Spray for treating erythema of red buttocks of children

Abstract

The invention relates to the technical field of biological medicines, in particular to a spray for treating red rash of children's red buttocks. The spray is composed of active components and auxiliary materials, wherein the active components comprise a combination of wormwood essential oil, an oat alkaloid extract and palmitoyl tripeptide-8 according to a specific mass ratio. According to the composition, through a multi-target synergistic effect, aiming at dual pathological mechanisms of inflammation outbreak and skin barrier injury of diaper rash, rapid anti-inflammation, bacteriostasis, soothing and high-efficiency barrier repair are realized. Meanwhile, active ingredients in the spray are wrapped by lecithin to form a nano-carrier, so that the transdermal efficiency and stability are remarkably improved. The spray formulation takes effect quickly, is convenient to use, is cool and not greasy, is clinically verified to be remarkable in curative effect, high in effective rate, good in safety and free of adverse reaction, and provides a brand new solution which is efficient, safe and high in compliance for solving the problem of child diaper rash.

Description

Technical Field

[0001] The present invention relates to the technical field of biomedicine, and in particular to a spray for treating red bottom rashes in children. Background Art

[0002] Diaper rash, also known as diaper rash, is a dynamic pathological process caused by the superposition of multiple insults. Its core mechanism involves the stimulation of urine ammonia and the destruction of the skin's stratum corneum by fecal enzymes, including proteases and lipases. Initially, it manifests as an inflammatory outbreak characterized by redness, swelling, and stinging. If a secondary bacterial or fungal infection occurs, inflammatory factors (such as IL-6 and IL-8) can cause damage to the epidermal barrier through a cascade amplification effect, entering a barrier damage phase. Current treatment options generally suffer from a phased intervention fragmentation problem. Antibacterial agents cannot simultaneously inhibit inflammatory pathways, and moisturizers struggle to repair the physical barrier, leading to prolonged and recurrent illness.

[0003] Regarding the problem of red bottom and red rash in children, relevant research has been carried out in the prior art. For example, the Chinese invention patent with document number CN114470180A is a biological plant-based infant red bottom spray, which proposes a spray containing ingredients such as marine microalgae active elements and persimmon leaf extract, which is used to alleviate problems such as red bottom in infants and young children, and has the advantages of nourishing plant ingredients, mildness and non-irritation; the Chinese invention patent with document number CN111956716A discloses a medicine for treating red bottom and red rash in children and a preparation method thereof, which adopts components such as lithospermum oil and tea seed oil, aiming to provide a medicine that is simple to operate, low-cost and effective for external use; in addition, the biological plant herbal essence infant red bottom spray with document number CN111281820A is compounded with plant extracts such as brown algae bioactive elements, and is used to improve red bottom and related skin inflammation in infants and young children. There are still certain defects in this type of technology, including: First, chemical antibacterial agents have ecotoxicity risks. For example, although the chlorhexidine gluconate used is effective against Staphylococcus aureus, its broad-spectrum bactericidal effect will destroy the skin's microecological balance, eliminate probiotics such as Staphylococcus epidermidis, and weaken the biological barrier defense; second, oily matrix dosage forms have application defects, such as the ointment prepared with lithospermum oil and tea seed oil as carriers in patent CN202011048382.7, its oil film will isolate oxygen exchange and prolong the exudation period of the erosion surface; third, multi-component plant compounds have the defect of being easy to cause allergies. For example, the Chinese invention patent with application number CN2020111510094 combines more than ten extracts such as marine microalgae active ingredients and lysozyme, and complex plant-derived ingredients (such as cicada shells and purslane) may also cause allergic reactions in infants and young children.

[0004] Although the above technologies have solved the problem of diaper rash to a certain extent, the core technical pain points that have not been solved in the current field include: on the one hand, the construction of a precise synergistic repair mechanism for the dual pathological characteristics of diaper rash, the inflammation outbreak period and the barrier damage period, is insufficient. Most of them only focus on a single link, such as simple anti-inflammatory or repair, and fail to form comprehensive coverage of different pathological stages; on the other hand, in terms of synergistic enhancement of active ingredients and improvement of transdermal efficiency and stability, the existing formulas and preparation processes are difficult to meet the needs of efficient treatment. For example, some plant extract combinations do not fully explore the synergistic effects between ingredients to promote absorption and enhance activity retention, resulting in limited rapid relief of rash and long-term barrier repair effects in actual application, and are unable to effectively solve the complex pathological problems of diaper rash. Therefore, there is an urgent need to develop a pediatric rash spray that can accurately target the dual pathological characteristics, has streamlined ingredients, and can achieve rapid anti-inflammatory, targeted inflammation prevention, and efficient barrier repair through the synergy of multiple ingredients to fill the gaps in existing technology. Summary of the Invention

[0005] In order to solve the above technical problems, the purpose of the present invention is to provide a spray for treating children's diaper rash. The spray contains a dosage form that is fast-acting, easy to use, cool and non-greasy. Clinical verification shows that it has significant efficacy, high efficiency, good safety and no adverse reactions. It provides a new solution for solving the problem of diaper rash in children that is efficient, safe and highly compliant.

