Gel and application thereof

Abstract

The invention provides a gel, and belongs to the technical field of biological medicine, the gel does not contain dihydric alcohol compounds, and the gel contains 20-40 wt% of glycerin; 30% to 40% by weight of ethanol; 0.1% to 1.5% by weight of a carbomer; and the balance of water, and the gel has the effects of promoting male erectile function and low skin irritation. When the gel is used for preparing a skin preparation, the gel can be used for cooling, improving or treating male erectile dysfunction and cooling, and meanwhile, the occurrence of anaphylactic reaction is reduced.

Description

Technical Field

[0001] The present disclosure belongs to the technical field of biomedicine, and particularly relates to a gel and its applications. Background Art

[0002] Gel preparations are common dosage forms for delivering active ingredients in the pharmaceutical, food, disinfectant, and cosmetic industries. Water and ethanol form simple gel carriers with polyvinyl chloride or cellulose derivatives, etc., which are usually called hydroalcoholic gels. However, although alcohols help increase the solubility of non-polar drugs, their use as co-solvents for hydrophilic polymers is often limited. It is also necessary to add many different types of co-solvents or excipients to increase the dissolution of the active ingredient in the gel mixture, maintain the stability and appropriate rheological behavior of the gel polymer, reduce the toxic effects of the carrier, and optimize the delivery of non-polar drugs, etc. Therefore, when designing and developing new hydroalcoholic gel systems, the difficulty often encountered is limited by the compatibility of the gelling agent and the co-solvent, so that it is difficult to develop safe, stable, aesthetic, and gel preparations with specific functions.

[0003] In recent years, many gel-based networks have been designed to be personalized to meet the needs of different applications. In any formulation including personal care, cosmetics, coatings, inks, pharmaceuticals, foods, and even chemicals therein, it is necessary to modify the rheology of the gel formulation system to achieve the advantageous characteristics of the product: 1) a formulation that is easy to mix during the manufacturing process and has the lowest energy consumption; 2) long-term physical and chemical stability; 3) the ease of use of the formulation type. To achieve the above goals, it is necessary to add thickeners and rheological modifiers for gels with specific rheological properties.

[0004] Propylene glycol (PG) is widely used as a solvent and humectant in cosmetics, foods, drugs, and other products. Propylene glycol was first prepared by hydrolysis of propylene diacetate. Later, it was used as a substitute for glycerol in pharmaceutical preparations or as a common ingredient in air fresheners. Over time, many of the properties and functions of propylene glycol have become popular in cosmetics, foods, drugs, and other products. It can be used as a solvent, humectant, emulsion stabilizer, and bactericide, and also as an intermediate in the production of polyester resins.

[0005] Numerous research reports have shown that propylene glycol can cause contact, systemic, and irritant skin reactions. It is a common contact allergen and can even cause generalized contact dermatitis in severe cases. Additionally, propylene glycol in diaper wipes and diapers can induce perineal dermatitis. Currently, the skin's reaction to propylene glycol has been classified into four mechanisms: (1) irritant contact dermatitis; (2) allergic contact dermatitis; (3) non-immune contact urticaria; and (4) subjective or sensory irritation. Reducing the use of propylene glycol can prevent the occurrence of allergic and contact dermatitis. Summary of the Invention

[0006] Based on the above research background and facts, the present disclosure intends to develop a gel and its applications. The gel does not contain allergenic diol compounds and has the effects of promoting male erectile function and low skin irritation.

[0007] According to a first aspect of the present disclosure, there is provided a gel that does not contain diol compounds, and the gel comprises: 20 to 40 wt% of glycerol; 30% to 50 wt% of ethanol; 0.1% to 1.5 wt% of carbomer; and the balance of water.

[0008] In some embodiments, the carbomer is selected from one or more of the following: carbomer homopolymers, carbomer copolymers, and carbomer interpolymers.

[0009] In some embodiments, the carbomer homopolymers are selected from one or more of the following: carbomer 980, carbomer 974, carbomer 5984, carbomer 934, and carbomer 940.

[0010] In some embodiments, the carbomer is carbomer 980.

[0011] In some embodiments, the carbomer copolymers are selected from one or more of the following: carbomer 1342, carbomer ETD2020, carbomer Ultrez20, and carbomer Ultrez 10.

[0012] In some embodiments, the gel comprises 0.1 wt%, 0.2 wt%, 0.3 wt%, 0.4 wt%, 0.5 wt%, 0.6 wt%, 0.7 wt%, 0.8 wt%, 0.9 wt%, 1.0 wt%, 1.1 wt%, 1.2 wt%, 1.3 wt%, 1.4 wt%, or 1.5 wt% of glycerol.

[0013] In some embodiments, the gel contains 0.5 wt% to 1.0 wt% of carbomer.

[0014] In some embodiments, the diol compound includes one or more of the following: ethylene glycol, propylene glycol, butylene glycol, pentylene glycol, dipentyl alcohol, hexylene glycol, cyclohexanediol, cyclohexanedimethanol, heptylene glycol, octylene glycol, nonylene glycol, decylene glycol, undecylene glycol, dodecylene glycol, tridecylene glycol, tetradecylene glycol, pentadecylene glycol, hexadecylene glycol, heptadecylene glycol, and octadecylene glycol.

[0015] In some embodiments, the gel contains 20 wt%, 21 wt%, 22 wt%, 23 wt%, 24 wt%, 25 wt%, 26 wt%, 27 wt%, 28 wt%, 29 wt%, 30 wt%, 31 wt%, 32 wt%, 33 wt%, 34 wt%, 35 wt%, 36 wt%, 37 wt%, 38 wt%, 39 wt%, 40 wt%, 41 wt%, 42 wt%, 44 wt%, 44 wt%, 45 wt%, 46 wt%, 47 wt%, 48 wt%, 49 wt% or 50 wt% ethanol.

[0016] In some embodiments, the gel contains 30 wt% to 40 wt% ethanol.

[0017] In some embodiments, the gel contains 33 wt% to 35 wt% ethanol.

[0018] In some embodiments, the water is selected from deionized water, distilled water, purified water, high-purity water or ultrapure water.

[0019] In some embodiments, the gel contains 30 wt% to 40 wt% water.

[0020] In some embodiments, the gel contains 30 wt%, 31 wt%, 32 wt%, 33 wt%, 34 wt%, 35 wt%, 36 wt%, 37 wt%, 38 wt%, 39 wt% or 40 wt% water.

[0021] In some embodiments, the gel contains 20 to 40 wt% glycerol, 30 wt% to 40 wt% ethanol, and 30 wt% to 40 wt% water.

[0022] In some embodiments, the gel contains 15 to 40 wt% glycerol, 33 wt% to 35 wt% ethanol, 30 wt% to 40 wt% water, and 0.1 wt% to 1.5 wt% carbomer.

[0023] In some embodiments, the gel further contains a neutralizing agent.

[0024] In some embodiments, the neutralizing agent is selected from one or more of the following: potassium hydroxide, sodium hydroxide, ammonium hydroxide, triethanolamine, triethanolamine arginine, aminomethylpropanol, tetrahydroxypropyl ethylenediamine, tromethamine, diisopropanolamine, and triisopropanolamine. More preferably, they are potassium hydroxide, sodium hydroxide, and triethanolamine.

[0025] In some embodiments, the neutralizing agent is selected from one or more of the following: potassium hydroxide, sodium hydroxide, and triethanolamine.

[0026] In some embodiments, the gel further comprises hyaluronic acid.

[0027] In some embodiments, the hyaluronic acid includes sulfated hyaluronic acid, or its ester, or its salt, or its disulfide, or its amide.

[0028] In some embodiments, the gel contains 0.05 wt% to 0.5 wt% of hyaluronic acid.

[0029] In some embodiments, the gel contains 0.05 wt%, 0.06 wt%, 0.07 wt%, 0.08 wt%, 0.09 wt%, 0.1 wt%, 0.2 wt%, 0.3 wt%, 0.4 wt%, or 0.5 wt% of hyaluronic acid.

[0030] Adding hyaluronic acid to the gel described in the present disclosure, on the premise of ensuring the safety of the gel, as an auxiliary component, it has a moisturizing and lubricating effect, which can not only improve the curative effect of the gel in treating ED, but also protect the reproductive system health of female partners and enhance the quality of the gel.

[0031] In some embodiments, the pH of the gel is selected from 4.5 to 6.0.

[0032] In some embodiments, the pH of the gel is selected from 4.5, 4.6, 4.7, 4.8, 4.9, 5, 5.1, 5.2, 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, or 6.0.

[0033] In some embodiments, the pH of the gel is selected from 5.1 to 5.8.

[0034] In some embodiments, the gel further comprises one or more of a preservative or an antioxidant.

[0035] In some embodiments, the gel does not contain any other active ingredients that promote male erectile function.

[0036] In some embodiments, the active ingredients include chemically synthesized and natural extracted active ingredients.

[0037] In some embodiments, the active ingredient includes one or more of the following: PDE5 inhibitor, local anesthetic, prostaglandin, and testosterone.

[0038] In some embodiments, the gel is selected from one or more of the following: gel, spray, and aerosol.

[0039] In some embodiments, the gel contains 25 wt% - 40 wt% glycerol, 30 wt% - 40 wt% ethanol, 30 wt% - 40 wt% water, 0.05 wt% - 0.5 wt% hyaluronic acid, and 0.1 wt% - 1.5 wt% carbomer 980.

[0040] In some embodiments, the gel contains 29 wt% glycerol, 35 wt% ethanol, 34.9 wt% water, 0.1 wt% hyaluronic acid, and 1.0 wt% carbomer 980.

[0041] In some embodiments, the gel contains 29 wt% glycerol, 35 wt% ethanol, 34.9 wt% water, 0.1 wt% hyaluronic acid, and 1.0 wt% carbomer Ultrez 10.

