Skin cosmetic formulation of papain, urea, zinc sulfate, and ubiquinol for treating and healing melasma

Abstract

The present patent application is characterized essentially by a chemical formulation based on papain, urea, zinc sulfate and ubiquinol, the aim of which is to treat and heal skin affected by melasma, the formulation being composed of: 10% papain; 5% urea; 6% zinc sulfate and 5% ubiquinol, in a cream base q.s. 100g. This formulation must be produced by a trained professional who understands chemical processes and the use of each composition for proper handling. The product is for nighttime topical use, for any type of skin, and must be applied to clean, dry skin. The formulation should be applied to the area of the melasma and, once absorbed into the skin, sunscreen should be used on top of the product. The minimum period of treatment should be 6 to 12 months. Said formulation is considered to combat cellular senescence, repair the stratum corneum and the phospholipid bilayer of the cells, combat lipidic peroxidation and local inflammation, eliminate excess free radicals in the intracellular environment, reorganize the structure of internal organelles and preserve DNA, thereby maintaining homeostasis and skin health, healing and reducing dark spots, and leaving the skin healthier, soft, bright and moisturized.

Description

[0001] DERMOCOSMETIC FORMULATION OF PAPAIN, UREA, ZINC SULFATE AND UBIQUINOL FOR THE TREATMENT AND CURE OF MELASMA

[0002] FIELD OF APPLICATION

[0003] 1. The aforementioned product, whose protection will be claimed in this report, was developed with the aim of addressing deficiencies, alleviating difficulties and solving problems previously encountered by users in the healthcare sector, more specifically, the dermatology and pharmacology sectors.

[0004] INTRODUCTION

[0005] 2. This patent application for invention privilege refers to a chemical formulation based on papain, urea, zinc sulfate and ubiquinol, the purpose of which is to treat and cure skin affected by melasma.

[0006] 3. The skin is the largest organ in the human body, consisting of the epidermis, dermis, and hypodermis. Normal human skin color is given by melanin, a dense brown pigment with a blackish appearance that absorbs ultraviolet (UV) light and is synthesized in the basal layer of the epidermis.

[0007] 4. However, melasma is a hypermelanotic disorder that presents as macules with irregular contours, ranging from brown to black, in photoexposed areas, mainly the face.

[0008] 5. They are most common in women of childbearing age between 20 and 50 years old, with darker skin types (III to VI). Therefore, it is estimated that nearly 2 billion people worldwide have some type of skin pigmentation disorder, mainly in tropical countries. In Brazil, women are the most affected, approximately 35%, and men less than 10%. Melasma constitutes the third largest group of diseases seen in dermatology offices.

[0009] 6. The pathophysiology of melasma is still unknown. It is known to be a chronic inflammation of the skin in sun-exposed areas, primarily caused by chronic sun exposure (UV). This exposure causes cellular senescence, activating the synthesis of metalloproteinases and degrading the extracellular matrix (ECM). This degradation causes intracellular disruption, triggering melanogenesis. Additionally, other factors such as intrinsic aging, hereditary factors, hormonal factors, cosmetic factors, and endocrine factors can contribute to the development of melasma.

[0010] 7. Although there are many treatment options available, such as topical depigmenting agents including acids, topical steroids, oral medications, and other protocols, such as lasers and peels, they do not provide a definitive solution for melasma and are ineffective and unsatisfactory. Ineffective treatments and persistent spots cause social and psychological impacts, affecting patients' self-esteem and quality of life.

[0011] 8. The aforementioned product stands out, fundamentally, for its most practical, simple and functional form in a dermocosmetic formulation for the treatment and cure of melasma, and is endowed with unique, exclusive and innovative functional aspects, which will be described below, making it an exclusive product on the market.

[0012] FEATURES

[0013] 9. The product in question, presented through this report, is composed of: papain 10%; urea 5%; zinc sulfate 6%, ubiquinol 5%, in a base cream qsp 100g, the manufacturing must be carried out by a qualified professional who knows the chemical processes and use of each composition for correct handling.

[0014] BRIEF DESCRIPTION OF THE FIGURES

[0015] 10. Initially, to better demonstrate such characteristics, and aiming at a clear and objective understanding of the provisions applied in this invention privilege, a drawing and flowchart will be presented for demonstration purposes, with reference to the report attached.

[0016] 11. FIGURE 1 illustrates the image containing before, 80% of the face with melasma (1), black color and skin aging, photo December 2022, without any treatment.

[0017] 12. FIGURE 2 illustrates the image containing after 4 months of assiduous treatment, with these chemical formulas presented, started in April, this photo is from August 2023, 95% of the face already free of melasma. However, it still presents the spots slightly in the center of the cheeks (2) and nose.

