Sunshool time-delay nursing essential oil and preparation method thereof

Abstract

The invention belongs to the technical field of plant care essential oil extraction, and particularly relates to sanshool delayed care essential oil and a preparation method thereof. The invention discloses a sanshool-enriched lipid composition which is prepared from the following components in parts by weight: 0.05 to 0.1 part of sanshool-enriched fraction, 1 to 2 parts of solid lipid, 1 to 1.5 parts of liquid lipid, 1.5 to 2.5 parts of stable surfactant, 1 to 2 parts of cosurfactant, 3 to 5 parts of glycerol, 0.2 to 0.5 part of soothing anti-irritation component, 0.05 to 0.1 part of sodium hyaluronate, 0.1 to 0.3 part of hydroxypropyl methyl cellulose, 0.05 to 0.1 part of antioxidant and the balance of purified water. According to the invention, sanshool is used as a core functional factor, and through collaborative design of supercritical extraction, molecular distillation purification, NLC carrier encapsulation and a soothing film-forming system, contradictions of effectiveness, mildness and the like in an existing scheme are solved, and mild desensitization, stable controlled release, reduction of stimulation and migration risks and improvement of tolerance and action consistency are realized.

Description

Technical Field

[0001] This invention belongs to the field of plant care essential oil extraction technology, specifically relating to a sanshool-based delayed-acting care essential oil and its preparation method. Background Technology

[0002] In the field of male intimate skin care, there is a demand for topical methods to reduce local sensitivity and enhance the duration of intimate intercourse. Compared with oral administration, topical preparations have the advantages of faster onset of action, localized action, and convenient use, thus topical delayed ejaculation care products have attracted attention in practical applications. However, the stratum corneum of the intimate area is thin, rich in nerve endings, and more sensitive to stimulation. Topical preparations must not only achieve effective sensitivity regulation but also ensure high skin compatibility and user comfort.

[0003] In existing technologies, common approaches to reduce local sensitivity and achieve delayed ejaculation include the following: First, using topical preparations containing local anesthetics or numbing active substances to decrease sensitivity by reducing sensory transmission intensity; second, using plant-derived extracts or compound systems to achieve auxiliary effects through stimulation threshold regulation, soothing and sedation, and reducing friction discomfort; third, using different dosage form carriers to improve the penetration, spread, and retention of active substances, such as emulsions, gels, sprays, and oils, in order to enhance local effects and user experience. Regarding plant-derived active substances, the sanshool compounds abundant in Zanthoxylum bungeanum plants can produce typical numbing or tingling sensations and have the potential to regulate local sensory stimulation thresholds; therefore, some existing technologies have attempted to use them in topical products related to delayed ejaculation. However, the above technologies still generally have several shortcomings in practical applications. Taking the direct external application of crude oil or simple solutions of Zanthoxylum bungeanum as an example, while sanshool compounds can provide a basis for reducing sensitivity, crude extraction systems are often complex in composition and easily carry a certain proportion of volatile irritants, strongly odorous components, and unstable impurities. This increases the probability of adverse reactions such as stinging, burning, and tightness, affecting user acceptance and willingness to repeat use. Furthermore, simple oil-phase or solution systems are prone to the instantaneous release and local accumulation of active substances on the surface, resulting in problems such as excessive initial irritation, uneven action, and insufficient persistence. This causes the effect to fluctuate significantly depending on the application location, dosage, and skin condition. At the same time, sanshool compounds are relatively sensitive to environmental factors such as oxygen, light, and heat. Without stabilization and protection measures, they are prone to degradation during storage or use, leading to decreased efficacy and batch-to-batch variations, further reducing product consistency and controllability.

[0004] Furthermore, existing topical delay care products often face a conflict between efficacy and safety: on the one hand, increasing the concentration of active ingredients or enhancing penetration can improve the reduction of sensitivity, but may also lead to increased irritation, excessive local numbness, and skin discomfort; on the other hand, adopting stronger film-forming, thickening, or blocking strategies to reduce irritation may reduce instantaneous stimulation, but may result in blocked release, insufficient efficacy, or increased stickiness and stuffiness. Moreover, topical products may migrate and transfer during use, potentially causing discomfort to partners or leading to instability in the site of action and intensity of action. These factors limit the further application and promotion of sorbitan-based topical delay care products. Summary of the Invention

[0005] In view of the shortcomings of the prior art, the purpose of this invention is to provide a sanshool-based delay care essential oil and its preparation method.

