Slow-release alternate cooling and heating far-infrared gel as well as preparation method and use method thereof

Abstract

The invention provides slow-release alternate cooling and heating far-infrared gel as well as a preparation method and a use method thereof, and belongs to the technical field of gel. The slow-release cold and heat alternating far infrared gel is of a three-layer composite structure composed of a bottom layer, a middle layer and a surface layer. The bottom layer is of a three-dimensional network structure formed by carbomer 940 and xanthan gum, and far infrared ceramic powder is loaded in the three-dimensional network structure; the middle layer is formed by encapsulating active ingredients with PEG-40 hydrogenated castor oil; and the surface layer is a pH responsive gel film formed by carbomer 940 and triethanolamine. Menthol and WS-3 are compounded to provide instantaneous cold feeling, vanillyl butyl ether is combined with far infrared radiation to provide continuous heat feeling, and the release time is regulated and controlled through polyhydric alcohol to realize a cold and heat alternating synergistic effect; carbomer 940 / xanthan gum is adopted to form a network with a specific aperture, and a low-speed stirring process ensures that the far infrared ceramic powder is uniformly dispersed and has an extremely low sedimentation rate; the network structure is used for limiting the preservative from diffusing to the skin surface.

Description

Technical Field

[0001] This invention relates to the field of gel technology, and in particular to a sustained-release, alternating hot and cold far-infrared gel, its preparation method, and its application method. Background Technology

[0002] Currently, traditional hot and cold gel products have the following problems: (1) Single function (only cold or only hot), short duration of action, and unstable temperature control. For example, disposable ice packs (only provide cold therapy, duration <30min) and iron powder heating patches (only provide heat therapy, temperature fluctuation ±5℃, posing a risk of burns). (2) The far-infrared functional materials (such as ceramic powder) in far-infrared patches are prone to sedimentation in the matrix (settling rate >15%), resulting in a difference of >30% in far-infrared radiation intensity in different areas of the same patch, leading to uneven and unstable therapeutic effects. (3) Commonly used preservatives in ordinary gel patches (such as propylparaben) diffuse freely in the gel, easily penetrate the skin, resulting in a high skin sensitization rate (>8%), posing a safety hazard.

[0003] Therefore, it is of great significance to provide a sustained-release, temperature-alternating far-infrared gel with alternating hot and cold effects, uniform far-infrared release, and directional fixation of preservatives, as well as its preparation method. Summary of the Invention

[0004] The purpose of this invention is to provide a sustained-release, alternating hot and cold far-infrared gel, its preparation method, and its usage method. The sustained-release, alternating hot and cold far-infrared gel is a three-layer composite structure gel that combines the alternating hot and cold effect, uniform sustained release of far-infrared rays, and directional fixation of preservatives. It aims to effectively solve the defects of existing technologies in terms of therapeutic efficacy, stability (anti-settling), and safety (low irritation), thereby improving the user experience.

[0005] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0006] This invention provides a sustained-release, alternating hot and cold far-infrared gel, which has a three-layer composite structure consisting of a bottom layer, a middle layer, and a top layer.

[0007] The bottom layer is a three-dimensional network structure formed by carbomer 940 and xanthan gum, and far-infrared ceramic powder is loaded in the three-dimensional network structure.

[0008] The middle layer is PEG-40 hydrogenated castor oil encapsulating active ingredients; the active ingredients are cold-sensing active ingredients and heat-sensing active ingredients, the cold-sensing active ingredients are menthol and N-ethyl-p-menthane-3-carboxamide, and the heat-sensing active ingredient is vanillyl butyl ether.

[0009] The surface layer is a pH-responsive gel membrane formed from carbomer 940 and triethanolamine.

[0010] Preferably, the far-infrared ceramic powder has a particle size ≤5μm and a pore size of 50~100μm for the three-dimensional network structure.

[0011] Preferably, the sustained-release, alternating hot and cold far-infrared gel comprises the following raw materials in the following mass fractions: 1-2.5% of the sum of carbomer 940 and xanthan gum, 3-8% of far-infrared ceramic powder, 0.8-1.2% of menthol, 0.1-0.3% of N-ethyl-p-menthane-3-carboxamide, 0.5-1.0% of vanillyl butyl ether, and 8-12% of PEG-40 hydrogenated castor oil; the mass ratio of carbomer 940 to xanthan gum is 8-10:1.

[0012] Preferably, the mass ratio of menthol to N-ethyl-p-menthane-3-carboxamide is 4 to 8:1.

[0013] Preferably, the sustained-release hot-cold alternating far-infrared gel further comprises the following raw materials in the indicated mass fractions: 0.4-0.7% preservative, 0.1-0.5% lavender essential oil, 17-20% glycerin, and 2.5-5% propylene glycol.

