Use of alkyl oxazolidinones in modulating skin microbial flora and products containing alkyl oxazolidinones

Abstract

The present application belongs to the technical field of skin microbial regulation and daily chemical products, and relates to the use of alkyl oxazolidinone in regulating skin microbial flora and products containing alkyl oxazolidinone. It is found that alkyl oxazolidinone, especially C8-14 alkyl oxazolidinone, has a significant inhibitory effect on regulating skin microbial flora, especially on Pityrosporum ovale and Propionibacterium acnes, and has a wide application in the preparation of anti-dandruff and / or itching-relieving and soothing acne-removing products and the preparation of drugs for treating and / or preventing skin diseases caused by imbalance of skin microbial flora.

Description

Technical Field

[0001] This invention belongs to the field of skin microbiome regulation and daily chemical products technology, and relates to the use of alkyl oxazolidinones in regulating skin microbiome and products containing alkyl oxazolidinones. Background Technology

[0002] The skin barrier consists of four main components: microbial, chemical, physical, and immune. These components work together to maintain skin integrity. The skin microbiome, including bacteria such as Corynebacterium, Propionibacterium, and coagulase-negative Staphylococcus, fungi such as Malassezia, and viruses, is a significant contributor 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 secreted by sebaceous glands, such as triglycerides, wax esters, and squalene, along with sweat and epidermal lipids, form the sebum film, a crucial component of the skin microecology for colonization. Excessive sebum secretion and inflammatory responses of keratinocytes can disrupt the balance of the skin barrier and skin microecology, leading to changes in surface microorganisms. Clinical practice has validated the therapeutic effects of microbial regulation on various skin conditions, including photodermatitis, atopic dermatitis, seborrheic dermatitis, and dandruff.

[0003] The growth of skin microbes depends on nutrients and other molecules provided by host cells; therefore, the skin exhibits differences in microbial composition across different parts of the body. Lipophilic skin microbes, such as *Propionibacterium acnes* and *Malassezia*, are widely present on the human skin surface, especially in areas with high sebaceous gland secretion, such as the scalp, chest, back, head, face, and neck. They secrete lipases, hydrolyzing triglycerides in sebum into free fatty acids, maintaining a low pH value in the epidermis, thereby resisting the invasion of pathogenic microbes and coexisting with the host. Therefore, these lipophilic microbes do not exhibit pathogenicity under normal circumstances, but can show pathogenic potential under certain conditions.

[0004] When the scalp's metabolic processes become abnormal, such as excessive sebum secretion leading to the overgrowth of Malassezia (a lipophilic fungus), causing an imbalance in the skin's microbiome, the scalp's protective barrier is severely weakened. This induces excessive shedding of keratinocytes, resulting in a large amount of visible dandruff. Besides Malassezia, another common lipophilic microorganism on the skin is Propionibacterium acnes. Because it cannot synthesize fatty acids, it prefers to reside in areas of the skin surface where sebaceous glands are highly active. It can break down triglycerides and esters secreted by hair follicle glands 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 formation. On the other hand, in an oxygen-deficient environment, Propionibacterium acnes can rapidly grow and multiply. It secretes lipases to break down sebum, generating free acids. These free acids irritate hair follicles, triggering an inflammatory response, which can damage or even rupture the hair follicle wall. Subsequently, the accumulated sebum seeps into the dermis, triggering an inflammatory response around the hair follicles to varying degrees, thus inducing acne.

