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WO2014075157A1 - Composition et formulation à base d'huile de café, et utilisations - Google Patents

Composition et formulation à base d'huile de café, et utilisations Download PDF

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Publication number
WO2014075157A1
WO2014075157A1 PCT/BR2013/000459 BR2013000459W WO2014075157A1 WO 2014075157 A1 WO2014075157 A1 WO 2014075157A1 BR 2013000459 W BR2013000459 W BR 2013000459W WO 2014075157 A1 WO2014075157 A1 WO 2014075157A1
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Prior art keywords
coffee
oil
healing
composition according
composition
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English (en)
Portuguese (pt)
Inventor
Comércio De Óleos Essenciais Ltda. Linax
Paulo Eduardo NEVES FERREIRA VELHO
Maia NILSON BORLINA
Lania BRUNO GROSSELLI
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INSTITUTO AGRONOMICO
Universidade Estadual de Campinas UNICAMP
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INSTITUTO AGRONOMICO
Universidade Estadual de Campinas UNICAMP
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/74—Rubiaceae (Madder family)
    • A61K36/742—Coffea, e.g. coffee
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/74—Rubiaceae (Madder family)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders

Definitions

  • the present invention relates to a coffee oil based composition. More specifically, the present invention relates to a topical use composition based on roasted coffee oil with skin healing ability. Furthermore, further objects are their use and a formulation comprising said composition.
  • the healing process can be more simply divided into three phases: inflammatory, proliferative and remodeling (Pittman, 2007).
  • inflammatory phase after hemostatic coagulation has begun, numerous chemical mediators are released by inflammatory cells.
  • the macrophage is the most important cell of this phase and will remain from the third to the tenth day.
  • Lymphocytes appear in the lesion approximately one week later.
  • the lymphokines released by them influence the action of macrophages (Mandelbaum, 2003). In addition to these, this phase relies on fibronectin.
  • the proliferation phase is responsible for the closure of the lesion itself. In it happens reepithelization by the migration of keratinocytes from the wound edges and attachments if they have been preserved (Dielgmann et al., 1981; Clark, 1985; Gentil Subscribe et al, 1999). Cytokines modulate the inflammatory process that is necessary in the healing process but can be harmful if excessive. They are also responsible for faster and more effective healing (Gentil Subscribe et al, 1999). Matrix formation depends, in addition to inflammatory and endothelial cells, on the fibroblast responsible for the production of substances important for both debridement and physiological remodeling (Van Winkle, 1967). The proliferation of vessels that occurs at this stage is essential for the supply of oxygen and nutrients for healing. Thus, it can be said that the proliferation phase is divided into reepithelization, fibroplasia and angiogenesis (Mandelbaum, 2003).
  • Remodeling is the last phase, lasting months and is responsible for increasing tensile strength and decreasing scar size.
  • Collagen reformulations, improvement in collagen fiber components, water resorption are events that allow for a connection that increases scar strength and decreases thickness (Doillon et al., 1985).
  • Local neovasculature decreases, and the normal healing area has about 80% of the normal tensile strength of the skin, is not bulky and is flat (Mandelbaum, 2003).
  • adiponectin adiponectin, leptin, interleukin (IL) 2, IL-4, IL-6, IL-12, tumor necrosis factor (TNF) ) -a, insulin-related growth factor (IGF) -1, interferon (IFN) -ae IFN- ⁇ .
  • IL interleukin
  • TNF tumor necrosis factor
  • IGF insulin-related growth factor
  • IFN interferon
  • Adiponectin is a protein that acts on glucose and lipid homeostasis. Circulating adiponectin levels are high, reaching approximately 0.01% of plasma proteins (Basu, 2009). It is induced during adipocyte differentiation and its secretion is stimulated by insulin. Adiponectin is an adipokine that influences systemic metabolism. It acts on glucose and fatty acid metabolism, being in some situations antagonistic to TNF- ⁇ (Yano, 2008). Induces a decrease in serum glucose and triglyceride levels, increases the level of glucagon.
  • adiponectin acts directly on keratinocytes, regulating the expression of immunomodulatory substances produced by these cells; This indicates that adiponectin acts indirectly on other cells through keratinocyte products. Another action would be the suppression of keratinocyte proliferation and differentiation, which would be beneficial in cases of hyperkeratinization (Kaway, 2008). A study conducted in Brazil indicates that overweight has the ability to increase healing time (Nascimento, 2006).
