Low-irritation comfrey oil nanoliposomes, diaper rash preparation and application thereof in diaper rash of infants and young children

Abstract

The application discloses a low-irritation borage oil nano-liposome, a diaper-care preparation and application of the diaper-care preparation in diaper rash of infants and young children, and belongs to the field of infant skin-care preparations. The nano-liposome is composed of the following components in percentage by weight: 0.5-2.0% of biodecolorized borage oil, 1.0-3.0% of chitosan oligosaccharide-ceramide binary membrane material, 0.3-1.0% of prebiotic skin flora regulator, 0.8-1.5% of pH 5.5 weak acid buffer system, 0.05-0.2% of edible-grade microencapsulated menthol, and the balance of sterile water for injection. The application also provides a diaper-care preparation containing the low-irritation borage oil nano-liposome, which is suitable for daily prevention and acute-phase intervention of infants and young children aged 0-36 months, has the characteristics of high bioavailability, low irritation, rapid repair and easy carrying, and has important clinical application value.

Description

Technical Field

[0001] This invention belongs to the field of infant skin care preparations, specifically relating to a low-irritation comfrey oil nanoliposome, a diaper rash preparation, and its application in infant diaper rash. Background Technology

[0002] Diaper dermatitis is one of the most common skin problems in infants aged 0-36 months, with an incidence rate of 50%-65%. Its pathogenesis is mainly related to prolonged contact with urine and feces, as well as the skin barrier damage, microbial imbalance, and inflammatory response caused by the enclosed environment of the diaper. Currently, zinc oxide paste or petrolatum-based ointments are routinely used clinically for isolation and protection. However, these preparations are thick, have poor breathability, easily clog pores, and increase friction damage. Furthermore, they lack the ability to rapidly repair existing acute inflammation such as erythema and erosion.

[0003] Comfrey oil, rich in naphthoquinone active ingredients such as shikonin and acetylshikonin, possesses anti-inflammatory, antibacterial, and healing-promoting effects and has been used as a traditional topical medicine for mild skin injuries. However, existing comfrey oil preparations mostly use petrolatum, lanolin, or a simple ethanol-glycerin system, which has the following shortcomings: ① Shikonin has low solubility and is easily oxidized and degraded, with a bioavailability of <30%; ② The base is greasy and has strong occlusive properties, which can easily aggravate irritation in the warm and humid environment of the diaper area; ③ It lacks the ability to regulate the skin microecology of sensitive infants; ④ Traditional application methods require repeated rubbing, which can easily cause secondary damage.

[0004] There are many comfrey oil-based preparations for diaper rash care in infants, but they all have drawbacks to varying degrees. These include low retention of active ingredients, poor bioavailability, high irritation to delicate infant skin, inconvenient application leading to secondary damage, and an inability to simultaneously address both prevention and acute intervention needs. Therefore, there is an urgent clinical need for a novel delivery system that retains the core efficacy of comfrey oil while also being low-irritant, providing rapid repair, being easy to use, and capable of regulating the skin's microecology, to meet the dual needs of diaper rash prevention and acute intervention in sensitive infants aged 0-36 months. Summary of the Invention

[0005] In view of the shortcomings of the prior art, the main objective of this invention is to provide a low-irritation comfrey oil nanoliposome, which uses bio-decolorized comfrey oil as the core active ingredient and encapsulates it into nano-sized liposomes using a chitosan oligosaccharide-ceramide binary membrane material, significantly improving the stability, skin adhesion and bioavailability of the active ingredient; at the same time, a prebiotic skin flora regulator, a pH 5.5 weakly acidic buffer system and microencapsulated menthol are added to achieve multiple effects such as rapid film formation, immediate itch relief, antibacterial and anti-inflammatory effects, barrier repair and microecological regulation.

[0006] Another objective of this invention is to provide a diaper rash treatment containing the aforementioned low-irritant comfrey oil nanoliposomes. The spray method avoids secondary damage caused by friction during application. Clinical trials have shown that continuous use for 3 days reduces the erythema area in children with mild to moderate diaper rash by 82.4%, with no adverse reactions such as allergic reactions or burning pain.

[0007] Another object of the present invention is to provide the use of the aforementioned low-irritation comfrey oil nanoliposomes or diaper rash preparation in the preparation of products or medicines for the prevention and rapid repair of mild to moderate diaper rash in infants aged 0-36 months, which have the characteristics of high bioavailability, low irritation, rapid repair and easy portability.