[0006] The technical effect described in this invention is achieved through the following technical solution: a sanshool-based delayed ejaculation care essential oil, comprising the following components by weight: 0.05-0.1 parts sanshool enriched fraction, 1-2 parts solid lipids, 1-1.5 parts liquid lipids, 0.3-0.5 parts oil-phase stabilized surfactant, 1.2-2 parts water-phase stabilized surfactant, 1-2 parts co-surfactant, 3-5 parts glycerin, 0.2-0.5 parts soothing and anti-irritant components, 0.05-0.1 parts sodium hyaluronate, 0.1-0.3 parts hydroxypropyl methylcellulose, and 0.05-0.1 parts antioxidant, with the remainder being purified water, to a total weight of 100 parts; Preferably, the specific preparation process of the sanshool-enriched fraction is as follows: S1: Mix equal proportions of green Sichuan pepper pericarp, red Sichuan pepper pericarp and mountain pepper pericarp, vacuum dry until the moisture content is ≤8%, pulverize and pass through a 40-80 mesh sieve, and set the powder aside. S2: Add the powder from step S1 into an extraction tank for extraction treatment. Remove alcohol from the extract under vacuum at 35-45℃ until the alcohol content is ≤0.5%. Add 0.1-0.2% tocopherol and then perform molecular distillation under nitrogen purging and light protection to obtain the sorbitol-enriched fraction. Preferably, in step S2, the specific parameters of the extraction process are: pressure 25-35 MPa, temperature 45-55℃, CO2 flow rate 10-25 kg / h, time 2-3 h, co-solvent is ethanol, the amount of ethanol used is 4-6% of the CO2 mass flow rate, the temperature of the first-stage separator is 35-45℃, and the pressure is 8-12 MPa; the temperature of the second-stage separator is 25-35℃, and the pressure is 3-6 MPa, and the oily extract is collected. Preferably, in step S2, the amount of tocopherol added is calculated based on the mass of the extract; Preferably, in step S2, the specific parameters of the molecular distillation are: evaporator temperature 90–115°C, vacuum degree 1–2 Pa, scraper rotation speed 200–400 rpm, condensation temperature 20–30°C, and feed rate 2–5 g / min; fractional collection, mainly collecting the heavy fraction in the middle and later stages, removing the light fraction in the first stage and the end residue; total sanshool in the intermediate is 10–30 wt%. It should be noted that the former is the front section, the section in which the target main peak is stably produced is the middle and rear section heavy fraction, and the end is the residual section collected when the evaporator temperature remains unchanged but the distillation rate decreases significantly. Preferably, the solid lipid is any one of glyceryl monostearate, hydrogenated vegetable oil, stearic acid, and cetyl alcohol; Preferably, the liquid lipid is any one of medium-chain triglycerides, squalane, and isopropyl myristate; Preferably, the oil-phase stabilizing surfactant is either polyglycerol fatty acid ester or lecithin; Preferably, the aqueous phase stabilizing surfactant is either Tween-80 or PEG-40 hydrogenated castor oil; Preferably, the co-surfactant is any one of propylene glycol, butylene glycol, and polyethylene glycol; Preferably, the soothing and anti-irritant component is composed of panthenol, allantoin, and dipotassium glycyrrhizate in a mass ratio of 1:0.3 to 0.8:0.5 to 1; Preferably, the antioxidant is any one of tocopherol, ascorbyl palmitate, and rosemary extract; Preferably, another aspect of the present invention provides a method for preparing a sanshool-based delay-effect essential oil, specifically comprising the following steps: S101: Solid lipids and liquid lipids are heated to complete melting in a water bath at 70-80°C, oil phase stabilizer surfactants are added and stirred until evenly dispersed, then sorbitan enrichment fraction and antioxidants are added and stirred until evenly dispersed to obtain NLC oil phase; S102: Heat purified water to 70-75℃, add glycerol, co-surfactant and aqueous phase stabilizer in sequence, stir until fully dispersed, then add soothing and anti-irritant components, stir to dissolve evenly, then sprinkle in hydroxypropyl methylcellulose, stir until no visible agglomerates are present, and obtain the aqueous phase; S103: Slowly add the oil phase from step S101 to the aqueous phase from step S102, emulsify at high speed and homogenize under high pressure, then immediately cool to 25°C with stirring at 300 rpm, add sodium hyaluronate, adjust the pH to 5.2-5.8 with citrate buffer, and pre-filter at 200 μm to obtain the care essential oil. Preferably, in step S103, the parameters for high-speed shear emulsification are: rotation speed 8000-12000 rpm, time 3-8 min; Preferably, in step S103, the parameters for the high-pressure homogenization process are: pressure 800-1000 bar, cycle 4-6 times.

[0007] The beneficial effects of this invention are as follows: This invention utilizes sanshools, abundant in Zanthoxylum bungeanum raw materials, as key functional factors. By modulating the local sensory stimulation threshold, it achieves a gentle reduction in sensitivity, providing a core effect basis for reducing local sensitivity. Compared to existing methods that rely on direct external application of crude oil or simple solutions, primarily depending on increasing dosage to enhance the numbing sensation, this invention does not achieve its effect by simply enhancing stimulation. Instead, it systematically designs solutions to address common contradictions such as the difficulty in achieving both effectiveness and gentleness, stability and efficacy, and local action and risk of metastasis. This allows sanshools to exert their effects more controllably, stably, and uniformly in external application scenarios. Without sacrificing the core sensitivity-reducing effect, it significantly improves irritation, stability, and consistency of action, enhancing daily acceptability and reusability. Specifically, this invention first constructs a standardizable sorbitan-enriched fraction through a combined purification process of supercritical fluid extraction and molecular distillation. Without introducing highly toxic solvents, this process enriches and stably retains sorbitan-like active components while selectively reducing volatile and unstable impurities in the raw materials that can cause stinging, burning, or overly pungent odors. This makes the composition of the intermediate's effective components more controllable and improves batch-to-batch consistency. This pre-purification and delivery strategy overcomes the dilemma of complex crude extract components leading to both amplified irritation and inactivation, reducing the probability of discomfort caused by direct external application of sorbitan from the source and providing a more suitable raw material basis for the stable construction of subsequent nanodelivery systems.