[0018] 13. It should be clarified that the images listed above illustrate the product for demonstration purposes and are not restrictive, and the design may vary in terms of measurements, raw material, dimensions, etc., without logically deviating from the main scope of the protection claimed.

[0019] FUNCTIONALITY

[0020] 14. Initially, the aforementioned product, described in this report, will be used in the health sector, more specifically in the dermatology and pharmacology sectors.

[0021] 15. The formulation contains: Papain 10%; Urea 5%; Zinc Sulfate 6%; and Ubiquinol 5%. The active ingredients in the formula are: carica papaya extract, urea, zinc, and ubiquinone.

[0022] 16. This is a topical nighttime product suitable for all skin types. The area to be used should be clean and dry. Apply the formula to the melasma area overnight. Once absorbed, apply sunscreen over the area.

[0023] 17. The minimum treatment period should be 6 to 12 months.

[0024] BACKGROUND OF THE INVENTION

[0025] 18. The skin is made up of the epidermis, the dermis, and the hypodermis. The epidermis is composed of the covering epithelium, which is a stratified, squamous, and keratinized tissue, that is, it consists of several layers of cells with different shapes and functions.

[0026] 19. The epidermis is subdivided into the corneal, granular, spinous, and basal layers. The main function of the epidermis is to form a protective barrier for the body, protecting it from external damage, such as ultraviolet radiation from the sun, and preventing the outflow of water and the entry of substances such as microbes into the body.

[0027] 20. It is worth noting that skin cells are constructed by the plasma membrane, a phospholipid bilayer, and the extracellular matrix (ECM). This is the junction of communication pathways between cells to form the tissue.

[0028] 21. The ECM ensures the physical maintenance of all cells and plays an active role in both cell proliferation, differentiation and migration, being a structural component of the tissue.

[0029] 22. Therefore, there are several components of the extracellular matrix, such as proteins, collagens, elastin, fibronectins, cadherins, laminins, tenascins, and others, as well as growth factors, for example: vascular endothelial growth factor (VEGF); fibroblast growth factor (FGF); transforming growth factor beta (TGF-beta). 23. Thus, matrix metalloproteinases (MMPs) are Zn2+-dependent proteolytic enzymes (endopeptidases) that act in the disintegration of the extracellular matrix. They are secreted as proenzymes, released by neutrophils, monocytes, macrophages, fibroblasts, and also by tumor cells in response to stimuli.

[0030] 24. The extracellular matrix is ​​divided into basement membrane and interstitial matrix. The basement membrane is composed of collagen IV, laminins, and fibronectins, while the interstitial matrix is ​​composed of collagens, elastins, and fibronectins. Interstitial proteins connect cells to each other, or cell-to-matrix.

[0031] 25. Continuing, the stratum corneum is the first layer of the epidermis, it acts as a skin barrier, being a natural protective shield and important for maintaining skin health, as it prevents water loss, maintains the natural hydration factor, and nutrients necessary for the life stages of keratinocytes.

[0032] 26. Keratinocytes originate from stem cells in the basal layer, which is located at the dermal-epidermal junction. These cells constitute more than 80% of the epidermis, at different stages of cellular maturation.

[0033] 27. Melanocytes have an octopus-like structure, meaning they have a cell body and several dendrites that communicate with the surface skin cells, known as keratinocytes. One melanocyte can pigment up to 36 keratinocytes.

[0034] 28. Thus, melanocytes are activated by ultraviolet rays to produce melanin, which is found in melanosomes. Melanin is then transported by dendrites and injected into the surface cells of keratinocytes, forming a kind of "umbrella" over each cell nucleus to protect the DNA from ultraviolet radiation.

[0035] 29. Therefore, skin pigmentation occurs through the action of melanin, a pigmented polymer with a brownish color, high molecular weight and dense, responsible for absorbing ultraviolet light (UVA), in order to protect cells against damage that the sun can cause.

[0036] 30. Melanocytes receive the DNA message to produce melanin from the oxidation of the protein tyrosine by the enzyme tyrosinase. This is transformed into L-Dopa, then into dopaquinone, then into leucodopachrome and then into dopachrome. 31. There are two pathways for the degradation of dopachrome: one forms the molecule 5,6-dihydroxyindole, and the second forms the molecule 5,6-dihydroxyindole-2-carboxylic acid. Both reactions occur through the tyrosinase-related proteins 1 and 2 (TRP-1 and TRP-2), the latter also called dopachrome tautomerase, which forms eumelanin.

[0037] 32. From now on, if there is the incorporation of glutathione or cysteine, it reacts with dopaquinone to form cysteine, which is oxidized into benzothiazine intermediates, producing pheomelanin. Eumelanin is an alkaline, insoluble molecule, but pheomelanin is soluble and alkaline.

[0038] 33. Thus, when the melassosome vesicles are full, they migrate to the keratinocytes of the epidermis, carrying this pigmentation that can vary from brown to black (eumelanin) to yellow-red (pheomelanin).