[0008] To achieve the above objectives, the present invention adopts the following technical solution:

[0009] In a first aspect, the present invention provides a low-irritation comfrey oil nanoliposome, comprising the following components by weight percentage: 0.5%-2.0% bio-decolorized comfrey oil, 1.0%-3.0% oligosaccharide-ceramide binary membrane material, 0.3%-1.0% prebiotic skin flora regulator, 0.8%-1.5% pH 5.5 weakly acidic buffer system, 0.05%-0.2% edible-grade microencapsulated menthol, with the balance being sterile water for injection.

[0010] Preferably, the low-irritation comfrey oil nanoliposomes are composed of the following components by weight percentage: 1.2% bio-decolorized comfrey oil, 2.0% oligochitosan-ceramide binary membrane material, 0.3% prebiotic skin flora regulator, 1.0% pH 5.5 weakly acidic buffer system, 0.08% edible-grade microencapsulated menthol, and the balance being sterile water for injection.

[0011] Preferably, the bio-decolorized comfrey oil contains shikonin ≥ 0.8 mg / mL, acetylshikonin ≥ 0.4 mg / mL, and deoxyshikonin ≥ 0.3 mg / mL.

[0012] Preferably, in the oligochitosan-ceramide binary membrane material, the oligochitosan has a weight-average molecular weight of 3-5 kDa and a degree of deacetylation ≥90%, and the ceramide is ceramide NP with a purity ≥95%.

[0013] Preferably, the prebiotic skin flora regulator is formed by compounding fructooligosaccharides and inulin in a mass ratio of 1-3:1, and both have a purity of ≥98%.

[0014] Preferably, the pH 5.5 weakly acidic buffer system is prepared by mixing lactic acid and sodium lactate in a molar ratio of 1.5:1, and has a buffer capacity ≥0.05 mol / (L·pH).

[0015] Preferably, the microcapsule wall material of the edible-grade microencapsulated menthol is sodium octenyl succinate starch with a particle size of 5-15 μm and a menthol loading of 20%-30%.

[0016] Preferably, the nanoliposomes have an average particle size of 80-120 nm, a polydispersity index (PDI) ≤ 0.15, a zeta potential of -25 to -35 mV, an encapsulation efficiency of bio-decolorized comfrey oil ≥ 90%, and a surface chitosan oligosaccharide amino density ≥ 0.8 mmol / g.

[0017] A second aspect of the present invention provides a method for preparing the low-irritation comfrey oil nanoliposomes, comprising the following steps:

[0018] S1. Preparation of oil phase: Biodecolorized comfrey oil, chitosan oligosaccharide, and ceramide are dissolved in an ethanol-water co-solvent at 50℃ at a mass ratio of 1:1.5-2.5:0.8-1.2, with an ethanol volume fraction of 30%-40%, to obtain the oil phase;

[0019] S2. Preparation of aqueous phase: Dissolve the prebiotic skin flora regulator and the pH 5.5 weakly acidic buffer system in sterile water for injection at 70-80℃ to obtain the aqueous phase;

[0020] S3. Microjet emulsification: Slowly inject the oil phase into the aqueous phase, and circulate it 3-5 times with a microjet at 800-1000 bar.

[0021] S4. Freeze-thaw treatment: Freeze at -80℃ for 2 hours, then thaw in a water bath at 25℃, repeat 2-3 times.

[0022] S5. Sterilization filtration: filtered through a 0.22 μm polyethersulfone membrane and packaged in a nitrogen-filled container.

[0023] In a third aspect, a buttock-protecting formulation comprises any of the aforementioned low-irritation comfrey oil nanoliposomes, and may further comprise 0.1%-0.3% vitamin E acetate as an antioxidant and 0.05%-0.15% sodium hyaluronate as a moisturizing enhancer.

[0024] Preferably, the diaper rash preparation is selected from at least one formulation of spray, ointment, or gel.

[0025] Preferably, the diaper rash treatment is a diaper rash spray, using a disposable, metal-free micro-dispensing pump as the spray device. The pump body is made of medical-grade cyclic olefin copolymer (COC), with a single spray volume of 0.12-0.15 mL, an average droplet diameter of D32 35-45 μm, and a spray angle of 45°-60°. The spray device is equipped with a silicone one-way valve with an opening pressure of 0.05-0.08 MPa. The bottle body is made of three-layer co-extruded light-proof PET with an oxygen permeability ≤0.1 cm. 3 / (m2 ·day).