[0008] Building upon this foundation, this invention employs a nanostructured lipid carrier constructed from solid and liquid lipids to encapsulate and uniformly disperse the sorbitan-enriched fraction. This transforms the direct surface exposure and instantaneous release of sorbitan in traditional systems into a gradual and sustained release carried by a lipid network. On one hand, the nanocarrier weakens the tendency of sorbitan to form localized high-concentration peaks on the skin surface, reducing discomfort and decreased tolerance caused by excessive instantaneous stimulation. On the other hand, the lipid network buffers and protects sorbitan, reducing the probability of direct contact with oxidative factors during storage and use, thereby enhancing activity retention and stability. While maintaining the effect of reduced sensitivity, it achieves a synergistic improvement in both reduced irritation and enhanced sustainability, overcoming the problems of fluctuating onset and rapid attenuation in traditional formulations. Furthermore, this invention introduces glycerin and soothing anti-irritant components to synergistically exert barrier-friendly and calming buffering effects. Without significantly weakening the core function of sorbitan, it reduces discomfort such as burning and tightness that may occur in the initial stage of topical application, further improving overall tolerance and reusability. This invention further introduces hydroxypropyl methylcellulose and sodium hyaluronate to form a mild film-forming adhesion and moisturizing support structure, making it easier for the nanocarrier to spread evenly and remain stably at the target site. This reduces the risk of instability in efficacy due to migration and diffusion, as well as contact transfer, improving safety and consistency of action. This film-forming structure works synergistically with the controlled-release properties of the nanocarrier, avoiding both the tendency of insufficient efficacy due to blocked release caused by simply thickening or strengthening the film, and the tendency of increased stimulation due to simply increasing instantaneous release. This achieves a more reasonable balance between sustained efficacy and mildness. The antioxidant system further forms a synergistic protective effect with the lipid carrier, creating a more stable microenvironment for sorbitol and reducing efficacy attenuation and batch-to-batch fluctuations caused by oxidative degradation. Attached Figure Description

[0009] Figure 1 This is a pH change graph for accelerated stability testing of Example 1 and Comparative Examples 1-4 of the present invention; Figure 2 This is a graph showing the particle size variation in accelerated stability tests of Example 1 and Comparative Examples 1-4 of the present invention; Figure 3 This is a pH change graph from the simulated test in use of Example 1 and Comparative Examples 1-4 of the present invention; Figure 4 This is a graph showing the particle size variation in simulated tests of Example 1 and Comparative Examples 1-4 of the present invention. Figure 5 These are the HPLC chromatograms of the salicornin-enriched fractions at each stage of Example 1 of the present invention; Figure 5 (A) is the supercritical oil after dealcoholization; Figure 5 (B) is the light fraction from the initial stage of molecular distillation; Figure 5 (C) represents the heavy fraction in the latter part of molecular distillation; Figure 5 (D) represents end residue / residue. Detailed Implementation

[0010] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Unless otherwise specified, the raw materials involved in the present invention are all purchased through conventional commercial channels. Experimental methods without specific conditions are conventional methods and conditions well known in the art, or according to the conditions recommended by the instrument manufacturer.

[0011] Example 1: A sanshool-based delay-enhancing essential oil, comprising the following components by weight: 0.08 parts sanshool enriched fraction, 1.5 parts solid lipids, 1.2 parts liquid lipids, 0.4 parts oil-phase stabilized surfactant, 1.5 parts water-phase stabilized surfactant, 1.5 parts co-surfactant, 4 parts glycerin, 0.35 parts soothing and anti-irritant components, 0.08 parts sodium hyaluronate, 0.2 parts hydroxypropyl methylcellulose, and 0.08 parts antioxidant, with the remainder being purified water, to a total weight of 100 parts; The specific preparation process of the sanshool-enriched fraction is as follows: S1: Mix equal proportions of green Sichuan pepper peel, red Sichuan pepper peel and mountain pepper peel, vacuum dry until the moisture content is ≤8%, pulverize and pass through a 60-mesh sieve, and set the powder aside. S2: Add the powder from step S1 to the extraction tank for extraction treatment at a pressure of 30 MPa, a temperature of 50℃, a CO2 flow rate of 18 kg / h, and a time of 2.5 h. The co-solvent is ethanol, and the amount of ethanol used is 6% of the CO2 mass flow rate. The temperature of the first-stage separator is 40℃ and the pressure is 10 MPa; the temperature of the second-stage separator is 30℃ and the pressure is 5 MPa. Collect the oily extract. De-alcoholize the extract under vacuum at 40℃ until the alcohol content is ≤0.5%. Add 0.15% tocopherol, and then carry out molecular distillation under nitrogen purging and light protection conditions. The evaporator temperature is 105℃, the vacuum degree is 1 Pa, the scraper rotation speed is 300 rpm, the condensation temperature is 25℃, and the feed rate is 3 g / min. Collect in stages, mainly collecting the heavy fraction in the middle and later stages, and removing the light fraction in the first stage and the end residue. The total sanshool in the intermediate is 20 wt%. A sanshool-enriched fraction is obtained. The preparation method of the sanshool-based delay-care essential oil specifically includes the following steps: S101: Glyceryl monostearate and medium-chain triglycerides were heated in a water bath at 75°C until completely melted. Lecithin was added and stirred until evenly dispersed. Then, the sorbitol enrichment fraction and tocopherol were added and stirred until evenly dispersed to obtain the NLC oil phase. S102: Heat purified water to 72°C, add glycerol, propylene glycol and Tween-80 in sequence, stir until fully dispersed, then add the soothing and anti-irritant component composed of panthenol, allantoin and dipotassium glycyrrhizate in a mass ratio of 1:0.5:0.8, stir until dissolved evenly, then sprinkle in hydroxypropyl methylcellulose, stir until no visible agglomerates are visible, and obtain the aqueous phase; S103: Slowly add the oil phase from step S101 to the aqueous phase from step S102, emulsify at 10000 rpm for 5 min and homogenize and circulate at 900 bar for 5 times; then immediately cool to 25°C with stirring at 300 rpm, add sodium hyaluronate, adjust the pH to 5.5 with citrate buffer, and pre-filter at 200 μm to obtain the care essential oil.

