KR102584738B1 - Composition for treating skin disease comprising colchicine - Google Patents

Abstract

The present invention relates to a composition for treating and improving skin diseases containing colchicine.
The composition according to the present invention can be used for skin wrinkle disease, pigmentation disease caused by skin photodamage, etc. through wrinkle improvement, pigmentation inhibition effect, ultraviolet ray protection effect, or skin regeneration effect, and for anti-aging, wrinkle improvement, and skin regeneration. It shows excellent effects as a composition for improving elasticity.

Description

Composition for treating skin diseases containing colchicine {COMPOSITION FOR TREATING SKIN DISEASE COMPRISING COLCHICINE}

The present invention relates to a composition for treating skin diseases containing colchicine.

The skin is anatomically located on the outermost side of the body, protecting the body from the external environment by blocking direct entry into the body of pathogenic microorganisms, viruses, chemicals, etc. in the air, and performs an important barrier function to prevent excessive leakage of body moisture. I'm doing it. Skin tissue has a layered structure consisting of a basal layer, a spinous and granular layer, and a cornified layer, and special expression markers are well known for each layer structure. Among them, Keratin 1 (K1) and Keratin 10 (K10) are expressed in the differentiation layer, and Filaggrin is expressed in the uppermost epithelium, including the stratum corneum, and is essential for the formation of the skin's inherent barrier function as described above. It is one of the major proteins.

Photoaging refers to a skin aging phenomenon that occurs when the skin is exposed to ultraviolet rays from the sun. This is a form of aging that is distinct from biological aging (senescence or biological aging) caused by the gradual decline of human body functions, and is generally the main cause of skin wrinkles, dryness, elastosis, and pigmentation.

The sun emits two types of ultraviolet rays, UV-A and UV-B, with wavelengths of 320 to 400 nm for UV-A and 290 to 320 nm for UV-B. Among the tissues damaged by UV rays, collagen is representative. Collagen is the main component of connective tissue, exists mainly in bones and skin, and is broadly classified into five types. Type 1 is the most abundant collagen found within skin connective tissue, followed by type 3.

Matrix metalloproteinases (MMP) are proteolytic enzymes that decompose collagen, the main component of human connective tissue, and their expression level increases by UV rays. Therefore, when the skin is exposed to ultraviolet rays, the expression of these Matrix Metalloproteinases (MMP) increases, destroying collagen in the dermal layer of the skin and causing photoaging such as skin wrinkles and pigmentation.

Colchicine is an oral prescription drug mainly used to control or prevent acute gouty arthritis. Currently, generic products (typical drug names Colcrys, Takeda Pharmaceuticals) are being sold by global pharmaceutical companies, and the first original patent has expired.

KR 1020150143725 KR 102177781

The present inventors found that colchicine not only has excellent therapeutic effects on diseases related to loss of skin elasticity and pigmentation diseases caused by photodamage through wrinkle improvement, ultraviolet ray protection effect, or skin regeneration effect, but also has an excellent anti-aging effect. After confirming that it was effective, the present invention was completed.

Accordingly, the present invention seeks to provide a pharmaceutical composition for preventing or treating skin diseases containing colchicine or a pharmaceutically acceptable salt thereof.

The present invention also seeks to provide an anti-aging composition containing colchicine or a pharmaceutically acceptable salt thereof.

In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating skin diseases containing colchicine or a pharmaceutically acceptable salt thereof.

The present invention provides an anti-aging cosmetic composition containing colchicine or a pharmaceutically acceptable salt thereof.

The present invention provides a quasi-drug composition for anti-aging containing colchicine or a pharmaceutically acceptable salt thereof.

The present invention provides an external skin composition for anti-aging containing colchicine or a pharmaceutically acceptable salt thereof.

The present invention provides a cosmetic composition for improving wrinkles and/or skin elasticity containing colchicine.

The present invention provides a quasi-drug composition for improving wrinkles and/or skin elasticity containing colchicine or a pharmaceutically acceptable salt thereof.