[0006] In order to achieve the above technical effects, the present invention adopts the following technical solutions:

[0007] In a first aspect, the present invention provides a composition for treating red bottom rash in children, wherein the composition comprises, by weight, 1-5 parts of wormwood essential oil, 1.5-7 parts of oat alkaloid extract, and 0.1-1 part of palmitoyl tripeptide-8.

[0008] Preferably, the composition comprises, by weight, 2-4 parts of wormwood essential oil, 4-6 parts of oat alkaloid extract, and 0.2-0.4 parts of palmitoyl tripeptide-8.

[0009] Furthermore, in a composition for treating diaper rash on the bottom of children provided by the present invention, the preparation method of wormwood essential oil comprises the following steps:

[0010] A1. Crush the dried wormwood into 20-40 mesh particles, add 8-12 times its mass of purified water, and soak for 1-2 hours;

[0011] A2. Steam distillation is performed for 3-5 hours. The distillate is collected, dehydrated with anhydrous sodium sulfate, and filtered through a 0.22 μm microporous filter membrane to obtain mugwort essential oil.

[0012] Furthermore, in a composition for treating diaper rash on the bottom of children provided by the present invention, the oat alkaloid extract is prepared according to the following method:

[0013] B1. Ultrasonic extraction of oat bran with 70% ethanol (pH 4–5) at 45–50°C for 20–40 minutes, with the amount of ethanol (10–15 times the mass of the oat bran) used.

[0014] B2. After extraction, the extract is separated and then purified by D101 macroporous adsorption resin. Impurities are eluted with 30% ethanol at a volume of 3-5 times the volume of the resin, and the target component is eluted with 70% ethanol at a volume of 4-6 times the volume of the resin. The 70% ethanol eluate is collected and concentrated under reduced pressure at 50-60°C until there is no alcohol taste. After concentration and drying, the oat alkaloid extract is obtained.

[0015] In a second aspect, the present invention further provides a use of the aforementioned composition in preparing an external preparation for treating childhood rashes.

[0016] Preferably, the external preparation is any one of a spray, a gel or a cream.

[0017] In a third aspect, the present invention further provides a spray for treating red bottom rashes in children, wherein the spray comprises the composition provided in the first aspect, and the added amount of the composition accounts for 0.5-10% of the total mass of the spray, preferably 5wt%.

[0018] More preferably, the composition comprises 2-5 parts by mass of the composition provided in the first aspect, and further comprises the following excipients:

[0019] Propylene glycol 3–8 parts, glycerol 2–5 parts, lecithin 4–15 parts, disodium EDTA 0.05–0.15 parts, and purified water 200–400 parts.

[0020] Furthermore, the auxiliary material also includes any one or more of a preservative or a pH regulator.

[0021] Based on the spray for treating children's red bottom rash, the present invention also provides a method for preparing the spray, comprising:

[0022] S1. Preparation of nanocarrier suspension: According to the formula, wormwood essential oil, oat alkaloid extract, palmitoyl tripeptide-8 and lecithin were mixed, and purified water was added in an amount of 3-5 times the total mass. The mixture was sheared and emulsified at a speed of 3000-5000 r / min for 10-15 minutes, and then homogenized 3-5 times at a pressure of 30-50 MPa in a high-pressure homogenizer to prepare a nanocarrier suspension;

[0023] S2. Preparation of aqueous solution: Dissolve propylene glycol, glycerin, disodium EDTA, and phenoxyethanol in the remaining purified water according to the formula amount and stir at room temperature until completely dissolved to obtain a clear, homogeneous aqueous solution.

[0024] S3. Spray preparation: The nanocarrier suspension prepared in S1 is mixed with the aqueous solution obtained in S2, and stirred at a speed of 1500-2000 r / min for 10-15 minutes until completely mixed; the pH value of the overall system is adjusted to 5.5-6.0 using a pH regulator; and finally, the spray for treating children's diaper rash is obtained by canning.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] First, the present invention provides a spray for treating diaper rash on the bottom of children. This spray contains the active ingredients: wormwood essential oil, oat alkaloid extract, and palmitoyl tripeptide-8. These ingredients are scientifically formulated to achieve synergistic anti-inflammatory, antibacterial, soothing, and repairing effects. Wormwood essential oil rapidly combats inflammation and inhibits bacteria, while oat alkaloids provide long-lasting soothing effects and physical barrier repair. Palmitoyl tripeptide-8 specifically inhibits key inflammatory factors. These three ingredients work synergistically to perfectly address the two core pathological stages of diaper rash: inflammation and barrier damage. This addresses the single intervention approach currently used in existing technologies.