[0012] Example 2: A sanshool-based delay-enhancing essential oil, comprising the following components by weight: 0.1 parts sanshool enriched fraction, 2 parts solid lipids, 1.5 parts liquid lipids, 0.5 parts oil-phase stabilized surfactant, 2 parts water-phase stabilized surfactant, 2 parts co-surfactant, 5 parts glycerin, 0.5 parts soothing and anti-irritant components, 0.1 parts sodium hyaluronate, 0.3 parts hydroxypropyl methylcellulose, and 0.1 parts antioxidant, with the remainder being purified water, to a total weight of 100 parts; The specific preparation process of the sanshool-enriched fraction is as follows: S1: Mix equal proportions of green Sichuan pepper pericarp, red Sichuan pepper pericarp and mountain pepper pericarp, vacuum dry until the moisture content is ≤8%, pulverize and pass through an 80-mesh sieve, and set the powder aside. S2: Add the powder from step S1 to the extraction tank for extraction treatment at a pressure of 35 MPa, a temperature of 55℃, a CO2 flow rate of 25 kg / h, and a time of 3 h. The co-solvent is ethanol, with the ethanol dosage being 6% of the CO2 mass flow rate. The temperature of the first-stage separator is 45℃ and the pressure is 12 MPa; the temperature of the second-stage separator is 35℃ and the pressure is 6 MPa. Collect the oily extract. De-alcoholize the extract under vacuum at 45℃ until the alcohol content is ≤0.5%. Add 0.2% tocopherol, and then perform molecular distillation under nitrogen purging and light protection conditions. The evaporator temperature is 115℃, the vacuum degree is 1 Pa, the scraper rotation speed is 400 rpm, the condensation temperature is 20℃, and the feed rate is 5 g / min. Collect in stages, mainly collecting the heavy fraction in the middle and later stages, and removing the light fraction in the first stage and the end residue. The total sanshool in the intermediate is 30 wt%; obtain the sanshool-enriched fraction. The preparation method of the sanshool-based delay-care essential oil specifically includes the following steps: S101: Stearic acid and squalane were heated to complete melting in an 80°C water bath, polyglycerol fatty acid ester was added and stirred until evenly dispersed, then sorbitan enriched fraction and rosemary extract were added and stirred until evenly dispersed to obtain NLC oil phase; S102: Heat purified water to 75°C, add glycerin, polyethylene glycol and PEG-40 hydrogenated castor oil in sequence, stir until fully dispersed, then add the soothing and anti-irritant component composed of panthenol, allantoin and dipotassium glycyrrhizate in a mass ratio of 1:0.8:1, stir to dissolve evenly, then sprinkle in hydroxypropyl methylcellulose, stir until no visible agglomerates are present, and obtain the aqueous phase; S103: Slowly add the oil phase from step S101 to the aqueous phase from step S102, emulsify at 12000 rpm for 3 min and homogenize and circulate at 1000 bar for 4 times; then immediately cool to 25°C with stirring at 300 rpm, add sodium hyaluronate, adjust the pH to 5.8 with citrate buffer, and pre-filter at 200 μm to obtain the care essential oil.

