Acne removing composition

Abstract

The present invention relates to an acne removing composition comprising salicylic acid and creatine wherein the weight ratio of creatine to salicylic acid is from about 1: 6 to 6: 4, preferably from about 1: 5 to 5: 4, more preferably from about 1: 4 to 4: 4, still more preferably from about 1: 3 to 3: 4.

Description

Technical Field

[0001] The present invention relates to an anti-acne composition comprising salicylic acid and creatine, wherein the weight ratio of creatine to salicylic acid is about 1:6-6:4, preferably about 1:5-5:4, more preferably about 1:4-4:4, still more preferably about 1:3-3:4. Background Art

[0002] With the continuous development of the cosmetics industry, the types of cosmetics used by consumers have increased and the frequency of replacement has increased, and the frequency of skin contact with irritants has increased simultaneously; at the same time, under the influence of irregular lifestyle, diet and work and rest, the number of people with various skin inflammation problems has increased sharply. Among them, acne is more common on the face, chest and back of people, and there are many types such as whiteheads, blackheads, pustular acne and nodular acne. It has become a type of chronic inflammatory skin problem that obviously troubles consumers. The occurrence of acne is closely related to factors such as excessive sebum secretion, blockage of the sebaceous gland ducts of the hair follicles, bacterial infection and inflammatory response. How to regulate the water and oil balance of the skin and inhibit bacterial reproduction to achieve effective acne removal is an important issue that needs to be urgently solved in the industry.

[0003] Salicylic acid, also known as o-hydroxybenzoic acid, is a fat-soluble organic acid that can soften the stratum corneum, loosen keratin plugs and unclog pores. It also has certain antibacterial and anti-inflammatory effects. It is often used in the cosmetics field as an active ingredient in acne products. Low-concentration salicylic acid products are generally considered safe, while high-concentration salicylic acid can cause mild chemical burns and have certain skin irritation. If consumers use salicylic acid improperly, it may cause dry skin and even uncomfortable symptoms such as itchy skin and desquamation. In addition, the solubility of salicylic acid in water is limited, and the pH of the system is required to be high when it is used in large quantities.

[0004] Chinese patent application 202010813470.5 discloses an anti-acne composition, which includes 4-hydroxyethylpiperazineethanesulfonic acid, salicylic acid derivatives, madecassoside and active zinc. Chinese patent application 202410418709.7 discloses an anti-acne composition, which includes salicylic acid, gum arabic and sodium shale oil sulfonate, wherein the gum arabic contains arabinoprotein, which can form a composition with salicylic acid through molecular coupling to achieve a sustained release effect, which can effectively reduce the penetration of salicylic acid into the skin, thereby reducing irritation, and will not affect the effect of salicylic acid, so that the irritation of salicylic acid is reduced, and gentle and effective acne removal is achieved. Chinese patent application 201310314954.5 discloses a soothing and anti-acne composition, which includes mandelic acid, capryloyl glycine, salicylic acid or salicylic acid derivatives, gentian root extract, golden chamomile extract and phospholipids, etc. The acne composition can reduce the side effects of salicylic acid and avoid erythema, itching, stinging or allergic phenomena on the skin due to the use of salicylic acid or salicylic acid derivatives. Chinese patent application 202211069762.8 discloses an antibacterial composition, which includes salicylic acid and zinc hyaluronate, wherein zinc hyaluronate and salicylic acid can synergistically inhibit Propionibacterium acnes, thereby reducing the amount of zinc hyaluronate and salicylic acid, which can reduce costs and reduce the irritation that may be caused by salicylic acid.

[0005] Therefore, in the prior art, most of the acne-removing compositions based on salicylic acid achieve a more comprehensive effect through a combination of multiple types, among which acid substances and plant extracts are usually used. Because there are many components involved, it poses a great challenge to the actual formulation application; moreover, this method is usually costly. In addition, the technology of using a single ingredient to enhance the effect of salicylic acid is also usually achieved by using a large amount of components that have been proven to have acne-removing effects, such as zinc hyaluronate with good antibacterial effects. This method still has the problems of high cost and difficult formulation application.