[0039] 34. Considering that the pathophysiology of melasma is not yet fully understood, it is known that chronic sun exposure is the main triggering factor, photoaging, but there are studies that point to intrinsic aging, and others believe in hereditary, hormonal, cosmetic and endocrine factors that can activate melanogenesis.

[0040] 35. Therefore, it is believed that premature cellular senescence induced by ultraviolet rays promotes functional changes that can trigger and perpetuate melanin production. Furthermore, it proves that some genes involved in lipid metabolism (lipid peroxidation) in melasma are altered, compromising the skin's protective barrier.

[0041] 36. Photoaging causes lipid peroxidation, which consists of a chain reaction of polyunsaturated fatty acids in cell membranes, generating free radicals that alter their permeability, fluidity and integrity, which will activate hyperpigmentation in melanocytes.

[0042] 37. Studies show that melasma cells undergo disruption, and in the upper dermis of skin with this condition, there is increased fibroblast activity, endothelial proliferation, and mast cell proliferation, as well as other factors such as inflammatory mediators, iNOS, NF-kB, endothelin, vascular endothelial growth factor (VEGF), and hepatocyte-derived, fibroblast-derived, and nerve growth factors. 38. Furthermore, there is increased elastotic degradation of collagen and its disorganization in the papillary dermis of melasma, suggesting inflammatory damage and protease activity. Pendulum melanocytes in the basal layer project toward the upper dermis.

[0043] 39. Above all, it presents changes in the basal membrane, there is a decrease in type I collagen associated with an increase in the activity of metalloproteins (MMP1, 2, 3 and 9), that is, they are proteins linked to one or more metal ions such as iron, which compromises this tissue with melasma.

[0044] 40. Since metalloproteinases are proenzymes released by neutrophils, monocytes, macrophages, fibroblasts, and also by tumor cells, they promote the degradation of the extracellular matrix.

[0045] 41. However, in the dermis of the skin, fibroblasts are the most common cell types, as they have a long lifespan and accumulate damage to their cellular structure, resulting in functional and morphological changes.

[0046] 42. Thus, there is a decrease in the number of proliferating fibroblasts in intrinsic senescence and photoaging. Fibroblasts play a central role in pigmentation and its transition to aging of this cell, presenting a modification of their autocrine and paracrine activity.

[0047] 43. Studies show that fibroblasts in melasma are more rigid, proving this autocrine and paracrine alteration, in addition to releasing more stem cell source factors and their epidermal receptor C-KIT11, degrading collagen through metalloproteinases (MMPs) that reduce mitotic potential, hindering the tissue repair process, and there is evident stromal degradation in the dermis with melasma.

[0048] 44. A cross-sectional study was conducted involving 20 women who underwent skin biopsies with and without melasma. In this study, they validated 256 skin proteins, and of these, 29 were differentially quantified in melasma skin. The most discrepancies were: HDB, EXPH5, ​​KRT1, KRT9, REV3L, ACAP9, ADGB, CAI, and the proteins ACTG1, ALB, SERPINA1, HBD, ALDOA, and FGG, which actively participate in various biological processes. 45. These processes, such as oxygen consumption, cellular transport phenomena, regulation of the melanogenesis pathway, hemostasis and coagulation, repair and healing, as well as response to oxidative stress, glycolysis, and gluconeogenesis, show increased metabolic activity in melasma skin.

[0049] 46. ​​In view of the above, it proves that the melasma process goes well beyond the hyperfunction of melanocytes, and rather the functional alterations of the cells involving the epidermomelanic unit, the basement membrane zone and the upper dermis, thus demonstrating the complexity of this hypermelanosis.

[0050] PAPAIN

[0051] 47. Carica papaya is a thiol proteinase consisting of a single polypeptide chain containing 212 amino acid residues, an enzyme complex of single chains with three disulfide bridges, and a group of sulfhydryl proteases (SH), belonging to the amino acid cysteine, found in the leaves, stem, fruits of the green papaya latex called papain.

[0052] 48. Sulfhydryl groups (SH) are necessary for enzyme activation and are considered the largest and most frequent antioxidants in plasma. After dilution, they have an odor similar to sulfur.

[0053] 49. These proteolytic enzymes and peroxidases cause the proteolysis of high molecular weight proteins in devitalized tissue. Their proteolytic activity is influenced by pH, with its optimum value ranging from 5 to 8.