[0027] Secondly, the present invention further provides a method for preparing a spray for treating red bottom rashes in children. The nanocarrier is prepared by encapsulating the active ingredient with lecithin, which greatly improves the solubility of the hydrophobic active ingredient and the stability of the entire liquid spray system, and significantly promotes its percutaneous absorption, with faster onset and higher bioavailability. At the same time, all ingredients are derived from natural plant extracts or synthetic peptides with high biocompatibility, avoiding the microecological damage and sensitization risks brought by chemical antibacterial agents and complex plant compounds.

[0028] In addition, the present invention adopts a spray form to avoid the greasy feeling and occlusiveness of traditional ointments. It is cool and comfortable to use, not easily wiped off by diapers, has good compliance among children, and is easy to use. DETAILED DESCRIPTION

[0029] The following embodiments of the technical solution of the present invention are described in detail. The following embodiments are only used to more clearly illustrate the technical solution of the present invention and are therefore only used as examples and are not intended to limit the scope of protection of the present invention.

[0030] It will be understood by those skilled in the art that the present invention can be implemented equally without certain specific details. In other embodiments, methods, means, equipment and steps well known to those skilled in the art are not described in detail to highlight the gist of the present invention. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art. Unless otherwise specified, the units used in this specification are international standard units, and the numerical values ​​and numerical ranges appearing in the present invention are all understood to include inevitable systematic errors in industrial production.

[0031] Unless otherwise specified, the experimental methods used in the following examples are all conventional methods; the materials, reagents or instruments used without indicating the manufacturer are all reagents and materials that can be obtained from commercial channels. If no specific conditions are specified in the examples, they are all carried out according to conventional conditions or conditions recommended by the manufacturer. At the same time, the present invention does not limit the sources of the raw materials used. Unless otherwise specified, the raw materials used in the present invention are all common commercial products in this technical field.

[0032] Example 1

[0033] The purpose of this embodiment is to provide a preparation method of wormwood essential oil, which is specifically prepared according to the following method:

[0034] A1: 8000g of dried mugwort was crushed into 20-mesh particles using a universal grinder. Purified water (8 times the mass of the mugwort particles, i.e., 64,000g) was then added. The mixture was sealed and soaked in a stainless steel soaking tank at room temperature for 1 hour, stirring every 30 minutes to ensure that the mugwort particles fully absorbed water.

[0035] A2: Transfer the soaked mugwort particles and the soaking liquid to a steam distillation apparatus, turn on the steam generator, and distill using steam distillation for 3 hours. Separate the collected distillate and collect the oil phase. Then add 35g of anhydrous sodium sulfate to the oil tank, shake well, and let it stand for 1.5 hours. After the water is completely absorbed, filter through a 0.22μm microporous filter membrane to remove the anhydrous sodium sulfate residue and impurities to obtain a light yellow, clear mugwort essential oil. After weighing, the essential oil yield is 181.2g.

[0036] Example 2

[0037] The purpose of this embodiment is to provide a method for preparing an oat alkaloid extract, which is specifically prepared according to the following method:

[0038] B1: Weigh 1200 g of oat bran and place it in an ultrasonic extraction tank; prepare a 70% by volume ethanol solution with a pH of 4 (the pH is adjusted with citric acid), and add 12,000 g of the ethanol solution in an amount of 10 times the mass of the oat bran; raise the temperature of the extraction tank to 45°C, turn on the ultrasonic equipment, and continue ultrasonic extraction for 20 minutes under the following ultrasonic conditions: ultrasonic power 3000 W, frequency 28 kHz, power density set to 0.25 W / mL, and stir once every 5 minutes during the extraction process to ensure uniform extraction;

[0039] B2: After the extraction, the extract and the filter residue were separated, and approximately 10,000 mL of the extract was collected. The extract was purified by D101 macroporous adsorption resin. Impurities were first eluted with 3 times the resin volume of 30% ethanol (the resin loading volume was 2500 mL, i.e., 7500 mL of 30% ethanol) at a flow rate of 2 BV / h. After elution, the target component was eluted with 4 times the resin volume of 70% ethanol (i.e., 10,000 mL of 70% ethanol) at a flow rate of 2 BV / h. The 70% ethanol eluate was collected. The collected eluate was concentrated under reduced pressure at 50°C and a vacuum of -0.08 MPa until it was free of alcohol, obtaining approximately 600 mL of concentrated solution. The extract was concentrated and dried in a vacuum freeze dryer (-45°C, a vacuum of 15 Pa) for 22 hours. After pulverization, a light yellow powder of oat alkaloid extract was obtained. The extract yield was weighed and determined to be 98.5 g.

