Skin external use composition with anti-eczema effect

Abstract

The present invention relates to use of birch sap in preparing a skin external composition with anti-eczema efficacy, and the skin external composition with anti-eczema efficacy, comprising birch sap.

Description

Technical Field

[0001] The present invention relates to the use of birch sap in preparing a skin external application composition with anti-eczema efficacy, and the skin external application composition with anti-eczema efficacy, comprising birch sap. The skin external application composition comprises a skin care cosmetic composition or a pharmaceutical composition. Background Art

[0002] 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 significant role in preventing soil erosion, improving the environment, and protecting against wind and sandstorms. Birch trees 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. 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-inflammatory properties.

[0003] Eczema is an inflammatory skin disease with a pronounced exudative tendency, caused by a variety of internal and external factors. It is accompanied by significant itching, impaired skin barrier function, and prone to recurrence. Eczema is often treated with moisturizing emollients, with glucocorticoids serving as the first-line anti-inflammatory and immunosuppressive treatment.

[0004] The inventors have discovered that birch sap has good anti-inflammatory and skin barrier repairing effects, thus showing significant therapeutic effects in the treatment of eczema. Summary of the Invention

[0005] In one aspect, the present invention relates to use of birch sap in preparing a topical skin composition having anti-eczema efficacy.

[0006] In another aspect, the present invention provides a composition for external use on skin having anti-eczema efficacy, comprising (A) birch sap.

[0007] Wherein, the skin external composition includes a skin care cosmetic composition or a pharmaceutical composition.

[0008] The birch sap is an aqueous solution with a concentration of 30% or more. In a preferred embodiment, the birch sap is a raw solution. In a more preferred embodiment, the birch sap is concentrated birch sap, and the concentration ratio is about 1.05-8 times, preferably about 1.1-4 times, and more preferably about 1.2-3 times.

[0009] 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.

[0010] The present inventors have found that the birch sap has significant moisturizing, barrier repair and anti-inflammatory and soothing effects, thereby suppressing the inflammatory response of eczema patients, repairing the skin barrier and then playing the effect of treating eczema. Wherein, in terms of moisturizing and barrier repair, it specifically manifests as promoting the expression of aquaporin AQP, tight junction proteins, and keratinocyte-sealed associated proteins in epidermal cells, promoting the proliferation and differentiation of keratinocytes, promoting hyaluronic acid generation, strengthening the structural integrity and functionality of the epidermis, dermis and dermal-epidermal junction, improving the skin barrier, and reducing transepidermal water loss. In terms of anti-inflammatory, it specifically manifests as having significant inhibition of mast cell degranulation, inhibition of inflammatory factors anti-thymic stromal lymphopoietin (TSLP), Th2 type cytokines interleukin-4 (IL-4), interleukin-13 (IL-13), and interleukin-17 (IL-17).

[0011] In the present invention, methods for concentrating birch sap to obtain concentrated birch sap are known in the art, such as heating concentration, low-temperature vacuum concentration, membrane concentration, etc. 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 introduced 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.

[0012] 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 multiples. Therefore, controlling the concentration multiple of birch sap is essential. In the present invention, the concentration multiple of birch sap is controlled to be approximately 1.05-8 times, preferably approximately 1.1-4 times, and more preferably approximately 1.2-3 times.

[0013] The skin external composition comprises 18-98%, preferably 20-95%, more preferably 22-90%, most preferably 30-90% of (A) birch sap.

[0014] In a preferred embodiment, the skin external composition of the present invention 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 of the present invention does not contain a chelating agent such as EDTA salt, sodium polyphosphate, sodium metaphosphate, or gluconic acid.

[0016] In addition to the birch sap (A), the skin topical composition may optionally contain (B) ingredients commonly used in skin topical compositions, which are known in the art. Those skilled in the art can select their types and amounts as needed. For example, the ingredients commonly used in component (B) skin topical compositions include, but are not limited to, vehicles, active ingredients, and excipients, and for example, the total content of component (B) is generally about 2-82%, 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 (B).

[0018] Such active ingredients include, for example, emollients, moisturizers, anti-inflammatory active ingredients, 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, squalane, 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, one or more of 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, and Murumuru seed butter. The content of the emollient in the skin external composition is known in the art, for example, it generally accounts for 1-50% of the total weight of component (B).

[0020] Examples of the moisturizer include, but are not limited to, glycerin, 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 / 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. One or more of the following. 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 (B).