[0006] Therefore, there is still a need for a method that can reduce the dosage and irritation of salicylic acid to achieve gentle and effective acne removal. Summary of the invention

[0007] In order to solve the above problems, the inventors have found through research that, within a certain ratio range, when creatine and salicylic acid are used in combination, the acne-removing effect of salicylic acid can be significantly increased, which shows that creatine has a significant synergistic effect on salicylic acid. The combination of the two can significantly reduce the inflammation caused by Propionibacterium acnes and significantly reduce the dosage of salicylic acid, thereby achieving the dual technical effects of reducing costs and reducing the irritation that may be caused by salicylic acid.

[0008] Moreover, unlike antibiotics, creatine and salicylic acid can be safely used by acne patients in daily skin care without causing dependence, and are safer.

[0009] Therefore, in one aspect, the present invention relates to a method for improving the anti-acne efficacy of salicylic acid, comprising introducing creatine into an anti-acne composition comprising salicylic acid, wherein the weight ratio of creatine to salicylic acid is about 1:6-6:4, preferably about 1:5-5:4, more preferably about 1:4-4:4, still more preferably about 1:3-3:4.

[0010] In yet another aspect, the present invention relates to the use of creatine in an anti-acne composition comprising salicylic acid, wherein the weight ratio of creatine to salicylic acid is about 1:6-6:4, preferably about 1:5-5:4, more preferably about 1:4-4:4, still more preferably about 1:3-3:4.

[0011] On the other hand, the present invention provides a reagent kit with acne-removing effect, which is composed of creatine and salicylic acid and optional solvents, preservatives and pH regulators, wherein the weight ratio of creatine to salicylic acid is about 1:6-6:4, preferably about 1:5-5:4, more preferably about 1:4-4:4, and still more preferably about 1:3-3:4.

[0012] The solvents are those known to those skilled in the art, including, for example, water, alcohols, and the like.

[0013] The preservatives are those known to those skilled in the art, including, for example, methylparaben, phenoxyethanol, 1,2-hexanediol, 1,2-pentanediol, and the like.

[0014] The pH adjusters are those known to those skilled in the art, including, for example, sodium hydroxide, tromethamine, triethanolamine, and the like.

[0015] In yet another aspect, the present invention provides an anti-acne composition comprising salicylic acid and creatine, wherein the weight ratio of creatine to salicylic acid is about 1:6-6:4, preferably about 1:5-5:4, more preferably about 1:4-4:4, still more preferably about 1:3-3:4.

[0016] In the above anti-acne composition, the content of salicylic acid is generally about 0.01-2%, preferably about 0.5-1.0%, and the content of creatine is generally about 0.01-1.5%, preferably about 0.3-1%, based on the total weight of the anti-acne composition.

[0017] The salicylic acid is an organic acid known in the prior art, and its chemical formula is C 7 H 6 O 3 , is a white crystalline powder, slightly soluble in cold water, easily soluble in hot water, ethanol, ether, acetone, and also soluble in hot benzene. Salicylic acid is commercially available, for example, from Merck Investment (China) Co., Ltd.

[0018] Creatine is a nitrogen-containing organic acid with a chemical formula of C4 H 9 N 3 O 2 , scientific name N-methylguanidinoacetic acid. Creatine is mainly stored in muscle tissue, which can reduce muscle fatigue and tension, enhance muscle elasticity, make muscles stronger, accelerate the synthesis of human protein, reduce cholesterol, blood lipids and blood sugar, delay the aging of the body, and play a role when energy demand is high. Creatine is commercially available, for example, from Evonik Specialty Chemicals (Shanghai) Co., Ltd.

[0019] The anti-acne composition of the present invention may be a composition for external use on the skin, including a pharmaceutical composition and a cosmetic composition.

[0020] In addition to the salicylic acid and creatine, the anti-acne composition optionally further comprises common components in pharmaceutical compositions and cosmetic compositions, including vehicles, active ingredients, and excipients, etc. The common components are known in the art, and those skilled in the art can select their types and amounts as needed. For example, the content of the common components is generally about 2-90%, based on the total weight of the anti-acne composition.

[0021] 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 usually accounts for 0.5-20% of the total weight of the common components.

