USO DE RAMNOLIPÍDEO, PROCESSO PARA A OBTENÇÃO DE RAMNOLIPÍDEOS, RAMNOLIPÍDEO, COMPOSIÇÃO COSMÉTICA PARA INFLAMAÇÃO ASSOCIADA AO ENVELHECIMENTO E / OU SENESCÊNCIA CELULAR, COMPOSIÇÃO COSMÉTICA E MÉTODO PARA TRATAMENTO DERMOCOSMÉTICO

Description

USE OF RHAMNOLIPID, PROCESS FOR OBTAINING RHAMNOLIPIDS, RHAMNOLIPID, COSMETIC COMPOSITION FOR INFLAMMATION ASSOCIATED WITH AGING AND / OR Cellular senescence, cosmetic composition and method for dermocosmetic treatment. FIELD OF THE INVENTION

[001] The present invention relates to the use of rhamnolipids for the prevention, attenuation and / or reversal of inflammation associated with aging (“inflammaging” in English) and / or cellular senescence, as well as a process for obtaining rhamnolipids, rhamnolipids, a cosmetic composition and a method of dermocosmetic treatment. BACKGROUND OF THE INVENTION

[002] Inflammaging, also known as inflammatory aging, is a chronic, low-grade, and asymptomatic inflammation that manifests during physiological aging, characterized by an increase in circulating levels of pro-inflammatory cytokines. This type of inflammation may be associated with immune system dysfunction and other age-related changes, and is considered a pathogenic factor in the development of several age-related diseases, such as atherosclerosis, type 2 diabetes, and Alzheimer's disease.

[003] “Inflammaging” is characterized by continuous activation of the innate immune system, with constant release of pro-inflammatory cytokines such as IL-6, TNF-α and β-1β, in addition to the activation of pathways such as NF-κB and inflammasomes. This chronic inflammatory state is driven by several factors, including cellular senescence, mitochondrial dysfunction, accumulation of advanced glycation end products (AGEs), alterations in the microbiota, and prolonged exposure to environmental stressors such as UV radiation and pollutants. Effects of "inflammaging" on the skin:

[004] - Functional and structural decline: aged skin becomes Petition 870260044168, dated 11 / 05 / 2026, page 6 / 63 2 / 22 more fragile and susceptible to infections. Degradation and disorganization of collagen and elastic fibers are observed in the dermis and dermoepidermal junction, resulting in decreased elasticity and tensile strength of the skin. Deterioration of epidermal cell-cell junctions also contributes to the greater fragility of the skin in the elderly.

[005] - Impaired wound healing: the ability of wounds to heal is impaired, which exacerbates the risk of infection.

[006] - Increased susceptibility to skin infections and diseases: Skin infections, for example, caused by staphylococci and streptococci, are frequent in the elderly due to the decline in skin barrier function and immune capabilities.

[007] - Changes in skin appearance: “Inflammaging” also contributes to changes in the function and appearance of aging skin, with the appearance of wrinkles, sagging, spots, dryness, among others.

[008] - Disruption of the Skin Barrier: disruption of the epidermal barrier is a common cause of skin inflammation, which can lead to local and systemic inflammation. Biological markers of "inflammaging"

[009] • Elevated Pro-inflammatory Cytokines:

[0010] IL-6 (Interleukin-6): It is produced by innate and non-immune immune cells that become dysfunctional with age. In addition, human fibroblasts from older individuals produce higher levels of IL-6 in response to infections or exposure to lipopolysaccharides (LPS). It is one of the most consistently elevated markers in serum levels of elderly individuals with “inflammaging”.

[0011] IL-8 (Interleukin-8): Elevated serum levels of IL-8 are characteristic of “inflammaging”. In addition, fibroblasts from aged skin exhibit a Senescence-Associated Secretory Phenotype (SASP) rich in IL-8. Petition 870260044168, dated 11 / 05 / 2026, page 7 / 63 3 / 22

[0012] TNF-α (Tumor Necrosis Factor alpha): This marker is also elevated in cases of "inflammaging". Its production can be increased by dysfunctional innate and non-immune immune cells in the elderly. TNF-α levels in the skin may increase after acute disruption of the skin barrier.

[0013] ^-1β (Interleukin-1 beta): Increases in ^-1β levels are observed in age-related diseases and contribute to “inflammaging”. It is secreted as part of SASP by senescent fibroblasts.

[0014] IFN-γ (Interferon gamma): It is one of the components of SASP (“senescence-associated secretory phenotype”) and SAASP (“skin aging-associated secretory phenotype”), which include cytokines and other inflammatory mediators. In elderly individuals, dysfunctional CD4+ and CD8+ T cells produce more TNF-α and IFN-γ, which contributes to the systemic “inflammaging” process.