[0013] Example 3: A sanshool-based delay-enhancing essential oil, comprising the following components by weight: 0.05 parts sanshool enriched fraction, 1 part solid lipid, 1 part liquid lipid, 0.3 parts oil-phase stabilized surfactant, 1.2 parts water-phase stabilized surfactant, 1 part co-surfactant, 3 parts glycerin, 0.2 parts soothing and anti-irritant components, 0.05 parts sodium hyaluronate, 0.1 parts hydroxypropyl methylcellulose, and 0.05 parts antioxidant, with the remainder being purified water, to a total weight of 100 parts; The specific preparation process of the sanshool-enriched fraction is as follows: S1: Mix equal proportions of green Sichuan pepper peel, red Sichuan pepper peel and mountain pepper peel, vacuum dry until the moisture content is ≤8%, pulverize and pass through a 40-mesh sieve, and set the powder aside. S2: Add the powder from step S1 to the extraction tank for extraction treatment at a pressure of 25 MPa, a temperature of 45℃, a CO2 flow rate of 10 kg / h, and a time of 2 h. The co-solvent is ethanol, and the amount of ethanol used is 4% of the CO2 mass flow rate. The temperature of the first-stage separator is 35℃ and the pressure is 8 MPa; the temperature of the second-stage separator is 25℃ and the pressure is 3 MPa. Collect the oily extract. De-alcoholize the extract under vacuum at 35℃ until the alcohol content is ≤0.5%. Add 0.1% tocopherol, and then carry out molecular distillation under nitrogen purging and light protection conditions. The evaporator temperature is 90℃, the vacuum degree is 2 Pa, the scraper speed is 200 rpm, the condensation temperature is 30℃, and the feed rate is 2 g / min. Collect in stages, mainly collecting the heavy fraction in the middle and later stages, and removing the light fraction in the first stage and the end residue. The total sanshool in the intermediate is 10 wt%; obtain the sanshool-enriched fraction. The preparation method of the sanshool-based delay-care essential oil specifically includes the following steps: S101: Hydrogenated vegetable oil and medium-chain triglycerides are heated in a water bath at 70°C until completely melted. Lecithin is added and stirred until evenly dispersed. Then, the sorbitan enriched fraction and ascorbate palmitate are added and stirred until evenly dispersed to obtain the NLC oil phase. S102: Heat purified water to 70°C, add glycerin, butylene glycol and PEG-40 hydrogenated castor oil in sequence, stir until fully dispersed, then add the soothing and anti-irritant component composed of panthenol, allantoin and dipotassium glycyrrhizate in a mass ratio of 1:0.3:0.5, stir until dissolved evenly, then sprinkle in hydroxypropyl methylcellulose, stir until no visible agglomerates are present, and obtain the aqueous phase; S103: Slowly add the oil phase from step S101 to the aqueous phase from step S102, emulsify at high speed of 8000 rpm for 8 min, and homogenize and circulate under high pressure of 800 bar 6 times; then immediately cool to 25°C with stirring at 300 rpm, add sodium hyaluronate, adjust the pH to 5.2 with citrate buffer, and pre-filter at 200 μm to obtain the care essential oil.

[0014] Comparative Example 1: In Comparative Example 1, molecular distillation was not used to collect and standardize the extracts of Zanthoxylum bungeanum. Instead, the oily extract obtained by supercritical CO2 extraction was directly used as the active ingredient after vacuum deethanolination. The remaining steps and parameters were the same as in Example 1.

[0015] Comparative Example 2: In Comparative Example 2, no nanostructured lipid carrier was constructed. Instead, solid lipids and liquid lipids were replaced with equal masses of inert oil-phase matrix medium-chain triglycerides. The remaining steps and parameters were the same as in Example 1.

[0016] Comparative Example 3: No soothing and anti-irritant components were added in Comparative Example 3. The missing mass was made up with an equal amount of purified water to maintain the total mass. The remaining steps and parameters were the same as in Example 1.

[0017] Comparative Example 4: Hydroxypropyl methylcellulose and sodium hyaluronate were not added in Comparative Example 4. The missing mass was made up with an equal amount of purified water to maintain the total mass. The remaining steps and parameters were the same as in Example 1.

[0018] Performance testing: Desensitization and safety testing: Sexually mature male and female SD rats were selected and housed under standard conditions of 22±2℃, 50-70% relative humidity, and a 12-hour light-dark cycle for 7 days to acclimatize. Mating behavior testing was conducted 4 hours after the start of the dark phase (red light illumination) to minimize the interference of circadian rhythms on sexual behavior. Experimental groups: blank control (no treatment), matrix control (containing only the same lipid / surfactant / film-forming and soothing system, without sorbitan-enriched fraction), Example 1 group, and Comparative Examples 1-4 groups (8 rats per group); groups were randomly assigned and blinded. To reduce noise from individual differences, male rats underwent pre-training for mating before formal drug administration: male rats were placed alone in an observation box (40cm×40cm×40cm transparent box) for 10 minutes to acclimatize before being introduced to accepting female rats, allowing 30 minutes of mating contact. This was repeated 3 times at 48-hour intervals. Male rats that did not exhibit mating behavior were removed and replaced with alternative male rats to complete the group numbers. Female mice were used for hormone induction. 48 hours before mating, each mouse was subcutaneously injected with 20 μg of estradiol benzoate, and 4 hours before mating, each mouse was subcutaneously injected with 1.0 mg of progesterone. For the formal experiment, the scrotum was shaved and marked 1 cm deep. 2 The area served as both the administration and stimulation zone. Male rats were placed on a grid platform for 10 minutes to acclimatize, and the 50% mechanical withdrawal threshold was determined using von Frey fibers via an up-down method as the baseline. Subsequently, 30 μL / cm² of medication was administered according to the group. 2 To maintain consistency across groups, the mice were allowed to rest for 10 minutes after administration. Thresholds were measured at 10 minutes (onset point) and 60 minutes (duration point). Immediately afterwards, mating behavior testing was conducted: male mice were placed in an observation box for 10 minutes to acclimatize, then female mice in estrus were introduced. Timing and recording began and continued until the first ejaculation, followed by another 10 minutes of observation (to record the post-ejaculatory refractory period). Recorded indicators included: first mounting latency (time from female entry into the box to first mounting), first penetration latency, ejaculation latency (time from first penetration to first ejaculation), number of pre-ejaculatory penetrations, number of pre-ejaculatory mountings, and post-ejaculatory refractory period. To exclude nonspecific... The pseudo-prolongation caused by sedation / motor inhibition was addressed by adding a general activity level assessment every other day (10 minutes in an open field, recording total walking distance). Local erythema / edema / scratching responses were recorded at 10 minutes and 60 minutes after drug administration (scores 0-5, 0 for no erythema or edema, no scratching; 1 for mild localized erythema, no edema, occasional slight scratching; 2 for significant erythema, mild edema, frequent scratching; 3 for erythema, moderate edema, severe scratching, mild skin damage; 4 for erythema, severe edema, skin damage and bleeding; 5 for severe erosion and ulceration, accompanied by systemic discomfort). The test results are shown in Tables 1, 2, and 3 below.