[0022] The active ingredients include antibacterial agents, anti-inflammatory agents, astringents, antioxidants, moisturizers, emollients, oil control agents, exfoliating ingredients, and the like.

[0023] The antibacterial agent includes, but is not limited to, one or more of ursolic acid, Hedyotis diffusa flavonoids, honeysuckle extract, tea tree essential oil, chitin, cassia twig extract, coral ginger volatile oil, clove extract, mushroom extract, aloe extract, wormwood extract, 1-pentadecanol and its derivatives, cedrene, caryophyllene, longifolene, birch leaf extract, birch bark extract, etc. The content of the antibacterial agent in the skin external composition is known in the art, for example, it usually accounts for 0.01-30% of the total weight of the common components.

[0024] The anti-inflammatory agent includes, but is not limited to, one or more of safflower yellow, dipotassium glycyrrhizinate, cattail pollen extract, arrowroot extract, asiatica glycoside, allantoin, cucumber extract, garlic extract, burdock extract, resveratrol, sophora flavescens extract, magnolia bark extract, etc. The content of the anti-inflammatory agent in the skin external composition is known in the art, for example, it usually accounts for 0.01-50% of the total weight of the common components.

[0025] 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, sulfur, raw rehmannia root, angelica, 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 usually accounts for 0.01-30% of the total weight of the common components.

[0026] The antioxidant includes, but is not limited to, one or more of white tea polyphenols, red ash alkaloids, hawthorn flavonoids, coenzyme Q10, grape seed extract, asparagus extract, radish extract, L-C stock solution, safflower water extract, asiatica glycoside, atractylodes polysaccharide, vitamin E and its derivatives, etc. The content of the antioxidant in the skin external composition is known in the art, for example, it usually accounts for 0.01-30% of the total weight of the common components.

[0027] Examples of the moisturizing agent 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, glycereth-5 lactate, sodium hyaluronate, hydrolyzed sodium hyaluronate, acetylated sodium hyaluronate, sodium polyglutamate, hydrolyzed sclerotium gum, budding pullulan polysaccharide, tremella polysaccharide, sour bean seed polysaccharide, and the like. One or more. The content of the moisturizer in the skin external composition is known in the art, for example, it generally accounts for 1-30% by weight of the total weight of the common components.

[0028] Examples of the emollient include, but are not limited to, olive oil, macadamia oil, sweet almond oil, grape seed oil, avocado oil, corn oil, sesame oil, soybean oil, peanut oil, white meadowfoam seed oil, safflower seed oil, dog rose 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, octyldodecanol 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, avocado tree butter, Murumuru star fruit palm seed butter, etc. 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 the common components.

[0029] 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, elm spirea extract, vitamin B5, calycosin, puerarin, Japanese cypress leaf extract, salvia miltiorrhiza root extract, lycopodiella tomato bark extract, angustifolia leaf extract, dendrobium extract, sage extract, avocado extract, etc. The content of the oil-controlling 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 the common components.

[0030] The exfoliating ingredients include, but are not limited to, one or more of bromelain, fruit acid, lactic acid, citric acid, enzyme 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 topical composition is known in the art, for example, it usually accounts for 0.01-30% of the total weight of the common components.

[0031] The auxiliary materials include, for example, emulsifiers, thickeners, preservatives, flavors, and the like.

[0032] 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. The content of the emulsifier in the skin external composition is known in the art, for example, it usually accounts for 0.5-10% of the total weight of the common components.

[0033] Examples of the thickener include, but are not limited to, one or more of high molecular polymers such as carbomers, acrylic acid (esters) and their derivatives, xanthan gum, gum arabic, polyethylene glycol-14M, polyethylene glycol-90M, succinoglycan, hydroxyethyl cellulose, hydroxypropyl cellulose, and hydroxypropyl methyl cellulose. The content of the thickener in the skin topical composition is known in the art, for example, it usually accounts for 0.01-50% of the total weight of the common components.

[0034] 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, peony root extract, etc. The content of the preservative in the skin external composition is known in the art, for example, it generally accounts for 0.01-50% of the total weight of the common components.