[0054] 50. Several studies show that the proteolytic effect of carica papaya degrades proteins into amino acids, and in addition to activating tissue regeneration, it has anti-inflammatory action without altering healthy tissue. This is due to a plasma antiprotease called alantitrypsin, a human globulin present only in healthy tissue that inactivates proteases, preventing the degradation of healthy tissue. Furthermore, papain only hydrolyzes proteins containing cysteine ​​residues and has no effect on collagen or elastin. UREA

[0055] 51. Urea is an amine, a white, deliquescent (water-soluble), crystalline solid. It is produced artificially in industry, but it can be found in the human body. Therefore, it is considered a diamide because it has two NH2 groups in its carboxyl bond. 52. Above all, it has hygroscopic properties, meaning it absorbs moisture from the atmosphere. Its natural presence in the stratum corneum is evidenced in the literature, constituting approximately 7% of the natural hydration factor. It also acts as a humectant, making it suitable for oily and acne-prone skin. For this to happen, the relative humidity of the air must be adequate for its proper functioning.

[0056] 53. Therefore, it facilitates natural skin exfoliation, inhibits the growth of microorganisms in the product, promotes the penetration and absorption of other active ingredients, relieves itching, leaves the skin soft and supple, and has anti-inflammatory, antiseptic, and deodorizing properties. It is used at a maximum of 8 to 10% in cosmetic formulations and may be found in higher concentrations in dermatological products. This demonstrates its effectiveness in skin treatments.

[0057] ZINC SULFATE

[0058] 54. Zinc is a transition metal, ZN 30, an inorganic ion that is solid at room temperature. It functions as a cofactor in reactions that require a redox-stable ion, participating in over 300 enzymatic reactions. It has catalytic or structural functions, is present in enzymes and proteins, and is involved in the metabolism of carbohydrates, lipids, and nucleic acids.

[0059] 55. Zinc, which can be found in zinc oxide or sulfate, acts as an antiseptic and astringent, meaning it can precipitate proteins, and is calming, drying, and anti-inflammatory. When deficient, tissue repair is impaired, as connective tissue formation decreases.

[0060] 56. Zinc is important in the formation of a protein structure called metallothionein. It is known that in oxidative stress this protein releases zinc, which in turn assumes antioxidant properties when cells are exposed to radiation, drugs and heavy metals.

[0061] 57. In this way, it prevents the propagation of free radicals through selective binding of pro-oxidant metal ions such as iron and copper, and potentially toxic ones such as mercury and cadmium. Therefore, zinc is essential in combating oxidative stress and free radicals in cells. 58. Zinc, in the skin, is located in its greatest quantity in the epidermis compared to the dermis. The main physiological functions of zinc are: it participates in all phases of keratinocytes, their proliferation, keratinocyte differentiation, and decreases their survival, increases ATP production, inflammatory cytokines, and iNos / NO in cells.

[0062] UBIOUINONAS

[0063] 59. Coenzyme Q10 is a benzoquinone, considered a fat-soluble provitamin with a long isoprenoid side chain. It was discovered in 1957, isolated from bovine heart mitochondria, known as ubiquinone or CoQ10, and present in all cells of the body, participating in ATP production processes. Its oxidized form is called ubiquinone, and its reduced form is called ubiquinol. It is the only endogenously synthesized lipid with a redox function.

[0064] 60. Ubiquinone is a powerful antioxidant in its reduced form, which prevents oxidative damage in cells, caused by the disordered synthesis of free radicals, so there are recent studies that show the relevance of ubiquinone in DNA resistance to oxidative damage.

[0065] 61. Above all, ubiquinone is evident in the role of oxidative stress in inducing vascular injury and inflammation.

[0066] DETAILED DESCRIPTION OF HOW THE CHEMICAL ELEMENTS PRESENTED ACT ON SKIN WITH MELASMA

[0067] 62. Melasma is nothing less and nothing more than skin cells reacting against an aggressive agent, the main one being the sun's rays, which cause damage to the skin barrier, the stratum corneum, the cell membrane, causing intracellular disruption and, consequently, a threat to the skin cell's DNA.

[0068] 63. Continuing, the skin barrier, its main function is to protect the human body from aggressive agents, hence the importance of maintaining the integrity of the corneocyte stratum, which occurs through lipids organized in sheets that fill the intercellular gaps, acting as lipid cements, and these are formed by fatty acids, ceramides, cholesterol, in addition to the natural moisturizing factor, which through the cleavage of filaggrin (protein responsible for the normal keratinization of the skin), results in by-products such as histidine, acting as an ultraviolet photoprotector.

[0069] 64. So, you now know that the stratum corneum is not a mass of dead cells, but beyond its barrier function, it also has other important functions. Above all, the corneocyte actively participates in the formation of the natural moisturizing factor, which prevents tissue dehydration.

[0070] 65. Therefore, zinc sulfate, together with urea, rebuilds the stratum corneum that has been worn down in skin with melasma, as a result of cellular aging, UV radiation, atopic dermatitis and other skin conditions, or changes in temperature, reduction in stratum moisture and the amount of amino acids such as serine, alanine and glycine, damaging the protective barrier of this skin.