[0019] Table 1. Test results of mechanical retraction threshold for each test group

[0020] Table 2. Results of Mating Behavior Indicators in Each Experimental Group

[0021] Table 3. Safety index records for each experimental group

[0022] Based on the results in Tables 1-3, Example 1 showed a more stable increase in the mechanical withdrawal threshold at both the onset and duration points, and exhibited a more pronounced trend of prolonged ejaculation latency in mating behavior tests. Simultaneously, there was no significant decrease in open-field activity, suggesting that this prolonged trend mainly stemmed from reduced local sensitivity rather than non-specific sedation or motor inhibition. These results highlight the dominant role of the sorbitan-enriched fraction as a key functional factor from an efficacy perspective; that is, it can achieve a mild reduction in sensitivity by modulating local sensory stimulation responses. In Comparative Example 2, after removing NLC, the increase in the onset threshold was limited, and the duration point essentially declined. The mating behavior indicators were also close to those of the control group, indicating that the presence of sorbitan alone is insufficient to achieve a stable and sustained effect. NLC encapsulation and uniform dispersion are the key structural basis for maintaining the duration effect and reducing fluctuations. In Comparative Example 4, after removing the film-forming adhesion system, an increase in the onset threshold was still observed, but the duration point significantly decreased, and the ejaculation latency was only moderately prolonged. This suggests that film formation and moisturizing support mainly ensure the consistency of action by enhancing local retention and distribution uniformity, and reducing the risk of attenuation caused by migration and diffusion. In Comparative Example 3, after removing the soothing and anti-irritant components, the threshold and ejaculation latency still showed a prolonged trend, but the stimulation score increased significantly and the latency of initiation behavior was lengthened. This reflects that the adverse feedback offsets the acceptability of use and affects behavioral initiation, indicating that the soothing system plays a key role in buffering stress, improving tolerance, and enhancing reusability without weakening the main effect of salicornin. In Comparative Example 1, after removing molecular distillation standardization, the increase in threshold and improvement in behavior decreased, while the stimulation score increased. This indicates that co-purification can selectively reduce easily irritating and unstable impurity components in the crude extract, reducing topical discomfort and fluctuations from the source, and providing a more controllable active intermediate for the stable construction of subsequent delivery systems.

[0023] Particle size distribution and encapsulation efficiency test: The Z-mean particle size and PDI of the samples were determined by dynamic light scattering (DLS). The samples of Examples 1-3 were diluted 50 times with purified water and tested at 25°C. The free sorbitan and the carrier-encapsulated part were separated by ultrafiltration centrifugation. The sorbitan content was quantified separately (liquid chromatography quantification). The encapsulation efficiency (%) was calculated based on the total amount and the free amount. The test results are shown in Table 4 below.

[0024] Table 4. Particle size distribution and encapsulation efficiency results of the examples

[0025] Based on the analysis of the results in Table 4, the particle size, PDI, and D of Examples 1-3 were analyzed. 90 The positive and negative differences in encapsulation efficiency are both small, indicating that the construction process of the nanostructured lipid carrier has good repeatability and controllability under the same process window. At the same time, the small fluctuation in encapsulation efficiency indicates that the sorbitan-enriched fraction has good compatibility with the lipid network and low tendency to extravasate, providing a stable structural basis for achieving mild controlled release, reducing local instantaneous peak stimulation, and maintaining consistent effects. In the context of topical delayed-release care, the uniformity of the nanocarrier structure and the stability of encapsulation are prerequisites for achieving overall synergistic effects: uniform particle size helps reduce stimulation fluctuations caused by local enrichment, and stable encapsulation helps suppress instantaneous release peaks and improve the stability of active ingredients in the formulation.

