Application of alkyl oxazolidinone in regulation and control of skin microbial flora and product containing alkyl oxazolidinone

Abstract

The invention belongs to the technical field of skin microorganism regulation and control and daily chemical products, and relates to application of alkyl oxazolidinone in regulation and control of skin microbial flora and a product containing the alkyl oxazolidinone. The invention finds that the alkyl oxazolidinone, especially C8-14 alkyl oxazolidinone, has a remarkable inhibition effect on regulating and controlling skin microbial flora, especially on malassezia furfur and propionibacterium acnes; the compound is widely applied to preparation of products for removing dandruff, relieving itching and / or relieving acne and preparation of medicines for treating and / or preventing skin diseases caused by imbalance of skin microbial flora.

Description

Technical Field

[0001] The invention belongs to the technical field of skin microbial regulation and daily chemical products, and relates to use of alkyl oxazolidinone in regulating skin microbial flora and products containing alkyl oxazolidinone. Background Art

[0002] The skin barrier is composed of four major components: microbial, chemical, physical, and immune. These components work together to maintain skin integrity. The skin microbiome, which includes bacteria such as Corynebacterium and Propionibacterium, coagulase-negative Staphylococci, fungi such as Malassezia, and viruses, actively contributes to maintaining skin barrier integrity. The composition of the skin microbiome is closely related not only to the moisture, dryness, and sebum content of the skin microenvironment, but is also influenced by external environmental factors and individual lifestyle habits. Sebum components such as triglycerides, wax esters, and squalene, secreted by sebaceous glands, together with sweat and epidermal lipids, form the sebum membrane, a crucial component of the microecology that colonizes the skin microbiome. Factors such as hypersecretion of sebaceous glands and inflammatory responses in keratinocytes can disrupt the balance between the skin barrier and the skin microbiome, leading to changes in the surface microbiome. Clinical practice has demonstrated that microbial regulation can be effective in treating a variety of skin conditions, including photodermatoses, atopic dermatitis, seborrheic dermatitis, and dandruff.

[0003] The growth of skin microbes depends on nutrients and other molecules provided by host cells, resulting in differences in the microbial composition of the skin in different parts of the body. Lipophilic skin microbes, such as Propionibacterium acnes and Malassezia species, are widely present on the human skin surface, particularly in areas with active sebaceous gland secretion, such as the scalp, chest, back, head, face, and neck. They secrete lipase, which hydrolyzes triglycerides in sebum into free fatty acids, maintaining a low epidermal pH and thus resisting the invasion of pathogens, allowing them to coexist with the host. Therefore, these lipophilic microbes are not pathogenic under normal circumstances, but can exhibit pathogenic potential under certain circumstances.

[0004] Abnormalities in the scalp's metabolic processes, such as excessive oil secretion leading to the overgrowth of Malassezia (a lipophilic fungus), can cause an imbalance in the skin's microbiome, severely weakening the scalp's protective barrier. This can trigger rapid keratinocyte shedding and the development of visible dandruff. In addition to Malassezia, other common lipophilic microorganisms on the skin include Propionibacterium acnes. Because they cannot synthesize fatty acids themselves, they prefer to inhabit areas of the skin's surface where sebaceous glands are active. They break down triglycerides and esters secreted by hair follicles into monoglycerides and free fatty acids, including oleic acid. These free fatty acids can cause skin irritation, and scalp inflammation can trigger abnormal proliferation of keratinocytes, ultimately leading to dandruff. Furthermore, in an oxygen-deficient environment, Propionibacterium acnes can rapidly grow and multiply. They secrete lipases to break down sebum, generating free acids that irritate hair follicles, triggering an inflammatory response and ultimately damaging or even rupturing the follicle wall. Subsequently, the accumulated sebum will penetrate into the dermis, causing an inflammatory response around the hair follicles to varying degrees, thereby inducing acne.

[0005] Currently, natural plant extracts and synthetic compounds are widely used to treat skin diseases such as dandruff and acne by inhibiting the growth of Malassezia and Propionibacterium acnes. Schmidt et al. (In vitro susceptibility of Malasseziafurfur. Arzneimittelforschung. 1996 Apr; 46(4):442-444) tested the antifungal activity of several antidandruff agents against Malassezia furfur and found the ranking was: climbazole > zinc pyrithione > selenium disulfide > piroctone olamine. However, climbazole has varying degrees of toxicity to aquatic organisms through food chain transmission and bioaccumulation. Furthermore, zinc pyrithione (ZPT) is a highly effective broad-spectrum biocide. However, recent studies have shown that it is a potentially harmful substance that can easily induce allergic contact dermatitis in humans and teratogenicity in fish. Xia Mingjing et al. (Inhibitory effects of 22 antibacterial and anti-inflammatory traditional Chinese medicine active ingredients on Propionibacterium acnes [J]. Chinese Journal of Dermatology, 2001, Vol. 6) found that extracts of various traditional Chinese medicine ingredients (such as baicalin, gentiopicroside, tanshinone, and aloin) significantly inhibited the growth of P. acnes. However, natural plant extracts are complex, and the composition and concentration of extracts may vary between batches, making quality control difficult. Furthermore, some natural plant extracts may degrade during storage and use, potentially rendering them less effective than synthetic antimicrobial agents. Therefore, there is an urgent need to identify highly effective, stable, safe, environmentally friendly, and inexpensive compounds.

