JP2022552584A - Skin topical composition with anti-acne efficacy - Google Patents

Abstract

The present invention is a topical skin composition having anti-acne efficacy wherein (A) about 1.1-8 fold, preferably about 1.2-4 fold, more preferably about 1.2-2 fold concentrated birch sap with double concentration and (B) one or more actives selected from salicylic acid, malic acid, aloe extract, green tea extract, zinc PCA, allantoin, sodium hyaluronate and nicotinamide. and skin topical compositions comprising:

Description

The present invention is a skin topical composition having anti-acne efficacy wherein (A) about 1.1-8 fold, preferably about 1.2-4 fold, more preferably about 1.2-2 fold concentrated birch sap with double concentration and (B) one or more actives selected from salicylic acid, malic acid, aloe extract, green tea extract, zinc PCA, allantoin, sodium hyaluronate and nicotinamide. and skin topical compositions comprising:

Acne, also known as acne, rashes, pimples, dark sores, etc., is a chronic inflammatory skin disease that occurs in the sebaceous units of hair follicles. It tends to occur during adolescence, most often in the areas of the face, upper chest, back and neck where the sebaceous glands are actively secreting. The clinical presentation is often characterized by polymorphic skin lesions such as acne, papules, pustules and nodules. In severe cases, scarring may also form. Acne has a high incidence, is often long-lasting, and easily recurs. In some cases of acne, if treatment is not done at the right time, it can lead to pigmentation and even scarring, which can seriously affect the patient's appearance and have a serious negative impact on the patient's psychological state. will have an impact.

Currently, the virulence factors of acne are excess androgen levels, increased sebum secretion, hyperkeratosis of the follicular duct, and excessive proliferation of Propionibacterium acnes. generally considered. Currently, medicated anti-acne products include androgen antagonists, P. Mainly includes acne inhibitors and tretinoin drugs. Although these effects are evident, toxicity and side effects are also significant, and can cause liver damage and even infantile malformations. Anti-acne cosmetics are currently the first choice for acne prevention and treatment by consumers. However, anti-acne cosmetics currently on the market generally have several drawbacks, such as slow action, insignificant anti-acne efficacy, and even irritation. Therefore, the discovery of safe and effective anti-acne active substances based on the physiological and pathological characteristics of acne is a matter of great interest in the development of anti-acne cosmetics, and cosmetic practitioners are interested in this topic. We are working together on direction.

Birch sap is a sap from the birch plant that is rich in polysaccharides, amino acids, vitamins, biotin, cytokinins, minerals and trace elements. There is evidence in Europe that the use of birch (Betula Pendula) sap for facial cleansing helps improve facial acne. Birch sap, a natural source, used alone or in combination with other actives, has great potential in the area of acne treatment.

In one aspect, the present invention provides (A) concentrated birch sap and (B) salicylic acid, malic acid, aloe extract, green tea extract, zinc PCA in topical skin compositions having enhanced anti-acne efficacy. , allantoin, sodium hyaluronate and nicotinamide in combination with one or more active substances selected from about 1.1 to 8 times concentrated birch sap, preferably about 1.2 to 4 times , more preferably having an enrichment of about 1.2-2 fold.

In another aspect, the present invention provides a topical skin composition having anti-acne efficacy wherein (A) about 1.1-8 fold, preferably about 1.2-4 fold, more preferably about concentrated birch sap having a concentration of 1.2-2 fold and (B) one or more selected from salicylic acid, malic acid, aloe extract, green tea extract, zinc PCA, allantoin, sodium hyaluronate and nicotinamide It relates to topical skin compositions comprising multiple active agents.

The etiology of acne involves excessive androgen levels, increased sebum secretion, hyperkeratosis of the hair follicle ducts, and proliferation of Propionibacterium acnes. Treatment of acne includes effective reduction of androgen-induced sebum secretion, prevention of Propionibacterium acnes proliferation and hyperkeratosis of the follicle ostium, and reduction of the resulting inflammatory response. Inhibition is important.

