Composition for alleviating skin irritation caused by external stimuli and / or retinol

Abstract

The present specification relates to a composition for alleviating skin irritation, the composition comprising cetyl-PG hydroxyethyl palmitamide as an active ingredient, and exhibiting a superior skin irritation alleviating effect compared to ceramide NP, which is widely known in the art.

Description

Composition for alleviating skin irritation caused by external stimuli and / or retinol

[0001] Cross-reference to related applications

[0002] This application claims priority to Republic of Korea Patent Application No. 10-2024-0098494, filed July 25, 2024, the entire contents of which are incorporated herein by reference.

[0003] The present specification discloses a composition comprising a similar ceramide (cetyl-pigylhydroxyethylpalmitamide) having superior skin irritation relief performance compared to existing ceramides.

[0004] As the skin's epidermal cells age or are exposed to external stimuli such as ultraviolet rays, cleansers, and temperature differences, their proliferation rate decreases, and as the rate of proliferation and differentiation becomes imbalanced, and as the activity of the sebaceous glands decreases and the amount of sebum secreted decreases, the barrier function is damaged, moisturizing power decreases, and the turnover cycle of the stratum corneum increases, which not only makes the skin dull but also causes sensitive skin.

[0005] Therefore, by promoting the proliferation of epidermal cells and normalizing the proliferation and differentiation cycle of epidermal cells, the skin's barrier function is improved and the turnover of new epidermal cells is accelerated, making the skin layer firmer, thereby protecting the skin from aging and external stimuli.

[0006] As a solution to this, we can consider a method of supplying ceramides and pseudo-ceramides that help maintain a strong skin barrier as skin lipid components.

[0007] In one aspect of the present disclosure, it is intended to provide a composition comprising a ceramide-like substance having superior skin irritation relief performance compared to conventionally known ceramides.

[0008] In one aspect, the present disclosure provides a composition for alleviating skin irritation comprising cetyl-PG Hydroxyethyl Palmitamide as an active ingredient.

[0009] In one aspect, the composition according to the present disclosure may have an excellent skin irritation relief effect by including cetyl-PG Hydroxyethyl Palmitamide as an active ingredient.

[0010] Figure 1 shows the skin irritation alleviation effect of a composition according to one embodiment of the present disclosure.

[0011] Figure 2 shows the skin irritation relief effect of retinol in a composition according to one embodiment of the present disclosure.

[0012] Hereinafter, the present invention will be described in more detail through the following examples. However, the following examples are provided solely for illustrative purposes to aid understanding of the present invention, and the scope and range of the present invention are not limited thereto.

[0013] In exemplary embodiments of the present disclosure, a composition for alleviating skin irritation is provided, which comprises cetyl-PG Hydroxyethyl Palmitamide as an active ingredient.

[0014] In another exemplary embodiment of the present disclosure, a method of soothing skin irritation is provided, comprising applying Cetyl-PG Hydroxyethyl Palmitamide to the skin.

[0015] In another exemplary embodiment of the present disclosure, the use of Cetyl-PG Hydroxyethyl Palmitamide for preparing a composition for soothing skin irritation is provided.

[0016] In another exemplary embodiment of the present disclosure, non-therapeutic uses of Cetyl-PG Hydroxyethyl Palmitamide are provided for soothing skin irritation.

[0017] Ceramides are important lipid second messenger molecules that regulate cell differentiation, proliferation, apoptosis, aging, and other vital functions. They are also a major component of human stratum corneum lipids. Psuedoceramides are similar in function and structure to ceramides, and cetyl-PG Hydroxyethyl Palmitamide (PGHP) is a ceramide analogue that is economical and effective in strengthening and maintaining skin barrier function.

[0018] The composition according to the present disclosure comprises a similar ceramide, cetyl-PG Hydroxyethyl Palmitamide (trade name: Ceramoist), as an active ingredient, and can exhibit a significantly superior irritation relief performance compared to the generally well-known ceramide-NP.

[0019] In one embodiment, the composition may be for alleviating skin irritation induced by retinol.

[0020] In one implementation example, the active ingredient may be used in an amount of 0.1 to 10 parts by weight based on 0.05 parts by weight of retinol.