[0014] The present invention also provides a method for preparing the sustained-release hot-cold alternating far-infrared gel, comprising the following steps:

[0015] 1) Disperse carbomer 940 and xanthan gum in water, stir and let stand sequentially to obtain a gel matrix;

[0016] 2) Menthol, N-ethyl-p-menthane-3-carboxamide, vanillyl butyl ether and PEG-40 hydrogenated castor oil were mixed and emulsified by stirring to obtain a microemulsion;

[0017] 3) After mixing the microemulsion and gel matrix, homogenize them to form an emulsion-gel matrix; add far-infrared ceramic powder to the emulsion-gel matrix and stir to obtain a reaction system; add triethanolamine dropwise to the reaction system to adjust the pH value, and finally add water to obtain a slow-release cold-heat alternating far-infrared gel.

[0018] Preferably, the water temperature in step 1) is 35-45°C, and the mixture is stirred until no visible particles are visible, and then left to stand for 22-26 hours.

[0019] Preferably, the stirring and emulsification speed in step 2) is 2700-3300 rpm, the stirring and emulsification time is 8-12 min, and the encapsulation rate of the microemulsion is ≥95%; the mixture is a mixture of menthol, N-ethyl-p-menthane-3-carboxamide, vanillyl butyl ether, lavender essential oil and PEG-40 hydrogenated castor oil.

[0020] Preferably, in step 3), the homogenization speed is 8000-12000 rpm and the homogenization time is 4-6 min; the stirring speed is ≤600 rpm and the stirring time is 12-18 min; the viscosity of the reaction system is 8000-12000 cP; the pH value of the reaction system is adjusted to 6.5-7.0, and water is added after adding preservatives, glycerin and propylene glycol.

[0021] The present invention also provides a method for using the sustained-release hot-cold alternating far-infrared gel, wherein the sustained-release hot-cold alternating far-infrared gel is prepared into a patch or tube gel.

[0022] The beneficial effects of this invention are:

[0023] 1) The sustained-release hot and cold alternating far-infrared gel of the present invention is a three-layer functional partition composite structure: a specific combination of the bottom layer (carbomer 940 / xanthan gum network to fix far-infrared ceramic powder), the middle layer (PEG-40 hydrogenated castor oil to encapsulate hot and cold active ingredients, and the top layer (carbomer 940 / triethanolamine) to neutralize and form a pH-responsive membrane).

[0024] 2) Synergistic cooling and heating formulation system: A specific ratio of menthol and WS-3 provides an instant cooling sensation, while vanillyl butyl ether combined with far-infrared radiation provides a continuous heating sensation. The release time is regulated by polyols (glycerol, propylene glycol) to achieve a synergistic cooling and heating effect.

[0025] 3) Anti-settling process: Carbomer 940 / xanthan gum is used to form a specific pore size network, and a low-speed stirring process of ≤600rpm is used when dispersing far-infrared ceramic powder to ensure uniform particle dispersion and extremely low sedimentation rate.

[0026] 4) Safe controlled-release design: The preservatives (sodium propylparaben + phenoxyethanol) are positioned in the middle / bottom layer, and their diffusion to the skin surface is restricted by the network structure. Combined with the pH-responsive layer as the surface layer, the controlled release is achieved, reducing skin irritation.

[0027] 5) The bottom layer of the sustained-release hot and cold alternating far-infrared gel of the present invention is an anti-settling layer / far-infrared fixing layer. The three-dimensional network structure of the bottom layer can effectively mechanically lock the far-infrared ceramic powder with a particle size ≤5μm, significantly reducing its sedimentation rate (≤0.6%) and ensuring uniform and stable far-infrared radiation. The middle layer is an active stabilizing layer / microcapsule layer. This microencapsulation treatment improves the stability of active ingredients, controls their release rate, and reduces interactions. The surface layer is a controlled-release layer / pH-responsive layer. This layer provides sustained release under the skin's pH environment (disintegration time >30min), playing a role in regulating the sustained release of active ingredients and far-infrared radiation, and prolonging the effective action time. Detailed Implementation

[0028] This invention provides a sustained-release, alternating hot and cold far-infrared gel, which has a three-layer composite structure consisting of a bottom layer, a middle layer, and a top layer.

[0029] The bottom layer is a three-dimensional network structure formed by carbomer 940 and xanthan gum, and far-infrared ceramic powder is loaded in the three-dimensional network structure.

[0030] The middle layer is PEG-40 hydrogenated castor oil encapsulating active ingredients; the active ingredients are a cooling active ingredient and a heating active ingredient, the cooling active ingredient is menthol and N-ethyl-p-menthane-3-carboxamide (WS-3), and the heating active ingredient is vanillyl butyl ether;

[0031] The surface layer is a pH-responsive gel membrane formed from carbomer 940 and triethanolamine (TEA).