[0006] Decyl oxazolidinone has a significant inhibitory effect on a variety of bacteria, including common Gram-positive and Gram-negative bacteria, and has potential application value in the cosmetics industry. For example, Chinese invention patent application CN114272175A discloses a mild shampoo in which lauryl pyridinium nitride and decyl oxazolidinone act as antipruritic agents, effectively reducing discomfort symptoms and postoperative discomfort in hair transplant patients, and increasing their postoperative comfort. Chinese invention patent application CN111888271A discloses a powder-based and liquid-based composite shampoo, its preparation method, and its use method. The powder base includes sodium cocoyl isethionate, disodium lauryl sulfosuccinate, dipotassium glycyrrhizate, betaine, niacinamide, arginine, and sodium lauroyl glutamate. The liquid base includes: Cocamidopropyl Betaine, Cocamidomethyl MEA, Sodium Lauroyl Sarcosinate, Sodium Methyl Cocoyl Taurate, PEG-7 Glyceryl Cocoate, Glycerin, Propylene Glycol, Sodium Lactate, Hydrolyzed Corn Starch, Sodium Cocamidopropyl PG-Dimonium Chloride Phosphate, Linoleamidopropyl PG-Dimonium Chloride Phosphate, Polyquaternium-10, Lauryl Pyridinium Chloride, C12-13 Alkyl Lactate, Decyl Oxazolidinone, Piroctone Olamine. This shampoo has anti-dandruff and anti-allergic effects, regulates hair moisture, softens hair, and improves wet and dry combing properties.

[0007] Scientists at Harvard Medical School in the United States have confirmed that Staphylococcus aureus can directly act on nerve cells, causing itching. In addition, the study also pointed out that fungi (Malassezia) and viruses and other microorganisms may also be related to itching. Itching relief is closely related to inhibiting the infection of these microorganisms.

[0008] Some antibacterial oxazolidinones can treat, prevent, or reduce the risk of skin infections. For example, Chinese invention patent CA2900372A1 and US invention patent US10471046B2 disclose that N-[3-(3-fluoro-4-morpholin-4-ylphenyl)-2-oxo-5-oxazolidinyl]acetamide (linezolid) and N-[[(5S)-3-[3-fluoro-4-[4-[(2H-tetrazol-4-ylmethylamino)methyl]phenyl]phenyl]-2-oxo-5-oxazolidinyl]methyl]acetamide can effectively treat localized microbial infections, such as Propionibacterium acnes and Malassezia fungi.

[0009] However, current studies have not yet found the role of alkyl oxazolidinones in controlling the growth of lipophilic microorganisms (such as Malassezia furfur and Propionibacterium acnes), nor have they studied the effects of cosmetics containing alkyl oxazolidinones in treating skin diseases such as dandruff and acne. Summary of the Invention

[0010] The present invention addresses the problems existing in the prior art and provides the use of alkyl oxazolidinones in regulating skin microbial flora and products containing alkyl oxazolidinones. The present invention finds that alkyl oxazolidinones, such as C8-C14 alkyl oxazolidinones, and particularly decyl oxazolidinones, can effectively inhibit the growth of skin microbial flora, such as Malassezia furfur and Propionibacterium acnes. These alkyl oxazolidinones have broad applications in medications for treating and / or preventing skin diseases caused by imbalanced skin microbial flora, or in products for treating corresponding skin problems, such as anti-dandruff, anti-itching, and acne-relief products.

[0011] The technical solutions of the present invention are as follows: The present invention provides use of alkyl oxazolidinone in preparing a product for regulating skin microbial flora.

[0012] Preferably, the alkyl oxazolidinone is a C8-14 alkyl oxazolidinone, and the general structural formula is as follows:

[0013] In the formula, R is a C8-14 alkyl group.

[0014] Preferably, R is a C8-12 alkyl group.

[0015] More preferably, R is a C10 or C12 alkyl group, and the structural formula is as follows:

[0016] Decyl oxazolidinone (corresponding to R being a C10 alkyl group)

[0017] Dodecane oxazolidinone (corresponding to R being a C12 alkyl group).

[0018] Furthermore, the microbial flora is Malassezia furfur / Pityrosporum orbiculare and / or Propionibacterium acnes.

[0019] The present invention also provides the use of alkyl oxazolidinone in preparing anti-dandruff, antipruritic, soothing, oil-controlling and / or anti-acne products.

[0020] Furthermore, the product is any one of a skin care product, a hair care product or a toiletries product.

[0021] Furthermore, the skin care product is any one of essence water, lotion, face cream, eye cream, facial mask and body lotion.

[0022] Furthermore, the hair care product is any one of shampoo and conditioner.

[0023] Furthermore, the toiletries are shower gels.

[0024] The present invention also provides use of alkyl oxazolidinone in preparing a drug for treating and / or preventing skin diseases caused by an imbalance of skin microbial flora.

[0025] Furthermore, the skin disease includes any one of folliculitis, solar dermatitis, seborrheic dermatitis, atopic dermatitis and acne.