[0042] Preferably, the gel has the functions of cooling and promoting male erection, as well as a low skin irritation effect.

[0043] According to a second aspect of the present disclosure, a method for preparing the gel described in the first aspect is provided.

[0044] In some embodiments, the method includes the following steps:

[0045] 1) Mix water and carbomer to disperse the carbomer.

[0046] 2) Then add glycerol and ethanol and stir evenly.

[0047] 3) After the carbomer in the product obtained in step 2) is dispersed, add a neutralizing agent.

[0048] In some embodiments, in step 2) of the method, glycerol, hyaluronic acid, and ethanol are further added.

[0049] In some embodiments, the step of stirring evenly in step 2) of the method includes: first stirring evenly at a rotation speed of ≤ 500 revolutions per minute, and then stirring at a rotation speed of > 500 revolutions per minute.

[0050] In some embodiments, the stirring at a rotation speed of > 500 revolutions per minute is performed using mechanical or magnetic stirring.

[0051] In some embodiments, the step of stirring evenly in step 2) of the method includes: first stirring evenly at a rotation speed of ≤ 500 revolutions per minute, and then stirring at a rotation speed of 500 - 700 revolutions per minute.

[0052] In some embodiments, the stirring at a rotation speed of 500 - 700 revolutions per minute is performed using mechanical or magnetic stirring.

[0053] In some embodiments, the step of stirring evenly in step 2) of the method includes: first stirring at a rotation speed of ≤ 500 revolutions per minute for 10 - 40 minutes, and then stirring at a rotation speed of > 500 revolutions per minute for 20 minutes to 1 hour.

[0054] In some embodiments, the step of stirring evenly in step 2) of the method includes: first stirring at a rotation speed of ≤ 500 revolutions per minute for 10 - 40 minutes, and then stirring at a rotation speed of 500 - 700 revolutions per minute for 20 minutes to 1 hour.

[0055] In some embodiments, the step of stirring evenly in step 2) of the method includes: first stirring at a rotation speed of 100 revolutions per minute, 110 revolutions per minute, 120 revolutions per minute, 130 revolutions per minute, 140 revolutions per minute, 150 revolutions per minute, 160 revolutions per minute, 170 revolutions per minute, 180 revolutions per minute, 190 revolutions per minute, 200 revolutions per minute, 210 revolutions per minute, 220 revolutions per minute, 230 revolutions per minute, 240 revolutions per minute, 250 revolutions per minute, 260 revolutions per minute, 270 revolutions per minute, 280 revolutions per minute, 290 revolutions per minute, 300 revolutions per minute, 310 revolutions per minute, 320 revolutions per minute, 330 revolutions per minute, 340 revolutions per minute, 350 revolutions per minute, 360 revolutions per minute, 370 revolutions per minute, 380 revolutions per minute, 390 revolutions per minute, 400 revolutions per minute, 410 revolutions per minute, 420 revolutions per minute, 430 revolutions per minute, 440 revolutions per minute, 450 revolutions per minute, 460 revolutions per minute, 470 revolutions per minute, 480 revolutions per minute, 490 revolutions per minute, or 500 revolutions per minute for 10 minutes, 11 minutes, 12 minutes, 13 minutes, 14 minutes, 15 minutes, 16 minutes, 17 minutes, 18 minutes, 19 minutes, 20 minutes, 21 minutes, 22 minutes, 23 minutes, 24 minutes, 25 minutes, 26 minutes, 27 minutes, 28 minutes, 29 minutes, 30 minutes, 31 minutes, 32 minutes, 33 minutes, 34 minutes, 35 minutes, 36 minutes, 37 minutes, 38 minutes, 39 minutes, or 40 minutes, and then stirring at a rotation speed of 500 revolutions per minute, 510 revolutions per minute, 520 revolutions per minute, 530 revolutions per minute, 540 revolutions per minute, 550 revolutions per minute, 560 revolutions per minute, 570 revolutions per minute, 580 revolutions per minute, 590 revolutions per minute, 600 revolutions per minute, 610 revolutions per minute, 620 revolutions per minute, 630 revolutions per minute, 640 revolutions per minute, 650 revolutions per minute, 660 revolutions per minute, 670 revolutions per minute, 680 revolutions per minute, or 690 revolutions per minute for 20 minutes, 21 minutes, 22 minutes, 23 minutes, 24 minutes, 25 minutes, 26 minutes, 27 minutes, 28 minutes, 29 minutes, 30 minutes, 31 minutes, 32 minutes, 33 minutes, 34 minutes, 35 minutes, 36 minutes, 37 minutes, 38 minutes, 39 minutes, 40 minutes, 41 minutes, 42 minutes, 43 minutes, 44 minutes, 45 minutes, 46 minutes, 47 minutes, 48 minutes, 49 minutes, 50 minutes, 51 minutes, 52 minutes, 53 minutes, 54 minutes, 55 minutes, 56 minutes, 57 minutes, 58 minutes, 59 minutes, or 60 minutes.

[0056] In some embodiments, in step 3) of the method, after the carbomer is dispersed, a neutralizing agent is added dropwise or gradually.

[0057] In some embodiments, the neutralizing agent is potassium hydroxide (KOH).

[0058] In some embodiments, a neutralizing agent is added to adjust the pH to about 4.5 to 6.0.

[0059] In some embodiments, a neutralizing agent is added to adjust the pH to about 5.1 to 5.8.

[0060] In some embodiments, the method comprises the following steps:

[0061] 1) Dissolve glycerol in a water / ethanol mixture;

[0062] 2) Then add carbomer and stir evenly;

[0063] 3) After the carbomer in the product obtained in step 2) is dispersed, add a neutralizing agent.

[0064] In some embodiments, in step 1) of the method, glycerol and hyaluronic acid are dissolved in a water / ethanol mixture.

[0065] In some embodiments, the step of stirring evenly in step 2) of the method includes: first stirring evenly at a rotation speed of ≤ 500 revolutions per minute, and then stirring at a rotation speed of > 500 revolutions per minute.

[0066] In some embodiments, the stirring at a rotation speed of more than 500 revolutions per minute is performed using mechanical or magnetic stirring.

[0067] In some embodiments, the step of stirring evenly in step 2) of the method includes: first stirring evenly at a rotation speed of ≤ 500 revolutions per minute, and then stirring at a rotation speed of 500 - 700 revolutions per minute.

[0068] In some embodiments, the stirring at a rotation speed of 500 - 700 revolutions per minute is performed using mechanical or magnetic stirring.

[0069] In some embodiments, the step of stirring evenly in step 2) of the method includes: first stirring evenly at a rotation speed of ≤ 500 revolutions per minute for 10 - 40 minutes, and then stirring at a rotation speed of > 500 revolutions per minute for 20 minutes to 1 hour.

[0070] In some embodiments, the step of stirring evenly in step 2) of the method includes: first stirring evenly at a rotation speed of ≤ 500 revolutions per minute for 10 - 40 minutes, and then stirring at a rotation speed of 500 - 700 revolutions per minute for 20 minutes to 1 hour.

[0071] In some embodiments, the step of stirring evenly in step 2) of the method includes: first stirring at a rotation speed of 100 revolutions per minute, 110 revolutions per minute, 120 revolutions per minute, 130 revolutions per minute, 140 revolutions per minute, 150 revolutions per minute, 160 revolutions per minute, 170 revolutions per minute, 180 revolutions per minute, 190 revolutions per minute, 200 revolutions per minute, 210 revolutions per minute, 220 revolutions per minute, 230 revolutions per minute, 240 revolutions per minute, 250 revolutions per minute, 260 revolutions per minute, 270 revolutions per minute, 280 revolutions per minute, 290 revolutions per minute, 300 revolutions per minute, 310 revolutions per minute, 320 revolutions per minute, 330 revolutions per minute, 340 revolutions per minute, 350 revolutions per minute, 360 revolutions per minute, 370 revolutions per minute, 380 revolutions per minute, 390 revolutions per minute, 400 revolutions per minute, 410 revolutions per minute, 420 revolutions per minute, 430 revolutions per minute, 440 revolutions per minute, 450 revolutions per minute, 460 revolutions per minute, 470 revolutions per minute, 480 revolutions per minute, 490 revolutions per minute, or 500 revolutions per minute for 10 minutes, 11 minutes, 12 minutes, 13 minutes, 14 minutes, 15 minutes, 16 minutes, 17 minutes, 18 minutes, 19 minutes, 20 minutes, 21 minutes, 22 minutes, 23 minutes, 24 minutes, 25 minutes, 26 minutes, 27 minutes, 28 minutes, 29 minutes, 30 minutes, 31 minutes, 32 minutes, 33 minutes, 34 minutes, 35 minutes, 36 minutes, 37 minutes, 38 minutes, 39 minutes, or 40 minutes, and then stirring at a rotation speed of 500 revolutions per minute, 510 revolutions per minute, 520 revolutions per minute, 530 revolutions per minute, 540 revolutions per minute, 550 revolutions per minute, 560 revolutions per minute, 570 revolutions per minute, 580 revolutions per minute, 590 revolutions per minute, 600 revolutions per minute, 610 revolutions per minute, 620 revolutions per minute, 630 revolutions per minute, 640 revolutions per minute, 650 revolutions per minute, 660 revolutions per minute, 670 revolutions per minute, 680 revolutions per minute, or 690 revolutions per minute for 20 minutes, 21 minutes, 22 minutes, 23 minutes, 24 minutes, 25 minutes, 26 minutes, 27 minutes, 28 minutes, 29 minutes, 30 minutes, 31 minutes, 32 minutes, 33 minutes, 34 minutes, 35 minutes, 36 minutes, 37 minutes, 38 minutes, 39 minutes, 40 minutes, 41 minutes, 42 minutes, 43 minutes, 44 minutes, 45 minutes, 46 minutes, 47 minutes, 48 minutes, 49 minutes, 50 minutes, 51 minutes, 52 minutes, 53 minutes, 54 minutes, 55 minutes, 56 minutes, 57 minutes, 58 minutes, 59 minutes, or 60 minutes.