[0032] In this invention, the particle size of the far-infrared ceramic powder is preferably ≤5μm, more preferably ≤4μm, and even more preferably ≤3μm; the pore size of the three-dimensional network structure is preferably 50-100μm, more preferably 60-90μm, and even more preferably 70-80μm.

[0033] In this invention, the sustained-release, alternating hot and cold far-infrared gel comprises the following raw materials in the following mass fractions: the sum of carbomer 940 and xanthan gum is preferably 1-2.5%, more preferably 1.5-2.2%, and even more preferably 1.8-2%; far-infrared ceramic powder is preferably 3-8%, more preferably 4-7%, and even more preferably 5-6%; menthol is preferably 0.8-1.2%, more preferably 0.9-1.1%, and even more preferably 1%; WS-3 is preferably 0.1-0.3%, more preferably 0.15-0.25%, and even more preferably 0.2%; vanillyl butyl ether is preferably 0.5-1.0%, more preferably 0.6-0.9%, and even more preferably 0.7-0.8%; PEG-40 hydrogenated castor oil is preferably 8-12%, more preferably 9-11%, and even more preferably 10%; the mass ratio of carbomer 940 to xanthan gum is preferably 8-10:1, more preferably 8.5-9.5:1, and even more preferably 9:1.

[0034] In this invention, the mass ratio of menthol to WS-3 is preferably 4 to 8:1, more preferably 5 to 7:1, and even more preferably 6:1.

[0035] In this invention, the sustained-release, alternating hot and cold far-infrared gel further comprises the following raw materials in the indicated mass fractions: preservative preferably 0.4-0.7%, more preferably 0.5-0.6%, and even more preferably 0.55%; lavender essential oil preferably 0.1-0.5%, more preferably 0.2-0.4%, and even more preferably 0.3%; glycerin preferably 17-20%, more preferably 18-19%; and propylene glycol preferably 2.5-5%, more preferably 3-4.5%, and even more preferably 3.5-4%.

[0036] In this invention, preservatives are fixed in the bottom and / or middle layers of the sustained-release hot-cold alternating far-infrared gel; lavender essential oil is in the middle layer of the sustained-release hot-cold alternating far-infrared gel, and glycerin and propylene glycol are in the surface layer of the sustained-release hot-cold alternating far-infrared gel; lavender essential oil is used to adjust the scent.

[0037] The sustained-release hot and cold alternating far-infrared gel of the present invention has a synergistic hot and cold effect mechanism: (1) Instantaneous cooling sensation: Menthol and WS-3 work together to act on the transient receptor potential M8 (TRPM8) channel of the skin, quickly producing a cooling sensation (the onset time is about 10s, and the score can reach 3-4 according to the ISO 13732.1 thermal sensitivity scale), effectively relieving acute pain and burning sensation; (2) Continuous warming sensation: Vanillyl butyl ether activates the transient receptor potential V1 (TRPV1) channel, and together with the radiant heat generated by the far-infrared ceramic powder, it maintains a mild and lasting warm sensation (the temperature is stable in the comfortable treatment range of 38-42℃); (3) Time-controlled sustained release: Glycerin and propylene glycol adjust the viscosity and hydrophilicity of the gel system, and work together with the pH response layer to regulate the release kinetics of the hot and cold active ingredients and the far-infrared effect, so that the hot and cold alternating effect can last for 2-3 hours.

[0038] In this invention, the surface layer of the slow-release, alternating hot and cold far-infrared gel is in direct contact with the skin, while the bottom layer is furthest from the skin.

[0039] The present invention also provides a method for preparing the sustained-release hot-cold alternating far-infrared gel, comprising the following steps:

[0040] 1) Disperse carbomer 940 and xanthan gum in water, stir and let stand sequentially to obtain a gel matrix;

[0041] 2) Menthol, WS-3, vanillyl butyl ether and PEG-40 hydrogenated castor oil were mixed and emulsified by stirring to obtain a microemulsion;

[0042] 3) After mixing the microemulsion and gel matrix, homogenize them to form an emulsion-gel matrix; add far-infrared ceramic powder to the emulsion-gel matrix and stir to obtain a reaction system; add triethanolamine dropwise to the reaction system to adjust the pH value, and finally add water to obtain a slow-release cold-heat alternating far-infrared gel.

[0043] In this invention, the temperature of the water in step 1) is preferably 35-45°C, more preferably 37-43°C, and even more preferably 40°C. The stirring is preferably carried out until no visible particles are visible. The settling time is preferably 22-26 hours, more preferably 23-25 ​​hours, and even more preferably 24 hours.

[0044] In this invention, the mass of water in step 1) is preferably 90-95% of the total mass of water, more preferably 91-94%, and even more preferably 92-93%.

