Skin external use composition with acne-removing effect

Abstract

The present invention provides a skin external composition with acne-removing efficacy, comprising (A) concentrated birch sap, wherein the concentration ratio is about 1.1-8 times, preferably about 1.2-4 times, and more preferably about 1.2-2 times, and (B) one or more substances selected from salicylic acid, malic acid, aloe extract, green tea extract, PCA zinc, allantoin, sodium hyaluronate, and niacinamide.

Description

Technical Field

[0001] The present invention relates to a skin external composition with acne-removing efficacy, comprising (A) concentrated birch sap, wherein the concentration ratio is about 1.1-8 times, preferably about 1.2-4 times, and more preferably about 1.2-2 times, and (B) one or more substances selected from salicylic acid, malic acid, aloe extract, green tea extract, PCA zinc, allantoin, sodium hyaluronate, and niacinamide. Background Art

[0002] Acne, also known as pimples, blackheads, and pimples, is a chronic inflammatory skin disease that occurs in the pilosebaceous follicle unit. It is most common in adolescents and often occurs in areas with active sebaceous gland secretion, such as the face, upper chest, back, and neck. Clinical manifestations are often characterized by polymorphic lesions such as comedones, papules, pustules, and nodules. In severe cases, scarring may also occur. Acne is highly prevalent, often lasting for a long time and prone to recurrence. Some cases of acne, if left untreated, can cause hyperpigmentation and even scarring, severely affecting the patient's appearance and having a negative psychological impact.

[0003] It is generally believed that the causes of acne include excessive androgen levels, increased sebum secretion, hyperkeratosis of the hair follicle duct, and overgrowth of Propionibacterium acnes. Currently, medicinal acne treatments often use androgen antagonists, Propionibacterium acnes inhibitors, and retinoids. While these treatments are effective, they also have significant side effects, potentially causing liver damage and even fetal malformations. Anti-acne cosmetics are currently the preferred choice for acne prevention and treatment among consumers. However, currently available acne cosmetics often suffer from slow onset, ineffective results, and even irritation. Therefore, the search for safe and effective acne-fighting active ingredients, based on the physiological and pathological characteristics of acne, is a hot topic in the development of acne cosmetics and a key area of ​​focus for the cosmetics industry.

[0004] Birch sap, the sap from the Betulaceae family, is rich in essential active ingredients such as polysaccharides, amino acids, vitamins, biotin, cytokinins, minerals, and trace elements. In Europe, using birch (Betula alba) sap as a facial wash has been documented to help improve facial acne. Naturally sourced birch sap, used alone or in combination with other active ingredients, holds great potential for acne treatment. Summary of the Invention

[0005] In one aspect, the present invention relates to use of a combination of (A) concentrated birch sap and (B) one or more selected from salicylic acid, malic acid, aloe vera extract, green tea extract, PCA zinc, allantoin, sodium hyaluronate, and niacinamide in a composition for external use on the skin having acne-removing efficacy, wherein the concentrated birch sap is concentrated at a multiple of about 1.1-8 times, preferably about 1.2-4 times, and more preferably about 1.2-2 times.

[0006] On the other hand, the present invention relates to a skin external composition with acne-removing efficacy, comprising (A) concentrated birch sap having a concentration ratio of about 1.1-8 times, preferably about 1.2-4 times, more preferably about 1.2-2 times, and (B) one or more substances selected from salicylic acid, malic acid, aloe extract, green tea extract, PCA zinc, allantoin, sodium hyaluronate and niacinamide.

[0007] The pathogenesis of acne involves elevated androgen levels, increased sebum secretion, hyperkeratosis of the hair follicle duct, and the proliferation of Propionibacterium acnes. Effectively reducing the hypersecretion of sebum caused by androgen, preventing the proliferation of Propionibacterium acnes and the hyperkeratosis of the hair follicle duct, and inhibiting the resulting inflammatory response, are key to treating acne.

