that the present invention enables excellent synergy between at least one boswellic acid and / or a plant extract comprising at least one boswellic acid present in a proportion of 0.1 to 15% by weight relative to the composition, and hyaluronan present in a proportion of 0.1 to 15% by weight relative to the composition, which is further enhanced by the presence of water in the excipient.

[0015] Indeed, boswellic acids have remarkable effects on the skin. Their most notable property is their powerful anti-inflammatory effect, which results from their ability to inhibit the production of inflammatory mediators such as 5-lipoxygenase and leukotrienes. This helps reduce redness, irritation, and skin inflammation, making them particularly suitable for sensitive skin or skin prone to conditions such as acne, eczema, or rosacea.

[0016] Furthermore, boswellic acids possess antioxidant properties, protecting the skin against damage caused by free radicals and thus slowing the effects of skin aging. They also contribute to skin regeneration by promoting the repair of damaged tissue and stimulating the activity of fibroblasts, which are essential for collagen production and maintaining skin elasticity. In addition, they have a soothing effect on sensations of discomfort, such as tightness or itching, while strengthening the skin barrier.

[0017] Some research suggests that boswellic acids may also support dermal structure by inhibiting enzymes responsible for collagen degradation, thus contributing to skin firmness and resilience.

[0018] Furthermore, hyaluronans have essential and varied effects on the skin. Their main property lies in their exceptional ability to retain water, which helps maintain intense hydration. This hydration improves skin elasticity, reduces feelings of dryness, and promotes softer, more supple skin. By filling the intercellular spaces, hyaluronans also provide a plumping effect that helps smooth fine lines and wrinkles, restoring volume to sagging areas of the skin.

[0019] By strengthening the skin's natural protective barrier, they limit transepidermal water loss and increase the skin's resistance to external aggressors. Furthermore, they play a key role in skin regeneration by stimulating the migration and proliferation of essential cells, such as keratinocytes and fibroblasts, thus contributing to skin repair and renewal.

[0020] Hyaluronans also have a soothing effect, helping to reduce irritation, redness, and discomfort, which is particularly beneficial for sensitive skin. Finally, albeit indirectly, they create an environment conducive to collagen synthesis in the dermis, thus strengthening the skin's firmness and structure.

[0021] Together, these components create a powerful synergistic effect. Boswellic acid inhibits enzymes responsible for the breakdown of skin firmness and elasticity, while hyaluronic acid and water hydrate and repair the skin. This holistic approach not only provides relief but also improves the elasticity and long-term health of skin tissue, making it a highly effective solution for managing dermatoporosis.

[0022] The term "at least one boswellic acid" refers to one or more individual molecules of boswellic acids, regardless of their origin. These molecules can be obtained in isolation, either by extraction and purification from a natural source such as Boswellia tree resin, or chemically synthesized in the laboratory, without any necessary link to a plant source. The term "as a plant extract" describes a complex substance obtained directly from a plant source, such as Boswellia resin. This extract contains not only boswellic acids, such as 3-boswellic acid, acetylboswellic acid, 1,1-ketoboswellic acid, 3-O-acetyl-1,1-ketoboswellic acid, and mixtures thereof, but also other compounds naturally present in the plant source, such as polysaccharides, essential oils, or other triterpenes.The plant extract may contain, for example, approximately 70% by mass of boswellic acids relative to the mass of the extract. This expression emphasizes the plant origin of the substance and stresses that the boswellic acids are present in a natural mixture rather than in isolation.

[0023] In the context of the present invention, the term "dermatoporose" refers to a specific chronic skin condition, distinct from simple physiological aging of the skin.

[0024] Dermatoporosis corresponds to a chronic skin insufficiency linked to a functional alteration of the skin, characterized by dermo-epidermal atrophy, a decrease in mechanical resistance, increased vascular fragility and delayed healing.

[0025] Clinically, this condition manifests as senile purpura, stellate pseudo-scars, spontaneous skin lacerations, and, in advanced forms, specific complications such as dissecting cutaneous hematomas.

[0026] Dermatoporosis thus constitutes a defined nosological entity, documented in the medical literature (notably Saurat et al., Med Hyg, 2004, 62: 476; Kaya et al., Rev Med Suisse, 2008, 4: 1078-1082), and should not be confused with aesthetic or superficial alterations of skin aging.

[0027] It results in particular from a failure of dermal structures linked to the degradation of the extracellular matrix, in particular of the metabolism of hyaluronic acid and the CD44 pathway, leading to a progressive loss of the protective and repairing properties of the skin.

[0028] Consequently, any reference to dermatoporosis in this application relates to a medical condition distinct from ordinary skin aging, characterized by a specific set of clinical, histological and functional signs such as marked skin atrophy, very thin and translucent skin, senile purpura, stellate pseudo-scars, and functional manifestations of fragility such as skin tears after minimal trauma, delayed wound healing. Advantageously, said at least one boswellic acid is selected from the group comprising [3-boswellic acid, acetyl-boswellic acid, 1 1-keto-boswellic acid, 3-O-acetyl-1 1-keto-boswellic acid, and mixtures thereof.