[0035] The anti-acne composition of the present invention can be prepared by any suitable method known in the art. For example, it is prepared using equipment such as a dissolving tank, an emulsifying pot, a disperser, and a delivery pump commonly used in the field of cosmetics. During preparation, the water-soluble substance is first put into the water phase dissolving pot, and the oil-soluble substance is put into the oil phase dissolving pot, and the temperature of the two pots 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 reduced to room temperature, and optional flavors, preservatives, etc. are added, and the pH of the product is adjusted as needed. The relevant test indicators are qualified before filling and shipment. The above preparation method can be deleted or adjusted according to the dosage form requirements.

[0036] The pharmaceutical composition or cosmetic composition in various dosage forms such as liquid, emulsion, ointment, cream or gel can be prepared as needed, and the composition can be in various forms such as lotion, spray, emulsion, essence water or essence milk, BB cream, sunscreen, etc. Example

[0037] The present invention is further described in detail below in conjunction with the examples. However, it should be understood that these examples and comparative examples are only used to illustrate the present invention in more detail and should not be construed as limiting the scope of the appended claims of the present invention in any form.

[0038] Example 1: Anti-inflammatory effects of different composition systems

[0039] In this example, the anti-inflammatory effects of salicylic acid, creatine and / or azelaic acid were evaluated based on a transgenic neutrophil green fluorescent zebrafish model.

[0040] Experimental animals: zebrafish 3 days after fertilization

[0041] Experimental materials: salicylic acid, azelaic acid, creatine, pentylene glycol, water

[0042] Experimental method: Randomly select zebrafish in a 6-well plate, 15 in each well; inject Propionibacterium acnes to establish a zebrafish inflammation model; water-soluble samples are given, and a normal control group and a model control group (zebrafish modeled with Propionibacterium acnes) are set up at the same time, with a volume of 3mL per well; incubate at 28°C in the dark for 3 hours; 10 zebrafish are randomly selected from each experimental group and photographed under a fluorescence microscope, and the data are analyzed and collected using advanced image processing software, and the number of zebrafish neutrophils (N) is analyzed, and the following formula is used to calculate and determine whether the sample has anti-inflammatory effect:

[0043] Anti-inflammatory efficacy (%) = [N (model control group) - N (sample group)] / [N (model control group - N (normal control group)] × 100% Table 1: Anti-inflammatory efficacy of different composition systems

[0044] Table 1: Anti-inflammatory effects of different composition systems

[0045] Note: The purpose of using sodium hydroxide is to adjust the pH of the system to 4.0-6.0; P<0.05 was considered to be significantly different. The difference is indicated by *, and P < 0.01 is considered to be extremely significant, indicated by **.

[0046] The results in the above table show that the addition of creatine significantly improves the anti-inflammatory and anti-acne effects of the composition system compared to the use of salicylic acid alone.

[0047] Example 2: Oil control effects of different composition systems

[0048] In this example, the effects of different composition systems on the oil secretion of sebaceous gland cells were investigated and compared.

[0049] Experimental materials: The cells used were sebaceous gland cells, batch number: 210829, provided by Guangdong Boxi Biotechnology Co., Ltd.

[0050] Cytotoxicity test to determine the maximum dosing concentration.

[0051] Oil control test

[0052] 1) Cell inoculation: After the cells are revived, when the plating rate reaches about 60%, inoculate the cells into a 24-well plate and incubate overnight in a CO2 incubator (37°C, 5% CO2).

[0053] 2) Solution preparation: Prepare the working solution of the test substance according to the test group (Table 2).

[0054] Table 2: Test groups

[0055] 3) Administration: Test groups were made according to Table 2. When the cell plating rate in the 24-well plate reached 40-60%, group administration was carried out, with 3 replicate wells in each group. 1 mL of culture medium was added to each well of the blank control group, 1 mL of culture medium containing isotretinoin was added to each well of the positive control group, and 1 mL of culture medium containing the sample to be tested at the corresponding concentration was added to each well of the sample group. After administration, the 24-well plate was placed in a CO2 incubator (37°C, 5% CO 2 ) for 72 h, during which the medium was changed and medication was administered every day.

