Composition for relieving skin itching or irritation containing thymol trimethoxycinnamate

Abstract

A composition for relieving skin itching or irritation, which contains thymol trimethoxycinnamate. This specification discloses a composition for relieving skin itching or irritation, which contains thymol trimethoxycinnamate, its stereoisomers, salts, hydrates or solvates as active ingredients, and a method for relieving skin itching or skin irritation by administering the composition to an individual in need of relieving skin itching or irritation. The composition disclosed in this specification has no side effects, and inhibits the voltage-gated sodium channel NaV1.7, thereby having an excellent effect of relieving skin itching or skin irritation.

Description

Technical Field

[0001] The present disclosure relates to a composition for relieving skin itching or irritation. Background Art

[0002] Itching, as a major symptom of skin diseases, can be said to be a feeling that induces the desire to scratch, and is an avoidance response to harmful stimuli. In addition to skin diseases, it may also be caused by systemic diseases or mental diseases.

[0003] Both central and peripheral mediators play important roles in pruritus. Pro-inflammatory mediators induce pruritus in inflammatory skin diseases such as rashes, and most of these mediators may trigger other precursors of inflammation, namely pain, erythema caused by vasodilation, increased vascular permeability, etc. In addition, itching may be induced by an increase in the activity of factors secreted by mast cells different from histamine or prostaglandins. In addition, itching signals can be transmitted by bile acids, proteolytic enzymes, cytokines, neuropeptides, and compounds such as chloroquine and opioids through various receptors distributed on peripheral nerves. Although antipruritics have been used for these various targets, drugs have limitations. The itching relief effect of topical calamine lotion is weak. Although steroids reduce inflammation and relieve itching, they are difficult to use for a long time. It is reported that in the case of calcineurin inhibitors, pain is temporarily induced and the risk of malignant tumors is increased. Menthol and capsaicin lotions can activate and act on ion channels (TRPM8, TRPV1, etc.) distributed on each nerve to help relieve itching, but they have the disadvantage of being very irritating. Antihistamines have limitations for pruritus such as rashes caused by histamine. (Journal of Allergy and Clinical Immunology 2018;142:1375 - 90 Etiology and (new) treatment methods of itching.)

[0004] On the other hand, local anesthetics such as lidocaine, pramoxine, and prilocaine also reduce the passage of sodium ions through the nerve membrane that conveys nerve signals, preventing the transmission of stimuli and itching signals, and thus are used for itching relief and pain relief.

[0005] Thus, receptors for various stimulatory, pain, and itch-inducing mediators are distributed in the skin and cutaneous nerves, which are the main peripheral tissues for perceiving stimuli. Each stimulus received by these receptors is transmitted from the nervous system to the central nervous system in the form of electrical signals. The ion channels that play this role are considered to be voltage-gated sodium channels. In particular, the association between the voltage-gated sodium channels and itch has recently been reported in papers. (Cell 157, 1393–1404, June 5, 2014, A monoclonal antibody against the voltage sensor of Nav1.7 channels for alleviating pain and itch; PAIN 155 (2014) 1702–1707, Paroxysmal itch caused by Nav1.7 gene mutation; International Journal of Molecular Sciences, 2019, 20, 6058, Antipruritic effect of 3'-O-methylisoborneol inhibiting voltage-gated sodium channel Nav1.7 in a histamine-dependent itch mouse model). In addition, local anesthetics such as lidocaine and pramoxine, which are used as antipruritic agents, are traditional non-selective sodium channel blockers.

[0006] (Non-Patent Document 1) Journal of Allergy and Clinical Immunology 2018; 142: 1375-90, Etiology and (novel) treatment methods of itch.

[0007] (Non-Patent Document 2) Cell 157, 1393–1404, June 5, 2014, A monoclonal antibody against the voltage sensor of the NaV1.7 channel for alleviating pain and itch.

[0008] (Non-Patent Document 2) PAIN 155 (2014) 1702–1707, Paroxysmal itch caused by Nav1.7 gene mutation.