[0026] In a fourth aspect, the invention provides the use of any of the aforementioned low-irritation comfrey oil nanoliposomes and diaper rash preparations in the preparation of products or medicines for the prevention and rapid repair of mild to moderate diaper rash in infants aged 0-36 months.

[0027] Preferably, the product or drug is used 4-8 times daily for 1-7 consecutive days.

[0028] Compared with the prior art, the beneficial effects of the present invention are as follows:

[0029] Through nanoliposome encapsulation technology, the cumulative skin penetration of shikonin is increased by 2.8 times in 24 hours, ensuring that the active ingredients quickly reach the inflamed area to achieve anti-inflammatory and antibacterial effects and promote wound healing. A breathable "liquid bandage" is formed through rapid film formation in 30 seconds, simultaneously replenishing ceramides to repair the stratum corneum, reducing transepidermal water loss by ≥30% within 24 hours, and minimizing secondary damage from urine, feces, and friction. Prebiotic components regulate the skin's microecology, increasing the relative abundance of Bifidobacterium by ≥1.5 log and decreasing the relative abundance of Escherichia coli by ≥1.2 log within 3 days, inhibiting pathogenic bacteria while rebuilding the skin's beneficial flora barrier and reducing the recurrence rate of diaper rash. A weakly acidic buffer system maintains the slightly acidic environment of infant skin, combined with microencapsulated menthol for immediate itch relief and soothing, achieving low irritation and high safety throughout the process, addressing both daily prevention and acute intervention needs. Detailed Implementation

[0030] To more fully understand and demonstrate the technical solutions, objectives, and advantages of the present invention, the technical effects produced by the present invention will be further described in detail and completely below with reference to specific embodiments. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of them. It should be noted that other embodiments obtained by those skilled in the art without departing from the concept of the present invention are all within the protection scope of the present invention.

[0031] Unless otherwise specified, all reagents and materials used in the following examples are commercially available.

[0032] Example 1

[0033] In this embodiment, low-irritant comfrey oil nanoliposomes were prepared based on 100 g of final product. The formulation was as follows: 1.2 g of bio-decolorized comfrey oil, 1.33 g of chitosan oligosaccharide, 0.67 g of ceramide NP, 0.18 g of fructooligosaccharide, 0.12 g of inulin, 0.62 g of lactic acid, 0.38 g of sodium lactate, 0.08 g of microencapsulated menthol, and the balance being sterile water for injection.

[0034] The bio-decolorized comfrey oil, after supercritical CO2 extraction and β-cyclodextrin decolorization, contained 0.9A mg / g of shikonin, 0.46 mg / g of acetylshikonin, and 0.32 mg / g of deoxyshikonin, with a peroxide value of 4.1 meq / kg and an acid value of 1.6 mg KOH / g. The oligosaccharides had a weight-average molecular weight of 4.1 kDa and a degree of deacetylation of 92%. The ceramide NP purity was 97%. The prebiotic fructooligosaccharide to inulin mass ratio was 1.5:1. The pH 5.5 weak acid buffer system had a buffer capacity of 0.057 mol / (L·pH). The microencapsulated menthol loading was 25%.

[0035] Prepare according to the following steps, as detailed below:

[0036] S1. Preparation of oil phase: Comfrey oil, chitosan oligosaccharide, and ceramide NP were stirred at 400 rpm for 30 min at 50℃ in 12g of 35% (v / v) ethanol-water to form a transparent oil phase.

[0037] S2. Aqueous phase preparation: Dissolve prebiotics, lactate-sodium lactate buffer system and microencapsulated menthol in 75g of water for injection at 70℃, and cool down to 50℃ under nitrogen protection.

[0038] S3, Microjet emulsification: The oil phase is injected into the aqueous phase at 10 mL / min and circulated 4 times through a 900 bar microjet, with the temperature controlled online at 37±2℃ throughout the process;

[0039] S4. Freeze-thaw treatment: Freeze at -80℃ for 2 hours, then thaw in a water bath at 25℃, repeat 3 times;

[0040] S5. Sterilization filtration: Sterilization is achieved by filtration through a 0.22μm polyethersulfone membrane.

