Skin external use composition with enhanced anti-eczema efficacy

Abstract

The present invention relates to a composition for external use on skin with enhanced anti-eczema efficacy, comprising (A) concentrated birch sap, wherein the concentration ratio is about 1.05-8 times, preferably about 1.1-4 times, and more preferably about 1.2-2 times, and (B) one or more substances selected from the group consisting of oat kernel extract, utilis utilis oil, calendula extract, allantoin, bisabolol, ceramide, panthenol, glycerin, and squalane.

Description

Technical Field

[0001] The present invention relates to a composition for external use on skin with enhanced anti-eczema efficacy, comprising (A) concentrated birch sap, wherein the concentration ratio is about 1.05-8 times, preferably about 1.1-4 times, and more preferably about 1.2-2 times, and (B) one or more substances selected from the group consisting of oat kernel extract, prurinifolia utilis oil, calendula officinalis flower extract, allantoin, bisabolol, ceramide, panthenol, glycerin, and squalane. Background Art

[0002] Eczema is an inflammatory skin disease with a pronounced exudative tendency, caused by a variety of internal and external factors. It's characterized by significant itching, impaired skin barrier function, and a high recurrence rate. Currently, oat kernel extract, calendula extract, allantoin, bisabolol, ceramides, panthenol, glycerin, squalane, and prickle fruit oil are the most common anti-eczema and moisturizing ingredients in commercially available cosmetics for eczema, but their effectiveness is often unsatisfactory.

[0003] Birch is a deciduous tree in the Betulaceae family. There are approximately 100 species worldwide, primarily distributed in northern and cold temperate zones. Approximately 29 species are found in my country, primarily in Northeast, Northwest, North China, and Southwest China. Birch trees play a vital role in preventing soil erosion, improving the environment, and protecting against wind and sandstorms. Birches primarily grow in remote mountainous areas with minimal human intervention and industrial pollution. Birch sap is the fresh sap that flows out of birch bark or when a hole is drilled in the trunk. It is colorless or light yellow, free of sediment and impurities, and has a light birch fragrance. It is rich in nutrients and, after ingestion, is metabolized into factors beneficial to health, thus providing health benefits for those with sub-health conditions. It is often used in beverages, such as beverages and alcohol, due to its excellent nutritional and health benefits. Birch sap contains a large amount of sugars, amino acids, vitamins, biotin, cytokinins, trace minerals, aromatic oils, betulin, saponins, and other compounds, offering excellent moisturizing and anti-eczema properties. Summary of the Invention

[0004] In one aspect, the present invention relates to use of a combination of (A) concentrated birch sap and (B) one or more selected from oat kernel extract, prurinifolia utilis oil, calendula officinalis extract, allantoin, bisabolol, ceramide, panthenol, glycerin and squalane in a skin external composition with enhanced anti-eczema efficacy, wherein the concentrated birch sap is concentrated at a multiple of about 1.05-8 times, preferably about 1.1-4 times, and more preferably about 1.2-2 times.

[0005] On the other hand, the present invention relates to a composition for external use on skin with enhanced anti-eczema efficacy, comprising (A) concentrated birch sap having a concentration factor of about 1.05-8 times, preferably about 1.1-4 times, and more preferably about 1.2-2 times, and (B) one or more substances selected from oat kernel extract, prurinifolia utilis oil, calendula officinalis flower extract, allantoin, bisabolol, ceramide, panthenol, glycerin, and squalane.

[0006] The birch sap used in the present invention is obtained from the genus Betula (Betulaceae), and can come from four species: Betula alba, Betula pubescens, Betula pendula, and Betula platyphylla. The birch sap is collected by drilling holes at the base of birch trunks between thawing and leafing in early spring. It is colorless, transparent, and free of sediment and debris, and has a refreshing birch fragrance and is rich in nutrients. The birch sap can be commercially obtained and used as is, for example, from Daxing'anling Chaoyue Wild Berry Development Co., Ltd.

[0007] The concentrated birch sap in the present invention is obtained by concentrating the commercially available product. Concentration methods are known in the art, such as heating concentration, low-temperature vacuum concentration, and membrane concentration. In the present invention, concentration is preferably performed by low-temperature freeze concentration or membrane concentration. For example, commercially available birch sap stock solution is fed into a low-temperature drying device, cooled to -40°C to -70°C, and vacuumed to 0.1-30 Pa for low-temperature vacuum concentration, thereby obtaining concentrated birch sap of varying concentration ratios.

[0008] Furthermore, the inventors have discovered that the anti-eczema efficacy of concentrated birch sap is not linearly correlated with its concentration level, but rather increases and then decreases with increasing concentration ratio. Therefore, controlling the concentration ratio of birch sap is crucial. In the present invention, the concentration ratio of birch sap is controlled to be 1.05-8 times, preferably about 1.1-4 times, and more preferably about 1.2-2 times.