[0005] Currently, plant extracts from natural sources and synthetic compounds are commonly used to treat skin diseases such as dandruff and acne by inhibiting the growth of Malassezia and Propionibacterium acnes. A Schmidt et al. (In vitrosusceptibility of Malasseziafurfur. Arzneimittelforschung. 1996 Apr; 46(4):442-444) tested several anti-dandruff agents and ranked their antifungal activity against Malassezia furfur as follows: clomibazole > zinc pyrithione > selenium disulfide > piroctone olamine. However, clomibazole exhibits varying degrees of toxicity to aquatic organisms through food chain transmission and bioaccumulation. In addition, zinc pyrithione (ZPT) is a highly effective broad-spectrum biocidal agent, but recent studies have shown that it is a potentially harmful substance that can easily induce allergic contact dermatitis in humans and deformities in fish. Xia Mingjing et al. (Inhibitory effects of 22 effective components of antibacterial and anti-inflammatory traditional Chinese medicine on Propionibacterium acnes [J]. Chinese Journal of Dermatology, 2001, Vol. 6) found that extracts of various traditional Chinese medicine components (baicalin, gentiopicrin, tanshinone, aloe-emodin, etc.) significantly inhibited the growth of Propionibacterium acnes. However, natural plant extracts have complex compositions, and the composition and concentration of extracts from different batches may vary, leading to difficulties in quality control. In addition, some natural plant extracts may degrade during storage and use, resulting in effects that may not be as significant as those of synthetic antibacterial drugs. Therefore, there is an urgent need to find a highly efficient, stable, safe, environmentally friendly, and inexpensive compound.

[0006] Decyl oxazolidinone exhibits significant inhibitory effects on various 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 laurylpyridine nitrogen compound and decyl oxazolidinone act as antipruritic agents, effectively reducing discomfort symptoms in hair transplant patients, shortening the time of post-operative inconvenience, and increasing post-operative comfort. Chinese invention patent application CN111888271A discloses a powder-based liquid-based composite shampoo and its preparation and usage methods. The powder base includes: sodium cocoyl ethanesulfonate, disodium lauryl sulfosuccinate, dipotassium glycyrrhizate, betaine, nicotinamide, 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-dimethylammonium chloride phosphate, linoleamide-propyl PG-dimethylammonium chloride phosphate, polyquaternium-10, laurylpyridinium chloride, C12-13 alcohol lactate, decyl oxazolidinone, and piroctone ketone ethanolamine. This shampoo has anti-dandruff and anti-sensitivity effects, and regulates hair moisture, smoothness, and dry / wet combing ability.

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

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

[0009] However, current research has not yet found any role of alkyl oxazolidinones in controlling the growth of lipophilic microorganisms (such as Malassezia furfur and Propionibacterium acnes), nor has it found any research on the use of cosmetics containing alkyl oxazolidinones in treating skin diseases such as dandruff and acne. Summary of the Invention

[0010] This invention addresses the problems existing in the prior art by providing the use of alkyl oxazolidinones in regulating the skin microbiota and products containing alkyl oxazolidinones. This invention discovers that alkyl oxazolidinones, such as C8-C14 alkylalkyloxazolidinones, especially decyl oxazolidinones, can effectively inhibit the growth of skin microbiota such as Malassezia furfur and Propionibacterium acnes. They have wide applications in drugs for treating and / or preventing skin diseases caused by skin microbiota imbalance, or in products for treating skin problems such as dandruff and itch relief, and soothing acne treatments.

[0011] The technical solution of the present invention is as follows: This invention provides the use of alkyl oxazolidinones in the preparation of products that regulate the skin microbiome.

[0012] Preferably, the alkyloxazolidinone is a C8-14 alkyloxazolidinone with the following general structural formula:

[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, with the following structural formula:

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

[0017] Dodecaneoxazolidinone (corresponding to alkyl groups where R is C12).

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

[0019] This invention also provides the use of alkyl oxazolidinones in the preparation of anti-dandruff, antipruritic, soothing, oil-controlling and / or acne-removing products.

[0020] Furthermore, the product is any one of skin care products, hair care products, or shampoo and conditioner.

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

[0022] Furthermore, the hair product is either shampoo or conditioner.

[0023] Furthermore, the aforementioned personal care product is a shower gel.

[0024] The present invention also provides the use of alkyl oxazolidinones in the preparation of medicaments for the treatment and / or prevention of skin diseases caused by skin microbiome imbalance.

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

[0026] The present invention also provides a composition containing an alkyl oxazolidinone, the composition comprising an alkyl oxazolidinone, and further comprising 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 hydroxypropyltrimethylammonium chloride.

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

[0029] The present invention also provides a shampoo containing alkyl oxazolidinone, the shampoo comprising the above-described composition and hair care-acceptable excipients.

