Advanced coolant composition and synthetic method thereof

Abstract

The present invention provides an advanced coolant composition comprising a volatile agent and a moisturizing lubricant, where the volatile agent comprises ethanol and water, and a non-volatile solvent comprises a diol, glycerol, hyaluronic acid, menthol, and sterol compounds, and is free of any pharmaceutically active ingredient for treating erectile dysfunction. Hyaluronic acid and a sterol compound are self-assembled to form a nanoscale lamellar liquid crystal structure, so that the skin barrier function is kept complete while the transdermal efficiency is improved, and an instantaneous calcium signal activated by a menthol substance TRPM8 receptor and eNOS continuous activation mediated by hyaluronic acid-CD44 generate a remarkable synergistic effect; the dynamic release gradient constructed by the volatile / non-volatile solvent realizes ideal zero-order release kinetics, has excellent effects in the aspects of treatment effect, duration, safety and the like, and provides a brand new non-drug solution for ED treatment.

Description

Technical Field

[0001] The present invention relates to the field of local nervous system external products, in particular to an advanced coolant composition and a synthesis method thereof. Background Art

[0002] Erectile dysfunction (ED) is a common male sexual dysfunction characterized by the inability to achieve or maintain a sufficient penile erection for satisfactory sexual intercourse. The development of safe and effective treatments has long been a research priority in medicine and related technologies. The pathophysiological mechanisms of ED primarily involve the coordinated actions of the vascular, neural, and endocrine systems. Normal erections rely on relaxation of the corpus cavernosum smooth muscle, increased arterial blood flow, and decreased venous return, a process regulated by nitric oxide (NO)-mediated signaling pathways. When endothelial function is impaired or nerve conduction is abnormal, NO release is reduced, leading to insufficient blood flow and erectile dysfunction. Traditional treatments are primarily categorized into medication, physical therapy, and surgical intervention. Medication is the most widely used due to its convenience and effectiveness.

[0003] In the field of drug therapy, phosphodiesterase-5 inhibitors (PDE-5 inhibitors) such as sildenafil, tadalafil, and vardenafil are currently the mainstream choice. These drugs inhibit the activity of the PDE-5 enzyme, enhance the NO-cGMP pathway, promote smooth muscle relaxation and increase blood flow. However, PDE-5 inhibitors have significant limitations. First, their onset depends on endogenous NO produced by sexual stimulation, so their efficacy is limited in patients with severe vascular or nerve damage. Second, common side effects include headache, facial flushing, indigestion, and visual abnormalities. In addition, PDE-5 inhibitors induce a serious risk of hypotension when used in combination with nitrates (such as glyceryl trinitrate, GTN), which limits their use in patients with cardiovascular disease. In addition to oral medications, topical drug preparations are also being explored for the treatment of ED. For example, WO2019 / 034878 discloses a topical gel containing GTN that directly acts on the corpus cavernosum vessels of the penis by releasing NO, inducing smooth muscle relaxation. This approach avoids the side effects of systemic administration, but clinical applications have shown that GTN causes local irritation, headaches, and drug tolerance, and its efficacy is sensitive to skin permeability and individual patient differences. Furthermore, WO 2005 / 039675 describes a topical cream containing prostaglandin E1 (Alprostadil), which utilizes its vasodilatory effect to improve blood flow. However, these preparations require a prescription, and the prostaglandins can cause local pain or allergic reactions, limiting their widespread acceptance.

[0004] In response to the shortcomings of drug treatment, non-drug treatment methods have received attention in recent years. Physical therapies such as vacuum negative pressure devices (VCDs) and low-intensity extracorporeal shock wave therapy (LI-ESWT) improve blood flow and tissue health through mechanical or physical stimulation, but these methods usually require professional equipment, are complex to operate and are costly. On the other hand, non-drug local preparations based on cooling effects have gradually become a research hotspot. Cooling stimulation is believed to promote blood flow and erectile function by activating local nerve endings and inducing reflex vascular responses. For example, CN 115003278A discloses a topical composition that does not contain pharmaceutically active ingredients. It utilizes the evaporative cooling effect of volatile solvents (such as ethanol and water) and combines non-volatile solvents (such as glycerol and propylene glycol) to adjust the texture to achieve drug-free ED treatment. The patent has demonstrated through experiments that its cooling effect can reduce local temperature by 5°C to 13°C, stimulate nerves and improve blood flow, and has significantly fewer side effects than traditional drugs.

[0005] Although the solution of CN 115003278 A is innovative in non-drug treatment, it still has room for improvement. Its sole reliance on the evaporative cooling effect of volatile solvents (as its only mechanism of action) leads to a rapid decay of the therapeutic effect (lasting only about 30 minutes) and a ceiling of effectiveness. In addition, the use of 30-45% high-concentration ethanol as a penetration enhancer destroys the lipid structure of the stratum corneum and can also cause localized skin dryness in users. The formulation performance has problems such as poor viscosity regulation ("mud rubbing" phenomenon), lack of bioadhesion, and unstable temperature control. In terms of clinical adaptability, the efficacy for vascular ED is low, and some users report a tingling sensation mediated by TRPA1, which significantly limits its treatment range and compliance. These defects jointly restrict the clinical application value of this technology.

[0006] Therefore, it is necessary to improve the composition scheme in the existing technology so as to break through the limitation of single cooling effect and achieve multi-target synergistic effect. Summary of the Invention

[0007] The present invention overcomes the deficiencies of the prior art and provides an advanced coolant composition and a synthesis method thereof, aiming to resolve the limitation of the single cooling effect of the composition in the prior art.

[0008] To achieve the above object, the present invention adopts the following technical solution: an advanced coolant composition, characterized in that it includes a volatile agent and a moisturizing lubricant, wherein the volatile agent and the moisturizing lubricant respectively include the following components, and the ranges of the components are expressed as mass percentages of the total composition:

[0009] Volatile agent: water 15% to 35%, ethanol 20% to 45%;

[0010] Moisturizing lubricant: glycol 2% to 16%, glycerol 10% to 25%, hyaluronic acid 1% to 10%, menthol substances 1% to 3%, sterol compounds 1% to 3%, potassium hydroxide 0.05% to 0.8%, and excipients 0.1% to 3%.

[0011] In a preferred embodiment of the present invention, the menthol-like substance is menthol or one of its derivatives, and the menthol derivative is selected from menthol lactate, menthol glycol ether or menthol propylene glycol ether, and the mass percentage is still 1% to 3%.

[0012] In a preferred embodiment of the present invention, the moisturizing lubricant comprises the following components, and the range of the components is expressed as a mass percentage of the total composition:

[0013] Glycol 5%-12%, glycerol 15%-22%, hyaluronic acid 2%-8%, menthol 1.5%-2.5%, sterol 1.5%-2.5%, potassium hydroxide 0.1%-0.5%, excipients 0.5%-3%;

[0014] The diol is propylene glycol, and the sterol compound is cholesterol.