[0045] In this invention, the stirring speed in step 2) is preferably 2700-3300 rpm, more preferably 2800-3200 rpm, and even more preferably 3000 rpm; the stirring time is preferably 8-12 min, more preferably 9-11 min, and even more preferably 10 min; the encapsulation rate of the microemulsion is preferably ≥95%, more preferably ≥96%, and even more preferably ≥97%; the mixing is preferably a mixture of menthol, WS-3, vanillyl butyl ether, lavender essential oil, and PEG-40 hydrogenated castor oil.

[0046] In this invention, the homogenization speed in step 3) is preferably 8000-12000 rpm, more preferably 9000-11000 rpm, and even more preferably 10000 rpm; the homogenization time is preferably 4-6 min, and even more preferably 5 min; the stirring speed is preferably ≤600 rpm, more preferably 300-550 rpm, and even more preferably 400-500 rpm; the stirring time is preferably 12-18 min, more preferably 13-17 min, and even more preferably 15 min; the viscosity of the reaction system is preferably 8000-12000 cP, more preferably 9000-11000 cP, and even more preferably 10000 cP; the pH value of the reaction system is preferably adjusted to 6.5-7.0, more preferably 6.6-6.9, and even more preferably 6.7-6.8; water is added after the preservative, glycerin, and propylene glycol are added.

[0047] The present invention also provides a method for using the sustained-release hot-cold alternating far-infrared gel, wherein the sustained-release hot-cold alternating far-infrared gel is prepared into a patch or tube gel.

[0048] The sustained-release, alternating hot and cold far-infrared gel of this invention is applied / smeared onto the painful or uncomfortable area in the form of a pre-coated patch or tube-packaged gel. It achieves a therapeutic effect through the synergistic effect of alternating hot and cold and the release of far-infrared rays. The pre-coated patch is made by coating the sustained-release, alternating hot and cold far-infrared gel onto a backing material, with the preferred coating amount being 20-30 g / 100 cm². 2 Further preferred is 22-28g / 100cm³ 2 More preferably, it is 25-26 g / 100cm³.2 The tube-packaged gel is a slow-release, hot-and-cold alternating far-infrared gel filled into a tube.

[0049] In this invention, the sustained-release hot and cold alternating far-infrared gel is used in the medical field, sports rehabilitation field, and home health care field;

[0050] In the medical field, it is used for postoperative swelling and pain relief in orthopedics, nursing care for acute arthritis attacks, and chronic pain management. The method of using the sustained-release hot and cold alternating far-infrared gel is to apply the sustained-release hot and cold alternating far-infrared gel to the painful area, using the hot and cold alternating effect to relieve acute inflammation and pain, and promoting deep blood circulation through far-infrared radiation.

[0051] In the field of sports rehabilitation, it is used for emergency treatment of sports injuries (such as muscle strains and contusions) and delayed onset muscle soreness (DOMS) care. The method of using the sustained-release hot and cold alternating far-infrared gel is to apply it to the affected area immediately after the injury or after exercise. It uses the instant cooling sensation to reduce swelling and burning pain, and the subsequent continuous heat sensation and far-infrared radiation promote recovery and relieve deep muscle soreness.

[0052] The home health care field includes daily care for joint pain in the elderly, home treatment of minor injuries in children (such as bumps and swelling), and daily health care; the method of using the sustained-release hot and cold alternating far-infrared gel is to apply / patch it to the uncomfortable area as needed, providing safe and convenient physical relief.

[0053] The technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0054] In the embodiments, the far-infrared ceramic powder is zirconium titanate type far-infrared ceramic powder; in the application examples, the commercially available cold compress gel is Yunnan Baiyao cold compress gel (National Drug Approval Number Z53020799), which contains 3.5% menthol; the commercially available heating patch is Kobayashi Pharmaceutical's warming analgesic patch (Import Registration Number BJ20180032), which contains an iron powder heating layer.

[0055] Example 1

[0056] The sustained-release, alternating hot and cold far-infrared gel was prepared from the following raw materials: 3g far-infrared ceramic powder (particle size 4μm), 0.9g carbomer 940, 0.1g xanthan gum, TEA (used to neutralize the pH of the reaction system to 6.8), 17.0g glycerin, 5g propylene glycol, 0.8g menthol, 0.1g WS-3, 0.5g vanillyl butyl ether, 0.1g sodium propylparaben, 0.4g phenoxyethanol, 0.1g lavender essential oil, 8g PEG-40 hydrogenated castor oil, and purified water to a total of 100g.