[0009] Unexpectedly, the present inventors found that compared with the use of concentrated birch sap, oat kernel extract, prickle oil, calendula extract, allantoin, bisabolol, ceramide, panthenol, glycerin or squalane alone, the combination of concentrated birch sap with oat kernel extract, prickle oil, calendula extract, allantoin, bisabolol, ceramide, panthenol, glycerin and / or squalane has significantly better anti-eczema efficacy, which is much higher than the combined effect of the two functions, indicating that a synergistic effect occurs between them.

[0010] The concentrated birch sap of component (A) is contained in an amount of about 18-98% by weight, preferably about 20-95% by weight, more preferably about 22-90% by weight, and most preferably about 30-90% by weight, based on the total weight of the external skin composition.

[0011] The oat kernel extract, prurinifolia utilis oil, calendula officinalis extract, allantoin, bisabolol, ceramide, panthenol, glycerin and squalane in the component (B) are all substances known in the art and are commercially available.

[0012] The content of the component (B) is about 0.01-10%, preferably 0.1-6%, more preferably 0.5-5%, based on the total weight of the skin external composition.

[0013] The skin external composition includes a pharmaceutical composition or a cosmetic composition.

[0014] The skin external composition does not contain any externally added water, but does not exclude moisture inherently contained in each component.

[0015] In a preferred embodiment, the skin external composition does not contain chelating agents such as EDTA salts, sodium polyphosphate, sodium metaphosphate, and gluconic acid.

[0016] In addition to components (A) and (B), the skin topical composition may optionally further comprise component (C), commonly used ingredients in skin topical compositions, including but not limited to vehicles, active ingredients, and excipients. Component (C) is known in the art, and those skilled in the art can select its type and amount as needed. For example, the total content of component (C) is generally about 2-80% based on the total weight of the skin topical composition.

[0017] The vehicle includes, for example, a diluent, a dispersant or a carrier, and examples thereof include, but are not limited to, ethanol, dipropylene glycol, butylene glycol, etc. The content of the vehicle in the skin external composition is known in the art, for example, it generally accounts for 0.5-20% of the total weight of component (C).

[0018] Such active ingredients include, for example, emollients, moisturizers, anti-eczema active ingredients, and the like.

[0019] Examples of the emollient include, but are not limited to, one or more of olive oil, macadamia nut oil, sweet almond oil, grape seed oil, avocado oil, corn oil, sesame oil, soybean oil, peanut oil, meadowfoam seed oil, safflower seed oil, rosa canina fruit oil, argania spinosa kernel oil, jojoba seed oil, sunflower seed oil, palm oil, ethylhexyl palmitate, isopropyl myristate, hydrogenated polyisobutene, isohexadecane, isododecane, diethylhexyl carbonate, dicaprylyl carbonate, isopropyl lauroyl sarcosinate, isononyl isononanoate, hydrogenated polydecene, triethylhexanoin, cetyl ethylhexanoate, bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate, caprylic / capric triglyceride, oleyl erucate, octyldodecyl myristate, octyldodecanol, dimethicone, caprylyl methicone, cetyl dimethicone, cyclopentasiloxane, and the like. Examples of solid emollients include, but are not limited to, cetyl alcohol, stearyl alcohol, cetearyl alcohol, behenyl alcohol, batyl alcohol, lauric acid, myristic acid, palmitic acid, stearic acid, beeswax, candelilla wax, carnauba wax, lanolin, ozokerite, jojoba seed wax, paraffin, microcrystalline wax, hydrogenated rice bran wax, hydrogenated coconut oil glycerides, glyceryl behenate / eicosate, myristyl myristate, bis-diglyceryl polyacyl adipate-2, shea butter, Murumuru seed butter, etc. One or more of the emollients are known in the art in the composition for external use on skin. For example, the emollients generally account for 1-50% of the total weight of component (C).

[0020] Examples of the moisturizing agent include, but are not limited to, diglycerin, butylene glycol, propylene glycol, 1,3-propanediol, dipropylene glycol, 1,2-pentanediol, polyethylene glycol-8, polyethylene glycol-32, methyl gluceth-10, methyl gluceth-20, PEG / PPG-17 / 6 copolymer, glycereth-7, glycereth-26, glyceryl glucoside, PPG-10 methyl gluceth, PPG-20 methyl gluceth, PEG / PPG / One or more of polybutylene glycol-8 / 5 / 3 glycerol, sucrose, trehalose, rhamnose, mannose, raffinose, betaine, erythritol, xylitol, urea, glyceryl polyether-5 lactate, sodium hyaluronate, hydrolyzed sodium hyaluronate, acetylated sodium hyaluronate, sodium polyglutamate, hydrolyzed sclerotium gum, budding pullulan polysaccharide, tremella polysaccharide, sour bean seed polysaccharide, 1,2-hexanediol, natural moisturizing factor, ceramide 2, ceramide 3, cholesterol, phospholipids, etc. The content of the moisturizing agent in the skin external composition is known in the art, for example, it generally accounts for 1-30% of the total weight of component (C).

