A highly viscous gel patch base and method of making

Abstract

The application relates to the technical field of medical products, in particular to a high-viscosity gel patch matrix and a preparation method, wherein the raw material of the high-viscosity gel patch matrix is modified polyacrylic acid sodium, a film forming agent, a penetration enhancer, a tackifier, a PH regulator, a humectant, a composite crosslinking agent and deionized water; the preparation steps comprise the following steps: step a, dispersing the modified polyacrylic acid sodium in the deionized water to obtain a gel patch matrix skeleton liquid; step b, adding the film forming agent, the penetration enhancer and the tackifier into the humectant to obtain a mixture A; step c, adding the gel patch matrix skeleton liquid, the composite crosslinking agent and the PH regulator into the mixture A, magnetically stirring, and naturally cooling to obtain the high-viscosity gel patch matrix. The high-viscosity gel patch matrix prepared by the application has the advantages of high viscosity, good tackiness and air permeability, good antibacterial performance, good biocompatibility, repeated peeling and sticking, no pain or skin damage caused by peeling.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medical products, and more particularly to a high-adhesion gel patch matrix and a preparation method thereof. BACKGROUND

[0002] Sodium polyacrylate hydrogel resin has shown wide application potential in many fields due to its advantages such as high water absorption, good water retention, good transparency, and multifunctionality, especially in the fields of medical and medical devices and medical cosmetology such as ointment preparations, fever-reducing patches, weight-loss patches, and facial masks.

[0003] However, although sodium polyacrylate hydrogel resin has so many advantages, existing products still have some defects. The most prominent problem is that the mechanical strength and adhesion are relatively weak. In actual use, the relatively weak mechanical strength often leads to easy breakage or deformation of the hydrogel resin, thereby seriously affecting the use effect and user experience. Meanwhile, the relatively weak adhesion also makes it difficult for these patches to be firmly attached to the skin for a long time, further limiting their application scenarios. SUMMARY

[0004] To solve the technical problems mentioned in the background, the present application provides a high-adhesion gel patch matrix and a preparation process thereof.

[0005] In a first aspect, the present application provides a high-adhesion gel patch matrix, which adopts the following technical solution:

[0006] A high-adhesion gel patch matrix is made of the following raw materials by weight: modified sodium polyacrylate 5-8 parts, film-forming agent 0.5-1 part, penetration enhancer 1-2 parts, tackifier 1-2 parts, PH adjuster 0.1-0.2 parts, humectant 15-20 parts, composite crosslinking agent 0.05-0.2 parts, and deionized water 10-12 parts.

[0007] Preferably, the preparation of the modified sodium polyacrylate includes the following steps:

[0008] Step S1, disperse acrylic acid, N-vinyl caprolactam, N-vinyl pyrrolidone, and a photoinitiator in deionized water, stir uniformly, add sodium hydroxide solution, and adjust the PH value to 7-7.5 to obtain reaction liquid A;

[0009] Step S2, transfer the reaction liquid A to a photoreactor, remove oxygen by nitrogen blowing for 15-30 min, perform photoinitiated polymerization at 20-25℃ for 2-5 min to form a first prepolymer;

[0010] Step S3, dissolving chitosan in dilute acid solution with PH value of 4-5, adding crosslinking agent, stirring for 2-3 h to prepare activated chitosan solution, and controlling the mass ratio of chitosan, crosslinking agent and dilute acid solution to be 3-5:0.1-0.5:50-60;

[0011] Step S4, mixing the activated chitosan solution and the first prepolymer, adding ammonium persulfate solution, stirring uniformly, and reacting at 45-60℃ for 3-4 h, and then cooling, filtering, washing, and drying at 60-80℃ until constant weight to obtain the modified sodium polyacrylate.

[0012] Preferably, the mass ratio of the acrylic acid, N-vinyl caprolactam, N-vinyl pyrrolidone and photoinitiator in step S1 is 8-10:1-3:0.5-1:0.05-0.1.

[0013] Preferably, the photoinitiator in step S1 is one or more of 2,2-dimethoxy-2-phenylacetophenone, 2,4,6-trimethylbenzoyl diphenyl phosphine oxide and 1-hydroxycyclohexyl phenyl ketone.

[0014] Preferably, the photopolymerization reaction in step S2 is ultraviolet light-induced polymerization, the wavelength of the ultraviolet light-induced polymerization is 200-400 nm, and the light intensity of the ultraviolet light-induced polymerization is 500-800 mW / cm 2 .

[0015] Preferably, the degree of deacetylation of the chitosan is ≥90%, and the viscosity is <50 mPa·s.

[0016] Preferably, the film-forming agent is crosslinked sodium carboxymethyl cellulose and / or polyvinyl alcohol.

[0017] Preferably, the penetration enhancer is isopropyl alcohol and / or peppermint oil.

[0018] Preferably, the tackifier is composed of rosin and dimethicone with a mass ratio of 1-2:0.1-0.3.

[0019] Preferably, the PH regulator is one of triethanolamine, potassium phosphate and amino acid salt.

[0020] Preferably, the humectant is one of glycerol, propylene glycol and polyethylene glycol.

[0021] Preferably, the composite crosslinking agent is composed of ethylene glycol dimethacrylate and zinc chloride with a mass ratio of 2-3:0.1-0.3.