[0072] In some embodiments, in step 3) of the method, after the carbomer is dispersed, a neutralizing agent is added dropwise or gradually.

[0073] In some embodiments, the neutralizing agent is potassium hydroxide (KOH).

[0074] In some embodiments, a neutralizing agent is added to adjust the pH to about 4.5 to 6.0.

[0075] In some embodiments, a neutralizing agent is added to adjust the pH to about 5.1 to 5.8.

[0076] In some embodiments, the method comprises the following steps:

[0077] 1) Wet the thickener with glycerol to obtain a wet slurry;

[0078] 2) Add water and an ethanol solution to the wet slurry obtained in step 1) and stir evenly;

[0079] 3) After the carbomer in the product obtained in step 2) is completely dispersed, add a neutralizing agent.

[0080] In some embodiments, in step 2) of the method, hyaluronic acid, water and an ethanol solution are added to the wet slurry obtained in step 1).

[0081] In some embodiments, the wet slurry in step 1) of the method is a uniform wet slurry.

[0082] In some embodiments, in step 2) of the method, water and an ethanol solution are gradually added to the wet slurry.

[0083] In some embodiments, in step 2) of the method, hyaluronic acid, water and an ethanol solution are gradually added to the wet slurry.

[0084] In some embodiments, the step of stirring evenly in step 2) of the method includes: first stirring evenly at a rotation speed of ≤ 500 revolutions per minute, and then stirring at a rotation speed of > 500 revolutions per minute.

[0085] In some embodiments, the stirring at a rotation speed of > 500 revolutions per minute is performed using mechanical or magnetic stirring.

[0086] In some embodiments, the step of stirring evenly in step 2) of the method includes: first stirring evenly at a rotation speed of ≤ 500 revolutions per minute, and then stirring at a rotation speed of 500 to 700 revolutions per minute.

[0087] In some embodiments, the stirring at a rotation speed of 500 to 700 revolutions per minute is performed using mechanical or magnetic stirring.

[0088] In some embodiments, the step of stirring evenly in step 2) of the method includes: first stirring evenly at a rotation speed of ≤ 500 revolutions per minute for 10 to 40 minutes, and then stirring at a rotation speed of > 500 revolutions per minute for 20 minutes to 1 hour.

[0089] In some embodiments, the step of stirring evenly in step 2) of the method includes: first stirring at a speed of ≤500 revolutions per minute for 10 to 40 minutes, and then stirring at a speed of 500 to 700 revolutions per minute for 20 minutes to 1 hour.

[0090] In some embodiments, the step of stirring evenly in step 2) of the method includes: first stirring at a speed of 100 revolutions per minute, 110 revolutions per minute, 120 revolutions per minute, 130 revolutions per minute, 140 revolutions per minute, 150 revolutions per minute, 160 revolutions per minute, 170 revolutions per minute, 180 revolutions per minute, 190 revolutions per minute, 200 revolutions per minute, 210 revolutions per minute, 220 revolutions per minute, 230 revolutions per minute, 240 revolutions per minute, 250 revolutions per minute, 260 revolutions per minute, 270 revolutions per minute, 280 revolutions per minute, 290 revolutions per minute, 300 revolutions per minute, 310 revolutions per minute, 320 revolutions per minute, 330 revolutions per minute, 340 revolutions per minute, 350 revolutions per minute, 360 revolutions per minute, 370 revolutions per minute, 380 revolutions per minute, 390 revolutions per minute, 400 revolutions per minute, 410 revolutions per minute, 420 revolutions per minute, 430 revolutions per minute, 440 revolutions per minute, 450 revolutions per minute, 460 revolutions per minute, 470 revolutions per minute, 480 revolutions per minute, 490 revolutions per minute, or 500 revolutions per minute for 10 minutes, 11 minutes, 12 minutes, 13 minutes, 14 minutes, 15 minutes, 16 minutes, 17 minutes, 18 minutes, 19 minutes, 20 minutes, 21 minutes, 22 minutes, 23 minutes, 24 minutes, 25 minutes, 26 minutes, 27 minutes, 28 minutes, 29 minutes, 30 minutes, 31 minutes, 32 minutes, 33 minutes, 34 minutes, 35 minutes, 36 minutes, 37 minutes, 38 minutes, 39 minutes, or 40 minutes, and then stirring at a speed of 500 revolutions per minute, 510 revolutions per minute, 520 revolutions per minute, 530 revolutions per minute, 540 revolutions per minute, 550 revolutions per minute, 560 revolutions per minute, 570 revolutions per minute, 580 revolutions per minute, 590 revolutions per minute, 600 revolutions per minute, 610 revolutions per minute, 620 revolutions per minute, 630 revolutions per minute, 640 revolutions per minute, 650 revolutions per minute, 660 revolutions per minute, 670 revolutions per minute, 680 revolutions per minute, or 690 revolutions per minute for 20 minutes, 21 minutes, 22 minutes, 23 minutes, 24 minutes, 25 minutes, 26 minutes, 27 minutes, 28 minutes, 29 minutes, 30 minutes, 31 minutes, 32 minutes, 33 minutes, 34 minutes, 35 minutes, 36 minutes, 37 minutes, 38 minutes, 39 minutes, 40 minutes, 41 minutes, 42 minutes, 43 minutes, 44 minutes, 45 minutes, 46 minutes, 47 minutes, 48 minutes, 49 minutes, 50 minutes, 51 minutes, 52 minutes, 53 minutes, 54 minutes, 55 minutes, 56 minutes, 57 minutes, 58 minutes, 59 minutes, or 60 minutes.

[0091] In some embodiments, in step 3) of the method, after the carbomer is dispersed, a neutralizing agent is added dropwise or gradually.

[0092] In some embodiments, the neutralizing agent is potassium hydroxide (KOH).

[0093] In some embodiments, a neutralizing agent is added to adjust the pH to about 4.5 - 6.0.

[0094] In some embodiments, a neutralizing agent is added to adjust the pH to about 5.1 - 5.8.

[0095] According to the third aspect of the present disclosure, there is provided an application of the gel described in the first aspect in the preparation of a skin preparation for cooling and / or for improving or treating male erectile dysfunction.

[0096] The present disclosure provides a gel that does not contain diol compounds, and the gel comprises: 20 - 40 wt% of glycerol; 30% - 40 wt% of ethanol; 0.1% - 1.5 wt% of carbomer; and the balance of water. The gel has the effects of promoting male erectile function and low skin irritation. The skin preparation prepared using the gel of the present disclosure can be used for cooling, improving or treating male erectile dysfunction, while reducing the occurrence of allergic reactions. Detailed Embodiments

[0097] To make the purpose, technical solutions and advantages of the present disclosure more clear, the following further describes the present disclosure in detail with reference to embodiments. The specific embodiments described herein are only used to explain the present disclosure and do not constitute any limitation to the present disclosure. In addition, in the following description, the description of well-known structures and technologies is omitted to avoid unnecessarily confusing the concepts of the present disclosure. Such structures and technologies are also described in many publications.

[0098] The present disclosure provides a gel that has the effects of promoting male erectile function and low skin irritation and does not contain propylene glycol.

[0099] More generally, the non - inclusion of propylene glycol means not containing diol compounds such as ethylene glycol and other compounds.

[0100] When the gel is topically applied to the penile skin, first, the ethanol in the gel preparation causes the local tissue temperature of the penis to drop, and then, as the ethanol quickly evaporates, it causes the local tissue temperature of the penis to quickly rise. This rapid temperature cooling - rapid rise temperature difference change promotes an increase in the blood circulation of the local penile tissue, the cavernous body expands, and the penis becomes erect.

[0101] In some embodiments, the gel does not contain any active ingredients that are chemically synthesized or naturally extracted and have the function of promoting male erection, such as active ingredients like PDE5 inhibitors, local anesthetics, prostaglandins, and testosterone.

[0102] In some embodiments, the gel contains a nearly non-toxic green solvent, glycerol, as the base solvent.

[0103] In some embodiments, the gel contains ethanol, and water and ethanol are diluted to the required concentrations in different proportions.

[0104] In some embodiments, the gel is finally prepared with glycerol / water / ethanol together as the main components.

[0105] In some embodiments, the gel contains a carbomer homopolymer thickener. The basic structural units constituting these homopolymers come from monomers of a single structural type. According to the properties of the structural monomers and the polymerization technology, the homopolymers have a network formed by a cross-linked backbone structure. The homopolymers do not contain additives such as steric stabilizers and long-chain alkyl groups. Common carbomer homopolymers include carbomer 980, carbomer 5984, carbomer 934, carbomer 937, carbomer 940, etc., which all belong to cross-linked polyacrylic acid resin chemically.

[0106] More preferably, the carbomer 980 thickener is a synthetic homopolymer cross-linked by polyacrylic acid and allyl sucrose or allyl pentaerythritol, polymerized into a high molecular compound in a co-solvent system, and has a high cross-linking level and viscosity range.

[0107] In some embodiments, the gel also includes carbomer copolymers and interpolymer thickeners, including but not limited to carbomer 1342 (hydrophobically modified copolymer), carbomer ETD2020, carbomer Ultrez20, carbomer Ultrez10 (all belong to acrylate / C10-30 alkyl acrylate cross-linked copolymers).

[0108] In some embodiments, the concentration of the carbomer homopolymer in the gel is between 0.1 and 1.5 wt%; preferably, the homopolymer concentration is 1.0 wt%, dissolved in a system mainly composed of water / glycerol / ethanol.

[0109] In some embodiments, the concentration of hyaluronic acid in the gel is between 0.05 and 0.5 wt%, and the molecular weight is 1000 - 30000; preferably, the hyaluronic acid concentration is 0.2 wt%, dissolved in a system mainly composed of water / glycerol / ethanol.