[0021] Examples of the anti-eczema active ingredient include, but are not limited to, one or more of dipotassium glycyrrhizate, purslane (Portulaca oleracea) extract, biosaccharide gum-1, β-glucan, fructan, scutellaria baicalensis (Scutellaria baicalensis) root extract, horse chestnut (Aesculus hippocastanum) extract, 4-tert-butyl cyclohexanol, ceramide 3, glycyrrhiza glabra (Glycyrrhiza glabra) extract, hydrolyzed royal jelly protein, oryzanol, phytosphingosine, quercetin, ginger root extract, rosemary leaf extract, etc. The content of the anti-eczema active ingredient in the skin external composition is known in the art, for example, it generally accounts for 0.01-10% of the total weight of component (C).

[0022] The auxiliary materials include, for example, emulsifiers, thickeners, preservatives, flavors, and the like.

[0023] Examples of the emulsifier include, but are not limited to, cetearyl olivate, sorbitan olivate, polysorbate 60, polysorbate 80, methyl glucose sesquistearate, PEG-20 methyl glucose sesquistearate, PEG-40 hydrogenated castor oil, PPG-26-buteth-26, PEG-4 polyglyceryl-2 stearate, PEG-60 hydrogenated castor oil, steareth-2, steareth-21, PPG-13-decyltetradeceth-24, cetearyl glucoside, PEG-100 stearate, glycerin. Stearate, glyceryl stearate SE, cocoyl glucoside, ceteareth-25, PEG-40 stearate, polyglyceryl-3 methylglucose distearate, glyceryl stearate citrate, polyglyceryl-10 stearate, polyglyceryl-10 myristate, polyglyceryl-10 dioleate, polyglyceryl-10 laurate, polyglyceryl-10 isostearate, polyglyceryl-10 oleate, polyglyceryl-10 diisostearate, polyglyceryl-6 laurate, polyglyceryl-6 myristate, sucrose stearate, sucrose polystearate, etc. One or more of the following. The content of the emulsifier in the skin external composition is known in the art, for example, it generally accounts for 0.5-10% of the total weight of component (C).

[0024] Examples of the thickener include, but are not limited to, one or more of carbomers, acrylic acid (esters) and their derivatives, xanthan gum, gum arabic, polyethylene glycol-14M, polyethylene glycol-90M, succinoglycan, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, and other high molecular weight polymers. The content of the thickener in the composition for external use on skin is known in the art, for example, it generally accounts for 0.1-10% of the total weight of component (C).

[0025] Examples of the preservative include, but are not limited to, one or more of methylparaben, propylparaben, phenoxyethanol, benzyl alcohol, phenylethyl alcohol, bis(hydroxymethyl)imidazolidinyl urea, potassium sorbate, sodium benzoate, chlorphenesin, sodium dehydroacetate, caprylhydroxamic acid, 1,2-hexanediol, 1,2-pentanediol, p-hydroxyacetophenone, caprylyl glycol, glyceryl caprylate, glyceryl undecylenate, sorbitan caprylate, ethylhexylglycerin, and peony root extract. The content of the preservative in the composition for external use on skin is known in the art, and for example, it generally accounts for 0.01-2% of the total weight of component (C).

[0026] The skin topical composition with enhanced anti-eczema efficacy of the present invention can be prepared by any suitable method known in the art. For example, it can be prepared using equipment such as dissolution tanks, emulsifying pots, dispersers, and delivery pumps commonly used in the cosmetics field. During preparation, the water-soluble substance is first put into the water phase dissolution kettle, and the oil-soluble substance is put into the oil phase dissolution kettle. The temperature of the two kettles is heated to about 80°C. For raw materials that are easy to agglomerate, they can be pre-dispersed with a disperser. After the dissolution is completed, the oil phase and the water phase are transported to the emulsifying pot and homogenized for about 5-15 minutes. After the emulsification is completed, the temperature of the material body is lowered to room temperature, and optional flavors, preservatives, etc. are added, and the pH of the product is adjusted as needed. The relevant test indicators are qualified before filling and shipment.

[0027] The above preparation method can be deleted or adjusted according to the dosage form requirements. As needed, the skin external use composition can be made into various dosage forms such as ointment, cream, lotion, essence, spray, gel, etc. Example

[0028] The present invention will be further described in detail below with reference to the examples. However, it should be understood that these examples and comparative examples are merely provided to illustrate the present invention in more detail and should not be construed as limiting the scope of the appended claims in any form.

[0029] Example 1 :Gene expression related to moisturizing and barrier repair in different material systems

[0030] This example investigates the effects of oat kernel extract, calendula officinalis extract and birch sap in combination on keratin transglutaminase TGM1, epidermal tight junction proteins (ZO-1 and CLDN1), filaggrin FLG and aquaporin AQP3.

[0031] The experimental method is as follows.

[0032] 1. Experimental instruments: fluorescence quantitative PCR instrument (Roche), ultra-clean bench (Sujing), carbon dioxide incubator (Binder), microplate reader (BIO-TEK), micro-oscillator.

[0033] 2. Experimental reagents and consumables: keratinocytes, 6-well plates, cell culture medium, RNA extraction kit, reverse transcription kit, Trizol lysis buffer, etc.

