Composition for treating acne

Abstract

A composition for treating acne, comprising salicylic acid and creatine, wherein the weight ratio of creatine to salicylic acid is about 1:6 to 6:4, preferably about 1:5 to 5:4, more preferably about 1:4 to 4:4, and still more preferably about 1:3 to 3:4.

Description

An acne treatment composition Technical Field

[0001] This invention relates to an acne treatment 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, and still more preferably about 1:3-3:4. Background Technology

[0002] With the continuous development of the cosmetics industry, consumers are using more and changing cosmetics more frequently, leading to a corresponding increase in skin contact with irritants. Simultaneously, irregular lifestyles, diets, and sleep patterns have resulted in a surge in various skin inflammation problems. Acne, which commonly occurs on the face, chest, and back, includes various types such as whiteheads, blackheads, pustules, and nodular acne, and has become a significant chronic inflammatory skin problem that greatly troubles consumers. The occurrence of acne is closely related to factors such as excessive sebum secretion, blockage of the pilosebaceous duct, bacterial infection, and inflammatory responses. How to regulate the skin's oil-water balance and inhibit bacterial growth to effectively treat acne is a crucial issue that urgently needs to be addressed within the industry.

[0003] Salicylic acid, also known as o-hydroxybenzoic acid, is a fat-soluble organic acid. It can soften the stratum corneum, loosen keratin plugs to unclog pores, and has certain antibacterial and anti-inflammatory effects. It is often used in cosmetics as an active ingredient in acne treatment products. Low concentrations of salicylic acid products are generally considered safe, while high concentrations can cause minor chemical burns and are somewhat irritating to the skin. Improper use of salicylic acid may lead to dry skin, and even symptoms such as itching and peeling. In addition, salicylic acid has limited solubility in water, and high pH requirements are necessary for large-scale applications.

[0004] Chinese patent application 202010813470.5 discloses an acne-removing composition comprising 4-hydroxyethylpiperazine ethanesulfonic acid, a salicylic acid derivative, hydroxyascorbic acid glycoside, and active zinc. Chinese patent application 202410418709.7 discloses an acne-removing composition comprising salicylic acid, gum arabic, and sodium shale oil sulfonate. The gum arabic contains arabinopolysaccharide protein, which can form a composition with salicylic acid through molecular coupling, thereby providing a sustained-release effect. This effectively reduces the penetration of salicylic acid into the skin, thus weakening irritation without affecting the efficacy of salicylic acid, resulting in a gentle and effective acne-removing effect. Chinese patent application 201310314954.5 discloses a soothing acne-reducing composition comprising mandelic acid, capryloyl glycine, salicylic acid or salicylic acid derivatives, gentian root extract, golden chamomile extract, and phospholipids. This acne composition can reduce the side effects of salicylic acid, preventing skin erythema, itching, stinging, or allergic reactions caused by the use of salicylic acid or salicylic acid derivatives. Chinese patent application 202211069762.8 discloses an antibacterial composition comprising salicylic acid and zinc hyaluronic acid. Zinc hyaluronic acid and salicylic acid synergistically inhibit Propionibacterium acnes, thus reducing the dosage of zinc hyaluronic acid and salicylic acid, lowering both cost and the potential irritation caused by salicylic acid.

[0005] Therefore, most existing salicylic acid-based acne treatment compositions achieve comprehensive effects through the combination of multiple types of compounds, typically using acids and plant extracts. Because of the large number of components involved, practical formulation application faces significant challenges; moreover, this method is usually costly. Furthermore, techniques that use a single ingredient to enhance the efficacy of salicylic acid usually employ large quantities of ingredients proven to have acne-fighting effects, such as zinc hyaluronic acid with good antibacterial properties. This method still suffers from high cost and difficulties in formulation application.

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

[0007] To address the aforementioned issues, the inventors discovered that, within a certain ratio range, combining creatine and salicylic acid significantly enhances the acne-fighting efficacy of salicylic acid. This indicates that creatine has a significant synergistic effect on salicylic acid, and the combination of the two can significantly reduce inflammation caused by Propionibacterium acnes while significantly reducing the dosage of salicylic acid. Thus, the dual technical effects of reducing costs and minimizing potential irritation from salicylic acid are achieved.

[0008] Moreover, unlike antibiotics, creatine and salicylic acid can be safely used by acne patients in their daily skincare routine without causing dependence, making them safer.