[0071] 66. Therefore, the maintenance and reconstruction of the comeal membrane is of fundamental importance for the cells, since in melasma this protective barrier is compromised, which harms the cells.

[0072] 67. Epidermal maintenance is extremely valuable for cell conservation, as it prevents moisture from escaping and keeps the natural moisturizing factor intact, preserving the skin's moisture, leaving it more hydrated and protected.

[0073] 68. Therefore, the use of urea, zinc sulfate and ubiquinones help to restore lipids in the corneal layer, which has been damaged by chronic sun exposure, photoaging and intrinsic aging, among the zinc deficiencies that are evident in skin with melasma.

[0074] 69. Other studies refer to the importance of ceramides in keeping the lipid mantle intact, as they act by retaining water in the stratum corneum, helping with skin hydration.

[0075] 70. It is clear that ceramides (a type of membrane lipid) in cosmetics are important for maintaining the skin barrier and preventing water loss, in addition to providing softness and elasticity to the skin. Thus, papain, urea, zinc sulfate, and ubiquinol stimulate the reconstruction of the skin barrier in skin with melasma.

[0076] 71. From this point of view, in addition to damage to the cell plasma membrane and extracellular matrix, the vast majority of studies categorically state that there is chronic inflammation in the skin with melasma, and this imbalance is associated with increased proliferation and activity of melanocytes, with photoaging as the main trigger, but they believe in the interference of other factors such as intrinsic aging, genetics, hormonal, cosmetic and endocrine factors.

[0077] 72. Melanogenesis triggers the overproduction of melanin, which is transferred to the keratinocytes of the epidermis. This imbalance causes a disorder in melasma cells, stimulating inflammatory mediators, lipid peroxidation in cell membranes, the generation of free radicals, fibroblast aging, and an increase in mast cells and prostaglandins that activate the signaling pathways involved in melanocyte growth, differentiation, and apoptosis.

[0078] 73. Studies show that in melasma-infected skin, intracellular organelles, mitochondria, the Golgi complex, and the rough endoplasmic reticulum are increased in number, supporting the theory of hyperfunctional melanocytes. Therefore, reorganization of the internal structures of these organelles and the plasma membrane is necessary.

[0079] 74. Due to the above, the use of papain helps to adjust this skin, making it healthy again, as it is a protease rich in an essential amino acid called L-cysteine, its power of action consists of reducing the action of tyrosinase 1, peroxidase and tyrosinase 2, this reaction is dependent on copper to occur.

[0080] 75. Hence the use of urea, papain, and zinc sulfate, as these components aid in the decomposition of copper. Without copper, the melanogenesis chain will be interrupted.

[0081] 76. Furthermore, copper has a high affinity for oxygen, consequently, it participates in the oxidative damage of cells, that is, without copper in circulation, in addition to preventing the action of tyrosinase, it prevents cellular oxidative stress.

[0082] 77. Papain, along with urea, are two skin exfoliants. They perform enzymatic debridement of the comeocyte membrane, facilitating the entry of other chemical elements into the membrane to act internally in cell organization. Therefore, the more l-cysteine ​​is available in the cytosol, the more pheomelanin is produced, and in the absence of cysteine, the greater the production of eumelanin. 78. Since papain is a proteolytic enzyme, it is rich in thio groups by sulfhydryl radicals. Sulfhydryl (SH) groups are considered the largest and most common antioxidants in plasma. These groups are characterized by a sulfur atom bonded to a hydrogen atom. Their chemical function is thiol, which are precursors of glutathione, the most potent cellular antioxidant.

[0083] 79. Based on this, studies show that the use of papain-urea in wound treatment is extremely effective, as papain has the function of destroying any protein that contains cysteine ​​residues.

[0084] 80. In melasma, growth factors such as Sscf, bFGF, NGF, and HGF are activated, and they contain cysteine ​​residues, which is why they are affected by papain. However, collagen and elastin are not affected by this action, as they do not contain cysteine ​​residues in their structure.

[0085] 81. Urea in this combination intensifies the effect of papain in its proteolytic action, by altering the three-dimensional structure of proteins, breaking hydrogen bonds.

[0086] 82. Since melasma is rich in hydrogen bonds, urea leads to the reduction of disulfide bonds and hydrogen bonds, and the exposure of cysteine ​​residues, which favors the action of papain. In this way, this association becomes twice as effective in the digestion of proteins that are affected by papain.

[0087] 83. Considering that urea easily associates with L-cysteine ​​present in papain, which easily passes through the plasma membrane (by osmosis), this helps to make cysteine ​​residues available in the cytosol of cells, facilitating the production of glutathione and the formation of pheomelanin.