[0034] 3. The steps for gene expression analysis based on keratinocytes are as follows:

[0035] (1) Seeding: Cells were seeded into 6-well plates at a seeding density of 2E5 / well and incubated overnight in a 37°C, 5% CO2 incubator.

[0036] (2) Liquid preparation: The specific test formula is shown in the following table:

[0037]

[0038] (3) Drug administration: When the cell plating rate in the 6-well plate reaches about 50%, add the test substance of each group, with 4 replicate wells for each group;

[0039] (4) Sample collection: After 24 hours in a 37°C, 5% CO2 incubator, the culture medium was discarded, 1 mL of Trizol was added to each well, and the cells were lysed by pipetting before the samples were collected;

[0040] (5) PCR detection: RNA was extracted, reverse transcribed into cDNA, and then fluorescence quantitative PCR was performed;

[0041] (6) Analysis: Using 2 -△△CT The results were calculated and statistically analyzed using the T-Test method. The results are shown in the following table:

[0042]

[0043]

[0044] Among them, 1.2 times, 4 times and 9 times birch sap concentrates are obtained by concentrating birch sap stock solution. The concentration process is: the fresh birch sap stock solution purchased from Daxinganling Chaoyue Wild Berry Development Co., Ltd. is input into low-temperature drying equipment, cooled to -65℃, vacuumed to 0.1Pa, and concentrated to 1.2 times, 4 times and 9 times.

[0045] The results in the table above demonstrate that when oat kernel extract and calendula extract are used in combination with birch sap, they significantly increase the expression of genes associated with moisturizing and barrier repair, such as transglutaminase TGM1, epidermal tight junction proteins (ZO-1 and CLDN1), filaggrin FLG, and aquaporin AQP3. Furthermore, compared to the original birch sap solution, the combination with a 1.2x concentrate demonstrated even greater efficacy.

[0046] Example 2 :Effects of birch sap on the expression of proteins related to moisturizing and barrier repair

[0047] This example investigates the effects of allantoin, bisabolol, and birch sap in combination on the expression of keratin transglutaminase TGM1, epidermal tight junction proteins (ZO-1 and CLDN1), filaggrin FLG, and aquaporin AQP3.

[0048] The experimental method is as follows.

[0049] 1. Experimental instruments: clean bench (Sujing), plate washer (BIO-RAD), microplate reader (BIO-TEK), CO2 incubator (Binder).

[0050] 2. Experimental reagents and consumables: primary human keratinocytes, 12-well plates, keratinocyte culture medium, ELISA kits for different indicators, etc.

[0051] 3. The test steps are as follows:

[0052] (1) Seeding: The cells were seeded into 12-well culture plates at a seeding density of 2E5 / well and cultured in a 37°C, 5% CO2 incubator. The culture medium was changed every two days.

[0053] (2) Drug administration: When the cell fusion reaches more than 60% again, add the test substance at different concentrations. Set up 6 replicate wells in each group. The formula is as follows:

[0054] Ingredients (g) Recipe 1 Recipe 2 Recipe 3 Recipe 4 Recipe 5 Recipe 6 Recipe 7 Recipe 8 Birch sap concentrate 95 95 100 1.2 times concentrated solution 95 95 100 Allantoin 5 5 5 Bisabolol 5 5 5 water 95 95

[0055] (3) Sample collection: After 48 hours in a 37°C, 5% CO2 incubator, the culture medium was discarded, 1 mL of Trizol was added to each well, and the cells were lysed by pipetting before the samples were collected;

[0056] (4) Detection: Measure the indicators according to the ELISA kit method;

[0057] (5) Analysis: T-Test method was used for statistical analysis. The results are shown in the following table:

[0058] sample TGM1 ZO-1 CLDN1 FLG AQP3 Recipe 1 2.754±0.121 2.978±0.216 2.948±0.451 2.924±0.147 3.249±0.159 Recipe 2 2.999±0.146 2.994±0.199 2.615±0.123 2.945±0.294 3.456±0.453 Recipe 3 1.761±0.251 1.897±0.146 1.521±0.101 1.921±0.194 1.994±0.094 Recipe 4 1.835±0.164 1.997±0.256 1.599±0.105 1.778±0.167 1.884±0.462 Recipe 5 0.613±0.075 0.655±0.052 0.773±0.050 0.847±0.024 0.703±0.095 Recipe 6 0.512±0.017 0.694±0.022 0.831±0.023 0.784±0.046 0.699±0.051 Recipe 7 1.113±0.243 1.455±0.172 1.273±0.140 1.347±0.254 1.303±0.145 Recipe 8 2.224±0.199 2.461±0.168 2.324±0.218 2.415±0.324 2.616±0.313

[0059] The results in the table above show that when allantoin and bisabolol are used in combination with birch sap, they significantly increase the expression of genes associated with moisturizing and barrier repair, such as transglutaminase TGM1, epidermal tight junction proteins (ZO-1 and CLDN1), filaggrin FLG, and aquaporin AQP3. Furthermore, compared to the original birch sap solution, the combination with a 1.2x concentrate showed even greater efficacy.