[0009] (Non-Patent Document 2) International Journal of Molecular Sciences 2019, 20, 6058, Antipruritic effect of 3′-O-methylisoborneol inhibiting voltage-gated sodium channel Nav1.7 in a histamine-dependent itch mouse model. SUMMARY OF THE INVENTION

[0010] In one aspect, an object of the present disclosure is to provide a composition having an excellent effect of alleviating skin itch or skin irritation.

[0011] In one aspect, an object of the present disclosure is to provide the use of thymol trimethoxycinnamate, its stereoisomers, salts, hydrates or solvates for preparing a composition for alleviating skin itch or skin irritation.

[0012] In one aspect, the present disclosure provides the use of thymol trimethoxycinnamate, its stereoisomers, salts, hydrates or solvates for preparing a composition for relieving skin itching or skin irritation.

[0013] In an exemplary implementation, it may be that the thymol trimethoxycinnamate is represented by the following Chemical Formula 1.

[0014] [Chemical Formula 1]

[0015]

[0016] In an exemplary implementation, it may be that the dosage of the thymol trimethoxycinnamate, its stereoisomers, salts, hydrates or solvates is 0.37 to 37 mg / kg / day.

[0017] In an exemplary implementation, it may be that the composition inhibits the voltage-gated sodium channel Nav1.7.

[0018] In an exemplary implementation, it may be that the skin itching or skin irritation is caused by a chemical substance.

[0019] In an exemplary implementation, the chemical substance may be veratrum alkaloid, and the veratrum alkaloid may be veratridine.

[0020] In an exemplary implementation, it may be that the composition is a topical skin composition.

[0021] In an exemplary implementation, it may be that the composition is a cosmetic or pharmaceutical composition.

[0022] In one aspect, the composition according to the present disclosure containing thymol trimethoxycinnamate, its stereoisomers, salts, hydrates or solvates has no side effects and has a significant skin itching relief effect.

[0023] In another aspect, the composition according to the present disclosure containing thymol trimethoxycinnamate, its stereoisomers, salts, hydrates or solvates has no side effects and has a significant skin irritation relief effect.

[0024] In another aspect, the composition according to the present disclosure containing thymol trimethoxycinnamate, its stereoisomers, salts, hydrates or solvates can inhibit the voltage-gated sodium channel Nav1.7. Description of the Drawings

[0025] Figure 1 It is a graph showing the inhibition rate of voltage-gated sodium channel Nav1.7 based on thymol trimethoxycinnamate treatment.

[0026] Figure 2 It is a graph showing the itching relief effect based on thymol trimethoxycinnamate treatment (corresponding specimens t - black **p < 0.1, ***p < 0.01). Detailed implementation mode

[0027] Hereinafter, the present disclosure will be described in detail.

[0028] In one aspect, the present disclosure provides a composition for relieving skin itching or irritation, which contains thymol trimethoxycinnamate, its stereoisomers, salts, hydrates or solvates.

[0029] In one aspect, the present disclosure provides the use of thymol trimethoxycinnamate, its stereoisomers, salts, hydrates or solvates for preparing a composition for relieving skin itching or skin irritation.

[0030] In one implementation example, the thymol trimethoxycinnamate is (5-methyl-2-propan-2-ylphenyl)(E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoic acid represented by the following Chemical Formula 1.

[0031] [Chemical Formula 1]

[0032]

[0033] In this specification, "stereoisomers" include optical isomers, for example, essentially pure enantiomers, essentially pure diastereomers or mixtures thereof.

[0034] In this specification, "essentially pure" means that, for example, when used in connection with enantiomers or diastereomers, a specific compound that can be exemplified by enantiomers or diastereomers is present in an amount of more than about 90%, preferably more than about 95%, more preferably more than about 97% or more than about 98%, still more preferably more than about 99%, and even more preferably more than about 99.5% (w / w).

[0035] In this specification, "salt" means a salt according to an aspect of the present invention that is pharmaceutically and cosmetically acceptable and has the preferred activity of the parent compound. The salt may include (1) formed from inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, etc.; or formed from organic acids such as acetic acid, propionic acid, hexanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid, lactic acid, malonic acid, succinic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphorsulfonic acid, 4-methylbicyclo[2,2,2]-oct-2-ene-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, tert-butylacetic acid, dodecylsulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, muconic acid, etc., which are acid addition salts; or (2) salts formed when the acidic protons present in the parent compound are replaced. Additionally, the salt may be a pharmaceutically acceptable salt.

