Composition for the prevention or improvement of psoriasis

Abstract

According to an embodiment of the present application, a composition for preventing or improving psoriasis is provided, comprising one or more of cannabidiol or cannabigerol as an active ingredient.

Description

Technology Field

[0001] This application relates to a composition for preventing or improving psoriasis. Background Technology

[0002] Psoriasis is an immune-mediated autoimmune skin disease induced by the chronic activation of inflammatory cell infiltration and dysregulation of epidermal keratinocytes. When psoriasis first develops, small, red, millet-sized rashes appear on the skin, which are covered by white keratinocytes, and the size of the rashes may gradually expand. Psoriasis is reported to be associated with complex mechanisms involving the interaction between inflammatory cytokines and the infiltration of immune cells, such as T cells.

[0003] Topical treatments applied directly to the skin are the first and most frequently used to control symptoms in psoriasis patients. However, side effects such as skin thinning, stretch marks, burns, irritation, and photosensitivity are known from topical treatments. Therefore, there is a need to develop psoriasis treatments that have a low risk of side effects and excellent therapeutic efficacy. Prior art literature

[0004] Republic of Korea Registered Patent No. 10-2354028 The problem to be solved

[0005] The purpose of this application is to provide a composition for preventing or improving psoriasis. means of solving the problem

[0006] According to an embodiment of the present application, a composition for preventing or improving psoriasis is provided, comprising one or more of cannabidiol or cannabigerol as an active ingredient.

[0007] In addition, the above composition can induce a decrease in the expression of JAK.

[0008] In addition, the above composition can induce a decrease in the expression of one or more of TNF-α, IFNγ, IL-17, or IL-23.

[0009] In addition, the above composition can induce the expression of filaggrin or aquaporins-3.

[0010] In addition, the above composition can induce a decrease in the expression of pI-κB or p-NF-κB.

[0011] In addition, according to an embodiment of the present application, a cosmetic composition comprising the above composition for preventing or improving psoriasis is provided. Effects of the invention

[0012] According to an embodiment of the present application, psoriasis can be prevented or improved by including one or more of cannabidiol or cannabigerol as active ingredients.

[0013] The effects obtainable from the embodiments of the present application are not limited to those mentioned above, and other unmentioned effects will be clearly understood by those skilled in the art to which the present application belongs from the description below. Brief explanation of the drawing

[0014] A brief description of each drawing is provided to help to better understand the drawings cited in this application. Figure 1 is a graph showing the experimental results confirming the inhibitory effects of major cannabinoids on JAK 1 to 3. Figures 2 to 5 are graphs showing the experimental results confirming the inhibitory effect of cannabidiol (CBD) or cannabigerol (CBG) on inflammatory cytokine expression. Figure 6 shows the experimental results confirming the skin moisturizing factor expression effect of cannabidiol (CBD) or cannabigerol (CBG), Figure 6a is a photograph showing the Western blot results, and Figure 6b is a graph quantifying the results. Figures 7 and 8 show experimental results confirming the inhibitory effect of cannabidiol (CBD) or cannabigerol (CBG) on skin hyperkeratosis factor expression, Figures 7a and 8a are photographs showing Western blot results, and Figures 7b and 8b are graphs quantifying each of these. Specific details for implementing the invention

[0015] The structural or functional descriptions of the embodiments disclosed in this specification are merely illustrative for the purpose of explaining embodiments according to the technical concept of this application. Furthermore, embodiments according to the technical concept of this application may be implemented in various forms other than those disclosed in this specification. Additionally, the technical concept of this application is not to be interpreted as being limited to the embodiments described in this specification.

[0016] Among the physical properties mentioned in this specification, if the measurement temperature affects the property, the property is the one measured at room temperature and pressure unless otherwise specifically stipulated.

[0017] Unless otherwise specifically defined among the physical properties mentioned in this specification, said physical properties may basically follow the SI unit system. For example, weight may be expressed in kg units, and length may be expressed in m units.

[0018] The term "room temperature" as used in this specification refers to a natural temperature that is not heated or cooled, and may mean, for example, any temperature within the range of 10°C to 30°C, for example, about 15°C or higher, about 18°C ​​or higher, about 20°C or higher, about 23°C or higher, about 27°C or lower, or 25°C. Unless specifically defined in this specification, the unit of temperature is Celsius (°C).