[0060] Example 3 :Effects of birch sap on proliferation and differentiation of keratinocytes

[0061] This example tests and compares the effects of ceramide, glycerin, and birch sap in combination on the proliferation and differentiation abilities of keratinocytes.

[0062] The experimental method is as follows.

[0063] 1. Cells: HACAT (human immortalized epidermal keratinocytes).

[0064] 2. Experimental instruments and consumables: 96-well plate, 1ml pipette, 5ml pipette, 1ml pipette tip, 5ml pipette tip, 15ml centrifuge tube, cell counter, 0.22um filter, pipette, pipette tank, DMEM cell culture medium, FBS, 100× triple antibody, 100× mycoplasma inhibitor, CCK-8 reagent.

[0065] 3. The experimental steps are as follows:

[0066] (1) Cultured HACAT cells were seeded into 96-well plates, with 100 μl per well and a cell density of 3000 cells per well;

[0067] (2) Place in a 37°C, 5% CO2 incubator and culture for 24 hours;

[0068] (3) 100 μl / well of drug is administered, the formula is as follows:

[0069]

[0070] (4) After incubation for 72 hours, the supernatant was discarded and 100 μl of culture medium containing 10% CCK-8 was added to each well;

[0071] (5) Incubate at 37°C for 2 hours, and then measure the OD value at 450 nm using a microplate reader;

[0072] The above experiments were performed in triplicate. Cells were collected from three culture flasks, and cell counting and experimental procedures were performed independently. The results are shown in the following table:

[0073] sample Cell viability Recipe 1 168±1.41 Recipe 2 171±3.14 Recipe 3 152.3±1.51 Recipe 4 140.3±1.32 Recipe 5 145±3.21 Recipe 6 141±1.64 Recipe 7 106±2.18 Recipe 8 110±1.98 Recipe 9 130±2.23 Recipe 10 151±3.55 Recipe 11 145.3±1.31 Recipe 12 135.1±2.34

[0074] The results in the table above show that when ceramide, glycerin, and birch sap are used in combination, they can significantly enhance the proliferation and differentiation of keratinocytes. Furthermore, compared to the original birch sap solution, the combination with the 1.2x concentrate showed even greater efficacy.

[0075] Example 4 :Effects of birch sap on mast cell degranulation

[0076] This example uses a zebrafish larval allergy model to test and compare the effects of panthenol, squalene, and birch sap in combination on mast cell degranulation, thereby verifying the efficacy of birch sap in treating eczema.

[0077] The experimental method is as follows.

[0078] 1. Experimental animals: zebrafish.

[0079] 2. Experimental procedures are as follows: AB wild-type zebrafish embryos were collected and cultured in E3 buffer in a 28.5°C incubator until 5 dpf (days post fertilization), with daily medium changes. 5 dpf zebrafish larvae were randomly transferred into 48-well cell culture plates at a rate of 10 per well and grouped into 4 replicate wells. The groupings were as follows:

[0080] Model group: RO water + 15μg / ml SP

[0081] Positive drug group: ketotifen + 15μg / ml SP

[0082] Sample group to be tested: The formula is as follows:

[0083] Ingredients (g) Recipe 1 Recipe 2 Recipe 3 Recipe 4 Recipe 5 Recipe 6 Recipe 7 Recipe 8 Birch sap concentrate 95 95 100 1.2 times concentrated solution 95 95 100 Panthenol 5 5 5 Squalene 5 5 5 water 95 95

[0084] Corresponding to the above-mentioned SP-induced degranulation groups, a negative control group (without SP) was set up, with 4 replicates per group; corresponding to the SP degranulation-induced group and the SP-free negative control group, a background control group (without zebrafish larvae) was set up, with 2 replicates per group. The residual E3 buffer in each well was aspirated and 250μl of the solution corresponding to each group was added. The cells were reacted in a 28.5℃ incubator in the dark for 60 minutes. After 60 minutes, 200μl of the supernatant from each group was taken to a 96-well cell culture plate, and the enzyme reaction substrate BAPNA was added to a concentration of 400μg / ml. The 96-well plate was covered and placed in a 28.5℃ incubator in the dark for 2 hours. After 2 hours, the light absorbance value of the entire plate at 405nm was measured once. The value reflects the release of tryptase from zebrafish mast cells.

[0085] The results of the zebrafish larvae mast cell protection model efficacy experiment are recorded in the table below:

[0086]

[0087]

[0088] The results in the table above show that when panthenol, squalene, and birch sap are used in combination, they significantly inhibit mast cell degranulation. Furthermore, when used in combination with a 1.2x concentrate, the efficacy was even greater than that of the birch sap concentrate.

[0089] Example 5 : Effects of birch sap on the production of inflammatory factors in the process of eczema

[0090] In this example, an eczema model was established in mice by sensitization and stimulation with 2,4-dinitrofluorobenzene (DNFB), and 1% hydrocortisone ointment was administered as a positive control to examine the effects of the combined use of oat kernel extract, utilis prickle oil, and birch sap on the production of inflammatory factors Th2 (IL-4, 13, 17) and TSLP.