[0030] Furthermore, the amount of the alkyl oxazolidinone used 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 by weight percentage: Phase A: 15%-17% sodium lauryl ether sulfate, 1.5%-2% sodium lauroyl amphoteric acid, 0.5%-0.7% cocamide DMA, 0.2%-0.5% cocamide MEA, 0.5%-0.8% PEG-120 methyl gluconate 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 gum hydroxypropyltrimethylammonium chloride and 1-5% balance deionized water; Phase C: 0.1%-0.3% glycerol, 0.3%-0.6% PEG-7 glycerol 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, the composition comprising alkyl oxazolidinone, and further comprising one or more of the following: lactic acid, asparagus root extract, chrysanthemum extract, gentian root extract and shea butter.

[0033] The present invention also provides an emulsion comprising the above-mentioned alkyl oxazolidinone, and further comprising one or more of the following: lactic acid, asparagus root extract, chrysanthemum extract, gentian root extract and shea butter; and cosmetically acceptable excipients.

[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 by mass percentage: 0.1%-0.5% lactic acid, 0.1%-0.4% asparagus root extract, 0.2%-0.5% chamomile extract, 0.3%-0.8% gentian 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 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 inhibitory effects on Malassezia furfur and Propionibacterium acnes. The effects are significantly superior to other existing oxazolidinone compounds with antibacterial properties. Furthermore, its specific applications in products for dandruff control, antipruritic effects, soothing (improving skin allergies or redness, relieving skin inflammation, etc.), oil control, and acne treatment have been verified. In addition, it points out that alkyl oxazolidinones, especially C8-C14 alkyl-substituted oxazolidinones, are particularly effective in inhibiting Malassezia furfur and Propionibacterium acnes, and hold promise for applications in the preparation of treatments and / or preventions of skin diseases caused by imbalanced skin microbiota, such as folliculitis, photodermatitis, seborrheic dermatitis, atopic dermatitis, and acne, thus expanding the applications of alkyl oxazolidinones. Attached Figure Description

[0037] Figure 1 The results of inhibition zones against Malassezia furfur were obtained from the blank control group, positive control group, and sample groups containing 1% of each alkyl oxazolidinone in Example 1. Figure 2The results show the inhibition zones of Propionibacterium acnes in the blank control group, positive control group, and sample group containing 1% alkyl oxazolidinone in Example 1. Detailed Implementation

[0038] To make the objectives, 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 described embodiments are only a part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort 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 alkyl oxazolidinone, which is composed of the following raw materials by weight percentage: Phase A: 16% sodium lauryl ether sulfate, 2% sodium lauroyl amphoteric acid, 0.6% cocamide DMA, 0.5% cocamide MEA, 0.5% PEG-120 methyl glucoside, 0.1% polyquaternium-10, 0.2% polyquaternium-7 and 10% deionized water; Phase B: 0.1% guar gum hydroxypropyltrimethylammonium chloride and 1% deionized water; Phase C: 0.2% glycerol, 0.5% PEG-7 glyceryl cocoate, 0.3% citric acid, 0.8% sodium chloride, 0.1-1% antibacterial active ingredient, 0.5% sodium benzoate, 0.5% phenoxyethanol and balance deionized water.

[0040] Shampoo 1 contains no antibacterial active ingredients, while shampoo 2 contains 1% ZPT (zinc pyrithione); shampoos 3-26 contain 0.1%, 0.3%, and 1% of linear hexyl oxazolidinone, linear octyl oxazolidinone, linear decyl oxazolidinone, branched decyl oxazolidinone, dodecanoic oxazolidinone, tetradecanoic oxazolidinone, pentadecanoic oxazolidinone, and N-[3-(3-fluoro-4-morpholino-4-phenyl)-2-oxo-5-oxazolidinyl]acetamide (linezolid).

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

[0042] 2) First, heat phase B to 60 degrees Celsius with cold water to disperse it, then add it to phase A and keep it warm while stirring until the solution is homogeneous.