[0015] • Chemokines:

[0016] CCL2 (Chemokine CC motif 2 ligand) and CCL5 (Chemokine CC motif 5 ligand): The production of these chemokines has been observed in mononuclear cells, and Resveratrol has demonstrated the ability to decrease them, indicating their role as markers of inflammation.

[0017] • Proteins and Other Systemic Markers:

[0018] C-reactive protein (CRP): Elevated CRP levels are a characteristic of “inflammaging”.

[0019] ICAM-1 (Intercellular Adhesion Molecule-1): It has been found at higher levels in patients with psoriasis (an inflammatory skin condition that can lead to systemic inflammation).

[0020] sCD40L (Soluble CD40 Ligand) and TGF-α (Transforming Growth Factor alpha): Both are found at significantly higher levels in elderly individuals, suggesting a role in age-related inflammation. Petition 870260044168, dated 11 / 05 / 2026, page 8 / 63 4 / 22

[0021] · Cellular and Molecular Phenotype:

[0022] SASP (Senescence-Associated Secretory Phenotype): Senescent cells accumulate in aged tissues, including the skin, and secrete SASP, a set of pro-inflammatory factors, chemokines, and matrix metalloproteinases (MMPs), which alter the tissue microenvironment and contribute to "inflammaging".

[0023] MMPs (Matrix Metalloproteinases): Various subtypes of MMPs (MMP1, MMP3, MMP7, MMP9, MMP10, MMP13, MMP14) are involved in the degradation of the extracellular matrix (ECM) and are markers of tissue damage in skin aging and inflammatory conditions.

[0024] TIMP1 (Tissue Inhibitor of Metalloproteinase 1): Although it is an inhibitor of MMPs, the increase in its transcriptional expression in aged skin (both chronologically and photo-exposed) suggests a protective and repair mechanism against collagen degradation associated with “inflammaging”.

[0025] FGF2 (Fibroblast Growth Factor 2): Increased FGF2 and TIMP1 in aged skin (chronologically and photoaged) may be associated with "inflammaging" and skin aging, as it is related to tissue repair and the control of collagen degradation mediated by MMPs. Elevated FGF2 may therefore be a compensatory response to this inflammatory state and tissue damage.

[0026] • Activation of Cellular Signaling Pathways:

[0027] NF-kB (Nuclear Factor kappa B): Activation of the NF-kB pathway is a key component of “inflammaging.” It increases with chronological age in the skin and other tissues, and is crucial in inducing senescence and SASP. NF-kB can also induce the expression of pro-inflammatory cytokines and regulate inflammatory T cells.

[0028] MAPK (Mitogen-Activated Protein Kinase): Activation Petition 870260044168, dated 11 / 05 / 2026, page 9 / 63 5 / 22 of the MAPK pathways (such as p38, JNK, ERK) are associated with "inflammaging".

[0029] AP-1 (Activator Protein 1): Its activation, resulting from the inflammatory cascade and the recruitment of proteins such as c-Fos and c-Jun, leads to the production of MMPs and inhibits TGF-β, which is important in collagen production.

[0030] • Oxidative Stress:

[0031] ROS (Reactive Oxygen Species): The accumulation of ROS and oxidative stress are factors that contribute to skin aging and "inflammaging," causing cellular damage and inflammation. Mitochondrial dysfunction is a known source of elevated ROS in aging.

[0032] Taken together, these markers reflect the chronic low-grade inflammatory state and the cellular and tissue dysfunctions characteristic of the “inflammaging” process. Cellular Senescence

[0033] Cellular senescence is an irreversible state of cell cycle arrest that cells enter in response to various types of stress, preventing their proliferation, but remaining metabolically active.

[0034] The main characteristics of cellular senescence include:

[0035] • Irreversible cell cycle arrest: Primarily in the G1 phase, mediated by cyclin-dependent kinase (CDK) inhibitors such as p21 and p16. These are commonly used markers to identify senescent cells.

[0036] • Senescence-Associated Secretory Phenotype (SASP): Senescent cells are metabolically active and secrete a variety of factors, including inflammatory cytokines (such as α-1β, IL-6, IL-8), chemokines (such as CCL2, CCL5, CXCL1), growth factors (such as TGF-β, EGF, GDF15), proteases (MMP1, MMP3), bioactive lipids, and non-coding nucleic acids. Petition 870260044168, dated 11 / 05 / 2026, page 10 / 63 6 / 22

[0037] · Increased resistance to apoptosis: Senescent cells activate pro-survival pathways, known as Senescent Cell Anti-Apoptotic Pathways (SCAPs), and decrease apoptotic mediators. Proteins such as BCL-2, BCL-W, and BCL-XL are examples of elevated anti-apoptotic proteins.

[0038] · Morphological changes: Senescent cells may exhibit enlarged nuclei, larger cell size, and a flattened appearance. A less common phenotype is the presence of multiple nuclei with enlarged vacuoles.