[0021] For example, based on 0.05 parts by weight of retinol, the active ingredient may be 0.1 parts by weight or more, 0.5 parts by weight or more, 1 parts by weight or more, 3 parts by weight or more, 5 parts by weight or more, 7 parts by weight or more, or 9 parts by weight or more, and may be 10 parts by weight or less, 8 parts by weight or less, 6 parts by weight or less, 4 parts by weight or less, 2 parts by weight or less, 1 part by weight or less, or 0.5 parts by weight or less.

[0022] In one embodiment, the concentration of the effective ingredient may be 0.01 to 10 parts by weight based on 100 parts by weight of the composition.

[0023] For example, the concentration of the effective ingredient may be 0.01 parts by weight or more, 0.1 parts by weight or more, 0.5 parts by weight or more, 1 part by weight or more, or 5 parts by weight or more, and may be 10 parts by weight or less, 5 parts by weight or less, 1 part by weight or less, 0.5 parts by weight or less, or 0.1 parts by weight or less, based on 100 parts by weight of the composition.

[0024] In one embodiment, the composition may be a topical skin preparation.

[0025] The above skin external agent is a general term that can include anything applied externally to the skin, and various types of cosmetics can be included here.

[0026] In one embodiment, the composition may be a cosmetic composition.

[0027] In one embodiment, the external form of the cosmetic composition may contain a cosmetically or dermatologically acceptable medium or base. This may be provided in any formulation suitable for topical application, for example, in the form of a solution, gel, solid, anhydrous paste, an emulsion obtained by dispersing an oil phase in an aqueous phase, a suspension, a microemulsion, a microcapsule, a microgranule, or a vesicular dispersion of ionic (liposomes) and non-ionic forms, or in the form of a cream, toner, lotion, powder, ointment, spray, or concealer stick. These compositions may be prepared according to methods conventional in the art. The composition according to the present disclosure may also be used in the form of a foam or in the form of an aerosol composition further containing a compressed propellant.

[0028] The cosmetic composition according to the present disclosure is not particularly limited in its formulation, and may be formulated as cosmetics such as, for example, a softening toner, an astringent toner, a nourishing toner, a nourishing cream, a massage cream, an essence, an eye cream, an eye essence, a cleansing cream, a cleansing foam, a cleansing water, a cleansing tissue containing the cosmetic composition, a pack, a powder, a body lotion, a body cream, a body oil, and a body essence.

[0029] When the formulation of the cosmetic composition according to the present disclosure is a paste, cream or gel, animal fiber, plant fiber, wax, paraffin, starch, tragacanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide may be used as a carrier component.

[0030] When the formulation of the cosmetic composition according to the present disclosure is a powder or spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used as a carrier component, and particularly in the case of a spray, a propellant such as chlorofluorohydrocarbon, propane / butane or dimethyl ether may be additionally included.

[0031] In the case where the formulation of the cosmetic composition according to the present disclosure is a solution or emulsion, a solvent, solvating agent or emulsifying agent is used as a carrier component, and examples thereof include water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol or fatty acid ester of sorbitan.

[0032] When the formulation of the cosmetic composition according to the present disclosure is a suspension, a liquid diluent such as water, ethanol or propylene glycol, a suspending agent such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, microcrystalline cellulose, aluminum metahydroxide, bentonite, agar or tragacanth, etc. can be used as a carrier component.

[0033] The cosmetic composition according to the present disclosure may further include functional additives and ingredients included in general cosmetic compositions. The functional additives may include ingredients selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, high molecular weight peptides, high molecular weight polysaccharides, squalane, sphingolipids, and seaweed extract.

[0034] The cosmetic composition according to the present disclosure may also contain, as necessary, ingredients included in general cosmetic compositions in addition to the functional additives described above. Examples of other ingredients to be contained include fat components, moisturizers, emollients, emulsifiers, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, sterilizers, antioxidants, plant extracts, pH adjusters, alcohols, pigments, fragrances, blood circulation promoters, cooling agents, antiperspirants, purified water, and the like.

[0035] In one embodiment, the composition may be a food composition.