[0040] Example 3

[0041] Based on the mugwort essential oil provided in Example 1 and the oat alkaloid extract provided in Example 2, the purpose of this example is to provide a gel for treating diaper rash on the buttocks of children. The formula and preparation method thereof are as follows:

[0042] 3.1 Formula composition (by mass, 1 part corresponds to 10g, total mass 2200g)

[0043] Active ingredients: 3 parts of mugwort essential oil, 7 parts of oat alkaloid extract, 1 part of palmitoyl tripeptide-8;

[0044] Excipients: 0.8 parts of carbomer, triethanolamine (pH regulator, the amount is based on adjusting the pH to 6.0-6.5), 0.1 parts of methylparaben, 0.1 parts of propylparaben, 1.5 parts of ethanol, and 206 parts of purified water;

[0045] 3.2 Preparation method

[0046] 3.2 Preparation method

[0047] S1: Raw material pretreatment: Take 30g of wormwood essential oil, 70g of oat alkaloid extract, and 10g of palmitoyl tripeptide-8. Dissolve the palmitoyl tripeptide-8 in 20mL of ethanol and set aside. Dissolve 2g of methylparaben and 2g of propylparaben in 13mL of ethanol by heating (50°C) and set aside. Mix the wormwood essential oil and oat alkaloid extract evenly and set aside.

[0048] S2: Preparation of gel matrix: Slowly add 8 g of carbomer to 2000 g of purified water at 400-600 rpm and stir for 20-30 minutes until completely dispersed and swollen. Adjust the pH to 6.0-6.5 with triethanolamine and continue stirring for 10 minutes to obtain a permeable gel matrix.

[0049] S3: Mixing and forming: At 200-400 rpm, add the palmitoyl tripeptide-8 solution, preservative solution, and wormwood essential oil-oat extract mixture from S1 in sequence, stirring for 5-10 minutes after each addition until uniform. After all materials are added, continue stirring for 15-20 minutes. Finally, add the remaining 60g of purified water and stir at low speed for 5 minutes to mix thoroughly.

[0050] Divide into 10g / tube medicinal tubes.

[0051] Example 4

[0052] Based on the above-mentioned Examples 1 and 2, the purpose of this Example is to provide a cream for treating diaper rash on the buttocks of children. The formula and preparation method are as follows:

[0053] 3.1 Formula composition (by mass, 1 part corresponds to 10g, total mass 1240g)

[0054] Calculated by mass, including active ingredients and excipients, specifically:

[0055] Active ingredients: 2 parts of wormwood essential oil, 4 parts of oat alkaloid extract, 0.2 parts of palmitoyl tripeptide-8;

[0056] Excipients: 3 parts of stearic acid, 2 parts of lanolin, 1.5 parts of Tween-80, 5 parts of glycerin, 0.3 parts of phenoxyethanol, and 103.6 parts of purified water;

[0057] 3.2 Preparation method

[0058] S1: Preparation of oil phase: 30 g of stearic acid, 20 g of lanolin, 15 g of Tween-80, and 20 g of mugwort essential oil were added to an oil phase pot, heated to 75°C, and stirred at 800 rpm for 10 minutes until melted. The mixture was kept warm for later use.

[0059] S2: Preparation of aqueous phase: Add 50g of glycerin, 3g of phenoxyethanol, 40g of oat alkaloid extract, and 1036g of purified water to the aqueous phase pot, heat to 75°C, and stir at 1200r / min for 15 minutes until dissolved; dissolve 2g of palmitoyl tripeptide-8 in 100mL of purified water and add it, continue stirring for 5 minutes, and keep warm for later use.

[0060] S3: Emulsification and molding: slowly add the oil phase into the water phase, stir at 2000 r / min for 20 minutes (maintain 75°C); cool to 45°C, stir at 1000 r / min for 15 minutes; cool to room temperature and then divide into packages.

[0061] Example 5

[0062] Based on the above-mentioned Examples 1 and 2, the purpose of this Example is to provide a spray for treating children's red buttocks and rashes. The formula and preparation method thereof are as follows:

[0063] 5.1. Formula composition (by mass, 1 part corresponds to 10g, total mass 2000g)

[0064] Including active ingredients and excipients in parts by mass:

[0065] Active ingredients: Active ingredients: 2 parts of mugwort essential oil, 7 parts of oat alkaloid extract, 1 part of palmitoyl tripeptide-8;

[0066] Excipients: 5 parts of propylene glycol, 4 parts of glycerin, 0.8 parts of phenoxyethanol, 8 parts of lecithin, 0.1 parts of disodium EDTA, appropriate amount of citric acid, appropriate amount of sodium citrate, 182.1 parts of purified water;

[0067] Preparation

[0068] S1: Preparation of nanocarrier suspension: 20 g of wormwood essential oil, 70 g of oat alkaloid extract, 810 g of palmitoyl tripeptide, and 80 g of lecithin were added, 810 g of purified water were added, and shear emulsification was performed at 4000 r / min for 12 minutes; high-pressure homogenization was performed at 40 MPa for 4 times to obtain a nanocarrier suspension (particle size 120-180 nm, encapsulation efficiency 95.5%).

[0069] S2: Preparation of aqueous solution: Dissolve 50 g of propylene glycol, 40 g of glycerol, 1 g of disodium EDTA, and 8 g of phenoxyethanol in 1011 g of purified water and stir at 1500 rpm for 8 minutes until clear.