[0039] • Increased activity of senescence-associated β-galactosidase (SA-p-gal): a lysosomal enzyme that is a common biomarker of senescent cells, also used for the identification of these cells.

[0040] • Nuclear lamina remodeling: The loss of laminin B1 is a biomarker associated with senescence.

[0041] • Disrupted metabolism: Including a metabolic shift to a more glycolytic state and lipid accumulation.

[0042] • Hyperadhesive phenotype: Associated with greater focal adhesions and reduced cell motility.

[0043] Senescence can be triggered by various physiological and pathological stressors, including:

[0044] • Telomere shortening (replicative senescence)

[0045] • Oncogene activation (oncogene-induced senescence)

[0046] • Persistent DNA damage (such as that caused by radiation) UV or oxidative stress)

[0047] • Mitochondrial dysfunction

[0048] • Mechanical stress

[0049] • Inflammatory cytokines and chemokines

[0050] • Nutrient imbalance Petition 870260044168, dated 11 / 05 / 2026, page 11 / 63 7 / 22

[0051] Although considered a tumor suppression mechanism, preventing the uncontrolled proliferation of damaged cells, cellular senescence has a pleiotropic and dynamic role, with both beneficial effects (such as in embryonic development, wound healing, and tissue regeneration) and detrimental effects (contributing to chronic inflammation, fibrosis, and age-related diseases, "inflammaging"). The transient or persistent nature of senescent cells is a key factor that determines their beneficial or detrimental effects. Cellular senescence and its effect on the skin

[0052] Cellular senescence in the skin is a complex process with dual effects, both beneficial and detrimental, which manifest in different ways in aging and in various pathological conditions. Detrimental Effects of Cellular Senescence in the Skin

[0053] The accumulation of senescent cells in the skin contributes to skin aging and various pathologies. The main ways in which this occurs are:

[0054] Proliferation Arrest and Tissue Repair Impairment: Senescent cells enter a state of irreversible cell cycle arrest, meaning they no longer contribute to tissue repair or regeneration. This leads to a progressive disruption of the skin's physiological structure and functions, causing compromised barrier function and impaired wound healing.

[0055] Senescence-Associated Secretory Phenotype (SASP): Senescent cells are metabolically active and secrete a variety of inflammatory factors and extracellular matrix (ECM) modifiers, collectively known as SASP. SASP in the skin can cause:

[0056] 1. Chronic Inflammation (“inflammaging”): The secretion of pro-inflammatory cytokines such as α-1β, IL-6, and IL-8 by senescent cells contributes to a state of low-grade chronic inflammation in aging, known as “inflammaging.” Petition 870260044168, dated 11 / 05 / 2026, page 12 / 63 8 / 22

[0057] 2. Extracellular Matrix (ECM) Degradation: SASP includes proteases such as MMPs (matrix metalloproteinases). These MMPs degrade essential ECM components, such as collagen and elastin, leading to epidermal thinning, flattening of the dermo-epidermal junction (DEJ), and loss of skin elasticity and integrity.

[0058] 3. Paracrine Propagation of Senescence: SASP can induce senescence in neighboring non-senescent cells, amplifying the negative effects on the tissue.

[0059] Visible Manifestations of Skin Aging: The accumulation of senescent cells is associated with typical characteristics of aged skin, such as:

[0060] 1. Wrinkles, sagging and thinning of the skin.

[0061] 2. Aberrant Pigmentation: An increase in senescent fibroblasts and melanocytes contributes to hyperpigmentation disorders (such as solar lentigo and melasma) and hypopigmentation, affecting melanin production.

[0062] 3. Delayed / Chronic Wound Healing: Although transient senescence is beneficial, the persistent accumulation of senescent cells in the wound bed impedes the healing process, as observed in chronic ulcers (e.g., venous ulcers, diabetic ulcers).

[0063] 4. Increased Susceptibility to Skin Cancers: The presence of senescent cells, especially through the pro-inflammatory and angiogenic factors of SASP, can promote the growth and progression of tumors in certain contexts. Pre-malignant lesions such as actinic keratoses also exhibit an accumulation of senescent keratinocytes.

[0064] 5. Hair Disorders: Dysfunction of dermal stem cells in the hair follicle, which exhibit senescent characteristics, has been associated with age-related hair loss. Beneficial Effects of Cellular Senescence on the Skin (Transient Senescence)

[0065] Cellular senescence is not exclusively harmful and can have important and beneficial physiological roles. Petition 870260044168, dated 11 / 05 / 2026, page 13 / 63 9 / 22

[0066] Wound Healing: A transient increase in senescent fibroblasts plays an essential role in optimal cutaneous wound healing. Through their SASP, these cells promote:

[0067] 1. Tissue Remodeling: Contributes to repair by inducing myofibroblast differentiation through the secretion of Platelet-Derived Growth Factor-AA (PDGF-AA), which promotes wound contraction.

