Male delay spray based on natural herbal components and preparation method thereof

Abstract

The invention discloses a male delay spray based on natural herbal components and a preparation method of the male delay spray. The method comprises the following steps: preparing calcined oyster-cherokee rose fruit sustained-release microspheres; preparing to obtain vinegar processed gallnut-fresh aloe-peach gum two-phase gel; the herba epimedii-fructus cnidii temperature-sensitive liposome is prepared and obtained; mixing the porous calcined oyster shell-fructus rosae laevigatae sustained-release microspheres, the vinegar-processed gallnut-zanthoxylum piperitum biphase nano latex and the herba epimedii-fructus cnidii temperature-sensitive liposome in deionized spring water, performing homogenization treatment, and adding a mussel mucin solution and oxidized hyaluronic acid to trigger a Schiff base cross-linking reaction; the mussel mucoprotein-hyaluronic acid double-network hydrogel is obtained; and adjusting the pH value of the mussel mucin-hyaluronic acid dual-network hydrogel, and sterilizing to obtain the male delay spray. According to the invention, an accurate, lasting and comfortable time delay effect can be realized.

Description

Technical Field

[0001] This application relates to a male delay spray, specifically a male delay spray based on natural herbal ingredients and its preparation method. Background Technology

[0002] Most male delay sprays on the market rely on local anesthetics (such as lidocaine or benzocaine) to reduce sensitivity by inhibiting nerve signal transmission. While this method has a certain immediate effect, it has significant drawbacks: First, anesthetic ingredients may cause excessive numbness of the skin and mucous membranes, burning or stinging sensations, or allergic reactions, affecting the natural experience and failing to fundamentally regulate physiological functions. Second, although some products using natural herbal ingredients (such as clove oil) attempt to avoid the side effects of chemical anesthetics, they are often produced using simple processes, mostly simple mixtures of crude extracts, resulting in unstable ingredients, poor absorption, short duration of action, and easy delamination, making it difficult to achieve efficient, long-lasting, and safe delay effects.

[0003] Therefore, developing a delayed ejaculation product that can avoid the side effects of chemical anesthetics and enhance the efficacy of natural ingredients through advanced formulation technology has become a clear need and a direction for technological breakthroughs in this field. Summary of the Invention

[0004] In view of the shortcomings of the prior art, the purpose of this application is to provide a male delay spray based on natural herbal ingredients and its preparation method. This application, through multi-stage sustained release and intelligent temperature-sensitive delivery technology, can achieve a precise, long-lasting and comfortable delay effect while completely avoiding the side effects of chemical anesthetics.

[0005] To achieve the above objectives, this application provides the following technical solution: A male delay spray based on natural herbal ingredients, wherein the components and their mass percentages are as follows: vinegar-processed gallnut micro-powder: 1.0% to 1.5%; calcined oyster shell powder: 0.5% to 2.0%; Rosa laevigata extract: 0.8% to 2.0%; yellow wine-processed Epimedium extract: 0.5% to 2.5%; fermented Sichuan pepper extract: 0.1% to 0.6%; pine needle oil: 0.05% to 0.3%; borneol: 0.05% to 0.4%; fresh aloe vera juice: 5% to 12%; Cnidium monnieri concentrate: 0.5% to 1.8%; honeysuckle flower dew: 3% to 8%; deionized spring water: balance.

[0006] This application also provides a method for preparing a male delay spray based on natural herbal ingredients. The method includes: preparing calcined oyster-Rosa laevigata sustained-release microspheres; preparing vinegar-processed gallnut-fresh aloe vera-peach gum biphasic gel; preparing epimedium-Cnidium monnieri thermosensitive liposomes; mixing the porous calcined oyster-Rosa laevigata sustained-release microspheres, the vinegar-processed gallnut-Zanthoxylum bungeanum biphasic nano-latex, and the epimedium-Cnidium monnieri thermosensitive liposomes in deionized spring water for homogenization; triggering a Schiff base cross-linking reaction by adding mussel adhesive protein solution and oxidized hyaluronic acid to obtain a mussel adhesive protein-hyaluronic acid dual-network hydrogel; adjusting the pH of the mussel adhesive protein-hyaluronic acid dual-network hydrogel; and obtaining the male delay spray after sterilization.

[0007] Optionally, the preparation of calcined oyster-Rosa laevigata sustained-release microspheres includes: ultrasonically dispersing calcined oyster powder in phosphate buffer to form a porous suspension; adding Rosa laevigata extract and sodium alginate to the porous suspension for stirring and self-assembly; adding calcium acetate solution to form microspheres; collecting and drying the microspheres to obtain porous calcined oyster-Rosa laevigata sustained-release microspheres.

[0008] Optionally, the drying of the microspheres includes: freeze-drying the microspheres at -50°C.