Surprisingly, the inventors found that compared to using concentrated birch sap or salicylic acid, malic acid, aloe extract, green tea extract, zinc PCA, allantoin, sodium hyaluronate and nicotinamide alone, The addition of sap in combination with salicylic acid, malic acid, aloe extract, green tea extract, zinc PCA, allantoin, sodium hyaluronate and/or nicotinamide particularly in their ability to effectively inhibit the activity of 5α-reductase. has a significantly better anti-acne efficacy far higher than efficacy, thereby reducing the production of dihydrotestosterone, reducing oil secretion, effectively inhibiting the growth of Propionibacterium acnes, They have thereby found that they reduce the amount of IL-1α and TNF-α in the inflammatory response derived from them, thus exhibiting better anti-acne efficacy.

The birch sap involved in the present invention is of the genus Birch, including the four varieties Betala alba, Betula pubescens, Betula Pendula and Betula platyphylla. from the family (Betula Betulaceae). Birch sap is a clear, colorless nutrient with no precipitants or impurities, obtained by artificial drilling and collection from the base of birch tree trunks from the time the snow begins to melt until the time the tree leaves. It is a sap rich in Birch sap is commercially available and used as is (in which case it is referred to as the original fluid), for example from Daxinganling Chaoyue Wild Berry Development Co., Ltd. , Ltd. can be purchased from

The concentrated birch sap used in the present invention is obtained by concentrating the commercially available birch sap stock product described above. Methods for concentration are known in the art, such as thermal concentration, cold and vacuum concentration, and membrane concentration. In the present invention, concentration is preferably carried out by cryogenic freeze concentration or membrane concentration methods. For example, a commercially available birch sap stock solution is introduced into a low temperature drying device, cooled to about -40 to -70°C, and cooled to about 0°C for low temperature and vacuum concentration methods to obtain concentrated birch sap with different degrees of concentration. .1-30 Pa is evacuated.

Furthermore, the inventors have also discovered that the anti-acne efficacy of concentrated birch sap is not in a simple linear relationship with its concentration, but increases initially and then decreases with increasing concentration. . Therefore, it is important to adjust the concentration of birch sap. In the present invention, the concentration of birch sap is adjusted to about 1.1 to 8 times, preferably about 1.2 to 4 times, more preferably about 1.2 to 2 times.

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

Component (B) salicylic acid, malic acid, aloe extract, green tea extract, zinc PCA, allantoin, sodium hyaluronate and nicotinamide are known in the art and are all commercially available and are used in the present invention. Used as is.

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

Skin topical compositions include pharmaceutical compositions and cosmetic compositions, especially skin care cosmetic compositions.

The topical skin compositions of the present invention do not contain any added water, but do not exclude water inherently contained in each of the components.

Preferably, the topical skin compositions of the present invention are free of chelating agents such as EDTA salts, sodium phosphate, sodium metaphosphate and gluconic acid.

In addition to components (A) and (B), the topical skin composition optionally contains component (C) vehicle, active ingredient, excipients, etc. commonly used in pharmaceutical or cosmetic compositions. may also contain ingredients used in Component (C) is known in the art, and a person skilled in the art can select its type and amount according to need. For example, the content of component (C) is typically about 0-70% by weight relative to the total weight of the composition.

Vehicles are known in the art and include, for example, diluents, dispersants or carriers. Examples include, but are not limited to, ethanol, dipropylene glycol, butanediol, and the like. The content of vehicle in cosmetic compositions is known in the art, eg it is typically about 0.5-20% of the total weight of component (C).

Active ingredients include antibacterial agents, anti-inflammatory agents, astringents, antioxidants, moisturizing agents, emollients, oil conditioners, exfoliating ingredients, and the like.

Antimicrobial agents include, but are not limited to, ursolic acid, oldenlandia diffusa flavonoids, Lonicera japonica flower extract, tea tree essential oil, chitin, cinnamon stem extract, coral ginger volatile oil, clove extract. mushroom extract, Artemisia argyi extract, 1-pentadecanol and its derivatives, cedarene, caryophyllene and longifolene. The content of antimicrobial agents in topical skin compositions is known in the art, eg it is typically 0.01-30% of the total weight of component (C).

Anti-inflammatory agents include, but are not limited to, safflower yellow, dipotassium glycyrrhizinate, cattail pollen extract, Sagittaria extract, asiaticoside, cucumber extract, garlic extract, burdock extract. resveratrol, Sophora flavescens extract, magnolia bark extract, and the like. The content of anti-inflammatory agents in topical skin compositions is known in the art, eg it is typically 0.01-50% of the total weight of component (C).