[0068] 2. Recruitment of Immune Cells: They recruit immune cells, especially phagocytic cells such as macrophages, which subsequently remove senescent cells, allowing tissue regeneration.

[0069] Inhibition of Fibrosis: In some models, senescence has been implicated in limiting tissue fibrosis, for example, in models of liver fibrosis, through ECM remodeling and NK cell activation to clear senescent cells.

[0070] Tumor Suppression: Senescence acts as an intrinsic barrier to the uncontrolled proliferation of damaged cells, being a mechanism of tumor suppression. Factors that contribute to skin senescence.

[0071] Senescence is triggered by a combination of factors:

[0072] Chronological Aging (Intrinsic Factors): Correlates with increased levels of senescence in various tissues, including the skin, due to the accumulation of DNA damage, telomere shortening, and immunosenescence that affects the immune system's ability to eliminate senescent cells.

[0073] Ultraviolet Radiation (UV - Extrinsic Factor): Chronic exposure to UV radiation (UVA and UVB) is one of the main inducers of skin senescence. It causes DNA damage and the generation of reactive oxygen species (ROS), leading to premature senescence in keratinocytes, fibroblasts, and endothelial cells. UV radiation can also compromise immune function. Petition 870260044168, dated 11 / 05 / 2026, page 14 / 63 10 / 22 which reduces the ability to eliminate senescent cells.

[0074] Pollution (Extrinsic Factor): Components of air pollution, such as particulate matter (PM2.5), induce DNA damage, oxidative stress (ROS), and the release of pro-inflammatory cytokines, contributing to premature skin aging, hyperpigmentation, and other skin disorders.

[0075] Other Stressors: Mitochondrial dysfunction, mechanical stress, and nutritional imbalances can also induce cellular senescence. Differences between Cellular Senescence and Aging

[0076] As described earlier, cellular senescence is a specific and irreversible state in which a cell stops dividing but remains metabolically active. Typically, this occurs in response to DNA damage, serving as an important anti-tumor function during an individual's life.

[0077] Aging, in turn, is a systemic and multifactorial process, influenced by genetic, environmental and behavioral factors, that occurs over time throughout the body and manifests itself both internally (e.g., chronic diseases) and externally (e.g., wrinkles, loss of skin elasticity).

[0078] Table 1 below illustrates the main differences between these two concepts: Table 1. Aspect: Cellular Senescence, Systemic Aging. Scope: Individual cells, Organism as a whole. Reversibility: Irreversible (generally), Progressive and multifactorial. Cause: Cellular stress, DNA damage, Genetics, environment, lifestyle. Consequence: Local inflammation, SASP (Systemic Aging Process), tissue dysfunction, Functional decline, age-related diseases. Petition 870260044168, dated 11 / 05 / 2026, page 15 / 63 11 / 22 Aspects: Cellular Senescence, Systemic Aging, Relationship with Inflammation, Directly Contributes to "inflammaging," Can be aggravated by "inflammaging." "Inflammaging" vs. Cellular Senescence

[0079] The relationship between “inflammaging” and cellular senescence is intrinsic and mutually influential, although they refer to distinct phenomena in the aging process.

[0080] The interaction between “inflammaging” and cellular senescence is complex and can be described as a vicious cycle:

[0081] • Senescence drives “inflammaging”: Senescent cells accumulate in aging skin and are a major driver of chronic inflammation. They exhibit a senescence-associated secretory phenotype (SASP). SASP is characterized by the release of a variety of factors, including pro-inflammatory cytokines (such as IL-6, IL-8, α-1β, TNF-α), chemokines, and matrix metalloproteinases (MMPs), which significantly alter the tissue microenvironment. Senescent fibroblasts, for example, increase in aging skin and contribute to extracellular matrix (ECM) remodeling, an important aspect of age-related changes. The activity of the transcription factor NF-κB, which is crucial in senescence and driving SASP, increases with chronological age in the skin, promoting chronic inflammation.

[0082] • Inflammation promotes Senescence: On the other hand, pro-inflammatory signals have been shown to be capable of inducing and accelerating cellular senescence. The NF-kB pathway, fundamental in inflammation, also plays a key role in the induction of SASP.

[0083] • Vicious Cycle: The interaction between cellular senescence, inflammation, and skin dysfunction can become cyclical and exaggerated throughout life. As protective countermeasures are overcome by the skin's inflammatory defense mechanisms, cell accumulation occurs. Petition 870260044168, dated 11 / 05 / 2026, page 16 / 63 12 / 22 Senescent immune cells and inadequate adaptive immune responses may facilitate the survival of senescent skin cells and the destruction and remodeling of the ECM.

[0084] Fundamental Differences

[0085] 1. “Inflammaging” is a state: It refers to a systemic state of chronic low-grade inflammation throughout the body, including the skin, characterized by the presence of elevated levels of circulating inflammatory mediators. It can be seen as a consequence of aging and cellular senescence, or as a driver of ineffective immune responses.