[0022] In a second aspect, the application also provides a high-viscosity gel patch matrix and a preparation method, comprising the following preparation steps:

[0023] Step a, disperse modified sodium polyacrylate in deionized water, stir evenly, and get gel patch matrix skeleton liquid;

[0024] Step b, add film forming agent, penetration enhancer and tackifier to humectant, stir and mix evenly, and get mixture A;

[0025] Step c, slowly add gel patch matrix skeleton liquid, complex crosslinking agent and PH regulator to mixture A, adjust PH to 6.8-7.4, constant temperature at 50-70℃, magnetic stirring for 2-3h, natural cooling, and get high viscosity gel patch matrix.

[0026] In summary, the present application has the following beneficial effects:

[0027] The present application uses acrylic acid, N-vinyl pyrrolidone and temperature-responsive N-vinyl caprolactam as polymerization monomers, and introduces chitosan during polymerization. The introduction of N-vinyl caprolactam, N-vinyl pyrrolidone and chitosan makes the copolymer have multiple functional groups such as carboxyl and amide groups, which can endow the polymer with more functions such as adsorption and chelation. By adjusting the ratio of acrylic acid, N-vinyl caprolactam and N-vinyl pyrrolidone and reaction conditions, the critical solution temperature, viscosity and crosslinking degree of the copolymer can be accurately controlled to adapt to different application requirements.

[0028] The present application prepares the skeleton of the gel patch matrix by using the complex crosslinking agent prepared by compounding ethylene glycol dimethacrylate and zinc chloride. Ethylene glycol dimethacrylate has strong chemical stability and good mechanical strength and toughness after crosslinking to form a three-dimensional network structure. Zinc chloride can form a crosslinking network with the carboxyl groups on the polymer chain (such as the carboxyl groups in polyacrylic acid) through ionic crosslinking, further enhancing the mechanical properties of the gel matrix. Moreover, ionic crosslinking has a certain reversibility, which can be adjusted by changing the pH value or adding chelating agents to fine-tune the performance of the gel matrix and adjust the viscosity of the gel patch matrix. The balance of the hydrophobicity and smoothness of dimethicone can also adjust the tackiness of rosin, increase the overall flexibility and air permeability. In addition, zinc chloride also has certain antibacterial and anti-inflammatory effects, which is suitable for skin care and treatment applications, and can play a synergistic antibacterial and anti-inflammatory effect with chitosan. Chitosan also has good biocompatibility, film forming property and cationic characteristics, which interacts with the negative charge groups on the skin surface to form a thin film, enhancing the adhesion of the patch matrix. The addition of chitosan, N-vinyl pyrrolidone and N-vinyl caprolactam can improve the air permeability of the patch matrix, reduce skin irritation and allergic reactions, and is suitable for long-term use and sensitive skin. In addition, the temperature responsiveness of N-vinyl caprolactam allows it to firmly adhere during use, but easily and conveniently remove it, improving the user's experience and comfort. DETAILED DESCRIPTION

[0029] The application is further described in detail below in conjunction with examples.

[0030] The acrylic acid used in the examples and comparative examples of the application was purchased from Shandong Langcheng Chemical Co., Ltd., the sodium polyacrylate was purchased from Shandong Huiheng Biological Technology Co., Ltd., the chitosan (food grade) was purchased from Nantong Lvsen Biological Engineering Co., Ltd., the N-vinyl caprolactam (model: kq-116) was purchased from Wuhan Kangqiong Biological Medicine Technology Co., Ltd., the N-vinyl pyrrolidone was purchased from Jiaozuo Zhongweitepin Pharmaceutical Co., Ltd., the rosin (product number: 5949463) was purchased from Guangzhou Qunlin Chemical Co., Ltd., the dimethicone, triethanolamine, isopropanol, cross-linked sodium carboxymethyl cellulose and polyvinyl alcohol were all purchased from Jiangxi Alpha High-tech Pharmaceutical Co., Ltd.

[0031] Examples 1-3 provide a high-viscosity gel patch matrix and a preparation process.

[0032] Example 1

[0033] A high-viscosity gel patch matrix is made from the following raw materials by weight: modified sodium polyacrylate 5 parts, film-forming agent 0.5 parts, penetration enhancer 1 part, tackifier 1 part, PH adjuster 0.1 part, humectant 15 parts, composite crosslinking agent 0.05 parts, deionized water 10 parts.

[0034] Among them, the film-forming agent is cross-linked sodium carboxymethyl cellulose; the penetration enhancer is isopropanol; the tackifier is composed of rosin and dimethicone with a mass ratio of 1:0.1; the PH adjuster is triethanolamine; the humectant is glycerol; the composite crosslinking agent is composed of ethylene glycol dimethacrylate and zinc chloride with a mass ratio of 2:0.1.