  • leptin Lack of leptin in animals as well as in humans can lead to weight gain and also to increased healing time. Direct administration of leptin leads to reduced healing time, with greater reepithelization, but without interfering with angiogenesis. Another fact observed in animals is the increased expression of leptin receptor genes locally, which indicates the importance of leptin for healing process. Leptin leads to an increase in application keratinocytes at the beginning of healing (Nascimento, 2006).
  • IL-2 is a pleiotropic cytokine (like most cytokines), ie it has multiple effects: a single cytokine can interact with more than one cell type, have multiple biological activities, interact with other cytokines with which it may have overlapping activities (Arai, 1990). Produced primarily by mitogenic or antigenically activated T lymphocytes. It has a key role in promoting clonal expansion of antigen-specific T cells. In addition, IL-2 is capable of mediating multiple immune responses in a variety of cell types.
  • IL-2 stimulates thymocyte proliferation, proliferation and differentiation of activated B cells; promotes monocyte growth and differentiation and cytocidal activity; induces the growth of natural killer cells and their production of cytokines and cytolytic activity; increases the production of lymphocyte-activated killer cells (LAK) and induces oligodendrocyte proliferation and differentiation (Goldsmith, 1994). In hypertrophic scarring and keloid situations, IL-2 is found in local lymphocytes, suggesting pro-scarring action (Armour, 2007).
  • IL-4 is also a pleiotropic cytokine that has multiple immune response modulation activities in a variety of cell types. It is a B cell activation / differentiation factor that regulates the isotope exchange of Ig, particularly IgG1 and IgE. It suppresses the development of IFN- ⁇ -producing CD4 + T cells and regulates the differentiation of naive helper T cells in the Th2 subset that mediates the allergic and humoral immune response.
  • TNF- ⁇ synergistically induces the expression of VCAM-1 (vascular cell adhesion molecule 1) in smooth endothelial and muscle cells, resulting in selective recruitment of eosinophils and lymphocytes at the inflammation site.
  • VCAM-1 vascular cell adhesion molecule 1
  • IL-4 negatively regulates the production of inflammatory mediators such as IL-, TNF- ⁇ , and prostaglandin 2 (PGE 2 ) in monocytes. Anti-tumor activity has been demonstrated both in vivo and in vitro.
  • the cells that secrete IL-4 are basophils, CD8 + T, memory CD4 + and naive Th2, mast cells, eosinophils, and virus-activated dendritic cells.
  • IL-4 is the -
  • tenascin an extracellular matrix glycoprotein, present as a thin layer in the adult papillary dermis, but which is restated in the healing process
  • fibroblasts in the earlier stages of collagen deposition and cell migration (Makhluf, 1996).
  • IL-6 is a cytokine that plays important roles in host defense, acute phase reactions, inflammation, hematopoiesis, bone metabolism, and cancer progression. IL-6 is essential for the transition from acute inflammation. It is secreted by various cell types and production is regulated by numerous signals such as mitogenic or antigenic stimuli, lipopolysaccharides, calcium, other cytokines, and viruses. Cytokines IL-4, IL-10 and IL-13 inhibit IL-6 expression in monocytes (Hirano, 1996). Elevated IL-6 serologic levels were observed in pathological situations such as viral and bacterial infections, trauma, autoimmune diseases and inflammation.
  • IL-6 increases early in the healing process and is important because it has mitogenic properties in keratinocytes as well as chemotactic to neutrophils and their infiltration to the affected area has the ability to increase local angiogenesis and increase local collagen deposition. of the wound (Lin, 2003).
  • IL-12 is a heterodimeric glycoprotein that enhances cytotoxic activity and induces IFN- ⁇ production in the natural killer, T and T dendritic cells of the epidermis. It also induces IFN- ⁇ production in macrophages.
  • This cytokine together with others of the same family (IL-23 and IL-27), is capable of promoting the development of immune response through CD4 + Th1 T cells;
  • IL-12 promotes Th1 cell production after IL-27 has transformed ThO into Th0 / 1; Together with IL-18, IL-12 creates memory Th1 cells from effector cells (Hamza, 2010). In healing processes, IL-12 has increased gene expression, causing macrophages to produce and secrete more IFN- ⁇ (Ishida, 2004).