[0019] The term "relatively high temperature relative to room temperature" as used in this specification refers to a temperature higher than room temperature, and may mean, for example, any temperature within the range of 30°C to 50°C, for example, about 35°C or higher, about 40°C or higher, or about 45°C or lower.

[0020] Among the physical properties mentioned in this specification, if the measured pressure affects the physical property, unless otherwise specifically defined, the physical property is the property measured at atmospheric pressure. The term atmospheric pressure used in this specification refers to natural pressure that is not pressurized or depressurized, and typically refers to atmospheric pressure within the range of about 700 mmHg to 800 mmHg.

[0021] As used in this specification, the terms a to b refer to a range between a and b, including a and b. For example, including a to b parts by weight is equivalent to including within the range of a to b parts by weight.

[0022] The terms used herein are for describing embodiments and are not intended to limit or / or restrict the present application. Singular expressions include plural expressions unless the context clearly indicates otherwise. Additionally, numbers used herein (e.g., First, Second, etc.) are merely identifiers to distinguish one component from another.

[0023] In this specification, when a part is described as being connected to another part, this includes not only cases where they are directly connected, but also cases where they are indirectly connected with other components in between. Furthermore, when a part is described as including a certain component, this means that, unless specifically stated otherwise, it does not exclude other components but may include additional components.

[0024] Furthermore, in this application, the term "or" is intended to mean an implicit "or" rather than an exclusive "or." That is, unless otherwise specified or evident from the context, "X uses A or B" is intended to mean one of the natural implicit substitutions. In other words, if X uses A; if X uses B; or if X uses both A and B, "X uses A or B" may apply to any of these cases. Additionally, the term "and / or" as used herein should be understood to refer to and include all possible combinations of one or more of the enumerated related configurations.

[0025] In this application, the term "active ingredient" refers to an ingredient that exhibits an effect of preventing or improving psoriasis, specifically an ingredient that induces a decrease in the expression of JAK, or induces a decrease in the expression of TNF-α, IFNγ, IL-17 or IL-23, or induces the expression of Filaggrin or Aquaporins-3, or induces a decrease in the expression of pI-κB or p-NF-κB.

[0026] Hereinafter, exemplary embodiments according to the present application will be described in detail with reference to the contents described in the attached drawings.

[0028] According to an embodiment of the present application, a composition for preventing or improving psoriasis is provided, comprising one or more of cannabidiol or cannabigerol as an active ingredient.

[0029] Among the cannabinoids found in cannabis, non-psychoactive compounds such as cannabidiol (CBD), cannabichromene (CBC), cannabinol (CBN), and cannabigerol (CBG) are known to possess various pharmacological effects.

[0030] In the examples, cannabidiol or cannabigerol can induce a decrease in the expression of JAK. JAK inhibitors can reduce inflammatory responses by blocking the excessive activation of the JAK / STAT pathway. One of the major causes of psoriasis is an inflammatory response associated with Th17 (T helper 17) cells, and inflammatory cytokines are secreted by Th17 cells, and JAK proteins such as JAK1, JAK2, and JAK3 bind to inflammatory cytokines and activate pathways that induce inflammation. That is, since cannabidiol or cannabigerol induced a decrease in the expression of JAK, psoriasis can be prevented or treated through the JAK inhibitory effect.

[0031] In the examples, cannabidiol or cannabigerol can induce a decrease in the expression of one or more of TNF-α, IFNγ, IL-17, or IL-23. TNF-α (Tumor Necrosis Factor-alpha) promotes skin inflammatory responses and induces excessive proliferation of keratinocytes. Increased secretion of TNF-α stimulates the proliferation of keratinocytes and fibroblasts, which may exacerbate psoriasis symptoms. IFN-γ (Interferon-gamma) is a cytokine that regulates immune responses and promotes defense against infection; it can disrupt the balance of the immune system and induce an excessive immune response, thereby exacerbating psoriasis symptoms, and can act in conjunction with TNF-α or IL-12 to intensify inflammation in psoriasis. IL-17 (Interleukin-17) can exacerbate inflammation by promoting the secretion of inflammatory cytokines, cause skin rashes, or stimulate keratinocytes to induce excessive skin cell proliferation. IL-23 (Interleukin-23) can enhance the inflammatory response in psoriasis by activating Th17 cells to secrete IL-17, and together with IL-17, it acts as a major inflammatory pathway in psoriasis to cause inflammation in the skin and promote keratinocyte proliferation. In other words, cannabidiol or cannabigerol can prevent or treat psoriasis by inducing a decrease in the expression of TNF-α, IFNγ, IL-17, or IL-23.