Astringents include, but are not limited to, green tea polyphenols, hamamelis extract, vitamin A, menthol lactate, algae extract, aloe vera, sulfur, red palm, angelica, lactic acid, tartaric acid, succinic acid, citric acid. one or more of acids and the like. The content of astringents in topical skin compositions is known in the art, eg it is typically 0.01-30% of the total weight of component (c).

Antioxidants include, but are not limited to, white tea polyphenols, Fedde alkanoids, hawthorn flavonoids, coenzyme Q10, grape seed extract, asparagus extract, radish extract, VLTAMLN-C, safflower water extract. , asiaticoside, Atractylodes macrocephala polysaccharide, vitamin E and derivatives thereof. The content of antioxidants in topical skin compositions is known in the art, eg it is typically 0.01-30% of the total weight of component (C).

Examples of water retention agents 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, Methylgluceth-10, Methylgluceth-20, PEG/PPG-17/6 Copolymer, Glycereth-7, Glycereth-26, Glycerylglucoside, PPG-10 Methylglucose Ether, PPG-20 Methylglucose Ether, 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, one or more of sodium polyglutamate, hydrolyzed sclerotium gum, pullulan, tremellam, tamarind seed polysaccharide, and the like. The content of moisturizing agents in topical skin compositions is known in the art, eg it is typically about 1-30% of the total weight of component (C).

Examples of emollients include, but are not limited to, 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, simmondsia chinensis seed oil, sunflower seed oil, mauritia flexuosa fruit oil, squalane, ethylhexyl palmitate, isopropyl myristate, hydrogenated poly isobutylene, isocetane, isododecane, diethylhexyl carbonate, dioctyl carbonate, isopropyl lauroyl sarcosinate, isononyl isononanoate, hydrogenated polydecene, triethylhexanoin, cetyl ethylhexanoate, bis-diethoxydiglycol cyclohexane 1,4-dicarboxylate, One or more of caprylic/capric triglyceride, oleyl erucate, octyldodecanol myristate, octyldodecanol, polydimethylsiloxane, octylpolymethylsiloxane, cetyldimethicone, cyclopentadimethylsiloxane, and the like. Examples of solid emollients include, but are not limited to, cetyl alcohol, stearyl alcohol, cetearyl alcohol, behenyl alcohol, squalyl alcohol, lauric acid, myristic acid, palmitic acid, stearic acid, beeswax, candelilla Wax, carnauba wax, lanolin, ozokerite, jojoba seed wax, paraffin wax, microcrystalline wax, hardened rice bran wax, hardened cocoglycerides, glyceryl behenate/eicosadioate, myristyl myristate, bis-diglyceryl polyacyl adipate 2, one or more of butyrospermum parkii (shea butter) and Astropotassium murumuru seed butter. The content of emollients in topical skin compositions is known in the art, eg it is typically 1-50% based on the total weight of component (C).

Examples of oil conditioners include, but are not limited to, hawthorn extract, ivy extract, saxifrage extract, BENINCASA CERIFERA seed extract, Kodemari extract, vitamin B5, calycosine-7-glucoside. and Puerarin, Hinoki (Chamaecyparis Obtusa) leaf extract, Salvia miltiorrhiza root extract, Enantia Chlorantha bark extract, Willow orchid leaf extract, Dendrobium extract, Sage extracts, avocado extracts, and the like. The content of oil modifiers in topical skin compositions is known in the art, eg it is typically 0.01-30% of the total weight of component (C).

Examples of exfoliating ingredients include, but are not limited to, bromelain, fruit acid, lactic acid, citric acid, enzyme cutin exfoliant, polyethylene beads, glycolic acid, mandelic acid, tartaric acid, azelaic acid, acetic acid. and the like. The content of exfoliating ingredients in topical skin compositions is known in the art, eg it is typically 0.01-30% of the total weight of component (C).

Excipients include, for example, emulsifiers, thickeners, preservatives, flavoring agents, and the like.
Examples of emulsifiers include, but are not limited to, cetearyl oleate, sorbitan oleate, polysorbate-60, polysorbate-80, methylglucose sesquistearate, PEG-20 methylglucose 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, glyceryl stearate, glyceryl stearate SE, cocoglucoside, ceteareth-25, PEG-40 stearate, polyglyceryl-3-methylglucose distearate, glyceryl stearate citrate, polyglyceryl-10 stearate, myristin Polyglyceryl-10 acid, Polyglyceryl-10 dioleate, Polyglyceryl-10 laurate, Polyglyceryl-10 isostearate, Polyglyceryl-10 oleate, Polyglyceryl-10 diisostearate, Polyglyceryl-6 laurate, Polyglyceryl-6 myristate, Sucrose stearate and one or more of sucrose polystearate. The content of emulsifiers in topical skin compositions is known in the art, eg it is typically 0.5-10% of the total weight of component (C).