  • TNF- ⁇ plays critical roles in normal host resistance to infection and growth of malignant tumors, serving as immunostimulants and as mediators of the inflammatory response. A lot of TNF production, however, has been implicated as playing a role in a number of pathological conditions, including cachexia, septic shock, and autoimmune diseases. TNF- ⁇ is produced by activation of macrophages and other cell types, including T and B cells, NK cells, endothelial cells, smooth muscle cells, and some tumor cells. In healing, the absence of receptors for this cytokine accelerates the process (Ware, 1996). In wounds, TNF- ⁇ is responsible for initiating the proinflammatory cascade and is responsible for healing strength and tension (Mast, 1996).
  • GF-I also known as somatomedin C, is a member of the insulin superfamily. It has been found to mediate hormone actions in somatic cell growth, but it has also been shown to be an important regulator of cell metabolism, differentiation and survival. IGF-I is synthesized as a preprotein that is proteolytically cleaved to generate mature protein (Humbel, 1990). IGF-1, together with platelet-derived growth factor 2 (PDGF-2), can increase skin thickness in wound healing (Lynch, 1989), and this substance is directly involved in the regeneration of various tissue types. , not just the epithelial (Chen, 2010).
  • PDGF-2 platelet-derived growth factor 2
  • IFN-cf is a cytokine family glycoprotein that participates in cell control and replication, host defense against foreign organisms such as viruses or bacteria and is a major type I interferon. It is produced by mononuclear phagocytes in response to viral infection. It has a role in inhibiting viral replication and enhancing the expression of type I (MHC type I) main histocompatibility complex molecules, either by autocrine or paracrine activity (Krause, 2005). Another form of action of IFN- ⁇ is to protect some cells against virus entry. Numerous investigations have shown that IFN is involved in cell growth regulation and immunomodulatory effect (Ferrantini, 2007).
  • IFN- ⁇ also known as type II interferon
  • type II interferon was initially identified as a product with anti-viral activity of mitogenically activated T lymphocytes.
  • Some of the most important functions are macrophage effector function stimulation, IL-12 induced Th1 differentiation, modulation of MHC molecule class I and II expression, regulation of immunoglobulin (Ig) class exchange and regulation of interactions between leukocytes and endothelium.
  • IFN- ⁇ has also been involved in physiological roles in sensory neurons and spermatogenesis (Neumann, 1997; Kanzaki, 1998).
  • Both interferons have anti-scarring action, inhibiting collagen synthesis and cell proliferation and may increase the production of metalloproteinases.
  • IFN- ⁇ may increase the production of collagenase enzyme, which increases its anti-scarring action.
  • both must have their values increased in the final phase of healing, preventing it from progressing to hypertrophic injury (Tredget, 2000).
  • the claimed formulation has anti-inflammatory action, it cannot be stated that it could be applied effectively in the treatment of skin ulcers. This is because the healing process requires a balance between the production of inflammatory and anti-inflammatory substances and in this case, although in vitro studies may indicate some possibility of application of the product in an anti-inflammatory situation, for example, the final result in vivo may be completely different, and may even make it impossible to use it for the aforementioned application. In the healing process, the same substance can behearted.
  • green coffee or crude bean oil does not promote healing action in vivo, but only roasted coffee bean oil had comparable action to AGE. ®, based on medium chain essential fatty acids and sunflower oil, which was used as one of the study controls. This shows that it is not any essential fatty acid, nor any coffee oil that has healing action.
  • the same substance may be anti-inflammatory and have no pro-healing action and it is necessary to compare and inventive work to obtain a product whose action in vivo proves to be beneficial in the healing process as a whole.
  • oil extracted from green or raw coffee (Coffea arabica), where most research is related to the pharmaceutical and cosmetic sector
  • oil extracted from roasted coffee obtained directly by pressing beans, is best known for its use in food sector, mainly as candies, candies and truffles fillings, liqueur formulation, flavor enhancer in soluble coffee, ice coffee, cappuccinos, various desserts, ice cream, puddings, sweets and milk-based preparations.
  • candies candies
  • truffles fillings, liqueur formulation, flavor enhancer in soluble coffee, ice coffee, cappuccinos, various desserts, ice cream, puddings, sweets and milk-based preparations.
  • the present invention relates to a coffee oil based composition, including roasted coffee beans, for the treatment of skin ulcers.
  • the topical use of this composition influences the systemic production - and not only at the site of application - of healing-related substances, suggesting that its use has a beneficial systemic healing action.
  • the proposed composition has advantages in several respects.
  • the characteristics of an effective wound care product should include ease of removal and comfort for the patient, good value for money, keeping the healing area moist and dry and protected, ease of application and adaptability (conformation to different parts of the body).