[0088] 84. Therefore, the chemical elements urea, ubiquinol, and zinc sulfate decompose and reduce the absorption of copper and iron at the cellular level, preventing the formation of free radicals. Iron binds to metalloproteins, causing cellular oxidation and degradation of the epidermal extracellular matrix. Therefore, these chemical elements are extremely important in rebuilding the extracellular matrix and the epidermal barrier.

[0089] 85. Above all, zinc participates in all cellular activities, being necessary for skin health, as it is essential for the construction of immune system cells, especially T cells, as well as neutrophils, peripheral blood monocytes, tissue macrophages and mast cells, all of which require excellent concentrations of zinc for their normal functioning, its deficiency can be responsible for several systemic skin diseases.

[0090] 86. It is known that although zinc reduces the absorption of copper and iron at the cellular level, it is capable of helping to deflect ultraviolet rays, acting as a photoprotector, protecting the skin against damage caused by the sun. Above all, it fights free radicals, has antibacterial effects, and is effective in the treatment of acne and other types of dermatitis.

[0091] 87. Continuing, in the area of ​​melasma, studies show that there is a disorder of collagen, papain provides alignment of collagen and elastin fibers, and together with urea, stimulates their production, as well as elastin, promoting growth and tissue repair.

[0092] 88. Since, in the dermis of melasma there is an increase in cellularity, endothelial proliferation and greater elastotic degradation of collagen, due to solar elastosis, and a disorganization of the same in the papillary dermis of melasma, suggesting that inflammatory damage and protease activity occur in that area, hence the importance of papain and urea in this tissue repair.

[0093] 89. When combining urea and papain, used to treat lesions in the dermis and epidermis, a greater increase in epidermal thickness and increased capillary network formation were observed, as well as an increase in thick collagen fibers and increased cytokeratin expression in the basal layer of the skin. Therefore, it is clear that the papain-urea combination benefits skin with melasma.

[0094] 90. Some studies confirm that under conditions of tissue stress, hemoglobin presents a high ratio in melasma, and this increase favors free iron and the formation of highly reactive oxygen species (ROS), such as hydroxyl radicals that can damage DNA and other macromolecules, leading to cell apaptosis.

[0095] 91. Other studies have found a greater presence of HBD, ACTG1, SERPIN 1, and KRT1 in melasma, due to oxidative stress sustained by the activity of mast cell tryptases and the secretory phenotype of upper dermal fibroblasts. This justifies all the chemical elements used in these dermatocosmetic formulas, as they correct the alterations listed above. 92. It is worth noting that cellular oxidation is part of the aerobic metabolism of human life and the production of free radicals. What cannot occur is an excess of free radicals in cells, such as superoxides, hydrogen peroxide, nitrous acid (HNO2), and nitrous oxide (NO).

[0096] 93. Since these are highly reactive in the body, attacking lipids, proteins and DNA, others are reactive only with lipids, causing peroxidation of membrane lipids, attacking tissue and membrane proteins, enzymes, carbohydrates and especially DNA.

[0097] 94. As in the body, free radicals are involved in energy production, phagocytosis, regulation of cell growth, intercellular signaling and synthesis of important biological substances, which justifies the use of ubiquinol and zinc sulfate in cell reconstruction, combating the excess of free radicals produced in skin with melasma.

[0098] 95. It is necessary to highlight that hydroxyl radicals can react with amino acids and proteins, and in the side chain they preferentially attack cysteine, histidine, tryptophan, methionine and phenylalanine, and in smaller proportions, arginine and asparagine.

[0099] 96. Attacks on the amino acids that make up proteins can cause damage such as bond cleavages with or without consequent loss of enzymatic activity, difficulties in active transport across cell membranes, cytolysis and cell death.

[0100] 97. Therefore, the excess of hydroxyl radicals attacking the cysteine ​​molecules facilitates the production of eumelanin (black melanin), rather than pheomelanin, perhaps which is why there is a greater presence of eumelanin in skin with melasma.

[0101] 98. However, with the presence of papain, which will make more cysteines available in the cytosol, this will facilitate the production of pheomelanin, the lightest melanin, in addition to the fact that cysteines favor the formation of intracellular glutathiones, combating excess hydroxyl radicals.

[0102] 99. In the human body, ubiquinones participate in the Krebs cycle through the process of oxidative phosphorylation, which is the form of energy used by the cell to carry out biological processes. 100. Since the energy-rich electrons captured in glycolysis are converted to (NADH) and in the Krebs cycle are converted to NADH and FADH2, they must subsequently be converted to ATP.

[0103] 101. Above all, this process takes place inside the mitochondria and is dependent on oxygen and the carriers that carry the electron chains.

[0104] 102. Therefore, the individual electron-carrying proteins are organized into a series of four multiprotein complexes (complex I to IV), each located within the mitochondrial membrane.

[0105] 103. This entire process depends on ubiquinones within the mitochondria. However, in the human body, its bioproduction continues until the age of 30, after which the body stops producing it. From this age onward, its decline begins, leading to cellular senescence.