[0041] The resulting liposomes had an average particle size of 102 nm, a PDI of 0.12, a Zeta potential of -29 mV, and an encapsulation efficiency of 92.3%, meeting the preset requirements and suitable for severe diaper rash or those requiring rapid relief.

[0042] Example 2

[0043] In this embodiment, low-irritant comfrey oil nanoliposomes were prepared based on 100 g of final product. The formulation was as follows: 2.0 g of bio-decolorized comfrey oil, 2.0 g of chitosan oligosaccharide, 1.0 g of ceramide NP, 0.3 g of fructooligosaccharide, 0.1 g of inulin, 0.93 g of lactic acid, 0.57 g of sodium lactate, 0.2 g of microencapsulated menthol, and the balance being sterile water for injection.

[0044] The bio-decolorized comfrey oil contains 1.62 mg / g of shikonin, 0.81 mg / g of acetyl shikonin, and 0.55 mg / g of deoxyshikonin; its peroxide value is ≤5 meq / kg and its acid value is ≤2 mg KOH / g; the mass ratio of prebiotic oligofructose to inulin is 3:1; and the microencapsulated menthol loading is 30%.

[0045] The preparation method is basically the same as in Example 1, except that the microjet pressure is increased to 1000 bar and cyclicated 5 times, while the other steps are the same.

[0046] The obtained liposomes had an average particle size of 107 nm, a PDI of 0.13, a Zeta potential of -31 mV, and an encapsulation efficiency of 90.5%, meeting the preset requirements and suitable for severe diaper rash or those requiring rapid relief.

[0047] Example 3

[0048] In this embodiment, low-irritant comfrey oil nanoliposomes were prepared based on 100 g of final product. The formulation was as follows: 0.5 g of bio-decolorized comfrey oil, 0.6 g of chitosan oligosaccharide, 0.4 g of ceramide NP, 0.225 g of fructooligosaccharide, 0.075 g of inulin, 0.48 g of lactic acid, 0.32 g of sodium lactate, 0.05 g of microencapsulated menthol, and the balance being sterile water for injection.

[0049] The mass ratio of prebiotic fructooligosaccharides to inulin is 3:1, and the other raw material indicators are the same as in Example 1.

[0050] The preparation method is the same as in Example 1. The resulting liposomes have an average particle size of 98 nm, a PDI of 0.14, a Zeta potential of -27 mV, and an encapsulation rate of 91.2%, which meets the preset index requirements and is suitable for daily preventive care scenarios.

[0051] Example 4

[0052] This embodiment uses 100g of final product as a basis to prepare low-irritant comfrey oil nanoliposomes. Based on the formulation of Example 1, 0.1g of vitamin E acetate and 0.1g of sodium hyaluronate are added. The remaining components and dosages are the same as in Example 1.

[0053] Preparation method: Vitamin E acetate was dissolved together with comfrey oil and film material in the oil phase of S1; sodium hyaluronate was added in the aqueous phase of S2 and fully swollen at 50°C. The remaining steps were completely consistent with those in Example 1.

[0054] The resulting product underwent an accelerated 60℃ test for 14 days, and the shikonin retention rate was 94%, significantly improving the stability of the active ingredients while enhancing moisturizing and repairing effects.

[0055] Example 5

[0056] This embodiment uses 100g of final product as a basis to prepare low-irritant comfrey oil nanoliposomes. Based on the formulation of Example 1, the prebiotics are adjusted to 0.45g of fructooligosaccharide and 0.15g of inulin (mass ratio 3:1, total amount 0.60g). The remaining components and quality grades are completely consistent with those of Example 1.

[0057] The preparation method is the same as in Example 1. The resulting liposomes have an average particle size of 104 nm, a PDI of 0.11, and an encapsulation rate of 91.8%, which can further amplify the effect of microecological regulation and reduce the risk of diaper rash recurrence.

[0058] Example 6: Preparation of a diaper rash spray formulation

[0059] Take the low-irritation comfrey oil nanoliposome filtrate from Example 1, fill it into a three-layer co-extruded light-proof PET bottle under Class A laminar flow and nitrogen positive pressure of 0.05 MPa, and equip it with a disposable metal-free spring micro metering pump, a silicone one-way valve and a safety lock cap, with a filling volume of 10 mL / bottle, to obtain the buttock-protecting spray formulation.