  • Another differential of the process described here is related to the systemic action that the technology has, where the serum levels of some substances have been altered, as well as being able to accelerate the healing process in relation to the type of collagen deposited in the site, being more effective than others. products commonly used for this purpose.
  • the present invention is a coffee oil based topical composition with high skin healing ability. Furthermore, the present invention also relates to the use and formulation of said composition.
  • Figure 1 shows the unhealed area of wounds (%) over 10 days of treatment of Group 1 animals (Witness).
  • Figure 2 shows the unhealed wound area (%) over 10 days of treatment of Group 2 animals (AGE).
  • Figure 3 shows the unhealed wound area (%) over 10 days of treatment of Group 3 animals (Crude Coffee Oil),
  • Figure 4 shows the unhealed wound area (%) over 10 days of treatment of Group 3 animals (Roasted Coffee Oil).
  • Figure 5 presents a graph regarding cellularity on the control side of the 4 groups.
  • Figure 6 presents a graph regarding the cellularity on the treated side in the 4 groups.
  • Annex 1 exemplifies the appearance of injuries on the fourth day of treatment in one of the visual evaluations performed.
  • the present invention describes a topical healing coffee oil based composition.
  • the main examples of products which may be prepared from the composition object of the present invention are:
  • composition of the present invention comprises the following components:
  • composition of the present invention may further comprise optional components to provide some desirable feature not achieved with the aforementioned components such as emollient, humectant, chelating agent, thickening system, antioxidant component, preservative system, colorants and flavorings.
  • optional components such as emollient, humectant, chelating agent, thickening system, antioxidant component, preservative system, colorants and flavorings.
  • compositions of the present invention as well as other components optionally added in the formulation will be described in more detail below.
  • concentrations and components may vary.
  • Coffee used as an oil extraction raw material may be of any type of beverage market classification: soft, hard or rinded and of any type of grain size or sieve used for grain size separation.
  • the roasting required for the process is the same industrial roasting used for the production of grain intended for consumption as a beverage, capable of generating the substances that promote the aroma and flavor characteristic of the beverage made by infusion with hot water.
  • the oil extraction process can be either by cold compression as used in the work developed, or by extraction with simple or supercritical solvents.
  • Studies carried out for the embodiment of the present invention make it possible to ensure that the cold pressed oil of roasted Coffea arabica obtained healing action in vivo.
  • the coffee used as raw material was purchased directly from the producer and later sent for roasting and oil extraction. This procedure was necessary because the commercialization system and scale used by the roasters are much larger than the 12 bags volume needed to obtain the oils used in the tests performed.
  • the coffee offered in the normal market does not have control of lots purchased by roasters, do not guarantee the harvest of the product (post harvest time), requires a purchase of at least 20 bags. and do not guarantee or specify storage conditions. To have a control of these factors, it was decided to buy from the producer and later industrialization.
  • roasting of the coffee was done in a commercial roaster (Lilla®) with water cooling and forced ventilation for six bags to ensure a homogeneous raw material volume, without contamination of other batches processed previously or later in the industry's silos.
  • the roasting treatment used was the conventional one applied to the production of coffee for internal drink, with a yield of 0.79 of raw / roasted coffee, which resulted in a total of 285kg of roasted coffee for extraction of roasted coffee oil.
  • Oil extraction and filtration The coffee oil employed in the present invention can be obtained by pressing the beans. Both cold compression extraction as used in the work developed, such as extraction with simple or supercritical solvents, are potentially capable of producing material suitable for treatment, provided that both the oil with the appropriate fatty acid composition and the substances, for example those responsible for the characteristic aroma and taste, generated in the roasting process are obtained.
  • the oil added to a pharmacologically acceptable carrier at a concentration ranging from 0.001% to 99.999%, preferably 70% may be used as a healing agent.
  • the dosage of coffee oil to be used depends on many factors such as the causative agent, the age, weight and clinical condition of the patient as well as the experience and judgment of the physician or practitioner administering the therapy.
  • the effective amount of coffee oil is the one that provides patient improvement detectable by a qualified practitioner.
  • the dosage range varies with the compound used, the route of administration and the potency of the particular compound.
  • both types of coffee raw and roasted
  • the equipment used was an "Expeller” (Piratininga®) press adapted for extracting oil from both raw and roasted coffee beans.
  • the machine has been retrofitted to receive suitable stainless steel hoppers, collection trays and vessels to obtain oil for use in the experiment, without contamination of other raw materials or extracted oils, yet ensuring a quality product that can be repeated for later industrialization. .