[0021] Examples of the anti-inflammatory active ingredient include, but are not limited to, one or more of dipotassium glycyrrhizate, purslane (Portulaca oleracea) extract, oat (AVENA SATIVA) kernel extract (avenous acyl anthranilic acid), panthenol, allantoin, biosaccharide gum-1, β-glucan, fructan, scutellaria baicalensis root extract, horse chestnut (Aesculus hippocastanum) extract, bisabolol, 4-tert-butylcyclohexanol, ceramide 3, hydrogenated lecithin, glycyrrhiza glabra (Glycyrrhiza glabra) extract, hydrolyzed royal jelly protein, oryzanol, phytosphingosine, quercetin, ginger root extract, rosemary leaf extract, etc. The content of the anti-inflammatory 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 (B).

[0022] Examples of the anti-eczema active ingredient include, but are not limited to, glucocorticoids (including glucocorticoids of all strengths), zinc oxide, calamine, boric acid solution, berberine hydrochloride, ethacridine solution, urea, salicylic acid, calcineurin inhibitors, salicylic acid, lactic acid, tretinoin, tar, vitamin C, calcium gluconate, zinc copper sulfate, etc. The content of the anti-eczema active ingredient in the skin external composition is known in the art.

[0023] The auxiliary materials include, for example, emulsifiers, thickeners, preservatives, flavors, and the like.

[0024] 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 (B).

[0025] 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 methyl cellulose, and the like. The content of the thickener in the composition for external use on skin is known in the art, and for example, it generally accounts for 0.1-10% of the total weight of component (B).

[0026] 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 (B).

[0027] The skin composition for external use 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 product can be filled and shipped only after all relevant test indicators are qualified.

[0028] The above preparation method can be deleted or adjusted according to the dosage form requirements, and skin external use compositions in the form of ointments, creams, lotions, essences, sprays, gels, etc., especially skin care cosmetic compositions, can be prepared as needed. Example

[0029] 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.

[0030] Example 1: Effects of birch sap on the expression of genes related to moisturizing and barrier repair

[0031] This example investigates the effects of birch sap on cuticle transglutaminase TGM1, epidermal tight junction proteins (ZO-1 and CLDN1), filaggrin FLG, and aquaporin AQP3.

[0032] The experimental method is as follows.

[0033] 1. Experimental instruments: fluorescence quantitative PCR instrument (Roche), ultra-clean bench (Sujing), carbon dioxide incubator (Binder), microplate reader (BIO-TEK), micro-oscillator.

[0034] 2. Experimental reagents and consumables: keratinocytes, 6-well plates, cell culture medium, RNA extraction kit, reverse transcription kit, Trizol lysis buffer, etc.

[0035] 3. The steps for gene expression analysis based on keratinocytes are as follows:

[0036] (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.

[0037] (2) Liquid preparation: preparing birch sap of different concentrations, namely 100%, 60%, 30%, 10%, 1.2 times concentrated juice, 2.5 times concentrated juice, and 6 times concentrated juice;

[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 Table 1 below.

[0042] Table 1:

[0043]

[0044] Note: * indicates significant difference compared with blank control, with P value less than 0.05; ** indicates extremely significant difference compared with blank control, with P value less than 0.01.

[0045] In the table above, 10% birch sap is a mixture of 10% birch sap concentrate and 90% deionized water, and so on. 100% birch sap refers to birch sap concentrate. 1.2x concentrated birch sap is obtained by concentrating birch sap concentrate. The concentration process involves feeding fresh birch sap concentrate purchased from Daxing'anling Chaoyue Wild Berry Development Co., Ltd. into a low-temperature drying machine, cooling it to -65°C and vacuuming it to 0.1 Pa. The concentrations were then concentrated to 1.2x, 2.5x, and 6x, respectively.

[0046] The results in Table 1 above demonstrate that birch sap, particularly at concentrations above 30%, significantly increases 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. These results also demonstrate that the effect of birch sap in its original form is particularly significant, and furthermore, 1.2- and 2.5-fold concentrated birch sap exhibit even greater efficacy.

[0047] Example 2: Effects of birch sap on the expression of proteins related to moisturizing and barrier repair

[0048] This example investigates the effects of birch sap on cuticle transglutaminase TGM1, epidermal tight junction proteins (ZO-1 and CLDN1), filaggrin FLG, and aquaporin AQP3.

[0049] The experimental method is as follows.

[0050] 1. Experimental instruments: clean bench (Sujing), plate washer (BIO-RAD), microplate reader (BIO-TEK), CO2 incubator (Binder).