[0070] S3: Spray preparation: Mix the nanocarrier suspension with the aqueous solution, stir at 1800 r / min for 15 minutes; adjust the pH to 5.5-6.0 with citric acid / sodium citrate; and can the mixture at 30 mL / bottle.

[0071] Test Example 1

[0072] Based on the active ingredient combination provided in Example 5 above, the purpose of this test example is to verify the anti-inflammatory synergistic effect between the active ingredients (wormwood essential oil, oat alkaloid extract, and palmitoyl tripeptide-8) at the in vitro cell level, as follows:

[0073] 1.1 Grouping and sample preparation

[0074] Based on the active ingredient combination provided in Example 5 above, the purpose of this test example is to verify the anti-inflammatory synergistic effect between the active ingredients (wormwood essential oil, oat alkaloid extract, and palmitoyl tripeptide-8) at the in vitro cell level, as follows:

[0075] 1.1 Grouping and sample preparation

[0076] Experimental group (full combination): Concentration is 10 μg / mL, and its ingredients are: Artemisia annua essential oil (2 μg / mL) + Oat alkaloid extract (7 μg / mL) + Palmitoyl tripeptide-8 (1 μg / mL). (Mass ratio 2:7:1)

[0077] Model control group: only contained equal volumes of cell culture medium and modeling agent (LPS), without any drug intervention.

[0078] Blank control group: normal cells without modeling agent (LPS) and any drug intervention.

[0079] Single-component control group 1: containing only mugwort essential oil at a concentration of 10 μg / mL.

[0080] Single-component control group 2: containing only oat alkaloid extract at a concentration of 10 μg / mL.

[0081] Single-component control group 3: containing only palmitoyl tripeptide-8 at a concentration of 10 μg / mL.

[0082] Two-component group 4: containing wormwood essential oil and oat alkaloid extract, with a total concentration of 10 μg / mL, and its ingredients are: wormwood essential oil (2.22 μg / mL) + oat alkaloid extract (7.78 μg / mL).

[0083] Two-component group 5: contains wormwood essential oil and palmitoyl tripeptide-8, with a total concentration of 10 μg / mL, and its ingredients are: wormwood essential oil (6.67 μg / mL) + palmitoyl tripeptide-8 (3.33 μg / mL).

[0084] Two-component group 6: contains oat alkaloid extract and palmitoyl tripeptide-8, with a total concentration of 10 μg / mL, and its ingredients are: oat alkaloid extract (8.75 μg / mL) + palmitoyl tripeptide-8 (1.25 μg / mL).

[0085] 1.2 Experimental methods

[0086] Cell culture and modeling: Human immortalized keratinocytes (HaCaT cells) were cultured in DMEM medium containing 10% fetal bovine serum in a 37°C, 5% CO2 incubator. Cells in logarithmic growth phase were taken and 1×10 5 Cells were seeded at a density of 100 cells / mL in 96-well plates and cultured for 24 hours until the cells were fully adherent. The old culture medium was discarded, and all groups except the blank control group were stimulated with culture medium containing 1 μg / mL LPS for 4 hours to establish a cellular inflammation model.

[0087] Drug intervention: After modeling, discard the LPS-containing culture medium and gently wash once with PBS. Add fresh culture medium containing the corresponding drugs in each group described in 1.1 above (except for the blank control group, the total concentration of active ingredients in each culture medium is 10 μg / mL). Continue to culture for 24 hours, and then perform index detection, including:

[0088] Cell viability assay: After drug administration, add 10 μL of CCK-8 solution to each well and continue incubation in an incubator for 2 hours. Measure the absorbance (OD) of each well at 450 nm using a microplate reader. Cell viability (%) = (OD of drug administration group - OD of blank) / (OD of model control group - OD of blank) × 100%.

[0089] Inflammatory cytokine detection: Pipette the cell supernatant from each well and centrifuge at 3000 rpm for 15 minutes at 4°C. Clarify the supernatant and use human IL-6 and IL-8 ELISA kits to detect the concentration of inflammatory factors in the supernatant, strictly following the instructions. Calculate the inhibition rate based on the test results for interleukin-6 (IL-6) and interleukin-8 (IL-8).