[0036] In this specification, "pharmaceutically acceptable" means that the following can be approved or recognized by a government or a government-equivalent regulatory agency, or included in a pharmacopoeia or recognized as other general pharmacopoeias: when used at a normal medicinal dosage, it avoids significant toxic effects and can thus be used in animals, more specifically in humans.

[0037] In this specification, "hydrate" means a compound combined with water and is a broad concept including an inclusion compound without chemical bonding force between water and the compound.

[0038] In this specification, "solvate" means a higher-order compound formed between the molecules or ions of a solute and the molecules or ions of a solvent.

[0039] In this specification, "active ingredient" means an ingredient that can exhibit the targeted activity alone or in combination with a carrier that is inactive by itself.

[0040] In one implementation example, it can be that, relative to the total weight of the composition, the content of thymol trimethoxycinnamate, its stereoisomers, salts, hydrates or solvates is 0.001% by weight to 20% by weight. When the content of thymol trimethoxycinnamate, its stereoisomers, salts, hydrates or solvates is less than 0.001% by weight, the effect of relieving skin itching or irritation is reduced, and when it exceeds 20% by weight, the dosage form stability is reduced. Specifically, the content of thymol trimethoxycinnamate, its stereoisomers, salts, hydrates or solvates is above 0.001% by weight, above 0.002% by weight, above 0.003% by weight, above 0.004% by weight, above 0.005% by weight, above 0.01% by weight, above 0.02% by weight, above 0.03% by weight, above 0.04% by weight, above 0.05% by weight, above 0.06% by weight, above 0.07% by weight, above 0.1% by weight, above 0.2% by weight, above 0.3% by weight, above 0.4% by weight, above 0.5% by weight, above 0.6% by weight, above 0.7% by weight, above 1% by weight, above 1.5% by weight, above 2% by weight, above 2.5% by weight, above 3% by weight, above 3.5% by weight, above 4% by weight, above 4.5% by weight or above 5% by weight, and at the same time, it is below 20% by weight, below 19.9% by weight, below 19.8% by weight, below 19.7% by weight, below 19.6% by weight, below 19.5% by weight, below 19.4% by weight, below 19.3% by weight, below 19.2% by weight, below 19.1% by weight, below 19% by weight, below 18.8% by weight, below 18.6% by weight, below 18.4% by weight, below 18.2% by weight, below 18% by weight, below 17.8% by weight, below 17.6% by weight, below 17.4% by weight, below 17.2% by weight, below 17% by weight, below 16.8% by weight, below 16.6% by weight, below 16.4% by weight, below 16.2% by weight, below 16% by weight, below 15.5% by weight, below 15% by weight, below 14.5% by weight, below 14% by weight, below 13.5% by weight, below 13% by weight, below 12.5% by weight, below 12% by weight, below 11.5% by weight, below 11% by weight, below 10.5% by weight or below 10% by weight.