[0009] Therefore, on one hand, the present invention relates to a method for improving the acne-removing efficacy of salicylic acid, which includes introducing creatine into an acne-removing composition containing 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, and still more preferably about 1:3-3:4.

[0010] In another aspect, the present invention relates to the use of creatine in acne-treating compositions containing 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, and still more preferably about 1:3-3:4.

[0011] On the other hand, the present invention provides a reagent kit with acne-removing effects, which is composed of creatine and salicylic acid, as well as optional solvents, preservatives and pH adjusters, 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 solvent is one known to those skilled in the art, including, for example, water and alcohols.

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

[0014] The pH adjuster is one known to those skilled in the art, including, for example, sodium hydroxide, tromethamine, and triethanolamine.

[0015] In another aspect, the present invention provides an acne-removing 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, and still more preferably about 1:3-3:4.

[0016] In the above-mentioned acne-removing 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 acne-removing composition.

[0017] The salicylic acid is an organic acid known in the prior art, with the chemical formula C7H6O3. It is a white crystalline powder, slightly soluble in cold water, readily 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 the chemical formula C4H9N3O2 and its scientific name N-methylguanidinoacetic acid. Creatine is primarily stored in muscle tissue, where it can reduce muscle fatigue and tension, enhance muscle elasticity, make muscles stronger, accelerate protein synthesis, lower cholesterol, blood lipids, and blood sugar, and slow down aging. It also plays a role when energy demands are high. Creatine is commercially available, for example, from Evonik Specialty Chemicals (Shanghai) Co., Ltd.

[0019] The acne-removing compositions of the present invention can be topical skin compositions, including pharmaceutical compositions and cosmetic compositions.

[0020] In addition to the salicylic acid and creatine, the acne-removing composition optionally includes components commonly used in pharmaceutical and cosmetic compositions, including carriers, active ingredients, and excipients. These commonly used components are known in the art, and those skilled in the art can select their type and dosage as needed. For example, the content of these commonly used components is typically about 2-90% based on the total weight of the acne-removing composition.

[0021] The medium includes, for example, a diluent, dispersant, or carrier, examples of which include, but are not limited to, ethanol, dipropylene glycol, and butylene glycol. The amount of the medium in the cosmetic composition is known in the art; for example, it typically constitutes 0.5-20% of the total weight of the commonly used components.

[0022] The active ingredients include antibacterial agents, anti-inflammatory agents, astringents, antioxidants, moisturizers, emollients, oil-controlling agents, exfoliating ingredients, etc.

[0023] The antibacterial agents include, but are not limited to, one or more of the following: ursolic acid, Hedyotis diffusa flavonoids, Lonicera japonica flower extract, tea tree oil, chitosan, Cinnamomum cassia twig extract, Zingiber officinale volatile oil, clove extract, mushroom extract, aloe vera extract, Artemisia argyi extract, 1-pentadecanol and its derivatives, cedrene, caryophyllene, phlorene, birch leaf extract, and birch bark extract. The content of the antibacterial agent in the topical skin composition is known in the art; for example, it typically accounts for 0.01-30% of the total weight of the commonly used components.

[0024] The anti-inflammatory agents include, but are not limited to, one or more of the following: safflower yellow pigment, dipotassium glycyrrhizate, cattail pollen extract, *Taxus chinensis* extract, asiaticoside, allantoin, cucumber extract, garlic extract, burdock extract, resveratrol, *Sophora flavescens* extract, and *Magnolia officinalis* extract. The content of the anti-inflammatory agents in the topical skin composition is known in the art; for example, it typically accounts for 0.01-50% of the total weight of the commonly used components.

[0025] The astringent includes, but is not limited to, one or more of the following: green tea polyphenols, witch hazel extract, vitamin A, menthol lactate, seaweed extract, indigo naturalis, sulfur, rehmannia root, angelica root, allantoin, lactic acid, tartaric acid, succinic acid, and citric acid. The content of the astringent in the topical skin composition is known in the art; for example, it typically constitutes 0.01-30% of the total weight of the commonly used components.

[0026] The antioxidants include, but are not limited to, one or more of the following: white tea polyphenols, red clover alkaloids, hawthorn flavonoids, coenzyme Q10, grape seed extract, asparagus extract, radish extract, L-ascorbic acid stock solution, safflower water extract, centella asiatica glycoside, atractylodes macrocephala polysaccharide, vitamin E and its derivatives. The content of the antioxidants in the topical skin composition is known in the art; for example, it typically accounts for 0.01-30% of the total weight of the commonly used components.