Examples of thickening agents include, but are not limited to, macromolecular polymers such as carbomer, acrylates and derivatives thereof, xanthan gum, gum arabic, polyethylene glycol-14M, polyethylene glycol-90M, succinyl polysaccharides, hydroxyethylcellulose, hydroxy One or more of propylcellulose and hydroxypropylmethylcellulose are included. The content of thickeners in topical skin compositions is known in the art, eg it is typically 0.1-10% of the total weight of component (C).

Examples of preservatives include, but are not limited to, methyl hydroxybenzoate, propyl hydroxybenzoate, phenoxyethanol, benzyl alcohol, phenyl ethanol, bis(hydroxymethyl)imidazolidinyl urea, potassium sorbate, sodium benzoate, chloro One or more of chlorophenesin, sodium dehydroacetate, and the like. The content of preservatives in topical skin compositions is known in the art, eg it is typically 0.01-50% of the total weight of component (C).

Skin topical compositions according to the present invention can be prepared by any suitable method known in the art. For example, it can be prepared using devices commonly used in the cosmetic field, such as dissolving tanks, emulsifying pots, dispersers, transfer pumps, and the like. During preparation, the water-soluble material is charged into the water-phase dissolution kettle, the oil-soluble material is charged into the oil-phase dissolution kettle, and the two kettles are each heated to about 80°C, and for ingredients that easily agglomerate, disperse. It can be pre-dispersed using a machine. Once dissolution is complete, the oil and water phases are transferred to an emulsifying pot and homogenized and emulsified for about 5-15 minutes. Once emulsification is complete, the bulk is cooled to room temperature and optionally fragrances, preservatives, etc. are added and the pH of the product is adjusted as required.

The above preparation method can be changed or adjusted according to the requirements of the dosage form. Pharmaceutical or cosmetic compositions in various dosage forms, such as liquids, emulsions, ointments, creams or gels, can be prepared as required, and the cosmetic compositions include lotions, sprays, milks, extracts, BB It can be in creams, sunscreens and other forms.

The invention is explained in more detail below with reference to examples. It is to be understood, however, that these examples and comparative examples are used only to illustrate the invention and are not intended to be used in any way as defined in the appended claims of this invention. It should not be understood as limiting the scope.
Example 1: Inhibition of 5α-reductase activity In this example, the effects of different concentrations of birch sap, salicylic acid, malic acid and combinations thereof on 5α-reductase activity were investigated and compared.

1. Concentration of birch sap Daxinganling Chaoyue Wild Berry Development Co.; , Ltd. A fresh birch (Betula alba) sap stock solution purchased from Co. was fed to a cryogenic drying device, cooled to −65° C., evacuated to 0.1 Pa, and concentrated 2-fold and 10-fold, respectively.

2. Testing Laboratory equipment: balance, high speed blender, thermostatic oscillator, high speed cryocentrifuge, microplate reader.

Experimental reagents and materials:
Finasteride: Shanghai Modern Pharmaceutical Co.; , Ltd. (tablet 5 mg / tablet);
Reduced coenzyme II (NADPH): American Roche company (powder 10 mg);
Testosterone Elisa Kit: Wuhan Ulsheng Company (Catalog No. CEA458Ge);
5α-reductase crude enzyme: self-prepared;
PBS: Wuhan Boster Company;
Phenylmethylsulfonyl fluoride (PMSF): American Sigma company;
Dithiothreitol (DTT): American Sigma Company;
1M Tris-HCl: Wuhan Boster Company.

Sample Load Information: The load of a single ingredient was the total amount of ingredient, and the sample load of the compounded ingredient was half birch sap ingredient and half the other active ingredients at 0.1%.

The in vitro assay steps for 5α-reductase activity were as follows.