[0057] The preparation process of the sustained-release, alternating hot and cold far-infrared gel is as follows:

[0058] Aqueous phase pre-swelling: Carbomer 940 and xanthan gum were dispersed in purified water at 40℃ (the mass of purified water was 90% of the total mass of water), stirred until no particles were visible to the naked eye, and allowed to stand for 24 hours to fully hydrate and swell, forming a three-dimensional network structure with a pore size of 50-100 μm, and a uniform gel matrix (aqueous phase) was obtained.

[0059] Oil phase encapsulation (microemulsion): Lavender essential oil, menthol, WS-3, vanillyl butyl ether and PEG-40 hydrogenated castor oil were mixed and emulsified at 3000 rpm for 10 min to obtain a microemulsion (oil phase) with an encapsulation rate of 96%.

[0060] Gradient blending:

[0061] The oil phase was slowly added to the aqueous phase, and homogenized at 10,000 rpm for 5 minutes to form a uniform and fine emulsion gel matrix. Far-infrared ceramic powder was added to the emulsion gel matrix, and the mixture was stirred at 600 rpm for 15 minutes to ensure uniform dispersion of the far-infrared ceramic powder without disrupting the formed network structure. The viscosity of the reaction system was controlled at 10,000 cp. TEA was slowly added dropwise to the reaction system while stirring continuously, and the pH of the reaction system was adjusted to 6.8. Sodium propylparaben, phenoxyethanol, glycerol, and propylene glycol were added, and the remaining purified water was added to bring the total volume to 100 g. The mixture was then vacuum-degassed at -0.09 MPa for 15 minutes to obtain a sustained-release, alternating hot and cold far-infrared gel. The resulting gel was filled into pharmaceutical low-density polyethylene tubing (5 mm diameter) to form a tube-packaged gel.

[0062] Example 2

[0063] The sustained-release, alternating hot and cold far-infrared gel was prepared from the following raw materials: 8g far-infrared ceramic powder (particle size 5μm), 1.8g carbomer 940, 0.2g xanthan gum, TEA (used to neutralize the pH of the reaction system to 6.6), 20.0g glycerin, 2.5g propylene glycol, 1.2g menthol, 0.3g WS-3, 0.8g vanillyl butyl ether, 0.08g sodium propylparaben, 0.6g phenoxyethanol, 0.5g lavender essential oil, 12g PEG-40 hydrogenated castor oil, and purified water to a total of 100g.

[0064] The preparation process of the sustained-release hot-cold alternating far-infrared gel is the same as that in Example 1.

[0065] Example 3

[0066] The sustained-release, alternating hot and cold far-infrared gel was prepared from the following raw materials: 5g far-infrared ceramic powder (particle size 4μm), 2g carbomer 940, 0.2g xanthan gum, TEA (used to neutralize the pH of the reaction system to 7.0), 18.0g glycerin, 3.5g propylene glycol, 0.8g menthol, 0.2g WS-3, 0.7g vanillyl butyl ether, 0.3g sodium propylparaben, 0.3g phenoxyethanol, 0.3g lavender essential oil, 10g PEG-40 hydrogenated castor oil, and purified water to a total of 100g.

[0067] The preparation process of the sustained-release hot-cold alternating far-infrared gel is the same as that in Example 1.

[0068] Application Example 1: Biocompatibility Test

[0069] The sustained-release, alternating hot and cold far-infrared gels prepared in Examples 1-3 were tested according to the biological evaluation standards for medical devices. In vitro cytotoxicity tests were conducted according to GB / T 16886.5-2017 "Biological Evaluation of Medical Devices - Part 5: In Vitro Cytotoxicity Tests"; skin irritation and sensitization tests were conducted according to GB / T 16886.10-2017 "Biological Evaluation of Medical Devices - Part 10: Irritation and Skin Sensitization Tests". The test results are shown in Table 1.

[0070] Table 1. Biocompatibility test results of the sustained-release, alternating hot and cold far-infrared gel

[0071]

[0072]

[0073] As shown in Table 1, the sustained-release cold and heat alternating far-infrared gel of the present invention has good biosafety, with a relative cell proliferation rate of ≥98.5%, and negative results in skin irritation and skin sensitization tests.

[0074] Application Example 2: Skin Cumulative Irritation Test

[0075] The sustained-release cold and heat alternating far-infrared gels prepared in Examples 1-3 were compared with commercially available cold compress gels and commercially available heating patches (as comparative examples). The test results are shown in Table 2.