[0035] The preparation of modified sodium polyacrylate includes the following steps:

[0036] Step S1, disperse acrylic acid, N-vinyl caprolactam, N-vinyl pyrrolidone and 1-hydroxy cyclohexyl phenyl ketone in deionized water, control the mass ratio of acrylic acid, N-vinyl caprolactam, N-vinyl pyrrolidone, 1-hydroxy cyclohexyl phenyl ketone and deionized water to be 8:1:0.5:0.05:25, stir at a stirring speed of 300 rpm at room temperature for 10 min, stir uniformly, add 0.1M sodium hydroxide solution, adjust the PH value to 7.0, and obtain reaction liquid A;

[0037] Step S2, transfer the reaction liquid A to a photoreactor, blow off oxygen for 15 min, initiate polymerization reaction under ultraviolet light at 20℃ for 2 min, the wavelength of the ultraviolet light is 365 nm, and the light intensity is 500 mW / cm 2 , to form a first prepolymer;

[0038] Step S3, dissolve chitosan in dilute acetic acid solution with PH value of 4, add glutaraldehyde, stir for 2h, stirring temperature 30℃, stirring speed 300rpm, prepare activated chitosan solution, control the mass ratio of chitosan, glutaraldehyde and dilute acetic acid solution is 3:0.1:50;

[0039] Step S4, mix the activated chitosan solution and the first prepolymer according to the mass ratio of 1:1 to obtain a mixed solution B, add ammonium persulfate solution to the mixed solution B, the addition amount of the ammonium persulfate solution accounts for 30% of the total volume of the mixed solution B, the concentration of the ammonium persulfate solution is 10wt%, stir at 45℃ with a stirring speed of 200rpm for 3h, cool, filter, wash, dry at 60℃ until constant weight to obtain modified sodium polyacrylate.

[0040] A preparation method of a high-viscosity gel patch matrix, specifically comprising the following steps:

[0041] Step a, disperse the modified sodium polyacrylate in deionized water, stir uniformly to obtain a gel patch matrix framework solution;

[0042] Step b, add a film-forming agent, a penetration enhancer and a tackifier to the humectant, stir at 20℃ with a stirring speed of 300rpm for 15min, stir and mix uniformly to obtain a mixed material A;

[0043] Step c, slowly add the gel patch matrix framework solution, the composite crosslinking agent and the PH regulator to the mixed material A, add for 30min, adjust the PH to 6.8, keep the temperature at 50℃, magnetically stir for 2h with a stirring speed of 100rpm, naturally cool to obtain a high-viscosity gel patch matrix.

[0044] Example 2

[0045] A high-viscosity gel patch matrix is made from the following raw materials by weight: modified sodium polyacrylate 7 parts, film-forming agent 0.8 parts, penetration enhancer 1.5 parts, tackifier 1.5 parts, PH regulator 0.15 parts, humectant 18 parts, composite crosslinking agent 0.01 parts, deionized water 11 parts.

[0046] Among them, the film-forming agent is polyvinyl alcohol; the penetration enhancer is isopropyl alcohol; the tackifier is composed of rosin and dimethicone with a mass ratio of 1.5:0.2; the PH regulator is triethanolamine; the humectant is glycerol; the composite crosslinking agent is composed of ethylene glycol dimethacrylate and zinc chloride with a mass ratio of 2.5:0.2.

[0047] The preparation of modified sodium polyacrylate includes the following steps:

[0048] Step S1, acrylic acid, N-vinyl caprolactam, N-vinyl pyrrolidone and 1-hydroxy cyclohexyl phenyl ketone are dispersed in deionized water, the mass ratio of acrylic acid, N-vinyl caprolactam, N-vinyl pyrrolidone, 1-hydroxy cyclohexyl phenyl ketone and deionized water is controlled to be 9:2:0.8:0.08:28, stirring at room temperature with stirring speed of 350 rpm for 12 min, stirring uniformly, adding 0.1M sodium hydroxide solution, adjusting the pH value to 7.2, to obtain reaction liquid A;

[0049] Step S2, the reaction liquid A is transferred to a photoreactor, nitrogen blowing is performed for 25 min to remove oxygen, ultraviolet light is used to initiate polymerization reaction at 22℃ for 3 min, the wavelength of the ultraviolet light is 365 nm, and the light intensity is 600 mW / cm 2 , to form a first prepolymer;

[0050] Step S3, chitosan is dissolved in a dilute acetic acid solution with pH value of 4.5, glutaraldehyde is added, stirring is performed for 2.5 h, the stirring temperature is 35℃, and the stirring speed is 350 rpm, to prepare an activated chitosan solution, and the mass ratio of chitosan, glutaraldehyde and dilute acetic acid solution is controlled to be 4:0.3:55;

[0051] Step S4, the activated chitosan solution and the first prepolymer are mixed according to the mass ratio of 1.3:1 to obtain a mixed liquid B, an ammonium persulfate solution is added to the mixed liquid B, the addition amount of the ammonium persulfate solution accounts for 35% of the total volume of the mixed liquid B, the concentration of the ammonium persulfate solution is 13 wt%, stirring is performed at 55℃ with stirring speed of 250 rpm for 3.5 h, and then cooling, filtering, washing and drying at 70℃ until the constant weight are performed, to obtain the modified sodium polyacrylate.

[0052] A preparation method of a high-viscosity gel patch matrix, specifically comprising the following steps:

[0053] Step a, the modified sodium polyacrylate is dispersed in deionized water, and after uniform stirring, a gel patch matrix framework liquid is obtained;

[0054] Step b, the film-forming agent, the penetration enhancer and the tackifier are added to the humectant, stirring is performed at 25℃ with stirring speed of 350 rpm for 18 min, and after uniform stirring and mixing, a mixed material A is obtained;

[0055] Step c, the gel patch matrix framework liquid, the composite crosslinking agent and the pH regulator are added to the mixed material A, the feeding is performed for 45 min, the pH value is adjusted to 7.2, magnetic stirring is performed at 60℃ for 2.5 h with stirring speed of 150 rpm, and then natural cooling is performed, to obtain the high-viscosity gel patch matrix.