The present invention provides a composition for external application for skin for improving wrinkles and/or skin elasticity containing colchicine or a pharmaceutically acceptable salt thereof.

The present invention provides a pharmaceutical composition for preventing or treating skin diseases containing colchicine or a pharmaceutically acceptable salt thereof.

As a result of repeatedly confirming the process of applying colchicine to a hairless mouse and then irradiating it with UV ultraviolet rays, the present inventors confirmed that colchicine has a wrinkle improvement effect, a protective effect against ultraviolet rays, a pigmentation suppression effect, and a skin regeneration effect. .

Colchicine of the present invention decomposes MMP-1 and MMP-9, which are enzymes that promote the decomposition of type 1 and type 3 collagen, which are mainly expressed in skin tissue, and type 1 collagen and regulates changes in the expression level of MMP-1. It shows excellent effects in regulating MMP-3 protein, which is a regulatory enzyme. Modulation of these MMP proteins can not only have a wrinkle improvement effect, a protection effect against ultraviolet rays, or a skin regeneration effect, but also an improvement effect on skin aging such as photoaging. In addition, treatment with colchicine according to the present invention can have an effect of inhibiting pigmentation in the skin.

In the present invention, the skin disease is preferably a disease related to skin wrinkles.

Specifically, the skin wrinkle-related disease may be a skin wrinkle-related disease caused by skin photodamage. “Skin photodamage” means skin damage caused by exposure of the skin to sunlight or UV light (in particular UV-B)

These skin wrinkle-related diseases include elastosis, thinning of the skin, skin atrophy, reduction of collagen fibers and elastic fibers, and loss of skin elasticity. It is one or more selected from the group consisting of skin elasticity, dryness, wrinkle formation, and premature skin aging.

In the present invention, the skin disease may preferably be a pigmentation disease caused by skin photodamage. For example, one or more selected from the group consisting of lentigines, freckles, hypopigmentation, and hyperpigmentation.

The protection against skin diseases may be, for example, “photoprotective”. It may mean blocking or alleviating adverse clinical effects, histological and immunological effects caused by the sun or ultraviolet rays. These effects include, in particular, chronic effects (eg elastosis and wrinkle formation).

The composition of the present invention contains colchicine or a pharmaceutically acceptable salt thereof as an active ingredient.

Colchicine is a compound having the structure of Formula 1 below.

[Formula 1]

In the present invention, pharmaceutically acceptable salts refer to salts commonly used in the pharmaceutical industry, such as inorganic ionic salts made of calcium, potassium, sodium and magnesium, hydrochloric acid, nitric acid, phosphoric acid, bromic acid, and iodic acid. , inorganic acid salts made from perchloric acid and sulfuric acid, acetic acid, trifluoroacetic acid, citric acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, mandelic acid, propionic acid, citric acid, lactic acid, glycolic acid, gluconic acid, galactu Organic acid salts made from ronic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carbonic acid, vanillic acid, hydroiodic acid, etc., methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid. There are sulfonates made from fonic acid and naphthalenesulfonic acid, amino acid salts made from glycine, arginine, lysine, etc., and amine salts made from trimethylamine, triethylamine, ammonia, pyridine, picoline, etc., but these are listed below. The types of salts within the meaning of the present invention are not limited by these salts. Here, pharmaceutically acceptable salts include all categories of salts that are foodologically and/or cosmetically usable or acceptable, and can be used interchangeably within the specification.

The composition of the present invention may further include pharmaceutically acceptable additives, wherein the pharmaceutically acceptable additives include starch, gelatinized starch, microcrystalline cellulose, lactose, povidone, colloidal silicon dioxide, calcium hydrogen phosphate, and lactose. , mannitol, taffy, gum arabic, pregelatinized starch, corn starch, powdered cellulose, hydroxypropyl cellulose, Opadry, sodium starch glycolate, lead carnauba, synthetic aluminum silicate, stearic acid, magnesium stearate, aluminum stearate, calcium stearate. , white sugar, dextrose, sorbitol, and talc can be used. The pharmaceutically acceptable additive according to the present invention is preferably contained in an amount of 0.1 to 90 parts by weight based on the composition, but is not limited thereto.