[0009] Optionally, the preparation of the vinegar-processed gallnut-fresh aloe vera-peach gum biphase gel includes: mixing pine needle oil, borneol and fermented Sichuan pepper extract in a water bath to form a homogeneous oil phase; dissolving vinegar-processed gallnut micropowder in fresh aloe vera juice and stirring to form a homogeneous aqueous phase; mixing the oil phase and aqueous phase, and shearing to obtain vinegar-processed gallnut-Sichuan pepper biphase nano-latex.

[0010] Optionally, the preparation of vinegar-rhubarb-fresh aloe vera-peach gum biphase gel further includes: adding chitosan solution to deposit and solidify an interface film on the surface of vinegar-rhubarb-pepper biphase nano-latex.

[0011] Optionally, the preparation of Epimedium-Cnidium thermosensitive liposomes includes: dissolving lecithin and cholesterol in chloroform to form a lipid film; hydrating Epimedium extract (processed with rice wine), Cnidium monnieri concentrate, and Lonicera japonica flower dew (5.5%), and encapsulating them in the lipid film to form crude liposomes; and homogenizing the crude liposomes to obtain Epimedium-Cnidium thermosensitive liposomes.

[0012] Optionally, the preparation of Epimedium-Cnidium thermosensitive liposomes further includes: surface modification of the Epimedium-Cnidium thermosensitive liposomes.

[0013] Optionally, the step of homogenizing the porous calcined oyster-Rosa laevigata sustained-release microspheres, the vinegar-processed gallnut-Sichuan pepper biphasic nano-latex, and the Epimedium-Cnidium monnieri thermosensitive liposomes in deionized spring water includes: performing primary and secondary homogenization treatments on the porous calcined oyster-Rosa laevigata sustained-release microspheres, the vinegar-processed gallnut-Sichuan pepper biphasic nano-latex, and the Epimedium-Cnidium monnieri thermosensitive liposomes mixed in the deionized spring water.

[0014] Optionally, the mussel adhesive protein-hyaluronic acid dual-network hydrogel is pH-adjusted and sterilized to obtain a male delay spray, including: sterilizing the pH-adjusted mussel adhesive protein-hyaluronic acid dual-network hydrogel by three-stage gradient filtration.

[0015] Compared with the prior art, the beneficial effects of this application are as follows: This application achieves outstanding comprehensive technical effects by constructing a multi-component synergistic system and advanced delivery technology: First, this application completely abandons chemical anesthetic components. By utilizing the astringent and consolidating properties of natural herbal ingredients such as vinegar-processed gallnut, calcined oyster shell, and Rosa laevigata, it gently reduces sensitivity at the physiological level, fundamentally avoiding the excessive numbness, burning sensation, and allergy risks caused by traditional products, thus significantly improving safety. Second, it employs a multi-level advanced delivery system, including calcined oyster shell-Rosa laevigata sustained-release microspheres, nano-latex, thermosensitive liposomes, and mussel adhesive protein-hyaluronic acid dual-network hydrogel, which greatly enhances the stability, skin permeability, mucosal adhesion, and duration of action of the drug, solving the pain points of poor absorption and easy inactivation of traditional herbal sprays. Attached Figure Description

[0016] Figure 1 This is a schematic flowchart illustrating a method for preparing a male delay spray based on natural herbal ingredients, according to one embodiment of this application. Detailed Implementation

[0017] The technical solutions of the embodiments of this application will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of this application, and not all of the embodiments. Based on the embodiments of this application, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of this application.

[0018] It should be noted that all directional indicators (such as up, down, left, right, front, back, etc.) in the embodiments of this application are only used to explain the relative positional relationship and movement of each component in a certain specific posture (as shown in the figure). If the specific posture changes, the directional indicator will also change accordingly.

[0019] In this application, unless otherwise expressly specified and limited, the terms "connection," "fixed," etc., should be interpreted broadly. For example, "fixed" can mean a fixed connection, a detachable connection, or an integral part; it can mean a mechanical connection or an electrical connection; it can mean a direct connection or an indirect connection through an intermediate medium; it can mean the internal communication of two components or the interaction between two components, unless otherwise expressly limited. Those skilled in the art can understand the specific meaning of the above terms in this application according to the specific circumstances.

[0020] Furthermore, if the embodiments of this application involve descriptions such as "first" or "second," these descriptions are for descriptive purposes only and should not be construed as indicating or implying their relative importance or implicitly specifying the number of technical features indicated. Therefore, a feature defined with "first" or "second" may explicitly or implicitly include at least one of those features. Additionally, the meaning of "and / or" throughout the text includes three parallel solutions; for example, "A and / or B" includes solution A, solution B, or a solution where both A and B are satisfied simultaneously. Furthermore, the technical solutions of the various embodiments can be combined with each other, but this must be based on the ability of those skilled in the art to implement them. When the combination of technical solutions is contradictory or impossible to implement, it should be considered that such a combination of technical solutions does not exist and is not within the scope of protection claimed in this application.