[0106] 104. Thus, the absence or deficit of ubiquinones in cells favors the overproduction of hydroxyl radicals and hydrogen superoxide and, consequently, of free radicals, damaging all intracellular metabolic processes.

[0107] 105. Superoxide distumase is a mitochondrial enzyme that is part of the cells' enzymatic antioxidant system. It is this enzyme that eliminates excess free radicals in the cytosol.

[0108] 106. Thus, studies show that skin with melasma has a significant increase in this enzyme, thus proving the presence of a state of cellular systemic oxidative stress, which reinforces the use of antioxidants in melasma treatments. Therefore, it reinforces the use of cellular antioxidants such as papain, ubiquinol, and zinc sulfate.

[0109] 107. It is worth noting that, inside cells, ubiquinones convert excess free radicals into water and oxygen molecules, preventing cellular oxidative stress, which is why it is a powerful antioxidant in its reduced form (ubiquinol).

[0110] 108. A healthy water concentration in cells promotes cellular hydration, preventing aging. The presence of ubiquinones in cells also reduces wrinkles and expression lines, activates collagen and elastin production, and leaves your skin healthier and more hydrated. Therefore, it plays an important role in the cellular aging process. 109. Ubiquinones are also important in inducing vascular lesions and inflammation, acting as an anti-inflammatory. Therefore, it is beneficial for skin with melasma, combating inflammation.

[0111] 110. All studies show that skin with melasma needs greater protection against UVB and UVA rays, which justifies the use of zinc sulfate and ubiquinones in this formulation. Both act as inorganic photoprotectors because they have photocatalytic properties, which form a physical barrier capable of reflecting and scattering visible UV rays that fall on the skin.

[0112] 111. Thus, it is concluded that this dermocosmetic formulation combats cellular senescence, recovers the stratum corneum and phospholipid bilayer of membranes, combats lipid peroxidation, local inflammation, eliminates excess free radicals from the intracellular environment, reorganizes the structures of internal organelles, preserves DNA integrity, maintaining homeostasis and skin health, healing them, gradually reducing dark spots, leaving the skin healthier, softer, brighter and hydrated.

[0113] BRIEF DESCRIPTION OF THE CLINICAL CASE

[0114] 112. As a clinical case, we have a 40-year-old patient, brown skin color, who started with melasma in 2005 in the cheek region only, with small irregular black spots. She started treatment with hydroquinone cream, after 2 months of continuous use, the spots lightened only initially, after finishing the treatment the spots recurred and increased in size.

[0115] 113. Because the spots are black, I continue to use other depigmenting agents such as Suavicid, kojoic acid, glycolic acid, chemical peels, etc. All of them had recurrence and an increase in the size of the spots and their extension, from the cheek region it spread to the forehead, nose and chin.

[0116] 114. Thus, the patient underwent acid treatments for 18 years, and this led to 80% facial pigmentation and skin aging.

[0117] 115. After four months of diligent treatment with this chemical formula, which began in April, this photo is from August 2023. 95% of the face is now melasma-free, and the face is 70% rejuvenated, with a significant reduction in wrinkles and expression lines. The spots still appear slightly in the center of the cheeks and nose. INNOVATION

[0118] 116. In general terms, the said product represents a solution with regard to a dermocosmetic formulation for the treatment and cure of melasma;

[0119] 117. Indicated for the treatment of melasma, but also useful for other dermatoses such as psoriasis, acne, folliculitis and skin rejuvenation;

[0120] 118. The period of use must be at least 6 to 12 months;

[0121] 119. This treatment can be used on all skin types and phototypes, except if there is an allergy to any of the active ingredients in the formula;

[0122] 120. Papain and urea both perform enzymatic peeling and exfoliation on the skin of the face (they have a proteolysis reaction in the stratum corneum). This stimulates cell renewal in the epidermis, gently removing dead cells without damaging this layer.

[0123] 121. In addition, it aligns collagen fibers and tissue repair, stimulating fibroplasty, activates the formation of new cells, and at the same time the amino acid L-cysteine ​​(papain is rich) enters the cells, its availability in the cytoplasm stimulates the formation of glutathione, a powerful cellular antioxidant;

[0124] 122. Cysteine ​​participates in the direct formation of melanin, inserted in the chain, it produces pheomelanin, the lightest melanin, and, consequently, gradually cures cellular alterations;

[0125] 123. Papain and zinc sulfate combat cell inflammation, as they act in the formation of the lipid chain of the plasma membrane, increasing the defense system, stimulating the formation of cytokines, leukotrienes, prostaglandins and other inflammatory mediators;

[0126] 124. Papain, urea, zinc sulfate, and ubiquinol are powerful cell regeneration agents, reducing wrinkles and expression lines by 70%, as they act on the superficial and deep layers of the skin. In the stratum corneum, they are essential for retaining moisture; intracellularly, they act on collagen and elastin fibers, activating them, and also promote tissue repair as cellular anti-aging agents.