[0032] In the examples, cannabidiol or cannabigerol can induce the expression of filaggrin or aquaporins-3. Filaggrin plays a role in strengthening the skin barrier in keratinocytes and preventing moisture loss. In patients with psoriasis, filaggrin expression is often reduced, and filaggrin deficiency can cause damage to the skin barrier and increase moisture loss, making the skin drier and more sensitive. When the skin barrier weakens, the reaction to external stimuli becomes excessive, which can induce inflammation and consequently worsen psoriasis symptoms. Additionally, filaggrin deficiency can induce an excessive immune response to stimuli, which can promote the inflammatory response in psoriasis. Aquaporins-3 are cell membrane transport proteins that assist in the movement of various small molecules, including water and glycerol, within skin cells and have the effect of maintaining skin moisture. Reduced expression of aquaporin-3 can intensify skin dryness and inflammatory responses, and skin inflammation can decrease aquaporin-3 expression or impair its function, potentially leading to a vicious cycle of psoriasis symptoms. In other words, cannabidiol or cannabigerol can prevent or treat psoriasis by inducing the expression of filaggrin or aquaporin-3.

[0033] In the examples, cannabidiol or cannabigerol can induce a decrease in the expression of pI-κB or p-NF-κB. NF-κB (Nuclear Factor kappa B) induces the expression of inflammatory cytokines, enhances inflammatory responses, and can promote the proliferation and apoptosis of keratinocytes. In psoriasis patients, the NF-κB pathway is excessively activated, which promotes inflammatory responses and can induce the proliferation of keratinocytes and inflammatory rashes in the skin. IκB (Inhibitor of NF-κB) is a protein that inhibits NF-κB from being activated. Under normal conditions, IκB binds to NF-κB and inhibits its activation. When IκB is phosphorylated and detached from NF-κB, it can promote the activation of NF-κB. In the examples, it was confirmed that the NF-κB pathway is inhibited as the expression of p-IκB and p-NF-κB decreases. In other words, cannabidiol or cannabigerol can prevent or treat psoriasis by inducing a decrease in the expression of pI-κB or p-NF-κB.

[0034] In the examples, an ointment containing cannabidiol or cannabigerol as an active ingredient may maintain potency for 6 months at temperatures below 40°C. For example, potency may be maintained for 6 months at room temperature (RT), 5°C, and 25°C.

[0035] In the example, an ointment containing 10% or less of cannabidiol or cannabigerol as an active ingredient can maintain its hardness for 8 weeks.

[0036] Specifically, the active ingredient may be included in the ointment at a concentration of 0.1 to 8%, for example, 0.5 to 5%. Within the above range, the hardness is appropriately maintained for 8 weeks, and the potency can be stably maintained for 6 months under room temperature (RT), 5°C, and 25°C conditions.

[0038] In addition, according to an embodiment of the present application, a cosmetic composition comprising a composition for preventing or improving psoriasis is provided.

[0039] In the examples, the cosmetic composition may further include additives commonly used in the art within a range that does not impair the effects of the examples of the present application. For example, the cosmetic composition may further include thickeners, pH adjusters, surfactants, stabilizers, preservatives, antiseptics, disinfectants, moisturizers, sunscreens, skin conditioning agents, whitening agents, coloring agents, organic pigments, inorganic pigments, fragrances, vitamins, natural colorants, pearls, and other functional ingredients. Here, the functional ingredients may include, for example, wrinkle-improving ingredients, whitening ingredients, antioxidant ingredients, anti-aging ingredients, plumping ingredients, exfoliating ingredients, scrub ingredients, moisturizing ingredients, skin barrier strengthening ingredients, skin elasticity-enhancing ingredients, etc. The amount of the above ingredients can be easily selected by a person skilled in the art within a range that does not impair the purpose and effects of the present application.