[0021] In one exemplary embodiment, this application provides a male delay spray based on natural herbal ingredients. The components of the spray and the mass percentage of each component are as follows: vinegar-processed gallnut micro powder: 1.0% to 1.5%; calcined oyster shell powder: 0.5% to 2.0%; Rosa laevigata extract: 0.8% to 2.0%; yellow wine-processed Epimedium extract: 0.5% to 2.5%; fermented Sichuan pepper extract: 0.1% to 0.6%; pine needle oil: 0.05% to 0.3%; borneol: 0.05% to 0.4%; fresh aloe vera juice: 5% to 12%; Cnidium monnieri concentrate: 0.5% to 1.8%; honeysuckle flower dew: 3% to 8%; deionized spring water: balance.

[0022] Figure 1 This is a schematic flowchart illustrating a method for preparing a male delay spray based on natural herbal ingredients, according to one embodiment of this application. The method includes the following steps: S100: Porous calcined oyster-Rosa laevigata sustained-release microspheres were prepared; S200: Prepared vinegar-processed gallnut-Zanthoxylum biphase nano-latex; S300: Preparation of Epimedium-Cnidium thermosensitive liposomes; S400: The porous calcined oyster-Rosa laevigata sustained-release microspheres, the vinegar-processed gallnut-Zanthoxylum bungeanum biphasic nano-latex and the Epimedium-Cnidium monnieri thermosensitive liposomes are mixed in deionized spring water and homogenized. By adding mussel adhesive protein solution and oxidized hyaluronic acid to trigger Schiff base cross-linking reaction, mussel adhesive protein-hyaluronic acid dual network hydrogel is obtained. S500: A male delay spray is obtained by adjusting the pH value of mussel adhesive protein-hyaluronic acid dual network hydrogel and sterilizing it.

[0023] The preparation method described above will now be described in detail with reference to specific embodiments.

[0024] Example 1 Step 1: Calcined oyster shell powder (1.2%) was ultrasonically dispersed in phosphate buffer (0.1M) at pH 8.5 to form a porous suspension. Rosa laevigata extract (1.4%) and sodium alginate were added to the porous suspension and stirred at 45°C for self-assembly (the process by which sodium alginate molecules spontaneously and orderly aggregate, entangle, and encapsulate Rosa laevigata extract and calcined oyster shell powder particles through non-covalent interactions (such as electrostatic attraction, hydrogen bonding, and hydrophobic interactions), thus forming a preliminary, relatively loosely structured pre-aggregate network). Next, calcium acetate solution (10% concentration) was added dropwise to induce Ca2+ aggregation. 2+ Ionic cross-linking with sodium alginate forms microspheres; the microspheres are collected by centrifugation and freeze-dried (-50℃, 24h) to obtain porous calcined oyster-Rosa laevigata sustained-release microspheres (50μm to 100μm in diameter).

[0025] In this step, the microspheres collected by centrifugation are freeze-dried at -50°C. The purpose is to rapidly solidify the water in the microsphere suspension into fine ice crystals through deep freezing, thereby maximally inhibiting ice crystal growth and recrystallization. This process effectively avoids puncturing or compressing the delicate porous structure of the microspheres due to ice crystal expansion or coarsening, ensuring that the sustained-release network constructed by the calcined oyster shell carrier and Rosa laevigata extract is completely preserved after dehydration. Ultimately, a stable microsphere morphology with high specific surface area, good resolubility, and the expected drug release kinetics is obtained. It should be noted that if the freeze-drying temperature is higher than -50℃ (e.g., -20℃ or -30℃), the water that is not completely frozen in the system will form larger ice crystals. The mechanical stress generated during their growth will pierce the pore walls of the microspheres, causing the porous structure to collapse and the specific surface area to decrease significantly, thereby affecting the drug loading and sustained-release performance. Conversely, if the temperature is too low (e.g., -70℃), although smaller ice crystals can be formed, excessive freezing will lead to a sharp increase in energy consumption and a longer cycle in the drying stage. It may also cause some active ingredients to become inactive due to excessive glass transition. At the same time, excessively low temperatures can easily increase the brittleness of the microspheres, making them prone to breakage or pulverization in subsequent processing, which will reduce the product yield and mechanical stability.