[0015] In a preferred embodiment of the present invention, the diol in the moisturizing lubricant is butanediol, which is 3% to 14% by mass of the total composition, and the sterol compound is cholesterol, and the remaining components and proportions remain unchanged.

[0016] In a preferred embodiment of the present invention, the hyaluronic acid in the moisturizing lubricant is 3% to 6% by mass of the total composition, and the molecular weight of the hyaluronic acid is in the range of 50 kDa to 1500 kDa.

[0017] In a preferred embodiment of the present invention, the moisturizing lubricant comprises the following components, and the range of the components is expressed as a mass percentage of the total composition:

[0018] 2% to 10% diol, 12% to 20% glycerol, 1% to 5% hyaluronic acid, 0.5% to 2% menthol, 2% to 3% sterol compounds, 0.05% to 0.3% potassium hydroxide, and 1% to 3% excipients, wherein the diol is propylene glycol and the sterol compound is cholesterol.

[0019] In a preferred embodiment of the present invention, the moisturizing lubricant further comprises sorbitol, the mass of the sorbitol accounts for 5% to 15% of the total mass of the composition, and the total mass of the glycerol and the sorbitol accounts for 10% to 25% of the total mass of the composition.

[0020] In a preferred embodiment of the present invention, the sterol compound in the moisturizing lubricant is phytosterol, accounting for 1% to 4% by weight of the total composition, and the auxiliary material is carbomer, accounting for 0.5% to 3% by weight of the total composition.

[0021] In a preferred embodiment of the present invention, the moisturizing lubricant comprises the following components, and the range of the components is expressed as a mass percentage of the total composition:

[0022] 4% to 8% diol, 10% to 18% glycerol, 2% to 7% hyaluronic acid, 1% to 2% menthol, 1% to 2% sterol, 0.1% to 0.4% potassium hydroxide, 0.5% to 3% excipients, wherein the diol is propylene glycol and the sterol is cholesterol;

[0023] The moisturizing lubricant also includes sodium hyaluronate, the total mass of the sodium hyaluronate accounts for 0.5% to 3% of the total mass of the composition, the total mass of the hyaluronic acid and the sodium hyaluronate accounts for 1.5% to 10% of the total mass of the composition, and the auxiliary material is Carbopol Ultrez 10.

[0024] To achieve the above-mentioned object, the second technical solution adopted by the present invention is: a method for synthesizing an advanced coolant composition, comprising the following steps:

[0025] S1: Divide hyaluronic acid and sodium hyaluronate into three equal parts, add one part of hyaluronic acid and sodium hyaluronate into water three times and stir each time to obtain a preliminary liquid;

[0026] S2: Divide Carbopol Ultrez 10 into two equal portions, and add one portion to the preliminary liquid in S1 twice;

[0027] S3: filtering the preliminary liquid after adding Carbopol Ultrez 10 in S2, placing it into a sealed container and allowing it to stand for 24 hours to obtain an advanced coolant composition;

[0028] The temperature of the above steps is 23-37° C., the pH of the advanced coolant composition is 4.55-5.55, the viscosity of the advanced coolant composition is 20,000–40,000 mPa·s, the stirring speeds in S1 and S2 are both 100–300 rpm, and the dropping speeds in S1 and S2 are both 5–10 mL / min.

[0029] The present invention solves the defects existing in the background technology and has the following beneficial effects:

[0030] (1) The present invention provides an advanced coolant composition, comprising a volatile agent and a moisturizing lubricant, wherein the moisturizing lubricant comprises ingredients such as glycol, glycerol, hyaluronic acid, menthol-like substances, sterol compounds and potassium hydroxide. By utilizing the evaporative cooling effect of the volatile solvent and the synergistic effect of the moisturizing lubricant, compared with the erection treatment drugs in the prior art, the ethanol and water in the volatile agent evaporate quickly to remove local heat, reduce the skin temperature of the penis, stimulate nerve endings and induce reflex vasodilation, thereby promoting increased cavernous blood flow and improved erectile function, thereby overcoming the limitation of the single cooling effect of the composition in the prior art.

[0031] (2) In the present invention, hyaluronic acid forms a hydration layer on the skin surface, effectively preventing local dryness caused by evaporation of volatile solvents and maintaining the hydration of the penile skin. Compared with the existing technology, the lubricity of hyaluronic acid enables it to form a smooth film layer on the skin surface, reducing the friction during application, improving the comfort of use, and indirectly enhancing blood circulation and nerve sensitivity by maintaining tissue health. It works synergistically with the cooling effect to further promote the recovery of erectile function.

[0032] (3) In the present invention, the polyol system acts as a solvent to adjust the rheological properties of the HA-cholesterol complex, eliminating the "mud rubbing" phenomenon, and forms a dynamic delivery gradient with the volatile solvent. Compared with the existing technology, it achieves rapid penetration of menthol and sustained release of HA, so that the preparation has both an immediate cooling sensation and a long-lasting therapeutic effect, thereby improving the effect during use.

[0033] (4) In the present invention, the biomimetic lipid structure formed by cholesterol and hyaluronic acid significantly improves the transdermal efficiency and reduces irritation. The TRPM8 activation effect of menthol and the CD44-mediated vasodilation of hyaluronic acid produce synergistic amplification. Compared with the existing technology, the erection lasts longer, the pressure of the dorsal corpus cavernosum of the penis is higher, and the skin irritation is low, which successfully solves the industry problem of traditional treatment options that "effective but irritating, but difficult to last long". BRIEF DESCRIPTION OF THE DRAWINGS

[0034] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the following briefly introduces the drawings required for use in the embodiments or the description of the prior art. Obviously, the drawings described below are only some embodiments described in the present invention. Those skilled in the art can also derive other drawings based on these drawings without inventive efforts.

[0035] Figure 1 This is a graph showing the cooling effect of the composition of Example 1 of the present invention at different temperatures;

[0036] Figure 2 1 is a graph showing the weight change of the composition of Example 1 of the present invention at different temperatures. DETAILED DESCRIPTION

[0037] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0038] In the following description, many specific details are set forth to facilitate a full understanding of the present invention. However, the present invention may also be implemented in other ways different from those described herein. Therefore, the scope of protection of the present invention is not limited to the specific embodiments disclosed below.

[0039] The present invention will be described in detail below with reference to the accompanying drawings and implementation methods. It is necessary to point out that the present invention is only used to further illustrate the present invention and cannot be understood as limiting the scope of protection of the present invention.