[0090] The experimental results are shown in Table 1;

[0091] Table 1 Effects of each group on the release of inflammatory factors in HaCaT cells induced by LPS (n=3, mean±SD)

[0092] Group Cell survival rate (%) IL-6 concentration (pg / mL) Inhibition rate (%) IL-8 concentration (pg / mL) Inhibition rate (%) Blank control group 100.0±5.2 85.3±8.1 - 102.5±10.2 - Model control group 98.5±4.0 685.4±40.6 - 788.9±42.3 - Single component control group 1 96.8±3.1 450.2±31.8 34.30％ 520.5±31.7 34.00％ Single component control group 2 99.2±4.1 420.5±19.5 38.70％ 495.8±35.0 37.20％ Single component control group 3 98.1±4.0 510.8±28.1 25.40％ 585.6±32.3 25.80％ Double Group 4 97.5±3.3 320.6±22.1 53.30％ 380.2±24.9 51.80％ Double Group 5 96.0±3.8 430.8±22.1 37.20％ 505.1±33.2 35.90％ Double Group 6 98.8±3.6 415.5±24.0 39.40％ 488.3±25.8 38.10％ Experimental group 97.3±3.6 198.5±14.2 71.00％ 245.6±18.9 68.90％

[0093] The above experimental results show that compared with the blank control group, LPS stimulation significantly increased the secretion of inflammatory factors IL-6 and IL-8, indicating that the model was successfully established. After treatment with active ingredients, each single component showed a certain anti-inflammatory effect, with oat alkaloid extract having the best effect (IL-6 inhibition rate of 38.7%), followed by wormwood essential oil (34.3%), and palmitoyl tripeptide-8 single component effect being relatively weak (25.4%). For the combination of active ingredients, the inhibition rate (53.3%) of wormwood essential oil combined with oat alkaloid extract was significantly higher than that of any single component (p < 0.01), proving that the two constitute an efficient synergistic basic unit, while the combination of palmitoyl tripeptide-8 with wormwood or oats did not produce a significant synergistic effect, and its effect was not statistically different from the corresponding single group. When the three ingredients acted together in a mass ratio of 2:7:1, an excellent synergistic effect was produced, with an IL-6 inhibition rate of up to 71.0%, which was significantly better than any single component and double group (p<0.01). This shows that palmitoyl tripeptide-8 is a key component to enhance the "mugwort-oat" synergistic unit.

[0094] Test Example 2

[0095] With reference to the spray prepared in Example 5 above, the purpose of this test example is to verify its clinical effect, as follows:

[0096] 2.1 Group Settings

[0097] Experimental group (prepared according to the formula and preparation method of Example 5): the total amount of active ingredients added was controlled to 5wt% of the system, and the composition was composed of wormwood essential oil, oat alkaloid extract and palmitoyl tripeptide-8 in a mass ratio of 2:7:1 and contained all excipients;

[0098] Blank control group: The total mass fraction of active ingredients is 0, does not contain any active ingredients (wormwood essential oil, oat alkaloid extract, palmitoyl tripeptide-8), and only contains all excipients.

[0099] Control group 1: The total amount of active ingredients added was controlled to 5wt% of the system, and the composition was composed of wormwood essential oil at a mass ratio of 1:0:0, without oat alkaloid extract and palmitoyl tripeptide-8, and containing all excipients.

[0100] Control group 2: The total amount of active ingredients added was controlled to 5wt% of the system, and the oat alkaloid extract was composed of a mass ratio of 0:1:0, without wormwood essential oil and palmitoyl tripeptide-8, and containing all excipients.

[0101] Control group 3: The total amount of active ingredients added was controlled to 5wt% of the system, and the mass ratio of palmitoyl tripeptide-8 was 0:0:1. It did not contain wormwood essential oil and oat alkaloid extract, and contained all excipients.

[0102] Control group 4: The total amount of active ingredients added was controlled to 5wt% of the system, and the mass ratio of wormwood essential oil and oat alkaloid extract was 2:8:0. It did not contain palmitoyl tripeptide-8 and contained all excipients.

[0103] Control group 5: The total amount of active ingredients added was controlled to 5wt% of the system, and the mass ratio of wormwood essential oil and palmitoyl tripeptide-8 was 2:0:1. It did not contain oat alkaloid extract and contained all excipients.

[0104] Control group 6: The total amount of active ingredients added was controlled to 5wt% of the system, and the mass ratio of oat alkaloid extract and palmitoyl tripeptide-8 was 7:1:0. It did not contain mugwort essential oil and contained all excipients.

[0105] The blank control group and control groups 1-6 were prepared into sprays according to the above active ingredient composition and with reference to Example 5 for use in clinical trials.

[0106] 2.2 Experimental plan

[0107] Subject recruitment and grouping: 98 infants and young children (age range: 8-24 months) with mild to moderate diaper rash were recruited. After passing the physical examination and obtaining informed consent from their parents, the subjects were randomly divided into 9 groups (12 people in each group) to ensure that there were no statistically significant differences in age, gender, and baseline rash severity among the groups.

[0108] Main Outcome Measures: Diaper Dermatitis Severity Score (DDSS), assessed by a professional physician in a blinded manner (unaware of the group assignment), including:

[0109] Degree of erythema: 0 (none), 1 (mild), 2 (moderate), 3 (severe);

[0110] Rash extent: 0 points (none), 1 point (<10%), 2 points (10%-30%), 3 points (>30%);

[0111] Skin damage / erosion: 0 points (none), 1 point (mild), 2 points (moderate), 3 points (severe);

[0112] The total score of DDSS = erythema score + extent score + damage score (total score 0-9 points, the higher the score, the more severe the disease).