[0051] 2. Experimental reagents and consumables: primary human keratinocytes, 12-well plates, keratinocyte culture medium, ELISA kits for different indicators, etc.

[0052] 3. The test steps are as follows:

[0053] (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.

[0054] (2) Administration: Prepare birch sap of different concentrations, including 100%, 60%, 30%, 10%, 1.2-fold concentrated juice, 2.5-fold concentrated juice, and 6-fold concentrated juice; when cell fusion reaches more than 60% again, add the test substance at different concentrations, with 6 replicate wells in each group;

[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 Table 2 below.

[0058] Table 2

[0059]

[0060] Note: * indicates significant difference compared with blank control, with P value less than 0.05; ** indicates extremely significant difference compared with blank control, with P value less than 0.01.

[0061] The results in Table 2 above demonstrate that birch sap, particularly at concentrations above 30%, significantly enhances the expression of proteins associated with moisturizing and barrier repair, thereby demonstrating significant efficacy in repairing the skin barrier. These results also demonstrate that the effect of birch sap concentrate is particularly significant, and furthermore, 1.2- and 2.5-fold concentrated birch sap exhibit even greater efficacy.

[0062] Example 3: Effects of birch sap on keratinocyte proliferation and differentiation

[0063] This example tests and compares the effects of different concentrations of birch sap on the proliferation and differentiation abilities of keratinocytes.

[0064] The experimental method is as follows.

[0065] 1. Cells: HACAT (human immortalized epidermal keratinocytes).

[0066] 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 slot, DMEM cell culture medium, FBS, 100× triple antibody, 100× mycoplasma inhibitor, CCK-8 reagent

[0067] 3. The experimental steps are as follows:

[0068] (1) Cultured HACAT cells were seeded into 96-well plates, with 100 μl per well and a cell density of 3000 cells per well;

[0069] (2) Place in a 37°C, 5% CO2 incubator and culture for 24 hours;

[0070] (3) Administration: Add 100 μl of birch sap culture medium containing different concentrations;

[0071] (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;

[0072] (5) Incubate at 37°C for 2 hours, and then measure the OD value at 450 nm using a microplate reader;

[0073] The above experiments were performed in triplicate. Cells were collected from three culture flasks, and cell counts and experimental procedures were performed independently. The results are shown in Table 3 below.

[0074] Table 3

[0075]

[0076] Note: * indicates significant difference compared with blank control, with P value less than 0.05; ** indicates extremely significant difference compared with blank control, with P value less than 0.01.

[0077] The results in Table 3 above show that birch sap at a concentration of 30% or more significantly enhances the proliferation and differentiation of keratinocytes. The results also show that the effect of birch sap concentrate is particularly significant, and further, 1.2- and 2.5-fold concentrated birch sap exhibit even greater efficacy.

[0078] Example 4: Effect of birch sap on mast cell degranulation

[0079] This example uses a zebrafish larval allergy model to test and compare the effects of different concentrations of birch sap on mast cell degranulation, thereby verifying the anti-inflammatory efficacy of birch sap.

[0080] The experimental method is as follows.

[0081] 1. Experimental animal: zebrafish.

[0082] 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:

[0083] Model group: RO water + 15μg / ml SP

[0084] Positive drug group: ketotifen + 15μg / ml SP

[0085] The test sample groups included 100%, 60%, 30%, 10% birch sap, 1.2-fold concentrated juice, 2.5-fold concentrated juice, and 6-fold concentrated juice + 15 μg / ml SP.

[0086] 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.

[0087] The results of the zebrafish larvae mast cell protection model efficacy experiments are recorded in Table 4 below.

[0088] Table 4

[0089] Group Mast cell protection rate Model - Ketotifen 90.63％** 100% birch sap 85.58％** 60% birch sap 80.37％** 30% birch sap 73.07％** 10% birch sap 30％* 1.2 times concentrated birch sap 96.1％** 2.5 times concentrated birch sap 93.9％** 6 times concentrated birch sap 87.99％**

[0090] Note: * indicates p < 0.05, ** indicates p < 0.01 (compared with the model group); mast cell protection rate greater than 100% was considered 100%.

[0091] The results in Table 4 above show that birch sap at a concentration of 30% or more significantly inhibits mast cell degranulation. The results also show that the effect of birch sap concentrate is particularly significant, and further, birch sap concentrated 1.2 times and 2.5 times exhibits even greater efficacy.