[0041] In one implementation example, the thymol trimethoxycinnamate, its stereoisomers, salts, hydrates or solvates based on the input of the composition can be administered at a dosage of 0.37 to 37 mg / kg / day. When the dosage of the thymol trimethoxycinnamate, its stereoisomers, salts, hydrates or solvates is less than 0.37 mg / kg / day, the effect of relieving skin itching or irritation is reduced, and when it exceeds 37 mg / kg / day, it can irritate the skin.Specifically, the dosage of thymol trimethoxycinnamate, its stereoisomers, salts, hydrates or solvates administered based on the input of the composition can be 0.37 mg / kg / day or more, 0.38 mg / kg / day or more, 0.39 mg / kg / day or more, 0.4 mg / kg / day or more, 0.41 mg / kg / day or more, 0.42 mg / kg / day or more, 0.43 mg / kg / day or more, 0.44 mg / kg / day or more, 0.45 mg / kg / day or more, 0.5 mg / kg / day or more, 0.55 mg / kg / day or more, 0.6 mg / kg / day or more, 0.65 mg / kg / day or more, 0.7 mg / kg / day or more, 0.8 mg / kg / day or more, 0.9 mg / kg / day or more, 1 mg / kg / day or more, 1.1 mg / kg / day or more, 1.2 mg / kg / day or more, 1.3 mg / kg / day or more, 1.5 mg / kg / day or more, 1.7 mg / kg / day or more, 2 mg / kg / day or more, 3 mg / kg / day or more, 4 mg / kg / day or more, 5 mg / kg / day or more, 6 mg / kg / day or more, 7 mg / kg / day or more, 8 mg / kg / day or more, 9 mg / kg / day or more, 10 mg / kg / day or more, 11 mg / kg / day or more, 12 mg / kg / day or more, 13 mg / kg / day or more, 14 mg / kg / day or more or 15 mg / kg / day or more, while being 37 mg / kg / day or less, 36.5 mg / kg / day or less, 36 mg / kg / day or less, 35.5 mg / kg / day or less, 35 mg / kg / day or less, 34.5 mg / kg / day or less, 34 mg / kg / day or less, 33.5 mg / kg / day or less, 33 mg / kg / day or less, 32.5 mg / kg / day or less, 32 mg / kg / day or less, 31.5 mg / kg / day or less, 31 mg / kg / day or less, 30.5 mg / kg / day or less, 30 mg / kg / day or less, 29.5 mg / kg / day or less, 29 mg / kg / day or less, 28.5 mg / kg / day or less, 28 mg / kg / day or less, 27.5 mg / kg / day or less, 27 mg / kg / day or less, 26.5 mg / kg / day or less, 26 mg / kg / day or less, 25.5 mg / kg / day or less, 25 mg / kg / day or less, 24.5 mg / kg / day or less, 24 mg / kg / day or less, 23.5 mg / kg / day or less or 23 mg / kg / day or less.

[0042] In one implementation example, the active ingredient can inhibit the voltage-gated sodium channel NaV1.7 (voltage-gated sodium channel Nav1.7).

[0043] In one implementation example, the skin itching or irritation may be caused by a chemical substance. For example, the chemical substance may be veratrum alkaloid, and preferably veratridine.

[0044] In one implementation example, the administration route of the composition is not limited, but preferably can be percutaneous or topical to the skin.

[0045] In one implementation example, the composition may be a cosmetic composition. The cosmetic composition may have, for example, soft lotion, astringent lotion, nutritive lotion, nutritive cream, massage cream, eye cream, eye essence, essence, cleansing cream, facial cleanser, foaming facial cleanser, makeup remover, facial mask, powder cake, body lotion, emollient cream, body essence, body wash, hair dye, shampoo, hair conditioner, hair styling agent, hair tonic, ointment, gel, cream, patch, spray, powder, and skin adhesive type, etc., but is not limited thereto.

[0046] In addition, in each dosage form, for other components except the above essential components, those skilled in the art can reasonably select and formulate them without difficulty according to the types or usage purposes of other topical agents.

[0047] The cosmetic composition can be provided in all dosage forms suitable for topical application. For example, it can be provided in the dosage forms of solution, emulsion obtained by dispersing an oil phase in an aqueous phase, solution obtained by dispersing an aqueous phase in an oil phase, suspension, solid, gel, powder, paste, microneedle, foam or aerosol composition. The composition of this dosage form can be prepared by conventional methods in the art.

[0048] In the cosmetic composition according to this specification, functional additives other than the compounds in this specification and components included in conventional cosmetic compositions can be additionally included. The functional additives may include components selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, high molecular peptides, high molecular polysaccharides, sphingolipids, and seaweed extracts. The cosmetic composition according to this specification can preferably include other components that can produce a synergistic effect on the main efficacy within the range of not impairing the main efficacy. In addition, the cosmetic composition according to this specification can further include a humectant, a lubricant, a surfactant, an ultraviolet absorber, a preservative, a bactericide, an antioxidant, a pH regulator, organic and inorganic pigments, a fragrance, a cooling agent, or an antiperspirant. Those skilled in the art can easily select the formulation amounts of the components within the range of not damaging the purpose and effect of this specification. It can be that, based on the total weight of the composition, the formulation amount is 0.001% by weight to 10% by weight, specifically 0.01% by weight to 3% by weight.