The composition of the present invention can be administered in various oral and parenteral formulations during actual clinical administration. When formulated, diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants are used. It can be prepared this way. Preferably, in the present invention, it can be used as a parenteral agent, especially as a coating agent.

The composition of the present invention can be administered orally or parenterally according to the desired method. When administered parenterally, it can be administered transdermally, externally on the skin, applied to the skin, intraperitoneal injection, intrarectal injection, subcutaneous injection, intravenous injection, or intramuscular injection. Alternatively, an intrathoracic injection method may be selected, for example, transdermal administration. The dosage range varies depending on the patient's weight, age, gender, health condition, diet, administration time, administration method, excretion rate, and severity of the disease. Preferably, the composition according to the present invention can be administered to the human body by parenteral administration, external application to the skin, or application to the skin.

When formulated for transdermal administration, it can be formulated in the form of ointments, creams, lotions, gels, external solutions, paste preparations, linear preparations, and aerol preparations.

Regarding the formulation of pharmaceutical compositions, it is known in the art, and specifically, references can be made to the literature [Remington's Pharmaceutical Sciences (19th ed., 1995)]. The above documents are considered part of this specification.

The composition according to the present invention is administered in a pharmaceutically effective amount. In the present invention, “pharmaceutically effective amount” means an amount sufficient to treat the disease with a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is determined by the type, severity, and activity of the patient's disease. , can be determined based on factors including sensitivity to the drug, time of administration, route of administration and excretion rate, duration of treatment, drugs used simultaneously, and other factors well known in the field of medicine. The composition of the present invention may be administered as an individual therapeutic agent or in combination with other therapeutic agents, may be administered sequentially or simultaneously with conventional therapeutic agents, and may be administered singly or multiple times. Considering all of the above factors, it is important to administer an amount that can achieve the maximum effect with the minimum amount without side effects, and this can be easily determined by a person skilled in the art.

Specifically, the effective amount of the compound according to the present invention may vary depending on the patient's age, gender, and weight, and is generally 0.1 mg to 100 mg, preferably 0.5 mg to 10 mg per kg of body weight, administered daily, every other day, or It can be administered 1 to 5 times a week or divided into 1 to 5 times a day. However, since it may increase or decrease depending on the route of administration, severity, gender, weight, age, etc., the above dosage does not limit the scope of the present invention in any way.

The present invention provides an anti-aging cosmetic composition containing colchicine or a pharmaceutically acceptable salt thereof.

The present invention provides a quasi-drug composition for anti-aging containing colchicine or a pharmaceutically acceptable salt thereof.

The present invention provides an external skin composition for anti-aging containing colchicine or a pharmaceutically acceptable salt thereof.

A composition containing colchicine or a pharmaceutically acceptable salt thereof as an active ingredient has an anti-aging effect.

The term “aging” in the present invention refers to a change in the function and condition of the body that progresses with the passage of time, and includes symptoms such as uneven skin and spots, wrinkles, and loss of elasticity due to pigmentation such as spots, freckles, and age spots, and ultraviolet rays. And oxidative stress is known to be the main cause. In particular, aging according to the present invention is photoaging, which is aging of the skin caused by stress caused by ultraviolet rays, etc.

The term “anti-aging” of the present invention means alleviating, reducing, preventing, delaying, improving or eliminating the symptoms of aging through wrinkle improvement, ultraviolet ray protection effect, or skin regeneration effect.

The cosmetic or pharmaceutical composition of the present invention may contain commonly accepted ingredients in addition to the above active ingredients without limitation, such as antioxidants, stabilizers, solubilizers, vitamins, conventional auxiliaries such as pigments and flavorings, and carriers. can do.

In addition, the cosmetic or pharmaceutical composition according to the present invention may be a solution, external ointment, cream, foam, nourishing lotion, softening lotion, pack, softening water, emulsion, makeup base, essence, soap, liquid cleanser, bath salt, sunscreen cream, sunscreen. Can be prepared in one or more formulations selected from the group consisting of oils, suspensions, emulsions, pastes, gels, lotions, powders, soaps, surfactant-containing cleansers, oils, powder foundations, emulsion foundations, wax foundations, patches and sprays. However, it is not limited to this.