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

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

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

[0046] (2) Microbial activation and culture: Activation and culture of Malassezia furfur: Malassezia furfur strain was inoculated into solid culture medium and activated for 48 h. Then, single colonies were isolated by streak plating. Single colonies were picked up with an inoculation loop and inoculated into liquid culture medium and incubated at 30 ℃ for 24 h.

[0047] Activation and culture of Propionibacterium acnes: Propionibacterium acnes was inoculated onto blood agar plates, placed in an anaerobic bag, and then placed in a constant temperature bacterial incubator at 37 ℃ for anaerobic culture for 48 h. Single colonies were picked and inoculated onto liquid culture medium, and the test tubes were placed in an anaerobic bag again and incubated at 37 ℃ for 48 h.

[0048] (3) Verification of antibacterial effect: In vitro antibacterial activity was tested using the Oxford cup method. 100 μL of activated bacteria at a concentration of 5 × 10⁻⁶ was inoculated onto the surface of a solid culture medium plate containing *Malassezia furfur* and *Propionibacterium acnes*. 7 CFU / mL of Malassezia furfur and a concentration of 1×10 7 A CFU / mL suspension of Propionibacterium acnes was spread evenly using a spreader. A sterile Oxford cup was gently placed into the culture dish using tweezers, and the Oxford cup was gently pressed with the tweezers to ensure better contact with the culture medium.

[0049] The above-mentioned Malassezia furfur culture medium and Propionibacterium acnes culture medium were randomly divided into 29 groups: a blank control group (with shampoo 1 added), a positive control group (with shampoo 2 added), and sample groups 1-24 (with shampoo 3-26 added), with a volume of 200 μL for each group. Malassezia furfur was cultured in a 30 ℃ biochemical incubator for 24 h, and the results were observed. Propionibacterium acnes was placed in an anaerobic bag and cultured in a 37 ℃ constant temperature incubator for 48 h, and the results were observed. The diameter of the inhibition zone was measured (unit: mm) using calipers and recorded. The experiment was repeated three times, and the average value was taken. The results are shown in Table 1. The inhibition zone photographs of the blank control group (shampoo 1), the positive control group (shampoo 2), and the sample groups (shampoo 19-26) containing 1% of each alkyl oxazolidinone 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 of Malassezia furfur showed that no inhibition zone was produced in the blank control group, while the average diameter of the inhibition zone in the positive control group was 29.3 mm, indicating that the experimental data were reliable and effective.

[0052] For oxazolidinones with different alkyl substituents, C8-14 alkyl oxazolidinones, within a concentration range of 0.1-1%, all exhibited inhibition zones larger than 15 mm in diameter, showing moderate sensitivity to Malassezia furfur. Decyl oxazolidinone showed the best effect, followed by C8, C12, and C14 alkyl oxazolidinones. Furthermore, the inhibitory ability of the C8-C14 alkyl oxazolidinones of this invention against Malassezia furfur is significantly superior to that of existing oxazolidinone drugs such as linezolid. Therefore, shampoos containing 0.1-1% decyl oxazolidinone can effectively inhibit the growth of Malassezia furfur and have potential anti-dandruff effects. Moreover, shampoos containing 1% decyl oxazolidinone showed better inhibitory effects against Malassezia furfur than 1% ZPT.

[0053] By analyzing Table 1 and Figure 2 The inhibition zone data of Propionibacterium acnes showed that no inhibition zone was produced in the blank control group, while the average diameter of the inhibition zone in the positive control group was 22.5 mm, indicating that the experimental data were reliable and effective.

[0054] For oxazolidinones with different alkyl substituents, C8-14 alkyl oxazolidinones are all larger than 15 mm, exhibiting moderate to high sensitivity to *Propionibacterium acnes*, with decyl oxazolidinone showing the best effect, followed by C8, C12, and C14 linear alkyl oxazolidinones. Furthermore, the inhibitory ability of the C8-C14 alkyl oxazolidinones of this invention against *Propionibacterium acnes* is far superior to that of existing oxazolidinone drugs such as linezolid. Therefore, shampoos containing 0.1-1% decyl oxazolidinone can effectively inhibit the growth of *Propionibacterium acnes*, possessing potential acne-reducing effects. Moreover, shampoos containing 1% decyl oxazolidinone show better inhibitory effects against *Propionibacterium acnes* than 1% ZPT.