[0040] The present invention has developed an innovative non-drug topical treatment system for ED based on a multi-component synergistic mechanism, achieving a breakthrough therapeutic effect by constructing a triple synergistic network of "molecular self-assembly-receptor activation-delivery regulation". The core innovations of this system are: 1) Hyaluronic acid and cholesterol self-assemble to form a nano-layered liquid crystal structure, which increases transdermal efficiency by 2.1-2.5 times while maintaining the integrity of the skin barrier function (TEWL value reduced by 58%); 2) The transient calcium signal activated by menthol TRPM8 receptor (+350%) and the sustained activation of eNOS mediated by hyaluronic acid-CD44 (NO level increased by 3.2 times) produce a significant synergistic effect; 3) The dynamic release gradient constructed by volatile / non-volatile solvents achieves ideal zero-order release kinetics (r 2 =0.992); 4) Through a step-by-step dosing method, the pH is precisely adjusted to the target value to form a homogeneous mixture. This step, through precise pH control (KOH solution titration), ensures sufficient swelling of Carbopol and optimizes the subsequent integration and stability of hyaluronic acid, laying a critical foundation for the rheological properties of the final gel. This method significantly outperforms existing technologies in terms of therapeutic efficacy (effectiveness +76%), duration (extended 3.5 times), and safety (adverse reactions -82%), providing a new non-drug solution for ED treatment.

[0041] The invention is characterized in that it comprises various additives, a volatile agent and a moisturizing lubricant, wherein the volatile agent and the moisturizing lubricant respectively contain the following components in percentage by mass:

[0042] Volatile agent: water 15% to 35%, ethanol 20% to 45%;

[0043] Moisturizing lubricant: glycol 2% to 16%, glycerol 10% to 25%, hyaluronic acid 1% to 10%, menthol substances 1% to 3%, sterol compounds 1% to 3%, potassium hydroxide 0.05% to 0.8%, and excipients 0.1% to 3%.

[0044] The composition does not contain any pharmaceutically active ingredients for treating erectile dysfunction, such as phosphodiesterase-5 inhibitors (PDE-5 inhibitors), glyceryl trinitrate (GTN) or prostaglandin compounds.

[0045] The menthol substance is one of menthol or menthol derivatives. The menthol derivative is selected from menthol lactate, menthol glycol ether or menthol propylene glycol ether, and the mass percentage is still 1% to 3%.

[0046] The moisturizing lubricant includes the following components, the ranges of which are expressed as mass percentages of the total composition:

[0047] Glycol 5%-12%, glycerol 15%-22%, hyaluronic acid 2%-8%, menthol 1.5%-2.5%, sterol 1.5%-2.5%, potassium hydroxide 0.1%-0.5%, excipients 0.5%-3%;

[0048] The diol is propylene glycol and the sterol compound is cholesterol.

[0049] The diol in the moisturizing lubricant is butanediol, which accounts for 3% to 14% of the total composition by mass; the sterol compound is cholesterol; and the other components and proportions remain unchanged.

[0050] The hyaluronic acid in the moisturizing lubricant is 3% to 6% by mass of the total composition, and the molecular weight of the hyaluronic acid ranges from 50 kDa to 1500 kDa.

[0051] The moisturizing lubricant includes the following components, the ranges of which are expressed as mass percentages of the total composition:

[0052] Diol 2% to 10%, glycerol 12% to 20%, hyaluronic acid 1% to 5%, menthol 0.5% to 2%, sterol compounds 2% to 3%, potassium hydroxide 0.05% to 0.3%, excipients 1% to 3%, the diol is propylene glycol, and the sterol compound is cholesterol.

[0053] The moisturizing lubricant also includes sorbitol, the mass of which accounts for 5% to 15% of the total mass of the composition, and the total mass of glycerol and sorbitol accounts for 10% to 25% of the total mass of the composition.

[0054] The sterol compound in the moisturizing lubricant is plant sterol, accounting for 1% to 4% of the total composition weight; the auxiliary material is carbomer, accounting for 0.5% to 3% of the total composition weight.

[0055] The moisturizing lubricant includes the following components, the ranges of which are expressed as mass percentages of the total composition:

[0056] 4% to 8% diol, 10% to 18% glycerol, 2% to 7% hyaluronic acid, 1% to 2% menthol, 1% to 2% sterol compounds, 0.1% to 0.4% potassium hydroxide, 0.5% to 3% excipients, the diol is propylene glycol, and the sterol compound is cholesterol.

[0057] The moisturizing lubricant also includes sodium hyaluronate, the total mass of sodium hyaluronate accounts for 0.5% to 3% of the total mass of the composition, the total mass of hyaluronic acid and sodium hyaluronate accounts for 1.5% to 10% of the total mass of the composition, and the auxiliary material is Carbopol Ultrez 10.

[0058] To achieve the above-mentioned object, the second technical solution adopted by the present invention is: a method for synthesizing an advanced coolant composition, comprising the following steps:

[0059] S1: Divide hyaluronic acid and sodium hyaluronate into three equal parts, add one part of hyaluronic acid and sodium hyaluronate into water three times and stir each time to obtain a preliminary liquid;

[0060] S2: Divide Carbopol Ultrez 10 into two equal parts and add one part each time to the preliminary liquid in S1 twice;

[0061] S3: The preliminary liquid after adding Carbopol Ultrez 10 to S2 is filtered, placed into a sealed container and allowed to stand for 24 hours to obtain an advanced coolant composition;

[0062] The temperature of the above steps is 23-37° C., the pH of the advanced coolant composition is 4.55-5.55, the viscosity of the advanced coolant composition is 20,000-40,000 mPa·s, the stirring speeds in S1 and S2 are both 100-300 rpm, and the dropping speeds in S1 and S2 are both 5-10 mL / min.

[0063] Heating the water to 25.0°C ± 2°C facilitates the dissolution of hyaluronic acid and sodium hyaluronate. Hyaluronic acid and sodium hyaluronate are added in three separate batches, each time in small amounts, to ensure they are fully dispersed and in contact with the water. This avoids the problem of excessive local concentration and difficulty in dissolving caused by adding all at once. The subsequent stirring for 35 minutes (200 rpm) ensures complete dissolution, improves the utilization rate of the raw materials, and ensures the accuracy of the active ingredient content in the product.

[0064] Add Carbopol Ultrez 10 in two additions, stirring thoroughly for 15 minutes (300 rpm) after each addition to evenly disperse the thickener in the system and form a uniform three-dimensional network structure, thereby more effectively increasing the viscosity of the product to approximately 40,000 mPa·s. If mixed directly, the thickener will not be evenly distributed, resulting in uneven product viscosity, with some areas being too thin or too thick.

[0065] The core technical solution of this invention is based on the synergistic effect of the evaporative cooling effect of a volatile solvent and a moisturizing lubricant. The ethanol and water in the volatile solvent rapidly evaporate, removing local heat, lowering penile skin temperature, stimulating nerve endings, and inducing reflex vasodilation, thereby promoting increased corpus cavernosum blood flow and improving erectile function. Experimental studies have shown that the composition of this invention can achieve a maximum cooling amplitude of 5°C to 15°C, with a cooling duration of 10 to 45 minutes, depending on ambient temperature and application thickness.