[0110] When a carbomer homopolymer is contained, the viscosity of the gel is pH-sensitive. It has a maximum viscosity in the range of pH 5 to 10. When the pH is above and below this range, the viscosity decreases significantly, so it must be neutralized with an alkali to the appropriate range to maintain an appropriate viscosity.

[0111] In some embodiments, when the pH value is between 4.5 and 6.0, the viscosity of the gel (containing a carbomer homopolymer) is the highest; when the pH is higher than 6.0 or lower than 4.0, the viscosity of the gel decreases and precipitation occurs.

[0112] In some embodiments, the pH value of the gel (containing a carbomer homopolymer) is maintained between 5.1 and 5.8 to maintain the maximum viscosity.

[0113] In some embodiments, a suitable neutralizing agent is selected according to the different carbomer homopolymers contained in the gel, including, but not limited to, potassium hydroxide, sodium hydroxide, ammonium hydroxide, triethanolamine, triethanolamine arginine, aminomethylpropanol, tetrahydroxypropyl ethylenediamine, tromethamine, diisopropanolamine, and triisopropanolamine, etc. Preferably, potassium hydroxide, sodium hydroxide, and triethanolamine.

[0114] In some embodiments, the ethanol concentration in the gel (containing a carbomer homopolymer and no propylene glycol) is between 30 wt% and 50 wt%. The preferred ethanol concentration is between 30 wt% and 40 wt%.

[0115] In some embodiments, the water concentration in the gel (containing a carbomer homopolymer and no propylene glycol) is between 30 wt% and 40 wt%.

[0116] In some embodiments, the glycerol concentration in the gel is between 25 wt% and 40 wt%. The preferred glycerol concentration is between 25 wt% and 35 wt%.

[0117] In some embodiments, the specific gravity of each component in the gel is expressed by weight as follows:

[0118]

[0119] In some embodiments, the specific gravity of each component in the gel is expressed by weight as follows:

[0120]

[0121] In some embodiments, in the gel containing a carbomer copolymer or a carbomer interpolymer, the specific gravity of each component is expressed by weight as follows:

[0122]

[0123] In some embodiments, the gel is a carbomer homopolymer or copolymer thickener gel with glycerol / water / ethanol as the main components, and the dosage form of the gel is an external gel, spray, aerosol, etc.

[0124] In some embodiments, the present disclosure provides a method for preparing the gel.

[0125] In some embodiments, the preparation method includes the following steps: Mix water and carbomer, disperse the carbomer with water, then add glycerol, hyaluronic acid, and ethanol, make up the volume with water, first stir evenly at a rotation speed of ≤500 revolutions per minute, and then stir at a rotation speed of 500 - 700 revolutions per minute. After the carbomer is completely dispersed, add the neutralizing agent KOH dropwise or gradually, and adjust the pH to about 5.1 - 5.8. The neutralizing agent must be added dropwise or gradually after the carbomer is completely dispersed.

[0126] In some embodiments, the gel formulation of the present disclosure can be prepared by the direct addition method, and this method is suitable for large-scale preparation.

[0127] In some embodiments, in the direct addition method, first dissolve glycerol and hyaluronic acid in a water / ethanol mixture. Then, add the thickener carbomer, first stir evenly at a rotation speed of ≤500 revolutions per minute, and then stir at a rotation speed of 500 - 700 revolutions per minute. After the carbomer is completely dispersed, add the neutralizing agent KOH dropwise or gradually, and adjust the pH to about 5.1 - 5.8. The neutralizing agent must be added dropwise or gradually after the carbomer is completely dispersed.

[0128] In some embodiments, the gel of the present disclosure can also be prepared by the reverse addition method, which is suitable for small-scale laboratory preparation. In the reverse addition preparation method, first use glycerol as a wetting agent to wet the carbomer thickener. When the thickener obtains a uniform wet slurry, then add hyaluronic acid, water, and ethanol solution; stir and mix evenly at a rotation speed of 500 - 700 revolutions per minute. Then adjust the pH according to the above direct preparation method, and measure and calculate the temperature change.

[0129] Definition

[0130] Unless otherwise defined, all technical and scientific terms used in the present disclosure have the same meaning as commonly used in the field to which the present disclosure belongs. For the purpose of explaining this specification, the following definitions will be applied, and where appropriate, terms used in the singular form will also include the plural form, and vice versa.

[0131] Unless the context clearly indicates otherwise, the expressions "a" and "an" used herein include plural referents.

[0132] As used herein, the term "about" is as understood by a person of ordinary skill in the art and varies within a certain range depending on the context in which it is used. If a person of ordinary skill in the art is not aware of the use of the term based on the context in which it is used, "about" shall mean up to plus or minus 10% of a particular value.

[0133] The term "propylene glycol" as used in the present disclosure: Propylene glycol most typically refers to mono propylene glycol (CH3-CHOH-CH2OH) in its dihydro form, but the term "propylene glycol" also encompasses the entire family of polypropylene glycols of different chain lengths. Alternative names include: 1,2-propanediol, 1,2-dihydroxypropane, methyl glycol, trimethyl glycol.

[0134] The term "Polymer Gel" as used in the present disclosure: Generally represents a polymer-solvent system, most often a binary system. There may be multiple solvents in the system, in which there is a three-dimensional network composed of macromolecules or their associates (aggregates) that can retain a large amount of solvent (tens to hundreds of times the polymer itself).

[0135] The term "thickener", also known as gelling agent, as used in the present disclosure is a substance that can increase the viscosity of latex or liquid. Thickeners can increase the viscosity of the system, keep the system in a uniform and stable suspension or emulsion state, or form a gel; most thickeners also have an emulsifying effect. They can be divided into two major categories: natural and synthetic. Natural thickeners are mainly obtained from plants and seaweeds containing polysaccharide viscous substances, such as starch, gum arabic, pectin, agar, etc. Synthetic thickeners include carboxymethyl cellulose, methyl cellulose, sodium carboxymethyl cellulose, sodium polyacrylate, etc.

[0136] The term "carbomer" used in the present disclosure, also known as carboxypolymethylene or polyacrylic acid thickener, is a series of synthetic, high molecular weight, molecularly crosslinked polyacrylic acid polymers with the molecular formula -[-CH2-CHn-]-COOH. It is a white, fluffy powder that can swell in water, ethanol, and glycerol. Calculated on a dry basis, the carbomer molecule contains 56%-68% carboxylic acid groups (-COOH). In the powder state, the carbomer molecular chain is in a coiled state. After dispersing it in water, some of the carboxyl groups of the carbomer molecular chain begin to dissociate and undergo hydration, and the molecular chain gradually unfolds. At this time, the aqueous dispersion is weakly acidic. Carbomer does not support the growth of bacteria and molds, has good acid resistance, and its gel has good thermoreversibility, high strength, is non-toxic and non-irritating, and its viscosity is not affected by temperature. It is widely used in the cosmetics and pharmaceutical industries for formulating semi-solid and oral liquid products of various concentrations. These polymers are effective thickeners, suspending agents, and stabilizers at very low concentrations (0.1-3% w / w). Carbomers differ in crosslinking agents and density, as well as the solvents used in the polymerization process. According to the type of crosslinking agent, carbomers can be divided into carbomer homopolymers: that is, acrylic acid crosslinked with allyl sucrose or allyl pentaerythritol; carbomer copolymers: that is, acrylic acid and C10-C30 alkyl acrylates crosslinked together with allyl pentaerythritol; carbomer interpolymers: including block copolymers formed by crosslinking carbomer homopolymers or carbomer copolymers with long-chain alkyl esters respectively. Each type of carbomer has low, medium, and high crosslinking densities, providing different types of polymers to increase the viscosity of the gel system. Carbomer has good adhesion, thickening, emulsifying, suspending and other properties, is easily soluble in water, ethanol, and glycerol, is relatively easy to prepare, has a transparent gel appearance and good stability, so it has broad application prospects. There are more than 10 grades of carbopol polymers, and they can be further divided into more categories according to the physical structure and chemical composition, crosslinking density, polymerization solvent, crosslinking type, network charge, and physical appearance of carbomer.

[0137] The synthetic raw materials of carbomer include five parts: synthetic monomers, solvents, cross-linking agents, initiators, salt-forming agents and additives. Synthetic monomers mainly refer to unsaturated carboxylic acids with polymerizable carbon-carbon double bonds and carboxyl groups, such as acrylic acid, polyacrylic acid, methacrylic acid, maleic acid, methyl methacrylate, butyl acrylate, etc. The synthesis process is as follows: A monomer mixture such as acrylic acid is dissolved in an organic solvent (cyclohexane, ethyl acetate, benzene), and then an initiator (such as azobisisobutyronitrile), a cross-linking agent (such as allyl ether cross-linking agent), a salt-forming agent (triethanolamine, sodium hydroxide, potassium hydroxide) and different types of additives (such as steric stabilizers, long-chain alkyl groups, etc.) are added for polymerization to obtain a high molecular polymer. Different types and different properties of carbomer can be obtained according to the differences in synthetic monomers, cross-linking agents, solvents and additives or the cross-linking methods among the above five types of polymerization raw materials. For example, carbomer homopolymers, carbomer copolymers, carbomer interpolymers, benzene solvent homopolymers, cosolvent homopolymers, hydrophobic modified copolymers, C10-30 alkyl acrylate cross-linked copolymers, a novel liquid acrylic rheological modifier, and a new type of easily dispersed copolymer. These different types of carbomer have different rheological properties, including different solution viscosities, swelling volume ratios, hydrophobicities, acidities and solution densities, etc. Under different conditions, they exhibit different solvent behaviors and can be used to prepare gel carriers with unique properties to meet the production application requirements of different products. For example, carbomer homopolymers (such as carbomer 980, carbomer 974 and carbomer 5984) are all polymers cross-linked by acrylic acid and allyl sucrose or allyl pentaerythritol, and have a higher cross-linking level and a high viscosity range.