[0092] Example 5: Effect of birch sap on the production of inflammatory factors in the process of eczema

[0093] 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. The effects of birch sap at different concentrations (100%, 60%, 30%, 10%, 1.2 times concentrated juice, 2.5 times concentrated juice, and 6 times concentrated juice) on the production of inflammatory factors Th2 (IL-4, 13, 17) and TSLP were evaluated to verify the anti-inflammatory efficacy of birch sap.

[0094] The experimental method is as follows.

[0095] 1. Experimental animals: ICR mice, male.

[0096] 2. Experimental materials: 0.5% DNFB acetone solution, 1% hydrocortisone ointment, depilatory cream, and dust mite extract.

[0097] 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, a positive group, and a birch sap group. One day before modeling, a depilatory cream was used to remove hair from an approximately 2 x 2 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.

[0098] 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 daily for seven consecutive days. The model group was sprayed with distilled water, while the positive group was coated with 1% hydrocortisone ointment, three times daily for seven consecutive days.

[0099] 4. Observation indicators: After 7 days of drug administration, serum was collected from the mice and the levels of inflammatory factors TSLP and Th2 (IL-4, 13, 17) in the serum were detected using ELISA kits. The results are shown in Table 5 below.

[0100] Table 5

[0101]

[0102] Note: * indicates p<0.05, ** indicates p<0.01 (compared with the model group)

[0103] The results in Table 5 above show that birch sap at a concentration of 30% or more has significant anti-inflammatory effects. The above results also show that the effect of birch sap concentrate is particularly significant, and further, 1.2 and 2.5 times concentrated birch sap show even better effects.

[0104] Example 6: Anti-eczema cream composition

[0105] The formula of the anti-eczema cream composition is as follows:

[0106]

[0107]

[0108] The above anti-eczema cream composition is prepared as follows:

[0109] 1. Disperse raw material 4 and raw material 11 evenly;

[0110] 2. Heat and dissolve raw material 7 and raw material 10;

[0111] 3. Put raw material 1 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, and 11 after raw material 12 is completely swollen, and heat to 80℃;

[0112] 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;

[0113] 5. Pump the raw materials in the water phase pot into the emulsification pot and homogenize at high speed for 5 minutes;

[0114] 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;

[0115] 7. Cool down to 50°C while stirring, add raw materials 23 and 24, and homogenize slowly for 3 minutes;

[0116] 8. Cool down to 40℃ while stirring;

[0117] 9. Discharge the material after passing the inspection.

[0118] In the present embodiment, 12 3-15 years old mild eczema children and 12 moderate eczema children are selected to carry out 3 weeks of treatment.Wherein 6 mild and 6 moderate eczema children use the anti-eczema cream, apply 2-3 times a day, each time 100-200g, and the remaining patients use the skin cream (control product, its formula is exactly the same as in the above table, but all birch sap is replaced by water) without birch sap, for three consecutive weeks, and the disease degree is scored on the 14th day.The results show that, compared to the control product, the anti-eczema cream significantly improves skin condition (p < 0.05), and further significantly improves (p < 0.01) on the 21st day.This shows that the anti-eczema cream can treat mild to moderate eczema.

[0119] Example 7: Anti-eczema essence composition

[0120] The formula of the anti-eczema essence composition is as follows:

[0121] Serial number Element weight% 1 <![CDATA[Birch sap Original solution > 77.41 2 Sodium polyglutamate 0.05 3 Xanthan gum 0.05 4 Allantoin 0.1 5 Methylparaben 0.2 6 PEG-60 hydrogenated castor oil 0.2 7 Hydrolyzed sodium hyaluronate 0.2 8 Trehalose 0.5 9 PEG / PPG-17 / 6 copolymer 1 10 Betaine 2 11 Dipropylene glycol 3 12 PEG-8 5 13 glycerin 6 14 Acrylates / C10-30 Alkyl Acrylate Crosspolymer 0.05 15 Carbomer 0.2 16 Glyceryl triethylhexanoate 0.5 17 Polydimethylsiloxane 1 18 Cetyl Ethylhexanoate 2 19 Tromethamine 0.14 20 Phenoxyethanol 0.4

[0122] The above-mentioned anti-eczema essence composition is prepared as follows:

[0123] 1. Disperse raw material 3 and raw material 11 evenly;

[0124] 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;

[0125] 3. Cool down to 50°C while stirring, add ingredients 16, 17 and 18, and homogenize at high speed for 5 minutes;

[0126] 4. Cool down to 50°C while stirring, and add raw materials 19 and 20;

[0127] 5. Cool down to 40℃ while stirring;

[0128] 6. Discharge the material after passing the inspection.