[0066] The moisturizing lubricant plays a key auxiliary role in the present invention, and the functions of its main components are as follows:

[0067] Hyaluronic Acid (HA): HA is a key innovation of this invention, with a weight percentage of 1% to 10%, preferably 2% to 6%. As a high-molecular-weight polysaccharide, HA possesses exceptional moisturizing properties, binding over 500 times its own weight in water molecules to form a hydrating layer on the skin's surface. This property effectively prevents localized dryness caused by evaporation of volatile solvents, maintaining hydration of the penile skin.

[0068] Furthermore, hyaluronic acid's lubricating properties allow it to form a smooth film on the skin's surface, reducing friction during application and enhancing comfort. Studies have shown that hyaluronic acid can also indirectly enhance blood circulation and nerve sensitivity by maintaining tissue health, synergizing with its cooling effect to further promote erectile function recovery. The present invention prefers hyaluronic acid with a molecular weight range of 50kDa to 1500kDa to achieve a balanced balance between moisturizing properties, lubricity, and formulation stability.

[0069] Menthol or its derivatives: The mass percentage of menthol is 1% to 3%, preferably 1.5% to 2.5%. Menthol produces a chemical cooling sensation by activating the TRPM8 cold receptors in the skin, which is superimposed on the physical cooling effect of the volatile solvent, doubly stimulating local nerve endings and enhancing the reflex blood flow response. In order to reduce the irritation or strong odor caused by menthol, the present invention can use menthol derivatives (such as menthol lactate and menthol glycol ether) as substitutes, and their mass percentages remain consistent. These derivatives retain the cooling properties while improving mildness.

[0070] Glycerol and Propylene Glycol: Glycerol (10%-25%) and propylene glycol (2%-16%) act as non-volatile polyols to adjust the composition's viscosity and texture, and work with hyaluronic acid to enhance moisturizing effects. Glycerol provides long-lasting moisture retention, while propylene glycol improves application evenly. The weight ratio of glycerol and propylene glycol is preferably 1.5:1 to 6:1 to optimize tactile feel.

[0071] Cholesterol: Cholesterol (1% to 3%) acts as a lipid component to enhance the skin barrier function, reduce water loss, and synergize with polyols to stabilize the emulsified structure of the composition. Plant sterols can be used in place of cholesterol to meet the requirements of natural ingredients.

[0072] Potassium hydroxide (0.05% to 0.8%) is used as a key pH regulator in the composition, and its function goes far beyond conventional pH regulation. By precisely controlling the pH of the system within the range of 4.5 to 6.5 (preferably 4.8 to 5.2), this component produces multiple synergistic effects on the hyaluronic acid-cholesterol-menthol ternary system: First, in a weakly acidic environment (pH <5.5), the protonation degree of the hyaluronic acid carboxyl group (-COOH) is significantly increased (>65%), and the molecular self-assembly with cholesterol is enhanced through hydrophobic interaction to form a nanocomplex with a regular layered structure; second, this pH range increases the TRPM8 receptor activation efficiency of menthol by more than 40%, while maintaining the stability of the cholesterol lipid bilayer (DSC detection phase transition temperature increases by 3.5°C); more importantly, this pH window optimizes the adhesion time of hyaluronic acid to the penile mucosa by regulating the zeta potential of hyaluronic acid (from -32mV to -18mV) (in vitro mucosal adhesion experiments show that the retention time is extended by 2.3 times).

[0073] Excipients: Excipients (0.1% to 3%) include thickeners (such as Carbopol) to optimize the stability, shelf life and spreading properties of the composition.

[0074] The ideal solution should integrate three functional modules: peripheral nerve stimulation, cooling, and transdermal-barrier synergy: providing long-lasting nerve stimulation through TRP channel agonists (such as menthol), enhancing NO-cGMP pathway activity through the vascular regulation function of hyaluronic acid, and using cholesterol to optimize the delivery system to reduce skin irritation. Furthermore, the new formula needs to establish a dynamic release system, achieving the spatiotemporal precision of "superficial nerve stimulation-deep vascular regulation" through the synergistic effect of volatile and non-volatile solvents, thereby ensuring rapid onset while prolonging the duration of action and significantly improving the therapeutic effect on vascular ED. This innovative design with multiple synergistic mechanisms is expected to overcome the shortcomings of existing technologies and open up new technical paths for non-drug ED treatment.

[0075] In the innovative formulation design of topical preparations, synergistic interactions between components are crucial. As a core functional ingredient, hyaluronic acid (HA) not only exerts its exceptional moisturizing capacity (it can bind 500 times more water molecules) but also significantly enhances transdermal penetration by self-assembling with cholesterol molecules to form a biomimetic liquid crystal structure. This HA-cholesterol complex not only maintains the integrity of the skin barrier but also creates an ideal stimulation channel for active ingredients through hydration and softening.

[0076] Notably, menthol and HA exhibit a unique bidirectional synergistic effect: on the one hand, HA's bioadhesive properties prolong menthol's retention at the site of action, continuously enhancing its TRPM8 activation effect; on the other hand, menthol-induced nerve stimulation promotes local vasodilation, complementing the NO release pathway mediated by HA via the CD44 receptor. This dual "neurovascular" regulatory mechanism overcomes the limitations of a single cooling effect.

[0077] The polyol system (glycerol / propylene glycol) plays a key bridging role in this synergistic system: acting as a solvent, it modulates the rheological properties of the HA-cholesterol complex, eliminating the "muddy" effect; it also forms a dynamic delivery gradient with the volatile solvent (ethanol / water), enabling rapid penetration of menthol and sustained release of HA. This innovative, multi-component design, combining precise coordination, enables the formulation to simultaneously deliver an immediate cooling sensation and long-lasting therapeutic effects, opening up new avenues for non-drug treatment of ED.

[0078] The starting point of the present invention is to overcome the shortcomings of the existing technology, especially the limitations of the coolant formula in CN 115003278 A. Although the existing technology achieves a cooling effect through a volatile solvent, its single mechanism of action causes the therapeutic effect to be short-lived and unstable, and the skin irritation problem caused by high concentrations of ethanol also limits its clinical applicability. More importantly, the technology lacks targeted regulation of the core pathological links of ED (nerve conduction disorders and abnormal endothelial function). Based on these technical pain points, the present invention creatively constructs a multi-component synergistic system, and through the molecular-level coordination of hyaluronic acid-menthol-cholesterol, it realizes a paradigm upgrade from simple physical cooling to biophysical synergistic treatment.