[0036] In one embodiment, the composition may be a non-therapeutic oral composition.

[0037] The food composition or non-therapeutic oral composition according to the present disclosure may be in the form of a liquid or solid formulation, and may be in the form of a tablet, capsule, soft capsule, pill, granule, beverage (drink), diet bar, chocolate, caramel formulation, or confectionery formulation, and the formulation is not particularly limited.

[0038] The food composition or non-therapeutic oral composition according to the present disclosure may further contain excipients, sugars, flavors, pigments, oils, proteins, etc., in addition to the above-described active ingredients, as needed.

[0039] In one embodiment, the composition may be a pharmaceutical composition.

[0040] In one embodiment, the pharmaceutical composition may be for improving, preventing, or treating one or more selected from the group consisting of atopy, itching, erythema, psoriasis, and dry skin.

[0041] A pharmaceutical composition according to one embodiment of the present disclosure may additionally contain pharmaceutical adjuvants such as preservatives, stabilizers, wetting agents or emulsifying agents, salts for osmotic pressure control, and / or buffers, and other therapeutically useful substances, and may be formulated into various oral or parenteral dosage forms according to conventional methods.

[0042] The oral dosage forms include, for example, tablets, pills, hard and soft capsules, solutions, suspensions, emulsions, syrups, powders, granules, granules, pellets, etc., and these dosage forms may contain, in addition to the active ingredient, a surfactant, a diluent (e.g., lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, and glycine), and a lubricant (e.g., silica, talc, stearic acid and its magnesium or calcium salts, and polyethylene glycol). The tablets may also contain binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, and polyvinylpyrrolidine, and optionally pharmaceutical additives such as disintegrating agents such as starch, agar, alginic acid or its sodium salt, absorbents, coloring agents, flavoring agents, and sweetening agents. The tablets may be manufactured by conventional mixing, granulating, or coating methods.

[0043] In addition, the above parenteral administration form may be a transdermal administration formulation, and examples thereof include, but are not limited to, injections, drops, ointments, lotions, gels, creams, sprays, suspensions, emulsions, suppositories, patches, etc.

[0044] Hereinafter, the present disclosure will be described in more detail through the following examples. However, the following examples are provided solely for illustrative purposes to aid understanding of the present disclosure, and the scope and range of the present disclosure are not limited thereto.

[0045] Example

[0046] 1. Skin irritation relief effect of Cetyl-PG Hydroxyethyl Palmitamide

[0047] 1-1) Test method

[0048] To confirm the skin irritation relief effect of Cetyl-PG Hydroxyethyl Palmitamide (brand name: Ceramoist), a single skin irritation test was conducted on 25 healthy adults (2 males, 23 females, average age: 42.1 years) (February 20, 2024 - February 23, 2024, Safety Lab, Amorepacific R&D Center).

[0049] On the first day of the study, a patch was attached to the upper back of the subject, and after 48 hours, the patch was removed. The first reading was performed 30 minutes later, and the second reading was performed 24 hours later. In order to determine the intensity of skin irritation of the sample, the average skin reactivity was calculated by assigning weights according to the degree of positive skin reaction and determining the skin irritation of the sample. The test was performed according to the terminology presented in Table 1, which is a modified test standard from the ICDRG, CTFA guideline (1981) and the test standard of Frosch & Kligman (1979). The test results were calculated as the average value of the reaction for each subject.

[0050] ① Test materials

[0051] - Van der Bend Patch test chambers (Van der Bend Medical Supplies, Netherlands), Marking pen; Oil ink pen

[0052] ② Criteria for judging skin reactions

[0053] [modified from Frosch & Kligman and CTFA safety testing guideline] (Table 1) (Table 1 below)

[0054] -No visible reaction1+Slight erythema, either spotty or diffuse2+Moderate uniform erythema3+Intense erythema with edema4+Intense erythema with edema & vesicles

[0055] 1-2) Test results

[0056] Compositions 1 to 3 were prepared as shown in Table 2 below and in the following order.

[0057] 1. Heat distilled water to 70℃.

[0058] 2. Disperse Carbomer in distilled water using a homogenizer.