[0086] 2. Cellular senescence is a cellular state or biological process: It is a condition in which individual cells stop dividing. Senescence is one of the fundamental mechanisms of aging that contributes to "inflammaging," primarily through the secretion of SASP. Rhamnolipids

[0087] Rhamnolipids are natural biosurfactants produced mainly by bacteria of the genus Pseudomonas, especially Pseudomonas aeruginosa. These compounds have an amphiphilic structure, composed of a lipid part (fatty acid) and a hydrophilic part (rhamnose, a type of sugar), which gives them surface tension reduction and emulsification properties. Due to their biological origin, rhamnolipids are biodegradable, less toxic, and environmentally safer compared to synthetic surfactants.

[0088] In addition to their industrial applications in cleaning formulations, petroleum, agriculture, and cosmetics, rhamnolipids have attracted increasing interest in the biomedical and pharmaceutical fields. They exhibit antimicrobial, anti-adherent, and immunomodulatory properties, and can act in the prevention of biofilms and in the modulation of inflammatory responses. This versatility makes rhamnolipids promising candidates for the development of sustainable products and Petition 870260044168, dated 11 / 05 / 2026, page 17 / 63 13 / 22 innovators in various technological areas.

[0089] Thus, the need persists for compositions comprising active ingredients aimed at preventing, attenuating and / or reversing the effects of "inflammaging" and / or cellular senescence in an individual in need thereof. BRIEF DESCRIPTION OF THE FIGURES

[0090] Figures 1 to 5 present the results of the quantification of IL-1β, IL-6, TRPV-1, NF-KB and STAT3, in which human fibroblast and keratinocyte cell cultures were incubated with the rhamnolipid ingredient (fermented extract) at a concentration of 0.0075% for 72 hours.

[0091] Figures 6 to 11 present the results of IL-8, IL-6, p16, p21, p53 and MMP-12 by enzyme-linked immunosorbent assay (ELISA), in which cell cultures were incubated with the rhamnolipid ingredient (fermented extract) at concentrations of 0.003%, 0.0015% and 0.00075% (0.001%, 0.0005%, and 0.00025% active ingredient purity, respectively) for 24 hours before UVB exposure. After this period, the cells were stimulated with a dose of 0.25 J / cm² and re-treated with the investigational product. For control and comparison purposes, a baseline control was performed without UVB stimulation, and a stressed control was performed with stimulation only. The process was repeated for a total of seven days. The supernatant or cell lysate was collected and used for assay of IL-8, IL-6, p16, p21, p53, and MMP-12 by enzyme-linked immunosorbent assay (ELISA). SUMMARY DESCRIPTION OF THE INVENTION

[0092] The present invention solves the problems of the prior art by providing the use of rhamnolipid, a natural biosurfactant, as an active ingredient, for the prevention, attenuation and / or reversal of cellular inflammation and / or senescence.

[0093] Among the advantages of the present invention, sustainability is cited. Petition 870260044168, dated 11 / 05 / 2026, page 18 / 63 14 / 22 The suitability of the compositions and green process claimed herein; for the process of the present invention utilizes microorganisms, such as bacteria, cultivated on renewable and low-cost substrates, such as vegetable oils, sugarcane molasses, glycerin (a byproduct of biodiesel production) and other agro-industrial residues. This avoids dependence on non-renewable sources, such as petroleum, which are the basis for most synthetic surfactants. Additionally, the production process of the present invention operates under milder conditions, such as lower temperature and pressure, decreasing energy consumption and the use of toxic solvents compared to traditional chemical synthesis processes.

[0094] Furthermore, the rhamnolipids used in the compositions of the present invention are biodegradable and exhibit low toxicity compared to synthetic surfactants, minimizing environmental impacts.

[0095] In a second aspect, there is a process for obtaining rhamnolipids comprising the following steps:

[0096] a) preparation of the inoculum;

[0097] b) fermentation process with foam recirculation;

[0098] c) separation of the microorganism from the culture medium; and

[0099] d) drying of the fermented broth; where the carbon source of the fermentation medium is andiroba, babassu, tucumã, patauá oil, or a mixture thereof.

[00100] In a third aspect, there is a rhamnolipid obtained from andiroba oil.

[00101] In a fourth aspect, there is the cosmetic composition for inflammaging and / or cellular senescence comprising rhamnolipid.

[00102] Advantages of the compositions of the invention include mitigating the effects of cellular senescence related to skin aging, promoting vitality and longevity in all skin types, including sensitive skin. Petition 870260044168, dated 11 / 05 / 2026, page 19 / 63 15 / 22

[00103] In a fifth aspect, there is the method for dermocosmetic treatment in “inflammaging” and / or cellular senescence comprising the application of a cosmetic composition on a keratinous substrate. DETAILED DESCRIPTION OF THE INVENTION

[00104] In a first aspect, the present invention relates to the use of rhamnolipid, a natural biosurfactant, as an active ingredient for the preparation of a composition for the prevention, attenuation and / or reversal of cellular inflammation and / or senescence.