[0026] The present invention also provides a composition containing alkyl oxazolidinone, which comprises alkyl oxazolidinone and one or more of sodium benzoate, phenoxyethanol and a cationic polymer.

[0027] Furthermore, the cationic polymer is selected from one or more of polyquaternium-7, polyquaternium-10 and guar hydroxypropyltrimonium chloride.

[0028] Furthermore, the composition comprises, by weight percentage, 0.1-1% of alkyl oxazolidinone, 0.1-0.5% of lactic acid, 0.1-0.4% of asparagus root extract, 0.2-0.5% of schizonepeta tenuifolia extract, 0.3-0.8% of gentian root extract, and 0.1%-0.3% of shea butter.

[0029] The present invention also provides a shampoo containing alkyl oxazolidinone, which comprises the above composition and auxiliary materials acceptable in hair cosmetics.

[0030] Furthermore, the amount of the alkyl oxazolidinone in the shampoo is 0.1-1 wt %.

[0031] In some specific embodiments of the present invention, the shampoo is composed of the following raw materials in terms of mass percentage: Phase A: 15%-17% Sodium Laureth Sulfate, 1.5%-2% Sodium Lauroamphoacetate, 0.5%-0.7% Cocamide DMA, 0.2%-0.5% Cocamide MEA, 0.5%-0.8% PEG-120 Methyl Glucose Dioleate, 0.05%-0.1% Polyquaternium-10, 0.2-0.3% Polyquaternium-7, and 5-10% Deionized Water; Phase B: 0.05-0.1% guar hydroxypropyltrimonium chloride and 1-5% balance deionized water; Phase C: 0.1%-0.3% glycerin, 0.3%-0.6% PEG-7 glyceryl cocoate, 0.2%-0.4% citric acid, 0.8%-1% sodium chloride, 0.1%-1% alkyl oxazolidinone, 0.3%-0.5% sodium benzoate, 0.3%-0.5% phenoxyethanol and the balance deionized water.

[0032] The present invention also provides another composition containing alkyl oxazolidinone, which comprises alkyl oxazolidinone and one or more of lactic acid, asparagus root extract, spilanthus extract, gentian root extract and shea butter.

[0033] The present invention also provides an emulsion, which comprises the alkyl oxazolidinone and further comprises: one or more of lactic acid, asparagus root extract, spilanthus extract, gentian root extract and shea butter; and cosmetically acceptable auxiliary materials.

[0034] Furthermore, the amount of the alkyl oxazolidinone in the emulsion is 0.1-1 wt %.

[0035] In some specific embodiments of the present invention, the emulsion is composed of the following raw materials in terms of mass percentage: 0.1%-0.5% lactic acid, 0.1%-0.4% asparagus root extract, 0.2-0.5% schisandra chinensis extract, 0.3%-0.8% gentiana root extract, 0.1%-0.3% shea butter, 0.4%-0.6% polysorbate 20, 0.2%-0.5% polysorbate 60, 0.1%-0.3% sorbitan stearate, 0.5%-2% glycerin, 0.5%-0.8% ethylhexyl palmitate, 0.2%-0.4% triethanolamine, 0.2%-0.4% carbomer, 1.5%-2% cetyl alcohol, 0.3%-0.5% vitamin E, 0.1-1% alkyl oxazolidinone and the balance deionized water.

[0036] Compared with the prior art, the present invention has the following beneficial effects: This invention clarifies the specific uses of alkyl oxazolidinones in microbial regulation, particularly their ability to inhibit Malassezia furfur and Propionibacterium acnes. These effects are significantly superior to other antibacterial oxazolidinone compounds known in the prior art. The invention also demonstrates their specific applications in products for dandruff removal, itching relief, soothing (improving skin allergies or redness, relieving skin inflammation, etc.), oil control, and acne treatment. Furthermore, the invention indicates that alkyl oxazolidinones, particularly C8-C14 alkyl-substituted oxazolidinones, are particularly effective in inhibiting Malassezia furfur and Propionibacterium acnes, and are expected to have potential applications in the preparation of treatments and / or prevention products for skin diseases caused by imbalances in the skin microbiome, such as folliculitis, photodermatosis, seborrheic dermatitis, atopic dermatitis, and acne, thus expanding the uses of alkyl oxazolidinones. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 The inhibition zone results of the blank control group, the positive control group, and the sample group containing 1% of each alkyl oxazolidinone against Malassezia furfur in Application Example 1 are shown; Figure 2These are the inhibition zone results of the blank control group, positive control group, and sample group containing 1% alkyl oxazolidinone against Propionibacterium acnes in Application Example 1. DETAILED DESCRIPTION

[0038] In order to make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the embodiments described are part of the embodiments of the present invention, rather than all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention. It is worth noting that the raw materials used in the present invention are all common commercially available products, and their sources are not specifically limited.

[0039] Example 1 This embodiment provides a shampoo containing an alkyl oxazolidinone, which is composed of the following raw materials in percentage by mass: Phase A: 16% sodium laureth sulfate, 2% sodium lauroamphoacetate, 0.6% cocamide DMA, 0.5% cocamide MEA, 0.5% PEG-120 methyl glucose dioleate, 0.1% polyquaternium-10, 0.2% polyquaternium-7, and 10% deionized water; Phase B: 0.1% guar hydroxypropyltrimonium chloride and 1% deionized water; Phase C: 0.2% glycerin, 0.5% PEG-7 glyceryl cocoate, 0.3% citric acid, 0.8% sodium chloride, 0.1-1% antibacterial active ingredients, 0.5% sodium benzoate, 0.5% phenoxyethanol and the balance deionized water.