[0129] In the present embodiment, 12 3-15 years old mild eczema children and 12 moderate eczema children are selected for 3-week treatment. Among them, 6 mild and 6 moderate eczema children use the anti-eczema essence, apply 2-3 times a day, each time 100-200g, and the remaining patients use the essence without birch sap (control product, its formula is exactly the same as in the above table, but all birch sap is replaced by water), for three consecutive weeks, and the disease degree is scored on the 14th day. The results show that, compared to the control product, the anti-eczema essence significantly improves skin condition (p < 0.05), and further significantly improves on the 21st day (p < 0.01). This shows that the anti-eczema essence can treat mild to moderate eczema.

[0130] Example 8 Anti-eczema emulsion composition

[0131] The formula of the anti-eczema emulsion composition is as follows:

[0132]

[0133]

[0134] The above-mentioned anti-eczema emulsion composition is prepared as follows:

[0135] 1. Disperse raw material 5 and raw material 10 evenly.

[0136] 2. Put raw material 1 into the emulsifying pot, sprinkle in raw material 12 while stirring, and add raw materials 2, 3, 4, 5, 6, 7, 8, 9, 10, and 11 after raw material 12 is completely swollen.

[0137] 3. Raise the temperature to 80°C while stirring, homogenize at high speed for 5 minutes, and keep warm for 10 minutes.

[0138] 4. Add ingredients 13 and 14, homogenize at high speed for 5 minutes, and keep warm for 10 minutes.

[0139] 5. Cool down to 60℃ while stirring and add raw material 15.

[0140] 6. Cool to 50°C, add ingredients 16 and 17, and homogenize slowly for 3 minutes.

[0141] 7. Cool down to 40℃ while stirring.

[0142] 8. discharging after passing the test. In the present embodiment, 12 3-15 years old mild eczema children and 12 moderate eczema children are selected to carry out 3-week treatment. Wherein 6 mild and 6 moderate eczema children use the anti-eczema emulsion, apply 2-3 times every day, each 100-200g, and the remaining patients use the emulsion (control product, its formula is exactly the same as in the above table, but all concentrated birch sap is replaced by birch sap sap) without birch sap, for three consecutive weeks, and the disease degree is scored on the 14th day. The result shows that, relative to the control product, the anti-eczema emulsion significantly improves skin condition (p < 0.05), and further significantly improves (p < 0.01) on the 21st day. This shows that the anti-eczema emulsion can treat mild to moderate eczema.

[0143] Example 9: Anti-eczema ointment composition

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

[0145] Serial number Element weight% 1 1.2 times concentrated birch sap 51 2 Hydrolyzed sodium hyaluronate 3.10 3 Xanthan gum 0.20 4 Allantoin 0.20 5 Dexamethasone acetate 0.02 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 19 ethanol 4

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

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

[0148] 2. Dissolve raw material 5 with raw material 19.

[0149] 3. Put raw material 1 into the water phase pot, add raw materials 2, 3, 4, 6, 7, and 8 while stirring, and raise the temperature to 80℃.

[0150] 4. Put 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℃ 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 the present embodiment, 12 3-15 years old mild eczema children and 12 moderate eczema children are selected to carry out 2-week treatment.Wherein 6 mild and 6 moderate eczema children use the anti-eczema ointment, apply 2 times a day, and the remaining patients use the ointment (control product, its formula is exactly the same as in the above table, but all birch sap is replaced by water) without birch sap, for three consecutive weeks, and the disease degree is scored on the 7th day.The results show that, relative to the control product, the anti-eczema ointment significantly improves skin condition (p < 0.05), and further significantly improves (p < 0.01) on the 14th day.This shows that the anti-eczema ointment can treat mild to moderate eczema.

[0157] The technical solutions of the above-described embodiments are preferred implementations of the present invention. Several improvements and changes may 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 concentrated birch sap in preparing a composition for external use on the skin having anti-eczema efficacy, wherein the concentration ratio of the concentrated birch sap is 1.2-3 times, and wherein the composition for external use on the skin does not contain any added water.

2. The method according to claim 1, wherein the concentrated birch sap is concentrated by 1.2 to 2.5 times.

3. The use according to claim 1 or 2, wherein the skin external composition is a skin care cosmetic composition or a pharmaceutical composition.

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