[0040] In the examples, the cosmetic composition can be manufactured into various products. For example, it can be manufactured into sun care products such as sun cream, sun stick, sun milk, sun lotion, and sun cushion. For example, it can be manufactured into functional cosmetics such as nourishing cream, essence, and ampoule, or into basic cosmetics such as toner and lotion. In addition, it can be manufactured into color cosmetics such as lipstick, lip balm, mascara, blush, shading, highlighter, makeup base, foundation, compact powder, concealer, and skin cover. Furthermore, it can be manufactured into products that are attached to the skin, such as packs and hydrogel slimming patches, or products that are sprayed onto the skin, such as mist and aerosol.

[0042] In the examples, the composition may be a topical skin composition. For example, the topical skin composition may have a formulation such as a solution, oil, paste, cream, gel, patch, spray, etc.

[0043] In the examples, the skin topical composition may appropriately incorporate ingredients commonly used in skin topical preparations such as cosmetics or pharmaceuticals, for example, aqueous ingredients, oily ingredients, powder ingredients, alcohols, moisturizers, thickeners, sunscreens, whitening agents, preservatives, antioxidants, surfactants, fragrances, colorants, fatty substances, solvents, thickeners, gelling agents, emollients, foaming agents, fragrances, metal ion chelating agents, chelating agents, vitamins, various skin nutrients, or combinations thereof as needed. The amount of the above ingredients can be easily selected by a person skilled in the art within a range that does not impair the purpose and effect of the present application.

[0045] In the examples, the composition may be a pharmaceutical composition. The pharmaceutical composition may further include a pharmaceutically acceptable salt to the extent that it does not impair the effects of the present invention. Here, the 'pharmaceutically acceptable salt' may be a salt that does not cause severe irritation to the organism to which the compound is administered and does not impair the biological activity and physical properties of the compound.

[0046] In the examples, the pharmaceutical composition may further include a pharmaceutically acceptable carrier or additive to the extent that it does not impair the effects of the present invention. Here, the 'pharmaceutically acceptable carrier' may be a compound that is commonly used in formulations, does not inhibit the activity of the active ingredient, does not possess toxicity beyond which the subject of application or prescription is tolerable, and facilitates the addition of the compound into cells or tissues.

[0047] In the examples, the pharmaceutical composition may be formulated as a solid or liquid formulation. For example, when formulated as a solid formulation, it may further include a carrier, flavoring agent, binder, preservative, disintegrant, lubricant, filler, etc., and when formulated as a liquid formulation, it may further include a solution such as water or propylene glycol solution, a suspension, an emulsion, etc., but is not limited thereto, and may further include a coloring agent, flavoring agent, stabilizer, viscosizing agent, etc.

[0048] In the examples, solid formulations may include powders, granules, tablets, capsules, suppositories, etc. For example, powders may be prepared by simply mixing a mixture of oregano extract and exosomes derived from Centella asiatica, which are the active ingredients of the present invention, with a carrier such as lactose, starch, or microcrystalline cellulose. Granules may be prepared by mixing a mixture of cannabidiol or cannabigerol of the present invention with a carrier and a binder such as polyvinylpyrrolidone or hydroxypropylcellulose, and then using a wet granulation method using a solvent such as water, ethanol, or isopropanol, or a dry granulation method using compression force. Additionally, tablets may be prepared by mixing granules with a lubricant such as magnesium stearate and then compressing them using a tablet press.

[0049] In the examples, the pharmaceutical composition may be administered as an oral preparation, an injectable preparation (e.g., intramuscular injection, intraperitoneal injection, intravenous injection, infusion, subcutaneous injection, implant), an inhalant, a nasal preparation, a vaginal preparation, a rectal preparation, a sublingual preparation, a transdermal preparation, a topical preparation, etc., depending on the disease to be treated or the condition of the individual, but is not limited thereto. Additionally, the pharmaceutical composition of the present invention may be formulated into a suitable administration unit formulation comprising a pharmaceutically acceptable carrier, an additive, and a vehicle that are commonly used and non-toxic according to the route of administration.