[0138] The term "Carbopol Homopolymer" used in the present disclosure: refers to a homopolymer formed by crosslinking acrylic acid with allyl sucrose or allyl pentaerythritol, and the molecule does not contain long-chain C10-C30 alkyl acrylates. Common Carbopol homopolymers such as: Carbopol 980, Carbopol 974, Carbopol 5984, Carbopol 934 or Carbopol 940. Among them, Carbopol 980 is a thickener for cationic polymers without benzene, with extremely short rheology, high viscosity, low ion tolerance; low shear tolerance. Carbopol 5984 has obvious crosslinking with allyl pentaerythritol or allyl sucrose; Carbopol 934 is an anionic thickener containing benzene solvent, with short rheology, medium / high viscosity, low ion tolerance and high shear tolerance, and low water solubility; Carbopol 974 is a medium-viscosity polymer; Carbopol 940 is a multifunctional hydroxypropyl methylcellulose ether containing benzene solvent, with extremely short rheology, high viscosity, low ion tolerance and shear tolerance.

[0139] The term "Copolymer" used in the present disclosure: refers to a copolymer formed by crosslinking acrylic acid and C10-C30 alkyl acrylates together with allyl pentaerythritol, and the molecule contains long-chain C10-C30 alkyl acrylates. Common Carbopol copolymers such as Carbopol 1342, Carbopol ETD2020, Carbopol Ultrez20 or Carbopol Ultrez10. Among them, Carbopol 1342 is a salt-tolerant hydrophobic modified Carbopol copolymer, with long flow characteristics, medium viscosity, high ion tolerance and high shear tolerance. Carbopol ETD2020 is a copolymer of acrylic acid and alkyl acrylate, and its long chain is connected with allyl amyl alcohol ether or sucrose through a transverse bond, with long rheology, medium viscosity, high endurance ionicity and shear tolerance.

[0140] The term "Interpolymer" used in the present disclosure: refers to a block interpolymer formed by crosslinking Carbopol homopolymer or Carbopol copolymer with long-chain alkyl esters respectively. For example, Carbopol Ultrez20 is an interpolymer, with long rheology, medium viscosity, medium ion tolerance and high shear tolerance; Carbopol Ultrez 10 is also a copolymer, with short rheology and high viscosity.

[0141] The term "glycerol" used in the present disclosure is also known as glycerin, with the chemical formula C3H8O3. It is colorless, odorless, sweet-tasting, and appears as a clear, viscous liquid. It is an organic compound that can absorb moisture from the air and is a skeletal component of triglyceride molecules. Glycerol is the only green solvent found so far that is similar to water, and it has the advantages of low toxicity, low price, high availability, renewability, high boiling point, and low vapor pressure. Glycerol has all the characteristics of becoming a core green solvent in catalysis, organic chemistry, materials chemistry, and biology, which helps to increase the combination of available green solvents to replace the traditionally used organic solvents. Glycerol has obvious advantages compared with most organic solvents. Glycerol is a non-toxic and non-flammable solvent that can be biodegradable and does not require special treatment measures or storage.

[0142] The term "Hyaluronic Acid" used in the present disclosure is an unsulfated glucosaminoglycan composed of repeating disaccharide units of N-acetylglucosamine (GlcNAc) and glucuronic acid (GlcUA), in which N-acetylglucosamine and glucuronic acid are linked together by alternating β-1,4 and β-1,3 glycosidic bonds. Hyaluronic acid is also known as hyaluronate, hyaluronate salt, or HA. The term "hyaluronic acid" in this article includes alkali metal salts, such as sodium, potassium, and lithium salts of hyaluronic acid. Hyaluronic acid naturally exists in the body and has various important physiological functions, such as lubricating joints, repairing wounds, and regulating electrolytes inside and outside cells. Hyaluronic acid has been widely used in the medical field, including aesthetic plastic surgery and skin care. Different specifications of hyaluronic acid have different functions and uses. As a natural lubricant, hyaluronic acid has been used in the treatment of patients with dry eye disease and knee osteoarthritis. Hyaluronic acid has excellent gelling properties and can quickly bind water. Therefore, hyaluronic acid has been widely regarded and applied as a skin moisturizer, lubricant, and repair agent. For example, it has been regarded as a functional ingredient in improving the quality of sexual life of both men and women and intervening in the health of the female reproductive system.

[0143] The term "erectile dysfunction (ED)" used in the present disclosure refers to the inability of a male penis to achieve or maintain sufficient erection.

[0144] The term "PDE5 inhibitor" used in the present disclosure is a phosphodiesterase type 5 inhibitor: a drug that selectively inhibits the activity of phosphodiesterase 5 and is widely used in the treatment of diseases such as male erectile dysfunction.

[0145] The term "local anaesthetics" used in the present disclosure is a class of drugs that can reversibly block the generation and transmission of sensory nerve impulses at the local site of drug administration. Under the condition of maintaining consciousness, it can reversibly cause the disappearance of local tissue pain sensation and is also used in the treatment of erectile dysfunction.

[0146] The term "prostaglandin" used in this disclosure is capable of effectively promoting blood flow in the penile arteries and prompting normal erection of the corpus cavernosum, and has the effects of improving male premature ejaculation, erectile dysfunction and other diseases.

[0147] Examples are provided below to assist in understanding this disclosure. However, it should be understood that these examples are only for illustrating this disclosure and do not constitute any limitation. The actual protection scope of this disclosure is set forth in the claims. It should be understood that any modifications and changes can be made without departing from the spirit of this disclosure.

[0148] Example

[0149] Determination of the cooling effect of Carbomer 937 homopolymer gel without propylene glycol in Example 1

[0150] 1. Formulation composition and ratio of each component (mass ratio): The experiment was divided into two groups, gels with and without propylene glycol. Carbomer 937 1%, deionized water 34%, absolute ethanol 35%, glycerol 24%, propylene glycol 6%, hyaluronic acid 0.1%.

[0151] 2. Prepare 25 g of gel, weigh 0.25 g of Carbomer 937, disperse it with 8.5 g of deionized water, then successively add 6.0 g of glycerol, 1.5 g of propylene glycol (not added in the group without propylene glycol) and 8.75 g of absolute ethanol, 0.01 g of hyaluronic acid. After making up the volume with water, first stir at a speed of 500 revolutions per minute for 30 minutes, and then stir at a speed of 700 revolutions per minute for 30 minutes.

[0152] 3. Neutralization: Adjust the pH value to 5.25 - 5.55 with 10% potassium hydroxide solution, and the gel becomes white and transparent.

[0153] 4. Temperature measurement method: The temperature probe method was used to measure the cooling effect of the gel. At a preset temperature of 26°C, insert the temperature probe into the bottom of the gel container (the head of the temperature probe cannot touch the container), and read and record the temperature value displayed by the temperature probe inserted into the gel; then quickly pull out the temperature probe from the container, and continuously observe and measure the temperature change within 20 minutes, and read and record the temperature change with time respectively. After the temperature probe is pulled out of the gel container, the temperature displayed by the temperature probe drops rapidly and then rises slowly. Calculate the maximum temperature drop according to the temperature change. The maximum temperature drop is the difference between the preset ambient temperature value and the lowest temperature value. The larger the maximum temperature drop value, the stronger the cooling ability of the gel.

[0154] 5. Experimental results: Determine the relationship between temperature change and time. First, read the temperature of the temperature probe in the gel, then pull out the probe from the gel, continuously observe the temperature change between 1 - 20 minutes and record it. The results are shown in Table 1.

[0155] Table 1. Relationship between the cooling ability of Carbomer 937 homopolymer gel and time

[0156]

[0157] 6 Experimental conclusions:

[0158] The above results show that in the homopolymer Carbomer 937 gel group without propylene glycol, there is a significant cooling effect, and it shows a better cooling trend than the homopolymer gel group containing propylene glycol. The lowest temperature appears at 150 seconds and lasts for about 2 minutes or more.

[0159] Determination of the cooling effect of Carbomer U10 gel without propylene glycol in Example 2

[0160] 1. Formulation composition and ratio of each component (mass ratio): The experiment is divided into two groups, gels with and without propylene glycol. Carbomer U10 1%, deionized water 34%, absolute ethanol 35%, glycerol 24%, propylene glycol 6%, hyaluronic acid 0.1%.

[0161] 2. Prepare 25 g of gel. Weigh 0.25 g of Carbomer U10, disperse it with 8.5 g of deionized water, then successively add 6.0 g of glycerol, 1.5 g of propylene glycol (not added in the group without propylene glycol) and 8.75 g of absolute ethanol, 0.01 g of hyaluronic acid. After making up the volume with water, first stir at a speed of 500 revolutions per minute for 30 minutes, and then stir at a speed of 700 revolutions per minute for 30 minutes.

[0162] 3. Neutralization: Adjust the pH value to 5.25 - 5.55 with 10% potassium hydroxide solution, and the gel becomes white and transparent.

[0163] 4. Temperature measurement method: Measure according to the method described in step 4 of Example 1.

[0164] 5. Experimental results: Determine the relationship between temperature change and time. First, read the temperature of the temperature probe in the gel, then pull out the probe from the gel, continuously observe the temperature change between 1 - 20 minutes and record it. The results are shown in Table 2.

[0165] Table 2. Relationship between the cooling ability of Carbomer U10 homopolymer gel and time

[0166]

[0167]

[0168] 6. Experimental conclusions

[0169] The above results indicate that in the homopolymer carbomer U10 gel group without propylene glycol, there is a significant cooling effect and a better cooling trend than the homopolymer gel group containing propylene glycol. The lowest temperature appears at 150 seconds and lasts for up to 2 minutes.