[0026] Step 2: Pine needle oil (0.2%), borneol (0.2%), and fermented Sichuan pepper extract (0.4%) were mixed and dissolved in a 60°C water bath to form a homogeneous oil phase. Simultaneously, under 60°C water bath heating conditions, vinegar-processed gallnut micro powder (1.3%) was dissolved in fresh aloe vera juice (8.5%), and the surfactant Tween-80 was added. After thorough stirring, a homogeneous aqueous phase was formed. Subsequently, the oil phase and aqueous phase were mixed and subjected to 3 to 4 cycles of shearing at 15000 psi using a high-pressure microjet emulsifier to form vinegar-processed gallnut-Sichuan pepper biphase nanoemulsion with a particle size of less than 200 nm. Finally, a 0.1% chitosan solution (pH=5.0) was added. Utilizing the electrostatic adsorption between the chitosan cations and the latex interface anions, an interfacial film was deposited and solidified on the surface of the nano-latex particles to form an interfacial film. This film generates electrostatic repulsion by imparting a positive charge to the surface of the nano-latex particles, and utilizes the steric hindrance effect provided by the chitosan polymer chains to effectively prevent collisions, aggregation, and stratification between the nano-latex particles (Ostwald ripening). This significantly enhances the physical stability of the vinegar-processed gallnut-Sichuan pepper biphase nano-latex.

[0027] Step 3: Lecithin (1.0%) and cholesterol (0.2%) were dissolved in chloroform, and the solvent was removed by rotary distillation (40℃) to form a lipid film (the purpose of which is to remove organic solvents so that lipid molecules are fixed on the inner wall of the container in a dry and uniform film form, providing a structural basis and precise composition ratio for liposome assembly); then, the extract of Epimedium brevicornu (1.5%), concentrated Cnidium monnieri (1.2%) and Lonicera japonica (5.5%) were hydrated and added to the container at 55℃. After vortexing (30 min), the lipid film detached from the container wall and spontaneously curled up using the amphiphilic properties of phospholipids to form multilayered, multi-sized crude liposomes encapsulating the drug; then, the multilayered, multi-sized crude liposomes were homogenized into uniformly sized (150±20nm) and completely encapsulated Epimedium-Cnidium monnieri thermosensitive liposomes using a microfluidic chip. Finally, the surface of the Epimedium-Cnidium thermosensitive liposomes was modified. The modification process specifically included: adding a 0.05% hyaluronic acid solution dropwise to the Epimedium-Cnidium thermosensitive liposome dispersion system under gentle stirring. Utilizing the electrostatic attraction between the negatively charged carboxyl groups on the hyaluronic acid chains and the cationic components on the surface of the Epimedium-Cnidium thermosensitive liposomes, the hyaluronic acid spontaneously adsorbed and anchored to the surface of the Epimedium-Cnidium thermosensitive liposomes. Simultaneously, the hyaluronic acid molecular chains formed an extensive hydrogen bond network with the polar head groups of the liposome phospholipid bilayer through their polyhydroxy structure, thereby constructing a stable hydrophilic biomimetic coating on the exterior of the Epimedium-Cnidium thermosensitive liposomes. This coating not only enhances the adhesion and retention of the liposomes to the mucosal surface but also utilizes the thermosensitive response characteristics of hyaluronic acid itself to undergo a conformational change triggered by body temperature, synergistically promoting the phase transition behavior of the liposome phospholipid bilayer to achieve intelligent on-demand drug release.

[0028] Step 4: The porous calcined oyster shell-Rosa laevigata sustained-release microspheres, vinegar-processed gallnut-Zanthoxylum bungeanum biphasic nano-latex, and Epimedium-Cnidium monnieri thermosensitive liposomes were mixed in deionized spring water at 4°C for homogenization. Specifically, the mixture was first homogenized using a high-speed shear disperser (e.g., 10,000 rpm to 15,000 rpm) for 3 to 5 minutes to rapidly break up large aggregates and achieve a preliminary macroscopic uniform distribution. Then, it was immediately transferred to a high-pressure homogenizer for secondary homogenization at a moderate pressure of 150 to 200 bar, repeated 2 to 3 times. This step utilizes the strong shear force, cavitation effect, and impaction generated by high pressure to further refine the nano-latex and liposomes and uniformly embed them into the pore network of the sustained-release microspheres, ultimately obtaining a stable suspension system with uniform particle distribution and full three-phase fusion.

[0029] After homogenization, mussel adhesive protein (MAP) solution (concentration 0.3%) and oxidized hyaluronic acid (concentration 0.2%) were added. Then, the mixture was injected into a micro vortex generator and a Schiff base cross-linking reaction was triggered under the condition of passing a trace amount of H2O2. This reaction refers to the nucleophilic addition and dehydration reaction between the aldehyde group (-CHO) on the oxidized hyaluronic acid molecular chain and the amino group (-NH2) on the mussel adhesive protein molecule, generating a Schiff base covalent bond containing a carbon-nitrogen double bond (C=N), thereby constructing a stable, pH-responsive three-dimensional dual-network hydrogel coating in situ on the carrier surface. Finally, a nano-mucus coating with a thickness of 50nm to 100nm was formed in situ on the carrier surface, obtaining a mussel adhesive protein-hyaluronic acid dual-network hydrogel.