[0055] Example 2: Dandruff control performance test of shampoos containing alkyl oxazolidinones Two hundred and forty volunteers aged 20-45 with dandruff and flat hair were divided into six groups of 40 each. Each group used shampoo 15-20ml every two days (without using any other related products). After 28 days, each volunteer was surveyed regarding their experience and feedback on the product's safety and dandruff-reducing efficacy. The criteria for evaluating dandruff-reducing efficacy were as follows: Highly effective: Excellent dandruff removal, significantly reduces dandruff, leaving hair clean and bouncy; Effective: It has some dandruff-reducing effect, and dandruff has been reduced somewhat; Invalid: No change before or after use; Effectiveness = (Number of highly effective people + Number of effective people) / Total number of people × 100%.

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

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

[0058] Analysis of the data in Table 2 shows that shampoos containing C8-14 alkyl oxazolidinones (shampoos 20-24) all have an anti-dandruff effectiveness rate greater than 70%, with decyl oxazolidinones, especially linear decyl oxazolidinones, exhibiting even higher effectiveness. This indicates that shampoos containing 1% C8-14 alkyl oxazolidinones have excellent anti-dandruff effects on hair, helping to keep the scalp clean and healthy.

[0059] Example 2 This embodiment provides an acne-removing lotion containing an alkyl oxazolidinone composition, which is composed of the following raw materials by weight percentage: 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% combination of alkyl oxazolidinones and plant extracts (0.5% lactic acid, 0.4% asparagus root extract, 0.5% chrysanthemum extract, 0.48% gentian root extract and 0.1% shea butter).

[0060] In this case, the acne treatment lotion 1: phase D was replaced with an equal amount of deionized water; Acne Treatment Lotion 2: Phase D contains only 0.1% decyloxazolidinone; Acne Treatment Lotion 3: Phase D contains only 1% decyloxazolidinone; Acne-reducing lotion 4: Phase D contains only 0.5% lactic acid, 0.1% asparagus root extract, 0.5% chamomile extract, 0.5% gentian root extract and 0.1% shea butter; Acne-removing lotion 5-16: In phase D, the alkyl alkyl oxazolidinones are 0.1% and 1% respectively, namely hexyl oxazolidinone, octyl oxazolidinone, decyl oxazolidinone, dodecyl oxazolidinone, tetradecyl oxazolidinone and N-[3-(3-fluoro-4-morpholino-4-phenyl)-2-oxo-5-oxazolidinyl]acetamide (linezolid).

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

[0062] Example 3: In vitro verification of the soothing effect of acne lotion containing alkyl oxazolidinone Zebrafish testing: Selected broodstock should not have obvious signs of infection or disease, and should not have undergone drug treatment within the past two months. Wild-type AB strain zebrafish aged 6-12 months should be selected. Before reproductive and spawning tests, the broodstock should be acclimatized to the laboratory for at least 14 days after being introduced.

[0063] Zebrafish farming: The water temperature for zebrafish farming should be controlled between 26℃ and 28.5℃, with a density of 1-2 fish per liter of water, and a fixed 12-16 hours of light per day. Feed at least twice a day, including at least one feeding of brine shrimp larvae, with feeding intervals of more than 3 hours to avoid overfeeding, which could affect water quality.

[0064] Zebrafish Spawning: Egg Collection in the Aquarium: The egg collection box should be placed in the aquarium where eggs will be collected the day before spawning and before the lights are turned off, or on the day of spawning and before the lights are turned on. To prevent the eggs from being eaten by the adult fish, the egg collection box should be covered with an inert net. Mating, fertilization, and spawning of zebrafish are completed within approximately 30 minutes after the lights are turned on, at which point the egg collection box should be removed from the aquarium. After the zebrafish eggs are removed from the egg collection box, the embryos should be cleaned with zebrafish embryo culture medium. Healthy zebrafish embryos should be observed and selected under a stereomicroscope, and cultured at a density of no more than one embryo per 200 μL of zebrafish embryo culture medium at 28℃±1℃ until 3 days post-fertilization.