[0049] In one implementation example, the composition may be a pharmaceutical composition. The pharmaceutical composition may be administered orally, parenterally, rectally, topically, transdermally, intravenously, intramuscularly, intraperitoneally, subcutaneously, etc. Dosage forms for oral administration may be tablets, pills, soft capsules, hard capsules, granules, suppositories, fine granules, liquid preparations, emulsions or pellets, but are not limited thereto. Dosage forms for parenteral administration may be solutions, suspensions, emulsions, gels, injections, drip infusions, adjuvants, patches or sprays, but are not limited thereto. The dosage forms can be easily prepared according to conventional methods in the art, and may additionally contain surfactants, excipients, hydrating agents, emulsification promoters, suspending agents, salts or buffers for osmotic pressure adjustment, colorants, spices, stabilizers, preservatives, storage agents or other commonly used adjuvants.

[0050] In another aspect, the present disclosure provides a method for relieving skin itching or skin irritation, including the step of administering to an individual in need of relieving skin itching or skin irritation a composition containing an effective amount of thymol trimethoxycinnamate, its stereoisomers, salts, hydrates or solvates. In one view, the administration of the method can be carried out according to the administration methods and administration doses described in this specification.

[0051] In another aspect, the present disclosure provides the use of thymol trimethoxycinnamate, its stereoisomers, salts, hydrates or solvates for preparing a composition for relieving skin itching or skin irritation.

[0052] In yet another aspect, the present disclosure provides the use of thymol trimethoxycinnamate, its stereoisomers, salts, hydrates or solvates for relieving skin itching or skin irritation.

[0053] Hereinafter, the present invention will be described in more detail through examples, etc. These examples are merely for illustrating the present invention, and it is obvious to those with ordinary knowledge in the art that the scope of the present invention should not be construed as being limited by these examples.

[0054] [Example 1] Thymol Trimethoxycinnamate

[0055] Thymol trimethoxycinnamate with CAS number 504394-57-4 was obtained from COSMANN (located in Hwaseong City, Gyeonggi-do, Korea).

[0056] [Experimental Example 1] Evaluation of the inhibitory effect on voltage-gated sodium channel NaV1.7

[0057] To evaluate the inhibitory effect of thymol trimethoxycinnamate on the voltage-gated sodium channel Nav1.7 as follows, the human Nav1.7–HEK293 cell line (Millipore) was used. The human Nav1.7–HEK293 cell line is a cell line that has been transfected with the human Nav1.7 gene and stabilized in HEK293 (human embryonic kidney 293) cells. One day before the experiment, human Nav1.7-HEK293 cells were aliquoted into 96-well plates at a cell density of 8x104 cells / well and cultured in a 37°C, 5% CO2 incubator for 24 hours. The culture medium used during the culture was DMEM / F12 medium containing 10% fetal bovine serum (FBS), and Geneticin ( Thermo Fisher Scientific) was added to maintain stable cells.

[0058] After 24 hours, the 96-well plates were washed once with 20 mM HEPES Hanks' Balanced Salt Solution (HBSS) buffer (hereinafter referred to as the reaction buffer, Thermo Fisher Scientific), and then the membrane potential fluorescence dye ( membrane potential fluorescence dye, Molecular Devices, USA) was added to the human Nav1.7-HEK293 cells. After reacting in a 37°C, 5% CO2 incubator for 40 minutes, the thymol trimethoxycinnamate of Example 1 was treated on the human Nav1.7-HEK293 cells. After reacting for 10 minutes, the membrane potential changes that occurred when 30 μM veratridine, the cause of the stimulus, was treated within 55 seconds were measured for each well using a fluorescence microplate reader, FlexStation3 (Molecular Device, USA).