[0076] Methods: 120 healthy subjects (20-50 years old) were enrolled. Using a self-comparison method, 30 subjects were included in each example and comparative study. 0.5g of gel sample was directly applied to a prepared skin area (2.5cm × 2.5cm) on the subject's back, and then covered and secured with hypoallergenic medical tape and nonwoven fabric. Each application lasted 4 hours. The nonwoven fabric was a spunlace medical-grade adhesive material (35±5g / m²). 2It conforms to YY / T 0471.1-2004 standard, and its fibers have no chemical bonding residue and an air permeability ≥1200g / m². 2 / 24h, ensuring the covering and fixation process does not introduce additional irritants. Apply once daily to the same site for 4 consecutive weeks (28 applications in total). Observe the skin reaction visually under natural or full-spectrum light 1 hour after each removal of the patch and at 24, 48, and 72 hours after the final removal of the patch.

[0077] Table 2 Results of cumulative skin irritation test for different gels

[0078] gel samples Cumulative skin irritation Gel of Example 1 0 / 30 cases of erythema and edema Gel of Example 2 0 / 30 cases of erythema and edema Gel of Example 3 0 / 30 cases of erythema and edema Commercially available cooling gels 3 / 30 cases of erythema Commercially available heating patches 5 / 30 cases of erythema

[0079] As shown in Table 2, the sustained-release hot and cold alternating far-infrared gel of the present invention has no cumulative irritation to the skin and has a mild effect; 3 or 5 cases of erythema reaction occurred in the commercially available control products.

[0080] Application Example 3: Cold and Hot Duration Test

[0081] The duration of hot and cold alternating far-infrared gels prepared in Examples 1-3 was compared with that of commercially available cold compress gels and commercially available heating patches (as comparative examples). The results are shown in Table 3.

[0082] Methods: Each example and comparative example involved 32 healthy subjects (aged 20–50 years), divided into two groups based on age: 20–30 years (n=16) and 40–50 years (n=16); a total of 128 subjects were included. Test samples: Gels from Examples 1–3, commercially available cooling gels, and commercially available heating patches. Test site: Flexor surface of the forearm. Test method: An equal amount (0.5g) of the test sample was evenly applied to the test site (approximately 4cm²). 2 According to the ISO 13732.1:2006 thermal sensation scale (0-4, where 0 is no sensation and 4 is very intense), subjects reported the onset and duration of a ≥2 level cold or hot sensation. The duration of cold sensation was tested using commercially available cooling gel; for commercially available heating patches, 0.5g of the iron powder gel layer was scraped from the patch, spread evenly, and the duration of hot sensation was tested; the time point at which the cold or hot sensation (based on the subject's primary sensation) disappeared was recorded. The average duration was calculated.

[0083] Table 3 Results of the hot and cold duration tests for different gels

[0084]

[0085] (P<0.05 vs. commercially available cooling gel / commercially available heating patch in the same age group)

[0086] As shown in Table 3, the gel of the present invention significantly prolongs the duration of alternating hot and cold sensation: In the young group (20-30 years old), the duration of hot and cold sensation lasted for 2.9-3.0 hours, which is 200% longer than that of commercially available cold compress gel (only 1.0 hour of cold sensation) and 100% longer than that of heating patch (only 1.5 hours of heat sensation); In the older group (40-50 years old), the duration of hot and cold sensation lasted for 2.5-2.6 hours, which is significantly better than that of commercially available cold compress gel (0.8 hours) and commercially available heating patch (1.1 hours) (P<0.05).

[0087] Application Example 4: Settlement Stability Test

[0088] The physical sedimentation stability of the sustained-release hot and cold alternating far-infrared gels prepared in Examples 1-3, commercially available cold compress gels, and commercially available heating patches (as comparative examples) were tested, and the results are shown in Table 4.

[0089] Static standing test: Take 50 mL of each sample from Examples 1-3 and the comparative example (3 parallel samples per group), place them in a 100 mL stoppered graduated cylinder, and let them stand at room temperature (25±2℃) in the dark for 72 h. Record the volume of sediment and calculate the sedimentation rate. Sedimentation rate (%) = height of sedimentation layer / initial total height of sample × 100%. The smaller the value, the better the stability.

[0090] Accelerated test: Take samples of the same specifications as above and place them in a constant temperature and humidity chamber at 40℃ and 75% relative humidity (40℃ / 75%RH). Take them out after 1 month, 2 months and 3 months respectively. After the room temperature is equilibrated, measure and calculate the sedimentation rate using the static test method described above.

[0091] Table 4. Sedimentation stability test results of different gels

[0092] Gel sample type Let stand for 72 hours Accelerate by 1 month Accelerate by 2 months Accelerate by 3 months Gel of Example 1 0.5±0.1％ 0.8±0.2％ 1.2±0.2％ 1.5±0.3％ Gel of Example 2 0.6±0.1％ 0.9±0.2％ 1.3±0.3％ 1.6±0.2％ Gel of Example 3 0.5±0.2％ 0.8±0.1％ 1.2±0.1％ 1.4±0.2％ Commercially available cooling gels 3.2±0.5％ 5.8±0.6％ 8.5±0.8％ 12.3±1.0％ Commercially available heating patches 4.1±0.6％ 7.2±0.7％ 10.5±0.9％ 15.0±1.2％

[0093] Note: Commercially available heating patches are Kobayashi Pharmaceutical's temperature-sensitive analgesic patches: the iron powder gel layer inside the patch was scraped off, homogenized into a uniform paste, and then tested using the same method (to ensure comparability); commercially available cold compress gels were tested directly using the original gel.