[00105] In one embodiment, rhamnolipid is used in an amount between 0.0001% and 0.01% (concentration of the active ingredient - rhamnolipid - within the extract).

[00106] In one embodiment, the rhamnolipid is obtained from andiroba, babassu, tucumã, patauá oil or a mixture thereof.

[00107] In one embodiment, the rhamnolipid comprises the modulation of IL6, IL8, p16, p21, p53, MMP-12, TRPV1, STAT3 and / or IL-1b.

[00108] In a second aspect, there is a green process for obtaining rhamnolipids comprising the steps of:

[00109] a) preparation of the inoculum;

[00110] b) fermentation process with foam recirculation; and

[00111] c) rhamnolipid recovery; in which the carbon source of the fermentation medium is andiroba, babassu, tucumã, patauá oil, or a mixture thereof.

[00112] In a third aspect, there is a rhamnolipid obtained from andiroba, babassu, tucumã, patauá oil or a mixture thereof.

[00113] In one embodiment, rhamnolipid is for use in inflammaging and / or cellular senescence.

[00114] In a fourth aspect, there is the cosmetic composition for inflammaging and / or cellular senescence comprising rhamnolipid and at least one cosmetically acceptable excipient. Petition 870260044168, dated 11 / 05 / 2026, page 20 / 63 16 / 22

[00115] In one embodiment, the cosmetic composition comprises from 0.01 to 99.9% rhamnolipid.

[00116] The cosmetic compositions according to the present invention may be in the form of emulsions, solutions, gels, powders, pastes, elixirs, among others, also including cosmetically appropriate vehicles for the chosen cosmetic form.

[00117] The cosmetic compositions according to the present invention are intended for topical application.

[00118] Cosmetically acceptable excipients may be selected from compounds known in the prior art. Without limitation, excipients may be selected from the group comprising emollients, antioxidants, humectants, emulsifiers, surfactants, sensory or viscosity modifiers, preservatives, chelating agents, stabilizers, lubricants, thickeners, dispersants, solubilizers and combinations thereof, among other cosmetically acceptable vehicles.

[00119] In a fifth aspect, there is the method for dermocosmetic treatment in “inflammaging” and / or cellular senescence comprising the application of a cosmetic composition on a keratinous substrate.

[00120] The following examples, without imposing any limitation, illustrate the present invention. EXAMPLES Example 1 - Rhamnolipid production process

[00121] Initially, Pseudomonas aeruginosa cells were propagated for inoculation of the fermenter. In this first stage, for a 120 L (Pilot) process, 1.2 L of pre-inoculum is required, equivalent to 1% of the fermentation volume. The inoculum ratio is 1 cryotube of 2 mL for every 100 mL of medium, and each 1 L Erlenmeyer flask is prepared with 200 mL of culture medium whose composition is presented in Table 2. Petition 870260044168, dated 11 / 05 / 2026, page 21 / 63 17 / 22 Table 2: Inoculum culture medium for rhamnolipid production Component Concentration (g / L) Andiroba oil 60 NaNOa 6 Yeast extract 3 KH2PO4 1 Na2HPO4 1 CaCl2.2H2O 0.1 MgSO4.7H2O 0.1

[00122] In this stage, conducted in an orbital shaker, the process conditions are: temperature around 30-40°C and agitation at 150-300 rpm for at least 10 hours.

[00123] After cell growth, Erlenmeyer flasks are used to inoculate the pilot fermenter (150-300 L) containing the culture medium. Table 3 shows the pre-inoculum medium. Table 3: Composition of the pre-inoculum medium Component Concentration (g / L) Andiroba oil 60 NaNOa 6 Yeast extract 3 KH2PO4 1 Na2HPO4 1 CaCl2.2H2O 0.1 MgSO4.7H2O inoculum 0.1

[00124] For bioreactor inoculation, the Erlenmeyer flasks are first mixed in a laminar flow flask, and after this process the material is transferred in a sterile manner to the bioreactor. At this stage, the cultivation conditions are: 15-45% dissolved oxygen. Adjust agitation and airflow to maintain the process within the desired dissolved oxygen range. The process time is approximately 10 hours and in this case the Petition 870260044168, dated 11 / 05 / 2026, page 22 / 63 The 18 / 22 foam recirculation system is still unnecessary.

[00125] With the pre-inoculum grown, the transfer of the medium is carried out using a peristaltic pump to the industrial bireactor containing culture medium as described in Table 3.