  • the six coffee bags for each type of raw coffee and the six roasted coffee generated respectively 23 and 38kg of crude oil. This volume was compatible with the minimum required volume of 20kg to operate the press type filter.
  • the hand-closing horizontal filter press is specially designed for high pressure filtration and clear oil production. the separation of filter sludge with high content of non-saponifiable material of interest for use in treatments. Table 1 shows the yields of the extraction process performed.
  • the material processed in the extraction and filtering was packed in sealed glass bottles with identified samples that were sent for gamma sterilization testing to a company that uses 60 Co radioisotope emitter.
  • the different materials (oil and coffee grounds) raw and roasted) properly identified were submitted to doses 3; 5; 7; 10; 12 and 15 KGy.
  • Chromatographic conditions programmed column temperature, initial temperature 120 ° C / 2min, heating from 120 ° C to 220 ° C on a scale of 2.2 ° C / min and from 220 to 235 ° C on a scale of 1.5 ° C / min remaining in
  • carrier gas hydrogen at a flow rate of 1 mL / min; make-up gas, nitrogen at 30 mL / min; injector temperature, 270 ° C; detector temperature, 310 ° C; injection volume 1 ⁇ L.
  • Quantification was performed by area normalization and the results were expressed in g / 100g of sample.
  • Table 2 presents the data on the fatty acid composition of oils as a function of grain roasting and gamma ray treatments. No significant differences were observed as a function of the application of any of the gamma rays applied.
  • Table 2 Composition (%) of fatty acids in raw and roasted coffee oils5 subjected to different doses of gamma radiation for sterilization purposes.
  • Local absorption and effectiveness of the present invention may be enhanced by using as appropriate carrier an appropriate amount of medium chain essential fatty acids or other chemical compounds known to facilitate absorption and delivery of the active compounds of the present invention used as a carrier for the preparation.
  • coffee oil This will be the preferred carrier of the composition of the present invention by a suitable percentage (q.s.p.) to achieve 100% of the formula based on the total weight of the composition.
  • Still other pharmaceutically acceptable carriers may be used as saline and buffers.
  • composition of the present invention may further comprise optional components such as:
  • EDTA ethylenediaminetetraacetic acid
  • PH adjusting agent such as triethanolamine or inorganic hydroxides
  • Preservative such as parabens, organic acids, imidazolidinines, diazolidines, phenolic alcohols; - Emollient such as alcohols and fatty acids, esters, ethers, mono-, di- or triglycerides, natural or synthetic hydrocarbons or organic carbonates and combinations thereof.
  • Humectant such as glycols, preferably glycerin, propylene glycol, butylene glycol and combinations thereof.
  • Bacteriostatic agent such as methyl hydroxybenzoate, propyl hydroxybenzoate, chlorocresol, benzalkonium chloride and the like.
  • Active ingredients such as antibiotics, anesthetics, pain killers and scaling.
  • Representative drugs within these classes include gentamicin, benzoyl peroxide, glucocorticoids, hydrocortisone, vitamin D3, methotrexate, cyclosporine, retinoids.
  • composition described in the present invention may be prepared employing any process known in the prior art.
  • Coffee oil extracted by pressing the beans may be mixed under sterile conditions with a pharmacologically acceptable carrier, and with any preservative, buffer or propellant as required.
  • Topical preparations can be made by combining coffee oil with conventional pharmaceutical diluents and commonly used carriers in dry, liquid, cream and aerosol topical formulations.
  • Ointments and creams may, for example, be formulated with an aqueous or lipid base with the addition of suitable thickening or gelling agents.
  • Ointments, creams, pastes and gels may also contain excipients such as vegetable and animal fats, oils, waxes, paraffins, starch, cellulose derivatives, talc, zinc oxide, silicones, polyethylene glycol, silicic acid among others.
  • Powders and sprays may contain excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicate and polyamide powder, or a mixture of these substances. Additionally, sprays may contain propellants such as chlorofluorohydrocarbon, butane and propane.
  • Example 1 In Vivo Testing For the tests we used isogenic rats of Rattus norvegicus albinus strain NTacUnib: SD (SpragueDawIey), with an average age of 7 weeks and weight between 220 to 270g. The experiment was approved by the Animal Research Ethics Committee of the State University of Campinas, according to Federal Law 6.638.
  • the animals were prepared to perform the wounds and began to receive daily treatments with the different types of oil, separated into "groups" as shown in Table 3 below. In each group of animals they were subdivided to be sacrificed on days 2, 4 and 10 after the first treatment application.