[0056] 4) Oil Red O staining: discard the old solution, wash with PBS, fix the cells with paraformaldehyde, add 300 μL of Oil Red O working solution to each well, stain for 15 minutes in the dark, wash with PBS, and observe with a microscope. Calculate the IOD value, which is the integrated optical density and reflects the oil content.

[0057] 5) Calculation of inhibition rate: Inhibition rate (%) = (blank control group - sample group) / blank control group × 100% .

[0058] 6) Statistical analysis of results: GraphPad Prism was used for graphing, and the results were expressed as Mean ± SD. The t-test was used for statistical analysis for comparison among groups. All statistical analyses were two-tailed.

[0059] 3. Test results

[0060] Table 3: Oil inhibition rate results

[0061] Note: P < 0.05 was considered to be significantly different, indicated by *, and P < 0.01 was considered to be extremely significantly different, indicated by **.

[0062] The results in the above table show that compared with the BC group, the oil content of the PC group decreased significantly, indicating that the positive control of this test is effective. Compared with the BC group, sample A1 and samples A5-A7 both resulted in a significant decrease in oil content, and samples A5-A7 resulted in a more significant oil inhibition effect.

[0063] Example 3: Preparation and performance testing of acne-removing essence composition

[0064] Four anti-acne essence composition samples were prepared according to the formula in Table 4 below and their performances were tested.

[0065] Table 4: Formula of anti-acne essence composition

[0066] The preparation process is as follows: weigh the raw materials of phase A, mix the components in phase A evenly and ensure that the components are completely dissolved, heat to 80°C, and keep warm for 30 minutes. When the temperature drops to 45°C while stirring, add phase B in sequence and stir evenly. Then add phase C and stir evenly to obtain the above four acne essence products.

[0067] In order to test the actual effect of the products, a population trial survey was conducted on the four acne-removing essence products. Samples were distributed to 125 acne patients aged 20-35 years old for trial. The subjects were randomly divided into 5 groups and tried the products for 10 days. They also filled out questionnaires and finally the results were statistically analyzed.

[0068] The criteria for grading are as follows:

[0069] Significantly effective: acne subsided by >60%

[0070] Effective: Acne subsides by 20-60%

[0071] Ineffective: Acne subsides by <20% or worsens.

[0072] The survey results of the population trial are shown in Table 5 below.

[0073] Table 5: Results of acne removal efficacy of acne removal essence products

[0074] The results in the above table show that the anti-acne essence composition containing a combination of creatine and salicylic acid is significantly better than the blank group and the comparative composition containing only salicylic acid in removing acne.

[0075] 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 protection scope of the present invention.

Claims

1. A method for improving the anti-acne efficacy of salicylic acid, comprising introducing creatine into an anti-acne composition comprising salicylic acid, wherein the weight ratio of creatine to salicylic acid is 1:6-6:4, preferably 1:5-5:4, more preferably 1:4-4:4, still more preferably 1:3-3:

4.

2. Use of creatine in an anti-acne composition comprising salicylic acid, wherein the weight ratio of creatine to salicylic acid is 1:6-6:4, preferably 1:5-5:4, more preferably 1:4-4:4, still more preferably 1:3-3:

4.

3. A reagent pack with acne-removing effect, which consists of creatine and salicylic acid and optionally a solvent, a preservative and a pH adjuster, wherein the weight ratio of creatine to salicylic acid is 1:6-6:4, preferably 1:5-5:4, more preferably 1:4-4:4, and still more preferably 1:3-3:

4.

4. An anti-acne composition comprising salicylic acid and creatine, wherein the weight ratio of creatine to salicylic acid is 1:6-6:4, preferably 1:5-5:4, more preferably 1:4-4:4, still more preferably 1:3-3:

4.

5. The anti-acne composition according to claim 4, wherein the content of salicylic acid is 0.01-2%, preferably 0.5-1.0%, based on the total weight of the anti-acne composition.

6. The anti-acne composition according to claim 4 or 5, wherein the content of creatine is 0.01-1.5%, preferably 0.3-1%, based on the total weight of the anti-acne composition.

7. The anti-acne composition according to claim 4 or 5, which is a cosmetic composition or a pharmaceutical composition.

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