[0008] Unexpectedly, the present inventors discovered that compared with the use of concentrated birch sap or salicylic acid, malic acid, aloe extract, green tea extract, PCA zinc, allantoin, sodium hyaluronate, and niacinamide alone, the combination of concentrated birch sap with salicylic acid, malic acid, aloe extract, green tea extract, PCA zinc, allantoin, sodium hyaluronate, and / or niacinamide has significantly better acne-removing efficacy, far exceeding the combined effect of the two functions. Specifically, it can effectively inhibit the activity of 5α-reductase, thereby reducing the production of dihydrotestosterone and the secretion of oil. It can also effectively inhibit the proliferation of Propionibacterium acnes and reduce the levels of IL-1α and TNF-α in the inflammatory response caused by it, thereby showing better acne-removing efficacy.

[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 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.

[0011] Furthermore, the inventors have discovered that the acne-removing 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 approximately 1.1-8 times, preferably 1.2-4 times, and more preferably 1.2-2 times.

[0012] The content of the (A) concentrated birch sap is about 10-98% by weight, preferably about 20-98% by weight, more preferably about 30-97% by weight, based on the total weight of the external skin composition having acne-removing efficacy.

[0013] The components (B) salicylic acid, malic acid, aloe extract, green tea extract, PCA zinc, allantoin, sodium hyaluronate and niacinamide are known in the art and are commercially available and can be used in the present invention as they are.

[0014] The total content of component (B) is about 0.0005-30% by weight, preferably about 0.001-10% by weight, more preferably about 0.1-5% by weight, and most preferably about 0.5-3% by weight, based on the total weight of the skin external composition having anti-acne efficacy.

[0015] The skin external composition includes pharmaceutical compositions and cosmetic compositions, especially skin care cosmetic compositions.

[0016] The skin external composition does not contain any externally added water, but does not exclude moisture inherently contained in each component.

[0017] Preferably, the skin external composition does not contain chelating agents such as EDTA salts, sodium polyphosphate, sodium metaphosphate, and gluconic acid.

[0018] In addition to the above components (A) and (B), the skin external composition may optionally further comprise component (C) of ingredients commonly used in pharmaceutical compositions or cosmetic compositions, including 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 content of component (C) is generally about 0-70% by weight, based on the total weight of the composition.

[0019] 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 cosmetic composition is known in the art, for example, it generally accounts for 0.5-20% of the total weight of component (C).

[0020] The active ingredients include antibacterial agents, anti-inflammatory agents, astringents, antioxidants, moisturizers, emollients, oil control agents, exfoliating ingredients, etc.

[0021] The antibacterial agent includes, but is not limited to, one or more of ursolic acid, Hedyotis diffusa flavonoids, honeysuckle flower extract, tea tree essential oil, chitin, cassia twig extract, coral ginger volatile oil, clove extract, mushroom extract, aloe vera extract, mugwort leaf extract, 1-pentadecanol and its derivatives, cedrene, caryophyllene, longifolene, etc. The content of the antibacterial agent in the skin external composition is known in the art, for example, it generally accounts for 0.01-30% of the total weight of component (C).

[0022] The anti-inflammatory agent includes, but is not limited to, one or more of safflower yellow, dipotassium glycyrrhizate, cattail pollen extract, arrowroot extract, asiaticoside, allantoin, cucumber extract, garlic extract, burdock extract, resveratrol, sophora flavescens extract, and magnolia bark extract. The content of the anti-inflammatory agent in the composition for external use on skin is known in the art, and for example, it generally accounts for 0.01-50% of the total weight of component (C).

[0023] The astringent includes, but is not limited to, one or more of green tea polyphenols, witch hazel extract, vitamin A, menthol lactate, seaweed extract, indigo naturalis, sulfur, raw rehmannia root, angelica sinensis, allantoin, lactic acid, tartaric acid, succinic acid, citric acid, etc. The content of the astringent in the skin external composition is known in the art, for example, it generally accounts for 0.01-30% of the total weight of component (C).