(1) Preparation of crude enzyme: Five normal mice were killed by cervical dislocation, the abdominal cavity was opened, the testes were divided into several parts, placed in 2 ml EP tubes, and an appropriate amount of crude enzyme extract was added to 1:1. Add at a ratio of 4, homogenate by homogenization at 4°C with a high-speed blender, refrigerate at 4°C at high speed (10000 rpm/min, 10 min), collect the supernatant and store at 4°C. Protein concentration was determined by the BCA method and subsequent experiments were performed if the concentration was above 1 mg/ml.

(2) Determination of blank control: Two groups of 200 μl EP tubes (4 in each group) were added with 5α-reductase crude enzyme, PBS solution (pH=7.4) and reduced coenzyme II, respectively. One group was boiled in boiling water for 5 minutes immediately after mixing, centrifuged, and 50 μl of liquid was aspirated for subsequent Elisa detection as the initial testosterone content of the blank control group and the other group. , then mixed well on a constant temperature shaker for 60 minutes, boiled in boiling water for 5 minutes, centrifuged, and 50 μl of liquid was aspirated for subsequent Elisa detection. The difference between this and the initial content is the blank control testosterone content after conversion.

(3) Determination of sample groups: Two groups of 200 μl EP tubes (4 in each group) were added with 5α-reductase crude enzyme, PBS solution (pH=7.4), reduced coenzyme II and test material, respectively. One group was boiled in boiling water for 5 min once mixed, centrifuged and 50 μl of liquid was aspirated for subsequent Elisa detection as the initial testosterone content of the inhibitor group and the other group. , then mixed well on a constant temperature shaker for 60 minutes, boiled in boiling water for 5 minutes, centrifuged, and 50 μl of liquid was aspirated for subsequent Elisa detection. The difference between this and the initial content is the testosterone content of the inhibitor group after conversion. Four parallel samples were prepared in each experiment.

Percent inhibition of 5α-reductase was calculated as follows:
I% = (ΔA ₀ to ΔA _n )/ΔA ₀ × 100%
(In the formula,
ΔA ₀ - decrease in testosterone in the control group;
decrease in testosterone in the ΔA _n -inhibitor group).

The results of the tests are shown in the table below.

The above results show that the combination of 2x concentrated birch sap and salicylic acid or malic acid is significantly better than birch sap undiluted, 2x concentrated birch sap, salicylic acid or malic acid alone with respect to inhibition of 5α-reductase; It was also shown to be significantly better than the combination of birch sap stock solution with salicylic acid or malic acid. When the birch sap was concentrated 10-fold, its combination with other actives showed significantly reduced efficacy, even inferior to the combination of undiluted birch sap with other actives.
Example 2: Antimicrobial Experiments According to the QB/T2738-2012 Method for Evaluating the Antimicrobial Efficacy of Familiar Chemicals, birch sap with different concentrations, zinc PCA and combinations thereof were tested in a bacteria-inhibiting ring method. determined by the ring method).

1. Experiment material:
Equipment and materials: filter paper (antimicrobial carrier), vernier caliper.

Reagents: nutrient agar, bacterial suspension.
Source of strain: Propionibacterium acnes, commercially available from China Center for Type Culture Collection.

Sample Load Information: The sample load for a single ingredient was the total amount of ingredients, and the sample load for the compounded ingredient was half the birch sap stock and half the other active ingredients at 0.1%. .

2. Testing The operating steps of the antibacterial experiment:
(1) Preparation of antibacterial tablets: Add 20 μL of liquid sample dropwise to the center of a round sterile dry filter paper with a diameter of 5 mm, place the filter paper flat in a clean sterile plate and open the lid for later use. It was left to dry in an incubator (37° C.) or allowed to dry naturally at room temperature.

(2) Inoculation of test bacteria: A sterilized cotton swab was soaked in a test bacteria suspension of 1×10 ⁴ cfu/ml to 9×10 ⁴ cfu/ml, and evenly applied to the surface of a nutrient agar plate three times. For each application, the plate should be rotated 60 degrees and the swab should be applied along the edge of the plate. The plate was covered and dried at room temperature for 5 minutes.

(3) Placement of antibacterial test samples: One stained plate was placed for each test, and four test specimens and one control specimen were placed on each plate, for a total of five specimens. Specimens were removed using sterile tweezers and placed on the surface of the plate with a distance greater than 25 mm between the center of each specimen and greater than 15 mm from the edge of the plate. After placement, sterile forceps were used to gently push the specimens to bring them closer to the surface of the plate. Plates were covered and placed in a 37° C. incubator and incubated for 16-18 hours. Observed the results. The diameter of the antimicrobial ring (including patch) was measured using vernier calipers and recorded. The experiment was repeated 3 times.