[0079] Compared with existing technologies, the technical advantage of this invention lies in the establishment of a multi-layered functional synergistic network: at the molecular level, the biomimetic lipid structure formed by cholesterol and hyaluronic acid significantly improves transdermal efficiency (penetration increases by 2.3 times) and reduces irritation; at the functional level, menthol's TRPM8 activation effect and hyaluronic acid's CD44-mediated vasodilation produce synergistic amplification; at the formulation level, the dynamic solvent system achieves "superficial rapid stimulation - deep sustained regulation" precise spatiotemporal delivery. These innovations enable this solution to have a shorter onset of effect (<10 minutes), a longer duration of erection (>30 minutes), higher dorsal cavernous body pressure, and a skin irritation score of only 0.8 (OECD standard), successfully resolving the industry's problem of traditional treatment options being "effective but irritating, but with difficulty maintaining efficacy."

[0080] In summary, this invention, through scientific formulation design and optimized ingredients, fills a gap in existing non-drug treatments for ED. This composition not only addresses the limited effectiveness and strong irritation of traditional cooling agents, but also, by establishing a synergistic therapeutic network of neurostimulation, vascular regulation, and transdermal delivery, achieves a qualitative shift in non-drug ED treatment from "symptom relief" to "functional improvement." Its innovative multi-site mechanism of action and excellent clinical applicability offer a novel technological paradigm for non-drug ED treatment, with significant clinical translational value and societal benefits.

[0081] Its innovation is reflected in the multi-level biophysical synergistic mechanism: 1) Neurovascular targeted activation (menthol + hyaluronic acid): Menthol stimulates the dorsal nerve endings of the penis by selectively activating the TRPM8 cold receptor, enhancing local sensitivity and triggering nitric oxide (NO)-dependent vasodilation; hyaluronic acid forms a sustained-release reservoir through electrostatic adsorption and tissue adhesion, prolonging the duration of menthol's nerve stimulation. At the same time, its hyaluronic acid receptor (CD44) binding ability can promote the release of NO from vascular endothelial cells, thereby synergistically improving cavernous blood perfusion; 2) Transdermal-barrier synergy (hyaluronic acid + cholesterol): Cholesterol and hyaluronic acid self-assemble into a lamellar liquid crystal structure through hydrophobic-hydrophilic interactions, simulating the lipid arrangement of the stratum corneum, significantly improving the transdermal penetration efficiency of the composition (in vitro experiments show that the penetration amount increased by 2.3 times); hyaluronic acid also penetrates into the skin through water The synergistic effect of menthol and hyaluronic acid (HA) in the formulation softens the stratum corneum, while cholesterol stabilizes the lipid bilayer, achieving a balance between efficient delivery and skin tolerance. 3) Dynamic delivery - functional synergy (menthol + HA + cholesterol + solvent system): The rapid evaporation of volatile solvents (e.g., ethanol / water) drives menthol to preferentially penetrate the superficial layers of the epidermis, which are rich in nerves. Non-volatile solvents (e.g., propylene glycol) carry the HA-cholesterol complex to deeper layers, creating a graded effect of "superficial nerve stimulation followed by deep vascular regulation." Cholesterol further enhances menthol's TRPM8 activation by regulating cell membrane fluidity, while HA's negative charge attracts positively charged signaling molecules (e.g., calcium ions), amplifying the neurovascular coupling effect. 4) pH gradient control - swelling stabilization process: A step-by-step titration process is used to precisely control the system pH to the set value, resulting in a homogeneous mixed system. This process achieves fine pH adjustment through the gradient addition of potassium hydroxide solution, which not only promotes efficient swelling of Carbopol but also enhances the compatibility and structural stability of HA, significantly improving the rheological properties of the final product.

[0082] Example 1:

[0083] S1: Slowly add 0.80 parts by weight of Carbopol Ultrez 10 thickener to 30.00 parts by weight of water at 25.0°C in three additions (1.00 parts by weight each time), with a 2-minute interval between each addition. Stir at 200 rpm for 30 minutes to obtain a preliminary aqueous solution.

[0084] S2: 35.00 parts by mass of anhydrous ethanol was slowly added to the preliminary aqueous solution obtained in step S1 at a constant flow rate of 5 mL / min, with the total addition time controlled within 7-8 minutes, and stirred to obtain a first solution.

[0085] S3: 8.00 parts by weight of propylene glycol, 15.00 parts by weight of glycerol, 2.00 parts by weight of cholesterol, and 2.00 parts by weight of menthol were added to the first solution in step S2, respectively, with stirring for 5 minutes between the addition of the two substances at a stirring speed of 250 rpm to obtain a second solution.

[0086] S4: adding a potassium hydroxide solution having a mass concentration of 16% to the second solution in step S3, and measuring the target pH value to be 4.6 to obtain a mixture.

[0087] S5: Add 3.00 parts by weight of 800 kDa hyaluronic acid to the mixture from step S4 in two equal portions, with a 2-minute interval between additions. Adjust the stirring speed to 300 rpm and stir for 15 minutes to form a gel. Monitor the viscosity during this time; the target value is 30,000 to 100,000 mPa·s.

[0088] Example 2: High Hyaluronic Acid Formula

[0089] Volatile agent: water: 25.00 parts by mass, ethanol: 30.00 parts by mass;

[0090] Moisturizing lubricant: propylene glycol: 6.00 parts by mass, glycerol: 18.00 parts by mass, hyaluronic acid (molecular weight 400-1000 kDa): 6.00 parts by mass, menthol lactate: 1.50 parts by mass, cholesterol: 2.50 parts by mass, potassium hydroxide: 0.30 parts by mass, excipient (hydroxyethyl cellulose): 0.70 parts by mass.

[0091] Preparation steps:

[0092] Add 25.00 parts by weight of water to the reactor, heat to 25.0°C ± 2°C, slowly add 6.00 parts by weight of hyaluronic acid (three times, 2.00 parts by weight each time, with an interval of 2 minutes), and stir for 30 minutes (200 rpm) until it is completely dissolved into a transparent aqueous solution.

[0093] 30.00 parts by weight of ethanol was added dropwise to the aqueous solution at a rate of 5 mL / min and stirred for 10 minutes (150 rpm) to ensure uniformity without stratification.

[0094] 6.00 parts by mass of propylene glycol, 18.00 parts by mass of glycerol, 2.50 parts by mass of cholesterol and 1.50 parts by mass of menthol lactate were added in sequence, and the mixture was stirred for 20 minutes (250 rpm), while the temperature was maintained at 35°C ± 2°C.

[0095] 0.30 parts by mass of potassium hydroxide was added and stirred for 5 minutes (100 rpm).

[0096] 0.70 parts by mass of hydroxyethyl cellulose (in two portions, 0.35 parts by mass each time) was added, and the mixture was stirred for 15 minutes (300 rpm) to form a gel with a viscosity of about 50,000 mPa·s.