[0050] In the examples, the dosage of the pharmaceutical composition may vary depending on the patient's condition and body weight, the severity of the disease, the form of the drug, the route of administration, and the duration, but may be appropriately selected by those skilled in the art. The form of administration, the route of administration, and the method of administration of the pharmaceutical composition may each be independent and are not particularly limited in such manner, and may follow any route of administration and method of administration as long as the pharmaceutical composition can reach the intended site. For example, the form of administration of the pharmaceutical composition according to the present invention may be used in the form of a pharmaceutically acceptable salt thereof, and may be used alone or in combination with other pharmaceutically active compounds, as well as in a suitable combination. Furthermore, for example, the method of administration of the pharmaceutical composition according to the present invention may include intravenous administration, intraperitoneal administration, intramuscular administration, transdermal administration, or subcutaneous administration, as well as methods of applying, spraying, or inhaling the composition to the disease site, but is not limited thereto.

[0052] The present invention will be explained below through manufacturing examples and experimental examples, but the scope of the present invention is not limited by the contents presented below.

[0054] Experimental Example

[0056] (1) Experimental Example 1: HaCaT cell-based JAK screening assay

[0057] Psoriasis is associated with the overactivation of the JAK / STAT pathway, and Janus Kinase (JAK) is involved in a signaling pathway that binds to cytokine receptors on the cell surface and activates intracellular Signal Transducer and Activator of Transcription (STAT) proteins. JAK inhibitors may show potential efficacy in the treatment of psoriasis. Candidate JAK inhibitors were screened as follows.

[0058] HaCaT cells were cultured in IMDM medium containing 10% FBS and 1% Penicillin-Streptomycin. 4×10 in a 96-well plate 4 After culturing at cells / mL for 24 hours, the existing medium was removed and replaced with serum-free medium, and the cells were pretreated with cannabidiol (CBD), cannabichromet (CBC), cannabinol (CBN), and cannabigerol (CBG) for 1 hour. To induce a psoriasis-like inflammatory response, HaCaT cells were treated with TNF-α, IFNγ, and IL-17A at 10 ng / mL each and cultured for an additional 24 hours. After 24 hours, the cell culture medium was removed, and the cells were fixed in a 4% formaldehyde solution at room temperature for 20 minutes. The expression levels of p-JAK1, p-JAK2, and p-JAK3 in HaCaT cells were evaluated using an ELISA kit according to the manufacturer's protocol. The blank group was the sample-free group with only serum-free medium added, the negative control group was the sample-free group treated with 10 ng / mL each of TNF-α, IFNγ, and IL-17A, and the experiment was conducted under the same conditions with the addition of dexamethasone as the positive control.

[0059] The experimental results are shown in Table 1 and Figure 1.

[0061] Sample Dexamethasone Cannabidiol (CBD) Cannabichromet (CBC) Concentration (μg / mL) 1 3 0.1 0.5 1 0.1 0.5 1 Expression reduction rate (%) p-JAK1 10 20 9 12 51 -5 1 7 p-JAK2 17 23 -11 -8 14 -10 1 5 p-JAK3 6 11 -7 -9 9 -14 1 8 Sample Cannabinol (CBN) Cannabigerol (CBG) Concentration (μg / mL) 0.1 0.5 1 0.1 0.5 1 Expression reduction rate (%) p-JAK1 -2 -9 -23 -10 -1 11 p-JAK2 -2 4 3 1 9 19 p-JAK3 -17 -7 1 -19 -6 -2

[0063] Experimental results showed that cannabidiol (CBD) significantly reduced the expression of JAK1 and JAK2, and cannabigerol (CBG) significantly reduced the expression of JAK2.

[0065] (2) Experimental Example 2: Evaluation of inhibition of inflammatory cytokine expression

[0066] Psoriasis is associated with the excessive secretion of inflammatory cytokines. Inflammatory cytokine expression was evaluated using cannabidiol (CBD) and cannabigerol (CBG), which showed significant results in Experimental Example 1.