[0094] As shown in Table 4, the sedimentation stability of the sustained-release, alternating hot and cold far-infrared gels in Examples 1-3 is significantly better than that of commercially available cold compress gels and commercially available heating patches. After standing for 72 hours, the sedimentation rate of the Example group was ≤0.6%, while that of the commercially available cold compress gel and commercially available heating patch reached 3.2% and 4.1%, respectively. After 3 months of accelerated testing, the sedimentation rate of the Example group was only 1.4-1.6%, while that of the commercially available cold compress gel and commercially available heating patch increased to 12.3% and 15.0%, respectively. This indicates that the three-dimensional network structure and low-speed dispersion process of the present invention can effectively prevent the sedimentation of functional particles and maintain the high homogeneity of the gel system under long-term storage and accelerated conditions.

[0095] Application Example 5: Stability Test of Far-Infrared Radiation Performance

[0096] The sustained-release hot and cold alternating far-infrared gels prepared in Examples 1-3, along with commercially available cold compress gels and commercially available heating patches (as comparative examples), were subjected to far-infrared radiation performance stability tests under accelerated aging conditions (40℃ / 75%RH, 3 months). The results are shown in Table 5.

[0097] The test was conducted according to the standard GB / T 7287-2008 "Test Methods for Infrared Radiation Heaters," where the normal emissivity (εn) test method was the comparative method (comparison with a reference blackbody) in Chapter 7, and the instrument was an FTIR spectrometer; the radiant flux density (W / m³) was also measured. 2 The test method is the direct measurement in Chapter 6, and the instrument is an infrared radiometer; the peak wavelength (μm) test method is the spectral distribution measurement in Appendix A (8-15μm band), and the instrument is an FTIR spectrometer.

[0098] Experimental steps:

[0099] Commercially available cooling gels were directly tested and confirmed to have no far-infrared radiation function; commercially available heating patches had their iron powder layer homogenized by scraping, eliminating interference from the backing material.

[0100] Initial test (0 days): All samples were equilibrated at 25℃ and 50%RH before benchmark far-infrared data were measured.

[0101] Accelerated aging: Spread the sample thin layer flat (avoid stacking) in a petri dish and place it in a 40℃ / 75%RH constant temperature and humidity chamber.

[0102] Regular testing: Every 30 days, take out each group of samples (one parallel sample from each group for testing), and after equilibration at room temperature, conduct far-infrared performance testing under the same initial testing conditions.

[0103] Table 5. Results of far-infrared radiation stability tests on different gels

[0104]

[0105]

[0106] Note: The main ingredients of commercially available cooling gels are water, carbomer, and menthol. They have no far-infrared function and an emissivity of ≈0.02 (background value). Commercially available heating patches: test by scraping off the iron powder gel layer inside the patch (iron powder oxidation heating ≠ far-infrared radiation).

[0107] As shown in Table 5, the sustained-release cold-heat alternating far-infrared gel of the present invention exhibits stable performance: the normal emissivity change rate decreased by only 1.11% after 90 days, significantly better than commercially available heating patches (decreased by 5.56%); the radiant flux attenuation rate was 11.93-14.49% in Examples 1-3, while that of commercially available heating patches was as high as 21.75%. Commercially available cold compress gels have no far-infrared function (radiation value ≈ 0), proving that they only provide a cooling sensation without deep heat therapy; the iron powder oxidation heat attenuation of commercially available heating patches is rapid (21.75%), and the peak wavelength is 9.2-9.4 μm (deviating from the optimal absorption band of the human body by 8-9 μm).

[0108] This invention achieves a radiation performance attenuation rate of <15% and a wavelength stable at 8.4–8.7 μm (matching the absorption peak of human tissue) through far-infrared ceramic powder (zirconium titanate type) and three-dimensional network design, ensuring the long-term effectiveness of physiotherapy.

[0109] The sustained-release, alternating hot and cold far-infrared gels of Examples 1-3 of this invention exhibit significantly better stability in far-infrared radiation performance than commercially available hot and cold gels (commercially available cooling gels and heating patches). Although all samples showed a decrease in radiant flux after accelerated aging, the gel of this invention showed a smaller decrease (90-day decrease rate ≤14.5%), far lower than commercially available products (21.8%). The normal emissivity retention rate was also higher. This is attributed to the effective fixation of the far-infrared ceramic powder by the three-dimensional network structure of this invention, reducing its shedding and aggregation under humid and hot conditions, and maintaining more stable radiation performance. The matrix of commercially available products is prone to cracking under humid and hot conditions, leading to filler shedding and significant performance degradation.