[0030] Step 5: Adjust the pH of the mussel adhesive protein-hyaluronic acid dual-network hydrogel to 5.5 to 6.0 using a citric acid-sodium citrate buffer solution (to simulate the physiological environment of the mucosa and avoid local irritation); then perform three-stage gradient filtration sterilization (passing through 1.0μm (retaining microparticle aggregates), 0.45μm (removing bacteria), and 0.22μm (sterilization grade) microporous membranes for sterilization in sequence). Subsequently, under nitrogen protection (oxygen content <0.5%), dispense the sterilized mussel adhesive protein-hyaluronic acid dual-network hydrogel into brown light-proof glass spray bottles and equip them with spray pumps (nozzle orifice diameter 0.2mm, atomized particle size 30μm to 50μm) to achieve precise control of the single-press administration volume of 0.15mL±0.02mL.

[0031] In this step, it should be noted that this application employs a three-stage gradient filtration sterilization method for the pH-adjusted mussel adhesive protein-hyaluronic acid dual-network hydrogel. The aim is to ensure the sterility of the final product while maximizing the protection of the integrity of its active ingredients and formulation structure through a step-by-step interception and graded filtration strategy. First, a 1.0 μm filter membrane pre-intercepts any trace particle aggregates or insufficiently dispersed carrier fragments that may exist in the system, effectively reducing the load on subsequent filter membranes and preventing premature clogging. Subsequently, a 0.45 μm filter membrane removes the vast majority of bacteria and fungal cells. Finally, a 0.22 μm sterilization-grade filter membrane reliably filters out all microorganisms (including bacteria and mold), ensuring sterility. This progressive filtration method not only improves the efficiency of the sterilization operation and the lifespan of the filter membrane but also prevents structural damage or activity loss of active ingredients (such as liposomes, nano-emulsions, and sustained-release microspheres) due to excessive single-stage filtration pressure or filter membrane clogging, thereby ensuring the physical stability and biological activity of the spray.

[0032] Example 2 Step 1: Calcined oyster shell powder (0.5%) was ultrasonically dispersed in phosphate buffer (0.1M) at pH 8.5 to form a porous suspension. Rosa laevigata extract (0.8%) and sodium alginate were added to the porous suspension, and the mixture was stirred and self-assembled at 45°C. Then, calcium acetate solution (10% concentration) was added dropwise to induce Ca2+ self-assembly. 2+ Ionic cross-linking with sodium alginate forms microspheres; the microspheres are collected by centrifugation and freeze-dried (-50℃, 24h) to obtain porous calcined oyster-Rosa laevigata sustained-release microspheres (50μm to 100μm in diameter).

[0033] Step 2: Pine needle oil (0.05%), borneol (0.05%), and fermented Sichuan pepper extract (0.1%) were mixed and dissolved in a 60°C water bath to form a homogeneous oil phase. Simultaneously, under 60°C water bath heating conditions, vinegar-processed gallnut micro powder (1.0%) was dissolved in fresh aloe vera juice (5%), and the surfactant Tween-80 was added. After thorough stirring, a homogeneous aqueous phase was formed. Subsequently, the oil phase and aqueous phase were mixed and subjected to 3 to 4 cycles of shearing at 15000 psi using a high-pressure microjet emulsifier to form vinegar-processed gallnut-Sichuan pepper biphase nano-emulsion with a particle size of less than 200 nm. Finally, a 0.1% chitosan solution (pH=5.0) was added. Utilizing the electrostatic adsorption between the chitosan cations and the latex interface anions, an interfacial film was deposited and solidified on the surface of the nano-latex particles to form an interfacial film. This film generates electrostatic repulsion by imparting a positive charge to the surface of the nano-latex particles, and utilizes the steric hindrance effect provided by the chitosan polymer chains to effectively prevent collisions, aggregation, and stratification between the nano-latex particles (Ostwald ripening). This significantly enhances the physical stability of the vinegar-processed gallnut-Sichuan pepper biphase nano-latex.