[0065] Drug treatment of zebrafish embryos: Zebrafish embryos were randomly selected into 6-well plates, 20 embryos per well. The blank control group was given 5 mL of fish embryo culture medium, the model control group was given 5 mL of fish embryo culture medium containing 10 µM anhydrous copper sulfate, the positive control group was given 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 given 5 mL of acne-removing lotion 1-16 (the acne-removing lotion was diluted with fish embryo culture medium to a concentration of 2% before being added). Each group was set up with 3 replicates and placed in a constant temperature incubator at 28℃±1℃ for 40 min to 45 min.

[0066] Staining and observation of zebrafish embryos: After fixing the embryos in paraformaldehyde for at least 1 hour, the embryos were treated with PBST three times for 5 minutes each time, followed by treatment with 50% ethanol for 3 minutes. The embryos were then stained with Sudan Black solution at room temperature for 1 hour, followed by rinsing with 70% ethanol four times for 5 minutes each time, and then treated with PBST twice for 5 minutes each time. Finally, the embryos were treated with a bleaching solution (a mixture of phosphate buffer + 0.1% Tween-20 as solvent, containing 1% hydrogen peroxide and 5% formamide) for 10 minutes, with the lid kept open during treatment. Then, treat with 70% ethanol solution for 5 min, PBST for 1 min, clarifying solution 1 (a mixture of phosphate buffer + 0.1% Tween-20, containing 50% glycerol and 0.1% Triton X-100) for 15 min, clarifying solution 2 (a mixture of phosphate buffer + 0.1% Tween-20, containing 80% glycerol and 0.1% Triton X-100) for 10 min, and finally PBST for 3 min. The fish embryos were then placed sideways, and their tails were photographed under a stereomicroscope.

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

[0068] Table 3. Number of centriole cells 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 not added, √ indicates added.

[0070] Analysis of the data in Table 3 shows 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 testing the soothing efficacy of zebrafish has been successfully constructed.

[0071] In acne-fighting lotions containing 0.1% alkyl oxazolidinones, the neutrophil inhibition rates of C8-14 alkyl oxazolidinones were all above 20%, with decyl oxazolidinone, especially linear decyl oxazolidinone, showing superior efficacy and significant differences compared to the model group. p <0.001), with a significant soothing effect; the alkyl oxazolidinone content in the acne-removing lotion was increased to 1%, and the neutrophil inhibition rate was further improved, resulting in an enhanced soothing effect.

[0072] Meanwhile, acne-removing lotions 2 and 3 contain only decyl oxazolidinone and no plant extract combination, and their neutrophil inhibition rate is higher than that of the positive control group. It can be seen that the alkyl oxazolidinone of the present invention, especially decyl oxazolidinone, has a significant inhibitory effect on neutrophils and has obvious soothing effect.

[0073] Furthermore, compared to Acne Treatment Lotions 2, 4, and 7, Acne Treatment Lotion 2 contains only alkyl oxazolidinones and no combination of plant extracts (0.5% lactic acid, 0.4% asparagus root extract, 0.5% chamomile extract, and 0.8% gentian root extract), while Acne Treatment Lotion 4 contains only a combination of plant extracts and no alkyl oxazolidinones. Although both have a certain soothing effect, they are all inferior to Acne Treatment Lotion 7. This shows that the combination of alkyl oxazolidinones and plant extracts has a significant synergistic effect in inhibiting neutrophils.

[0074] Compared to acne treatment lotions 3, 4, and 13, they showed the same trend, further validating the above conclusions.

[0075] Example 4: Verification of the soothing and oil-controlling effects of acne-fighting lotion Volunteer Enrollment: 297 volunteers were selected who showed no adverse skin reactions after patch testing and had sensitive skin (lactic acid stinging score ≥3), oily skin, and forehead oil content >120 μg / cm². 2 (Data before face washing) Healthy volunteers with reddened facial skin were randomly divided into 9 groups of 33 people each (there were no significant differences in lactic acid stinging scores, forehead oil content, etc. among the groups). All volunteers voluntarily participated in the trial, signed a written informed consent form, and promised to strictly abide by the trial protocol unless there were special circumstances.