[0127] 125. Papain and ubiquinol act as powerful cellular antioxidants, eliminating free radicals and reducing cellular acidity, consequently preventing premature aging, making cells healthier; 126. Reduction in pigmentation, since the elements of the formulation (papain, urea, and zinc sulfate) remove copper and iron from circulation (to form melanin, these chemical elements participate directly in the process), so by removing them from circulation, there is no melanin formation;

[0128] 127. Papain and ubiquinol act in the recovery of blood vessels, strengthening them and preventing cellular inflammation;

[0129] 128. Zinc sulfate and ubiquinol increase protection against UVB and UVA damage. UVB rays cause DNA damage and lead to cell apoptosis. Ubiquinol also acts in energy production, in the cellular glycolysis process, and fights free radicals, corrects alterations in plasma membranes and DNA, enhances the skin's natural defenses, and increases resistance to UVB rays.

[0130] 129. Papain and ubiquinol act on oxidative stress by eliminating free radicals. The Krebs cycle, which contributes to energy production, and the oxygen cycle in melasma cells is compromised, resulting in the production of free radicals, which become toxic to the cell. Ubiquinol converts excess free radicals into O2 and water.

[0131] 130. Papain and urea stimulate the production of collagen and elastin, making cells healthier and more resistant;

[0132] 131. Ubiquinol is the active and bioavailable form of coenzyme Q10, being a powerful cellular antioxidant, it has greater interaction in the body's energy production, that is, it further facilitates cellular metabolism by acting on the cellular energy process (which is compromised in melasma), acting on the glycolysis process;

[0133] 132. Ubiquinol and zinc sulfate combat cellular senescence, rebuild the lipid bilayer of cells, recovering the skin barrier, rejuvenating skin cells;

[0134] 133. The product uses chemicals never before used to treat melasma. It is a formula to treat and heal this skin, which is damaged by ultraviolet rays and intrinsic aging, causing cellular senescence, more specifically of fibroblasts. Consequently, it activates melanogenesis, inflammatory mediators, growth factors, and metalloproteinase enzymes, degrading the extracellular membrane (ECM) and the stratum corneum, causing internal organelle imbalances, activating DNA and consequently the epidermal barrier.

[0135] 134. So, the chemical elements used are to align all the disorganization that exists in this skin, restructure the skin barrier, maintaining the skin's natural hydration factor, the plasma membrane zone, the extracellular matrix, stimulate the production of new fibroblasts and elastin, rebuild the phospholipid layer of the plasma membrane, the internal organelles, protecting the DNA, combating oxidative stress in the cells with the use of papain, urea, zinc sulfate, ubiquinone;

[0136] 135. This is a unique, exclusive and innovative product, highly reliable and recommended for use when treating and curing skin with melasma and will certainly be a great differentiator for the sector for which it is intended.

[0137] DESCRIPTION OF THE STATE OF THE TECHNIQUE

[0138] 136. During the development of the aforementioned product, numerous studies were carried out to identify the existence of possible prior art or similar products. However, these studies did not indicate the existence of any other product with the same predominant technical or functional characteristics.

[0139] 137. The search carried out found processes that superficially mention the combination in whole or in part of the words “system, pumping, water, piston”, such as BR 11 2021 025797 7, BR 102019021208 0, BR 102019011839 3, BR 13 2017 003992 6, BR 102016 015213 5 and PI 0504874-5, however, such processes describe more simplified products and with formulations containing compositions different from those claimed in the present patent application.

[0140] 138. Additionally, it was not possible to find in the searches carried out a formulation that, in addition to treating skin with melasma, is also capable of reorganizing the internal structure of the cells.

[0141] 139. In view of this need and commercial opportunity, the aforementioned product was created, more precisely a formulation, whose function is to repair and treat skin with melasma and reorganize the cells so that melasma does not recur. 140. Therefore, in accordance with Article 8 o of the Industrial Property Law No. 9,279 / 96 and for all the aspects presented in this report, the object of this patent application is worthy of protection as an invention privilege, which is now being sought.

Claims

CLAIM 1. DERMOCOSMETIC FORMULATION OF PAPAIN, UREA, ZINC SULFATE AND UBIQUINOL FOR THE TREATMENT AND CURE OF MELASMA - This is a chemical formulation based on papain, urea, zinc sulfate and ubiquinol, whose objective is to treat and cure skin affected by melasma, characterized by: papain 10%; urea 5%; zinc sulfate 6%, ubiquinol 5%, in a base cream qsp 100g, the manufacturing must be carried out by a qualified professional who knows the chemical processes and use of each composition for correct handling.

Images