[0026] Accelerated stability test: The dispensed samples (Example 1 and Comparative Examples 1-4) were placed in a constant temperature incubator at 40°C and 75% relative humidity, protected from light. Samples were taken and tested on days 0, 7, 14, 21, and 28. Before sampling, the samples were brought back to 25°C and allowed to stand for 30 minutes, then gently inverted and mixed 10 times. Changes in appearance, odor, pH, and particle size were then recorded. In-use simulation test: Samples were opened daily and exposed to air for 2 minutes before being sealed to simulate in-use conditions. The caps were then restored to a sealed state and the in-use conditions were continued. Continue storage; record changes in appearance, odor, pH, and particle size on days 0, 3, 7, and 14; changes in appearance and odor during accelerated testing and in-use simulation testing are shown in Tables 5 and 6 below (grading explanation: appearance: A = homogeneous, no stratification / precipitation; B = slightly turbid or slightly flocculated, recoverable by shaking; C = visible flocculation / slight stratification; D = obvious stratification or precipitation, difficult to recover; odor: 0 = no change; 1 = slight change; 2 = significant change / increased irritation; 3 = significant deterioration (pungent, rancid tendency)); pH and particle size changes are as follows: Figure 1 , Figure 2 , Figure 3 and Figure 4 As shown.

[0027] Table 5. Results of appearance and odor changes in each experimental group under accelerated testing

[0028] Table 6. Results of appearance and odor changes in each experimental group under simulated testing.

[0029] Based on Table 5-6 and Figure 1-4Analysis of the results showed that, under accelerated conditions of 40℃ / 75%RH in the dark, Example 1 maintained a uniform appearance throughout the entire observation period, without significant stratification or irreversible flocculation. Odor changes were slight, pH fluctuations were minimal, and particle size showed only a slow, acceptable upward trend, indicating that the system possesses good structural and chemical stability under thermal stress and high humidity. This stability advantage is highly consistent with the multi-module synergistic design of this invention: on the one hand, the sanshool-enriched fraction obtained by molecular distillation is more controllable at the component level, with fewer volatile irritating impurities and unstable components, reducing the risk of oxidative degradation and interfacial disturbances from the source; on the other hand, the NLC lipid network has a carrying and buffering effect on the active ingredients and oil phase, which can slow down aggregation and droplet growth at high temperatures; simultaneously, the film-forming adhesion and moisturizing support system enhances the structural strength and local adhesion of the aqueous phase, helping to inhibit particle migration and aggregation and reduce the tendency of stratification; the antioxidant system further provides protection in the formulation microenvironment, thus resulting in overall greater stability in appearance, odor, pH, and particle size. Comparative Example 1, after removing molecular distillation standardization, showed more significant odor deterioration, pH decrease, and particle size increase over time, indicating that residual volatile and unstable impurities in the crude extract accelerate oxidation and interfacial instability. Comparative Example 2, after removing NLC, showed a significant increase in particle size and easier stratification, indicating that simply replacing it with an inert oil phase cannot provide a stable nanocarrier structure, and aggregation is more likely to occur under thermal stress. Comparative Example 4, after removing HPMC and sodium hyaluronate, showed accelerated deterioration in appearance and particle size, proving that film adhesion and moisturizing support play a key role in resisting stratification and aggregation. Comparative Example 3, after removing the soothing component, showed a slight decrease in stability but was still significantly better than Comparative Examples 1 / 2 / 4, consistent with the common sense that the soothing component mainly contributes to tolerability and user comfort, while its impact on physical stability is relatively minor. Under simulated conditions, the odor changes and pH downward trend of each group were more sensitive than those of accelerated storage. Example 1 still showed relatively small fluctuations, while Comparative Examples 1 and 2 / 4 showed odor changes and particle size increases earlier. This indicates that the system of the present invention has a stronger resistance to oxidation and interface disturbances caused by repeated exposure to air, thereby better ensuring the consistency and safety of the effect in actual use and providing a stable and reliable formulation basis for external delayed ejaculation care applications.

[0030] HPLC chromatograms: HPLC tracking chromatogram analysis was performed on the supercritical oil, the light fraction from the first stage of molecular distillation, the heavy fraction from the second stage of molecular distillation, and the terminal residue / residue in the preparation process of the salicornin-enriched fraction of Example 1. The results are as follows: Figure 5 As shown.

[0031] based on Figure 5 Results analysis, Figure 5 (A) is the supercritical oil after alcohol removal. It can be seen that there are many chromatographic peaks and complex fingerprints. Although there are corresponding peak signals in the target retention time range, there are also many accompanying peaks, indicating that the raw oil components are complex and the target components are not concentrated. Figure 5 (B) is the light fraction in the pre-molecular distillation stage. Its chromatographic response is mainly concentrated in the shorter retention time range. The peak signal is significantly weakened in the target retention time range, indicating that the light volatile accompanying components are preferentially separated and removed from the system. Figure 5 (C) is the heavy fraction in the later stage of molecular distillation. It can be seen that the main peak signal is significantly enhanced and the impurity peaks are significantly reduced in the target retention time interval, indicating that the target component is effectively enriched in this segment and the components are simplified and standardized. Figure 5 (D) represents the terminal residue / residue, whose chromatographic response is dominated by a longer retention time range, with a weaker peak signal in the target region. This indicates that the high-boiling-point heavy components are directionally concentrated in the residual phase and do not enter the enriched fraction. Based on this, the supercritical extraction combined with molecular distillation fractionation process of the present invention can achieve the directional enrichment of the target component and simultaneously reduce light volatile byproducts and high-boiling-point heavy impurities, thereby obtaining a sanshool-enriched fraction that is more suitable for subsequent topical formulation construction.