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

[0077] Instructions for use: After cleansing your face in the morning and evening, take 2 grams of the acne-removing lotion 1, 3, 4, 11-16 provided in Example 2 of this invention, apply it evenly to the facial skin, and massage in circular motions until fully absorbed (do not use any other products with similar effects during this period).

[0078] Instrumental Testing: Before the test (D0), staff used VISIA7 and PRIMOS CR to acquire images of the volunteers' facial skin, and counted the number of porphyrins and the area of ​​redness; a Sebumeter SM815 was used to measure skin oil content; and a Colorimeter CL400 was used to measure skin color (red-green) a* value. Fourteen days after the test (D14), the same staff used the same instruments to acquire images of the volunteers' facial skin again, and the above parameters were recorded.

[0079] Data Analysis: 1) Normality Test: Analysis was performed using IBM SPSS Statistic 26.0 software, and the Shapiro-Wilks method was used to verify the normality of the data. The asymptotic significance (two-tailed) of the normality test was calculated. p If the mean is greater than 0.05, then the data series follows a normal distribution. Otherwise, it does not follow a normal distribution. 2) Difference analysis: Perform difference analysis on the means. When both sets of data are normally distributed, use a paired t-test to analyze the difference between the two sets of data; when the two sets of data are not both normally distributed, use a Wilcoxon rank-sum test to analyze the difference between the two sets of data. p A value <0.05 indicates that the data is statistically significant.

[0080] Evaluation criteria: (1) Oil control efficacy: Referencing "T / GDCDC-024-2022 Test Method for Oil Control Efficacy of Cosmetics" and "T / ZHCA002-2018 Test Method for Oil Control Efficacy of Cosmetics". At any visit time point before and after sample use, the skin oil content or porphyrin number showed a significant decrease ( p If the value is less than 0.050, the test sample is considered to have oil-controlling effect.

[0081] (2) Soothing effect: Referring to "T / BDCA 0005-2023 Test method for soothing effect of cosmetics: human lactic acid stinging test" and "Comparison of evaluation methods for human soothing effect of cosmetics based on skin color analysis", at any visit time point before and after using the sample, the skin color (red-green) value a* value and the red area of ​​the sensitive skin subjects showed a significant decrease ( p If the value is less than 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 number in volunteers (mean ± standard deviation)

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

[0084] Table 5. Variations in skin color values ​​(a*) and red area in volunteers (mean ± standard deviation)

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

[0086] The results showed that, compared with a concentration of 0.1%, a 1% concentration of C8-14 alkyl oxazolidinone composition acne-reducing lotion had a better soothing effect and could be further tested in humans.

[0087] Analysis of the data in Tables 4 and 5 shows that, compared with before use, after using the acne-removing lotion 3 and 13 of this invention, the oil content, porphyrin number (the porphyrin number was also significantly reduced, indicating a significant reduction in the number of Propionibacterium acnes that produces endogenous porphyrins), red area a* value, and red area all decreased significantly. p<0.001), indicating that the acne lotion containing 1% linear decyl oxazolidinone and the combination of 1% linear decyl oxazolidinone and plant extracts have oil-controlling, redness-improving, and soothing effects; lotions 12, 14, and 15 are second best; acne lotions 4, 11, and 20 are slightly worse; it can be seen that the alkyl oxazolidinones containing C6-14 of the present invention have good oil-controlling, redness-improving, and soothing effects, preferably C8-14 alkyl oxazolidinones, and more preferably C10 alkyl oxazolidinones (decyl oxazolidinone).

[0088] Furthermore, compared to acne lotion 3, 4, and 13, the combination of alkyl oxazolidinone and plant extracts also revealed a significant synergistic effect in oil control, redness reduction, and soothing.

[0089] Example 5: Verification of the acne-fighting efficacy of acne-fighting lotion on human body Volunteer Enrollment: 270 healthy volunteers with no adverse skin reactions after patch testing and facial acne, assessed by clinicians as having acne grade 1-2, were selected. All volunteers voluntarily participated in the trial, signed written informed consent forms, and pledged to strictly adhere to the trial protocol unless there were special circumstances.