[0024] The antioxidant includes, but is not limited to, one or more of white tea polyphenols, erythrorhizon alkaloids, hawthorn flavonoids, coenzyme Q10, grape seed extract, asparagus extract, radish extract, L-C stock solution, safflower water extract, asiaticoside, Atractylodes macrocephala polysaccharide, vitamin E and its derivatives. The content of the antioxidant in the skin external composition is known in the art, for example, it generally accounts for 0.01-30% of the total weight of component (C).

[0025] Examples of the moisturizing agent include, but are not limited to, one or more of 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, glycereth-5 lactate, sodium hyaluronate, hydrolyzed sodium hyaluronate, acetylated sodium hyaluronate, sodium polyglutamate, hydrolyzed sclerotium gum, budding pullulan polysaccharide, tremella polysaccharide, and sour bean seed polysaccharide. The content of the moisturizing agent in the skin external composition is known in the art, for example, it generally accounts for 1 to 30% by weight of the total weight of component (C).

[0026] 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, 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).

[0027] Examples of the oil-controlling agent include, but are not limited to, one or more of hawthorn extract, ivy extract, saxifrage extract, wax gourd seed extract, spirea ulmaria extract, vitamin B5, calycosin and puerarin, Japanese cypress leaf extract, salvia miltiorrhiza root extract, lycopodiella vulgaris bark extract, angustifolia leaf extract, dendrobium officinale extract, sage extract, and avocado extract. The content of the oil-controlling agent in the skin external composition is known in the art, and for example, it generally accounts for 0.01-30% of the total weight of component (C).

[0028] The exfoliating ingredients include, but are not limited to, one or more of bromelain, salicylic acid, fruit acid, lactic acid, citric acid, enzymatic exfoliants, polyethylene beads, glycolic acid, mandelic acid, malic acid, tartaric acid, azelaic acid, acetic acid, etc. The content of the exfoliating ingredients in the skin external composition is known in the art, for example, it generally accounts for 0.01-30% of the total weight of component (C).

[0029] The auxiliary materials include, for example, emulsifiers, thickeners, preservatives, flavors, and the like.

[0030] 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).

[0031] 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).

[0032] Examples of the preservative include, but are not limited to, one or more of methylparaben, ethylparaben, propylparaben, phenoxyethanol, benzyl alcohol, phenylethyl alcohol, bis(hydroxymethyl)imidazolidinyl urea, potassium sorbate, sodium benzoate, chlorphenesin, sodium dehydroacetate, etc. The content of the preservative in the composition for external use on skin is known in the art, for example, it generally accounts for 0.01-50% of the total weight of component (C).

[0033] 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.

[0034] The above preparation method can be omitted or adjusted according to dosage form requirements. Pharmaceutical compositions or cosmetic compositions in various dosage forms, such as liquids, emulsions, ointments, creams, or gels, can be prepared as needed. The cosmetic compositions can be in the form of lotions, sprays, emulsions, essence water or essence milk, BB creams, sunscreens, and the like. Example

[0035] 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.

[0036] Example 1 : Inhibition of 5α-reductase activity

[0037] In this example, the effects of birch sap, salicylic acid, malic acid at different concentrations, and their combination on 5α-reductase activity were investigated and compared.

[0038] 1. Birch sap concentration

[0039] Fresh birch sap stock solution purchased from Daxinganling Chaoyue Wild Berry Development Co., Ltd. was input into low-temperature drying equipment, cooled to -65°C, vacuumed to 0.1Pa, and concentrated 2 and 10 times.

[0040] 2. Testing

[0041] Experimental instruments: balance, wall breaking machine, constant temperature oscillator, high-speed refrigerated centrifuge, microplate reader.