[0032] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A sanshool-based delay-enhancing essential oil, characterized in that, Its composition includes the following components by weight: 0.05-0.1 parts of sanshool-enriched fraction, 1-2 parts of solid lipids, 1-1.5 parts of liquid lipids, 0.3-0.5 parts of oil-phase stabilized surfactant, 1.2-2 parts of aqueous-phase stabilized surfactant, 1-2 parts of co-surfactant, 3-5 parts of glycerol, 0.2-0.5 parts of soothing and anti-irritant components, 0.05-0.1 parts of sodium hyaluronate, 0.1-0.3 parts of hydroxypropyl methylcellulose, and 0.05-0.1 parts of antioxidant, with the balance being purified water, to a total weight of 100 parts.

2. The sanshool-based delay-enhancing essential oil according to claim 1, characterized in that, The specific preparation process of the sanshool-enriched fraction is as follows: S1: Mix equal proportions of green Sichuan pepper peel, red Sichuan pepper peel and mountain pepper peel, vacuum dry, pulverize and sieve, and set aside the powder. S2: Add the powder from step S1 into an extraction tank for extraction treatment. Vacuum de-alcoholize the extract, add tocopherol, and then perform molecular distillation under nitrogen purging and light-proof conditions to obtain the sorbitol-enriched fraction. In step S2, the specific parameters of the extraction process are as follows: pressure 25-35 MPa, temperature 45-55℃, CO2 flow rate 10-25 kg / h, time 2-3 h, co-solvent is ethanol, the amount of ethanol used is 4-6% of the CO2 mass flow rate, the temperature of the first-stage separator is 35-45℃, and the pressure is 8-12 MPa; the temperature of the second-stage separator is 25-35℃, and the pressure is 3-6 MPa, and the oily extract is collected. In step S2, the specific parameters of the molecular distillation are as follows: evaporator temperature 90-115℃, vacuum degree 1-2Pa, scraper rotation speed 200-400rpm, condensation temperature 20-30℃, and feed rate 2-5g / min; segmented collection, mainly collecting the heavy fraction in the middle and later stages, and removing the light fraction in the front stage and the end residue; the total sanshool in the intermediate is 10-30wt%.

3. The sanshool-based delay-enhancing essential oil according to claim 1, characterized in that, The solid lipid is any one of glyceryl monostearate, hydrogenated vegetable oil, stearic acid, and cetyl alcohol.

4. The sanshool-based delay-enhancing essential oil according to claim 1, characterized in that, The liquid lipid is any one of medium-chain triglycerides, squalane, and isopropyl myristate.

5. The sanshool-based delay-enhancing essential oil according to claim 1, characterized in that, The oil-phase stabilizing surfactant is either polyglycerol fatty acid ester or lecithin; the aqueous-phase stabilizing surfactant is either Tween-80 or PEG-40 hydrogenated castor oil.

6. The sanshool-based delay-enhancing essential oil according to claim 1, characterized in that, The co-surfactant is any one of propylene glycol, butylene glycol, and polyethylene glycol.

7. The sanshool-based delay-enhancing essential oil according to claim 1, characterized in that, The soothing and anti-irritant component is composed of panthenol, allantoin, and dipotassium glycyrrhizate in a mass ratio of 1:0.3 to 0.8:0.5 to 1.

8. The sanshool-based delay-enhancing essential oil according to claim 1, characterized in that, The antioxidant is any one of tocopherol, ascorbyl palmitate, and rosemary extract.

9. A method for preparing a sanshool-based delayed-ejaculation essential oil according to any one of claims 1-8, characterized in that, Specifically, the following steps are included: S101: Solid lipids and liquid lipids are heated in a water bath until completely melted, oil phase stabilizer surfactants are added and stirred until evenly dispersed, then sorbitan enrichment fraction and antioxidants are added and stirred until evenly dispersed to obtain NLC oil phase; S102: Heat purified water, add glycerol, co-surfactant and aqueous phase stabilizer in sequence, stir until fully dispersed, then add soothing and anti-irritant components, stir to dissolve evenly, then sprinkle in hydroxypropyl methylcellulose, stir until no visible agglomerates are present, and obtain the aqueous phase; S103: Slowly add the oil phase from step S101 to the aqueous phase from step S102, emulsify by high-speed shearing and homogenize under high pressure, then immediately cool while stirring, add sodium hyaluronate and citrate buffer to adjust the pH, filter, and obtain the care essential oil.

10. A method for preparing the sanshool-based delayed-ejaculation essential oil according to claim 9, characterized in that, In step S103, the parameters for high-speed shear emulsification are: rotation speed 8000-12000 rpm, time 3-8 min; the parameters for high-pressure homogenization are: pressure 800-1000 bar, cycle 4-6 times.

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