[0060] The resulting product has a single spray volume of 0.12-0.15 mL, an average droplet diameter (D32) of 35-45 μm, and a spray angle of 45°-60°, which can evenly cover 10 cm² of skin. The silicone one-way valve opens at a pressure of 0.05-0.08 MPa and closes within 0.5 seconds after use to prevent external contamination. The bottle's oxygen permeability is ≤0.1 cm³ / (m²·day), which can effectively inhibit the oxidative degradation of shikonin and improve product stability.

[0061] Example 7: Preparation of a diaper rash ointment formulation

[0062] Take the low-irritation comfrey oil nanoliposomes from Example 12, add 8-10 times the amount of medical petrolatum and lanolin matrix, stir in a 60°C water bath until uniform, cool to room temperature, and dispense into sterile ointment tubes to obtain the diaper rash ointment formulation.

[0063] Example 8: Preparation of a diaper rash gel formulation

[0064] Take the low-irritant comfrey oil nanoliposomes from Example 3, add carbomer, glycerin and other gel matrices, stir and swell, adjust the pH to 5.5 with triethanolamine, stir evenly, sterilize and filter, and dispense into sterile gel tubes to obtain the buttock-protecting gel formulation.

[0065] Example 9: Scale-up preparation

[0066] The formulation of Example 1 was scaled up 500 times, with a total formulation of 500 kg: 6.00 kg of bio-decolorized comfrey oil, 6.67 kg of chitosan oligosaccharide, 3.33 kg of ceramide NP, 0.90 kg of fructooligosaccharide, 0.60 kg of inulin, 3.10 kg of lactic acid, 1.90 kg of sodium lactate, 0.40 kg of microencapsulated menthol, and 477.10 kg of water for injection.

[0067] Preparation method: Microjet pressure was 1000 bar for 4 cycles, followed by freeze-thaw cycles for 3 cycles, and filtration through a 0.22 μm polyethersulfone membrane. Particle size was monitored online using DLS. The inter-batch particle size RSD was 2.1%, the encapsulation efficiency RSD was 1.8%, and the pH change was 0.05 units, all meeting GMP release standards. Nitrogen-filled 50 mL metal-free pump bottles were used, with a spray volume of 0.15 g per bottle and a droplet size of 3244 μm. The batch-scale inhibition zones, 24-hour release curves, and clinical trial results showed no statistically significant differences compared to Example 1 (P>0.05), demonstrating the feasibility of linear scale-up and meeting the requirements for commercial production.

[0068] Example 10: Stability Test

[0069] The diaper rash spray formulation prepared in Example 6 was subjected to extreme temperature cycling stability tests and accelerated stability tests, respectively:

[0070] 1. Extreme temperature cycling test: The finished product was placed at -20℃ to 40℃ for 10 cycles, 12 hours each time, for a total of 20 days. The results showed that the product had a clear appearance, pH 5.52→5.48, particle size 102→104nm, encapsulation efficiency 92.3→91.8%, and antibacterial activity maintained >99%, with all indicators changing by Δ<5%, meeting the ICHQ1A stability requirements.

[0071] 2. Accelerated stability test: The same batch of liquid was filled into a metal-free spring micro metering pump (experimental group) and a traditional 304 stainless steel spring pump (control group), and placed at 40℃ / 75%RH for 4 weeks. The results showed that the shikonin content in the experimental group decreased by 3%, with no significant changes in appearance, particle size, or spray performance; while the shikonin content in the control group decreased by 18%, the droplet size increased, visible oxide particles appeared, and the spray performance decreased significantly, proving that the metal-free design can significantly improve the long-term stability of the product.

[0072] Example 11: Clinical Validation Trial

[0073] 1. Materials and Methods

[0074] 1.1 Clinical Data

[0075] The study included infants aged 0-36 months diagnosed with mild to moderate diaper rash. A total of 120 cases were observed and randomly divided into an experimental group and a control group, with 60 cases in each group. There were no statistically significant differences between the two groups in baseline characteristics such as age, sex, severity of diaper rash, and duration of illness (P>0.05), making them comparable.

[0076] 1.2 Diagnostic Criteria

[0077] The diagnostic criteria for mild to moderate diaper rash in infants and young children were formulated with reference to the "Guidelines for Skin Care of Chinese Children": erythema and papules appear in the diaper-covered areas such as the buttocks and perineum, with or without mild erosion, the lesion area is <25cm², and there is no severe ulceration or infection.