[0042] Experimental reagents and consumables:

[0043] Finasteride: Shanghai Modern Pharmaceutical Co., Ltd. (tablets 5 mg / tablet);

[0044] Reduced coenzyme II (NADPH): Roche, USA (powder 10 mg);

[0045] Testosterone Elisa kit: Wuhan Urosun Biotechnology Co., Ltd. (Cat. No.: CEA458Ge);

[0046] 5α-reductase crude enzyme: self-prepared;

[0047] PBS: Wuhan Boster Company;

[0048] Phenylmethylsulfonyl fluoride (PMSF): Sigma, USA;

[0049] Dithiothreitol (DTT): Sigma, USA;

[0050] 1M Tris-HCl: Wuhan Boster Company.

[0051] Sample loading information:

[0052] The loading amount of a single raw material is one whole portion of raw material; the compound raw material is half a portion of birch sap raw material plus half a portion of 0.1% of other active raw materials.

[0053] The steps for in vitro 5α-reductase activity analysis are as follows:

[0054] (1) Preparation of crude enzyme: Five normal healthy mice were killed by cervical dislocation. The abdominal cavity was opened and the testicles were removed and divided into several portions. The testicles were placed in 2 mL EP tubes. An appropriate amount of crude enzyme extract was added at a ratio of 1:4. The testicles were broken into a homogenate at 4°C using a wall breaking machine. The homogenate was centrifuged at 4°C at high speed (10,000 rpm / min, 10 minutes). The supernatant was stored at 4°C. The protein concentration was determined by BCA method. Subsequent experiments were performed if the protein concentration was above 1 mg / mL.

[0055] (2) Determination of blank control: Take two groups of 200 μL EP tubes (4 in each group), add crude 5α-reductase, PBS solution (pH=7.4), and reduced coenzyme II to each group. After mixing, one group is immediately placed in boiling water and boiled for 5 minutes. After centrifugation, 50 μL of liquid is drawn for subsequent Elisa detection, which is the initial testosterone content of the blank control group; after mixing, the other group is placed in a constant temperature shaker and mixed for 60 minutes, placed in boiling water and boiled for 5 minutes. After centrifugation, 50 μL of liquid is drawn for subsequent Elisa detection. The difference between the initial content and the initial content is the converted testosterone content of the blank control group.

[0056] (3) Determination of sample groups: Take two groups of 200 μL EP tubes (4 in each group) and add crude 5α-reductase, PBS solution (pH = 7.4), reduced coenzyme II and test materials to each group. After mixing, one group is immediately placed in boiling water and boiled for 5 minutes. After centrifugation, 50 μL of the liquid is aspirated for subsequent ELISA detection. This is the initial testosterone content of the inhibitor group; the other group is placed in a constant temperature shaker for 60 minutes, boiled in boiling water for 5 minutes, centrifuged, and aspirated for subsequent ELISA detection. The difference between the initial content and the initial content is the converted testosterone content of the inhibitor group. Four parallel samples are tested each time.

[0057] The 5α-reductase inhibition rate was calculated according to the following formula:

[0058] I%=(ΔA0-ΔA n ) / ΔA0 x100%

[0059] in:

[0060] ΔA0----the reduction of testosterone in the control group;

[0061] ΔA n ----The amount of testosterone decreased in the inhibitor group.

[0062] The test results are shown in the following table.

[0063] sample Inhibition rate Birch sap concentrate 19％±2％ 2x concentrated birch sap 48％±4％ 10x concentrated birch sap 26％±3％ salicylic acid 10％±1％ Malic acid 9％±1％ Birch sap extract + salicylic acid 35％±6％ Birch sap extract + malic acid 38％±5％ 2x concentrated birch sap + salicylic acid 68％±9％ 2x concentrated birch sap + malic acid 77％±7％ 10x concentrated birch sap + salicylic acid 32％±3％ 10x concentrated birch sap + malic acid 34％±5％

[0064] These results demonstrate that the combination of 2x concentrated birch sap and salicylic acid or malic acid significantly outperformed birch sap alone, 2x concentrated birch sap and salicylic acid or malic acid, and significantly outperformed the combination of birch sap and salicylic acid or malic acid in inhibiting 5α-reductase. However, when birch sap was concentrated to 10x, its effectiveness in combination with other active ingredients was significantly diminished, even surpassing the effectiveness of the combination of birch sap and other active ingredients.