[0059] 3. Dissolve ceramide in 1,3-BG (butylene glycol) at 70℃ using an azimuth mixer.

[0060] 4. Add the dissolved ceramide solution 3 times to distilled water and disperse it using an azimuth mixer.

[0061] 5. Cool to room temperature.

[0062] The vehicle prescription containing 60% DI Water, 39.6% 1,3-BG (butylene glycol), and 0.4% CARBOMER showed a 1-point reaction in 5 subjects in the first test and a 1-point reaction in 4 subjects in the second test, showing an average stimulation score of 0.36 points. The second prescription containing 5% CERAMIDE NP in the vehicle prescription showed a 1-point reaction in 7 subjects in the first test and a 1-point reaction in 2 subjects in the second test, showing an average stimulation score of 0.36 points, confirming that it had the same level of irritation as the first prescription.

[0063] In the third prescription containing 5% Cetyl-PG Hydroxyethyl Palmitamide in the vehicle prescription, a 1-point reaction was observed in one person in the first test, and in the second test, no irritation was observed in any subject, confirming the average irritation as 0.04 points. It was confirmed that the prescription containing 5% Cetyl-PG Hydroxyethyl Palmitamide was statistically significantly different from the vehicle prescription (Wilcoxon signed-rank test, p=0.014).

[0064] As a result, referring to Tables 2 and 3 and Fig. 1 below, irritation was reduced by 88.8% in formulation 3 containing Cetyl-PG Hydroxyethyl Palmitamide compared to the vehicle. On the other hand, the formulation containing Ceramide NP did not have an irritation-reducing effect. In addition, Cetyl-PG Hydroxyethyl Palmitamide showed a skin irritation relief effect that was 9 times better than Ceramide NP.

[0065] 48-hour patch test

[0066] NO Test Sample 1st Test 2nd Test Stimulus Mean Standard Deviation 123412341Vehicle (DI Water 60%, 1,3-BG 39.6%, CARBOMER 0.4%) 500040000.360.6382CERAMIDE NP 5%+DI Water 55%, 1,3-BG 39.6%, CARBOMER 0.4% 700020000.360.5693Cetyl-PG Hydroxyethyl Palmitamide 5%+DI Water 55%, 1,3-BG 39.6%, CARBOMER 0.4% 100000000.040.2

[0067] Subject information and subject-specific data

[0068] 1 2 3 Number Gender Age 1st Test 2nd Test 1st Test 2nd Test 1st Test 2nd Test 1F 360000002M 320000003M 430010004F 330000005F 421010006F 390000007F 511010008F 470000009F 4411110010F 4301010011F 4800000012F 2701000013F4300000014F4411100015F4400000016F4100100017F3500000018F450000001 9F5700000020F5300000021F4700000022F4100000023F5000000024M3310101025F35000000

[0069] 2. Cetyl-PG Hydroxyethyl Palmitamide's skin irritation-relieving effect on "retinol"

[0070] 2-1) Testing method

[0071] To confirm the skin irritation relief effect of cetyl-PG Hydroxyethyl Palmitamide on retinol, a cumulative skin irritation evaluation was conducted on 14 healthy adults (0 males, 14 females, average age: 48.4 years) (February 19, 2024 - March 4, 2024, Safety Lab, Amorepacific R&D Center).

[0072] On the first day of the study, the first formulation containing Cetyl-PG Hydroxyethyl Palmitamide was applied to the upper back of the subject, followed by a formulation containing 1500 IU of retinol, which was applied to the same area using a Finn chamber. The patches were removed after 24 hours, and the first reading was taken 30 minutes later. The same method was repeated for a total of six patches on the same skin area over a period of two weeks.

[0073] The examination was conducted according to the terminology presented in [Table 1], which is a modified version of the ICDRG, CTFA guideline (1981) and Frosch & Kligman (1979) examination criteria. If skin irritation occurred, patch application was discontinued, and the response value for each subject was calculated based on the last examination date, and the average skin irritation response for all subjects was calculated.