In addition, the cosmetic composition of the present invention may additionally include one or more cosmetically acceptable carriers that are blended with general skin cosmetics, and common ingredients include, for example, oil, water, surfactant, moisturizer, lower alcohol, Thickeners, chelating agents, pigments, preservatives, fragrances, etc. may be appropriately mixed, but are not limited thereto.

Pharmaceutically acceptable or cosmetically acceptable carriers included in the cosmetic or pharmaceutical composition of the present invention vary depending on the formulation.

When the formulation of the present invention is an ointment, paste, cream or gel, the carrier ingredients include animal oil, vegetable oil, wax, paraffin, starch, tracant, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc, zinc oxide or Mixtures of these can be used.

When the formulation of the present invention is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silcate, polyamide powder, or mixtures thereof may be used as the carrier ingredient, and especially in the case of a spray, chloro May contain propellants such as fluorohydrocarbons, propane/butane or dimethyl ether.

When the formulation of the present invention is a solution or emulsion, a solvent, solubilizing agent or emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-Butyl glycol oils may be used, in particular cottonseed oil, peanut oil, corn germ oil, olive oil, castor oil and sesame oil, aliphatic esters of glycerol, fatty acid esters of polyethylene glycol or sorbitan. there is.

When the formulation of the present invention is a suspension, the carrier ingredients include water, a liquid diluent such as ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, and polyoxyethylene sorbitan ester, and miso. Crystalline cellulose, aluminum metahydroxide, bentonite, agar, or tracant may be used.

When the formulation of the present invention is soap, alkali metal salts of fatty acids, hemiester salts of fatty acids, fatty acid protein hydrolyzates, isethionates, lanolin derivatives, fatty alcohols, vegetable oils, glycerol, sugars, etc. may be used as carrier ingredients. You can.

When the formulation of the present invention is a surfactant-containing cleansing agent, the carrier ingredients include aliphatic alcohol sulfate, aliphatic alcohol ether sulfate, sulfosuccinic acid monoester, isethionate, imidazolinium derivative, methyl taurate, sarcosite, and fatty acid amide. Ether sulfate, alkylamidobetaine, fatty alcohol, fatty acid glyceride, fatty acid diethanolamide, vegetable oil, lanolin derivative, or ethoxylated glycerol fatty acid ester can be used.

The pharmaceutical composition of the present invention can be administered parenterally (for example, topically applied to the skin) according to the desired method, and the dosage is determined by the patient's weight, age, gender, health condition, diet, administration time, and administration method. , the range varies depending on the excretion rate and severity of the disease. The daily dosage (e.g., application amount) of colchicine is about 0.01 to 1000 mg/kg, preferably 0.05 to 100 mg/kg, and can be administered once or in divided doses several times a day.

The cosmetic or pharmaceutical composition according to the present invention may contain 0.01 to 20% by weight of colchicine or a pharmaceutically acceptable salt thereof based on the total weight of the composition.

In another aspect of the present invention, an anti-aging quasi-drug composition is provided, comprising colchicine or a pharmaceutically acceptable salt thereof as an active ingredient.

In the present invention, the quasi-drug composition may be a quasi-drug composition for improving wrinkles, blocking ultraviolet rays, or regenerating skin.

The term "quasi-drug" used in the present invention refers to products with a milder effect than pharmaceuticals among products used for the purpose of diagnosing, treating, improving, alleviating, treating or preventing diseases in humans or animals. For example, according to the Pharmaceutical Affairs Act. According to it, quasi-drugs are products excluding those used for medicinal purposes, such as textile and rubber products used for the treatment or prevention of diseases in humans and animals, products that have a minor or no direct effect on the human body, and are not instruments or machines and similar items. This includes sterilization and pesticides to prevent infectious diseases.