[0027] Examples of the moisturizers include, but are not limited to, one or more of the following: glycerin, diglycerin, butylene glycol, propylene glycol, 1,3-propanediol, dipropylene glycol, 1,2-pentanediol, polyethylene glycol-8, polyethylene glycol-32, methyl glucetol polyether-10, methyl glucetol polyether-20, PEG / PPG-17 / 6 copolymer, glycerin polyether-7, glycerin polyether-26, glyceryl glucoside, PPG-10 methyl glucose ether, PPG-20 methyl glucose ether, PEG / PPG / polybutylene glycol-8 / 5 / 3 glycerin, sucrose, trehalose, rhamnose, mannose, raffinose, betaine, erythritol, xylitol, urea, glyceryl polyether-5 lactate, sodium hyaluronate, hydrolyzed sodium hyaluronate, acetylated sodium hyaluronate, sodium polyglutamate, hydrolyzed sclerotium gum, budding short stem enzyme polysaccharide, tremella polysaccharide, and soybean seed polysaccharide. The amount of the moisturizer in the topical skin composition is known in the art; for example, it typically accounts for 1-30% of the total weight of the commonly used components.

[0028] Examples of the emollients include, but are not limited to, one or more of the following: 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, rosehip oil, argan kernel oil, jojoba seed oil, sunflower seed oil, murrilla palm oil, squalane, ethylhexyl palmitate, isopropyl myristate, hydrogenated polyisobutylene, isohexadecane, isododecane, diethylhexyl carbonate, dioctyl carbonate, lauroyl sarcosinate isopropyl, isononyl isononanoate, hydrogenated polydecene, triglycerides (ethylhexanoate), cetyl ethylhexanoate, bis-diethoxydiethylene cyclohexane 1,4-dicarboxylic acid ester, caprylic / capric triglyceride, oleyl erucic acid ester, octyl dodecyl myristate, octyl dodecyl alcohol, polydimethylsiloxane, octyl polymethylsiloxane, cetyl polydimethylsiloxane, cyclopentamethoxydimethylsiloxane, etc. Examples of solid emollients include, but are not limited to, one or more of cetyl alcohol, stearyl alcohol, cetearyl alcohol, behenyl alcohol, squalene, lauric acid, myristic acid, palmitic acid, stearic acid, beeswax, candelilla wax, carnauba wax, lanolin, ceresin, jojoba seed wax, paraffin wax, microcrystalline wax, hydrogenated rice bran wax, hydrogenated coconut oil glycerides, glyceryl behenate / eicosyl ester, myristyl myristate, bis-diglyceride polyacryl adipate-2, shea butter, and muscaria seed butter. The emollient in the topical skin composition is known in the art, and typically comprises 1-50% by weight of the commonly used components.

[0029] Examples of the oil-controlling agent include, but are not limited to, one or more of the following: hawthorn extract, ivy extract, saxifrage extract, winter melon seed extract, meadowsweet extract, vitamin B5, verbascoside, puerarin, Japanese cypress leaf extract, salvia root extract, green-flowered tomato bark extract, willowherb leaf extract, dendrobium extract, sage extract, and avocado extract. The content of the oil-controlling agent in the topical skin composition is known in the art; for example, it typically constitutes 0.01-30% of the total weight of the commonly used components.

[0030] The exfoliating ingredients include, but are not limited to, one or more of the following: bromelain, fruit acid, lactic acid, citric acid, enzymatic exfoliants, polyethylene beads, glycolic acid, mandelic acid, malic acid, tartaric acid, azelaic acid, and acetic acid. The content of the exfoliating ingredient in the topical skin composition is known in the art; for example, it typically constitutes 0.01-30% of the total weight of the commonly used components.

[0031] The excipients include, for example, emulsifiers, thickeners, preservatives, and fragrances.

[0032] Examples of such emulsifiers include, but are not limited to, cetearyl oleate, sorbitan oleate, polysorbate-60, polysorbate-80, methyl glucose sesquistearate, PEG-20 methyl glucose sesquistearate, PEG-40 hydrogenated castor oil, PPG-26-butanol polyether-26, PEG-4 polyglycerol-2 stearate, PEG-60 hydrogenated castor oil, stearyl oleate-2, stearyl oleate-21, PPG-13-decyltetradecyl alcohol polyether-24, cetearyl glucoside, PEG-100 stearate, and glycerin. The emulsifier is selected from one or more of the following: stearate, glyceryl stearate SE, cocoyl glucoside, cetearyl alcohol polyether-25, PEG-40 stearate, polyglycerol-3-methylglucose distearate, glyceryl stearate citrate, polyglycerol-10 stearate, polyglycerol-10 myristate, polyglycerol-10 dioleate, polyglycerol-10 laurate, polyglycerol-10 isostearate, polyglycerol-10 oleate, polyglycerol-10 diisostearate, polyglycerol-6 laurate, polyglycerol-6 myristate, sucrose stearate, and sucrose polystearate. The amount of the emulsifier in the topical skin composition is known in the art, and for example, it typically constitutes 0.5-10% of the total weight of the commonly used components.