[0091] The experimental method is as follows.

[0092] 1. Experimental animals: ICR mice, male.

[0093] 2. Experimental materials: 0.5% DNFB acetone solution, depilatory cream, dust mite extract, birch sap, oat kernel extract, and pruinosa fruit oil.

[0094] 3. The experimental procedures were as follows: ICR mice were randomly divided into 12 groups according to body weight, each consisting of a normal group, a model group, and a sample group. One day before modeling, a depilatory cream was used to remove hair from an approximately 2x2 cm area on the back of each group of mice. The experimental area on the back of the mice was determined, and the stratum corneum was removed by repeated application of wide transparent tape eight times. All animals were then sensitized with dust mite extract on days 1, 3, 5, and 7 of the first week. Sensitization with dust mite extract was performed on days 10, 13, and 2 of the second week. Sensitization with dust mite extract was performed weekly from week 3 to week 6, and acetone patches were also applied. Acetone (DNCB) was diluted to a 0.5% solution in double-distilled water. The mice were then fixed on the back of the mice as described above, with 100 μL of 0.5% DNCB applied every other day in week 2, and 70 μL every other day from week 2 onward for a total of 6 weeks.

[0095] Twelve hours after successful modeling, the mice were evenly sprayed with birch sap of varying concentrations on their backs using an aerosol bottle, three times a day for seven consecutive days. The model group was sprayed with distilled water three times a day for seven consecutive days.

[0096] The formula of the sample to be tested is as follows:

[0097] Ingredients (g) Recipe 1 Recipe 2 Recipe 3 Recipe 4 Recipe 5 Recipe 6 Recipe 7 Recipe 8 Birch sap concentrate 95 95 100 1.2 times concentrated solution 95 95 100 Oat Kernel Extract 5 5 5 Prikia purpurogena oil 5 5 5 water 95 95

[0098] 4. Observation indicators: After 7 days of medication, the serum of mice was collected and the levels of inflammatory factors TSLP and Th2 (IL-4, 13, 17) in the serum of mice were detected using ELISA kits. The results are shown in the following table:

[0099] IL-4 (pg / ml) IL-13 (pg / ml) IL-17 (pg / ml) TSLP Model Group 58.9±0.32 36.21±1.27 61.39±1.46 89.79±1.27 Normal group 21.61±0.46 12.97±2.44 34.21±2.19 40.61±1.99 Recipe 1 26.94±2.94 14.61±0.49 38.94±3.44 35.91±2.22 Recipe 2 27.25±1.24 15.11±2.44 39.19±2.22 44.21±2.91 Recipe 3 28.33±3.21 18.22±1.54 34.59±2.21 45.31±3.21 Recipe 4 31.89±2.99 18.86±0.71 39.21±1.44 46.21±1.22 Recipe 5 49.13±1.88 38.24±1.29 48.94±1.29 66.21±5.21 Recipe 6 52.11±1.07 41.22±3.14 53.21±3.22 69.21±6.11 Recipe 7 35.29±2.03 22.76±2.89 45.23±3.56 51.24±3.56 Recipe 8 32.25±1.24 18.59±2.31 42.51±1.25 48.91±1.61

[0100] The results in the table above show that when oat kernel extract, utilia utilis oil and birch sap are used in combination, they show significant anti-eczema efficacy. Furthermore, compared with the birch sap concentrate, the combination with the 1.2-fold concentrate showed better efficacy.

[0101] Example 6 : Anti-eczema cream composition

[0102] The formula of the anti-eczema cream composition is as follows:

[0103] Serial number Element weight% 1 1.2 times concentrated birch sap 55 2 Sodium polyglutamate 0.1 3 Hydrolyzed sodium hyaluronate 0.1 4 Xanthan gum 0.2 5 Allantoin 0.2 6 Methylparaben 0.2 7 hydrogenated lecithin 0.5 8 Panthenol 0.5 9 Betaine 3 10 Butanediol 4 11 glycerin 6 12 Carbomer 0.2 13 Propylparaben 0.1 14 Phytosteryl / Octyldodecyl Lauroyl Glutamate 1 15 microcrystalline wax 1 16 C10-18 fatty acid triglycerides 2 17 Cetearyl Glucoside, Cetearyl Alcohol 2 18 Cetearyl Alcohol 2 19 PEG-100 Stearate, Glyceryl Stearate 3 20 Caprylic / capric triglyceride 4 21 Coco-Caprylate / Caprate 5 22 Polydimethylsiloxane 2 23 Tromethamine 0.2 24 Phenoxyethanol 0.5 25 Oat Kernel Extract 7.2

[0104] The above anti-eczema cream composition is prepared as follows:

[0105] 1. Disperse raw material 4 and raw material 11 evenly;

[0106] 2. Heat and dissolve raw material 7 and raw material 10;

[0107] 3. Put raw materials 1 and 25 into the water phase pot, sprinkle in raw material 12 while stirring, and add raw materials 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 25 after raw material 12 is completely swollen, and heat to 80℃;

[0108] 4. Add raw materials 13, 14, 15, 16, 17, 18, 19, 20, 21, and 22 into the oil phase pot and heat to 80°C;

[0109] 5. Pump the raw materials in the water phase pot into the emulsification pot and homogenize at high speed for 5 minutes;

[0110] 6. Pump the raw materials in the oil phase pot into the emulsifying pot, homogenize at high speed for 5 minutes, and keep warm for 10 minutes;

[0111] 7. Cool down to 50°C while stirring, add raw materials 23 and 24, and homogenize slowly for 3 minutes;

[0112] 8. Cool down to 40℃ while stirring;

[0113] 9. Discharge the material after passing the inspection.