[0059] The difference between the initial value and the maximum value of the value obtained by measuring the change in fluorescence within 55 seconds after treatment with Example 1, reaction buffer, and veratridine was determined separately. The difference in the value when only the reaction buffer was treated in the veratridine treatment was compared with the value when only the reaction buffer was treated in the Example 1 treatment, and the inhibition rate was calculated. After calculating the inhibition rate of lidocaine (Sigma), which is used as a local anesthetic and pruritus reliever, in the same manner and comparing it with Example 1, the results are shown in Table 1 below and Figure 1 shown in

[0060] [Table 1]

[0061] Example 1 Lidocaine IC50 (μM) 3.1 28.7

[0062] As a result, it was confirmed that thymol trimethoxycinnamate of Example 1 inhibits the voltage-gated sodium channel NaV1.7 in a concentration-dependent manner and can relieve skin pruritus and skin irritation. In addition, it was confirmed that the inhibitory effect of the voltage-gated sodium channel NaV1.7 of Example 1 is excellent compared to lidocaine at the same concentration.

[0063] [Experimental Example 2] Patch clamp evaluation (automated patch clamp analysis based on Nav1.7 human sodium ion channel cells)

[0064] Patch clamp evaluation was performed using an automated patch clamp analysis based on Nav1.7 human sodium ion channel cells (Nav1.7 Human Sodium Ion Channel Cell Based Automated Patch Clamp Assay) (Eurofins, CYL8011QP2). In the control step, current amplitudes exceeding 200 pA were analyzed. The amplitude of the current was measured and calculated as the difference between the peak inward current when stepping to -10 mV (i.e., the peak of the current) and the current remaining at the end of the step. The current was evaluated under vehicle control conditions and then evaluated 5 minutes after the application of each chemical.

[0065] Sodium channels exist in a) a deactivated or closed state at -120 mV, c) a non-activated state at 0 mV, and b) a non-activated transient open state. Open-channel inhibition (pulse 1) is measured by determining the sodium current within 1 - 2 ms at 0 mV. To fully activate the sodium channels and facilitate drug binding in a non-activated state-dependent manner, the channels are held in the open state (0 mV) for a longer time and then returned stepwise to -120 mV within 10 ms to recover to the deactivated or closed state in the non-activated state. Also, to measure the sodium channels that can be opened, they are stepped into 0 mV within 50 ms to evaluate the inhibition in the non-activated state (pulse 2). Each concentration of the compound was applied for 5 minutes, and the results are shown in Table 2 below.

[0066] [Table 2]

[0067]

[0068] From the results in Table 2, it can be confirmed that Example 1 showed inhibitory effects in both Pulse 1 and Pulse 2 according to the concentration.

[0069] [Experimental Example 3] Evaluation of the Clinical Efficacy of Itch Relief

[0070] An itch relief efficacy evaluation was conducted on subjects who had long felt itchy due to reasons such as usual dry skin, atopic dermatitis, and sensitive skin. When itching occurred for more than 30 minutes, a lotion containing 0.5% concentration of Example 1 was applied, and evaluation was carried out using a Numerical Rating Scale based on the itching degree before and after application. When using the scale of itching degree from 0 (no itching) to 10 (the most severe imaginable itching), when itching occurred in different subjects, after evaluations at 2 minutes, 10 minutes, and 30 minutes, the results are shown in Figure 2 (**p < 0.01, ***p < 0.001). The components of the lotion containing Example 1 are shown in Table 3 below.

[0071] [Table 3]

[0072] Ingredient Content (wt%) Glyceryl Stearate Citrate 1.5 C12-15 Alkyl Benzoate, C12-15 Alcohol 7.5 Octyldodecanol 3.0 Cetearyl Alcohol 1.0 Example 1 0.5 Tromethamine 0.1 Carbomer 0.15 Ethylhexylglycerin 0.05 Glyceryl Caprylate 0.1 Hexylene Glycol 0.9 Purified Water Balance Total 100.0

[0073] As Figure 2 shown, by making a paired comparison of the same time before and after applying the lotion containing Example 1, it can be seen that itching was significantly inhibited at all times.

[0074] [Formulation Example 1] Skin Toner

[0075] A skin toner was prepared by a conventional method according to the components listed in Table 4 below.

[0076] [Table 4]

[0077] Ingredient Content (wt%) Thymol Trimethoxycinnamate 0.1 Glycerol 3.0 Butylene Glycol 2.0 Propylene Glycol 2.0 Carboxyvinyl Polymer 0.1 PEG 12 Laureth 0.2 Polysorbate 80 0.4 Ethanol 10.0 pH Regulator 0.1 Preservative, Pigment, Flavor 0.1 Purified Water Balance Total 100

[0078] [Formulation Example 2] Facial Cream

[0079] Prepare the facial cream by a conventional method according to the components described in Table 5 below.