[0056] Example 3

[0057] A high-viscosity gel patch matrix is ​​made from the following raw materials in parts by weight: 8 parts modified sodium polyacrylate, 1 part film-forming agent, 2 parts penetration enhancer, 2 parts tackifier, 0.2 parts pH adjuster, 20 parts humectant, 0.2 parts composite crosslinking agent, and 12 parts deionized water.

[0058] The film-forming agent is croscarmellose sodium; the penetration enhancer is isopropanol; the thickener is composed of rosin and dimethicone in a mass ratio of 2:0.3; the pH adjuster is triethanolamine; the humectant is glycerin; and the composite crosslinking agent is composed of ethylene glycol dimethacrylate and zinc chloride in a mass ratio of 1:0.1.

[0059] The preparation of modified sodium polyacrylate includes the following steps:

[0060] Step S1: Disperse acrylic acid, N-vinylcaprolactam, N-vinylpyrrolidone, and 1-hydroxycyclohexylphenyl ketone in deionized water, controlling the mass ratio of acrylic acid, N-vinylcaprolactam, N-vinylpyrrolidone, 1-hydroxycyclohexylphenyl ketone, and deionized water to be 10:3:1:0.1:30. Stir at room temperature for 15 minutes at a stirring speed of 400 rpm until homogeneous. Add 0.1M sodium hydroxide solution to adjust the pH to 7.5 to obtain reaction solution A.

[0061] Step S2: Transfer reaction solution A to the photoreactor, remove oxygen by nitrogen blowing for 30 minutes, and initiate the polymerization reaction with ultraviolet light at 25°C for 5 minutes. The wavelength of the ultraviolet light is 365 nm and the light intensity is 800 mW / cm². 2 This forms the first prepolymer;

[0062] Step S3: Dissolve chitosan in a dilute acetic acid solution with a pH of 5, add glutaraldehyde, stir for 3 hours, stir at 40°C and 400 rpm to prepare an activated chitosan solution, and control the mass ratio of chitosan, glutaraldehyde and dilute acetic acid solution to be 5:0.5:60.

[0063] Step S4: Mix the activated chitosan solution and the first prepolymer at a mass ratio of 1.5:1 to obtain mixture B. Add ammonium persulfate solution to mixture B. The amount of ammonium persulfate solution added accounts for 40% of the total volume of mixture B. The concentration of ammonium persulfate solution is 15wt%. Stir and react at 60°C and a stirring speed of 300 rpm for 4 hours. Cool, filter, wash, and dry at 80°C to constant weight to obtain modified sodium polyacrylate.

[0064] A method for preparing a high-viscosity gel patch matrix specifically includes the following steps:

[0065] Step a: Disperse the modified sodium polyacrylate in deionized water and stir until homogeneous to obtain the gel patch matrix skeleton liquid;

[0066] Step b, add film forming agent, penetration enhancer and tackifier into humectant, stir at 30℃ with stirring speed of 400rpm for 20min, after mixing evenly, get mixture A;

[0067] Step c, slowly add gel patch matrix skeleton liquid, composite crosslinking agent and PH regulator into mixture A, feeding time is 60min, adjust PH value to 7.4, constant temperature at 70℃, magnetic stirring for 3h with stirring speed of 200rpm, natural cooling, get high viscosity gel patch matrix.

[0068] Comparative example 1

[0069] A high viscosity gel patch matrix is made of the following raw materials by weight: sodium polyacrylate 5 parts, film forming agent 0.5 parts, penetration enhancer 1 part, tackifier 1 part, PH regulator 0.1 part, humectant 15 parts, composite crosslinking agent 0.05 parts, deionized water 10 parts.

[0070] Among them, the film forming agent is crosslinked sodium carboxymethyl cellulose; the penetration enhancer is isopropyl alcohol; the tackifier is composed of rosin and dimethicone with a mass ratio of 1:0.1; the PH regulator is triethanolamine; the humectant is glycerol; the composite crosslinking agent is composed of ethylene glycol dimethacrylate and zinc chloride with a mass ratio of 2:0.1.

[0071] A preparation method of a high viscosity gel patch matrix, specifically comprising the following steps:

[0072] Step a, disperse sodium polyacrylate in deionized water, after stirring evenly, get gel patch matrix skeleton liquid;

[0073] Step b, add film forming agent, penetration enhancer and tackifier into humectant, stir at 20℃ with stirring speed of 300rpm for 15min, after mixing evenly, get mixture A;

[0074] Step c, slowly add gel patch matrix skeleton liquid, composite crosslinking agent and PH regulator into mixture A, feeding time is 30min, adjust PH value to 6.8, constant temperature at 50℃, magnetic stirring for 2h with stirring speed of 100rpm, natural cooling, get high viscosity gel patch matrix.

[0075] Comparative example 2

[0076] A high viscosity gel patch matrix is made of the following raw materials by weight: modified sodium polyacrylate 5 parts, film forming agent 0.5 parts, penetration enhancer 1 part, tackifier 1 part, PH regulator 0.1 part, humectant 15 parts, composite crosslinking agent 0.05 parts, deionized water 10 parts.