[0065] Example 2 : Antibacterial experiment

[0066] According to QB / T 2738-2012, the evaluation method for the antibacterial and antimicrobial effects of daily chemical products, the antibacterial ring method was used to determine the antibacterial activity of different concentrations of birch sap, PCA zinc, and their combination.

[0067] 1. Experimental Materials

[0068] Equipment and consumables: filter paper (antibacterial agent carrier); vernier caliper.

[0069] Reagents: nutrient agar medium; bacterial suspension.

[0070] Source of bacteria: Propionibacterium acnes was purchased from China Center for Type Culture Collection.

[0071] Sample loading information: The loading amount of a single raw material is one whole portion of the raw material; the compound raw material is half a portion of birch sap raw material plus half a portion of 0.1% other active raw materials.

[0072] 2. Testing

[0073] Antibacterial experiment operation steps:

[0074] (1) Preparation of antibacterial sheet: Take a 5 mm diameter circular sterile dry filter paper, add 20 μL of the liquid sample to the center of the antibacterial sheet, and then place the filter paper flat in a clean sterile dish. Open the lid and place it in a constant temperature box (37°C) to dry, or place it at room temperature to dry naturally before use.

[0075] (2) Inoculation of test bacteria: Use a sterile cotton swab to inoculate a sample with a concentration of 1×10 4 cfu / ml~9×10 4 Apply the test bacterial suspension (cfu / ml) evenly three times to the surface of a nutrient agar plate. Rotate the plate 60 degrees after each application. Finally, swab the plate around the edge. Cover the plate and allow it to dry at room temperature for 5 minutes.

[0076] (3) Antibacterial test sample placement: Place one contaminated plate for each test, with four test samples and one control sample placed on each plate, for a total of five samples. Use sterile tweezers to place the sample on the surface of the plate, with the center of each sample at least 25 mm apart and at least 15 mm away from the edge of the plate. After placement, use sterile tweezers to gently press the sample to make it stick to the surface of the plate, cover the plate, place it in a 37°C constant temperature box, and observe the results after incubation for 16 to 18 hours. Use a vernier caliper to measure the diameter of the antibacterial ring (including the patch) and record it. Repeat the test three times.

[0077] The test results are shown in the following table.

[0078]

[0079]

[0080] Antibacterial testing results showed that the combination of 2x concentrated birch sap and PCA zinc significantly improved the ability to inhibit the growth of Propionibacterium acnes compared to using birch sap concentrate, 2x concentrated birch sap, PCA zinc, or a combination of birch sap concentrate and PCA zinc alone. When birch sap was concentrated 10x, its effect in combination with other active ingredients was significantly weakened, even falling short of the effect of the combination of birch sap concentrate and other active ingredients.

[0081] Example 3 :Rat auricle model experiment

[0082] In this example, based on a mouse auricle model experiment, the ability of different concentrations of birch sap and aloe extract, green tea extract, allantoin, niacinamide, and their combination to counteract IL-1α and TNF-α in serum was investigated.

[0083] 1. Materials

[0084] Experimental animals: SPF-grade SD male healthy rats, weighing (200±20) g, were provided by Zhejiang Academy of Medical Sciences.

[0085] Drugs and reagents: 100% oleic acid; ELISA IL-1α kit; ELISA TNF-α kit.

[0086] Sample loading information: The loading amount of a single raw material is one whole portion of the raw material; the compound raw material is half a portion of birch sap raw material plus half a portion of 0.1% other active raw materials.