[0114] In this example, 12 children aged 3-15 with mild eczema and 12 children with moderate eczema were selected for a three-week treatment. Six children with mild eczema and six children with moderate eczema used the anti-eczema cream, applying 100-200 g 2-3 times daily, while the remaining patients used a skin cream without birch sap (a control product with the same formula as in the table above, except that all birch sap was replaced with water) for three consecutive weeks, and the disease severity was scored on the 14th day.

[0115] The results showed that the anti-eczema cream significantly improved skin condition compared to the control product (p<0.05), with further significant improvement on day 21 (p<0.01). This suggests that the anti-eczema cream can treat mild to moderate eczema.

[0116] Example 7 : Anti-eczema essence composition

[0117] The formula of the anti-eczema essence composition is as follows:

[0118]

[0119]

[0120] The above-mentioned anti-eczema essence composition is prepared as follows:

[0121] 1. Disperse raw material 3 and raw material 11 evenly;

[0122] 2. Pour raw material 1 into the emulsifying pot, sprinkle in raw materials 14 and 15 while stirring, wait until raw materials 14 and 15 are completely swollen, then add raw materials 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and raw material 13, stir while heating to 80℃, homogenize at high speed for 5 minutes, and keep warm for 10 minutes;

[0123] 3. Cool down to 50°C while stirring, add ingredients 16, 17 and 18, and homogenize at high speed for 5 minutes;

[0124] 4. Cool down to 50°C while stirring, and add raw materials 19 and 20;

[0125] 5. Cool down to 40℃ while stirring;

[0126] 6. Discharge the material after passing the inspection.

[0127] In this example, 12 children aged 3-15 with mild eczema and 12 children with moderate eczema were selected for a three-week treatment. Six children with mild eczema and six children with moderate eczema were treated with the anti-eczema essence, applied 2-3 times daily, 100-200 g each time. The remaining patients were treated with an essence without birch sap (a control product with the same formula as in the table above, except that all birch sap was replaced with water) for three consecutive weeks, and the severity of the disease was scored on the 14th day.

[0128] The results showed that the anti-eczema serum significantly improved skin condition compared to the control product (p<0.05), with further significant improvement on day 21 (p<0.01). This suggests that the anti-eczema serum can treat mild to moderate eczema.

[0129] Example 8 : Anti-eczema lotion composition

[0130] The formula of the anti-eczema emulsion composition is as follows:

[0131] 1 1.2 times concentrated birch sap 76 2 Hydrolyzed sodium hyaluronate 0.05 3 Calendula extract 4.05 4 Xanthan gum 0.1 5 Methylparaben 0.2 6 Polysorbate 60 0.3 7 PEG-60 hydrogenated castor oil 0.5 8 Betaine 1 9 Dipropylene glycol 4 10 Ceramide 4 11 glycerin 7.1 12 Carbomer 0.2 13 Phytosteryl / Octyldodecyl Lauroyl Glutamate 1 14 Tromethamine 0.1 15 PEG / PPG-17 / 6 copolymer 1 16 Phenoxyethanol 0.4

[0132] The above-mentioned anti-eczema emulsion composition is prepared as follows:

[0133] 1. Disperse raw material 4 and raw material 9 evenly;

[0134] 2. Add raw material 1 into the emulsifying pot, sprinkle in raw material 11 while stirring, and add raw materials 2, 3, 4, 5, 6, 7, 8, 9, and 10 after raw material 11 is completely swollen;

[0135] 3. Heat to 80°C while stirring, homogenize at high speed for 5 minutes, and keep warm for 10 minutes;

[0136] 4. Add ingredient 12, homogenize at high speed for 5 minutes, and keep warm for 10 minutes;

[0137] 5. Cool down to 60°C while stirring, and add raw material 13;

[0138] 6. Cool down to 50°C, add raw materials 14 and 15, and homogenize slowly for 3 minutes;

[0139] 7. Cool down to 40℃ while stirring;

[0140] 8. Discharge the material after passing the inspection.

[0141] In this example, 12 children aged 3-15 with mild eczema and 12 children with moderate eczema were selected for a three-week treatment. Six children with mild eczema and six children with moderate eczema were treated with the anti-eczema lotion, applied 2-3 times daily, 100-200 g each time, while the remaining patients were treated with a lotion without birch sap (a control product with the same formula as in the table above, except that all concentrated birch sap was replaced with original birch sap) for three consecutive weeks, and the severity of the disease was scored on the 14th day.