[0034] Step 3: Lecithin (1.0%) and cholesterol (0.2%) were dissolved in chloroform, and the solvent was removed by rotary distillation (40°C) to form a lipid film. Subsequently, the extract of Epimedium brevicornu (0.5%) processed with rice wine, the concentrated extract of Cnidium monnieri (0.5%), and Lonicera japonica flower dew (3%) were combined with water at 55°C and added to a container. After vortexing (30 min), the lipid film detached from the container wall and spontaneously curled up due to the amphiphilic properties of phospholipids, forming multilayered, multi-sized crude liposomes encapsulating the drug. Then, using a microfluidic chip, the multilayered, multi-sized crude liposomes were homogenized into uniformly sized (150±20 nm) and completely encapsulated Epimedium-Cnidium monnieri thermosensitive liposomes. Finally, the surface of the Epimedium-Cnidium monnieri thermosensitive liposomes was modified as described in Example 1.

[0035] Step 4: Porous calcined oyster-Rosa laevigata sustained-release microspheres, vinegar-processed gallnut-Zanthoxylum bungeanum biphasic nano-latex, and Epimedium-Cnidium monnieri thermosensitive liposomes were mixed in deionized spring water at 4°C and homogenized (homogenization method as described in Example 1). Mussel adhesive protein (MAP) solution (concentration 0.3%) and oxidized hyaluronic acid (concentration 0.2%) were added, and then injected into a micro vortex generator. Under the condition of introducing a trace amount of H2O2, a Schiff base cross-linking reaction was triggered. Finally, a nano-mucus coating with a thickness of 50nm to 100nm was formed in situ on the carrier surface to obtain a mussel adhesive protein-hyaluronic acid dual-network hydrogel.

[0036] Step 5: Adjust the pH of the mussel adhesive protein-hyaluronic acid dual-network hydrogel to 5.5 to 6.0 using a citric acid-sodium citrate buffer solution (to simulate the physiological environment of the mucosa and avoid local irritation); then perform three-stage gradient filtration sterilization (the specific sterilization process is as described in Example 1). Subsequently, under nitrogen protection (oxygen content <0.5%), dispense the sterilized mussel adhesive protein-hyaluronic acid dual-network hydrogel into brown light-proof glass spray bottles and equip them with spray pumps (nozzle orifice diameter 0.2 mm, atomized particle size 30 μm to 50 μm) to achieve precise control of the single-press administration volume of 0.15 mL ± 0.02 mL.

[0037] Example 3 Step 1: Calcined oyster shell powder (2.0%) was ultrasonically dispersed in phosphate buffer (0.1M) at pH 8.5 to form a porous suspension. Rosa laevigata extract (2.0%) and sodium alginate were added to the porous suspension, and the mixture was stirred and self-assembled at 45°C. Then, calcium acetate solution (10% concentration) was added dropwise to induce Ca2+ self-assembly. 2+ Ionic cross-linking with sodium alginate forms microspheres; the microspheres are collected by centrifugation and freeze-dried (-50℃, 24h) to obtain porous calcined oyster-Rosa laevigata sustained-release microspheres (50μm to 100μm in diameter).

[0038] Step 2: Pine needle oil (0.3%), borneol (0.4%), and fermented Sichuan pepper extract (0.6%) were mixed and dissolved in a 60°C water bath to form a homogeneous oil phase. Simultaneously, under 60°C water bath heating conditions, vinegar-processed gallnut micro powder (1.5%) was dissolved in fresh aloe vera juice (12%), and the surfactant Tween-80 was added. After thorough stirring, a homogeneous aqueous phase was formed. Subsequently, the oil phase and aqueous phase were mixed and subjected to 3 to 4 cycles of shearing at 15000 psi using a high-pressure microjet emulsifier to form vinegar-processed gallnut-Sichuan pepper biphase nanoemulsion with a particle size of less than 200 nm. Finally, a 0.1% chitosan solution (pH=5.0) was added. Utilizing the electrostatic adsorption between the chitosan cations and the latex interface anions, an interfacial film was deposited and solidified on the surface of the nano-latex particles to form an interfacial film. This film generates electrostatic repulsion by imparting a positive charge to the surface of the nano-latex particles, and utilizes the steric hindrance effect provided by the chitosan polymer chains to effectively prevent collisions, aggregation, and stratification between the nano-latex particles (Ostwald ripening). This significantly enhances the physical stability of the vinegar-processed gallnut-Sichuan pepper biphase nano-latex.

[0039] Step 3: Lecithin (1.0%) and cholesterol (0.2%) were dissolved in chloroform to form a lipid film, which was then removed by rotary distillation (40°C). Subsequently, the extract of Epimedium (processed with rice wine) (2.5%), concentrated Cnidium monnieri extract (1.8%), and Lonicera japonica flower dew (8%) were combined with water at 55°C and added to a container. After vortexing (30 min), the lipid film detached from the container wall and spontaneously curled up due to the amphiphilic properties of phospholipids, forming multilayered, multi-sized crude liposomes encapsulating the drug. Then, using a microfluidic chip, the multilayered, multi-sized crude liposomes were homogenized into uniformly sized (150±20 nm) and completely encapsulated Epimedium-Cnidium monnieri thermosensitive liposomes. Finally, the surface of the Epimedium-Cnidium monnieri thermosensitive liposomes was modified as described in Example 1.