[0077] The film-forming agent is croscarmellose sodium; the penetration enhancer is isopropanol; the thickener is composed of rosin and dimethicone in a mass ratio of 1:0.1; the pH adjuster is triethanolamine; the humectant is glycerin; and the composite crosslinking agent is composed of ethylene glycol dimethacrylate and zinc chloride in a mass ratio of 2:0.1.

[0078] The preparation of modified sodium polyacrylate includes the following steps:

[0079] Step S1: Disperse acrylic acid, N-vinylpyrrolidone and 1-hydroxycyclohexylphenyl ketone in deionized water, controlling the mass ratio of acrylic acid, N-vinylpyrrolidone, 1-hydroxycyclohexylphenyl ketone and deionized water to be 8:0.5:0.05:25. Stir at room temperature for 10 minutes at a stirring speed of 300 rpm until homogeneous. Add 0.1M sodium hydroxide solution to adjust the pH to 7.0 to obtain reaction solution A.

[0080] Step S2: Transfer reaction solution A to the photoreactor, remove oxygen by nitrogen blowing for 15 minutes, and initiate the polymerization reaction with ultraviolet light at 20°C for 2 minutes. The wavelength of the ultraviolet light is 365 nm and the light intensity is 500 mW / cm². 2 This forms the first prepolymer;

[0081] Step S3: Dissolve chitosan in a dilute acetic acid solution with a pH of 4, add glutaraldehyde, stir for 2 hours, stir at 30°C and 300 rpm to prepare an activated chitosan solution, and control the mass ratio of chitosan, glutaraldehyde and dilute acetic acid solution to be 3:0.1:50.

[0082] Step S4: Mix the activated chitosan solution and the first prepolymer at a mass ratio of 1:1 to obtain mixture B. Add ammonium persulfate solution to mixture B. The amount of ammonium persulfate solution added accounts for 30% of the total volume of mixture B. The concentration of ammonium persulfate solution is 10wt%. Stir and react at 45°C and a stirring speed of 200 rpm for 3 hours. Cool, filter, wash, and dry at 60°C to constant weight to obtain modified sodium polyacrylate.

[0083] A method for preparing a high-viscosity gel patch matrix specifically includes the following steps:

[0084] Step a: Disperse the modified sodium polyacrylate in deionized water and stir until homogeneous to obtain the gel patch matrix skeleton liquid;

[0085] Step b: Add film-forming agent, penetration enhancer and thickener to humectant, stir at 300 rpm for 15 minutes at 20°C until evenly mixed to obtain mixture A;

[0086] Step c, slowly add gel patch matrix skeleton liquid, composite crosslinking agent and PH regulator to the mixture A, the feeding time is 30 min, adjust the PH to 6.8, constant temperature at 50℃, magnetic stirring for 2h, the stirring speed is 100rpm, natural cooling, get high viscosity gel patch matrix.

[0087] Comparative example 3

[0088] A high viscosity gel patch matrix is made of the following raw materials by weight: modified sodium polyacrylate 5 parts, film forming agent 0.5 parts, penetration enhancer 1 part, tackifier 1 part, PH regulator 0.1 part, humectant 15 parts, composite crosslinking agent 0.05 parts, deionized water 10 parts.

[0089] Among them, the film forming agent is crosslinked sodium carboxymethyl cellulose; the penetration enhancer is isopropyl alcohol; the tackifier is composed of rosin and dimethicone with a mass ratio of 1:0.1; the PH regulator is triethanolamine; the humectant is glycerol; the composite crosslinking agent is composed of ethylene glycol dimethyl acrylate and zinc chloride with a mass ratio of 2:0.1.

[0090] The preparation of modified sodium polyacrylate includes the following steps:

[0091] Step S1, disperse acrylic acid, N-vinyl caprolactam and 1-hydroxy cyclohexyl phenyl ketone in deionized water, control the mass ratio of acrylic acid, N-vinyl caprolactam and deionized water to be 8:1:0.05:25, stir at room temperature with a stirring speed of 300rpm for 10min, stir uniformly, add 0.1M sodium hydroxide solution, adjust the PH value to 7.0, get reaction liquid A;

[0092] Step S2, transfer the reaction liquid A to a photoreactor, blow off oxygen with nitrogen for 15min, initiate polymerization reaction under ultraviolet light at 20℃ for 2min, the wavelength of ultraviolet light is 365nm, the light intensity is 500mW / cm 2 , form a first prepolymer;

[0093] Step S3, dissolve chitosan in dilute acetic acid solution with a PH value of 4, add glutaraldehyde, stir for 2h, the stirring temperature is 30℃, the stirring speed is 300rpm, prepare an activated chitosan solution, control the mass ratio of chitosan, glutaraldehyde and dilute acetic acid solution to be 3:0.1:50;

[0094] Step S4, mix the activated chitosan solution and the first prepolymer according to the mass ratio of 1:1 to get a mixture B, add ammonium persulfate solution to the mixture B, the addition amount of ammonium persulfate solution accounts for

[0095] 30%, the concentration of ammonium persulfate solution is 10wt%, the stirring speed is 200rpm at 45℃, the reaction is stirred for 3h, and then the modified sodium polyacrylate is obtained by cooling, filtering, washing, and drying at 60℃ until the weight is constant.