[0040] Among them, Shampoo 1 does not contain antibacterial active ingredients, Shampoo 2 contains 1% ZPT (zinc pyrithione) as the antibacterial active ingredient; Shampoos 3-26 contain linear hexyl oxazolidinone, linear octyl oxazolidinone, linear decyl oxazolidinone, branched decyl oxazolidinone, n-dodecyl oxazolidinone, n-tetradecyl oxazolidinone, n-pentadecanoxilide, and N-[3-(3-fluoro-4-morpholin-4-phenyl)-2-oxo-5-oxazolidinyl]acetamide (linezolid) at concentrations of 0.1%, 0.3%, and 1%, respectively.

[0041] The preparation method of shampoo is as follows: 1) Heat phase A to 80-85 degrees Celsius and stir evenly. Keep warm for an appropriate time until the solution is uniform, then cool to 60 degrees Celsius.

[0042] 2) Heat phase B to 60 degrees Celsius with cold water and disperse it, then add it to phase A. Keep warm and stir until the solution is uniform.

[0043] 3) Cool down to 45 degrees Celsius again, add phase C and stir until uniform.

[0044] Effect Example 1: In vitro inhibition zone method to verify the antibacterial effect on lipophilic skin microorganisms (1) Experimental preparation: Preparation of solid culture medium for Malassezia furfur: Weigh 48 g of malt extract agar, 20 g of ox bile powder, 10 g of Tween-40, 2.5 g of glycerol monooleate, and 0.5 g of agar, dissolve them in 1000 mL of distilled water, and sterilize them by high-pressure steam at 121°C for 15 min.

[0045] Preparation of solid culture medium for Propionibacterium acnes: Weigh 10 g of peptone, 10 g of beef powder, 3 g of yeast powder, 5 g of glucose, 1 g of soluble starch, 5 g of sodium chloride, 3 g of sodium acetate, 0.5 g of L-cysteine ​​hydrochloride, and 0.5 g of agar in 1000 mL of distilled water, adjust the pH to 6.7-6.9, and sterilize by high-pressure steam at 121°C for 15 min.

[0046] (2) Microbial activation and cultivation: Activation and culture of Malassezia furfur: The strain of Malassezia furfur was inoculated into solid culture medium and activated for 48 hours. Then, a single colony was isolated by the plate streak method. A single colony was picked with an inoculation loop and inoculated into liquid culture medium, which was incubated at a constant temperature of 30°C for 24 hours.

[0047] Activation and culture of Propionibacterium acnes: Inoculate the strain of Propionibacterium acnes onto a blood agar plate, place it in an anaerobic bag, and then place it in a constant temperature bacterial incubator for anaerobism at 37°C for 48 hours. Pick out a single colony and inoculate it into liquid culture medium. Place the test tube again in an anaerobic bag and place it in a constant temperature incubator at 37°C for 48 hours.

[0048] (3) Verification of antibacterial effect: The in vitro antibacterial activity test was carried out using the Oxford cup method. 100 μL of activated bacteria with a concentration of 5×10 7 CFU / mL of Malassezia furfur and a concentration of 1×10 7 CFU / mL of Propionibacterium acnes suspension was evenly applied with an applicator, and the sterile Oxford cup was gently placed into the culture dish with tweezers. The Oxford cup was gently pressed with tweezers to make it fit better with the culture medium.

[0049] The above-mentioned Malassezia furfur culture medium and Propionibacterium acnes culture medium were randomly divided into 29 groups, namely blank control group (added with shampoo 1), positive control group (added with shampoo 2), and sample groups 1-24 (added with shampoo 3-26), with the addition amount of 200 μL. Malassezia furfur was cultured in a 30°C biochemical incubator for 24 hours and the results were observed; Propionibacterium acnes was placed in an anaerobic bag and cultured in a 37°C constant temperature incubator for 48 hours and the results were observed. The diameter of the inhibition zone was measured with a vernier caliper (unit: millimeter; mm) and recorded. The experiment was repeated 3 times and the average value was taken. The results are shown in Table 1; the photos of the inhibition zones of the blank control group (shampoo 1), positive control group (shampoo 2), and sample groups containing 1% of each alkyl oxazolidinone (shampoo 19-26) against Malassezia furfur and Propionibacterium acnes are shown in Table 1. Figure 1 and Figure 2 .

[0050] Table 1 Antibacterial effects of shampoos containing different antibacterial active ingredients

[0051] By analyzing Table 1 and Figure 1 The inhibition zone data results of Malassezia furfur show that: no inhibition zone was produced in the blank control group, and the average diameter of the inhibition zone of the positive control was 29.3 mm, indicating that the test data is reliable and valid.