[0029] Preferably, hyaluronan is chosen from the group including hyaluronic acid, sodium hyaluronate, potassium hyaluronate, calcium hyaluronate, magnesium hyaluronate, zinc hyaluronate, and mixtures thereof.

[0030] Advantageously, hyaluronate is composed of low molecular weight hyaluronate and high molecular weight hyaluronate.

[0031] High molecular weight (HMP) hyaluronan consists of large molecules, generally exceeding 500 kDa. These molecules remain on the skin's surface, where they form a protective film that prevents dehydration by limiting transepidermal water loss. This type of hyaluronan acts primarily as a surface moisturizer, providing an immediate smoothing and plumping effect while strengthening the skin barrier.

[0032] Low molecular weight (LMWH) hyaluronan is composed of smaller molecules, generally less than 500 kDa. Thanks to their reduced size, these molecules can penetrate deeper into the layers of the epidermis and sometimes as far as the dermis. They stimulate deep hydration and promote biological processes such as cell regeneration and collagen production. LMWH thus helps improve skin elasticity and reduce the appearance of wrinkles and fine lines more lastingly.

[0033] Preferably, the weight ratio between low molecular weight hyaluronate and high molecular weight hyaluronate is between 5 and 20. Preferably, said excipient phase comprises, in addition to water, at least one fat body selected from the group including paraffin oil, petrolatum oil, vegetable oils, vegetable fats, animal oils, animal fats, glycerides, waxes, polyalkylsiloxanes, esters of lanolic acid, oleic acid, lauric acid, stearic acid, fatty esters, fatty acids with at least 12 carbon atoms, fatty alcohols with at least 12 carbon atoms, silicone oils, fatty acid-modified polysiloxanes, fatty alcohols, polyoxyalkylenes, and mixtures thereof.

[0034] Vegetable oils can be, for example, sunflower oil, sweet almond oil, argan oil, jojoba oil, coconut oil, avocado oil.

[0035] Vegetable fats can be, for example, shea butter, cocoa butter, mango butter, cupuaçu butter, murumuru butter.

[0036] Animal oils can be, for example, cod liver oil, mink oil, emu oil

[0037] Animal fats can be, for example, lanolin, tallow.

[0038] Preferably, this excipient phase includes glycerol (glycerin). Glycerol is a fatty substance that helps to hydrate and repair dry skin.

[0039] Advantageously, said excipient phase comprises a preservative selected from the group comprising phenoxyethanol, benzoic acid and its salts, sorbic acid and its salts, benzyl alcohol, dehydroacetic acid, sodium benzoate, potassium sorbate, sorbitan caprylate, and mixtures thereof.

[0040] Preferably, said excipient phase comprises an emulsifying agent selected from the group comprising sorbitan esters, monoglycerides, fatty alcohols, sulfated fatty alcohols, polysorbates, fatty acid esters, and mixtures thereof.

[0041] Advantageously, said excipient phase includes a binding agent, for example maltodextrin.

[0042] Preferably, said excipient phase includes a thickening agent, for example xanthan gum.

[0043] Advantageously, said excipient phase includes a humectant agent, for example propanediol.

[0044] Preferably, said excipient phase includes an antioxidant agent, for example tocopherol.

[0045] Advantageously, said excipient phase includes a pH regulating agent, for example sodium hydroxide.

[0046] Preferably, the composition is presented in the form of an ointment, a cream, or a lotion.

[0047] Other embodiments of the composition according to the invention are indicated in the attached claims.

[0048] Other features, details and advantages of the invention will become apparent from the description given below, by way of non-limitation and with reference to the drawings and examples.

[0049] Example 1

[0050] A composition for the treatment of dermatoporosis was prepared comprising 70.25% by weight of water, 0.30% by weight of sodium benzoate, 6% by weight of glycerin, 1% by weight of low molecular weight hyaluronic acid, 0.1% by weight of high molecular weight hyaluronic acid, 0.5% by weight of xanthan gum, 3% by weight of shea butter, 2% by weight of C15-C19 branched alkanes, 8.03% by weight of sunflower oil, 5% by weight of glyceryl stearate, and 0.07% by weight of ratio to the weight of the tocopherol composition, 0,81% by weight relative to the weight of the sorbitan caprylate composition, 0.25% by weight relative to the weight of the propanediol composition, 0.19% by weight relative to the weight of the benzoic acid composition, 2% by weight relative to the weight of the Boswellia Serrata resin extract composition standardized to 65% by mass of boswellic acids relative to the mass of the extract, 0.5% by weight relative to the weight of the maltodextrin composition and a sufficient quantity of sodium hydroxide 10%.