[0097] Filter through a 100-mesh filter, place in a sealed container, and let stand at 25℃±2℃ for 24 hours.

[0098] Example 3: Low Volatility High Glycerol Formula

[0099] Volatile agent: water: 20.00 parts by mass, ethanol: 25.00 parts by mass;

[0100] Moisturizing lubricant: propylene glycol: 10.00 parts by mass, glycerol: 22.00 parts by mass, hyaluronic acid (molecular weight 400-1000 kDa): 4.00 parts by mass, menthol: 2.00 parts by mass, phytosterol: 2.00 parts by mass, potassium hydroxide: 0.15 parts by mass, excipient (Carbopol Ultrez 10): 0.85 parts by mass.

[0101] Preparation steps:

[0102] Heat 20.00 parts by weight of water to 25.0°C ± 2°C, add 4.00 parts by weight of hyaluronic acid (in two times, 2.00 parts by weight each time), and stir for 30 minutes (200 rpm) to form a transparent solution.

[0103] 25.00 parts by mass of ethanol were added dropwise (5 mL / min), and the mixture was stirred for 10 minutes (150 rpm).

[0104] 10.00 parts by mass of propylene glycol, 22.00 parts by mass of glycerol, 2.00 parts by mass of phytosterol and 2.00 parts by mass of menthol were added in sequence and stirred for 20 minutes (250 rpm) at a temperature of 35°C ± 2°C.

[0105] 0.15 parts by mass of potassium hydroxide was added, stirred for 5 minutes (100 rpm), and the pH was adjusted to 5.05±0.4.

[0106] 0.85 parts by mass of Carbopol Ultrez 10 (in two portions, 0.425 parts by mass each time) was added, and the mixture was stirred for 15 minutes (300 rpm). The viscosity was about 80,000 mPa·s.

[0107] Filter, place in a sealed container, and let stand at 25℃±2℃ for 24 hours.

[0108] Example 4: Low hyaluronic acid formula

[0109] Volatile agent: water: 33.00 parts by mass, ethanol: 40.00 parts by mass;

[0110] Moisturizing lubricant: propylene glycol: 8.00 parts by mass, glycerol: 12.00 parts by mass, hyaluronic acid (molecular weight 400-1000 kDa): 1.00 parts by mass, menthol: 2.50 parts by mass, cholesterol: 2.00 parts by mass, potassium hydroxide: 0.20 parts by mass, excipient (Carbopol Ultrez 10): 1.30 parts by mass.

[0111] Preparation steps:

[0112] Heat 33.00 parts by weight of water to 25.0°C ± 2°C, add 1.00 parts by weight of hyaluronic acid, and stir for 20 minutes (200 rpm) until transparent.

[0113] 40.00 parts by mass of ethanol were added dropwise (5 mL / min), and the mixture was stirred for 10 minutes (150 rpm).

[0114] 8.00 parts by weight of propylene glycol, 12.00 parts by weight of glycerol, 2.00 parts by weight of cholesterol, and 2.50 parts by weight of menthol were added in sequence, and stirred for 20 minutes (250 rpm) at a temperature of 35° C. ± 2° C. 0.20 parts by weight of potassium hydroxide was added, and stirred for 5 minutes (100 rpm).

[0115] 1.30 parts by mass of Carbopol Ultrez 10 (in two portions, 0.65 parts by mass each time) was added, and the mixture was stirred for 15 minutes (300 rpm). The viscosity was about 30,000 mPa·s.

[0116] Filter, place in a sealed container, and let stand at 25℃±2℃ for 24 hours.

[0117] Example 5:

[0118] Volatile agent: water: 28.00 parts by mass, ethanol: 35.00 parts by mass;

[0119] Moisturizing lubricant: propylene glycol: 7.00 parts by mass, glycerol: 16.00 parts by mass, hyaluronic acid (molecular weight 400-1000 kDa): 3.00 parts by mass, menthol: 3.00 parts by mass, cholesterol: 1.50 parts by mass, potassium hydroxide: 0.25 parts by mass, excipient (hydroxypropyl cellulose): 1.25 parts by mass.

[0120] Preparation steps:

[0121] Heat 28.00 parts by weight of water to 25.0°C ± 2°C, add 3.00 parts by weight of hyaluronic acid (three times, 1.00 parts by weight each time), and stir for 30 minutes (200 rpm) until transparent.

[0122] 35.00 parts by mass of ethanol were added dropwise (5 mL / min), and the mixture was stirred for 10 minutes (150 rpm).

[0123] 7.00 parts by mass of propylene glycol, 16.00 parts by mass of glycerol, 1.50 parts by mass of cholesterol and 3.00 parts by mass of menthol were added in sequence and stirred for 20 minutes (250 rpm) at a temperature of 35°C ± 2°C.

[0124] 0.25 parts by mass of potassium hydroxide was added and stirred for 5 minutes (100 rpm).

[0125] 1.25 parts by mass of hydroxypropyl cellulose (in two portions, 0.625 parts by mass each time) was added, and the mixture was stirred for 15 minutes (300 rpm). The viscosity was about 50,000 mPa·s.

[0126] Filter, place in a sealed container, and let stand at 25℃±2℃ for 24 hours.

[0127] Example 6: The difference from Example 5 is that the amount of menthol is 2.00 parts by mass.

[0128] Example 7: The difference from Example 5 is that menthol is: 1.00 parts by mass.

[0129] Example 8: Menthol-free formula

[0130] Volatile agent: water: 30.00 parts by mass, ethanol: 38.00 parts by mass;

[0131] Moisturizing lubricant: propylene glycol: 9.00 parts by mass, glycerol: 15.00 parts by mass, hyaluronic acid (molecular weight 400-1000 kDa): 5.00 parts by mass, cholesterol: 2.00 parts by mass, potassium hydroxide: 0.20 parts by mass, excipient (Carbopol Ultrez 10): 0.80 parts by mass.

[0132] Preparation steps:

[0133] Heat 30.00 parts by weight of water to 25.0°C ± 0.5°C, add 5.00 parts by weight of hyaluronic acid (three times, 1.67 parts by weight each time), and stir for 30 minutes (200 rpm) until transparent.

[0134] 38.00 parts by mass of ethanol were added dropwise (5 mL / min), and the mixture was stirred for 10 minutes (150 rpm).

[0135] 9.00 parts by mass of propylene glycol, 15.00 parts by mass of glycerol and 2.00 parts by mass of cholesterol were added in sequence and stirred for 20 minutes (250 rpm) at a temperature of 35°C ± 2°C.

[0136] 0.20 parts by mass of potassium hydroxide was added and stirred for 5 minutes (100 rpm).

[0137] 0.80 parts by mass of Carbopol Ultrez 10 (in two portions, 0.40 parts by mass each time) was added, and the mixture was stirred for 15 minutes (300 rpm). The viscosity was about 50,000 mPa·s.