[0040] Step 4: Porous calcined oyster-Rosa laevigata sustained-release microspheres, vinegar-processed gallnut-Zanthoxylum bungeanum biphasic nano-latex, and Epimedium-Cnidium monnieri thermosensitive liposomes were mixed in deionized spring water at 4°C and homogenized (homogenization method as described in Example 1). Mussel adhesive protein (MAP) solution (concentration 0.3%) and oxidized hyaluronic acid (concentration 0.2%) were added, and then injected into a micro vortex generator. Under the condition of introducing a trace amount of H2O2, a Schiff base cross-linking reaction was triggered. Finally, a nano-mucus coating with a thickness of 50nm to 100nm was formed in situ on the carrier surface to obtain a mussel adhesive protein-hyaluronic acid dual-network hydrogel.

[0041] Step 5: Adjust the pH of the mussel adhesive protein-hyaluronic acid dual-network hydrogel to 5.5 to 6.0 using a citric acid-sodium citrate buffer solution (to simulate the physiological environment of the mucosa and avoid local irritation); then perform three-stage gradient filtration sterilization (the specific sterilization process is as described in Example 1). Subsequently, under nitrogen protection (oxygen content <0.5%), dispense the sterilized mussel adhesive protein-hyaluronic acid dual-network hydrogel (i.e., male delay spray) into brown light-proof glass spray bottles and equip them with spray pumps (nozzle orifice diameter 0.2mm, atomized particle size 30μm to 50μm) to achieve precise control of the single press dosage of 0.15mL±0.02mL.

[0042] Below, this application compares the performance of the male delay sprays prepared based on Examples 1 to 3. The comparison results are shown in Table 1: Table 1

[0043] The performance data in Table 1 were obtained through a series of standardized in vitro, in vitro, and human sensory evaluation experiments. Specifically, these included: recording the average onset and duration of action after spray use through volunteer sensory testing; assessing drug permeability and duration of action using Franz diffusion cells and in vitro skin models; scoring irritation through human patch testing and skin resistance measurement; monitoring the appearance, pH, content, and microbiological indicators of the formulation in accelerated and long-term stability tests to determine shelf life; and calculating the coefficient of variation (CV%) of spray uniformity by repeatedly measuring the single spray volume using a laser particle size analyzer and a precision balance. All data are averages from multiple independent experiments to ensure the scientific validity and reliability of the results.

[0044] Furthermore, among Examples 1 to 3, Example 1 was determined to be the best example because it not only demonstrated excellent balance in key efficacy indicators, with an average delay time of 18.5 minutes and rapid onset of action (5.2 minutes), significantly better than Example 2, but also slightly better than Example 3 in terms of irritation (0.8 points) and spray uniformity (CV=8.5%). More importantly, all of its component ratios were near the median of the optimal concentration range (e.g., 1.3% vinegar-processed gallnut micropowder and 8.5% fresh aloe vera juice). This ensured that the active ingredients could fully exert their synergistic effect, while avoiding potential irritation risks or increased costs due to excessively high concentrations of certain components (such as the high content of Sichuan pepper extract and borneol in Example 3). At the same time, its stability for more than 12 months was on par with Example 3, comprehensively demonstrating the best safety, efficacy, stability, and feasibility for industrial production. Furthermore, this application compares the spray prepared based on this application with existing sprays, as shown in Table 2: Table 2

[0045] As shown in Table 2, the spray provided in this application (represented by Example 1) exhibits significant comprehensive advantages compared to the two existing mainstream products: Compared to chemical anesthetic sprays that rely on chemical anesthetics (such as lidocaine) for delayed onset, which, although taking effect slightly faster, easily cause significant numbness and tingling (irritation score 2.5-3.5) and have a short duration of action (1-2 hours), this application, while completely avoiding chemical anesthetic components, achieves a more lasting delayed effect (18.5 minutes) and long-lasting effect (4 hours) through physiological astringency and advanced delivery technology, and has extremely low irritation (0.8 points); Compared to existing herbal sprays that are simply mixed with ingredients, easily inactivated and layered, and have short-lasting and unstable effects, this application, with its high stability (≥12 months), strong mucosal adhesion, and intelligent sustained-release characteristics, has achieved comprehensive improvements in onset time, duration of action, and overall reliability, fundamentally solving the pain points of poor absorption and weak effect of traditional herbal preparations.

[0046] The above are merely preferred embodiments of this application and do not limit the patent scope of this application. Any equivalent structural or procedural transformations made using the content of this application's specification and drawings, or direct or indirect applications in other related technical fields, are similarly included within the patent protection scope of this application.