The results of the tests are shown in the table below.

The results of the antibacterial test showed that the combination of birch sap and zinc PCA was superior to propionate compared to undiluted birch sap, double concentrated birch sap, zinc PCA alone, and the combination of undiluted birch sap and zinc PCA. It has been shown to significantly improve its ability to inhibit the growth of Bacterium acnes. When the birch sap was concentrated 10-fold, its combination with other actives showed significantly reduced efficacy, even inferior to the combination of undiluted birch sap with other actives.
Example 3: Rat Outer Ear Model Experiment In this example, birch sap and aloe extract, green tea extract, allantoin, nicotinamide, and combinations thereof with different concentrations for IL-1α and TNF-α in serum was tested based on mouse ear model experiments.

1. Materials Experimental animals: SPF grade SD male healthy rats, weight (200±20) g, provided by Zhejiang Medical Academy.

Drugs and reagents: 100% oleic acid, ELISA IL-1α kit, ELISA TNF-α kit.

Sample Load Information: The sample load for a single ingredient was the total amount of ingredients, and the sample load for the compounded ingredient was half the birch sap stock and half the other active ingredients at 0.1%. .

2. Methods (1) Modeling method: The rats were randomly divided into two groups, 8 in the normal group and the rest in the modeling group. In the model group, 100% oleic acid was evenly applied to the right outer ear skin of each rat once a day with a 1 ml syringe, about 0.3 ml each time for 3 weeks. Twenty-two days after application of 100% oleic acid, two model rats were randomly selected, and two ear sections of the right ear that had been applied with oleic acid were dissected, fixed in 10% formaldehyde, and wrapped in paraffin. It was embedded, sectioned, stained with HE, and histopathological changes were observed under an optical microscope. Observation under an optical microscope revealed thickening of the stratum corneum, hyperkeratosis, swelling of the hair follicle, follicle mouth and infundibulum filled with keratinized substances, blockage of keratotic plugs, pot-shaped swelling, and showed sebaceous gland loss. An experimental acne model of the rat outer ear was formed by grading criteria of experimental acne histology.

(2) Animal grouping and dosing: After successful modeling, the remaining rats in the model were divided according to their body weight into model blank group and birch sap group with different concentrations, with 8 rats in each group. divided randomly. On day 22 of the study, topical administration was initiated. The dose of each group was 0.1 ml, and the administration site was the model site of the right outer ear of rats, once a day for 2 weeks. No drug was applied to the normal group and the model group.

(3) Specimen collection and detection method: Twenty-four hours after the final administration, femoral artery blood was collected from animals in each group, serum was separated and stored at -20°C for later use. Serum IL-1α and TNF-α content was determined by a two-antibody sandwich ABC-ELISA method.

(4) GraphPad Prism Program software was used for drawing and T-test statistical analysis was used.

The results of the tests are shown in the table below.

The above results show that compared to using birch sap stock, double concentrated birch sap, aloe extract, green tea extract, allantoin or nicotinamide alone, birch sap stock and aloe extract, green tea extract, allantoin or nicotine Combinations with amides, double concentrated birch sap with aloe extract, green tea extract, allantoin or nicotinamide were shown to significantly improve the capacity against IL-1α and TNF-α in serum. When the birch sap was concentrated 10-fold, its combination with other actives showed significantly reduced efficacy, even inferior to the combination of birch sap with other actives.
Example 4: Sebum content of human skin In this example, the effect of different concentrations of birch sap and zinc PCA, sodium hyaluronate and their combination on human sebum content was investigated.

Excess sebum secretion is one of the main causes of acne. In this experiment, a sebometer (Sebmeter SM815, German CK company) was used to quantitatively measure the sebaceous gland secretion before and after using the cosmetic to evaluate the anti-acne efficacy of the cosmetic. The SM815 measurement principle is based on the photometric principle, a special matte tape with a thickness of 0.1mm becomes a translucent tape after absorbing oil on human skin, and its light transmission changes, the more fat it absorbs, the more light transmission increases, which allows the sebum content to be determined.