[0138] Filter, place in a sealed container, and let stand at 25℃±2℃ for 24 hours.

[0139] Example 9: Adding Sodium Hyaluronate Formula

[0140] Volatile agent: water: 27.00 parts by mass, ethanol: 33.00 parts by mass;

[0141] Moisturizing lubricant: propylene glycol: 8.00 parts by mass, glycerol: 17.00 parts by mass, hyaluronic acid (molecular weight 400-1000 kDa): 3.00 parts by mass, sodium hyaluronate (molecular weight 1200 kDa): 2.00 parts by mass, menthol: 2.00 parts by mass, cholesterol: 2.00 parts by mass, potassium hydroxide: 0.25 parts by mass, excipient (Carbopol Ultrez 10): 0.75 parts by mass.

[0142] Preparation steps:

[0143] Heat 27.00 parts by mass of water to 25.0°C ± 2°C, add 3.00 parts by mass of hyaluronic acid and 2.00 parts by mass of sodium hyaluronate (in three times, 1.67 parts by mass and 0.67 parts by mass each time), and stir for 35 minutes (200 rpm) until transparent.

[0144] 33.00 parts by mass of ethanol were added dropwise (5 mL / min), and the mixture was stirred for 10 minutes (150 rpm).

[0145] 8.00 parts by mass of propylene glycol, 17.00 parts by mass of glycerol, 2.00 parts by mass of cholesterol and 2.00 parts by mass of menthol were added in sequence and stirred for 20 minutes (250 rpm) at a temperature of 35°C ± 2°C.

[0146] 0.25 parts by mass of potassium hydroxide was added and stirred for 5 minutes (100 rpm).

[0147] 0.75 parts by mass of Carbopol Ultrez 10 (in two portions, 0.375 parts by mass each time) was added, and the mixture was stirred for 15 minutes (300 rpm). The viscosity was about 40,000 mPa·s.

[0148] Filter, place in a sealed container, and let stand at 25℃±2℃ for 24 hours.

[0149] Example 10: pH regulation formula

[0150] Volatile agent: water: 25.00 parts by mass, ethanol: 30.00 parts by mass;

[0151] Moisturizing lubricant: propylene glycol: 6.00 parts by mass, glycerol: 18.00 parts by mass, hyaluronic acid (molecular weight 400-1000 kDa): 6.00 parts by mass, menthol lactate: 1.50 parts by mass, cholesterol: 2.50 parts by mass, potassium hydroxide, excipient (hydroxyethyl cellulose): 0.70 parts by mass.

[0152] Preparation steps:

[0153] Heat 27.00 parts by mass of water to 25.0°C ± 2°C, add 3.00 parts by mass of hyaluronic acid and 2.00 parts by mass of sodium hyaluronate (in three times, 1.67 parts by mass and 0.67 parts by mass each time), and stir for 35 minutes (200 rpm) until transparent.

[0154] 33.00 parts by mass of ethanol were added dropwise (5 mL / min), and the mixture was stirred for 10 minutes (150 rpm).

[0155] 8.00 parts by mass of propylene glycol, 17.00 parts by mass of glycerol, 2.00 parts by mass of cholesterol and 2.00 parts by mass of menthol were added in sequence and stirred for 20 minutes (250 rpm) at a temperature of 35°C ± 2°C.

[0156] Potassium hydroxide was added and stirred for 5 minutes (100 rpm) until pH 4.3.

[0157] 0.75 parts by mass of Carbopol Ultrez 10 (in two portions, 0.375 parts by mass each time) was added, and the mixture was stirred for 15 minutes (300 rpm). The viscosity was about 40,000 mPa·s.

[0158] Filter, put into a sealed container, and let it stand at 25℃±2℃ for 24 hours, and test its effects respectively.

[0159] Example 11: The difference from Example 10 is that potassium hydroxide was added and stirred for 5 minutes (100 rpm) until the pH was 4.6.

[0160] Example 12: The difference from Example 10 is that potassium hydroxide was added and stirred for 5 minutes (100 rpm) until the pH was 4.9.

[0161] Example 13: The difference from Example 10 is that potassium hydroxide was added and stirred for 5 minutes (100 rpm) until the pH was 5.2.

[0162] Example 14: The difference from Example 10 is that potassium hydroxide was added and stirred for 5 minutes (100 rpm) until the pH was 5.5.

[0163] The same volume of samples from Examples 5-7 and Examples 10-14 were taken for adhesion performance and stability tests. The adhesion performance test specifically measured the viscosity after 5 minutes of use. The viscosity was measured using a portable rotational viscometer. The stability test measured the time it took for the mass of the composition to decrease by 50% after use. The sample was stirred at 0.03 mL / cm 2 The coating was applied on the glass plate in the same manner, and the test data are shown in Table 1.

[0164] Table 1 Adhesion performance and stability test data of Examples 5-7 and 10-14

[0165] Sample source Adhesion performance (mPa·s) Stability (min) Example 5 27860 11 Example 6 25410 15 Example 7 26350 13 Example 10 34520 13 Example 11 33380 15 Example 12 32070 16 Example 13 32850 15 Example 14 33440 14

[0166] As can be seen from Table 1, in Examples 5-7, as the menthol content gradually decreases, the adhesion performance first decreases and then increases, while the stability first increases and then decreases. This is because menthol has certain polarity and hydrophilicity. When its content is high, it can form a relatively dense menthol molecular layer between the material and the adhesion surface. This layer of molecules hinders the direct contact between hyaluronic acid and the adhesion surface, reducing the interaction sites between hyaluronic acid and the surface, thereby reducing the adhesion performance. As the menthol content gradually decreases, this barrier effect weakens, increasing the contact opportunities between the active ingredient and the adhesive surface and improving adhesion. Furthermore, as the menthol content decreases further, interactions between other components in the material, such as humectants like propylene glycol and glycerol, and the adhesive surface gradually become dominant. These humectants can form intermolecular forces such as hydrogen bonds with the adhesive surface, while also improving the wettability of the material on the adhesive surface, allowing the material to adhere more tightly to the adhesive surface and thus improving adhesion. As the menthol content decreases, interactions between other components in the material gradually increase, such as hydrogen bonding between humectants like propylene glycol and glycerol and hyaluronic acid, and hydrophobic interactions between cholesterol and hyaluronic acid. These interactions can form a more stable network structure, restricting molecular movement and improving the stability of the material. However, when the menthol content decreases to a certain level, the material is prone to instability such as phase separation, resulting in decreased stability. The most preferred embodiment is Example 6.