The type or formulation of the quasi-drug composition of the present invention is not particularly limited, but preferably may be a disinfectant cleaner, shower foam, gargle, wet tissue, detergent soap, hand wash, humidifier filler, mask, ointment, or filter filler.

When the composition of the present invention is included in a quasi-drug for anti-aging purposes, the composition can be used as is or together with other quasi-drug ingredients, and can be used appropriately according to conventional methods. The mixing amount of the active ingredient can be appropriately determined depending on the purpose of use, and the quasi-drug composition according to the present invention may contain 0.01 to 20% by weight of the colchicine or a pharmaceutically acceptable salt thereof based on the total weight of the composition.

In another aspect of the present invention, an anti-aging external skin composition is provided, comprising colchicine or a pharmaceutically acceptable salt thereof as an active ingredient.

In the present invention, the composition for external application for skin may be a composition for external application for skin, for improving wrinkles, protecting skin against ultraviolet rays, or regenerating skin.

The composition for external skin application according to the present invention includes, for example, ointment, lotion, soluble burn, suspension, emulsion, cream, gel, spray, patch, warning agent, patch, or water paste, but is not limited to these. and can be mixed with any base well known in the art. The composition for topical skin application according to the present invention may contain 0.01 to 20% by weight of colchicine or a pharmaceutically acceptable salt thereof based on the total weight of the composition.

The present invention provides a cosmetic composition for improving wrinkles and/or skin elasticity containing colchicine.

The present invention provides a quasi-drug composition for improving wrinkles and/or skin elasticity containing colchicine or a pharmaceutically acceptable salt thereof.

The present invention provides a composition for external application for skin for improving wrinkles and/or skin elasticity containing colchicine or a pharmaceutically acceptable salt thereof.

The terms “wrinkle improvement” and/or “skin elasticity improvement” in the present invention mean improving wrinkles by inhibiting enzymes that decompose collagen or elastin or promoting collagen synthesis. Collagen and elastin constitute the dermal layer of the skin, and it is known that reduction or deformation of collagen and elastin is involved in wrinkle formation and decreased skin elasticity. Additionally, the composition according to the present invention may be effective in improving wrinkles by reducing the expression of MMP proteins involved in skin wrinkles.

The terms “protection against ultraviolet rays” and “protection against photoaging” in the present invention refer to protecting cells against stress caused by light such as ultraviolet rays, and the ultraviolet rays may be ultraviolet B.

The term “skin regeneration” of the present invention means improving the proliferation of skin cells or promoting recovery of damaged skin.

In one embodiment of the present invention, colchicine or a pharmaceutically acceptable salt thereof can be used as an anti-aging cosmetic or pharmaceutical composition due to colchicine's wrinkle improvement, ultraviolet ray protection effect, and skin regeneration effect.

The present invention provides a method of treating skin diseases comprising applying a therapeutically effective amount of colchicine or a pharmaceutically acceptable salt thereof to the skin of a subject.

The present invention provides a method for anti-aging skin, improving wrinkles, and/or improving skin elasticity, comprising applying an effective amount of colchicine or a pharmaceutically acceptable salt thereof to the skin of a subject.

The subject refers to an animal, and typically may be a mammal that can exhibit beneficial effects from treatment with the colchicine of the present invention or a pharmaceutically acceptable salt thereof. Preferred examples of such subjects may include primates such as humans. In addition, such subjects include those with symptoms of skin disease, specifically skin wrinkle disease and/or pigmentation disease caused by skin photodamage, or subjects at risk of having such symptoms, anti-aging of the skin, wrinkle improvement, and/or Any object that requires improvement of skin elasticity, etc. may be included.

The invention also provides the use of colchicine in the manufacture of medicaments for the treatment of skin diseases.

The present invention also provides a composition comprising colchicine or a pharmaceutically acceptable salt thereof for use in the treatment of skin diseases.

The present invention also provides a cosmetic composition containing colchicine or a pharmaceutically acceptable salt thereof for use in anti-aging, improving wrinkles, and/or improving skin elasticity.

The present invention also provides the use of colchicine or a pharmaceutically acceptable salt thereof for the treatment of skin diseases.