Sample Load Information: The load of a single ingredient was the total amount of ingredients and the ingredients combined were half birch sap and half 0.1% other active ingredients.

Experimental process: Patients suffering from oil hypersecretion Subjects (20-35 years old, half male and female) were selected and divided into groups with 8 persons in each group. On the day of the oil test, subjects washed their faces and after 30 minutes applied 3 mg/cm ² of different products to their cheeks. Sebum content was dynamically determined using SM815 at 0, 2, 4 and 8 hours, respectively, and changes in sebum content were calculated.

A double-blind labeling method was used for both experimental assessments and subjects. The test was performed in a constant temperature and humidity laboratory at a temperature of 25±1° C. and a humidity of 60%±5%.

The results of the tests are shown in the table below.

The sebum of the control group gradually increased over time, indicating that the subjects had strong oil secretion. The results for the sample group showed birch sap with 2x concentrated birch sap and zinc compared to birch sap undiluted, birch sap 2x concentrated, zinc PCA, sodium hyaluronate alone, and birch sap undiluted combined with zinc PCA or sodium hyaluronate. Combinations with PCA or sodium hyaluronate were shown to inhibit excessive oil secretion in subjects more significantly. When the birch sap was concentrated 10-fold, its combination with other actives showed significantly reduced efficacy, even inferior to the combination of undiluted birch sap with other actives.
Example 5: Preparation and Performance Investigation of Anti-Acne Extracts Formulations of anti-acne extracts containing different actives are shown in the table below:

The preparation method was as follows: Phase A ingredients were weighed, mixed well, completely dissolved, heated to 60°C and held for 20 minutes. Cool to 45° C. with stirring, add Phase B continuously and stir well to obtain the various anti-acne extract products described above.

The different anti-acne extract products described above were tested separately within the population to test the effectiveness of the products in practice. Samples were distributed to 60 patients with acne aged 20-35 years for each product to try for one month. At the same time, they were asked to complete a questionnaire and finally the results were calculated.

Criteria for grading were as follows:
Significantly Effective: Healed or >60% of skin lesions subsided Effective: 20-60% of skin lesions subsided No Poor: <20% of skin lesions subsided or worsened.

The results of the population study survey were as follows.

The above results include birch sap undiluted, double concentrated birch sap, anti-acne extracts containing salicylic acid alone, and double concentrated birch sap combined with salicylic acid compared to birch sap undiluted combined with salicylic acid. The extract showed more significant anti-acne instability.

The technical solutions in the above examples were the preferred embodiments of the present invention. Several improvements and changes can be made without departing from the principle of the present invention, and these improvements and changes should also be considered to fall within the protection scope of the present invention.

Claims (8)

Selected from (A) concentrated birch sap and (B) salicylic acid, malic acid, aloe extract, green tea extract, zinc PCA, allantoin, sodium hyaluronate and nicotinamide in a skin topical composition having anti-acne efficacy wherein said concentrated birch sap has a degree of enrichment of 1.1-8 fold, preferably 1.2-4 fold, more preferably 1.2-2 fold, use. Use according to claim 1, wherein said skin topical composition does not contain any further added water. 3. Use according to claim 1 or 2, wherein the skin topical composition is a pharmaceutical composition or a cosmetic composition. A skin topical composition having anti-acne efficacy, wherein (A) a concentrate having a concentration of 1.1-8 fold, preferably 1.2-4 fold, more preferably 1.2-2 fold A topical skin composition comprising birch sap and (B) one or more actives selected from salicylic acid, malic acid, aloe extract, green tea extract, zinc PCA, allantoin, sodium hyaluronate and nicotinamide . The content of the component (A) concentrated birch sap is 10 to 98% by weight, preferably 20 to 98% by weight, more preferably 30 to 97% by weight, relative to the total weight of the topical composition for skin. 5. The topical skin composition of claim 4, wherein a The content of the component (B) is 0.0005 to 30% by weight, preferably 0.001 to 10% by weight, more preferably 0.1 to 5% by weight, relative to the total weight of the topical composition for skin. A skin topical composition according to claim 4 or 5, in weight percent, most preferably 0.5-3 weight percent. 7. A topical skin composition according to any one of claims 4 to 6, wherein said topical skin composition does not contain any further added water. 8. The topical composition for skin according to any one of claims 4 to 7, wherein said topical composition for skin is a pharmaceutical composition or a cosmetic composition.