[0067] HaCaT cells were cultured in IMDM medium containing 10% FBS and 1% Penicillin-Streptomycin. 8×10⁻⁴ cells were placed in a 24-well plate. 4 After culturing at cells / mL for 24 hours, the existing medium was removed and replaced with serum-free medium, and cannabidiol (CBD) and cannabigerol (CBG) were pretreated for 1 hour. To induce a psoriasis-like inflammatory response, HaCaT cells were treated with TNF-α, IFNγ, and IL-17A at 10 ng / mL each and cultured for an additional 24 hours. The expression levels of TNF-α, IFNγ, IL-17, and IL-23 in the culture medium of HaCaT cells were evaluated using an ELISA kit according to the manufacturer's protocol. The Blank group was the sample-free group with only serum-free medium added, the Negative control group was the sample-free group treated with TNF-α, IFNγ, and IL-17A at 10 ng / mL each, and the experiment was conducted under identical conditions with the addition of Dexamethasone as the positive control.

[0068] The experimental results confirming the expression of the inflammatory cytokine TNF-α are shown in Table 2 and Figure 2.

[0070] Sample Dexamethasone Cannabidiol (CBD) Cannabigerol (CBG) Concentration (μg / mL) 3 0.1 0.5 1 0.1 0.5 1 Expression reduction rate (%) 10 6 5 5 9 11 14

[0072] The experimental results confirming the expression of the inflammatory cytokine IFNγ are shown in Table 3 and Figure 3.

[0074] Sample Dexamethasone Cannabidiol (CBD) Cannabigerol (CBG) Concentration (μg / mL) 3 0.1 0.5 1 0.1 0.5 1 Expression reduction rate (%) 55 16 25 52 0 4 31

[0076] The experimental results confirming the expression of the inflammatory cytokine IL-17 are shown in Table 4 and Figure 4.

[0078] Sample Dexamethasone Cannabidiol (CBD) Cannabigerol (CBG) Concentration (μg / mL) 3 0.1 0.5 1 0.1 0.5 1 Expression reduction rate (%) 25 15 23 30 6 19 32

[0080] The experimental results confirming the expression of the inflammatory cytokine IL-23 are shown in Table 5 and Figure 5.

[0082] Sample Dexamethasone Cannabidiol (CBD) Cannabigerol (CBG) Concentration (μg / mL) 3 0.1 0.5 1 0.1 0.5 1 Expression reduction rate (%) 20 13 11 12 9 14 14

[0084] Experimental results confirmed that cannabidiol (CBD) and cannabigerol (CBG) reduce the expression of TNF-α, IFNγ, IL-17, and IL-23.

[0086] (3) Experimental Example 3: Evaluation of skin moisturizing factors

[0087] Psoriasis leads to excessive moisture loss due to impaired skin barrier function, which can result in a decrease in the expression of skin moisturizing factors. The expression of skin moisturizing factors was evaluated by treating with cannabidiol (CBD) and cannabigerol (CBG), which showed significant results in Experimental Example 1. Filaggrin is a protein that maintains the skin barrier and plays a role in preserving skin moisture. Aquaporins-3 are channel proteins that deliver moisture to the skin and play a role in maintaining skin moisture homeostasis.

[0088] HaCaT cells were cultured in IMDM medium containing 10% FBS and 1% Penicillin-Streptomycin. 2 mL of the cell line was dispensed into 60 mm dishes at the appropriate concentration per well and cultured for 24 hours in a 37°C, 5% CO2 incubator. After 24 hours of culture, the existing medium was removed and replaced with serum-free medium, and cannabidiol (CBD) and cannabigerol (CBG) were pretreated for 1 hour. To induce a psoriasis-like inflammatory response, HaCaT cells were treated with TNF-α, IFNγ, and IL-17A at 10 ng / mL each and cultured for an additional 24 hours.