[0052] For oxazolidinones with different alkyl substituents, the diameter of the inhibition zone of C8-14 alkyl oxazolidinones is greater than 15 mm in the concentration range of 0.1-1%, and they are moderately sensitive to Malassezia furfur. Decyl oxazolidinone has the best effect, followed by C8, C12, and C14 alkyl oxazolidinones. In addition, the C8-C14 alkyl oxazolidinones of the present invention are also far superior to the oxazolidinone drugs disclosed in the prior art, such as linezolid, in their ability to inhibit Malassezia furfur. It can be seen that shampoo containing 0.1-1% decyl oxazolidinone can effectively inhibit the growth of Malassezia furfur and has potential anti-dandruff efficacy. Moreover, the shampoo sample containing 1% decyl oxazolidinone has a better inhibitory effect on Malassezia furfur than 1% ZPT.

[0053] By analyzing Table 1 and Figure 2 The inhibition zone data results of Propionibacterium acnes show that: no inhibition zone was produced in the blank control group, and the average diameter of the inhibition zone of the positive control was 22.5 mm, indicating that the test data is reliable and valid.

[0054] For oxazolidinones with different alkyl substituents, C8-14 alkyl oxazolidinones were all greater than 15 mm and were moderately or highly sensitive to P. acnes, with decyl oxazolidinone having the best effect, followed by C8, C12, and C14 straight-chain alkyl oxazolidinones. In addition, the C8-C14 alkyl oxazolidinones of the present invention also showed far superior inhibitory effects on P. acnes than oxazolidinone drugs disclosed in the prior art, such as linezolid. Thus, shampoos containing 0.1-1% decyl oxazolidinone can effectively inhibit the growth of P. acnes and have potential acne-removing effects. Moreover, shampoo samples containing 1% decyl oxazolidinone showed better inhibitory effects on P. acnes than 1% ZPT.

[0055] Effect Example 2: Anti-dandruff Performance Test of Shampoo Containing Alkyl Oxazolidinone 240 volunteers aged 20-45 with dandruff and flat hair were divided into 6 groups, 40 in each group. They used shampoo 15-20 once every two days (without using any other related functional products during this period). After 28 days, each volunteer was surveyed on their usage and their feedback on product safety and anti-dandruff efficacy was recorded. The anti-dandruff efficacy evaluation criteria are as follows: Very effective: The anti-dandruff effect is very good, dandruff is significantly reduced, and the hair is refreshed and fluffy; Effective: It has a certain anti-dandruff effect and reduces dandruff to some extent; Ineffective: No change before and after use; Effectiveness = (number of very effective people + number of effective people) / total number of people × 100%.

[0056] The anti-dandruff effects of shampoos containing different alkyl oxazolidinones were analyzed, as shown in Table 2.

[0057] Table 2 Evaluation results of anti-dandruff effects of shampoos containing different alkyl oxazolidinones

[0058] Analysis of the data in Table 2 shows that the shampoos containing C8-14 alkyl oxazolidinone (Shampoos 20-24) all exhibited an anti-dandruff efficacy exceeding 70%, with decyl oxazolidinone, particularly linear decyl oxazolidinone, exhibiting an even higher efficacy. This indicates that shampoos containing 1% C8-14 alkyl oxazolidinone have a strong anti-dandruff effect on hair, helping to maintain a clean and healthy scalp.

[0059] Example 2 This embodiment provides an anti-acne lotion containing an alkyl oxazolidinone composition, which is composed of the following raw materials in percentage by mass: Phase A: 1% glycerol, 0.2% carbomer, and the balance deionized water; Phase B: 0.5% polysorbate 20, 0.5% polysorbate 60, 0.2% sorbitan stearate, 0.5% ethylhexyl palmitate, 2% cetyl alcohol, 0.5% vitamin E; Phase C: 0.2% triethanolamine; Phase D: 0.1%-1% alkyl oxazolidinone and a combination of plant extracts (0.5% lactic acid, 0.4% asparagus root extract, 0.5% spilanthus extract, 0.48% gentiana root extract, and 0.1% shea butter).

[0060] Among them, anti-acne lotion 1: Phase D was replaced with an equal amount of deionized water; Anti-Acne Lotion 2: Phase D contains only 0.1% decyl oxazolidinone; Anti-Acne Lotion 3: Phase D contains only 1% decyl oxazolidinone; Anti-acne Lotion 4: Phase D contains only 0.5% lactic acid, 0.1% asparagus root extract, 0.5% schizonepeta tenuifolia extract, 0.5% gentiana root extract, and 0.1% shea butter; Anti-acne Lotion 5-16: The alkyl oxazolidinones in phase D are 0.1% and 1% of hexyl oxazolidinone, octyl oxazolidinone, decyl oxazolidinone, dodecyl oxazolidinone, tetradecyl oxazolidinone, and N-[3-(3-fluoro-4-morpholin-4-phenyl)-2-oxo-5-oxazolidinyl]acetamide (linezolid), respectively.

[0061] The preparation method is as follows: (1) Weigh the raw materials of phase A into containers in sequence and heat them in a water bath at 80-85°C for 30 minutes for later use; weigh the raw materials of phase B into containers in sequence and heat them in a water bath at 80-85°C for 30 minutes for later use; (2) Add phase B to phase A and homogenize for 5-10 minutes, stir and cool down, add phase C raw materials at 60℃, stir evenly, and continue to cool down; (3) Add Phase D raw materials at room temperature, homogenize for 5-10 minutes, and stir for 5-10 minutes.