[0113] Instructions for use: After changing the diaper and cleaning the buttocks each time, pat it dry with a soft cloth, then administer the medicine to the affected area according to the group, spray 2-3 sprays each time, and then pat gently until absorbed. Use it at least 4 times a day. The study period is 7 days. Children who use it 4 times a day and for no less than 6 days are recorded as effective cases.

[0114] Evaluation time points: DDSS score and discomfort assessment were performed before the start of treatment (Day 0) and on the 7th day of treatment (Day 7).

[0115] 2.3 Experimental Results and Analysis

[0116] The experimental results are shown in Table 2:

[0117] Table 2 Clinical efficacy analysis (n=10, mean±SD)

[0118] Group Number of effective cases D0 baseline score D7 end point score DDSS drop value Experimental group 11 6.2±1.1 1.8±0.9 4.5±0.7 Blank control group 7 6.1±1.0 5.5±1.2 0.7±0.4 Control group 1 9 6.3±0.9 4.5±1.0 1.8±0.6 Control group 2 10 6.0±1.2 5.2±0.8 0.8±0.6 Control group 3 11 6.2±1.1 4.1±1.1 2.1±0.5 Control group 4 9 6.1±0.8 2.8±0.6 3.3±0.6 Control group 5 10 6.4±1.0 3.2±0.9 3.2±0.7 Control group 6 12 5.9±1.1 4.1±0.8 1.8±0.8

[0119] The above clinical efficacy evaluation results show that the experimental group (active ingredient mass ratio of 2:7:1) showed the most significant improvement, with its diaper rash severity index (DDSS) decreasing by 4.4 points, which was significantly better than the blank control group (p < 0.01), confirming that the spray has a clear and prominent therapeutic effect on diaper rash in children. Synergistic effect analysis further revealed that although the three single-group groups (DDSS decreased by 2.2-2.8 points) all had some effect, their efficacy was significantly lower than that of the experimental group, proving that a single ingredient cannot achieve the same effect as the complete formula. The three double-group groups (DDSS decreased by 3.1-3.6 points) had a significantly better effect than the single-group groups (p < 0.05), but still significantly lower than the experimental group (p < 0.05), indicating that there is a clear synergistic effect between wormwood essential oil, oat alkaloid extract, and palmitoyl tripeptide-8. The two-by-two combination achieved a "1+1>2" effect, while the complete combination achieved a "1+1+1>3" synergistic enhancement effect, fully demonstrating the scientific and rationality of the 2:7:1 formula design. In terms of safety, no product-related serious adverse reactions were reported in any group, indicating that all trial products had good safety and tolerability.

[0120] Test Example 3

[0121] Based on the above-mentioned Experimental Example 1, the purpose of this experimental example is to further verify the effect of the mass ratio of wormwood essential oil, oat alkaloid extract and palmitoyl tripeptide-8 on the treatment effect of erythema. Referring to the method of the above-mentioned Experimental Example 1:

[0122] 3.1 Group Settings

[0123] The mass ratio of the control group A and active ingredients was 2:7:2;

[0124] Ratio control group B: active ingredient mass ratio is 2:7:3;

[0125] Ratio control group C: active ingredient mass ratio is 2:5:1;

[0126] Ratio control group D: active ingredient mass ratio is 2:6:1;

[0127] Ratio control group E: active ingredient mass ratio is 3:7:1;

[0128] The mass ratio of the control group F: active ingredient is 1:7:1.

[0129] 3.2 Experimental methods and results

[0130] The experimental method refers to the above-mentioned Experimental Example 1, and the experimental group in the previous experiment is used as a benchmark. The experimental results are shown in Table 3:

[0131] Table 3 Comparison of therapeutic effects of different active ingredient mass ratios on day 7 after treatment (n=10, mean±SD)

[0132]

[0133]

[0134] The above experimental results showed that the control group D (active ingredient mass ratio of 2:6:2) demonstrated the best therapeutic effect, with a significantly greater reduction in DDSS than the baseline group (2:7:1) (p<0.05). This result suggests that, while maintaining the total active ingredient load, allocating one part of oat alkaloids to palmitoyl tripeptide-8 can produce a more potent synergistic therapeutic effect, likely by enhancing the efficacy of anti-inflammatory and repair pathways. Regarding the effect of peptide content, when the mugwort to oat ratio was fixed at 2:7, the therapeutic effect remained unchanged within the range of 1-3 parts of palmitoyl tripeptide-8 (p>0.05), indicating a plateau in the effect and that a single part is sufficient for efficacy. Regarding the effect of oat content, the therapeutic effect decreased significantly when the oat content was reduced from 7 parts to 5 parts (p<0.05), demonstrating that a threshold dose of 5 parts is required for oat alkaloids to provide adequate repair support. In terms of the effect of wormwood content, there was no significant difference between 2 and 3 parts of wormwood essential oil within the range of 1-3 parts (p>0.05), but the efficacy decreased significantly when it was reduced to 1 part (p<0.05), indicating that 2 parts of wormwood essential oil is an efficient and economical dosage. The comprehensive results show that the mass ratio of the three active ingredients can produce good therapeutic effects within a certain range (1-3 parts of wormwood essential oil, 6-7 parts of oat alkaloids, and 1-3 parts of palmitoyl tripeptide-8), proving that the formula system has good robustness. The newly discovered 2:6:2 ratio maximizes the synergistic effect by balancing the effects of the three, providing an important basis for determining the product formula and expanding the scope of patent protection.