[0080] [Table 5]

[0081] Ingredient Content (wt%) Thymol Trimethoxycinnamate 1 Polysorbate 80 1.5 Sorbitan Sesquioleate 0.5 PEG 60 Hydrogenated Castor Oil 2.0 Liquid Paraffin 10.0 Squalane 5.0 Caprylic / Capric Triglyceride 5.0 Glycerol 5 Butylene Glycol 3.0 Propylene Glycol 3.0 pH Regulator 0.2 Preservative, Pigment, Flavor 0.1 Purified Water Balance Total 100

[0082] [Formulation Example 3] Emulsion

[0083] Prepare the emulsion by a conventional method according to the components described in Table 6 below.

[0084] [Table 6]

[0085] Ingredient Content (wt%) Glyceryl Stearate Citrate 1.5 C12-15 Alkyl Benzoate, C12-15 Alcohol 7.5 Octyldodecanol 3.0 Cetearyl Alcohol 1.0 Thymol Trimethoxycinnamate 0.5 Tromethamine 0.1 Carbomer 0.15 Ethylhexylglycerin 0.05 Glyceryl Caprylate 0.1 Hexylene Glycol 0.9 Purified Water Balance Total 100.0

[0086] [Formulation Example 4] Massage Cream

[0087] Prepare the massage cream by a conventional method according to the components described in Table 7 below.

[0088] [Table 7]

[0089] Ingredient Content (wt%) Thymol Trimethoxycinnamate 0.5 Beeswax 10.0 Polysorbate 80 1.5 PEG 60 Hydrogenated Castor Oil 2.0 Sorbitan Sesquioleate 0.8 Liquid Paraffin 40 Squalane 5.0 Caprylic / Capric Triglyceride 4.0 Glycerol 5.0 Butylene Glycol 3.0 Propylene Glycol 3.0 pH Regulator 0.2 Preservative, Pigment, Flavor 0.1 Purified Water Balance Total 100

[0090] [Formulation Example 5] Facial Mask

[0091] Prepare the facial mask by a conventional method according to the components described in Table 8 below.

[0092] [Table 8]

[0093] Ingredient Content (wt%) Thymol Trimethoxycinnamate 1 Polyvinyl Alcohol 13.0 Sodium Carboxymethylcellulose 0.2 Glycerol 5.0 Allantoin 0.1 Ethanol 6.0 PEG12 Laureth 0.3 Polysorbate 60 0.3 Preservative, Pigment, Flavor 0.1 Purified Water Balance Total 100

[0094] [Formulation Example 6] Gel

[0095] Prepare the gel by a conventional method according to the components described in Table 9 below.

[0096] [Table 9]

[0097]

[0098]

[0099] [Formulation Example 7] Ointment

[0100] Prepare the ointment by a conventional method according to the components described in Table 10 below.

[0101] [Table 10]

[0102] Ingredient Content (wt%) Thymol Trimethoxycinnamate 1.0 Glycerol 8.0 Butylene Glycol 4.0 Liquid Paraffin 15.0 β-Glucan 7.0 Carbomer 0.1 Caprylic / Capric Triglyceride 3.0 Squalane 1.0 Cetearyl Glucoside 1.5 Sorbitan Stearate 0.4 Cetearyl Alcohol 1.0 Beeswax 4.0 Preservative, Pigment, Flavor 0.1 Purified Water Balance Total 100

[0103] [Formulation Example 8] Shampoo

[0104] Prepare the shampoo by a conventional method according to the components described in Table 9 below.

[0105] [Table 11]

[0106]

[0107]

[0108] [Formulation Example 9] Soft Capsule

[0109] Mix 100 mg of thymol trimethoxycinnamate, 160 mg of L-carnitine, 320 mg of soybean oil, 2 mg of palm oil, 8 mg of vegetable hardening oil, 4 mg of yellow wax, and 6 mg of lecithin, and fill 1 capsule according to the conventional method to prepare a soft capsule.