[0062] Effect Example 3: In vitro verification of the soothing effect of an acne-removing lotion containing alkyl oxazolidinone Zebrafish testing: Broodstock should be free of visible signs of infection or disease and should not have been treated with medication within the past two months. Broodstock should be wild-type AB strain zebrafish aged 6-12 months. Broodstock should be acclimated for at least 14 days after introduction to the laboratory before spawning testing.

[0063] Zebrafish farming: Zebrafish should be kept in a water temperature of 26°C-28.5°C, with a density of 1-2 fish per liter of water and a consistent daily light intensity of 12-16 hours. Feed at least twice daily, including at least one with brine shrimp larvae, with an interval of at least three hours between feedings to avoid overfeeding that could affect water quality.

[0064] Zebrafish Spawning: Collecting Eggs in a Zebrafish Tank: Place the egg collection box in the aquarium before lights out the day before spawning or before lights on the day of spawning. Cover the egg collection box with an inert net to prevent adult fish from ingesting the eggs. Mating, fertilization, and spawning are completed within approximately 30 minutes of turning on the lights, at which point the egg collection box should be removed from the aquarium. After removing the eggs from the egg collection box, clean the embryos with zebrafish embryo culture medium. Observe and select healthy zebrafish embryos under a stereomicroscope and culture at a density of no more than one embryo per 200 μL of zebrafish embryo culture medium at 28°C ± 1°C until three days post-fertilization.

[0065] Drug treatment of zebrafish embryos: Zebrafish embryos were randomly selected and placed in a 6-well plate, with 20 embryos per well. The blank control group was added with 5 mL of fish embryo culture medium, the model control group was added with 5 mL of fish embryo culture medium containing 10 µM anhydrous copper sulfate, the positive control group was added with 5 mL of fish embryo culture medium containing 10 µM anhydrous copper sulfate and 10 µM indomethacin, and the sample treatment groups 1-16 were added with 5 mL of 10 µM anhydrous copper sulfate and acne lotion 1-16 (acne lotion was diluted with fish embryo culture medium to a concentration of 2%). Three replicate wells were set up for each group and the cells were placed in a constant temperature incubator at 28°C ± 1°C and cultured for 40 to 45 minutes.

[0066] Zebrafish embryo staining and observation: After fixing embryos in paraformaldehyde for at least 1 hour, each test group was treated with PBST three times for 5 minutes each, followed by treatment with 50% ethanol for 3 minutes. The embryos were stained with Sudan Black staining solution at room temperature for 1 hour, then rinsed four times with 70% ethanol for 5 minutes each, followed by treatment with PBST twice for 5 minutes each. The embryos were then treated with bleach solution (a mixture of phosphate buffered saline with 0.1% Tween-20, 1% hydrogen peroxide, and 5% formamide) for 10 minutes, with the lid open. The fish were then treated with 70% ethanol for 5 minutes, PBST for 1 minute, Permeabilization Solution 1 (a mixture of phosphate buffered saline with 0.1% Tween-20, containing 50% glycerol and 0.1% Triton X-100) for 15 minutes, Permeabilization Solution 2 (a mixture of phosphate buffered saline with 0.1% Tween-20, containing 80% glycerol and 0.1% Triton X-100) for 10 minutes, and PBST for 3 minutes. The fish embryos were placed sideways, and their tails were photographed under a stereomicroscope.

[0067] Formula for calculating neutrophil aggregation inhibition rate: Inhibition rate = (MT) / M × 100% Where: T is the average number of neutrophils in zebrafish embryos in the sample treatment group or the positive control group; M is the average number of neutrophils in zebrafish embryos in the model control group.

[0068] Table 3 Number of centrosomes in zebrafish embryos

[0069] Note: Compared with the blank group, ### p <0.001. Compared with the model group, *** p <0.001, ** p <0.01, * p <0.05, NS express p >0.05. / indicates no addition, √ indicates addition.

[0070] By analyzing the data in Table 3, it can be seen that compared with the blank group, the number of neutrophils in the zebrafish embryos in the model group was significantly increased, indicating that the model for zebrafish soothing efficacy testing has been successfully constructed.

[0071] In the acne-removing lotion containing 0.1% alkyl oxazolidinone, the inhibition rate of neutrophils of C8-14 alkyl oxazolidinone was above 20%, among which decyl oxazolidinone, especially straight-chain decyl oxazolidinone, had the best effect, which was significantly different from the model group ( p <0.001), with a significant soothing effect; the alkyl oxazolidinone content in the anti-acne lotion was increased to 1%, and the neutrophil inhibition rate was further increased, and the soothing effect was enhanced.

[0072] Meanwhile, the acne-removing lotions 2 and 3, which only contain decyl oxazolidinone but not the plant extract combination, have a higher neutrophil inhibition rate than the positive control group. This shows that the alkyl oxazolidinone of the present invention, especially decyl oxazolidinone, has a significant inhibitory effect on neutrophils and has a significant soothing effect.