[0170] Determination of the cooling effect of carbomer 980 homopolymer gel without propylene glycol in Example 3

[0171] 1. Formulation composition and ratio of each component (mass ratio): The experiment is divided into two groups, gels with and without propylene glycol. Carbomer 980 1%, deionized water 34%, absolute ethanol 35%, glycerol 24%, propylene glycol 6%, hyaluronic acid 0.1%.

[0172] 2. Prepare 25 g of gel. Weigh 0.25 g of carbomer 980, disperse it with 8.5 g of deionized water, then successively add 6.0 g of glycerol, 1.5 g of propylene glycol (not added in the group without propylene glycol) and 8.75 g of absolute ethanol, 0.01 g of hyaluronic acid. After making up the volume with water, first stir at a speed of 500 revolutions per minute for 30 minutes, and then stir at a speed of 700 revolutions per minute for 30 minutes.

[0173] 3. Neutralization: Adjust the pH value to 5.25 - 5.55 with 10% potassium hydroxide solution, and the gel becomes white and transparent.

[0174] 4. Temperature measurement method: Measure according to the method described in step 4 of Example 1.

[0175] 5. Experimental results: Determine the relationship between temperature change and time. First, read the temperature of the temperature probe in the gel, then pull out the probe from the gel, continuously observe the temperature change between 1 and 20 minutes and record it. The results are shown in Table 3.

[0176] Table 3. Relationship between the cooling ability of carbomer 980 homopolymer gel and time

[0177]

[0178] 6. Experimental conclusion

[0179] The above results indicate that in the homopolymer carbomer 980 gel group without propylene glycol, there is a significant cooling effect and a better cooling trend than the homopolymer gel group containing propylene glycol. The lowest temperature appears at 120 seconds.

[0180] Determination of the cooling effect of carbomer 934 gel without propylene glycol in Example 4

[0181] 1. Composition of the formula and ratios of each component (by mass): The experiment was divided into two groups, gels with and without propylene glycol. Carbomer 934 1%, deionized water 34%, absolute ethanol 35%, glycerol 24%, propylene glycol 6%, hyaluronic acid 0.1%.

[0182] 2. Prepare 25 g of gel. Weigh 0.25 g of Carbomer 934, disperse it with 8.5 g of deionized water, then successively add 6.0 g of glycerol, 1.5 g of propylene glycol (not added in the group without propylene glycol), 0.01 g of hyaluronic acid, and 8.75 g of absolute ethanol. After making up the volume with water, first stir at a speed of 500 revolutions per minute for 30 minutes, and then stir at a speed of 700 revolutions per minute for 30 minutes.

[0183] 3. Neutralization: Adjust the pH value to 5.25 - 5.55 with 10% potassium hydroxide solution, and the gel becomes white and transparent.

[0184] 4. Method for measuring temperature: Measure according to the method described in step 4 of Example 1.

[0185] 5. Experimental results: Measure the relationship between temperature change and time. First, read the temperature of the temperature probe in the gel, then pull out the probe from the gel, continuously observe the temperature change between 1 - 20 minutes and record it. The results are shown in Table 4.

[0186] Table 4. Relationship between the cooling ability of Carbomer 934 homopolymer gel and time

[0187]

[0188] 6: Experimental conclusion

[0189] The above results show that among the two groups of Carbomer 934 homopolymer gels, there is an obvious cooling effect, and it shows a better cooling trend than the homopolymer gel group containing propylene glycol. The lowest temperature appears at 120 seconds.

[0190] Determination of the cooling effect of Carbomer 940 gel without propylene glycol in Example 5

[0191] 1. Composition of the formula and ratios of each component (by mass): The experiment was divided into two groups, gels with and without propylene glycol. Carbomer 940 1%, deionized water 34%, absolute ethanol 35%, glycerol 24%, propylene glycol 6%, hyaluronic acid 0.1%.

[0192] 2. Prepare 25 g of gel. Weigh 0.25 g of Carbomer 940, disperse it with 8.5 g of deionized water, then successively add 6.0 g of glycerol, 1.5 g of propylene glycol (not added in the group without propylene glycol), 0.01 g of hyaluronic acid, and 8.75 g of absolute ethanol. After making up the volume with water, first stir at a speed of 500 revolutions per minute for 30 minutes, and then stir at a speed of 700 revolutions per minute for 30 minutes.

[0193] 3. Neutralization: Adjust the pH value to 5.25 - 5.55 with 10% potassium hydroxide solution until the gel becomes white and transparent.

[0194] 4. Temperature measurement method: Measure according to the method described in step 4 of Example 1.

[0195] 5. Experimental results: Measure the relationship between temperature change and time. First, read the temperature of the temperature probe in the gel, then pull out the probe from the gel, continuously observe the temperature change between 1 - 20 minutes and record it. The results are shown in Table 5.

[0196] Table 5. Relationship between the cooling ability of Carbomer 940 homopolymer gel and time

[0197]

[0198] 6. Experimental conclusion

[0199] The above results show that in the homopolymer Carbomer 940 gel group without propylene glycol, there is a significant cooling effect and a better cooling trend than the homopolymer gel group containing propylene glycol. The lowest temperature appears at 110 seconds.

[0200] Determination of the cooling effect of Carbomer 1342 gel without propylene glycol in Example 6

[0201] 1. Formulation composition and component ratios (mass ratio): The experiment is divided into two groups, gels with and without propylene glycol. Carbomer 1342 1%, deionized water 34%, absolute ethanol 35%, glycerol 24%, propylene glycol 6%, hyaluronic acid 0.1%.

[0202] 2. Prepare 25 g of gel. Weigh 0.25 g of Carbomer 1342, disperse it with 8.5 g of deionized water, then successively add 6.0 g of glycerol, 1.5 g of propylene glycol (not added in the group without propylene glycol), 0.01 g of hyaluronic acid and 8.75 g of absolute ethanol. After making up the volume with water, first stir at a speed of 500 revolutions per minute for 30 minutes, and then stir at a speed of 700 revolutions per minute for 30 minutes.

[0203] 3. Neutralization: Adjust the pH value to 5.25 - 5.55 with 10% potassium hydroxide solution until the gel becomes white and transparent.

[0204] 4. Temperature measurement method: Measure according to the method described in step 4 of Example 1.

[0205] 5. Experimental results: Measure the relationship between temperature change and time. First, read the temperature of the temperature probe in the gel, then pull out the probe from the gel, continuously observe the temperature change between 1 - 20 minutes and record it. The results are shown in Table 6.

[0206] Table 6. Relationship between the cooling ability of Carbomer 1342 homopolymer gel and time

[0207]

[0208]

[0209] 6. Experimental conclusions

[0210] The above results show that in the homopolymer Carbomer 1342 gel group without propylene glycol, there is a significant cooling effect, and it shows a better cooling trend than the homopolymer gel group containing propylene glycol. The maximum cooling occurs at 110 seconds.

[0211] Determination of the cooling effect of Carbomer 5984 gel without propylene glycol in Example 7

[0212] 1. Formulation composition and ratio of each component (mass ratio): The experiment is divided into two groups, gels with and without propylene glycol. Carbomer 5984 1%, deionized water 34%, absolute ethanol 35%, glycerol 24%, propylene glycol 6%, hyaluronic acid 0.1%.

[0213] 2. Preparation of 25 g of gel: Weigh 0.25 g of Carbomer 5984, disperse it with 8.5 g of deionized water, then sequentially add 6.0 g of glycerol, 1.5 g of propylene glycol (not added in the group without propylene glycol), 0.01 g of hyaluronic acid and 8.75 g of absolute ethanol. After making up the volume with water, first stir at a speed of 500 revolutions per minute for 30 minutes, and then stir at a speed of 700 revolutions per minute for 30 minutes.

[0214] 3. Neutralization: Adjust the pH value to 5.25 - 5.55 with 10% potassium hydroxide solution, and the gel becomes white and transparent.

[0215] 4. Temperature measurement method: Measure according to the method described in step 4 of Example 1.

[0216] 5. Experimental results: Determine the relationship between temperature change and time. First, read the temperature of the temperature probe in the gel, then pull out the probe from the gel, continuously observe the temperature change between 1 - 20 minutes and record it. The results are shown in Table 7.

[0217] Table 7. Relationship between the cooling ability of Carbomer 5984 homopolymer gel and time

[0218]

[0219] 6: Experimental conclusions

[0220] The above results indicate that in the homopolymer carbomer 5984 gel group without propylene glycol, there is a significant cooling effect and a better cooling trend than the homopolymer gel group containing propylene glycol. The temperature drops to the lowest point at 120 seconds, and the maximum cooling time of the homopolymer gel group containing propylene glycol is 150 seconds.

[0221] Determination of the cooling effect of carbomer U20 gel without propylene glycol in Example 8

[0222] 1. Formulation composition and ratio of each component (mass ratio): The experiment is divided into two groups, gels with and without propylene glycol. Carbomer U20 1%, deionized water 34%, absolute ethanol 35%, glycerol 24%, propylene glycol 6%, hyaluronic acid 0.1%.

[0223] 2. Prepare 25 g of gel. Weigh 0.25 g of carbomer U20 and disperse it with 8.5 g of deionized water. Then add 6.0 g of glycerol, 1.5 g of propylene glycol (not added in the group without propylene glycol), 0.01 g of hyaluronic acid and 8.75 g of absolute ethanol in sequence. After making up the volume with water, first stir at a speed of 500 revolutions per minute for 30 minutes, and then stir at a speed of 700 revolutions per minute for 30 minutes.

[0224] 3. Neutralization: Adjust the pH value to 5.25 - 5.55 with 10% potassium hydroxide solution, and the gel becomes white and transparent.

[0225] 4. Temperature measurement method: Measure according to the method described in step 4 of Example 1.