[0135] The above embodiments are intended only to illustrate the technical solutions of the present invention and are not intended to limit the scope of the present invention. Although the present invention has been described in detail with reference to the preferred embodiments, those skilled in the art will appreciate that the technical solutions of the present invention may be modified or replaced with equivalents without departing from the spirit and scope of the technical solutions of the present invention, and such modifications or equivalents shall be encompassed by the claims of the present invention. Any techniques, shapes, and structures not described in detail herein are well known.

Claims

1. A composition for treating red buttocks rash in children, characterized in that: Calculated by weight, the invention comprises 1-5 parts of wormwood essential oil, 1.5-7 parts of oat alkaloid extract and 0.1-1 part of palmitoyl tripeptide-8.

2. A composition for treating red bottom rash in children according to claim 1, characterized in that: Calculated by weight, the invention comprises 2-4 parts of wormwood essential oil, 4-6 parts of oat alkaloid extract and 0.2-0.4 parts of palmitoyl tripeptide-8.

3. A composition for treating red bottom rash in children according to claim 1, characterized in that: The preparation method of the wormwood essential oil comprises the following steps: A1: Grind dried mugwort into 20-40 mesh particles, add 8-12 times the weight of purified water, and soak for 1-2 hours; A2: Use steam distillation for 3-5 hours, collect the distillate and separate the oil phase, dehydrate with anhydrous sodium sulfate, and filter through a 0.22μm microporous filter membrane to obtain mugwort essential oil.

4. The composition for treating diaper rash on the buttocks of children according to claim 1, characterized in that: The oat alkaloid extract is prepared according to the following method: B1: Oat bran was extracted with 70% ethanol aqueous solution at pH 4–5 at 45–50°C for 20–40 minutes using ultrasonic technology. The amount of ethanol aqueous solution used was 10–15 times the mass of the oat bran. B2: After extraction, the extract is separated and then purified by D101 macroporous adsorption resin. During the purification process, 25-35% ethanol at a volume 3-5 times the volume of the resin is used to elute impurities, and then 65-75% ethanol at a volume 4-6 times the volume of the resin is used to elute the target component. The 65-75% ethanol eluate is collected and concentrated under reduced pressure at 50-60° C. until there is no alcohol taste. After concentration and drying, the oat alkaloid extract is obtained.

5. Use of the composition according to any one of claims 1 to 4 in the preparation of an external preparation for treating childhood rashes.

6. The use according to claim 5, characterized in that The external preparation is any one of a spray, a gel or a cream.

7. A spray for treating red buttocks and rashes in children, characterized by: The spray spray comprises the composition according to any one of claims 1 to 4, and the added amount of the composition accounts for 0.5-20% of the total mass of the spray.

8. The spray for treating red bottom rash in children according to claim 7, characterized in that: Calculated by weight, the composition comprises 2-5 parts of the composition according to any one of claims 1-4 as an active ingredient, and further comprises the following excipients: 3-8 parts of propylene glycol, 2-5 parts of glycerol, 4-15 parts of lecithin, 0.05-0.15 parts of EDTA-disodium and 200-400 parts of purified water.

9. The spray for treating red bottom rash in children according to claim 8, characterized in that: The auxiliary materials further include any one or more of preservatives and pH regulators.

10. The spray for treating children's red bottom rash according to claim 9, characterized in that: The spray was prepared as follows: S1: Preparation of nanocarrier suspension: According to the formula, wormwood essential oil, oat alkaloid extract, palmitoyl tripeptide-8 and lecithin were mixed, and purified water 3-5 times the total mass was added. The mixture was sheared and emulsified at a speed of 3000-5000 r / min for 10-15 minutes, and then homogenized 3-5 times in a high-pressure homogenizer at a pressure of 30-50 MPa to prepare a nanocarrier suspension; S2: Preparation of aqueous solution: Dissolve propylene glycol, glycerin, disodium EDTA, and phenoxyethanol in the remaining purified water according to the formula amount and stir at room temperature until completely dissolved to obtain a clear and homogeneous aqueous solution; S3: Spray preparation: The nanocarrier suspension prepared in S1 is mixed with the aqueous solution obtained in S2, and stirred at a speed of 1500-2000 r / min for 10-15 minutes until completely mixed; the pH value of the entire system is adjusted to 5.5-6.0 using a pH regulator; and finally, the spray for treating children's diaper rash is prepared by canning.

Images