[0073] In addition, compared with Anti-Acne Lotions 2, 4, and 7, Anti-Acne Lotion 2 only contains alkyl oxazolidinone but does not contain a combination of plant extracts (0.5% lactic acid, 0.4% asparagus root extract, 0.5% schizonepeta tenuifolia extract, and 0.8% gentian root extract), and Anti-Acne Lotion 4 only contains a combination of plant extracts but does not contain alkyl oxazolidinone. Although they have a certain soothing effect, they are all different from Anti-Acne Lotion 7. It can be seen that the combination of alkyl oxazolidinone and plant extracts has a significant synergistic effect in inhibiting neutrophils.

[0074] The same trend was shown when comparing acne-removing lotions 3, 4, and 13, which further verified the above conclusion.

[0075] Effect Example 4: Verification of the Soothing and Oil Control Efficacy of Acne-Removing Lotion Volunteer enrollment: 297 volunteers were screened and had no adverse reactions to the skin after the patch test. They had sensitive skin (lactic acid stinging score ≥3), oily skin, and forehead oil content >120 μg / cm 2 Healthy volunteers with red facial skin were randomly divided into nine groups, each consisting of 33 participants (data before washing their faces). There were no significant differences in indicators such as lactic acid stinging scores and forehead oil content between the groups. All volunteers voluntarily participated in the trial and signed written informed consent, promising to strictly adhere to the trial protocol unless there were special circumstances.

[0076] Test type: single-blind, randomized, before-after control.

[0077] Usage: After cleansing your face in the morning and evening, take 2 grams of the anti-acne lotion 1, 3, 4, 11-16 provided in Example 2 of the present invention, apply it evenly to the facial skin, and massage in circles until it is completely absorbed (do not use any other products with related functions during this period).

[0078] Instrumental testing: Before the test (D0), staff used VISIA7 and PRIMOS CR to capture facial skin images of the volunteers and counted the number of porphyrins and red area. A Sebumeter SM815 sebum meter was used to measure skin oil content, and a Colorimeter CL400 skin color (red-green) a* values ​​were measured. Fourteen days after the test (D14), the same staff again captured facial skin images of the volunteers using the aforementioned instruments and calculated the aforementioned parameters.

[0079] Data analysis: 1) Normal distribution test: IBM SPSS Statistic 26.0 software was used for analysis, and the Shapiro-Wilks method was used to verify the normal distribution of the data. Normality test Asymptotic significance (two-sided) value p >0.05, the data series obeys the normal distribution. Otherwise, it does not obey the normal distribution. 2) Difference analysis: Perform difference analysis on the mean. When the two groups of data are both normally distributed, use the paired T test to analyze the difference between the two groups of data; when the two groups of data are not both normally distributed, use the Wilcoxon rank sum test to analyze the difference between the two groups of data. p When the value is <0.05, the data are statistically significant.

[0080] Evaluation basis: (1) Oil control efficacy: refer to "T / GDCDC-024-2022 Cosmetic Oil Control Efficacy Test Method" and "T / ZHCA002-2018 Cosmetic Oil Control Efficacy Test Method". At any visit time point before and after using the sample, the skin oil content or porphyrin count showed a significant decrease ( p <0.050), the test sample is considered to have oil control effect.

[0081] (2) Soothing effect: Referring to "T / BDCA 0005-2023 Cosmetic Soothing Efficacy Test: Human Lactic Acid Stinging Test Method" and "Comparison of Cosmetic Soothing Efficacy Evaluation Methods Based on Skin Color Analysis", the skin color (red-green) value a* value and red zone area of ​​sensitive skin subjects showed a significant decrease at any visit time point before and after the use of the sample ( p <0.050), the test sample is considered to have the effect of improving redness and soothing.

[0082] Table 4 Changes in lipid content and porphyrin counts in volunteers (mean ± SD)

[0083] Note: Compared with before use, *** p <0.001, ** p <0.01, * p <0.01.

[0084] Table 5 Changes in skin color a* values ​​and red zone areas of volunteers (mean ± SD)

[0085] Note: Compared with before use, *** p <0.001, ** p <0.01, * p <0.01.

[0086] The results show that compared with the 0.1% concentration, the 1% concentration of C8-14 alkyl oxazolidinone composition acne lotion has better soothing effect and can continue human efficacy testing.

[0087] By analyzing the data in Table 4 and Table 5, it can be seen that after using the anti-acne lotions 3 and 13 of the present invention, the oil content, the number of porphyrins (the number of porphyrins was also significantly reduced, indicating that the number of Propionibacterium acnes that produces endogenous porphyrins was significantly reduced), the red zone a* value and the red zone area were significantly reduced ( p<0.001), indicating that the anti-acne lotions containing 1% linear decyl oxazolidinone and the combination of 1% linear decyl oxazolidinone and plant extracts have oil control, redness improvement, and soothing effects; Lotions 12, 14, and 15 are second best; and anti-acne lotions 4, 11, and 20 are slightly worse. It can be seen that the C6-14 alkyl oxazolidinones of the present invention all have good oil control, redness improvement, and soothing effects, preferably C8-14 alkyl oxazolidinones, and more preferably C10 alkyl oxazolidinones (decyl oxazolidinone).

[0088] In addition, compared with acne lotions 3, 4, and 13, the combination of alkyl oxazolidinone and plant extracts also revealed a significant synergistic effect in oil control, redness improvement, and soothing.