[00126] It should be noted that foam recirculation occurs at this stage. The foam recirculation system is as described in Xu et al., 2020 (XU, Ning et al. Enhanced rhamnolipids production using a novel bioreactor system based on integrated foam-control and repeated fedbatch fermentation strategy. Biotechnology for Biofuels, v. 13, n. 80, p. 1-13, 2020).

[00127] The fermentation process takes between 5-7 days and at the end a fermented extract is obtained containing between 20-22 g / L of rhamnolipid.

[00128] After the production stage, the preservative system is added and the "downstream" process begins, that is, the cell separation and product concentration stage. The first stage consists of separating the cells through a centrifugation process, and then the material is spray-dried, resulting in a yellowish powder. Example 2 - Inflammaging protein analysis tests

[00129] NF-κB and STAT3 are essential transcription factors and act at the interface of the transition from chronic inflammation in response to cytokines (IL-1 α and β, IL-6, IL-10) and growth factors. While STAT3 controls cellular processes such as proliferation, survival, and apoptosis, the NF-κB protein plays a fundamental role in regulating the immune response and is also activated by stimuli such as free radicals (like superoxide and hydroxyl radicals through oxidative phosphorylation) and ultraviolet radiation.

[00130] In the process of responding to endogenous and exogenous skin stresses, several pro-inflammatory interleukins (cytokines) are synthesized, which are protein molecules (glycosylated or not) that send Petition 870260044168, dated 11 / 05 / 2026, page 23 / 63 19 / 22 different stimulatory, modulatory or even inhibitory signals for the different cells of the immune system.

[00131] The IL-1 cytokine family is well known for its role in initiating inflammatory pathways in response to noxious signals. Interleukin 1 (IL-1) has been established as capable of simultaneously regulating inflammation and angiogenesis, directly or indirectly, through the induction of pro-angiogenic factors such as vascular endothelial growth factor (VEGF). Proteome profiling has revealed considerable overlaps in the pathways and biological functions regulated by IL-1β and VEGF in activated endothelial cells, particularly the mitogen-activated protein kinase (MAPK) cascade, which is induced by both IL-1β and VEGF, and may potentially play a role in the overlapping effects caused by inflammatory and angiogenic signaling.

[00132] IL-6 is a pleiotropic cytokine that influences antigen-specific immune responses and inflammatory reactions, being one of the main mediators of the acute phase of inflammation. IL-6 expression is also known to be one of the main activators of STAT3. Like IL-1, IL-6 also stimulates the production of ACTH (adrenocorticotropic hormone) by the pituitary gland, establishing a negative feedback loop between the immune system and the neuroendocrine axis.

[00133] As one of the effects on the skin, the local inflammatory response increases the sensitivity of nociceptors such as TRPV1 (transient vanilloid receptor of channel V1), initiating hyperalgesia and, in addition, stimulating the further production of more inflammatory mediators.

[00134] Thus, evaluating the effect on transcription factors and interleukins involved in inflammatory processes, as well as on nociceptors, are pertinent investigations for products intended to combat cutaneous inflammatory processes and relieve pain, especially after local aesthetic procedures or exposure to environmental stresses. Petition 870260044168, dated 11 / 05 / 2026, page 24 / 63 20 / 22

[00135] Human fibroblast and keratinocyte cell cultures were incubated with rhamnolipid (fermented extract) at a concentration of 0.0075% for 72 hours. After this period, the lysate and cell supernatant were collected for quantification of IL-1β, IL-6, TRPV-1, NF-κB, and STAT3.

[00136] The results of the analyses are presented in figures 1 to 5.

[00137] According to the graphs presented, it can be seen that rhamnolipid (fermented extract), at the evaluated concentration, did not promote a significant difference in the concentration of IL-6 and NF-kB in both cell lines evaluated. For IL-1β, a 23.91% reduction was observed in fibroblasts. It promoted an 82.25% and 51.75% reduction in the concentration of STAT3 in fibroblasts and keratinocytes, respectively. TRPV-1 expression was reduced by 83.04% in fibroblasts. Thus, we can conclude that the ingredient is capable of acting by inhibiting the biological markers associated with the state of chronic inflammation associated with aging, called Inflammaging. Cellular senescence

[00138] Cellular senescence occurs in response to various triggers, including DNA damage, telomere dysfunction, oncogene activation, and organellar stress, and has been associated with processes such as tumor suppression, tissue repair, embryogenesis, and organismal aging. Hayflick and Moorhead demonstrated in 1961 that cultured human fibroblasts normally exhibit a finite capacity for cell division before entering an irreversible growth arrest known as replicative senescence.

[00139] Senescence can also be induced by extrinsic factors. Extrinsic aging is caused by cumulative exposure to external stimuli, such as ultraviolet (UV) radiation, the most harmful external component that threatens the skin. For this reason, extrinsic aging is also called photoaging. Petition 870260044168, dated 11 / 05 / 2026, page 25 / 63 21 / 22 because UV radiation penetrates the skin and induces senescence patterns, such as the senescence-associated secretory phenotype (SASP), cell cycle arrest, and increased metalloproteinases (MMPs).