[0089] After the completion of culture, pellet lysis buffer was added, and the sample was incubated at -20°C for 20 minutes to extract the protein. The extracted protein was centrifuged at 4°C and 13,000 rpm for 10 minutes, the supernatant was collected, and the protein was quantified. The sample was then subjected to electrophoresis on a 10% SDS polyacrylamide gel, and the separated protein was transferred to an NC membrane and blocked with 5% BSA for 2 hours. The primary antibodies, Filaggrin, Aquaporins-3, and β-actin, were diluted in 5% BSA according to the respective ratios and incubated overnight at 4°C. Subsequently, the samples were washed four times with TBST for 5 minutes each, and the secondary antibodies were diluted to the appropriate ratio and incubated at room temperature for 2 hours. After washing four times with TBST for 5 minutes, the samples were treated with ECL solution, and the results were measured using Chemi-DOC (Bio-rad) via a chemiluminescence assay (Amersham Pharmacia Biotech, NJ, USA). The blank group was the sample-untreated group, with only serum-free medium added; the negative control group was the sample-untreated group treated with 10 ng / mL each of TNF-α, IFNγ, and IL-17A; and the positive control group was the positive control, with dexamethasone added, and the experiment was conducted under the same conditions.

[0090] The experimental results confirming the expression of skin moisturizing factors are shown in Table 6 and Figure 6.

[0092] Sample Dexamethasone Cannabidiol (CBD) Cannabigerol (CBG) Concentration (μg / mL) 3 0.1 0.5 1 0.1 0.5 1 Expression increase rate (%) Filaggrin 29 16 28 21 17 31 31 AQP-3 22 -8 3 14 -2 6 12

[0094] Experimental results confirmed that cannabidiol (CBD) and cannabigerol (CBG) increase the expression of Filaggrin and AQP-3.

[0096] (4) Experimental Example 4: Evaluation of skin hyperkeratosis mechanism

[0097] Psoriasis can thicken the stratum corneum of the skin. IκB (Inhibitor of kappa B) and NF-κB (Nuclear Factor kappa B) are signaling factors that play an important role in inflammatory and immune responses associated with skin hyperkeratosis. Phosphorylation of IκB and NF-κB was evaluated by treating with cannabidiol (CBD) and cannabigerol (CBG), which showed significant results in Experimental Example 1.

[0098] HaCaT cells were cultured in IMDM medium containing 10% FBS and 1% Penicillin-Streptomycin. 2 ml of the cell line was dispensed at the appropriate concentration per well into 60 mm dishes and cultured for 24 hours in a 37°C, 5% CO2 incubator. After 24 hours of culture, the existing medium was removed and replaced with serum-free medium, and the cells were pretreated with cannabidiol (CBD) and cannabigerol (CBG) for 1 hour. To induce a psoriasis-like inflammatory response, HaCaT cells were treated with TNF-α, IFNγ, and IL-17A at 10 ng / mL each and cultured for an additional 24 hours.

[0099] After the completion of culture, pellet lysis buffer was added, and the sample was incubated at -20°C for 20 minutes to extract the protein. The extracted protein was centrifuged at 4°C and 13,000 rpm for 10 minutes, the supernatant was collected, and the protein was quantified. The sample was then subjected to electrophoresis on a 10% SDS polyacrylamide gel, and the separated protein was transferred to an NC membrane and blocked with 5% BSA for 2 hours. The primary antibodies were diluted in 5% BSA according to the appropriate ratios and incubated overnight at 4°C. Subsequently, the samples were washed four times with TBST for 5 minutes each, and the secondary antibodies were diluted to the appropriate ratio and incubated at room temperature for 2 hours. After washing four times with TBST for 5 minutes, the samples were treated with ECL solution, and the results were measured using Chemi-DOC (Bio-rad) via a chemiluminescence assay (Amersham Pharmacia Biotech, NJ, USA). The blank group was the sample-untreated group, with only serum-free medium added; the negative control group was the sample-untreated group treated with 10 ng / mL each of TNF-α, IFNγ, and IL-17A; and the positive control group was the positive control, with dexamethasone added, and the experiment was conducted under the same conditions.

[0100] The experimental results confirming the expression of p-IκB are shown in Table 7 and Figure 7.

[0102] Sample Dexamethasone Cannabidiol (CBD) Cannabigerol (CBG) Concentration (μg / mL) 3 0.1 0.5 1 0.1 0.5 1 Expression reduction rate (%) p-IκB 35 31 37 63 37 69 77

[0104] The experimental results confirming the expression of p-NF-κB are shown in Table 8 and Figure 8.