[0089] Effect Example 5: Verification of the Anti-Acne Efficacy of Anti-Acne Lotion on Human Body Volunteer Enrollment: 270 healthy volunteers with no adverse skin reactions after patch testing, facial acne, and acne grade 1-2 as assessed by a clinician were screened. All volunteers voluntarily participated in the trial and signed a written informed consent form, promising to strictly adhere to the trial protocol unless there were special circumstances.

[0090] Test type: single-blind, randomized, before-after control.

[0091] Usage: After cleansing your face in the morning and evening, take 2 grams of the anti-acne lotion 1, 3, 4, 11-16 provided in Example 2, apply evenly to the facial skin, and massage in circular motions until completely absorbed.

[0092] Instrumental Testing: Before testing (D0), staff used VISIA7 and PRIMOS CR to image the volunteers' facial skin and counted the volume of acne. Dermatologists assessed the number of acne spots on the volunteers' faces. After testing (D14), the same staff used the aforementioned instruments to image the volunteers' facial skin again and calculate the aforementioned parameters.

[0093] Data analysis: The data statistical analysis method is the same as that in Example 5.

[0094] Evaluation basis: Reference to "T / CNMIA 0012-2020 Clinical Evaluation Standards for Acne-Removing Functional Skin Care Products". At any visit time point before and after using the sample, the number, volume or height of acne showed a significant decrease ( p <0.050), the test sample is considered to have acne-removing efficacy.

[0095] Table 6 Changes in the number and volume of acne in volunteers (mean ± SD)

[0096] Note: Compared with before use, ***p <0.001, ** p <0.01, * p <0.01.

[0097] By analyzing the data in Table 6, it can be seen that after using the anti-acne lotion 3 and 13 of the present invention, the number and volume of skin acne were significantly reduced compared with before use ( p <0.001), indicating that acne-removing lotions containing 1% decyl oxazolidinone and a combination of 1% decyl oxazolidinone and plant extracts have acne-removing efficacy. Furthermore, compared to acne-removing lotion 3, acne-removing lotion 13 was more effective in reducing the number and volume of acne. This indicates that, at the same concentration of decyl oxazolidinone, the acne-removing lotion containing 0.5% lactic acid, 0.4% asparagus root extract, 0.5% spilanthus extract, and 0.8% gentian root extract exhibited greater acne-removing efficacy. Emulsions 12, 14, and 15 performed second best, while acne-removing lotions 4, 11, and 16 performed slightly worse. This indicates that all C6-14 alkyl oxazolidinones of the present invention exhibited good acne-removing efficacy, with C8-14 alkyl oxazolidinones being preferred, and C10 alkyl oxazolidinones being even more preferred.

[0098] In addition, compared with Anti-Acne Lotions 3, 4, and 13, the acne removal effect of Anti-Acne Lotion 13 is also better than that of Anti-Acne Lotions 3 and 4, indicating that in terms of acne removal, the combination of alkyl oxazolidinone and plant extracts also has a significant synergistic effect.

[0099] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. Use of alkyl oxazolidinone in the preparation of products for regulating skin microbial flora.

2. The use according to claim 1, characterized in that The alkyl oxazolidinone is a C8-14 alkyl substituted oxazolidinone, preferably a C8-12 alkyl substituted oxazolidinone, and more preferably a decyl oxazolidinone.

3. The use according to claim 1, characterized in that The microbial flora is Malassezia furfur and / or Propionibacterium acnes.

4. Use of alkyl oxazolidinone in the preparation of anti-dandruff, antipruritic, soothing, oil-control and / or acne-removing products.

5. The use according to any one of claims 1 to 4, characterized in that The product is any one of skin care products, hair care products or toiletries; the skin care product is any one of essence water, lotion, face cream, eye cream, face mask and body lotion; the hair care product is any one of shampoo and conditioner; the toiletries are shower gel.

6. Use of an alkyl oxazolidinone in the preparation of a medicament for treating and / or preventing skin diseases caused by an imbalance of skin microbial flora, characterized in that: The skin disease includes any one of folliculitis, solar dermatitis, seborrheic dermatitis, atopic dermatitis and acne.

7. A composition containing an alkyl oxazolidinone, characterized in that The composition includes alkyl oxazolidinone and one or more of sodium benzoate, phenoxyethanol and a cationic polymer; the cationic polymer is selected from one or more of polyquaternium-7, polyquaternium-10 and guar hydroxypropyltrimonium chloride.

8. A shampoo containing an alkyl oxazolidinone, characterized in that: The shampoo comprises the composition according to claim 7 and excipients acceptable for hair cosmetics; preferably, the amount of the alkyl oxazolidinone in the shampoo is 0.1-1 wt %.

9. A composition containing an alkyl oxazolidinone, characterized in that The composition comprises an alkyl oxazolidinone and further comprises one or more of lactic acid, asparagus root extract, spilanthus chrysantha extract, gentian root extract and shea butter.

10. An emulsion, characterized in that The emulsion comprises the composition according to claim 9 and cosmetically acceptable excipients; preferably, the amount of the alkyl oxazolidinone in the emulsion is 0.1-1 wt%.

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