[0110] [Formulation Example 10] Tablet

[0111] Mix 120 mg of thymol trimethoxycinnamate, 500 mg of galactooligosaccharide, 80 mg of lactose, and 220 mg of maltose. After granulating with a fluidized bed dryer, add 6 mg of sugar ester and press with a tableting machine to prepare a tablet.

[0112] [Formulation Example 11] Granule

[0113] Mix 100 mg of thymol trimethoxycinnamate, 250 mg of anhydrous crystalline glucose, and 550 mg of starch. After forming into granules using a fluidized bed granulator, pack them into bags to prepare granules.

[0114] [Formulation Example 12] Beverage

[0115] Mix 120 mg of thymol trimethoxycinnamate, 10 g of glucose, 0.6 g of citric acid, and 25 g of liquid oligosaccharide, then add 500 ml of purified water and fill 200 ml into each bottle. After filling into the bottles, sterilize at 130 °C for 4 - 5 seconds to prepare a beverage.

[0116] This specification is further illustrated by the following implementation examples that do not limit the claims.

[0117] Example 1: Use of thymol trimethoxycinnamate, its stereoisomers, salts, hydrates or solvates for preparing a composition for relieving skin itching or irritation.

[0118] Example of implementation 2: For the use described in Example of implementation 1, the thymol trimethoxycinnamate is represented by the following Chemical Formula 1.

[0119] [Chemical Formula 1]

[0120]

[0121] Example of implementation 3: For the use described in Example of implementation 1 or Example of implementation 2, the dosage of the thymol trimethoxycinnamate, its stereoisomers, salts, hydrates or solvates is 0.37 to 37 mg / kg / day.

[0122] Example of implementation 4: For any of the uses described in Examples of implementation 1 to 3, the content of the thymol trimethoxycinnamate, its stereoisomers, salts, hydrates or solvates is 0.001 to 20% by weight based on the total weight of the composition.

[0123] Example of implementation 5: For any of the uses described in Examples of implementation 1 to 4, the composition inhibits the voltage-gated sodium channel NaV1.7.

[0124] Example of implementation 6: For any of the uses described in Examples of implementation 1 to 5, the skin itching or skin irritation is caused by a chemical substance.

[0125] Example of implementation 7: For any of the uses described in Examples of implementation 1 to 6, the composition is a topical skin composition.

[0126] Example of implementation 9: For any of the uses described in Examples of implementation 1 to the Examples, the composition is a cosmetic composition.

[0127] Example of implementation 10: For any of the uses described in Examples of implementation 1 to 9, the composition is a pharmaceutical composition.

Claims

1. Use of thymol trimethoxycinnamate or its salt for preparing a composition for relieving skin itching.

2. The use according to claim 1, wherein, the thymol trimethoxycinnamate is represented by the following Chemical Formula 1: [Chemical Formula 1] 3. The use according to claim 1, wherein, the dosage of the thymol trimethoxycinnamate or its salt is 0.37 to 37 mg / kg / day.

4. The use according to claim 1, wherein, the content of the thymol trimethoxycinnamate or its salt is 0.001 to 20% by weight based on the total weight of the composition.

5. The use according to claim 1, wherein, the composition inhibits voltage-gated sodium channel NaV1.

7.

6. The use according to claim 1, wherein, the skin itching is caused by a chemical substance.

7. The use according to any one of claims 1 to 6, wherein, the composition is a topical skin composition.

8. The use according to any one of claims 1 to 6, wherein, the composition is a cosmetic composition.

9. The use according to any one of claims 1 to 6, wherein, the composition is a pharmaceutical composition.

10. Use of thymol trimethoxycinnamate or its salt for preparing a cosmetic composition for relieving skin irritation.

11. The use according to claim 10, wherein, the thymol trimethoxycinnamate is represented by the following Chemical Formula 1: [Chemical Formula 1] 12. The use according to claim 10, wherein, the dosage of the thymol trimethoxycinnamate or its salt is 0.37 to 37 mg / kg / day.

13. The use according to claim 10, wherein, the content of the thymol trimethoxycinnamate or its salt is 0.001 to 20% by weight based on the total weight of the composition.

14. The use according to claim 10, wherein, the composition inhibits voltage-gated sodium channel NaV1.7.

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