[0142] The results showed that the anti-eczema lotion significantly improved skin condition compared to the control product (p<0.05), with further significant improvement on day 21 (p<0.01). This suggests that the anti-eczema lotion can treat mild to moderate eczema.

[0143] Example 9: Anti-eczema ointment

[0144] The formula of the anti-eczema ointment is as follows:

[0145] Serial number Element weight% 1 1.2 times concentrated birch sap 51.02 2 Hydrolyzed sodium hyaluronate 3.10 3 Xanthan gum 0.20 4 Prikia purpurogena oil 0.20 5 ethanol 4 6 Panthenol 0.50 7 Betaine 3 8 glycerin 10 9 White petrolatum 5 10 C12-15 Alkyl Benzoate 5 11 liquid paraffin 4 12 Cetearyl Alcohol 3 13 stearic acid 3 14 Glyceryl Stearate / PEG-100 Stearate 2.50 15 Sorbitan stearate 2 16 Polysorbate 60 1 17 Polydimethylsiloxane 2 18 Phenoxyethanol 0.50

[0146] The above-mentioned anti-eczema ointment is prepared as follows:

[0147] 1. Disperse raw material 3 and raw material 8 evenly;

[0148] 2. Dissolve raw material 5 with raw material 6;

[0149] 3. Put raw material 1 into the water phase pot, add raw materials 2, 3, 4, 7, and 8 while stirring, and raise the temperature to 80℃;

[0150] 4. Add raw materials 9, 10, 11, 12, 13, 14, 15, 16, and 17 into the oil phase pot and heat it to 80°C;

[0151] 5. Pump the raw materials in the water phase pot into the emulsification pot and homogenize at high speed for 5 minutes;

[0152] 6. Pump the raw materials in the oil phase pot into the emulsifying pot, homogenize at high speed for 5 minutes, and keep warm for 10 minutes;

[0153] 7. Cool down to 50°C while stirring, add raw materials 5, 19 and raw material 18, and homogenize slowly for 3 minutes;

[0154] 8. Cool down to 40℃ while stirring;

[0155] 9. Discharge the material after passing the inspection.

[0156] In this example, 12 children aged 3-15 with mild eczema and 12 children with moderate eczema were selected for a two-week treatment. Six children with mild eczema and six children with moderate eczema were treated with the anti-eczema ointment twice daily, while the remaining patients were treated with an ointment without birch sap (a control product with the same formula as in the table above, except that all birch sap was replaced with water) for three consecutive weeks. The severity of the disease was scored on the seventh day.

[0157] The results showed that the anti-eczema cream significantly improved skin condition compared to the control product (p<0.05), with further significant improvement on day 14 (p<0.01). This suggests that the anti-eczema cream can treat mild to moderate eczema.

[0158] The technical solutions of the above embodiments are preferred implementations of the present invention. Several improvements and changes can be made without departing from the principles of the present invention. These improvements and changes should also be considered to be within the scope of protection of the present invention.

Claims

1. Use of a combination of (A) concentrated birch sap and (B) one or more selected from oat kernel extract, prurinifolia utilis oil, calendula officinalis extract, allantoin, ceramide, glycerin and squalane in the preparation of a skin external use composition with anti-eczema efficacy, wherein the concentrated birch sap is concentrated to a multiple of 1.2 to 8 times, and wherein the skin external use composition does not contain any added water.

2. The method according to claim 1, wherein the concentrated birch sap is concentrated by a multiple of 1.2 to 4 times.

3. The method according to claim 2, wherein the concentrated birch sap is concentrated by a multiple of 1.2 to 2 times.

4. The use according to any one of claims 1 to 3, wherein the external skin composition is a pharmaceutical composition or a cosmetic composition.

5. A skin composition for external use with anti-eczema efficacy, comprising (A) concentrated birch sap having a concentration ratio of 1.2-8 times, and (B) one or more substances selected from oat kernel extract, pruritis utilis oil, calendula extract, allantoin, ceramide, glycerin and squalane, wherein the skin composition for external use does not contain any added water. The composition for external use on skin according to claim 5 , wherein the concentrated birch sap is concentrated at a ratio of 1.2 to 4 times.

7. The composition for external use on skin according to claim 6, wherein the concentrated birch sap is concentrated at a ratio of 1.2 to 2 times.

8. The composition for external use on skin according to claim 5, wherein the content of the concentrated birch sap of the component (A) is 18 to 98% by weight based on the total weight of the composition for external use on skin.

9. The composition for external use on skin according to claim 5, wherein the content of component (B) is 0.01 to 10% based on the total weight of the composition for external use on skin.

10. The composition for external use on skin according to claim 9, wherein the content of component (B) is 0.1 to 6%.

11. The composition for external use on skin according to claim 10, wherein the content of component (B) is 0.5 to 5%. 12 . The composition for external use on skin according to claim 5 , wherein the composition for external use on skin is a pharmaceutical composition or a cosmetic composition.

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