[0226] 5. Experimental results: Measure the relationship between temperature change and time. First, read the temperature of the temperature probe in the gel, then pull out the probe from the gel, continuously observe the temperature change between 1 and 20 minutes and record it. The results are shown in Table 8.

[0227] Table 8. Relationship between the cooling ability and time of carbomer U20 homopolymer gel

[0228]

[0229] 6. Experimental conclusion

[0230] The above results indicate that in the homopolymer carbomer U20 gel group without propylene glycol, there is a significant cooling effect and a better cooling trend than the homopolymer gel group containing propylene glycol. The temperature drops to the lowest point at 120 seconds.

[0231] Determination of the cooling effect of carbomer ETD 2020 gel without propylene glycol in Example 9

[0232] 1. Composition of the formula and ratios of each component (by mass): The experiment was divided into two groups, gels with and without propylene glycol. Carbomer 2020 1%, deionized water 34%, absolute ethanol 35%, glycerol 24%, propylene glycol 6%, hyaluronic acid 0.1%.

[0233] 2. Prepare 25 g of gel. Weigh 0.25 g of Carbomer 2020, disperse it with 8.5 g of deionized water, then sequentially add 6.0 g of glycerol, 1.5 g of propylene glycol (not added in the group without propylene glycol), 0.01 g of hyaluronic acid, and 8.75 g of absolute ethanol. After making up the volume with water, first stir at a speed of 500 revolutions per minute for 30 minutes, and then stir at a speed of 700 revolutions per minute for 30 minutes.

[0234] 3. Neutralization: Adjust the pH value to 5.25 - 5.55 with 10% potassium hydroxide solution, and the gel becomes white and transparent.

[0235] 4. Method for temperature measurement: Measure according to the method described in step 4 of Example 1.

[0236] 5. Experimental results: Measure the relationship between temperature change and time. First, read the temperature of the temperature probe in the gel, then pull out the probe from the gel, continuously observe the temperature change between 1 - 20 minutes and record it. The results are shown in Table 9.

[0237] Table 9. Relationship between the cooling ability of Carbomer ETD 2020 homopolymer gel and time

[0238]

[0239] 6. Experimental conclusion

[0240] The above results show that in the homopolymer Carbomer 2020 gel group without propylene glycol, there is a significant cooling effect and a better cooling trend than the homopolymer gel group containing propylene glycol. The temperature drops to the lowest point at 120 seconds, and the maximum cooling time of the homopolymer gel group containing propylene glycol is 150 seconds.

[0241] Effect of different concentrations of glycerol in Example 10 on the cooling ability of Carbomer Ultrez 10 gel without propylene glycol

[0242] 1. Composition of the formula and ratios of each component (by mass): The experiment was divided into two groups, 30% glycerol, Carbomer Ultrez 10 (abbreviated as Carbomer U10) 1%, deionized water 34%, absolute ethanol 35% and 24% glycerol, hyaluronic acid 0.1%, Carbomer U10 1%, deionized water 40%, absolute ethanol 35%.

[0243] 2. Prepare 25 g of gel. Weigh 0.25 g of Carbomer U10, disperse it with 8.5 g and 10.0 g of deionized water respectively, then add 6.0 g and 7.5 g of glycerol, 0.01 g of hyaluronic acid, and 8.75 g of absolute ethanol respectively. First, stir at a speed of 500 revolutions per minute for 30 minutes, and then stir at a speed of 700 revolutions per minute for 30 minutes.

[0244] 3. Neutralization: Adjust the pH value to 5.25 - 5.55 with 10% potassium hydroxide solution, and the gel becomes white and transparent.

[0245] 4. Temperature measurement method: Measure according to the method described in step 4 of Example 1.

[0246] 5. Experimental results: Measure the relationship between temperature change and time. First, read the temperature of the temperature probe in the gel, then pull out the probe from the gel, continuously observe the temperature change between 1 and 20 minutes and record it. The results are shown in Table 10.

[0247] Table 10. Relationship between the cooling ability of Carbomer U10 homopolymer gel and time

[0248]

[0249] 6: Experimental conclusion

[0250] The above results show that among the gels with two different glycerol contents, the temperature drops to the lowest at 5 minutes, but the cooling effect of the gel group containing 24% glycerol homopolymer Carbomer U10 has an obvious tendency to be superior to that of the 30% glycerol gel group.

[0251] Example 11 Influence of different concentrations of glycerol on Carbomer 980 homopolymer gel without propylene glycol

[0252] Influence on the cooling ability

[0253] 1. Formulation composition and component ratios (mass ratio): The experiment is divided into two groups, 30% glycerol, 1% Carbomer 980, 34% deionized water, 35% absolute ethanol, 0.1% hyaluronic acid, 24% glycerol, 1% Carbomer 980, 40% deionized water, 35% absolute ethanol.

[0254] 2. Prepare 25 g of gel. Weigh 0.25 g of Carbomer 980, disperse it with 8.5 g and 10.0 g of deionized water respectively, then add 6.0 g and 7.5 g of glycerol, 0.01 g of hyaluronic acid, and 8.75 g of absolute ethanol respectively. First, stir at a speed of 500 revolutions per minute for 30 minutes, and then stir at a speed of 700 revolutions per minute for 30 minutes.

[0255] 3. Neutralization: Adjust the pH value to 5.25 - 5.55 with 10% potassium hydroxide solution, and the gel becomes white and transparent.

[0256] 4. Temperature measurement method: Measure according to the method described in step 4 of Example 1.

[0257] 5. Experimental results: Measure the relationship between temperature change and time. First, read the temperature of the temperature probe in the gel, then pull out the probe from the gel, continuously observe the temperature change between 1 and 20 minutes and record it. The results are shown in Table 11.

[0258] Table 11. Relationship between the cooling capacity of Carbomer 980 homopolymer gel and time

[0259]

[0260] 6. Experimental conclusion

[0261] The above results show that among the gels with two different glycerol contents, the temperature drops to the lowest at 5 minutes, but the cooling effect of the Carbomer 980 gel containing 24% glycerol homopolymer is significantly better than that of the 30% glycerol gel group.

[0262] Example 12 Effect of different concentrations of glycerol on Carbomer 940 homopolymer gel without propylene glycol

[0263] Effect on cooling capacity

[0264] 1. Formulation composition and ratio of each component (mass ratio): The experiment is divided into two groups, 30% glycerol, 1% Carbomer 940, 34% deionized water, 35% absolute ethanol, 0.1% hyaluronic acid, 24% glycerol, 1% Carbomer 940, 40% deionized water, 35% absolute ethanol.

[0265] 2. Prepare 25 g of gel. Weigh 0.25 g of Carbomer 940, disperse it with 8.5 g and 10.0 g of deionized water respectively, then add 6.0 g and 7.5 g of glycerol, 0.01 g of hyaluronic acid, and 8.75 g of absolute ethanol respectively. First, stir at a speed of 500 revolutions per minute for 30 minutes, and then stir at a speed of 700 revolutions per minute for 30 minutes.

[0266] 3. Neutralization: Adjust the pH value to 5.25 - 5.55 with 10% potassium hydroxide solution, and the gel is white and transparent.

[0267] 4. Temperature measurement method: Measure according to the method described in step 4 of Example 1.

[0268] 5. Experimental results: Measure the relationship between temperature change and time. First, read the temperature of the temperature probe in the gel, then pull out the probe from the gel, continuously observe the temperature change between 1 and 20 minutes and record it. The results are shown in Table 12.

[0269] Table 12. Relationship between the cooling capacity of Carbomer 940 homopolymer gel with different glycerol concentrations and time

[0270]

[0271] 6. Experimental conclusions

[0272] The above results show that in the gels with two different glycerol contents, the temperature drops to the lowest at 5 minutes, but the temperature drop of the gel group containing 24% glycerol homopolymer carbomer 940 is significantly better than that of the 30% glycerol gel group.

[0273] Example 13 Influence of Different Ethanol Concentrations on the Cooling Capacity of Carbomer 980 Homopolymer Gel without Propylene Glycol

[0274] 1. Composition of the formulation and ratios of each component: The experiment was divided into four groups with ethanol contents of 33%, 35%, 37%, and 40% respectively, and the remaining components were 1% carbomer 980, 24% glycerol, 0.1% hyaluronic acid, and made up to 100% with deionized water.

[0275] 2. Prepare 25 g of gel. Weigh 0.25 g of carbomer 980, disperse it with deionized water, stir evenly, then add 6.0 g of glycerol respectively, and then add 8.25 g, 8.75 g, 9.25 g, and 10.0 g of absolute ethanol respectively. First, stir at a speed of 500 revolutions per minute for 30 minutes, and then stir at a speed of 700 revolutions per minute for 30 minutes.

[0276] 3. Neutralization: Adjust the pH value to 5.25 - 5.55 with 10% potassium hydroxide solution, and the gel is white and transparent.

[0277] 4. Temperature measurement method: Measure according to the method described in step 4 of Example 1.

[0278] 5. Experimental results: Measure the relationship between temperature change and time. First, read the temperature of the temperature probe in the gel, then pull out the probe from the gel, continuously observe the temperature change between 1 - 20 minutes and record it. The results are shown in Table 13.

[0279] Table 13. Relationship between the Cooling Capacity of Carbomer Gel Homopolymer with Different Ethanol Concentrations and Time

[0280]

[0281]

[0282] 6. Experimental conclusions

[0283] The above results show that all four different ethanol concentrations have an obvious cooling effect, and the temperature drop trend is more obvious in the ethanol gels with concentrations of 33% and 35%.

[0284] Example 14 Determination of the Cooling of Homopolymer Gel without Propylene Glycol with Different Carbomer 980 Concentrations

[0285] 1. Composition of the formula and ratios of each component (by mass): The experiment was divided into two groups: Carbomer 980 at 0.5% and Carbomer 980 at 1%. The remaining components were 24% glycerol, 35% absolute ethanol, 0.1% hyaluronic acid, and deionized water was added to make up 100%.