[00140] Components of the (SASP), primarily the pro-inflammatory cytokines interleukin-6 (IL-6) and IL-8, can be used at transcription and protein levels to assess overall senescence in tissues or cell cultures. However, SASP alone cannot be used as a reliable biomarker of senescence: in fact, senescence triggered by p16 overexpression does not imply an altered SASP transcriptional program.

[00141] In addition, p21 and p16 are two cyclin-dependent kinase inhibitors that are components of the p53- and RB-governed tumor suppressor pathways, and frequently accumulate in senescent cells. Because p21 and p16 expression levels are sufficient to establish and maintain senescence-associated growth arrest, they are used to identify senescent cells in tissues and cultured cells.

[00142] In the case of MMPs, this class of enzymes is capable of degrading the extracellular matrix during embryonic development, which is important for morphogenesis, reproduction, and tissue reabsorption and remodeling, but leads to more disorganized skin tissue during adulthood, accelerating skin aging.

[00143] In conclusion, prevention against the effects of photoaging is important to maintain healthy skin aspects and may be involved in preventing the expression of the markers discussed earlier.

[00144] Cell cultures were incubated with the rhamnolipid ingredient (fermented extract) at concentrations of 0.003%, 0.0015%, and 0.00075% (0.001%, 0.0005%, and 0.00025% active ingredient purity, respectively) for 24 hours before UVB exposure. After this period, the cells were stimulated with a dose of 0.25 Petition 870260044168, dated 11 / 05 / 2026, page 26 / 63 22 / 22 J / cm2 and depicted with the investigational product. For control and comparison purposes, a baseline control was performed without UVB stimulation and a stressed control was performed with stimulation only. The process was repeated for a total of seven days. The supernatant or cell lysate was collected and used for measurement of IL-8, IL-6, p16, p21, p53 and MMP-12 by enzyme-linked immunosorbent assay (ELISA).

[00145] The results of the analyses are presented in figures 6 to 11.

[00146] According to the results presented, we can conclude that rhamnolipid (fermented extract), at the tested concentrations, promoted a significant difference in the concentration of IL-8, IL-6, p21, p53, and MMP-12, at least at the highest concentration tested (0.003%). These results are an interesting indication that the evaluated product is capable of reducing the effects of UV radiation on the skin and helping to prevent skin aging. Thus, we can conclude that the ingredient in question is capable of preventing the onset of premature cellular senescence, contributing to skin health.

[00147] Finally, considering the results presented, it can be concluded that the rhamnolipid ingredient has anti-inflammatory action and prevents premature cellular senescence, and its use is indicated considering the application range of 0.0001% and 0.01% of active ingredient within the extract (purity).

[00148] The skilled person will readily be able to assess, through the teachings contained in the text and the examples presented, the advantages of the invention and propose equivalent variations and alternatives for its implementation, without departing from the scope of the invention, as defined in the appended claims.

Claims

1. Use of rhamnolipid, characterized by the fact that it is for the preparation of a composition for the prevention, attenuation and / or reversal of inflammation associated with aging and / or cellular senescence.

2. Use of rhamnolipid, according to claim 1, characterized in that it comprises from 0.01 to 99.9% rhamnolipid in a cosmetic composition.

3. Use of rhamnolipid, according to claim 1 or 2, characterized in that it is rhamnolipid obtained from andiroba oil as a substrate.

4. Use of rhamnolipid, according to any one of claims 1 to 3, characterized in that it comprises the modulation of IL6, IL8, p16, p21, p53, MMP-12, TRPV1, STAT3 or IL-1b.

5. Process for obtaining rhamnolipids, characterized by the fact that it comprises the steps of: a) inoculum preparation; b) fermentation process with foam recirculation; c) separation of the microorganism from the culture medium; d) drying of the fermented broth; wherein the carbon source of the fermentation medium is andiroba oil.

6. Rhamnolipid, characterized by the fact that it is obtained from a fermentation process using andiroba oil as a substrate.

7. Rhamnolipid, according to claim 6, characterized in that it is for use in inflammation associated with aging and / or cellular senescence.

8. Cosmetic composition for inflammaging and / or cellular senescence, characterized by the fact that it comprises rhamnolipid and Petition 870260044168, dated 11 / 05 / 2026, page 28 / 63 2 / 2 at least one cosmetically acceptable excipient.

9. Cosmetic composition, according to claim 8, characterized in that it comprises from 0.01 to 99.9% rhamnolipid.

10. A method for dermocosmetic treatment of inflammation associated with aging and / or cellular senescence, characterized in that it comprises the application of a cosmetic composition, as defined in claim 9, to a keratinous substrate.

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