[0087] 2. Methods

[0088] (1) Modeling method Rats were randomly divided into two groups, including 8 normal groups and the rest as modeling groups. In the right auricle of each rat in the modeling group, 100% oleic acid was evenly applied intradermally using a 1ml syringe, once a day, about 0.3ml each time, for 3 consecutive weeks. After applying 100% oleic acid for 22 days, two modeling rats were randomly selected, and two ear pieces at the right ear where oleic acid was applied were cut off. The pieces were fixed with 10% formaldehyde, embedded in paraffin, sliced, and stained with HE. Histopathological changes were observed under a light microscope. Observation under a light microscope showed: thickening of the stratum corneum, hyperkeratosis, dilation of the hair follicles, filling of the follicle openings and infundibulum with keratinized substances, blockage of the keratin plugs, enlargement of the keratin plugs into a pot shape, and disappearance of the sebaceous glands. According to the experimental acne histological grading standard, the experimental acne model of the rat auricle has been formed.

[0089] (2) Animal grouping and drug administration After successful modeling, the remaining rats in the modeling group were randomly divided into a model blank group and a birch sap group with different concentrations according to body weight, with 8 rats in each group. On the 22nd day of the experiment, topical application began. The dosage for each group was 0.1 ml, and the administration site was the modeling site of the right auricle of the rat, once a day, for 2 consecutive weeks. No drugs were applied to the normal group and the model group.

[0090] (3) Sample Collection and Detection Methods 24 hours after the last administration, femoral arterial blood was collected from each group of animals, serum was separated, and stored at -20°C for later use. The serum IL-1α and TNF-α levels were determined using the double antibody sandwich ABC-ELISA method.

[0091] (4) GraphPad Prism Program software was used for graphing, and T-test was used for statistical analysis between groups.

[0092] The test results are shown in the following table.

[0093]

[0094]

[0095] Note: * indicates that the difference is significant compared with the model group, with a p-value less than 0.05; ** indicates that the difference is extremely significant compared with the model group, with a p-value less than 0.01.

[0096] The above results show that compared with the use of birch sap concentrate, 2x concentrated birch sap, aloe extract, green tea extract, allantoin, or niacinamide alone, or the combination of birch sap concentrate and aloe extract, green tea extract, allantoin, or niacinamide, the combination of 2x concentrated birch sap with aloe extract, green tea extract, allantoin, or niacinamide significantly improved the ability to inhibit IL-1α and TNF-α in serum. When birch sap was concentrated to 10x, the effect of combining it with other active ingredients was significantly weakened, even less than the effect of the combination of birch sap concentrate and other active ingredients.

[0097] Example 4 : Human skin oil content

[0098] In this example, the effects of different concentrations of birch sap, PCA zinc, sodium hyaluronate, and their combination on the oil content of human skin were investigated.

[0099] Excessive skin oil secretion is one of the main causes of acne. This experiment used a skin oil meter (SM815 from CK, Germany) to quantitatively measure skin oil gland secretions before and after cosmetic application, thereby evaluating the anti-acne efficacy of cosmetics. The SM815's measurement principle is based on a photometer. A special 0.1mm thick matte tape absorbs oil from the skin, becoming translucent. The tape's light transmittance changes; the more oil absorbed, the greater the light transmittance, allowing the skin's oil content to be measured.

[0100] Sample loading information: The loading amount of a single raw material is one whole portion of the raw material; the compound raw material is half a portion of birch sap raw material plus half a portion of 0.1% other active raw materials.

[0101] Experimental process: Patients with excessive oil secretion (aged 20 to 35, half male and half female) were selected and divided into 8 groups. On the day of the oil test, the face was cleaned and 30 minutes later, 3mg / cm2 was applied to the cheeks. 2 The skin oil content was dynamically measured using SM815 at 0, 2, 4, and 8 hours, and the changes in skin oil content were calculated.

[0102] The experimental evaluation and testers were double-blind, and the test was conducted in a constant temperature and humidity laboratory with a temperature of 25±1°C and a humidity of 60%±5%.

[0103] The test results are shown in the following table.