[0096] A preparation method of a high-viscosity gel patch matrix, specifically comprising the following steps:

[0097] Step a: dispersing the modified sodium polyacrylate in deionized water, stirring uniformly, and then obtaining a gel patch matrix framework liquid;

[0098] Step b: adding a film-forming agent, a penetration enhancer, and a tackifier into the humectant, stirring at a speed of 300rpm at 20℃ for 15min, and then obtaining a mixture A after uniform stirring and mixing;

[0099] Step c: slowly adding the gel patch matrix framework liquid, a composite crosslinking agent, and a PH regulator into the mixture A, adjusting the PH to 6.8, maintaining the temperature at 50℃, magnetically stirring for 2h at a speed of 100rpm, and then obtaining a high-viscosity gel patch matrix after natural cooling.

[0100] Comparative Example 4

[0101] A high-viscosity gel patch matrix is prepared from the following raw materials by weight: 5 parts of modified sodium polyacrylate, 0.5 parts of a film-forming agent, 1 part of a penetration enhancer, 1 part of a tackifier, 0.1 part of a PH regulator, 15 parts of a humectant, 0.05 parts of a composite crosslinking agent, and 10 parts of deionized water.

[0102] The film-forming agent is cross-linked sodium carboxymethyl cellulose, the penetration enhancer is isopropyl alcohol, the tackifier is composed of rosin and dimethicone at a mass ratio of 1:0.1, the PH regulator is triethanolamine, the humectant is glycerol, and the composite crosslinking agent is composed of ethylene glycol dimethacrylate and zinc chloride at a mass ratio of 2:0.1.

[0103] The preparation of the modified sodium polyacrylate comprises the following steps:

[0104] Step S1: dispersing acrylic acid, N-vinyl caprolactam, N-vinyl pyrrolidone, and 1-hydroxy cyclohexyl phenyl ketone in deionized water, controlling the mass ratio of acrylic acid, N-vinyl caprolactam, 1-hydroxy cyclohexyl phenyl ketone, and deionized water to be 8:1:0.5:0.05:25, stirring at a speed of 300rpm at room temperature for 10min, stirring uniformly, adding a 0.1M sodium hydroxide solution, and adjusting the PH value to 7.0 to obtain a reaction liquid A;

[0105] Step S2, the reaction liquid A is transferred to the photo-reactor, nitrogen is blown to remove oxygen for 15 min, and the polymerization reaction is initiated by ultraviolet light at 20℃ for 2 min, the wavelength of the ultraviolet light is 365 nm, and the light intensity is 500 mW / cm 2 to form a first prepolymer;

[0106] Step S3, the dilute acetic acid solution with a pH value of 4 and the first prepolymer are mixed at a mass ratio of 1:1 to obtain a mixed liquid B, an ammonium persulfate solution is added to the mixed liquid B, the addition amount of the ammonium persulfate solution is 30% of the total volume of the mixed liquid B, the concentration of the ammonium persulfate solution is 10 wt%, the stirring speed is 200 rpm at 45℃, and the stirring reaction is performed for 3 h, and then the modified sodium polyacrylate is obtained by cooling, filtering, washing, and drying at 60℃ until the weight is constant.

[0107] A preparation method of a high-viscosity gel patch matrix, specifically comprising the following steps:

[0108] Step a, the modified sodium polyacrylate is dispersed in deionized water, and after uniform stirring, a gel patch matrix framework liquid is obtained;

[0109] Step b, the film-forming agent, the penetration enhancer, and the tackifier are added to the humectant, the stirring speed is 300 rpm at 20℃, and the stirring is performed for 15 min, and then the mixed material A is obtained after uniform stirring and mixing;

[0110] Step c, the gel patch matrix framework liquid, the composite crosslinking agent, and the PH regulator are slowly added to the mixed material A, the feeding time is 30 min, the PH is adjusted to 6.8, the temperature is kept at 50℃, the magnetic stirring is performed for 2 h at a stirring speed of 100 rpm, and then the high-viscosity gel patch matrix is obtained after natural cooling.

[0111] Comparative Example 5

[0112] A high-viscosity gel patch matrix is prepared from the following raw materials by weight: modified sodium polyacrylate 5 parts, film-forming agent 0.5 parts, penetration enhancer 1 part, tackifier 1 part, PH regulator 0.1 part, humectant 15 parts, composite crosslinking agent 0.05 parts, and deionized water 10 parts.

[0113] The film-forming agent is cross-linked sodium carboxymethyl cellulose, the penetration enhancer is isopropyl alcohol, the tackifier is rosin, the PH regulator is triethanolamine, the humectant is glycerol, and the composite crosslinking agent is composed of ethylene glycol dimethacrylate and zinc chloride at a mass ratio of 2:0.1.