[0078] 1.3 Inclusion Criteria

[0079] ① Meets the Western medical diagnostic criteria for mild to moderate diaper rash;

[0080] ② Children aged 0-36 months must have their informed consent signed by their guardian;

[0081] ③ No other topical or oral medications for diaper rash have been used in the past week;

[0082] ④ Able to cooperate in completing treatment and follow-up.

[0083] 1.4 Exclusion Criteria

[0084] ① Individuals with congenital skin diseases, immune deficiencies, or severe liver or kidney dysfunction;

[0085] ② Those with skin lesions complicated by severe bacterial or fungal infection, or ulceration area > 5% of body surface area;

[0086] ③ Individuals allergic to the test drug or its components;

[0087] ④ Those with poor compliance who are unable to complete the treatment as required.

[0088] 1.5 Treatment Methods

[0089] Experimental group: The diaper rash spray preparation prepared in Example 6 of this invention was used. After cleaning and drying the affected area, it was sprayed 4-6 times a day for 7 consecutive days.

[0090] Control group: Commercially available zinc oxide cream was used, applied twice daily after cleaning and drying the affected area, for 7 consecutive days.

[0091] During the treatment, both groups maintained the usual diaper changing frequency and did not use any other topical or oral medications.

[0092] 1.6 Efficacy Evaluation Criteria

[0093] ①Efficacy Index (EI) = (Pre-treatment lesion area and symptom score - Post-treatment lesion area and symptom score) / Pre-treatment lesion area and symptom score × 100%;

[0094] ② Efficacy is determined based on the efficacy index: Cure: EI≥90%, Significant effect: 60%≤EI<90%, Improvement: 30%≤EI<60%, Ineffective: EI<30%;

[0095] ③Effective rate = (Number of cured + Number of significantly effective + Number of improved) / Total number of people × 100%;

[0096] ④ Observation indicators: changes in erythema area after 3 days and 7 days of treatment, changes in transepidermal water loss (TEWL), and occurrence of adverse reactions.

[0097] 1.7 Statistical Analysis

[0098] Count data were analyzed using the χ² test; continuous data were expressed as mean ± standard deviation. The t-test was used for comparisons between groups, and P < 0.05 was considered statistically significant.

[0099] 2. Results

[0100] 2.1 Comparison of clinical efficacy

[0101] After 3 days of treatment, the average erythema area in the experimental group decreased by 82.4%, while the average erythema area in the control group decreased by 61.2%, and the difference between the two groups was statistically significant (P<0.05). After 7 days of treatment, the clinical efficacy of the two groups was compared in Table 1.

[0102] Table 1

[0103]

[0104] Note: The difference in the overall effective rate between the two groups was statistically significant (P<0.05), with the experimental group showing significantly better efficacy than the control group.

[0105] 2.2 Skin barrier repair effect

[0106] Seven days after treatment, the transepidermal water loss rate (TEWL) of the affected area in the experimental group decreased by 42.3% compared with before treatment, and the rate in the control group decreased by 21.5% compared with before treatment. The difference between the two groups was statistically significant (P<0.05), proving that the product of this invention can significantly repair the damaged skin barrier of infants and young children.

[0107] 2.3 Safety Evaluation

[0108] During the experiment, no adverse reactions such as allergies, burning pain, or increased erythema occurred in the experimental group, and the skin irritation index (PII) was ≤0.5. In the control group, 3 cases experienced increased local skin oiliness and pore blockage. The difference in the incidence of adverse reactions between the two groups was statistically significant (P<0.05), proving that the product of this invention is highly safe and does not irritate the delicate skin of infants and young children.

[0109] The above are merely preferred embodiments of the present invention and are not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A low-irritation comfrey oil nanoliposome, characterized in that, It is composed of the following components by weight percentage: 0.5%-2.0% bio-decolorized comfrey oil, 1.0%-3.0% oligosaccharide-ceramide binary membrane material, 0.3%-1.0% prebiotic skin flora regulator, 0.8%-1.5% pH 5.5 weakly acidic buffer system, 0.05%-0.2% edible-grade microencapsulated menthol, and the balance being sterile water for injection.