[0106] Sample Dexamethasone Cannabidiol (CBD) Cannabigerol (CBG) Concentration (μg / mL) 3 0.1 0.5 1 0.1 0.5 1 Expression reduction rate (%) p-NF-κB 16 29 45 41 40 50 54

[0108] Experimental results confirmed that cannabidiol (CBD) and cannabigerol (CBG) reduce the expression of p-IκB and p-NF-κB.

[0110] (5) Experimental Example 5: Analysis of potency and hardness of an ointment containing cannabidiol

[0111] As shown in Table 9, an ointment containing cannabidiol was prepared, and the potency and hardness of cannabidiol were analyzed.

[0113] division Preparation Example 1 Preparation Example 2 Preparation Example 3 solvent polyethylene glycol 7 7 7 chief ingredient Cannabidiol 1 2 4 Gije White Vaseline 74 73 71 Light liquid paraffin 18 18 18

[0115] To test the stability of the ointment, potency measurements were performed using HLPC, and the change in potency (%) over time compared to before storage is shown in Table 10 below.

[0117] Storage conditions and changes in potency condition 1 day 1 week 2 weeks 4 weeks 2 months 3 months 5 months 6 months Preparation Example 1 (1% ointment) RT 134.1 144.2 133.6 104.8 111 96 111 152 5℃ 127.5 135.6 127.8 103.2 97 88 123 147 25℃ 120.7 144 121.7 100.7 106 104 123 128 40℃ 126.5 152.6 127.7 70.4 76 82 45 - 50℃ 87.1 64.3 86.5 41.8 42 36 34 - Preparation Example 2 (2% ointment) RT 137.1 113.95 140.1 100 101 98 126 132 5℃ 136.65 36.1 143.2 96 92 89 119 132 25℃ 138.1 112.35 135 101 94 93 97 130 40℃ 40.2 116.95 61.6 84 103 36 67 - 50℃ 45.45 112.85 53 125 78 94 57 - Preparation Example 3 (4% ointment) RT 125.9 159.3 113.25 107.4 89 130 121 159 5℃ 121.9 157 114.75 108.7 86 145 121 140 25℃ 122.8 154.4 110.58 114.63 87 124 113 136 40℃ 142.8 166.9 47.3 130 77 141 110 - 50℃ 42.3 33.2 19.7 33.18 55 99 127 -

[0119] As a result of potency analysis, the potency was stably maintained under RT (room temperature), 5℃, and 25℃ conditions, confirming that the cannabidiol (CBD) content in the formulation was maintained.

[0120] On the other hand, at high temperatures of 40°C or 50°C, the formulation collapsed, and the potency of cannabidiol (CBD) could not be maintained stably.

[0122] Change in hardness value (g / cm²) based on 0 days using an Asker CL-150 (constant loader for durometer, Japan) as a hardness tester 2 ) is shown in Table 11.

[0124] 0 days 1 day 1 week 2 weeks 4 weeks 8 weeks Preparation Example 1 (1% ointment) 58 41 71 109 104 74 Preparation Example 2 (2% ointment) 47 39 67 102 116 84 Preparation Example 3 (4% ointment) 40 38 70 109 117 90

[0126] Hardness analysis results confirmed that there was no difference in hardness regardless of the cannabidiol (CBD) content.

[0128] Foregoing, specific parts of the contents of this application have been described in detail. It will be apparent to those skilled in the art that such specific descriptions are merely preferred embodiments and do not limit the scope of this application. Accordingly, the actual scope of this application is defined by the appended claims and their equivalents.

Claims

Claim 1 A composition for preventing or improving psoriasis, comprising one or more of cannabidiol or cannabigerol as active ingredients. Claim 2 In claim 1, the composition is a composition for preventing or improving psoriasis that induces a reduction in the expression of JAK. Claim 3 In claim 1, the composition is a composition for preventing or improving psoriasis that induces a reduction in the expression of one or more of TNF-α, IFNγ, IL-17, or IL-23. Claim 4 In claim 1, the composition is a composition for preventing or improving psoriasis that induces the expression of filaggrin or aquaporins-3. Claim 5 In claim 1, the composition is a composition for preventing or improving psoriasis that induces a reduction in the expression of pI-κB or p-NF-κB. Claim 6 A cosmetic composition comprising the composition for preventing or improving psoriasis of claim 1.

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