[0051] Example 2

[0052] A study was conducted on 33 patients, using the product described in Example 1 twice daily. Patients assessed changes in their skin's appearance in terms of firmness, plumpness, and smoothness using a questionnaire completed at the beginning of the study, and again after 30 and 60 days of use. This study was conducted in comparison with a control sample containing the same formulation as Example 1, but without the Boswellia serrata resin extract, which was replaced by water, resulting in a total water content of 72.25% by weight in the control product. Both products were evaluated using the same methodology.

[0053] The results show that applying the product according to Example 1 leads to a 41% increase in skin firmness after 30 days, and a 101% increase after 60 days compared to the initial value. In comparison, the control sample lacking boswellic acids only induces a 30% increase after 60 days of application. Regarding skin plumpness, the product in Example 1 generates a 55% improvement after 30 days and a 119% improvement after 60 days, while the comparator product only leads to a 40% improvement after 60 days. The skin smoothness assessment also indicates significant progress, with a 57% increase after 30 days and a 114% increase after 60 days of applying the product according to Example 1.

[0054] It is understood that the present invention is in no way limited to the embodiments described above and that many modifications can be made to it without departing from the scope of the attached claims.

Claims

DEMANDS 1. Composition for use in the treatment of dermatoporosis comprising: at least one boswellic acid, optionally in the form of a plant extract in a proportion of 0.1 to 15% by weight relative to the weight of the composition, preferably 0.5% to 5% by weight relative to the weight of the composition, one hyaluronan in a proportion of 0.1 to 15% by weight relative to the weight of the composition, preferably 0.5% to 5% by weight relative to the weight of the composition, said composition further having a weight proportion between boswellic acid and hyaluronan of between 0.5 and 2 and an excipient phase in a proportion of 99.8% to 70% by weight relative to the weight of the composition, said excipient phase being aqueous-based.

2. Composition for use in the treatment of dermatoporosis according to claim 1, wherein said at least one boswellic acid is selected from the group comprising [3-boswellic acid, acetyl-boswellic acid, 1 1-keto-boswellic acid, 3-O-acetyl-1 1-keto-boswellic acid, and mixtures thereof.

3. Composition for use in the treatment of dermatoporosis according to claim 1 or 2, wherein the hyaluronan is selected from the group comprising hyaluronic acid, sodium hyaluronate, potassium hyaluronate, calcium hyaluronate, magnesium hyaluronate, zinc hyaluronate, and mixtures thereof.

4. Composition for use in the treatment of dermatoporosis according to any one of the preceding claims, wherein the hyaluronate is composed of low molecular weight hyaluronate and high molecular weight hyaluronate.

5. Composition for use in the treatment of dermatoporosis according to claim 4, wherein the weight ratio between low molecular weight hyaluronate and high molecular weight hyaluronate is between 5 and 20.

6. Composition for use in the treatment of dermatoporosis according to any one of the preceding claims, wherein said excipient phase comprises, in addition to water, at least one fatty substance selected from the group including paraffin oil, petrolatum oil, vegetable oils, vegetable fats, animal oils, animal fats, glycerides, waxes, polyalkylsiloxanes, esters of lanolic acid, oleic acid, lauric acid, stearic acid, fatty esters, fatty acids with at least 12 carbon atoms, fatty alcohols with at least 12 carbon atoms, silicone oils, fatty acid-modified polysiloxanes, fatty alcohols, polyoxyalkylenes, and mixtures thereof.

7. Composition for use in the treatment of dermatoporosis according to any one of the preceding claims, wherein said excipient phase comprises a preservative selected from the group comprising phenoxyethanol, benzoic acid and its salts, sorbic acid and its salts, benzyl alcohol, dehydroacetic acid, sodium benzoate, potassium sorbate, sorbitan caprylate, and mixtures thereof.

8. Composition for use in the treatment of dermatoporosis according to any one of the preceding claims, wherein said excipient phase comprises an emulsifying agent selected from the group comprising sorbitan esters, monoglycerides, fatty alcohols, sulfated fatty alcohols, polysorbates, fatty acid esters, and mixtures thereof.

9. Composition for use in the treatment of dermatoporosis according to any one of the preceding claims, wherein said excipient phase comprises a binding agent, for example maltodextrin.

10. Composition for use in the treatment of dermatoporosis according to any one of the preceding claims, wherein said excipient phase comprises a thickening agent, for example xanthan gum.

1. A composition for use in the treatment of dermatoporosis according to any one of the preceding claims, wherein said excipient phase comprises a humectant, for example, propanediol.

12. A composition for use in the treatment of dermatoporosis according to any one of the preceding claims, wherein said excipient phase comprises an antioxidant, for example, tocopherol.

13. Composition for use in the treatment of dermatoporosis according to any one of the preceding claims, wherein said excipient phase comprises a pH regulating agent, for example sodium hydroxide.

14. Composition for use in the treatment of dermatoporosis according to any one of the preceding claims, in the form of an ointment, a cream, a lotion.