2. The low-irritation comfrey oil nanoliposomes according to claim 1, characterized in that, The low-irritation comfrey oil nanoliposomes are composed of the following components by weight percentage: 1.2% bio-decolorized comfrey oil, 2.0% oligosaccharide-ceramide binary membrane material, 0.3% prebiotic skin flora regulator, 1.0% pH 5.5 weakly acidic buffer system, 0.08% edible-grade microencapsulated menthol, and the balance being sterile water for injection.

3. The low-irritation comfrey oil nanoliposomes according to claim 1, characterized in that, The bio-decolorized comfrey oil contains shikonin ≥ 0.8 mg / mL, acetylshikonin ≥ 0.4 mg / mL, and deoxyshikonin ≥ 0.3 mg / mL. And / or in the aforementioned chitosan oligosaccharide-ceramide binary membrane material, the chitosan oligosaccharide has a weight-average molecular weight of 3-5 kDa and a degree of deacetylation ≥90%, and the ceramide is ceramide NP with a purity ≥95%; And / or the prebiotic skin flora regulator is formed by compounding fructooligosaccharides and inulin in a mass ratio of 1-3:1, and both have a purity of ≥98%; And / or the pH 5.5 weakly acidic buffer system is prepared by mixing lactic acid and sodium lactate in a molar ratio of 1.5:1, with a buffer capacity ≥0.05 mol / (L·pH); And / or the microcapsule wall material of the edible-grade microencapsulated menthol is sodium octenyl succinate starch with a particle size of 5-15 μm and a menthol loading of 20%-30%.

4. The low-irritation comfrey oil nanoliposomes according to claim 1, characterized in that, The nanoliposomes have an average particle size of 80-120 nm, a polydispersity index (PDI) ≤ 0.15, a zeta potential of -25 to -35 mV, an encapsulation efficiency of bio-decolorized comfrey oil ≥ 90%, and a surface chitosan oligosaccharide amino density ≥ 0.8 mmol / g.

5. The method for preparing low-irritation comfrey oil nanoliposomes according to any one of claims 1 to 4, characterized in that, Includes the following steps: S1. Preparation of oil phase: Biodecolorized comfrey oil, chitosan oligosaccharide, and ceramide are dissolved in an ethanol-water co-solvent at 50℃ in a mass ratio of 1:1.5-2.5:0.8-1.2, with an ethanol volume fraction of 30%-40%, to obtain the oil phase; S2. Preparation of aqueous phase: Dissolve the prebiotic skin flora regulator and the pH 5.5 weakly acidic buffer system in sterile water for injection at 70-80℃ to obtain the aqueous phase; S3. Microjet emulsification: Slowly inject the oil phase into the aqueous phase, and circulate it 3-5 times with a microjet at 800-1000 bar. S4. Freeze-thaw treatment: Freeze at -80℃ for 2 hours, then thaw in a water bath at 25℃, repeat 2-3 times. S5. Sterilization filtration: filtered through a 0.22 μm polyethersulfone membrane and packaged in a nitrogen-filled container.

6. A diaper rash protectant, characterized in that, It comprises the low-irritant comfrey oil nanoliposomes as described in any one of claims 1 to 4, and further comprises 0.1%-0.3% vitamin E acetate as an antioxidant and 0.05%-0.15% sodium hyaluronate as a moisturizing enhancer.

7. The diaper rash protectant according to claim 6, characterized in that, The diaper rash preparation is selected from at least one formulation of spray, ointment, or gel.

8. The diaper rash protectant according to claim 7, characterized in that, The described diaper rash treatment is a spray formulation, using a disposable, metal-free micro-dispensing pump as the spray device. The pump body is made of medical-grade cyclic olefin copolymer (COC), with a single spray volume of 0.12-0.15 mL, an average droplet diameter of D32 35-45 μm, and a spray angle of 45°-60°. The spray device is equipped with a silicone one-way valve with an opening pressure of 0.05-0.08 MPa. The bottle body is made of three-layer co-extruded light-proof PET with an oxygen permeability ≤0.1 cm³. 3 / (m 2 ·day).

9. The use of the low-irritation comfrey oil nanoliposomes according to any one of claims 1 to 4 and the diaper rash preparation according to any one of claims 6 to 8 in the preparation of products or medicines for the prevention and rapid repair of mild to moderate diaper rash in infants aged 0-36 months.

10. The application according to claim 9, characterized in that, The product or drug is to be used 4-8 times daily for 1-7 consecutive days.

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