  • Table 3 schematically shows the distribution of wounds and treatments received by each group of animals.
  • the animal received the first application of the wound-specific product as stipulated in Table 3, which was covered with gauze on each side of the animal to prevent contamination of the different oils applied to the same animal.
  • the gauze was attached by micropore-type adhesive and reinforced with external adhesive.
  • the wounds were cleaned daily with saline, the treatments repeated with the respective oils and the bandages replaced until the day determined for the sacrifice.
  • the animals were not anesthetized so that there was no interference with hepatic metabolism, since all animals accepted all procedures without aggression and were tolerant to manipulation.
  • the back and each wound of each animal were photographed with camera and digital magnifying glass, respectively, for later evaluation.
  • the skin of the trichotomized areas of the dorsal region was excised to the fascia, separating the proximal halves, with two wounds on each side. side for 10% formal fixation until slide preparation for histopathological evaluation.
  • New biopsies with circular slides of the same diameter were made at the four points of the anterior biopsies in the caudal portion of the excised skin.
  • Each of the four dermis or skin fragments removed were immediately identified and placed in a container containing liquid nitrogen and cryopreserved at -80 ° C at the end of the experiment until preparation for the real time PCR of apoptosis-associated substances. .
  • G1 39 G2 0 G3 0 G4 0
  • Figures 1, 2, 3 and 4 respectively, show the curves of the second degree polynomial regression, of the percentage of unhealed wound area in the Group (control), Group 2 (AGE), Group 3 (Raw Coffee Oil) animals. ) and Group 4 (Roasted Coffee Oil).
  • X-axis shows the number of days of treatment and Y-axis the percentage of the unhealed area, considering that on day zero all injuries were in the same area (100%).
  • the red vertical bars represent when the average healing curve reached 75% wound and 25% healed and the black bars represent when 50% of the area was healed.
  • Figure 1 shows that 25% and 50% healing was achieved at 4.7 and 7.7 days after the start of treatment.
  • Parameter (a) of the first degree equations represents the maximum point of the second degree regressions and indicates the time required in days for the curve to reach zero value, ie the total wound healing. So the farther from zero, the lower the initial healing effect of the treatment. Thus, AGE treatment was found to have a better initial effect than all others.
  • Parameter (b) indicates the slope of the line, in the case with negative values, is the graphical representation of the area without healing. The more inclined, the faster the healing rate. The slope of the curves represents the accumulated effects over time, corroborating with clinical observations that animals treated with roasted coffee oil showed a significant improvement after the fourth day of treatment.
  • Table 8 summarizes the days required to achieve 25% and 50% initial wound healing and the second degree derivative of the curves. Since the numbers analyzed correspond to the percentage of the area without healing, the negative value of the second degree derivative of polynomial function represents the healing acceleration (% of healing divided by the time square) of each treatment. Table 8. Number of days for healing of 25% and 50% of the treated areas and value of the second degree derivative.
  • the Witness treatment followed by Raw Coffee Oil, AGE and Roasted Coffee Oil.
  • the preparation of slides for histological analysis was performed as follows: the proximal portion injuries were preserved initially in alcohol and later in formaldehyde in individual bottles properly identified for the preparation of slides for histological analysis. After extraction of each wound from a longitudinal section covering the entire remaining wound or scar, the piece was stained by the Hematoxylin and Eosin (HE) method and contained in paraffin block for microtome work and assembly of the referred blade.
  • HE Hematoxylin and Eosin
  • the blades were subjectively and objectively analyzed to estimate the wound healing rate blindly, that is, without the evaluators knowing the identification of the blade they were examining. 1) Subjective histological evaluation
  • Subjective histological evaluation was done blindly, that is, the dermatopathologist who participated in the project made the evaluation without knowing the identification of the slides she was examining.
  • cycloid there are 30 half circles. Each nucleus that touched one of the cycloids or half circles was counted. This is a comparative method that shows whether healing is developed (adult, composed of fibrocytes) or if it is still young (composed of fibroblasts). In the “adult phase” the number of nuclei is small; In the “young phase”, the number of nuclei is higher. Thus, if a sample has many nuclei, it can be said that the tissue is young (it is still at the beginning of the healing process).
  • the evaluated inflammatory cytokines have different actions on the healing process and some have more intense action in the early stages of healing. For this reason the dosages, besides the histological evaluation, were also made in the different healing phases: D2, inflammatory phase; D4, proliferative phase and D10, beginning of remodeling phase that extends for months.