The composition according to the present invention can be used for skin wrinkle disease, pigmentation disease caused by skin photodamage, etc. through wrinkle improvement, pigmentation inhibition effect, ultraviolet ray protection effect, or skin regeneration effect, and for anti-aging, wrinkle improvement, and skin regeneration. It shows excellent effects as a composition for improving elasticity.

Figure 1 shows the results of measuring the degree to which the expression level of MMP protein is suppressed by the application of colchicine by measuring the expression level of MMP protein in a control group that was irradiated only with ultraviolet rays and an experimental group that applied colchicine to the skin and then irradiated with ultraviolet rays.
Figure 2 shows the results of measuring the degree of pigmentation in a control group that was irradiated only with ultraviolet rays and an experimental group that applied colchicine to the skin and then irradiated with ultraviolet rays, respectively, to confirm the degree to which pigmentation was suppressed by the application of colchicine.
Figure 3 shows the results of observing that treatment with intracellular TNF induces NF-kB activation and then treatment with colchicine inhibits the NF-kB signaling process by reducing Phospho p65 in a concentration-dependent manner (proportional to concentration).
Figure 4 shows the results measured using a cell-based reporter assay to show that treatment with intracellular TNF induces NF-kB activation and then treatment with colchicine inhibits the NF-kB signaling process in a concentration-dependent manner. .

Hereinafter, the present invention will be described in detail by examples. However, the following examples are merely illustrative of the present invention, and the present invention is not limited by the following examples.

Example 1. Verification of the skin wrinkle improvement effect of colchicine

Colchicine (10 mM, 100 ul) was applied to the back of a 7-week-old Hairless mouse, and the process of irradiating UV rays 30 minutes later was repeated more than 5 times to induce photoaging (particularly, wrinkle improvement). In order to compare and verify the efficacy of colchicine, a negative control group without any treatment and a positive control irradiated only with UV-B were reflected in the experiment.

After completion of the application experiment, skin tissue was collected from each mouse, pulverized with a tissue crusher, and RNA was extracted. After reverse transcription of the extracted RNA into cDNA, the amounts of MMP-1, MMP-3, and MMP-9 present in skin tissue were measured using a real-time PCR machine using quantitative PCR (qPCR).

Specifically, the photoaging inhibitory effect of colchicine was measured by measuring changes in the protein expression level of Matrix Metalloproteinases (MMP) described above. That is, the expression level of MMP protein was measured in the control group that was irradiated only with ultraviolet rays and the experimental group that was irradiated with ultraviolet rays after applying colchicine to the skin, and the degree to which the expression level of MMP protein was suppressed by the application of colchicine was measured.

The results are shown in Figure 1.

MMP-1 and MMP-9 are enzymes that promote the decomposition of type 1 and type 3 collagen, which are mainly expressed in skin tissue, and MMP-3 is a regulatory enzyme that decomposes type 1 collagen and regulates changes in the expression level of MMP-1. As, it is an MMP protein that has a very important effect on photoaging.

As can be seen in Figure 1, when colchicine is applied to the skin, the expression level of MMP-1 decreases by 61%, MMP-3 by 68%, and MMP-9 by 64% compared to the control group irradiated only with ultraviolet rays. was confirmed. In this way, it was verified that the application of colchicine suppressed the protein expression level of Matrix Metalloproteinases (MMP), and the overall effect of suppressing photoaging caused by UV ultraviolet rays was confirmed.

Example 2. Verification of the pigmentation improvement effect of colchicine

Pigmentation was induced by applying colchicine to a 7-week-old hairless mouse and irradiating it with UV rays 30 minutes later, repeating the process more than 5 times. Specifically, solvent or Colchicine (10 mM, 100 ul) was applied to 7-week-old Hairless mice (more than 10 mice per group), then UV irradiation (180mJ/cm ² ) was repeated 3 times a week (total of 30 weeks). .

In order to compare and verify the efficacy of colchicine, a negative control group without any treatment and a positive control irradiated only with UV-B were reflected in the experiment.