[0104]

[0105] Skin oil levels in the control group gradually increased over time, indicating high oil secretion in the subjects. Results from the sample groups showed that the combination of 2x concentrated birch sap with zinc PCA or sodium hyaluronate significantly suppressed excessive oil secretion in the subjects, compared to birch sap concentrate, 2x concentrated birch sap, zinc PCA, sodium hyaluronate, or combinations of birch sap concentrate with zinc PCA or sodium hyaluronate. When birch sap was concentrated to 10x, the effect of combining it with other active ingredients was significantly weakened, even surpassing the effect of combining birch sap concentrate with other active ingredients.

[0106] Example 5 :Preparation and performance investigation of anti-acne essence lotion

[0107] The formulas of acne serums containing different active ingredients are shown in the following table:

[0108]

[0109] The preparation process is as follows: Weigh Phase A ingredients, mix the components thoroughly and ensure they are completely dissolved, heat to 60°C, and maintain for 20 minutes. Once cooled to 45°C while stirring, add Phase B in sequence and stir thoroughly to obtain the various acne-fighting essence products described above.

[0110] In order to test the actual effect of the products, a trial survey was conducted on the different acne-removing essence products mentioned above. Samples were distributed to acne patients aged 20-35 years old for trial. There were 60 subjects for each product. The trial lasted for one month and they filled out the questionnaire at the same time. Finally, the results were counted.

[0111] The criteria for grading are as follows:

[0112] Significantly effective: Healed or skin lesions disappeared by >60%

[0113] Effective: Skin lesions subside by 20% to 60%

[0114] Ineffective: skin lesions disappear by <20% or worsen.

[0115] The results of the population trial survey are as follows.

[0116] sample Significantly effective / case Effective / Example Invalid / Example Blank 0 3 57 Birch sap concentrate 24 14 22 2x concentrated birch sap 30 12 18 salicylic acid 11 14 35 Birch sap extract + salicylic acid 31 15 14 2x birch sap concentrate + salicylic acid 38 14 8

[0117] The above results show that compared with the acne-removing serum containing birch sap concentrate, 2x concentrated birch sap, salicylic acid, and the combination of birch sap concentrate and salicylic acid, the serum containing 2x concentrated birch sap and salicylic acid has a more significant acne-removing ability.

[0118] 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 a combination of (A) concentrated birch sap and (B) one or more selected from salicylic acid, malic acid, PCA zinc, allantoin, sodium hyaluronate, and niacinamide in preparing a skin composition for external use with acne-removing efficacy, wherein the concentrated birch sap is concentrated to a multiple of 1.2 to 4 times, and wherein the skin composition for external use 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 2 times.

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

4. A composition for external use on the skin having an acne-removing effect, comprising (A) concentrated birch sap having a concentration factor of 1.2-4, and (B) one or more substances selected from salicylic acid, malic acid, PCA zinc, allantoin, sodium hyaluronate, and niacinamide, wherein the composition for external use on the skin does not contain any added water. The composition for external use on skin according to claim 4 , wherein the concentrated birch sap is concentrated at a ratio of 1.2 to 4 times.

6. The composition for external use on skin according to claim 4, wherein the content of the concentrated birch sap of the component (A) is 10 to 98% by weight based on the total weight of the composition for external use on skin.

7. The composition for external use on skin according to claim 4, wherein the content of the component (B) is 0.0005 to 30% by weight based on the total weight of the composition for external use on skin.

8. The external composition for skin application according to claim 7, wherein the content of the component (B) is 0.001 to 10% by weight.

9. The external composition for skin application according to claim 8, wherein the content of the component (B) is 0.1 to 5% by weight.

10. The external composition for skin application according to claim 9, wherein the content of the component (B) is 0.5 to 3% by weight.

11. The composition for external use on skin according to any one of claims 4 to 10, wherein the composition for external use on skin is a pharmaceutical composition or a cosmetic composition.

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