  • the GAPD Rat gene (TaqMan TM - Applied Biosystems), Part number 4352338E, was chosen as the endogenous control of the reaction, which serves to normalize the expression of the gene of interest in the different samples.
  • the catheter GAPD is labeled with VIC fluorophore, while target primers are labeled with FAM fluorophore.
  • a scatter plot was constructed, which aims to define the range of concentrations for which the system is efficient.
  • the same logarithm values of the concentration of the samples on the X axis were used and the difference between the means of the endogenous control Cts and the means of the gene of interest for each concentration on the Y axis.
  • a trend line for these values was obtained, which has a line equation in which it is possible to verify the slope value of this line.
  • the slope value must be less than 0.1 (the closer this value is to zero, the smaller the slope of the curve is and, therefore, the more constant is the difference between the mean Cts of the gene of interest and the endogenous control).
  • the points on the graph corresponding to the concentrations that are closest to the trend line are considered validated (the system has 100% efficiency at these concentrations).
  • sample concentration validated as efficient for the adiponectin, leptin and GAPD genes was 40.0 ng cDNA.
  • Methods for Relative Quantification of Gene Expression allow quantifying differences in the level of expression of a specific gene (target) between different samples. Data production is expressed as a change or difference in the number of times in expression levels.
  • a sample was chosen as calibrator and an endogenous gene was also chosen to normalize the results. The standardized results obtained are always relative to the calibrator data.
  • the calibrator sample used for all groups presented the median value between the three measurements taken for each day of treatment (two, four or ten days).
  • adiponectin was tissue increased in D4 and D10 in group 3 when compared to the control group and increased in group 4 when compared to the contralateral side.
  • IGF-1 was increased on days 2 and 4 in group 3 when compared to the control group and both in group 3 and group 2 when compared to the contralateral side.
  • IL-6 presented better tissue results in group 3 and group 2 when compared to control and in group 3 and group 4 in D2 when compared to the contralateral side.
  • IFN-alpha showed better results in the early days (2 and 4) in group 2 and group 4 and, on day 10, in group 3 when compared to the control group. In comparison with the contralateral wound, group 2 presented better results.
  • IFN-gamma showed better results in groups 2 and 4 compared to control group and group 2 compared to contralateral wounds.
  • IL-12 which as IFN has anti-healing action, had lower levels in group 4 compared to control group and group 2 compared to contralateral wounds.
  • TNF-alpha and leptin showed better results in group 3 when compared to the control group.
  • Leptin was increased in group 2 compared to the contralateral wound.
  • IL-2 was increased in group 3 as compared to the control group and contralateral wounds. This cytokine was also increased in group 4 when compared to the control group. No significant variations were observed regarding IL-4.
  • This assay employs the quantitative sandwich immunoassay technique.
  • a target substance-specific monoclonal antibody is pre-added to a microplate at the factory.
  • Samples, controls and standards are pipetted into the wells and if the test substance is present it will be bound by the immobilized antibody.
  • a substance-specific enzyme-linked polyclonal antibody is added to the wells.
  • a substrate solution is added to the wells.
  • the reaction enzyme produces a blue product that turns yellow when the Stop Solution is added.
  • the color measurement intensity is in proportion to the amount of target substance bound in the initial step.
  • the sample values are then read from the standard curve.
  • the plates of the 5 kits were analyzed on the Bio Rad 680 Microplate Reader, BioRad Laboratories (Hercules, CA, USA) at 490 and 570nm wavelengths as recommended by the manufacturers.
  • the cytokines that favored healing in group 3 were the
  • IGF-1 INF-alpha
  • IL-12 IGF-1, INF-alpha and IL-12 (on day 10).
  • Adiponectin was systemically favorable for healing that occurred in group 2.
  • IL-12 was elevated in this group, acting favorably in the early days (2 and 4).
  • IL-4 was elevated in the group, favoring healing.
  • Example 5 Statistical interpretation of evaluations of inflammatory (Real-T ⁇ me PCR) and systemic (Elisa) scar tissue cytokines
  • PCR which evaluates the amount of cytokines in the tissue, it was possible to determine a statistically significant difference favorable to group 3 (raw coffee oil) when compared to the control group for cytokines: IGF-1 and leptin (only on day 4).
  • group 3 raw coffee oil
  • cytokines IGF-1 and leptin (only on day 4).
  • the cytokines found at levels favorable for healing in group 3 were INF-alpha and gamma and leptin (on day 4).