[0114] The preparation of the modified sodium polyacrylate comprises the following steps:

[0115] Step S1, acrylic acid, N-vinyl caprolactam, N-vinyl pyrrolidone and 1-hydroxy cyclohexyl phenyl ketone were dispersed in deionized water, the mass ratio of acrylic acid, N-vinyl caprolactam, N-vinyl pyrrolidone, 1-hydroxy cyclohexyl phenyl ketone and deionized water was controlled to be 8:1:0.5:0.05:25, stirred at room temperature with stirring speed of 300 rpm for 10 min, stirred uniformly, 0.1M sodium hydroxide solution was added, and the PH value was adjusted to 7.0 to obtain reaction liquid A;

[0116] Step S2, the reaction liquid A was transferred to a photoreactor, and the oxygen was removed by nitrogen blowing for 15 min, and the polymerization reaction was initiated by ultraviolet light at 20℃ for 2 min, the wavelength of the ultraviolet light was 365 nm, and the light intensity was 500 mW / cm 2 , to form a first prepolymer;

[0117] Step S3, chitosan was dissolved in dilute acetic acid solution with PH value of 4, glutaraldehyde was added, and stirred for 2 h at stirring temperature of 30℃ and stirring speed of 300 rpm to prepare an activated chitosan solution, and the mass ratio of chitosan, glutaraldehyde and dilute acetic acid solution was controlled to be 3:0.1:50;

[0118] Step S4, the activated chitosan solution and the first prepolymer were mixed according to the mass ratio of 1:1 to obtain a mixed liquid B, ammonium persulfate solution was added to the mixed liquid B, the addition amount of the ammonium persulfate solution accounted for 30% of the total volume of the mixed liquid B, the concentration of the ammonium persulfate solution was 10 wt%, and the stirring reaction was carried out at 45℃ and stirring speed of 200 rpm for 3 h, and then the mixture was cooled, filtered, washed, and dried at 60℃ until the constant weight to obtain the modified sodium polyacrylate.

[0119] A preparation method of a high-viscosity gel patch matrix, specifically comprising the following steps:

[0120] Step a, the modified sodium polyacrylate was dispersed in deionized water, and after stirring uniformly, a gel patch matrix framework liquid was obtained;

[0121] Step b, the film forming agent, penetration enhancer and tackifier were added to the humectant, stirred at 300 rpm at 20℃ for 15 min, and after stirring and mixing uniformly, a mixed material A was obtained;

[0122] Step c, the gel patch matrix framework liquid, the composite crosslinking agent and the PH regulator were slowly added to the mixed material A, the feeding time was 30 min, the PH was adjusted to 6.8, the temperature was kept at 50℃, the magnetic stirring was carried out for 2 h at stirring speed of 100 rpm, and then the mixture was naturally cooled to obtain the high-viscosity gel patch matrix.

[0123] Comparative example 6

[0124] A high-viscosity gel patch matrix is made from the following raw materials by weight: modified sodium polyacrylate 5 parts, film forming agent 0.5 parts, penetration enhancer 1 part, tackifier 1 part, PH regulator 0.1 part, humectant 15 parts, crosslinking agent 0.05 parts, deionized water 10 parts.

[0125] The film forming agent is crosslinked sodium carboxymethyl cellulose; the penetration enhancer is isopropyl alcohol; the tackifier is composed of rosin and dimethicone in a mass ratio of 1:0.1; the PH regulator is triethanolamine; the humectant is glycerol; and the crosslinking agent is ethylene glycol dimethacrylate.

[0126] The preparation of modified sodium polyacrylate includes the following steps:

[0127] Step S1, disperse acrylic acid, N-vinyl caprolactam, N-vinyl pyrrolidone and 1-hydroxy cyclohexyl phenyl ketone in deionized water, control the mass ratio of acrylic acid, N-vinyl caprolactam, N-vinyl pyrrolidone, 1-hydroxy cyclohexyl phenyl ketone and deionized water to be 8:1:0.5:0.05:25, stir at room temperature with a stirring speed of 300 rpm for 10 min, stir uniformly, add 0.1M sodium hydroxide solution, adjust the PH value to 7.0, and obtain reaction liquid A;

[0128] Step S2, transfer the reaction liquid A to a photoreactor, blow off oxygen with nitrogen for 15 min, initiate polymerization reaction under ultraviolet light at 20℃ for 2 min, the wavelength of the ultraviolet light is 365 nm, and the light intensity is 500 mW / cm 2 , to form a first prepolymer;

[0129] Step S3, dissolve chitosan in a dilute acetic acid solution with a PH value of 4, add glutaraldehyde, stir and react for 2 h at a stirring temperature of 30℃ and a stirring speed of 300 rpm, prepare an activated chitosan solution, and control the mass ratio of chitosan, glutaraldehyde and dilute acetic acid solution to be 3:0.1:50;

[0130] Step S4, mix the activated chitosan solution and the first prepolymer according to a mass ratio of 1:1 to obtain a mixed liquid B, add an ammonium persulfate solution to the mixed liquid B, the addition amount of the ammonium persulfate solution accounts for 30% of the total volume of the mixed liquid B, the concentration of the ammonium persulfate solution is 10 wt%, stir at a stirring speed of 200 rpm at 45℃ for 3 h, cool, filter, wash, dry at 60℃ until the weight is constant, and thus modified sodium polyacrylate is obtained.

[0131] A preparation method of a high-viscosity gel patch matrix, specifically including the following steps:

[0132] Step a, disperse the modified sodium polyacrylate in deionized water, stir uniformly, and obtain a gel patch matrix skeleton liquid;

[0133] Step b, add film forming agent, penetration enhancer and tackifier into the humectant, stir at 20℃ with stirring speed of 300rpm for 15min, mix evenly, get mixture A;

[0134] Step c, slowly add gel patch matrix skeleton liquid, crosslinking agent and PH regulator into mixture A, add for 30min, adjust PH to 6.8, constant temperature at 50℃, magnetic stirring for 2h with stirring speed of 100rpm, natural cooling, get high viscosity gel patch matrix.