[0074] ①Test materials

[0075] -Finn chamber® (Smart Practice, USA), Marking pen; Oil ink pen

[0076] ② Criteria for judging skin reactions

[0077] [modified from Frosch & Kligman and CTFA safety testing guideline] (Table 1) (same as Table 1 above)

[0078] 2-2) Test results

[0079] By applying the first formulation as shown in Table 5 below to the skin and patching 1500 IU of Retinol, the degree of relief of skin irritation by Retinol by the first formulation was confirmed.

[0080] When the first formulation was applied to the skin as a vehicle prescription and Retinol 1500IU was patched, the total skin irritation score was 27 points with 6 cumulative applications, and when the first formulation was made into a vehicle containing 0.5% Cetyl-PG Hydroxyethyl Palmitamide, the total skin irritation score was confirmed to be reduced to 17 points. In addition, when the first formulation was made into a vehicle containing 1.5% Cetyl-PG Hydroxyethyl Palmitamide, the total skin irritation score was confirmed to be 21 points.

[0081] Referring to Tables 4 and 5 and Fig. 2 below, skin irritation was reduced when the content containing Cetyl-PG Hydroxyethyl Palmitamide was applied first compared to the vehicle, followed by the second application of 1500 IU of retinol. When Cetyl-PG Hydroxyethyl Palmitamide was contained at 0.5%, skin irritation was reduced by 37%, and when it was contained at 1.5%, skin irritation was reduced by 22%.

[0082] Cumulative stimulation test

[0083] No. 1st Formulation 2nd Formulation Total Skin Irritation 1Vehicle (DI Water 87.8%, 1,3-BG 10%, CARBOMER 0.2%, EtOH 2%) Retinol 1500IU (Vehicle: DI Water 70%, 1,3-BG 30%) 272 Cetyl-PG Hydroxyethyl Palmitamide 0.5%+ DI Water 87.3%, 1,3-BG 10%, CARBOMER 0.2%, EtOH 2% 173 Cetyl-PG Hydroxyethyl Palmitamide 1.5%+ DI Water 86.3%, 1,3-BG 10%, CARBOMER 0.2%, EtOH 2% 21

[0084] Subject information and subject-specific data

[0085] No. Age / Gender 1st 2nd 3rd 150F211241F422351F112452F322548F211649F212742F121843F112953F1011055F2331151F3131238F2211358F2001447F100

[0086] Specific examples

[0087] Specific example 1: A composition for alleviating skin irritation, comprising cetyl-PG Hydroxyethyl Palmitamide as an active ingredient.

[0088] Specific example 2: In specific example 1,

[0089] The composition is for alleviating skin irritation induced by retinol.

[0090] Specific example 3: In specific example 1 or 2,

[0091] A composition wherein the effective ingredient is used in an amount of 0.1 to 10 parts by weight based on 0.05 parts by weight of retinol.

[0092] Specific example 4: In any one of Specific examples 1 to 3,

[0093] A composition wherein the concentration of the effective ingredient is 0.01 to 10 parts by weight based on 100 parts by weight of the composition.

[0094] Specific example 5: In any one of Specific examples 1 to 4,

[0095] The above composition is a composition for external use on the skin.

[0096] Specific example 6: In any one of Specific examples 1 to 5,

[0097] The composition above is a cosmetic composition.

[0098] Specific example 7: In any one of Specific examples 1 to 6,

[0099] The above composition is a food composition.

[0100] Specific example 8: In any one of Specific examples 1 to 7,

[0101] The composition above is a pharmaceutical composition.

Claims

1. A composition for relieving skin irritation, comprising cetyl-PG Hydroxyethyl Palmitamide as an active ingredient.

2. In paragraph 1, The composition is for alleviating skin irritation induced by retinol.

3. In paragraph 2, A composition wherein the effective ingredient is used in an amount of 0.1 to 10 parts by weight based on 0.05 parts by weight of retinol.

4. In paragraph 1, A composition wherein the concentration of the effective ingredient is 0.01 to 10 parts by weight based on 100 parts by weight of the composition.

5. In paragraph 1, The above composition is a composition for external use on the skin.

6. In paragraph 1, The composition above is a cosmetic composition.

7. In paragraph 1, The above composition is a food composition.

8. In paragraph 1, The composition above is a pharmaceutical composition.

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