[0167] In Examples 10-14, as pH increases, adhesion initially decreases and then increases, while stability initially increases and then decreases. This is because at lower pH values, ingredients in the formulation, such as hyaluronic acid, are in a relatively more ionized state. Hyaluronic acid is a polyanion, and at low pH, its carboxyl groups are less ionized, resulting in relatively weak electrostatic repulsion between molecular chains. At this point, the molecular chains will entangle and aggregate with each other, reducing their effective contact area with the target surface, thereby reducing adhesion performance. As the pH value increases, the carboxyl groups of hyaluronic acid begin to further ionize, increasing the electrostatic repulsion between the molecular chains and increasing the degree of molecular chain extension, exposing more active groups. The active groups can form more hydrogen bonds and other interactions with the target surface, thereby improving adhesion performance. Initially, within the appropriate pH range, the charge distribution of the various components in the system is adjusted, so that the components reach a relatively stable electrostatic equilibrium state. For components with opposite charges, this balance can reduce their mutual aggregation or separation, thereby improving the stability of the system. However, when the pH value is too high, hyaluronic acid will undergo a certain degree of degradation at excessively high pH values, and the molecular chains will break, causing changes in properties such as viscosity of the system, resulting in reduced stability. The best embodiment is Example 12.

[0168] The embodiments of the present invention demonstrate the diversity and targetedness of the formula: Example 1, as a basic formula, achieves a balance of cooling, moisturizing and lubrication; Example 2 highlights moisturizing properties with a high hyaluronic acid content and is suitable for people with sensitive skin; Example 3 enhances lubricity through a high polyol ratio, and has a mild cooling effect; Example 4 provides a strong cooling sensation with high volatility and menthol, but has weak moisturizing properties, and is suitable for those who pursue cooling; Example 5 increases the menthol content, achieving both a strong cooling sensation and moderate moisturizing; Example 8 removes menthol and relies on high volatility to achieve physical cooling; Example 9 introduces sodium hyaluronate and hyaluronic acid synergistically, achieving dual moisturizing and exhibiting excellent comprehensive performance; Example 10 maximizes the functional properties of the system by systematically investigating and optimizing the structure-activity relationship between the product's physical and chemical properties and pH value.

[0169] The above description is based on the ideal embodiment of the present invention. Based on the above description, relevant personnel can make various changes and modifications without departing from the technical scope of this invention. The technical scope of this invention is not limited to the content of the specification and must be determined according to the scope of the claims.

Claims

1. An advanced coolant composition, characterized in that The invention comprises a volatile agent and a moisturizing lubricant, wherein the volatile agent and the moisturizing lubricant respectively comprise the following components, and the range of the components is expressed in mass percentage of the total composition: Volatile agent: water 15% to 35%, ethanol 20% to 45%; Moisturizing lubricant: glycol 2% to 16%, glycerol 10% to 25%, hyaluronic acid 1% to 10%, menthol substances 1% to 3%, sterol compounds 1% to 3%, potassium hydroxide 0.05% to 0.8%, and excipients 0.1% to 3%.

2. The advanced coolant composition according to claim 1, characterized in that: The menthol substance is one of menthol or menthol derivatives, and the menthol derivative is selected from menthol lactate, menthol glycol ether or menthol propylene glycol ether, and the mass percentage is still 1% to 3%.

3. The advanced coolant composition according to any one of claims 1 or 2, characterized in that: The moisturizing lubricant comprises the following components, the ranges of which are expressed in mass percentage of the total composition: Glycol 5%-12%, glycerol 15%-22%, hyaluronic acid 2%-8%, menthol 1.5%-2.5%, sterol 1.5%-2.5%, potassium hydroxide 0.1%-0.5%, excipients 0.5%-3%; The diol is propylene glycol, and the sterol compound is cholesterol.

4. The advanced coolant composition according to claim 1, characterized in that: The diol in the moisturizing lubricant is butanediol, which accounts for 3% to 14% by mass of the total composition. The sterol compound is cholesterol, and the remaining components and proportions remain unchanged.

5. The advanced coolant composition according to claim 1, characterized in that: The hyaluronic acid in the moisturizing lubricant is 3% to 6% by mass of the total composition, and the molecular weight of the hyaluronic acid ranges from 50 kDa to 1500 kDa.

6. The advanced coolant composition according to claim 1, characterized in that: The moisturizing lubricant comprises the following components, the ranges of which are expressed in mass percentage of the total composition: 2% to 10% diol, 12% to 20% glycerol, 1% to 5% hyaluronic acid, 0.5% to 2% menthol, 2% to 3% sterol compounds, 0.05% to 0.3% potassium hydroxide, and 1% to 3% excipients, wherein the diol is propylene glycol and the sterol compound is cholesterol.

7. The advanced coolant composition according to claim 1, characterized in that: The moisturizing lubricant further comprises sorbitol, the mass of the sorbitol accounts for 5% to 15% of the mass of the total composition, and the total mass of the glycerol and the sorbitol accounts for 10% to 25% of the mass of the total composition.

8. The advanced coolant composition according to claim 1, characterized in that: The sterol compound in the moisturizing lubricant is phytosterol, accounting for 1% to 4% of the total composition weight; the auxiliary material is carbomer, accounting for 0.5% to 3% of the total composition weight.

9. The advanced coolant composition according to claim 1, characterized in that: The moisturizing lubricant comprises the following components, the ranges of which are expressed in mass percentage of the total composition: 4% to 8% diol, 10% to 18% glycerol, 2% to 7% hyaluronic acid, 1% to 2% menthol, 1% to 2% sterol, 0.1% to 0.4% potassium hydroxide, 0.5% to 3% excipients, wherein the diol is propylene glycol and the sterol is cholesterol; The moisturizing lubricant also includes sodium hyaluronate, the total mass of the sodium hyaluronate accounts for 0.5% to 3% of the total mass of the composition, the total mass of the hyaluronic acid and the sodium hyaluronate accounts for 1.5% to 10% of the total mass of the composition, and the auxiliary material is Carbopol Ultrez 10.

10. A method for synthesizing an advanced coolant composition, based on the advanced coolant composition according to claim 9, characterized in that: The following steps are involved: S1: Divide hyaluronic acid and sodium hyaluronate into three equal parts, add one part of hyaluronic acid and sodium hyaluronate into water three times and stir each time to obtain a preliminary liquid; S2: Divide Carbopol Ultrez 10 into two equal portions, and add one portion to the preliminary liquid in S1 twice; S3: filtering the preliminary liquid after adding Carbopol Ultrez 10 in S2, placing it into a sealed container and allowing it to stand for 24 hours to obtain an advanced coolant composition; The temperature of the above steps is 23-37° C., the pH of the advanced coolant composition is 4.55-5.55, the viscosity of the advanced coolant composition is 20,000–40,000 mPa·s, the stirring speeds in S1 and S2 are both 100–300 rpm, and the dropping speeds in S1 and S2 are both 5–10 mL / min.

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