[0135] Performance test

[0136] The comprehensive performance of the high viscosity gel patch matrix prepared in Examples 1-3 and Comparative Examples 1-6 of the present application is as follows:

[0137] Initial tack test: refer to national standard GB / T 4852-2002 "Test method for initial tack of pressure sensitive adhesive tape (ball method)";

[0138] Adhesion retention test: refer to national standard GB / T 4851-2014 "Test method for adhesion retention of adhesive tape";

[0139] Peeling strength test: refer to national standard GB / T 2792-2014 "Test method for peeling strength of adhesive tape";

[0140] Bacteriostatic rate: refer to national standard GB 15979-2002 "Hygienic standard for disposable hygienic products";

[0141] Air permeability: take a surface dish with bottom area (S), inject 2 / 3 volume of distilled water, weigh and record as (W1), take a large enough uniform pressed gel patch matrix sample, seal the above water containing surface dish, place in an environment with temperature of 25℃ and relative humidity of 65%, place for 24h, remove the gel patch matrix sample, weigh and record as (W2), calculate the moisture air permeability: moisture air permeability = (W1-W2) / S;

[0142] The specific test results are shown in Table 1 below.

[0143] Table 1 Performance parameters of high viscosity gel patch matrix in Examples 1-3 and Comparative Examples 1-6

[0144]

[0145] As shown in Table 1, the high viscosity gel patch matrix prepared in the present application has high viscosity, good adhesion retention, can be firmly attached to the skin for a long time, has good air permeability and biocompatibility, and has good antibacterial performance, can be repeatedly peeled off and attached, and will not cause pain or damage to the skin when peeled off.

[0146] The embodiments are only illustrative of the present application, and are not intended to limit the present application. Those skilled in the art can make modifications to the embodiments according to the present application without creative contribution, as long as the modifications are within the scope of the claims of the present application.

Claims

1. A high viscosity gel patch substrate, characterized by, The high-viscosity gel patch matrix is made of the following raw materials by weight: modified sodium polyacrylate 5-8 parts, film-forming agent 0.5-1 part, penetration enhancer 1-2 parts, tackifier 1-2 parts, PH regulator 0.1-0.2 parts, humectant 15-20 parts, composite crosslinking agent 0.05-0.2 parts, and deionized water 10-12 parts; The preparation of the modified sodium polyacrylate includes the following steps: Step S1, disperse acrylic acid, N-vinyl caprolactam, N-vinyl pyrrolidone and photoinitiator in deionized water, stir uniformly, add sodium hydroxide solution, adjust the pH value to 7-7.5, and obtain reaction liquid A; Step S2, transfer the reaction liquid A into a photoreactor, blow off oxygen for 15-30 min, initiate polymerization reaction at 20-25℃ for 2-5 min, and form a first prepolymer; Step S3, dissolve chitosan in a dilute acid solution with a pH of 4-5, add a crosslinking agent, stir for 2-3 h to prepare an activated chitosan solution, and control the mass ratio of chitosan, crosslinking agent and dilute acid solution to be 3-5:0.1-0.5:50-60; Step S4, mix the activated chitosan solution and the first prepolymer, add ammonium persulfate solution, stir uniformly, react at 45-60℃ for 3-4 h, cool, filter, wash, dry at 60-80℃ until constant weight, and obtain the modified sodium polyacrylate; The mass ratio of acrylic acid, N-vinyl caprolactam, N-vinyl pyrrolidone and photoinitiator in step S1 is 8-10:1-3:0.5-1:0.05-0.1; The photoinitiator in step S1 is one or more of 2,2-dimethoxy-2-phenylphenylacetophenone, 2,4,6-trimethylbenzoyl diphenyl phosphine oxide and 1-hydroxycyclohexyl phenyl ketone; The photo-initiated polymerization in step S2 is ultraviolet light-initiated polymerization, the wavelength of the ultraviolet light-initiated polymerization is 200-400 nm, and the light intensity of the ultraviolet light-initiated polymerization is 500-800 mW / cm 2 ; The film-forming agent is crosslinked sodium carboxymethyl cellulose and / or polyvinyl alcohol; The penetration enhancer is isopropyl alcohol and / or peppermint oil; The tackifier is composed of rosin and dimethicone with a mass ratio of 1-2:0.1-0.3; The humectant is one of glycerol, propylene glycol and polyethylene glycol; The composite crosslinking agent is composed of ethylene glycol dimethacrylate and zinc chloride with a mass ratio of 2-3:0.1-0.

3.

2. The high viscosity gel patch of claim 1, wherein, The PH regulator is one of triethanolamine, potassium phosphate and amino acid salt.

3. A process for the preparation of a high viscosity gel patch substrate according to any one of claims 1-2, characterized in that, The specific preparation steps are as follows: Step a, disperse the modified sodium polyacrylate in deionized water, stir uniformly, and obtain a gel patch matrix skeleton liquid; Step b, add the film-forming agent, penetration enhancer and tackifier to the humectant, stir and mix uniformly, and obtain a mixed material A; Step c, slowly add the gel patch matrix skeleton liquid, composite crosslinking agent and PH regulator to the mixed material A, adjust the PH to 6.8-7.4, maintain the temperature at 50-70℃, magnetically stir for 2-3 h, and naturally cool to obtain the high-viscosity gel patch matrix.

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