After completion of the application, changes in skin appearance were confirmed, and the results are shown in Figure 2.

As can be seen in Figure 2, irradiation with UV ultraviolet rays induced severe pigmentation. However, treatment with colchicine not only suppressed the symptoms significantly, but also showed an excellent effect to the extent that the level of recovery was close to that of the normal control group.

Example 3. Confirmation of photoaging inhibition mechanism of colchicine

The generation of ROS (Reactive Oxygen Species) due to UV irradiation has the potential to activate NF-kB, thereby promoting the transcription of MMPs and decomposing collagen and elastin. Accordingly, NF-κB activation was induced by treatment with intracellular TNF, and then treatment with colchicine was performed in a concentration-dependent manner (proportional to concentration), and changes in the expression of Phospho p65 were confirmed through RT-PCR.

The results are shown in Figure 3.

As can be seen in Figure 3, the expression of Phospho p65, which is a phosphorylated p65 protein and an activator of the NF-kB signaling process, was decreased in a concentration-dependent manner of colchicine.

In addition, through a cell-based reporter assay, it was confirmed that treating intracellular TNF to induce NF-kB activation and then treating it with colchicine inhibits the NF-kB signaling process in a concentration-dependent manner. As a result, is shown in Figure 4.

As can be seen in Figure 4, treatment with colchicine according to the present invention inhibited NF-kB signal transduction similar to TPCA1, a control substance known as an NF-kB signal transduction inhibitor.

Claims (13)

A pharmaceutical composition for preventing or treating diseases related to skin wrinkles or pigmentation diseases caused by skin photodamage, comprising colchicine or a pharmaceutically acceptable salt thereof as a single active ingredient. According to paragraph 1,
The skin wrinkle-related diseases include elastosis, thinning of the skin, skin atrophy, reduction of collagen fibers and elastic fibers, and loss of skin elasticity. A pharmaceutical composition that is selected from the group consisting of skin elasticity, dryness, wrinkle formation, and premature skin aging. According to paragraph 1,
A pharmaceutical composition wherein the pigmentation disease caused by skin photodamage is at least one selected from the group consisting of lentigines, freckles, hypopigmentation, and hyperpigmentation. According to any one of claims 1 to 3,
The pharmaceutical composition is administered by skin application. The pharmaceutical composition according to any one of claims 1 to 3, wherein the pharmaceutical composition is any one selected from the group consisting of ointments, creams, lotions, gels, topical solutions, paste preparations, liniment preparations, and aerol preparations. A pharmaceutical composition in dosage form. A cosmetic composition for protecting skin against ultraviolet rays or for skin regeneration, comprising colchicine or a pharmaceutically acceptable salt thereof as a single active ingredient. delete The cosmetic composition according to claim 6, wherein the cosmetic composition includes solution, external ointment, cream, foam, nourishing lotion, softening lotion, pack, softening water, emulsion, makeup base, essence, soap, liquid cleanser, bath salt, sunscreen cream, sun oil, Skin protection against ultraviolet radiation in one or more formulations selected from the group consisting of suspensions, emulsions, pastes, gels, lotions, powders, soaps, surfactant-containing cleansers, oils, powder foundations, emulsion foundations, wax foundations, patches and sprays. Cosmetic composition for protection or skin regeneration. A quasi-drug composition for skin protection against ultraviolet rays or for skin regeneration, comprising colchicine or a pharmaceutically acceptable salt thereof as a single active ingredient. A composition for external application for skin for protecting the skin against ultraviolet rays or for skin regeneration, comprising colchicine or a pharmaceutically acceptable salt thereof as a single active ingredient. A cosmetic composition for improving wrinkles and skin elasticity comprising colchicine or a pharmaceutically acceptable salt thereof as a single active ingredient. A quasi-drug composition for improving wrinkles and skin elasticity containing colchicine or a pharmaceutically acceptable salt thereof as a single active ingredient. An external skin composition for improving wrinkles and skin elasticity comprising colchicine or a pharmaceutically acceptable salt thereof as a single active ingredient.