  • AGE favorably interfered with tissue production of IGF-, IFN-alpha and IL-12 when compared to the control group and ITN-alpha when compared to the contralateral wound.
  • Roasted coffee oil produced tissue healing action with significant statistical difference when dosing adiponectin and INF-gamma and the systemic dosage of adiponectin, IFN-alpha and gamma and IL-2 suggesting the relevance of these cytokines in the healing process.
  • This systemic effect signals a possible medicinal use of coffee oil, since many dermatoses and other diseases are related to the high production of TNF- ⁇ , for example as psoriasis and various rheumatological diseases. This systemic effect was particularly evident on the second day of the experiment.

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Abstract

La présente invention concerne une composition et sa formulation à base d'huile de café, à usage topique et à haute capacité de cicatrisation cutanée. Cette composition est capable de maintenir la zone cicatricielle à un niveau d'humidité idéal et les zones périphériques sèches et protégées, outre le fait de présenter une action systémique, facteurs qui accélèrent le processus cicactriciel.
PCT/BR2013/000459 2012-11-13 2013-11-01 Composition et formulation à base d'huile de café, et utilisations Ceased WO2014075157A1 (fr)

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BR102012029163A BR102012029163B8 (pt) 2012-11-13 2012-11-13 Uso do óleo de café torrado da espécie coffee arábica
BRBR1020120291630 2012-11-13

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023088698A1 (fr) * 2021-11-16 2023-05-25 Unilever Ip Holdings B.V. Composition de soin de la peau

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4793990A (en) * 1980-04-02 1988-12-27 L'oreal Use of coffee bean oil as a sun filter
WO1999063963A1 (fr) * 1998-06-11 1999-12-16 Sederma Compositions a usage cosmetique ou dermopharmaceutique contenant un melange d'extraits de cafe vert et de beurre de karite
US6716437B1 (en) * 1993-09-13 2004-04-06 E-L Management Corporation Topical composition and method for enhancing lipid barrier synthesis
BRPI0602842A (pt) * 2006-07-20 2008-03-04 Chemyunion Quimica Ltda uso do óleo de café verde (coffea arabica) em formulações cosméticas e farmacêuticas para a manutenção das propriedades da pele
WO2012013764A2 (fr) * 2010-07-30 2012-02-02 Nestec S.A. Utilisation de grains de café torréfiés pour réguler la pigmentation de la peau
MX2013001076A (es) * 2010-07-30 2013-03-12 Oreal Uso de una mezcla de granos de cafe tostados y verdes para regular pigmentacion de la piel.

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4793990A (en) * 1980-04-02 1988-12-27 L'oreal Use of coffee bean oil as a sun filter
US6716437B1 (en) * 1993-09-13 2004-04-06 E-L Management Corporation Topical composition and method for enhancing lipid barrier synthesis
WO1999063963A1 (fr) * 1998-06-11 1999-12-16 Sederma Compositions a usage cosmetique ou dermopharmaceutique contenant un melange d'extraits de cafe vert et de beurre de karite
BRPI0602842A (pt) * 2006-07-20 2008-03-04 Chemyunion Quimica Ltda uso do óleo de café verde (coffea arabica) em formulações cosméticas e farmacêuticas para a manutenção das propriedades da pele
WO2012013764A2 (fr) * 2010-07-30 2012-02-02 Nestec S.A. Utilisation de grains de café torréfiés pour réguler la pigmentation de la peau
MX2013001076A (es) * 2010-07-30 2013-03-12 Oreal Uso de una mezcla de granos de cafe tostados y verdes para regular pigmentacion de la piel.

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
REUTER J ET AL.: "Botanicals in dermatology: an evidence- based review.", AM J CLINICAL DERMATOL, vol. 11, no. 4, 2010, pages 247 - 267, XP009156810, DOI: doi:10.2165/11533220-000000000-00000 *
WAGEMAKER T: "Variabilidade do teor de óleo, de seu fator de proteção solar e de outros componentes da fraçâo lipidica do gênero Coffea visando usos alternativos aos grãos.", DISSERTAÇÃO DE MESTRADO. INSTITUTO AGRONÔMICO DE CAMPINAS, 2009, Campinas, SP., pages 15 - 17 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023088698A1 (fr) * 2021-11-16 2023-05-25 Unilever Ip Holdings B.V. Composition de soin de la peau

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BR102012029163B1 (pt) 2022-02-22
BR102012029163A2 (pt) 2014-07-15

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