[0110] The differences between the sustained-release hot and cold alternating far-infrared gel of the present invention and commercially available hot and cold gel agents in the prior art are shown in Table 6.

[0111] Table 6. Differences between the sustained-release hot-cold alternating far-infrared gel of this invention and commercially available hot-cold gels.

[0112]

[0113]

[0114] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A sustained-release, alternating hot and cold far-infrared gel, characterized in that, The sustained-release hot and cold alternating far-infrared gel has a three-layer composite structure, which consists of a bottom layer, a middle layer and a top layer. The bottom layer is a three-dimensional network structure formed by carbomer 940 and xanthan gum, and far-infrared ceramic powder is loaded in the three-dimensional network structure. The middle layer is PEG-40 hydrogenated castor oil encapsulating active ingredients; the active ingredients are cold-sensing active ingredients and heat-sensing active ingredients, the cold-sensing active ingredients are menthol and N-ethyl-p-menthane-3-carboxamide, and the heat-sensing active ingredient is vanillyl butyl ether. The surface layer is a pH-responsive gel membrane formed from carbomer 940 and triethanolamine.

2. The sustained-release, alternating hot and cold far-infrared gel according to claim 1, characterized in that, The far-infrared ceramic powder has a particle size of ≤5μm and a pore size of 50~100μm in its three-dimensional network structure.

3. The sustained-release, alternating hot and cold far-infrared gel according to claim 1 or 2, characterized in that, The sustained-release, alternating hot and cold far-infrared gel comprises the following raw materials in the following mass fractions: 1-2.5% of the sum of carbomer 940 and xanthan gum, 3-8% of far-infrared ceramic powder, 0.8-1.2% of menthol, 0.1-0.3% of N-ethyl-p-menthane-3-carboxamide, 0.5-1.0% of vanillyl butyl ether, and 8-12% of PEG-40 hydrogenated castor oil; the mass ratio of carbomer 940 to xanthan gum is 8-10:

1.

4. The sustained-release, alternating hot and cold far-infrared gel according to claim 3, characterized in that, The mass ratio of menthol to N-ethyl-p-menthane-3-carboxamide is 4 to 8:

1.

5. The sustained-release, alternating hot and cold far-infrared gel according to claim 1, characterized in that, The sustained-release, alternating hot and cold far-infrared gel also contains the following raw materials in the indicated mass fractions: 0.4-0.7% preservative, 0.1-0.5% lavender essential oil, 17-20% glycerin, and 2.5-5% propylene glycol.

6. The method for preparing the sustained-release, alternating hot and cold far-infrared gel according to any one of claims 1 to 5, characterized in that, It includes the following steps: 1) Disperse carbomer 940 and xanthan gum in water, stir and let stand sequentially to obtain a gel matrix; 2) Menthol, N-ethyl-p-menthane-3-carboxamide, vanillyl butyl ether and PEG-40 hydrogenated castor oil were mixed and emulsified by stirring to obtain a microemulsion; 3) After mixing the microemulsion and gel matrix, homogenize them to form an emulsion-gel matrix; add far-infrared ceramic powder to the emulsion-gel matrix and stir to obtain a reaction system; add triethanolamine dropwise to the reaction system to adjust the pH value, and finally add water to obtain a slow-release cold-heat alternating far-infrared gel.

7. The preparation method according to claim 6, characterized in that, Step 1) The water temperature is 35-45℃, and it is stirred until no visible particles are visible. The standing time is 22-26 hours.

8. The preparation method according to claim 6 or 7, characterized in that, Step 2) The stirring and emulsification speed is 2700-3300 rpm, the stirring and emulsification time is 8-12 min, and the encapsulation rate of the microemulsion is ≥95%; the mixture is a mixture of menthol, N-ethyl-p-menthane-3-carboxamide, vanillyl butyl ether, lavender essential oil and PEG-40 hydrogenated castor oil.

9. The preparation method according to claim 8, characterized in that, Step 3) The homogenization speed is 8000-12000 rpm, and the homogenization time is 4-6 min; the stirring speed is ≤600 rpm, and the stirring time is 12-18 min; the viscosity of the reaction system is 8000-12000 cP; the pH value of the reaction system is adjusted to 6.5-7.0, and water is added after adding preservatives, glycerin and propylene glycol.

10. The method of using the sustained-release hot-cold alternating far-infrared gel according to any one of claims 1 to 5, characterized in that, Slow-release, alternating hot and cold far-infrared gels are prepared into patches or tubes.

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