[0033] Examples of the thickener include, but are not limited to, one or more of the following polymers: carbomers, acrylates and their derivatives, xanthan gum, gum arabic, polyethylene glycol-14M, polyethylene glycol-90M, succinopolysaccharides, hydroxyethyl cellulose, hydroxypropyl cellulose, and hydroxypropyl methylcellulose. The amount of the thickener in the topical skin composition is known in the art; for example, it typically constitutes 0.01-50% of the total weight of the commonly used components.

[0034] Examples of the preservatives include, but are not limited to, one or more of the following: methylparaben, propylparaben, phenoxyethanol, benzyl alcohol, phenethyl alcohol, bis(hydroxymethyl)imidazolidinyl urea, potassium sorbate, sodium benzoate, chlorphenesin, sodium dehydroacetate, capryloyl hydroxamic acid, 1,2-hexanediol, 1,2-pentanediol, p-hydroxyacetophenone, caprylyl glycol, glyceryl caprylate, undecylenoic acid glyceride, sorbitan caprylate, ethylhexylglycerin, and peony root extract. The amount of the preservative in the topical skin composition is known in the art; for example, it typically constitutes 0.01-50% of the total weight of the commonly used components.

[0035] The acne-removing composition of the present invention can be prepared by any suitable method known in the art. For example, it can be prepared using equipment commonly used in the cosmetics industry, such as dissolving tanks, emulsifying pots, dispersers, and delivery pumps. During preparation, water-soluble substances are first added to an aqueous phase dissolving vessel, and oil-soluble substances are added to an oil phase dissolving vessel. The temperature of both vessels is heated to approximately 80°C. For raw materials prone to clumping, they can be pre-dispersed using a disperser. After dissolution, the oil and aqueous phases are transferred to an emulsifying pot and homogenized for approximately 5-15 minutes. After emulsification, the material temperature is lowered to room temperature, and optional fragrances, preservatives, etc., are added. The pH of the product is adjusted as needed. The product can only be packaged and shipped after all relevant test indicators have passed. The above preparation method can be modified or adjusted according to dosage form requirements.

[0036] Pharmaceutical or cosmetic compositions in various dosage forms, such as liquids, emulsions, ointments, creams, or gels, can be prepared as needed. The compositions can be in various forms, such as toners, sprays, emulsions, essences or serums, BB creams, and sunscreens. Example

[0037] The present invention will be further described in detail below with reference to embodiments. However, it should be understood that these embodiments and comparative examples are merely for illustrating the present invention in more detail and should not be construed as limiting the scope of the appended claims in any way.

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

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

[0040] Laboratory animals: Zebrafish 3 days after fertilization

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

[0042] Experimental Methods: Zebrafish were randomly selected into 6-well plates, 15 fish per well; a zebrafish inflammation model was established by injection of Propionibacterium acnes; the sample was administered in water solution, and a normal control group and a model control group (zebrafish modeled with Propionibacterium acnes) were set up, with a volume of 3 mL per well; the samples were incubated at 28℃ in the dark for 3 h; 10 zebrafish from each experimental group were randomly selected and photographed under a fluorescence microscope, and the data were analyzed and collected using advanced image processing software. The number of neutrophils (N) in the zebrafish was analyzed, and the anti-inflammatory effect of the sample was calculated and determined according to the following formula:

[0043] Anti-inflammatory efficacy (%) = [N(model control group) - N(sample group)] / [N(model control group - N(normal control group)] × 100%

[0044] Table 1: Anti-inflammatory effects of different composition systems Note: Sodium hydroxide is used to adjust the pH of the system to 4.0-6.0; P<0.05 is considered significant and is indicated by *, P<0.01 is considered highly significant and is indicated by **.

[0045] The results in the table above show that, compared with salicylic acid alone, the addition of creatine significantly improved the anti-inflammatory and acne-reducing effects of the composition system.