Claims

1. A male delay spray based on natural herbal ingredients, characterized in that, The components of the spray and the mass percentage of each component are as follows: Vinegar-processed gallnut powder: 1.0% to 1.5%; Calcined oyster shell powder: 0.5% to 2.0%; Rosa laevigata extract: 0.8% to 2.0%; Extract of Epimedium prepared with rice wine: 0.5% to 2.5%; Fermented Sichuan pepper extract: 0.1% to 0.6%; Pine needle oil: 0.05% to 0.3%; Borneol: 0.05% to 0.4%; Fresh aloe vera juice: 5% to 12%; Cnidium monnieri concentrate: 0.5% to 1.8%; Honeysuckle flower dew: 3% to 8%; Deionized spring water: Balance.

2. A method for preparing a male delay spray based on natural herbal ingredients, characterized in that, The method includes: Calcined oyster-Rosa laevigata sustained-release microspheres were prepared; A biphasic gel of vinegar-processed gallnut-fresh aloe vera-peach gum was prepared. Epimedium-Cnidium thermosensitive liposomes were prepared. The porous calcined oyster-Rosa laevigata sustained-release microspheres, the vinegar-processed gallnut-Zanthoxylum bungeanum biphasic nano-latex and the Epimedium-Cnidium monnieri thermosensitive liposomes were mixed in deionized spring water and homogenized. By adding mussel adhesive protein solution and oxidized hyaluronic acid to trigger Schiff base cross-linking reaction, mussel adhesive protein-hyaluronic acid dual network hydrogel was obtained. A male delay spray was obtained by adjusting the pH value of mussel adhesive protein-hyaluronic acid dual-network hydrogel and sterilizing it.

3. The method according to claim 2, characterized in that, The preparation of calcined oyster-Rosa laevigata sustained-release microspheres includes: Calcined oyster shell powder was ultrasonically dispersed in phosphate buffer to form a porous suspension; Rosa laevigata extract and sodium alginate were added to a porous suspension and stirred to self-assemble. Calcium acetate solution was then added to form microspheres. The microspheres were collected and dried to obtain porous calcined oyster-Rosa laevigata sustained-release microspheres.

4. The method according to claim 3, characterized in that, The drying of the microspheres includes: The microspheres were freeze-dried at -50°C.

5. The method according to claim 2, characterized in that, The preparation of the vinegar-rhubarb-fresh aloe vera-peach gum biphasic gel includes: Pine needle oil, borneol and fermented Sichuan pepper extract were mixed in a water bath to form a homogeneous oil phase. The vinegar-processed gallnut powder was dissolved in fresh aloe vera juice and stirred to form a homogeneous aqueous phase. The oil and water phases were mixed and sheared to obtain vinegar-processed gallnut-Sichuan pepper biphase nano-latex.

6. The method according to claim 5, characterized in that, The preparation of the vinegar-rhubarb-fresh aloe vera-peach gum biphasic gel also includes: Chitosan solution was added, and an interfacial film was deposited and solidified on the surface of vinegar-processed gallnut-Sichuan pepper biphase nano-latex to form an interface film.

7. The method according to claim 2, characterized in that, The preparation of Epimedium-Cnidium thermosensitive liposomes includes: Lecithin and cholesterol are dissolved in chloroform to form a lipid film; The extract of Epimedium cooked in rice wine, the concentrated extract of Cnidium monnieri, and Lonicera japonica flower dew (5.5%) were hydrated and then encapsulated in a lipid membrane to form crude liposomes. The crude liposomes were homogenized into Epimedium-Cnidium thermosensitive liposomes.

8. The method according to claim 7, characterized in that, The preparation of the Epimedium-Cnidium thermosensitive liposomes further includes: Surface modification of Epimedium-Cnidium thermosensitive liposomes.

9. The method according to claim 2, characterized in that, The process of mixing the porous calcined oyster-Rosa laevigata sustained-release microspheres, the vinegar-processed gallnut-Zanthoxylum bungeanum biphasic nano-latex, and the Epimedium-Cnidium monnieri thermosensitive liposomes in deionized spring water for homogenization includes: The porous calcined oyster-Rosa laevigata sustained-release microspheres, the vinegar-processed gallnut-Zanthoxylum bungeanum biphasic nano-latex, and the Epimedium-Cnidium monnieri thermosensitive liposomes mixed in deionized spring water were subjected to primary and secondary homogenization treatments.

10. The method according to claim 2, characterized in that, After pH adjustment and sterilization of mussel adhesive protein-hyaluronic acid dual-network hydrogel, a male delay spray was obtained, including: The mussel adhesive protein-hyaluronic acid dual-network hydrogel, after pH adjustment, was sterilized by triple gradient filtration.

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