[0286] 2. Preparation of 25 g of gel: Weigh 0.125 g and 0.25 g of Carbomer 980 respectively, disperse them with deionized water, then add 6.0 g of glycerol, 0.01 g of hyaluronic acid, and 8.75 g of absolute ethanol respectively. First, stir at a speed of 500 revolutions per minute for 30 minutes, and then stir at a speed of 700 revolutions per minute for 30 minutes.

[0287] 3. Neutralization: Adjust the pH value to 5.25 - 5.55 with 10% potassium hydroxide solution, and the gel becomes white and transparent.

[0288] 4. Method for measuring temperature: Measure according to the method described in step 4 of Example 1.

[0289] 5. Experimental results: Measure the relationship between temperature change and time. First, read the temperature of the temperature probe in the gel, then pull out the probe from the gel, continuously observe the temperature change between 1 and 20 minutes and record it. The results are shown in Table 14.

[0290] Table 14. Influence of different Carbomer concentrations on the temperature reduction of Carbomer 980 homopolymer gel without propylene glycol

[0291]

[0292] 6. Experimental conclusion

[0293] The above results show that there is no significant difference in the temperature reduction ability of the gel between the two groups with different Carbomer concentrations.

[0294] Evaluation of erectile function in Example 15

[0295] 1. Evaluation criteria for erectile function

[0296] According to "The International Index of Erectile Function - Erectile Function domain (IIEF-EF)", also known as IIEF-EF or IIEF-5, the treatment effect of male erectile dysfunction is evaluated. The IIEF-EF domain has high sensitivity and specificity and has a good correlation with other measurements of treatment outcomes. Therefore, it is widely accepted as a standard for evaluating male erectile function in ED clinical trials (JCCappelleri et al, An assessment of patient-reported outcomes for men with erectile dysfunction: Pfizer’s perspective International Journal of Impotence Research (2008) 20, 343–357. Rosen R C et al. Minimal Clinically Important Differences in the Erectile Function Domain of the International Index of Erectile Function Scale. EUROPEAN UROLOGY 2011, 60: 1010–1016).

[0297] 1) International Index of Erectile Function questionnaire (IIEF-5). Patients are classified into mild (12 ≤ IIEF-5 ≤ 21), moderate (8 ≤ IIEF-5 ≤ 11), and severe (IIEF-5 < 7) using the IIEF-5 score. The answers to each question are based on the male's experiences in the past 4 weeks, and the lower the score value, the more severe the sexual dysfunction.

[0298] 2) Successful penetration rate (SEP-2); evaluated at baseline before treatment and at the end of the study.

[0299] 3) Successful intercourse completion rate (SEP3); evaluated at baseline before treatment and at the end of the study.

[0300] 2. Test drugs and grouping

[0301] This trial was divided into two groups: the gel preparation group of the present disclosure and the positive control MED3000 group.

[0302] 1) Gel preparation group of the present disclosure: The formula components include ethanol: 35% (mass ratio), water: 35% (mass ratio), glycerol: 29% (mass ratio), hyaluronic acid 0.1%, carbomer 980: 1.0% (mass ratio). First, all components were dissolved in a water / ethanol mixture. Then, the thickener carbomer and glycerol were added, and preferably slowly sieved, and the mixture solution was strongly stirred with a magnetic stirrer. After the polymer was completely dispersed, the neutralizing agent potassium hydroxide was added dropwise to adjust the gel solution to pH 5.3, and a transparent topical skin gel preparation was made for use on the skin.

[0303] 2) The positive control drug was the commercially available MED3000 topical gel preparation (EROXON).

[0304] 3. Statistical processing method

[0305] Statistical software programs were used to analyze the data. All variable results were expressed as mean ± standard deviation. The differences between the pre-treatment baseline measurements and the measurements at the end point of the study were evaluated using analysis of variance. The data of SEP2 and SEP3 were analyzed using the chi-square test. A threshold of P < 0.05 was considered statistically significant.

[0306] 4. Results

[0307] 1) Efficacy evaluation: At the 12th week of treatment, when the gel preparation group of the present disclosure and the commercial drug MED3000 group were compared with the baseline respectively, the average IIEF-5 score increased significantly (P < 0.05). The IIEF-5 score of the gel preparation group of the present disclosure increased from 8.35 ± 2.96 in the baseline group to 17.73 ± 3.85 (P < 0.05), while the IIEF-5 score of the MED3000 group increased from 8.42 ± 3.49 in the baseline group to 16.52 ± 3.67 (P < 0.05), indicating that both the gel preparation of the present disclosure and MED3000 can improve the erectile function of men. On the other hand, in the gel preparation group of the present disclosure and the treatment group of the commercial drug MED3000, the percentage of the positive response rate of SEP-2 in the gel preparation group of the present disclosure increased from 29.3% to 76.8% (P < 0.05), and the percentage of the positive response rate of SEP3 increased from 25.7% to 73.5% (P < 0.05), while the percentage of the positive response rate of SEP-2 of MED3000 increased from 28.4 to 74.9% (P < 0.05), and the percentage of the positive response rate of SEP3 increased from 24.2% to 71.1% (P < 0.05), indicating that both the gel preparation of the present disclosure and the commercial drug MED3000 significantly improved the penetration success rate (SEP-2) and the coital completion rate (SEP-3). (The test results are shown in Table 15).

[0308] Table 15 Efficacy of the gel preparation of the present disclosure at the 12th week endpoint of treatment

[0309]

[0310] 2) Safety evaluation

[0311] As shown in Table 16, at the 12th week endpoint of treatment, no skin irritation effect was observed in the gel preparation of the present disclosure, and no headache symptoms were observed in female partners. The "propylene glycol-free" formulation further provided safety against skin irritation.

[0312] Table 16 Adverse reactions of the gel preparation of the present disclosure at the 12th week endpoint of treatment

[0313]

[0314] The technical solution of the present disclosure is not limited to the limitations of the above specific embodiments. Any technical deformation made according to the technical solution of the present disclosure falls within the protection scope of the present disclosure.

Claims

1. A gel, characterized in that, The gel does not contain diol compounds, and the gel comprises: 20 to 40 wt% of glycerol; 30% to 50 wt% of ethanol; 0.1% to 1.5 wt% of carbomer; and the balance of water.

2. The gel according to claim 1, characterized in that, The carbomer is selected from one or more of the following: carbomer homopolymers, carbomer copolymers, and carbomer interpolymers; Preferably, the carbomer homopolymer is selected from one or more of the following: carbomer 980, carbomer 974, carbomer 5984, carbomer 934, and carbomer 940, more preferably carbomer 980; Preferably, the carbomer copolymer is selected from one or more of the following: carbomer 1342, carbomer ETD2020, carbomer Ultrez 20, and carbomer Ultrez 10; Preferably, the gel comprises 0.5 wt% to 1.0 wt% of carbomer.

3. The gel according to claim 1, characterized in that, The diol compounds include one or more of the following: ethylene glycol, propylene glycol, butylene glycol, pentylene glycol, dipentylene glycol, hexylene glycol, cyclohexylene glycol, cyclohexanedimethanol, heptylene glycol, octylene glycol, nonylene glycol, decylene glycol, undecylene glycol, dodecylene glycol, tridecylene glycol, tetradecylene glycol, pentadecylene glycol, hexadecylene glycol, heptadecylene glycol, and octadecylene glycol.

4. The gel according to claim 1, characterized in that, The gel comprises 25 to 40 wt% of glycerol; Preferably, the gel comprises 33 to 35 wt% of ethanol; Preferably, the gel further comprises a neutralizing agent; Preferably, the neutralizing agent is selected from one or more of the following: potassium hydroxide, sodium hydroxide, ammonium hydroxide, triethanolamine, triethanolamine arginine, aminomethylpropanol, tetrahydroxypropyl ethylenediamine, tromethamine, diisopropanolamine, and triisopropanolamine; more preferably potassium hydroxide, sodium hydroxide, and triethanolamine.

5. The gel according to claim 1, characterized in that, The gel further comprises hyaluronic acid, Preferably, the hyaluronic acid comprises sulfated hyaluronic acid, or its ester, or its salt, or its disulfide, or its amide; Preferably, the gel comprises 0.05% to 0.5 wt% of hyaluronic acid; Preferably, the pH of the gel is selected from 4.5 to 6.0; preferably 5.1 to 5.8; Preferably, the gel has the functions of cooling and promoting male erection, as well as a low skin irritation effect; Preferably, the gel does not contain any other active ingredients having the function of promoting male erection; Preferably, the active ingredients include chemically synthesized and naturally extracted active ingredients; Preferably, the active ingredients include one or more of the following: PDE5 inhibitors, local anesthetics, prostaglandins, and testosterone.

6. A method for preparing the gel according to any one of claims 1 to 5.

7. The method according to claim 6, characterized in that, The method comprises the following steps: 1) Mix water and carbomer to disperse the carbomer; 2) Then add glycerol and ethanol and stir evenly; 3) After the carbomer in the product obtained in step 2) is dispersed, add a neutralizing agent.

8. The method according to claim 6, characterized in that, The method comprises the following steps: 1) Dissolve glycerol in a water / ethanol mixture; 2) Then add carbomer and stir evenly; 3) After the carbomer in the product obtained in step 2) is dispersed, add a neutralizing agent.

9. The method according to claim 6, characterized in that, The method comprises the following steps: 1) Wet carbomer with glycerol to obtain a wet slurry; 2) Add water and an ethanol solution to the wet slurry obtained in step 1) and stir evenly; 3) After the carbomer in the product obtained in step 2) is dispersed, a neutralizing agent is added.

10. Use of the gel according to any one of claims 1 to 5 in the preparation of a skin preparation for cooling and / or for improving or treating male erectile dysfunction.

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