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

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

[0092] Instrument detection: Before the test (D0), staff used VISIA7 and PRIMOS CR to acquire images of the volunteers' facial skin and count the volume of acne; a dermatologist assessed the number of acne lesions on the volunteers' faces. After the test (D14), the same staff used the above instruments to acquire images of the volunteers' facial skin again and counted the above parameters.

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

[0094] Evaluation criteria: Based on "T / CNMIA 0012-2020 Clinical Evaluation Standards for Acne-Fighting Efficacy Skincare Products". At any visit time point before and after sample use, the number, size, or severity of acne significantly decreased. p If the value is less than 0.050, the test sample is considered to have acne-removing effects.

[0095] Table 6. Changes in the number and size of acne lesions in volunteers (mean ± standard deviation)

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

[0097] Analysis of the data in Table 6 shows that, compared with before use, the number and size of acne lesions on the skin significantly decreased after using the acne-removing lotion 3 and 13 of this invention. p <0.001), indicating that the acne lotion containing 1% decyl oxazolidinone and the combination of 1% decyl oxazolidinone and plant extracts have acne-reducing effects; and, compared with acne lotion 3, acne lotion 13 has a better effect in reducing the number and size of acne. This shows that under the same concentration of decyl oxazolidinone, the acne lotion containing 0.5% lactic acid, 0.4% asparagus root extract, 0.5% chamomile extract, and 0.8% gentian root extract has a better acne-reducing effect. Lotions 12, 14, and 15 are next; acne lotions 4, 11, and 16 are slightly worse; it can be seen that the alkyl oxazolidinones containing C6-14 of the present invention have good acne-reducing effects, preferably C8-14 alkyl oxazolidinones, and more preferably C10 alkyl oxazolidinones.

[0098] Furthermore, compared to acne lotions 3, 4, and 13, acne lotion 13 showed better acne-removing effects than acne lotions 3 and 4, indicating that the combination of alkyl oxazolidinones and plant extracts also has a significant synergistic effect in acne removal.

[0099] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, and is not intended to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions made by those skilled in the art to the technical solution of the present invention do not depart from the essence and scope of the technical solution of the present invention.

Claims

1. The use of alkyl oxazolidinones in the preparation of products that regulate skin microbiota, characterized in that, The alkyl oxazolidinone is a C8-14 alkyl-substituted oxazolidinone; the microbial flora is Malassezia furfur and Propionibacterium acnes.

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

3. The use according to claim 2, characterized in that, The alkyl oxazolidinone is decyl oxazolidinone.

4. The use of alkyl oxazolidinones in the preparation of anti-dandruff, antipruritic, soothing, oil-controlling, and acne-removing products, characterized in that, The alkyl oxazolidinone achieves dandruff removal, itch relief, soothing, oil control, and acne treatment by regulating the skin microbiome; the microbiome consists of Malassezia furfur and Propionibacterium acnes; and the alkyl oxazolidinone is a C8-14 alkyl-substituted oxazolidinone.

5. The use according to any one of claims 1-4, characterized in that, The product is a 3-in-1 shampoo, body wash, and facial cleanser.

6. The use according to any one of claims 1-4, characterized in that, The products also include: lactic acid, asparagus root extract, chrysanthemum extract, gentian root extract, and shea butter.

7. The use according to claim 6, characterized in that, The product is an emulsion and also includes cosmetically acceptable excipients.

8. The use according to claim 7, characterized in that, The amount of the alkyl oxazolidinone used in the emulsion is 0.1-1 wt%.

9. The use of alkyl oxazolidinones in the preparation of medicaments for the treatment and / or prevention of skin diseases caused by dysbiosis of the skin microbiota, characterized in that, The skin disease includes either folliculitis or seborrheic dermatitis; the alkyl oxazolidinone is a C8-14 alkyl-substituted oxazolidinone; the microbial flora is Malassezia furfur and Propionibacterium acnes.

Images