[0046] Example 2: Oil-controlling effects of different composition systems

[0047] In this embodiment, the effects of different composition systems on sebum secretion from sebaceous gland cells were investigated and compared.

[0048] Experimental materials: The cells used were sebaceous gland cells, batch number: 210829, provided by Guangdong Boxi Biotechnology Co., Ltd.

[0049] 1. Cytotoxicity test to determine the maximum dosing concentration.

[0050] 2. Oil control test

[0051] 1) Cell seeding: After cell resuscitation, when the cell plating rate reaches about 60%, seed the cells into 24-well plates and incubate overnight in a CO2 incubator (37°C, 5% CO2).

[0052] 2) Solution preparation: Prepare the working solution of the test substance according to the test group (Table 2).

[0053] Table 2: Test Groups

[0054] 3) Drug administration: Test groups were established according to Table 2. When the cell deposition rate in the 24-well plate reached 40-60%, drug administration was performed in each group, with 3 replicates per 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 corresponding concentration of the test sample was added to each well of the sample group. After drug administration, the 24-well plate was placed in a CO2 incubator (37℃, 5% CO2) for 72 hours, with daily medium changes and drug administration during the incubation period.

[0055] 4) Oil Red O staining: Discard the old solution, wash with PBS, fix cells with paraformaldehyde, add 300 μL of Oil Red O working solution to each well, stain in the dark for 15 min, wash with PBS, and observe under a microscope. Calculate the IOD value, which is the integrated optical density, reflecting the lipid content.

[0056] 5) Inhibition rate calculation: Inhibition rate (%) = (blank control group - sample group) / blank control group × 100%.

[0057] 6) Statistical Analysis of Results: GraphPadPrism was used for plotting, and the results are expressed as Mean ± SD. t-tests were used for comparisons between groups. All statistical analyses were two-tailed.

[0058] 3. Test Results

[0059] Table 3: Results of Oil Inhibition Rate Note: P<0.05 is considered statistically significant and is indicated by *, while P<0.01 is considered highly statistically significant and is indicated by **.

[0060] The results in the table above show that the oil content in the PC group was significantly lower than that in the BC group, indicating that the positive control in this test was effective. Compared with the BC group, samples A1 and A5-A7 both resulted in a significant decrease in oil content, and samples A5-A7 showed a more significant oil inhibition effect.

[0061] Example 3: Preparation and performance testing of acne-removing essence composition

[0062] Four acne-removing essence composition samples were prepared according to the formulas in Table 4 below, and their performance was tested.

[0063] Table 4: Formulation of Acne Treatment Essence Combination

[0064] The preparation process is as follows: Weigh phase A raw material, mix all components in phase A evenly and ensure complete dissolution, heat to 80℃, and keep warm for 30 minutes. While stirring, cool down to 45℃, then add phase B sequentially and stir evenly. Then add phase C and stir evenly to obtain the above four acne-removing essence products.

[0065] To test the actual effectiveness of the products, a trial survey was conducted on the four acne-removing essence products. Samples were distributed to 125 acne patients aged 20-35 years. The subjects were randomly divided into 5 groups and used the products for 10 days. They also filled out a questionnaire. The results were then statistically analyzed.

[0066] The criteria for grading are as follows:

[0067] Significantly effective: Acne reduction >60%

[0068] Effective: Acne reduces by 20-60%

[0069] Ineffective: Acne reduction <20% or worsening.

[0070] The survey results of the trial population are shown in Table 5 below.

[0071] Table 5: Results of Acne-Clearing Efficacy of Acne-Clearing Essence Products

[0072] The results in the table above show that the acne-fighting serum composition containing a combination of creatine and salicylic acid is significantly superior to the control group and the comparative composition containing only salicylic acid in terms of acne treatment.

[0073] The technical solutions described above are preferred embodiments of the present invention. Several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered to be within the protection scope of the present invention.

Claims

1. A method for improving the acne-fighting efficacy of salicylic acid, comprising introducing creatine into an acne-fighting composition containing 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, and still more preferably 1:3-3:

4.

2. Use of creatine in an acne treatment composition containing 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, and still more preferably 1:3-3:

4.

3. A reagent kit with acne-removing effects, comprising creatine and salicylic acid, and optionally a solvent, preservative and 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 acne-removing 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, and still more preferably 1:3-3:

4.

5. The acne-removing 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 acne-removing composition.

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

7. The acne-removing composition according to claim 4 or 5, wherein it is a cosmetic composition or a pharmaceutical composition.

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